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Sample records for conformation avec modulation

  1. Conformationally selective RNA aptamers allosterically modulate the β2-adrenoceptor.

    PubMed

    Kahsai, Alem W; Wisler, James W; Lee, Jungmin; Ahn, Seungkirl; Cahill Iii, Thomas J; Dennison, S Moses; Staus, Dean P; Thomsen, Alex R B; Anasti, Kara M; Pani, Biswaranjan; Wingler, Laura M; Desai, Hemant; Bompiani, Kristin M; Strachan, Ryan T; Qin, Xiaoxia; Alam, S Munir; Sullenger, Bruce A; Lefkowitz, Robert J

    2016-09-01

    G-protein-coupled receptor (GPCR) ligands function by stabilizing multiple, functionally distinct receptor conformations. This property underlies the ability of 'biased agonists' to activate specific subsets of a given receptor's signaling profile. However, stabilizing distinct active GPCR conformations to enable structural characterization of mechanisms underlying GPCR activation remains difficult. These challenges have accentuated the need for receptor tools that allosterically stabilize and regulate receptor function through unique, previously unappreciated mechanisms. Here, using a highly diverse RNA library combined with advanced selection strategies involving state-of-the-art next-generation sequencing and bioinformatics analyses, we identify RNA aptamers that bind a prototypical GPCR, the β2-adrenoceptor (β2AR). Using biochemical, pharmacological, and biophysical approaches, we demonstrate that these aptamers bind with nanomolar affinity at defined surfaces of the receptor, allosterically stabilizing active, inactive, and ligand-specific receptor conformations. The discovery of RNA aptamers as allosteric GPCR modulators significantly expands the diversity of ligands available to study the structural and functional regulation of GPCRs. PMID:27398998

  2. Disorder transitions and conformational diversity cooperatively modulate biological function in proteins.

    PubMed

    Zea, Diego Javier; Monzon, Alexander Miguel; Gonzalez, Claudia; Fornasari, María Silvina; Tosatto, Silvio C E; Parisi, Gustavo

    2016-06-01

    Structural differences between conformers sustain protein biological function. Here, we studied in a large dataset of 745 intrinsically disordered proteins, how ordered-disordered transitions modulate structural differences between conformers as derived from crystallographic data. We found that almost 50% of the proteins studied show no transitions and have low conformational diversity while the rest show transitions and a higher conformational diversity. In this last subset, 60% of the proteins become more ordered after ligand binding, while 40% more disordered. As protein conformational diversity is inherently connected with protein function our analysis suggests differences in structure-function relationships related to order-disorder transitions.

  3. Conformational modulation mediated by polyglutamine expansion in CAG repeat expansion disease-associated proteins.

    PubMed

    Verani, Margherita; Bustamante, Maria; Martufi, Paola; Daldin, Manuel; Cariulo, Cristina; Azzollini, Lucia; Fodale, Valentina; Puglisi, Francesca; Weiss, Andreas; Macdonald, Douglas; Petricca, Lara; Caricasole, Andrea

    2016-09-16

    We have previously reported TR-FRET based immunoassays to detect a conformational change imparted on huntingtin protein by the polyglutamine expansion, which we confirmed using biophysical methodologies. Using these immunoassays, we now report that polyglutamine expansion influences the conformational properties of other polyglutamine disease proteins, exemplified by the androgen receptor (associated with spinal bulbar muscular atrophy) and TATA binding protein (associated with spinocerebellar ataxia 17). Using artificial constructs bearing short or long polyglutamine expansions or a multimerized, unrelated epitope (mimicking the increase in anti-polyglutamine antibody epitopes present in polyglutamine repeats of increasing length) we confirmed that the conformational TR-FRET based immunoassay detects an intrinsic conformational property of polyglutamine repeats. The TR-FRET based conformational immunoassay may represent a rapid, scalable tool to identify modulators of polyglutamine-mediated conformational change in different proteins associated with CAG triplet repeat disorders. PMID:27520369

  4. Photochemical modulation of DNA conformation by organic dications.

    PubMed

    Zinchenko, Anatoly A; Tanahashi, Mao; Murata, Shizuaki

    2012-01-01

    A group of azobenzene derivatives containing two quaternary ammonium groups with various intercharge distances between them was synthesised and used to control photochemically the conformation of genomic DNA by switching the distance between cationic ammonium groups in the dications. It was found that isomerisation of either dication from the trans form to cis resulted in an increase in the dication's efficiency for DNA compaction; this is associated with a decrease in intercharge distance between ammonium groups and leads to a better match of the binder's cationic groups to adjacent phosphate groups of DNA. Ammonium dications have several important advantages over the photosensitive surfactant type of diazobenzene reported earlier: they can be used at significantly lower (>100-fold) concentrations than photosensitive surfactants, and DNA conformation control can be performed over a broader concentration range of dications. The influence of intercharge distance in photosensitive dications on photo-induced DNA binding discrimination is discussed, and the molecular mechanism is proposed. PMID:22109974

  5. Engineering a hyper-catalytic enzyme by photo-activated conformation modulation

    SciTech Connect

    Agarwal, Pratul K

    2012-01-01

    Enzyme engineering for improved catalysis has wide implications. We describe a novel chemical modification of Candida antarctica lipase B that allows modulation of the enzyme conformation to promote catalysis. Computational modeling was used to identify dynamical enzyme regions that impact the catalytic mechanism. Surface loop regions located distal to active site but showing dynamical coupling to the reaction were connected by a chemical bridge between Lys136 and Pro192, containing a derivative of azobenzene. The conformational modulation of the enzyme was achieved using two sources of light that alternated the azobenzene moiety in cis and trans conformations. Computational model predicted that mechanical energy from the conformational fluctuations facilitate the reaction in the active-site. The results were consistent with predictions as the activity of the engineered enzyme was found to be enhanced with photoactivation. Preliminary estimations indicate that the engineered enzyme achieved 8-52 fold better catalytic activity than the unmodulated enzyme.

  6. Modulations in restricted amide rotation by steric induced conformational trapping

    NASA Astrophysics Data System (ADS)

    Krishnan, V. V.; Thompson, William B.; Goto, Joy J.; Maitra, Kalyani; Maitra, Santanu

    2012-01-01

    The rotation around the amide bond in N,N-diethyl-m-toluamide (m-DEET) has been studied extensively and often used in laboratory instructions to demonstrate the phenomenon of chemical exchange. Herein, we show that a simple modification to N,N-diethyl-o-toluamide (o-DEET) significantly alters the dynamics of the restricted rotation around the amide bond due to steric interactions between the ring methyl group and the two N-ethyl groups. This alters the classic two-site exchange due to restricted rotation around the amide bond, to a three-site exchange, with the third conformation trapped at a higher-energy state compared to the other two. This often overlooked phenomenon is elucidated using variable-temperature NMR, two-dimensional exchange spectroscopy and molecular modeling studies.

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

    PubMed

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

    2016-07-19

    Thrombin exists as an ensemble of active (E) and inactive (E*) conformations that differ in their accessibility to the active site. Here we show that redistribution of the E*-E equilibrium can be achieved by perturbing the electrostatic properties of the enzyme. Removal of the negative charge of the catalytic Asp102 or Asp189 in the primary specificity site destabilizes the E form and causes a shift in the 215-217 segment that compromises substrate entrance. Solution studies and existing structures of D102N document stabilization of the E* form. A new high-resolution structure of D189A also reveals the mutant in the collapsed E* form. These findings establish a new paradigm for the control of the E*-E equilibrium in the trypsin fold. PMID:27347732

  8. Allosteric modulation of the human P-glycoprotein involves conformational changes mimicking catalytic transition intermediates.

    PubMed

    Ghosh, Pratiti; Moitra, Karobi; Maki, Nazli; Dey, Saibal

    2006-06-01

    The drug transport function of human P-glycoprotein (Pgp, ABCB1) can be inhibited by a number of pharmacological agents collectively referred to as modulators or reversing agents. In this study, we demonstrate that certain thioxanthene-based Pgp modulators with an allosteric mode of action induce a distinct conformational change in the cytosolic domain of Pgp, which alters susceptibility to proteolytic digestion. Both cis and trans-isomers of the Pgp modulator flupentixol confer considerable protection of an 80 kDa Pgp fragment against trypsin digestion, that is recognized by a polyclonal antibody specific for the NH(2)-terminal half to Pgp. The protection by flupentixol is abolished in the Pgp F983A mutant that is impaired in modulation by flupentixols, indicating involvement of the allosteric site in generating the conformational change. A similar protection to an 80 kDa fragment is conferred by ATP, its nonhydrolyzable analog ATPgammaS, and by trapping of ADP-vanadate at the catalytic domain, but not by transport substrate vinblastine or by the competitive modulator cyclosporin A, suggesting different outcomes from modulator interaction at the allosteric site and at the substrate site. In summary, we demonstrate that allosteric interaction of flupentixols with Pgp generates conformational changes that mimic catalytic transition intermediates induced by nucleotide binding and hydrolysis, which may play a crucial role in allosteric inhibition of Pgp-mediated drug transport.

  9. Functional Modulation of a G Protein-Coupled Receptor Conformational Landscape in a Lipid Bilayer.

    PubMed

    Casiraghi, Marina; Damian, Marjorie; Lescop, Ewen; Point, Elodie; Moncoq, Karine; Morellet, Nelly; Levy, Daniel; Marie, Jacky; Guittet, Eric; Banères, Jean-Louis; Catoire, Laurent J

    2016-09-01

    Mapping the conformational landscape of G protein-coupled receptors (GPCRs), and in particular how this landscape is modulated by the membrane environment, is required to gain a clear picture of how signaling proceeds. To this end, we have developed an original strategy based on solution-state nuclear magnetic resonance combined with an efficient isotope labeling scheme. This strategy was applied to a typical GPCR, the leukotriene B4 receptor BLT2, reconstituted in a lipid bilayer. Because of this, we are able to provide direct evidence that BLT2 explores a complex landscape that includes four different conformational states for the unliganded receptor. The relative distribution of the different states is modulated by ligands and the sterol content of the membrane, in parallel with the changes in the ability of the receptor to activate its cognate G protein. This demonstrates a conformational coupling between the agonist and the membrane environment that is likely to be fundamental for GPCR signaling.

  10. Advances in three-dimensional conformal radiation therapy physics with intensity modulation.

    PubMed

    Webb, S

    2000-09-01

    Intensity-modulated radiation therapy, a specific form of conformal radiation therapy, is currently attracting a lot of attention, and there are high expectations for this class of treatment techniques. Several new technologies are in development, but physicists are still working to improve the physical basis of radiation therapy.

  11. Modulation of a pre-existing conformational equilibrium tunes adenylate kinase activity.

    PubMed

    Ådén, Jörgen; Verma, Abhinav; Schug, Alexander; Wolf-Watz, Magnus

    2012-10-10

    Structural plasticity is often required for distinct microscopic steps during enzymatic reaction cycles. Adenylate kinase from Escherichia coli (AK(eco)) populates two major conformations in solution; the open (inactive) and closed (active) state, and the overall turnover rate is inversely proportional to the lifetime of the active conformation. Therefore, structural plasticity is intimately coupled to enzymatic turnover in AK(eco). Here, we probe the open to closed conformational equilibrium in the absence of bound substrate with NMR spectroscopy and molecular dynamics simulations. The conformational equilibrium in absence of substrate and, in turn, the turnover number can be modulated with mutational- and osmolyte-driven perturbations. Removal of one hydrogen bond between the ATP and AMP binding subdomains results in a population shift toward the open conformation and a resulting increase of k(cat). Addition of the osmolyte TMAO to AK(eco) results in population shift toward the closed conformation and a significant reduction of k(cat). The Michaelis constants (K(M)) scale with the change in k(cat), which follows from the influence of the population of the closed conformation for substrate binding affinity. Hence, k(cat) and K(M) are mutually dependent, and in the case of AK(eco), any perturbation that modulates k(cat) is mirrored with a proportional response in K(M). Thus, our results demonstrate that the equilibrium constant of a pre-existing conformational equilibrium directly affects enzymatic catalysis. From an evolutionary perspective, our findings suggest that, for AK(eco), there exists ample flexibility to obtain a specificity constant (k(cat)/K(M)) that commensurate with the exerted cellular selective pressure.

  12. Pancreatic cancer planning: Complex conformal vs modulated therapies.

    PubMed

    Chapman, Katherine L; Witek, Matthew E; Chen, Hongyu; Showalter, Timothy N; Bar-Ad, Voichita; Harrison, Amy S

    2016-01-01

    To compare the roles of intensity-modulated radiation therapy (IMRT) and volumetric- modulated arc therapy (VMAT) therapy as compared to simple and complex 3-dimensional chemoradiotherpy (3DCRT) planning for resectable and borderline resectable pancreatic cancer. In all, 12 patients who received postoperative radiotherapy (8) or neoadjuvant concurrent chemoradiotherapy (4) were evaluated retrospectively. Radiotherapy planning was performed for 4 treatment techniques: simple 4-field box, complex 5-field 3DCRT, 5 to 6-field IMRT, and single-arc VMAT. All volumes were approved by a single observer in accordance with Radiation Therapy Oncology Group (RTOG) Pancreas Contouring Atlas. Plans included tumor/tumor bed and regional lymph nodes to 45Gy; with tumor/tumor bed boosted to 50.4Gy, at least 95% of planning target volume (PTV) received the prescription dose. Dose-volume histograms (DVH) for multiple end points, treatment planning, and delivery time were assessed. Complex 3DCRT, IMRT, and VMAT plans significantly (p < 0.05) decreased mean kidney dose, mean liver dose, liver (V30, V35), stomach (D10%), stomach (V45), mean right kidney dose, and right kidney (V15) as compared with the simple 4-field plans that are most commonly reported in the literature. IMRT plans resulted in decreased mean liver dose, liver (V35), and left kidney (V15, V18, V20). VMAT plans decreased small bowel (D10%, D15%), small bowel (V35, V45), stomach (D10%, D15%), stomach (V35, V45), mean liver dose, liver (V35), left kidney (V15, V18, V20), and right kidney (V18, V20). VMAT plans significantly decreased small bowel (D10%, D15%), left kidney (V20), and stomach (V45) as compared with IMRT plans. Treatment planning and delivery times were most efficient for simple 4-field box and VMAT. Excluding patient setup and imaging, average treatment delivery was within 10minutes for simple and complex 3DCRT, IMRT, and VMAT treatments. This article shows significant improvements in 3D plan performance

  13. Combinational use of conformal and intensity-modulated beams in radiotherapy planning

    NASA Astrophysics Data System (ADS)

    Coolens, Catherine; Webb, Steve; Evans, Phil M.; Seco, Joao

    2003-06-01

    Intensity-modulated (IM) beam profiles computed by inverse-planning systems tend to be complex and may have multiple spatial minima and maxima. In addition to the structure originating from the treatment objectives, beam profiles might contain stochastic structure or noise and numerical artefacts, which present certain practical difficulties. The combinational use of conformal and intensity-modulated beams could be a different method of making the total fluence distribution less noisy and deliverable without compromising the advantages of IMRT. The investigation of this possibility provided the basis for this paper. A treatment-planning study was performed to compare plans combining modulated and unmodulated beams with a 5-field, equally spaced, full IMRT plan for treating the prostate and seminal vesicles in three patients. Beam angles for this study were 0°, 72°, 144°, 216° and 288°. Additionally, a study was performed on a patient with a different beam arrangement (36°, 108°, 180°, 252°, 324°) from the first study to test the obtained results. This study has demonstrated that it is possible to substitute up to two conformal beams in the originally full IMRT plan when carefully selecting the conformal beam angles. Making the anterior beam (0°) and an anterior oblique beam (between 0° and 90°) conformal leads to a reduction in the total number of monitor units and segments of about 15% and 39%, respectively. Additionally, these two open fields can be used for simpler treatment verification.

  14. Net charge per residue modulates conformational ensembles of intrinsically disordered proteins

    PubMed Central

    Mao, Albert H.; Crick, Scott L.; Vitalis, Andreas; Chicoine, Caitlin L.; Pappu, Rohit V.

    2010-01-01

    Intrinsically disordered proteins (IDPs) adopt heterogeneous ensembles of conformations under physiological conditions. Understanding the relationship between amino acid sequence and conformational ensembles of IDPs can help clarify the role of disorder in physiological function. Recent studies revealed that polar IDPs favor collapsed ensembles in water despite the absence of hydrophobic groups—a result that holds for polypeptide backbones as well. By studying highly charged polypeptides, a different archetype of IDPs, we assess how charge content modulates the intrinsic preference of polypeptide backbones for collapsed structures. We characterized conformational ensembles for a set of protamines in aqueous milieus using molecular simulations and fluorescence measurements. Protamines are arginine-rich IDPs involved in the condensation of chromatin during spermatogenesis. Simulations based on the ABSINTH implicit solvation model predict the existence of a globule-to-coil transition, with net charge per residue serving as the discriminating order parameter. The transition is supported by quantitative agreement between simulation and experiment. Local conformational preferences partially explain the observed trends of polymeric properties. Our results lead to the proposal of a schematic protein phase diagram that should enable prediction of polymeric attributes for IDP conformational ensembles using easily calculated physicochemical properties of amino acid sequences. Although sequence composition allows the prediction of polymeric properties, interresidue contact preferences of protamines with similar polymeric attributes suggest that certain details of conformational ensembles depend on the sequence. This provides a plausible mechanism for specificity in the functions of IDPs. PMID:20404210

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

    PubMed Central

    Yanamala, Naveena; Tirupula, Kalyan C; Klein-Seetharaman, Judith

    2008-01-01

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

  16. Modulation of Calmodulin Lobes by Different Targets: An Allosteric Model with Hemiconcerted Conformational Transitions

    PubMed Central

    Lai, Massimo; Brun, Denis; Edelstein, Stuart J.; Le Novère, Nicolas

    2015-01-01

    Calmodulin is a calcium-binding protein ubiquitous in eukaryotic cells, involved in numerous calcium-regulated biological phenomena, such as synaptic plasticity, muscle contraction, cell cycle, and circadian rhythms. It exibits a characteristic dumbell shape, with two globular domains (N- and C-terminal lobe) joined by a linker region. Each lobe can take alternative conformations, affected by the binding of calcium and target proteins. Calmodulin displays considerable functional flexibility due to its capability to bind different targets, often in a tissue-specific fashion. In various specific physiological environments (e.g. skeletal muscle, neuron dendritic spines) several targets compete for the same calmodulin pool, regulating its availability and affinity for calcium. In this work, we sought to understand the general principles underlying calmodulin modulation by different target proteins, and to account for simultaneous effects of multiple competing targets, thus enabling a more realistic simulation of calmodulin-dependent pathways. We built a mechanistic allosteric model of calmodulin, based on an hemiconcerted framework: each calmodulin lobe can exist in two conformations in thermodynamic equilibrium, with different affinities for calcium and different affinities for each target. Each lobe was allowed to switch conformation on its own. The model was parameterised and validated against experimental data from the literature. In spite of its simplicity, a two-state allosteric model was able to satisfactorily represent several sets of experiments, in particular the binding of calcium on intact and truncated calmodulin and the effect of different skMLCK peptides on calmodulin’s saturation curve. The model can also be readily extended to include multiple targets. We show that some targets stabilise the low calcium affinity T state while others stabilise the high affinity R state. Most of the effects produced by calmodulin targets can be explained as modulation

  17. Retrospective evaluation of dosimetric quality for prostate carcinomas treated with 3D conformal, intensity modulated and volumetric modulated arc radiotherapy

    SciTech Connect

    Crowe, Scott B; Kairn, Tanya; Middlebrook, Nigel; Hill, Brendan; Christie, David R H; Knight, Richard T; Kenny, John; Langton, Christian M; Trapp, Jamie V

    2013-12-15

    This study examines and compares the dosimetric quality of radiotherapy treatment plans for prostate carcinoma across a cohort of 163 patients treated across five centres: 83 treated with three-dimensional conformal radiotherapy (3DCRT), 33 treated with intensity modulated radiotherapy (IMRT) and 47 treated with volumetric modulated arc therapy (VMAT). Treatment plan quality was evaluated in terms of target dose homogeneity and organs at risk (OAR), through the use of a set of dose metrics. These included the mean, maximum and minimum doses; the homogeneity and conformity indices for the target volumes; and a selection of dose coverage values that were relevant to each OAR. Statistical significance was evaluated using two-tailed Welch's T-tests. The Monte Carlo DICOM ToolKit software was adapted to permit the evaluation of dose metrics from DICOM data exported from a commercial radiotherapy treatment planning system. The 3DCRT treatment plans offered greater planning target volume dose homogeneity than the other two treatment modalities. The IMRT and VMAT plans offered greater dose reduction in the OAR: with increased compliance with recommended OAR dose constraints, compared to conventional 3DCRT treatments. When compared to each other, IMRT and VMAT did not provide significantly different treatment plan quality for like-sized tumour volumes. This study indicates that IMRT and VMAT have provided similar dosimetric quality, which is superior to the dosimetric quality achieved with 3DCRT.

  18. Integrable perturbations of conformal field theories and Yetter-Drinfeld modules

    SciTech Connect

    Bücher, David; Runkel, Ingo

    2014-11-15

    In this paper we relate a problem in representation theory — the study of Yetter-Drinfeld modules over certain braided Hopf algebras — to a problem in two-dimensional quantum field theory, namely, the identification of integrable perturbations of a conformal field theory. A prescription that parallels Lusztig's construction allows one to read off the quantum group governing the integrable symmetry. As an example, we illustrate how the quantum group for the loop algebra of sl(2) appears in the integrable structure of the perturbed uncompactified and compactified free boson.

  19. Small molecule modulation of nuclear receptor conformational dynamics: implications for function and drug discovery.

    PubMed

    Kojetin, Douglas J; Burris, Thomas P

    2013-01-01

    Nuclear receptors are targets for a wide range of ligands, both natural and synthetic, that regulate their activity and provide a means to pharmacologically modulate the receptor. Recent emphasis in the nuclear receptor field has focused on selective nuclear receptor modulators, which can display graded transcriptional responses and tissue selective pharmacological responses that deviate from the prototypical agonist or antagonist. Understanding the molecular mechanism of action of these selective modulators will provide significant insight toward the development of the next generation of modulators. Although most nuclear receptor structural studies have primarily focused on obtaining ligand-receptor cocrystal structures, recent studies implicate an important role for protein dynamics in the mechanism of action of nuclear receptor ligands. Here we review nuclear receptor studies reporting how ligands modulate the conformational dynamics of the nuclear receptor ligand-binding domain (LBD). A particular emphasis is placed on protein NMR and hydrogen/deuterium exchange (HDX) techniques and how they provide complementary information that, when combined with crystallography, provide detailed insight into the function of nuclear receptors.

  20. Four types of (super)conformal mechanics: D-module reps and invariant actions

    NASA Astrophysics Data System (ADS)

    Holanda, N. L.; Toppan, F.

    2014-06-01

    (Super)conformal mechanics in one dimension is induced by parabolic or hyperbolic/trigonometric transformations, either homogeneous (for a scaling dimension λ) or inhomogeneous (at λ = 0, with ρ an inhomogeneity parameter). Four types of (super)conformal actions are thus obtained. With the exclusion of the homogeneous parabolic case, dimensional constants are present. Both the inhomogeneity and the insertion of λ generalize the construction of Papadopoulos [Class. Quant. Grav. 30, 075018 (2013); e-print arXiv:1210.1719]. Inhomogeneous D-module reps are presented for the d = 1 superconformal algebras osp(1|2), sl(2|1), B(1, 1), and A(1, 1). For centerless superVirasoro algebras, D-module reps are presented (in the homogeneous case for N=1,2,3,4; in the inhomogeneous case for N=1,2,3). The four types of d = 1 superconformal actions are derived for N=1,2,4 systems. When N=4, the homogeneously induced actions are D(2, 1; α)-invariant (α is critically linked to λ); the inhomogeneously induced actions are A(1, 1)-invariant.

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

    PubMed

    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.

  2. Modulation of conformational changes in helix 69 mutants by pseudouridine modifications

    PubMed Central

    Jiang, Jun; Kharel, Daya Nidhi; Chow, Christine S.

    2015-01-01

    Centrally located at the ribosomal subunit interface and mRNA tunnel, helix 69 (H69) from 23S rRNA participates in key steps of translation. Ribosome activity is influenced by three pseudouridine modifications, which modulate the structure and conformational behavior of H69. To understand how H69 is affected by the presence of pseudouridine in combination with sequence changes, the biophysical properties of wild-type H69 and representative mutants (A1912G, U1917C, and A1919G) were examined. Results from NMR and circular dichroism spectroscopy indicate that pH-dependent structural changes of wild-type H69 and the chosen mutants are modulated by pseudouridine and loop sequence. The effects of the mutations on global stability of H69 are negligible, however, pseudouridine stabilizes H69 at low pH conditions. Alterations to induced conformational changes of H69 likely result in compromised function, as indicated by previous biological studies. PMID:25800680

  3. Interaction between cyclodextrin and neuronal membrane results in modulation of GABAA receptor conformational transitions

    PubMed Central

    Pytel, Maria; Mercik, Katarzyna; Mozrzymas, Jerzy W

    2006-01-01

    Cyclodextrins (CDs) are nanostructures widely applied in biotechnology and chemistry. Owing to partially hydrophobic character, CDs interact with biological membranes. While the mechanisms of CDs interactions with lipids were widely studied, their effects on proteins are less understood. In the present study we investigated the effects of beta cyclodextrin (βCD) on GABAA receptor (GABAAR) gating. To reliably resolve the kinetics of conformational transitions, currents were elicited by ultrafast gamma-aminobutyric acid (GABA) applications to outside-out patches from rat cultured hippocampal neurons. βCD increased the amplitude of responses to saturating GABA concentration ([GABA]) in a dose-dependent manner and this effect was accompanied by profound alterations in the current kinetics. Current deactivation was slowed down by βCD but this effect was biphasic with a maximum at around 0.5 mM βCD. While the fast deactivation time constant was monotonically slowed down within considered βCD concentration range, the slow component first increased and then, at millimolar βCD concentration, decreased. The rate and extent of desensitization was decreased by βCD in a dose-dependent manner. The analysis of current responses to nonsaturating [GABA] indicated that βCD affected the GABAAR agonist binding site by slowing down the unbinding rate. Modulation of GABAAR desensitization and binding showed different concentration-dependence suggesting different modualtory sites with higher affinity of the latter one. All the βCD effects were fully reversible indicating that cholesterol uptake into βCD was not the primary mechanism. We conclude that βCD is a strong modulator of GABAAR conformational transitions. PMID:16702996

  4. Interaction between cyclodextrin and neuronal membrane results in modulation of GABA(A) receptor conformational transitions.

    PubMed

    Pytel, Maria; Mercik, Katarzyna; Mozrzymas, Jerzy W

    2006-06-01

    Cyclodextrins (CDs) are nanostructures widely applied in biotechnology and chemistry. Owing to partially hydrophobic character, CDs interact with biological membranes. While the mechanisms of CDs interactions with lipids were widely studied, their effects on proteins are less understood. In the present study we investigated the effects of beta cyclodextrin (betaCD) on GABA(A) receptor (GABA(A)R) gating. To reliably resolve the kinetics of conformational transitions, currents were elicited by ultrafast gamma-aminobutyric acid (GABA) applications to outside-out patches from rat cultured hippocampal neurons. betaCD increased the amplitude of responses to saturating GABA concentration ([GABA]) in a dose-dependent manner and this effect was accompanied by profound alterations in the current kinetics. Current deactivation was slowed down by betaCD but this effect was biphasic with a maximum at around 0.5 mM betaCD. While the fast deactivation time constant was monotonically slowed down within considered betaCD concentration range, the slow component first increased and then, at millimolar betaCD concentration, decreased. The rate and extent of desensitization was decreased by betaCD in a dose-dependent manner. The analysis of current responses to nonsaturating [GABA] indicated that betaCD affected the GABA(A)R agonist binding site by slowing down the unbinding rate. Modulation of GABA(A)R desensitization and binding showed different concentration-dependence suggesting different modualtory sites with higher affinity of the latter one. All the betaCD effects were fully reversible indicating that cholesterol uptake into betaCD was not the primary mechanism. We conclude that betaCD is a strong modulator of GABA(A)R conformational transitions.

  5. Whole pelvic radiotherapy for prostate cancer using 3D conformal and intensity-modulated radiotherapy

    SciTech Connect

    Ashman, Jonathan B.; Zelefsky, Michael J. . E-mail: zelefskm@mskcc.org; Hunt, Margie S.; Leibel, Steven A.; Fuks, Zvi

    2005-11-01

    Purpose: To investigate the correlations between observed clinical morbidity and dosimetric parameters for whole pelvic radiotherapy (WPRT) for prostate cancer using either three-dimensional conformal radiotherapy (3D-CRT) or intensity-modulated radiotherapy (IMRT). Methods and Materials: Between December 1996 and January 2002, 27 patients with prostate adenocarcinoma were treated with conformal WPRT as part of their definitive treatment. WPRT was delivered with 3D-CRT in 14 patients and with IMRT in 13 patients. For each of the patients treated with IMRT, optimized conventional two-dimensional (2D) and 3D-CRT plans were retrospectively generated for the whole pelvic phase of the treatment. Dose-volume histograms for the bowel, bladder, and rectum were compared for the three techniques. Acute toxicities were evaluated for all 27 patients, and late toxicities were evaluated for 25 patients with sufficient follow-up. Toxicities were scored according to the Radiation Therapy Oncology Group morbidity grading scales. Median follow-up was 30 months. Results: Three-dimensional-CRT resulted in a 40% relative reduction (p < 0.001) in the volume of bowel receiving 45 Gy compared with 2D, and IMRT provided a further 60% reduction relative to 3D-CRT (p < 0.001). Compared with either 2D or 3D-CRT, IMRT reduced the volume of rectum receiving 45 Gy by 90% (p < 0.001). Overall, 9 patients (33%) experienced acute Grade 2 gastrointestinal (GI) toxicity, and only 1 of these patients was treated with IMRT. Antidiarrhea medication was required for 6 patients (22%). However, 5 of these 6 patients also received chemotherapy, and none were treated with IMRT. No Grade 3 or higher acute or late GI toxicities were observed. No cases of late radiation enteritis were observed. Acute and late genitourinary toxicity did not appear significantly increased by the addition of conformal WPRT. Conclusions: Compared to conventional 2D planning, conformal planning for WPRT resulted in significant

  6. Cardiac Exposure in the Dynamic Conformal Arc Therapy, Intensity-Modulated Radiotherapy and Volumetric Modulated Arc Therapy of Lung Cancer

    PubMed Central

    Ming, Xin; Feng, Yuanming; Liu, Huan; Zhang, Ying; Zhou, Li; Deng, Jun

    2015-01-01

    Purpose To retrospectively evaluate the cardiac exposure in three cohorts of lung cancer patients treated with dynamic conformal arc therapy (DCAT), intensity-modulated radiotherapy (IMRT), or volumetric modulated arc therapy (VMAT) at our institution in the past seven years. Methods and Materials A total of 140 lung cancer patients were included in this institutional review board approved study: 25 treated with DCAT, 70 with IMRT and 45 with VMAT. All plans were generated in a same commercial treatment planning system and have been clinically accepted and delivered. The dose distribution to the heart and the effects of tumor laterality, the irradiated heart volume and the beam-to-heart distance on the cardiac exposure were investigated. Results The mean dose to the heart among all 140 plans was 4.5 Gy. Specifically, the heart received on average 2.3, 5.2 and 4.6 Gy in the DCAT, IMRT and VMAT plans, respectively. The mean heart doses for the left and right lung tumors were 4.1 and 4.8 Gy, respectively. No patients died with evidence of cardiac disease. Three patients (2%) with preexisting cardiac condition developed cardiac disease after treatment. Furthermore, the cardiac exposure was found to increase linearly with the irradiated heart volume while decreasing exponentially with the beam-to-heart distance. Conclusions Compared to old technologies for lung cancer treatment, modern radiotherapy treatment modalities demonstrated better heart sparing. But the heart dose in lung cancer radiotherapy is still higher than that in the radiotherapy of breast cancer and Hodgkin’s disease where cardiac complications have been extensively studied. With strong correlations of mean heart dose with beam-to-heart distance and irradiated heart volume, cautions should be exercised to avoid long-term cardiac toxicity in the lung cancer patients undergoing radiotherapy. PMID:26630566

  7. Exploring the active conformation of cyclohexane carboxylate positive allosteric modulators of the type 4 metabotropic glutamate receptor.

    PubMed

    Rovira, Xavier; Harrak, Youssef; Trapero, Ana; González-Bulnes, Patricia; Malhaire, Fanny; Pin, Jean-Philippe; Goudet, Cyril; Giraldo, Jesús; Llebaria, Amadeu

    2014-12-01

    The active conformation of a family of metabotropic glutamate receptor subtype 4 (mGlu4 ) positive allosteric modulators (PAMs) with the cyclohexane 1,2-dicarboxylic scaffold present in cis-2-(3,5-dichlorophenylcarbamoyl)cyclohexanecarboxylic acid (VU0155041) was investigated by testing structurally similar six-membered ring compounds that have a locked conformation. The norbornane and cyclohexane molecules designed as mGlu4 conformational probes and the enantiomers of the trans diastereomer were computationally characterized and tested in mGlu4 pharmacological assays. The results support a VU0155041 active conformation, with the chair cyclohexane having the aromatic amide substituent in an axial position and the carboxylate in an equatorial position. Moreover, the receptor displays enantiomeric discrimination of the chiral PAMs. The constructed pharmacophore characterized a highly constrained mGlu4 allosteric binding site, thus providing a step forward in structure-based drug design for mGlu4 PAMs.

  8. Real-time visualization of conformational changes within single MloK1 cyclic nucleotide-modulated channels.

    PubMed

    Rangl, Martina; Miyagi, Atsushi; Kowal, Julia; Stahlberg, Henning; Nimigean, Crina M; Scheuring, Simon

    2016-09-20

    Eukaryotic cyclic nucleotide-modulated (CNM) ion channels perform various physiological roles by opening in response to cyclic nucleotides binding to a specialized cyclic nucleotide-binding domain. Despite progress in structure-function analysis, the conformational rearrangements underlying the gating of these channels are still unknown. Here, we image ligand-induced conformational changes in single CNM channels from Mesorhizobium loti (MloK1) in real-time, using high-speed atomic force microscopy. In the presence of cAMP, most channels are in a stable conformation, but a few molecules dynamically switch back and forth (blink) between at least two conformations with different heights. Upon cAMP depletion, more channels start blinking, with blinking heights increasing over time, suggestive of slow, progressive loss of ligands from the tetramer. We propose that during gating, MloK1 transitions from a set of mobile conformations in the absence to a stable conformation in the presence of ligand and that these conformations are central for gating the pore.

  9. Real-time visualization of conformational changes within single MloK1 cyclic nucleotide-modulated channels

    PubMed Central

    Rangl, Martina; Miyagi, Atsushi; Kowal, Julia; Stahlberg, Henning; Nimigean, Crina M.; Scheuring, Simon

    2016-01-01

    Eukaryotic cyclic nucleotide-modulated (CNM) ion channels perform various physiological roles by opening in response to cyclic nucleotides binding to a specialized cyclic nucleotide-binding domain. Despite progress in structure-function analysis, the conformational rearrangements underlying the gating of these channels are still unknown. Here, we image ligand-induced conformational changes in single CNM channels from Mesorhizobium loti (MloK1) in real-time, using high-speed atomic force microscopy. In the presence of cAMP, most channels are in a stable conformation, but a few molecules dynamically switch back and forth (blink) between at least two conformations with different heights. Upon cAMP depletion, more channels start blinking, with blinking heights increasing over time, suggestive of slow, progressive loss of ligands from the tetramer. We propose that during gating, MloK1 transitions from a set of mobile conformations in the absence to a stable conformation in the presence of ligand and that these conformations are central for gating the pore. PMID:27647260

  10. Real-time visualization of conformational changes within single MloK1 cyclic nucleotide-modulated channels.

    PubMed

    Rangl, Martina; Miyagi, Atsushi; Kowal, Julia; Stahlberg, Henning; Nimigean, Crina M; Scheuring, Simon

    2016-01-01

    Eukaryotic cyclic nucleotide-modulated (CNM) ion channels perform various physiological roles by opening in response to cyclic nucleotides binding to a specialized cyclic nucleotide-binding domain. Despite progress in structure-function analysis, the conformational rearrangements underlying the gating of these channels are still unknown. Here, we image ligand-induced conformational changes in single CNM channels from Mesorhizobium loti (MloK1) in real-time, using high-speed atomic force microscopy. In the presence of cAMP, most channels are in a stable conformation, but a few molecules dynamically switch back and forth (blink) between at least two conformations with different heights. Upon cAMP depletion, more channels start blinking, with blinking heights increasing over time, suggestive of slow, progressive loss of ligands from the tetramer. We propose that during gating, MloK1 transitions from a set of mobile conformations in the absence to a stable conformation in the presence of ligand and that these conformations are central for gating the pore. PMID:27647260

  11. Intensity-Modulated vs. Conformal Radiotherapy of Parotid Gland Tumors: Potential Impact on Hearing Loss

    SciTech Connect

    Lamers-Kuijper, E. Schwarz, M.; Rasch, C.; Mijnheer, B.

    2007-01-01

    In 3-dimensional (3D) conformal radiotherapy of parotid gland tumors, little effort is made to avoid the auditory system or the oral cavity. Damage may occur when the ear is located inside the treatment field. The purpose of this study was to design and evaluate an intensity-modulation radiotherapy (IMRT) class solution, and to compare this technique to a 3D conformal approach with respect to hearing loss. Twenty patients with parotid gland cancer were retrospectively planned with 2 different techniques using the original planning target volume (PTV). First, a conventional technique using a wedged beam pair was applied, yielding a dose distribution conformal to the shape of the PTV. Next, an IMRT technique using a fluence map optimization with predefined constraints was designed. A dose of 66 Gy in the PTV was given at the International Commission on Radiation Units and Measures (ICRU) dose prescription point. Dose-volume histograms of the PTV and organs at risk (OARs), such as auditory system, oral cavity, and spinal cord, were compared. The dose in the OARs was lower in the IMRT plans. The mean volume of the middle ear receiving a dose higher than 50 Gy decreased from 66.5% to 33.4%. The mean dose in the oral cavity decreased from 19.4 Gy to 16.6 Gy. The auditory system can be spared if the distance between the inner ear and the PTV is 0.6 cm or larger, and if the overlap between the middle ear and the PTV is smaller than 10%. The maximum dose in the spinal cord was below 40 Gy in all treatment plans. The mean volume of the PTV receiving less than 95% of the prescribed dose increased in the IMRT plan slightly from 3.3% to 4.3 % (p = 0.01). The mean volume receiving more than 107% increased from 0.9% to 2.5% (p = 0.02). It can be concluded that the auditory system, as well as the oral cavity, can be spared with IMRT, but at the cost of a slightly larger dose inhomogeneity in the PTV. The IMRT technique can therefore, in most cases, be recommended as the treatment

  12. Dosimetric effect of Elekta Beam Modulator micromultileaf in three-dimensional conformal radiotherapy and intensity-modulated radiotherapy for prostate cancer

    SciTech Connect

    Carosi, Alessandra Ingrosso, Gianluca; Ponti, Elisabetta; Tolu, Barbara; Murgia, Alessandra; Cristino, Daniela di; Santoni, Riccardo

    2014-07-01

    The purpose of this study is to analyze the dosimetric effect of Elekta Beam Modulator in 3-dimensional conformal radiation therapy (3DCRT) and in intensity-modulated radiation therapy (IMRT) for localized prostate cancer. We compared treatment plans developed with 2 different Elekta multileaf collimators (MLC): Beam Modulator micro-MLC (mMLC) (4-mm leaf width at the isocenter) and standard MLC (10-mm leaf width at the isocenter). The comparison was performed for 15 patients with localized prostate cancer in 3DCRT and IMRT delivery; a total of 60 treatment plans were processed. The dose-volume histograms were used to provide the quantitative comparison between plans. In particular, we analyzed differences between rectum and bladder sparing in terms of a set of appropriate Vx (percentage of organ at risk [OAR] volume receiving the x dose) and differences between target conformity and coverage in terms of coverage factor and conformation number. Our analysis demonstrates that in 3DCRT there is an advantage in the use of Elekta Beam Modulator mMLC in terms of organ sparing; in particular, a significant decrease in rectal V{sub 60} and V{sub 50} (p = 0.001) and in bladder V{sub 70} and V{sub 65} (p = 0.007 and 0.002, respectively) was found. Moreover, a better target dose conformity was obtained (p = 0.002). IMRT plans comparison demonstrated no significant differences between the use of the 4 or 10-mm MLCs. Our analysis shows that in 3DCRT the use of the Elekta Beam Modulator mMLC gives a gain in target conformity and in OARs dose sparing whereas in IMRT plans there is no advantage.

  13. Estimating the costs of intensity-modulated and 3-dimensional conformal radiotherapy in Ontario

    PubMed Central

    Yong, J.H.E.; McGowan, T.; Redmond-Misner, R.; Beca, J.; Warde, P.; Gutierrez, E.; Hoch, J.S.

    2016-01-01

    Background Radiotherapy is a common treatment for many cancers, but up-to-date estimates of the costs of radiotherapy are lacking. In the present study, we estimated the unit costs of intensity-modulated radiotherapy (imrt) and 3-dimensional conformal radiotherapy (3D-crt) in Ontario. Methods An activity-based costing model was developed to estimate the costs of imrt and 3D-crt in prostate cancer. It included the costs of equipment, staff, and supporting infrastructure. The framework was subsequently adapted to estimate the costs of radiotherapy in breast cancer and head-and-neck cancer. We also tested various scenarios by varying the program maturity and the use of volumetric modulated arc therapy (vmat) alongside imrt. Results From the perspective of the health care system, treating prostate cancer with imrt and 3D-crt respectively cost $12,834 and $12,453 per patient. The cost of radiotherapy ranged from $5,270 to $14,155 and was sensitive to analytic perspective, radiation technique, and disease site. Cases of head-and-neck cancer were the most costly, being driven by treatment complexity and fractions per treatment. Although imrt was more costly than 3D-crt, its cost will likely decline over time as programs mature and vmat is incorporated. Conclusions Our costing model can be modified to estimate the costs of 3D-crt and imrt for various disease sites and settings. The results demonstrate the important role of capital costs in studies of radiotherapy cost from a health system perspective, which our model can accommodate. In addition, our study established the need for future analyses of imrt cost to consider how vmat affects time consumption. PMID:27330359

  14. Carcinoma of the anal canal: Intensity modulated radiation therapy (IMRT) versus three-dimensional conformal radiation therapy (3DCRT)

    PubMed Central

    Sale, Charlotte; Moloney, Phillip; Mathlum, Maitham

    2013-01-01

    Introduction Patients with anal canal carcinoma treated with standard conformal radiotherapy frequently experience severe acute and late toxicity reactions to the treatment area. Roohipour et al. (Dis Colon Rectum 2008; 51: 147–53) stated a patient's tolerance of chemoradiation to be an important prediction of treatment success. A new intensity modulated radiation therapy (IMRT) technique for anal carcinoma cases has been developed at the Andrew Love Cancer Centre aimed at reducing radiation to surrounding healthy tissue. Methods A same-subject repeated measures design was used for this study, where five anal carcinoma cases at the Andrew Love Cancer Centre were selected. Conformal and IMRT plans were generated and dosimetric evaluations were performed. Each plan was prescribed a total of 54 Gray (Gy) over a course of 30 fractions to the primary site. Results The IMRT plans resulted in improved dosimetry to the planning target volume (PTV) and reduction in radiation to the critical structures (bladder, external genitalia and femoral heads). Statistically there was no difference between the IMRT and conformal plans in the dose to the small and large bowel; however, the bowel IMRT dose–volume histogram (DVH) doses were consistently lower. Conclusion The IMRT plans were superior to the conformal plans with improved dose conformity and reduced radiation to the surrounding healthy tissue. Anecdotally it was found that patients tolerated the IMRT treatment better than the three-dimensional (3D) conformal radiation therapy. This study describes and compares the planning techniques. PMID:26229623

  15. Carcinoma of the anal canal: Intensity modulated radiation therapy (IMRT) versus three-dimensional conformal radiation therapy (3DCRT)

    SciTech Connect

    Sale, Charlotte; Moloney, Phillip; Mathlum, Maitham

    2013-12-15

    Patients with anal canal carcinoma treated with standard conformal radiotherapy frequently experience severe acute and late toxicity reactions to the treatment area. Roohipour et al. (Dis Colon Rectum 2008; 51: 147–53) stated a patient's tolerance of chemoradiation to be an important prediction of treatment success. A new intensity modulated radiation therapy (IMRT) technique for anal carcinoma cases has been developed at the Andrew Love Cancer Centre aimed at reducing radiation to surrounding healthy tissue. A same-subject repeated measures design was used for this study, where five anal carcinoma cases at the Andrew Love Cancer Centre were selected. Conformal and IMRT plans were generated and dosimetric evaluations were performed. Each plan was prescribed a total of 54 Gray (Gy) over a course of 30 fractions to the primary site. The IMRT plans resulted in improved dosimetry to the planning target volume (PTV) and reduction in radiation to the critical structures (bladder, external genitalia and femoral heads). Statistically there was no difference between the IMRT and conformal plans in the dose to the small and large bowel; however, the bowel IMRT dose–volume histogram (DVH) doses were consistently lower. The IMRT plans were superior to the conformal plans with improved dose conformity and reduced radiation to the surrounding healthy tissue. Anecdotally it was found that patients tolerated the IMRT treatment better than the three-dimensional (3D) conformal radiation therapy. This study describes and compares the planning techniques.

  16. Compact multileaf collimator for conformal and intensity modulated fast neutron therapy: electromechanical design and validation.

    PubMed

    Farr, J B; Maughan, R L; Yudelev, M; Blosser, E; Brandon, J; Horste, T; Forman, J D

    2006-09-01

    The electromechanical properties of a 120-leaf, high-resolution, computer-controlled, fast neutron multileaf collimator (MLC) are presented. The MLC replaces an aging, manually operated multirod collimator. The MLC leaves project 5 mm in the isocentric plane perpendicular to the beam axis. A taper is included on the leaves matching beam divergence along one axis. The 5-mm leaf projection width is chosen to give high-resolution conformality across the entire field. The maximum field size provided is 30 x 30 cm2. To reduce the interleaf transmission a 0.254-mm blocking step is included. End-leaf steps totaling 0.762 mm are also provided allowing opposing leaves to close off within the primary radiation beam. The neutron MLC also includes individual 45 degrees and 60 degrees automated universal tungsten wedges. The automated high-resolution neutron collimation provides an increase in patient throughput capacity, enables a new modality, intensity modulated neutron therapy, and limits occupational radiation exposure by providing remote operation from a shielded console area. PMID:17022226

  17. Disease Control After Reduced Volume Conformal and Intensity Modulated Radiation Therapy for Childhood Craniopharyngioma

    SciTech Connect

    Merchant, Thomas E.; Kun, Larry E.; Hua, Chia-Ho; Wu, Shengjie; Xiong, Xiaoping; Sanford, Robert A.; Boop, Frederick A.

