Phenolic Lipids Affect the Activity and Conformation of Acetylcholinesterase from Electrophorus electricus (Electric eel)

Science.gov (United States)

Stasiuk, Maria; Janiszewska, Alicja; Kozubek, Arkadiusz

2014-01-01

Phenolic lipids were isolated from rye grains, cashew nutshell liquid (CNSL) from Anacardium occidentale, and fruit bodies of Merrulius tremellosus, and their effects on the electric eel acetylcholinesterase activity and conformation were studied. The observed effect distinctly depended on the chemical structure of the phenolic lipids that were available for interaction with the enzyme. All of the tested compounds reduced the activity of acetylcholinesterase. The degree of inhibition varied, showing a correlation with changes in the conformation of the enzyme tested by the intrinsic fluorescence of the Trp residues of the protein. PMID:24787269

Targeting the autolysis loop of urokinase-type plasminogen activator with conformation-specific monoclonal antibodies

DEFF Research Database (Denmark)

Bøtkjær, Kenneth Alrø; Fogh, Sarah; Bekes, Erin C

2011-01-01

Tight regulation of serine proteases is essential for their physiological function, and unbalanced states of protease activity have been implicated in a variety of human diseases. One key example is the presence of uPA (urokinase-type plasminogen activator) in different human cancer types......, demonstrating a direct link between conformational changes of the autolysis loop and the creation of a catalytically mature active site. All three antibodies are potent inhibitors of uPA activity, the two pro-uPA-specific ones by inhibiting conversion of pro-uPA to active uPA and the active u......PA-specific antibody by shielding the access of plasminogen to the active site. Furthermore, using immunofluorescence, the conformation-specific antibodies mAb-112 and mAb-12E6B10 enabled us to selectively stain pro-uPA or active uPA on the surface of cultured cells. Moreover, in various independent model systems...

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

Directory of Open Access Journals (Sweden)

Cuiling Xu

2009-10-01

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

Rapid Modulation of Aromatase Activity in the Vertebrate Brain

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Thierry D. Charlier

2013-01-01

Full Text Available Numerous steroid hormones, including 17β-estradiol (E2, activate rapid and transient cellular, physiological, and behavioral changes in addition to their well-described genomic effects. Aromatase is the key-limiting enzyme in the production of estrogens, and the rapid modulation of this enzymatic activity could produce rapid changes in local E2 concentrations. The mechanisms that might mediate such rapid enzymatic changes are not fully understood but are currently under intense scrutiny. Recent studies in our laboratory indicate that brain aromatase activity is rapidly inhibited by an increase in intracellular calcium concentration resulting from potassium-induced depolarization or from the activation of glutamatergic receptors. Phosphorylating conditions also reduce aromatase activity within minutes, and this inhibition is blocked by the addition of multiple protein kinase inhibitors. This rapid modulation of aromatase activity by phosphorylating conditions is a general mechanism observed in different cell types and tissues derived from a variety of species, including human aromatase expressed in various cell lines. Phosphorylation processes affect aromatase itself and do not involve changes in aromatase protein concentration. The control of aromatase activity by multiple kinases suggests that several amino acids must be concomitantly phosphorylated to modify enzymatic activity but site-directed mutagenesis of several amino acids alone or in combination has not to date revealed the identity of the targeted residue(s. Altogether, the phosphorylation processes affecting aromatase activity provide a new general mechanism by which the concentration of estrogens can be rapidly altered in the brain.

Rate of hydrolysis in ATP synthase is fine-tuned by  -subunit motif controlling active site conformation

KAUST Repository

Beke-Somfai, T.; Lincoln, P.; Norden, B.

2013-01-01

Computer-designed artificial enzymes will require precise understanding of how conformation of active sites may control barrier heights of key transition states, including dependence on structure and dynamics at larger molecular scale. F(o)F(1) ATP synthase is interesting as a model system: a delicate molecular machine synthesizing or hydrolyzing ATP using a rotary motor. Isolated F(1) performs hydrolysis with a rate very sensitive to ATP concentration. Experimental and theoretical results show that, at low ATP concentrations, ATP is slowly hydrolyzed in the so-called tight binding site, whereas at higher concentrations, the binding of additional ATP molecules induces rotation of the central γ-subunit, thereby forcing the site to transform through subtle conformational changes into a loose binding site in which hydrolysis occurs faster. How the 1-Å-scale rearrangements are controlled is not yet fully understood. By a combination of theoretical approaches, we address how large macromolecular rearrangements may manipulate the active site and how the reaction rate changes with active site conformation. Simulations reveal that, in response to γ-subunit position, the active site conformation is fine-tuned mainly by small α-subunit changes. Quantum mechanics-based results confirm that the sub-Ångström gradual changes between tight and loose binding site structures dramatically alter the hydrolysis rate.

Rate of hydrolysis in ATP synthase is fine-tuned by  -subunit motif controlling active site conformation

KAUST Repository

Beke-Somfai, T.

2013-01-23

Computer-designed artificial enzymes will require precise understanding of how conformation of active sites may control barrier heights of key transition states, including dependence on structure and dynamics at larger molecular scale. F(o)F(1) ATP synthase is interesting as a model system: a delicate molecular machine synthesizing or hydrolyzing ATP using a rotary motor. Isolated F(1) performs hydrolysis with a rate very sensitive to ATP concentration. Experimental and theoretical results show that, at low ATP concentrations, ATP is slowly hydrolyzed in the so-called tight binding site, whereas at higher concentrations, the binding of additional ATP molecules induces rotation of the central γ-subunit, thereby forcing the site to transform through subtle conformational changes into a loose binding site in which hydrolysis occurs faster. How the 1-Å-scale rearrangements are controlled is not yet fully understood. By a combination of theoretical approaches, we address how large macromolecular rearrangements may manipulate the active site and how the reaction rate changes with active site conformation. Simulations reveal that, in response to γ-subunit position, the active site conformation is fine-tuned mainly by small α-subunit changes. Quantum mechanics-based results confirm that the sub-Ångström gradual changes between tight and loose binding site structures dramatically alter the hydrolysis rate.

Conformal Nets II: Conformal Blocks

Science.gov (United States)

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

2017-08-01

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

Active Polymers — Emergent Conformational and Dynamical Properties: A Brief Review

Science.gov (United States)

Winkler, Roland G.; Elgeti, Jens; Gompper, Gerhard

2017-10-01

Active matter exhibits a wealth of emerging nonequilibrium behaviours. A paradigmatic example is the interior of cells, where active components, such as the cytoskeleton, are responsible for its structural organization and the dynamics of the various components. Of particular interest are the properties of polymers and filaments. The intimate coupling of thermal and active noise, hydrodynamic interactions, and polymer conformations implies the emergence of novel structural and dynamical features. In this article, we review recent theoretical and simulation developments and results for the structural and dynamical properties of polymers exposed to activity. Two- and three-dimensional filaments are considered propelled by different mechanisms such as active Brownian particles or hydrodynamically-coupled force dipoles.

Neural signatures of social conformity: A coordinate-based activation likelihood estimation meta-analysis of functional brain imaging studies.

Science.gov (United States)

Wu, Haiyan; Luo, Yi; Feng, Chunliang

2016-12-01

People often align their behaviors with group opinions, known as social conformity. Many neuroscience studies have explored the neuropsychological mechanisms underlying social conformity. Here we employed a coordinate-based meta-analysis on neuroimaging studies of social conformity with the purpose to reveal the convergence of the underlying neural architecture. We identified a convergence of reported activation foci in regions associated with normative decision-making, including ventral striatum (VS), dorsal posterior medial frontal cortex (dorsal pMFC), and anterior insula (AI). Specifically, consistent deactivation of VS and activation of dorsal pMFC and AI are identified when people's responses deviate from group opinions. In addition, the deviation-related responses in dorsal pMFC predict people's conforming behavioral adjustments. These are consistent with current models that disagreement with others might evoke "error" signals, cognitive imbalance, and/or aversive feelings, which are plausibly detected in these brain regions as control signals to facilitate subsequent conforming behaviors. Finally, group opinions result in altered neural correlates of valuation, manifested as stronger responses of VS to stimuli endorsed than disliked by others. Copyright © 2016 Elsevier Ltd. All rights reserved.

Whirling orbits around twirling black holes from conformal symmetry

Energy Technology Data Exchange (ETDEWEB)

Hadar, Shahar [Department of Applied Mathematics and Theoretical Physics, University of Cambridge,Wilberforce Road, Cambridge CB3 0WA (United Kingdom); Porfyriadis, Achilleas P. [Department of Physics, UCSB,Santa Barbara, CA 93106 (United States)

2017-03-03

Dynamics in the throat of rapidly rotating Kerr black holes is governed by an emergent near-horizon conformal symmetry. The throat contains unstable circular orbits at radii extending from the ISCO down to the light ring. We show that they are related by conformal transformations to physical plunges and osculating trajectories. These orbits have angular momentum arbitrarily higher than that of ISCO. Using the conformal symmetry we compute analytically the radiation produced by the physical orbits. We also present a simple formula for the full self-force on such trajectories in terms of the self-force on circular orbits.

SCR activity of conformed CuOx/ZrO2-SO4 catalysts

DEFF Research Database (Denmark)

Rasmussen, Søren Birk; Yates, Malcolm; Due-Hansen, Johannes

2010-01-01

CuOX/ZrO2-SO4 catalysts have been synthesised as conformed materials with the use of sepiolite as agglomerant and the performance in the NH3-SCR reaction with relation to biomass fired boiler units have been studied. The optimal Cu-loading of the catalysts is 3 wt.% CuO, both in terms of activity...

Reversible conformational change in herpes simplex virus glycoprotein B with fusion-from-without activity is triggered by mildly acidic pH

Directory of Open Access Journals (Sweden)

Nicola Anthony V

2010-12-01

Full Text Available Abstract Background The pre-fusion form of the herpes simplex virus (HSV fusion protein gB undergoes pH-triggered conformational change in vitro and during viral entry (Dollery et al., J. Virol. 84:3759-3766, 2010. The antigenic structure of gB from the fusion-from-without (FFWO strain of HSV-1, ANG path, resembles wild type gB that has undergone pH-triggered changes. Together, changes in the antigenic and oligomeric conformation of gB correlate with fusion activity. We tested whether the pre-fusion form of FFWO gB undergoes altered conformational change in response to low pH. Results A pH of 5.5 - 6.0 altered the conformation of Domains I and V of FFWO gB, which together comprise the functional region containing the hydrophobic fusion loops. The ANG path gB oligomer was altered at a similar pH. All changes were reversible. In wild type HSV lacking the UL45 protein, which has been implicated in gB-mediated fusion, gB still underwent pH-triggered changes. ANG path entry was inactivated by pretreatment of virions with low pH. Conclusion The pre-fusion conformation of gB with enhanced fusion activity undergoes alteration in antigenic structure and oligomeric conformation in response to acidic pH. We propose that endosomal pH triggers conformational change in mutant gB with FFWO activity in a manner similar to wild type. Differences apart from this trigger may account for the increased fusion activity of FFWO gB.

A lipid-mediated conformational switch modulates the thermosensing activity of DesK.

Science.gov (United States)

Inda, María Eugenia; Vandenbranden, Michel; Fernández, Ariel; de Mendoza, Diego; Ruysschaert, Jean-Marie; Cybulski, Larisa Estefanía

2014-03-04

The thermosensor DesK is a multipass transmembrane histidine-kinase that allows the bacterium Bacillus subtilis to adjust the levels of unsaturated fatty acids required to optimize membrane lipid fluidity. The cytoplasmic catalytic domain of DesK behaves like a kinase at low temperature and like a phosphatase at high temperature. Temperature sensing involves a built-in instability caused by a group of hydrophilic residues located near the N terminus of the first transmembrane (TM) segment. These residues are buried in the lipid phase at low temperature and partially "buoy" to the aqueous phase at higher temperature with the thinning of the membrane, promoting the required conformational change. Nevertheless, the core question remains poorly understood: How is the information sensed by the transmembrane region converted into a rearrangement in the cytoplasmic catalytic domain to control DesK activity? Here, we identify a "linker region" (KSRKERERLEEK) that connects the TM sensor domain with the cytoplasmic catalytic domain involved in signal transmission. The linker adopts two conformational states in response to temperature-dependent membrane thickness changes: (i) random coiled and bound to the phospholipid head groups at the water-membrane interface, promoting the phosphatase state or (ii) unbound and forming a continuous helix spanning a region from the membrane to the cytoplasm, promoting the kinase state. Our results uphold the view that the linker is endowed with a helix/random coil conformational duality that enables it to behave like a transmission switch, with helix disruption decreasing the kinase/phosphatase activity ratio, as required to modulate the DesK output response.

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

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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.

Can Crystal Symmetry and Packing Influence the Active Site Conformation of Homohexameric Purine Nucleoside Phosphorylases?

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Marija Luić

2016-06-01

Full Text Available It is generaly believed that enzymes retain most of their functionality in the crystal form due to the large solvent content of protein crystals. This is facilitated by the fact that their natural environment in solution is not too far from the one found in the crystal form. Nevertheless, if the nature of the enzyme is such to require conformational changes, overcoming of the crystal packing constraints may prove to be too difficult. Such conformational change is present in one class of enzymes (purine nucleoside phosphorylases, that is the subject of our scientific interest for many years. The influence of crystal symmetry and crystal packing on the conformation of the active sites in the case of homohexameric purine nucleoside phosphorylases is presented and analysed. This work is licensed under a Creative Commons Attribution 4.0 International License.

Synthesis, anticancer activity, and inhibition of tubulin polymerization by conformationally restricted analogues of lavendustin A.

Science.gov (United States)

Mu, Fanrong; Hamel, Ernest; Lee, Debbie J; Pryor, Donald E; Cushman, Mark

2003-04-24

Compounds in the lavendustin A series have been shown to inhibit both protein-tyrosine kinases (PTKs) and tubulin polymerization. Since certain lavendustin A derivatives can exist in conformations that resemble both the trans-stilbene structure of the PTK inhibitor piceatannol and the cis-stilbene structure of the tubulin polymerization inhibitor combretastatin A-4, the possibility exists that the ratio of the two types of activities of the lavendustins could be influenced through the synthesis of conformationally restricted analogues. Accordingly, the benzylaniline structure of a series of pharmacologically active lavendustin A fragments was replaced by either their cis- or their trans-stilbene relatives, and effects on both inhibition of tubulin polymerization and cytotoxicity in cancer cell cultures were monitored. Both dihydrostilbene and 1,2-diphenylalkyne congeners were also prepared and evaluated biologically. Surprisingly, conformational restriction of the bridge between the two aromatic rings of the lavendustins had no significant effect on biological activity. On the other hand, conversion of the three phenolic hydroxyl groups of the lavendustin A derivatives to their corresponding methyl ethers consistently abolished their ability to inhibit tubulin polymerization and usually decreased cytotoxicity in cancer cell cultures as well, indicating the importance of at least one of the phenolic hydroxyl groups. Further investigation suggested that the phenolic hydroxyl group in the salicylamide ring was required for activity, while the two phenol moieties in the hydroquinone ring could be methylated with retention of activity. Two of the lavendustin A derivatives displayed IC(50) values of 1.4 microM for inhibition of tubulin polymerization, which ranks them among the most potent of the known tubulin polymerization inhibitors.

Reactions driving conformational movements (molecular motors) in gels: conformational and structural chemical kinetics.

Science.gov (United States)

Otero, Toribio F

2017-01-18

In this perspective the empirical kinetics of conducting polymers exchanging anions and solvent during electrochemical reactions to get dense reactive gels is reviewed. The reaction drives conformational movements of the chains (molecular motors), exchange of ions and solvent with the electrolyte and structural (relaxation, swelling, shrinking and compaction) gel changes. Reaction-driven structural changes are identified and quantified from electrochemical responses. The empirical reaction activation energy (E a ), the reaction coefficient (k) and the reaction orders (α and β) change as a function of the conformational energy variation during the reaction. This conformational energy becomes an empirical magnitude. E a , k, α and β include and provide quantitative conformational and structural information. The chemical kinetics becomes structural chemical kinetics (SCK) for reactions driving conformational movements of the reactants. The electrochemically stimulated conformational relaxation model describes empirical results and some results from the literature for biochemical reactions. In parallel the development of an emerging technological world of soft, wet, multifunctional and biomimetic tools and anthropomorphic robots driven by reactions of the constitutive material, as in biological organs, can be now envisaged being theoretically supported by the kinetic model.

Activity and conformation of lysozyme in molecular solvents, protic ionic liquids (PILs) and salt-water systems.

Science.gov (United States)

Wijaya, Emmy C; Separovic, Frances; Drummond, Calum J; Greaves, Tamar L

2016-09-21

Improving protein stabilisation is important for the further development of many applications in the pharmaceutical, specialty chemical, consumer product and agricultural sectors. However, protein stabilization is highly dependent on the solvent environment and, hence, it is very complex to tailor protein-solvent combinations for stable protein maintenance. Understanding solvent features that govern protein stabilization will enable selection or design of suitable media with favourable solution environments to retain protein native conformation. In this work the structural conformation and activity of lysozyme in 29 solvent systems were investigated to determine the role of various solvent features on the stability of the enzyme. The solvent systems consisted of 19 low molecular weight polar solvents and 4 protic ionic liquids (PILs), both at different water content levels, and 6 aqueous salt solutions. Small angle X-ray scattering, Fourier transform infrared spectroscopy and UV-vis spectroscopy were used to investigate the tertiary and secondary structure of lysozyme along with the corresponding activity in various solvation systems. At low non-aqueous solvent concentrations (high water content), the presence of solvents and salts generally maintained lysozyme in its native structure and enhanced its activity. Due to the presence of a net surface charge on lysozyme, electrostatic interactions in PIL-water systems and salt solutions enhanced lysozyme activity more than the specific hydrogen-bond interactions present in non-ionic molecular solvents. At higher solvent concentrations (lower water content), solvents with a propensity to exhibit the solvophobic effect, analogous to the hydrophobic effect in water, retained lysozyme native conformation and activity. This solvophobic effect was observed particularly for solvents which contained hydroxyl moieties. Preferential solvophobic effects along with bulky chemical structures were postulated to result in less

Conformal field theory in conformal space

International Nuclear Information System (INIS)

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

1999-01-01

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

Structure of protease-cleaved Escherichia coli α-2-macroglobulin reveals a putative mechanism of conformational activation for protease entrapment

International Nuclear Information System (INIS)

Fyfe, Cameron D.; Grinter, Rhys; Josts, Inokentijs; Mosbahi, Khedidja; Roszak, Aleksander W.; Cogdell, Richard J.; Wall, Daniel M.; Burchmore, Richard J. S.; Byron, Olwyn; Walker, Daniel

2015-01-01

The X-ray structure of protease-cleaved E. coli α-2-macroglobulin is described, which reveals a putative mechanism of activation and conformational change essential for protease inhibition. Bacterial α-2-macroglobulins have been suggested to function in defence as broad-spectrum inhibitors of host proteases that breach the outer membrane. Here, the X-ray structure of protease-cleaved Escherichia coli α-2-macroglobulin is described, which reveals a putative mechanism of activation and conformational change essential for protease inhibition. In this competitive mechanism, protease cleavage of the bait-region domain results in the untethering of an intrinsically disordered region of this domain which disrupts native interdomain interactions that maintain E. coli α-2-macroglobulin in the inactivated form. The resulting global conformational change results in entrapment of the protease and activation of the thioester bond that covalently links to the attacking protease. Owing to the similarity in structure and domain architecture of Escherichia coli α-2-macroglobulin and human α-2-macroglobulin, this protease-activation mechanism is likely to operate across the diverse members of this group

Structure of protease-cleaved Escherichia coli α-2-macroglobulin reveals a putative mechanism of conformational activation for protease entrapment

Energy Technology Data Exchange (ETDEWEB)

Fyfe, Cameron D.; Grinter, Rhys; Josts, Inokentijs; Mosbahi, Khedidja [University of Glasgow, Glasgow G12 8QQ, Scotland (United Kingdom); Roszak, Aleksander W. [University of Glasgow, Glasgow G12 8QQ, Scotland (United Kingdom); University of Glasgow, Glasgow G12 8QQ, Scotland (United Kingdom); Cogdell, Richard J.; Wall, Daniel M.; Burchmore, Richard J. S.; Byron, Olwyn; Walker, Daniel, E-mail: daniel.walker@glasgow.ac.uk [University of Glasgow, Glasgow G12 8QQ, Scotland (United Kingdom)

2015-06-30

The X-ray structure of protease-cleaved E. coli α-2-macroglobulin is described, which reveals a putative mechanism of activation and conformational change essential for protease inhibition. Bacterial α-2-macroglobulins have been suggested to function in defence as broad-spectrum inhibitors of host proteases that breach the outer membrane. Here, the X-ray structure of protease-cleaved Escherichia coli α-2-macroglobulin is described, which reveals a putative mechanism of activation and conformational change essential for protease inhibition. In this competitive mechanism, protease cleavage of the bait-region domain results in the untethering of an intrinsically disordered region of this domain which disrupts native interdomain interactions that maintain E. coli α-2-macroglobulin in the inactivated form. The resulting global conformational change results in entrapment of the protease and activation of the thioester bond that covalently links to the attacking protease. Owing to the similarity in structure and domain architecture of Escherichia coli α-2-macroglobulin and human α-2-macroglobulin, this protease-activation mechanism is likely to operate across the diverse members of this group.

A key agonist-induced conformational change in the cannabinoid receptor CB1 is blocked by the allosteric ligand Org 27569.

Science.gov (United States)

Fay, Jonathan F; Farrens, David L

2012-09-28

Allosteric ligands that modulate how G protein-coupled receptors respond to traditional orthosteric drugs are an exciting and rapidly expanding field of pharmacology. An allosteric ligand for the cannabinoid receptor CB1, Org 27569, exhibits an intriguing effect; it increases agonist binding, yet blocks agonist-induced CB1 signaling. Here we explored the mechanism behind this behavior, using a site-directed fluorescence labeling approach. Our results show that Org 27569 blocks conformational changes in CB1 that accompany G protein binding and/or activation, and thus inhibit formation of a fully active CB1 structure. The underlying mechanism behind this behavior is that simultaneous binding of Org 27569 produces a unique agonist-bound conformation, one that may resemble an intermediate structure formed on the pathway to full receptor activation.

Conformational Fluctuations in G-Protein-Coupled Receptors

Science.gov (United States)

Brown, Michael F.

2014-03-01

G-protein-coupled receptors (GPCRs) comprise almost 50% of pharmaceutical drug targets, where rhodopsin is an important prototype and occurs naturally in a lipid membrane. Rhodopsin photoactivation entails 11-cis to all-trans isomerization of the retinal cofactor, yielding an equilibrium between inactive Meta-I and active Meta-II states. Two important questions are: (1) Is rhodopsin is a simple two-state switch? Or (2) does isomerization of retinal unlock an activated conformational ensemble? For an ensemble-based activation mechanism (EAM) a role for conformational fluctuations is clearly indicated. Solid-state NMR data together with theoretical molecular dynamics (MD) simulations detect increased local mobility of retinal after light activation. Resultant changes in local dynamics of the cofactor initiate large-scale fluctuations of transmembrane helices that expose recognition sites for the signal-transducing G-protein. Time-resolved FTIR studies and electronic spectroscopy further show the conformational ensemble is strongly biased by the membrane lipid composition, as well as pH and osmotic pressure. A new flexible surface model (FSM) describes how the curvature stress field of the membrane governs the energetics of active rhodopsin, due to the spontaneous monolayer curvature of the lipids. Furthermore, influences of osmotic pressure dictate that a large number of bulk water molecules are implicated in rhodopsin activation. Around 60 bulk water molecules activate rhodopsin, which is much larger than the number of structural waters seen in X-ray crystallography, or inferred from studies of bulk hydrostatic pressure. Conformational selection and promoting vibrational motions of rhodopsin lead to activation of the G-protein (transducin). Our biophysical data give a paradigm shift in understanding GPCR activation. The new view is: dynamics and conformational fluctuations involve an ensemble of substates that activate the cognate G-protein in the amplified visual

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

African Journals Online (AJOL)

The role of conformational space in drug action is presented. Two examples of molecules in different 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 ...

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

Yeast surface display platform for rapid discovery of conformationally selective nanobodies

DEFF Research Database (Denmark)

McMahon, Conor; Baier, Alexander S.; Pascolutti, Roberta

2018-01-01

this problem, we report a fully in vitro platform for nanobody discovery based on yeast surface display. We provide a blueprint for identifying nanobodies, demonstrate the utility of the library by crystallizing a nanobody with its antigen, and most importantly, we utilize the platform to discover...... conformationally selective nanobodies to two distinct human GPCRs. To facilitate broad deployment of this platform, the library and associated protocols are freely available for nonprofit research....

Conformation and activity alteration of horseradish peroxidase induced by the interaction with gene carrier polyethyleneimines

Science.gov (United States)

Huang, Aimin; Wei, Bangzhi; Mo, Junyong; Wang, Yajing; Ma, Lin

2018-01-01

Polyethyleneimine (PEI) has long been considered as "golden standard" for polymeric gene delivery carriers. However the molecular basis of the cytotoxicity of PEI is poorly understood. Little is known about the effects of PEI on the structure and functions of biomacromolecules. In this work, fluorescence, UV-vis absorption, circular dichroism spectroscopy were conducted to investigate the influence of PEI of average molecular weight 25, 10 and 1.8 kDa (denoted as PEI25k, PEI10k and PEI1.8k) on the conformation of horseradish peroxidase (HRP) and its catalytic efficiency. Zeta-potential measurement and isothermal titration calorimetry were used to reveal the mechanism of the interaction between PEIs and HRP. PEIs were found to bind onto the surface of HRP predominantly via hydrophobic interaction and hydrogen bond or van der Waals interaction. The complex formation between HRP and PEI induced a more compact conformation of the enzyme and an increased hydrophobicity of the microenvironment surrounding heme pocket. The conformational change of HRP had little impact on the affinity towards H2O2 and phenol. However, the increase in the non-planarity of porphyrin ring in the heme group led to an increase in the exposure degree of the active center and thus an enhancement of catalytic efficiency of HRP in the presence of high molecular weight PEIs (PEI25k and PEI10k). The polymer size played an important role in PEI-HRP interaction. PEI of low molecular weight (PEI1.8k) was less efficient to alter the conformation and catalytic activity of HRP in aqueous solutions.

The conforming brain and deontological resolve.

Science.gov (United States)

Pincus, Melanie; LaViers, Lisa; Prietula, Michael J; Berns, Gregory

2014-01-01

Our personal values are subject to forces of social influence. Deontological resolve captures how strongly one relies on absolute rules of right and wrong in the representation of one's personal values and may predict willingness to modify one's values in the presence of social influence. Using fMRI, we found that a neurobiological metric for deontological resolve based on relative activity in the ventrolateral prefrontal cortex (VLPFC) during the passive processing of sacred values predicted individual differences in conformity. Individuals with stronger deontological resolve, as measured by greater VLPFC activity, displayed lower levels of conformity. We also tested whether responsiveness to social reward, as measured by ventral striatal activity during social feedback, predicted variability in conformist behavior across individuals but found no significant relationship. From these results we conclude that unwillingness to conform to others' values is associated with a strong neurobiological representation of social rules.

The conforming brain and deontological resolve.

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Melanie Pincus

Full Text Available Our personal values are subject to forces of social influence. Deontological resolve captures how strongly one relies on absolute rules of right and wrong in the representation of one's personal values and may predict willingness to modify one's values in the presence of social influence. Using fMRI, we found that a neurobiological metric for deontological resolve based on relative activity in the ventrolateral prefrontal cortex (VLPFC during the passive processing of sacred values predicted individual differences in conformity. Individuals with stronger deontological resolve, as measured by greater VLPFC activity, displayed lower levels of conformity. We also tested whether responsiveness to social reward, as measured by ventral striatal activity during social feedback, predicted variability in conformist behavior across individuals but found no significant relationship. From these results we conclude that unwillingness to conform to others' values is associated with a strong neurobiological representation of social rules.

Unveiling the water-associated conformational mobility in the active site of ascorbate peroxidase.

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Chao, Wei-Chih; Lin, Li-Ju; Lu, Jyh-Feng; Wang, Jinn-Shyan; Lin, Tzu-Chieh; Chen, Yi-Han; Chen, Yi-Ting; Yang, Hsiao-Ching; Chou, Pi-Tai

2018-03-01

We carried out comprehensive spectroscopic studies of wild type and mutants of ascorbate peroxidase (APX) to gain understanding of the conformational mobility of the active site. In this approach, three unnatural tryptophans were applied to replace the distal tryptophan (W41) in an aim to probe polarity/water environment near the edge of the heme-containing active site. 7-azatryptophan ((7-aza)Trp) is sensitive to environment polarity, while 2,7-azatryptophan ((2,7-aza)Trp) and 2,6-diazatryptophan ((2,6-aza)Trp) undergo excited-state water-catalyzed double and triple proton transfer, respectively, and are sensitive to the water network. The combination of their absorption, emission bands and the associated relaxation dynamics of these fluorescence probes, together with the Soret-band difference absorption and resonance Raman spectroscopy, lead us to unveil the water associated conformational mobility in the active site of APX. The results are suggestive of the existence of equilibrium between two different environments surrounding W41 in APX, i.e., the water-rich and water-scant forms with distinct fluorescence relaxation. Our results thus demonstrate for the first time the power of integrating multiple sensors (7-aza)Trp, (2,7-aza)Trp and (2,6-aza)Trp in probing the water environment of a specifically targeted Trp in proteins. Copyright © 2017 Elsevier B.V. All rights reserved.

Conformational Rigidity and Protein Dynamics at Distinct Timescales Regulate PTP1B Activity and Allostery.

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Choy, Meng S; Li, Yang; Machado, Luciana E S F; Kunze, Micha B A; Connors, Christopher R; Wei, Xingyu; Lindorff-Larsen, Kresten; Page, Rebecca; Peti, Wolfgang

2017-02-16

Protein function originates from a cooperation of structural rigidity, dynamics at different timescales, and allostery. However, how these three pillars of protein function are integrated is still only poorly understood. Here we show how these pillars are connected in Protein Tyrosine Phosphatase 1B (PTP1B), a drug target for diabetes and cancer that catalyzes the dephosphorylation of numerous substrates in essential signaling pathways. By combining new experimental and computational data on WT-PTP1B and ≥10 PTP1B variants in multiple states, we discovered a fundamental and evolutionarily conserved CH/π switch that is critical for positioning the catalytically important WPD loop. Furthermore, our data show that PTP1B uses conformational and dynamic allostery to regulate its activity. This shows that both conformational rigidity and dynamics are essential for controlling protein activity. This connection between rigidity and dynamics at different timescales is likely a hallmark of all enzyme function. Copyright © 2017 Elsevier Inc. All rights reserved.

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

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Sullivan, David C; Lim, Carmay

2006-08-24

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

Conformational Clusters of Phosphorylated Tyrosine.

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

2017-12-06

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

Investigation of calcium-dependent activity and conformational dynamics of zebra fish 12-lipoxygenase.

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Mittal, Monica; Hasan, Mahmudul; Balagunaseelan, Navisraj; Fauland, Alexander; Wheelock, Craig; Rådmark, Olof; Haeggström, Jesper Z; Rinaldo-Matthis, Agnes

2017-08-01

A 12-lipoxygenase in zebra fish (zf12-LOX) was found to be required for normal embryonic development and LOXs are of great interest for targeted drug designing. In this study, we investigate the structural-functional aspects of zf12-LOX in response to calcium. A soluble version of zf12-LOX was created by mutagenesis. Based on multiple sequence alignment, we mutated the putative calcium-responsive amino acids in N-PLAT domain of soluble zf12-LOX. Using a series of biophysical methods, we ascertained the oligomeric state, stability, structural integrity and conformational changes of zf12-LOX in response to calcium. We also compared the biophysical properties of soluble zf12-LOX with the mutant in the absence and presence of calcium. Here we provide a detailed characterization of soluble zf12-LOX and the mutant. Both proteins exist as compact monomers in solution, however the enzyme activity of soluble zf12-LOX is significantly increased in presence of calcium. We find that the stimulatory effect of calcium on zf12-LOX is related to a change in protein structure as observed by SAXS, adopting an open-state. In contrast, enzyme with a mutated calcium regulatory site has reduced activity-response to calcium and restricted large re-modeling, suggesting that it retains a closed-state in response to calcium. Taken together, our study suggests that Ca 2+ -dependent regulation is associated with different domain conformation(s) that might change the accessibility to substrate-binding site in response to calcium. The study can be broadly implicated in better understanding the mode(s) of action of LOXs, and the enzymes regulated by calcium in general. Copyright © 2017 Elsevier B.V. All rights reserved.

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

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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.

Conformationally restrained aromatic analogues of fosmidomycin and FR900098.

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Kurz, Thomas; Schlüter, Katrin; Pein, Miriam; Behrendt, Christoph; Bergmann, Bärbel; Walter, Rolf D

2007-07-01

The synthesis and in-vitro antimalarial activity of conformationally restrained bis(pivaloyloxymethyl) ester analogues of the natural product fosmidomycin is presented. In contrast to alpha-aryl-substituted analogues, conformationally restrained aromatic analogues exhibit only moderate in-vitro antimalarial activity against the chloroquine-sensitive strain 3D7 of Plasmodium falciparum. The most active derivative displays an IC(50) value of 47 microM.

Conformation radiotherapy and conformal radiotherapy

International Nuclear Information System (INIS)

Morita, Kozo

1999-01-01

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

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

An RNA aptamer specific to Hsp70-ATP conformation inhibits its ATPase activity independent of Hsp40.

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Thirunavukarasu, Deepak; Shi, Hua

2015-04-01

The highly conserved and ubiquitous molecular chaperone heat shock protein 70 (Hsp70) plays a critical role in protein homeostasis (proteostasis). Controlled by its ATPase activity, Hsp70 cycles between two conformations, Hsp70-ATP and Hsp70-ADP, to bind and release its substrate. Chemical tools with distinct modes of action, especially those capable of modulating the ATPase activity of Hsp70, are being actively sought after in the mechanistic dissection of this system. Here, we report a conformation-specific RNA aptamer that binds only to Hsp70-ATP but not to Hsp70-ADP. We have refined this aptamer and demonstrated its inhibitory effect on Hsp70's ATPase activity. We have also shown that this inhibitory effect on Hsp70 is independent of its interaction with the Hsp40 co-chaperone. As Hsp70 is increasingly being recognized as a drug target in a number of age related diseases such as neurodegenerative, protein misfolding diseases and cancer, this aptamer is potentially useful in therapeutic applications. Moreover, this work also demonstrates the feasibility of using aptamers to target ATPase activity as a general therapeutic strategy.

Active site loop conformation regulates promiscuous activity in a lactonase from Geobacillus kaustophilus HTA426.

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Yu Zhang

Full Text Available Enzyme promiscuity is a prerequisite for fast divergent evolution of biocatalysts. A phosphotriesterase-like lactonase (PLL from Geobacillus kaustophilus HTA426 (GkaP exhibits main lactonase and promiscuous phosphotriesterase activities. To understand its catalytic and evolutionary mechanisms, we investigated a "hot spot" in the active site by saturation mutagenesis as well as X-ray crystallographic analyses. We found that position 99 in the active site was involved in substrate discrimination. One mutant, Y99L, exhibited 11-fold improvement over wild-type in reactivity (kcat/Km toward the phosphotriesterase substrate ethyl-paraoxon, but showed 15-fold decrease toward the lactonase substrate δ-decanolactone, resulting in a 157-fold inversion of the substrate specificity. Structural analysis of Y99L revealed that the mutation causes a ∼6.6 Å outward shift of adjacent loop 7, which may cause increased flexibility of the active site and facilitate accommodation and/or catalysis of organophosphate substrate. This study provides for the PLL family an example of how the evolutionary route from promiscuity to specificity can derive from very few mutations, which promotes alteration in the conformational adjustment of the active site loops, in turn draws the capacity of substrate binding and activity.

Squaraine rotaxanes with boat conformation macrocycles.

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Fu, Na; Baumes, Jeffrey M; Arunkumar, Easwaran; Noll, Bruce C; Smith, Bradley D

2009-09-04

Mechanical encapsulation of fluorescent, deep-red bis(anilino)squaraine dyes inside Leigh-type tetralactam macrocycles produces interlocked squaraine rotaxanes. The surrounding macrocycles are flexible and undergo rapid exchange of chair and boat conformations in solution. A series of X-ray crystal structures show how the rotaxane co-conformational exchange process involves simultaneous lateral oscillation of the macrocycle about the center of the encapsulated squaraine thread. Rotaxane macrocycles with 1,4-phenylene sidewalls and 2,6-pyridine dicarboxamide bridging units are more likely to adopt boat conformations in the solid state than analogous squaraine rotaxane systems with isophthalamide-containing macrocycles. A truncated squaraine dye, with a secondary amine attached directly to the central C(4)O(2) core, is less electrophilic than the extended bis(anilino)squaraine analogue, but it is still susceptible to chemical and photochemical bleaching. Its stability is greatly enhanced when it is encapsulated as an interlocked squaraine rotaxane. An X-ray crystal structure of this truncated squaraine rotaxane shows the macrocycle in a boat conformation, and NMR studies indicate that the boat is maintained in solution. Encapsulation as a rotaxane increases the dye's brightness by a factor of 6. The encapsulation process appears to constrain the dye and reduce deformation of the chromophore from planarity. This study shows how mechanical encapsulation as a rotaxane can be used as a rational design parameter to fine-tune the chemical and photochemical properties of squaraine dyes.

Replacement between conformity and counter-conformity in consumption decisions.

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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.

Conformation-induced remote meta-C-H activation of amines

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Tang, Ri-Yuan; Li, Gang; Yu, Jin-Quan

2014-03-01

Achieving site selectivity in carbon-hydrogen (C-H) functionalization reactions is a long-standing challenge in organic chemistry. The small differences in intrinsic reactivity of C-H bonds in any given organic molecule can lead to the activation of undesired C-H bonds by a non-selective catalyst. One solution to this problem is to distinguish C-H bonds on the basis of their location in the molecule relative to a specific functional group. In this context, the activation of C-H bonds five or six bonds away from a functional group by cyclometallation has been extensively studied. However, the directed activation of C-H bonds that are distal to (more than six bonds away) functional groups has remained challenging, especially when the target C-H bond is geometrically inaccessible to directed metallation owing to the ring strain encountered in cyclometallation. Here we report a recyclable template that directs the olefination and acetoxylation of distal meta-C-H bonds--as far as 11 bonds away--of anilines and benzylic amines. This template is able to direct the meta-selective C-H functionalization of bicyclic heterocycles via a highly strained, tricyclic-cyclophane-like palladated intermediate. X-ray and nuclear magnetic resonance studies reveal that the conformational biases induced by a single fluorine substitution in the template can be enhanced by using a ligand to switch from ortho- to meta-selectivity.

A constitutively activating mutation alters the dynamics and energetics of a key conformational change in a ligand-free G protein-coupled receptor.

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Tsukamoto, Hisao; Farrens, David L

2013-09-27

G protein-coupled receptors (GPCRs) undergo dynamic transitions between active and inactive conformations. Usually, these conversions are triggered when the receptor detects an external signal, but some so-called constitutively activating mutations, or CAMs, induce a GPCR to bind and activate G proteins in the absence of external stimulation, in ways still not fully understood. Here, we investigated how a CAM alters the structure of a GPCR and the dynamics involved as the receptor transitions between different conformations. Our approach used site-directed fluorescence labeling (SDFL) spectroscopy to compare opsin, the ligand-free form of the GPCR rhodopsin, with opsin containing the CAM M257Y, focusing specifically on key movements that occur in the sixth transmembrane helix (TM6) during GPCR activation. The site-directed fluorescence labeling data indicate opsin is constrained to an inactive conformation both in detergent micelles and lipid membranes, but when it contains the M257Y CAM, opsin is more dynamic and can interact with a G protein mimetic. Further study of these receptors using tryptophan-induced quenching (TrIQ) methods indicates that in detergent, the CAM significantly increases the population of receptors in the active state, but not in lipids. Subsequent Arrhenius analysis of the TrIQ data suggests that, both in detergent and lipids, the CAM lowers the energy barrier for TM6 movement, a key transition required for conversion between the inactive and active conformations. Together, these data suggest that the lowered energy barrier is a primary effect of the CAM on the receptor dynamics and energetics.

Use of a conformational switching aptamer for rapid and specific ex vivo identification of central nervous system lymphoma in a xenograft model

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Georges, Joseph F.; Liu, Xiaowei; Eschbacher, Jennifer; Nichols, Joshua; Mooney, Michael A.; Joy, Anna; Spetzler, Robert F.; Feuerstein, Burt G.; Anderson, Trent; Preul, Mark C.; Yan, Hao; Nakaji, Peter

2018-02-01

Improved tools for providing specific intraoperative diagnoses could improve patient care. In neurosurgery, intraoperatively differentiating non-operative lesions can be challenging, often necessitating immunohistochemical (IHC) procedures which require up to 24-48 hours. Here, we evaluate the feasibility of generating rapid ex vivo specific labeling using a novel lymphoma-specific fluorescent switchable aptamer. Our B-cell lymphoma-specific switchable aptamer produced only low-level fluorescence in its unbound conformation and generated an 8-fold increase in fluorescence once bound to its target on CD20-positive lymphoma cells. The aptamer demonstrated strong binding to B-cell lymphoma cells within 10 minutes of incubation. We applied the switchable aptamer to ex vivo xenograft tissue harboring B-cell lymphoma and astrocytoma, and within one hour specific visual identification of lymphoma was routinely possible. In this proof-of-concept study in human cell culture and orthotopic xenografts, we conclude that a fluorescent switchable aptamer can provide rapid and specific labeling of B-cell lymphoma, and that developing aptamer-based labeling approaches could simplify tissue staining and drastically reduce time to histopathological diagnoses compared with IHC-based methods. We propose that switchable aptamers could enhance expeditious, accurate intraoperative decision-making.