    2013-03-15

    Purpose: To estimate the rate of disease control after conformal radiation therapy using reduced clinical target volume (CTV) margins and to determine factors that predict for tumor progression. Methods and Materials: Eighty-eight children (median age, 8.5 years; range, 3.2-17.6 years) received conformal or intensity modulated radiation therapy between 1998 and 2009. The study group included those prospectively treated from 1998 to 2003, using a 10-mm CTV, defined as the margin surrounding the solid and cystic tumor targeted to receive the prescription dose of 54 Gy. The CTV margin was subsequently reduced after 2003, yielding 2 groups of patients: those treated with a CTV margin greater than 5 mm (n=26) and those treated with a CTV margin less than or equal to 5 mm (n=62). Disease progression was estimated on the basis of additional variables including sex, race, extent of resection, tumor interventions, target volume margins, and frequency of weekly surveillance magnetic resonance (MR) imaging during radiation therapy. Median follow-up was 5 years. Results: There was no difference between progression-free survival rates based on CTV margins (>5 mm vs ≤5 mm) at 5 years (88.1% ± 6.3% vs 96.2% ± 4.4% [P=.6386]). There were no differences based on planning target volume (PTV) margins (or combined CTV plus PTV margins). The PTV was systematically reduced from 5 to 3 mm during the time period of the study. Factors predictive of superior progression-free survival included Caucasian race (P=.0175), no requirement for cerebrospinal fluid shunting (P=.0066), and number of surveillance imaging studies during treatment (P=.0216). Patients whose treatment protocol included a higher number of weekly surveillance MR imaging evaluations had a lower rate of tumor progression. Conclusions: These results suggest that targeted volume reductions for radiation therapy using smaller margins are feasible and safe but require careful monitoring. We are currently investigating

  18. p97 Disease Mutations Modulate Nucleotide-Induced Conformation to Alter Protein-Protein Interactions.

    PubMed

    Bulfer, Stacie L; Chou, Tsui-Fen; Arkin, Michelle R

    2016-08-19

    The AAA+ ATPase p97/VCP adopts at least three conformations that depend on the binding of ADP and ATP and alter the orientation of the N-terminal protein-protein interaction (PPI) domain into "up" and "down" conformations. Point mutations that cause multisystem proteinopathy 1 (MSP1) are found at the interface of the N domain and D1-ATPase domain and potentially alter the conformational preferences of p97. Additionally, binding of "adaptor" proteins to the N-domain regulates p97's catalytic activity. We propose that p97/adaptor PPIs are coupled to p97 conformational states. We evaluated the binding of nucleotides and the adaptor proteins p37 and p47 to wild-type p97 and MSP1 mutants. Notably, p47 and p37 bind 8-fold more weakly to the ADP-bound conformation of wild-type p97 compared to the ATP-bound conformation. However, MSP1 mutants lose this nucleotide-induced conformational coupling because they destabilize the ADP-bound, "down" conformation of the N-domain. Loss in conformation coupling to PPIs could contribute to the mechanism of MSP1. PMID:27267671

  19. Outcomes After Intensity-Modulated Versus Conformal Radiotherapy in Older Men With Nonmetastatic Prostate Cancer

    SciTech Connect

    Bekelman, Justin E.; Mitra, Nandita; Efstathiou, Jason; Liao Kaijun; Sunderland, Robert; Yeboa, Deborah N.; Armstrong, Katrina

    2011-11-15

    Purpose: There is little evidence comparing complications after intensity-modulated (IMRT) vs. three-dimensional conformal radiotherapy (CRT) for prostate cancer. The study objective was to test the hypothesis that IMRT, compared with CRT, is associated with a reduction in bowel, urinary, and erectile complications in elderly men with nonmetastatic prostate cancer. Methods and Materials: We undertook an observational cohort study using registry and administrative claims data from the SEER-Medicare database. We identified men aged 65 years or older diagnosed with nonmetastatic prostate cancer in the United States between 2002 and 2004 who received IMRT (n = 5,845) or CRT (n = 6,753). The primary outcome was a composite measure of bowel complications. Secondary outcomes were composite measures of urinary and erectile complications. We also examined specific subsets of bowel (proctitis/hemorrhage) and urinary (cystitis/hematuria) events within the composite complication measures. Results: IMRT was associated with reductions in composite bowel complications (24-month cumulative incidence 18.8% vs. 22.5%; hazard ratio [HR] 0.86; 95% confidence interval [CI], 0.79-0.93) and proctitis/hemorrhage (HR 0.78; 95% CI, 0.64-0.95). IMRT was not associated with rates of composite urinary complications (HR 0.93; 95% CI, 0.83-1.04) or cystitis/hematuria (HR 0.94; 95% CI, 0.83-1.07). The incidence of erectile complications involving invasive procedures was low and did not differ significantly between groups, although IMRT was associated with an increase in new diagnoses of impotence (HR 1.27, 95% CI, 1.14-1.42). Conclusion: IMRT is associated with a small reduction in composite bowel complications and proctitis/hemorrhage compared with CRT in elderly men with nonmetastatic prostate cancer.

  20. Comparative outcomes for three-dimensional conformal versus intensity-modulated radiation therapy for esophageal cancer.

    PubMed

    Freilich, J; Hoffe, S E; Almhanna, K; Dinwoodie, W; Yue, B; Fulp, W; Meredith, K L; Shridhar, R

    2015-01-01

    Emerging data suggests a benefit for using intensity modulated radiation therapy (IMRT) for the management of esophageal cancer. We retrospectively reviewed patients treated at our institution who received definitive or preoperative chemoradiation with either IMRT or 3D conformal radiation therapy (3DCRT) between October 2000 and January 2012. Kaplan Meier analysis and the Cox proportional hazard model were used to evaluate survival outcomes. We evaluated a total of 232 patients (138 IMRT, 94 3DCRT) who received a median dose of 50.4 Gy (range, 44-64.8) to gross disease. Median follow up for all patients, IMRT patients alone, and 3DCRT patients alone was 18.5 (range, 2.5-124.2), 16.5 (range, 3-59), and 25.9 months (range, 2.5-124.2), respectively. We observed no significant difference based on radiation technique (3DCRT vs. IMRT) with respect to median overall survival (OS) (median 29 vs. 32 months; P = 0.74) or median relapse free survival (median 20 vs. 25 months; P = 0.66). On multivariable analysis (MVA), surgical resection resulted in improved OS (HR 0.444; P < 0.0001). Superior OS was also associated on MVA with stage I/II disease (HR 0.523; P = 0.010) and tumor length ≤5 cm (HR 0.567; P = 0.006). IMRT was also associated on univariate analysis with a significant decrease in acute weight loss (mean 6% + 4.3% vs 9% + 7.4%, P = 0.012) and on MVA with a decrease in objective grade ≥3 toxicity, defined as any hospitalization, feeding tube, or >20% weight loss (OR 0.51; P = 0.050). Our data suggest that while IMRT-based chemoradiation for esophageal cancer does not impact survival there was significantly less toxicity. In the IMRT group there was significant decrease in weight loss and grade ≥3 toxicity compared to 3DCRT.

  1. Modulation of gramicidin channel conformation and organization by hydrophobic mismatch in saturated phosphatidylcholine bilayers.

    PubMed

    Kelkar, Devaki A; Chattopadhyay, Amitabha

    2007-05-01

    The matching of hydrophobic lengths of integral membrane proteins and the surrounding lipid bilayer is an important factor that influences both structure and function of integral membrane proteins. The ion channel gramicidin is known to be uniquely sensitive to membrane properties such as bilayer thickness and membrane mechanical properties. The functionally important carboxy terminal tryptophan residues of gramicidin display conformation-dependent fluorescence which can be used to monitor gramicidin conformations in membranes [S.S. Rawat, D.A. Kelkar, A. Chattopadhyay, Monitoring gramicidin conformations in membranes: a fluorescence approach, Biophys. J. 87 (2004) 831-843]. We have examined the effect of hydrophobic mismatch on the conformation and organization of gramicidin in saturated phosphatidylcholine bilayers of varying thickness utilizing the intrinsic conformation-dependent tryptophan fluorescence. Our results utilizing steady state and time-resolved fluorescence spectroscopic approaches, in combination with circular dichroism spectroscopy, show that gramicidin remains predominantly in the channel conformation and gramicidin tryptophans are at the membrane interfacial region over a range of mismatch conditions. Interestingly, gramicidin conformation shifts toward non-channel conformations in extremely thick gel phase membranes although it is not excluded from the membrane. In addition, experiments utilizing self quenching of tryptophan fluorescence indicate peptide aggregation in thicker gel phase membranes.

  2. Delivery confirmation of bolus electron conformal therapy combined with intensity modulated x-ray therapy

    SciTech Connect

    Kavanaugh, James A.; Hogstrom, Kenneth R.; Fontenot, Jonas P.; Henkelmann, Gregory; Chu, Connel; Carver, Robert A.

    2013-02-15

    Purpose: The purpose of this study was to demonstrate that a bolus electron conformal therapy (ECT) dose plan and a mixed beam plan, composed of an intensity modulated x-ray therapy (IMXT) dose plan optimized on top of the bolus ECT plan, can be accurately delivered. Methods: Calculated dose distributions were compared with measured dose distributions for parotid and chest wall (CW) bolus ECT and mixed beam plans, each simulated in a cylindrical polystyrene phantom that allowed film dose measurements. Bolus ECT plans were created for both parotid and CW PTVs (planning target volumes) using 20 and 16 MeV beams, respectively, whose 90% dose surface conformed to the PTV. Mixed beam plans consisted of an IMXT dose plan optimized on top of the bolus ECT dose plan. The bolus ECT, IMXT, and mixed beam dose distributions were measured using radiographic films in five transverse and one sagittal planes for a total of 36 measurement conditions. Corrections for film dose response, effects of edge-on photon irradiation, and effects of irregular phantom optical properties on the Cerenkov component of the film signal resulted in high precision measurements. Data set consistency was verified by agreement of depth dose at the intersections of the sagittal plane with the five measured transverse planes. For these same depth doses, results for the mixed beam plan agreed with the sum of the individual depth doses for the bolus ECT and IMXT plans. The six mean measured planar dose distributions were compared with those calculated by the treatment planning system for all modalities. Dose agreement was assessed using the 4% dose difference and 0.2 cm distance to agreement. Results: For the combined high-dose region and low-dose region, pass rates for the parotid and CW plans were 98.7% and 96.2%, respectively, for the bolus ECT plans and 97.9% and 97.4%, respectively, for the mixed beam plans. For the high-dose gradient region, pass rates for the parotid and CW plans were 93.1% and 94

  3. Comparison of Three-Dimensional (3D) Conformal Proton Radiotherapy (RT), 3D Conformal Photon RT, and Intensity-Modulated RT for Retroperitoneal and Intra-Abdominal Sarcomas

    SciTech Connect

    Swanson, Erika L.; Indelicato, Daniel J.; Louis, Debbie; Flampouri, Stella; Li, Zuofeng; Morris, Christopher G.; Paryani, Nitesh; Slopsema, Roelf

    2012-08-01

    Purpose: To compare three-dimensional conformal proton radiotherapy (3DCPT), intensity-modulated photon radiotherapy (IMRT), and 3D conformal photon radiotherapy (3DCRT) to predict the optimal RT technique for retroperitoneal sarcomas. Methods and Materials: 3DCRT, IMRT, and 3DCPT plans were created for treating eight patients with retroperitoneal or intra-abdominal sarcomas. The clinical target volume (CTV) included the gross tumor plus a 2-cm margin, limited by bone and intact fascial planes. For photon plans, the planning target volume (PTV) included a uniform expansion of 5 mm. For the proton plans, the PTV was nonuniform and beam-specific. The prescription dose was 50.4 Gy/Cobalt gray equivalent CGE. Plans were normalized so that >95% of the CTV received 100% of the dose. Results: The CTV was covered adequately by all techniques. The median conformity index was 0.69 for 3DCPT, 0.75 for IMRT, and 0.51 for 3DCRT. The median inhomogeneity coefficient was 0.062 for 3DCPT, 0.066 for IMRT, and 0.073 for 3DCRT. The bowel median volume receiving 15 Gy (V15) was 16.4% for 3DCPT, 52.2% for IMRT, and 66.1% for 3DCRT. The bowel median V45 was 6.3% for 3DCPT, 4.7% for IMRT, and 15.6% for 3DCRT. The median ipsilateral mean kidney dose was 22.5 CGE for 3DCPT, 34.1 Gy for IMRT, and 37.8 Gy for 3DCRT. The median contralateral mean kidney dose was 0 CGE for 3DCPT, 6.4 Gy for IMRT, and 11 Gy for 3DCRT. The median contralateral kidney V5 was 0% for 3DCPT, 49.9% for IMRT, and 99.7% for 3DCRT. Regardless of technique, the median mean liver dose was <30 Gy, and the median cord V50 was 0%. The median integral dose was 126 J for 3DCPT, 400 J for IMRT, and 432 J for 3DCRT. Conclusions: IMRT and 3DCPT result in plans that are more conformal and homogenous than 3DCRT. Based on Quantitative Analysis of Normal Tissue Effects in Clinic benchmarks, the dosimetric advantage of proton therapy may be less gastrointestinal and genitourinary toxicity.

  4. Dosimetric comparison of three-dimensional conformal radiotherapy, intensity modulated radiotherapy, and helical tomotherapy for lung stereotactic body radiotherapy

    PubMed Central

    Kinhikar, Rajesh Ashok; Ghadi, Yogesh G.; Sahoo, Priyadarshini; Laskar, Sarbani Ghosh; Deshpande, Deepak D.; Shrivastava, Shyam K.; Agarwal, Jaiprakash

    2015-01-01

    To compare the treatment plans generated with three-dimensional conformal radiation therapy (3DCRT), intensity modulated radiotherapy (IMRT), and helical tomotherapy (HT) for stereotactic body radiotherapy of lung, twenty patients with medically inoperable (early nonsmall cell lung cancer) were retrospectively reviewed for dosimetric evaluation of treatment delivery techniques (3DCRT, IMRT, and HT). A dose of 6 Gy per fraction in 8 fractions was prescribed to deliver 95% of the prescription dose to 95% volume of planning target volume (PTV). Plan quality was assessed using conformity index (CI) and homogeneity index (HI). Doses to critical organs were assessed. Mean CI with 3DCRT, IMRT, and HT was 1.19 (standard deviation [SD] 0.13), 1.18 (SD 0.11), and 1.08 (SD 0.04), respectively. Mean HI with 3DCRT, IMRT, and HT was 1.14 (SD 0.05), 1.08 (SD 0.02), and 1.07 (SD 0.04), respectively. Mean R50% values for 3DCRT, IMRT, and HT was 8.5 (SD 0.35), 7.04 (SD 0.45), and 5.43 (SD 0.29), respectively. D2cm was found superior with IMRT and HT. Significant sparing of critical organs can be achieved with highly conformal techniques (IMRT and HT) without compromising the PTV conformity and homogeneity. PMID:26865754

  5. A comparison between cobalt and linear accelerator-based treatment plans for conformal and intensity-modulated radiotherapy.

    PubMed

    Adams, E J; Warrington, A P

    2008-04-01

    The simplicity of cobalt units gives them the advantage of reduced maintenance, running costs and downtime when compared with linear accelerators. However, treatments carried out on such units are typically limited to simple techniques. This study has explored the use of cobalt beams for conformal and intensity-modulated radiotherapy (IMRT). Six patients, covering a range of treatment sites, were planned using both X-ray photons (6/10 MV) and cobalt-60 gamma rays (1.17 and 1.33 MeV). A range of conformal and IMRT techniques were considered, as appropriate. Conformal plans created using cobalt beams for small breast, meningioma and parotid cases were found to compare well with those created using X-ray photons. By using additional fields, acceptable conformal plans were also created for oesophagus and prostate cases. IMRT plans were found to be of comparable quality for meningioma, parotid and thyroid cases on the basis of dose-volume histogram analysis. We conclude that it is possible to plan high-quality radical radiotherapy treatments for cobalt units. A well-designed beam blocking/compensation system would be required to enable a practical and efficient alternative to multileaf collimator (MLC)-based linac treatments to be offered. If cobalt units were to have such features incorporated into them, they could offer considerable benefits to the radiotherapy community.

  6. Media effects in modulating the conformational equilibrium of a model compound for tumor necrosis factor converting enzyme inhibition

    NASA Astrophysics Data System (ADS)

    Banchelli, Martina; Guardiani, Carlo; Sandberg, Robert B.; Menichetti, Stefano; Procacci, Piero; Caminati, Gabriella

    2015-07-01

    Small-molecule inhibitors of Tumor Necrosis Factor α Converting Enzyme (TACE) are a promising therapeutic tool for Rheumatoid Arthritis, Multiple Sclerosis and other autoimmune diseases. Here we report on an extensive chemical-physical analysis of the media effects in modulating the conformational landscape of MBET306, the common scaffold and a synthetic precursor of a family of recently discovered tartrate-based TACE inhibitors. The structural features of this molecule with potential pharmaceutical applications have been disclosed by interpreting extensive photophysical measurements in various solvents with the aid of enhanced sampling molecular dynamics simulations and time dependent density functional calculations. Using a combination of experimental and computational techniques, the paper provides a general protocol for studying the structure in solution of molecular systems characterized by the existence of conformational metastable states.

  7. Dosimetric and radiobiologic comparison of 3D conformal versus intensity modulated planning techniques for prostate bed radiotherapy.

    PubMed

    Koontz, Bridget F; Das, Shiva; Temple, Kathy; Bynum, Sigrun; Catalano, Suzanne; Koontz, Jason I; Montana, Gustavo S; Oleson, James R

    2009-01-01

    Adjuvant radiotherapy for locally advanced prostate cancer improves biochemical and clinical disease-free survival. While comparisons in intact prostate cancer show a benefit for intensity modulated radiation therapy (IMRT) over 3D conformal planning, this has not been studied for post-prostatectomy radiotherapy (RT). This study compares normal tissue and target dosimetry and radiobiological modeling of IMRT vs. 3D conformal planning in the postoperative setting. 3D conformal plans were designed for 15 patients who had been treated with IMRT planning for salvage post-prostatectomy RT. The same computed tomography (CT) and target/normal structure contours, as well as prescription dose, was used for both IMRT and 3D plans. Normal tissue complication probabilities (NTCPs) were calculated based on the dose given to the bladder and rectum by both plans. Dose-volume histogram and NTCP data were compared by paired t-test. Bladder and rectal sparing were improved with IMRT planning compared to 3D conformal planning. The volume of the bladder receiving at least 75% (V75) and 50% (V50) of the dose was significantly reduced by 28% and 17%, respectively (p = 0.002 and 0.037). Rectal dose was similarly reduced, V75 by 33% and V50 by 17% (p = 0.001 and 0.004). While there was no difference in the volume of rectum receiving at least 65 Gy (V65), IMRT planning significant reduced the volume receiving 40 Gy or more (V40, p = 0.009). Bladder V40 and V65 were not significantly different between planning modalities. Despite these dosimetric differences, there was no significant difference in the NTCP for either bladder or rectal injury. IMRT planning reduces the volume of bladder and rectum receiving high doses during post-prostatectomy RT. Because of relatively low doses given to the bladder and rectum, there was no statistically significant improvement in NTCP between the 3D conformal and IMRT plans.

  8. Modulation of Amyloid-β Conformation by Charge State of N-Terminal Disordered Region

    NASA Astrophysics Data System (ADS)

    Xi, Wen-Hui; Li, Wen-Fei; Wang, Wei

    2012-08-01

    Based on molecular dynamics simulations, we show that variations of the charge states of the histidines, which are the main effects of pH-value change and metal binding, can lead to a drastic change of the intra-peptide interactions of the segment 17-42 and the conformational distribution of the monomeric amyloid-β (Aβ). Since we already knew that the conformational distribution of monomeric Aβ can largely affect Aβ fibrillar aggregation, our results suggest that the pH value change and metal binding can affect the Aβ aggregation by much more complex mechanism than just affecting the inter-peptide interactions. To fully understand the mechanism of metal binding and pH-value induced Aβ aggregation, we also need to consider their effects on the conformational distribution of monomeric Aβ.

  9. Intensity-modulated radiotherapy, not 3D conformal, is the preferred technique for treating locally advanced lung cancer

    PubMed Central

    Chang, Joe Y.

    2015-01-01

    When used to treat lung cancer, intensity-modulated radiotherapy (IMRT) can deliver higher dose to the targets and spare more critical organs in lung cancer than can 3D conformal radiotherapy (3DCRT). However, tumor-motion management and optimized radiotherapy planning based on four-dimensional computed tomography (4D CT) scanning are crucial to maximize the benefit of IMRT and to eliminate or minimize potential uncertainties. This article summarizes these strategies and reviews published findings supporting the safety and efficacy of IMRT for lung cancer. PMID:25771415

  10. A novel conformity index for intensity modulated radiation therapy plan evaluation

    SciTech Connect

    Cheung, Fion W. K.; Law, Maria Y. Y.

    2012-09-15

    Purpose: Intensity modulated radiation therapy (IMRT) has gained popularity in the treatment of cancers. Manual evaluation of IMRT plans for head-and-neck cancers has been especially challenging necessitating efficient and objective assessment tools. In this work, the authors address this issue by developing a personalized conformity index (CI) for comparison of IMRT plans for head-and-neck cancers and evaluating its plan quality discerning power in comparison with other widely used CIs. Methods: A two-dimensional CI with dose and distance incorporated (CI{sub DD}) was developed using the MATLAB program language, to quantify the planning target volume (PTV) coverage. Valuable information contained in the digital imaging and communication in medicine (DICOM) RT objects were harvested for computation of each of the CI{sub DD} components. Apart from the dose penalty factor, a distance-based exponential function was employed by varying the penalty weight associated with the location of cold spots within the PTV. With the goal of deriving a customized penalty factor, the distances between individual pixel and its nearest PTV boundary was found. Using the exponential function, the impact of distance penalty was substantially larger for cold spots closer to the PTV centroid but petered out quickly wherever they were situated in the vicinity of PTV border. In order to evaluate the CI{sub DD} scoring system, three CT image data sets of nasopharyngeal carcinoma (NPC) patients were collected. Ten IMRT plans with degrading qualities were generated from each dataset and were ranked based on CI{sub DD} and other existing indices. The coefficient of variance was calculated for each dataset to compare the degree of variation. Results: The CI{sub DD} scoring system that considered spatial importance of each voxel within the PTV was successfully developed. The results demonstrated that the CI{sub DD} including four discrete factors could provide accurate rankings of plan quality by

  11. Regulation of ES cell differentiation by functional and conformational modulation of p53.

    PubMed Central

    Sabapathy, K; Klemm, M; Jaenisch, R; Wagner, E F

    1997-01-01

    Embryonic stem (ES) cell lines were used to examine the role of p53 during in vitro differentiation. Undifferentiated ES cells express high levels of p53 exclusively in the wild-type conformation, immunoprecipitable by monoclonal antibody PAb246, and p53 was found to be functionally active as determined by its ability to bind DNA specifically and to activate transcription of target genes. Differentiation in vitro resulted in a decrease in the levels of p53 and in a shift in its conformational status to the mutant form, detectable by monoclonal antibody PAb240, with a concomitant loss of functional activity. The presence of functional p53 in the undifferentiated ES cells renders them hypersensitive to UV irradiation, whereas the differentiated cells were resistant to UV treatment. ES cells lacking p53 exhibit enhanced proliferation in both the undifferentiated and differentiated state, and apoptosis accompanying differentiation was found to be reduced. Furthermore, wild-type ES cells undergoing apoptosis expressed functional p53. Expression of the temperature-sensitive p53val135 mutant in wild-type ES cells resulted in a reduction of apoptosis accompanying differentiation when it adopted a mutant conformation at 39 degrees C. These data demonstrate that functional inactivation of p53 allows differentiating cells to escape from apoptosis, and suggest that the conformational switch could regulate the inactivation process. PMID:9321401

  12. 3D-Conformal Versus Intensity-Modulated Postoperative Radiotherapy of Vaginal Vault: A Dosimetric Comparison

    SciTech Connect

    Cilla, Savino; Macchia, Gabriella Digesu, Cinzia; Deodato, Francesco; Romanella, Michele; Ferrandina, Gabriella; Padula, Gilbert; Picardi, Vincenzo; Scambia, Giovanni; Morganti, Alessio Giuseppe

    2010-07-01

    We evaluated a step-and-shoot IMRT plan in the postoperative irradiation of the vaginal vault compared with equispaced beam arrangements (3-5) 3D-radiotherapy (RT) optimized plans. Twelve patients were included in this analysis. Four plans for each patient were compared in terms of dose-volume histograms, homogeneity index (HI), and conformity index (CI): (1) 3 equispaced beam arrangement 3D-RT; (2) 4 equispaced beam arrangement 3D-RT; (3) 5 equispaced beam arrangement 3D-RT; (4) step-and-shoot IMRT technique. CI showed a good discrimination between the four plans. The mean scores of CI were 0.58 (range: 0.38-0.67) for the 3F-CRT plan, 0.58 (range: 0.41-0.66) for 4F-CRT, 0.62 (range: 0.43-0.68) for 5F-CRT and 0.69 (range: 0.58-0.78) for the IMRT plan. A significant improvement of the conformity was reached by the IMRT plan (p < 0.001 for all comparisons). As expected, the increment of 3D-CRT fields was associated with an improvement of target dose conformity and homogeneity; on the contrary, in the IMRT plans, a better conformity was associated to a worse target dose homogeneity. A significant reduction in terms of D{sub mean}, V90%, V95%, V100% was recorded for rectal and bladder irradiation with the IMRT plan. Surprisingly, IMRT supplied a significant dose reduction also for rectum and bladder V30% and V50%. A significant dosimetric advantage of IMRT over 3D-RT in the adjuvant treatment of vaginal vault alone in terms of treatment conformity and rectum and bladder sparing is shown.

  13. Solution conformation of C-linked antifreeze glycoprotein analogues and modulation of ice recrystallization.

    PubMed

    Tam, Roger Y; Rowley, Christopher N; Petrov, Ivan; Zhang, Tianyi; Afagh, Nicholas A; Woo, Tom K; Ben, Robert N

    2009-11-01

    Antifreeze glycoproteins (AFGPs) are a unique class of proteins that are found in many organisms inhabiting subzero environments and ensure their survival by preventing ice growth in vivo. During the last several years, our laboratory has synthesized functional C-linked AFGP analogues (3 and 5) that possess custom-tailored antifreeze activity suitable for medical, commercial, and industrial applications. These compounds are potent inhibitors of ice recrystallization and do not exhibit thermal hysteresis. The current study explores how changes in the length of the amide-containing side chain between the carbohydrate moiety and the polypeptide backbone in 5 influences ice recrystallization inhibition (IRI) activity. Analogue 5 (n = 3, where n is the number of carbons in the side chain) was a potent inhibitor of ice recrystallization, while 4, 6, and 7 (n = 4, 2, and 1, respectively) exhibited no IRI activity. The solution conformation of the polypeptide backbone in C-linked AFGP analogues 4-7 was examined using circular dichroism (CD) spectroscopy. The results suggested that all of the analogues exhibit a random coil conformation in solution and that the dramatic increase in IRI activity observed with 5 is not due to a change in long-range solution conformation. Variable-temperature (1)H NMR studies on truncated analogues 26-28 failed to elucidate the presence of persistent intramolecular bonds between the amide in the side chain and the peptide backbone. Molecular dynamics simulations performed on these analogues also failed to show persistent intramolecular hydrogen bonds. However, the simulations did indicate that the side chain of IRI-active analogue 26 (n = 3) adopts a unique short-range solution conformation in which it is folded back onto the peptide backbone, orienting the more hydrophilic face of the carbohydrate moiety away from the bulk solvent. In contrast, the solution conformation of IRI-inactive analogues 25, 27, and 28 had fully extended side chains

  14. Modulation of plasminogen activator inhibitor 1 by Triton X-100--identification of two consecutive conformational transitions.

    PubMed

    Gils, A; Declerck, P J

    1998-08-01

    Plasminogen activator inhibitor-1 (PAI-1) is a unique member of the serpin superfamily because of its conformational and functional flexibility. In the present study, we have evaluated the influence of the non-ionic detergent Triton X-100 (TX-100) on the functional stability and conformational transitions of PAI-1. At 37 degrees C, TX-100 induced a concentration-dependent decrease of the functional half-life of PAI-1 resulting in half-lives of 177 +/- 54 min (mean +/- SD, n = 3), 19 +/- 2 min, 1.7 +/- 0.3 min and 0.53 +/- 0.03 min in the presence of 0.005, 0.010, 0.020 and 0.2% TX-100, respectively, compared to a half-life of 270 +/- 146 min in the absence of TX-100. Conformational analysis at various time points and at different temperatures (0 degrees C, 25 degrees C, 37 degrees C) revealed that this inactivation proceeds through the formation of a substrate-like intermediate followed by the formation of the latent form. Kinetic evaluation demonstrated that this conversion fits to two consecutive first-order transitions, i.e. active k1--> substrate k2--> latent. The k1 value was strongly dependent on the concentration of TX-100 (e.g. 0.002 +/- 0.0006 s(-1) and 0.029 +/- 0.003 s(-1) for 0.01% and 0.2% TX-100 at 37 degrees C) whereas the conversion of substrate to latent (k2) was virtually independent of the TX-100 concentration (i.e. 0.012 +/- 0.002 s(-1) and 0.011 +/- 0.001 s(-1) for 0.01 and 0.2% TX-100 at 37 degrees C). Experiments with a variety of other non-ionic amphiphilic compounds revealed that the amphiphilic character of the compound is, at least in part, responsible for the observed effects and strongly indicate that the currently reported mechanism of inactivation is of general importance for the conformational transitions in PAI-1. In conclusion, TX- 100 changes the initial conformation of PAI-1 resulting in altered functional properties. This observation allows us to develop a new model for the mechanism involved in the conformational flexibility of

  15. Three-dimensional conformal intensity-modulated radiation therapy of left femur foci does not damage the sciatic nerve

    PubMed Central

    Xu, Wanlong; Zhao, Xibin; Wang, Qing; Sun, Jungang; Xu, Jiangbo; Zhou, Wenzheng; Wang, Hao; Yan, Shigui; Yuan, Hong

    2014-01-01

    During radiotherapy to kill femoral hydatid tapeworms, the sciatic nerve surrounding the focus can be easily damaged by the treatment. Thus, it is very important to evaluate the effects of radiotherapy on the surrounding nervous tissue. In the present study, we used three-dimensional, conformal, intensity-modulated radiation therapy to treat bilateral femoral hydatid disease in Meriones meridiani. The focus of the hydatid disease on the left femur was subjected to radiotherapy (40 Gy) for 14 days, and the right femur received sham irradiation. Hematoxylin-eosin staining, electron microscopy, and terminal deoxynucleotidyl transferase-dUTP nick end labeling assays on the left femurs showed that the left sciatic nerve cell structure was normal, with no obvious apoptosis after radiation. Trypan blue staining demonstrated that the overall protoscolex structure in bone parasitized with Echinococcus granulosus disappeared in the left femur of the animals after treatment. The mortality of the protoscolex was higher in the left side than in the right side. The succinate dehydrogenase activity in the protoscolex in bone parasitized with Echinococcus granulosus was lower in the left femur than in the right femur. These results suggest that three-dimensional conformal intensity-modulated radiation therapy achieves good therapeutic effects on the secondary bone in hydatid disease in Meriones meridiani without damaging the morphology or function of the sciatic nerve. PMID:25422645

  16. Limited Advantages of Intensity-Modulated Radiotherapy Over 3D Conformal Radiation Therapy in the Adjuvant Management of Gastric Cancer

    SciTech Connect

    Alani, Shlomo; Soyfer, Viacheslav; Strauss, Natan; Schifter, Dan; Corn, Benjamin W.

    2009-06-01

    Purpose: Although chemoradiotherapy was considered the standard adjuvant treatment for gastric cancer, a recent Phase III trial (Medical Research Council Adjuvant Gastric Infusional Chemotherapy [MAGIC]) did not include radiotherapy in the randomization scheme because it was considered expendable. Given radiotherapy's potential, efforts needed to be made to optimize its use for treating gastric cancer. We assessed whether intensity-modulated radiotherapy (IMRT) could improve upon our published results in patients treated with three-dimensional (3D) conformal therapy. Methods and Materials: Fourteen patients with adenocarcinoma of the stomach were treated with adjuvant chemoradiotherapy using a noncoplanar four-field arrangement. Subsequently, a nine-field IMRT plan was designed using a CMS Xio IMRT version 4.3.3 module. Two IMRT beam arrangements were evaluated: beam arrangement 1 consisted of gantry angles of 0 deg., 53 deg., 107 deg., 158 deg., 204 deg., 255 deg., and 306 deg.. Beam arrangement 2 consisted of gantry angles of 30 deg., 90 deg., 315 deg., and 345 deg.; a gantry angle of 320 deg./couch, 30 deg.; and a gantry angle of 35{sup o}/couch, 312{sup o}. Both the target volume coverage and the dose deposition in adjacent critical organs were assessed in the plans. Dose-volume histograms were generated for the clinical target volume, kidneys, spine, and liver. Results: Comparison of the clinical target volumes revealed satisfactory coverage by the 95% isodose envelope using either IMRT or 3D conformal therapy. However, IMRT was only marginally better than 3D conformal therapy at protecting the spine and kidneys from radiation. Conclusions: IMRT confers only a marginal benefit in the adjuvant treatment of gastric cancer and should be used only in the small subset of patients with risk factors for kidney disease or those with a preexisting nephropathy.

  17. Comparison of three dimensional conformal radiation therapy, intensity modulated radiation therapy and volumetric modulated arc therapy for low radiation exposure of normal tissue in patients with prostate cancer.

    PubMed

    Cakir, Aydin; Akgun, Zuleyha; Fayda, Merdan; Agaoglu, Fulya

    2015-01-01

    Radiotherapy has an important role in the treatment of prostate cancer. Three-dimensional conformal radiation therapy (3D-CRT), intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) techniques are all applied for this purpose. However, the risk of secondary radiation-induced bladder cancer is significantly elevated in irradiated patients compared surgery-only or watchful waiting groups. There are also reports of risk of secondary cancer with low doses to normal tissues. This study was designed to compare received volumes of low doses among 3D-CRT, IMRT and VMAT techniques for prostate patients. Ten prostate cancer patients were selected retrospectively for this planning study. Treatment plans were generated using 3D-CRT, IMRT and VMAT techniques. Conformity index (CI), homogenity index (HI), receiving 5 Gy of the volume (V5%), receiving 2 Gy of the volume (V2%), receiving 1 Gy of the volume (V1%) and monitor units (MUs) were compared. This study confirms that VMAT has slightly better CI while thev olume of low doses was higher. VMAT had lower MUs than IMRT. 3D-CRT had the lowest MU, CI and HI. If target coverage and normal tissue sparing are comparable between different treatment techniques, the risk of second malignancy should be a important factor in the selection of treatment.

  18. Volumetric Modulated Arc Therapy for Delivery of Prostate Radiotherapy: Comparison With Intensity-Modulated Radiotherapy and Three-Dimensional Conformal Radiotherapy

    SciTech Connect

    Palma, David Vollans, Emily; James, Kerry; Nakano, Sandy; Moiseenko, Vitali; Shaffer, Richard; McKenzie, Michael; Morris, James; Otto, Karl

    2008-11-15

    Purpose: Volumetric modulated arc therapy (VMAT) is a novel form of intensity-modulated radiotherapy (IMRT) optimization that allows the radiation dose to be delivered in a single gantry rotation of up to 360{sup o}, using either a constant dose rate (cdr-VMAT) or variable dose rate (vdr-VMAT) during rotation. The goal of this study was to compare VMAT prostate RT plans with three-dimensional conformal RT (3D-CRT) and IMRT plans. Patients and Methods: The 3D-CRT, five-field IMRT, cdr-VMAT, and vdr-VMAT RT plans were created for 10 computed tomography data sets from patients undergoing RT for prostate cancer. The parameters evaluated included the doses to organs at risk, equivalent uniform doses, dose homogeneity and conformality, and monitor units required for delivery of a 2-Gy fraction. Results: The IMRT and both VMAT techniques resulted in lower doses to normal critical structures than 3D-CRT plans for nearly all dosimetric endpoints analyzed. The lowest doses to organs at risk and most favorable equivalent uniform doses were achieved with vdr-VMAT, which was significantly better than IMRT for the rectal and femoral head dosimetric endpoints (p < 0.05) and significantly better than cdr-VMAT for most bladder and rectal endpoints (p < 0.05). The vdr-VMAT and cdr-VMAT plans required fewer monitor units than did the IMRT plans (relative reduction of 42% and 38%, respectively; p = 0.005) but more than for the 3D-CRT plans (p = 0.005). Conclusion: The IMRT and VMAT techniques achieved highly conformal treatment plans. The vdr-VMAT technique resulted in more favorable dose distributions than the IMRT or cdr-VMAT techniques, and reduced the monitor units required compared with IMRT.

  19. A neglected modulator of insulin-degrading enzyme activity and conformation: The pH.

    PubMed

    Grasso, Giuseppe; Satriano, Cristina; Milardi, Danilo

    2015-01-01

    Insulin-degrading enzyme (IDE), a ubiquitously expressed zinc metalloprotease, has multiple activities in addition to insulin degradation and its malfunction is believed to connect type 2 diabetes with Alzheimer's disease. IDE has been found in many different cellular compartments, where it may experience significant physio-pathological pH variations. However, the exact role of pH variations on the interplay between enzyme conformations, stability, oligomerization state and catalysis is not understood. Here, we use ESI mass spectrometry, atomic force microscopy, surface plasmon resonance and circular dichroism to investigate the structure-activity relationship of IDE at different pH values. We show that acidic pH affects the ability of the enzyme to bind the substrate and decrease the stability of the protein by inducing an α-helical bundle conformation with a concomitant dissociation of multi-subunit IDE assemblies into monomeric units and loss of activity. These effects suggest a major role played by electrostatic forces in regulating multi-subunit enzyme assembly and function. Our results clearly indicate a pH dependent coupling among enzyme conformation, assembly and stability and suggest that cellular acidosis can have a large effect on IDE oligomerization state, inducing an enzyme inactivation and an altered insulin degradation that could have an impact on insulin signaling.

  20. The cytosolic domain of human Tom22 modulates human Bax mitochondrial translocation and conformation in yeast.

    PubMed

    Renault, Thibaud T; Grandier-Vazeille, Xavier; Arokium, Hubert; Velours, Gisèle; Camougrand, Nadine; Priault, Muriel; Teijido, Oscar; Dejean, Laurent M; Manon, Stéphen

    2012-01-20

    The role of the mitochondrial protein receptor Tom22p in the interaction of pro-apoptotic protein Bax with yeast mitochondria was investigated. Co-immunoprecipitation assays showed that human Bax interacted with different TOM subunits, including Tom22p. Expression of the cytosolic receptor domain of human Tom22 increased Bax mitochondrial localization, but decreased the proportion of active Bax. BN-PAGE showed that the cytosolic domain of Tom22 interfered with the oligomerization of Bax. These data suggest that the interaction with the cytosolic domain of Tom22 helps Bax to acquire a conformation able to interact with the outer mitochondrial membrane. PMID:22198199

  1. The amino terminal helix modulates light activated conformational changes in AsLOV2

    PubMed Central

    Zayner, Josiah P.; Antoniou, Chloe; Sosnick, Tobin R.

    2012-01-01

    The mechanism of light-triggered conformational change and signaling in light-oxygen-voltage (LOV) domains remains elusive in spite of extensive investigation and their use in optogenetic studies. The LOV2 domain of Avena Sativa phototropin1 (AsLOV2), a member of the Per-Arnt-Sim (PAS) family, contains an FMN chromophore that forms a covalent bond with a cysteine upon illumination. This event leads to the release of the carboxy terminal Jα helix, the biological output signal. Using mutational analysis, circular dichroism and NMR, we find that the largely ignored amino terminal helix is a control element in AsLOV2’s light-activated conformational change. We further identify a direct amino-to-carboxy terminal “input-output” signaling pathway. These findings provide a framework to rationalize the LOV domain architecture, as well as the signaling mechanisms in both isolated and tandem arrangements of PAS domains. This knowledge can be applied in engineering LOV-based photoswitches, opening up new design strategies and improving existing ones. PMID:22406525

  2. Balancing between affinity and speed in target DNA search by zinc-finger proteins via modulation of dynamic conformational ensemble.

    PubMed

    Zandarashvili, Levani; Esadze, Alexandre; Vuzman, Dana; Kemme, Catherine A; Levy, Yaakov; Iwahara, Junji

    2015-09-15

    Although engineering of transcription factors and DNA-modifying enzymes has drawn substantial attention for artificial gene regulation and genome editing, most efforts focus on affinity and specificity of the DNA-binding proteins, typically overlooking the kinetic properties of these proteins. However, a simplistic pursuit of high affinity can lead to kinetically deficient proteins that spend too much time at nonspecific sites before reaching their targets on DNA. We demonstrate that structural dynamic knowledge of the DNA-scanning process allows for kinetically and thermodynamically balanced engineering of DNA-binding proteins. Our current study of the zinc-finger protein Egr-1 (also known as Zif268) and its nuclease derivatives reveals kinetic and thermodynamic roles of the dynamic conformational equilibrium between two modes during the DNA-scanning process: one mode suitable for search and the other for recognition. By mutagenesis, we were able to shift this equilibrium, as confirmed by NMR spectroscopy. Using fluorescence and biochemical assays as well as computational simulations, we analyzed how the shifts of the conformational equilibrium influence binding affinity, target search kinetics, and efficiency in displacing other proteins from the target sites. A shift toward the recognition mode caused an increase in affinity for DNA and a decrease in search efficiency. In contrast, a shift toward the search mode caused a decrease in affinity and an increase in search efficiency. This accelerated site-specific DNA cleavage by the zinc-finger nuclease, without enhancing off-target cleavage. Our study shows that appropriate modulation of the dynamic conformational ensemble can greatly improve zinc-finger technology, which has used Egr-1 (Zif268) as a major scaffold for engineering.

  3. Mapping light-driven conformational changes within the photosensory module of plant phytochrome B

    PubMed Central

    von Horsten, Silke; Straß, Simon; Hellwig, Nils; Gruth, Verena; Klasen, Ramona; Mielcarek, Andreas; Linne, Uwe; Morgner, Nina; Essen, Lars-Oliver

    2016-01-01

    Organisms developed different photoreceptors to be able to adapt to changing environmental light conditions. Phytochromes are red/far-red (r/fr) photochromic photoreceptors that belong to the classical photoreceptors along with cryptochromes and phototropins. They convert absorbed light into a biological signal by switching between two states in a light-dependent manner therefore enabling the light control downstream signalling. Their Pfr conformation is the biological active form in plants, but until now only a structure of the ground state (Pr) was solved. Here, the authors provide information about structural changes occurring during photoconversion within phytochrome B and identify possible interaction sites for its N-terminal extension (NTE) utilising hydrogen/deuterium exchange rate analyses of its amide backbone. Especially, the newly identified light-dependency of two regions in the NTE are of particular interest for understanding the involvement of the phytochrome’s NTE in the regulation of its downstream signalling. PMID:27694986

  4. Terminal Interface Conformations Modulate Dimer Stability Prior to Amino Terminal Autoprocessing of HIV-1 Protease

    SciTech Connect

    Agniswamy, Johnson; Sayer, Jane M.; Weber, Irene T.; Louis, John M.

    2012-04-17

    The HIV-1 protease (PR) mediates its own release (autoprocessing) from the polyprotein precursor, Gag-Pol, flanked by the transframe region (TFR) and reverse transcriptase at its N- and C-termini, respectively. Autoprocessing at the N-terminus of PR mediates stable dimer formation essential for catalytic activity, leading to the formation of infectious virus. An antiparallel {beta}-sheet interface formed by the four N- and C-terminal residues of each subunit is important for dimer stability. Here, we present the first high-resolution crystal structures of model protease precursor-clinical inhibitor (PI darunavir or saquinavir) complexes, revealing varying conformations of the N-terminal flanking (S{sup -4}FNF{sup -1}) and interface residues (P{sup 1}QIT{sup 4}). A 180{sup o} rotation of the T{sup 4}-L{sup 5} peptide bond is accompanied by a new Q{sup 2}-L{sup 5} hydrogen bond and complete disengagement of PQIT from the {beta}-sheet dimer interface, which may be a feature for intramolecular autoprocessing. This result is consistent with drastically lower thermal stability by 14-20 C of PI complexes of precursors and the mature PR lacking its PQIT residues (by 18.3 C). Similar to the TFR-PR precursor, this deletion also results in a darunavir dissociation constant (2 x 10{sup 4})-fold higher and a markedly increased dimer dissociation constant relative to the mature PR. The terminal {beta}-sheet perturbations of the dimeric structure likely account for the drastically poorer inhibition of autoprocessing of TFR-PR relative to the mature PR, even though significant differences in active site-PI interactions in these structures were not observed. The novel conformations of the dimer interface may be exploited to target selectively the protease precursor prior to its N-terminal cleavage.

  5. Image-guided volumetric modulated arc therapy for breast cancer: a feasibility study and plan comparison with three-dimensional conformal and intensity-modulated radiotherapy

    PubMed Central

    Kaul, D; Nadobny, J; Wille, B; Sehouli, J; Budach, V

    2013-01-01

    Objective: To test the feasibility of volumetric modulated arc therapy (VMAT) in breast cancer and to compare it with three-dimensional conformal radiotherapy (3D-CRT) as conventional tangential field radiotheraphy (conTFRT). Methods: 12 patients (Stage I, 8: 6 left breast cancer and 2 right breast cancer; Stage II, 4: 2 on each side). Three plans were calculated for each case after breast-conserving surgery. Breast was treated with 50 Gy in four patients with supraclavicular lymph node inclusion, and in eight patients without the node inclusion. Multiple indices and dose parameters were measured. Results: V95% was not achieved by any modality. Heterogeneity index: 0.16 (VMAT), 0.13 [intensity-modulated radiotherapy (IMRT)] and 0.14 (conTFRT). Conformity index: 1.06 (VMAT), 1.15 (IMRT) and 1.69 (conTFRT). For both indices, IMRT was more effective than VMAT (p=0.009, p=0.002). Dmean and V20 for ipsilateral lung were lower for IMRT than VMAT (p=0.0001, p=0.003). Dmean, V2 and V5 of contralateral lung were lower for IMRT than VMAT (p>0.0001, p=0.005). Mean dose and V5 to the heart were lower for IMRT than for VMAT (p=0.015, p=0.002). Conclusion: The hypothesis of equivalence of VMAT to IMRT was not confirmed for planning target volume parameter or dose distribution to organs at risk. VMAT was inferior to IMRT and 3D-CRT with regard to dose distribution to organs at risk, especially at the low dose level. Advances in knowledge: New technology VMAT is not superior to IMRT or conventional radiotherapy in breast cancer in any aspect. PMID:24167182

  6. Volumetric-modulated arc radiotherapy for pancreatic malignancies: Dosimetric comparison with sliding-window intensity-modulated radiotherapy and 3-dimensional conformal radiotherapy

    SciTech Connect

    Nabavizadeh, Nima Simeonova, Anna O.; Waller, Joseph G.; Romer, Jeanna L.; Monaco, Debra L.; Elliott, David A.; Tanyi, James A.; Fuss, Martin; Thomas, Charles R.; Holland, John M.

    2014-10-01

    Volumetric-modulated arc radiotherapy (VMAT) is an iteration of intensity-modulated radiotherapy (IMRT), both of which deliver highly conformal dose distributions. Studies have shown the superiority of VMAT and IMRT in comparison with 3-dimensional conformal radiotherapy (3D-CRT) in planning target volume (PTV) coverage and organs-at-risk (OARs) sparing. This is the first study examining the benefits of VMAT in pancreatic cancer for doses more than 55.8 Gy. A planning study comparing 3D-CRT, IMRT, and VMAT was performed in 20 patients with pancreatic cancer. Treatments were planned for a 25-fraction delivery of 45 Gy to a large field followed by a reduced-volume 8-fraction external beam boost to 59.4 Gy in total. OARs and PTV doses, conformality index (CI) deviations from 1.0, monitor units (MUs) delivered, and isodose volumes were compared. IMRT and VMAT CI deviations from 1.0 for the large-field and the boost plans were equivalent (large field: 0.032 and 0.046, respectively; boost: 0.042 and 0.037, respectively; p > 0.05 for all comparisons). Both IMRT and VMAT CI deviations from 1.0 were statistically superior to 3D-CRT (large field: 0.217, boost: 0.177; p < 0.05 for all comparisons). VMAT showed reduction of the mean dose to the boost PTV (VMAT: 61.4 Gy, IMRT: 62.4 Gy, and 3D-CRT: 62.3 Gy; p < 0.05). The mean number of MUs per fraction was significantly lower for VMAT for both the large-field and the boost plans. VMAT delivery time was less than 3 minutes compared with 8 minutes for IMRT. Although no statistically significant dose reduction to the OARs was identified when comparing VMAT with IMRT, VMAT showed a reduction in the volumes of the 100% isodose line for the large-field plans. Dose escalation to 59.4 Gy in pancreatic cancer is dosimetrically feasible with shorter treatment times, fewer MUs delivered, and comparable CIs for VMAT when compared with IMRT.

  7. Quantitative analysis of tomotherapy, linear-accelerator-based 3D conformal radiation therapy, intensity-modulated radiation therapy, and 4D conformal radiation therapy

    NASA Astrophysics Data System (ADS)

    Cho, Jae-Hwan; Lee, Hae-Kag; Dong, Kyung-Rae; Chung, Woon-Kwan; Lee, Jong-Woong; Park, Hoon-Hee

    2012-04-01

    This study quantified, evaluated and analyzed the radiation dose to which tumors and normal tissues were exposed in 3D conformal radiation therapy (CRT), intensity-modulated radiation therapy (IMRT) and tomotherapy by using a dose volume histogram (DVH) that represented the volume dose and the dose distribution of anatomical structures in the evaluation of treatment planning. Furthermore, a comparison was made for the dose to the gross tumor volume (GTV) and the planning target volume (PTV) of organ to be treated based on the change in field size for three- and four-dimensional computed tomography (3D-CT and 4D-CT) (gating based) and in the histogram with a view to proving the usefulness of 4D-CT therapy, which corresponds to respiration-gated radiation therapy. According to the study results, a comparison of 3D CRT, IMRT with a linear accelerator (LINAC), and tomotherapy demonstrated that the GTV of the cranium was higher for tomotherapy than for 3D CRT and IMRT with a LINAC by 5.2% and 4.6%, respectively. The GTV of the neck was higher for tomotherapy than for 3D CRT and IMRT with a LINAC by 6.5% and 2.0%, respectively. The GTV of the pelvis was higher for tomotherapy than for 3D CRT and IMRT with a LINAC by 8.6% and 3.7%, respectively. When the comparison was made for the 3D-CT and the 4D-CT (gating based) treatment equipment, the GTV and the PTV became smaller for 4D-CT treatment planning than for 3D-CT, which could reduce the area in which normal tissues in the surroundings are exposed to an unnecessary radiation dose. In addition, when 4D-CT treatment planning (gating based) was used, the radiation dose could be concentrated on the GTV, CTV or PTV, which meant that the treatment area exceeded that when 3D-CT's treatment planning was used. Moreover, the radiation dose on nearby normal tissues could be reduced. When 4D-CT treatment planning (gating based) was utilized, unnecessary areas that were exposed to a radiation dose could be reduced more than they could

  8. Conformational state-dependent anion binding in prestin: evidence for allosteric modulation.

    PubMed

    Song, Lei; Santos-Sacchi, Joseph

    2010-02-01

    Outer hair cells boost auditory performance in mammals. This amplification relies on an expansive array of intramembranous molecular motors, identified as prestin, that drive somatic electromotility. By measuring nonlinear capacitance, the electrical signature of electromotility, we are able to assess prestin's conformational state and interrogate the effectiveness of anions on prestin's activity. We find that the affinity of anions depends on the state of prestin that we set with a variety of perturbations (in membrane tension, temperature, and voltage), and that movement into the expanded state reduces the affinity of prestin for anions. These data signify that anions work allosterically on prestin. Consequently, anions are released from prestin's binding site during expansion, i.e., during hyperpolarization. This is at odds with the extrinsic voltage sensor model, which suggests that prestin-bound intracellular anions are propelled deep into the membrane. Furthermore, we hypothesize that prestin's susceptibility to many biophysical forces, and notably its piezoelectric nature, may reflect anion interactions with the motor. PMID:20141749

  9. Multiple disulfide bridges modulate conformational stability and flexibility in hyperthermophilic archaeal purine nucleoside phosphorylase.

    PubMed

    Bagarolo, Maria Libera; Porcelli, Marina; Martino, Elisa; Feller, Georges; Cacciapuoti, Giovanna

    2015-10-01

    5'-Deoxy-5'-methylthioadenosine phosphorylase from Sulfolobus solfataricus is a hexameric hyperthermophilic protein containing in each subunit two pairs of disulfide bridges, a CXC motif, and one free cysteine. The contribution of each disulfide bridge to the protein conformational stability and flexibility has been assessed by comparing the thermal unfolding and the limited proteolysis of the wild-type enzyme and its variants obtained by site-directed mutagenesis of the seven cysteine residues. All variants catalyzed efficiently MTA cleavage with specific activity similar to the wild-type enzyme. The elimination of all cysteine residues caused a substantial decrease of ΔHcal (850 kcal/mol) and Tmax (39°C) with respect to the wild-type indicating that all cysteine pairs and especially the CXC motif significantly contribute to the enzyme thermal stability. Disulfide bond Cys200-Cys262 and the CXC motif weakly affected protein flexibility while the elimination of the disulfide bond Cys138-Cys205 lead to an increased protease susceptibility. Experimental evidence from limited proteolysis, differential scanning calorimetry, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reducing and nonreducing conditions also allowed to propose a stabilizing role for the free Cys164.

  10. The nicotinic acetylcholine receptor and its prokaryotic homologues: Structure, conformational transitions & allosteric modulation.

    PubMed

    Cecchini, Marco; Changeux, Jean-Pierre

    2015-09-01

    Pentameric ligand-gated ion channels (pLGICs) play a central role in intercellular communications in the nervous system by converting the binding of a chemical messenger - a neurotransmitter - into an ion flux through the postsynaptic membrane. Here, we present an overview of the most recent advances on the signal transduction mechanism boosted by X-ray crystallography of both prokaryotic and eukaryotic homologues of the nicotinic acetylcholine receptor (nAChR) in conjunction with time-resolved analyses based on single-channel electrophysiology and Molecular Dynamics simulations. The available data consistently point to a global mechanism of gating that involves a large reorganization of the receptor mediated by two distinct quaternary transitions: a global twisting and a radial expansion/contraction of the extracellular domain. These transitions profoundly modify the organization of the interface between subunits, which host several sites for orthosteric and allosteric modulatory ligands. The same mechanism may thus mediate both positive and negative allosteric modulations of pLGICs ligand binding at topographically distinct sites. The emerging picture of signal transduction is expected to pave the way to new pharmacological strategies for the development of allosteric modulators of nAChR and pLGICs in general. This article is part of the Special Issue entitled 'The Nicotinic Acetylcholine Receptor: From Molecular Biology to Cognition'.

  11. Complex interactions between cis-regulatory modules in native conformation are critical for Drosophila snail expression.

    PubMed

    Dunipace, Leslie; Ozdemir, Anil; Stathopoulos, Angelike

    2011-09-01

    It has been shown in several organisms that multiple cis-regulatory modules (CRMs) of a gene locus can be active concurrently to support similar spatiotemporal expression. To understand the functional importance of such seemingly redundant CRMs, we examined two CRMs from the Drosophila snail gene locus, which are both active in the ventral region of pre-gastrulation embryos. By performing a deletion series in a ∼25 kb DNA rescue construct using BAC recombineering and site-directed transgenesis, we demonstrate that the two CRMs are not redundant. The distal CRM is absolutely required for viability, whereas the proximal CRM is required only under extreme conditions such as high temperature. Consistent with their distinct requirements, the CRMs support distinct expression patterns: the proximal CRM exhibits an expanded expression domain relative to endogenous snail, whereas the distal CRM exhibits almost complete overlap with snail except at the anterior-most pole. We further show that the distal CRM normally limits the increased expression domain of the proximal CRM and that the proximal CRM serves as a `damper' for the expression levels driven by the distal CRM. Thus, the two CRMs interact in cis in a non-additive fashion and these interactions may be important for fine-tuning the domains and levels of gene expression. PMID:21813571

  12. Complex interactions between cis-regulatory modules in native conformation are critical for Drosophila snail expression

    PubMed Central

    Dunipace, Leslie; Ozdemir, Anil; Stathopoulos, Angelike

    2011-01-01

    It has been shown in several organisms that multiple cis-regulatory modules (CRMs) of a gene locus can be active concurrently to support similar spatiotemporal expression. To understand the functional importance of such seemingly redundant CRMs, we examined two CRMs from the Drosophila snail gene locus, which are both active in the ventral region of pre-gastrulation embryos. By performing a deletion series in a ∼25 kb DNA rescue construct using BAC recombineering and site-directed transgenesis, we demonstrate that the two CRMs are not redundant. The distal CRM is absolutely required for viability, whereas the proximal CRM is required only under extreme conditions such as high temperature. Consistent with their distinct requirements, the CRMs support distinct expression patterns: the proximal CRM exhibits an expanded expression domain relative to endogenous snail, whereas the distal CRM exhibits almost complete overlap with snail except at the anterior-most pole. We further show that the distal CRM normally limits the increased expression domain of the proximal CRM and that the proximal CRM serves as a `damper' for the expression levels driven by the distal CRM. Thus, the two CRMs interact in cis in a non-additive fashion and these interactions may be important for fine-tuning the domains and levels of gene expression. PMID:21813571

  13. Mutation in the β-hairpin of the Bordetella pertussis adenylate cyclase toxin modulates N-lobe conformation in calmodulin

    SciTech Connect

    Springer, Tzvia I.; Goebel, Erich; Hariraju, Dinesh; Finley, Natosha L.

    2014-10-10

    Highlights: • Bordetella pertussis adenylate cyclase toxin modulates bi-lobal structure of CaM. • The structure and stability of the complex rely on intermolecular associations. • A novel mode of CaM-dependent activation of the adenylate cyclase toxin is proposed. - Abstract: Bordetella pertussis, causative agent of whooping cough, produces an adenylate cyclase toxin (CyaA) that is an important virulence factor. In the host cell, the adenylate cyclase domain of CyaA (CyaA-ACD) is activated upon association with calmodulin (CaM), an EF-hand protein comprised of N- and C-lobes (N-CaM and C-CaM, respectively) connected by a flexible tether. Maximal CyaA-ACD activation is achieved through its binding to both lobes of intact CaM, but the structural mechanisms remain unclear. No high-resolution structure of the intact CaM/CyaA-ACD complex is available, but crystal structures of isolated C-CaM bound to CyaA-ACD shed light on the molecular mechanism by which this lobe activates the toxin. Previous studies using molecular modeling, biochemical, and biophysical experiments demonstrate that CyaA-ACD’s β-hairpin participates in site-specific interactions with N-CaM. In this study, we utilize nuclear magnetic resonance (NMR) spectroscopy to probe the molecular association between intact CaM and CyaA-ACD. Our results indicate binding of CyaA-ACD to CaM induces large conformational perturbations mapping to C-CaM, while substantially smaller structural changes are localized primarily to helices I, II, and IV, and the metal-binding sites in N-CaM. Site-specific mutations in CyaA-ACD’s β-hairpin structurally modulate N-CaM, resulting in conformational perturbations in metal binding sites I and II, while no significant structural modifications are observed in C-CaM. Moreover, dynamic light scattering (DLS) analysis reveals that mutation of the β-hairpin results in a decreased hydrodynamic radius (R{sub h}) and reduced thermal stability in the mutant complex. Taken

  14. SU-E-T-62: Cardiac Toxicity in Dynamic Conformal Arc Therapy, Intensity-Modulated Radiation Therapy and Volumetric Modulated Arc Therapy of Lung Cancers

    SciTech Connect

    Ming, X; Zhang, Y; Feng, Y; Zhou, L; Deng, J

    2014-06-01

    Purpose: The cardiac toxicity for lung cancer patients, each treated with dynamic conformal arc therapy (DAT), intensity-modulated radiation therapy (IMRT), or volumetric modulated arc therapy (VMAT) is investigated. Methods: 120 lung patients were selected for this study: 25 treated with DAT, 50 with IMRT and 45 with VMAT. For comparison, all plans were generated in the same treatment planning system, normalized such that the 100% isodose lines encompassed 95% of planning target volume. The plan quality was evaluated in terms of homogeneity index (HI) and 95% conformity index (%95 CI) for target dose coverage and mean dose, maximum dose, V{sub 30} Gy as well as V{sub 5} Gy for cardiac toxicity analysis. Results: When all the plans were analyzed, the VMAT plans offered the best target coverage with 95% CI = 0.992 and HI = 1.23. The DAT plans provided the best heart sparing with mean heart dose = 2.3Gy and maximum dose = 11.6Gy, as compared to 5.7 Gy and 31.1 Gy by IMRT as well as 4.6 Gy and 30.9 Gy by VMAT. The mean V30Gy and V5Gy of the heart in the DAT plans were up to 11.7% lower in comparison to the IMRT and VMAT plans. When the tumor volume was considered, the VMAT plans spared up to 70.9% more doses to the heart when the equivalent diameter of the tumor was larger than 4cm. Yet the maximum dose to the heart was reduced the most in the DAT plans with up to 139.8% less than that of the other two plans. Conclusion: Overall, the VMAT plans achieved the best target coverage among the three treatment modalities, and would spare the heart the most for the larger tumors. The DAT plans appeared advantageous in delivering the least maximum dose to the heart as compared to the IMRT and VMAT plans.

  15. Dosimetric Comparison of Three-Dimensional Conformal Proton Radiotherapy, Intensity-Modulated Proton Therapy, and Intensity-Modulated Radiotherapy for Treatment of Pediatric Craniopharyngiomas

    SciTech Connect

    Boehling, Nicholas S.; Grosshans, David R.; Bluett, Jaques B.; Palmer, Matthew T.; Song, Xiaofei; Amos, Richard A.; Sahoo, Narayan; Meyer, Jeffrey J.; Mahajan, Anita; Woo, Shiao Y.

    2012-02-01

    Purpose: Cranial irradiation in pediatric patients is associated with serious long-term adverse effects. We sought to determine whether both three-dimensional conformal proton radiotherapy (3D-PRT) and intensity-modulated proton therapy (IMPT) compared with intensity-modulated radiotherapy (IMRT) decrease integral dose to brain areas known to harbor neuronal stem cells, major blood vessels, and other normal brain structures for pediatric patients with craniopharyngiomas. Methods and Materials: IMRT, forward planned, passive scattering proton, and IMPT plans were generated and optimized for 10 pediatric patients. The dose was 50.4 Gy (or cobalt Gy equivalent) delivered in 28 fractions with the requirement for planning target volume (PTV) coverage of 95% or better. Integral dose data were calculated from differential dose-volume histograms. Results: The PTV target coverage was adequate for all modalities. IMRT and IMPT yielded the most conformal plans in comparison to 3D-PRT. Compared with IMRT, 3D-PRT and IMPT plans had a relative reduction of integral dose to the hippocampus (3D-PRT, 20.4; IMPT, 51.3%{sup Asterisk-Operator }), dentate gyrus (27.3, 75.0%{sup Asterisk-Operator }), and subventricular zone (4.5, 57.8%{sup Asterisk-Operator }). Vascular organs at risk also had reduced integral dose with the use of proton therapy (anterior cerebral arteries, 33.3{sup Asterisk-Operator }, 100.0%{sup Asterisk-Operator }; middle cerebral arteries, 25.9%{sup Asterisk-Operator }, 100%{sup Asterisk-Operator }; anterior communicating arteries, 30.8{sup Asterisk-Operator }, 41.7%{sup Asterisk-Operator }; and carotid arteries, 51.5{sup Asterisk-Operator }, 77.6{sup Asterisk-Operator }). Relative reduction of integral dose to the infratentorial brain (190.7{sup Asterisk-Operator }, 109.7%{sup Asterisk-Operator }), supratentorial brain without PTV (9.6, 26.8%{sup Asterisk-Operator }), brainstem (45.6, 22.4%{sup Asterisk-Operator }), and whole brain without PTV (19.4{sup Asterisk

  16. Accuracy of Real-time Couch Tracking During 3-dimensional Conformal Radiation Therapy, Intensity Modulated Radiation Therapy, and Volumetric Modulated Arc Therapy for Prostate Cancer

    SciTech Connect

    Wilbert, Juergen; Baier, Kurt; Hermann, Christian; Flentje, Michael; Guckenberger, Matthias

    2013-01-01

    Purpose: To evaluate the accuracy of real-time couch tracking for prostate cancer. Methods and Materials: Intrafractional motion trajectories of 15 prostate cancer patients were the basis for this phantom study; prostate motion had been monitored with the Calypso System. An industrial robot moved a phantom along these trajectories, motion was detected via an infrared camera system, and the robotic HexaPOD couch was used for real-time counter-steering. Residual phantom motion during real-time tracking was measured with the infrared camera system. Film dosimetry was performed during delivery of 3-dimensional conformal radiation therapy (3D-CRT), step-and-shoot intensity modulated radiation therapy (IMRT), and volumetric modulated arc therapy (VMAT). Results: Motion of the prostate was largest in the anterior-posterior direction, with systematic ( N-Ary-Summation ) and random ({sigma}) errors of 2.3 mm and 2.9 mm, respectively; the prostate was outside a threshold of 5 mm (3D vector) for 25.0%{+-}19.8% of treatment time. Real-time tracking reduced prostate motion to N-Ary-Summation =0.01 mm and {sigma} = 0.55 mm in the anterior-posterior direction; the prostate remained within a 1-mm and 5-mm threshold for 93.9%{+-}4.6% and 99.7%{+-}0.4% of the time, respectively. Without real-time tracking, pass rates based on a {gamma} index of 2%/2 mm in film dosimetry ranged between 66% and 72% for 3D-CRT, IMRT, and VMAT, on average. Real-time tracking increased pass rates to minimum 98% on average for 3D-CRT, IMRT, and VMAT. Conclusions: Real-time couch tracking resulted in submillimeter accuracy for prostate cancer, which transferred into high dosimetric accuracy independently of whether 3D-CRT, IMRT, or VMAT was used.

  17. Longitudinal assessment of quality of life after surgery, conformal brachytherapy, and intensity-modulated radiation therapy for prostate cancer

    PubMed Central

    Zelefsky, Michael J.; Poon, Bing Ying; Eastham, James; Vickers, Andrew; Pei, Xin; Scardino, Peter T.

    2016-01-01

    Purpose We evaluated quality-of-life changes (QoL) in 907 patients treated with either radical prostatectomy (open or laparoscopic), real-time planned conformal brachytherapy, or high-dose intensity-modulated radiotherapy (IMRT) on a prospective IRB-approved longitudinal study. Methods Validated questionnaires given pretreatment (baseline) and at 3, 6, 9, 12, 15, 18, 24, 36, and 48 months addressed urinary function, urinary bother, bowel function, bowel bother, sexual function, and sexual bother. Results At 48 months, surgery had significantly higher urinary incontinence than others (both P<.001), but fewer urinary irritation/obstruction symptoms (all P<.001). Very low levels of bowel dysfunction were observed and only small subsets in each group showed rectal bleeding. Brachytherapy and IMRT showed better sexual function than surgery accounting for baseline function and other factors (delta 14.29 of 100, 95% CI, 8.57–20.01; and delta 10.5, 95% CI, 3.78–17.88). Sexual bother was similar. Four-year outcomes showed persistent urinary incontinence for surgery with more obstructive urinary symptoms for radiotherapy. Using modern radiotherapy delivery, bowel function deterioration is less-often observed. Sexual function was strongly affected in all groups yet significantly less for radiotherapy. Conclusions Treatment selection should include patient preferences and balance predicted disease-free survival over a projected time vs potential impairment of QoL important for the patient. PMID:26780999

  18. Comparison of volumetric-modulated arc therapy and dynamic conformal arc treatment planning for cranial stereotactic radiosurgery.

    PubMed

    Molinier, Jessica; Kerr, Christine; Simeon, Sebastien; Ailleres, Norbert; Charissoux, Marie; Azria, David; Fenoglietto, Pascal

    2016-01-08

    The aim was to analyze arc therapy techniques according to the number and position of the brain lesions reported by comparing dynamic noncoplanar conformal arcs (DCA), two coplanar full arcs (RAC) with volumetric-modulated arc therapy (VMAT), multiple noncoplanar partial arcs with VMAT (RANC), and two full arcs with VMAT and 10° table rotation (RAT). Patients with a single lesion (n= 10), multiple lesions (n = 10) or a single lesion close to organs at risk (n = 5) and previously treated with DCA were selected. For each patient, the DCA treatment was replanned with all VMAT techniques. All DCA plans were compared with VMAT plans and evaluated in regard to the different quality indices and dosimetric parameters. For single lesion, homogeneity index (HI) better results were found for the RANC technique (0.17 ± 0.05) compared with DCA procedure (0.27± 0.05). Concerning conformity index (CI), the RAT technique gave higher and better values (0.85 ± 0.04) compared with those obtained with the DCA technique (0.77 ± 0.05). DCA improved healthy brain protection (8.35 ± 5.61 cc vs. 10.52 ± 6.40 cc for RANC) and reduced monitor unit numbers (3046 ± 374 MU vs. 4651 ± 736 for RANC), even if global room occupation was higher. For multiple lesions, VMAT techniques provided better HI (0.16) than DCA (0.24 ± 0.07). The CI was improved with RAT (0.8 ± 0.08 for RAT vs. 0.71 ± 0.08 for DCA). The V10Gy healthy brain was better protected with DCA (9.27 ± 4.57 cc). Regarding the MU numbers: RANC < RAT< RAC < DCA. For a single lesion close to OAR, RAT achieved high degrees of homogeneity (0.27 ± 0.03 vs. 0.53 ± 0.2 for DCA) and conformity (0.72± 0.06vs. 0.56 ± 0.13 for DCA) while sparing organs at risk (Dmax = 12.36 ± 1.05Gyvs. 14.12 ± 0.59 Gy for DCA, and Dmean = 3.96 ± 3.57Gyvs. 4.72 ± 3.28Gy for DCA). On the other hand, MU numbers were lower with DCA (2254 ± 190 MUvs. 3438 ± 457 MU for RANC) even if overall time was inferior with RAC. For a single lesion, DCA

  19. A Comparison of Helical Intensity-Modulated Radiotherapy, Intensity-Modulated Radiotherapy, and 3D-Conformal Radiation Therapy for Pancreatic Cancer

    SciTech Connect

    Poppe, Matthew M.; Narra, Venkat; Yue, Ning J.; Zhou Jinghao; Nelson, Carl; Jabbour, Salma K.

    2011-01-01

    We assessed dosimetric differences in pancreatic cancer radiotherapy via helical intensity-modulated radiotherapy (HIMRT), linac-based IMRT, and 3D-conformal radiation therapy (3D-CRT) with regard to successful plan acceptance and dose to critical organs. Dosimetric analysis was performed in 16 pancreatic cases that were planned to 54 Gy; both post-pancreaticoduodenectomy (n = 8) and unresected (n = 8) cases were compared. Without volume modification, plans met constraints 75% of the time with HIMRT and IMRT and 13% with 3D-CRT. There was no statistically significantly improvement with HIMRT over conventional IMRT in reducing liver V35, stomach V45, or bowel V45. HIMRT offers improved planning target volume (PTV) dose homogeneity compared with IMRT, averaging a lower maximum dose and higher volume receiving the prescription dose (D100). HIMRT showed an increased mean dose over IMRT to bowel and liver. Both HIMRT and IMRT offer a statistically significant improvement over 3D-CRT in lowering dose to liver, stomach, and bowel. The results were similar for both unresected and resected patients. In pancreatic cancer, HIMRT offers improved dose homogeneity over conventional IMRT and several significant benefits to 3D-CRT. Factors to consider before incorporating IMRT into pancreatic cancer therapy are respiratory motion, dose inhomogeneity, and mean dose.

  20. Involved-Site Image-Guided Intensity Modulated Versus 3D Conformal Radiation Therapy in Early Stage Supradiaphragmatic Hodgkin Lymphoma

    SciTech Connect

    Filippi, Andrea Riccardo; Ciammella, Patrizia; Piva, Cristina; Ragona, Riccardo; Botto, Barbara; Gavarotti, Paolo; Merli, Francesco; Vitolo, Umberto; Iotti, Cinzia; Ricardi, Umberto

    2014-06-01

    Purpose: Image-guided intensity modulated radiation therapy (IG-IMRT) allows for margin reduction and highly conformal dose distribution, with consistent advantages in sparing of normal tissues. The purpose of this retrospective study was to compare involved-site IG-IMRT with involved-site 3D conformal RT (3D-CRT) in the treatment of early stage Hodgkin lymphoma (HL) involving the mediastinum, with efficacy and toxicity as primary clinical endpoints. Methods and Materials: We analyzed 90 stage IIA HL patients treated with either involved-site 3D-CRT or IG-IMRT between 2005 and 2012 in 2 different institutions. Inclusion criteria were favorable or unfavorable disease (according to European Organization for Research and Treatment of Cancer criteria), complete response after 3 to 4 cycles of an adriamycin- bleomycin-vinblastine-dacarbazine (ABVD) regimen plus 30 Gy as total radiation dose. Exclusion criteria were chemotherapy other than ABVD, partial response after ABVD, total radiation dose other than 30 Gy. Clinical endpoints were relapse-free survival (RFS) and acute toxicity. Results: Forty-nine patients were treated with 3D-CRT (54.4%) and 41 with IG-IMRT (45.6%). Median follow-up time was 54.2 months for 3D-CRT and 24.1 months for IG-IMRT. No differences in RFS were observed between the 2 groups, with 1 relapse each. Three-year RFS was 98.7% for 3D-CRT and 100% for IG-IMRT. Grade 2 toxicity events, mainly mucositis, were recorded in 32.7% of 3D-CRT patients (16 of 49) and in 9.8% of IG-IMRT patients (4 of 41). IG-IMRT was significantly associated with a lower incidence of grade 2 acute toxicity (P=.043). Conclusions: RFS rates at 3 years were extremely high in both groups, albeit the median follow-up time is different. Acute tolerance profiles were better for IG-IMRT than for 3D-CRT. Our preliminary results support the clinical safety and efficacy of advanced RT planning and delivery techniques in patients affected with early stage HL, achieving complete

  1. Mutation in the β-hairpin of the Bordetella pertussis adenylate cyclase toxin modulates N-lobe conformation in calmodulin.

    PubMed

    Springer, Tzvia I; Goebel, Erich; Hariraju, Dinesh; Finley, Natosha L

    2014-10-10

    Bordetella pertussis, causative agent of whooping cough, produces an adenylate cyclase toxin (CyaA) that is an important virulence factor. In the host cell, the adenylate cyclase domain of CyaA (CyaA-ACD) is activated upon association with calmodulin (CaM), an EF-hand protein comprised of N- and C-lobes (N-CaM and C-CaM, respectively) connected by a flexible tether. Maximal CyaA-ACD activation is achieved through its binding to both lobes of intact CaM, but the structural mechanisms remain unclear. No high-resolution structure of the intact CaM/CyaA-ACD complex is available, but crystal structures of isolated C-CaM bound to CyaA-ACD shed light on the molecular mechanism by which this lobe activates the toxin. Previous studies using molecular modeling, biochemical, and biophysical experiments demonstrate that CyaA-ACD's β-hairpin participates in site-specific interactions with N-CaM. In this study, we utilize nuclear magnetic resonance (NMR) spectroscopy to probe the molecular association between intact CaM and CyaA-ACD. Our results indicate binding of CyaA-ACD to CaM induces large conformational perturbations mapping to C-CaM, while substantially smaller structural changes are localized primarily to helices I, II, and IV, and the metal-binding sites in N-CaM. Site-specific mutations in CyaA-ACD's β-hairpin structurally modulate N-CaM, resulting in conformational perturbations in metal binding sites I and II, while no significant structural modifications are observed in C-CaM. Moreover, dynamic light scattering (DLS) analysis reveals that mutation of the β-hairpin results in a decreased hydrodynamic radius (Rh) and reduced thermal stability in the mutant complex. Taken together, our data provide new structural insights into the β-hairpin's role in stabilizing interactions between CyaA-ACD and N-CaM.

  2. Salivary gland sparing and improved target irradiation by conformal and intensity modulated irradiation of head and neck cancer.

    PubMed

    Eisbruch, Avraham; Ship, Jonathan A; Dawson, Laura A; Kim, Hyungjin M; Bradford, Carol R; Terrell, Jeffrey E; Chepeha, Douglas B; Teknos, Theodore N; Hogikyan, Norman D; Anzai, Yoshimi; Marsh, Lon H; Ten Haken, Randall K; Wolf, Gregory T

    2003-07-01

    The goals of this study were to facilitate sparing of the major salivary glands while adequately treating tumor targets in patients requiring comprehensive bilateral neck irradiation (RT), and to assess the potential for improved xerostomia. Since 1994 techniques of target irradiation and locoregional tumor control with conformal and intensity modulated radiation therapy (IMRT) have been developed. In patients treated with these modalities, the salivary flow rates before and periodically after RT have been measured selectively from each major salivary gland and the residual flows correlated with glands' dose volume histograms (DVHs). In addition, subjective xerostomia questionnaires have been developed and validated. The pattern of locoregional recurrence has been examined from computed tomography (CT) scans at the time of recurrence, transferring the recurrence volumes to the planning CT scans, and regenerating the dose distributions at the recurrence sites. Treatment plans for target coverage and dose homogeneity using static, multisegmental IMRT were found to be significantly better than standard RT plans. In addition, significant parotid gland sparing was achieved in the conformal plans. The relationships among dose, irradiated volume, and the residual saliva flow rates from the parotid glands were characterized by dose and volume thresholds. A mean radiation dose of 26 Gy was found to be the threshold for preserved stimulated saliva flow. Xerostomia questionnaire scores suggested that xerostomia was significantly reduced in patients irradiated with bilateral neck, parotid-sparing RT, compared to patients with similar tumors treated with standard RT. Examination of locoregional tumor recurrence patterns revealed that the large majority of recurrences occurred inside targets, in areas that had been judged to be at high risk and that had received RT doses according to the perceived risk. Tangible gains in salivary gland sparing and target coverage are being

  3. Cost-Effectiveness Analysis of Intensity Modulated Radiation Therapy Versus 3-Dimensional Conformal Radiation Therapy for Anal Cancer

    SciTech Connect

    Hodges, Joseph C.; Beg, Muhammad S.; Das, Prajnan; Meyer, Jeffrey

    2014-07-15

    Purpose: To compare the cost-effectiveness of intensity modulated radiation therapy (IMRT) and 3-dimensional conformal radiation therapy (3D-CRT) for anal cancer and determine disease, patient, and treatment parameters that influence the result. Methods and Materials: A Markov decision model was designed with the various disease states for the base case of a 65-year-old patient with anal cancer treated with either IMRT or 3D-CRT and concurrent chemotherapy. Health states accounting for rates of local failure, colostomy failure, treatment breaks, patient prognosis, acute and late toxicities, and the utility of toxicities were informed by existing literature and analyzed with deterministic and probabilistic sensitivity analysis. Results: In the base case, mean costs and quality-adjusted life expectancy in years (QALY) for IMRT and 3D-CRT were $32,291 (4.81) and $28,444 (4.78), respectively, resulting in an incremental cost-effectiveness ratio of $128,233/QALY for IMRT compared with 3D-CRT. Probabilistic sensitivity analysis found that IMRT was cost-effective in 22%, 47%, and 65% of iterations at willingness-to-pay thresholds of $50,000, $100,000, and $150,000 per QALY, respectively. Conclusions: In our base model, IMRT was a cost-ineffective strategy despite the reduced acute treatment toxicities and their associated costs of management. The model outcome was sensitive to variations in local and colostomy failure rates, as well as patient-reported utilities relating to acute toxicities.

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

    SciTech Connect

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

    2008-10-01

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

  5. The conserved disulfide bond of human tear lipocalin modulates conformation and lipid binding in a ligand selective manner

    PubMed Central

    Gasymov, Oktay K.; Abduragimov, Adil R.; Glasgow, Ben J.

    2011-01-01

    The primary aim of this study is the elucidation of the mechanism of disulfide induced alteration of ligand binding in human tear lipocalin (TL). Disulfide bonds may act as dynamic scaffolds to regulate conformational changes that alter protein function including receptor-ligand interactions. A single disulfide bond, (Cys61-Cys153), exists in TL that is highly conserved in the lipocalin superfamily. Circular dichroism and fluorescence spectroscopies were applied to investigate the mechanism by which disulfide bond removal effects protein stability, dynamics and ligand binding properties. Although the secondary structure is not altered by disulfide elimination, TL shows decreased stability against urea denaturation. Free energy change (ΔG0) decreases from 4.9± 0.2 to 2.1± 0.3 kcal/mol with removal of the disulfide bond. Furthermore, ligand binding properties of TL without the disulfide vary according to the type of ligand. The binding of a bulky ligand, NBD-cholesterol, has a decreased time constant (from 11.8± 0.2 to 3.3 s). In contrast, the NBD-labeled phospholipid shows a moderate decrease in the time constant for binding, from 33.2± 0.2 to 22.2± 0.4 s. FRET experiments indicate that the hairpin CD is directly involved in modulation of both ligand binding and flexibility of TL. In TL complexed with palmitc acid (PA-TL), the distance between the residues 62 of strand D and 81 of loop EF is decreased by disulfide bond reduction. Consequently, removal of the disulfide bond boosts flexibility of the protein to reach a CD-EF loop distance (24.3 Å, between residues 62 and 81), which is not accessible for the protein with an intact disulfide bond (26.2 Å). The results suggest that enhanced flexibility of the protein promotes a faster accommodation of the ligand inside the cavity and energetically favorable ligand-protein complex. PMID:21466861

  6. Intensity modulated radiotherapy in early stage Hodgkin lymphoma patients: Is it better than three dimensional conformal radiotherapy?

    PubMed Central

    2012-01-01

    Background Cure rate of early Hodgkin Lymphoma are high and avoidance of late toxicities is of paramount importance. This comparative study aims to assess the normal tissue sparing capability of intensity-modulated radiation therapy (IMRT) versus standard three-dimensional conformal radiotherapy (3D-CRT) in terms of dose-volume parameters and normal tissue complication probability (NTCP) for different organs at risk in supradiaphragmatic Hodgkin Lymphoma (HL) patients. Methods Ten HL patients were actually treated with 3D-CRT and all treatments were then re-planned with IMRT. Dose-volume parameters for thyroid, oesophagus, heart, coronary arteries, lung, spinal cord and breast were evaluated. Dose-volume histograms generated by TPS were analyzed to predict the NTCP for the considered organs at risk, according to different endpoints. Results Regarding dose-volume parameters no statistically significant differences were recorded for heart and origin of coronary arteries. We recorded statistically significant lower V30 with IMRT for oesophagus (6.42 vs 0.33, p = 0.02) and lungs (4.7 vs 0.1 p = 0.014 for the left lung and 2.59 vs 0.1 p = 0.017 for the right lung) and lower V20 for spinal cord (17.8 vs 7.2 p = 0.02). Moreover the maximum dose to the spinal cord was lower with IMRT (30.2 vs 19.9, p <0.001). Higher V10 with IMRT for thyroid (64.8 vs 95, p = 0.0019) and V5 for lungs (30.3 vs 44.8, p = 0.03, for right lung and 28.9 vs 48.1, p = 0.001 for left lung) were found, respectively. Higher V5 and V10 for breasts were found with IMRT (V5: 4.14 vs 20.6, p = 0.018 for left breast and 3.3 vs 17, p = 0.059 for right breast; V10: 2.5 vs 13.6 p = 0.035 for left breast and 1.7 vs 11, p = 0.07 for the right breast.) As for the NTCP, our data point out that IMRT is not always likely to significantly increase the NTCP to OARs. Conclusions In HL male patients IMRT seems feasible and accurate while for women HL patients IMRT should be

  7. High-dose radiotherapy in inoperable nonsmall cell lung cancer: comparison of volumetric modulated arc therapy, dynamic IMRT and 3D conformal radiotherapy.

    PubMed

    Bree, Ingrid de; van Hinsberg, Mariëlle G E; van Veelen, Lieneke R

    2012-01-01

    Conformal 3D radiotherapy (3D-CRT) combined with chemotherapy for inoperable non-small cell lung cancer (NSCLC) to the preferable high dose is often not achievable because of dose-limiting organs. This reduces the probability of regional tumor control. Therefore, the surplus value of using intensity-modulated radiation therapy (IMRT) techniques, specifically volumetric modulated arc therapy (RapidArc [RA]) and dynamic IMRT (d-IMRT) has been investigated. RA and d-IMRT plans were compared with 3D-CRT treatment plans for 20 patients eligible for concurrent high-dose chemoradiotherapy, in whom a dose of 60 Gy was not achievable. Comparison of dose delivery in the target volume and organs at risk was carried out by evaluating 3D dose distributions and dose-volume histograms. Quality of the dose distribution was assessed using the inhomogeneity and conformity index. For most patients, a higher dose to the target volume can be delivered using RA or d-IMRT; in 15% of the patients a dose ≥60 Gy was possible. Both IMRT techniques result in a better conformity of the dose (p < 0.001). There are no significant differences in homogeneity of dose in the target volume. IMRT techniques for NSCLC patients allow higher dose to the target volume, thus improving regional tumor control. PMID:22459649

  8. Intensity-modulated radiotherapy (IMRT) and conventional three-dimensional conformal radiotherapy for high-grade gliomas: Does IMRT increase the integral dose to normal brain?

    SciTech Connect

    Hermanto, Ulrich; Frija, Erik K.; Lii, MingFwu J.; Chang, Eric L.; Mahajan, Anita; Woo, Shiao Y. . E-mail: SYWoo@mdanderson.org

    2007-03-15

    Purpose: To determine whether intensity-modulated radiotherapy (IMRT) treatment increases the total integral dose of nontarget tissue relative to the conventional three-dimensional conformal radiotherapy (3D-CRT) technique for high-grade gliomas. Methods and Materials: Twenty patients treated with 3D-CRT for glioblastoma multiforme were selected for a comparative dosimetric evaluation with IMRT. Original target volumes, organs at risk (OAR), and dose-volume constraints were used for replanning with IMRT. Predicted isodose distributions, cumulative dose-volume histograms of target volumes and OAR, normal tissue integral dose, target coverage, dose conformity, and normal tissue sparing with 3D-CRT and IMRT planning were compared. Statistical analyses were performed to determine differences. Results: In all 20 patients, IMRT maintained equivalent target coverage, improved target conformity (conformity index [CI] 95% 1.52 vs. 1.38, p < 0.001), and enabled dose reductions of normal tissues, including brainstem (D{sub mean} by 19.8% and D{sub max} by 10.7%), optic chiasm (D{sub mean} by 25.3% and D{sub max} by 22.6%), right optic nerve (D{sub mean} by 37.3% and D{sub max} by 28.5%), and left optic nerve (D{sub mean} by 40.6% and D{sub max} by 36.7%), p {<=} 0.01. This was achieved without increasing the total nontarget integral dose by greater than 0.5%. Overall, total integral dose was reduced by 7-10% with IMRT, p < 0.001, without significantly increasing the 0.5-5 Gy low-dose volume. Conclusions: These results indicate that IMRT treatment for high-grade gliomas allows for improved target conformity, better critical tissue sparing, and importantly does so without increasing integral dose and the volume of normal tissue exposed to low doses of radiation.

  9. Comparison of Heart and Coronary Artery Doses Associated With Intensity-Modulated Radiotherapy Versus Three-Dimensional Conformal Radiotherapy for Distal Esophageal Cancer

    SciTech Connect

    Kole, Thomas P.; Aghayere, Osarhieme; Kwah, Jason; Yorke, Ellen D.; Goodman, Karyn A.

    2012-08-01

    Purpose: To compare heart and coronary artery radiation exposure using intensity-modulated radiotherapy (IMRT) vs. four-field three-dimensional conformal radiotherapy (3D-CRT) treatment plans for patients with distal esophageal cancer undergoing chemoradiation. Methods and Materials: Nineteen patients with distal esophageal cancers treated with IMRT from March 2007 to May 2008 were identified. All patients were treated to 50.4 Gy with five-field IMRT plans. Theoretical 3D-CRT plans with four-field beam arrangements were generated. Dose-volume histograms of the planning target volume, heart, right coronary artery, left coronary artery, and other critical normal tissues were compared between the IMRT and 3D-CRT plans, and selected parameters were statistically evaluated using the Wilcoxon rank-sum test. Results: Intensity-modulated radiotherapy treatment planning showed significant reduction (p < 0.05) in heart dose over 3D-CRT as assessed by average mean dose (22.9 vs. 28.2 Gy) and V30 (24.8% vs. 61.0%). There was also significant sparing of the right coronary artery (average mean dose, 23.8 Gy vs. 35.5 Gy), whereas the left coronary artery showed no significant improvement (mean dose, 11.2 Gy vs. 9.2 Gy), p = 0.11. There was no significant difference in percentage of total lung volume receiving at least 10, 15, or 20 Gy or in the mean lung dose between the planning methods. There were also no significant differences observed for the kidneys, liver, stomach, or spinal cord. Intensity-modulated radiotherapy achieved a significant improvement in target conformity as measured by the conformality index (ratio of total volume receiving 95% of prescription dose to planning target volume receiving 95% of prescription dose), with the mean conformality index reduced from 1.56 to 1.30 using IMRT. Conclusions: Treatment of patients with distal esophageal cancer using IMRT significantly decreases the exposure of the heart and right coronary artery when compared with 3D

  10. Epac and the high affinity rolipram binding conformer of PDE4 modulate neurite outgrowth and myelination using an in vitro spinal cord injury model

    PubMed Central

    Boomkamp, S D; McGrath, M A; Houslay, M D; Barnett, S C

    2014-01-01

    Background and Purpose cAMP and pharmacological inhibition of PDE4, which degrades it, are promising therapeutic targets for the treatment of spinal cord injury (SCI). Using our previously described in vitro SCI model, we studied the mechanisms by which cAMP modulators promote neurite outgrowth and myelination using enantiomers of the PDE4-specific inhibitor rolipram and other modulators of downstream signalling effectors. Experimental Approach Rat mixed neural cell myelinating cultures were cut with a scalpel and treated with enantiomers of the PDE4-specific inhibitor rolipram, Epac agonists and PKA antagonists. Neurite outgrowth, density and myelination were assessed by immunocytochemistry and cytokine levels analysed by qPCR. Key Results Inhibition of the high-affinity rolipram-binding state (HARBS), rather than the low-affinity rolipram binding state (LARBS) PDE4 conformer promoted neurite outgrowth and myelination. These effects were mediated through the activation of Epac and not through PKA. Expression of the chemokine CXCL10, known to inhibit myelination, was markedly elevated in astrocytes after Rho inhibition and this was blocked by inhibition of Rho kinase or PDE4. Conclusions and Implications PDE4 inhibitors targeted at the HARBS conformer or Epac agonists may provide promising novel targets for the treatment of SCI. Our study demonstrates the differential mechanisms of action of these compounds, as well as the benefit of a combined pharmacological approach and highlighting potential promising targets for the treatment of SCI. These findings need to be confirmed in vivo. PMID:24467222

  11. Whole breast and excision cavity radiotherapy plan comparison: Conformal radiotherapy with sequential boost versus intensity-modulated radiation therapy with a simultaneously integrated boost

    SciTech Connect

    Small, Katherine; Kelly, Chris; Beldham-Collins, Rachael; Gebski, Val

    2013-03-15

    A comparative study was conducted comparing the difference between (1) conformal radiotherapy (CRT) to the whole breast with sequential boost excision cavity plans and (2) intensity-modulated radiation therapy (IMRT) to the whole breast with simultaneously integrated boost to the excision cavity. The computed tomography (CT) data sets of 25 breast cancer patients were used and the results analysed to determine if either planning method produced superior plans. CT data sets from 25 past breast cancer patients were planned using (1) CRT prescribed to 50 Gy in 25 fractions (Fx) to the whole-breast planning target volume (PTV) and 10 Gy in 5Fx to the excision cavity and (2) IMRT prescribed to 60 Gy in 25Fx, with 60 Gy delivered to the excision cavity PTV and 50 Gy delivered to the whole-breast PTV, treated simultaneously. In total, 50 plans were created, with each plan evaluated by PTV coverage using conformity indices, plan maximum dose, lung dose, and heart maximum dose for patients with left-side lesions. CRT plans delivered the lowest plan maximum doses in 56% of cases (average CRT = 6314.34 cGy, IMRT = 6371.52 cGy). They also delivered the lowest mean lung dose in 68% of cases (average CRT = 1206.64 cGy, IMRT = 1288.37 cGy) and V20 in 88% of cases (average CRT = 20.03%, IMRT = 21.73%) and V30 doses in 92% of cases (average CRT = 16.82%, IMRT = 17.97%). IMRT created more conformal plans, using both conformity index and conformation number, in every instance, and lower heart maximum doses in 78.6% of cases (average CRT = 5295.26 cGy, IMRT = 5209.87 cGy). IMRT plans produced superior dose conformity and shorter treatment duration, but a slightly higher planning maximum and increased lung doses. IMRT plans are also faster to treat on a daily basis, with shorter fractionation.