Conformational dependence of a protein kinase phosphate transfer reaction

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Labute, Montiago; Henkelman, Graeme; Tung, Chang-Shung; Fenimore, Paul; McMahon, Ben

2007-03-01

Atomic motions and energetics for a phosphate transfer reaction catalyzed by the cAMP-dependent protein kinase have been calculated using plane-wave density functional theory, starting from structures of proteins crystallized in both the reactant conformation (RC) and the transition-state conformation (TC). In TC, we calculate that the reactants and products are nearly isoenergetic with a 20-kJ/mol barrier, whereas phosphate transfer is unfavorable by 120 kJ/mol in the RC, with an even higher barrier. Our results demonstrate that the phosphate transfer reaction occurs rapidly and reversibly in a particular conformation of the protein, and that the reaction can be gated by changes of a few tenths of an angstrom in the catalytic site [1]. [1] G.H. Henkelman, M.X. LaBute, C.-S. Tung, P.W. Fenimore, B.H. McMahon, Proc. Natl. Acad. Sci. USA vol. 102, no. 43:15347-15351 (2005).

A remote palm domain residue of RB69 DNA polymerase is critical for enzyme activity and influences the conformation of the active site.

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Agata Jacewicz

Full Text Available Non-conserved amino acids that are far removed from the active site can sometimes have an unexpected effect on enzyme catalysis. We have investigated the effects of alanine replacement of residues distant from the active site of the replicative RB69 DNA polymerase, and identified a substitution in a weakly conserved palm residue (D714A, that renders the enzyme incapable of sustaining phage replication in vivo. D714, located several angstroms away from the active site, does not contact the DNA or the incoming dNTP, and our apoenzyme and ternary crystal structures of the Pol(D714A mutant demonstrate that D714A does not affect the overall structure of the protein. The structures reveal a conformational change of several amino acid side chains, which cascade out from the site of the substitution towards the catalytic center, substantially perturbing the geometry of the active site. Consistent with these structural observations, the mutant has a significantly reduced k pol for correct incorporation. We propose that the observed structural changes underlie the severe polymerization defect and thus D714 is a remote, non-catalytic residue that is nevertheless critical for maintaining an optimal active site conformation. This represents a striking example of an action-at-a-distance interaction.

Rapid optical determination of β-lactamase and antibiotic activity

Science.gov (United States)

2014-01-01

Background The absence of rapid tests evaluating antibiotic susceptibility results in the empirical prescription of antibiotics. This can lead to treatment failures due to escalating antibiotic resistance, and also furthers the emergence of drug-resistant bacteria. This study reports a rapid optical method to detect β-lactamase and thereby assess activity of β-lactam antibiotics, which could provide an approach for targeted prescription of antibiotics. The methodology is centred on a fluorescence quenching based probe (β-LEAF – β-Lactamase Enzyme Activated Fluorophore) that mimics the structure of β-lactam antibiotics. Results The β-LEAF assay was performed for rapid determination of β-lactamase production and activity of β-lactam antibiotic (cefazolin) on a panel of Staphylococcus aureus ATCC strains and clinical isolates. Four of the clinical isolates were determined to be lactamase producers, with the capacity to inactivate cefazolin, out of the twenty-five isolates tested. These results were compared against gold standard methods, nitrocefin disk test for β-lactamase detection and disk diffusion for antibiotic susceptibility, showing results to be largely consistent. Furthermore, in the sub-set of β-lactamase producers, it was demonstrated and validated that multiple antibiotics (cefazolin, cefoxitin, cefepime) could be assessed simultaneously to predict the antibiotic that would be most active for a given bacterial isolate. Conclusions The study establishes the rapid β-LEAF assay for β-lactamase detection and prediction of antibiotic activity using S. aureus clinical isolates. Although the focus in the current study is β-lactamase-based resistance, the overall approach represents a broad diagnostic platform. In the long-term, these studies form the basis for the development of assays utilizing a broader variety of targets, pathogens and drugs. PMID:24708478

The Large-scale Effect of Environment on Galactic Conformity

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

2018-04-01

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

Conformal house

DEFF Research Database (Denmark)

Ryttov, Thomas Aaby; Sannino, Francesco

2010-01-01

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

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

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

2010-01-01

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

Rapid Response Team activation for pediatric patients on the acute pain service.

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Teets, Maxwell; Tumin, Dmitry; Walia, Hina; Stevens, Jenna; Wrona, Sharon; Martin, David; Bhalla, Tarun; Tobias, Joseph D

2017-11-01

Untreated pain or overly aggressive pain management may lead to adverse physiologic consequences and activation of the hospital's Rapid Response Team. This study is a quality improvement initiative that attempts to identify patient demographics and patterns associated with Rapid Response Team consultations for patients on the acute pain service. A retrospective review of all patients on the acute pain service from February 2011 until June 2015 was cross-referenced with inpatients requiring consultation from the Rapid Response Team. Two independent practitioners reviewed electronic medical records to determine which events were likely associated with pain management interventions. Over a 4-year period, 4872 patients were admitted to the acute pain service of whom 135 unique patients required Rapid Response Team consults. There were 159 unique Rapid Response Team activations among 6538 unique acute pain service consults. A subset of 27 pain management-related Rapid Response Team consultations was identified. The largest percentage of patients on the acute pain service were adolescents aged 12-17 (36%). Compared to this age group, the odds of Rapid Response Team activation were higher among infants Team consultations may help to identify patients at risk for clinical decompensation. © 2017 John Wiley & Sons Ltd.

The tertiary origin of the allosteric activation of E. coli glucosamine-6-phosphate deaminase studied by sol-gel nanoencapsulation of its T conformer.

Directory of Open Access Journals (Sweden)

Sergio Zonszein

Full Text Available The role of tertiary conformational changes associated to ligand binding was explored using the allosteric enzyme glucosamine-6-phosphate (GlcN6P deaminase from Escherichia coli (EcGNPDA as an experimental model. This is an enzyme of amino sugar catabolism that deaminates GlcN6P, giving fructose 6-phosphate and ammonia, and is allosterically activated by N-acetylglucosamine 6-phosphate (GlcNAc6P. We resorted to the nanoencapsulation of this enzyme in wet silica sol-gels for studying the role of intrasubunit local mobility in its allosteric activation under the suppression of quaternary transition. The gel-trapped enzyme lost its characteristic homotropic cooperativity while keeping its catalytic properties and the allosteric activation by GlcNAc6P. The nanoencapsulation keeps the enzyme in the T quaternary conformation, making possible the study of its allosteric activation under a condition that is not possible to attain in a soluble phase. The involved local transition was slowed down by nanoencapsulation, thus easing the fluorometric analysis of its relaxation kinetics, which revealed an induced-fit mechanism. The absence of cooperativity produced allosterically activated transitory states displaying velocity against substrate concentration curves with apparent negative cooperativity, due to the simultaneous presence of subunits with different substrate affinities. Reaction kinetics experiments performed at different tertiary conformational relaxation times also reveal the sequential nature of the allosteric activation. We assumed as a minimal model the existence of two tertiary states, t and r, of low and high affinity, respectively, for the substrate and the activator. By fitting the velocity-substrate curves as a linear combination of two hyperbolic functions with Kt and Kr as KM values, we obtained comparable values to those reported for the quaternary conformers in solution fitted to MWC model. These results are discussed in the

MUFASA: the strength and evolution of galaxy conformity in various tracers

Science.gov (United States)

Rafieferantsoa, Mika; Davé, Romeel

2018-03-01

We investigate galaxy conformity using the MUFASA cosmological hydrodynamical simulation. We show a bimodal distribution in galaxy colour with radius, albeit with too many low-mass quenched satellite galaxies compared to observations. MUFASA produces conformity in observed properties such as colour, specific star formation rate (sSFR), and H I content, i.e. neighbouring galaxies have similar properties. We see analogous trends in other properties such as in environment, stellar age, H2 content, and metallicity. We introduce quantifying conformity using S(R), measuring the relative difference in upper and lower quartile properties of the neighbours. We show that low-mass and non-quenched haloes have weak conformity (S(R)≲ 0.5) extending to large projected radii R in all properties, while high-mass and quenched haloes have strong conformity (S(R)˜ 1) that diminishes rapidly with R and disappears at R ≳ 1 Mpc. S(R) is strongest for environment in low-mass haloes, and sSFR (or colour) in high-mass haloes, and is dominated by one-halo conformity with the exception of H I in small haloes. Metallicity shows a curious anticonformity in massive haloes. Tracking the evolution of conformity for z = 0 galaxies back in time shows that conformity broadly emerges as a late-time (z ≲ 1) phenomenon. However, for fixed halo mass bins, conformity is fairly constant with redshift out to z ≳ 2. These trends are consistent with the idea that strong conformity only emerges once haloes grow above MUFASA's quenching mass scale of ˜1012 M⊙. A quantitative measure of conformity in various properties, along with its evolution, thus represents a new and stringent test of the impact of quenching on environment within current galaxy formation models.

Conformation-Induced Remote meta-C–H Activation of Amines

Science.gov (United States)

Tang, Ri-Yuan; Li, Gang; Yu, Jin-Quan

2014-01-01

Achieving site selectivity in C–H functionalization is a long-standing challenge in organic synthesis. The small differences in intrinsic reactivity of C–H bonds in a given organic molecule often lead to poor discrimination by a catalyst. One solution to this problem is to distinguish C–H bonds based on their location with respect to a particular functional group. In this context, the activation of C–H bonds 5 or 6 bonds away from a functional group via cyclometalation has been extensively studied.1-13 However, directed activation of C–H bonds that are distal (>6 bonds away) from functional groups has remained difficult, especially when the target C–H bonds are geometrically inaccessible through directed metalation due to the ring strain encountered in cyclometalation.14,15 Herein we report a recyclable template that directs the olefination and acetoxyation of distal meta-C–H bonds (as far as 11 bonds away) of anilines and benzylic amines. Remarkably, this template is able to direct the meta-selective C–H functionalization of bicyclic heterocycles via highly strained tricyclic cyclophane-like palladated intermediates. X-ray and NMR studies reveal that the conformational biases induced by a single fluorine substitution in the template can be enhanced by a ligand to switch from ortho- to meta-selectivity. PMID:24622200

Clinical utility of RapidArc™ radiotherapy technology

International Nuclear Information System (INIS)

Infusino, Erminia

2015-01-01

RapidArc™ is a radiation technique that delivers highly conformal dose distributions through the complete rotation (360°) and speed variation of the linear accelerator gantry. This technique, called volumetric modulated arc therapy (VMAT), compared with conventional radiotherapy techniques, can achieve high-target volume coverage and sparing damage to normal tissues. RapidArc delivers precise dose distribution and conformity similar to or greater than intensity-modulated radiation therapy in a short time, generally a few minutes, to which image-guided radiation therapy is added. RapidArc has become a currently used technology in many centers, which use RapidArc technology to treat a large number of patients. Large and small hospitals use it to treat the most challenging cases, but more and more frequently for the most common cancers. The clinical use of RapidArc and VMAT technology is constantly growing. At present, a limited number of clinical data are published, mostly concerning planning and feasibility studies. Clinical outcome data are increasing for a few tumor sites, even if only a little. The purpose of this work is to discuss the current status of VMAT techniques in clinical use through a review of the published data of planning systems and clinical outcomes in several tumor sites. The study consisted of a systematic review based on analysis of manuscripts retrieved from the PubMed, BioMed Central, and Scopus databases by searching for the keywords “RapidArc”, “Volumetric modulated arc radiotherapy”, and “Intensity-modulated radiotherapy”

New open conformation of SMYD3 implicates conformational selection and allostery

Directory of Open Access Journals (Sweden)

Nicholas Spellmon

2016-12-01

Full Text Available 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.

Understanding modern magnets through conformal mapping

International Nuclear Information System (INIS)

Halbach, K.

1989-10-01

I want to show with the help of a number of examples that conformal mapping is a unique and enormously powerful tool for thinking about, and solving, problems. Usually one has to write down only a few equations, and sometimes none at all exclamation point When I started getting involved in work for which conformal mapping seemed to be a powerful tool, I did not think that I would ever be able to use that technique successfully because it seemed to require a nearly encyclopedic memory, an impression that was strengthened when I saw K. Kober's Dictionary of Conformal Representations. This attitude changed when I started to realize that beyond the basics of the theory of a function of a complex variable, I needed to know only about a handful of conformal maps and procedures. Consequently, my second goal for this talk is to show that in most cases conformal mapping functions can be obtained by formulating the underlying physics appropriately. This means particularly that encyclopedic knowledge of conformal maps is not necessary for successful use of conformal mapping techniques. To demonstrate these facts I have chosen examples from an area of physics/engineering in which I am active, namely accelerator physics. In order to do that successfully I start with a brief introduction into high energy charged particle storage ring technology, even though not all examples used in this paper to elucidate my points come directly from this particular field of accelerator technology

Acyclic peptides incorporating the d-Phe-2-Abz turn motif: Investigations on antimicrobial activity and propensity to adopt β-hairpin conformations.

Science.gov (United States)

Cameron, Alan J; Varnava, Kyriakos G; Edwards, Patrick J B; Harjes, Elena; Sarojini, Vijayalekshmi

2018-06-14

Three linear peptides incorporating d-Phe-2-Abz as the turn motif are reported. Peptide 1, a hydrophobic β-hairpin, served as a proof of principle for the design strategy with both NMR and CD spectra strongly suggesting a β-hairpin conformation. Peptides 2 and 3, designed as amphipathic antimicrobials, exhibited broad spectrum antimicrobial activity, with potency in the nanomolar range against Staphylococcus aureus. Both compounds possess a high degree of selectivity, proving non-haemolytic at concentrations 500 to 800 times higher than their respective minimal inhibitory concentrations (MICs) against S. aureus. Peptide 2 induced cell membrane and cell wall disintegration in both S. aureus and Pseudomonas aeruginosa as observed by transmission electron microscopy. Peptide 2 also demonstrated moderate antifungal activity against Candida albicans with an MIC of 50 μM. Synergism was observed with sub-MIC levels of amphotericin B (AmB), leading to nanomolar MICs against C. albicans for peptide 2. Based on circular dichroism spectra, both peptides 2 and 3 appear to exist as a mixture of conformers with the β-hairpin as a minor conformer in aqueous solution, and a slight increase in hairpin population in 50% trifluoroethanol, which was more pronounced for peptide 3. NMR spectra of peptide 2 in a 1:1 CD 3 CN/H 2 O mixture and 30 mM deuterated sodium dodecyl sulfate showed evidence of an extended backbone conformation of the β-strand residues. However, inter-strand rotating frame Overhauser effects (ROE) could not be detected and a loosely defined divergent hairpin structure resulted from ROE structure calculation in CD 3 CN/H 2 O. The loosely defined hairpin conformation is most likely a result of the electrostatic repulsions between cationic strand residues which also probably contribute towards maintaining low haemolytic activity. Copyright © 2018 European Peptide Society and John Wiley & Sons, Ltd.

Irradiation of head-and-neck tumors with intensity modulated radiotherapy (IMRT). Comparison between two IMRT techniques with 3D conformal irradiation

International Nuclear Information System (INIS)

Heeger, Jonas

2013-01-01

For 12 patients with inoperable head-neck carcinoma that were treated with 3D conformal irradiation techniques additional irradiation plans using IMRT were developed. It was shown that the IMRT techniques are superior to the 3D conformal technique. The new rapid arc technique is unclear with respect to the critical organs (parotid glands, spinal canal and mandibles) but is significantly advantageous for the other normal tissue with respect to conformity (steeper dose gradients) and thus radiation dose reduction. The resulting lower irradiation time and the reduced radiation exposure being important for the treatment economy and patients' comfort should favor the more planning intensive rapid arc technique.

Use of a conformational switching aptamer for rapid and specific ex vivo identification of central nervous system lymphoma in a xenograft model.

Directory of Open Access Journals (Sweden)

Joseph F Georges

Full Text Available Improved tools for providing specific intraoperative diagnoses could improve patient care. In neurosurgery, intraoperatively differentiating non-operative lesions such as CNS B-cell lymphoma from operative lesions can be challenging, often necessitating immunohistochemical (IHC procedures which require up to 24-48 hours. Here, we evaluate the feasibility of generating rapid ex vivo specific labeling using a novel lymphoma-specific fluorescent switchable aptamer. Our B-cell lymphoma-specific switchable aptamer produced only low-level fluorescence in its unbound conformation and generated an 8-fold increase in fluorescence once bound to its target on CD20-positive lymphoma cells. The aptamer demonstrated strong binding to B-cell lymphoma cells within 15 minutes of incubation as observed by flow cytometry. We applied the switchable aptamer to ex vivo xenograft tissue harboring B-cell lymphoma and astrocytoma, and within one hour specific visual identification of lymphoma was routinely possible. In this proof-of-concept study in human cell culture and orthotopic xenografts, we conclude that a fluorescent switchable aptamer can provide rapid and specific labeling of B-cell lymphoma, and that developing aptamer-based labeling approaches could simplify tissue staining and drastically reduce time to histopathological diagnoses compared with IHC-based methods. We propose that switchable aptamers could enhance expeditious, accurate intraoperative decision-making.

Use of a conformational switching aptamer for rapid and specific ex vivo identification of central nervous system lymphoma in a xenograft model.

Science.gov (United States)

Georges, Joseph F; Liu, Xiaowei; Eschbacher, Jennifer; Nichols, Joshua; Mooney, Michael A; Joy, Anna; Spetzler, Robert F; Feuerstein, Burt G; Preul, Mark C; Anderson, Trent; Yan, Hao; Nakaji, Peter

2015-01-01

Improved tools for providing specific intraoperative diagnoses could improve patient care. In neurosurgery, intraoperatively differentiating non-operative lesions such as CNS B-cell lymphoma from operative lesions can be challenging, often necessitating immunohistochemical (IHC) procedures which require up to 24-48 hours. Here, we evaluate the feasibility of generating rapid ex vivo specific labeling using a novel lymphoma-specific fluorescent switchable aptamer. Our B-cell lymphoma-specific switchable aptamer produced only low-level fluorescence in its unbound conformation and generated an 8-fold increase in fluorescence once bound to its target on CD20-positive lymphoma cells. The aptamer demonstrated strong binding to B-cell lymphoma cells within 15 minutes of incubation as observed by flow cytometry. We applied the switchable aptamer to ex vivo xenograft tissue harboring B-cell lymphoma and astrocytoma, and within one hour specific visual identification of lymphoma was routinely possible. In this proof-of-concept study in human cell culture and orthotopic xenografts, we conclude that a fluorescent switchable aptamer can provide rapid and specific labeling of B-cell lymphoma, and that developing aptamer-based labeling approaches could simplify tissue staining and drastically reduce time to histopathological diagnoses compared with IHC-based methods. We propose that switchable aptamers could enhance expeditious, accurate intraoperative decision-making.

Nontargeted, Rapid Screening of Extra Virgin Olive Oil Products for Authenticity Using Near-Infrared Spectroscopy in Combination with Conformity Index and Multivariate Statistical Analyses.

Science.gov (United States)

Karunathilaka, Sanjeewa R; Kia, Ali-Reza Fardin; Srigley, Cynthia; Chung, Jin Kyu; Mossoba, Magdi M

2016-10-01

A rapid tool for evaluating authenticity was developed and applied to the screening of extra virgin olive oil (EVOO) retail products by using Fourier-transform near infrared (FT-NIR) spectroscopy in combination with univariate and multivariate data analysis methods. Using disposable glass tubes, spectra for 62 reference EVOO, 10 edible oil adulterants, 20 blends consisting of EVOO spiked with adulterants, 88 retail EVOO products and other test samples were rapidly measured in the transmission mode without any sample preparation. The univariate conformity index (CI) and the multivariate supervised soft independent modeling of class analogy (SIMCA) classification tool were used to analyze the various olive oil products which were tested for authenticity against a library of reference EVOO. Better discrimination between the authentic EVOO and some commercial EVOO products was observed with SIMCA than with CI analysis. Approximately 61% of all EVOO commercial products were flagged by SIMCA analysis, suggesting that further analysis be performed to identify quality issues and/or potential adulterants. Due to its simplicity and speed, FT-NIR spectroscopy in combination with multivariate data analysis can be used as a complementary tool to conventional official methods of analysis to rapidly flag EVOO products that may not belong to the class of authentic EVOO. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

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...

C-metric solution for conformal gravity with a conformally coupled scalar field

Energy Technology Data Exchange (ETDEWEB)

Meng, Kun, E-mail: mengkun@tjpu.edu.cn [School of Science, Tianjin Polytechnic University, Tianjin 300387 (China); Zhao, Liu, E-mail: lzhao@nankai.edu.cn [School of Physics, Nankai University, Tianjin 300071 (China)

2017-02-15

The C-metric solution of conformal gravity with a conformally coupled scalar field is presented. The solution belongs to the class of Petrov type D spacetimes and is conformal to the standard AdS C-metric appeared in vacuum Einstein gravity. For all parameter ranges, we identify some of the physically interesting static regions and the corresponding coordinate ranges. The solution may contain a black hole event horizon, an acceleration horizon, either of which may be cut by the conformal infinity or be hidden behind the conformal infinity. Since the model is conformally invariant, we also discussed the possible effects of the conformal gauge choices on the structure of the spacetime.

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.

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.

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.

Non-conformable, partial and conformable transposition

DEFF Research Database (Denmark)

König, Thomas; Mäder, Lars Kai

2013-01-01

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

A multi-directional rapidly exploring random graph (mRRG) for protein folding

KAUST Repository

Nath, Shuvra Kanti; Thomas, Shawna; Ekenna, Chinwe; Amato, Nancy M.

2012-01-01

Modeling large-scale protein motions, such as those involved in folding and binding interactions, is crucial to better understanding not only how proteins move and interact with other molecules but also how proteins misfold, thus causing many devastating diseases. Robotic motion planning algorithms, such as Rapidly Exploring Random Trees (RRTs), have been successful in simulating protein folding pathways. Here, we propose a new multi-directional Rapidly Exploring Random Graph (mRRG) specifically tailored for proteins. Unlike traditional RRGs which only expand a parent conformation in a single direction, our strategy expands the parent conformation in multiple directions to generate new samples. Resulting samples are connected to the parent conformation and its nearest neighbors. By leveraging multiple directions, mRRG can model the protein motion landscape with reduced computational time compared to several other robotics-based methods for small to moderate-sized proteins. Our results on several proteins agree with experimental hydrogen out-exchange, pulse-labeling, and F-value analysis. We also show that mRRG covers the conformation space better as compared to the other computation methods. Copyright © 2012 ACM.

Ligand-induced conformational changes: Improved predictions of ligand binding conformations and affinities

DEFF Research Database (Denmark)

Frimurer, T.M.; Peters, Günther H.J.; Iversen, L.F.

2003-01-01

tyrosine phosphatase 1 B (PTP1B) are known. To obtain a quantitative measure of the impact of conformational changes induced by the inhibitors, these were docked to the active site region of various structures of PTP1B using the docking program FlexX. Firstly, the inhibitors were docked to a PTP1B crystal...

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)

Conformal Gravity

International Nuclear Information System (INIS)

Hooft, G.

2012-01-01

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

An Efficient Null Model for Conformational Fluctuations in Proteins

DEFF Research Database (Denmark)

Harder, Tim Philipp; Borg, Mikael; Bottaro, Sandro

2012-01-01

Protein dynamics play a crucial role in function, catalytic activity, and pathogenesis. Consequently, there is great interest in computational methods that probe the conformational fluctuations of a protein. However, molecular dynamics simulations are computationally costly and therefore are often...... limited to comparatively short timescales. TYPHON is a probabilistic method to explore the conformational space of proteins under the guidance of a sophisticated probabilistic model of local structure and a given set of restraints that represent nonlocal interactions, such as hydrogen bonds or disulfide...... on conformational fluctuations that is in correspondence with experimental measurements. TYPHON provides a flexible, yet computationally efficient, method to explore possible conformational fluctuations in proteins....

Conformal dimension theory and application

CERN Document Server

Mackay, John M

2010-01-01

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

Self-objectification, feminist activism and conformity to feminine norms among female vegetarians, semi-vegetarians, and non-vegetarians.

Science.gov (United States)

Brinkman, Britney G; Khan, Aliya; Edner, Benjamin; Rosén, Lee A

2014-01-01

Recent research has suggested that vegetarians may be at an increased risk for developing disordered eating or body image issues when compared to non-vegetarians. However, the results of such studies are mixed, and no research has explored potential connections between vegetarianism and self-objectification. In the current study, the authors examine factors that predicted body surveillance, body shame, and appearance control beliefs; three aspects of self-objectification. Surveys were completed by 386 women from the United States who were categorized as vegetarian, semi-vegetarian, or non-vegetarian. The three groups differed regarding dietary motivations, levels of feminist activism, and body shame, but did not differ on their conformity to feminine norms. While conformity to feminine norms predicted body surveillance and body shame levels among all three groups of women, feminist activism predicted appearance control beliefs among non-vegetarians only. These findings suggest that it is important for researchers and clinicians to distinguish among these three groups when examining the relationship between vegetarianism and self-objectification. Copyright © 2013 Elsevier Ltd. All rights reserved.

Rapid Active Power Control of Photovoltaic Systems for Grid Frequency Support

Energy Technology Data Exchange (ETDEWEB)

Hoke, Anderson; Shirazi, Mariko; Chakraborty, Sudipta; Muljadi, Eduard; Maksimovic, Dragan

2017-01-01

As deployment of power electronic coupled generation such as photovoltaic (PV) systems increases, grid operators have shown increasing interest in calling on inverter-coupled generation to help mitigate frequency contingency events by rapidly surging active power into the grid. When responding to contingency events, the faster the active power is provided, the more effective it may be for arresting the frequency event. This paper proposes a predictive PV inverter control method for very fast and accurate control of active power. This rapid active power control method will increase the effectiveness of various higher-level controls designed to mitigate grid frequency contingency events, including fast power-frequency droop, inertia emulation, and fast frequency response, without the need for energy storage. The rapid active power control method, coupled with a maximum power point estimation method, is implemented in a prototype PV inverter connected to a PV array. The prototype inverter's response to various frequency events is experimentally confirmed to be fast (beginning within 2 line cycles and completing within 4.5 line cycles of a severe test event) and accurate (below 2% steady-state error).

Structures of closed and open conformations of dimeric human ATM

Science.gov (United States)

Baretić, Domagoj; Pollard, Hannah K.; Fisher, David I.; Johnson, Christopher M.; Santhanam, Balaji; Truman, Caroline M.; Kouba, Tomas; Fersht, Alan R.; Phillips, Christopher; Williams, Roger L.

2017-01-01

ATM (ataxia-telangiectasia mutated) is a phosphatidylinositol 3-kinase–related protein kinase (PIKK) best known for its role in DNA damage response. ATM also functions in oxidative stress response, insulin signaling, and neurogenesis. Our electron cryomicroscopy (cryo-EM) suggests that human ATM is in a dynamic equilibrium between closed and open dimers. In the closed state, the PIKK regulatory domain blocks the peptide substrate–binding site, suggesting that this conformation may represent an inactive or basally active enzyme. The active site is held in this closed conformation by interaction with a long helical hairpin in the TRD3 (tetratricopeptide repeats domain 3) domain of the symmetry-related molecule. The open dimer has two protomers with only a limited contact interface, and it lacks the intermolecular interactions that block the peptide-binding site in the closed dimer. This suggests that the open conformation may be more active. The ATM structure shows the detailed topology of the regulator-interacting N-terminal helical solenoid. The ATM conformational dynamics shown by the structures represent an important step in understanding the enzyme regulation. PMID:28508083

A Novel, Low-Cost Conformable Lander

Data.gov (United States)

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

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

Conformational Activation of Argonaute by Distinct yet Coordinated Actions of the Hsp70 and Hsp90 Chaperone Systems.

Science.gov (United States)

Tsuboyama, Kotaro; Tadakuma, Hisashi; Tomari, Yukihide

2018-05-17

Loading of small RNAs into Argonaute, the core protein in RNA silencing, requires the Hsp70/Hsp90 chaperone machinery. This machinery also activates many other clients, including steroid hormone receptors and kinases, but how their structures change during chaperone-dependent activation remains unclear. Here, we utilized single-molecule Förster resonance energy transfer (smFRET) to probe the conformational changes of Drosophila Ago2 mediated by the chaperone machinery. We found that empty Ago2 exists in various closed conformations. The Hsp70 system (Hsp40 and Hsp70) and the Hsp90 system (Hop, Hsp90, and p23) together render Ago2 into an open, active form. The Hsp70 system, but not the Hsp90 system alone, is sufficient for Ago2 to partially populate the open form. Instead, the Hsp90 system is required to extend the dwell time of Ago2 in the open state, which must be transiently primed by the Hsp70 system. Our data uncover distinct and coordinated actions of the chaperone machinery, where the Hsp70 system expands the structural ensembles of Ago2 and the Hsp90 system captures and stabilizes the active form. Copyright © 2018 Elsevier Inc. All rights reserved.

Fluorescence-tracking of activation gating in human ERG channels reveals rapid S4 movement and slow pore opening.

Directory of Open Access Journals (Sweden)

Zeineb Es-Salah-Lamoureux

2010-05-01

Full Text Available hERG channels are physiologically important ion channels which mediate cardiac repolarization as a result of their unusual gating properties. These are very slow activation compared with other mammalian voltage-gated potassium channels, and extremely rapid inactivation. The mechanism of slow activation is not well understood and is investigated here using fluorescence as a direct measure of S4 movement and pore opening.Tetramethylrhodamine-5-maleimide (TMRM fluorescence at E519 has been used to track S4 voltage sensor movement, and channel opening and closing in hERG channels. Endogenous cysteines (C445 and C449 in the S1-S2 linker bound TMRM, which caused a 10 mV hyperpolarization of the V((1/2 of activation to -27.5+/-2.0 mV, and showed voltage-dependent fluorescence signals. Substitution of S1-S2 linker cysteines with valines allowed unobstructed recording of S3-S4 linker E519C and L520C emission signals. Depolarization of E519C channels caused rapid initial fluorescence quenching, fit with a double Boltzmann relationship, F-V(ON, with V((1/2 (,1 = -37.8+/-1.7 mV, and V((1/2 (,2 = 43.5+/-7.9 mV. The first phase, V((1/2 (,1, was approximately 20 mV negative to the conductance-voltage relationship measured from ionic tail currents (G-V((1/2 = -18.3+/-1.2 mV, and relatively unchanged in a non-inactivating E519C:S620T mutant (V((1/2 = -34.4+/-1.5 mV, suggesting the fast initial fluorescence quenching tracked S4 voltage sensor movement. The second phase of rapid quenching was absent in the S620T mutant. The E519C fluorescence upon repolarization (V((1/2 = -20.6+/-1.2, k = 11.4 mV and L520C quenching during depolarization (V((1/2 = -26.8+/-1.0, k = 13.3 mV matched the respective voltage dependencies of hERG ionic tails, and deactivation time constants from -40 to -110 mV, suggesting they detected pore-S4 rearrangements related to ionic current flow during pore opening and closing.THE DATA INDICATE: 1 that rapid environmental changes occur at the

Rapid sampling of molecular motions with prior information constraints.

Science.gov (United States)

Raveh, Barak; Enosh, Angela; Schueler-Furman, Ora; Halperin, Dan

2009-02-01

Proteins are active, flexible machines that perform a range of different functions. Innovative experimental approaches may now provide limited partial information about conformational changes along motion pathways of proteins. There is therefore a need for computational approaches that can efficiently incorporate prior information into motion prediction schemes. In this paper, we present PathRover, a general setup designed for the integration of prior information into the motion planning algorithm of rapidly exploring random trees (RRT). Each suggested motion pathway comprises a sequence of low-energy clash-free conformations that satisfy an arbitrary number of prior information constraints. These constraints can be derived from experimental data or from expert intuition about the motion. The incorporation of prior information is very straightforward and significantly narrows down the vast search in the typically high-dimensional conformational space, leading to dramatic reduction in running time. To allow the use of state-of-the-art energy functions and conformational sampling, we have integrated this framework into Rosetta, an accurate protocol for diverse types of structural modeling. The suggested framework can serve as an effective complementary tool for molecular dynamics, Normal Mode Analysis, and other prevalent techniques for predicting motion in proteins. We applied our framework to three different model systems. We show that a limited set of experimentally motivated constraints may effectively bias the simulations toward diverse predicates in an outright fashion, from distance constraints to enforcement of loop closure. In particular, our analysis sheds light on mechanisms of protein domain swapping and on the role of different residues in the motion.

Rapid sampling of molecular motions with prior information constraints.

Directory of Open Access Journals (Sweden)

Barak Raveh

2009-02-01

Full Text Available Proteins are active, flexible machines that perform a range of different functions. Innovative experimental approaches may now provide limited partial information about conformational changes along motion pathways of proteins. There is therefore a need for computational approaches that can efficiently incorporate prior information into motion prediction schemes. In this paper, we present PathRover, a general setup designed for the integration of prior information into the motion planning algorithm of rapidly exploring random trees (RRT. Each suggested motion pathway comprises a sequence of low-energy clash-free conformations that satisfy an arbitrary number of prior information constraints. These constraints can be derived from experimental data or from expert intuition about the motion. The incorporation of prior information is very straightforward and significantly narrows down the vast search in the typically high-dimensional conformational space, leading to dramatic reduction in running time. To allow the use of state-of-the-art energy functions and conformational sampling, we have integrated this framework into Rosetta, an accurate protocol for diverse types of structural modeling. The suggested framework can serve as an effective complementary tool for molecular dynamics, Normal Mode Analysis, and other prevalent techniques for predicting motion in proteins. We applied our framework to three different model systems. We show that a limited set of experimentally motivated constraints may effectively bias the simulations toward diverse predicates in an outright fashion, from distance constraints to enforcement of loop closure. In particular, our analysis sheds light on mechanisms of protein domain swapping and on the role of different residues in the motion.

RapidRMSD: Rapid determination of RMSDs corresponding to motions of flexible molecules.

Science.gov (United States)

Neveu, Emilie; Popov, Petr; Hoffmann, Alexandre; Migliosi, Angelo; Besseron, Xavier; Danoy, Grégoire; Bouvry, Pascal; Grudinin, Sergei

2018-03-15

The root mean square deviation (RMSD) is one of the most used similarity criteria in structural biology and bioinformatics. Standard computation of the RMSD has a linear complexity with respect to the number of atoms in a molecule, making RMSD calculations time-consuming for the large-scale modeling applications, such as assessment of molecular docking predictions or clustering of spatially proximate molecular conformations. Previously we introduced the RigidRMSD algorithm to compute the RMSD corresponding to the rigid-body motion of a molecule. In this study we go beyond the limits of the rigid-body approximation by taking into account conformational flexibility of the molecule. We model the flexibility with a reduced set of collective motions computed with e.g. normal modes or principal component analysis. The initialization of our algorithm is linear in the number of atoms and all the subsequent evaluations of RMSD values between flexible molecular conformations depend only on the number of collective motions that are selected to model the flexibility. Therefore, our algorithm is much faster compared to the standard RMSD computation for large-scale modeling applications. We demonstrate the efficiency of our method on several clustering examples, including clustering of flexible docking results and molecular dynamics (MD) trajectories. We also demonstrate how to use the presented formalism to generate pseudo-random constant-RMSD structural molecular ensembles and how to use these in cross-docking. We provide the algorithm written in C ++ as the open-source RapidRMSD library governed by the BSD-compatible license, which is available at http://team.inria.fr/nano-d/software/RapidRMSD/. The constant-RMSD structural ensemble application and clustering of MD trajectories is available at http://team.inria.fr/nano-d/software/nolb-normal-modes/. sergei.grudinin@inria.fr. Supplementary data are available at Bioinformatics.

Rapid tryptic mapping using enzymatically active mass spectrometer probe tips

Energy Technology Data Exchange (ETDEWEB)

Dogruel, D.; Williams, P.; Nelson, R.W. [Arizona State Univ., Tempe, AZ (United States)

1995-12-01

A method has been developed for rapid, sensitive, and accurate tryptic mapping of polypeptides using matrix-assisted laser desorption/ionization time-of-flight mass analysis. The technique utilizes mass spectrometer probe tips which have been activated through the covalent immobilization of trypsin. The enzymatically active probe tips were used for the tryptic mapping of chicken egg lysozyme and the results compared with those obtained using either free trypsin or agarose-immobilized trypsin. A significant increase in the overall sensitivity of the process was observed using the active probe tips, as well as the production of more characteristic proteolytic fragments and the elimination of background signals due to the autolysis of the trypsin. Further, probe tip digestions were found to be rapid and convenient. 19 refs., 6 figs., 2 tabs.

Conformal symmetry in two-dimensional space: recursion representation of conformal block

International Nuclear Information System (INIS)

Zamolodchikov, A.B.

1988-01-01

The four-point conformal block plays an important part in the analysis of the conformally invariant operator algebra in two-dimensional space. The behavior of the conformal block is calculated in the present paper in the limit in which the dimension Δ of the intermediate operator tends to infinity. This makes it possible to construct a recursion relation for this function that connects the conformal block at arbitrary Δ to the blocks corresponding to the dimensions of the zero vectors in the degenerate representations of the Virasoro algebra. The relation is convenient for calculating the expansion of the conformal block in powers of the uniformizing parameters q = i π tau

Relationship between Oversulfation and Conformation of Low and High Molecular Weight Fucoidans and Evaluation of Their in Vitro Anticancer Activity

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Myoung Lae Cho

2010-12-01

Full Text Available Low and high molecular weight fucoidans (F5-30K and F>30K were chemically modified through the addition of sulfate groups, and the effect of oversulfation on the in vitro anticancer activity was investigated. After the addition of sulfate groups, a considerable increase of 35.5 to 56.8% was observed in the sulfate content of the F5-30K fraction, while the sulfate content of the F>30K fraction increased to a lesser extent (from 31.7 to 41.2%. Significant differences in anticancer activity were observed between the oversulfated F5–30K and F>30K fractions, with activities of 37.3–68.0% and 20.6–35.8%, respectively. This variation in the anticancer activity of oversulfated fucoidan derivatives was likely due to differences in their sulfate content. The results suggest that the molecular conformation of these molecules is closely related to the extent of sulfation in the fucan backbones and that the sulfates are preferably substituted when the fucoidan polymers are in a loose molecular conformation.

Conformational flexibility of aspartame.

Science.gov (United States)

Toniolo, Claudio; Temussi, Pierandrea

2016-05-01

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

Neural mechanisms underlying social conformity in an ultimatum game

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Zhenyu eWei

2013-12-01

Full Text Available When individuals’ actions are incongruent with those of the group they belong to, they may change their initial behavior in order to conform to the group norm. This phenomenon is known as social conformity. In the present study, we used event-related functional magnetic resonance imaging (fMRI to investigate brain activity in response to group opinion during an ultimatum game. Results showed that participants changed their choices when these choices conflicted with the normative opinion of the group they were members of, especially in conditions of unfair treatment. The fMRI data revealed that a conflict with group norms activated the brain regions involved in norm violations and behavioral adjustment. Furthermore, in the reject-unfair condition, we observed that a conflict with group norms activated the medial frontal gyrus. These findings contribute to recent research examining neural mechanisms involved in detecting violations of social norms, and provide information regarding the neural representation of conformity behavior in an economic game.

Conformational Changes Allow Processing of Bulky Substrates by a Haloalkane Dehalogenase with a Small and Buried Active Site.

Science.gov (United States)

Kokkonen, Piia; Bednar, David; Dockalova, Veronika; Prokop, Zbynek; Damborsky, Jiri

2018-06-01

Haloalkane dehalogenases catalyze the hydrolysis of halogen-carbon bonds in organic halogenated compounds and as such are of great utility as biocatalysts. The crystal structures of the haloalkane dehalogenase DhlA from the bacterium from Xanthobacter autotrophicus GJ10, specifically adapted for the conversion of the small 1,2-dichloroethane (DCE) molecule, display the smallest catalytic site (110 Å3) within this enzyme family. However, during a substrate-specificity screening, we noted that DhlA can catalyze the conversion of far bulkier substrates, such as the 4-(bromomethyl)-6,7-dimethoxy-coumarin (220 Å3). This large substrate cannot bind to DhlA without conformational alterations. These conformational changes have been previously inferred from kinetic analysis, but their structural basis has not been understood. Using molecular dynamic simulations, we demonstrate here the intrinsic flexibility of part of the cap domain that allows DhlA to accommodate bulky substrates. The simulations displayed two routes for transport of substrates to the active site, one of which requires the conformational change and which is likely the route for bulky substrates. These results provide insights into the structure-dynamics-function relationships in enzymes with deeply buried active sites. Moreover, understanding the structural basis for the molecular adaptation of DhlA to DCE introduced into the biosphere during the industrial revolution provides a valuable lesson in enzyme design by nature. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

Replacement of Ser108 in Plasmodium falciparum enolase results in weak Mg(II) binding: role of a parasite-specific pentapeptide insert in stabilizing the active conformation of the enzyme.