  12. A comprehensive dosimetric study of pancreatic cancer treatment using three-dimensional conformal radiation therapy (3DCRT), intensity-modulated radiation therapy (IMRT), volumetric-modulated radiation therapy (VMAT), and passive-scattering and modulated-scanning proton therapy (PT)

    SciTech Connect

    Ding, Xuanfeng; Dionisi, Francesco; Tang, Shikui; Ingram, Mark; Hung, Chun-Yu; Prionas, Evangelos; Lichtenwalner, Phil; Butterwick, Ian; Zhai, Huifang; Yin, Lingshu; Lin, Haibo; Kassaee, Alireza; Avery, Stephen

    2014-07-01

    With traditional photon therapy to treat large postoperative pancreatic target volume, it often leads to poor tolerance of the therapy delivered and may contribute to interrupted treatment course. This study was performed to evaluate the potential advantage of using passive-scattering (PS) and modulated-scanning (MS) proton therapy (PT) to reduce normal tissue exposure in postoperative pancreatic cancer treatment. A total of 11 patients with postoperative pancreatic cancer who had been previously treated with PS PT in University of Pennsylvania Roberts Proton Therapy Center from 2010 to 2013 were identified. The clinical target volume (CTV) includes the pancreatic tumor bed as well as the adjacent high-risk nodal areas. Internal (iCTV) was generated from 4-dimensional (4D) computed tomography (CT), taking into account target motion from breathing cycle. Three-field and 4-field 3D conformal radiation therapy (3DCRT), 5-field intensity-modulated radiation therapy, 2-arc volumetric-modulated radiation therapy, and 2-field PS and MS PT were created on the patients’ average CT. All the plans delivered 50.4 Gy to the planning target volume (PTV). Overall, 98% of PTV was covered by 95% of the prescription dose and 99% of iCTV received 98% prescription dose. The results show that all the proton plans offer significant lower doses to the left kidney (mean and V{sub 18} {sub Gy}), stomach (mean and V{sub 20} {sub Gy}), and cord (maximum dose) compared with all the photon plans, except 3-field 3DCRT in cord maximum dose. In addition, MS PT also provides lower doses to the right kidney (mean and V{sub 18} {sub Gy}), liver (mean dose), total bowel (V{sub 20} {sub Gy} and mean dose), and small bowel (V{sub 15} {sub Gy} absolute volume ratio) compared with all the photon plans and PS PT. The dosimetric advantage of PT points to the possibility of treating tumor bed and comprehensive nodal areas while providing a more tolerable treatment course that could be used for dose

  13. The role of Cobalt-60 source in Intensity Modulated Radiation Therapy: From modeling finite sources to treatment planning and conformal dose delivery

    NASA Astrophysics Data System (ADS)

    Dhanesar, Sandeep Kaur

    Cobalt-60 (Co-60) units played an integral role in radiation therapy from the mid-1950s to the 1970s. Although they continue to be used to treat cancer in some parts of the world, their role has been significantly reduced due to the invention of medical linear accelerators. A number of groups have indicated a strong potential for Co-60 units in modern radiation therapy. The Medical Physics group at the Cancer Center of the Southeastern Ontario and Queen's University has shown the feasibility of Intensity Modulated Radiation Therapy (IMRT) via simple conformal treatment planning and dose delivery using a Co-60 unit. In this thesis, initial Co-60 tomotherapy planning investigations on simple uniform phantoms are extended to actual clinical cases based on patient CT data. The planning is based on radiation dose data from a clinical Co-60 unit fitted with a multileaf collimator (MLC) and modeled in the EGSnrc Monte Carlo system. An in house treatment planning program is used to calculate IMRT dose distributions. Conformal delivery in a single slice on a uniform phantom based on sequentially delivered pencil beams is verified by Gafchromic film. Volumetric dose distributions for Co-60 serial tomotherapy are then generated for typical clinical sites that had been treated at our clinic by conventional 6MV IMRT using Varian Eclipse treatment plans. The Co-60 treatment plans are compared with the clinical IMRT plans using conventional matrices such as dose volume histograms (DVH). Dose delivery based on simultaneously opened MLC leaves is also explored and a novel MLC segmentation method is proposed. In order to increase efficiency of dose calculations, a novel convolution based fluence model for treatment planning is also proposed. The ion chamber measurements showed that the Monte Carlo modeling of the beam data under the MIMiC MLC is accurate. The film measurements from the uniform phantom irradiations confirm that IMRT plans from our in-house treatment planning system

  14. Intensity-Modulated Radiation Therapy, Proton Therapy, or Conformal Radiation Therapy and Morbidity and Disease Control in Localized Prostate Cancer

    PubMed Central

    Sheets, Nathan C.; Goldin, Gregg H.; Meyer, Anne-Marie; Wu, Yang; Chang, YunKyung; Stürmer, Til; Holmes, Jordan A.; Reeve, Bryce B.; Godley, Paul A.; Carpenter, William R.; Chen, Ronald C.

    2013-01-01

    Context There has been rapid adoption of newer radiation treatments such as intensitymodulated radiation therapy (IMRT) and proton therapy despite greater cost and limited demonstrated benefit compared with previous technologies. Objective To determine the comparative morbidity and disease control of IMRT, proton therapy, and conformal radiation therapy for primary prostate cancer treatment. Design, Setting, and Patients Population-based study using Surveillance, Epidemiology, and End Results–Medicare-linked data from 2000 through 2009 for patients with nonmetastatic prostate cancer. Main Outcome Measures Rates of gastrointestinal and urinary morbidity, erectile dysfunction, hip fractures, and additional cancer therapy. Results Use of IMRT vs conformal radiation therapy increased from 0.15% in 2000 to 95.9% in 2008. In propensity score–adjusted analyses (N=12 976), men who received IMRT vs conformal radiation therapy were less likely to receive a diagnosis of gastrointestinal morbidities (absolute risk, 13.4 vs 14.7 per 100 person-years; relative risk [RR], 0.91; 95% CI, 0.86–0.96) and hip fractures (absolute risk, 0.8 vs 1.0 per 100 person-years; RR, 0.78; 95% CI, 0.65–0.93) but more likely to receive a diagnosis of erectile dysfunction (absolute risk, 5.9 vs 5.3 per 100 person-years; RR, 1.12; 95% CI, 1.03–1.20). Intensitymodulated radiation therapy patients were less likely to receive additional cancer therapy (absolute risk, 2.5 vs 3.1 per 100 person-years; RR, 0.81; 95% CI, 0.73–0.89). In a propensity score–matched comparison between IMRT and proton therapy (n=1368), IMRT patients had a lower rate of gastrointestinal morbidity (absolute risk, 12.2 vs 17.8 per 100 person-years; RR, 0.66; 95% CI, 0.55–0.79). There were no significant differences in rates of other morbidities or additional therapies between IMRT and proton therapy. Conclusions Among patients with nonmetastatic prostate cancer, the use of IMRT compared with conformal radiation

  15. Potential for Improved Intelligence Quotient Using Volumetric Modulated Arc Therapy Compared With Conventional 3-Dimensional Conformal Radiation for Whole-Ventricular Radiation in Children

    SciTech Connect

    Qi, X. Sharon; Stinauer, Michelle; Rogers, Brion; Madden, Jennifer R.; Wilkening, Greta N.; Liu, Arthur K.

    2012-12-01

    Purpose: To compare volumetric modulated arc therapy (VMAT) with 3-dimensional conformal radiation therapy (3D-CRT) in the treatment of localized intracranial germinoma. We modeled the effect of the dosimetric differences on intelligence quotient (IQ). Method and Materials: Ten children with intracranial germinomas were used for planning. The prescription doses were 23.4 Gy to the ventricles followed by 21.6 Gy to the tumor located in the pineal region. For each child, a 3D-CRT and full arc VMAT was generated. Coverage of the target was assessed by computing a conformity index and heterogeneity index. We also generated VMAT plans with explicit temporal lobe sparing and with smaller ventricular margin expansions. Mean dose to the temporal lobe was used to estimate IQ 5 years after completion of radiation, using a patient age of 10 years. Results: Compared with the 3D-CRT plan, VMAT improved conformality (conformity index 1.10 vs 1.85), with slightly higher heterogeneity (heterogeneity index 1.09 vs 1.06). The averaged mean doses for left and right temporal lobes were 31.3 and 31.7 Gy, respectively, for VMAT plans and 37.7 and 37.6 Gy for 3D-CRT plans. This difference in mean temporal lobe dose resulted in an estimated IQ difference of 3.1 points at 5 years after radiation therapy. When the temporal lobes were explicitly included in the VMAT optimization, the mean temporal lobe dose was reduced 5.6-5.7 Gy, resulting in an estimated IQ difference of an additional 3 points. Reducing the ventricular margin from 1.5 cm to 0.5 cm decreased mean temporal lobe dose 11.4-13.1 Gy, corresponding to an estimated increase in IQ of 7 points. Conclusion: For treatment of children with intracranial pure germinomas, VMAT compared with 3D-CRT provides increased conformality and reduces doses to normal tissue. This may result in improvements in IQ in these children.

  16. Stereotactic Radiotherapy of Central Nervous System and Head and Neck Lesions, Using a Conformal Intensity-Modulated Radiotherapy System (Peacock™ System)

    PubMed Central

    Ammirati, Mario; Bernardo, Antonio; Ramsinghani, Nilam; Yakoob, Richard; Al-Ghazi, Matthew; Kuo, Jeffrey; Ammirati, Giuseppe

    2001-01-01

    The objective of this article is to evaluate single-fraction or fractionated stereotactic radiotherapy of central nervous system (CNS) and head and neck lesions using intensity-modulated radiotherapy (IMRT) with a commercially available system (Peacock™, Nomos Corporation, Sewickley, PA). This system allows tomotherapeutic delivery of intensity-modulated radiation, that is, the slice-by-slice treatment of the volume of interest with an intensity-modulated beam, making the delivery of highly conformal radiation to the target possible in both single or multiple fractions mode. During an 18-month period, 43 (21 males and 22 females) patients were treated, using a removable cranial screw-fixation device. Ages ranged from 10 to 77 years (mean, 52.2; median, 53.5). Intra- and extra-axial lesions, including head and neck malignancies and spine metastases, were treated. Clinical target volume ranged from 0.77 to 195 cm3 (mean, 47.8; median, 29.90). The dose distribution was normalized to the maximum and was prescribed, in most cases, at the 80% or 90% isodose line (range, 65 to 96%; median, 85%; mean, 83.4%) and ranged from 14 to 80 Gy (mean, 48; median, 50). The number of fractions ranged from 1 to 40 (mean, 23; median, 25). In all but one patient, 90% of the prescription isodose line covered 100% of the clinical target volume. The heterogeneity index (the ratio between the maximum radiation dose and the prescribed dose) ranged between 1.0 and 1.50, whereas the conformity index (the ratio between the volume encompassed by the prescription isodose line and the clinical target volume) ranged between 1.0 and 4.5. There were no complications related to the radiation treatment. With a median follow-up of 6 months, more than 70% of our patients showed decreased lesion size. Stereotactic IMRT of CNS and head and neck lesions can be delivered safely and accurately. The Peacock system delivers stereotactic radiation in single or multiple fractions and has no volume limitations

  17. Residues in the membrane-spanning domain core modulate conformation and fusogenicity of the HIV-1 envelope glycoprotein

    SciTech Connect

    Shang Liang; Hunter, Eric

    2010-09-01

    The membrane-spanning domain (MSD) of human immunodeficiency virus type I (HIV-1) envelope glycoprotein (Env) is critical for its biological activity. Initial studies have defined an almost invariant 'core' structure in the MSD and demonstrated that it is crucial for anchoring Env in the membrane and virus entry. We show here that amino acid substitutions in the MSD 'core' do not influence specific virus-cell attachment, nor CD4 receptor and CXCR4 coreceptor recognition by Env. However, substitutions within the MSD 'core' delayed the kinetics and reduced the efficiency of cell-cell fusion mediated by Env. Although we observed no evidence that membrane fusion mediated by the MSD core mutants was arrested at a hemifusion stage, impaired Env fusogenicity was correlated with minor conformational changes in the V2, C1, and C5 regions in gp120 and the immunodominant loop in gp41. These changes could delay initiation of the conformational changes required in the fusion process.

  18. Ser¹¹⁹ phosphorylation modulates the activity and conformation of PRRXL1, a homeodomain transcription factor.

    PubMed

    Soares-dos-Reis, Ricardo; Pessoa, Ana S; Matos, Mariana R; Falcão, Miguel; Mendes, Vera M; Manadas, Bruno; Monteiro, Filipe A; Lima, Deolinda; Reguenga, Carlos

    2014-05-01

    PRRXL1 [paired related homeobox-like 1; also known as DRG11 (dorsal root ganglia 11)] is a paired-like homeodomain transcription factor expressed in DRG and dSC (dorsal spinal cord) nociceptive neurons. PRRXL1 is crucial for the establishment and maintenance of nociceptive circuitry, as Prrxl1(-/-) mice present neuronal loss, reduced pain sensitivity and failure to thrive. In the present study, we show that PRRXL1 is highly phosphorylated in vivo, and that its multiple band pattern on electrophoretic analysis is the result of different phosphorylation states. PRRXL1 phosphorylation appears to be differentially regulated along the dSC and DRG development and it is mapped to two functional domains. One region comprises amino acids 107-143, whereas the other one encompasses amino acids 227-263 and displays repressor activity. Using an immunoprecipitation-MS approach, two phosphorylation sites were identified, Ser¹¹⁹ and Ser²³⁸. Phosphorylation at Ser¹¹⁹ is shown to be determinant for PRRXL1 conformation and transcriptional activity. Ser¹¹⁹ phosphorylation is thus proposed as a mechanism for regulating PRRXL1 function and conformation during nociceptive system development.

  19. pH-Dependent Conformational Changes in the HCV NS3 Protein Modulate Its ATPase and Helicase Activities

    PubMed Central

    Ventura, Gustavo Tavares; da Costa, Emmerson Corrêa Brasil; Capaccia, Anne Miranda; Mohana-Borges, Ronaldo

    2014-01-01

    The hepatitis C virus (HCV) infects 170 to 200 million people worldwide and is, therefore, a major health problem. The lack of efficient treatments that specifically target the viral proteins or RNA and its high chronicity rate make hepatitis C the cause of many deaths and hepatic transplants annually. The NS3 protein is considered an important target for the development of anti-HCV drugs because it is composed of two domains (a serine protease in the N-terminal portion and an RNA helicase/NTPase in the C-terminal portion), which are essential for viral replication and proliferation. We expressed and purified both the NS3 helicase domain (NS3hel) and the full-length NS3 protein (NS3FL) and characterized pH-dependent structural changes associated with the increase in their ATPase and helicase activities at acidic pH. Using intrinsic fluorescence experiments, we have observed that NS3hel was less stable at pH 6.4 than at pH 7.2. Moreover, binding curves using an extrinsic fluorescent probe (bis-ANS) and ATPase assays performed under different pH conditions demonstrated that the hydrophobic clefts of NS3 are significantly more exposed to the aqueous medium at acidic pH. Using fluorescence spectroscopy and anisotropy assays, we have also observed more protein interaction with DNA upon pH acidification, which suggests that the hydrophobic clefts exposure on NS3 might be related to a loss of stability that could lead it to adopt a more open conformation. This conformational change at acidic pH would stimulate both its ATPase and helicase activities, as well as its ability to bind DNA. Taken together, our results indicate that the NS3 protein adopts a more open conformation due to acidification from pH 7.2 to 6.4, resulting in a more active form at a pH that is found near Golgi-derived membranes. This increased activity could better allow NS3 to carry out its functions during HCV replication. PMID:25551442

  20. [Radiotherapy of a glioma in a pregnant woman: evaluation of the foetal dose in conformational 3D or intensity-modulated].

    PubMed

    Lefebvre, L; Doyeux, K; Linca, S; Challand, T; Hanzen, C

    2014-12-01

    The purpose was to assess three treatments planning techniques including one in intensity-modulated radiation therapy (IMRT) for cerebral irradiation of pregnant woman, in order to limit the dose delivered to the foetus. The treatment provided was 60 Gy to the planning target volume. Estimated foetal dose was measured using an anthropomorphic phantom, on the upper and middle part of the uterus. The first plan consisted in four beams in conformational technique delivered from a Varian accelerator with a 120 leaves collimator, the second one used non-coplanar fields and the third one assessed IMRT. With the conformational technique, the dose at the upper part of the uterus was 8.3 mGy and 6.3 mGy at the middle part. The dose delivered to the foetus was higher with the non-coplanar fields. In IMRT, the dose at the upper part of the uterus was 23.8 mGy and 14.3 mGy at the middle part. The three plans used 6 MV X-rays. Because of the use of leaves and non-coplanar fields, IMRT does not seem to be the optimal technique for the treatment of pregnant woman. However, the dose delivered to the foetus remains low and below the dose of 100 mGy recommended by the International Commission of Radiological Protection. It seems possible to consider the use of this technique for a better sparing of organs at risk for the mother.

  1. Modulation of Ultrafast Conformational Dynamics in Allosteric Interaction of Gal Repressor Protein with Different Operator DNA Sequences.

    PubMed

    Choudhury, Susobhan; Naiya, Gitashri; Singh, Priya; Lemmens, Peter; Roy, Siddhartha; Pal, Samir Kumar

    2016-04-01

    Although all forms of dynamical behaviour of a protein under allosteric interaction with effectors are predicted, little evidence of ultrafast dynamics in the interaction has been reported. Here, we demonstrate the efficacy of a combined approach involving picosecond-resolved FRET and polarisation-gated fluorescence for the exploration of ultrafast dynamics in the allosteric interaction of the Gal repressor (GalR) protein dimer with DNA operator sequences OE and OI . FRET from the single tryptophan residue to a covalently attached probe IAEDANS at a cysteine residue in the C-terminal domain of GalR shows structural perturbation and conformational dynamics during allosteric interaction. Polarisation-gated fluorescence spectroscopy of IAEDANS and another probe (FITC) covalently attached to the operator directly revealed the essential dynamics for cooperativity in the protein-protein interaction. The ultrafast resonance energy transfer from IAEDANS in the protein to FITC also revealed different dynamic flexibility in the allosteric interaction. An attempt was made to correlate the dynamic changes in the protein dimers with OE and OI with the consequent protein-protein interaction (tetramerisation) to form a DNA loop encompassing the promoter segment.

  2. Conformational Analysis of the Streptococcus pneumoniae Hyaluronate Lyase and Characterization of Its Hyaluronan-specific Carbohydrate-binding Module*

    PubMed Central

    Suits, Michael D. L.; Pluvinage, Benjamin; Law, Adrienne; Liu, Yan; Palma, Angelina S.; Chai, Wengang; Feizi, Ten; Boraston, Alisdair B.

    2014-01-01

    For a subset of pathogenic microorganisms, including Streptococcus pneumoniae, the recognition and degradation of host hyaluronan contributes to bacterial spreading through the extracellular matrix and enhancing access to host cell surfaces. The hyaluronate lyase (Hyl) presented on the surface of S. pneumoniae performs this role. Using glycan microarray screening, affinity electrophoresis, and isothermal titration calorimetry we show that the N-terminal module of Hyl is a hyaluronan-specific carbohydrate-binding module (CBM) and the founding member of CBM family 70. The 1.2 Å resolution x-ray crystal structure of CBM70 revealed it to have a β-sandwich fold, similar to other CBMs. The electrostatic properties of the binding site, which was identified by site-directed mutagenesis, are distinct from other CBMs and complementary to its acidic ligand, hyaluronan. Dynamic light scattering and solution small angle x-ray scattering revealed the full-length Hyl protein to exist as a monomer/dimer mixture in solution. Through a detailed analysis of the small angle x-ray scattering data, we report the pseudoatomic solution structures of the monomer and dimer forms of the full-length multimodular Hyl. PMID:25100731

  3. Origin of the conformational modulation of the 13C NMR chemical shift of methoxy groups in aromatic natural compounds.

    PubMed

    Toušek, Jaromír; Straka, Michal; Sklenář, Vladimír; Marek, Radek

    2013-01-24

    The interpretation of nuclear magnetic resonance (NMR) parameters is essential to understanding experimental observations at the molecular and supramolecular levels and to designing new and more efficient molecular probes. In many aromatic natural compounds, unusual (13)C NMR chemical shifts have been reported for out-of-plane methoxy groups bonded to the aromatic ring (~62 ppm as compared to the typical value of ~56 ppm for an aromatic methoxy group). Here, we analyzed this phenomenon for a series of aromatic natural compounds using Density Functional Theory (DFT) calculations. First, we checked the methodology used to optimize the structure and calculate the NMR chemical shifts in aromatic compounds. The conformational effects of the methoxy group on the (13)C NMR chemical shift then were interpreted by the Natural Bond Orbital (NBO) and Natural Chemical Shift (NCS) approaches, and by excitation analysis of the chemical shifts, breaking down the total nuclear shielding tensor into the contributions from the different occupied orbitals and their magnetic interactions with virtual orbitals. We discovered that the atypical (13)C NMR chemical shifts observed are not directly related to a different conjugation of the lone pair of electrons of the methoxy oxygen with the aromatic ring, as has been suggested. Our analysis indicates that rotation of the methoxy group induces changes in the virtual molecular orbital space, which, in turn, correlate with the predominant part of the contribution of the paramagnetic deshielding connected with the magnetic interactions of the BD(CMet-H)→BD*(CMet-OMet) orbitals, resulting in the experimentally observed deshielding of the (13)C NMR resonance of the out-of-plane methoxy group.

  4. A 4 MV flattening filter-free beam: commissioning and application to conformal therapy and volumetric modulated arc therapy.

    PubMed

    Stevens, S W; Rosser, K E; Bedford, J L

    2011-07-01

    Recent studies have indicated that radiotherapy treatments undertaken on a flattening filter-free (FFF) linear accelerator have a number of advantages over treatments undertaken on a conventional linear accelerator. In addition, 4 MV photon beams may give improved isodose coverage for some treatment volumes at air/tissue interfaces, compared to when utilizing the clinical standard of 6 MV photons. In order to investigate these benefits, FFF beams were established on an Elekta Beam Modulator linear accelerator for 4 MV photons. Commissioning beam data were obtained for open and wedged fields. The measured data were then imported into a treatment planning system and a beam model was commissioned. The beam model was optimized to improve dose calculations at shallow, clinically relevant depths. Following verification, the beam model was utilized in a treatment planning study, including volumetric modulated arc therapy, for a selection of lung, breast/chest wall and larynx patients. Increased dose rates of around 800 MU min(-1) were recorded for open fields (relative to 320 MU min(-1) for filtered open fields) and reduced head scatter was inferred from output factor measurements. Good agreement between planned and delivered dose was observed in verification of treatment plans. The planning study indicated that with a FFF beam, equivalent (and in some cases improved) isodose profiles could be achieved for small lung and larynx treatment volumes relative to 4 MV filtered treatments. Furthermore, FFF treatments with wedges could be replicated using open fields together with an 'effective wedge' technique and isocentre shift. Clinical feasibility of a FFF beam was therefore demonstrated, with beam modelling, treatment planning and verification being successfully accomplished.

  5. A 4 MV flattening filter-free beam: commissioning and application to conformal therapy and volumetric modulated arc therapy

    NASA Astrophysics Data System (ADS)

    Stevens, S. W.; Rosser, K. E.; Bedford, J. L.

    2011-07-01

    Recent studies have indicated that radiotherapy treatments undertaken on a flattening filter-free (FFF) linear accelerator have a number of advantages over treatments undertaken on a conventional linear accelerator. In addition, 4 MV photon beams may give improved isodose coverage for some treatment volumes at air/tissue interfaces, compared to when utilizing the clinical standard of 6 MV photons. In order to investigate these benefits, FFF beams were established on an Elekta Beam Modulator linear accelerator for 4 MV photons. Commissioning beam data were obtained for open and wedged fields. The measured data were then imported into a treatment planning system and a beam model was commissioned. The beam model was optimized to improve dose calculations at shallow, clinically relevant depths. Following verification, the beam model was utilized in a treatment planning study, including volumetric modulated arc therapy, for a selection of lung, breast/chest wall and larynx patients. Increased dose rates of around 800 MU min-1 were recorded for open fields (relative to 320 MU min-1 for filtered open fields) and reduced head scatter was inferred from output factor measurements. Good agreement between planned and delivered dose was observed in verification of treatment plans. The planning study indicated that with a FFF beam, equivalent (and in some cases improved) isodose profiles could be achieved for small lung and larynx treatment volumes relative to 4 MV filtered treatments. Furthermore, FFF treatments with wedges could be replicated using open fields together with an 'effective wedge' technique and isocentre shift. Clinical feasibility of a FFF beam was therefore demonstrated, with beam modelling, treatment planning and verification being successfully accomplished.

  6. Superiority of helical tomotherapy on liver sparing and dose escalation in hepatocellular carcinoma: a comparison study of three-dimensional conformal radiotherapy and intensity-modulated radiotherapy

    PubMed Central

    Zhao, Qianqian; Wang, Renben; Zhu, Jian; Jin, Linzhi; Zhu, Kunli; Xu, Xiaoqing; Feng, Rui; Jiang, Shumei; Qi, Zhonghua; Yin, Yong

    2016-01-01

    Background and purpose To compare the difference of liver sparing and dose escalation between three-dimensional conformal radiotherapy (3DCRT), intensity-modulated radiotherapy (IMRT), and helical tomotherapy (HT) for hepatocellular carcinoma. Patients and methods Sixteen unresectable HCC patients were enrolled in this study. First, some evaluation factors of 3DCRT, IMRT, and HT plans were calculated with prescription dose at 50 Gy/25 fractions. Then, the doses were increased using HT or IMRT independently until either the plans reached 70 Gy or any normal tissue reached the dose limit according to quantitative analysis of normal tissue effects in the clinic criteria. Results The conformal index of 3DCRT was lower than that of IMRT (P<0.001) or HT (P<0.001), and the homogeneity index of 3DCRT was higher than that of IMRT (P<0.001) or HT (P<0.001). HT took the longest treatment time (P<0.001). For V50% (fraction of normal liver treated to at least 50% of the isocenter dose) of the normal liver, there was a significant difference: 3DCRT > IMRT > HT (P<0.001). HT had a lower Dmean (mean dose) and V20 (Vn, the percentage of organ volume receiving ≥n Gy) of liver compared with 3DCRT (P=0.005 and P=0.005, respectively) or IMRT (P=0.508 and P=0.007, respectively). Dmean of nontarget normal liver and V30 of liver were higher for 3DCRT than IMRT (P=0.005 and P=0.005, respectively) or HT (P=0.005 and P=0.005, respectively). Seven patients in IMRT (43.75%) and nine patients in HT (56.25%) reached the isodose 70 Gy, meeting the dose limit of the organs at risk. Conclusion HT may provide significantly better liver sparing and allow more patients to achieve higher prescription dose in HCC radiotherapy. PMID:27445485

  7. Dosimetric comparison study between intensity modulated radiation therapy and three-dimensional conformal proton therapy for pelvic bone marrow sparing in the treatment of cervical cancer.

    PubMed

    Song, William Y; Huh, Soon N; Liang, Yun; White, Greg; Nichols, R Charles; Watkins, W Tyler; Mundt, Arno J; Mell, Loren K

    2010-08-15

    The objective was to compare intensity-modulated radiation therapy (IMRT) with 3D conformal proton therapy (3DCPT) in the treatment of cervical cancer. In particular, each technique's ability to spare pelvic bone marrow (PBM) was of primary interest in this study. A total of six cervical cancer patients (3 postoperative and 3 intact) were planned and analyzed. All plans had uniform 1.0 cm CTV-PTV margin and satisfied the 95% PTV with 100% isodose (prescription dose = 45 Gy) coverage. Dose-volume histograms (DVH) were analyzed for comparison. The overall PTV and PBM volumes were 1035.9 ± 192.2 cc and 1151.4 ± 198.3 cc, respectively. In terms of PTV dose conformity index (DCI) and dose homogeneity index (DHI), 3DCPT was slightly superior to IMRT with 1.00 ± 0.001, 1.01 ± 0.02, and 1.10 ± 0.02, 1.13 ± 0.01, respectively. In addition, 3DCPT demonstrated superiority in reducing lower doses (i.e., V30 or less) to PBM, small bowel and bladder. Particularly in PBM, average V10 and V20 reductions of 10.8% and 7.4% (p = 0.001 and 0.04), respectively, were observed. However, in the higher dose range, IMRT provided better sparing (> V30). For example, in small bowel and PBM, average reductions in V45 of 4.9% and 10.0% (p = 0.048 and 0.008), respectively, were observed. Due to its physical characteristics such as low entrance dose, spread-out Bragg peak and finite particle range of protons, 3DCPT illustrated superior target coverage uniformity and sparing of the lower doses in PBM and other organs. Further studies are, however, needed to fully exploit the benefits of protons for general use in cervical cancer.

  8. Single-arc volumetric-modulated arc therapy (sVMAT) as adjuvant treatment for gastric cancer: Dosimetric comparisons with three-dimensional conformal radiotherapy (3D-CRT) and intensity-modulated radiotherapy (IMRT)

    SciTech Connect

    Wang, Xin; Li, Guangjun; Zhang, Yingjie; Bai, Sen; Xu, Feng; Wei, Yuquan; Gong, Youling

    2013-01-01

    To compare the dosimetric differences between the single-arc volumetric-modulated arc therapy (sVMAT), 3-dimensional conformal radiotherapy (3D-CRT), and intensity-modulated radiotherapy (IMRT) techniques in treatment planning for gastric cancer as adjuvant radiotherapy. Twelve patients were retrospectively analyzed. In each patient's case, the parameters were compared based on the dose-volume histogram (DVH) of the sVMAT, 3D-CRT, and IMRT plans, respectively. Three techniques showed similar target dose coverage. The maximum and mean doses of the target were significantly higher in the sVMAT plans than that in 3D-CRT plans and in the 3D-CRT/IMRT plans, respectively, but these differences were clinically acceptable. The IMRT and sVMAT plans successfully achieved better target dose conformity, reduced the V{sub 20/30}, and mean dose of the left kidney, as well as the V{sub 20/30} of the liver, compared with the 3D-CRT plans. And the sVMAT technique reduced the V{sub 20} of the liver much significantly. Although the maximum dose of the spinal cord were much higher in the IMRT and sVMAT plans, respectively (mean 36.4 vs 39.5 and 40.6 Gy), these data were still under the constraints. Not much difference was found in the analysis of the parameters of the right kidney, intestine, and heart. The IMRT and sVMAT plans achieved similar dose distribution to the target, but superior to the 3D-CRT plans, in adjuvant radiotherapy for gastric cancer. The sVMAT technique improved the dose sparings of the left kidney and liver, compared with the 3D-CRT technique, but showed few dosimetric advantages over the IMRT technique. Studies are warranted to evaluate the clinical benefits of the VMAT treatment for patients with gastric cancer after surgery in the future.

  9. Proton Arc Reduces Range Uncertainty Effects and Improves Conformality Compared With Photon Volumetric Modulated Arc Therapy in Stereotactic Body Radiation Therapy for Non-Small Cell Lung Cancer

    SciTech Connect

    Seco, Joao; Gu, Guan; Marcelos, Tiago; Kooy, Hanne; Willers, Henning

    2013-09-01

    Purpose: To describe, in a setting of non-small cell lung cancer (NSCLC), the theoretical dosimetric advantages of proton arc stereotactic body radiation therapy (SBRT) in which the beam penumbra of a rotating beam is used to reduce the impact of range uncertainties. Methods and Materials: Thirteen patients with early-stage NSCLC treated with proton SBRT underwent repeat planning with photon volumetric modulated arc therapy (Photon-VMAT) and an in-house-developed arc planning approach for both proton passive scattering (Passive-Arc) and intensity modulated proton therapy (IMPT-Arc). An arc was mimicked with a series of beams placed at 10° increments. Tumor and organ at risk doses were compared in the context of high- and low-dose regions, represented by volumes receiving >50% and <50% of the prescription dose, respectively. Results: In the high-dose region, conformality index values are 2.56, 1.91, 1.31, and 1.74, and homogeneity index values are 1.29, 1.22, 1.52, and 1.18, respectively, for 3 proton passive scattered beams, Passive-Arc, IMPT-Arc, and Photon-VMAT. Therefore, proton arc leads to a 30% reduction in the 95% isodose line volume to 3-beam proton plan, sparing surrounding organs, such as lung and chest wall. For chest wall, V30 is reduced from 21 cm{sup 3} (3 proton beams) to 11.5 cm{sup 3}, 12.9 cm{sup 3}, and 8.63 cm{sup 3} (P=.005) for Passive-Arc, IMPT-Arc, and Photon-VMAT, respectively. In the low-dose region, the mean lung dose and V20 of the ipsilateral lung are 5.01 Gy(relative biological effectiveness [RBE]), 4.38 Gy(RBE), 4.91 Gy(RBE), and 5.99 Gy(RBE) and 9.5%, 7.5%, 9.0%, and 10.0%, respectively, for 3-beam, Passive-Arc, IMPT-Arc, and Photon-VMAT, respectively. Conclusions: Stereotactic body radiation therapy with proton arc and Photon-VMAT generate significantly more conformal high-dose volumes than standard proton SBRT, without loss of coverage of the tumor and with significant sparing of nearby organs, such as chest wall. In addition

  10. Assessment of Extended-Field Radiotherapy for Stage IIIC Endometrial Cancer Using Three-Dimensional Conformal Radiotherapy, Intensity-Modulated Radiotherapy, and Helical Tomotherapy

    SciTech Connect

    Lian Jidong Mackenzie, Marc; Joseph, Kurian; Pervez, Nadeem; Dundas, George; Urtasun, Raul; Pearcey, Robert

    2008-03-01

    Purpose: To perform a dosimetric comparison of three-dimensional conformal radiotherapy (3D-CRT), intensity-modulated radiotherapy (IMRT), and helical tomotherapy (HT) plans for pelvic and para-aortic RT in postoperative endometrial cancer patients; and to evaluate the integral dose (ID) received by critical structures within the radiation fields. Methods and Materials: We selected 10 patients with Stage IIIC endometrial cancer. For each patient, three plans were created with 3D-CRT, IMRT, and HT. The IMRT and HT plans were both optimized to keep the mean dose to the planning target volume (PTV) the same as that with 3D-CRT. The dosimetry and ID for the critical structures were compared. A paired two-tailed Student t test was used for data analysis. Results: Compared with the 3D-CRT plans, the IMRT plans resulted in lower IDs in the organs at risk (OARs), ranging from -3.49% to -17.59%. The HT plans showed a similar result except that the ID for the bowel increased 0.27%. The IMRT and HT plans both increased the IDs to normal tissue (see and text for definition), pelvic bone, and spine (range, 3.31-19.7%). The IMRT and HT dosimetry showed superior PTV coverage and better OAR sparing than the 3D-CRT dosimetry. Compared directly with IMRT, HT showed similar PTV coverage, lower Ids, and a decreased dose to most OARs. Conclusion: Intensity-modulated RT and HT appear to achieve excellent PTV coverage and better sparing of OARs, but at the expense of increased IDs to normal tissue and skeleton. HT allows for additional improvement in dosimetry and sparing of most OARs.

  11. Changes in Pulmonary Function After Three-Dimensional Conformal Radiotherapy, Intensity-Modulated Radiotherapy, or Proton Beam Therapy for Non-Small-Cell Lung Cancer

    SciTech Connect

    Lopez Guerra, Jose L.; Gomez, Daniel R.; Zhuang Yan; Levy, Lawrence B.; Eapen, George; Liu, Hongmei; Mohan, Radhe; Komaki, Ritsuko; Cox, James D.; Liao Zhongxing

    2012-07-15

    Purpose: To investigate the extent of change in pulmonary function over time after definitive radiotherapy for non-small-cell lung cancer (NSCLC) with modern techniques and to identify predictors of changes in pulmonary function according to patient, tumor, and treatment characteristics. Patients and Methods: We analyzed 250 patients who had received {>=}60 Gy radio(chemo)therapy for primary NSCLC in 1998-2010 and had undergone pulmonary function tests before and within 1 year after treatment. Ninety-three patients were treated with three-dimensional conformal radiotherapy, 97 with intensity-modulated radiotherapy, and 60 with proton beam therapy. Postradiation pulmonary function test values were evaluated among individual patients compared with the same patient's preradiation value at the following time intervals: 0-4 (T1), 5-8 (T2), and 9-12 (T3) months. Results: Lung diffusing capacity for carbon monoxide (DLCO) was reduced in the majority of patients along the three time periods after radiation, whereas the forced expiratory volume in 1 s per unit of vital capacity (FEV1/VC) showed an increase and decrease after radiation in a similar percentage of patients. There were baseline differences (stage, radiotherapy dose, concurrent chemotherapy) among the radiation technology groups. On multivariate analysis, the following features were associated with larger posttreatment declines in DLCO: pretreatment DLCO, gross tumor volume, lung and heart dosimetric data, and total radiation dose. Only pretreatment DLCO was associated with larger posttreatment declines in FEV1/VC. Conclusions: Lung diffusing capacity for carbon monoxide is reduced in the majority of patients after radiotherapy with modern techniques. Multiple factors, including gross tumor volume, preradiation lung function, and dosimetric parameters, are associated with the DLCO decline. Prospective studies are needed to better understand whether new radiation technology, such as proton beam therapy or

  12. Conformation of the C-terminal secretion signal of the Serratia marcescens haem acquisition protein (HasA) in amphipols solution, a new class of surfactant

    NASA Astrophysics Data System (ADS)

    Wolff, N.; Delepierre, M.

    1998-02-01

    The conformation of a peptide, CterH, encompassing the last 56 C-terminal residues of Serratia marcescens haem acquisition protein HasA was examined by Circular Dichroism in amphipols solutions. The peptide, which contains the secretion signal of HasA, is unstructured in aqueous solution and adopts an helical structure upon the amphiphilic polymer addition. Furthermore, the helical content of CterH is modulated by the ionic strengh of the solution. These results are compared to those obtained with CterH in membrane mimetic environments. La conformation d'un peptide. CterH, comprenant les 56 derniers résidus C-terminaux de l'hémoprotéine HasA de Serratia marcescens a été examinée par Dichroïsme Circulaire dans des solutions d'amphipols. Ce peptide, qui contient le signal de secrétion de HasA, n'est pas structuré dans l'eau et adopte une structure helicoïdale avec l'ajout du polymère amphiphile. De plus, le contenu en hélice de CterH est modulé par la force ionique de la solution. Ces résultats sont comparés à ceux obtenus avec CterH dans des environnements mimant la membrane.

  13. Temporal characterization and in vitro comparison of cell survival following the delivery of 3D-conformal, intensity-modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT)

    NASA Astrophysics Data System (ADS)

    McGarry, Conor K.; Butterworth, Karl T.; Trainor, Colman; O'Sullivan, Joe M.; Prise, Kevin M.; Hounsell, Alan R.

    2011-04-01

    A phantom was designed and implemented for the delivery of treatment plans to cells in vitro. Single beam, 3D-conformal radiotherapy (3D-CRT) plans, inverse planned five-field intensity-modulated radiation therapy (IMRT), nine-field IMRT, single-arc volumetric modulated arc therapy (VMAT) and dual-arc VMAT plans were created on a CT scan of the phantom to deliver 3 Gy to the cell layer and verified using a Farmer chamber, 2D ionization chamber array and gafchromic film. Each plan was delivered to a 2D ionization chamber array to assess the temporal characteristics of the plan including delivery time and 'cell's eye view' for the central ionization chamber. The effective fraction time, defined as the percentage of the fraction time where any dose is delivered to each point examined, was also assessed across 120 ionization chambers. Each plan was delivered to human prostate cancer DU-145 cells and normal primary AGO-1522b fibroblast cells. Uniform beams were delivered to each cell line with the delivery time varying from 0.5 to 20.54 min. Effective fraction time was found to increase with a decreasing number of beams or arcs. For a uniform beam delivery, AGO-1552b cells exhibited a statistically significant trend towards increased survival with increased delivery time. This trend was not repeated when the different modulated clinical delivery methods were used. Less sensitive DU-145 cells did not exhibit a significant trend towards increased survival with increased delivery time for either the uniform or clinical deliveries. These results confirm that dose rate effects are most prevalent in more radiosensitive cells. Cell survival data generated from uniform beam deliveries over a range of dose rates and delivery times may not always be accurate in predicting response to more complex delivery techniques, such as IMRT and VMAT.

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

    PubMed

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

    2012-05-01

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

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

    PubMed

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

    2012-05-01

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

  16. Conformal superalgebras via tractor calculus

    NASA Astrophysics Data System (ADS)

    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.

  17. Propensity Score-based Comparison of Long-term Outcomes With 3-Dimensional Conformal Radiotherapy vs Intensity-Modulated Radiotherapy for Esophageal Cancer

    SciTech Connect

    Lin, Steven H.; Wang Lu; Myles, Bevan; Thall, Peter F.; Hofstetter, Wayne L.; Swisher, Stephen G.; Ajani, Jaffer A.; Cox, James D.; Komaki, Ritsuko; Liao Zhongxing

    2012-12-01

    Purpose: Although 3-dimensional conformal radiotherapy (3D-CRT) is the worldwide standard for the treatment of esophageal cancer, intensity modulated radiotherapy (IMRT) improves dose conformality and reduces the radiation exposure to normal tissues. We hypothesized that the dosimetric advantages of IMRT should translate to substantive benefits in clinical outcomes compared with 3D-CRT. Methods and Materials: An analysis was performed of 676 nonrandomized patients (3D-CRT, n=413; IMRT, n=263) with stage Ib-IVa (American Joint Committee on Cancer 2002) esophageal cancers treated with chemoradiotherapy at a single institution from 1998-2008. An inverse probability of treatment weighting and inclusion of propensity score (treatment probability) as a covariate were used to compare overall survival time, interval to local failure, and interval to distant metastasis, while accounting for the effects of other clinically relevant covariates. The propensity scores were estimated using logistic regression analysis. Results: A fitted multivariate inverse probability weighted-adjusted Cox model showed that the overall survival time was significantly associated with several well-known prognostic factors, along with the treatment modality (IMRT vs 3D-CRT, hazard ratio 0.72, P<.001). Compared with IMRT, 3D-CRT patients had a significantly greater risk of dying (72.6% vs 52.9%, inverse probability of treatment weighting, log-rank test, P<.0001) and of locoregional recurrence (P=.0038). No difference was seen in cancer-specific mortality (Gray's test, P=.86) or distant metastasis (P=.99) between the 2 groups. An increased cumulative incidence of cardiac death was seen in the 3D-CRT group (P=.049), but most deaths were undocumented (5-year estimate, 11.7% in 3D-CRT vs 5.4% in IMRT group, Gray's test, P=.0029). Conclusions: Overall survival, locoregional control, and noncancer-related death were significantly better after IMRT than after 3D-CRT. Although these results need

  18. Dosimetric Comparison Between Intensity-Modulated with Coplanar Field and 3D Conformal Radiotherapy with Noncoplanar Field for Postocular Invasion Tumor

    SciTech Connect

    Tu Wenyong; Liu Lu Zeng Jun; Yin Weidong; Li Yun

    2010-07-01

    This study presents a dosimetric optimization effort aiming to compare noncoplanar field (NCF) on 3 dimensions conformal radiotherapy (3D-CRT) and coplanar field (CF) on intensity-modulated radiotherapy (IMRT) planning for postocular invasion tumor. We performed a planning study on the computed tomography data of 8 consecutive patients with localized postocular invasion tumor. Four fields NCF 3D-CRT in the transverse plane with gantry angles of 0-10 deg., 30-45 deg., 240-270 deg., and 310-335 deg. degrees were isocentered at the center of gravity of the target volume. The geometry of the beams was determined by beam's eye view. The same constraints were prepared with between CF IMRT optimization and NCF 3D-CRT treatment. The maximum point doses (D max) for the different optic pathway structures (OPS) with NCF 3D-CRT treatment should differ in no more than 3% from those with the NCF IMRT plan. Dose-volume histograms (DVHs) were obtained for all targets and organ at risk (OAR) with both treatment techniques. Plans with NCF 3D-CRT and CF IMRT constraints on target dose in homogeneity were computed, as well as the conformity index (CI) and homogeneity index (HI) in the target volume. The PTV coverage was optimal with both NCF 3D-CRT and CF IMRT plans in the 8 tumor sites. No difference was noted between the two techniques for the average D{sub max} and D{sub min} dose. NCF 3D-CRT and CF IMRT will yield similar results on CI. However, HI was a significant difference between NCF 3D-CRT and CF IMRT plan (p < 0.001). Physical endpoints for target showed the mean target dose to be low in the CF IMRT plan, caused by a large target dose in homogeneity (p < 0.001). The impact of NCF 3D-CRT versus CF IMRT set-up is very slight. NCF3D-CRT is one of the treatment options for postocular invasion tumor. However, constraints for OARs are needed.

  19. Volumetric Modulation Arc Radiotherapy With Flattening Filter-Free Beams Compared With Static Gantry IMRT and 3D Conformal Radiotherapy for Advanced Esophageal Cancer: A Feasibility Study

    SciTech Connect

    Nicolini, Giorgia; Ghosh-Laskar, Sarbani; Shrivastava, Shyam Kishore; Banerjee, Sushovan; Chaudhary, Suresh; Agarwal, Jai Prakash; Munshi, Anusheel; Clivio, Alessandro; Fogliata, Antonella; Mancosu, Pietro; Vanetti, Eugenio; Cozzi, Luca

    2012-10-01

    Purpose: A feasibility study was performed to evaluate RapidArc (RA), and the potential benefit of flattening filter-free beams, on advanced esophageal cancer against intensity-modulated radiotherapy (IMRT) and three-dimensional conformal radiotherapy (3D-CRT). Methods and Materials: The plans for 3D-CRT and IMRT with three to seven and five to seven fixed beams were compared against double-modulated arcs with avoidance sectors to spare the lungs for 10 patients. All plans were optimized for 6-MV photon beams. The RA plans were studied for conventional and flattening filter-free (FFF) beams. The objectives for the planning target volume were the volume receiving {>=}95% or at most 107% of the prescribed dose of <1% with a dose prescription of 59.4 Gy. For the organs at risk, the lung volume (minus the planning target volume) receiving {>=}5 Gy was <60%, that receiving 20 Gy was <20%-30%, and the mean lung dose was <15.0 Gy. The heart volume receiving 45 Gy was <20%, volume receiving 30 Gy was <50%. The spinal dose received by 1% was <45 Gy. The technical delivery parameters for RA were assessed to compare the normal and FFF beam characteristics. Results: RA and IMRT provided equivalent coverage and homogeneity, slightly superior to 3D-CRT. The conformity index was 1.2 {+-} 0.1 for RA and IMRT and 1.5 {+-} 0.2 for 3D-CRT. The mean lung dose was 12.2 {+-} 4.5 for IMRT, 11.3 {+-} 4.6 for RA, and 10.8 {+-} 4.4 for RA with FFF beams, 18.2 {+-} 8.5 for 3D-CRT. The percentage of volume receiving {>=}20 Gy ranged from 23.6% {+-} 9.1% to 21.1% {+-} 9.7% for IMRT and RA (FFF beams) and 39.2% {+-} 17.0% for 3D-CRT. The heart and spine objectives were met by all techniques. The monitor units for IMRT and RA were 457 {+-} 139, 322 {+-} 20, and 387 {+-} 40, respectively. RA with FFF beams showed, compared with RA with normal beams, a {approx}20% increase in monitor units per Gray, a 90% increase in the average dose rate, and 20% reduction in beam on time (owing to different

  20. Analysis of Intensity-Modulated Radiation Therapy (IMRT), Proton and 3D Conformal Radiotherapy (3D-CRT) for Reducing Perioperative Cardiopulmonary Complications in Esophageal Cancer Patients

    PubMed Central

    Ling, Ted C.; Slater, Jerry M.; Nookala, Prashanth; Mifflin, Rachel; Grove, Roger; Ly, Anh M.; Patyal, Baldev; Slater, Jerry D.; Yang, Gary Y.

    2014-01-01

    Background. While neoadjuvant concurrent chemoradiotherapy has improved outcomes for esophageal cancer patients, surgical complication rates remain high. The most frequent perioperative complications after trimodality therapy were cardiopulmonary in nature. The radiation modality utilized can be a strong mitigating factor of perioperative complications given the location of the esophagus and its proximity to the heart and lungs. The purpose of this study is to make a dosimetric comparison of Intensity-Modulated Radiation Therapy (IMRT), proton and 3D conformal radiotherapy (3D-CRT) with regard to reducing perioperative cardiopulmonary complications in esophageal cancer patients. Materials. Ten patients with esophageal cancer treated between 2010 and 2013 were evaluated in this study. All patients were simulated with contrast-enhanced CT imaging. Separate treatment plans using proton radiotherapy, IMRT, and 3D-CRT modalities were created for each patient. Dose-volume histograms were calculated and analyzed to compare plans between the three modalities. The organs at risk (OAR) being evaluated in this study are the heart, lungs, and spinal cord. To determine statistical significance, ANOVA and two-tailed paired t-tests were performed for all data parameters. Results. The proton plans showed decreased dose to various volumes of the heart and lungs in comparison to both the IMRT and 3D-CRT plans. There was no difference between the IMRT and 3D-CRT plans in dose delivered to the lung or heart. This finding was seen consistently across the parameters analyzed in this study. Conclusions. In patients receiving radiation therapy for esophageal cancer, proton plans are technically feasible while achieving adequate coverage with lower doses delivered to the lungs and cardiac structures. This may result in decreased cardiopulmonary toxicity and less morbidity to esophageal cancer patients. PMID:25489937

  1. A comparative analysis of 3D conformal deep inspiratory–breath hold and free-breathing intensity-modulated radiation therapy for left-sided breast cancer

    SciTech Connect

    Reardon, Kelli A.; Read, Paul W.; Morris, Monica M.; Reardon, Michael A.; Geesey, Constance; Wijesooriya, Krishni

    2013-07-01

    Patients undergoing radiation for left-sided breast cancer have increased rates of coronary artery disease. Free-breathing intensity-modulated radiation therapy (FB-IMRT) and 3-dimensional conformal deep inspiratory–breath hold (3D-DIBH) reduce cardiac irradiation. The purpose of this study is to compare the dose to organs at risk in FB-IMRT vs 3D-DIBH for patients with left-sided breast cancer. Ten patients with left-sided breast cancer had 2 computed tomography scans: free breathing and voluntary DIBH. Optimization of the IMRT plan was performed on the free-breathing scan using 6 noncoplanar tangential beams. The 3D-DIBH plan was optimized on the DIBH scan and used standard tangents. Mean volumes of the heart, the left anterior descending coronary artery (LAD), the total lung, and the right breast receiving 5% to 95% (5% increments) of the prescription dose were calculated. Mean volumes of the heart and the LAD were lower (p<0.05) in 3D-DIBH for volumes receiving 5% to 80% of the prescription dose for the heart and 5% for the LAD. Mean dose to the LAD and heart were lower in 3D-DIBH (p≤0.01). Mean volumes of the total lung were lower in FB-IMRT for dose levels 20% to 75% (p<0.05), but mean dose was not different. Mean volumes of the right breast were not different for any dose; however, mean dose was lower for 3D-DIBH (p = 0.04). 3D-DIBH is an alternative approach to FB-IMRT that provides a clinically equivalent treatment for patients with left-sided breast cancer while sparing organs at risk with increased ease of implementation.

  2. Two-Year and Lifetime Cost-Effectiveness of Intensity Modulated Radiation Therapy Versus 3-Dimensional Conformal Radiation Therapy for Head-and-Neck Cancer

    SciTech Connect

    Kohler, Racquel E.; Sheets, Nathan C.; Wheeler, Stephanie B.; Nutting, Chris; Hall, Emma; Chera, Bhishamjit S.

    2013-11-15

    Purpose: To assess the cost-effectiveness of intensity modulated radiation therapy (IMRT) versus 3-dimensional conformal radiation therapy (3D-CRT) in the treatment of head-and neck-cancer (HNC). Methods and Materials: We used a Markov model to simulate radiation therapy-induced xerostomia and dysphagia in a hypothetical cohort of 65-year-old HNC patients. Model input parameters were derived from PARSPORT (CRUK/03/005) patient-level trial data and quality-of-life and Medicare cost data from published literature. We calculated average incremental cost-effectiveness ratios (ICERs) from the US health care perspective as cost per quality-adjusted life-year (QALY) gained and compared our ICERs with current cost-effectiveness standards whereby treatment comparators less than $50,000 per QALY gained are considered cost-effective. Results: In the first 2 years after initial treatment, IMRT is not cost-effective compared with 3D-CRT, given an average ICER of $101,100 per QALY gained. However, over 15 years (remaining lifetime on the basis of average life expectancy of a 65-year-old), IMRT is more cost-effective at $34,523 per QALY gained. Conclusion: Although HNC patients receiving IMRT will likely experience reduced xerostomia and dysphagia symptoms, the small quality-of-life benefit associated with IMRT is not cost-effective in the short term but may be cost-effective over a patient's lifetime, assuming benefits persist over time and patients are healthy and likely to live for a sustained period. Additional data quantifying the long-term benefits of IMRT, however, are needed.

  3. Quality of Life and Survival Outcome for Patients With Nasopharyngeal Carcinoma Receiving Three-Dimensional Conformal Radiotherapy vs. Intensity-Modulated Radiotherapy-A Longitudinal Study

    SciTech Connect

    Fang, F.-M. Chien, C.-Y.; Tsai, W.-L.; Chen, H.-C.; Hsu, H.-C.; Lui, C.-C.; Huang, T.-L.

    2008-10-01

    Purpose: To investigate the changes of quality of life (QoL) and survival outcomes for patients with nasopharyngeal carcinoma (NPC) treated by three-dimensional conformal radiotherapy (3D-CRT) vs. intensity-modulated radiotherapy (IMRT). Methods and Materials: Two hundred and three newly diagnosed NPC patients, who were curatively treated by 3D-CRT (n = 93) or IMRT (n = 110) between March 2002 and July 2004, were analyzed. The distributions of clinical stage according to American Joint Committee on Cancer 1997 were I: 15 (7.4%), II: 78 (38.4%), III: 74 (36.5%), and IV: 36 (17.7%). QoL was longitudinally assessed by the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and the EORTC QLQ-H and N35 questionnaires at the five time points: before RT, during RT (36 Gy), and 3 months, 12 months, and 24 months after RT. Results: The 3-year locoregional control, metastasis-free survival, and overall survival rates were 84.8%, 76.7%, and 81.7% for the 3D-CRT group, respectively, compared with 84.2%, 82.6%, and 85.4% for the IMRT group (p value > 0.05). A general trend of maximal deterioration in most QoL scales was observed during RT, followed by a gradual recovery thereafter. There was no significant difference in most scales between the two groups at each time point. The exception was that patients treated by IMRT had a both statistically and clinically significant improvement in global QoL, fatigue, taste/smell, dry mouth, and feeling ill at the time point of 3 months after RT. Conclusions: The potential advantage of IMRT over 3D-CRT in treating NPC patients might occur in QoL outcome during the recovery phase of acute toxicity.

  4. On the cohomology of Leibniz conformal algebras

    NASA Astrophysics Data System (ADS)

    Zhang, Jiao

    2015-04-01

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

  5. eIF4B, eIF4G and RNA regulate eIF4A activity in translation initiation by modulating the eIF4A conformational cycle.

    PubMed

    Harms, Ulf; Andreou, Alexandra Zoi; Gubaev, Airat; Klostermeier, Dagmar

    2014-07-01

    Eukaryotic translation initiation factor eIF4A is a DEAD-box helicase that resolves secondary structure elements in the 5'-UTR of mRNAs during ribosome scanning. Its RNA-stimulated ATPase and ATP-dependent helicase activities are enhanced by other translation initiation factors, but the underlying mechanisms are unclear. DEAD-box proteins alternate between open and closed conformations during RNA unwinding. The transition to the closed conformation is linked to duplex destabilization. eIF4A is a special DEAD-box protein that can adopt three different conformations, an open state in the absence of ligands, a half-open state stabilized by the translation initiation factor eIF4G and a closed state in the presence of eIF4G and eIF4B. We show here that eIF4A alone does not measurably sample the closed conformation. The translation initiation factors eIF4B and eIF4G accelerate the eIF4A conformational cycle. eIF4G increases the rate of closing more than the opening rate, and eIF4B selectively increases the closing rate. Strikingly, the rate constants and the effect of eIF4B are different for different RNAs, and are related to the presence of single-stranded regions. Modulating the kinetics of the eIF4A conformational cycle is thus central for the multi-layered regulation of its activity, and for its role as a regulatory hub in translation initiation. PMID:24848014

  6. Intensity-Modulated Radiotherapy Causes Fewer Side Effects than Three-Dimensional Conformal Radiotherapy When Used in Combination With Brachytherapy for the Treatment of Prostate Cancer

    SciTech Connect

    Forsythe, Kevin; Blacksburg, Seth; Stone, Nelson; Stock, Richard G.

    2012-06-01

    Purpose: To measure the benefits of intensity-modulated radiotherapy (IMRT) compared with three-dimensional conformal radiotherapy (3D-CRT) when used in combination with brachytherapy for the treatment of prostate cancer. Methods and Materials: We conducted a retrospective review of all patients with localized prostate cancer who received external-beam radiotherapy (EBRT) in combination with brachytherapy with at least 1 year follow-up (n = 812). Combination therapy consisted of {sup 103}Pd or {sup 125}I implant, followed by a course of EBRT. From 1993 to March 2003 521 patients were treated with 3D-CRT, and from April 2003 to March 2009 291 patients were treated with IMRT. Urinary symptoms were prospectively measured with the International Prostate Symptom Score questionnaire with a single quality of life (QOL) question; rectal bleeding was assessed per the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer Late Radiation Morbidity Scoring Schema. The Pearson {chi}{sup 2} test was used to compare toxicities experienced by patients who were treated with either IMRT or 3D-CRT. Logistic regression analyses were also performed to rule out possible confounding factors. Results: Within the first 3 months after treatment, patients treated with 3D-CRT scored their urinary symptoms as follows: 19% mild, 44% moderate, and 37% severe; patients treated with IMRT scored their urinary symptoms as follows: 36% mild, 47% moderate, and 17% severe (p < 0.001). The 3D-CRT patients rated their QOL as follows: 35% positive, 20% neutral, and 45% negative; IMRT patients rated their QOL as follows: 51% positive, 18% neutral, and 31% negative (p < 0.001). After 1 year of follow-up there was no longer any difference in urinary morbidity between the two groups. Logistic regression confirmed the differences in International Prostate Symptom Score and QOL in the acute setting (p < 0.001 for both). Grade {>=}2 rectal bleeding was reported by 11% of 3D

  7. Improvement in toxicity in high risk prostate cancer patients treated with image-guided intensity-modulated radiotherapy compared to 3D conformal radiotherapy without daily image guidance

    PubMed Central

    2014-01-01

    Background Image-guided radiotherapy (IGRT) facilitates the delivery of a very precise radiation dose. In this study we compare the toxicity and biochemical progression-free survival between patients treated with daily image-guided intensity-modulated radiotherapy (IG-IMRT) and 3D conformal radiotherapy (3DCRT) without daily image guidance for high risk prostate cancer (PCa). Methods A total of 503 high risk PCa patients treated with radiotherapy (RT) and endocrine treatment between 2000 and 2010 were retrospectively reviewed. 115 patients were treated with 3DCRT, and 388 patients were treated with IG-IMRT. 3DCRT patients were treated to 76 Gy and without daily image guidance and with 1–2 cm PTV margins. IG-IMRT patients were treated to 78 Gy based on daily image guidance of fiducial markers, and the PTV margins were 5–7 mm. Furthermore, the dose-volume constraints to both the rectum and bladder were changed with the introduction of IG-IMRT. Results The 2-year actuarial likelihood of developing grade > = 2 GI toxicity following RT was 57.3% in 3DCRT patients and 5.8% in IG-IMRT patients (p < 0.001). For GU toxicity the numbers were 41.8% and 29.7%, respectively (p = 0.011). On multivariate analysis, 3DCRT was associated with a significantly increased risk of developing grade > = 2 GI toxicity compared to IG-IMRT (p < 0.001, HR = 11.59 [CI: 6.67-20.14]). 3DCRT was also associated with an increased risk of developing GU toxicity compared to IG-IMRT. The 3-year actuarial biochemical progression-free survival probability was 86.0% for 3DCRT and 90.3% for IG-IMRT (p = 0.386). On multivariate analysis there was no difference in biochemical progression-free survival between 3DCRT and IG-IMRT. Conclusion The difference in toxicity can be attributed to the combination of the IMRT technique with reduced dose to organs-at-risk, daily image guidance and margin reduction. PMID:24495815

  8. Recursion relations for conformal blocks

    NASA Astrophysics Data System (ADS)

    Penedones, João; Trevisani, Emilio; Yamazaki, Masahito

    2016-09-01

    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 Δ 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 [1] 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.

  9. Prostate and seminal vesicle volume based consideration of prostate cancer patients for treatment with 3D-conformal or intensity-modulated radiation therapy

    SciTech Connect

    Reddy, Nandanuri M. S.; Nori, Dattatreyudu; Chang, Hyesook; Lange, Christopher S.; Ravi, Akkamma

    2010-07-15

    Purpose: The purpose of this article was to determine the suitability of the prostate and seminal vesicle volumes as factors to consider patients for treatment with image-guided 3D-conformal radiation therapy (3D-CRT) or intensity-modulated radiation therapy (IMRT), using common dosimetry parameters as comparison tools. Methods: Dosimetry of 3D and IMRT plans for 48 patients was compared. Volumes of prostate, SV, rectum, and bladder, and prescriptions were the same for both plans. For both 3D and IMRT plans, expansion margins to prostate+SV (CTV) and prostate were 0.5 cm posterior and superior and 1 cm in other dimensions to create PTV and CDPTV, respectively. Six-field 3D plans were prepared retrospectively. For 3D plans, an additional 0.5 cm margin was added to PTV and CDPTV. Prescription for both 3D and IMRT plans was the same: 45 Gy to CTV followed by a 36 Gy boost to prostate. Dosimetry parameters common to 3D and IMRT plans were used for comparison: Mean doses to prostate, CDPTV, SV, rectum, bladder, and femurs; percent volume of rectum and bladder receiving 30 (V30), 50 (V50), and 70 Gy (V70), dose to 30% of rectum and bladder, minimum and maximum point dose to CDPTV, and prescription dose covering 95% of CDPTV (D95). Results: When the data for all patients were combined, mean dose to prostate and CDPTV was higher with 3D than IMRT plans (P<0.01). Mean D95 to CDPTV was the same for 3D and IMRT plans (P>0.2). On average, among all cases, the minimum point dose was less for 3D-CRT plans and the maximum point dose was greater for 3D-CRT than for IMRT (P<0.01). Mean dose to 30% rectum with 3D and IMRT plans was comparable (P>0.1). V30 was less (P<0.01), V50 was the same (P>0.2), and V70 was more (P<0.01) for rectum with 3D than IMRT plans. Mean dose to bladder was less with 3D than IMRT plans (P<0.01). V30 for bladder with 3D plans was less than that of IMRT plans (P<0.01). V50 and V70 for 3D plans were the same for 3D and IMRT plans (P>0.2). Mean dose to femurs

  10. Comparison of bone marrow sparing intensity modulated radiotherapy (IMRT) and three-dimensional conformal radiotherapy (3DCRT) in carcinoma of anal canal: a prospective study

    PubMed Central

    Rattan, Rajit; Bahl, Amit; Gupta, Rajesh; Oinam, Arun S.; Kaur, Satinder

    2016-01-01

    Background Chemoradiation (CRT) is the standard of care in anal canal carcinoma. CRT leads to suppression of iliac bone marrow (BM) leading to hematological toxicity. Intensity modulated radiation therapy (IMRT) technique can be used to decrease radiation dose to iliac BM and thus decrease haematological toxicity. This study aims to compare the haematological and gastrointestinal toxicity in BM sparing IMRT with three-dimensional conformal radiation therapy (3DCRT) in anal carcinoma patients. Methods Twenty untreated, biopsy proven anal canal carcinoma (stages I–III) patients were randomized into IMRT and 3DCRT arm. All patients received CRT with 45 Gy in 25 fractions at 1.8 Gy/fraction and weekly concurrent inj. cisplatin and 5-FU. Patients were evaluated for acute haematological and gastrointestinal toxicity during treatment. Additional dosimetric comparison was made between the two groups. Results Incidence of worst hematological toxicity grade II (GII) and GIII was seen in 40% [4] vs. 30% [3] and 20% [2] vs. 0% [0] respectively, in 3DCRT and IMRT group. However these did not come as statistically significant (P=0.228). Incidence of worst gastrointestinal toxicity during treatment in terms of GII was 30% [3] vs. 50% [5] and GIII was 60% [6] vs. 0% [0] in 3DCRT and IMRT group respectively (P=0.010). Other parameters indicating better tolerance of treatment with IMRT arm than 3DCRT arm were lesser need for administration of parenteral fluid 10% [1] vs. 60% [6] (P=0.019); lesser need for blood transfusion 0% [0] vs. 20% [2] (P=0.060) in IMRT arm than in 3DCRT arm respectively. Patient requiring supportive care during treatment like need for anti-motility drugs and WHO. Step II analgesics also favored IMRT arm. Overall treatment time for Arm B (33.40 days) was less than what was seen in Arm A patients (36.8 days), although difference was not statistically significant (P=0.569). In terms of dosimetric analysis, arm B with the use of IMRT showed superiority over arm

  11. Modulation of Conformational Equilibria in the S-Adenosylmethionine (SAM) II Riboswitch by SAM, Mg(2+), and Trimethylamine N-Oxide.

    PubMed

    McPhie, Peter; Brown, Patrick; Chen, Bin; Dayie, Theodore K; Minton, Allen P

    2016-09-13

    The dependence of the conformation of the S-adenosylmethionine (SAM) II riboswitch on the concentration of added Mg(2+) ions and SAM, individually and in mixtures, was monitored by circular dichroism (CD) spectroscopy and by measurement of the diffusion coefficient. The results are analyzed in the context of two complementary quantitative models, both of which are consistent with a single underlying physical model. Magnesium binding sites in the open state have an affinity on average higher than the affinity of those in the compact state, but formation of the compact state is accompanied by an increase in the number of binding sites. Consequently, at low Mg(2+) concentrations, Mg(2+) binds preferentially to the open state, favoring its formation, but at high concentrations, Mg(2+) binds preferentially to the compact state. The affinity of the riboswitch for SAM increases drastically with an increased level of binding of Mg(2+) to the compact pseudoknot conformation. The effect of increasing concentrations of trimethylamine N-oxide (TMAO), a well-studied molecular crowding agent, on the conformation of the riboswitch and its affinity for SAM were also monitored by CD spectroscopy and measurement of diffusion. In the absence of added Mg(2+), high concentrations of TMAO were found to induce a conformational change compatible with the formation of the pseudoknot form but have only a small effect on the affinity of the RNA for SAM. PMID:27552169

  12. Conformable seal

    DOEpatents

    Neef, W.S.; Lambert, D.R.

    1982-08-10

    Sealing apparatus and method, comprising first and second surfaces or membranes, at least one of which surfaces is deformable, placed in proximity to one another. Urging means cause these surfaces to contact one another in a manner such that the deformable surface deforms to conform to the geometry of the other surface, thereby creating a seal. The seal is capable of undergoing multiple cycles of sealing and unsealing.

  13. Health-Related Quality of Life in Patients With Locally Advanced Prostate Cancer After 76 Gy Intensity-Modulated Radiotherapy vs. 70 Gy Conformal Radiotherapy in a Prospective and Longitudinal Study

    SciTech Connect

    Lips, Irene Dehnad, Human; Kruger, Arto Boeken; Moorselaar, Jeroen van; Heide, Uulke van; Battermann, Jan; Vulpen, Marco van

    2007-11-01

    Purpose: To compare quality of life (QoL) after 70 Gy conformal radiotherapy with QoL after 76 Gy intensity-modulated radiotherapy (IMRT) in patients with locally advanced prostate carcinoma. Methods and Materials: Seventy-eight patients with locally advanced prostate cancer were treated with 70 Gy three-field conformal radiotherapy, and 92 patients received 76 Gy IMRT with fiducial markers for position verification. Quality of life was measured by RAND-36, the European Organization for Research and Treatment of Cancer core questionnaire (EORTC QLQ-C30(+3)), and the prostate-specific EORTC QLQ-PR25, before radiotherapy (baseline) and 1 month and 6 months after treatment. Quality of life changes in time (baseline vs. 1 month and baseline vs. 6 months) of {>=}10 points were considered clinically relevant. Results: Differences between the treatment groups for QoL changes over time occurred in several QoL domains. The 76-Gy group revealed no significant deterioration in QoL compared with the 70-Gy group. The IMRT 76-Gy group even demonstrated a significantly better change in QoL from baseline to 1 month in several domains. The conformal 70-Gy group revealed temporary deterioration in pain, role functioning, and urinary symptoms; for the IMRT 76-Gy group a better QoL in terms of change in health existed after 1 month, which persisted after 6 months. For both treatment groups temporary deterioration in physical role restriction occurred after 1 month, and an improvement in emotional role restriction occurred after 6 months. Sexual activity was reduced after treatment for both groups and remained decreased after 6 months. Conclusions: Intensity-modulated radiotherapy and accurate position verification seem to provide a possibility to increase the radiation dose for prostate cancer without deterioration in QoL.

  14. Disentangling the coil: modulation of conformational and dynamic properties by site-directed mutation in the non-native state of hen egg white lysozyme.

    PubMed

    Sziegat, Friederike; Silvers, Robert; Hähnke, Martin; Jensen, Malene Ringkjøbing; Blackledge, Martin; Wirmer-Bartoschek, Julia; Schwalbe, Harald

    2012-04-24

    The conformational analysis of non-native states of proteins remains one of the most difficult problems in structural biology, because such states are represented by a superimposition of several states that are rapidly interconverting. Hence, model building of the conformational ensemble remains challenging, although many different biophysical observables can be determined in non-native states of proteins. Here, we present a comprehensive analysis of non-native states of wild-type and mutant forms of the model protein lysozyme by nuclear magnetic resonance spectroscopy. Relaxation rates, chemical shifts, backbone and side chain coupling constants, residual dipolar couplings, diffusion rate constants, and small-angle scattering data merged with computational approaches, such as flexible meccano and ASTEROIDS, allow the description of the non-native state of hen egg white lysozyme in unprecedented detail.

  15. Role of cytochrome B5 in modulating peroxide-supported cyp3a4 activity: evidence for a conformational transition and cytochrome P450 heterogeneity.

    PubMed

    Kumar, Santosh; Davydov, Dmitri R; Halpert, James R

    2005-08-01

    The role of cytochrome b(5) (b(5)) in the alpha-naphthoflavone (alpha-NF)-mediated inhibition of H(2)O(2)-supported 7-benzyloxyquinoline (7-BQ) debenzylation by heterologously expressed and purified cytochrome P450 3A4 (CYP3A4) was studied. Although alpha-NF showed negligible effect in an NADPH-dependent reconstituted system, inhibition of 7-BQ oxidation was observed in the H(2)O(2) system. Analysis of the effect of various constituents of a standard reconstituted system on H(2)O(2)-supported activity showed that b(5) alone resulted in a 2.5-fold increase in the k(cat) value and reversed the inhibitory effect of alpha-NF. In addition, titration with b(5) suggested that only 65% of the CYP3A4 participated in the interaction with b(5), consistent with cytochrome P450 (P450) heterogeneity. Study of the influence of b(5) on the kinetics of H(2)O(2)-dependent destruction of the P450 heme moiety suggested two distinct conformers of CYP3A4 with different sensitivity to heme loss. In the absence of b(5), 66% of the wild-type enzyme was bleached in the fast phase, whereas the addition of b(5) decreased the fraction of the fast phase to 16%. Finally, to locate amino acid residues that might influence b(5) action, several active site mutants were tested. Substitution of Ser-119, Ile-301, Ala-305, Ile-369, or Ala-370 with the larger Phe or Trp decreased or even abolished the activation by b(5). Ser-119 is in the B'-C loop, a predicted b(5)-P450 interaction site, and Ile-301 and Ala-305 are closest to the heme. In conclusion, the interaction of b(5) with P450 apparently leads to a conformational transition, which results in redistribution of the CYP3A4 pool. PMID:15870379

  16. Differential conformational modulations of MreB folding upon interactions with GroEL/ES and TRiC chaperonin components

    PubMed Central

    Moparthi, Satish Babu; Carlsson, Uno; Vincentelli, Renaud; Jonsson, Bengt-Harald; Hammarström, Per; Wenger, Jérôme

    2016-01-01

    Here, we study and compare the mechanisms of action of the GroEL/GroES and the TRiC chaperonin systems on MreB client protein variants extracted from E. coli. MreB is a homologue to actin in prokaryotes. Single-molecule fluorescence correlation spectroscopy (FCS) and time-resolved fluorescence polarization anisotropy report the binding interaction of folding MreB with GroEL, GroES and TRiC. Fluorescence resonance energy transfer (FRET) measurements on MreB variants quantified molecular distance changes occurring during conformational rearrangements within folding MreB bound to chaperonins. We observed that the MreB structure is rearranged by a binding-induced expansion mechanism in TRiC, GroEL and GroES. These results are quantitatively comparable to the structural rearrangements found during the interaction of β-actin with GroEL and TRiC, indicating that the mechanism of chaperonins is conserved during evolution. The chaperonin-bound MreB is also significantly compacted after addition of AMP-PNP for both the GroEL/ES and TRiC systems. Most importantly, our results showed that GroES may act as an unfoldase by inducing a dramatic initial expansion of MreB (even more than for GroEL) implicating a role for MreB folding, allowing us to suggest a delivery mechanism for GroES to GroEL in prokaryotes. PMID:27328749

  17. Synthesis and solution-phase conformation of the RG-I fragment of the plant polysaccharide pectin reveals a modification-modulated assembly mechanism.

    PubMed

    Scanlan, Eoin M; Mackeen, Mukram M; Wormald, Mark R; Davis, Benjamin G

    2010-06-01

    The syntheses of pure RG-I fragments of key plant matrix biomolecule pectin using a counterintuitive late-stage convergent cis-glycosylation has allowed detailed analyses of their solution-phase conformations, metal binding affinities, pK(a) values, self-assembly equilibria, and diffusional kinetics. These reveal a striking, right-handed 3(1)-helix that provides an effective and repeating lateral display of putative liganding carboxylates. Moreover, these heteropolymeric structures allow units as short as tetrasaccharides to self-assemble through carbohydrate-carbohydrate interactions that are induced by the presence of Ca(II), a known dynamic trigger in planta. These self-assembly properties can be switched simply by the addition or removal of a single methyl group in this repeating unit through methyl (de)esterification, another known dynamic trigger in planta. Together, the combined effect of Ca(II) and methylation revealed here suggests a concerted molecular basis for these two major dynamic modifications in planta.

  18. James Webb Space Telescope (JWST) Integrated Science Instruments Module (ISIM) Electronics Compartment (IEC) Conformal Shields Composite Bond Structure Qualification Test Method

    NASA Technical Reports Server (NTRS)

    Yew, Calinda; Stephens, Matt

    2015-01-01

    The JWST IEC conformal shields are mounted onto a composite frame structure that must undergo qualification testing to satisfy mission assurance requirements. The composite frame segments are bonded together at the joints using epoxy, EA 9394. The development of a test method to verify the integrity of the bonded structure at its operating environment introduces challenges in terms of requirements definition and the attainment of success criteria. Even though protoflight thermal requirements were not achieved, the first attempt in exposing the structure to cryogenic operating conditions in a thermal vacuum environment resulted in approximately 1 bonded joints failure during mechanical pull tests performed at 1.25 times the flight loads. Failure analysis concluded that the failure mode was due to adhesive cracks that formed and propagated along stress concentrated fillets as a result of poor bond squeeze-out control during fabrication. Bond repairs were made and the structures successfully re-tested with an improved LN2 immersion test method to achieve protoflight thermal requirements.

  19. Intensity modulated radiotherapy and 3D conformal radiotherapy for whole breast irradiation: a comparative dosimetric study and introduction of a novel qualitative index for plan evaluation, the normal tissue index

    PubMed Central

    Yim, Jackie; Suttie, Clare; Bromley, Regina; Morgia, Marita; Lamoury, Gillian

    2015-01-01

    Introduction We report on a retrospective dosimetric study, comparing 3D conformal radiotherapy (3DCRT) and hybrid intensity modulated radiotherapy (hIMRT). We evaluated plans based on their planning target volume coverage, dose homogeneity, dose to organs at risk (OARs) and exposure of normal tissue to radiation. The Homogeneity Index (HI) was used to assess the dose homogeneity in the target region, and we describe a new index, the normal tissue index (NTI), to assess the dose in the normal tissue inside the tangent treatment portal. Methods Plans were generated for 25 early-stage breast cancer patients, using a hIMRT technique. These were compared with the 3DCRT plans of the treatment previously received by the patients. Plan quality was evaluated using the HI, NTI and dose to OARs. Results The hIMRT technique was significantly more homogenous than the 3DCRT technique, while maintaining target coverage. The hIMRT technique was also superior at minimising the amount of tissue receiving D105% and above (P < 0.0001). The ipsilateral lung and contralateral breast maximum were significantly lower in the hIMRT plans (P < 0.05 and P < 0.005), but the 3DCRT technique achieved a lower mean heart dose in left-sided breast cancer patients (P < 0.05). Conclusion Hybrid intensity modulated radiotherapy plans achieved improved dose homogeneity compared to the 3DCRT plans and superior outcome with regard to dose to normal tissues. We propose that the addition of both HI and NTI in evaluating the quality of intensity modulated radiotherapy (IMRT) breast plans provides clinically relevant comparators which more accurately reflect the new paradigm of treatment goals and outcomes in the era of breast IMRT. PMID:26451240

  20. Intensity-Modulated and 3D-Conformal Radiotherapy for Whole-Ventricular Irradiation as Compared With Conventional Whole-Brain Irradiation in the Management of Localized Central Nervous System Germ Cell Tumors

    SciTech Connect

    Chen, Michael Jenwei; Silva Santos, Adriana da; Sakuraba, Roberto Kenji; Lopes, Cleverson Perceu; Goncalves, Vinicius Demanboro; Weltman, Eduardo; Ferrigno, Robson; Cruz, Jose Carlos

    2010-02-01

    Purpose: To compare the sparing potential of cerebral hemispheres with intensity-modulated radiotherapy (IMRT) and three-dimensional conformal radiotherapy (3D-CRT) for whole-ventricular irradiation (WVI) and conventional whole-brain irradiation (WBI) in the management of localized central nervous system germ cell tumors (CNSGCTs). Methods and Materials: Ten cases of patients with localized CNSGCTs and submitted to WVI by use of IMRT with or without a 'boost' to the primary lesion were selected. For comparison purposes, similar treatment plans were produced by use of 3D-CRT (WVI with or without boost) and WBI (opposed lateral fields with or without boost), and cerebral hemisphere sparing was evaluated at dose levels ranging from 2 Gy to 40 Gy. Results: The median prescription dose for WVI was 30.6 Gy (range, 25.2-37.5 Gy), and that for the boost was 16.5 Gy (range, 0-23.4 Gy). Mean irradiated cerebral hemisphere volumes were lower for WVI with IMRT than for 3D-CRT and were lower for WVI with 3D-CRT than for WBI. Intensity-modulated radiotherapy was associated with the lowest irradiated volumes, with reductions of 7.5%, 12.2%, and 9.0% at dose levels of 20, 30, and 40 Gy, respectively, compared with 3D-CRT. Intensity-modulated radiotherapy provided statistically significant reductions of median irradiated volumes at all dose levels (p = 0.002 or less). However, estimated radiation doses to peripheral areas of the body were 1.9 times higher with IMRT than with 3D-CRT. Conclusions: Although IMRT is associated with increased radiation doses to peripheral areas of the body, its use can spare a significant amount of normal central nervous system tissue compared with 3D-CRT or WBI in the setting of CNSGCT treatment.

  1. Intensity modulated radiotherapy and 3D conformal radiotherapy for whole breast irradiation: a comparative dosimetric study and introduction of a novel qualitative index for plan evaluation, the normal tissue index

    SciTech Connect

    Yim, Jackie; Suttie, Clare; Bromley, Regina; Morgia, Marita; Lamoury, Gillian

    2015-09-15

    We report on a retrospective dosimetric study, comparing 3D conformal radiotherapy (3DCRT) and hybrid intensity modulated radiotherapy (hIMRT). We evaluated plans based on their planning target volume coverage, dose homogeneity, dose to organs at risk (OARs) and exposure of normal tissue to radiation. The Homogeneity Index (HI) was used to assess the dose homogeneity in the target region, and we describe a new index, the normal tissue index (NTI), to assess the dose in the normal tissue inside the tangent treatment portal. Plans were generated for 25 early-stage breast cancer patients, using a hIMRT technique. These were compared with the 3DCRT plans of the treatment previously received by the patients. Plan quality was evaluated using the HI, NTI and dose to OARs. The hIMRT technique was significantly more homogenous than the 3DCRT technique, while maintaining target coverage. The hIMRT technique was also superior at minimising the amount of tissue receiving D{sub 105%} and above (P < 0.0001). The ipsilateral lung and contralateral breast maximum were significantly lower in the hIMRT plans (P < 0.05 and P < 0.005), but the 3DCRT technique achieved a lower mean heart dose in left-sided breast cancer patients (P < 0.05). Hybrid intensity modulated radiotherapy plans achieved improved dose homogeneity compared to the 3DCRT plans and superior outcome with regard to dose to normal tissues. We propose that the addition of both HI and NTI in evaluating the quality of intensity modulated radiotherapy (IMRT) breast plans provides clinically relevant comparators which more accurately reflect the new paradigm of treatment goals and outcomes in the era of breast IMRT.

  2. Propensity score based comparison of long term outcomes with 3D conformal radiotherapy (3DCRT) versus Intensity Modulated Radiation Therapy (IMRT) in the treatment of esophageal cancer

    PubMed Central

    Lin, Steven H.; Wang, Lu; Myles, Bevan; Thall, Peter F.; Hofstetter, Wayne L.; Swisher, Stephen G.; Ajani, Jaffer A.; Cox, James D.; Komaki, Ritsuko; Liao, Zhongxing

    2014-01-01

    Purpose Although 3DCRT is the worldwide standard for the treatment of esophageal cancers, IMRT improves dose conformality and reduces radiation exposure to normal tissues. We hypothesized that the dosimetric advantages of IMRT should translate to substantive benefits in clinical outcomes compared to 3DCRT. Methods and Materials Analysis was performed on 676 nonrandomized patients (3DCRT=413, IMRT=263) with stage Ib-IVa (AJCC 2002) esophageal cancers treated with chemoradiation at a single institution from 1998–2008. An inverse probability of treatment weighting (IPW) and inclusion of propensity score (treatment probability) as a covariate were used to compare overall survival (OS) time, time to local failure, and time to distant metastasis, while accounting for effects of other clinically relevant covariates. Propensity scores were estimated using logistic regression. Results A fitted multivariate inverse probability weighted (IPW)-adjusted Cox model showed that OS time was significantly associated with several well-known prognostic factors, along with radiation modality (IMRT vs 3DCRT, HR=0.72, p<0.001). Compared to IMRT, 3DCRT patients had a significantly greater risk of dying (72.6% vs 52.9%, IPW log rank test: p<0.0001) and for local-regional recurrence (LRR) (p=0.0038). There was no difference in cancer-specific mortality (Gray’s test, p=0.86), or distant metastasis (p=0.99) between the two groups. An increased cumulative incidence of cardiac deaths was seen in the 3DCRT group (p=0.049), but most deaths were undocumented (5 year estimate: 11.7% in 3DCRT vs 5.4% in IMRT, Gray’s test, p=0.0029). Conclusions Overall survival, locoregional control, and non-cancer related deaths were significantly better for IMRT compared to 3DCRT. Although these results need confirmation, IMRT should be considered for the treatment of esophageal cancer. PMID:22867894

  3. Poly(NaSS) functionalization modulates the conformation of fibronectin and collagen type I to enhance osteoblastic cell attachment onto Ti6Al4V.

    PubMed

    Felgueiras, Helena P; Sommerfeld, Sven D; Murthy, N Sanjeeva; Kohn, Joachim; Migonney, Véronique

    2014-08-12

    Functionalization of surfaces with poly(sodium styrenesulfonate) (poly(NaSS)) has recently been found to enhance osteointegration of implantable materials. Radical polymerization of poly(NaSS) on titanium (Ti)-based substrates has been used to improve their long-term performance by preventing fibrosis and consequently implant loosening. However, the influence of the sulfonate groups on the early cell behavior and the associated molecular phenomena remains to be understood. In this work, we used quartz crystal microbalance with dissipation (QCM-D) to elucidate the role of poly(NaSS) in enhancing osteoblastic cell attachment. This was measured by following the cell attachment using the MC3T3-E1 cell line, on fetal bovine serum (FBS) preadsorbed surfaces and on substrates adsorbed with a series of relevant proteins, bovine serum albumin (BSA), fibronectin (Fn), and collagen type I (Col I). Comparison of the performance of poly(NaSS) with other clinically important substrates such as Ti alloy Ti6Al4V, gold, and poly(desamino-tyrosyl-tyrosine ethyl ester carbonate) (poly(DTEc)) indicates poly(NaSS) to be a superior substrate for MC3T3-E1 cells attachment. This attachment was found to be integrin mediated in the presence of Fn and Col I. Antibodies specific to the RGD peptide and the N- and C-terminal HB-binding domains reacted more intensively with Fn adsorbed on poly(NaSS). Fn adapts a conformation favorable to RGD mediated cell attachment when adsorbed onto poly(NaSS).

  4. The Effect of Flattening Filter Free on Three-dimensional Conformal Radiation Therapy (3D-CRT), Intensity-Modulated Radiation Therapy (IMRT), and Volumetric Modulated Arc Therapy (VMAT) Plans for Metastatic Brain Tumors from Non-small Cell Lung Cancer.

    PubMed

    Shi, Li-Wan; Lai, You-Qun; Lin, Qin; Ha, Hui-Ming; Fu, Li-Rong

    2015-07-01

    Flattening filter free (FFF) may affect outcome measures of radiotherapy. The objective of this study is to compare the dosimetric parameters in three types of radiotherapy plans, three-dimensional conformal radiation therapy (3D-CRT), intensity-modulated radiation therapy (IMRT), and volumetric modulated arc therapy (VMAT), with or without the flattening filter (FF), developed for the treatment of metastatic brain tumors from non-small cell lung cancer (NSCLC). From July 2013 to October 2013, 3D-CRT, IMRT, and VMAT treatment plans were designed using 6 MV and 10 MV, with and without FF, for 10 patients with brain metastasis from NSCLC. The evaluation of the treatment plans included homogeneity index (HI), conformity index (CI), monitor units (MU), mean dose (Dmean), treatment time, and the influence of FFF on volumes. There was no difference in CI or HI between FFF and FF models with 3D-CRT, IMRT, and VMAT plans. At 6 MV, a lower Dmean was seen in the FFF model of 3D-CRT and in the VMAT plan at 10 MV. In the IMRT 6 MV, IMRT 10 MV, and VMAT 10 MV plans, higher MUs were seen in the FFF models. FFF treatments are similar in quality to FF plans, generally lead to more monitor units, and are associated with shorter treatment times. FFF plans ranked by the order of superiority in terms of a time advantage are VMAT, 3D-CRT, and IMRT.

  5. The Effect of Flattening Filter Free on Three-dimensional Conformal Radiation Therapy (3D-CRT), Intensity-Modulated Radiation Therapy (IMRT), and Volumetric Modulated Arc Therapy (VMAT) Plans for Metastatic Brain Tumors from Non-small Cell Lung Cancer.

    PubMed

    Shi, Li-Wan; Lai, You-Qun; Lin, Qin; Ha, Hui-Ming; Fu, Li-Rong

    2015-07-01

    Flattening filter free (FFF) may affect outcome measures of radiotherapy. The objective of this study is to compare the dosimetric parameters in three types of radiotherapy plans, three-dimensional conformal radiation therapy (3D-CRT), intensity-modulated radiation therapy (IMRT), and volumetric modulated arc therapy (VMAT), with or without the flattening filter (FF), developed for the treatment of metastatic brain tumors from non-small cell lung cancer (NSCLC). From July 2013 to October 2013, 3D-CRT, IMRT, and VMAT treatment plans were designed using 6 MV and 10 MV, with and without FF, for 10 patients with brain metastasis from NSCLC. The evaluation of the treatment plans included homogeneity index (HI), conformity index (CI), monitor units (MU), mean dose (Dmean), treatment time, and the influence of FFF on volumes. There was no difference in CI or HI between FFF and FF models with 3D-CRT, IMRT, and VMAT plans. At 6 MV, a lower Dmean was seen in the FFF model of 3D-CRT and in the VMAT plan at 10 MV. In the IMRT 6 MV, IMRT 10 MV, and VMAT 10 MV plans, higher MUs were seen in the FFF models. FFF treatments are similar in quality to FF plans, generally lead to more monitor units, and are associated with shorter treatment times. FFF plans ranked by the order of superiority in terms of a time advantage are VMAT, 3D-CRT, and IMRT. PMID:26011493

  6. Caspase Allostery and Conformational Selection.

    PubMed

    Clark, A Clay

    2016-06-01

    The role of caspase proteases in regulated processes such as apoptosis and inflammation has been studied for more than two decades, and the activation cascades are known in detail. Apoptotic caspases also are utilized in critical developmental processes, although it is not known how cells maintain the exquisite control over caspase activity in order to retain subthreshold levels required for a particular adaptive response while preventing entry into apoptosis. In addition to active site-directed inhibitors, caspase activity is modulated by post-translational modifications or metal binding to allosteric sites on the enzyme, which stabilize inactive states in the conformational ensemble. This review provides a comprehensive global view of the complex conformational landscape of caspases and mechanisms used to select states in the ensemble. The caspase structural database provides considerable detail on the active and inactive conformations in the ensemble, which provide the cell multiple opportunities to fine tune caspase activity. In contrast, the current database on caspase modifications is largely incomplete and thus provides only a low-resolution picture of global allosteric communications and their effects on the conformational landscape. In recent years, allosteric control has been utilized in the design of small drug compounds or other allosteric effectors to modulate caspase activity.

  7. Is intensity-modulated radiotherapy better than conventional radiation treatment and three-dimensional conformal radiotherapy for mediastinal masses in patients with Hodgkin's disease, and is there a role for beam orientation optimization and dose constraints assigned to virtual volumes?

    SciTech Connect

    Girinsky, Theodore . E-mail: girinsky@igr.fr; Pichenot, Charlotte; Beaudre, Anne; Ghalibafian, Mithra; Lefkopoulos, Dimitri

    2006-01-01

    Purpose: To evaluate the role of beam orientation optimization and the role of virtual volumes (VVs) aimed at protecting adjacent organs at risk (OARs), and to compare various intensity-modulated radiotherapy (IMRT) setups with conventional treatment with anterior and posterior fields and three-dimensional conformal radiotherapy (3D-CRT). Methods and Materials: Patients with mediastinal masses in Hodgkin's disease were treated with combined modality therapy (three to six cycles of adriamycin, bleomycin, vinblastine, and dacarbazine [ABVD] before radiation treatment). Contouring and treatment planning were performed with Somavision and CadPlan Helios (Varian Systems, Palo Alto, CA). The gross tumor volume was determined according to the prechemotherapy length and the postchemotherapy width of the mediastinal tumor mass. A 10-mm isotropic margin was added for the planning target volume (PTV). Because dose constraints assigned to OARs led to unsatisfactory PTV coverage, VVs were designed for each patient to protect adjacent OARs. The prescribed dose was 40 Gy to the PTV, delivered according to guidelines from International Commission on Radiation Units and Measurements Report No. 50. Five different IMRT treatment plans were compared with conventional treatment and 3D-CRT. Results: Beam orientation was important with respect to the amount of irradiated normal tissues. The best compromise in terms of PTV coverage and protection of normal tissues was obtained with five equally spaced beams (5FEQ IMRT plan) using dose constraints assigned to VVs. When IMRT treatment plans were compared with conventional treatment and 3D-CRT, dose conformation with IMRT was significantly better, with greater protection of the heart, coronary arteries, esophagus, and spinal cord. The lungs and breasts in women received a slightly higher radiation dose with IMRT compared with conventional treatments. The greater volume of normal tissue receiving low radiation doses could be a cause for

  8. Conformal operators in QCD

    SciTech Connect

    Makeenko, Y.M.

    1981-03-01

    Utilizing the properties of the representations of the conformal group, we obtain new expressions for the conformal operators composed of spinor or scalar fields of arbitrary dimension in terms of Jacobi polynomials. These expressions generalize the known formulas in terms of Gegenbauer polynomials. Using the conformal Ward identities, we prove the multiplicative renormalizability of conformal operators in the leading logarithmic approximation.

  9. Radiological and Clinical Pneumonitis After Stereotactic Lung Radiotherapy: A Matched Analysis of Three-Dimensional Conformal and Volumetric-modulated Arc Therapy Techniques

    SciTech Connect

    Palma, David A.; Senan, Suresh; Haasbeek, Cornelis J.A.; Verbakel, Wilko F.A.R.; Vincent, Andrew; Lagerwaard, Frank

    2011-06-01

    Purpose: Lung fibrosis is common after stereotactic body radiotherapy (SBRT) for lung tumors, but the influence of treatment technique on rates of clinical and radiological pneumonitis is not well described. After implementing volumetric modulated arc therapy (RapidArc [RA]; Varian Medical Systems, Palo Alto, CA) for SBRT, we scored the early pulmonary changes seen with arc and conventional three-dimensional SBRT (3D-CRT). Methods and Materials: Twenty-five SBRT patients treated with RA were matched 1:2 with 50 SBRT patients treated with 3D-CRT. Dose fractionations were based on a risk-adapted strategy. Clinical pneumonitis was scored using Common Terminology Criteria for Adverse Events version 3.0. Acute radiological changes 3 months posttreatment were scored by three blinded observers. Relationships among treatment type, baseline factors, and outcomes were assessed using Spearman's correlation, Cochran-Mantel-Haenszel tests, and logistic regression. Results: The RA and 3D-CRT groups were well matched. Forty-three patients (57%) had radiological pneumonitis 3 months after treatment. Twenty-eight patients (37%) had computed tomography (CT) findings of patchy or diffuse consolidation, and 15 patients (20%) had ground-glass opacities only. Clinical pneumonitis was uncommon, and no differences were seen between 3D-CRT vs. RA patients in rates of grade 2/3 clinical pneumonitis (6% vs. 4%, respectively; p = 0.99), moderate/severe radiological changes (24% vs. 36%, respectively, p = 0.28), or patterns of CT changes (p = 0.47). Radiological severity scores were associated with larger planning target volumes (p = 0.09) and extended fractionation (p = 0.03). Conclusions: Radiological changes after lung SBRT are common with both approaches, but no differences in early clinical or radiological findings were observed after RA. Longer follow-up will be required to exclude late changes.

  10. Acute Toxicity After Image-Guided Intensity Modulated Radiation Therapy Compared to 3D Conformal Radiation Therapy in Prostate Cancer Patients

    SciTech Connect

    Wortel, Ruud C.; Incrocci, Luca; Pos, Floris J.; Lebesque, Joos V.; Witte, Marnix G.; Heide, Uulke A. van der; Herk, Marcel van; Heemsbergen, Wilma D.