Science.gov (United States)

Dutta, Sneha; Mukherjee, Debanjan; Jarori, Gotam K

2015-06-01

A distinct structural feature of Plasmodium falciparum enolase (Pfeno) is the presence of a five amino acid insert -104EWGWS108- that is not found in host enolases. Its conservation among apicomplexan enolases has raised the possibility of its involvement in some important physiological function(s). Deletion of this sequence is known to lower k(cat)/K(m), increase K(a) for Mg(II) and convert dimer into monomers (Vora HK, Shaik FR, Pal-Bhowmick I, Mout R & Jarori GK (2009) Arch Biochem Biophys 485, 128-138). These authors also raised the possibility of the formation of an H-bond between Ser108 and Leu49 that could stabilize the apo-Pfeno in an active closed conformation that has high affinity for Mg(II). Here, we examined the effect of replacement of Ser108 with Gly/Ala/Thr on enzyme activity, Mg(II) binding affinity, conformational states and oligomeric structure and compared it with native recombinant Pfeno. The results obtained support the view that Ser108 is likely to be involved in the formation of certain crucial H-bonds with Leu49. The presence of these interactions can stabilize apo-Pfeno in an active closed conformation similar to that of Mg(II) bound yeast enolase. As predicted, S108G/A-Pfeno variants (where Ser108-Leu49 H-bonds are likely to be disrupted) were found to exist in an open conformation and had low affinity for Mg(II). They also required Mg(II) induced conformational changes to acquire the active closed conformational state essential for catalysis. The possible physiological relevance of apo-Pfeno being in such an active state is discussed. © 2015 FEBS.

Dynamic Conformations of Nucleosome Arrays in Solution from Small-Angle X-ray Scattering

Energy Technology Data Exchange (ETDEWEB)

Howell, Steven C. [George Washington Univ., Washington, DC (United States)

2016-01-31

We set out to determine quantitative information regarding the dynamic conformation of nucleosome arrays in solution using experimental SAXS. Toward this end, we developed a CG simulation algorithm for dsDNA which rapidly generates ensembles of structures through Metropolis MC sampling of a Markov chain.

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.

Conformal Infinity.

Science.gov (United States)

Frauendiener, Jörg

2004-01-01

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

Paper based Flexible and Conformal SERS Substrate for Rapid Trace Detection on Real-world Surfaces

Science.gov (United States)

Singamaneni, Srikanth; Lee, Chang; Tian, Limei

2011-03-01

One of the important but often overlooked considerations in the design of surface enhanced Raman scattering (SERS) substrates for trace detection is the efficiency of sample collection. Conventional designs based on rigid substrates such as silicon, alumina, and glass resist conformal contact with the surface under investigation, making the sample collection inefficient. We demonstrate a novel SERS substrate based on common filter paper adsorbed with gold nanorods, which allows conformal contact with real-world surfaces, thus dramatically enhancing the sample collection efficiency compared to conventional rigid substrates. We demonstrate the detection of trace amounts of analyte (140 pg spread over 4 cm2) by simply swabbing the surface under investigation with the novel SERS substrate. The hierarchical fibrous structure of paper serves as a 3D vasculature for easy uptake and transport of the analytes to the electromagnetic hot spots in the paper. Simple yet highly efficient and cost effective SERS substrate demonstrated here brings SERS based trace detection closer to real-world applications. We acknowledge the financial support from Center for Materials Innovation at Washington University.

Exploiting conformational ensembles in modeling protein-protein interactions on the proteome scale

Science.gov (United States)

Kuzu, Guray; Gursoy, Attila; Nussinov, Ruth; Keskin, Ozlem

2013-01-01

Cellular functions are performed through protein-protein interactions; therefore, identification of these interactions is crucial for understanding biological processes. Recent studies suggest that knowledge-based approaches are more useful than ‘blind’ docking for modeling at large scales. However, a caveat of knowledge-based approaches is that they treat molecules as rigid structures. The Protein Data Bank (PDB) offers a wealth of conformations. Here, we exploited ensemble of the conformations in predictions by a knowledge-based method, PRISM. We tested ‘difficult’ cases in a docking-benchmark dataset, where the unbound and bound protein forms are structurally different. Considering alternative conformations for each protein, the percentage of successfully predicted interactions increased from ~26% to 66%, and 57% of the interactions were successfully predicted in an ‘unbiased’ scenario, in which data related to the bound forms were not utilized. If the appropriate conformation, or relevant template interface, is unavailable in the PDB, PRISM could not predict the interaction successfully. The pace of the growth of the PDB promises a rapid increase of ensemble conformations emphasizing the merit of such knowledge-based ensemble strategies for higher success rates in protein-protein interaction predictions on an interactome-scale. We constructed the structural network of ERK interacting proteins as a case study. PMID:23590674

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

FXR agonist activity of conformationally constrained analogs of GW 4064.

Science.gov (United States)

Akwabi-Ameyaw, Adwoa; Bass, Jonathan Y; Caldwell, Richard D; Caravella, Justin A; Chen, Lihong; Creech, Katrina L; Deaton, David N; Madauss, Kevin P; Marr, Harry B; McFadyen, Robert B; Miller, Aaron B; Navas, Frank; Parks, Derek J; Spearing, Paul K; Todd, Dan; Williams, Shawn P; Bruce Wisely, G

2009-08-15

Two series of conformationally constrained analogs of the FXR agonist GW 4064 1 were prepared. Replacement of the metabolically labile stilbene with either benzothiophene or naphthalene rings led to the identification of potent full agonists 2a and 2g.

The RNA Exosome Channeling and Direct Access Conformations Have Distinct In Vivo Functions

Directory of Open Access Journals (Sweden)

Jaeil Han

2016-09-01

Full Text Available The RNA exosome is a 3′–5′ ribonuclease complex that is composed of nine core subunits and an essential catalytic subunit, Rrp44. Two distinct conformations of Rrp44 were revealed in previous structural studies, suggesting that Rrp44 may change its conformation to exert its function. In the channeling conformation, (Rrp44ch, RNA accesses the active site after traversing the central channel of the RNA exosome, whereas in the other conformation, (Rrp44da, RNA gains direct access to the active site. Here, we show that the Rrp44da exosome is important for nuclear function of the RNA exosome. Defects caused by disrupting the direct access conformation are distinct from those caused by channel-occluding mutations, indicating specific functions for each conformation. Our genetic analyses provide in vivo evidence that the RNA exosome employs a direct-access route to recruit specific substrates, indicating that the RNA exosome uses alternative conformations to act on different RNA substrates.

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.

XF-73, a novel antistaphylococcal membrane-active agent with rapid bactericidal activity.

Science.gov (United States)

Ooi, Nicola; Miller, Keith; Hobbs, Joanne; Rhys-Williams, William; Love, William; Chopra, Ian

2009-10-01

XF-73 is a novel porphyrin antibacterial agent previously reported to inhibit a range of gram-positive bacterial species, including Staphylococcus aureus. Its mode of action is unknown. Using S. aureus as a model organism we sought to examine the basis of its antibacterial activity. The effects of XF-73 on the growth and survival of S. aureus SH1000 were investigated by viable count and culture absorbance techniques. Inhibition of macromolecular synthesis and disruption of membrane integrity after exposure to XF-73 were examined by radiolabelling experiments, the BacLight fluorescent dye assay and measurement of K(+) and ATP leakage from the cell. The effect of XF-73 on a staphylococcal coupled transcription-translation system was also investigated. XF-73 was rapidly bactericidal against S. aureus SH1000 and demonstrated more rapid killing kinetics than all other comparator agents when tested at an equivalent multiple (4x) of the MIC. Exposure of S. aureus to XF-73 for 10 min completely inhibited DNA, RNA and protein synthesis. XF-73 had no effect on transcription and translation in vitro. Cells exposed to XF-73 gave a positive response in the BacLight assay, which detects membrane damage. The drug also caused substantial loss of K(+) and ATP from the cell, but did not promote bacterial lysis. XF-73 exhibited rapid membrane-perturbing activity, which is likely to be responsible for inhibition of macromolecular synthesis and the death of staphylococci exposed to the drug.

Space and Time Resolved Detection of Platelet Activation and von Willebrand Factor Conformational Changes in Deep Suspensions.

Science.gov (United States)

Biasetti, Jacopo; Sampath, Kaushik; Cortez, Angel; Azhir, Alaleh; Gilad, Assaf A; Kickler, Thomas S; Obser, Tobias; Ruggeri, Zaverio M; Katz, Joseph

2017-01-01

Tracking cells and proteins' phenotypic changes in deep suspensions is critical for the direct imaging of blood-related phenomena in in vitro replica of cardiovascular systems and blood-handling devices. This paper introduces fluorescence imaging techniques for space and time resolved detection of platelet activation, von Willebrand factor (VWF) conformational changes, and VWF-platelet interaction in deep suspensions. Labeled VWF, platelets, and VWF-platelet strands are suspended in deep cuvettes, illuminated, and imaged with a high-sensitivity EM-CCD camera, allowing detection using an exposure time of 1 ms. In-house postprocessing algorithms identify and track the moving signals. Recombinant VWF-eGFP (rVWF-eGFP) and VWF labeled with an FITC-conjugated polyclonal antibody are employed. Anti-P-Selectin FITC-conjugated antibodies and the calcium-sensitive probe Indo-1 are used to detect activated platelets. A positive correlation between the mean number of platelets detected per image and the percentage of activated platelets determined through flow cytometry is obtained, validating the technique. An increase in the number of rVWF-eGFP signals upon exposure to shear stress demonstrates the technique's ability to detect breakup of self-aggregates. VWF globular and unfolded conformations and self-aggregation are also observed. The ability to track the size and shape of VWF-platelet strands in space and time provides means to detect pro- and antithrombotic processes.

A new facility for rapid neutron activation analysis

International Nuclear Information System (INIS)

Zeisler, R.; Makarewicz, M.; Grass, F.; Casta, J.

1996-01-01

Many research groups have undertaken efforts on the utilization of short-lived nuclides in a broad spectrum of neutron activation analysis (NAA) applications. The advantages of these approaches are obvious because the information on the sample can be extracted more rapidly. In addition to its other advantages, NAA can become extremely competitive in price and analysis time. Nevertheless, NAA with short-lived nuclides has not gained broad popularity, perhaps because of some difficulties in accuracy and the availability of suitable irradiation facilities. This report discusses the ASTRA reactor for neutron activation analysis capabilities

Rapid response of a hydrologic system to volcanic activity: Masaya volcano, Nicaragua

Science.gov (United States)

Pearson, S.C.P.; Connor, C.B.; Sanford, W.E.

2008-01-01

Hydrologic systems change in response to volcanic activity, and in turn may be sensitive indicators of volcanic activity. Here we investigate the coupled nature of magmatic and hydrologic systems using continuous multichannel time series of soil temperature collected on the flanks of Masaya volcano, Nicaragua, one of the most active volcanoes in Central America. The soil temperatures were measured in a low-temperature fumarole field located 3.5 km down the flanks of the volcano. Analysis of these time series reveals that they respond extremely rapidly, on a time scale of minutes, to changes in volcanic activity also manifested at the summit vent. These rapid temperature changes are caused by increased flow of water vapor through flank fumaroles during volcanism. The soil temperature response, ~5 °C, is repetitive and complex, with as many as 13 pulses during a single volcanic episode. Analysis of the frequency spectrum of these temperature time series shows that these anomalies are characterized by broad frequency content during volcanic activity. They are thus easily distinguished from seasonal trends, diurnal variations, or individual rainfall events, which triggered rapid transient increases in temperature during 5% of events. We suggest that the mechanism responsible for the distinctive temperature signals is rapid change in pore pressure in response to magmatism, a response that can be enhanced by meteoric water infiltration. Monitoring of distal fumaroles can therefore provide insight into coupled volcanic-hydrologic-meteorologic systems, and has potential as an inexpensive monitoring tool.

Rapid deuterium exchange-in time for probing conformational change

International Nuclear Information System (INIS)

Dharmasiri, K.; Smith, D.L.

1995-01-01

Isotopic exchange of protein backbone amide hydrogens has been used extensively as a sensitive probe of protein structure. One of the salient features of hydrogen exchange is the vast range of exchange rates in one protein. Isotopic exchange methods have been used to study the structural features including protein folding and unfolding (1), functionally different forms of proteins (2), protein-protein complexation (3), and protein stability parameter. Many backbone amide protons that are surface accessible and are not involved in hydrogen bonding undergo rapid deuterium exchange. In order to study, fast exchanging amide protons, fast exchange-in times are necessary

Investigating ion channel conformational changes using voltage clamp fluorometry.

Science.gov (United States)

Talwar, Sahil; Lynch, Joseph W

2015-11-01

Ion channels are membrane proteins whose functions are governed by conformational changes. The widespread distribution of ion channels, coupled with their involvement in most physiological and pathological processes and their importance as therapeutic targets, renders the elucidation of these conformational mechanisms highly compelling from a drug discovery perspective. Thanks to recent advances in structural biology techniques, we now have high-resolution static molecular structures for members of the major ion channel families. However, major questions remain to be resolved about the conformational states that ion channels adopt during activation, drug modulation and desensitization. Patch-clamp electrophysiology has long been used to define ion channel conformational states based on functional criteria. It achieves this by monitoring conformational changes at the channel gate and cannot detect conformational changes occurring in regions distant from the gate. Voltage clamp fluorometry involves labelling cysteines introduced into domains of interest with environmentally sensitive fluorophores and inferring structural rearrangements from voltage or ligand-induced fluorescence changes. Ion channel currents are monitored simultaneously to verify the conformational status. By defining real time conformational changes in domains distant from the gate, this technique provides unexpected new insights into ion channel structure and function. This review aims to summarise the methodology and highlight recent innovative applications of this powerful technique. This article is part of the Special Issue entitled 'Fluorescent Tools in Neuropharmacology'. Copyright © 2015 Elsevier Ltd. All rights reserved.

Quantum-chemical study on the bioactive conformation of epothilones.

Science.gov (United States)

Jiménez, Verónica A

2010-12-27

Herein, I report a DFT study on the bioactive conformation of epothilone A based on the analysis of 92 stable conformations of free and bound epothilone to a reduced model of tubulin receptor. The equilibrium structures and relative energies were studied using B3LYP and X3LYP functionals and the 6-31G(d) standard basis set, which was considered appropriate for the size of the systems under study. Calculated relative energies of free and bound epothilones led me to propose a new model for the bioactive conformation of epothilone A, which accounts for several structure-activity data.

Logarithmic conformal field theory through nilpotent conformal dimensions

International Nuclear Information System (INIS)

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

2001-01-01

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

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....

Relationship between structure, conformational flexibility, and biological activity of agonists and antagonists at the N-methyl-D-aspartic acid subtype of excitatory amino acid receptors

DEFF Research Database (Denmark)

Madsen, U; Brehm, L; Schaumburg, Kjeld

1990-01-01

The relationship between conformational flexibility and agonist or antagonist actions at the N-Methyl-D-aspartic acid (NMDA) subtype of central L-glutamic acid (GLU) receptors of a series of racemic piperidinedicarboxylic acids (PDAs) was studied. The conformational analyses were based on 1H NMR...... receptors. Each of the three cyclic acidic amino acids showing NMDA agonist activities was found to exist as an equilibrium mixture of two conformers in aqueous solution. In contrast, the NMDA antagonists cis-2,3-PDA and cis-2,4-PDA as well as the inactive compounds trans-2,5-PDA and cis-2,6-PDA were shown...

Unveiling the Sweet Conformations of Ketohexoses

Science.gov (United States)

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

2013-06-01

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

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

Directory of Open Access Journals (Sweden)

Soares Alexei S

2007-11-01

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

Analysis of calcium-induced effects on the conformation of fengycin.

Science.gov (United States)

Nasir, Mehmet Nail; Laurent, Pascal; Flore, Christelle; Lins, Laurence; Ongena, Marc; Deleu, Magali

2013-06-01

Fengycin is a natural lipopeptide with antifungal and eliciting properties and able to inhibit the activity of phospholipase A2. A combination of CD, FT-IR, NMR and fluorescence spectroscopic techniques was applied to elucidate its conformation in a membrane-mimicking environment and to investigate the effect of calcium ions on it. We mainly observed that fengycin adopts a turn conformation. Our results showed that calcium ions are bound by the two charged glutamates. The calcium binding has an influence on the fengycin conformation and more particularly, on the environment of the tyrosine residues. The modulation of the fengycin conformation by the environmental conditions may influence its biological properties. Copyright © 2013 Elsevier B.V. All rights reserved.

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.)

[Experimental rationale for the parameters of a rapid method for oxidase activity determination].

Science.gov (United States)

Butorina, N N

2010-01-01

Experimental rationale is provided for the parameters of a rapid (1-2-min) test to concurrently determine the oxidase activity of all bacteria grown on the membrane filter after water filtration. Oxidase reagents that are the aqueous solutions of tetramethyl-p-phenylenediamine dihydrochloride and demethyl-p-phenylenediamine dihydrochloride have been first ascertained to exert no effect on the viability and enzymatic activity of bacteria after one-hour contact. An algorithm has been improved for the rapid oxidase activity test: the allowable time for bacteria to contact oxidase reagents and procedures for minimizing the effect on bacterial biochemical activity following the contact. An accelerated method based on lactose medium with tergitol 7 and Endo agar has been devised to determine coliform bacteria, by applying the rapid oxidase test: the time of a final response is 18-24 hours. The method has been included into GOST 52426-2005.

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.

A Rapid Method for Measuring Strontium-90 Activity in Crops in China

Science.gov (United States)

Pan, Lingjing Pan; Yu, Guobing; Wen, Deyun; Chen, Zhi; Sheng, Liusi; Liu, Chung-King; Xu, X. George

2017-09-01

A rapid method for measuring Sr-90 activity in crop ashes is presented. Liquid scintillation counting, combined with ion exchange columns 4`, 4"(5")-di-t-butylcyclohexane-18-crown-6, is used to determine the activity of Sr-90 in crops. The yields of chemical procedure are quantified using gravimetric analysis. The conventional method that uses ion-exchange resin with HDEHP could not completely remove all the bismuth when comparatively large lead and bismuth exist in the samples. This is overcome by the rapid method. The chemical yield of this method is about 60% and the MDA for Sr-90 is found to be 2:32 Bq/kg. The whole procedure together with using spectrum analysis to determine the activity only takes about one day, which is really a large improvement compared with the conventional method. A modified conventional method is also described here to verify the value of the rapid one. These two methods can meet di_erent needs of daily monitoring and emergency situation.

Non-Critical-Care Nurses' Perceptions of Facilitators and Barriers to Rapid Response Team Activation.

Science.gov (United States)

Jenkins, Sheryl Henry; Astroth, Kim Schafer; Woith, Wendy Mann

2015-01-01

Rapid response teams can save lives but are only effective when activated. We surveyed 50 nurses for their perceptions of facilitators and barriers to activation. Findings showed that participants need more education on their role and when to activate the rapid response team. Nurses who comprise the team need help building their communication skills. We recommend nursing professional development specialists increase the frequency of offerings and expand the focus on roles, activation criteria, and communication skills.

L-Alanyl-L-alanine Conformational Changes Induced by pH As Monitored by the Raman Optical Activity Spectra

Czech Academy of Sciences Publication Activity Database

Šebek, Jiří; Kapitán, Josef; Šebestík, Jaroslav; Baumruk, V.; Bouř, Petr

2009-01-01

Roč. 113, č. 27 (2009), s. 7760-7768 ISSN 1089-5639 R&D Projects: GA ČR GA202/07/0732; GA ČR GA203/07/1517; GA AV ČR IAA400550702 Institutional research plan: CEZ:AV0Z40550506 Keywords : Raman optical activity * peptides * conformation Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 2.899, year: 2009

Conformation guides molecular efficacy in docking screens of activated β-2 adrenergic G protein coupled receptor.

Science.gov (United States)

Weiss, Dahlia R; Ahn, SeungKirl; Sassano, Maria F; Kleist, Andrew; Zhu, Xiao; Strachan, Ryan; Roth, Bryan L; Lefkowitz, Robert J; Shoichet, Brian K

2013-05-17

A prospective, large library virtual screen against an activated β2-adrenergic receptor (β2AR) structure returned potent agonists to the exclusion of inverse-agonists, providing the first complement to the previous virtual screening campaigns against inverse-agonist-bound G protein coupled receptor (GPCR) structures, which predicted only inverse-agonists. In addition, two hits recapitulated the signaling profile of the co-crystal ligand with respect to the G protein and arrestin mediated signaling. This functional fidelity has important implications in drug design, as the ability to predict ligands with predefined signaling properties is highly desirable. However, the agonist-bound state provides an uncertain template for modeling the activated conformation of other GPCRs, as a dopamine D2 receptor (DRD2) activated model templated on the activated β2AR structure returned few hits of only marginal potency.

Tribological Behavior of Oil-Lubricated Laser Textured Steel Surfaces in Conformal Flat and Non-Conformal Contacts

Energy Technology Data Exchange (ETDEWEB)

Kovalchenko, A. M. [Inst. for Problems of Materials Science, Dept. 7, 3 Krzhizhanovsky Street, Kyiv 03142, UA (Corresponding author), e-mail: andrii.kovalchenko@gatech.edu; Erdemir, A. [Argonne National Lab., Energy Systems Division, 9700 South Cass Avenue, Argonne, IL 60439 US; Ajayi, O. O. [Argonne National Lab., Energy Systems Division, 9700 South Cass Avenue, Argonne, IL 60439 US; Etsion, I. [Technion-Israel Inst. of Technology, Dept. of Mechanical Engineering, Haifa 32000, IL

2017-01-30

Changing the surface texture of sliding surfaces is an effective way to manipulate friction and wear of lubricated surfaces. Having realized its potential, we have done very extensive studies on the effects of laser surface texturing (LST, which involves the creation of an array of microdimples on a surface) on friction and wear behavior of oil-lubricated steel surfaces in the early 2000s. In this paper, we reviewed some of our research accomplishments and assessed future directions of the laser texturing field in many diverse industrial applications. Our studies specifically addressed the impact of laser texturing on friction and wear of both the flat conformal and initial non-conformal point contact configurations using a pin-on-disk test rig under fully-flooded synthetic oil lubricants with different viscosities. Electrical resistance measurement between pin and LST disks was also used to determine the operating lubrication regimes in relation to friction. In conformal contact, we confirmed that LST could significantly expand the operating conditions for hydrodynamic lubrication to significantly much higher loads and slower speeds. In particular, with LST and higher viscosity oils, the low-friction full hydrodynamic regime was shifted to the far left in the Stribeck diagram. Overall, the beneficial effects of laser surface texturing were more pronounced at higher speeds and loads and with higher viscosity oil. LST was also observed to reduce the magnitude of friction coefficients in the boundary regime. For the non-conformal contact configuration, we determined that LST would produce more abrasive wear on the rubbing counterface compared to the untreated surfaces due to a reduction in lubricant fluid film thickness, as well as the highly uneven and rough nature of the textured surfaces. However, this higher initial wear rate has led to faster generation of a conformal contact, and thus transition from the high-friction boundary to lower friction mixed

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.

Small molecules CK-666 and CK-869 inhibit actin-related protein 2/3 complex by blocking an activating conformational change.

Science.gov (United States)

Hetrick, Byron; Han, Min Suk; Helgeson, Luke A; Nolen, Brad J

2013-05-23

Actin-related protein 2/3 (Arp2/3) complex is a seven-subunit assembly that nucleates branched actin filaments. Small molecule inhibitors CK-666 and CK-869 bind to Arp2/3 complex and inhibit nucleation, but their modes of action are unknown. Here, we use biochemical and structural methods to determine the mechanism of each inhibitor. Our data indicate that CK-666 stabilizes the inactive state of the complex, blocking movement of the Arp2 and Arp3 subunits into the activated filament-like (short pitch) conformation, while CK-869 binds to a serendipitous pocket on Arp3 and allosterically destabilizes the short pitch Arp3-Arp2 interface. These results provide key insights into the relationship between conformation and activity in Arp2/3 complex and will be critical for interpreting the influence of the inhibitors on actin filament networks in vivo. Copyright © 2013 Elsevier Ltd. All rights reserved.

Analysis of third-party certification approaches using an occupational health and safety conformity-assessment model.

Science.gov (United States)

Redinger, C F; Levine, S P

1998-11-01

The occupational health and safety conformity-assessment model presented in this article was developed (1) to analyze 22 public and private programs to determine the extent to which these programs use third parties in conformity-assessment determinations, and (2) to establish a framework to guide future policy developments related to the use of third parties in occupational health and safety conformity-assessment activities. The units of analysis for this study included select Occupational Safety and Health Administration programs and standards, International Organization for Standardization-based standards and guidelines, and standards and guidelines developed by nongovernmental bodies. The model is based on a 15-cell matrix that categorizes first-, second-, and third-party activities in terms of assessment, accreditation, and accreditation-recognition activities. The third-party component of the model has three categories: industrial hygiene/safety testing and sampling; product, equipment, and laboratory certification; and, occupational health and safety management system registration/certification. Using the model, 16 of the 22 programs were found to have a third-party component in their conformity-assessment structure. The analysis revealed that (1) the model provides a useful means to describe and analyze various third-party approaches, (2) the model needs modification to capture aspects of traditional governmental conformity-assessment/enforcement activities, and (3) several existing third-party conformity-assessment systems offer robust models that can guide future third-party policy formulation and implementation activities.

A conformational switch in the inhibitory gamma-subunit of PDE6 upon enzyme activation by transducin.

Science.gov (United States)

Granovsky, A E; Artemyev, N O

2001-11-06

In response to light, a photoreceptor G protein, transducin, activates cGMP-phosphodiesterase (PDE6) by displacing the inhibitory gamma-subunits (Pgamma) from the enzyme's catalytic sites. Evidence suggests that the activation of PDE6 involves a conformational change of the key inhibitory C-terminal domain of Pgamma. In this study, the C-terminal region of Pgamma, Pgamma-73-85, has been targeted for Ala-scanning mutagenesis to identify the point-to-point interactions between Pgamma and the PDE6 catalytic subunits and to probe the nature of the conformational change. Pgamma mutants were tested for their ability to inhibit PDE6 and a chimeric PDE5-conePDE6 enzyme containing the Pgamma C-terminus-binding site of cone PDE. This analysis has revealed that in addition to previously characterized Ile86 and Ile87, important inhibitory contact residues of Pgamma include Asn74, His75, and Leu78. The patterns of mutant PDE5-conePDE6 enzyme inhibition suggest the interaction between the PgammaAsn74/His75 sequence and Met758 of the cone PDE6alpha' catalytic subunit. This interaction, and the interaction between the PgammaIle86/Ile87 and PDE6alpha'Phe777/Phe781 residues, is most consistent with an alpha-helical structure of the Pgamma C-terminus. The analysis of activation of PDE6 enzymes containing Pgamma mutants with Ala-substituted transducin-contact residues demonstrated the critical role of PgammaLeu76. Accordingly, we hypothesize that the initial step in PDE6 activation involves an interaction of transducin-alpha with PgammaLeu76. This interaction introduces a bend into the alpha-helical structure of the Pgamma C-terminus, allowing transducin-alpha to further twist the C-terminus thereby uncovering the catalytic pocket of PDE6.

The influence of conformational fluctuations on enzymatic activity: modelling the functional motion of β-secretase

International Nuclear Information System (INIS)

Neri, M; Cascella, M; Micheletti, C

2005-01-01

Considerable insight into the functional activity of proteins and enzymes can be obtained by studying the low energy conformational distortions that the biopolymer can sustain. We carry out the characterization of these large scale structural changes for a protein of considerable pharmaceutical interest, the human β-secretase. Starting from the crystallographic structure of the protein, we use the recently introduced β-Gaussian model to identify, with negligible computational expenditure, the most significant distortions occurring in thermal equilibrium and the associated timescales. The application of this strategy helps us to gain considerable insight into the putative functional movements and, furthermore, allows us to identify a handful of key regions in the protein which have an important mechanical influence on the enzymatic activity despite being spatially distant from the active site. The results obtained within the Gaussian model are validated through an extensive comparison against an all-atom molecular dynamics simulation

The cytosolic DNA sensor cGAS forms an oligomeric complex with DNA and undergoes switch-like conformational changes in the activation loop.

Science.gov (United States)

Zhang, Xu; Wu, Jiaxi; Du, Fenghe; Xu, Hui; Sun, Lijun; Chen, Zhe; Brautigam, Chad A; Zhang, Xuewu; Chen, Zhijian J

2014-02-13

The presence of DNA in the cytoplasm is a danger signal that triggers immune and inflammatory responses. Cytosolic DNA binds to and activates cyclic GMP-AMP (cGAMP) synthase (cGAS), which produces the second messenger cGAMP. cGAMP binds to the adaptor protein STING and activates a signaling cascade that leads to the production of type I interferons and other cytokines. Here, we report the crystal structures of human cGAS in its apo form, representing its autoinhibited conformation as well as in its cGAMP- and sulfate-bound forms. These structures reveal switch-like conformational changes of an activation loop that result in the rearrangement of the catalytic site. The structure of DNA-bound cGAS reveals a complex composed of dimeric cGAS bound to two molecules of DNA. Functional analyses of cGAS mutants demonstrate that both the protein-protein interface and the two DNA binding surfaces are critical for cGAS activation. These results provide insights into the mechanism of DNA sensing by cGAS. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

The Cytosolic DNA Sensor cGAS Forms an Oligomeric Complex with DNA and Undergoes Switch-like Conformational Changes in the Activation Loop

Directory of Open Access Journals (Sweden)

Xu Zhang

2014-02-01

Full Text Available The presence of DNA in the cytoplasm is a danger signal that triggers immune and inflammatory responses. Cytosolic DNA binds to and activates cyclic GMP-AMP (cGAMP synthase (cGAS, which produces the second messenger cGAMP. cGAMP binds to the adaptor protein STING and activates a signaling cascade that leads to the production of type I interferons and other cytokines. Here, we report the crystal structures of human cGAS in its apo form, representing its autoinhibited conformation as well as in its cGAMP- and sulfate-bound forms. These structures reveal switch-like conformational changes of an activation loop that result in the rearrangement of the catalytic site. The structure of DNA-bound cGAS reveals a complex composed of dimeric cGAS bound to two molecules of DNA. Functional analyses of cGAS mutants demonstrate that both the protein-protein interface and the two DNA binding surfaces are critical for cGAS activation. These results provide insights into the mechanism of DNA sensing by cGAS.

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.

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.

Theoretical investigation of the conformational space of baicalin.

Science.gov (United States)

Martínez Medina, Juan J; Ferrer, Evelina G; Williams, Patricia A M; Okulik, Nora B

2017-09-01

Flavonoids are a large group of polyphenolic compounds ubiquitously present in plants. They are important components of human diet. They are recognized as potential drug candidates to be used in the treatment and prevention of a lot of pathological disorders, due to their protective effects. Baicalin (7-glucuronic acid 5, 6-dihydroxyflavone) is one of the main single active constituents isolated from the dried roots of Scutellaria baicalensis Georgi. The great interest on this flavonoid is due to its various pharmacological properties, such as antioxidant, antimicrobial, anti-inflammatory, anticancer and so on, and its high accumulation in the roots of S. baicalensis. The aim of our work was to analyze the geometric and electronic properties of baicalin conformers (BCL), thus performing a complete search on the conformational space of this flavonoid in gas phase and in aqueous solution. The results indicate that the conformational space of baicalin is formed by eight conformers in gas phase and five conformers in aqueous solution optimized at B3LYP/6-311++G** theory level. BCLa2 TT and BCLa1 TT conformers have low stability in gas phase and very high stability in aqueous solution. This variation is related to a modification in the τ 1 angle that represents the relative position of the glucuronide unit respect to the central rings of the flavan nucleus (A and C). This modification was successfully explained by examining the changes in the hydrogen bond (HB) interactions that occur in the region around the hydroxyl group located in position 6 of ring A. Besides, the molecular electrostatic potential (MEP) and frontier molecular orbital (FMO) analyses indicate that BCLa2 TT and BCLa1 TT conformers are the most favorable conformers for interacting with positively charged species (such as metal ions) in aqueous media (such as biological fluids). Copyright © 2017 Elsevier Inc. All rights reserved.

Histone H4 hyperacetylation and rapid turnover of its acetyl groups in transcriptionally inactive rooster testis spermatids.

Science.gov (United States)

Oliva, R; Mezquita, C

1982-01-01

In order to study the relationship between acetylation of histones, chromatin structure and gene activity, the distribution and turnover of acetyl groups among nucleosomal core histones and the extent of histone H4 acetylation were examined in rooster testis cell nuclei at different stages of spermatogenesis. Histone H4 was the predominant acetylated histone in mature testes. Hyperacetylation of H4 and rapid turnover of its acetyl groups are not univocally correlated with transcriptional activity since they were detected in both genetically active testicular cells and genetically inactive elongated spermatids. During the transition from nucleohistone to nucleoprotamine in elongated spermatids the chromatin undergoes dramatic structural changes with exposition of binding sites on DNA (1). Hyperacetylation of H4 and rapid turnover of its acetyl groups could be correlated with the particular conformation of chromatin in elongated spermatids and might represent a necessary condition for binding of chromosomal proteins to DNA. Images PMID:7162988

Electron paramagnetic resonance study of conformational effects in alkyl-substituted 2-cyclohexanonyl radicals in an adamantane matrix

International Nuclear Information System (INIS)

Walter, H.F.

1975-01-01

Electron paramagnetic resonance spectra have been obtained for radicals produced by x-irradiation of cyclohexanone and various alkyl-substituted cyclohexanones trapped in an adamantane matrix. Temperature variation of these spectra permits determination of the enthalpy and entropy of activation for interconversion between the two half-chair conformations. In those cases where the two conformations have intrinsically different energies, the enthalpy and entropy differences between conformations are determined. For 2-cyclohexanonyl radical, the enthalpy of activation is 3.90 +- 0.07 kcal/mole and the entropy of activation is -2.3 +- 0.3 e.u. Methyl substitution on C 3 or C 5 gives a radical with activation parameters similar to the parent radical, indicating moderate realignment of atoms during the conformational change. Methyl substitution on C 4 gives a radical with lower activation parameters, which are interpreted to indicate conformational change mainly be a folding along the diagonal through the radical site. Larger groups attached to C 3 influence enthalpy and entropy differences between conformations much less than when they are attached to C 5 . Very large groups attached to C 5 apparently flatten the ring; it is not known whether or not this is a matrix effect. Deuteration seems to cause a slight reduction in the activation parameters for 2-cyclohexanonyl radical

On the advancements of conformal transformations and their associated symmetries in geometry and theoretical physics

International Nuclear Information System (INIS)

Kastrup, H.A.

2008-08-01

The historical developments of conformal transformations and symmetries are sketched: Their origin from stereographic projections of the globe, their blossoming in two dimensions within the eld of analytic complex functions, the generic role of transformations by reciprocal radii in dimensions higher than two and their linearization in terms of polyspherical coordinates by Darboux, Weyl's attempt to extend General Relativity, the slow rise of nite dimensional conformal transformations in classical eld theories and the problem of their interpretation, then since about 1970 the rapid spread of their acceptance for asymptotic and structural problems in quantum eld theories and beyond, up to the current AdS=CFT conjecture. The occasion for the present article: hundred years ago Bateman and Cunningham discovered the form invariance of Maxwell's equations for electromagnetism with respect to conformal space-time transformations. (orig.)

On the advancements of conformal transformations and their associated symmetries in geometry and theoretical physics

Energy Technology Data Exchange (ETDEWEB)

Kastrup, H A [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany). Theory Group

2008-08-15

The historical developments of conformal transformations and symmetries are sketched: Their origin from stereographic projections of the globe, their blossoming in two dimensions within the eld of analytic complex functions, the generic role of transformations by reciprocal radii in dimensions higher than two and their linearization in terms of polyspherical coordinates by Darboux, Weyl's attempt to extend General Relativity, the slow rise of nite dimensional conformal transformations in classical eld theories and the problem of their interpretation, then since about 1970 the rapid spread of their acceptance for asymptotic and structural problems in quantum eld theories and beyond, up to the current AdS=CFT conjecture. The occasion for the present article: hundred years ago Bateman and Cunningham discovered the form invariance of Maxwell's equations for electromagnetism with respect to conformal space-time transformations. (orig.)

Specific phosphopeptide binding regulates a conformational change in the PI 3-kinase SH2 domain associated with enzyme activation.

Science.gov (United States)

Shoelson, S E; Sivaraja, M; Williams, K P; Hu, P; Schlessinger, J; Weiss, M A

1993-01-01

SH2 (src-homology 2) domains define a newly recognized binding motif that mediates the physical association of target phosphotyrosyl proteins with downstream effector enzymes. An example of such phosphoprotein-effector coupling is provided by the association of phosphatidylinositol 3-kinase (PI 3-kinase) with specific phosphorylation sites within the PDGF receptor, the c-Src/polyoma virus middle T antigen complex and the insulin receptor substrate IRS-1. Notably, phosphoprotein association with the SH2 domains of p85 also stimulates an increase in catalytic activity of the PI 3-kinase p110 subunit, which can be mimicked by phosphopeptides corresponding to targeted phosphoprotein phosphorylation sites. To investigate how phosphoprotein binding to the p85 SH2 domain stimulates p110 catalytic activation, we have examined the differential effects of phosphotyrosine and PDGF receptor-, IRS-1- and c-Src-derived phosphopeptides on the conformation of an isolated SH2 domain of PI 3-kinase. Although phosphotyrosine and both activating and non-activating phosphopeptides bind to the SH2 domain, activating phosphopeptides bind with higher affinity and induce a qualitatively distinct conformational change as monitored by CD and NMR spectroscopy. Amide proton exchange and protease protection assays further show that high affinity, specific phosphopeptide binding induces non-local dynamic SH2 domain stabilization. Based on these findings we propose that specific phosphoprotein binding to the p85 subunit induces a change in SH2 domain structure which is transmitted to the p110 subunit and regulates enzymatic activity by an allosteric mechanism. Images PMID:8382612

Crystal structure of the plexin A3 intracellular region reveals an autoinhibited conformation through active site sequestration

Energy Technology Data Exchange (ETDEWEB)

He, Huawei; Yang, Taehong; Terman, Jonathan R.; Zhang, Xuewu; (UTSMC)

2010-01-20

Plexin cell surface receptors bind to semaphorin ligands and transduce signals for regulating neuronal axon guidance. The intracellular region of plexins is essential for signaling and contains a R-Ras/M-Ras GTPase activating protein (GAP) domain that is divided into two segments by a Rho GTPase-binding domain (RBD). The regulation mechanisms for plexin remain elusive, although it is known that activation requires both binding of semaphorin to the extracellular region and a Rho-family GTPase (Rac1 or Rnd1) to the RBD. Here we report the crystal structure of the plexin A3 intracellular region. The structure shows that the N- and C-terminal portions of the GAP homologous regions together form a GAP domain with an overall fold similar to other Ras GAPs. However, the plexin GAP domain adopts a closed conformation and cannot accommodate R-Ras/M-Ras in its substrate-binding site, providing a structural basis for the autoinhibited state of plexins. A comparison with the plexin B1 RBD/Rnd1 complex structure suggests that Rnd1 binding alone does not induce a conformational change in plexin, explaining the requirement of both semaphorin and a Rho GTPase for activation. The structure also identifies an N-terminal segment that is important for regulation. Both the N-terminal segment and the RBD make extensive interactions with the GAP domain, suggesting the presence of an allosteric network connecting these three domains that integrates semaphorin and Rho GTPase signals to activate the GAP. The importance of these interactions in plexin signaling is shown by both cell-based and in vivo axon guidance assays.

Recent activity of the Rapid Burster (MXB 1730-335)

DEFF Research Database (Denmark)

Kuulkers, E.; Brandt, Søren Kristian; Markwardt, C.

2008-01-01

Observations taken as part of the INTEGRAL Galactic bulge monitoring program (see ATel #1385) on 2008, February 23 13:32-17:13 (UT) showed bursting activity from the X-ray transient, the Rapid Burster (MXB 1730-335). During one of the 1800-sec pointings when the source was in the field- of-view o...

Helical Tomotherapy-Based STAT RT: Dosimetric Evaluation for Clinical Implementation of a Rapid Radiation Palliation Program

International Nuclear Information System (INIS)

McIntosh, Alyson; Dunlap, Neal; Sheng, Ke; Geezey, Constance; Turner, Benton; Blackhall, Leslie; Weiss, Geoffrey; Lappinen, Eric; Larner, James M.; Read, Paul W.

2010-01-01

Helical tomotherapy-based STAT radiation therapy (RT) uses an efficient software algorithm for rapid intensity-modulated treatment planning, enabling conformal radiation treatment plans to be generated on megavoltage computed tomography (MVCT) scans for CT simulation, treatment planning, and treatment delivery in one session. We compared helical tomotherapy-based STAT RT dosimetry with standard linac-based 3D conformal plans and standard helical tomotherapy-based intensity-modulated radiation therapy (IMRT) dosimetry for palliative treatments of whole brain, a central obstructive lung mass, multilevel spine disease, and a hip metastasis. Specifically, we compared the conformality, homogeneity, and dose with regional organs at risk (OARs) for each plan as an initial step in the clinical implementation of a STAT RT rapid radiation palliation program. Hypothetical planning target volumes (PTVs) were contoured on an anthropomorphic phantom in the lung, spine, brain, and hip. Treatment plans were created using three planning techniques: 3D conformal on Pinnacle 3 , helical tomotherapy, and helical tomotherapy-based STAT RT. Plan homogeneity, conformality, and dose to OARs were analyzed and compared. STAT RT and tomotherapy improved conformality indices for spine and lung plans (CI spine = 1.21, 1.17; CI lung = 1.20, 1.07, respectively) in comparison with standard palliative anteroposterior/posteroanterior (AP/PA) treatment plans (CI spine = 7.01, CI lung = 7.30), with better sparing of heart, esophagus, and spinal cord. For palliative whole-brain radiotherapy, STAT RT and tomotherapy reduced maximum and mean doses to the orbits and lens (maximum/mean lens dose: STAT RT = 2.94/2.65 Gy, tomotherapy = 3.13/2.80 Gy, Lateral opposed fields = 7.02/3.65 Gy), with an increased dose to the scalp (mean scalp dose: STAT RT = 16.19 Gy, tomotherapy = 15.61 Gy, lateral opposed fields = 14.01 Gy). For bony metastatic hip lesions, conformality with both tomotherapy techniques (CI = 1

The conformal method and the conformal thin-sandwich method are the same

International Nuclear Information System (INIS)

Maxwell, David

2014-01-01

The conformal method developed in the 1970s and the more recent Lagrangian and Hamiltonian conformal thin-sandwich methods are techniques for finding solutions of the Einstein constraint equations. We show that they are manifestations of a single conformal method: there is a straightforward way to convert back and forth between the parameters for these methods so that the corresponding solutions of the Einstein constraint equations agree. The unifying idea is the need to clearly distinguish tangent and cotangent vectors to the space of conformal classes on a manifold, and we introduce a vocabulary for working with these objects without reference to a particular representative background metric. As a consequence of these conceptual advantages, we demonstrate how to strengthen previous near-CMC (constant mean curvature) existence and non-existence theorems for the original conformal method to include metrics with scalar curvatures that change sign. (paper)

Rapid Arc, helical tomotherapy, sliding window intensity modulated radiotherapy and three dimensional conformal radiation for localized prostate cancer: A dosimetric comparison

Directory of Open Access Journals (Sweden)

Rajesh A Kinhikar

2014-01-01

Full Text Available Objective: The objective of this study was to investigate the potential role of RapidArc (RA compared with helical tomotherapy (HT, sliding window intensity modulated radiotherapy (SW IMRT and three-dimensional conformal radiation therapy (3D CRT for localized prostate cancer. Materials and Methods: Prescription doses ranged from 60 Gy to planning target volume (PTV and 66.25 Gy for clinical target volume prostate (CTV-P over 25-30 fractions. PTV and CTV-P coverage were evaluated by conformity index (CI and homogeneity index (HI. Organ sparing comparison was done with mean doses to rectum and bladder. Results: CI 95 were 1.0 ± 0.01 (RA, 0.99 ± 0.01 (HT, 0.97 ± 0.02 (IMRT, 0.98 ± 0.02 (3D CRT for PTV and 1.0 ± 0.00 (RA, HT, SW IMRT and 3D CRT for CTV-P. HI was 0.11 ± 0.03 (RA, 0.16 ± 0.08 (HT, 0.12 ± 0.03 (IMRT, 0.06 ± 0.01 (3D CRT for PTV and 0.03 ± 0.00 (RA, 0.05 ± 0.01 (HT, 0.03 ± 0.01 (SW IMRT and 3D CRT for CTV-P. Mean dose to bladder were 23.68 ± 13.23 Gy (RA, 24.55 ± 12.51 Gy (HT, 19.82 ± 11.61 Gy (IMRT and 23.56 ± 12.81 Gy (3D CRT, whereas mean dose to rectum was 36.85 ± 12.92 Gy (RA, 33.18 ± 11.12 Gy (HT, IMRT and 38.67 ± 12.84 Gy (3D CRT. Conclusion: All studied intensity-modulated techniques yield treatment plans of significantly improved quality when compared with 3D CRT, with HT providing best organs at risk sparing and RA being the most efficient treatment option, reducing treatment time to 1.45-3.7 min and monitor unit to <400 for a 2 Gy fraction.

Molecular conformation, receptor binding, and hormone action of natural and synthetic estrogens and antiestrogens.

Science.gov (United States)

Duax, W L; Griffin, J F; Weeks, C M; Korach, K S

1985-01-01

The X-ray crystallographic structural determinations of synthetic estrogens and antiestrogens provide reliable information on the global minimum energy conformation of these molecules or a local minimum energy conformation that is within 1 or 2 kcal/mole of the global minimum. In favorable cases, state-of-the-art molecular mechanics calculations provide quantitative agreement with X-ray results and information on the relative energy of other local minimum energy conformations not observed crystallographically. Because the conformation of diethylstilbestrol (DES) observed in solvated crystals has an overall conformation and dipole moment more similar to estradiol it is the form more likely to bind to the receptor and produce hormone activity. Either phenol ring of DES can successfully mimic the estradiol A-ring in binding to the receptor. Indenestrol A (INDA) and indenestrol B (INDB) have nearly identical fully extended planar conformations. Either the alpha or gamma rings of these compounds may mimic the A ring of estradiol and compete for the estrogen receptor. Although there are eight distinct ways in which molecules of a racemic mixture of INDA or INDB can bind to the receptor, not all of them may be able to elicit a hormonal response. This may account for the reduced biological activity of the compounds despite their successful competition for receptor binding. The minimum energy conformations of Z-pseudodiethylstilbestrol (ZPD) and E-pseudodiethylstilbestrol (EPD) are bent in a fashion similar to that of indanestrol (INDC). These molecules have good binding affinity suggesting that the receptor does not require a flat molecule. Therefore these conformations would appear to be compatible with receptor binding, but only the Z isomer has an energetically allowed extended conformation that accounts for its observed biological activity relative to DES. PMID:3905370

Rapid monitoring of autolysis process of proteases by capillary electrophoresis.

Science.gov (United States)

Chen, Xiu-Lan; Shun, Cai-Yun; Zhang, Yu-Zhong; Gao, Pei-Ji

2003-10-01

A protease, MCP-01, produced by a deep-sea psychrotrophic strain of Pseudoaltermonas sp. SM9913 was purified and its autolysis reaction at 20 degrees C-50 degrees C was monitored by capillary electrophoresis. Capillary electrophoresis provides a rapid assay because the degree and state of autolysis of protease MCP-01 could be observed within 6 min. The autolysis rate increased as the temperature rose in the tested range. After 30 min incubation at 30 degrees C, 77% of MCP-01 autolyzed into peptides. However, its activity for the hydrolysis of casein was reduced by only 4%. The rate of loss of activity of MCP-01 was thus slower than that of autolysis of MCP-01 at 30 degrees C. Similar results were obtained when MCP-01 was incubated at 20 degrees C, 40 degrees C and 50 degrees C. Large peptides produced by autolysis of MCP-01 therefore still have catalytic activity. When these large peptides autolyzed further into smaller peptides, the enzyme conformation that retained its catalytic activity was destroyed and activity was lost.

Structure of Mycobacterium tuberculosis phosphopantetheine adenylyltransferase in complex with the feedback inhibitor CoA reveals only one active-site conformation

Energy Technology Data Exchange (ETDEWEB)

Wubben, T.; Mesecar, A.D. (Purdue); (UIC)

2014-10-02

Phosphopantetheine adenylyltransferase (PPAT) catalyzes the penultimate step in the coenzyme A (CoA) biosynthetic pathway, reversibly transferring an adenylyl group from ATP to 4'-phosphopantetheine to form dephosphocoenzyme A (dPCoA). To complement recent biochemical and structural studies on Mycobacterium tuberculosis PPAT (MtPPAT) and to provide further insight into the feedback regulation of MtPPAT by CoA, the X-ray crystal structure of the MtPPAT enzyme in complex with CoA was determined to 2.11 {angstrom} resolution. Unlike previous X-ray crystal structures of PPAT-CoA complexes from other bacteria, which showed two distinct CoA conformations bound to the active site, only one conformation of CoA is observed in the MtPPAT-CoA complex.

Conformational elasticity can facilitate TALE-DNA recognition.

Science.gov (United States)

Lei, Hongxing; Sun, Jiya; Baldwin, Enoch P; Segal, David J; Duan, Yong

2014-01-01

Sequence-programmable transcription activator-like effector (TALE) proteins have emerged as a highly efficient tool for genome engineering. Recent crystal structures depict a transition between an open unbound solenoid and more compact DNA-bound solenoid formed by the 34 amino acid repeats. How TALEs switch conformation between these two forms without substantial energetic compensation, and how the repeat-variable di-residues (RVDs) discriminate between the cognate base and other bases still remain unclear. Computational analysis on these two aspects of TALE-DNA interaction mechanism has been conducted in order to achieve a better understanding of the energetics. High elasticity was observed in the molecular dynamics simulations of DNA-free TALE structure that started from the bound conformation where it sampled a wide range of conformations including the experimentally determined apo and bound conformations. This elastic feature was also observed in the simulations starting from the apo form which suggests low free energy barrier between the two conformations and small compensation required upon binding. To analyze binding specificity, we performed free energy calculations of various combinations of RVDs and bases using Poisson-Boltzmann surface area (PBSA) and other approaches. The PBSA calculations indicated that the native RVD-base structures had lower binding free energy than mismatched structures for most of the RVDs examined. Our theoretical analyses provided new insight on the dynamics and energetics of TALE-DNA binding mechanism. © 2014 Elsevier Inc. All rights reserved.

Conversion of functionally undefined homopentameric protein PbaA into a proteasome activator by mutational modification of its C-terminal segment conformation.

Science.gov (United States)

Yagi-Utsumi, Maho; Sikdar, Arunima; Kozai, Toshiya; Inoue, Rintaro; Sugiyama, Masaaki; Uchihashi, Takayuki; Yagi, Hirokazu; Satoh, Tadashi; Kato, Koichi

2018-01-01

Recent bioinformatic analyses identified proteasome assembly chaperone-like proteins, PbaA and PbaB, in archaea. PbaB forms a homotetramer and functions as a proteasome activator, whereas PbaA does not interact with the proteasome despite the presence of an apparent C-terminal proteasome activation motif. We revealed that PbaA forms a homopentamer predominantly in the closed conformation with its C-terminal segments packed against the core domains, in contrast to the PbaB homotetramer with projecting C-terminal segments. This prompted us to create a novel proteasome activator based on a well-characterized structural framework. We constructed a panel of chimeric proteins comprising the homopentameric scaffold of PbaA and C-terminal segment of PbaB and subjected them to proteasome-activating assays as well as small-angle X-ray scattering and high-speed atomic force microscopy. The results indicated that the open conformation and consequent proteasome activation activity could be enhanced by replacement of the crystallographically disordered C-terminal segment of PbaA with the corresponding disordered segment of PbaB. Moreover, these effects can be produced just by incorporating two glutamate residues into the disordered C-terminal segment of PbaA, probably due to electrostatic repulsion among the negatively charged segments. Thus, we successfully endowed a functionally undefined protein with proteasome-activating activity by modifying its C-terminal segment. © The Author(s) 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Role and structural mechanism of WASP-triggered conformational changes in branched actin filament nucleation by Arp2/3 complex.

Science.gov (United States)

Rodnick-Smith, Max; Luan, Qing; Liu, Su-Ling; Nolen, Brad J

2016-07-05

The Arp2/3 (Actin-related proteins 2/3) complex is activated by WASP (Wiskott-Aldrich syndrome protein) family proteins to nucleate branched actin filaments that are important for cellular motility. WASP recruits actin monomers to the complex and stimulates movement of Arp2 and Arp3 into a "short-pitch" conformation that mimics the arrangement of actin subunits within filaments. The relative contribution of these functions in Arp2/3 complex activation and the mechanism by which WASP stimulates the conformational change have been unknown. We purified budding yeast Arp2/3 complex held in or near the short-pitch conformation by an engineered covalent cross-link to determine if the WASP-induced conformational change is sufficient for activity. Remarkably, cross-linked Arp2/3 complex bypasses the need for WASP in activation and is more active than WASP-activated Arp2/3 complex. These data indicate that stimulation of the short-pitch conformation is the critical activating function of WASP and that monomer delivery is not a fundamental requirement for nucleation but is a specific requirement for WASP-mediated activation. During activation, WASP limits nucleation rates by releasing slowly from nascent branches. The cross-linked complex is inhibited by WASP's CA region, even though CA potently stimulates cross-linking, suggesting that slow WASP detachment masks the activating potential of the short-pitch conformational switch. We use structure-based mutations and WASP-Arp fusion chimeras to determine how WASP stimulates movement toward the short-pitch conformation. Our data indicate that WASP displaces the autoinhibitory Arp3 C-terminal tail from a hydrophobic groove at Arp3's barbed end to destabilize the inactive state, providing a mechanism by which WASP stimulates the short-pitch conformation and activates Arp2/3 complex.

Conformational Dynamics of Thermus aquaticus DNA Polymerase I during Catalysis

OpenAIRE

Xu, Cuiling; Maxwell, Brian A.; Suo, Zucai

2014-01-01

Despite the fact that DNA polymerases have been investigated for many years and are commonly used as tools in a number of molecular biology assays, many details of the kinetic mechanism they use to catalyze DNA synthesis remain unclear. Structural and kinetic studies have characterized a rapid, pre-catalytic open-to-close conformational change of the Finger domain during nucleotide binding for many DNA polymerases including Thermus aquaticus DNA polymerase I (Taq Pol), a thermostable enzyme c...

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.

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.

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.

FlyMAD: rapid thermogenetic control of neuronal activity in freely walking Drosophila.

Science.gov (United States)

Bath, Daniel E; Stowers, John R; Hörmann, Dorothea; Poehlmann, Andreas; Dickson, Barry J; Straw, Andrew D

2014-07-01

Rapidly and selectively modulating the activity of defined neurons in unrestrained animals is a powerful approach in investigating the circuit mechanisms that shape behavior. In Drosophila melanogaster, temperature-sensitive silencers and activators are widely used to control the activities of genetically defined neuronal cell types. A limitation of these thermogenetic approaches, however, has been their poor temporal resolution. Here we introduce FlyMAD (the fly mind-altering device), which allows thermogenetic silencing or activation within seconds or even fractions of a second. Using computer vision, FlyMAD targets an infrared laser to freely walking flies. As a proof of principle, we demonstrated the rapid silencing and activation of neurons involved in locomotion, vision and courtship. The spatial resolution of the focused beam enabled preferential targeting of neurons in the brain or ventral nerve cord. Moreover, the high temporal resolution of FlyMAD allowed us to discover distinct timing relationships for two neuronal cell types previously linked to courtship song.

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.

Conformal Infinity

OpenAIRE

Frauendiener, J?rg

2000-01-01

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

Conformal superalgebras via tractor calculus

Science.gov (United States)

Lischewski, Andree

2015-01-01

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

Uncoupling of dynamin polymerization and GTPase activity revealed by the conformation-specific nanobody dynab.

Science.gov (United States)

Galli, Valentina; Sebastian, Rafael; Moutel, Sandrine; Ecard, Jason; Perez, Franck; Roux, Aurélien

2017-10-12

Dynamin is a large GTPase that forms a helical collar at the neck of endocytic pits, and catalyzes membrane fission (Schmid and Frolov, 2011; Ferguson and De Camilli, 2012). Dynamin fission reaction is strictly dependent on GTP hydrolysis, but how fission is mediated is still debated (Antonny et al., 2016): GTP energy could be spent in membrane constriction required for fission, or in disassembly of the dynamin polymer to trigger fission. To follow dynamin GTP hydrolysis at endocytic pits, we generated a conformation-specific nanobody called dynab, that binds preferentially to the GTP hydrolytic state of dynamin-1. Dynab allowed us to follow the GTPase activity of dynamin-1 in real-time. We show that in fibroblasts, dynamin GTP hydrolysis occurs as stochastic bursts, which are randomly distributed relatively to the peak of dynamin assembly. Thus, dynamin disassembly is not coupled to GTPase activity, supporting that the GTP energy is primarily spent in constriction.

Conformational switching in the coiled-coil domains of a proteasomal ATPase regulates substrate processing.

Science.gov (United States)

Snoberger, Aaron; Brettrager, Evan J; Smith, David M

2018-06-18

Protein degradation in all domains of life requires ATPases that unfold and inject proteins into compartmentalized proteolytic chambers. Proteasomal ATPases in eukaryotes and archaea contain poorly understood N-terminally conserved coiled-coil domains. In this study, we engineer disulfide crosslinks in the coiled-coils of the archaeal proteasomal ATPase (PAN) and report that its three identical coiled-coil domains can adopt three different conformations: (1) in-register and zipped, (2) in-register and partially unzipped, and (3) out-of-register. This conformational heterogeneity conflicts with PAN's symmetrical OB-coiled-coil crystal structure but resembles the conformational heterogeneity of the 26S proteasomal ATPases' coiled-coils. Furthermore, we find that one coiled-coil can be conformationally constrained even while unfolding substrates, and conformational changes in two of the coiled-coils regulate PAN switching between resting and active states. This switching functionally mimics similar states proposed for the 26S proteasome from cryo-EM. These findings thus build a mechanistic framework to understand regulation of proteasome activity.

On the advancements of conformal transformations and their associated symmetries in geometry and theoretical physics

Energy Technology Data Exchange (ETDEWEB)

Kastrup, H.A. [Deutsches Elektronen-Synchrotron (DESY), Hamburg (Germany). Theory Group

2008-08-15

The historical developments of conformal transformations and symmetries are sketched: Their origin from stereographic projections of the globe, their blossoming in two dimensions within the eld of analytic complex functions, the generic role of transformations by reciprocal radii in dimensions higher than two and their linearization in terms of polyspherical coordinates by Darboux, Weyl's attempt to extend General Relativity, the slow rise of nite dimensional conformal transformations in classical eld theories and the problem of their interpretation, then since about 1970 the rapid spread of their acceptance for asymptotic and structural problems in quantum eld theories and beyond, up to the current AdS=CFT conjecture. The occasion for the present article: hundred years ago Bateman and Cunningham discovered the form invariance of Maxwell's equations for electromagnetism with respect to conformal space-time transformations. (orig.)

Variable-temperature NMR and conformational analysis of Oenothein B

International Nuclear Information System (INIS)

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

2014-01-01

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

Variable-temperature NMR and conformational analysis of Oenothein B

Energy Technology Data Exchange (ETDEWEB)

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

2014-02-15

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

Conformal sequestering simplified

International Nuclear Information System (INIS)

Schmaltz, Martin; Sundrum, Raman

2006-01-01

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

Characterization of the conformational equilibrium between the two major substates of RNase A using NMR chemical shifts.

Science.gov (United States)

Camilloni, Carlo; Robustelli, Paul; De Simone, Alfonso; Cavalli, Andrea; Vendruscolo, Michele

2012-03-07

Following the recognition that NMR chemical shifts can be used for protein structure determination, rapid advances have recently been made in methods for extending this strategy for proteins and protein complexes of increasing size and complexity. A remaining major challenge is to develop approaches to exploit the information contained in the chemical shifts about conformational fluctuations in native states of proteins. In this work we show that it is possible to determine an ensemble of conformations representing the free energy surface of RNase A using chemical shifts as replica-averaged restraints in molecular dynamics simulations. Analysis of this surface indicates that chemical shifts can be used to characterize the conformational equilibrium between the two major substates of this protein. © 2012 American Chemical Society

Conformity index: A review

International Nuclear Information System (INIS)

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

2006-01-01

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

Dynamic and Progressive Control of DNA Origami Conformation by Modulating DNA Helicity with Chemical Adducts.

Science.gov (United States)

Chen, Haorong; Zhang, Hanyu; Pan, Jing; Cha, Tae-Gon; Li, Shiming; Andréasson, Joakim; Choi, Jong Hyun

2016-05-24

DNA origami has received enormous attention for its ability to program complex nanostructures with a few nanometer precision. Dynamic origami structures that change conformation in response to environmental cues or external signals hold great promises in sensing and actuation at the nanoscale. The reconfiguration mechanism of existing dynamic origami structures is mostly limited to single-stranded hinges and relies almost exclusively on DNA hybridization or strand displacement. Here, we show an alternative approach by demonstrating on-demand conformation changes with DNA-binding molecules, which intercalate between base pairs and unwind DNA double helices. The unwinding effect modulates the helicity mismatch in DNA origami, which significantly influences the internal stress and the global conformation of the origami structure. We demonstrate the switching of a polymerized origami nanoribbon between different twisting states and a well-constrained torsional deformation in a monomeric origami shaft. The structural transformation is shown to be reversible, and binding isotherms confirm the reconfiguration mechanism. This approach provides a rapid and reversible means to change DNA origami conformation, which can be used for dynamic and progressive control at the nanoscale.

Fermion-scalar conformal blocks

Energy Technology Data Exchange (ETDEWEB)

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

2016-04-13

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

Fabrication challenges associated with conformal optics

Science.gov (United States)

Schaefer, John; Eichholtz, Richard A.; Sulzbach, Frank C.

2001-09-01

A conformal optic is typically an optical window that conforms smoothly to the external shape of a system platform to improve aerodynamics. Conformal optics can be on-axis, such as an ogive missile dome, or off-axis, such as in a free form airplane wing. A common example of conformal optics is the automotive head light window that conforms to the body of the car aerodynamics and aesthetics. The unusual shape of conformal optics creates tremendous challenges for design, manufacturing, and testing. This paper will discuss fabrication methods that have been successfully demonstrated to produce conformal missile domes and associated wavefront corrector elements. It will identify challenges foreseen with more complex free-form configurations. Work presented in this paper was directed by the Precision Conformal Optics Consortium (PCOT). PCOT is comprised of both industrial and academic members who teamed to develop and demonstrate conformal optical systems suitable for insertion into future military programs. The consortium was funded under DARPA agreement number MDA972-96-9-08000.

RAPID KNEE-EXTENSIONS TO INCREASE QUADRICEPS MUSCLE ACTIVITY IN PATIENTS WITH TOTAL KNEE ARTHROPLASTY

DEFF Research Database (Denmark)

Husted, Rasmus Skov; Wilquin, Lousia; Jakobsen, Thomas Linding

2017-01-01

rapid knee-extensions were associated with greater voluntary quadriceps muscle activity during an experimental strength training session, compared to that elicited using slow knee-extensions. STUDY DESIGN: A randomized cross-over study. METHODS: Twenty-four patients (age 66.5) 4-8 weeks post total knee...... agonist muscle activity, especially if the exercise is conducted using rapid muscle contractions. PURPOSE: The purpose of this study was to examine if patients with total knee arthroplasty could perform rapid knee-extensions using a 10 RM load four to eight weeks after surgery, and the degree to which...... arthroplasty randomly performed one set of five rapid, and one set of five slow knee-extensions with the operated leg, using a load of their 10 repetition maximum, while surface electromyography recordings were obtained from the vastus medialis and lateralis of the quadriceps muscle. RESULTS: Data from 23...

Rapid knee-extensions to increase quadriceps muscle activity in patients with total knee arthroplasty

DEFF Research Database (Denmark)

Husted, Rasmus Skov; Wilquin, Lousia; Jakobsen, Thomas Linding

2017-01-01

rapid knee-extensions were associated with greater voluntary quadriceps muscle activity during an experimental strength training session, compared to that elicited using slow knee-extensions. STUDY DESIGN: A randomized cross-over study. METHODS: Twenty-four patients (age 66.5) 4-8 weeks post total knee...... agonist muscle activity, especially if the exercise is conducted using rapid muscle contractions. PURPOSE: The purpose of this study was to examine if patients with total knee arthroplasty could perform rapid knee-extensions using a 10 RM load four to eight weeks after surgery, and the degree to which...... arthroplasty randomly performed one set of five rapid, and one set of five slow knee-extensions with the operated leg, using a load of their 10 repetition maximum, while surface electromyography recordings were obtained from the vastus medialis and lateralis of the quadriceps muscle. RESULTS: Data from 23...

[Osteogenic activity of porous calcium phosphate ceramics fabricated by rapid prototyping].

Science.gov (United States)

He, Chenguang; Zhao, Li; Lin, Liulan; Gu, Huijie; Zhou, Heng; Cui, Lei

2010-07-01

Calcium phosphate bioceramics has a broad application prospect because of good biocompatibility, but porous scaffolds with complex shape can not be prepared by the traditional methods. To fabricate porous calcium phosphate ceramics by rapid prototyping and to investigate the in vitro osteogenic activities. The porous calcium phosphate ceramics was fabricated by rapid prototyping. The bone marrow mesenchymal stem cells (BMSCs) were isolated from bone marrow of Beagle canine, and the 3rd passage BMSCs were seeded onto the porous ceramics. The cell/ceramics composite cultured in osteogenic medium were taken as the experimental group (group A) and the cell/ceramics composite cultured in growth medium were taken as the control group (group B). Meanwhile, the cells seeded on the culture plate were cultured in osteogenic medium or growth medium respectively as positive control (group C) or negative control (group D). After 1, 3, and 7 days of culture, the cell proliferation and osteogenic differentiation on the porous ceramics were evaluated by DNA quantitative analysis, histochemical staining and alkaline phosphatase (ALP) activity. After DiO fluorescent dye, the cell adhesion, growth, and proliferation on the porous ceramics were also observed by confocal laser scanning microscope (CLSM). DNA quantitative analysis results showed that the number of BMSCs in all groups increased continuously with time. Plateau phase was not obvious in groups A and B, but it was clearly observed in groups C and D. The CLSM observation indicated that the activity of BMSCs was good and the cells spread extensively, showing good adhesion and proliferation on the porous calcium phosphate ceramics prepared by rapid prototyping. ALP quantitative analysis results showed that the stain of cells on the ceramics became deeper and deeper with time in groups A and B, the staining degree in group A were stronger than that in group B. There was no significant difference in the change of the ALP activity

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.)

Stratification of nitrification activity in rapid sand filters for drinking water treatment

DEFF Research Database (Denmark)

Tatari, Karolina; Smets, Barth F.; Musovic, Sanin

2013-01-01

Rapid sand filters used in groundwater treatment remove ammonium, iron and manganese from the water. Ammonium is removed biologically by nitrifying microorganisms attached on the sand surface. Nitrification kinetics and activity is strongly affected by filter design and operation, which are the key...... and maximum nitrification capacity are derived and used to quantify nitrification activity. Nitrification activity was concentrated at the top 10 cm of filter depth, and maximum nitrification capacity was 7 g NH4+-N/ m3 sand/h compared with 0.8-0.4 g NH4+-N/ m3 sand/h in the middle and bottom layers. A water...... of this study is to investigate nitrification activity in a rapid sand filter, with focus on its homogeneity and how it relates to filter performance. Two groundwater treatment plants in Denmark were selected for the experimental investigations. Plant 1 operates a single line of pre and after filters and has...

Conformal description of spinning particles

International Nuclear Information System (INIS)

Todorov, I.T.

1986-01-01

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

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....

Structure of rapidity divergences in multi-parton scattering soft factors

Science.gov (United States)

Vladimirov, Alexey

2018-04-01

We discuss the structure of rapidity divergences that are presented in the soft factors of transverse momentum dependent (TMD) factorization theorems. To provide the discussion on the most general level we consider soft factors for multi-parton scattering. We show that the rapidity divergences are result of the gluon exchanges with the distant transverse plane, and are structurally equivalent to the ultraviolet divergences. It allows to formulate and to prove the renormalization theorem for rapidity divergences. The proof is made with the help the conformal transformation which maps rapidity divergences to ultraviolet divergences. The theorem is the systematic form of the factorization of rapidity divergences, which is required for the definition of TMD parton distributions. In particular, the definition of multi parton distributions is presented. The equivalence of ultraviolet and rapidity divergences leads to the exact relation between soft and rapidity anomalous dimensions. Using this relation we derive the rapidity anomalous dimension at the three-loop order.

Conformally connected universes

International Nuclear Information System (INIS)

Cantor, M.; Piran, T.

1983-01-01

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

Tyr66 acts as a conformational switch in the closed-to-open transition of the SHP-2 N-SH2-domain phosphotyrosine-peptide binding cleft

Directory of Open Access Journals (Sweden)

MacKerell Alexander D

2007-03-01

Full Text Available Abstract Background The N-terminal SH2 domain (N-SH2 of the non-receptor tyrosine phosphatase SHP-2 is involved both in localization of SHP-2 by recognition of phosphotyrosine (pY peptides and self-inhibition of SHP-2 phosphatase activity through the formation of a protein – protein interface with the phosphatase domain. Mutations that disrupt this interface break the coupling between pY-peptide binding cleft conformation and self-inhibition, thereby increasing both SHP-2 phosphatase activity and pY-peptide binding affinity, and are associated with the congenital condition Noonan syndrome and various pediatric leukemias. To better characterize the molecular process involved in N-SH2 pY-dependent binding, we have applied explicit-solvent molecular dynamics simulations to study the closed-to-open transition of the N-SH2 pY-peptide binding cleft. Results The existence of stable conformations in the left-handed helical and the extended regions of Tyr66 φ/ψ space prevent rapid interconversion of the backbone and create a conformational switch such that Tyr66 in a left-handed helical backbone conformation results in an open cleft and in an extended backbone conformation results in a closed cleft. The stable conformations arise from deep, well-localized free-energy minima in the left-handed helical and extended regions of the Tyr66 φ/ψ map. Changing the Tyr66 backbone conformation from extended to left-handed helical induces a closed-to-open transition in the cleft, and the reverse change in backbone conformation induces the reverse, open-to-closed transition. In the open-cleft state, weak solvent-exposed interactions involving the sidechains of Tyr66, Asp40, Lys55, and Gln57 serve to anchor the Tyr66 sidechain to the surface of the protein and away from the binding cleft entrance, thereby facilitating pY-peptide access to the binding cleft. Conclusion The simulations point to a regulatory role for Tyr66 and surrounding residues in SHP-2 function

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 ...

Guiding exploration in conformational feature space with Lipschitz underestimation for ab-initio protein structure prediction.

Science.gov (United States)

Hao, Xiaohu; Zhang, Guijun; Zhou, Xiaogen

2018-04-01

Computing conformations which are essential to associate structural and functional information with gene sequences, is challenging due to the high dimensionality and rugged energy surface of the protein conformational space. Consequently, the dimension of the protein conformational space should be reduced to a proper level, and an effective exploring algorithm should be proposed. In this paper, a plug-in method for guiding exploration in conformational feature space with Lipschitz underestimation (LUE) for ab-initio protein structure prediction is proposed. The conformational space is converted into ultrafast shape recognition (USR) feature space firstly. Based on the USR feature space, the conformational space can be further converted into Underestimation space according to Lipschitz estimation theory for guiding exploration. As a consequence of the use of underestimation model, the tight lower bound estimate information can be used for exploration guidance, the invalid sampling areas can be eliminated in advance, and the number of energy function evaluations can be reduced. The proposed method provides a novel technique to solve the exploring problem of protein conformational space. LUE is applied to differential evolution (DE) algorithm, and metropolis Monte Carlo(MMC) algorithm which is available in the Rosetta; When LUE is applied to DE and MMC, it will be screened by the underestimation method prior to energy calculation and selection. Further, LUE is compared with DE and MMC by testing on 15 small-to-medium structurally diverse proteins. Test results show that near-native protein structures with higher accuracy can be obtained more rapidly and efficiently with the use of LUE. Copyright © 2018 Elsevier Ltd. All rights reserved.

Computational study of the activity, dynamics, energetics and conformations of insulin analogues using molecular dynamics simulations: Application to hyperinsulinemia and the critical residue B26

Directory of Open Access Journals (Sweden)

Anastasios Papaioannou

2017-09-01

Full Text Available Due to the increasing prevalence of diabetes, finding therapeutic analogues for insulin has become an urgent issue. While many experimental studies have been performed towards this end, they have limited scope to examine all aspects of the effect of a mutation. Computational studies can help to overcome these limitations, however, relatively few studies that focus on insulin analogues have been performed to date. Here, we present a comprehensive computational study of insulin analogues—three mutant insulins that have been identified with hyperinsulinemia and three mutations on the critical B26 residue that exhibit similar binding affinity to the insulin receptor—using molecular dynamics simulations with the aim of predicting how mutations of insulin affect its activity, dynamics, energetics and conformations. The time evolution of the conformers is studied in long simulations. The probability density function and potential of mean force calculations are performed on each insulin analogue to unravel the effect of mutations on the dynamics and energetics of insulin activation. Our conformational study can decrypt the key features and molecular mechanisms that are responsible for an enhanced or reduced activity of an insulin analogue. We find two key results: 1 hyperinsulinemia may be due to the drastically reduced activity (and binding affinity of the mutant insulins. 2 Y26BS and Y26BE are promising therapeutic candidates for insulin as they are more active than WT-insulin. The analysis in this work can be readily applied to any set of mutations on insulin to guide development of more effective therapeutic analogues.

Conformal algebra of Riemann surfaces

International Nuclear Information System (INIS)

Vafa, C.

1988-01-01

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

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.

Male Wistar rats show individual differences in an animal model of conformity.

Science.gov (United States)

Jolles, Jolle W; de Visser, Leonie; van den Bos, Ruud

2011-09-01

Conformity refers to the act of changing one's behaviour to match that of others. Recent studies in humans have shown that individual differences exist in conformity and that these differences are related to differences in neuronal activity. To understand the neuronal mechanisms in more detail, animal tests to assess conformity are needed. Here, we used a test of conformity in rats that has previously been evaluated in female, but not male, rats and assessed the nature of individual differences in conformity. Male Wistar rats were given the opportunity to learn that two diets differed in palatability. They were subsequently exposed to a demonstrator that had consumed the less palatable food. Thereafter, they were exposed to the same diets again. Just like female rats, male rats decreased their preference for the more palatable food after interaction with demonstrator rats that had eaten the less palatable food. Individual differences existed for this shift, which were only weakly related to an interaction between their own initial preference and the amount consumed by the demonstrator rat. The data show that this conformity test in rats is a promising tool to study the neurobiology of conformity.

1H nuclear magnetic resonance studies of the conformation of an ATP analogue at the active site of Na,K-ATPase from kidney medulla

International Nuclear Information System (INIS)

Stewart, J.M.M.; Grisham, C.M.

1988-01-01

1 H nuclear magnetic relaxation measurements have been used to determine the three-dimensional conformation of an ATP analogue, Co(NH 3 ) 4 ATP, at the active site of sheep kidney Na,K-ATPase. Previous studies have shown that Co(NH 4 ) 4 ATP is a competitive inhibitor with respect to MnATP for the Na,K-ATPase and that Mn 2+ bound to a single, high-affinity site on the ATPase can be an effective paramagnetic probe for nuclear relaxation studies of the Na-K-ATPase. From the paramagnetic effect of Mn 2+ bound to the APTase on the longitudinal relaxation rates of the protons of Co(NH 3 ) 4 ATP at the substrate site (at 300 and 361 MHz), Mn-H distances to seven protons on the bound nucleotide were determined. Taken together with previous 31 P nuclear relaxation data, these measurements are consistent with a single nucleotide conformation at the active site. The nucleotide adopts a bent configuration, in which the triphosphate chain lies nearly parallel to the adenine moiety. The glycosidic torsion angle is 35 0 , and the conformation of the ribose ring is slightly N-type. The bound Mn 2+ lies above and in the plane of the adenine ring. The distances from Mn 2+ to N 6 and N 7 are too large for first coordination sphere complexes but are appropriate for second-sphere complexes involving, for example, intervening hydrogen-bonded water molecules. The NMR data also indicate that the structure of the bound ATP analogue is independent of the conformational state of the enzyme

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...

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

DEFF Research Database (Denmark)

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

2012-01-01

Based on a rare, natural Glu for Ala204(C+6) variant located six residues after the conserved Cys residue in extracellular loop 2 (ECL2b) associated with selective elimination of the high constitutive signaling of the ghrelin receptor, this loop was subjected to a detailed structure functional....... Moreover, the constitutive activity of the receptor was inhibited by Zn(2+) binding in an engineered metal-ion site stabilizing an a-helical conformation of this loop segment. It is concluded that the high constitutive activity of the ghrelin receptor is dependent upon flexibility in the C-terminal segment...

Evidence for an intermediate conformational state of LacY.

Science.gov (United States)

Jiang, Xiaoxu; Guan, Lan; Zhou, Yonggang; Hong, Wen-Xu; Zhang, Qinghai; Kaback, H Ronald

2012-03-20

LacY mutant Cys154 → Gly exhibits a periplasmic-closed crystal structure identical to the WT, but is periplasmic-open in the membrane. The mutant hardly catalyzes transport, but binds galactosides from either side of the membrane with the same affinity and is resistant to site-directed proteolysis relative to the pseudo-WT. Site-directed alkylation was also applied to 11 single-Cys mutants in Cys154 → Gly LacY in right-side-out membrane vesicles or after solubilization and purification in dodecyl-β-D-maltopyranoside (DDM). Unlike the pseudo-WT, Cys replacements on the periplasmic side of the Cys154 → Gly mutant label rapidly in the membrane without sugar, but labeling decreases markedly after the mutant proteins are purified. Thus, Cys154 → Gly LacY likely favors a higher-energy intermediate periplasmic-open conformation in situ, but collapses to a lower-energy periplasmic-closed conformation in DDM after purification. Notably, branched-chain or neopentyl glycol maltoside detergents stabilize Cys154 → Gly LacY in the membrane-embedded form.

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.

The logarithmic conformal field theories

International Nuclear Information System (INIS)

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

1997-01-01

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

Recent advancements in conformal gravity

International Nuclear Information System (INIS)

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

2017-01-01

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

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.

Conformational adaptation of Asian macaque TRIMCyp directs lineage specific antiviral activity.

Directory of Open Access Journals (Sweden)

Laura M J Ylinen

2010-08-01

Full Text Available TRIMCyps are anti-retroviral proteins that have arisen independently in New World and Old World primates. All TRIMCyps comprise a CypA domain fused to the tripartite domains of TRIM5alpha but they have distinct lentiviral specificities, conferring HIV-1 restriction in New World owl monkeys and HIV-2 restriction in Old World rhesus macaques. Here we provide evidence that Asian macaque TRIMCyps have acquired changes that switch restriction specificity between different lentiviral lineages, resulting in species-specific alleles that target different viruses. Structural, thermodynamic and viral restriction analysis suggests that a single mutation in the Cyp domain, R69H, occurred early in macaque TRIMCyp evolution, expanding restriction specificity to the lentiviral lineages found in African green monkeys, sooty mangabeys and chimpanzees. Subsequent mutations have enhanced restriction to particular viruses but at the cost of broad specificity. We reveal how specificity is altered by a scaffold mutation, E143K, that modifies surface electrostatics and propagates conformational changes into the active site. Our results suggest that lentiviruses may have been important pathogens in Asian macaques despite the fact that there are no reported lentiviral infections in current macaque populations.

Conformal and Nearly Conformal Theories at Large N

Science.gov (United States)

Tarnoplskiy, Grigory M.

In this thesis we present new results in conformal and nearly conformal field theories in various dimensions. In chapter two, we study different properties of the conformal Quantum Electrodynamics (QED) in continuous dimension d. At first we study conformal QED using large Nf methods, where Nf is the number of massless fermions. We compute its sphere free energy as a function of d, ignoring the terms of order 1/Nf and higher. For finite Nf we use the epsilon-expansion. Next we use a large Nf diagrammatic approach to calculate the leading corrections to CT, the coefficient of the two-point function of the stress-energy tensor, and CJ, the coefficient of the two-point function of the global symmetry current. We present explicit formulae as a function of d and check them versus the expectations in 2 and 4 - epsilon dimensions. In chapter three, we discuss vacuum stability in 1 + 1 dimensional conformal field theories with external background fields. We show that the vacuum decay rate is given by a non-local two-form. This two-form is a boundary term that must be added to the effective in/out Lagrangian. The two-form is expressed in terms of a Riemann-Hilbert decomposition for background gauge fields, and is given by its novel "functional'' version in the gravitational case. In chapter four, we explore Tensor models. Such models possess the large N limit dominated by the melon diagrams. The quantum mechanics of a real anti-commuting rank-3 tensor has a large N limit similar to the Sachdev-Ye-Kitaev (SYK) model. We also discuss the quantum mechanics of a complex 3-index anti-commuting tensor and argue that it is equivalent in the large N limit to a version of SYK model with complex fermions. Finally, we discuss models of a commuting tensor in dimension d. We study the spectrum of the large N quantum field theory of bosonic rank-3 tensors using the Schwinger-Dyson equations. We compare some of these results with the 4 - epsilon expansion, finding perfect agreement. We

Conformal Fabrication of Colloidal Quantum Dot Solids for Optically Enhanced Photovoltaics

KAUST Repository

Labelle, André J.

2015-05-26

© 2015 American Chemical Society. Colloidal quantum dots (CQD) are an attractive thin-film material for photovoltaic applications due to low material costs, ease of fabrication, and size-tunable band gap. Unfortunately, today they suffer from a compromise between light absorption and photocarrier extraction, a fact that currently prevents the complete harvest of incoming above-band-gap solar photons. We have investigated the use of structured substrates and/or electrodes to increase the effective light path through the active material and found that these designs require highly conformal application of the light-absorbing films to achieve the greatest enhancement. This conformality requirement derives from the need for maximal absorption enhancement combined with shortest-distance charge transport. Here we report on a means of processing highly conformal layer-by-layer deposited CQD absorber films onto microstructured, light-recycling electrodes. Specifically, we engineer surface hydrophilicity to achieve conformal deposition of upper layers atop underlying ones. We show that only with the application of conformal coating can we achieve optimal quantum efficiency and enhanced power conversion efficiency in structured-electrode CQD cells.

Conformal prediction for reliable machine learning theory, adaptations and applications

CERN Document Server

Balasubramanian, Vineeth; Vovk, Vladimir

2014-01-01

The conformal predictions framework is a recent development in machine learning that can associate a reliable measure of confidence with a prediction in any real-world pattern recognition application, including risk-sensitive applications such as medical diagnosis, face recognition, and financial risk prediction. Conformal Predictions for Reliable Machine Learning: Theory, Adaptations and Applications captures the basic theory of the framework, demonstrates how to apply it to real-world problems, and presents several adaptations, including active learning, change detection, and anomaly detecti

Structure-activity relationships of pyrethroid insecticides. Part 2. The use of molecular dynamics for conformation searching and average parameter calculation

Science.gov (United States)

Hudson, Brian D.; George, Ashley R.; Ford, Martyn G.; Livingstone, David J.

1992-04-01

Molecular dynamics simulations have been performed on a number of conformationally flexible pyrethroid insecticides. The results indicate that molecular dynamics is a suitable tool for conformational searching of small molecules given suitable simulation parameters. The structures derived from the simulations are compared with the static conformation used in a previous study. Various physicochemical parameters have been calculated for a set of conformations selected from the simulations using multivariate analysis. The averaged values of the parameters over the selected set (and the factors derived from them) are compared with the single conformation values used in the previous study.