    2015-03-15

    Purpose: Image-guided intensity modulated radiation therapy (IG-IMRT) allows significant dose reductions to organs at risk in prostate cancer patients. However, clinical data identifying the benefits of IG-IMRT in daily practice are scarce. The purpose of this study was to compare dose distributions to organs at risk and acute gastrointestinal (GI) and genitourinary (GU) toxicity levels of patients treated to 78 Gy with either IG-IMRT or 3D-CRT. Methods and Materials: Patients treated with 3D-CRT (n=215) and IG-IMRT (n=260) receiving 78 Gy in 39 fractions within 2 randomized trials were selected. Dose surface histograms of anorectum, anal canal, and bladder were calculated. Identical toxicity questionnaires were distributed at baseline, prior to fraction 20 and 30 and at 90 days after treatment. Radiation Therapy Oncology Group (RTOG) grade ≥1, ≥2, and ≥3 endpoints were derived directly from questionnaires. Univariate and multivariate binary logistic regression analyses were applied. Results: The median volumes receiving 5 to 75 Gy were significantly lower (all P<.001) with IG-IMRT for anorectum, anal canal, and bladder. The mean dose to the anorectum was 34.4 Gy versus 47.3 Gy (P<.001), 23.6 Gy versus 44.6 Gy for the anal canal (P<.001), and 33.1 Gy versus 43.2 Gy for the bladder (P<.001). Significantly lower grade ≥2 toxicity was observed for proctitis, stool frequency ≥6/day, and urinary frequency ≥12/day. IG-IMRT resulted in significantly lower overall RTOG grade ≥2 GI toxicity (29% vs 49%, respectively, P=.002) and overall GU grade ≥2 toxicity (38% vs 48%, respectively, P=.009). Conclusions: A clinically meaningful reduction in dose to organs at risk and acute toxicity levels was observed in IG-IMRT patients, as a result of improved technique and tighter margins. Therefore reduced late toxicity levels can be expected as well; additional research is needed to quantify such reductions.

  11. Evolutionary Conserved Positions Define Protein Conformational Diversity.

    PubMed

    Saldaño, Tadeo E; Monzon, Alexander M; Parisi, Gustavo; Fernandez-Alberti, Sebastian

    2016-03-01

    Conformational diversity of the native state plays a central role in modulating protein function. The selection paradigm sustains that different ligands shift the conformational equilibrium through their binding to highest-affinity conformers. Intramolecular vibrational dynamics associated to each conformation should guarantee conformational transitions, which due to its importance, could possibly be associated with evolutionary conserved traits. Normal mode analysis, based on a coarse-grained model of the protein, can provide the required information to explore these features. Herein, we present a novel procedure to identify key positions sustaining the conformational diversity associated to ligand binding. The method is applied to an adequate refined dataset of 188 paired protein structures in their bound and unbound forms. Firstly, normal modes most involved in the conformational change are selected according to their corresponding overlap with structural distortions introduced by ligand binding. The subspace defined by these modes is used to analyze the effect of simulated point mutations on preserving the conformational diversity of the protein. We find a negative correlation between the effects of mutations on these normal mode subspaces associated to ligand-binding and position-specific evolutionary conservations obtained from multiple sequence-structure alignments. Positions whose mutations are found to alter the most these subspaces are defined as key positions, that is, dynamically important residues that mediate the ligand-binding conformational change. These positions are shown to be evolutionary conserved, mostly buried aliphatic residues localized in regular structural regions of the protein like β-sheets and α-helix. PMID:27008419

  12. Evolutionary Conserved Positions Define Protein Conformational Diversity

    PubMed Central

    Saldaño, Tadeo E.; Monzon, Alexander M.; Parisi, Gustavo; Fernandez-Alberti, Sebastian

    2016-01-01

    Conformational diversity of the native state plays a central role in modulating protein function. The selection paradigm sustains that different ligands shift the conformational equilibrium through their binding to highest-affinity conformers. Intramolecular vibrational dynamics associated to each conformation should guarantee conformational transitions, which due to its importance, could possibly be associated with evolutionary conserved traits. Normal mode analysis, based on a coarse-grained model of the protein, can provide the required information to explore these features. Herein, we present a novel procedure to identify key positions sustaining the conformational diversity associated to ligand binding. The method is applied to an adequate refined dataset of 188 paired protein structures in their bound and unbound forms. Firstly, normal modes most involved in the conformational change are selected according to their corresponding overlap with structural distortions introduced by ligand binding. The subspace defined by these modes is used to analyze the effect of simulated point mutations on preserving the conformational diversity of the protein. We find a negative correlation between the effects of mutations on these normal mode subspaces associated to ligand-binding and position-specific evolutionary conservations obtained from multiple sequence-structure alignments. Positions whose mutations are found to alter the most these subspaces are defined as key positions, that is, dynamically important residues that mediate the ligand-binding conformational change. These positions are shown to be evolutionary conserved, mostly buried aliphatic residues localized in regular structural regions of the protein like β-sheets and α-helix. PMID:27008419

  13. Conformational implications of asparagine-linked glycosylation.

    PubMed Central

    Imperiali, B; Rickert, K W

    1995-01-01

    The effects of cotranslational protein modification on the process of protein folding are poorly understood. Time-resolved fluorescence energy transfer has been used to assess the impact of glycosylation on the conformational dynamics of flexible oligopeptides. The peptide sequences examined are selected from glycoproteins of known three-dimensional structure. The energy transfer modulation associated with N-linked glycosylation is consistent with the glycopeptides sampling different conformational profiles in water. Results show that glycosylation causes the modified peptides to adopt a different ensemble of conformations, and for some peptides this change may lead to conformations that are more compact and better approximate the conformation of these peptides in the final folded protein. This result further implies that cotranslational glycosylation can trigger the timely formation of structural nucleation elements and thus assist in the complex process of protein folding. PMID:7816856

  14. Dosimetric and clinical toxicity comparison of critical organ preservation with three-dimensional conformal radiotherapy, intensity-modulated radiotherapy, and RapidArc for the treatment of locally advanced cancer of the pancreatic head

    PubMed Central

    Jin, L.; Wang, R.; Jiang, S.; Yue, J.; Liu, T.; Dou, X.; Zhu, K.; Feng, R.; Xu, X.; Chen, D.; Yin, Y.

    2016-01-01

    Purpose We compared dosimetry and clinical toxicity for 3-dimensional conformal radiotherapy (3D-crt), intensity-modulated radiotherapy (imrt), and RapidArc (Varian Medical Systems, Palo Alto, CA, U.S.A.) in locally advanced pancreatic cancer (lapcc). We hypothesized that the technique with better sparing of organs at risk (oars) and better target dose distributions could lead to decreased clinical toxicity. Methods The study analyzed 280 patients with lapcc who had undergone radiotherapy. The dosimetry comparison was performed using 20 of those patients. Dose–volume histograms for the target volume and the oars were compared. The clinical toxicity comparison used the 280 patients who received radiation with 3D-crt, imrt, or RapidArc. Results Compared with 3D-crt, RapidArc and imrt both achieved a better conformal index, homogeneity index, V95%, and V110%. Compared with 3D-crt or imrt, RapidArc reduced the V10, V20, and mean dose to duodenum, the V20 of the right kidney, and the liver mean dose. Compared with 3D-crt, RapidArc reduced the V35, and V45 of duodenum, the mean dose to small bowel, and the V15 of right kidney. The incidences of grades 3 and 4 diarrhea (p = 0.037) and anorexia (p = 0.042) were lower with RapidArc than with 3D-crt, and the incidences of grades 3 and 4 diarrhea (p = 0.027) were lower with RapidArc than with imrt. Conclusions Compared with 3D-crt or imrt, RapidArc showed better sparing of oars, especially duodenum, small bowel, and right kidney. Also, fewer acute grades 3 and 4 gastrointestinal toxicities were seen with RapidArc than with 3D-crt or imrt. A technique with better sparing of oars and better target dose distributions could result in decreased clinical toxicities during radiation treatment for lapcc. PMID:26966412

  15. Constituent Components of Out-of-Field Scatter Dose for 18-MV Intensity Modulated Radiation Therapy Versus 3-Dimensional Conformal Radiation Therapy: A Comparison With 6-MV and Implications for Carcinogenesis

    SciTech Connect

    Ruben, Jeremy D.; Smith, Ryan; Lancaster, Craig M.; Haynes, Matthew; Jones, Phillip; Panettieri, Vanessa

    2014-11-01

    Purpose: To characterize and compare the components of out-of-field dose for 18-MV intensity modulated radiation therapy (IMRT) versus 3-dimensional conformal radiation therapy (3D-CRT) and their 6-MV counterparts and consider implications for second cancer induction. Methods and Materials: Comparable plans for each technique/energy were delivered to a water phantom with a sloping wall; under full scatter conditions; with field edge abutting but outside the bath to prevent internal/phantom scatter; and with shielding below the linear accelerator head to attenuate head leakage. Neutron measurements were obtained from published studies. Results: Eighteen-megavolt IMRT produces 1.7 times more out-of-field scatter than 18-MV 3D-CRT. In absolute terms, however, differences are just approximately 0.1% of central axis dose. Eighteen-megavolt IMRT reduces internal/patient scatter by 13%, but collimator scatter (C) is 2.6 times greater than 18-MV 3D-CRT. Head leakage (L) is minimal. Increased out-of-field photon scatter from 18-MV IMRT carries out-of-field second cancer risks of approximately 0.2% over and above the 0.4% from 18-MV 3D-CRT. Greater photoneutron dose from 18-MV IMRT may result in further maximal, absolute increased risk to peripheral tissue of approximately 1.2% over 18-MV 3D-CRT. Out-of-field photon scatter remains comparable for the same modality irrespective of beam energy. Machine scatter (C+L) from 18 versus 6 MV is 1.2 times higher for IMRT and 1.8 times for 3D-CRT. It is 4 times higher for 6-MV IMRT versus 3D-CRT. Reduction in internal scatter with 18 MV versus 6 MV is 27% for 3D-CRT and 29% for IMRT. Compared with 6-MV 3D-CRT, 18-MV IMRT increases out-of-field second cancer risk by 0.2% from photons and adds 0.28-2.2% from neutrons. Conclusions: Out-of-field photon dose seems to be independent of beam energy for both techniques. Eighteen-megavolt IMRT increases out-of-field scatter 1.7-fold over 3D-CRT because of greater collimator scatter despite

  16. [Conformal radiotherapy of brain tumors].

    PubMed

    Haie-Meder, C; Beaudré, A; Breton, C; Biron, B; Cordova, A; Dubray, B; Mazeron, J J

    1999-01-01

    Conformal irradiation of brain tumours is based on the three-dimensional reconstruction of the targeted volumes and at-risk organ images, the three-dimensional calculation of the dose distribution and a treatment device (immobilisation, beam energy, collimation, etc.) adapted to the high precision required by the procedure. Each step requires an appropriate methodology and a quality insurance program. Specific difficulties in brain tumour management are related to GTV and CTV definition depending upon the histological type, the quality of the surgical resection and the medical team. Clinical studies have reported dose escalation trials, mostly in high-grade gliomas and tumours at the base of the skull. Clinical data are now providing a better knowledge of the tolerance of normal tissues. As for small tumours, the implementation of beam intensity modulation is likely to narrow the gap between conformal and stereotaxic radiotherapy. PMID:10572510

  17. Preliminary Toxicity Analysis of 3-Dimensional Conformal Radiation Therapy Versus Intensity Modulated Radiation Therapy on the High-Dose Arm of the Radiation Therapy Oncology Group 0126 Prostate Cancer Trial

    SciTech Connect

    Michalski, Jeff M.; Yan, Yan; Watkins-Bruner, Deborah; Bosch, Walter R.; Winter, Kathryn; Galvin, James M.; Bahary, Jean-Paul; Morton, Gerard C.; Parliament, Matthew B.; Sandler, Howard M.

    2013-12-01

    Purpose: To give a preliminary report of clinical and treatment factors associated with toxicity in men receiving high-dose radiation therapy (RT) on a phase 3 dose-escalation trial. Methods and Materials: The trial was initiated with 3-dimensional conformal RT (3D-CRT) and amended after 1 year to allow intensity modulated RT (IMRT). Patients treated with 3D-CRT received 55.8 Gy to a planning target volume that included the prostate and seminal vesicles, then 23.4 Gy to prostate only. The IMRT patients were treated to the prostate and proximal seminal vesicles to 79.2 Gy. Common Toxicity Criteria, version 2.0, and Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer late morbidity scores were used for acute and late effects. Results: Of 763 patients randomized to the 79.2-Gy arm of Radiation Therapy Oncology Group 0126 protocol, 748 were eligible and evaluable: 491 and 257 were treated with 3D-CRT and IMRT, respectively. For both bladder and rectum, the volumes receiving 65, 70, and 75 Gy were significantly lower with IMRT (all P<.0001). For grade (G) 2+ acute gastrointestinal/genitourinary (GI/GU) toxicity, both univariate and multivariate analyses showed a statistically significant decrease in G2+ acute collective GI/GU toxicity for IMRT. There were no significant differences with 3D-CRT or IMRT for acute or late G2+ or 3+ GU toxicities. Univariate analysis showed a statistically significant decrease in late G2+ GI toxicity for IMRT (P=.039). On multivariate analysis, IMRT showed a 26% reduction in G2+ late GI toxicity (P=.099). Acute G2+ toxicity was associated with late G3+ toxicity (P=.005). With dose–volume histogram data in the multivariate analysis, RT modality was not significant, whereas white race (P=.001) and rectal V70 ≥15% were associated with G2+ rectal toxicity (P=.034). Conclusions: Intensity modulated RT is associated with a significant reduction in acute G2+ GI/GU toxicity. There is a trend for a

  18. Infinite rank Schrödinger-Virasoro type Lie conformal algebras

    NASA Astrophysics Data System (ADS)

    Fan, Guangzhe; Su, Yucai; Xia, Chunguang

    2016-08-01

    Motivated by the structure of certain modules over the loop Virasoro Lie conformal algebra and the Lie structures of Schrödinger-Virasoro algebras, we construct a class of infinite rank Lie conformal algebras CSV(a, b), where a, b are complex numbers. The conformal derivations of CSV(a, b) are uniformly determined. The rank one conformal modules and ℤ-graded free intermediate series modules over CSV(a, b) are classified. Corresponding results of the conformal subalgebra CHV(a, b) of CSV(a, b) are also presented.

  19. A critical evaluation of secondary cancer risk models applied to Monte Carlo dose distributions of 2-dimensional, 3-dimensional conformal and hybrid intensity-modulated radiation therapy for breast cancer

    NASA Astrophysics Data System (ADS)

    Joosten, A.; Bochud, F.; Moeckli, R.

    2014-08-01

    The comparison of radiotherapy techniques regarding secondary cancer risk has yielded contradictory results possibly stemming from the many different approaches used to estimate risk. The purpose of this study was to make a comprehensive evaluation of different available risk models applied to detailed whole-body dose distributions computed by Monte Carlo for various breast radiotherapy techniques including conventional open tangents, 3D conformal wedged tangents and hybrid intensity modulated radiation therapy (IMRT). First, organ-specific linear risk models developed by the International Commission on Radiological Protection (ICRP) and the Biological Effects of Ionizing Radiation (BEIR) VII committee were applied to mean doses for remote organs only and all solid organs. Then, different general non-linear risk models were applied to the whole body dose distribution. Finally, organ-specific non-linear risk models for the lung and breast were used to assess the secondary cancer risk for these two specific organs. A total of 32 different calculated absolute risks resulted in a broad range of values (between 0.1% and 48.5%) underlying the large uncertainties in absolute risk calculation. The ratio of risk between two techniques has often been proposed as a more robust assessment of risk than the absolute risk. We found that the ratio of risk between two techniques could also vary substantially considering the different approaches to risk estimation. Sometimes the ratio of risk between two techniques would range between values smaller and larger than one, which then translates into inconsistent results on the potential higher risk of one technique compared to another. We found however that the hybrid IMRT technique resulted in a systematic reduction of risk compared to the other techniques investigated even though the magnitude of this reduction varied substantially with the different approaches investigated. Based on the epidemiological data available, a reasonable

  20. A critical evaluation of secondary cancer risk models applied to Monte Carlo dose distributions of 2-dimensional, 3-dimensional conformal and hybrid intensity-modulated radiation therapy for breast cancer.

    PubMed

    Joosten, A; Bochud, F; Moeckli, R

    2014-08-21

    The comparison of radiotherapy techniques regarding secondary cancer risk has yielded contradictory results possibly stemming from the many different approaches used to estimate risk. The purpose of this study was to make a comprehensive evaluation of different available risk models applied to detailed whole-body dose distributions computed by Monte Carlo for various breast radiotherapy techniques including conventional open tangents, 3D conformal wedged tangents and hybrid intensity modulated radiation therapy (IMRT). First, organ-specific linear risk models developed by the International Commission on Radiological Protection (ICRP) and the Biological Effects of Ionizing Radiation (BEIR) VII committee were applied to mean doses for remote organs only and all solid organs. Then, different general non-linear risk models were applied to the whole body dose distribution. Finally, organ-specific non-linear risk models for the lung and breast were used to assess the secondary cancer risk for these two specific organs. A total of 32 different calculated absolute risks resulted in a broad range of values (between 0.1% and 48.5%) underlying the large uncertainties in absolute risk calculation. The ratio of risk between two techniques has often been proposed as a more robust assessment of risk than the absolute risk. We found that the ratio of risk between two techniques could also vary substantially considering the different approaches to risk estimation. Sometimes the ratio of risk between two techniques would range between values smaller and larger than one, which then translates into inconsistent results on the potential higher risk of one technique compared to another. We found however that the hybrid IMRT technique resulted in a systematic reduction of risk compared to the other techniques investigated even though the magnitude of this reduction varied substantially with the different approaches investigated. Based on the epidemiological data available, a reasonable

  1. CONSENSUS AND CONFORMITY.

    ERIC Educational Resources Information Center

    ALLEN, VERNON L.; LEVINE, JOHN M.

    IN THIS STUDY, PROFESSOR ALLEN EMPLOYS TWO METHODS OF BREAKING GROUP CONSENSUS, AND HE MEASURES THE EFFECTS ON THE RESPONSES OF COLLEGE SUBJECTS TO BOTH OBJECTIVE AND SUBJECTIVE STIMULI. THE RESULTS SUGGEST THE NEED FOR MODIFICATION OF EXISTING THEORIES OF CONFORMITY BEHAVIOR. IN ADDITION, THESE RESULTS EMPHASIZE THE DIFFERENCES IN CONFORMITY OF…

  2. Rapid roll inflation with conformal coupling

    SciTech Connect

    Kofman, Lev; Mukohyama, Shinji

    2008-02-15

    Usual inflation is realized with a slow rolling scalar field minimally coupled to gravity. In contrast, we consider dynamics of a scalar with a flat effective potential, conformally coupled to gravity. Surprisingly, it contains an attractor inflationary solution with the rapidly rolling inflaton field. We discuss models with the conformal inflaton with a flat potential (including hybrid inflation). There is no generation of cosmological fluctuations from the conformally coupled inflaton. We consider realizations of modulated (inhomogeneous reheating) or curvaton cosmological fluctuations in these models. We also implement these unusual features for the popular string-theoretic warped inflationary scenario, based on the interacting D3-D3 branes. The original warped brane inflation suffers a large inflaton mass due to conformal coupling to 4-dimensional gravity. Instead of considering this as a problem and trying to cure it with extra engineering, we show that warped inflation with the conformally coupled, rapidly rolling inflaton is yet possible with N=37 efoldings, which requires low-energy scales 1-100 TeV of inflation. Coincidentally, the same warping numerology can be responsible for the hierarchy. It is shown that the scalars associated with angular isometries of the warped geometry of compact manifold (e.g. S{sup 3} of Klebanov-Strassler (KS) geometry) have solutions identical to conformally coupled modes and also cannot be responsible for cosmological fluctuations. We discuss other possibilities.

  3. Conformal Geometry of the Supercotangent and Spinor Bundles

    NASA Astrophysics Data System (ADS)

    Michel, J.-P.

    2012-06-01

    We study the actions of local conformal vector fields {X \\in conf(M,g)} on the spinor bundle of ( M, g) and on its classical counterpart: the supercotangent bundle {{M}} of ( M, g). We first deal with the classical framework and determine the Hamiltonian lift of conf ( M, g) to {{M}} . We then perform the geometric quantization of the supercotangent bundle of ( M, g), which constructs the spinor bundle as the quantum representation space. The Kosmann Lie derivative of spinors is obtained by quantization of the comoment map. The quantum and classical actions of conf ( M, g) turn, respectively, the space of differential operators acting on spinor densities and the space of their symbols into conf ( M, g)-modules. They are filtered and admit a common associated graded module. In the conformally flat case, the latter helps us determine the conformal invariants of both conf ( M, g)-modules, in particular the conformally odd powers of the Dirac operator.

  4. Notes on conformal invariance of gauge fields

    NASA Astrophysics Data System (ADS)

    Barnich, Glenn; Bekaert, Xavier; Grigoriev, Maxim

    2015-12-01

    In Lagrangian gauge systems, the vector space of global reducibility parameters forms a module under the Lie algebra of symmetries of the action. Since the classification of global reducibility parameters is generically easier than the classification of symmetries of the action, this fact can be used to constrain the latter when knowing the former. We apply this strategy and its generalization for the non-Lagrangian setting to the problem of conformal symmetry of various free higher spin gauge fields. This scheme allows one to show that, in terms of potentials, massless higher spin gauge fields in Minkowski space and partially massless (PM) fields in (A)dS space are not conformal for spin strictly greater than one, while in terms of curvatures, maximal-depth PM fields in four dimensions are also not conformal, unlike the closely related, but less constrained, maximal-depth Fradkin-Tseytlin fields.

  5. Assemblies of Conformal Tanks

    NASA Technical Reports Server (NTRS)

    DeLay, Tom

    2009-01-01

    Assemblies of tanks having shapes that conform to each other and/or conform to other proximate objects have been investigated for use in storing fuels and oxidizers in small available spaces in upper stages of spacecraft. Such assemblies might also prove useful in aircraft, automobiles, boats, and other terrestrial vehicles in which space available for tanks is limited. The basic concept of using conformal tanks to maximize the utilization of limited space is not new in itself: for example, conformal tanks are used in some automobiles to store windshield -washer liquid and coolant that overflows from radiators. The novelty of the present development lies in the concept of an assembly of smaller conformal tanks, as distinguished from a single larger conformal tank. In an assembly of smaller tanks, it would be possible to store different liquids in different tanks. Even if the same liquid were stored in all the tanks, the assembly would offer an advantage by reducing the mechanical disturbance caused by sloshing of fuel in a single larger tank: indeed, the requirement to reduce sloshing is critical in some applications. The figure shows a prototype assembly of conformal tanks. Each tank was fabricated by (1) copper plating a wax tank mandrel to form a liner and (2) wrapping and curing layers of graphite/epoxy composite to form a shell supporting the liner. In this case, the conformal tank surfaces are flat ones where they come in contact with the adjacent tanks. A band of fibers around the outside binds the tanks together tightly in the assembly, which has a quasi-toroidal shape. For proper functioning, it would be necessary to maintain equal pressure in all the tanks.

  6. Logarithmic conformal field theory

    NASA Astrophysics Data System (ADS)

    Gainutdinov, Azat; Ridout, David; Runkel, Ingo

    2013-12-01

    theories including those with boundaries, supersymmetry and galilean relativity. Gurarie has written an historical overview of his seminal contributions to this field, putting his results (and those of his collaborators) in the context of understanding applications to condensed matter physics. This includes the link between the non-diagonalisability of L0 and logarithmic singularities, a study of the c → 0 catastrophe, and a proposed resolution involving supersymmetric partners for the stress-energy tensor and its logarithmic partner field. Henkel and Rouhani describe a direction in which logarithmic singularities are observed in correlators of non-relativistic field theories. Their review covers the appropriate modifications of conformal invariance that are appropriate to non-equilibrium statistical mechanics, strongly anisotropic critical points and certain variants of TMG. The main variation away from the standard relativistic idea of conformal invariance is that time is explicitly distinguished from space when considering dilations and this leads to a variety of algebraic structures to explore. In this review, the link between non-diagonalisable representations and logarithmic singularities in correlators is generalised to these algebras, before two applications of the theory are discussed. Huang and Lepowsky give a non-technical overview of their work on braided tensor structures on suitable categories of representations of vertex operator algebras. They also place their work in historic context and compare it to related approaches. The authors sketch their construction of the so-called P(z)-tensor product of modules of a vertex operator algebra, and the construction of the associativity isomorphisms for this tensor product. They proceed to give a guide to their works leading to the first authorrsquo;s proof of modularity for a class of vertex operator algebras, and to their works, joint with Zhang, on logarithmic intertwining operators and the resulting tensor

  7. Protein Conformational Populations and Functionally Relevant Sub-states

    SciTech Connect

    Agarwal, Pratul K; Burger, Virginia; Savol, Andrej; Ramanathan, Arvind; Chennubhotla, Chakra

    2013-01-01

    it to attain the transition state, therefore promoting the reaction mechanism. In the long term, this emerging view of proteins with conformational substates has broad implications for improving our understanding of enzymes, enzyme engineering, and better drug design. Researchers have already used photoactivation to modulate protein conformations as a strategy to develop a hypercatalytic enzyme. In addition, the alteration of the conformational substates through binding of ligands at locations other than the active site provides the basis for the design of new medicines through allosteric modulation.

  8. Charged conformal Killing spinors

    SciTech Connect

    Lischewski, Andree

    2015-01-15

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

  9. Memory, metamemory, and social cues: Between conformity and resistance.

    PubMed

    Zawadzka, Katarzyna; Krogulska, Aleksandra; Button, Roberta; Higham, Philip A; Hanczakowski, Maciej

    2016-02-01

    When presented with responses of another person, people incorporate these responses into memory reports: a finding termed memory conformity. Research on memory conformity in recognition reveals that people rely on external social cues to guide their memory responses when their own ability to respond is at chance. In this way, conforming to a reliable source boosts recognition performance but conforming to a random source does not impair it. In the present study we assessed whether people would conform indiscriminately to reliable and unreliable (random) sources when they are given the opportunity to exercise metamemory control over their responding by withholding answers in a recognition test. In Experiments 1 and 2, we found the pattern of memory conformity to reliable and unreliable sources in 2 variants of a free-report recognition test, yet at the same time the provision of external cues did not affect the rate of response withholding. In Experiment 3, we provided participants with initial feedback on their recognition decisions, facilitating the discrimination between the reliable and unreliable source. This led to the reduction of memory conformity to the unreliable source, and at the same time modulated metamemory decisions concerning response withholding: participants displayed metamemory conformity to the reliable source, volunteering more responses in their memory report, and metamemory resistance to the random source, withholding more responses from the memory report. Together, the results show how metamemory decisions dissociate various types of memory conformity and that memory and metamemory decisions can be independent of each other.

  10. Extended conformal field theories

    NASA Astrophysics Data System (ADS)

    Taormina, Anne

    1990-08-01

    Some extended conformal field theories are briefly reviewed. They illustrate how non minimal models of the Virasoro algebra (c≥1) can become minimal with respect to a larger algebra. The accent is put on N-extended superconformal algebras, which are relevant in superstring compactification.

  11. Conformational changes in biopolymers

    NASA Astrophysics Data System (ADS)

    Ivanov, Vassili

    2005-12-01

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

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

    PubMed

    Sullivan, David C; Lim, Carmay

    2006-08-24

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

  13. Conformational flexibility of aspartame.

    PubMed

    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. PMID:27038223

  14. Conformal complementarity maps

    NASA Astrophysics Data System (ADS)

    Barbón, José L. F.; Rabinovici, Eliezer

    2013-12-01

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

  15. Multiscale conformal pattern transfer.

    PubMed

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

    2016-01-01

    We demonstrate a method for seamless transfer from a parent flat substrate of basically any lithographic top-down or bottom-up pattern onto essentially any kind of surface. The nano- or microscale patterns, spanning macroscopic surface areas, can be transferred with high conformity onto a large variety of surfaces when such patterns are produced on a thin carbon film, grown on top of a sacrificial layer. The latter allows lifting the patterns from the flat parent substrate onto a water-air interface to be picked up by the host surface of choice. We illustrate the power of this technique by functionalizing broad range of materials including glass, plastics, metals, rough semiconductors and polymers, highlighting the potential applications in in situ colorimetry of the chemistry of materials, anti-counterfeit technologies, biomolecular and biomedical studies, light-matter interactions at the nanoscale, conformal photovoltaics and flexible electronics. PMID:27329824

  16. Multiscale conformal pattern transfer

    PubMed Central

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

    2016-01-01

    We demonstrate a method for seamless transfer from a parent flat substrate of basically any lithographic top-down or bottom-up pattern onto essentially any kind of surface. The nano- or microscale patterns, spanning macroscopic surface areas, can be transferred with high conformity onto a large variety of surfaces when such patterns are produced on a thin carbon film, grown on top of a sacrificial layer. The latter allows lifting the patterns from the flat parent substrate onto a water-air interface to be picked up by the host surface of choice. We illustrate the power of this technique by functionalizing broad range of materials including glass, plastics, metals, rough semiconductors and polymers, highlighting the potential applications in in situ colorimetry of the chemistry of materials, anti-counterfeit technologies, biomolecular and biomedical studies, light-matter interactions at the nanoscale, conformal photovoltaics and flexible electronics. PMID:27329824

  17. Multiscale conformal pattern transfer

    NASA Astrophysics Data System (ADS)

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

    2016-06-01

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

  18. Conformational flexibility of aspartame.

    PubMed

    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.

  19. Conformal scalar field wormholes

    NASA Technical Reports Server (NTRS)

    Halliwell, Jonathan J.; Laflamme, Raymond

    1989-01-01

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

  20. The conformal bootstrap

    NASA Astrophysics Data System (ADS)

    Poland, David; Simmons-Duffin, David

    2016-06-01

    The conformal bootstrap was proposed in the 1970s as a strategy for calculating the properties of second-order phase transitions. After spectacular success elucidating two-dimensional systems, little progress was made on systems in higher dimensions until a recent renaissance beginning in 2008. We report on some of the main results and ideas from this renaissance, focusing on new determinations of critical exponents and correlation functions in the three-dimensional Ising and O(N) models.

  1. Conformations of organophosphine oxides

    SciTech Connect

    De Silva, Nuwan; Zahariev, Federico; Hay, Benjamin P.; Gordon, Mark S.; Windus, Theresa L.

    2015-07-17

    The conformations of a series of organophosphine oxides, OP(CH3)2R, where R = methyl, ethyl, isopropyl, tert-butyl, vinyl, and phenyl, are predicted using the MP2/cc-pVTZ level of theory. Comparison of potential energy surfaces for rotation about P–C bonds with crystal structure data reveals a strong correlation between predicted location and energetics of minima and histograms of dihedral angle distributions observed in the solid state. In addition, the most stable conformers are those that minimize the extent of steric repulsion between adjacent rotor substituents, and the torsional barriers tend to increase with the steric bulk of the rotating alkyl group. MM3 force field parameters were adjusted to fit the MP2 results, providing a fast and accurate model for predicting organophosphine oxides shapes—an essential part of understanding the chemistry of these compounds. As a result, the predictive power of the modified MM3 model was tested against MP2/cc-pVTZ conformations for triethylphosphine oxide, OP(CH2CH3)3, and triphenylphosphine oxide, OP(Ph)3.

  2. Conformational stability of apoflavodoxin.

    PubMed Central

    Genzor, C. G.; Beldarraín, A.; Gómez-Moreno, C.; López-Lacomba, J. L.; Cortijo, M.; Sancho, J.

    1996-01-01

    Flavodoxins are alpha/beta proteins that mediate electron transfer reactions. The conformational stability of apoflavodoxin from Anaboena PCC 7119 has been studied by calorimetry and urea denaturation as a function of pH and ionic strength. At pH > 12, the protein is unfolded. Between pH 11 and pH 6, the apoprotein is folded properly as judged from near-ultraviolet (UV) circular dichroism (CD) and high-field 1H NMR spectra. In this pH interval, apoflavodoxin is a monomer and its unfolding by urea or temperature follows a simple two-state mechanism. The specific heat capacity of unfolding for this native conformation is unusually low. Near its isoelectric point (3.9), the protein is highly insoluble. At lower pH values (pH 3.5-2.0), apoflavodoxin adopts a conformation with the properties of a molten globule. Although apoflavodoxin at pH 2 unfolds cooperatively with urea in a reversible fashion and the fluorescence and far-UV CD unfolding curves coincide, the transition midpoint depends on the concentration of protein, ruling out a simple two-state process at acidic pH. Apoflavodoxin constitutes a promising system for the analysis of the stability and folding of alpha/beta proteins and for the study of the interaction between apoflavoproteins and their corresponding redox cofactors. PMID:8819170

  3. Conformations of organophosphine oxides

    DOE PAGES

    De Silva, Nuwan; Zahariev, Federico; Hay, Benjamin P.; Gordon, Mark S.; Windus, Theresa L.

    2015-07-17

    The conformations of a series of organophosphine oxides, OP(CH3)2R, where R = methyl, ethyl, isopropyl, tert-butyl, vinyl, and phenyl, are predicted using the MP2/cc-pVTZ level of theory. Comparison of potential energy surfaces for rotation about P–C bonds with crystal structure data reveals a strong correlation between predicted location and energetics of minima and histograms of dihedral angle distributions observed in the solid state. In addition, the most stable conformers are those that minimize the extent of steric repulsion between adjacent rotor substituents, and the torsional barriers tend to increase with the steric bulk of the rotating alkyl group. MM3 forcemore » field parameters were adjusted to fit the MP2 results, providing a fast and accurate model for predicting organophosphine oxides shapes—an essential part of understanding the chemistry of these compounds. As a result, the predictive power of the modified MM3 model was tested against MP2/cc-pVTZ conformations for triethylphosphine oxide, OP(CH2CH3)3, and triphenylphosphine oxide, OP(Ph)3.« less

  4. Logarithmic conformal field theory: beyond an introduction

    NASA Astrophysics Data System (ADS)

    Creutzig, Thomas; Ridout, David

    2013-12-01

    This article aims to review a selection of central topics and examples in logarithmic conformal field theory. It begins with the remarkable observation of Cardy that the horizontal crossing probability of critical percolation may be computed analytically within the formalism of boundary conformal field theory. Cardy’s derivation relies on certain implicit assumptions which are shown to lead inexorably to indecomposable modules and logarithmic singularities in correlators. For this, a short introduction to the fusion algorithm of Nahm, Gaberdiel and Kausch is provided. While the percolation logarithmic conformal field theory is still not completely understood, there are several examples for which the formalism familiar from rational conformal field theory, including bulk partition functions, correlation functions, modular transformations, fusion rules and the Verlinde formula, has been successfully generalized. This is illustrated for three examples: the singlet model \\mathfrak {M} (1,2), related to the triplet model \\mathfrak {W} (1,2), symplectic fermions and the fermionic bc ghost system; the fractional level Wess-Zumino-Witten model based on \\widehat{\\mathfrak {sl}} \\left( 2 \\right) at k=-\\frac{1}{2}, related to the bosonic βγ ghost system; and the Wess-Zumino-Witten model for the Lie supergroup \\mathsf {GL} \\left( 1 {\\mid} 1 \\right), related to \\mathsf {SL} \\left( 2 {\\mid} 1 \\right) at k=-\\frac{1}{2} and 1, the Bershadsky-Polyakov algebra W_3^{(2)} and the Feigin-Semikhatov algebras W_n^{(2)}. These examples have been chosen because they represent the most accessible, and most useful, members of the three best-understood families of logarithmic conformal field theories. The logarithmic minimal models \\mathfrak {W} (q,p), the fractional level Wess-Zumino-Witten models, and the Wess-Zumino-Witten models on Lie supergroups (excluding \\mathsf {OSP} \\left( 1 {\\mid} 2n \\right)). In this review, the emphasis lies on the representation theory

  5. Conformation and hydration of aspartame.

    PubMed

    Kang, Y K

    1991-07-01

    Conformational free energy calculations using an empirical potential (ECEPP/2) and the hydration shell model were carried out on the neutral, acidic, zwitterionic, and basic forms of aspartame in the hydrated state. The results indicate that as the molecule becomes more charged, the number of low energy conformations becomes smaller and the molecule becomes less flexible. The calculated free energies of hydration of charged aspartames show that hydration has a significant effect on the conformation in solution. Only two feasible conformations were found for the zwitterionic form, and these are consistent with the conformations deduced from NMR and X-ray diffraction experiments. The calculated free energy difference between these two conformations was 1.25 kcal/mol. The less favored of the two solvated conformations can be expected to be stabilized by hydrophobic interaction of the phenyl groups in the crystal.

  6. Leaf growth is conformal

    NASA Astrophysics Data System (ADS)

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

    2016-10-01

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

  7. Leaf growth is conformal.

    PubMed

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

    2016-01-01

    Growth pattern dynamics lie at the heart of morphogenesis. Here, we investigate the growth of plant leaves. We compute the conformal transformation that maps the contour of a leaf at a given stage onto the contour of the same leaf at a later stage. Based on the mapping we predict the local displacement field in the leaf blade and find it to agree with the experimentally measured displacement field to 92%. This approach is applicable to any two-dimensional system with locally isotropic growth, enabling the deduction of the whole growth field just from observation of the tissue contour. PMID:27597439

  8. OSI Conformance Testing for Bibliographic Applications.

    ERIC Educational Resources Information Center

    Arbez, Gilbert; Swain, Leigh

    1990-01-01

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

  9. General conformal transformation method based on Schwarz-Christoffel approach

    NASA Astrophysics Data System (ADS)

    Tang, Linlong; Yin, Jinchan; Yuan, Guishan; Du, Jinglei; Gao, Hongtao; Dong, Xiaochun; Lu, Yueguang; Du, Chunlei

    2011-08-01

    A general conformal transformation method (CTM) is proposed to construct the conformal mapping between two irregular geometries. In order to find the material parameters corresponding to the conformal transformation between two irregular geometries, two polygons are utilized to approximate the two irregular geometries, and an intermediate geometry is used to connect the mapping relations between the two polygons. Based on these manipulations, the approximate material parameters for TE and TM waves are finally obtained by calculating the Schwarz-Christoffel (SC) mappings. To demonstrate the validity of the method, a phase modulator and a plane focal surface Luneburg lens are designed and simulated by the finite element method. The results show that the conformal transformation can be expanded to the cases that the transformed objects are with irregular geometries.

  10. Targeting Inactive Enzyme Conformation

    PubMed Central

    Liu, Sijiu; Zeng, Li-Fan; Wu, Li; Yu, Xiao; Xue, Ting; Gunawan, Andrea M.; Ya-Qiu, Long; Zhang, Zhong-Yin

    2009-01-01

    There has been considerable interest in protein tyrosine phosphatase 1B (PTP1B) as a therapeutic target for diabetes, obesity, as well as cancer. Identifying inhibitory compounds with good bioavailability is a major challenge of drug discovery programs targeted toward PTPs. Most current PTP active site-directed pharmacophores are negatively charged pTyr mimetics which cannot readily enter the cell. This lack of cell permeability limits the utility of such compounds in signaling studies and further therapeutic development. We identify aryl diketoacids as novel pTyr surrogates and show that neutral amide-linked aryl diketoacid dimers also exhibit excellent PTP inhibitory activity. Kinetic studies establish that these aryl diketoacid derivatives act as noncompetitive inhibitors of PTP1B. Crystal structures of ligand-bound PTP1B reveal that both the aryl diketoacid and its dimeric derivative bind PTP1B at the active site, albeit with distinct modes of interaction, in the catalytically inactive, WPD loop open conformation. Furthermore, dimeric aryl diketoacids are cell permeable and enhance insulin signaling in hepatoma cells, suggesting that targeting the inactive conformation may provide a unique opportunity for creating active site-directed PTP1B inhibitors with improved pharmacological properties. PMID:19012396

  11. Conformally symmetric traversable wormholes

    SciTech Connect

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

    2007-10-15

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

  12. Eikonalization of conformal blocks

    SciTech Connect

    Fitzpatrick, A. Liam; Kaplan, Jared; Walters, Matthew T.; Wang, Junpu

    2015-09-03

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

  13. Eikonalization of conformal blocks

    DOE PAGES

    Fitzpatrick, A. Liam; Kaplan, Jared; Walters, Matthew T.; Wang, Junpu

    2015-09-03

    Classical field configurations such as the Coulomb potential and Schwarzschild solution are built from the t-channel exchange of many light degrees of freedom. We study the CFT analog of this phenomenon, which we term the 'eikonalization' of conformal blocks. We show that when an operator T appears in the OPE Ο(x)Ο(0), then the large spin Fock space states [TT···T]ℓ also appear in this OPE with a computable coefficient. The sum over the exchange of these Fock space states in an correlator build the classical 'T field' in the dual AdS description. In some limits the sum of all Fock spacemore » exchanges can be represented as the exponential of a single T exchange in the 4-pt correlator of O. Our results should be useful for systematizing 1/ℓ perturbation theory in general CFTs and simplifying the computation of large spin OPE coefficients. As examples we obtain the leading log ℓ dependence of Fock space conformal block coefficients, and we directly compute the OPE coefficients of the simplest ‘triple-trace’ operators.« less

  14. Probing RNA Native Conformational Ensembles with Structural Constraints.

    PubMed

    Fonseca, Rasmus; van den Bedem, Henry; Bernauer, Julie

    2016-05-01

    Noncoding ribonucleic acids (RNA) play a critical role in a wide variety of cellular processes, ranging from regulating gene expression to post-translational modification and protein synthesis. Their activity is modulated by highly dynamic exchanges between three-dimensional conformational substates, which are difficult to characterize experimentally and computationally. Here, we present an innovative, entirely kinematic computational procedure to efficiently explore the native ensemble of RNA molecules. Our procedure projects degrees of freedom onto a subspace of conformation space defined by distance constraints in the tertiary structure. The dimensionality reduction enables efficient exploration of conformational space. We show that the conformational distributions obtained with our method broadly sample the conformational landscape observed in NMR experiments. Compared to normal mode analysis-based exploration, our procedure diffuses faster through the experimental ensemble while also accessing conformational substates to greater precision. Our results suggest that conformational sampling with a highly reduced but fully atomistic representation of noncoding RNA expresses key features of their dynamic nature.

  15. Probing RNA Native Conformational Ensembles with Structural Constraints.

    PubMed

    Fonseca, Rasmus; van den Bedem, Henry; Bernauer, Julie

    2016-05-01

    Noncoding ribonucleic acids (RNA) play a critical role in a wide variety of cellular processes, ranging from regulating gene expression to post-translational modification and protein synthesis. Their activity is modulated by highly dynamic exchanges between three-dimensional conformational substates, which are difficult to characterize experimentally and computationally. Here, we present an innovative, entirely kinematic computational procedure to efficiently explore the native ensemble of RNA molecules. Our procedure projects degrees of freedom onto a subspace of conformation space defined by distance constraints in the tertiary structure. The dimensionality reduction enables efficient exploration of conformational space. We show that the conformational distributions obtained with our method broadly sample the conformational landscape observed in NMR experiments. Compared to normal mode analysis-based exploration, our procedure diffuses faster through the experimental ensemble while also accessing conformational substates to greater precision. Our results suggest that conformational sampling with a highly reduced but fully atomistic representation of noncoding RNA expresses key features of their dynamic nature. PMID:27028235

  16. Plasmonic organic thin-film solar cell: light trapping by using conformal vs. non-conformal relief gratings

    NASA Astrophysics Data System (ADS)

    Keshmiri, Hamid; Dostlek, Jakub

    2015-05-01

    Theoretical study of light management in thin film organic photovoltaic cell that utilizes diffraction coupling to guided waves is presented. As a model system, a regular solar cell geometry with P3HT:PCBM active layer, transparent ITO electrode and Al backside electrode is used. The paper discusses enhancement of absorption of incident photons selectively in the active layer by the interplay of surface plasmon polariton and optical waveguide waves, the effect on the profile of their field and damping that affects the spatial distribution of dissipated light energy in the layer structure. The model shows that for optimized grating period and modulation depth the number of absorbed photons in the active layer can be increased by 24 per cent. The comparison of the geometry with conformal and non-conformally corrugated layers reveals that the conformal structure outperforms the non-conformal in the enhancing of photon absorption in the wavelength range of 350-800 nm.

  17. Recent Advances in Conformal Gravity

    NASA Astrophysics Data System (ADS)

    O'Brien, James; Chaykov, Spasen

    2016-03-01

    In recent years, significant advances have been made in alternative gravitational theories. Although MOND remains the leading candidate among the alternative models, Conformal Gravity has been studied by Mannheim and O'Brien to solve the rotation curve problem without the need for dark matter. Recently, Mannheim, O'Brien and Chaykov have begun solving other gravitational questions in Conformal Gravity. In this presentation, we highlight the new work of Conformal Gravity's application to random motions of clusters (the original Zwicky problem), gravitational bending of light, gravitational lensing and a very recent survey of dwarf galaxy rotation curves. We will show in each case that Conformal Gravity can provide an accurate explanation and prediction of the data without the need for dark matter. Coupled with the fact that Conformal Gravity is a fully re-normalizable metric theory of gravity, these results help to push Conformal Gravity onto a competitive stage against other alternative models.

  18. Development of conformal respirator monitoring technology

    SciTech Connect

    Shonka, J.J.; Weismann, J.J.; Logan, R.J.

    1997-04-01

    This report summarizes the results of a Small Business Innovative Research Phase II project to develop a modular, surface conforming respirator monitor to improve upon the manual survey techniques presently used by the nuclear industry. Research was performed with plastic scintillator and gas proportional modules in an effort to find the most conducive geometry for a surface conformal, position sensitive monitor. The respirator monitor prototype developed is a computer controlled, position-sensitive detection system employing 56 modular proportional counters mounted in molds conforming to the inner and outer surfaces of a commonly used respirator (Scott Model 801450-40). The molds are housed in separate enclosures and hinged to create a {open_quotes}waffle-iron{close_quotes} effect so that the closed monitor will simultaneously survey both surfaces of the respirator. The proportional counter prototype was also designed to incorporate Shonka Research Associates previously developed charge-division electronics. This research provided valuable experience into pixellated position sensitive detection systems. The technology developed can be adapted to other monitoring applications where there is a need for deployment of many traditional radiation detectors.

  19. Fermion-scalar conformal blocks

    DOE PAGES

    Iliesiu, Luca; Kos, Filip; Poland, David; Pufu, Silviu S.; Simmons-Duffin, David; Yacoby, Ran

    2016-04-13

    In this study, we compute the conformal blocks associated with scalar-scalar-fermionfermion 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. In addition, 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.

  20. Killing and conformal Killing tensors

    NASA Astrophysics Data System (ADS)

    Heil, Konstantin; Moroianu, Andrei; Semmelmann, Uwe

    2016-08-01

    We introduce an appropriate formalism in order to study conformal Killing (symmetric) tensors on Riemannian manifolds. We reprove in a simple way some known results in the field and obtain several new results, like the classification of conformal Killing 2-tensors on Riemannian products of compact manifolds, Weitzenböck formulas leading to non-existence results, and construct various examples of manifolds with conformal Killing tensors.

  1. Reflections on conformal spectra

    NASA Astrophysics Data System (ADS)

    Kim, Hyungrok; Kravchuk, Petr; Ooguri, Hirosi

    2016-04-01

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

  2. Capturing Chromosome Conformation

    NASA Astrophysics Data System (ADS)

    Dekker, Job; Rippe, Karsten; Dekker, Martijn; Kleckner, Nancy

    2002-02-01

    We describe an approach to detect the frequency of interaction between any two genomic loci. Generation of a matrix of interaction frequencies between sites on the same or different chromosomes reveals their relative spatial disposition and provides information about the physical properties of the chromatin fiber. This methodology can be applied to the spatial organization of entire genomes in organisms from bacteria to human. Using the yeast Saccharomyces cerevisiae, we could confirm known qualitative features of chromosome organization within the nucleus and dynamic changes in that organization during meiosis. We also analyzed yeast chromosome III at the G1 stage of the cell cycle. We found that chromatin is highly flexible throughout. Furthermore, functionally distinct AT- and GC-rich domains were found to exhibit different conformations, and a population-average 3D model of chromosome III could be determined. Chromosome III emerges as a contorted ring.