Conformal radiotherapy: principles and classification

International Nuclear Information System (INIS)

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

1999-01-01

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

S-Adenosylmethionine conformations in solution and in protein complexes: Conformational influences of the sulfonium group

DEFF Research Database (Denmark)

Markham, George D.; Norrby, Per-Ola; Bock, Charles W.

2002-01-01

S-Adenosylmethionine (AdoMet) and other sulfonium ions play central roles in the metabolism of all organisms. The conformational preferences of AdoMet and two other biologically important sulfonium ions, S-methylmethionine and dimethylsulfonioproprionic acid, have been investigated by NMR...... and computational studies. Molecular mechanics parameters for the sulfonium center have been developed for the AMBER force field to permit analysis of NMR results and to enable comparison of the relative energies of the different conformations of AdoMet that have been found in crystal structures of complexes...... with proteins. S-Methylmethionine and S-dimethylsulfonioproprionate adopt a variety of conformations in aqueous solution; a conformation with an electrostatic interaction between the sulfonium sulfur and the carboxylate group is not noticeably favored, in contrast to the preferred conformation found by in vacuo...

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.

Conformal Killing vectors in Robertson-Walker spacetimes

International Nuclear Information System (INIS)

Maartens, R.; Maharaj, S.d.

1986-01-01

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

Conformal transformations in superspace

International Nuclear Information System (INIS)

Dao Vong Duc

1977-01-01

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

Towards conformal loop quantum gravity

International Nuclear Information System (INIS)

Wang, Charles H-T

2006-01-01

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

Conformational study of melectin and antapin antimicrobial peptides in model membrane environments

Science.gov (United States)

Kocourková, Lucie; Novotná, Pavlína; Čujová, Sabína; Čeřovský, Václav; Urbanová, Marie; Setnička, Vladimír

2017-01-01

Antimicrobial peptides have long been considered as promising compounds against drug-resistant pathogens. In this work, we studied the secondary structure of antimicrobial peptides melectin and antapin using electronic (ECD) and vibrational circular dichroism (VCD) spectroscopies that are sensitive to peptide secondary structures. The results from quantitative ECD spectral evaluation by Dichroweb and CDNN program and from the qualitative evaluation of the VCD spectra were compared. The antimicrobial activity of the selected peptides depends on their ability to adopt an amphipathic α-helical conformation on the surface of the bacterial membrane. Hence, solutions of different zwitterionic and negatively charged liposomes and micelles were used to mimic the eukaryotic and bacterial biological membranes. The results show a significant content of α-helical conformation in the solutions of negatively charged liposomes mimicking the bacterial membrane, thus correlating with the antimicrobial activity of the studied peptides. On the other hand in the solutions of zwitterionic liposomes used as models of the eukaryotic membranes, the fraction of α-helical conformation was lower, which corresponds with their moderate hemolytic activity.

Book-tax conformity in Polish private companies

Directory of Open Access Journals (Sweden)

Anna Białek-Jaworska

2016-12-01

Full Text Available The purpose of this paper is to identify whether financial income differs significantly from the tax base in Poland and what determines these differences between accounting and taxable results in Polish private entities that are not listed on the stock exchange. In this paper, besides examining the level of book-tax conformity in Poland, we investigate the determinants of book-tax differences in the one-book and twobook accounting systems, with deferred income tax. We use the single factor ANOVA variance analysis, robust fixed effects estimator and the fixed effects linear model with an AR(1 disturbance estimator for panel data of 26,657 private limited liability and non-public joint-stock companies for the period of 2003–2014 (177,667 firm-year observations. The originality of this paper results from the deep quantita-tive analysis of the determinants of book-tax conformity on a novel dataset of Polish private firms. We confirm a strong significant influence of tax law on the shape of the one-book accounting system in Poland. Larger enterprises show fewer book-tax differences. Book-tax conformity is lower in private companies that incur financial losses and in private companies conducting the one-book accounting system. Family-owned companies have higher mean and median book-tax conformity than businessgroups members, due to higher demand for information from their accounts to support stewardship func-tions and to monitor the activities of the management board in the business groups.

A rapid stereoselective synthesis of fluorinated carbohydrates

International Nuclear Information System (INIS)

Adam, M.J.; Neeser, J-R.; Hall, L.D.; Pate, B.D.

1983-01-01

Acetyl hypofluorite has been added to six unsaturated carbohydrates which contain the vinyl ether moiety. All reactions were rapid (less than 5 min.) at -78 degrees C and gave, with one exception, high yields of isomerically pure products. The hypofluorite was shown to add exclusively in a cis mode and with a strong preference for a particular 'face' of the double bond. As well as the syntheses, NMR data and preferred conformations for the fluorinated products are also discussed

Mass generation within conformal invariant theories

International Nuclear Information System (INIS)

Flato, M.; Guenin, M.

1981-01-01

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

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

Conformal field theories and critical phenomena

International Nuclear Information System (INIS)

Xu, Bowei

1993-01-01

In this article we present a brief review of the conformal symmetry and the two dimensional conformal quantum field theories. As concrete applications of the conformal theories to the critical phenomena in statistical systems, we calculate the value of central charge and the anomalous scale dimensions of the Z 2 symmetric quantum chain with boundary condition. The results are compatible with the prediction of the conformal field theories

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

Science.gov (United States)

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

2016-04-01

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

QCD-instantons and conformal inversion symmetry

Energy Technology Data Exchange (ETDEWEB)

Klammer, D.

2006-07-15

Instantons are an essential and non-perturbative part of Quantum Chromodynamics, the theory of strong interactions. One of the most relevant quantities in the instanton calculus is the instanton-size distribution, which can be described on the one hand within the framework of instanton perturbation theory and on the other hand investigated numerically by means of lattice computations. A rapid onset of a drastic discrepancy between these respective results indicates that the underlying physics is not yet well understood. In this work we investigate the appealing possibility of a symmetry under conformal inversion of space-time leading to this deviation. The motivation being that the lattice data seem to be invariant under an inversion of the instanton size. Since the instanton solution of a given size turns into an anti-instanton solution having an inverted size under conformal inversion of space-time, we ask in a first investigation, whether this property is transferred to the quantum level. In order to introduce a new scale, which is indicated by the lattice data and corresponds to the average instanton size as inversion radius, we project the instanton calculus onto the four-dimensional surface of a five-dimensional sphere via stereographic projection. The radius of this sphere is associated with the average instanton size. The result for the instanton size-distribution projected onto the sphere agrees surprisingly well with the lattice data at qualitative level. The resulting symmetry under an inversion of the instanton size is almost perfect. (orig.)

QCD-instantons and conformal inversion symmetry

International Nuclear Information System (INIS)

Klammer, D.

2006-07-01

Instantons are an essential and non-perturbative part of Quantum Chromodynamics, the theory of strong interactions. One of the most relevant quantities in the instanton calculus is the instanton-size distribution, which can be described on the one hand within the framework of instanton perturbation theory and on the other hand investigated numerically by means of lattice computations. A rapid onset of a drastic discrepancy between these respective results indicates that the underlying physics is not yet well understood. In this work we investigate the appealing possibility of a symmetry under conformal inversion of space-time leading to this deviation. The motivation being that the lattice data seem to be invariant under an inversion of the instanton size. Since the instanton solution of a given size turns into an anti-instanton solution having an inverted size under conformal inversion of space-time, we ask in a first investigation, whether this property is transferred to the quantum level. In order to introduce a new scale, which is indicated by the lattice data and corresponds to the average instanton size as inversion radius, we project the instanton calculus onto the four-dimensional surface of a five-dimensional sphere via stereographic projection. The radius of this sphere is associated with the average instanton size. The result for the instanton size-distribution projected onto the sphere agrees surprisingly well with the lattice data at qualitative level. The resulting symmetry under an inversion of the instanton size is almost perfect. (orig.)

Ward identities for conformal models

International Nuclear Information System (INIS)

Lazzarini, S.; Stora, R.

1988-01-01

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

Effects of Pulsed Electric Field (PEF) Treatment on Enhancing Activity and Conformation of α-Amylase.

Science.gov (United States)

Tian, Mei-ling; Fang, Ting; Du, Mu-ying; Zhang, Fu-sheng

2016-04-01

To explore an efficient, safe, and speedy application of pulsed electric field (PEF) technology for enzymatic modification, effects of PEF treatment on the enzymatic activity, property and kinetic parameters of α-amylase were investigated. Conformational transitions were also studied with the aid of circular dichroism (CD) and fluorescence spectra. The maximum enzymatic activity of α-amylase was obtained under 15 kV/cm electric field intensity and 100 mL/min flow velocity PEF treatment, in which the enzymatic activity increased by 22.13 ± 1.14% compared with control. The activation effect could last for 18 h at 4 °C. PEF treatment could widen the range of optimum temperature for α-amylase, however, it barely exerted any effect on the optimum pH. On the other hand, α-amylase treated by PEF showed an increase of Vmax, t1/2 and ΔG, whereas a decrease of Km and k were observed. Furthermore, it can be observed from fluorescence and CD spectra that PEF treatment had increased the number of amino acid residues, especially that of tryptophan, on α-amylase surface with enhanced α-helices by 34.76% and decreased random coil by 12.04% on α-amylase when compared with that of untreated. These changes in structure had positive effect on enhancing α-amylase activity and property.

Evaluation of antimicrobial activity of selected plant extracts by rapid XTT colorimetry and bacterial enumeration.

Science.gov (United States)

Al-Bakri, Amal G; Afifi, Fatma U

2007-01-01

The aim of this study was to screen and evaluate the antimicrobial activity of indigenous Jordanian plant extracts, dissolved in dimethylsulfoxide, using the rapid XTT assay and viable count methods. XTT rapid assay was used for the initial screening of antimicrobial activity for the plant extracts. Antimicrobial activity of potentially active plant extracts was further assessed using the "viable plate count" method. Four degrees of antimicrobial activity (high, moderate, weak and inactive) against Bacillus subtilis, Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa, respectively, were recorded. The plant extracts of Hypericum triquetrifolium, Ballota undulata, Ruta chalepensis, Ononis natrix, Paronychia argentea and Marrubium vulgare had shown promising antimicrobial activity. This study showed that while both XTT and viable count methods are comparable when estimating the overall antimicrobial activity of experimental substances, there is no strong linear correlation between the two methods.

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).

The effect of tensile stress on the conformational free energy landscape of disulfide bonds.

Directory of Open Access Journals (Sweden)

Padmesh Anjukandi

Full Text Available Disulfide bridges are no longer considered to merely stabilize protein structure, but are increasingly recognized to play a functional role in many regulatory biomolecular processes. Recent studies have uncovered that the redox activity of native disulfides depends on their C-C-S-S dihedrals, χ2 and χ'2. Moreover, the interplay of chemical reactivity and mechanical stress of disulfide switches has been recently elucidated using force-clamp spectroscopy and computer simulation. The χ2 and χ'2 angles have been found to change from conformations that are open to nucleophilic attack to sterically hindered, so-called closed states upon exerting tensile stress. In view of the growing evidence of the importance of C-C-S-S dihedrals in tuning the reactivity of disulfides, here we present a systematic study of the conformational diversity of disulfides as a function of tensile stress. With the help of force-clamp metadynamics simulations, we show that tensile stress brings about a large stabilization of the closed conformers, thereby giving rise to drastic changes in the conformational free energy landscape of disulfides. Statistical analysis shows that native TDi, DO and interchain Ig protein disulfides prefer open conformations, whereas the intrachain disulfide bridges in Ig proteins favor closed conformations. Correlating mechanical stress with the distance between the two a-carbons of the disulfide moiety reveals that the strain of intrachain Ig protein disulfides corresponds to a mechanical activation of about 100 pN. Such mechanical activation leads to a severalfold increase of the rate of the elementary redox S(N2 reaction step. All these findings constitute a step forward towards achieving a full understanding of functional disulfides.

Dissecting the large-scale galactic conformity

Science.gov (United States)

Seo, Seongu

2018-01-01

Galactic conformity is an observed phenomenon that galaxies located in the same region have similar properties such as star formation rate, color, gas fraction, and so on. The conformity was first observed among galaxies within in the same halos (“one-halo conformity”). The one-halo conformity can be readily explained by mutual interactions among galaxies within a halo. Recent observations however further witnessed a puzzling connection among galaxies with no direct interaction. In particular, galaxies located within a sphere of ~5 Mpc radius tend to show similarities, even though the galaxies do not share common halos with each other ("two-halo conformity" or “large-scale conformity”). Using a cosmological hydrodynamic simulation, Illustris, we investigate the physical origin of the two-halo conformity and put forward two scenarios. First, back-splash galaxies are likely responsible for the large-scale conformity. They have evolved into red galaxies due to ram-pressure stripping in a given galaxy cluster and happen to reside now within a ~5 Mpc sphere. Second, galaxies in strong tidal field induced by large-scale structure also seem to give rise to the large-scale conformity. The strong tides suppress star formation in the galaxies. We discuss the importance of the large-scale conformity in the context of galaxy evolution.

Entanglement evolution across a conformal interface

Science.gov (United States)

Wen, Xueda; Wang, Yuxuan; Ryu, Shinsei

2018-05-01

For two-dimensional conformal field theories (CFTs) in the ground state, it is known that a conformal interface along the entanglement cut can suppress the entanglement entropy from to , where L is the length of the subsystem A, and is the effective central charge which depends on the transmission property of the conformal interface. In this work, by making use of conformal mappings, we show that a conformal interface has the same effect on entanglement evolution in non-equilibrium cases, including global, local and certain inhomogeneous quantum quenches. I.e. a conformal interface suppresses the time evolution of entanglement entropy by effectively replacing the central charge c with , where is exactly the same as that in the ground state case. We confirm this conclusion by a numerical study on a critical fermion chain. Furthermore, based on the quasi-particle picture, we conjecture that this conclusion holds for an arbitrary quantum quench in CFTs, as long as the initial state can be described by a regularized conformal boundary state.

Insight the C-site pocket conformational changes responsible for sirtuin 2 activity using molecular dynamics simulations.

Directory of Open Access Journals (Sweden)

Sugunadevi Sakkiah

Full Text Available Sirtuin belongs to a family of typical histone deacetylase which regulates the fundamental cellular biological processes including gene expression, genome stability, mitosis, nutrient metabolism, aging, mitochondrial function, and cell motility. Michael et. al. reported that B-site mutation (Q167A and H187A decreased the SIRT2 activity but still the structural changes were not reported. Hence, we performed 5 ns molecular dynamics (MD simulation on SIRT2 Apo-form and complexes with substrate/NAD(+ and inhibitor of wild type (WT, Q167A, and H187A. The results revealed that the assembly and disassembly of C-site induced by presence of substrate/NAD(+ and inhibitor, respectively. This assembly and disassembly was mainly due to the interaction between the substrate/NAD(+ and inhibitor and F96 and the distance between F96 and H187 which are present at the neck of the C-site. MD simulations suggest that the conformational change of L3 plays a major role in assembly and disassembly of C-site. Our current results strongly suggest that the distinct conformational change of L3 as well as the assembly and disassembly of C-site plays an important role in SIRT2 deacetylation function. Our study unveiled the structural changes of SIRT2 in presence of NAD(+ and inhibitor which should be helpful to improve the inhibitory potency of SIRT2.

Long, partial-short, and special conformal fields

Energy Technology Data Exchange (ETDEWEB)

Metsaev, R.R. [Department of Theoretical Physics, P.N. Lebedev Physical Institute,Leninsky prospect 53, Moscow 119991 (Russian Federation)

2016-05-17

In the framework of metric-like approach, totally symmetric arbitrary spin bosonic conformal fields propagating in flat space-time are studied. Depending on the values of conformal dimension, spin, and dimension of space-time, we classify all conformal field as long, partial-short, short, and special conformal fields. An ordinary-derivative (second-derivative) Lagrangian formulation for such conformal fields is obtained. The ordinary-derivative Lagrangian formulation is realized by using double-traceless gauge fields, Stueckelberg fields, and auxiliary fields. Gauge-fixed Lagrangian invariant under global BRST transformations is obtained. The gauge-fixed BRST Lagrangian is used for the computation of partition functions for all conformal fields. Using the result for the partition functions, numbers of propagating D.o.F for the conformal fields are also found.

Structure of Human Pancreatic Lipase-Related Protein 2 with the Lid in an Open Conformation

Energy Technology Data Exchange (ETDEWEB)

Eydoux, Cecilia; Spinelli, Silvia; Davis, Tara L.; Walker, John R.; Seitova, Alma; Dhe-Paganon, Sirano; De Caro, Alain; Cambillau, Christian; Carriere, Frederic (CNRS-UMR); (Toronto)

2008-10-02

Access to the active site of pancreatic lipase (PL) is controlled by a surface loop, the lid, which normally undergoes conformational changes only upon addition of lipids or amphiphiles. Structures of PL with their lids in the open and functional conformation have required cocrystallization with amphiphiles. Here we report two crystal structures of wild-type and unglycosylated human pancreatic lipase-related protein 2 (HPLRP2) with the lid in an open conformation in the absence of amphiphiles. These structures solved independently are strikingly similar, with some residues of the lid being poorly defined in the electron-density map. The open conformation of the lid is however different from that previously observed in classical liganded PL, suggesting different kinetic properties for HPLRP2. Here we show that the HPLRP2 is directly inhibited by E600, does not present interfacial activation, and acts preferentially on substrates forming monomers or small aggregates (micelles) dispersed in solution like monoglycerides, phospholipids and galactolipids, whereas classical PL displays reverse properties and a high specificity for unsoluble substrates like triglycerides and diglycerides forming oil-in-water interfaces. These biochemical properties imply that the lid of HPLRP2 is likely to spontaneously adopt in solution the open conformation observed in the crystal structure. This open conformation generates a large cavity capable of accommodating the digalactose polar head of galactolipids, similar to that previously observed in the active site of the guinea pig PLRP2, but absent from the classical PL. Most of the structural and kinetic properties of HPLRP2 were found to be different from those of rat PLRP2, the structure of which was previously obtained with the lid in a closed conformation. Our findings illustrate the essential role of the lid in determining the substrate specificity and the mechanism of action of lipases.

Maxwell equations in conformal invariant electrodynamics

International Nuclear Information System (INIS)

Fradkin, E.S.; AN SSSR, Novosibirsk. Inst. Avtomatiki i Ehlektrometrii); Kozhevnikov, A.A.; Palchik, M.Ya.; Pomeransky, A.A.

1983-01-01

We consider a conformal invariant formulation of quantum electrodynamics. Conformal invariance is achieved with a specific mathematical construction based on the indecomposable representations of the conformal group associated with the electromagnetic potential and current. As a corolary of this construction modified expressions for the 3-point Green functions are obtained which both contain transverse parts. They make it possible to formulate a conformal invariant skeleton perturbation theory. It is also shown that the Euclidean Maxwell equations in conformal electrodynamics are manifestations of its kinematical structure: in the case of the 3-point Green functions these equations follow (up to constants) from the conformal invariance while in the case of higher Green functions they are equivalent to the equality of the kernels of the partial wave expansions. This is the manifestation of the mathematical fast of a (partial) equivalence of the representations associated with the potential, current and the field tensor. (orig.)

Conformal symmetries of FRW accelerating cosmologies

International Nuclear Information System (INIS)

Kehagias, A.; Riotto, A.

2014-01-01

We show that any accelerating Friedmann–Robertson–Walker (FRW) cosmology with equation of state w<−1/3 (and therefore not only a de Sitter stage with w=−1) exhibits three-dimensional conformal symmetry on future constant-time hypersurfaces if the bulk theory is invariant under bulk conformal Killing vectors. We also offer an alternative derivation of this result in terms of conformal Killing vectors and show that long wavelength comoving curvature perturbations of the perturbed FRW metric are just conformal Killing motions of the FRW background. We then extend the boundary conformal symmetry to the bulk for accelerating cosmologies. Our findings indicate that one can easily generate perturbations of scalar fields which are not only scale invariant, but also fully conformally invariant on super-Hubble scales. Measuring a scale-invariant power spectrum for the cosmological perturbation does not automatically imply that the universe went through a de Sitter stage

Probing Protein Multidimensional Conformational Fluctuations by Single-Molecule Multiparameter Photon Stamping Spectroscopy

Science.gov (United States)

2015-01-01

understanding of the enzymatic reaction turnover dynamics associated with overall enzyme as well as the specific active-site conformational fluctuations that are not identifiable and resolvable in the conventional ensemble-averaged experiment. PMID:25222115

Conformers, infrared spectrum, UV-induced photochemistry, and near-IR-induced generation of two rare conformers of matrix-isolated phenylglycine

Science.gov (United States)

Borba, Ana; Gómez-Zavaglia, Andrea; Fausto, Rui

2014-10-01

The conformational space of α-phenylglycine (PG) have been investigated theoretically at both the DFT/B3LYP/6-311++G(d,p) and MP2/6-311++G(d,p) levels of approximation. Seventeen different minima were found on the investigated potential energy surfaces, which are characterized by different dominant intramolecular interactions: type I conformers are stabilized by hydrogen bonds of the type N-H...O=C, type II by a strong O-H...N hydrogen bond, type III by weak N-H...O-H hydrogen bonds, and type IV by a C=O...H-C contact. The calculations indicate also that entropic effects are relevant in determining the equilibrium populations of the conformers of PG in the gas phase, in particular in the case of conformers of type II, where the strong intramolecular O-H...N hydrogen bond considerably diminishes entropy by reducing the conformational mobility of the molecule. In consonance with the relative energies of the conformers and barriers for conformational interconversion, only 3 conformers of PG were observed for the compound isolated in cryogenic Ar, Xe, and N2 matrices: the conformational ground state (ICa), and forms ICc and IITa. All other significantly populated conformers existing in the gas phase prior to deposition convert either to conformer ICa or to conformer ICc during matrix deposition. The experimental observation of ICc had never been achieved hitherto. Narrowband near-IR irradiation of the first overtone of νOH vibrational mode of ICa and ICc in nitrogen matrices (at 6910 and 6930 cm-1, respectively) led to selective generation of two additional conformers of high-energy, ITc and ITa, respectively, which were also observed experimentally for the first time. In addition, these experiments also provided the key information for the detailed vibrational characterization of the 3 conformers initially present in the matrices. On the other hand, UV irradiation (λ = 255 nm) of PG isolated in a xenon matrix revealed that PG undergoes facile photofragmentation

Conformers, infrared spectrum, UV-induced photochemistry, and near-IR-induced generation of two rare conformers of matrix-isolated phenylglycine

International Nuclear Information System (INIS)

Borba, Ana; Fausto, Rui; Gómez-Zavaglia, Andrea

2014-01-01

The conformational space of α-phenylglycine (PG) have been investigated theoretically at both the DFT/B3LYP/6-311++G(d,p) and MP2/6-311++G(d,p) levels of approximation. Seventeen different minima were found on the investigated potential energy surfaces, which are characterized by different dominant intramolecular interactions: type I conformers are stabilized by hydrogen bonds of the type N–H···O=C, type II by a strong O–H···N hydrogen bond, type III by weak N–H···O–H hydrogen bonds, and type IV by a C=O···H–C contact. The calculations indicate also that entropic effects are relevant in determining the equilibrium populations of the conformers of PG in the gas phase, in particular in the case of conformers of type II, where the strong intramolecular O–H···N hydrogen bond considerably diminishes entropy by reducing the conformational mobility of the molecule. In consonance with the relative energies of the conformers and barriers for conformational interconversion, only 3 conformers of PG were observed for the compound isolated in cryogenic Ar, Xe, and N 2 matrices: the conformational ground state (ICa), and forms ICc and IITa. All other significantly populated conformers existing in the gas phase prior to deposition convert either to conformer ICa or to conformer ICc during matrix deposition. The experimental observation of ICc had never been achieved hitherto. Narrowband near-IR irradiation of the first overtone of νOH vibrational mode of ICa and ICc in nitrogen matrices (at 6910 and 6930 cm −1 , respectively) led to selective generation of two additional conformers of high-energy, ITc and ITa, respectively, which were also observed experimentally for the first time. In addition, these experiments also provided the key information for the detailed vibrational characterization of the 3 conformers initially present in the matrices. On the other hand, UV irradiation (λ = 255 nm) of PG isolated in a xenon matrix revealed that PG

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...

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.

40 CFR 91.106 - Certificate of conformity.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Certificate of conformity. 91.106... Provisions § 91.106 Certificate of conformity. (a) Every manufacturer of a new marine SI engine produced... obtain a certificate of conformity covering each engine family. The certificate of conformity must be...

A Novel Method Using Abstract Convex Underestimation in Ab-Initio Protein Structure Prediction for Guiding Search in Conformational Feature Space.

Science.gov (United States)

Hao, Xiao-Hu; Zhang, Gui-Jun; Zhou, Xiao-Gen; Yu, Xu-Feng

2016-01-01

To address the searching problem of protein conformational space in ab-initio protein structure prediction, a novel method using abstract convex underestimation (ACUE) based on the framework of evolutionary algorithm was proposed. Computing such conformations, essential to associate structural and functional information with gene sequences, is challenging due to the high-dimensionality and rugged energy surface of the protein conformational space. As a consequence, the dimension of protein conformational space should be reduced to a proper level. In this paper, the high-dimensionality original conformational space was converted into feature space whose dimension is considerably reduced by feature extraction technique. And, the underestimate space could be constructed according to abstract convex theory. Thus, the entropy effect caused by searching in the high-dimensionality conformational space could be avoided through such conversion. The tight lower bound estimate information was obtained to guide the searching direction, and the invalid searching area in which the global optimal solution is not located could be eliminated in advance. Moreover, instead of expensively calculating the energy of conformations in the original conformational space, the estimate value is employed to judge if the conformation is worth exploring to reduce the evaluation time, thereby making computational cost lower and the searching process more efficient. Additionally, fragment assembly and the Monte Carlo method are combined to generate a series of metastable conformations by sampling in the conformational space. The proposed method provides a novel technique to solve the searching problem of protein conformational space. Twenty small-to-medium structurally diverse proteins were tested, and the proposed ACUE method was compared with It Fix, HEA, Rosetta and the developed method LEDE without underestimate information. Test results show that the ACUE method can more rapidly and more

Single-strand conformation polymorphism analysis of ribosomal DNA for detection of Phytophthora ramorum directly from plant tissues

Science.gov (United States)

Ping Kong; Patricia A. Richardson; Chuanxue Hong; Thomas L. Kubisiak

2006-01-01

At the first Sudden Oak Death Science Symposium, we reported on the use of a single strand conformation polymorphism (SSCP) analysis for rapid identification of Phytophthora ramorum in culture. We have since assessed and improved the fingerprinting technique for detecting this pathogen directly from plant tissues. The improved SSCP protocol uses a...

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...

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...

/sup 1/H nuclear magnetic resonance studies of the conformation of an ATP analogue at the active site of Na,K-ATPase from kidney medulla

Energy Technology Data Exchange (ETDEWEB)

MacD. Stewart, J.M.; Grisham, C.M.

1988-06-28

/sup 1/H nuclear magnetic relaxation measurements have been used to determine the three-dimensional conformation of an ATP analogue, Co(NH/sub 3/)/sub 4/ATP, at the active site of sheep kidney Na,K-ATPase. Previous studies have shown that Co(NH/sub 4/)/sub 4/ATP is a competitive inhibitor with respect to MnATP for the Na,K-ATPase and that Mn/sup 2 +/ bound to a single, high-affinity site on the ATPase can be an effective paramagnetic probe for nuclear relaxation studies of the Na-K-ATPase. From the paramagnetic effect of Mn/sup 2 +/ bound to the APTase on the longitudinal relaxation rates of the protons of Co(NH/sub 3/)/sub 4/ATP at the substrate site (at 300 and 361 MHz), Mn-H distances to seven protons on the bound nucleotide were determined. Taken together with previous /sup 31/P nuclear relaxation data, these measurements are consistent with a single nucleotide conformation at the active site. The nucleotide adopts a bent configuration, in which the triphosphate chain lies nearly parallel to the adenine moiety. The glycosidic torsion angle is 35/sup 0/, and the conformation of the ribose ring is slightly N-type. The bound Mn/sup 2 +/ lies above and in the plane of the adenine ring. The distances from Mn/sup 2 +/ to N/sub 6/ and N/sub 7/ are too large for first coordination sphere complexes but are appropriate for second-sphere complexes involving, for example, intervening hydrogen-bonded water molecules. The NMR data also indicate that the structure of the bound ATP analogue is independent of the conformational state of the enzyme.

Lie algebra of conformal Killing–Yano forms

International Nuclear Information System (INIS)

Ertem, Ümit

2016-01-01

We provide a generalization of the Lie algebra of conformal Killing vector fields to conformal Killing–Yano forms. A new Lie bracket for conformal Killing–Yano forms that corresponds to slightly modified Schouten–Nijenhuis bracket of differential forms is proposed. We show that conformal Killing–Yano forms satisfy a graded Lie algebra in constant curvature manifolds. It is also proven that normal conformal Killing–Yano forms in Einstein manifolds also satisfy a graded Lie algebra. The constructed graded Lie algebras reduce to the graded Lie algebra of Killing–Yano forms and the Lie algebras of conformal Killing and Killing vector fields in special cases. (paper)

Universal hydrodynamics of non-conformal branes

International Nuclear Information System (INIS)

Kanitscheider, Ingmar; Skenderis, Kostas

2009-01-01

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

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.)

47 CFR 2.906 - Declaration of Conformity.

Science.gov (United States)

2010-10-01

... 47 Telecommunication 1 2010-10-01 2010-10-01 false Declaration of Conformity. 2.906 Section 2.906... Conformity. (a) A Declaration of Conformity is a procedure where the responsible party, as defined in § 2.909... of Conformity attaches to all items subsequently marketed by the responsible party which are...

Conformation of hindered piperidines: Spectroscopic evidence for ...

Indian Academy of Sciences (India)

Administrator

presence of an equilibrium mixture of boat forms B1 and B2 for Z isomers of 5–8. For the E isomers of. 5–8, boat form B1 ... C NMR; conformational analysis; boat forms. 1. Introduction. Many piperidine derivatives are found to possess pharmacological activity and form an essential part of the molecular structure of important ...

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.)

Nature vs. nurture in human sociality: multi-level genomic analyses of social conformity.

Science.gov (United States)

Chen, Biqing; Zhu, Zijian; Wang, Yingying; Ding, Xiaohu; Guo, Xiaobo; He, Mingguang; Fang, Wan; Zhou, Qin; Zhou, Shanbi; Lei, Han; Huang, Ailong; Chen, Tingmei; Ni, Dongsheng; Gu, Yuping; Liu, Jianing; Rao, Yi

2018-05-01

Social conformity is fundamental to human societies and has been studied for more than six decades, but our understanding of its mechanisms remains limited. Individual differences in conformity have been attributed to social and cultural environmental influences, but not to genes. Here we demonstrate a genetic contribution to conformity after analyzing 1,140 twins and single-nucleotide polymorphism (SNP)-based studies of 2,130 young adults. A two-step genome-wide association study (GWAS) revealed replicable associations in 9 genomic loci, and a meta-analysis of three GWAS with a sample size of ~2,600 further confirmed one locus, corresponding to the NAV3 (Neuron Navigator 3) gene which encodes a protein important for axon outgrowth and guidance. Further multi-level (haplotype, gene, pathway) GWAS strongly associated genes including NAV3, PTPRD (protein tyrosine phosphatase receptor type D), ARL10 (ADP ribosylation factor-like GTPase 10), and CTNND2 (catenin delta 2), with conformity. Magnetic resonance imaging of 64 subjects shows correlation of activation or structural features of brain regions with the SNPs of these genes, supporting their functional significance. Our results suggest potential moderate genetic influence on conformity, implicate several specific genetic elements in conformity and will facilitate further research on cellular and molecular mechanisms underlying human conformity.

21 CFR 26.70 - Conformity assessment bodies.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 1 2010-04-01 2010-04-01 false Conformity assessment bodies. 26.70 Section 26.70...Frameworkâ Provisions § 26.70 Conformity assessment bodies. Each party recognizes that the conformity... conformity in relation to its requirements as specified in subpart B of this part. The parties shall specify...

Tetrahymena telomerase protein p65 induces conformational changes throughout telomerase RNA (TER) and rescues telomerase reverse transcriptase and TER assembly mutants.

Science.gov (United States)

Berman, Andrea J; Gooding, Anne R; Cech, Thomas R

2010-10-01

The biogenesis of the Tetrahymena telomerase ribonucleoprotein particle (RNP) is enhanced by p65, a La family protein. Single-molecule and biochemical studies have uncovered a hierarchical assembly of the RNP, wherein the binding of p65 to stems I and IV of telomerase RNA (TER) causes a conformational change that facilitates the subsequent binding of telomerase reverse transcriptase (TERT) to TER. We used purified p65 and variants of TERT and TER to investigate the conformational rearrangements that occur during RNP assembly. Nuclease protection assays and mutational analysis revealed that p65 interacts with and stimulates conformational changes in regions of TER beyond stem IV. Several TER mutants exhibited telomerase activity only in the presence of p65, revealing the importance of p65 in promoting the correct RNP assembly pathway. In addition, p65 rescued TERT assembly mutants but not TERT activity mutants. Taken together, these results suggest that p65 stimulates telomerase assembly and activity in two ways. First, by sequestering stems I and IV, p65 limits the ensemble of structural conformations of TER, thereby presenting TERT with the active conformation of TER. Second, p65 acts as a molecular buttress within the assembled RNP, mutually stabilizing TER and TERT in catalytically active conformations.

Conformational analysis of lignin models

International Nuclear Information System (INIS)

Santos, Helio F. dos

2001-01-01

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

On the linear conformal gravitation

International Nuclear Information System (INIS)

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

1984-01-01

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

Conformal Symmetry Patterns in Baryon Spectra

International Nuclear Information System (INIS)

Kirchbach, Mariana; Compean, Cliffor B

2011-01-01

Attention is drawn to the fact that the spectra of the baryons of the lightest flavors, the nucleon and the Δ, carry quantum numbers characteristic for an unitary representation of the conformal group. We show that the above phenomenon is well explained for baryons whose internal structure is dominated by a quark-diquark configuration that resides in a conformally compactified Minkowski space time, R 1 x S 3 , and is described by means of the conformal scale equation there. The R 1 x S 3 space-time represents the boundary of the conformally compactified AdS 5 , on which one expects to encounter a conformal theory in accord with the gauge-gravity duality. Within this context, our model is congruent with AdS 5 /CFT 4 .

[Conformation analysis of the N-glycosylation site Asn-X-Thr/Ser in glycoproteins].

Science.gov (United States)

Avanov, A Ia; Lipkind, G M

1990-03-01

Theoretical conformational analysis of oligopeptides CH3CO-Asn-X-Thr-NHCH3 (X = Gly, Ala, Pro), modelling N-glycosylation site, and their glycosylated derivatives CH3CO-(GlcNAc beta 1-4GlcNAc beta 1) Asn-X-Thr-NHCH3 has been carried out. Active conformations of the site are found, corresponding to structural prerequisities of N-glycosylation: Asn residue's position in beta-turn and hydrogen bond formation between side chains of Asn and Thr/Ser residues. In this case the L conformation of the central residue X is most probable. Since Pro residue does not possess this conformation, sequences with X = Pro are not glycosylated. It is shown that glycosylation of the above-mentioned sites is accompanied by reorientation of the Asn residue's side chains.

Structure, conformation in aqueous solution and antimicrobial activity of ulvan extracted from green seaweed Ulva reticulata.

Science.gov (United States)

Tran, Thi Thanh Van; Truong, Hai Bang; Tran, Nguyen Ha Vy; Quach, Thi Minh Thu; Nguyen, Thi Nu; Bui, Minh Ly; Yuguchi, Yoshiaki; Thanh, Thi Thu Thuy

2017-12-04

The aim of this study is to elucidate the structure and investigate the antimicrobial activity of an ulvan obtained by water extraction from green seaweed Ulva reticulata collected at Nha Trang sea of Vietnam by using IR, NMR, SEC-MALLS and SAXS methods. The ulvan is composed of rhamnose, galactose, xylose, manose and glucose (mole ratio Rha: Gal: Xyl: Man: Glu = 1:0.12:0.1:0.06:0.03), uronic acid (22.5%) and sulphate groups (17.6%). Chemically structural determination showed that the ulvan mainly composed of disaccharide [→4)β-D-GlcA(1→4)α-L-Rha3S-(1→]. The results from SAXS indicated that ulvan under study has a rod-like bulky chain conformation. Ulvan from U. reticulata showed high antimicrobial activity, with inhibition zone diameter of 20 mm against Enterobacter cloace and 18 mm against Escherichia coli.

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.

Conformational cooling and conformation selective aggregation in dimethyl sulfite isolated in solid rare gases

OpenAIRE

Borba, Ana; Gómez-Zavaglia, Andrea; Fausto, Rui

2006-01-01

Dimethyl sulfite has three conformers of low energy, GG, GT and GG0, which have significant populations in the gas phase at room temperature. According to theoretical predictions, the GT and GG0 conformers are higher in energy than the GG conformer by 0.83 and 1.18 kJ molK1, respectively, while the barriers associated with the GG0/GT and GT/GG isomerizations are 1.90 and 9.64 kJ molK1, respectively. Experimental data obtained for the compound isolated in solid argon, krypton and xenon demonst...

A rapid and sensitive method for measuring N-acetylglucosaminidase activity in cultured cells.

Directory of Open Access Journals (Sweden)

Victor Mauri

Full Text Available A rapid and sensitive method to quantitatively assess N-acetylglucosaminidase (NAG activity in cultured cells is highly desirable for both basic research and clinical studies. NAG activity is deficient in cells from patients with Mucopolysaccharidosis type IIIB (MPS IIIB due to mutations in NAGLU, the gene that encodes NAG. Currently available techniques for measuring NAG activity in patient-derived cell lines include chromogenic and fluorogenic assays and provide a biochemical method for the diagnosis of MPS IIIB. However, standard protocols require large amounts of cells, cell disruption by sonication or freeze-thawing, and normalization to the cellular protein content, resulting in an error-prone procedure that is material- and time-consuming and that produces highly variable results. Here we report a new procedure for measuring NAG activity in cultured cells. This procedure is based on the use of the fluorogenic NAG substrate, 4-Methylumbelliferyl-2-acetamido-2-deoxy-alpha-D-glucopyranoside (MUG, in a one-step cell assay that does not require cell disruption or post-assay normalization and that employs a low number of cells in 96-well plate format. We show that the NAG one-step cell assay greatly discriminates between wild-type and MPS IIIB patient-derived fibroblasts, thus providing a rapid method for the detection of deficiencies in NAG activity. We also show that the assay is sensitive to changes in NAG activity due to increases in NAGLU expression achieved by either overexpressing the transcription factor EB (TFEB, a master regulator of lysosomal function, or by inducing TFEB activation chemically. Because of its small format, rapidity, sensitivity and reproducibility, the NAG one-step cell assay is suitable for multiple procedures, including the high-throughput screening of chemical libraries to identify modulators of NAG expression, folding and activity, and the investigation of candidate molecules and constructs for applications in

Thickenings and conformal gravity

Science.gov (United States)

Lebrun, Claude

1991-07-01

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

Thickenings and conformal gravity

International Nuclear Information System (INIS)

LeBrun, C.

1991-01-01

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

On the bioactive conformation of R(+)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepin-7-ol

Science.gov (United States)

Verdonk, M. L.; Voogd, K.; Kanters, J. A.; Kroon, J.; van Duijneveldt, F. B.

1994-07-01

A redetermination of the X-ray structure of the title compound is reported. In this structure a partially occupied position of a water molecule was found that was not observed in an earlier structure determination. This water molecule appears to have an important role in the crystal packing. Molecular mechanics calculations were performed on 12 conformations of the protonated title compound, complexed to a chloride anion. This anion represents the anionic binding site of the receptors at which the title compound exerts its biological activity. Crystal-structure statistics and ab initio calculations were used to generate starting geometries for the molecular mechanics calculations. It appears that the conformation that is assumed to be the active conformation for the D 1 receptor is the lowest-energy conformation. It is concluded that this conformation may, therefore, also be the active conformation for other receptors.

Conformational analysis of phloroglucinols from hypericum Brasiliense by using x-ray diffraction and molecular modeling

Energy Technology Data Exchange (ETDEWEB)

Leal, Katia Z.; Lindgren, Eric B.; Correa, Arthur L., E-mail: kzleal@uol.com.b [Universidade Federal Fluminense (UFF), Niteroi, RJ (Brazil). Inst. de Quimica. Dept. de Fisico-Quimica; Yoneda, Julliane D. [Universidade Federal Fluminense (UFF), Volta Redonda, RJ (Brazil). Polo Universitario de Volta Redonda; Pinheiro, Carlos B. [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Dept. de Fisica; Franca, Hildegardo S. [Universidade Federal Fluminense (UFF), Niteroi, RJ (Brazil). Faculdade de Farmacia. Dept. de Tecnologia Farmaceutica

2010-07-01

In this work we intend to verify the applicability of a computational methodology to predict structural features of organic compounds with biological activity. We selected three phloroglucinols and compared their calculated conformational data with their X-ray crystallographic structure. The results showed that conformations obtained by conformational analysis with the AM1 method followed by geometry optimization by using the DFT B3LYP/6-31 G(d,p) basis set are in very good agreement with X-ray data, indicating that the methodology employed here seems to be a very useful tool in order to predict the conformational preference for this class of compounds. (author)

Conformal symmetry inheritance in null fluid spacetimes

International Nuclear Information System (INIS)

Tupper, B O J; Keane, A J; Hall, G S; Coley, A A; Carot, J

2003-01-01

We define inheriting conformal Killing vectors for null fluid spacetimes and find the maximum dimension of the associated inheriting Lie algebra. We show that for non-conformally flat null fluid spacetimes, the maximum dimension of the inheriting algebra is seven and for conformally flat null fluid spacetimes the maximum dimension is eight. In addition, it is shown that there are two distinct classes of non-conformally flat generalized plane wave spacetimes which possess the maximum dimension, and one class in the conformally flat case

Conformal maps between pseudo-Finsler spaces

Science.gov (United States)

Voicu, Nicoleta

The paper aims to initiate a systematic study of conformal mappings between Finsler spacetimes and, more generally, between pseudo-Finsler spaces. This is done by extending several results in pseudo-Riemannian geometry which are necessary for field-theoretical applications and by proposing a technique that reduces some problems involving pseudo-Finslerian conformal vector fields to their pseudo-Riemannian counterparts. Also, we point out, by constructing classes of examples, that conformal groups of flat (locally Minkowskian) pseudo-Finsler spaces can be much richer than both flat Finslerian and pseudo-Euclidean conformal groups.

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

Extended conformal algebras

International Nuclear Information System (INIS)

Goddard, Peter

1990-01-01

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

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.)

Perspectives on electrostatics and conformational motions in enzyme catalysis.

Science.gov (United States)

Hanoian, Philip; Liu, C Tony; Hammes-Schiffer, Sharon; Benkovic, Stephen

2015-02-17

CONSPECTUS: Enzymes are essential for all living organisms, and their effectiveness as chemical catalysts has driven more than a half century of research seeking to understand the enormous rate enhancements they provide. Nevertheless, a complete understanding of the factors that govern the rate enhancements and selectivities of enzymes remains elusive, due to the extraordinary complexity and cooperativity that are the hallmarks of these biomolecules. We have used a combination of site-directed mutagenesis, pre-steady-state kinetics, X-ray crystallography, nuclear magnetic resonance (NMR), vibrational and fluorescence spectroscopies, resonance energy transfer, and computer simulations to study the implications of conformational motions and electrostatic interactions on enzyme catalysis in the enzyme dihydrofolate reductase (DHFR). We have demonstrated that modest equilibrium conformational changes are functionally related to the hydride transfer reaction. Results obtained for mutant DHFRs illustrated that reductions in hydride transfer rates are correlated with altered conformational motions, and analysis of the evolutionary history of DHFR indicated that mutations appear to have occurred to preserve both the hydride transfer rate and the associated conformational changes. More recent results suggested that differences in local electrostatic environments contribute to finely tuning the substrate pKa in the initial protonation step. Using a combination of primary and solvent kinetic isotope effects, we demonstrated that the reaction mechanism is consistent across a broad pH range, and computer simulations suggested that deprotonation of the active site Tyr100 may play a crucial role in substrate protonation at high pH. Site-specific incorporation of vibrational thiocyanate probes into the ecDHFR active site provided an experimental tool for interrogating these microenvironments and for investigating changes in electrostatics along the DHFR catalytic cycle

Thickenings and conformal gravity

Energy Technology Data Exchange (ETDEWEB)

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

1991-07-01

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

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....

Rapid effects of hearing song on catecholaminergic activity in the songbird auditory pathway.

Directory of Open Access Journals (Sweden)

Lisa L Matragrano

Full Text Available Catecholaminergic (CA neurons innervate sensory areas and affect the processing of sensory signals. For example, in birds, CA fibers innervate the auditory pathway at each level, including the midbrain, thalamus, and forebrain. We have shown previously that in female European starlings, CA activity in the auditory forebrain can be enhanced by exposure to attractive male song for one week. It is not known, however, whether hearing song can initiate that activity more rapidly. Here, we exposed estrogen-primed, female white-throated sparrows to conspecific male song and looked for evidence of rapid synthesis of catecholamines in auditory areas. In one hemisphere of the brain, we used immunohistochemistry to detect the phosphorylation of tyrosine hydroxylase (TH, a rate-limiting enzyme in the CA synthetic pathway. We found that immunoreactivity for TH phosphorylated at serine 40 increased dramatically in the auditory forebrain, but not the auditory thalamus and midbrain, after 15 min of song exposure. In the other hemisphere, we used high pressure liquid chromatography to measure catecholamines and their metabolites. We found that two dopamine metabolites, dihydroxyphenylacetic acid and homovanillic acid, increased in the auditory forebrain but not the auditory midbrain after 30 min of exposure to conspecific song. Our results are consistent with the hypothesis that exposure to a behaviorally relevant auditory stimulus rapidly induces CA activity, which may play a role in auditory responses.

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 ...

Gauge fixing problem in the conformal QED

International Nuclear Information System (INIS)

Ichinose, Shoichi

1986-01-01

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

Rapid analysis method for the determination of 14C specific activity in irradiated graphite.

Science.gov (United States)

Remeikis, Vidmantas; Lagzdina, Elena; Garbaras, Andrius; Gudelis, Arūnas; Garankin, Jevgenij; Plukienė, Rita; Juodis, Laurynas; Duškesas, Grigorijus; Lingis, Danielius; Abdulajev, Vladimir; Plukis, Artūras

2018-01-01

14C is one of the limiting radionuclides used in the categorization of radioactive graphite waste; this categorization is crucial in selecting the appropriate graphite treatment/disposal method. We propose a rapid analysis method for 14C specific activity determination in small graphite samples in the 1-100 μg range. The method applies an oxidation procedure to the sample, which extracts 14C from the different carbonaceous matrices in a controlled manner. Because this method enables fast online measurement and 14C specific activity evaluation, it can be especially useful for characterizing 14C in irradiated graphite when dismantling graphite moderator and reflector parts, or when sorting radioactive graphite waste from decommissioned nuclear power plants. The proposed rapid method is based on graphite combustion and the subsequent measurement of both CO2 and 14C, using a commercial elemental analyser and the semiconductor detector, respectively. The method was verified using the liquid scintillation counting (LSC) technique. The uncertainty of this rapid method is within the acceptable range for radioactive waste characterization purposes. The 14C specific activity determination procedure proposed in this study takes approximately ten minutes, comparing favorably to the more complicated and time consuming LSC method. This method can be potentially used to radiologically characterize radioactive waste or used in biomedical applications when dealing with the specific activity determination of 14C in the sample.

Rapid analysis method for the determination of 14C specific activity in irradiated graphite.

Directory of Open Access Journals (Sweden)

Vidmantas Remeikis

Full Text Available 14C is one of the limiting radionuclides used in the categorization of radioactive graphite waste; this categorization is crucial in selecting the appropriate graphite treatment/disposal method. We propose a rapid analysis method for 14C specific activity determination in small graphite samples in the 1-100 μg range. The method applies an oxidation procedure to the sample, which extracts 14C from the different carbonaceous matrices in a controlled manner. Because this method enables fast online measurement and 14C specific activity evaluation, it can be especially useful for characterizing 14C in irradiated graphite when dismantling graphite moderator and reflector parts, or when sorting radioactive graphite waste from decommissioned nuclear power plants. The proposed rapid method is based on graphite combustion and the subsequent measurement of both CO2 and 14C, using a commercial elemental analyser and the semiconductor detector, respectively. The method was verified using the liquid scintillation counting (LSC technique. The uncertainty of this rapid method is within the acceptable range for radioactive waste characterization purposes. The 14C specific activity determination procedure proposed in this study takes approximately ten minutes, comparing favorably to the more complicated and time consuming LSC method. This method can be potentially used to radiologically characterize radioactive waste or used in biomedical applications when dealing with the specific activity determination of 14C in the sample.

Manufacturing and metrology for IR conformal windows and domes

Science.gov (United States)

Ferralli, Ian; Blalock, Todd; Brunelle, Matt; Lynch, Timothy; Myer, Brian; Medicus, Kate

2017-05-01

Freeform and conformal optics have the potential to dramatically improve optical systems by enabling systems with fewer optical components, reduced aberrations, and improved aerodynamic performance. These optical components differ from standard components in their surface shape, typically a non-symmetric equation based definition, and material properties. Traditional grinding and polishing tools are unable to handle these freeform shapes. Additionally, standard metrology tools cannot measure these surfaces. Desired substrates are typically hard ceramics, including poly-crystalline alumina or aluminum oxynitride. Notwithstanding the challenges that the hardness provides to manufacturing, these crystalline materials can be highly susceptible to grain decoration creating unacceptable scatter in optical systems. In this presentation, we will show progress towards addressing the unique challenges of manufacturing conformal windows and domes. Particular attention is given to our robotic polishing platform. This platform is based on an industrial robot adapted to accept a wide range of tooling and parts. The robot's flexibility has provided us an opportunity to address the unique challenges of conformal windows. Slurries and polishing active layers can easily be changed to adapt to varying materials and address grain decoration. We have the flexibility to change tool size and shape to address the varying sizes and shapes of conformal optics. In addition, the robotic platform can be a base for a deflectometry-based metrology tool to measure surface form error. This system, whose precision is independent of the robot's positioning accuracy, will allow us to measure optics in-situ saving time and reducing part risk. In conclusion, we will show examples of the conformal windows manufactured using our developed processes.

Rapid decreases in preoptic aromatase activity and brain monoamine concentrations after engaging in male sexual behavior.

Science.gov (United States)

Cornil, C A; Dalla, C; Papadopoulou-Daifoti, Z; Baillien, M; Dejace, C; Ball, G F; Balthazart, J

2005-09-01

In Japanese quail, as in rats, the expression of male sexual behavior over relatively long time periods (days to weeks) is dependent on the local production of estradiol in the preoptic area via the aromatization of testosterone. On a short-term basis (minutes to hours), central actions of dopamine as well as locally produced estrogens modulate behavioral expression. In rats, a view of and sexual interaction with a female increase dopamine release in the preoptic area. In quail, in vitro brain aromatase activity (AA) is rapidly modulated by calcium-dependent phosphorylations that are likely to occur in vivo as a result of changes in neurotransmitter activity. Furthermore, an acute estradiol injection rapidly stimulates copulation in quail, whereas a single injection of the aromatase inhibitor vorozole rapidly inhibits this behavior. We hypothesized that brain aromatase and dopaminergic activities are regulated in quail in association with the expression of male sexual behavior. Visual access as well as sexual interactions with a female produced a significant decrease in brain AA, which was maximal after 5 min. This expression of sexual behavior also resulted in a significant decrease in dopaminergic as well as serotonergic activity after 1 min, which returned to basal levels after 5 min. These results demonstrate for the first time that AA is rapidly modulated in vivo in parallel with changes in dopamine activity. Sexual interactions with the female decreased aromatase and dopamine activities. These data challenge established views about the causal relationships among dopamine, estrogen action, and male sexual behavior.

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.

Two dimensional infinite conformal symmetry

International Nuclear Information System (INIS)

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

1993-01-01

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

Virtual and solution conformations of oligosaccharides

International Nuclear Information System (INIS)

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

1987-01-01

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

Conformation evolution of oil contaminants onto aluminum oxide surface in aqueous solution: The effect of surface coverage

Energy Technology Data Exchange (ETDEWEB)

Xie, Wenkun; Liu, Haitao, E-mail: xwk584523412@126.com; Sun, Yazhou; Fu, Hongya; Liang, Yingchun

2017-01-15

Highlights: • The dynamic conformational change of oil contaminations, at various surface coverages onto perfect α-Al{sub 2}O{sub 3}(0001) surface in aqueous solution is given. • The effect of surface coverage of oil molecules on the driving forces for the conformational change of oil contaminations is described. • The effect of interfacial water on the conformational change and even detachment of oil contaminations is considered. - Abstract: The microscopic conformational change process of oil contaminants adhered onto perfect α-Al{sub 2}O{sub 3} (0001) surface in aqueous solution was investigated by using all-atom classic molecular dynamics simulations. The change in removal mechanism of oil contaminants induced by surface coverage (surface area per molecule) was emphatically explored. Our simulation results strongly reveal that the increase in oil surface coverage induces an evident difference in microscopic detachment processes of oil contaminants. At a low surface coverage, oil contaminants can be thoroughly detached from solid surface. The whole detachment process could be divided into multi stages, including conformational change of oil contaminants on solid surface, dynamic motion of those in bulk solution and rapid migration of those from bulk solution to air/water interface. With surface coverage increasing, water diffusion becomes the key to induce conformational change and promote the detachment of oil contaminants. When oil surface coverage exceeds a threshold value, oil contaminants also undertake an evident conformational change process exhibiting typical characteristics but an incomplete detachment process occurs. All findings of the present study are helpful for the interpretation of the removal mechanism of oil contaminants on solid surface.

Uniform stable conformal convolutional perfectly matched layer for enlarged cell technique conformal finite-difference time-domain method

International Nuclear Information System (INIS)

Wang Yue; Wang Jian-Guo; Chen Zai-Gao

2015-01-01

Based on conformal construction of physical model in a three-dimensional Cartesian grid, an integral-based conformal convolutional perfectly matched layer (CPML) is given for solving the truncation problem of the open port when the enlarged cell technique conformal finite-difference time-domain (ECT-CFDTD) method is used to simulate the wave propagation inside a perfect electric conductor (PEC) waveguide. The algorithm has the same numerical stability as the ECT-CFDTD method. For the long-time propagation problems of an evanescent wave in a waveguide, several numerical simulations are performed to analyze the reflection error by sweeping the constitutive parameters of the integral-based conformal CPML. Our numerical results show that the integral-based conformal CPML can be used to efficiently truncate the open port of the waveguide. (paper)

Total dural irradiation: RapidArc versus static-field IMRT: A case study

Energy Technology Data Exchange (ETDEWEB)

Kelly, Paul J., E-mail: paulj.kelly@hse.ie [Department of Radiation Oncology, Dana Farber/Brigham and Women' s Cancer Center, Harvard Medical School, Boston, MA (United States); Mannarino, Edward; Lewis, John Henry; Baldini, Elizabeth H.; Hacker, Fred L. [Department of Radiation Oncology, Dana Farber/Brigham and Women' s Cancer Center, Harvard Medical School, Boston, MA (United States)

2012-07-01

The purpose of this study was to compare conventional fixed-gantry angle intensity-modulated radiation therapy (IMRT) with RapidArc for total dural irradiation. We also hypothesize that target volume-individualized collimator angles may produce substantial normal tissue sparing when planning with RapidArc. Five-, 7-, and 9-field fixed-gantry angle sliding-window IMRT plans were generated for comparison with RapidArc plans. Optimization and normal tissue constraints were constant for all plans. All plans were normalized so that 95% of the planning target volume (PTV) received at least 100% of the dose. RapidArc was delivered using 350 Degree-Sign clockwise and counterclockwise arcs. Conventional collimator angles of 45 Degree-Sign and 315 Degree-Sign were compared with 90 Degree-Sign on both arcs. Dose prescription was 59.4 Gy in 33 fractions. PTV metrics used for comparison were coverage, V{sub 107}%, D1%, conformality index (CI{sub 95}%), and heterogeneity index (D{sub 5}%-D{sub 95}%). Brain dose, the main challenge of this case, was compared using D{sub 1}%, Dmean, and V{sub 5} Gy. Dose to optic chiasm, optic nerves, globes, and lenses was also compared. The use of unconventional collimator angles (90 Degree-Sign on both arcs) substantially reduced dose to normal brain. All plans achieved acceptable target coverage. Homogeneity was similar for RapidArc and 9-field IMRT plans. However, heterogeneity increased with decreasing number of IMRT fields, resulting in unacceptable hotspots within the brain. Conformality was marginally better with RapidArc relative to IMRT. Low dose to brain, as indicated by V5Gy, was comparable in all plans. Doses to organs at risk (OARs) showed no clinically meaningful differences. The number of monitor units was lower and delivery time was reduced with RapidArc. The case-individualized RapidArc plan compared favorably with the 9-field conventional IMRT plan. In view of lower monitor unit requirements and shorter delivery time, Rapid

Noncommutative geometry and twisted conformal symmetry

International Nuclear Information System (INIS)

Matlock, Peter

2005-01-01

The twist-deformed conformal algebra is constructed as a Hopf algebra with twisted coproduct. This allows for the definition of conformal symmetry in a noncommutative background geometry. The twisted coproduct is reviewed for the Poincare algebra and the construction is then extended to the full conformal algebra. The case of Moyal-type noncommutativity of the coordinates is considered. It is demonstrated that conformal invariance need not be viewed as incompatible with noncommutative geometry; the noncommutativity of the coordinates appears as a consequence of the twisting, as has been shown in the literature in the case of the twisted Poincare algebra

Superintegrability of d-dimensional conformal blocks

International Nuclear Information System (INIS)

Isachenkov, Mikhail

2016-02-01

We observe that conformal blocks of scalar 4-point functions in a d-dimensional conformal field theory can mapped to eigenfunctions of a 2-particle hyperbolic Calogero-Sutherland Hamiltonian. The latter describes two coupled Poeschl-Teller particles. Their interaction, whose strength depends smoothly on the dimension d, is known to be superintegrable. Our observation enables us to exploit the rich mathematical literature on Calogero-Sutherland models in deriving various results for conformal field theory. These include an explicit construction of conformal blocks in terms of Heckman-Opdam hypergeometric functions and a remarkable duality that relates the blocks of theories in different dimensions.

Superintegrability of d-dimensional conformal blocks

Energy Technology Data Exchange (ETDEWEB)

Isachenkov, Mikhail [Weizmann Institute of Science, Rehovot (Israel). Dept. of Particle Physics and Astronomy; Schomerus, Volker [DESY Theory Group, Hamburg (Germany)

2016-02-15

We observe that conformal blocks of scalar 4-point functions in a d-dimensional conformal field theory can mapped to eigenfunctions of a 2-particle hyperbolic Calogero-Sutherland Hamiltonian. The latter describes two coupled Poeschl-Teller particles. Their interaction, whose strength depends smoothly on the dimension d, is known to be superintegrable. Our observation enables us to exploit the rich mathematical literature on Calogero-Sutherland models in deriving various results for conformal field theory. These include an explicit construction of conformal blocks in terms of Heckman-Opdam hypergeometric functions and a remarkable duality that relates the blocks of theories in different dimensions.

Induced quantum conformal gravity

International Nuclear Information System (INIS)

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

1988-11-01

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

Structure-Activity Relationship and Molecular Mechanics Reveal the Importance of Ring Entropy in the Biosynthesis and Activity of a Natural Product.

Science.gov (United States)

Tran, Hai L; Lexa, Katrina W; Julien, Olivier; Young, Travis S; Walsh, Christopher T; Jacobson, Matthew P; Wells, James A

2017-02-22

Macrocycles are appealing drug candidates due to their high affinity, specificity, and favorable pharmacological properties. In this study, we explored the effects of chemical modifications to a natural product macrocycle upon its activity, 3D geometry, and conformational entropy. We chose thiocillin as a model system, a thiopeptide in the ribosomally encoded family of natural products that exhibits potent antimicrobial effects against Gram-positive bacteria. Since thiocillin is derived from a genetically encoded peptide scaffold, site-directed mutagenesis allows for rapid generation of analogues. To understand thiocillin's structure-activity relationship, we generated a site-saturation mutagenesis library covering each position along thiocillin's macrocyclic ring. We report the identification of eight unique compounds more potent than wild-type thiocillin, the best having an 8-fold improvement in potency. Computational modeling of thiocillin's macrocyclic structure revealed a striking requirement for a low-entropy macrocycle for activity. The populated ensembles of the active mutants showed a rigid structure with few adoptable conformations while inactive mutants showed a more flexible macrocycle which is unfavorable for binding. This finding highlights the importance of macrocyclization in combination with rigidifying post-translational modifications to achieve high-potency binding.

Conformal invariance in harmonic superspace

International Nuclear Information System (INIS)

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

1987-01-01

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

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.

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.

Conformational cooling and conformation selective aggregation in dimethyl sulfite isolated in solid rare gases

Science.gov (United States)

Borba, Ana; Gómez-Zavaglia, Andrea; Fausto, Rui

2006-08-01

Dimethyl sulfite has three conformers of low energy, GG, GT and GG', which have significant populations in the gas phase at room temperature. According to theoretical predictions, the GT and GG' conformers are higher in energy than the GG conformer by 0.83 and 1.18 kJ mol -1, respectively, while the barriers associated with the GG'→GT and GT→GG isomerizations are 1.90 and 9.64 kJ mol -1, respectively. Experimental data obtained for the compound isolated in solid argon, krypton and xenon demonstrated that the GG'→GT energy barrier is low enough to allow an extensive conversion of the GG' form into the GT conformer during deposition of the matrices, the extent of the conversion increasing along the series Arconformers could be trapped in both argon and krypton matrices, but, at a given temperature, the amount of GG' form trapped in krypton is considerably smaller than in argon, while the amount of GT form increases in relation to the most stable GG form. In addition, when xenon is used, no bands due to GG' are observed in the as-deposited spectra ( Tsubstrate≥10 K, the minimum substrate temperature accessible to our experimental set up), indicating that when the best relaxant gas is used the GG'→GT conversion during deposition of the matrix is complete even at 10 K. Annealing of the argon and krypton matrices shows that the increase of the temperature of the matrix first promotes the GG'→GT isomerization, and only at higher temperatures the GT→GG conversion starts to occur, in consonance with the relative energy barriers associated with these two processes. The results also indicate that dimethyl sulfite exhibits conformation selective aggregation, with the most stable form, which has the highest dipole moment, aggregating more easily than the remaining experimentally relevant conformers (GT and GG').

Conformal hyperbolicity of Lorentzian warped products

International Nuclear Information System (INIS)

Markowitz, M.J.

1982-01-01

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

Conformal hyperbolicity of Lorentzian warped products

Energy Technology Data Exchange (ETDEWEB)

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

1982-12-01

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

Binding of Cimetidine to Balb/C Mouse Liver Catalase; Kinetics and Conformational Studies.

Science.gov (United States)

Jahangirvand, Mahboubeh; Minai-Tehrani, Dariush; Yazdi, Fatemeh; Minai-Tehrani, Arash; Razmi, Nematollah

2016-01-01

Catalase is responsible for converting hydrogen peroxide (H2O2) into water and oxygen in cells. This enzyme has high affinity for hydrogen peroxide and can protect the cells from oxidative stress damage. Catalase is a tetramer protein and each monomer contains a heme group. Cimetidine is a histamine H2 receptor blocker which inhibits acid release from stomach and is used for gasterointestinal diseases. In this research, effect of cimetidine on the activity of liver catalase was studied and the kinetic parameters of this enzyme and its conformational changes were investigated. Cell free extract of mouse liver was used for the catalase assay. The activity of the catalase was detected in the absence and presence of cimetidine by monitoring hydrogen peroxide reduction absorbance at 240 nm. The purified enzyme was used for conformational studies by Fluorescence spectrophotometry. The data showed that cimetidine could inhibit the enzyme in a non-competitive manner. Ki and IC50 values of the drug were determined to be about 0.75 and 0.85 uM, respectively. The Arrhenius plot showed that activation energy was 6.68 and 4.77 kJ/mol in the presence and absence of the drug, respectively. Fluorescence spectrophotometry revealed that the binding of cimetidine to the purified enzyme induced hyperchromicity and red shift which determined the conformational change on the enzyme. Cimetidine could non-competitively inhibit the liver catalase with high affinity. Binding of cimetidine to the enzyme induced conformational alteration in the enzyme.

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

Science.gov (United States)

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

2017-06-14

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

Synthesis of Conformal Phased Antenna Arrays With A Novel Multiobjective Invasive Weed Optimization Algorithm

Science.gov (United States)

Li, Wen Tao; Hei, Yong Qiang; Shi, Xiao Wei

2018-04-01

By virtue of the excellent aerodynamic performances, conformal phased arrays have been attracting considerable attention. However, for the synthesis of patterns with low/ultra-low sidelobes of the conventional conformal arrays, the obtained dynamic range ratios of amplitude excitations could be quite high, which results in stringent requirements on various error tolerances for practical implementation. Time-modulated array (TMA) has the advantages of low sidelobe and reduced dynamic range ratio requirement of amplitude excitations. This paper takes full advantages of conformal antenna arrays and time-modulated arrays. The active-element-pattern, including element mutual coupling and platform effects, is employed in the whole design process. To optimize the pulse durations and the switch-on instants of the time-modulated elements, multiobjective invasive weed optimization (MOIWO) algorithm based on the nondominated sorting of the solutions is proposed. A S-band 8-element cylindrical conformal array is designed and a S-band 16-element cylindrical-parabolic conformal array is constructed and tested at two different steering angles.

Non-linear realizations of conformal symmetry and effective field theory for the pseudo-conformal universe

International Nuclear Information System (INIS)

Hinterbichler, Kurt; Joyce, Austin; Khoury, Justin

2012-01-01

The pseudo-conformal scenario is an alternative to inflation in which the early universe is described by an approximate conformal field theory on flat, Minkowski space. Some fields acquire a time-dependent expectation value, which breaks the flat space so(4,2) conformal algebra to its so(4,1) de Sitter subalgebra. As a result, weight-0 fields acquire a scale invariant spectrum of perturbations. The scenario is very general, and its essential features are determined by the symmetry breaking pattern, irrespective of the details of the underlying microphysics. In this paper, we apply the well-known coset technique to derive the most general effective lagrangian describing the Goldstone field and matter fields, consistent with the assumed symmetries. The resulting action captures the low energy dynamics of any pseudo-conformal realization, including the U(1)-invariant quartic model and the Galilean Genesis scenario. We also derive this lagrangian using an alternative method of curvature invariants, consisting of writing down geometric scalars in terms of the conformal mode. Using this general effective action, we compute the two-point function for the Goldstone and a fiducial weight-0 field, as well as some sample three-point functions involving these fields

General Conformity

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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.

The Presence of Two Cyclase Thioesterases Expands the Conformational Freedom of the Cyclic Peptide Occidiofungin

Science.gov (United States)

Ravichandran, Akshaya; Gu, Ganyu; Escano, Jerome; Lu, Shi-En; Smith, Leif

2014-01-01

Occidiofungin is a cyclic nonribosomally synthesized antifungal peptide with submicromolar activity produced by Gram-negative bacterium Burkholderia contaminans. The biosynthetic gene cluster was confirmed to contain two cyclase thioesterases. NMR analysis revealed that the presence of both thioesterases is used to increase the conformational repertoire of the cyclic peptide. The loss of the OcfN cyclic thioesterase by mutagenesis results in a reduction of conformational variants and an appreciable decrease in bioactivity against Candida species. Presumably, the presence of both asparagine and β-hydroxyasparagine variants coordinate the enzymatic function of both of the cyclase thioesterases. OcfN has presumably evolved to be part of the biosynthetic gene cluster due to its ability to produce structural variants that enhance antifungal activity against some fungi. The enhancement of the antifungal activity from the incorporation of an additional cyclase thioesterase into the biosynthetic gene cluster of occidiofungin supports the need to explore new conformational variants of other therapeutic or potentially therapeutic cyclic peptides. PMID:23394257

Conformal displays: human factor analysis of innovative landing aids

Science.gov (United States)

Schmerwitz, Sven; Lueken, Thomas; Doehler, Hans-Ullrich; Peinecke, Niklas; Ernst, Johannes M.; da Silva Rosa, David L.

2017-05-01

In the past couple of years, research on display content for helicopter operations headed in a new direction. The already reached goals could evolve into a paradigm change for information visualization. Technology advancements allow implementing three-dimensional and conformal content on a helmet-mounted see-through device. This superimposed imagery inherits the same optical flow as the environment. It is supposed to ease switching between display information and environmental cues. The concept is neither pathbreaking nor new, but it has not been successfully established in aviation yet. Nevertheless, there are certainly some advantages to expect-at least from perspective of a human-centered system design. Within the following pages, the next generation displays will be presented and discussed with a focus on human factors. Beginning with recalling some human factor related research facts, an experiment comparing the former two-dimensional research displays will be presented. Before introducing the DLR conformal symbol set and the three experiments about an innovative drift, indication related research activities toward conformal symbol sets will be addressed.

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.

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.

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

Conformational change of adenosine deaminase during ligand-exchange in a crystal.

Science.gov (United States)

Kinoshita, Takayoshi; Tada, Toshiji; Nakanishi, Isao

2008-08-15

Adenosine deaminase (ADA) perpetuates chronic inflammation by degrading extracellular adenosine which is toxic for lymphocytes. ADA has two distinct conformations: open form and closed form. From the crystal structures with various ligands, the non-nucleoside type inhibitors bind to the active site occupying the critical water-binding-position and sustain the open form of apo-ADA. In contrast, substrate mimics do not occupy the critical position, and induce the large conformational change to the closed form. However, it is difficult to predict the binding of (+)-erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA), as it possesses characteristic parts of both the substrate and the non-nucleoside inhibitors. The crystal structure shows that EHNA binds to the open form through a novel recognition of the adenine base accompanying conformational change from the closed form of the PR-ADA complex in crystalline state.

47 CFR 68.320 - Supplier's Declaration of Conformity.

Science.gov (United States)

2010-10-01

... 47 Telecommunication 3 2010-10-01 2010-10-01 false Supplier's Declaration of Conformity. 68.320... Approval § 68.320 Supplier's Declaration of Conformity. (a) Supplier's Declaration of Conformity is a... Supplier's Declaration of Conformity attaches to all items subsequently marketed by the responsible party...

Conformational effects in photoelectron circular dichroism

Science.gov (United States)

Turchini, S.

2017-12-01

Photoelectron circular dichroism (PECD) is a novel type of spectroscopy, which presents surprising sensitivity to conformational effects in chiral systems. While classical photoelectron spectroscopy mainly responds to conformational effects in terms of energy level shifts, PECD provides a rich and detailed response to tiny changes in electronic and structural properties by means of the intensity dispersion of the circular dichroism as a function of photoelectron kinetic energy. In this work, the basics of PECD will be outlined, emphasizing the role of interference from the l,l+/- 1 outgoing partial wave of the photoelectron in the PECD transition matrix element, which is responsible for the extreme sensitivity to conformational effects. Examples using molecular systems and interfaces will shed light on the powerful application of PECD to classical conformational effects such as group substitution, isomerism, conformer population and clustering. Moreover, the PECD results will be reported in challenging new fields where conformations play a key role, such as vibrational effects, transient chirality and time- resolved experiments. To date, PECD has mostly been based on synchrotron radiation facilities, but it also has a future as a table-top lab experiment by means of multiphoton ionization. An important application of PECD as an analytical tool will be reported. The aim of this review is to illustrate that in PECD, the presence of conformational effects is essential for understanding a wide range of effects from a new perspective, making it different from classical spectroscopy.

Accessing a hidden conformation of the maltose binding protein using accelerated molecular dynamics.

Directory of Open Access Journals (Sweden)

Denis Bucher

2011-04-01

Full Text Available Periplasmic binding proteins (PBPs are a large family of molecular transporters that play a key role in nutrient uptake and chemotaxis in Gram-negative bacteria. All PBPs have characteristic two-domain architecture with a central interdomain ligand-binding cleft. Upon binding to their respective ligands, PBPs undergo a large conformational change that effectively closes the binding cleft. This conformational change is traditionally viewed as a ligand induced-fit process; however, the intrinsic dynamics of the protein may also be crucial for ligand recognition. Recent NMR paramagnetic relaxation enhancement (PRE experiments have shown that the maltose binding protein (MBP - a prototypical member of the PBP superfamily - exists in a rapidly exchanging (ns to µs regime mixture comprising an open state (approx 95%, and a minor partially closed state (approx 5%. Here we describe accelerated MD simulations that provide a detailed picture of the transition between the open and partially closed states, and confirm the existence of a dynamical equilibrium between these two states in apo MBP. We find that a flexible part of the protein called the balancing interface motif (residues 175-184 is displaced during the transformation. Continuum electrostatic calculations indicate that the repacking of non-polar residues near the hinge region plays an important role in driving the conformational change. Oscillations between open and partially closed states create variations in the shape and size of the binding site. The study provides a detailed description of the conformational space available to ligand-free MBP, and has implications for understanding ligand recognition and allostery in related proteins.

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.

Gluon amplitudes as 2 d conformal correlators

Science.gov (United States)

Pasterski, Sabrina; Shao, Shu-Heng; Strominger, Andrew

2017-10-01

Recently, spin-one wave functions in four dimensions that are conformal primaries of the Lorentz group S L (2 ,C ) were constructed. We compute low-point, tree-level gluon scattering amplitudes in the space of these conformal primary wave functions. The answers have the same conformal covariance as correlators of spin-one primaries in a 2 d CFT. The Britto-Cachazo-Feng-Witten (BCFW) recursion relation between three- and four-point gluon amplitudes is recast into this conformal basis.

Multichannel conformal blocks for scattering amplitudes

Science.gov (United States)

Belitsky, A. V.

2018-05-01

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

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.

The pseudo-conformal universe: scale invariance from spontaneous breaking of conformal symmetry

International Nuclear Information System (INIS)

Hinterbichler, Kurt; Khoury, Justin

2012-01-01

We present a novel theory of the very early universe which addresses the traditional horizon and flatness problems of big bang cosmology and predicts a scale invariant spectrum of perturbations. Unlike inflation, this scenario requires no exponential accelerated expansion of space-time. Instead, the early universe is described by a conformal field theory minimally coupled to gravity. The conformal fields develop a time-dependent expectation value which breaks the flat space so(4,2) conformal symmetry down to so(4,1), the symmetries of de Sitter, giving perturbations a scale invariant spectrum. The solution is an attractor, at least in the case of a single time-dependent field. Meanwhile, the metric background remains approximately flat but slowly contracts, which makes the universe increasingly flat, homogeneous and isotropic, akin to the smoothing mechanism of ekpyrotic cosmology. Our scenario is very general, requiring only a conformal field theory capable of developing the appropriate time-dependent expectation values, and encompasses existing incarnations of this idea, specifically the U(1) model of Rubakov and the Galileon Genesis scenario. Its essential features depend only on the symmetry breaking pattern and not on the details of the underlying lagrangian. It makes generic observational predictions that make it potentially distinguishable from standard inflation, in particular significant non-gaussianities and the absence of primordial gravitational waves

Arbitrary spin conformal fields in (A)dS

International Nuclear Information System (INIS)

Metsaev, R.R.

2014-01-01

Totally symmetric arbitrary spin conformal fields in (A)dS space of even dimension greater than or equal to four are studied. Ordinary-derivative and gauge invariant Lagrangian formulation for such fields is obtained. Gauge symmetries are realized by using auxiliary fields and Stueckelberg fields. We demonstrate that Lagrangian of conformal field is decomposed into a sum of gauge invariant Lagrangians for massless, partial-massless, and massive fields. We obtain a mass spectrum of the partial-massless and massive fields and confirm the conjecture about the mass spectrum made in the earlier literature. In contrast to conformal fields in flat space, the kinetic terms of conformal fields in (A)dS space turn out to be diagonal with respect to fields entering the Lagrangian. Explicit form of conformal transformation which maps conformal field in flat space to conformal field in (A)dS space is obtained. Covariant Lorentz-like and de-Donder like gauge conditions leading to simple gauge-fixed Lagrangian of conformal fields are proposed. Using such gauge-fixed Lagrangian, which is invariant under global BRST transformations, we explain how the partition function of conformal field is obtained in the framework of our approach

Inversion theory and conformal mapping

CERN Document Server

Blair, David E

2000-01-01

It is rarely taught in an undergraduate or even graduate curriculum that the only conformal maps in Euclidean space of dimension greater than two are those generated by similarities and inversions in spheres. This is in stark contrast to the wealth of conformal maps in the plane. The principal aim of this text is to give a treatment of this paucity of conformal maps in higher dimensions. The exposition includes both an analytic proof in general dimension and a differential-geometric proof in dimension three. For completeness, enough complex analysis is developed to prove the abundance of conformal maps in the plane. In addition, the book develops inversion theory as a subject, along with the auxiliary theme of circle-preserving maps. A particular feature is the inclusion of a paper by Carath�odory with the remarkable result that any circle-preserving transformation is necessarily a M�bius transformation, not even the continuity of the transformation is assumed. The text is at the level of advanced undergr...

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.

Dynamics and diffusive-conformational coupling in polymer bulk samples and surfaces: a molecular dynamics study

International Nuclear Information System (INIS)

Vree, C; Mayr, S G

2010-01-01

The impact of free surfaces on the mobility and conformational fluctuations of model polymer chains is investigated with the help of classical molecular dynamics simulations over a broad temperature range. Below a critical temperature, T*, similar to the critical temperature of the mode coupling theory, the center-of-mass displacements and temporal fluctuations of the radius of gyration of individual chains-as a fingerprint of structural reconfigurations-reveal a strong enhancement close to surfaces, while this effect diminishes with increasing temperature and observation time. Interpreting conformational fluctuations as a random walk in conformational space, identical activation enthalpies for structural reconfigurations and diffusion are obtained within the error bars in the bulk and at the surfaces, thus indicating a coupling of diffusive and conformational dynamics.

On functional representations of the conformal algebra

Energy Technology Data Exchange (ETDEWEB)

Rosten, Oliver J.

2017-07-15

Starting with conformally covariant correlation functions, a sequence of functional representations of the conformal algebra is constructed. A key step is the introduction of representations which involve an auxiliary functional. It is observed that these functionals are not arbitrary but rather must satisfy a pair of consistency equations corresponding to dilatation and special conformal invariance. In a particular representation, the former corresponds to the canonical form of the exact renormalization group equation specialized to a fixed point whereas the latter is new. This provides a concrete understanding of how conformal invariance is realized as a property of the Wilsonian effective action and the relationship to action-free formulations of conformal field theory. Subsequently, it is argued that the conformal Ward Identities serve to define a particular representation of the energy-momentum tensor. Consistency of this construction implies Polchinski's conditions for improving the energy-momentum tensor of a conformal field theory such that it is traceless. In the Wilsonian approach, the exactly marginal, redundant field which generates lines of physically equivalent fixed points is identified as the trace of the energy-momentum tensor. (orig.)

Exploratory conformational study of (+)-catechin. Modeling of the polarizability and electric dipole moment.

Science.gov (United States)

Bentz, Erika N; Pomilio, Alicia B; Lobayan, Rosana M

2014-12-01

The extension of the study of the conformational space of the structure of (+)-catechin at the B3LYP/6-31G(d,p) level of theory is presented in this paper. (+)-Catechin belongs to the family of the flavan-3-ols, which is one of the five largest phenolic groups widely distributed in nature, and whose biological activity and pharmaceutical utility are related to the antioxidant activity due to their ability to scavenge free radicals. The effects of free rotation around all C-O bonds of the OH substituents at different rings are taken into account, obtaining as the most stable conformer, one that had not been previously reported. One hundred seven structures, and a study of the effects of charge delocalization and stereoelectronic effects at the B3LYP/6-311++G(d,p) level are reported by natural bond orbital analysis, streamlining the order of these structures. For further analysis of the structural and molecular properties of this compound in a biological environment, the calculation of polarizabilities, and the study of the electric dipole moment are performed considering the whole conformational space described. The results are analyzed in terms of accumulated knowledge for (4α → 6″, 2α → O → 1″)-phenylflavans and (+)-catechin in previous works, enriching the study of both types of structures, and taking into account the importance of considering the whole conformational space in modeling both the polarizability and the electric dipole moment, also proposing to define a descriptive subspace of only 16 conformers.

Conformational changes in a hyperthermostable glycoside hydrolase: enzymatic activity is a consequence of the loop dynamics and protonation balance.

Directory of Open Access Journals (Sweden)

Leandro C de Oliveira

Full Text Available Endo-β-1, 4-mannanase from Thermotoga petrophila (TpMan is a modular hyperthermostable enzyme involved in the degradation of mannan-containing polysaccharides. The degradation of these polysaccharides represents a key step for several industrial applications. Here, as part of a continuing investigation of TpMan, the region corresponding to the GH5 domain (TpManGH5 was characterized as a function of pH and temperature. The results indicated that the enzymatic activity of the TpManGH5 is pH-dependent, with its optimum activity occurring at pH 6. At pH 8, the studies demonstrated that TpManGH5 is a molecule with a nearly spherical tightly packed core displaying negligible flexibility in solution, and with size and shape very similar to crystal structure. However, TpManGH5 experiences an increase in radius of gyration in acidic conditions suggesting expansion of the molecule. Furthermore, at acidic pH values, TpManGH5 showed a less globular shape, probably due to a loop region slightly more expanded and flexible in solution (residues Y88 to A105. In addition, molecular dynamics simulations indicated that conformational changes caused by pH variation did not change the core of the TpManGH5, which means that only the above mentioned loop region presents high degree of fluctuations. The results also suggested that conformational changes of the loop region may facilitate polysaccharide and enzyme interaction. Finally, at pH 6 the results indicated that TpManGH5 is slightly more flexible at 65°C when compared to the same enzyme at 20°C. The biophysical characterization presented here is well correlated with the enzymatic activity and provide new insight into the structural basis for the temperature and pH-dependent activity of the TpManGH5. Also, the data suggest a loop region that provides a starting point for a rational design of biotechnological desired features.

40 CFR 89.105 - Certificate of conformity.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Certificate of conformity. 89.105... and Certification Provisions § 89.105 Certificate of conformity. Every manufacturer of a new nonroad compression-ignition engine must obtain a certificate of conformity covering the engine family, as described...

A note on fashion cycles, novelty and conformity

OpenAIRE

Federica Alberti

2013-01-01

We develop a model in which novelty and conformity motivate fashion behavior. Fashion cycles occur if conformity is not too high. The duration of fashion cycles depends on individual-specific conformity, novelty, and the number of available styles. The use of individual-specific novelty and conformity allows us to also identify fashion leaders.