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

    PubMed

    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. PMID:23654033

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

    PubMed

    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.

  5. Conformal gravity and time

    NASA Astrophysics Data System (ADS)

    Hazboun, Jeffrey Shafiq

    2014-10-01

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

  6. Conformal Transformations and Space Travel.

    PubMed

    Gupta, S N

    1961-10-27

    Conformal transformations are applied to the motion of a space ship experiencing a constant acceleration. The role of proper time is interpreted in terms of atomic periods, and the relationship between the conformal transformations and the general theory of relativity is clarified.

  7. Counselor Identity: Conformity or Distinction?

    ERIC Educational Resources Information Center

    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.

  8. [Conformal radiotherapy: principles and classification].

    PubMed

    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.

  9. Conformal Fermi Coordinates

    SciTech Connect

    Dai, Liang; Pajer, Enrico; Schmidt, Fabian E-mail: Enrico.pajer@gmail.com

    2015-11-01

    Fermi Normal Coordinates (FNC) are a useful frame for isolating the locally observable, physical effects of a long-wavelength spacetime perturbation. Their cosmological application, however, is hampered by the fact that they are only valid on scales much smaller than the horizon. We introduce a generalization that we call Conformal Fermi Coordinates (CFC). CFC preserve all the advantages of FNC, but in addition are valid outside the horizon. They allow us to calculate the coupling of long- and short-wavelength modes on all scales larger than the sound horizon of the cosmological fluid, starting from the epoch of inflation until today, by removing the complications of the second order Einstein equations to a large extent, and eliminating all gauge ambiguities. As an application, we present a calculation of the effect of long-wavelength tensor modes on small scale density fluctuations. We recover previous results, but clarify the physical content of the individual contributions in terms of locally measurable effects and ''projection'' terms.

  10. Dynamics of protein conformations

    NASA Astrophysics Data System (ADS)

    Stepanova, Maria

    2010-10-01

    A novel theoretical methodology is introduced to identify dynamic structural domains and analyze local flexibility in proteins. The methodology employs a multiscale approach combining identification of essential collective coordinates based on the covariance analysis of molecular dynamics trajectories, construction of the Mori projection operator with these essential coordinates, and analysis of the corresponding generalized Langevin equations [M.Stepanova, Phys.Rev.E 76(2007)051918]. Because the approach employs a rigorous theory, the outcomes are physically transparent: the dynamic domains are associated with regions of relative rigidity in the protein, whereas off-domain regions are relatively soft. This also allows scoring the flexibility in the macromolecule with atomic-level resolution [N.Blinov, M.Berjanskii, D.S.Wishart, and M.Stepanova, Biochemistry, 48(2009)1488]. The applications include the domain coarse-graining and characterization of conformational stability in protein G and prion proteins. The results are compared with published NMR experiments. Potential applications for structural biology, bioinformatics, and drug design are discussed.

  11. Flexible backbone sampling methods to model and design protein alternative conformations.

    PubMed

    Ollikainen, Noah; Smith, Colin A; Fraser, James S; Kortemme, Tanja

    2013-01-01

    Sampling alternative conformations is key to understanding how proteins work and engineering them for new functions. However, accurately characterizing and modeling protein conformational ensembles remain experimentally and computationally challenging. These challenges must be met before protein conformational heterogeneity can be exploited in protein engineering and design. Here, as a stepping stone, we describe methods to detect alternative conformations in proteins and strategies to model these near-native conformational changes based on backrub-type Monte Carlo moves in Rosetta. We illustrate how Rosetta simulations that apply backrub moves improve modeling of point mutant side-chain conformations, native side-chain conformational heterogeneity, functional conformational changes, tolerated sequence space, protein interaction specificity, and amino acid covariation across protein-protein interfaces. We include relevant Rosetta command lines and RosettaScripts to encourage the application of these types of simulations to other systems. Our work highlights that critical scoring and sampling improvements will be necessary to approximate conformational landscapes. Challenges for the future development of these methods include modeling conformational changes that propagate away from designed mutation sites and modulating backbone flexibility to predictively design functionally important conformational heterogeneity.

  12. Towards conformal loop quantum gravity

    NASA Astrophysics Data System (ADS)

    H-T Wang, Charles

    2006-03-01

    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.

  13. Logarithmic conformal field theory

    NASA Astrophysics Data System (ADS)

    Gainutdinov, Azat; Ridout, David; Runkel, Ingo

    2013-12-01

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

  14. CONFORMANCE IMPROVEMENT USING GELS

    SciTech Connect

    Randall S. Seright

    2002-02-28

    This technical progress report describes work performed from June 20 through December 19, 2001, for the project, ''Conformance Improvement Using Gels''. Interest has increased in some new polymeric products that purport to substantially reduce permeability to water while causing minimum permeability reduction to oil. In view of this interest, we are currently studying BJ's Aqua Con. Results from six corefloods revealed that the Aqua Con gelant consistently reduced permeability to water more than that to oil. However, the magnitude of the disproportionate permeability reduction varied significantly for the various experiments. Thus, as with most materials tested to date, the issue of reproducibility and control of the disproportionate permeability remains to be resolved. Concern exists about the ability of gels to resist washout after placement in fractures. We examined whether a width constriction in the middle of a fracture would cause different gel washout behavior upstream versus downstream of the constriction. Tests were performed using a formed Cr(III)-acetate-HPAM gel in a 48-in.-long fracture with three sections of equal length, but with widths of 0.08-, 0.02-, and 0.08-in., respectively. The pressure gradients during gel extrusion (i.e., placement) were similar in the two 0.08-in.-wide fracture sections, even though they were separated by a 0.02-in.-wide fracture section. The constriction associated with the middle fracture section may have inhibited gel washout during the first pulse of brine injection after gel placement. However, during subsequent phases of brine injection, the constriction did not inhibit washout in the upstream fracture section any more than in the downstream section.

  15. Conformational Landscape of Nicotinoids: Solving the "conformational - Rity" of Anabasine

    NASA Astrophysics Data System (ADS)

    Lesarri, Alberto; Cocinero, Emilio J.; Evangelisti, Luca; Suenram, Richard D.; Caminati, Walther; Grabow, Jens-Uwe

    2010-06-01

    The conformational landscape of the alkaloid anabasine (neonicotine) has been investigated using rotational spectroscopy and ab initio calculations. The results allow a detailed comparison of the structural properties of the prototype piperidinic and pyrrolidinic nicotinoids (anabasine vs. nicotine). Anabasine adopts two most stable conformations in isolation conditions, for which we determined accurate rotational and nuclear quadrupole coupling parameters. The preferred conformations are characterized by an equatorial pyridine moiety and additional N-H equatorial stereochemistry at the piperidine ring (Eq-Eq). The two rings of anabasine are close to a bisecting arrangement, with the observed conformations differing in a ca. 180° rotation of the pyridine subunit, denoted either Syn or Anti. The preference of anabasine for the Eq-Eq-Syn conformation has been established by relative intensity measurements (Syn/Anti˜5(2)). The conformational preferences of free anabasine are directed by a N\\cdot\\cdot\\cdotH-C weak hydrogen bond interaction between the nitrogen lone pair at piperidine and the closest hydrogen bond in pyridine, with N\\cdot\\cdot\\cdotN distances ranging from 4.750 Å (Syn) to 4.233 Å (Anti). R. J. Lavrich, R. D. Suenram, D. F. Plusquellic and S. Davis, 58^th OSU Int. Symp. on Mol. Spectrosc., Columbus, OH, 2003, Comm. RH13.

  16. Ligand-driven conformational changes of MurD visualized by paramagnetic NMR

    PubMed Central

    Saio, Tomohide; Ogura, Kenji; Kumeta, Hiroyuki; Kobashigawa, Yoshihiro; Shimizu, Kazumi; Yokochi, Masashi; Kodama, Kota; Yamaguchi, Hiroto; Tsujishita, Hideki; Inagaki, Fuyuhiko

    2015-01-01

    Proteins, especially multi-domain proteins, often undergo drastic conformational changes upon binding to ligands or by post-translational modifications, which is a key step to regulate their function. However, the detailed mechanisms of such dynamic regulation of the functional processes are poorly understood because of the lack of an efficient tool. We here demonstrate detailed characterization of conformational changes of MurD, a 47 kDa protein enzyme consisting of three domains, by the use of solution NMR equipped with paramagnetic lanthanide probe. Quantitative analysis of pseudocontact shifts has identified a novel conformational state of MurD, named semi-closed conformation, which is found to be the key to understand how MurD regulates the binding of the ligands. The modulation of the affinity coupled with conformational changes accentuates the importance of conformational state to be evaluated in drug design. PMID:26582338

  17. CONFORMANCE IMPROVEMENT USING GELS

    SciTech Connect

    Randall S. Seright

    2004-09-30

    This report describes work performed during the third and final year of the project, ''Conformance Improvement Using Gels.'' Corefloods revealed throughput dependencies of permeability reduction by polymers and gels that were much more prolonged during oil flow than water flow. This behavior was explained using simple mobility ratio arguments. A model was developed that quantitatively fits the results and predicts ''clean up'' times for oil productivity when production wells are returned to service after application of a polymer or gel treatment. X-ray computed microtomography studies of gels in strongly water-wet Berea sandstone and strongly oil-wet porous polyethylene suggested that oil penetration through gel-filled pores occurs by a gel-dehydration mechanism, rather than gel-ripping or gel-displacement mechanisms. In contrast, analysis of data from the University of Kansas suggests that the gel-ripping or displacement mechanisms are more important in more permeable, strongly water-wet sandpacks. These findings help to explain why aqueous gels can reduce permeability to water more than to oil under different conditions. Since cement is the most commonly used material for water shutoff, we considered when gels are preferred over cements. Our analysis and experimental results indicated that cement cannot be expected to completely fill (top to bottom) a vertical fracture of any width, except near the wellbore. For vertical fractures with apertures less than 4 mm, the cement slurry will simply not penetrate very far into the fracture. For vertical fractures with apertures greater than 4 mm, the slurry may penetrate a substantial distance into the bottom part of the fracture. However, except near the wellbore, the upper part of the fracture will remain open due to gravity segregation. We compared various approaches to plugging fractures using gels, including (1) varying polymer content, (2) varying placement (extrusion) rate, (3) using partially formed gels, (4

  18. CONFORMANCE IMPROVEMENT USING GELS

    SciTech Connect

    Randall S. Seright

    2004-03-01

    This technical progress report describes work performed from September 1, 2003, through February 29, 2004, for the project, ''Conformance Improvement Using Gels.'' We examined the properties of several ''partially formed'' gels that were formulated with a combination of high and low molecular weight HPAM polymers. After placement in 4-mm-wide fractures, these gels required about 25 psi/ft for brine to breach the gel (the best performance to date in fractures this wide). After this breach, stabilized residual resistance factors decreased significantly with increased flow rate. Also, residual resistance factors were up to 9 times greater for water than for oil. Nevertheless, permeability reduction factors were substantial for both water and oil flow. Gel with 2.5% chopped fiberglass effectively plugged 4-mm-wide fractures if a 0.5-mm-wide constriction was present. The ability to screen-out at a constriction appears crucial for particulate incorporation to be useful in plugging fractures. In addition to fiberglass, we examined incorporation of polypropylene fibers into gels. Once dispersed in brine or gelant, the polypropylene fibers exhibited the least gravity segregation of any particulate that we have tested to date. In fractures with widths of at least 2 mm, 24-hr-old gels (0.5% high molecular weight HPAM) with 0.5% fiber did not exhibit progressive plugging during placement and showed extrusion pressure gradients similar to those of gels without the fiber. The presence of the fiber roughly doubled the gel's resistance to first breach by brine flow. The breaching pressure gradients were not as large as for gels made with high and low molecular weight polymers (mentioned above). However, their material requirements and costs (i.e., polymer and/or particulate concentrations) were substantially lower than for those gels. A partially formed gel made with 0.5% HPAM did not enter a 0.052-mm-wide fracture when applying a pressure gradient of 65 psi/ft. This result

  19. Radial coordinates for conformal blocks

    NASA Astrophysics Data System (ADS)

    Hogervorst, Matthijs; Rychkov, Slava

    2013-05-01

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

  20. Conformal mapping of rectangular heptagons

    SciTech Connect

    Bogatyrev, Andrei B

    2012-12-31

    A new effective approach to calculating the direct and inverse conformal mapping of rectangular polygons onto a half-plane is put forward; it is based on the use of Riemann theta functions. Bibliography: 14 titles.

  1. Lattice Simulations and Infrared Conformality

    DOE PAGES

    Appelquist, Thomas; Fleming, George T.; Lin, Meifeng; Neil, Ethan T.; Schaich, David A

    2011-09-01

    We examine several recent lattice-simulation data sets, asking whether they are consistent with infrared conformality. We observe, in particular, that for an SU(3) gauge theory with 12 Dirac fermions in the fundamental representation, recent simulation data can be described assuming infrared conformality. Lattice simulations include a fermion mass m which is then extrapolated to zero, and we note that this data can be fit by a small-m expansion, allowing a controlled extrapolation. We also note that the conformal hypothesis does not work well for two theories that are known or expected to be confining and chirally broken, and that itmore » does work well for another theory expected to be infrared conformal.« less

  2. Solution NMR conformation of glycosaminoglycans.

    PubMed

    Pomin, Vitor H

    2014-04-01

    Nuclear magnetic resonance (NMR) spectroscopy has been giving a pivotal contribution to the progress of glycomics, mostly by elucidating the structural, dynamical, conformational and intermolecular binding aspects of carbohydrates. Particularly in the field of conformation, NOE resonances, scalar couplings, residual dipolar couplings, and chemical shift anisotropy offsets have been the principal NMR parameters utilized. Molecular dynamics calculations restrained by NMR-data input are usually employed in conjunction to generate glycosidic bond dihedral angles. Glycosaminoglycans (GAGs) are a special class of sulfated polysaccharides extensively studied worldwide. Besides regulating innumerous physiological processes, these glycans are also widely explored in the global market as either clinical or nutraceutical agents. The conformational aspects of GAGs are key regulators to the quality of interactions with the functional proteins involved in biological events. This report discusses the solution conformation of each GAG type analyzed by one or more of the above-mentioned methods.

  3. Scale invariance vs conformal invariance

    NASA Astrophysics Data System (ADS)

    Nakayama, Yu

    2015-03-01

    In this review article, we discuss the distinction and possible equivalence between scale invariance and conformal invariance in relativistic quantum field theories. Under some technical assumptions, we can prove that scale invariant quantum field theories in d = 2 space-time dimensions necessarily possess the enhanced conformal symmetry. The use of the conformal symmetry is well appreciated in the literature, but the fact that all the scale invariant phenomena in d = 2 space-time dimensions enjoy the conformal property relies on the deep structure of the renormalization group. The outstanding question is whether this feature is specific to d = 2 space-time dimensions or it holds in higher dimensions, too. As of January 2014, our consensus is that there is no known example of scale invariant but non-conformal field theories in d = 4 space-time dimensions under the assumptions of (1) unitarity, (2) Poincaré invariance (causality), (3) discrete spectrum in scaling dimensions, (4) existence of scale current and (5) unbroken scale invariance in the vacuum. We have a perturbative proof of the enhancement of conformal invariance from scale invariance based on the higher dimensional analogue of Zamolodchikov's c-theorem, but the non-perturbative proof is yet to come. As a reference we have tried to collect as many interesting examples of scale invariance in relativistic quantum field theories as possible in this article. We give a complementary holographic argument based on the energy-condition of the gravitational system and the space-time diffeomorphism in order to support the claim of the symmetry enhancement. We believe that the possible enhancement of conformal invariance from scale invariance reveals the sublime nature of the renormalization group and space-time with holography. This review is based on a lecture note on scale invariance vs conformal invariance, on which the author gave lectures at Taiwan Central University for the 5th Taiwan School on Strings and

  4. Takiff superalgebras and conformal field theory

    NASA Astrophysics Data System (ADS)

    Babichenko, Andrei; Ridout, David

    2013-03-01

    A class of non-semisimple extensions of Lie superalgebras is studied. They are obtained by adjoining to the superalgebra its adjoint representation as an Abelian ideal. When the superalgebra is of affine Kac-Moody type, a generalization of Sugawara’s construction is shown to give rise to a copy of the Virasoro algebra and so, presumably, to a conformal field theory. Evidence for this is detailed for the extension of the affinization of the superalgebra \\mathfrak {gl} ( 1 \\vert 1): its highest weight irreducible modules are classified using spectral flow, the irreducible supercharacters are computed and a continuum version of the Verlinde formula is verified to give non-negative integer structure coefficients. Interpreting these coefficients as those of the Grothendieck ring of fusion, partial results on the true fusion ring and its indecomposable structures are deduced.

  5. CONFORMANCE IMPROVEMENT USING GELS

    SciTech Connect

    Randall S. Seright

    2003-09-01

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

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

    PubMed

    Yu, Rongjun; Sun, Sai

    2013-01-01

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

  7. Microwave Spectroscopy of Alkaloids: the Conformational Shapes of Nicotine

    NASA Astrophysics Data System (ADS)

    Grabow, Jens-Uwe; Mata, S.; López, J. C.; Peńa, I.; Cabezas, C.; Blanco, S.; Alonso, J. L.

    2010-06-01

    Nicotinoid alkaloids consist of two ring systems connected via a C-C σ-bond: Joining pyridine either with a (substituted) pyrrolidine or piperidine ring system, pyrrolidinic or piperidinic nicotinoids are formed. Nicotine itself, consisting of pyridine and N-methylpyrrolidine, is the prototype pyrrolidinic nicotinoid. Its coupled heteoaromatic and heteroaliphatic ring systems exhibit three sites that allow for conformational flexibility: (I) puckering of the pyrrolidine ring (Eq./Ax. positions of the pyridine), (II) inversion of the N-methyl group (Eq./Ax. positions of the hydrogen), and (III) relative orientation of the two rings (Syn-Anti). Two conformations of nicotine have been observed using the In-phase/quadrature-phase-Modulation Passage-Acquired-Coherence Technique (IMPACT) Fourier Transform Microwave (FTMW) spectrometer in Valladolid. The preferred conformations are characterized by an equatorial (Eq.) pyridine moiety and equatorial (Eq.) N-CH_3 stereochemistry. The planes of two rings are almost perpendicular with respect to each other while exhibiting two low energy conformations, Syn and Anti, that differ by a 180° rotation about the C-C σ-bond. The Eq.-Eq. conformational preference is likely due to a weak hydrogen bond interaction between the nitrogen lone pair at the N-methylpyrroline and the closest hydrogen in pyridine. Supporting quantum-chemical calculations are also provided. Lavrich, R. J.; Suenram, R. D.; Plusquellic, D. F.; Davis, S. 58th International Symposium on Molecular Spectroscopy, Columbus, OH 2003, RH13.

  8. Solvation energetics and conformational change in EF-hand proteins.

    PubMed

    Ababou, A; Desjarlais, J R

    2001-02-01

    Calmodulin and other members of the EF-hand protein family are known to undergo major changes in conformation upon binding Ca(2+). However, some EF-hand proteins, such as calbindin D9k, bind Ca(2+) without a significant change in conformation. Here, we show the importance of a precise balance of solvation energetics to conformational change, using mutational analysis of partially buried polar groups in the N-terminal domain of calmodulin (N-cam). Several variants were characterized using fluorescence, circular dichroism, and NMR spectroscopy. Strikingly, the replacement of polar side chains glutamine and lysine at positions 41 and 75 with nonpolar side chains leads to dramatic enhancement of the stability of the Ca(2+)-free state, a corresponding decrease in Ca(2+)-binding affinity, and an apparent loss of ability to change conformation to the open form. The results suggest a paradigm for conformational change in which energetic strain is accumulated in one state in order to modulate the energetics of change to the alternative state. PMID:11266616

  9. HAMP domain conformers that propagate opposite signals in bacterial chemoreceptors.

    PubMed

    Airola, Michael V; Sukomon, Nattakan; Samanta, Dipanjan; Borbat, Peter P; Freed, Jack H; Watts, Kylie J; Crane, Brian R

    2013-01-01

    HAMP domains are signal relay modules in >26,000 receptors of bacteria, eukaryotes, and archaea that mediate processes involved in chemotaxis, pathogenesis, and biofilm formation. We identify two HAMP conformations distinguished by a four- to two-helix packing transition at the C-termini that send opposing signals in bacterial chemoreceptors. Crystal structures of signal-locked mutants establish the observed structure-to-function relationships. Pulsed dipolar electron spin resonance spectroscopy of spin-labeled soluble receptors active in cells verify that the crystallographically defined HAMP conformers are maintained in the receptors and influence the structure and activity of downstream domains accordingly. Mutation of HR2, a key residue for setting the HAMP conformation and generating an inhibitory signal, shifts HAMP structure and receptor output to an activating state. Another HR2 variant displays an inverted response with respect to ligand and demonstrates the fine energetic balance between "on" and "off" conformers. A DExG motif found in membrane proximal HAMP domains is shown to be critical for responses to extracellular ligand. Our findings directly correlate in vivo signaling with HAMP structure, stability, and dynamics to establish a comprehensive model for HAMP-mediated signal relay that consolidates existing views on how conformational signals propagate in receptors. Moreover, we have developed a rational means to manipulate HAMP structure and function that may prove useful in the engineering of bacterial taxis responses.

  10. Pyranopterin conformation defines the function of molybdenum and tungsten enzymes.

    PubMed

    Rothery, Richard A; Stein, Benjamin; Solomonson, Matthew; Kirk, Martin L; Weiner, Joel H

    2012-09-11

    We have analyzed the conformations of 319 pyranopterins in 102 protein structures of mononuclear molybdenum and tungsten enzymes. These span a continuum between geometries anticipated for quinonoid dihydro, tetrahydro, and dihydro oxidation states. We demonstrate that pyranopterin conformation is correlated with the protein folds defining the three major mononuclear molybdenum and tungsten enzyme families, and that binding-site micro-tuning controls pyranopterin oxidation state. Enzymes belonging to the bacterial dimethyl sulfoxide reductase (DMSOR) family contain a metal-bis-pyranopterin cofactor, the two pyranopterins of which have distinct conformations, with one similar to the predicted tetrahydro form, and the other similar to the predicted dihydro form. Enzymes containing a single pyranopterin belong to either the xanthine dehydrogenase (XDH) or sulfite oxidase (SUOX) families, and these have pyranopterin conformations similar to those predicted for tetrahydro and dihydro forms, respectively. This work provides keen insight into the roles of pyranopterin conformation and oxidation state in catalysis, redox potential modulation of the metal site, and catalytic function.

  11. Imagerie médicale avec des sources X créées parlaser

    NASA Astrophysics Data System (ADS)

    Dorchies, F.; Chen, L. M.; Ichalalene, Z.; Jiang, Z.; Kieffer, J. C.; Chamberlain, C. C.; Krol, A.

    2003-06-01

    L'interaction d'une impulsion laser femtoseconde avec une cible solide peut induire une émission intense de rayonnement X dans la gamme de quelques dizaines de keV. Ce type de source présente potentiellement plusieurs avantages sur les installations X conventionnelles en termes de performances (taille de la source, ganinie de longueur d'onde accessible) et de coût. Ce papier réunit les différents résultats obtenus dans le cadre du projet d'imagerie médicale de I'INRS à Varennes, Québec, Canada. Ces travaux concernent d'une part l'étude quantitative de la source de rayons X-durs: intensité, spectre et taille de la source. D'autre part. des expériences de faisabilité ont montré la pertinence de leur application à l'imagerie médicale. notamment dans le domaine de l'imagerie à grande résolution spatiale (mammographie) et dans celui de l'imagerie par soustraction d'images A deux longueurs d'onde (angiographie cardiaque). La principale limitation de ces expériences était la puissance moyenne de la source bridée par la faible cadence de l'installation laser. Les lois d'échelle déduites des expériences présentées laissent présager la poursuite de ces travaux dans des conditions cliniques réalistes avec le développement actuel de chaîne laser de hautes cadences (100Hz 1kHz).

  12. 40 CFR 93.154 - Conformity analysis.

    Code of Federal Regulations, 2010 CFR

    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...

  13. Universality class in conformal inflation

    SciTech Connect

    Kallosh, Renata; Linde, Andrei E-mail: alinde@stanford.edu

    2013-07-01

    We develop a new class of chaotic inflation models with spontaneously broken conformal invariance. Observational consequences of a broad class of such models are stable with respect to strong deformations of the scalar potential. This universality is a critical phenomenon near the point of enhanced symmetry, SO(1,1), in case of conformal inflation. It appears because of the exponential stretching of the moduli space and the resulting exponential flattening of scalar potentials upon switching from the Jordan frame to the Einstein frame in this class of models. This result resembles stretching and flattening of inhomogeneities during inflationary expansion. It has a simple interpretation in terms of velocity versus rapidity near the Kähler cone in the moduli space, similar to the light cone of special theory of relativity. This effect makes inflation possible even in the models with very steep potentials. We describe conformal and superconformal versions of this cosmological attractor mechanism.

  14. Cyclic AMP Analog Blocks Kinase Activation by Stabilizing Inactive Conformation: Conformational Selection Highlights a New Concept in Allosteric Inhibitor Design*

    PubMed Central

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

    2011-01-01

    The regulatory (R) subunit of protein kinase A serves to modulate the activity of protein kinase A in a cAMP-dependent manner and exists in two distinct and structurally dissimilar, end point cAMP-bound “B” and C-subunit-bound “H”-conformations. Here we report mechanistic details of cAMP action as yet unknown through a unique approach combining x-ray crystallography with structural proteomics approaches, amide hydrogen/deuterium exchange and ion mobility mass spectrometry, applied to the study of a stereospecific cAMP phosphorothioate analog and antagonist((Rp)-cAMPS). X-ray crystallography shows cAMP-bound R-subunit in the B form but surprisingly the antagonist Rp-cAMPS-bound R-subunit crystallized in the H conformation, which was previously assumed to be induced only by C-subunit-binding. Apo R-subunit crystallized in the B form as well but amide exchange mass spectrometry showed large differences between apo, agonist and antagonist-bound states of the R-subunit. Further ion mobility reveals the apo R-subunit as an ensemble of multiple conformations with collisional cross-sectional areas spanning both the agonist and antagonist-bound states. Thus contrary to earlier studies that explained the basis for cAMP action through “induced fit” alone, we report evidence for conformational selection, where the ligand-free apo form of the R-subunit exists as an ensemble of both B and H conformations. Although cAMP preferentially binds the B conformation, Rp-cAMPS interestingly binds the H conformation. This reveals the unique importance of the equatorial oxygen of the cyclic phosphate in mediating conformational transitions from H to B forms highlighting a novel approach for rational structure-based drug design. Ideal inhibitors such as Rp-cAMPS are those that preferentially “select” inactive conformations of target proteins by satisfying all “binding” constraints alone without inducing conformational changes necessary for activation. PMID:21081668

  15. Conformation-sensitive capillary electrophoresis.

    PubMed

    Ashton, Emma Jane

    2011-01-01

    Conformation-sensitive capillary electrophoresis (CSCE) is a rapid, high-throughput screening method that can be applied to any region of a genome for detection of sequence variants. Slab gel-based conformation-sensitive gel electrophoresis was first described by Ganguly et al., and the transfer from slab gels to capillaries for higher throughput was reported by Rozycka et al. CSCE is based on the principle that DNA homoduplexes and heteroduplexes migrate at different rates during electrophoresis under mildly denaturing conditions. Fragments showing an altered peak morphology compared to the wild type are then sequenced to determine the precise nature of the sequence variant detected.

  16. Dynamic Conformational Changes in MUNC18 Prevent Syntaxin Binding

    PubMed Central

    Bar-On, Dana; Nachliel, Esther; Gutman, Menachem; Ashery, Uri

    2011-01-01

    The Sec1/munc18 protein family is essential for vesicle fusion in eukaryotic cells via binding to SNARE proteins. Protein kinase C modulates these interactions by phosphorylating munc18a thereby reducing its affinity to one of the central SNARE members, syntaxin-1a. The established hypothesis is that the reduced affinity of the phosphorylated munc18a to syntaxin-1a is a result of local electrostatic repulsion between the two proteins, which interferes with their compatibility. The current study challenges this paradigm and offers a novel mechanistic explanation by revealing a syntaxin-non-binding conformation of munc18a that is induced by the phosphomimetic mutations. In the present study, using molecular dynamics simulations, we explored the dynamics of the wild-type munc18a versus phosphomimetic mutant munc18a. We focused on the structural changes that occur in the cavity between domains 3a and 1, which serves as the main syntaxin-binding site. The results of the simulations suggest that the free wild-type munc18a exhibits a dynamic equilibrium between several conformations differing in the size of its cavity (the main syntaxin-binding site). The flexibility of the cavity's size might facilitate the binding or unbinding of syntaxin. In silico insertion of phosphomimetic mutations into the munc18a structure induces the formation of a conformation where the syntaxin-binding area is rigid and blocked as a result of interactions between residues located on both sides of the cavity. Therefore, we suggest that the reduced affinity of the phosphomimetic mutant/phosphorylated munc18a is a result of the closed-cavity conformation, which makes syntaxin binding energetically and sterically unfavorable. The current study demonstrates the potential of phosphoryalation, an essential biological process, to serve as a driving force for dramatic conformational changes of proteins modulating their affinity to target proteins. PMID:21390273

  17. Dynamic conformational changes in munc18 prevent syntaxin binding.

    PubMed

    Bar-On, Dana; Nachliel, Esther; Gutman, Menachem; Ashery, Uri

    2011-03-01

    The Sec1/munc18 protein family is essential for vesicle fusion in eukaryotic cells via binding to SNARE proteins. Protein kinase C modulates these interactions by phosphorylating munc18a thereby reducing its affinity to one of the central SNARE members, syntaxin-1a. The established hypothesis is that the reduced affinity of the phosphorylated munc18a to syntaxin-1a is a result of local electrostatic repulsion between the two proteins, which interferes with their compatibility. The current study challenges this paradigm and offers a novel mechanistic explanation by revealing a syntaxin-non-binding conformation of munc18a that is induced by the phosphomimetic mutations. In the present study, using molecular dynamics simulations, we explored the dynamics of the wild-type munc18a versus phosphomimetic mutant munc18a. We focused on the structural changes that occur in the cavity between domains 3a and 1, which serves as the main syntaxin-binding site. The results of the simulations suggest that the free wild-type munc18a exhibits a dynamic equilibrium between several conformations differing in the size of its cavity (the main syntaxin-binding site). The flexibility of the cavity's size might facilitate the binding or unbinding of syntaxin. In silico insertion of phosphomimetic mutations into the munc18a structure induces the formation of a conformation where the syntaxin-binding area is rigid and blocked as a result of interactions between residues located on both sides of the cavity. Therefore, we suggest that the reduced affinity of the phosphomimetic mutant/phosphorylated munc18a is a result of the closed-cavity conformation, which makes syntaxin binding energetically and sterically unfavorable. The current study demonstrates the potential of phosphorylation, an essential biological process, to serve as a driving force for dramatic conformational changes of proteins modulating their affinity to target proteins. PMID:21390273

  18. Temperature: Human Regulating, Ants Conforming

    ERIC Educational Resources Information Center

    Clopton, Joe R.

    2007-01-01

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

  19. Conformal coating using parylene polymers.

    PubMed

    Noordegraaf, J

    1997-01-01

    Parylene, a conformal polymer film, is being used increasingly in Europe to provide environmental and dielectric isolation. Application areas include electronic circuitry, sensors, and medical substrates. This article describes the variants of parylene and their characteristics, together with the process and applications of parylene coating. PMID:10167681

  20. The conformational analysis of 2-halocyclooctanones.

    PubMed

    Rozada, Thiago C; Gauze, Gisele F; Rosa, Fernanda A; Favaro, Denize C; Rittner, Roberto; Pontes, Rodrigo M; Basso, Ernani A

    2015-02-25

    The establishment of the most stable structures of eight membered rings is a challenging task to the field of conformational analysis. In this work, a series of 2-halocyclooctanones were synthesized (including fluorine, chlorine, bromine and iodine derivatives) and submitted to conformational studies using a combination of theoretical calculation and infrared spectroscopy. For each compound, four conformations were identified as the most important ones. These conformations are derived from the chair-boat conformation of cyclooctanone. The pseudo-equatorial (with respect to the halogen) conformer is preferred in vacuum and in low polarity solvents for chlorine, bromine and iodine derivatives. For 2-fluorocyclooctanone, the preferred conformation in vacuum is pseudo-axial. In acetonitrile, the pseudo-axial conformer becomes the most stable for the chlorine derivative. According to NBO calculations, the conformational preference is not dictated by electron delocalization, but by classical electrostatic repulsions.

  1. Conformational studies of nucleic acids

    SciTech Connect

    Pearlman, D.A.

    1984-11-01

    Techniques are developed for thorough examinations of the conformational energetics of nucleic acids and their constituents. The first one is a method for modeling the furanose sugar ring in nucleic acids. This method allows the coordinates corresponding to any sugar conformation to be generated rapidly and unambiguously from just the phase angle of pseudorotation. Taking advantage of this simplification, we carry out the first calculations to completely explore the conformational spaces available to the eight commonly occurring nucleosides using experimentally consistent furanose geometries and an appropriate classical potential energy force field. Results are in excellent agreement with experiment. We also develop empirically fit multiple correlation functions between the torsion angles of nucleic acids. This reduces the number of conformations which need to be considered in a thorough energetic survey for a nucleic acid. Such surveys are then carried out for two single-stranded nucleic acid tetramers: d(ApApApA) and ApApApA. We create energy contour maps for each of the 21 possible torsion angle pairs in a nucleotide repeating unit. The maps are quite consistent with the experimental distribution of oligonucleotide data and provide rationalizations for several experimentally observed angle-angle correlations. Complete energy minimization is carried out on all local minima found in the surveys. Both the maps and minimizations indicate DNA and RNA to be highly polymorphic. Conformational changes in DNA upon damage by uv radiation are also studied using energy minimization techniques. Finally, we derive a set of partial charges for a nucleotide (2'-deoxycytidine 5'-monophosphate monohydrate) from high resolution x-ray data.

  2. Conformal consistency relations for single-field inflation

    SciTech Connect

    Creminelli, Paolo; Noreña, Jorge; Simonović, Marko E-mail: jorge.norena@gmail.com

    2012-07-01

    We generalize the single-field consistency relations to capture not only the leading term in the squeezed limit — going as 1/q{sup 3}, where q is the small wavevector — but also the subleading one, going as 1/q{sup 2}. This term, for an (n+1)-point function, is fixed in terms of the variation of the n-point function under a special conformal transformation; this parallels the fact that the 1/q{sup 3} term is related with the scale dependence of the n-point function. For the squeezed limit of the 3-point function, this conformal consistency relation implies that there are no terms going as 1/q{sup 2}. We verify that the squeezed limit of the 4-point function is related to the conformal variation of the 3-point function both in the case of canonical slow-roll inflation and in models with reduced speed of sound. In the second case the conformal consistency conditions capture, at the level of observables, the relation among operators induced by the non-linear realization of Lorentz invariance in the Lagrangian. These results mean that, in any single-field model, primordial correlation functions of ζ are endowed with an SO(4,1) symmetry, with dilations and special conformal transformations non-linearly realized by ζ. We also verify the conformal consistency relations for any n-point function in models with a modulation of the inflaton potential, where the scale dependence is not negligible. Finally, we generalize (some of) the consistency relations involving tensors and soft internal momenta.

  3. Shear-induced conformation change in α-crystalline nylon6

    SciTech Connect

    Arabnejad, Saeid; Manzhos, Sergei; Shim, V. P. W.; He, Chaobin

    2014-12-01

    A study of shear deformation of α-crystalline nylon6 is undertaken, using dispersion-corrected density functional theory. The shear stress-strain relationship and shear strength for interlayer shear deformation are computed. A conformation change induced by shear is identified along twinning deformation, whereby the conformation of chains, specifically the location of non-H-bonded hydrogen atoms, changes continuously. This paves a way for the modulation of properties of this group of materials by small shear deformation, if the non-H-bonded hydrogens are chemically substituted to form non-equivalent conformations when deformed.

  4. Fake conformal symmetry in unimodular gravity

    NASA Astrophysics Data System (ADS)

    Oda, Ichiro

    2016-08-01

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

  5. Calibration of Two Difrerent Types of Modulators for an Application in Spectroscopic Phase Modulated Ellipsometry

    NASA Astrophysics Data System (ADS)

    Kouko, S. L.; Llinares, C.

    1995-08-01

    In order to choose a photoelastic modulator for an application in spectroscopic phase modulated ellipsometry a complete calibration of two different types of photoelastic modulators is achieved. First the model that describes the behavior of each of them is accurately determined since the calibration procedure depends on it. Both modulators behave as a static strain model with a phase shift of the form δ = δ_0 + {\\cal A}sin ω t. Using the suitable procedures, the driving voltage V_mod and the static strain δ_0 of both devices are accurately determined as a function of the wavelength from 0.25 μm to 0.75 μm. A method to reduce the errors due to incorrect settings of the modulation voltage and the static birefringence is also proposed. An accuracy check of the calibration done by comparing the indexes of refraction of two silica prisms obtained with our ellipsometer and with the high precision goniometer method shows a very good agreement. Dans le but de choisir un modulateur photoélastique pour une application en ellipsométrie spectroscopique à modulation de phase, le calibrage de deux modulateurs a été réalisé. Dans un premier temps, le modèle décrivant chacun des modulateurs a été déterminé avec précision vu que la procédure de calibrage dépend de celui-ci : les deux modulateurs fonctionnent suivant le modèle avec biréfringence statique ayant un déphasage de la forme δ = δ_0 + {\\cal A}sin ω t. En utilisant les procédures de calibrage appropriées, la tension de pilotage V_mod et la biréfringence statique δ_0 ont été déterminées avec précision en fonction de la longueur d'onde dans la gamme spectrale s'étendant de 0,25 μm à 0,75 μm. Une méthode pour réduire les erreurs dues au calibrage de la tension de modulation et à la biréfringence résiduelle est également proposée. Un test de la précision du calibrage fait en comparant les indices de réfraction de deux prismes de silice obtenus avec notre ellipsomètre et avec

  6. Clinical Applications of 3-D Conformal Radiotherapy

    NASA Astrophysics Data System (ADS)

    Miralbell, Raymond

    Although a significant improvement in cancer cure (i.e. 20% increment) has been obtained in the last 2-3 decades, 30-40% of patients still fail locally after curative radiotherapy. In order to improve local tumor control rates with radiotherapy high doses to the tumor volume are frequently necessary. Three-dimensional conformal radiation therapy (3-D CRT) is used to denote a spectrum of radiation planning and delivery techniques that rely on three-dimensional imaging to define the target (tumor) and to distinguish it from normal tissues. Modern, high-precision radiotherapy (RT) techniques are needed in order to implement the goal of optimal tumor destruction delivering minimal dose to the non-target normal tissues. A better target definition is nowadays possible with contemporary imaging (computerized tomography, magnetic resonance imaging, and positron emission tomography) and image registration technology. A highly precise dose distributions can be obtained with optimal 3-D CRT treatment delivery techniques such as stereotactic RT, intensity modulated RT (IMRT), or protontherapy (the latter allowing for in-depth conformation). Patient daily set-up repositioning and internal organ immobilization systems are necessary before considering to undertake any of the above mentioned high-precision treatment approaches. Prostate cancer, brain tumors, and base of skull malignancies are among the sites most benefitting of dose escalation approaches. Nevertheless, a significant dose reduction to the normal tissues in the vicinity of the irradiated tumor also achievable with optimal 3-D CRT may also be a major issue in the treatment of pediatric tumors in order to preserve growth, normal development, and to reduce the risk of developing radiation induced diseases such as cancer or endocrinologic disorders.

  7. On staggered indecomposable Virasoro modules

    NASA Astrophysics Data System (ADS)

    Kytölä, Kalle; Ridout, David

    2009-12-01

    In this article, certain indecomposable Virasoro modules are studied. Specifically, the Virasoro mode L0 is assumed to be nondiagonalizable, possessing Jordan blocks of rank 2. Moreover, the module is further assumed to have a highest weight submodule, the "left module," and that the quotient by this submodule yields another highest weight module, the "right module." Such modules, which have been called staggered, have appeared repeatedly in the logarithmic conformal field theory literature, but their theory has not been explored in full generality. Here, such a theory is developed for the Virasoro algebra using rather elementary techniques. The focus centers on two different but related questions typically encountered in practical studies: How can one identify a given staggered module, and how can one demonstrate the existence of a proposed staggered module. Given just the values of the highest weights of the left and right modules, themselves subject to simple necessary conditions, invariants are defined which together with the knowledge of the left and right modules uniquely identify a staggered module. The possible values of these invariants form a vector space of dimension 0, 1, or 2, and the structures of the left and right modules limit the isomorphism classes of the corresponding staggered modules to an affine subspace (possibly empty). The number of invariants and affine restrictions is purely determined by the structures of the left and right modules. Moreover, in order to facilitate applications, the expressions for the invariants and restrictions are given by formulas as explicit as possible (they generally rely on expressions for Virasoro singular vectors). Finally, the text is liberally peppered throughout with examples illustrating the general concepts. These have been carefully chosen for their physical relevance or for the novel features they exhibit.

  8. Conformal Gravity rotation curves with a conformal Higgs halo

    NASA Astrophysics Data System (ADS)

    Horne, Keith

    2016-06-01

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

  9. Conformal Window and Correlation Functions in Lattice Conformal QCD

    NASA Astrophysics Data System (ADS)

    Iwasaki, Y.

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

  10. Association de neuroleptiques atypiques avec les anticonvulsivants et syndrome malin (à propos de deux cas)

    PubMed Central

    Nabih, Fadoua Oueriagli; Benali, Abdeslam; adali, Imane; Manoudi, Fatiha; Asri, Fatima

    2014-01-01

    Le syndrome malin des neuroleptiques (SMN) est une complication rare mais grave du traitement par les neuroleptiques, pouvant engager le pronostic vital. Les auteurs rapportent deux observations, la première d'une jeune patiente de 18 ans, suivie pour une épilepsie partielle temporale, sous carbamazépine (800mg/jour) depuis 13 ans, et qui a développé un SMN après introduction d'amisulpride (600 mg/jour). La deuxième observation d'un jeune patient de 28 ans sous valproate sodium (750mg/jour) depuis 10 ans et qui a présenté un SMN après association d'olanzapine (20mg/jour). Les cliniciens doivent être vigilants par rapport au risque d'induction d'un SMN après introduction de neuroleptiques atypiques chez des patients traités pendant une longue durée avec des anticonvulsivants. PMID:25422695

  11. Conformal triality of the Kepler problem

    NASA Astrophysics Data System (ADS)

    Cariglia, Marco

    2016-08-01

    We show that the Kepler problem is projectively equivalent to null geodesic motion on the conformal compactification of Minkowski-4 space. This space realises the conformal triality of Minkowski, dS and AdS spaces.

  12. Gauge natural formulation of conformal gravity

    SciTech Connect

    Campigotto, M.; Fatibene, L.

    2015-03-15

    We consider conformal gravity as a gauge natural theory. We study its conservation laws and superpotentials. We also consider the Mannheim and Kazanas spherically symmetric vacuum solution and discuss conserved quantities associated to conformal and diffeomorphism symmetries.

  13. Killing Initial Data on spacelike conformal boundaries

    NASA Astrophysics Data System (ADS)

    Paetz, Tim-Torben

    2016-08-01

    We analyze Killing Initial Data on Cauchy surfaces in conformally rescaled vacuum space-times satisfying Friedrich's conformal field equations. As an application, we derive the KID equations on a spacelike ℐ-.

  14. The Conformational Behaviour of Glucosamine

    NASA Astrophysics Data System (ADS)

    Peña, Isabel; Kolesniková, Lucie; Cabezas, Carlos; Bermúdez, Celina; Berdakin, Matías; Simao, Alcides; Alonso, José L.

    2014-06-01

    A laser ablation method has been successfully used to vaporize the bioactive amino monosaccharide D-glucosamine. Three cyclic α-4C1 pyranose forms have been identified using a combination of CP-FTMW and LA-MB-FTMW spectroscopy. Stereoelectronic hyperconjugative factors, like those associated with anomeric or gauche effects, as well as the cooperative OH\\cdotsO, OH\\cdotsN and NH\\cdotsO chains, extended along the entire molecule, are the main factors driving the conformational behavior. All observed conformers exhibit a counter-clockwise arrangement (cc) of the network of intramolecular hydrogen bonds. The results are compared with those recently obtained for D-glucose. J. L. Alonso, M. A. Lozoya, I. Peña, J. C. López, C. Cabezas, S. Mata, S. Blanco, Chem. Sci. 2014, 5, 515.

  15. The conformational cycle of kinesin.

    PubMed Central

    Cross, R A; Crevel, I; Carter, N J; Alonso, M C; Hirose, K; Amos, L A

    2000-01-01

    The stepping mechanism of kinesin can be thought of as a programme of conformational changes. We briefly review protein chemical, electron microscopic and transient kinetic evidence for conformational changes, and working from this evidence, outline a model for the mechanism. In the model, both kinesin heads initially trap Mg x ADP. Microtubule binding releases ADP from one head only (the trailing head). Subsequent ATP binding and hydrolysis by the trailing head progressively accelerate attachment of the leading head, by positioning it closer to its next site. Once attached, the leading head releases its ADP and exerts a sustained pull on the trailing head. The rate of closure of the molecular gate which traps ADP on the trailing head governs its detachment rate. A speculative but crucial coordinating feature is that this rate is strain sensitive, slowing down under negative strain and accelerating under positive strain. PMID:10836499

  16. Elements optiques diffractifs concus avec des ouvertures trapezoidales et polygonales et de nouveaux algorithmes d'optimisation

    NASA Astrophysics Data System (ADS)

    Gillet, Jean-Numa

    Nous avons realise de nouveaux encodages et algorithmes d'optimisation destines aux elements optiques diffractis et hologrammes generes par ordinateur (HGO). Un algorithme novateur de condensation rapide simulee iterative permet la resolution de problemes avec plusieurs milliers de variables. Malgre un horaire de refroidissement rapide, de nombreuses solutions sous-optimales sont evitees par des reechelonnements de temperature ramenant le systeme a l'equilibre thermodynamique. L'etat final atteint par le nouvel algorithme a une energie beaucoup plus basse que celle obtenue par d'autres algorithmes. Les generateurs de tableaux irreguliers de points lumineux concus avec la condensation rapide simulee iterative et des ouvertures trapezoidales de hauteurs variables presentent de meilleures performances et beaucoup moins d'ouvertures comparativement a ceux concus avec d'autres methodes. Nous avons aussi realise un HGO multiplexe de taille extremement grande forme d'ouvertures polygonales et le nouvel algorithme iteratif de conception des sous-hologrammes pour generer des images de tres grandes dimensions. Nous utilisons la transformee d'Abbe pour calculer la diffraction des ouvertures polygonales, ce qui permet d'accelerer substantiellement le calcul de la transformee de Fourier de l'hologramme total. La taille en pixels de l'HGO multiplexe forme d'ouvertures polygonales est plus de mille fois superieure a celle d'un HGO conventionnel et sa fenetre objet beaucoup plus grande. L'HGO multiplexe forme d'ouvertures polygonales presente des performances beaucoup plus elevees que celles d'HGO conventionnels ou multiplexes concus avec les methodes precedentes.