Nonperturbative results for two-index conformal windows

Energy Technology Data Exchange (ETDEWEB)

Bergner, Georg [Albert Einstein Center for Fundamental Physics,Institute for Theoretical Physics, University of Bern,Sidlerstrasse 5, CH-3012 Bern (Switzerland); Ryttov, Thomas A.; Sannino, Francesco [CP-Origins and the Danish IAS, University of Southern Denmark,5230 Odense M (Denmark)

2015-12-10

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

Nonperturbative results for two-index conformal windows

International Nuclear Information System (INIS)

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

2015-01-01

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

Measuring the mechanical properties of molecular conformers

Science.gov (United States)

Jarvis, S. P.; Taylor, S.; Baran, J. D.; Champness, N. R.; Larsson, J. A.; Moriarty, P.

2015-09-01

Scanning probe-actuated single molecule manipulation has proven to be an exceptionally powerful tool for the systematic atomic-scale interrogation of molecular adsorbates. To date, however, the extent to which molecular conformation affects the force required to push or pull a single molecule has not been explored. Here we probe the mechanochemical response of two tetra(4-bromophenyl)porphyrin conformers using non-contact atomic force microscopy where we find a large difference between the lateral forces required for manipulation. Remarkably, despite sharing very similar adsorption characteristics, variations in the potential energy surface are capable of prohibiting probe-induced positioning of one conformer, while simultaneously permitting manipulation of the alternative conformational form. Our results are interpreted in the context of dispersion-corrected density functional theory calculations which reveal significant differences in the diffusion barriers for each conformer. These results demonstrate that conformational variation significantly modifies the mechanical response of even simple porpyhrins, potentially affecting many other flexible molecules.

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.

Peer influence: neural mechanisms underlying in-group conformity.

Science.gov (United States)

Stallen, Mirre; Smidts, Ale; Sanfey, Alan G

2013-01-01

People often conform to the behavior of others with whom they identify. However, it is unclear what fundamental mechanisms underlie this type of conformity. Here, we investigate the processes mediating in-group conformity by using functional magnetic resonance imaging (fMRI). Participants completed a perceptual decision-making task while undergoing fMRI, during which they were exposed to the judgments of both in-group and out-group members. Our data suggest that conformity to the in-group is mediated by both positive affect as well as the cognitive capacity of perspective taking. Examining the processes that drive in-group conformity by utilizing a basic decision-making paradigm combined with neuroimaging methods provides important insights into the potential mechanisms of conformity. These results may provide an integral step in developing more effective campaigns using group conformity as a tool for behavioral change.

47 CFR 2.1072 - Limitation on Declaration of Conformity.

Science.gov (United States)

2010-10-01

... 47 Telecommunication 1 2010-10-01 2010-10-01 false Limitation on Declaration of Conformity. 2.1072... Conformity § 2.1072 Limitation on Declaration of Conformity. (a) The Declaration of Conformity signifies that...'s rules. (b) A Declaration of Conformity by the responsible party is effective until a termination...

Conformity index for brain cancer patients

International Nuclear Information System (INIS)

Petkovska, Sonja; Tolevska, Cveta; Kraleva, Slavica; Petreska, Elena

2010-01-01

The purpose of this study is to present the level of conformity achieved by using 3D conformal radiotherapy for brain cancer patients. Conformity index is a helpful quantitative tool for assessing (evaluating) the quality of a treatment plan. Treatment plans made for ninety patients with brain tumor are worked on this paper. The patients are in supine position and immobilized with thermoplastic masks for the head. Computed tomography data sets with 5 mm scan thickness are used to create a 3D image. All structures of interest are contoured. In order to obtain an optimal dose distribution, treatment fields are fit around target volume with set-up margins of 7mm in each direction. The conformity index values are between 1.21 and 2.04. Value of 1.8 is exceeded in eighteen cases; nine of them are bigger than 1.9 and only three of them are above 2. The target volume for each of these extreme CI values is ideal covered (between 95% and 105% of the prescribed dose). The most acceptable conformity index value in this paper belongs to the plan with the lowest minimal dose (84.7%). It can be concluded that conformity index is necessary but not sufficient factor for assessing radiation treatment plan conformity. To be able to estimate the acceptability of some treatment plan in daily practice, additional information as minimal, maximal and mean dose into target volume, as well as health tissues coverage must be taken into account.(Author)

Conformational Restriction of Peptides Using Dithiol Bis-Alkylation.

Science.gov (United States)

Peraro, L; Siegert, T R; Kritzer, J A

2016-01-01

Macrocyclic peptides are highly promising as inhibitors of protein-protein interactions. While many bond-forming reactions can be used to make cyclic peptides, most have limitations that make this chemical space challenging to access. Recently, a variety of cysteine alkylation reactions have been used in rational design and library approaches for cyclic peptide discovery and development. We and others have found that this chemistry is versatile and robust enough to produce a large variety of conformationally constrained cyclic peptides. In this chapter, we describe applications, methods, mechanistic insights, and troubleshooting for dithiol bis-alkylation reactions for the production of cyclic peptides. This method for efficient solution-phase macrocyclization is highly useful for the rapid production and screening of loop-based inhibitors of protein-protein interactions. © 2016 Elsevier Inc. All rights reserved.

Renormalization, conformal ward identities and the origin of a conformal anomaly pole

Science.gov (United States)

Corianò, Claudio; Maglio, Matteo Maria

2018-06-01

We investigate the emergence of a conformal anomaly pole in conformal field theories in the case of the TJJ correlator. We show how it comes to be generated in dimensional renormalization, using a basis of 13 form factors (the F-basis), where only one of them requires renormalization (F13), extending previous studies. We then combine recent results on the structure of the non-perturbative solutions of the conformal Ward identities (CWI's) for the TJJ in momentum space, expressed in terms of a minimal set of 4 form factors (A-basis), with the properties of the F-basis, and show how the singular behaviour of the corresponding form factors in both basis can be related. The result proves the centrality of such massless effective interactions induced by the anomaly, which have recently found realization in solid state, in the theory of topological insulators and of Weyl semimetals. This pattern is confirmed in massless abelian and nonabelian theories (QED and QCD) investigated at one-loop.

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.

40 CFR 90.106 - Certificate of conformity.

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 20 2010-07-01 2010-07-01 false Certificate of conformity. 90.106... Standards and Certification Provisions § 90.106 Certificate of conformity. (a)(1) Except as provided in § 90... certificate of conformity covering such engines; however, engines manufactured during an annual production...

SCit: web tools for protein side chain conformation analysis

OpenAIRE

Gautier, R.; Camproux, A.-C.; Tufféry, P.

2004-01-01

SCit is a web server providing services for protein side chain conformation analysis and side chain positioning. Specific services use the dependence of the side chain conformations on the local backbone conformation, which is described using a structural alphabet that describes the conformation of fragments of four-residue length in a limited library of structural prototypes. Based on this concept, SCit uses sets of rotameric conformations dependent on the local backbone conformation of each...

SCit: web tools for protein side chain conformation analysis.

Science.gov (United States)

Gautier, R; Camproux, A-C; Tufféry, P

2004-07-01

SCit is a web server providing services for protein side chain conformation analysis and side chain positioning. Specific services use the dependence of the side chain conformations on the local backbone conformation, which is described using a structural alphabet that describes the conformation of fragments of four-residue length in a limited library of structural prototypes. Based on this concept, SCit uses sets of rotameric conformations dependent on the local backbone conformation of each protein for side chain positioning and the identification of side chains with unlikely conformations. The SCit web server is accessible at http://bioserv.rpbs.jussieu.fr/SCit.

Conformal Killing horizons and their thermodynamics

Science.gov (United States)

Nielsen, Alex B.; Shoom, Andrey A.

2018-05-01

Certain dynamical black hole solutions can be mapped to static spacetimes by conformal metric transformations. This mapping provides a physical link between the conformal Killing horizon of the dynamical black hole and the Killing horizon of the static spacetime. Using the Vaidya spacetime as an example, we show how this conformal relation can be used to derive thermodynamic properties of such dynamical black holes. Although these horizons are defined quasi-locally and can be located by local experiments, they are distinct from other popular notions of quasi-local horizons such as apparent horizons. Thus in the dynamical Vaidya spacetime describing constant accretion of null dust, the conformal Killing horizon, which is null by construction, is the natural horizon to describe the black hole.

Molecular dynamics studies of the conformation of sorbitol

Science.gov (United States)

Lerbret, A.; Mason, P.E.; Venable, R.M.; Cesàro, A.; Saboungi, M.-L.; Pastor, R.W.; Brady, J.W.

2009-01-01

Molecular dynamics simulations of a 3 m aqueous solution of D-sorbitol (also called D-glucitol) have been performed at 300 K, as well as at two elevated temperatures to promote conformational transitions. In principle, sorbitol is more flexible than glucose since it does not contain a constraining ring. However, a conformational analysis revealed that the sorbitol chain remains extended in solution, in contrast to the bent conformation found experimentally in the crystalline form. While there are 243 staggered conformations of the backbone possible for this open-chain polyol, only a very limited number were found to be stable in the simulations. Although many conformers were briefly sampled, only eight were significantly populated in the simulation. The carbon backbones of all but two of these eight conformers were completely extended, unlike the bent crystal conformation. These extended conformers were stabilized by a quite persistent intramolecular hydrogen bond between the hydroxyl groups of carbon C-2 and C-4. The conformational populations were found to be in good agreement with the limited available NMR data except for the C-2–C-3 torsion (spanned by the O-2–O-4 hydrogen bond), where the NMR data supports a more bent structure. PMID:19744646

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

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.

14 CFR 21.130 - Statement of conformity.

Science.gov (United States)

2010-01-01

... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Statement of conformity. 21.130 Section 21... conformity. Each holder or licensee of a type certificate only, for a product manufactured in the United... Administrator a statement of conformity (FAA Form 317). This statement must be signed by an authorized person...

14 CFR 21.53 - Statement of conformity.

Science.gov (United States)

2010-01-01

... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Statement of conformity. 21.53 Section 21... CERTIFICATION PROCEDURES FOR PRODUCTS AND PARTS Type Certificates § 21.53 Statement of conformity. Link to an... conformity (FAA Form 317) to the Administrator for each aircraft engine and propeller presented to the...

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....

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

International Nuclear Information System (INIS)

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

2012-01-01

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

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.

Synthesis and biological evaluation of conformationally restricted and nucleobase-modified analogs of the anticancer compound 3'-C-ethynylcytidine (ECyd)

DEFF Research Database (Denmark)

Hrdlicka, Patrick J; Jepsen, Jan S; Wengel, Jesper

2005-01-01

A series of conformationally restricted and nucleobase-modified analogs of the anticancer compound 3'-C-ethynylcytidine (ECyd) and its uracil analog (EUrd) have been synthesized. While none of the conformationally restricted analogs displayed anticancer activity, 5-iodo-EUrd and 5-bromo-EUrd disp......-EUrd displayed potent anticancer activity with IC50 values of 35 nM and 0. 73 microM....

Conformal collineations and anisotropic fluids in general relativity

International Nuclear Information System (INIS)

Duggal, K.L.; Sharma, R.

1986-01-01

Recently, Herrera et al. [L. Herrera, J. Jimenez, L. Leal, J. Ponce de Leon, M. Esculpi, and V. Galino, J. Math. Phys. 25, 3274 (1984)] studied the consequences of the existence of a one-parameter group of conformal motions for anisotropic matter. They concluded that for special conformal motions, the stiff equation of state (p = μ) is singled out in a unique way, provided the generating conformal vector field is orthogonal to the four-velocity. In this paper, the same problem is studied by using conformal collineations (which include conformal motions as subgroups). It is shown that, for a special conformal collineation, the stiff equation of state is not singled out. Non-Einstein Ricci-recurrent spaces are considered as physical models for the fluid matter

Saturating representation of loop conformational fragments in structure databanks

Directory of Open Access Journals (Sweden)

Fiser András

2006-07-01

Full Text Available Abstract Background Short fragments of proteins are fundamental starting points in various structure prediction applications, such as in fragment based loop modeling methods but also in various full structure build-up procedures. The applicability and performance of these approaches depend on the availability of short fragments in structure databanks. Results We studied the representation of protein loop fragments up to 14 residues in length. All possible query fragments found in sequence databases (Sequence Space were clustered and cross referenced with available structural fragments in Protein Data Bank (Structure Space. We found that the expansion of PDB in the last few years resulted in a dense coverage of loop conformational fragments. For each loops of length 8 in the current Sequence Space there is at least one loop in Structure Space with 50% or higher sequence identity. By correlating sequence and structure clusters of loops we found that a 50% sequence identity generally guarantees structural similarity. These percentages of coverage at 50% sequence cutoff drop to 96, 94, 68, 53, 33 and 13% for loops of length 9, 10, 11, 12, 13, and 14, respectively. There is not a single loop in the current Sequence Space at any length up to 14 residues that is not matched with a conformational segment that shares at least 20% sequence identity. This minimum observed identity is 40% for loops of 12 residues or shorter and is as high as 50% for 10 residue or shorter loops. We also assessed the impact of rapidly growing sequence databanks on the estimated number of new loop conformations and found that while the number of sequentially unique sequence segments increased about six folds during the last five years there are almost no unique conformational segments among these up to 12 residues long fragments. Conclusion The results suggest that fragment based prediction approaches are not limited any more by the completeness of fragments in databanks but

Are spontaneous conformational interconversions a molecular basis for long-period oscillations in enzyme activity?

Science.gov (United States)

Queiroz-Claret, C; Valon, C; Queiroz, O

1988-01-01

An unconventional hypothesis to the molecular basis of enzyme rhythms is that the intrinsic physical instability of the protein molecules which, in an aqueous medium, tend to move continuously from one conformational state to another could lead, in the population of enzyme molecules, to sizeable long-period oscillations in affinity for substrate and sensitivity to ligands and regulatory effects. To investigate this hypothesis, malate dehydrogenase was extracted and purified from leaves of the plant Kalanchoe blossfeldiana. The enzyme solutions were maintained under constant conditions and sampled at regular intervals for up to 40 or 70 h for measurements of activity as a function of substrate concentration, Km for oxaloacetic acid and sensitivity to the action of 2,3-butanedione, a modifier of active site arginyl residues. The results show that continuous slow oscillations in the catalytic capacity of the enzyme occur in all the extracts checked, together with fluctuations in Km. Apparent circadian periodicities were observed in accordance with previous data established during long run (100 h) experiments. The saturation curves for substrate showed multiple kinetic functions, with various pronounced intermediary plateaus and "bumps" depending on the time of sampling. Variation in the response to the effect of butanedione indicated fluctuation in the accessibility to the active site. Taken together, the results suggest that, under constant conditions, the enzyme in solution shifts continuously and reversibly between different configurations. This was confirmed by parallel studies on the proton-NMR spectrum of water aggregates in the enzyme solution and proton exchange rates.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholinesterase inhibitors rapidly activate Trk neurotrophin receptors in the mouse hippocampus

Science.gov (United States)

Autio, Henri; Mätlik, Kert; Rantamäki, Tomi; Lindemann, Lothar; Hoener, Marius C; Chao, Moses; Arumäe, Urmas; Castrén, Eero

2014-01-01

Acetylcholinesterase inhibitors are first-line therapies for Alzheimer's disease. These drugs increase cholinergic tone in the target areas of the cholinergic neurons of the basal forebrain. Basal forebrain cholinergic neurons are dependent upon trophic support by nerve growth factor (NGF) through its neurotrophin receptor, TrkA. In the present study, we investigated whether the acetylcholinesterase inhibitors donepezil and galantamine could influence neurotrophin receptor signaling in the brain. Acute administration of donepezil (3 mg/kg, i.p.) led to the rapid autophosphorylation of TrkA and TrkB neurotrophin receptors in the adult mouse hippocampus. Similarly, galantamine dose-dependently (3, 9 mg/kg, i.p.) increased TrkA and TrkB phosphorylation in the mouse hippocampus. Both treatments also increased the phosphorylation of transcription factor CREB and tended to increase the phosphorylation of AKT kinase but did not alter the activity of MAPK42/44. Chronic treatment with galantamine (3 mg/kg, i.p., 14 days), did not induce changes in hippocampal NGF and BDNF synthesis or protein levels. Our findings show that acetylcholinesterase inhibitors are capable of rapidly activating hippocampal neurotrophin signaling and thus suggest that therapies targeting Trk signaling may already be in clinical use in the treatment of AD. PMID:21820453

Bioactive focus in conformational ensembles: a pluralistic approach

Science.gov (United States)

Habgood, Matthew

2017-12-01

Computational generation of conformational ensembles is key to contemporary drug design. Selecting the members of the ensemble that will approximate the conformation most likely to bind to a desired target (the bioactive conformation) is difficult, given that the potential energy usually used to generate and rank the ensemble is a notoriously poor discriminator between bioactive and non-bioactive conformations. In this study an approach to generating a focused ensemble is proposed in which each conformation is assigned multiple rankings based not just on potential energy but also on solvation energy, hydrophobic or hydrophilic interaction energy, radius of gyration, and on a statistical potential derived from Cambridge Structural Database data. The best ranked structures derived from each system are then assembled into a new ensemble that is shown to be better focused on bioactive conformations. This pluralistic approach is tested on ensembles generated by the Molecular Operating Environment's Low Mode Molecular Dynamics module, and by the Cambridge Crystallographic Data Centre's conformation generator software.

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 ...

Conformal invariance in harmonic superspace

International Nuclear Information System (INIS)

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

1985-01-01

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

Consumer participation in early detection of the deteriorating patient and call activation to rapid response systems: a literature review.

Science.gov (United States)

Vorwerk, Jane; King, Lindy

2016-01-01

This review investigated the impact of consumer participation in recognition of patient deterioration and response through call activation in rapid response systems. Nurses and doctors have taken the main role in recognition and response to patient deterioration through hospital rapid response systems. Yet patients and visitors (consumers) have appeared well placed to notice early signs of deterioration. In response, many hospitals have sought to partner health professionals with consumers in detection and response to early deterioration. However, to date, there have been no published research-based reviews to establish the impact of introducing consumer involvement into rapid response systems. A critical research-based review was undertaken. A comprehensive search of databases from 2006-2014 identified 11 studies. Critical appraisal of these studies was undertaken and thematic analysis of the findings revealed four major themes. Following implementation of the consumer activation programmes, the number of calls made by the consumers following detection of deterioration increased. Interestingly, the number of staff calls also increased. Importantly, mortality numbers were found to decrease in one major study following the introduction of consumer call activation. Consumer and staff knowledge and satisfaction with the new programmes indicated mixed results. Initial concerns of the staff over consumer involvement overwhelming the rapid response systems did not eventuate. Evaluation of successful consumer-activated programmes indicated the importance of: effective staff education and training; ongoing consumer education by nurses and clear educational materials. Findings indicated positive patient outcomes following introduction of consumer call activation programmes within rapid response systems. Effective consumer programmes included information that was readily accessible, easy-to-understand and available in a range of multimedia materials accompanied by the

Reciprocity Outperforms Conformity to Promote Cooperation.

Science.gov (United States)

Romano, Angelo; Balliet, Daniel

2017-10-01

Evolutionary psychologists have proposed two processes that could give rise to the pervasiveness of human cooperation observed among individuals who are not genetically related: reciprocity and conformity. We tested whether reciprocity outperformed conformity in promoting cooperation, especially when these psychological processes would promote a different cooperative or noncooperative response. To do so, across three studies, we observed participants' cooperation with a partner after learning (a) that their partner had behaved cooperatively (or not) on several previous trials and (b) that their group members had behaved cooperatively (or not) on several previous trials with that same partner. Although we found that people both reciprocate and conform, reciprocity has a stronger influence on cooperation. Moreover, we found that conformity can be partly explained by a concern about one's reputation-a finding that supports a reciprocity framework.

Conformational Footprint in Hydrolysis-Induced Nanofibrillation and Crystallization of Poly(lactic acid).

Science.gov (United States)

Xu, Huan; Yang, Xi; Xie, Lan; Hakkarainen, Minna

2016-03-14

The origin of hydrolysis-induced nanofibrillation and crystallization, at the molecular level, was revealed by mapping the conformational ordering during long-term hydrolytic degradation of initially amorphous poly(lactic acid) (PLA), a representative model for degradable aliphatic polyesters generally displaying strong interplay between crystallization and hydrolytic erosion. The conformational regularization of chain segments was essentially the main driving force for the morphological evolution of PLA during hydrolytic degradation. For hydrolysis at 37 °C, no significant structural variations were observed due to the immobilization of "frozen" PLA chains. In contrast, conformational ordering in PLA was immediately triggered during hydrolysis at 60 °C and was responsible for the transition from random coils to disordered trans and, further, to quasi-crystalline nanospheres. On the surfaces, the head-by-head absorption and joining of neighboring nanospheres led to nanofibrillar assemblies following a "gluttonous snake"-like manner. The length and density of nanofibers formed were in close relation to the hydrolytic evolution, both of which showed a direct rise in the initial 60 days and then a gradual decline. In the interior, presumably the high surface energy of the nanospheres allowed for the preferential anchoring and packing of conformationally ordered chains into lamellae. In accordance with the well-established hypothesis, the amorphous regions were attacked prior to the erosion of crystalline entities, causing a rapid increase of crystallinity during the initial 30 days, followed by a gradual fall until 90 days. In addition to adequate illustration of hydrolysis-induced variations of crystallinity, our proposed model elucidates the formation of spherulitic nuclei featuring an extremely wide distribution of diameters ranging from several nanometers to over 5 μm, as well as the inferior resistance to hydrolysis observed for the primary nuclei. Our work

Irreversibility and higher-spin conformal field theory

Science.gov (United States)

Anselmi, Damiano

2000-08-01

I discuss the properties of the central charges c and a for higher-derivative and higher-spin theories (spin 2 included). Ordinary gravity does not admit a straightforward identification of c and a in the trace anomaly, because it is not conformal. On the other hand, higher-derivative theories can be conformal, but have negative c and a. A third possibility is to consider higher-spin conformal field theories. They are not unitary, but have a variety of interesting properties. Bosonic conformal tensors have a positive-definite action, equal to the square of a field strength, and a higher-derivative gauge invariance. There exists a conserved spin-2 current (not the canonical stress tensor) defining positive central charges c and a. I calculate the values of c and a and study the operator-product structure. Higher-spin conformal spinors have no gauge invariance, admit a standard definition of c and a and can be coupled to Abelian and non-Abelian gauge fields in a renormalizable way. At the quantum level, they contribute to the one-loop beta function with the same sign as ordinary matter, admit a conformal window and non-trivial interacting fixed points. There are composite operators of high spin and low dimension, which violate the Ferrara-Gatto-Grillo theorem. Finally, other theories, such as conformal antisymmetric tensors, exhibit more severe internal problems. This research is motivated by the idea that fundamental quantum field theories should be renormalization-group (RG) interpolations between ultraviolet and infrared conformal fixed points, and quantum irreversibility should be a general principle of nature.

Essential role of conformational selection in ligand binding.

Science.gov (United States)

Vogt, Austin D; Pozzi, Nicola; Chen, Zhiwei; Di Cera, Enrico

2014-02-01

Two competing and mutually exclusive mechanisms of ligand recognition - conformational selection and induced fit - have dominated our interpretation of ligand binding in biological macromolecules for almost six decades. Conformational selection posits the pre-existence of multiple conformations of the macromolecule from which the ligand selects the optimal one. Induced fit, on the other hand, postulates the existence of conformational rearrangements of the original conformation into an optimal one that are induced by binding of the ligand. In the former case, conformational transitions precede the binding event; in the latter, conformational changes follow the binding step. Kineticists have used a facile criterion to distinguish between the two mechanisms based on the dependence of the rate of relaxation to equilibrium, kobs, on the ligand concentration, [L]. A value of kobs decreasing hyperbolically with [L] has been seen as diagnostic of conformational selection, while a value of kobs increasing hyperbolically with [L] has been considered diagnostic of induced fit. However, this simple conclusion is only valid under the rather unrealistic assumption of conformational transitions being much slower than binding and dissociation events. In general, induced fit only produces values of kobs that increase with [L] but conformational selection is more versatile and is associated with values of kobs that increase with, decrease with or are independent of [L]. The richer repertoire of kinetic properties of conformational selection applies to kinetic mechanisms with single or multiple saturable relaxations and explains the behavior of nearly all experimental systems reported in the literature thus far. Conformational selection is always sufficient and often necessary to account for the relaxation kinetics of ligand binding to a biological macromolecule and is therefore an essential component of any binding mechanism. On the other hand, induced fit is never necessary and

Conformational analysis of HAMLET, the folding variant of human alpha-lactalbumin associated with apoptosis.

Science.gov (United States)

Casbarra, Annarita; Birolo, Leila; Infusini, Giuseppe; Dal Piaz, Fabrizio; Svensson, Malin; Pucci, Piero; Svanborg, Catharina; Marino, Gennaro

2004-05-01

A combination of hydrogen/deuterium (H/D) exchange and limited proteolysis experiments coupled to mass spectrometry analysis was used to depict the conformation in solution of HAMLET, the folding variant of human alpha-lactalbumin, complexed to oleic acid, that induces apoptosis in tumor and immature cells. Although near- and far-UV CD and fluorescence spectroscopy were not able to discriminate between HAMLET and apo-alpha-lactalbumin, H/D exchange experiments clearly showed that they correspond to two distinct conformational states, with HAMLET incorporating a greater number of deuterium atoms than the apo and holo forms. Complementary proteolysis experiments revealed that HAMLET and apo are both accessible to proteases in the beta-domain but showed substantial differences in accessibility to proteases at specific sites. The overall results indicated that the conformational changes associated with the release of Ca2+ are not sufficient to induce the HAMLET conformation. Metal depletion might represent the first event to produce a partial unfolding in the beta-domain of alpha-lactalbumin, but some more unfolding is needed to generate the active conformation HAMLET, very likely allowing the protein to bind the C18:1 fatty acid moiety. On the basis of these data, a putative binding site of the oleic acid, which stabilizes the HAMLET conformation, is proposed.

Rotational Spectroscopy Unveils Eleven Conformers of Adrenaline

Science.gov (United States)

Cabezas, C.; Cortijo, V.; Mata, S.; Lopez, J. C.; Alonso, J. L.

2013-06-01

Recent improvements in our LA-MB-FTMW instrumentation have allowed the characterization of eleven and eight conformers for the neurotransmitters adrenaline and noradrenaline respectively. The observation of this rich conformational behavior is in accordance with the recent observation of seven conformers for dopamine and in sharp contrast with the conformational reduction proposed for catecholamines. C. Cabezas, I. Peña, J. C. López, J. L. Alonso J. Phys. Chem. Lett. 2013, 4, 486. H. Mitsuda, M. Miyazaki, I. B. Nielsen, P. Carcabal,C. Dedonder, C. Jouvet, S. Ishiuchi, M. Fujii J. Phys. Chem. Lett. 2010, 1, 1130.

Ion mobility-mass spectrometry reveals conformational flexibility in the deubiquitinating enzyme USP5.

Science.gov (United States)

Scott, Daniel; Layfield, Robert; Oldham, Neil J

2015-08-01

Many proteins exhibit conformation flexibility as part of their biological function, whether through the presence of a series of well-defined states or by the existence of intrinsic disorder. Ion mobility spectrometry, in combination with MS (IM-MS), offers a rapid and sensitive means of probing ensembles of protein structures through measurement of gas-phase collisional cross sections. We have applied IM-MS analysis to the multidomain deubiquitinating enzyme ubiquitin specific protease 5 (USP5), which is believed to exhibit significant conformational flexibility. Native ESI-MS measurement of the 94-kDa USP5 revealed two distinct charge-state distributions: [M + 17H](+) to [M + 21H](+) and [M + 24H](+) to [M + 29H](+). The collisional cross sections of these ions revealed clear groupings of 52 ± 4 nm(2) for the lower charges and 66 ± 6 nm(2) for the higher charges. Molecular dynamics simulation of a compact form of USP5, based on a crystal structure, produced structures of 53-54 nm(2) following 2 ns in the gas phase, while simulation of an extended form (based on small-angle X-ray scattering data) led to structures of 64 nm(2). These data demonstrate that IM-MS is a valuable tool in studying proteins with different discrete conformational states. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Rapidly assessing the activation conditions and porosity of metal-organic frameworks using thermogravimetric analysis.

Science.gov (United States)

McDonald, Thomas M; Bloch, Eric D; Long, Jeffrey R

2015-03-25

A methodology utilizing a thermogravimetric analyzer to monitor propane uptake following incremental increases of the temperature is demonstrated as a means of rapidly identifying porous materials and determining the optimum activation conditions of metal-organic frameworks.

Dilogarithm identities in conformal field theory

International Nuclear Information System (INIS)

Nahm, W.; Recknagel, A.; Terhoeven, M.

1992-11-01

Dilogarithm identities for the central charges and conformal dimensions exist for at least large classes of rational conformally invariant quantum field theories in two dimensions. In many cases, proofs are not yet known but the numerical and structural evidence is convincing. In particular, close relations exist to fusion rules and partition identities. We describe some examples and ideas, and present conjectures useful for the classification of conformal theories. The mathematical structures seem to be dual to Thurston's program for the classification of 3-manifolds. (orig.)

Conformational dynamics data bank: a database for conformational dynamics of proteins and supramolecular protein assemblies.

Science.gov (United States)

Kim, Do-Nyun; Altschuler, Josiah; Strong, Campbell; McGill, Gaël; Bathe, Mark

2011-01-01

The conformational dynamics data bank (CDDB, http://www.cdyn.org) is a database that aims to provide comprehensive results on the conformational dynamics of high molecular weight proteins and protein assemblies. Analysis is performed using a recently introduced coarse-grained computational approach that is applied to the majority of structures present in the electron microscopy data bank (EMDB). Results include equilibrium thermal fluctuations and elastic strain energy distributions that identify rigid versus flexible protein domains generally, as well as those associated with specific functional transitions, and correlations in molecular motions that identify molecular regions that are highly coupled dynamically, with implications for allosteric mechanisms. A practical web-based search interface enables users to easily collect conformational dynamics data in various formats. The data bank is maintained and updated automatically to include conformational dynamics results for new structural entries as they become available in the EMDB. The CDDB complements static structural information to facilitate the investigation and interpretation of the biological function of proteins and protein assemblies essential to cell function.

Crystal structure and conformational flexibility of the unligated FK506-binding protein FKBP12.6

Energy Technology Data Exchange (ETDEWEB)

Chen, Hui; Mustafi, Sourajit M. [New York State Department of Health, Empire State Plaza, Albany, NY 12201 (United States); LeMaster, David M. [New York State Department of Health, Empire State Plaza, Albany, NY 12201 (United States); University at Albany – SUNY, Empire State Plaza, Albany, NY 12201 (United States); Li, Zhong [New York State Department of Health, Empire State Plaza, Albany, NY 12201 (United States); Héroux, Annie [Brookhaven National Laboratory, Upton, NY 11973 (United States); Li, Hongmin; Hernández, Griselda, E-mail: griselda@wadsworth.org [New York State Department of Health, Empire State Plaza, Albany, NY 12201 (United States); University at Albany – SUNY, Empire State Plaza, Albany, NY 12201 (United States)

2014-03-01

Two crystal forms of unligated FKBP12.6 exhibit multiple conformations in the active site and in the 80s loop, the primary site for known protein-recognition interactions. The previously unreported NMR backbone assignment of FKBP12.6 revealed extensive doubling of amide resonances, which reflects a slow conformational transition centered in the 80s loop. The primary known physiological function of FKBP12.6 involves its role in regulating the RyR2 isoform of ryanodine receptor Ca{sup 2+} channels in cardiac muscle, pancreatic β islets and the central nervous system. With only a single previously reported X-ray structure of FKBP12.6, bound to the immunosuppressant rapamycin, structural inferences for this protein have been drawn from the more extensive studies of the homologous FKBP12. X-ray structures at 1.70 and 1.90 Å resolution from P2{sub 1} and P3{sub 1}21 crystal forms are reported for an unligated cysteine-free variant of FKBP12.6 which exhibit a notable diversity of conformations. In one monomer from the P3{sub 1}21 crystal form, the aromatic ring of Phe59 at the base of the active site is rotated perpendicular to its typical orientation, generating a steric conflict for the immunosuppressant-binding mode. The peptide unit linking Gly89 and Val90 at the tip of the protein-recognition ‘80s loop’ is flipped in the P2{sub 1} crystal form. Unlike the >30 reported FKBP12 structures, the backbone conformation of this loop closely follows that of the first FKBP domain of FKBP51. The NMR resonances for 21 backbone amides of FKBP12.6 are doubled, corresponding to a slow conformational transition centered near the tip of the 80s loop, as recently reported for 31 amides of FKBP12. The comparative absence of doubling for residues along the opposite face of the active-site pocket in FKBP12.6 may in part reflect attenuated structural coupling owing to increased conformational plasticity around the Phe59 ring.

Conformation of flexibly linked triterpene dimers by using RDC-enhanced NMR spectroscopy

Science.gov (United States)

Lakshmi, Jerripothula K.; Pattnaik, Banita; Kavitha, Rachineni; Mallavadhani, Uppuluri V.; Jagadeesh, Bharatam

2018-06-01

Dimers of flexibly linked pentacyclic triterpene ursolic acid (UA) and its related frameworks such as asiatic acid (AA) and oleanolic acid (OA) have recently attracted significant attention due to their enhanced anti-cancer and anti-HCV activity compared to their respective monomers. Determination of conformation/inter-monomer orientation of these molecules is very important to understand their structure-activity relationship and to develop new scaffolds, which, however, is difficult through conventional NOE based solution-state NMR spectroscopy, due to lack of long-range NOEs. In the present work, we report a precise determination of conformation of two 1,2,3-triazole-linked triterpene dimer molecules, UA-AA and UA-OA, by employing one-bond Csbnd H residual dipolar couplings (RDCs) as additional long-range orientational restraints, measured in anisotropic PDMS/CDCl3 solvent medium.

The history of N-methanocarbathymidine: the investigation of a conformational concept leads to the discovery of a potent and selective nucleoside antiviral agent.

Science.gov (United States)

Marquez, Victor E; Hughes, Stephen H; Sei, Shizuko; Agbaria, Riad

2006-09-01

Conformationally locked (North)-methanocarbathymidine (N-MCT) and (South)-methanocarbathymidine (S-MCT) have been used to investigate the conformational preferences of kinases and polymerases. The herpes kinases show a distinct bias for S-MCT, while DNA polymerases almost exclusively incorporate the North 5'-triphosphate (N-MCT-TP). Only N-MCT demonstrated potent antiviral activity against herpes simplex viruses (HSV-1 and 2) and Kaposi's sarcoma-associated herpesvirus (KSHV). The activity of N-MCT depends on its metabolic transformation to N-MCT-TP by the herpes kinases (HSV-tk or KSHV-tk), which catalyze the mono and diphosphorylation steps; cellular kinases generate the triphosphate. N-MCT at a dose of 5.6 mg/kg was totally protective for mice inoculated intranasally with HSV-1. Tumor cells that are not responsive to antiviral therapy became sensitive to N-MCT if the cells expressed HSV-tk. N-MCT given twice daily (100 mg/kg) for 7 days completely inhibited the growth of MC38 tumors derived from cells that express HSV-tk in mice while exhibiting no effect on tumors derived from non-transduced cells. After i.p. administration, N-MCT was rapidly absorbed and distributed in all organs examined with slow penetration into brain and testes. N-MCT-TP was also a potent inhibitor of HIV replication in human osteosarcoma (HOS) cells expressing HSV-tk.

Conformational Analysis of Contrast Media for X-Ray Diagnostic Radiology

International Nuclear Information System (INIS)

Solieman, A.H.M.

2010-01-01

The conformational analysis of iodinated non-ionic contrast agent, Iobitridol, was carried out using theoretical calculations to explore its conformational space, and to study different aspects connected with application of different search techniques. Monte Carlo (MC), random search (RS) and molecular dynamics (MD) based conformational search techniques were used to extract a reasonable-size sample that adequately represents and has an average behavior of the entire conformational ensemble.While MC is good for quick search for lowest energy conformer, RS is better in obtaining conformational sample that cover the whole conformational space and MD is the best for investigation of isomeric preferences inside the conformational ensemble at thermal equilibrium. Conformational analysis of the produced gas phase samples reveals that RS and MD methods could sufficiently present the 18 distinct isomeric classes that constitute the total conformational space of the Iobitridol. S samples of conformational space of Iobitridol are extensively studied, as it hypothetically cover the total conformational space. They are used to test the suitability of different methods (charge distribution methods, energy calculation methods) for Iobitridol molecular computations and internal structure forces (steric hindrance, resonance interaction), as well as dependences among the internal coordinates (dihedral angles correlations and coincidences). The atomic partial charge distribution is found to greatly affect the energy calculation for the molecular mechanics based conformational energy distributions. Further energy minimization of conformational sample by the quantum molecular orbital methods is crucial to obtain charge independent as well as energy balanced conformational sample.

Conformations of 1,3,3,5,7,7-Hexamethyl-1,5-diazacyclooctane and Its Bis-BH(3) Adduct. Mono- and Bis-BH(3) Adducts of Di-Tertiary Amines.

Science.gov (United States)

Livant, P.; Majors, A. W.; Webb, T. R.

1996-05-03

A variable-temperature (1)H- and (13)C-NMR study revealed a conformational equilibrium for 1,3,3,5,7,7-hexamethyl-1,5-diazacyclooctane (4) having DeltaG() = 8.8 +/- 0.6 kcal/mol at 184 K. This activation barrier connects a major and a minor form of 4. Molecular mechanics calculations on 4 led to the conclusion that the major form is a set of twist-chair-chairs interconverting rapidly via the chair-chair and that the minor form is most likely a set of twist-boat-boats interconverting rapidly via the boat-boat. The proximity of the two nitrogen lone pairs in the major form of 4 made plausible the expectation that 4, as well as a related diamine with apposed nitrogens, 3,7-dimethyl-3,7-diazabicyclo[3.3.1]nonane (3), might bind a Lewis acid, namely BH(3), using both lone pairs simultaneously and equally. This proved not to be the case: for 3 only the bis-BH(3) adduct was found and for 4 the mono-BH(3) adduct utilized only one nitrogen lone pair. The structure of the bis-BH(3) adduct of 4 (12) was determined by X-ray crystallography to be a twist-boat-boat with BH(3)s cis. Molecular mechanics calculations on 12 were consistent with the solid state conformation found.

Rapid Detection of Glycogen Synthase Kinase-3 Activity in Mouse Sperm Using Fluorescent Gel Shift Electrophoresis

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Hoseok Choi

2016-04-01

Full Text Available Assaying the glycogen synthase kinase-3 (GSK3 activity in sperm is of great importance because it is closely implicated in sperm motility and male infertility. While a number of studies on GSK3 activity have relied on labor-intensive immunoblotting to identify phosphorylated GSK3, here we report the simple and rapid detection of GSK3 activity in mouse sperm using conventional agarose gel electrophoresis and a fluorescent peptide substrate. When a dye-tethered and prephosphorylated (primed peptide substrate for GSK3 was employed, a distinct mobility shift in the fluorescent bands on the agarose was observed by GSK3-induced phosphorylation of the primed peptides. The GSK3 activity in mouse testes and sperm were quantifiable by gel shift assay with low sample consumption and were significantly correlated with the expression levels of GSK3 and p-GSK3. We suggest that our assay can be used for reliable and rapid detection of GSK3 activity in cells and tissue extracts.

Rapid Detection of Glycogen Synthase Kinase-3 Activity in Mouse Sperm Using Fluorescent Gel Shift Electrophoresis

Science.gov (United States)

Choi, Hoseok; Choi, Bomi; Seo, Ju Tae; Lee, Kyung Jin; Gye, Myung Chan; Kim, Young-Pil

2016-01-01

Assaying the glycogen synthase kinase-3 (GSK3) activity in sperm is of great importance because it is closely implicated in sperm motility and male infertility. While a number of studies on GSK3 activity have relied on labor-intensive immunoblotting to identify phosphorylated GSK3, here we report the simple and rapid detection of GSK3 activity in mouse sperm using conventional agarose gel electrophoresis and a fluorescent peptide substrate. When a dye-tethered and prephosphorylated (primed) peptide substrate for GSK3 was employed, a distinct mobility shift in the fluorescent bands on the agarose was observed by GSK3-induced phosphorylation of the primed peptides. The GSK3 activity in mouse testes and sperm were quantifiable by gel shift assay with low sample consumption and were significantly correlated with the expression levels of GSK3 and p-GSK3. We suggest that our assay can be used for reliable and rapid detection of GSK3 activity in cells and tissue extracts. PMID:27092510

Conformational changes in the G protein Gs induced by the β2 adrenergic receptor

DEFF Research Database (Denmark)

Chung, Ka Young; Rasmussen, Søren Gøgsig Faarup; Liu, Tong

2011-01-01

and initiation of downstream signalling cascades. Despite a wealth of biochemical and biophysical studies on inactive and active conformations of several heterotrimeric G proteins, the molecular underpinnings of G protein activation remain elusive. To characterize this mechanism, we applied peptide amide...

Static validation of licence conformance policies

DEFF Research Database (Denmark)

Hansen, Rene Rydhof; Nielson, Flemming; Nielson, Hanne Riis

2008-01-01

Policy conformance is a security property gaining importance due to commercial interest like Digital Rights Management. It is well known that static analysis can be used to validate a number of more classical security policies, such as discretionary and mandatory access control policies, as well...... as communication protocols using symmetric and asymmetric cryptography. In this work we show how to develop a Flow Logic for validating the conformance of client software with respect to a licence conformance policy. Our approach is sufficiently flexible that it extends to fully open systems that can admit new...

The decomposition of global conformal invariants

CERN Document Server

Alexakis, Spyros

2012-01-01

This book addresses a basic question in differential geometry that was first considered by physicists Stanley Deser and Adam Schwimmer in 1993 in their study of conformal anomalies. The question concerns conformally invariant functionals on the space of Riemannian metrics over a given manifold. These functionals act on a metric by first constructing a Riemannian scalar out of it, and then integrating this scalar over the manifold. Suppose this integral remains invariant under conformal re-scalings of the underlying metric. What information can one then deduce about the Riemannian scalar? Dese

77 FR 14979 - Transportation Conformity Rule Restructuring Amendments

Science.gov (United States)

2012-03-14

... Transportation Conformity Rule Restructuring Amendments AGENCY: Environmental Protection Agency (EPA). ACTION: Final rule. SUMMARY: EPA is amending the transportation conformity rule to finalize provisions that were proposed on August 13, 2010. These amendments restructure several sections of the transportation conformity...

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...

The Conformational Dynamics of Cas9 Governing DNA Cleavage Are Revealed by Single-Molecule FRET

Directory of Open Access Journals (Sweden)

Mengyi Yang

2018-01-01

Full Text Available Summary: Off-target binding and cleavage by Cas9 pose major challenges in its application. How the conformational dynamics of Cas9 govern its nuclease activity under on- and off-target conditions remains largely unknown. Here, using intra-molecular single-molecule fluorescence resonance energy transfer measurements, we revealed that Cas9 in apo, sgRNA-bound, and dsDNA/sgRNA-bound forms spontaneously transits among three major conformational states, mainly reflecting significant conformational mobility of the catalytic HNH domain. We also uncovered surprising long-range allosteric communication between the HNH domain and the RNA/DNA heteroduplex at the PAM-distal end to ensure correct positioning of the catalytic site, which demonstrated that a unique proofreading mechanism served as the last checkpoint before DNA cleavage. Several Cas9 residues were likely to mediate the allosteric communication and proofreading step. Modulating interactions between Cas9 and heteroduplex at the PAM-distal end by introducing mutations on these sites provides an alternative route to improve and optimize the CRISPR/Cas9 toolbox. : Yang et al. revealed significant conformational dynamics of Cas9 at global and local scales using single-molecule FRET. They uncovered surprising long-range allosteric communication between the HNH nuclease domain and the RNA/DNA heteroduplex at the PAM-distal end that serves as a proofreading checkpoint to govern the nuclease activity and specificity of Cas9. Keywords: CRISPR, Cas9, single-molecule, FRET, conformational dynamics, proofreading, off-target, allosteric communication, genome editing

Elucidation of the conformational free energy landscape in H.pylori LuxS and its implications to catalysis

Directory of Open Access Journals (Sweden)

Bhattacharyya Moitrayee

2010-08-01

Full Text Available Abstract Background One of the major challenges in understanding enzyme catalysis is to identify the different conformations and their populations at detailed molecular level in response to ligand binding/environment. A detail description of the ligand induced conformational changes provides meaningful insights into the mechanism of action of enzymes and thus its function. Results In this study, we have explored the ligand induced conformational changes in H.pylori LuxS and the associated mechanistic features. LuxS, a dimeric protein, produces the precursor (4,5-dihydroxy-2,3-pentanedione for autoinducer-2 production which is a signalling molecule for bacterial quorum sensing. We have performed molecular dynamics simulations on H.pylori LuxS in its various ligand bound forms and analyzed the simulation trajectories using various techniques including the structure network analysis, free energy evaluation and water dynamics at the active site. The results bring out the mechanistic details such as co-operativity and asymmetry between the two subunits, subtle changes in the conformation as a response to the binding of active and inactive forms of ligands and the population distribution of different conformations in equilibrium. These investigations have enabled us to probe the free energy landscape and identify the corresponding conformations in terms of network parameters. In addition, we have also elucidated the variations in the dynamics of water co-ordination to the Zn2+ ion in LuxS and its relation to the rigidity at the active sites. Conclusions In this article, we provide details of a novel method for the identification of conformational changes in the different ligand bound states of the protein, evaluation of ligand-induced free energy changes and the biological relevance of our results in the context of LuxS structure-function. The methodology outlined here is highly generalized to illuminate the linkage between structure and function in

Conformational analysis of 9β,19-cyclopropyl sterols: Detection of the pseudoplanar conformer by nuclear Overhauser effects and its functional implications

International Nuclear Information System (INIS)

Nes, W.D.; Benson, M.; Lundin, R.E.; Le, P.H.

1988-01-01

Nuclear Overhauser difference spectroscopy and variable temperature studies of the 9β,19-cyclopropyl sterols 24,25-dehydropollinastanol (4,4-desmethyl-5α-cycloart-24-en-3β-ol) and cyclolaudenol [(24S)-24-methyl-5α-cycloart-25(27)-en-3β-ol] have shown the solution conformation of the B/C rings to be twist-chair/twist-boat rather than boat/chair as suggested in the literature. This is very similar to the known crystal structure conformation of 9β,19-cyclopropyl sterols. The effect of these conformations on the molecular shape is highly significant; the first conformation orients into a pseudoplanar or flat shape analogous to lanosterol, whereas the latter conformation exhibits a bent shape. The results are interpreted to imply that, for conformational reasons, cyclopropyl sterols can be expected to maintain the pseudoplanar shape in membrane bilayers

Defects in conformal field theory

International Nuclear Information System (INIS)

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

2016-01-01

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

Defects in conformal field theory

Energy Technology Data Exchange (ETDEWEB)

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

2016-04-15

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

Molecular Dynamics Simulations of Insulin: Elucidating the Conformational Changes that Enable Its Binding.

Directory of Open Access Journals (Sweden)

Anastasios Papaioannou

Full Text Available A sequence of complex conformational changes is required for insulin to bind to the insulin receptor. Recent experimental evidence points to the B chain C-terminal (BC-CT as the location of these changes in insulin. Here, we present molecular dynamics simulations of insulin that reveal new insights into the structural changes occurring in the BC-CT. We find three key results: 1 The opening of the BC-CT is inherently stochastic and progresses through an open and then a "wide-open" conformation--the wide-open conformation is essential for receptor binding, but occurs only rarely. 2 The BC-CT opens with a zipper-like mechanism, with a hinge at the Phe24 residue, and is maintained in the dominant closed/inactive state by hydrophobic interactions of the neighboring Tyr26, the critical residue where opening of the BC-CT (activation of insulin is initiated. 3 The mutation Y26N is a potential candidate as a therapeutic insulin analogue. Overall, our results suggest that the binding of insulin to its receptor is a highly dynamic and stochastic process, where initial docking occurs in an open conformation and full binding is facilitated through interactions of insulin receptor residues with insulin in its wide-open conformation.

UV conformal window for asymptotic safety

Science.gov (United States)

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

2018-02-01

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

Irregular conformal block, spectral curve and flow equations

International Nuclear Information System (INIS)

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

2016-01-01

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

Scalar perturbations and conformal transformation

International Nuclear Information System (INIS)

Fabris, J.C.; Tossa, J.

1995-11-01

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

49 CFR 577.9 - Conformity to statutory requirements.

Science.gov (United States)

2010-10-01

... 49 Transportation 7 2010-10-01 2010-10-01 false Conformity to statutory requirements. 577.9 Section 577.9 Transportation Other Regulations Relating to Transportation (Continued) NATIONAL HIGHWAY... NOTIFICATION § 577.9 Conformity to statutory requirements. A notification that does not conform to the...

20 CFR 604.6 - Conformity and substantial compliance.

Science.gov (United States)

2010-04-01

... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Conformity and substantial compliance. 604.6... FOR ELIGIBILITY FOR UNEMPLOYMENT COMPENSATION § 604.6 Conformity and substantial compliance. (a) In... for the administration of its UC program. (b) Resolving Issues of Conformity and Substantial...

Optimal 3-D conformal treatment planning of posterior lateral supratentorial tumors

International Nuclear Information System (INIS)

Gius, David; Klein, Eric; Oehmke, Fred

1995-01-01

percentage of normal brain tissue spared, when 60.0 Gy covers 100% of the target volume. The percentage of normal brain receiving greater than 45.0 Gy was; 31% for the opposed laterals; 32% for the posterior wedge pair, 19% for the three field, single tier wedge; and 15% for the three field two tier wedge plan. The film dosimetry confirmed the isodose distributions for all beam arrangements to within 5%. Conclusions: Treatment of a posterior or posterior-lateral supratentorial brain lesion present a unique problem in terms of radiation therapy treatment planning due to the rapidly changing contours of the calvarium, resulting in diverging concave anatomical surfaces contained within a single beam port. The use of a multiple field, two tier wedge beam arrangement offers the unique ability to tightly conform the dose in areas of rapidly changing external surfaces while sparing normal tissues

Vertex operator algebras and conformal field theory

International Nuclear Information System (INIS)

Huang, Y.Z.

1992-01-01

This paper discusses conformal field theory, an important physical theory, describing both two-dimensional critical phenomena in condensed matter physics and classical motions of strings in string theory. The study of conformal field theory will deepen the understanding of these theories and will help to understand string theory conceptually. Besides its importance in physics, the beautiful and rich mathematical structure of conformal field theory has interested many mathematicians. New relations between different branches of mathematics, such as representations of infinite-dimensional Lie algebras and Lie groups, Riemann surfaces and algebraic curves, the Monster sporadic group, modular functions and modular forms, elliptic genera and elliptic cohomology, Calabi-Yau manifolds, tensor categories, and knot theory, are revealed in the study of conformal field theory. It is therefore believed that the study of the mathematics involved in conformal field theory will ultimately lead to new mathematical structures which would be important to both mathematics and physics

Rapid shifts in Atta cephalotes fungus-garden enzyme activity after a change in fungal substrate (Attini, Formicidae)

DEFF Research Database (Denmark)

Kooij, P W; Schiøtt, M; Boomsma, J J

2011-01-01

Fungus gardens of the basidiomycete Leucocoprinus gongylophorus sustain large colonies of leaf-cutting ants by degrading the plant material collected by the ants. Recent studies have shown that enzyme activity in these gardens is primarily targeted toward starch, proteins and the pectin matrix......, we measured the changes in enzyme activity after a controlled shift in fungal substrate offered to six laboratory colonies of Atta cephalotes. An ant diet consisting exclusively of grains of parboiled rice rapidly increased the activity of endo-proteinases and some of the pectinases attacking...... from the rice diet, relative to the leaf diet controls. Enzyme activity in the older, bottom sections of fungus gardens decreased, indicating a faster processing of the rice substrate compared to the leaf diet. These results suggest that leaf-cutting ant fungus gardens can rapidly adjust enzyme...

The butane condensed matter conformational problem

NARCIS (Netherlands)

Weber, A.C.J.; de Lange, C.A.; Meerts, W.L.; Burnell, E.E.

2010-01-01

From the dipolar couplings of orientationally ordered n-butane obtained by NMR spectroscopy we have calculated conformer probabilities using the modified Chord (Cd) and Size-and-Shape (CI) models to estimate the conformational dependence of the order matrix. All calculation methods make use of

Conformal invariance and two-dimensional physics

International Nuclear Information System (INIS)

Zuber, J.B.

1993-01-01

Actually, physicists and mathematicians are very interested in conformal invariance: geometric transformations which keep angles. This symmetry is very important for two-dimensional systems as phase transitions, string theory or node mathematics. In this article, the author presents the conformal invariance and explains its usefulness

Impact of graphene-based nanomaterials (GBNMs) on the structural and functional conformations of hepcidin peptide

Science.gov (United States)

Singh, Krishna P.; Baweja, Lokesh; Wolkenhauer, Olaf; Rahman, Qamar; Gupta, Shailendra K.

2018-03-01

Graphene-based nanomaterials (GBNMs) are widely used in various industrial and biomedical applications. GBNMs of different compositions, size and shapes are being introduced without thorough toxicity evaluation due to the unavailability of regulatory guidelines. Computational toxicity prediction methods are used by regulatory bodies to quickly assess health hazards caused by newer materials. Due to increasing demand of GBNMs in various size and functional groups in industrial and consumer based applications, rapid and reliable computational toxicity assessment methods are urgently needed. In the present work, we investigate the impact of graphene and graphene oxide nanomaterials on the structural conformations of small hepcidin peptide and compare the materials for their structural and conformational changes. Our molecular dynamics simulation studies revealed conformational changes in hepcidin due to its interaction with GBMNs, which results in a loss of its functional properties. Our results indicate that hepcidin peptide undergo severe structural deformations when superimposed on the graphene sheet in comparison to graphene oxide sheet. These observations suggest that graphene is more toxic than a graphene oxide nanosheet of similar area. Overall, this study indicates that computational methods based on structural deformation, using molecular dynamics (MD) simulations, can be used for the early evaluation of toxicity potential of novel nanomaterials.

Conformational dynamism for DNA interaction in the Salmonella RcsB response regulator.

Science.gov (United States)

Casino, Patricia; Miguel-Romero, Laura; Huesa, Juanjo; García, Pablo; García-Del Portillo, Francisco; Marina, Alberto

2018-01-09

The RcsCDB phosphorelay system controls an extremely large regulon in Enterobacteriaceae that involves processes such as biofilm formation, flagella production, synthesis of extracellular capsules and cell division. Therefore, fine-tuning of this system is essential for virulence in pathogenic microorganisms of this group. The final master effector of the RcsCDB system is the response regulator (RR) RcsB, which activates or represses multiple genes by binding to different promoter regions. This regulatory activity of RcsB can be done alone or in combination with additional transcriptional factors in phosphorylated or dephosphorylated states. The capacity of RcsB to interact with multiple promoters and partners, either dephosphorylated or phosphorylated, suggests an extremely conformational dynamism for this RR. To shed light on the activation mechanism of RcsB and its implication on promoter recognition, we solved the crystal structure of full-length RcsB from Salmonella enterica serovar Typhimurium in the presence and absence of a phosphomimetic molecule BeF3-. These two novel structures have guided an extensive site-directed mutagenesis study at the structural and functional level that confirms RcsB conformational plasticity and dynamism. Our data allowed us to propose a β5-T switch mechanism where phosphorylation is coupled to alternative DNA binding ways and which highlights the conformational dynamism of RcsB to be so pleiotropic. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Kinetic Dissection of the Pre-existing Conformational Equilibrium in the Trypsin Fold*

Science.gov (United States)

Vogt, Austin D.; Chakraborty, Pradipta; Di Cera, Enrico

2015-01-01

Structural biology has recently documented the conformational plasticity of the trypsin fold for both the protease and zymogen in terms of a pre-existing equilibrium between closed (E*) and open (E) forms of the active site region. How such plasticity is manifested in solution and affects ligand recognition by the protease and zymogen is poorly understood in quantitative terms. Here we dissect the E*-E equilibrium with stopped-flow kinetics in the presence of excess ligand or macromolecule. Using the clotting protease thrombin and its zymogen precursor prethrombin-2 as relevant models we resolve the relative distribution of the E* and E forms and the underlying kinetic rates for their interconversion. In the case of thrombin, the E* and E forms are distributed in a 1:4 ratio and interconvert on a time scale of 45 ms. In the case of prethrombin-2, the equilibrium is shifted strongly (10:1 ratio) in favor of the closed E* form and unfolds over a faster time scale of 4.5 ms. The distribution of E* and E forms observed for thrombin and prethrombin-2 indicates that zymogen activation is linked to a significant shift in the pre-existing equilibrium between closed and open conformations that facilitates ligand binding to the active site. These findings broaden our mechanistic understanding of how conformational transitions control ligand recognition by thrombin and its zymogen precursor prethrombin-2 and have direct relevance to other members of the trypsin fold. PMID:26216877

Geometrical formulation of the conformal Ward identity

International Nuclear Information System (INIS)

Kachkachi, M.

2002-08-01

In this paper we use deep ideas in complex geometry that proved to be very powerful in unveiling the Polyakov measure on the moduli space of Riemann surfaces and lead to obtain the partition function of perturbative string theory for 2, 3, 4 loops. Indeed, a geometrical interpretation of the conformal Ward identity in two dimensional conformal field theory is proposed: the conformal anomaly is interpreted as a deformation of the complex structure of the basic Riemann surface. This point of view is in line with the modern trend of geometric quantizations that are based on deformations of classical structures. Then, we solve the conformal Ward identity by using this geometrical formalism. (author)

Riemann monodromy problem and conformal field theories

International Nuclear Information System (INIS)

Blok, B.

1989-01-01

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

Rapid assessment of disaster damage using social media activity.

Science.gov (United States)

Kryvasheyeu, Yury; Chen, Haohui; Obradovich, Nick; Moro, Esteban; Van Hentenryck, Pascal; Fowler, James; Cebrian, Manuel

2016-03-01

Could social media data aid in disaster response and damage assessment? Countries face both an increasing frequency and an increasing intensity of natural disasters resulting from climate change. During such events, citizens turn to social media platforms for disaster-related communication and information. Social media improves situational awareness, facilitates dissemination of emergency information, enables early warning systems, and helps coordinate relief efforts. In addition, the spatiotemporal distribution of disaster-related messages helps with the real-time monitoring and assessment of the disaster itself. We present a multiscale analysis of Twitter activity before, during, and after Hurricane Sandy. We examine the online response of 50 metropolitan areas of the United States and find a strong relationship between proximity to Sandy's path and hurricane-related social media activity. We show that real and perceived threats, together with physical disaster effects, are directly observable through the intensity and composition of Twitter's message stream. We demonstrate that per-capita Twitter activity strongly correlates with the per-capita economic damage inflicted by the hurricane. We verify our findings for a wide range of disasters and suggest that massive online social networks can be used for rapid assessment of damage caused by a large-scale disaster.

Does rapid and physiological astrocyte–neuron signalling amplify epileptic activity?

Science.gov (United States)

2016-01-01

Abstract The hippocampus is a key brain region in the pathophysiology of mesial temporal lobe epilepsy. Long‐term changes of its architecture and function on the network and cellular level are well documented in epilepsy. Astrocytes can control many aspects of neuronal function and their long‐term alterations over weeks, months and years play an important role in epilepsy. However, a pathophysiological transformation of astrocytes does not seem to be required for astrocytes to contribute to epileptic activity. Some of the properties of physiological astrocyte–neuron communication could allow these cells to exacerbate or synchronize neuronal firing on shorter time scales of milliseconds to minutes. Therefore, these astrocyte–neuron interactions are increasingly recognized as potential contributors to epileptic activity. Fast and reciprocal communication between astrocytes and neurons is enabled by a diverse set of mechanisms that could both amplify and counteract epileptic activity. They may thus promote or cause development of epileptic activity or inhibit it. Mechanisms of astrocyte–neuron interactions that can quickly increase network excitability involve, for example, astrocyte Ca2+ and Na+ signalling, K+ buffering, gap junction coupling and metabolism. However, rapid changes of astrocyte neurotransmitter uptake and morphology may also underlie or support development of network hyperexcitability. The temporal characteristics of these interactions, their ability to synchronize neuronal activity and their net effect on network activity will determine their contribution to the emergence or maintenance of epileptic activity. PMID:27106234

Does rapid and physiological astrocyte-neuron signalling amplify epileptic activity?

Science.gov (United States)

Henneberger, Christian

2017-03-15

The hippocampus is a key brain region in the pathophysiology of mesial temporal lobe epilepsy. Long-term changes of its architecture and function on the network and cellular level are well documented in epilepsy. Astrocytes can control many aspects of neuronal function and their long-term alterations over weeks, months and years play an important role in epilepsy. However, a pathophysiological transformation of astrocytes does not seem to be required for astrocytes to contribute to epileptic activity. Some of the properties of physiological astrocyte-neuron communication could allow these cells to exacerbate or synchronize neuronal firing on shorter time scales of milliseconds to minutes. Therefore, these astrocyte-neuron interactions are increasingly recognized as potential contributors to epileptic activity. Fast and reciprocal communication between astrocytes and neurons is enabled by a diverse set of mechanisms that could both amplify and counteract epileptic activity. They may thus promote or cause development of epileptic activity or inhibit it. Mechanisms of astrocyte-neuron interactions that can quickly increase network excitability involve, for example, astrocyte Ca 2+ and Na + signalling, K + buffering, gap junction coupling and metabolism. However, rapid changes of astrocyte neurotransmitter uptake and morphology may also underlie or support development of network hyperexcitability. The temporal characteristics of these interactions, their ability to synchronize neuronal activity and their net effect on network activity will determine their contribution to the emergence or maintenance of epileptic activity. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

TRIP13 is a protein-remodeling AAA+ ATPase that catalyzes MAD2 conformation switching.

Science.gov (United States)

Ye, Qiaozhen; Rosenberg, Scott C; Moeller, Arne; Speir, Jeffrey A; Su, Tiffany Y; Corbett, Kevin D

2015-04-28

The AAA+ family ATPase TRIP13 is a key regulator of meiotic recombination and the spindle assembly checkpoint, acting on signaling proteins of the conserved HORMA domain family. Here we present the structure of the Caenorhabditis elegans TRIP13 ortholog PCH-2, revealing a new family of AAA+ ATPase protein remodelers. PCH-2 possesses a substrate-recognition domain related to those of the protein remodelers NSF and p97, while its overall hexameric architecture and likely structural mechanism bear close similarities to the bacterial protein unfoldase ClpX. We find that TRIP13, aided by the adapter protein p31(comet), converts the HORMA-family spindle checkpoint protein MAD2 from a signaling-active 'closed' conformer to an inactive 'open' conformer. We propose that TRIP13 and p31(comet) collaborate to inactivate the spindle assembly checkpoint through MAD2 conformational conversion and disassembly of mitotic checkpoint complexes. A parallel HORMA protein disassembly activity likely underlies TRIP13's critical regulatory functions in meiotic chromosome structure and recombination.

TRIP13 is a protein-remodeling AAA+ ATPase that catalyzes MAD2 conformation switching

Energy Technology Data Exchange (ETDEWEB)

Ye, Qiaozhen [Ludwig Institute for Cancer Research, San Diego Branch, La Jolla, United States; Rosenberg, Scott C. [Ludwig Institute for Cancer Research, San Diego Branch, La Jolla, United States; Moeller, Arne [National Resource for Automated Molecular Microscopy, Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, United States; Speir, Jeffrey A. [National Resource for Automated Molecular Microscopy, Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, United States; Su, Tiffany Y. [Ludwig Institute for Cancer Research, San Diego Branch, La Jolla, United States; Corbett, Kevin D. [Ludwig Institute for Cancer Research, San Diego Branch, La Jolla, United States; Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, United States

2015-04-28

The AAA+ family ATPase TRIP13 is a key regulator of meiotic recombination and the spindle assembly checkpoint, acting on signaling proteins of the conserved HORMA domain family. Here we present the structure of the Caenorhabditis elegans TRIP13 ortholog PCH-2, revealing a new family of AAA+ ATPase protein remodelers. PCH-2 possesses a substrate-recognition domain related to those of the protein remodelers NSF and p97, while its overall hexameric architecture and likely structural mechanism bear close similarities to the bacterial protein unfoldase ClpX. We find that TRIP13, aided by the adapter protein p31(comet), converts the HORMA-family spindle checkpoint protein MAD2 from a signaling-active ‘closed’ conformer to an inactive ‘open’ conformer. We propose that TRIP13 and p31(comet) collaborate to inactivate the spindle assembly checkpoint through MAD2 conformational conversion and disassembly of mitotic checkpoint complexes. A parallel HORMA protein disassembly activity likely underlies TRIP13's critical regulatory functions in meiotic chromosome structure and recombination.

Interactions of plasminogen activator inhibitor-1 with vitronectin involve an extensive binding surface and induce mutual conformational rearrangements

DEFF Research Database (Denmark)

Blouse, Grant E; Dupont, Daniel Miotto; Schar, Christine R

2009-01-01

In order to explore early events during the association of plasminogen activator inhibitor-1 (PAI-1) with its cofactor vitronectin, we have applied a robust strategy that combines protein engineering, fluorescence spectroscopy, and rapid reaction kinetics. Fluorescence stopped-flow experiments de...

Conformal field theories and tensor categories. Proceedings

Energy Technology Data Exchange (ETDEWEB)

Bai, Chengming [Nankai Univ., Tianjin (China). Chern Institute of Mathematics; Fuchs, Juergen [Karlstad Univ. (Sweden). Theoretical Physics; Huang, Yi-Zhi [Rutgers Univ., Piscataway, NJ (United States). Dept. of Mathematics; Kong, Liang [Tsinghua Univ., Beijing (China). Inst. for Advanced Study; Runkel, Ingo; Schweigert, Christoph (eds.) [Hamburg Univ. (Germany). Dept. of Mathematics

2014-08-01

First book devoted completely to the mathematics of conformal field theories, tensor categories and their applications. Contributors include both mathematicians and physicists. Some long expository articles are especially suitable for beginners. The present volume is a collection of seven papers that are either based on the talks presented at the workshop ''Conformal field theories and tensor categories'' held June 13 to June 17, 2011 at the Beijing International Center for Mathematical Research, Peking University, or are extensions of the material presented in the talks at the workshop. These papers present new developments beyond rational conformal field theories and modular tensor categories and new applications in mathematics and physics. The topics covered include tensor categories from representation categories of Hopf algebras, applications of conformal field theories and tensor categories to topological phases and gapped systems, logarithmic conformal field theories and the corresponding non-semisimple tensor categories, and new developments in the representation theory of vertex operator algebras. Some of the papers contain detailed introductory material that is helpful for graduate students and researchers looking for an introduction to these research directions. The papers also discuss exciting recent developments in the area of conformal field theories, tensor categories and their applications and will be extremely useful for researchers working in these areas.

Conformal field theories and tensor categories. Proceedings

International Nuclear Information System (INIS)

Bai, Chengming; Fuchs, Juergen; Huang, Yi-Zhi; Kong, Liang; Runkel, Ingo; Schweigert, Christoph

2014-01-01

First book devoted completely to the mathematics of conformal field theories, tensor categories and their applications. Contributors include both mathematicians and physicists. Some long expository articles are especially suitable for beginners. The present volume is a collection of seven papers that are either based on the talks presented at the workshop ''Conformal field theories and tensor categories'' held June 13 to June 17, 2011 at the Beijing International Center for Mathematical Research, Peking University, or are extensions of the material presented in the talks at the workshop. These papers present new developments beyond rational conformal field theories and modular tensor categories and new applications in mathematics and physics. The topics covered include tensor categories from representation categories of Hopf algebras, applications of conformal field theories and tensor categories to topological phases and gapped systems, logarithmic conformal field theories and the corresponding non-semisimple tensor categories, and new developments in the representation theory of vertex operator algebras. Some of the papers contain detailed introductory material that is helpful for graduate students and researchers looking for an introduction to these research directions. The papers also discuss exciting recent developments in the area of conformal field theories, tensor categories and their applications and will be extremely useful for researchers working in these areas.

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

International Nuclear Information System (INIS)

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

1995-01-01

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

Conformal anomaly actions for dilaton interactions

Directory of Open Access Journals (Sweden)

Rose Luigi Delle

2014-01-01

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

Invariants for minimal conformal supergravity in six dimensions

Energy Technology Data Exchange (ETDEWEB)

Butter, Daniel [Nikhef Theory Group,Science Park 105, 1098 XG Amsterdam (Netherlands); Kuzenko, Sergei M. [School of Physics M013, The University of Western Australia,35 Stirling Highway, Crawley W.A. 6009 (Australia); Novak, Joseph; Theisen, Stefan [Max-Planck-Institut für Gravitationsphysik, Albert-Einstein-Institut,Am Mühlenberg 1, D-14476 Golm (Germany)

2016-12-15

We develop a new off-shell formulation for six-dimensional conformal supergravity obtained by gauging the 6D N=(1,0) superconformal algebra in superspace. This formulation is employed to construct two invariants for 6D N=(1,0) conformal supergravity, which contain C{sup 3} and C◻C terms at the component level. Using a conformal supercurrent analysis, we prove that these exhaust all such invariants in minimal conformal supergravity. Finally, we show how to construct the supersymmetric F◻F invariant in curved superspace.

A Mediated Moderation Model of Conformative Peer Bullying

Science.gov (United States)

Cho, Yoonju; Chung, Ock-Boon

2012-01-01

We investigated the relationship between conformative peer bullying and issues of peer conformity among adolescents. This relationship is examined through the establishment of a mediated moderation model for conformative peer bullying using structural equation modeling in a sample of 391 second-year middle school students in Seoul, South Korea. We…

{kappa}-deformed realization of D=4 conformal algebra

Energy Technology Data Exchange (ETDEWEB)

Klimek, M. [Technical Univ. of Czestochowa, Inst. of Mathematics and Computer Science, Czestochowa (Poland); Lukierski, J. [Universite de Geneve, Department de Physique Theorique, Geneve (Switzerland)

1995-07-01

We describe the generators of {kappa}-conformal transformations, leaving invariant the {kappa}-deformed d`Alembert equation. In such a way one obtains the conformal extension of-shell spin spin zero realization of {kappa}-deformed Poincare algebra. Finally the algebraic structure of {kappa}-deformed conformal algebra is discussed. (author). 23 refs.

Selective stimulation of conformational conversions in free molecules

International Nuclear Information System (INIS)

Ismailzade, G.I.; Movsumov, I.Z.; Menzeleev, M.R.; Kazymova, S.B.

2014-01-01

Application of double-resonance (RF-MW, IR-MW, MW-MW) methods to enhance studies of unstable isomeric structures was discussed. The use of infrared pump radiation to excite conformational energy levels in order to stimulate selectively conformational conversions and to correct spectral line intensities of separate conformations was substantiated. (authors)

PAK4 crystal structures suggest unusual kinase conformational movements.

Science.gov (United States)

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

2018-02-01

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

Rapid Conformational Analysis of Protein Drugs in Formulation by Hydrogen/Deuterium Exchange Mass Spectrometry (HDX-MS)

DEFF Research Database (Denmark)

Esmail Nazari, Zeinab; van de Weert, Marco; Bou-Assaf, George

2016-01-01

Hydrogen Deuterium Exchange coupled to Mass Spectrometry (HDX-MS) has become an established method for analysis of protein higher-order structure. Here, we use HDX-MS methodology based on manual Solid-Phase Extraction (SPE) to allow fast and simplified conformational analysis of proteins under...... pharmaceutically relevant formulation conditions. Of significant practical utility, the methodology allows global HDX-MS analyses to be performed without refrigeration or external cooling of the setup. In Mode 1, we used DMSO-containing solvents for SPE, allowing the HDX-MS analysis to be performed at acceptable...... in formulation, using an internal HDX reference peptide (P7I) to control for any sample-to-sample variations in back exchange. Advantages of the methodology include low sample use, optimized excipient removal using multiple solvents, and fast data acquisition. Our results indicate that the SPE-HDX-MS system can...

Elementary introduction to conformal invariance

International Nuclear Information System (INIS)

Grandati, Y.

1992-01-01

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

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....

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

Non-local Effects of Conformal Anomaly

Science.gov (United States)

Meissner, Krzysztof A.; Nicolai, Hermann

2018-03-01

It is shown that the nonlocal anomalous effective actions corresponding to the quantum breaking of the conformal symmetry can lead to observable modifications of Einstein's equations. The fact that Einstein's general relativity is in perfect agreement with all observations including cosmological or recently observed gravitational waves imposes strong restrictions on the field content of possible extensions of Einstein's theory: all viable theories should have vanishing conformal anomalies. It is shown that a complete cancellation of conformal anomalies in D=4 for both the C^2 invariant and the Euler (Gauss-Bonnet) invariant can only be achieved for N-extended supergravity multiplets with N ≥ 5.

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...

Differential Effect of Solution Conditions on the Conformation of the Actinoporins Sticholysin II and Equinatoxin II

Directory of Open Access Journals (Sweden)

EDSON V.F. FAUTH

2014-12-01

Full Text Available Actinoporins are a family of pore-forming proteins with hemolytic activity. The structural basis for such activity appears to depend on their correct folding. Such folding encompasses a phosphocholine binding site, a tryptophan-rich region and the activity-related N-terminus segment. Additionally, different solution conditions are known to be able to influence the pore formation by actinoporins, as for Sticholysin II (StnII and Equinatoxin II (EqtxII. In this context, the current work intends to characterize the influence of distinct solution conditions in the conformational behavior of these proteins through molecular dynamics (MD simulations. The obtained data offer structural insights into actinoporins dynamics in solution, characterizing its conformational behavior at the atomic level, in accordance with previous experimental data on StnII and EqtxII hemolytic activities.

Seed conformal blocks in 4D CFT

Energy Technology Data Exchange (ETDEWEB)

Echeverri, Alejandro Castedo; Elkhidir, Emtinan; Karateev, Denis [SISSA and INFN,Via Bonomea 265, I-34136 Trieste (Italy); Serone, Marco [SISSA and INFN,Via Bonomea 265, I-34136 Trieste (Italy); ICTP,Strada Costiera 11, I-34151 Trieste (Italy)

2016-02-29

We compute in closed analytical form the minimal set of “seed' conformal blocks associated to the exchange of generic mixed symmetry spinor/tensor operators in an arbitrary representation (ℓ,ℓ̄) of the Lorentz group in four dimensional conformal field theories. These blocks arise from 4-point functions involving two scalars, one (0,|ℓ−ℓ̄|) and one (|ℓ−ℓ̄|,0) spinors or tensors. We directly solve the set of Casimir equations, that can elegantly be written in a compact form for any (ℓ,ℓ̄), by using an educated ansatz and reducing the problem to an algebraic linear system. Various details on the form of the ansatz have been deduced by using the so called shadow formalism. The complexity of the conformal blocks depends on the value of p=|ℓ−ℓ̄| and grows with p, in analogy to what happens to scalar conformal blocks in d even space-time dimensions as d increases. These results open the way to bootstrap 4-point functions involving arbitrary spinor/tensor operators in four dimensional conformal field theories.

Conformal invariance in the long-range Ising model

Directory of Open Access Journals (Sweden)

Miguel F. Paulos

2016-01-01

Full Text Available We consider the question of conformal invariance of the long-range Ising model at the critical point. The continuum description is given in terms of a nonlocal field theory, and the absence of a stress tensor invalidates all of the standard arguments for the enhancement of scale invariance to conformal invariance. We however show that several correlation functions, computed to second order in the epsilon expansion, are nontrivially consistent with conformal invariance. We proceed to give a proof of conformal invariance to all orders in the epsilon expansion, based on the description of the long-range Ising model as a defect theory in an auxiliary higher-dimensional space. A detailed review of conformal invariance in the d-dimensional short-range Ising model is also included and may be of independent interest.

Conformal Invariance in the Long-Range Ising Model

CERN Document Server

Paulos, Miguel F; van Rees, Balt C; Zan, Bernardo

2016-01-01

We consider the question of conformal invariance of the long-range Ising model at the critical point. The continuum description is given in terms of a nonlocal field theory, and the absence of a stress tensor invalidates all of the standard arguments for the enhancement of scale invariance to conformal invariance. We however show that several correlation functions, computed to second order in the epsilon expansion, are nontrivially consistent with conformal invariance. We proceed to give a proof of conformal invariance to all orders in the epsilon expansion, based on the description of the long-range Ising model as a defect theory in an auxiliary higher-dimensional space. A detailed review of conformal invariance in the d-dimensional short-range Ising model is also included and may be of independent interest.

Conformal invariance in the long-range Ising model

Energy Technology Data Exchange (ETDEWEB)

Paulos, Miguel F. [CERN, Theory Group, Geneva (Switzerland); Rychkov, Slava, E-mail: slava.rychkov@lpt.ens.fr [CERN, Theory Group, Geneva (Switzerland); Laboratoire de Physique Théorique de l' École Normale Supérieure (LPTENS), Paris (France); Faculté de Physique, Université Pierre et Marie Curie (UPMC), Paris (France); Rees, Balt C. van [CERN, Theory Group, Geneva (Switzerland); Zan, Bernardo [Institute of Physics, Universiteit van Amsterdam, Amsterdam (Netherlands)

2016-01-15

We consider the question of conformal invariance of the long-range Ising model at the critical point. The continuum description is given in terms of a nonlocal field theory, and the absence of a stress tensor invalidates all of the standard arguments for the enhancement of scale invariance to conformal invariance. We however show that several correlation functions, computed to second order in the epsilon expansion, are nontrivially consistent with conformal invariance. We proceed to give a proof of conformal invariance to all orders in the epsilon expansion, based on the description of the long-range Ising model as a defect theory in an auxiliary higher-dimensional space. A detailed review of conformal invariance in the d-dimensional short-range Ising model is also included and may be of independent interest.

Conformational stability and self-association equilibrium in biologics.

Science.gov (United States)

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

2016-02-01

Biologics exist in equilibrium between native, partially denatured, and denatured conformational states. The population of any of these states is dictated by their Gibbs energy and can be altered by changes in physical and solution conditions. Some conformations have a tendency to self-associate and aggregate, an undesirable phenomenon in protein therapeutics. Conformational equilibrium and self-association are linked thermodynamic functions. Given that any associative reaction is concentration dependent, conformational stability studies performed at different protein concentrations can provide early clues to future aggregation problems. This analysis can be applied to the selection of protein variants or the identification of better formulation solutions. In this review, we discuss three different aggregation situations and their manifestation in the observed conformational equilibrium of a protein. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

Conformal Cosmology and Supernova Data

OpenAIRE

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

2000-01-01

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

Single Molecule Cluster Analysis Identifies Signature Dynamic Conformations along the Splicing Pathway

Science.gov (United States)

Blanco, Mario R.; Martin, Joshua S.; Kahlscheuer, Matthew L.; Krishnan, Ramya; Abelson, John; Laederach, Alain; Walter, Nils G.

2016-01-01

The spliceosome is the dynamic RNA-protein machine responsible for faithfully splicing introns from precursor messenger RNAs (pre-mRNAs). Many of the dynamic processes required for the proper assembly, catalytic activation, and disassembly of the spliceosome as it acts on its pre-mRNA substrate remain poorly understood, a challenge that persists for many biomolecular machines. Here, we developed a fluorescence-based Single Molecule Cluster Analysis (SiMCAn) tool to dissect the manifold conformational dynamics of a pre-mRNA through the splicing cycle. By clustering common dynamic behaviors derived from selectively blocked splicing reactions, SiMCAn was able to identify signature conformations and dynamic behaviors of multiple ATP-dependent intermediates. In addition, it identified a conformation adopted late in splicing by a 3′ splice site mutant, invoking a mechanism for substrate proofreading. SiMCAn presents a novel framework for interpreting complex single molecule behaviors that should prove widely useful for the comprehensive analysis of a plethora of dynamic cellular machines. PMID:26414013

Elucidating Ligand-Modulated Conformational Landscape of GPCRs Using Cloud-Computing Approaches.

Science.gov (United States)

Shukla, Diwakar; Lawrenz, Morgan; Pande, Vijay S

2015-01-01

G-protein-coupled receptors (GPCRs) are a versatile family of membrane-bound signaling proteins. Despite the recent successes in obtaining crystal structures of GPCRs, much needs to be learned about the conformational changes associated with their activation. Furthermore, the mechanism by which ligands modulate the activation of GPCRs has remained elusive. Molecular simulations provide a way of obtaining detailed an atomistic description of GPCR activation dynamics. However, simulating GPCR activation is challenging due to the long timescales involved and the associated challenge of gaining insights from the "Big" simulation datasets. Here, we demonstrate how cloud-computing approaches have been used to tackle these challenges and obtain insights into the activation mechanism of GPCRs. In particular, we review the use of Markov state model (MSM)-based sampling algorithms for sampling milliseconds of dynamics of a major drug target, the G-protein-coupled receptor β2-AR. MSMs of agonist and inverse agonist-bound β2-AR reveal multiple activation pathways and how ligands function via modulation of the ensemble of activation pathways. We target this ensemble of conformations with computer-aided drug design approaches, with the goal of designing drugs that interact more closely with diverse receptor states, for overall increased efficacy and specificity. We conclude by discussing how cloud-based approaches present a powerful and broadly available tool for studying the complex biological systems routinely. © 2015 Elsevier Inc. All rights reserved.

Detailed conformation dynamics and activation process of wild type c-Abl and T315I mutant

Science.gov (United States)

Yang, Li-Jun; Zhao, Wen-Hua; Liu, Qian

2014-10-01

Bcr-Abl is an important target for therapy against chronic myelogenous leukemia (CML) and acute lymphocytic leukemia (ALL). The synergistic effect between myristyl pocket and the ATP pocket has been found. But its detailed information based on molecular level still has not been achieved. In this study, conventional molecular dynamics (CMD) and target molecular dynamics (TMD) simulations were performed to explore the effect of T315I mutation on dynamics and activation process of Abl containing the N-terminal cap (Ncap). The CMD simulation results reveal the increasing flexibility of ATP pocket in kinase domain (KD) after T315I mutation which confirms the disability of ATP-pocket inhibitors to the Abl-T315I mutant. On the contrary, the T315I mutation decreased the flexibility of remote helix αI which suggests the synergistic effect between them. The mobility of farther regions containing Ncap, SH3, SH2 and SH2-KD linker were not affected by T315I mutation. The TMD simulation results show that the activation process of wild type Abl and Abl-T315I mutant experienced global conformation change. Their differences were elucidated by the activation motion of subsegments including A-loop, P-loop and Ncap. Besides, the T315I mutation caused decreasing energy barrier and increasing intermediate number in activation process, which results easier activation process. The TMD and CMD results indicate that a drug targeting only the ATP pocket is not enough to inhibit the Abl-T315I mutant. An effective way to inhibit the abnormal activity of Abl-T315I mutant is to combine the ATP-pocket inhibitors with inhibitors binding at non-ATP pockets mainly related to Ncap, SH2-KD linker and myristyl pocket.

Conformal Symmetry as a Template for QCD

Energy Technology Data Exchange (ETDEWEB)

Brodsky, S

2004-08-04

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

Conformal Symmetry as a Template for QCD

International Nuclear Information System (INIS)

Brodsky, S

2004-01-01

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

The location of splenic NKT cells favours their rapid activation by blood-borne antigen