  17. Holographic multiverse and conformal invariance

    SciTech Connect

    Garriga, Jaume; Vilenkin, Alexander E-mail: vilenkin@cosmos.phy.tufts.edu

    2009-11-01

    We consider a holographic description of the inflationary multiverse, according to which the wave function of the universe is interpreted as the generating functional for a lower dimensional Euclidean theory. We analyze a simple model where transitions between inflationary vacua occur through bubble nucleation, and the inflating part of spacetime consists of de Sitter regions separated by thin bubble walls. In this model, we present some evidence that the dual theory is conformally invariant in the UV.

  18. Anomalous dimensions of conformal baryons

    NASA Astrophysics Data System (ADS)

    Pica, Claudio; Sannino, Francesco

    2016-10-01

    We determine the anomalous dimensions of baryon operators for the three-color theory as functions of the number of massless flavors within the conformal window to the maximum known order in perturbation theory. We show that the anomalous dimension of the baryon is controllably small, within the δ expansion, for a wide range of number of flavors. We also find that this is always smaller than the anomalous dimension of the fermion mass operator. These findings challenge the partial compositeness paradigm.

  19. Stabilizing the boat conformation of cyclohexane rings

    SciTech Connect

    Dasgupta, S.; Goddard, W.A. III; Moldowan, J.M.; Carlson, R.M.K.; Goddard, W.A. III.

    1995-06-21

    In calculating the energetics for various conformers of the A, B, and C series of hopanoid hydrocarbons present in mature oil reservoirs, we find that the B series prefers the boat conformation (by 1.3-2.5 kcal/mol) for the D cyclohexane ring. We analyze the structural elements responsible for stabilizing this boat conformation, identify the key features, and illustrate how one might stabilize boat conformations of other systems. 5 refs., 3 figs., 2 tabs.

  20. Anomalies, conformal manifolds, and spheres

    NASA Astrophysics Data System (ADS)

    Gomis, Jaume; Hsin, Po-Shen; Komargodski, Zohar; Schwimmer, Adam; Seiberg, Nathan; Theisen, Stefan

    2016-03-01

    The two-point function of exactly marginal operators leads to a universal contribution to the trace anomaly in even dimensions. We study aspects of this trace anomaly, emphasizing its interpretation as a sigma model, whose target space {M} is the space of conformal field theories (a.k.a. the conformal manifold). When the underlying quantum field theory is supersymmetric, this sigma model has to be appropriately supersymmetrized. As examples, we consider in some detail {N}=(2,2) and {N}=(0,2) supersymmetric theories in d = 2 and {N}=2 supersymmetric theories in d = 4. This reasoning leads to new information about the conformal manifolds of these theories, for example, we show that the manifold is Kähler-Hodge and we further argue that it has vanishing Kähler class. For {N}=(2,2) theories in d = 2 and {N}=2 theories in d = 4 we also show that the relation between the sphere partition function and the Kähler potential of {M} follows immediately from the appropriate sigma models that we construct. Along the way we find several examples of potential trace anomalies that obey the Wess-Zumino consistency conditions, but can be ruled out by a more detailed analysis.

  1. Conformal Invariance of Graphene Sheets.

    PubMed

    Giordanelli, I; Posé, N; Mendoza, M; Herrmann, H J

    2016-03-10

    Suspended graphene sheets exhibit correlated random deformations that can be studied under the framework of rough surfaces with a Hurst (roughness) exponent 0.72 ± 0.01. Here, we show that, independent of the temperature, the iso-height lines at the percolation threshold have a well-defined fractal dimension and are conformally invariant, sharing the same statistical properties as Schramm-Loewner evolution (SLEκ) curves with κ = 2.24 ± 0.07. Interestingly, iso-height lines of other rough surfaces are not necessarily conformally invariant even if they have the same Hurst exponent, e.g. random Gaussian surfaces. We have found that the distribution of the modulus of the Fourier coefficients plays an important role on this property. Our results not only introduce a new universality class and place the study of suspended graphene membranes within the theory of critical phenomena, but also provide hints on the long-standing question about the origin of conformal invariance in iso-height lines of rough surfaces.

  2. Limit cycles and conformal invariance

    NASA Astrophysics Data System (ADS)

    Fortin, Jean-François; Grinstein, Benjamín; Stergiou, Andreas

    2013-01-01

    There is a widely held belief that conformal field theories (CFTs) require zero beta functions. Nevertheless, the work of Jack and Osborn implies that the beta functions are not actually the quantites that decide conformality, but until recently no such behavior had been exhibited. Our recent work has led to the discovery of CFTs with nonzero beta functions, more precisely CFTs that live on recurrent trajectories, e.g., limit cycles, of the beta-function vector field. To demonstrate this we study the S function of Jack and Osborn. We use Weyl consistency conditions to show that it vanishes at fixed points and agrees with the generator Q of limit cycles on them. Moreover, we compute S to third order in perturbation theory, and explicitly verify that it agrees with our previous determinations of Q. A byproduct of our analysis is that, in perturbation theory, unitarity and scale invariance imply conformal invariance in four-dimensional quantum field theories. Finally, we study some properties of these new, "cyclic" CFTs, and point out that the a-theorem still governs the asymptotic behavior of renormalization-group flows.

  3. The Conformational Landscape of Serinol

    NASA Astrophysics Data System (ADS)

    Sanz, M. Eugenia; Loru, Donatella; Peña, Isabel; Alonso, José L.

    2014-06-01

    The rotational spectrum of the amino alcohol serinol CH_2OH--CH(NH_2)--CH_2OH, which constitutes the hydrophilic head of the lipid sphingosine, has been investigated using chirped-pulsed Fourier transform microwave spectroscopy in combination with laser ablation Five different forms of serinol have been observed and conclusively identified by the comparison between the experimental values of their rotational and 14N quadrupole coupling constants and those predicted by ab initio calculations. In all observed conformers several hydrogen bonds are established between the two hydroxyl groups and the amino groups in a chain or circular arrangement. The most abundant conformer is stabilised by O--H···N and N--H···O hydrogen bonds forming a chain rather than a cycle. One of the detected conformers presents a tunnelling motion of the hydrogen atoms of the functional groups similar to that observed in glycerol. S. Mata, I. Peña, C. Cabezas, J. C. López, J. L. Alonso, J. Mol. Spectrosc. 2012, 280, 91 V. V. Ilyushin, R. A. Motiyenko, F. J. Lovas, D. F. Plusquellic, J. Mol. Spectrosc. 2008, 251, 129.

  4. Anomalies, conformal manifolds, and spheres

    DOE PAGES

    Gomis, Jaume; Hsin, Po-Shen; Komargodski, Zohar; Schwimmer, Adam; Seiberg, Nathan; Theisen, Stefan

    2016-03-04

    The two-point function of exactly marginal operators leads to a universal contribution to the trace anomaly in even dimensions. We study aspects of this trace anomaly, emphasizing its interpretation as a sigma model, whose target space $M$ is the space of conformal field theories (a.k.a. the conformal manifold). When the underlying quantum field theory is supersymmetric, this sigma model has to be appropriately supersymmetrized. As examples, we consider in some detail $N$ = (2; 2) and $N$ = (0; 2) supersymmetric theories in d = 2 and $N$ = 2 supersymmetric theories in d = 4. This reasoning leads tomore » new information about the conformal manifolds of these theories, for example, we show that the manifold is K ahler-Hodge and we further argue that it has vanishing K ahler class. For $N$ = (2; 2) theories in d = 2 and N = 2 theories in d = 4 we also show that the relation between the sphere partition function and the K ahler potential of $M$ follows immediately from the appropriate sigma models that we construct. Ultimately, along the way we find several examples of potential trace anomalies that obey the Wess-Zumino consistency conditions, but can be ruled out by a more detailed analysis.« less

  5. Electrophysiological precursors of social conformity.

    PubMed

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

    2013-10-01

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

  6. Conformal Invariance of Graphene Sheets

    PubMed Central

    Giordanelli, I.; Posé, N.; Mendoza, M.; Herrmann, H. J.

    2016-01-01

    Suspended graphene sheets exhibit correlated random deformations that can be studied under the framework of rough surfaces with a Hurst (roughness) exponent 0.72 ± 0.01. Here, we show that, independent of the temperature, the iso-height lines at the percolation threshold have a well-defined fractal dimension and are conformally invariant, sharing the same statistical properties as Schramm-Loewner evolution (SLEκ) curves with κ = 2.24 ± 0.07. Interestingly, iso-height lines of other rough surfaces are not necessarily conformally invariant even if they have the same Hurst exponent, e.g. random Gaussian surfaces. We have found that the distribution of the modulus of the Fourier coefficients plays an important role on this property. Our results not only introduce a new universality class and place the study of suspended graphene membranes within the theory of critical phenomena, but also provide hints on the long-standing question about the origin of conformal invariance in iso-height lines of rough surfaces. PMID:26961723

  7. Electrophysiological precursors of social conformity.

    PubMed

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

    2013-10-01

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

  8. Flexible ligand docking using conformational ensembles.

    PubMed Central

    Lorber, D. M.; Shoichet, B. K.

    1998-01-01

    Molecular docking algorithms suggest possible structures for molecular complexes. They are used to model biological function and to discover potential ligands. A present challenge for docking algorithms is the treatment of molecular flexibility. Here, the rigid body program, DOCK, is modified to allow it to rapidly fit multiple conformations of ligands. Conformations of a given molecule are pre-calculated in the same frame of reference, so that each conformer shares a common rigid fragment with all other conformations. The ligand conformers are then docked together, as an ensemble, into a receptor binding site. This takes advantage of the redundancy present in differing conformers of the same molecule. The algorithm was tested using three organic ligand protein systems and two protein-protein systems. Both the bound and unbound conformations of the receptors were used. The ligand ensemble method found conformations that resembled those determined in X-ray crystal structures (RMS values typically less than 1.5 A). To test the method's usefulness for inhibitor discovery, multi-compound and multi-conformer databases were screened for compounds known to bind to dihydrofolate reductase and compounds known to bind to thymidylate synthase. In both cases, known inhibitors and substrates were identified in conformations resembling those observed experimentally. The ligand ensemble method was 100-fold faster than docking a single conformation at a time and was able to screen a database of over 34 million conformations from 117,000 molecules in one to four CPU days on a workstation. PMID:9568900

  9. 40 CFR 52.799 - Transportation conformity.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 3 2014-07-01 2014-07-01 false Transportation conformity. 52.799... (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS Indiana § 52.799 Transportation conformity. On June 4, 2010, Indiana submitted the Transportation Conformity Consultation SIP consisting...

  10. 40 CFR 52.799 - Transportation conformity.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 3 2012-07-01 2012-07-01 false Transportation conformity. 52.799... (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS Indiana § 52.799 Transportation conformity. On June 4, 2010, Indiana submitted the Transportation Conformity Consultation SIP consisting...

  11. 40 CFR 52.799 - Transportation conformity.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 3 2013-07-01 2013-07-01 false Transportation conformity. 52.799... (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS Indiana § 52.799 Transportation conformity. On June 4, 2010, Indiana submitted the Transportation Conformity Consultation SIP consisting...

  12. 40 CFR 52.799 - Transportation conformity.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 3 2011-07-01 2011-07-01 false Transportation conformity. 52.799... (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS Indiana § 52.799 Transportation conformity. On June 4, 2010, Indiana submitted the Transportation Conformity Consultation SIP consisting...

  13. 40 CFR 51.854 - Conformity analysis.

    Code of Federal Regulations, 2010 CFR

    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...

  14. Conformational Switching in the Fungal Light Sensor Vivid

    SciTech Connect

    Zoltowski,B.; Schwerdtgeger, C.; Widom, J.; Loros, J.; Bilwes, A.; Dunlap, J.; Crane, B.

    2007-01-01

    The Neurospora crassa photoreceptor Vivid tunes blue-light responses and modulates gating of the circadian clock. Crystal structures of dark-state and light-state Vivid reveal a light, oxygen, or voltage Per-Arnt-Sim domain with an unusual N-terminal cap region and a loop insertion that accommodates the flavin cofactor. Photoinduced formation of a cystein-flavin adduct drives flavin protonation to induce an N-terminal conformational change. A cysteine-to-serine substitution remote from the flavin adenine dinucleotide binding site decouples conformational switching from the flavin photocycle and prevents Vivid from sending signals in Neurospora. Key elements of this activation mechanism are conserved by other photosensors such as White Collar-1, ZEITLUPE, ENVOY, and flavin-binding, kelch repeat, F-BOX 1 (FKF1).

  15. On probing conformation of microtubules by second-harmonic generation

    NASA Astrophysics Data System (ADS)

    Sharoukhov, Denis; Lim, Hyungsik

    2016-01-01

    Microtubule (MT) is a component of cytoskeleton playing an important role in a variety of cellular processes. Altering the structure of MT is a crucial mechanism of modulating the function, but it is difficult to measure the in vivo conformation. We present here the use of second-harmonic generation (SHG) for acquiring information about the architecture of MTs in living tissue. Axonal MTs were imaged by polarization-resolved SHG and anisotropy in the molecular structure was determined by means of the second-order tensor analysis. The feasibility of the second-order tensor analysis was tested for measuring the conformational changes induced by MT-stabilizing drug. It demonstrates that the new optical contrast may be useful for investigating the dynamics of MT cytoskeleton in vivo.

  16. Conformational dynamics of amyloid proteins at the aqueous interface

    NASA Astrophysics Data System (ADS)

    Armbruster, Matthew; Horst, Nathan; Aoki, Brendy; Malik, Saad; Soto, Patricia

    2013-03-01

    Amyloid proteins is a class of proteins that exhibit distinct monomeric and oligomeric conformational states hallmark of deleterious neurological diseases for which there are not yet cures. Our goal is to examine the extent of which the aqueous/membrane interface modulates the folding energy landscape of amyloid proteins. To this end, we probe the dynamic conformational ensemble of amyloids (monomer prion protein and Alzheimer's Ab protofilaments) interacting with model bilayers. We will present the results of our coarse grain molecular modeling study in terms of the existence of preferential binding spots of the amyloid to the bilayer and the response of the bilayer to the interaction with the amyloid. NSF Nebraska EPSCoR First Award

  17. Understanding the sequence determinants of conformational switching using protein design.

    PubMed Central

    Dalal, S.; Regan, L.

    2000-01-01

    An important goal of protein design is to understand the forces that stabilize a particular fold in preference to alternative folds. Here, we describe an extension of earlier studies in which we successfully designed a stable, native-like helical protein that is 50% identical in sequence to a predominantly beta-sheet protein, the B1 domain of Streptococcal IgG-binding protein G. We report the characteristics of a series of variants of our original design that have even higher sequence identity to the B1 domain. Their properties illustrate the extent to which protein stability and conformation can be modulated through careful manipulation of key amino acid residues. Our results have implications for understanding conformational change phenomena of central biological importance and in probing the malleability of the sequence/structure relationship. PMID:11045612

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

    PubMed

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

    2016-07-27

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

  19. Probing the conformation of the fibronectin III1-2 domain by fluorescence resonance energy transfer.

    PubMed

    Karuri, Nancy W; Lin, Zong; Rye, Hays S; Schwarzbauer, Jean E

    2009-02-01

    Fibronectin (FN) matrix is crucial for cell and tissue functions during embryonic development, wound healing, and oncogenesis. Assembly of FN matrix fibrils requires FN domains that mediate interactions with integrin receptors and with other FN molecules. In addition, regulation of FN matrix assembly depends on the first two FN type III modules, III(1) and III(2), which harbor FN-binding sites. We propose that interactions between these two modules sequester FN-binding sites in soluble FN and that these sites become exposed by FN conformational changes during assembly. To test the idea that III(1-2) has a compact conformation, we constructed CIIIY, a conformational sensor of III(1-2) based on fluorescent resonance energy transfer between cyan and yellow fluorescent proteins conjugated at its N and C termini. We demonstrate energy transfer in CIIIY and show that fluorescent resonance energy transfer was eliminated by proteolysis and by treatment with mild denaturants that disrupted intramolecular interactions between the two modules. We also show that mutations of key charged residues resulted in conformational changes that exposed binding sites for the N-terminal 70-kDa FN fragment. Collectively, these results support a conformation-dependent mechanism for the regulation of FN matrix assembly by III(1-2).

  20. Conformance Testing: Measurement Decision Rules

    NASA Technical Reports Server (NTRS)

    Mimbs, Scott M.

    2010-01-01

    The goal of a Quality Management System (QMS) as specified in ISO 9001 and AS9100 is to provide assurance to the customer that end products meet specifications. Measuring devices, often called measuring and test equipment (MTE), are used to provide the evidence of product conformity to specified requirements. Unfortunately, processes that employ MTE can become a weak link to the overall QMS if proper attention is not given to the measurement process design, capability, and implementation. Documented "decision rules" establish the requirements to ensure measurement processes provide the measurement data that supports the needs of the QMS. Measurement data are used to make the decisions that impact all areas of technology. Whether measurements support research, design, production, or maintenance, ensuring the data supports the decision is crucial. Measurement data quality can be critical to the resulting consequences of measurement-based decisions. Historically, most industries required simplistic, one-size-fits-all decision rules for measurements. One-size-fits-all rules in some cases are not rigorous enough to provide adequate measurement results, while in other cases are overly conservative and too costly to implement. Ideally, decision rules should be rigorous enough to match the criticality of the parameter being measured, while being flexible enough to be cost effective. The goal of a decision rule is to ensure that measurement processes provide data with a sufficient level of quality to support the decisions being made - no more, no less. This paper discusses the basic concepts of providing measurement-based evidence that end products meet specifications. Although relevant to all measurement-based conformance tests, the target audience is the MTE end-user, which is anyone using MTE other than calibration service providers. Topics include measurement fundamentals, the associated decision risks, verifying conformance to specifications, and basic measurement

  1. The Biological Bases of Conformity

    PubMed Central

    Morgan, T. J. H.; Laland, K. N.

    2012-01-01

    Humans are characterized by an extreme dependence on culturally transmitted information and recent formal theory predicts that natural selection should favor adaptive learning strategies that facilitate effective copying and decision making. One strategy that has attracted particular attention is conformist transmission, defined as the disproportionately likely adoption of the most common variant. Conformity has historically been emphasized as significant in the social psychology literature, and recently there have also been reports of conformist behavior in non-human animals. However, mathematical analyses differ in how important and widespread they expect conformity to be, and relevant experimental work is scarce, and generates findings that are both mutually contradictory and inconsistent with the predictions of the models. We review the relevant literature considering the causation, function, history, and ontogeny of conformity, and describe a computer-based experiment on human subjects that we carried out in order to resolve ambiguities. We found that only when many demonstrators were available and subjects were uncertain was subject behavior conformist. A further analysis found that the underlying response to social information alone was generally conformist. Thus, our data are consistent with a conformist use of social information, but as subjects’ behavior is the result of both social and asocial influences, the resultant behavior may not be conformist. We end by relating these findings to an embryonic cognitive neuroscience literature that has recently begun to explore the neural bases of social learning. Here conformist transmission may be a particularly useful case study, not only because there are well-defined and tractable opportunities to characterize the biological underpinnings of this form of social learning, but also because early findings imply that humans may possess specific cognitive adaptations for effective social learning. PMID:22712006

  2. Conformance Verification of Privacy Policies

    NASA Astrophysics Data System (ADS)

    Fu, Xiang

    Web applications are both the consumers and providers of information. To increase customer confidence, many websites choose to publish their privacy protection policies. However, policy conformance is often neglected. We propose a logic based framework for formally specifying and reasoning about the implementation of privacy protection by a web application. A first order extension of computation tree logic is used to specify a policy. A verification paradigm, built upon a static control/data flow analysis, is presented to verify if a policy is satisfied.

  3. Chromosome Conformation Capture in Drosophila.

    PubMed

    Li, Hua-Bing

    2016-01-01

    Linear chromatin fiber is packed inside the nuclei as a complex three-dimensional structure, and the organization of the chromatin has important roles in the appropriate spatial and temporal regulation of gene expression. To understand how chromatin organizes inside nuclei, and how regulatory proteins physically interact with genes, chromosome conformation capture (3C) technique provides a powerful and sensitive tool to detect both short- and long-range DNA-DNA interaction. Here I describe the 3C technique to detect the DNA-DNA interactions mediated by insulator proteins that are closely related to PcG in Drosophila, which is also broadly applicable to other systems. PMID:27659987

  4. Conformational Transitions in Molecular Systems

    NASA Astrophysics Data System (ADS)

    Bachmann, M.; Janke, W.

    2008-11-01

    Proteins are the "work horses" in biological systems. In almost all functions specific proteins are involved. They control molecular transport processes, stabilize the cell structure, enzymatically catalyze chemical reactions; others act as molecular motors in the complex machinery of molecular synthetization processes. Due to their significance, misfolds and malfunctions of proteins typically entail disastrous diseases, such as Alzheimer's disease and bovine spongiform encephalopathy (BSE). Therefore, the understanding of the trinity of amino acid composition, geometric structure, and biological function is one of the most essential challenges for the natural sciences. Here, we glance at conformational transitions accompanying the structure formation in protein folding processes.

  5. Toward TeV Conformality

    SciTech Connect

    Appelquist, T; Avakian, A; Babich, R; Brower, R C; Cheng, M; Clark, M A; Cohen, S D; Fleming, G T; Kiskis, J; Neil, E T; Osborn, J C; Rebbi, C; Schaich, D; Soltz, R; Vranas, P

    2009-11-30

    We study the chiral condensate <{bar {psi}}{psi}> for an SU(3) gauge theory with N{sub f} massless Dirac fermions in the fundamental representation when N{sub f} is increased from 2 to 6. For N{sub f} = 2, our lattice simulations of <{bar {psi}}{psi}>/F{sup 3}, where F is the Nambu-Goldstone-boson decay constant, agree with the measured QCD value. For N{sub f} = 6, this ratio shows significant enhancement, presaging an even larger enhancement anticipated as N{sub f} increases further, toward the critical value for transition from confinement to infrared conformality.

  6. Ion Mobility Mass Spectrometry of a Rotary ATPase Reveals ATP-induced Reduction in Conformational Flexibility

    PubMed Central

    Davies, Roberta; Liko, Idlir; Wu, Kuan-Jung; Stewart, Alastair G.; Stock, Daniela; Robinson, Carol V.

    2014-01-01

    Rotary ATPases play fundamental roles in energy conversion, their catalytic rotation being associated with inter-domain fluctuations and heterogeneity of conformational states. Using ion mobility mass spectrometry (IM-MS) we compare the conformational dynamics of the intact ATPase from Thermus thermophilus (TtATPase) with its membrane and soluble subcomplexes. Our results define regions with enhanced flexibility assigned to distinct subunits within the overall assembly. To provide a structural context for our experimental data we performed molecular dynamics (MD) simulations and observed conformational changes of the peripheral stalks reflecting their intrinsic flexibility. By isolating complexes at different phases of cell growth and manipulating nucleotides, metal ions and pH during isolation, we reveal differences that can be related to conformational changes in the Vo complex, triggered by ATP binding. Together these results implicate nucleotides in modulating flexibility of the stator components and uncover mechanistic detail underlying operation and regulation in the context of the holo-enzyme. PMID:24557135

  7. Conformational gating of DNA conductance

    PubMed Central

    Artés, Juan Manuel; Li, Yuanhui; Qi, Jianqing; Anantram, M. P.; Hihath, Joshua

    2015-01-01

    DNA is a promising molecule for applications in molecular electronics because of its unique electronic and self-assembly properties. Here we report that the conductance of DNA duplexes increases by approximately one order of magnitude when its conformation is changed from the B-form to the A-form. This large conductance increase is fully reversible, and by controlling the chemical environment, the conductance can be repeatedly switched between the two values. The conductance of the two conformations displays weak length dependencies, as is expected for guanine-rich sequences, and can be fit with a coherence-corrected hopping model. These results are supported by ab initio electronic structure calculations that indicate that the highest occupied molecular orbital is more disperse in the A-form DNA case. These results demonstrate that DNA can behave as a promising molecular switch for molecular electronics applications and also provide additional insights into the huge dispersion of DNA conductance values found in the literature. PMID:26648400

  8. Metrics with Galilean conformal isometry

    SciTech Connect

    Bagchi, Arjun; Kundu, Arnab

    2011-03-15

    The Galilean conformal algebra (GCA) arises in taking the nonrelativistic limit of the symmetries of a relativistic conformal field theory in any dimensions. It is known to be infinite dimensional in all spacetime dimensions. In particular, the 2d GCA emerges out of a scaling limit of linear combinations of two copies of the Virasoro algebra. In this paper, we find metrics in dimensions greater than 2 which realize the finite 2d GCA (the global part of the infinite algebra) as their isometry by systematically looking at a construction in terms of cosets of this finite algebra. We list all possible subalgebras consistent with some physical considerations motivated by earlier work in this direction and construct all possible higher-dimensional nondegenerate metrics. We briefly study the properties of the metrics obtained. In the standard one higher-dimensional ''holographic'' setting, we find that the only nondegenerate metric is Minkowskian. In four and five dimensions, we find families of nontrivial metrics with a rather exotic signature. A curious feature of these metrics is that all but one of them are Ricci-scalar flat.

  9. Charged gravastars admitting conformal motion

    NASA Astrophysics Data System (ADS)

    Usmani, A. A.; Rahaman, F.; Ray, Saibal; Nandi, K. K.; Kuhfittig, Peter K. F.; Rakib, Sk. A.; Hasan, Z.

    2011-07-01

    We propose a new model of a gravastar admitting conformal motion. While retaining the framework of the Mazur-Mottola model, the gravastar is assumed to be internally charged, with an exterior defined by a Reissner-Nordström instead of a Schwarzschild line element. The solutions, obtained by exploiting an assumed conformal Killing vector, involve (i) the interior region, (ii) the shell, and (iii) the exterior region of the sphere. Of these three cases the first one is of primary interest since the total gravitational mass here turns out to be an electromagnetic mass under some specific conditions. This suggests that the interior de Sitter vacuum of a charged gravastar is essentially an electromagnetic mass model that must generate gravitational mass which provides a stable configuration by balancing the repulsive pressure arising from charge with its attractive gravity to avert a singularity. Therefore the present model, like the Mazur-Mottola model, results in the construction of a compact astrophysical object, as an alternative to a black hole. We have also analyzed various other aspects such as the stress energy tensor in the thin shell and the entropy of the system.

  10. Conformational gating of DNA conductance.

    PubMed

    Artés, Juan Manuel; Li, Yuanhui; Qi, Jianqing; Anantram, M P; Hihath, Joshua

    2015-01-01

    DNA is a promising molecule for applications in molecular electronics because of its unique electronic and self-assembly properties. Here we report that the conductance of DNA duplexes increases by approximately one order of magnitude when its conformation is changed from the B-form to the A-form. This large conductance increase is fully reversible, and by controlling the chemical environment, the conductance can be repeatedly switched between the two values. The conductance of the two conformations displays weak length dependencies, as is expected for guanine-rich sequences, and can be fit with a coherence-corrected hopping model. These results are supported by ab initio electronic structure calculations that indicate that the highest occupied molecular orbital is more disperse in the A-form DNA case. These results demonstrate that DNA can behave as a promising molecular switch for molecular electronics applications and also provide additional insights into the huge dispersion of DNA conductance values found in the literature. PMID:26648400

  11. Quantifying macromolecular conformational transition pathways

    NASA Astrophysics Data System (ADS)

    Seyler, Sean; Kumar, Avishek; Thorpe, Michael; Beckstein, Oliver

    2015-03-01

    Diverse classes of proteins function through large-scale conformational changes that are challenging for computer simulations. A range of fast path-sampling techniques have been used to generate transitions, but it has been difficult to compare paths from (and assess the relative strengths of) different methods. We introduce a comprehensive method (pathway similarity analysis, PSA) for quantitatively characterizing and comparing macromolecular pathways. The Hausdorff and Fréchet metrics (known from computational geometry) are used to quantify the degree of similarity between polygonal curves in configuration space. A strength of PSA is its use of the full information available from the 3 N-dimensional configuration space trajectory without requiring additional specific knowledge about the system. We compare a sample of eleven different methods for the closed-to-open transitions of the apo enzyme adenylate kinase (AdK) and also apply PSA to an ensemble of 400 AdK trajectories produced by dynamic importance sampling MD and the Geometrical Pathways algorithm. We discuss the method's potential to enhance our understanding of transition path sampling methods, validate them, and help guide future research toward deeper physical insights into conformational transitions.

  12. Conformal inflation coupled to matter

    SciTech Connect

    Brax, Philippe

    2014-05-01

    We formulate new conformal models of inflation and dark energy which generalise the Higgs-Dilaton scenario. We embed these models in unimodular gravity whose effect is to break scale invariance in the late time Universe. In the early Universe, inflation occurs close to a maximum of both the scalar potential and the scalar coupling to the Ricci scalar in the Jordan frame. At late times, the dilaton, which decouples from the dynamics during inflation, receives a potential term from unimodular gravity and leads to the acceleration of the Universe. We address two central issues in this scenario. First we show that the Damour-Polyalov mechanism, when non-relativistic matter is present prior to the start of inflation, sets the initial conditions for inflation at the maximum of the scalar potential. We then show that conformal invariance implies that matter particles are not coupled to the dilaton in the late Universe at the classical level. When fermions acquire masses at low energy, scale invariance is broken and quantum corrections induce a coupling between the dilaton and matter which is still small enough to evade the gravitational constraints in the solar system.

  13. Modeling conformational changes in cyclosporin A.

    PubMed Central

    O'Donohue, M. F.; Burgess, A. W.; Walkinshaw, M. D.; Treutlein, H. R.

    1995-01-01

    NMR and X-ray structures for the immunosuppressant cyclosporin A (CsA) reveal a remarkable difference between the unbound (free) conformation in organic solvents and the conformation bound to cyclophilin. We have performed computer simulations of the molecular dynamics of CsA under a variety of conditions and confirmed the stability of these two conformations at room temperature in water and in vacuum. However, when the free conformation was modeled in vacuum at 600 K, a transition pathway leading to the bound conformation was observed. This involved a change in the cis MeLeu-9 peptide bond to a trans conformation and the movement of the side chains forming the dominant hydrophobic cluster (residues MeBmt-1, MeLeu-4, MeLeu-6, and MeLeu-10) to the opposite side of the plane formed by the backbone atoms in the molecular ring. The final conformation had a backbone RMS deviation from the bound conformation of 0.53 A and was as stable in dynamics simulations as the bound conformation. Our calculations allowed us to make a detailed analysis of a transition pathway between the free and the bound conformations of CsA and to identify two distinct regions of coordinated movement in CsA, both of which underwent transitions independently. PMID:8535256

  14. A quantitative measure for protein conformational heterogeneity

    PubMed Central

    Lyle, Nicholas; Das, Rahul K.; Pappu, Rohit V.

    2013-01-01

    Conformational heterogeneity is a defining characteristic of proteins. Intrinsically disordered proteins (IDPs) and denatured state ensembles are extreme manifestations of this heterogeneity. Inferences regarding globule versus coil formation can be drawn from analysis of polymeric properties such as average size, shape, and density fluctuations. Here we introduce a new parameter to quantify the degree of conformational heterogeneity within an ensemble to complement polymeric descriptors. The design of this parameter is guided by the need to distinguish between systems that couple their unfolding-folding transitions with coil-to-globule transitions and those systems that undergo coil-to-globule transitions with no evidence of acquiring a homogeneous ensemble of conformations upon collapse. The approach is as follows: Each conformation in an ensemble is converted into a conformational vector where the elements are inter-residue distances. Similarity between pairs of conformations is quantified using the projection between the corresponding conformational vectors. An ensemble of conformations yields a distribution of pairwise projections, which is converted into a distribution of pairwise conformational dissimilarities. The first moment of this dissimilarity distribution is normalized against the first moment of the distribution obtained by comparing conformations from the ensemble of interest to conformations drawn from a Flory random coil model. The latter sets an upper bound on conformational heterogeneity thus ensuring that the proposed measure for intra-ensemble heterogeneity is properly calibrated and can be used to compare ensembles for different sequences and across different temperatures. The new measure of conformational heterogeneity will be useful in quantitative studies of coupled folding and binding of IDPs and in de novo sequence design efforts that are geared toward controlling the degree of heterogeneity in unbound forms of IDPs. PMID:24089719

  15. Module Configuration

    DOEpatents

    Oweis, Salah; D'Ussel, Louis; Chagnon, Guy; Zuhowski, Michael; Sack, Tim; Laucournet, Gaullume; Jackson, Edward J.

    2002-06-04

    A stand alone battery module including: (a) a mechanical configuration; (b) a thermal management configuration; (c) an electrical connection configuration; and (d) an electronics configuration. Such a module is fully interchangeable in a battery pack assembly, mechanically, from the thermal management point of view, and electrically. With the same hardware, the module can accommodate different cell sizes and, therefore, can easily have different capacities. The module structure is designed to accommodate the electronics monitoring, protection, and printed wiring assembly boards (PWAs), as well as to allow airflow through the module. A plurality of modules may easily be connected together to form a battery pack. The parts of the module are designed to facilitate their manufacture and assembly.

  16. DEFECT ASSESSMENT USING CONFORMABLE ARRAY DATA

    SciTech Connect

    Alfred E. Crouch

    2003-07-01

    The conformable array data acquisition system consists of the array, the data acquisition and analysis hardware, and the data acquisition and analysis software. The following decisions were made in the development of the system. Array design decisions include the following: (a) The flexible array board will be approximately 8 by 12 inches square with the active coil section confined to a smaller 6-inch-square section at the center of the board. The outer edges of the board will be used for switching and other circuitry. (b) The diameter of the array coils will be approximately 0.375 inch (9.5 mm). Data acquisition strategy includes: (a) The corrosion spots will be mapped by successive interrogations of the active section of the array board. Approximately 10,000 samples will be acquired for each coil. The 10,000 readings will be averaged to produce one lower-noise value for each coil. This will be repeated for each coil in the array in a sequential manner. The total corrosion image for the sector will be built from the individual coil data. (b) Corrosion larger than the operational portion of the array board will be measured using a grid technique. Uniquely identified areas in the grid will overlay a corroded area, and data collected for each area will be connected by the display and assessment software to form a composite image for the corroded area. (c) Defect assessment will be invoked on the corrosion image by ''boxing'' selected areas on the color contour map. Software decisions consisted of selecting the appropriate LABVIEW modules running in a Windows XP operating system to obtain the required functionality. This third quarterly report of the project presents the activity and conclusions reached to date. Specifically, the design of the conformable array was completed and work was started on obtaining the data acquisition hardware. Southwest Research Institute (SwRI) and Clock Spring{reg_sign} staff met at the SwRI facilities in June 2003 to discuss the

  17. Photomodulation of conformational states. II. Mono- and bicyclic peptides with (4-aminomethyl)phenylazobenzoic acid as backbone constituent.

    PubMed

    Renner, C; Cramer, J; Behrendt, R; Moroder, L

    2000-12-01

    It has been reported that backbone cyclization of octapeptides with the photoresponsive (4-aminomethyl)phenylazobenzoic acid imparts sufficient restraints to induce and stabilize ordered conformations of the peptide backbone in both the cis- and trans-azo-isomers (L. Ulysse, J. Cubillos, and J. Chmielewski, Journal of the American Chemical Society, 1995, Vol. 117, pp. 8466-8467). Correspondingly, the active-site octapeptide fragment H-Ala-Cys-Ala-Thr-Cys-Asp-Gly-Phe-OH [134-141] of thioredoxin reductase, with its high preference for a 3(10)-helix turn conformation centered on the Thr-Cys sequence, was backbone cyclized with this azobenzene moiety in the attempt to design a photoresponsive system where the conformational states of the peptide backbone are dictated by the configuration of the azobenzene and can be further modulated by the disulfide bridge. Nuclear magnetic resonance conformational analysis of the monocyclic compound clearly revealed the presence of two conformational families in both the cis- and trans-azo configuration. Of the higher populated conformational families, the structure of the trans-isomer seems like a pretzel-like folding, while the cis-isomer relaxes into a significantly less defined conformational state that does not exhibit any regular structural elements. Further restrictions imparted by disulfide bridging of the peptide moiety leads to an even better defined conformation for the trans-azo-isomer, whereas the cis-isomer can be described as a frustrated system without pronounced energy minima and thus with little conformational preferences. Our findings would suggest that this photoresponsive peptide template may not be of general usefulness for light-induced conformational transitions between two well-defined conformational states at least under the experimental conditions employed, even in the bicyclic form. However, trans --> cis isomerization of the bicyclic peptide is accompanied by a switch from a well-defined conformation to

  18. Measuring the mechanical properties of molecular conformers

    NASA Astrophysics Data System (ADS)

    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.

  19. L’identification et traitement du trouble panique avec ou sans agoraphobie

    PubMed Central

    Foldes-Busque, Guillaume; Marchand, André; Landry, Pierre

    2007-01-01

    RÉSUMÉ OBJECTIF Renseigner les médecins de première ligne au sujet de l’identification précoce, du diagnostic et du traitement du trouble panique avec ou sans agoraphobie (TP/A). QUALITÉ DES DONNÉES Les données et recommandations présentées proviennent d’une recension des écrits scientifiques réalisée via les banques de données PsycLIT, PsyINFO et MEDLINE (1985 à 2006) en utilisant les descripteurs panic disorder, psychotherapy, psychosocial treatment, treatment et pharmacotherapy. Les recommandations formulées par les auteurs s’appuient sur des données probantes provenant d’études d’excellente qualité. Les informations concernant le diagnostic et l’évaluation du TP/A proviennent d’études épidémiologiques récentes, de consensus et d’opinions d’experts. PRINCIPAL MESSAGE Le TP/A est un trouble psychiatrique souvent rencontré en médecine de première ligne, mais il est fréquemment sous-diagnostiqué et sous-traité. L’identification précoce de ce trouble demande une attention particulière aux symptômes médicalement inexpliqués et, le cas échéant, le médecin doit utiliser des questions spécifiques permettant d’identifier d’éventuelles attaques de panique et de cerner leur signification pour le patient. Le traitement de premier choix pour ce trouble est une psychothérapie d’orientation cognitivo-comportementale administrée par un psychologue ou un psychiatre spécialisé. Si de telles ressources ne sont pas disponibles, le médecin peut opter pour un traitement psychopharmacologique. CONCLUSION Les médecins de famille peuvent jouer un rôle central dans l’identification et le traitement des patients souffrant d’un TP/A. PMID:17934032

  20. Conformal Electromagnetic Particle in Cell: A Review

    SciTech Connect

    Meierbachtol, Collin S.; Greenwood, Andrew D.; Verboncoeur, John P.; Shanker, Balasubramaniam

    2015-10-26

    We review conformal (or body-fitted) electromagnetic particle-in-cell (EM-PIC) numerical solution schemes. Included is a chronological history of relevant particle physics algorithms often employed in these conformal simulations. We also provide brief mathematical descriptions of particle-tracking algorithms and current weighting schemes, along with a brief summary of major time-dependent electromagnetic solution methods. Several research areas are also highlighted for recommended future development of new conformal EM-PIC methods.

  1. Conformal frame dependence of inflation

    SciTech Connect

    Domènech, Guillem; Sasaki, Misao E-mail: misao@yukawa.kyoto-u.ac.jp

    2015-04-01

    Physical equivalence between different conformal frames in scalar-tensor theory of gravity is a known fact. However, assuming that matter minimally couples to the metric of a particular frame, which we call the matter Jordan frame, the matter point of view of the universe may vary from frame to frame. Thus, there is a clear distinction between gravitational sector (curvature and scalar field) and matter sector. In this paper, focusing on a simple power-law inflation model in the Einstein frame, two examples are considered; a super-inflationary and a bouncing universe Jordan frames. Then we consider a spectator curvaton minimally coupled to a Jordan frame, and compute its contribution to the curvature perturbation power spectrum. In these specific examples, we find a blue tilt at short scales for the super-inflationary case, and a blue tilt at large scales for the bouncing case.

  2. Conformal approach to cylindrical DLA

    NASA Astrophysics Data System (ADS)

    Taloni, A.; Caglioti, E.; Loreto, V.; Pietronero, L.

    2006-09-01

    We extend the conformal mapping approach elaborated for the radial diffusion limited aggregation model (DLA) to cylindrical geometry. We introduce in particular a complex function which allows a cylindrical cluster to be grown using as an intermediate step a radial aggregate. The aggregate grown exhibits the same self-affine features as the original cylindrical DLA. The specific choice of the transformation allows us to study the relationship between the radial and the cylindrical geometry. In particular the cylindrical aggregate can be seen as a radial aggregate with particles of size increasing with the radius. On the other hand, the radial aggregate can be seen as a cylindrical aggregate with particles of size decreasing with the height. This framework, which shifts the point of view from the geometry to the size of the particles, can open the way to more quantitative studies on the relationship between radial and cylindrical DLA.

  3. Conformable eddy current array delivery

    NASA Astrophysics Data System (ADS)

    Summan, Rahul; Pierce, Gareth; Macleod, Charles; Mineo, Carmelo; Riise, Jonathan; Morozov, Maxim; Dobie, Gordon; Bolton, Gary; Raude, Angélique; Dalpé, Colombe; Braumann, Johannes

    2016-02-01

    The external surface of stainless steel containers used for the interim storage of nuclear material may be subject to Atmospherically Induced Stress Corrosion Cracking (AISCC). The inspection of such containers poses a significant challenge due to the large quantities involved; therefore, automating the inspection process is of considerable interest. This paper reports upon a proof-of-concept project concerning the automated NDT of a set of test containers containing artificially generated AISCCs. An Eddy current array probe with a conformable padded surface from Eddyfi was used as the NDT sensor and end effector on a KUKA KR5 arc HW robot. A kinematically valid cylindrical raster scan path was designed using the KUKA|PRC path planning software. Custom software was then written to interface measurement acquisition from the Eddyfi hardware with the motion control of the robot. Preliminary results and analysis are presented from scanning two canisters.

  4. Approaching Conformality with Ten Flavors

    SciTech Connect

    Appelquist, Thomas; Brower, Richard C.; Buchoff, Michael I.; Cheng, Michael; Cohen, Saul D.; Fleming, George T.; Kiskis, Joe; Lin, Meifeng; Na, Heechang; Neil, Ethan T.; Osborn, James C.

    2012-04-01

    We present first results for lattice simulations, on a single volume, of the low-lying spectrum of an SU(3) Yang-Mills gauge theory with N{sub f} = 10 light fermions in the fundamental representation. Fits to the fermion mass dependence of various observables are found to be globally consistent with the hypothesis that this theory is within or just outside the strongly-coupled edge of the conformal window, with mass anomalous dimension {gamma}* {approx} 1 over the range of scales simulated. We stress that we cannot rule out the possibility of spontaneous chiral-symmetry breaking at scales well below our infrared cutoff. We discuss important systematic effects, including finite-volume corrections, and consider directions for future improvement.

  5. Electromagnetic characterization of conformal antennas

    NASA Technical Reports Server (NTRS)

    Volakis, John L.; Kempel, Leo C.; Alexanian, Angelos; Jin, J. M.; Yu, C. L.; Woo, Alex C.

    1992-01-01

    The ultimate objective of this project is to develop a new technique which permits an accurate simulation of microstrip patch antennas or arrays with various feed, superstrate and/or substrate configurations residing in a recessed cavity whose aperture is planar, cylindrical or otherwise conformed to the substructure. The technique combines the finite element and boundary integral methods to formulate a system suitable for solution via the conjugate gradient method in conjunction with the fast Fourier transform. The final code is intended to compute both scattering and radiation patterns of the structure with an affordable memory demand. With upgraded capabilities, the four included papers examined the radar cross section (RCS), input impedance, gain, and resonant frequency of several rectangular configurations using different loading and substrate/superstrate configurations.

  6. Rotational Spectroscopy Unveils Eleven Conformers of Adrenaline

    NASA Astrophysics Data System (ADS)

    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.

  7. Pyrrolidine nucleotide analogs with a tunable conformation

    PubMed Central

    Poštová Slavětínská, Lenka; Rejman, Dominik

    2014-01-01

    Summary Conformational preferences of the pyrrolidine ring in nucleotide analogs 7–14 were investigated by means of NMR and molecular modeling. The effect of the relative configuration of hydroxy and nucleobase substituents as well as the effect of the alkylation or acylation of the pyrrolidine nitrogen atom on the conformation of the pyrrolidine ring were studied. The results of a conformational analysis show that the alkylation/acylation can be effectively used for tuning the pyrrolidine conformation over the whole pseudorotation cycle. PMID:25246956

  8. Fabrication challenges associated with conformal optics

    NASA Astrophysics Data System (ADS)

    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.

  9. Conformational Sampling and Binding Site Assessment of Suppression of Tumorigenicity 2 Ectodomain

    PubMed Central

    Yang, Chao-Yie; Delproposto, James; Chinnaswamy, Krishnapriya; Brown, William Clay; Wang, Shuying; Stuckey, Jeanne A.; Wang, Xinquan

    2016-01-01

    Suppression of Tumorigenicity 2 (ST2), a member of the interleukin-1 receptor (IL-1R) family, activates type 2 immune responses to pathogens and tissue damage via binding to IL-33. Dysregulated responses contribute to asthma, graft-versus-host and autoinflammatory diseases and disorders. To study ST2 structure for inhibitor development, we performed the principal component (PC) analysis on the crystal structures of IL1-1R1, IL1-1R2, ST2 and the refined ST2 ectodomain (ST2ECD) models, constructed from previously reported small-angle X-ray scattering data. The analysis facilitates mapping of the ST2ECD conformations to PC subspace for characterizing structural changes. Extensive coverage of ST2ECD conformations was then obtained using the accelerated molecular dynamics simulations started with the IL-33 bound ST2ECD structure as instructed by their projected locations on the PC subspace. Cluster analysis of all conformations further determined representative conformations of ST2ECD ensemble in solution. Alignment of the representative conformations with the ST2/IL-33 structure showed that the D3 domain of ST2ECD (containing D1-D3 domains) in most conformations exhibits no clashes with IL-33 in the crystal structure. Our experimental binding data informed that the D1-D2 domain of ST2ECD contributes predominantly to the interaction between ST2ECD and IL-33 underscoring the importance of the D1-D2 domain in binding. Computational binding site assessment revealed one third of the total detected binding sites in the representative conformations may be suitable for binding to potent small molecules. Locations of these sites include the D1-D2 domain ST2ECD and modulation sites conformed to ST2ECD conformations. Our study provides structural models and analyses of ST2ECD that could be useful for inhibitor discovery. PMID:26735493

  10. Un syndrome confusionnel révélant un syndrome de Fahr avec hyperparathyroïdie

    PubMed Central

    Rharrabti, Souad; Darouich, Ilhame; Benbrahim, Mohamed; Belahsen, Fawzi; Rammouz, Ismail; Alouane, Rachid

    2013-01-01

    Le syndrome de Fahr est une entité anatomo-clinique rare, caractérisée par des calcifications intracérébrales bilatérales et symétriques, localisées dans les noyaux gris centraux, le plus souvent associées à des troubles du métabolisme phosphocalcique. L'hypoparathyroïdie, primitive ou postopératoire, est l'anomalie la plus classique. L'hyperparathyroïdie est exceptionnellement rapportée comme cause du syndrome de Fahr. Nous rapportons le cas d'une fille de 17 ans suivie depuis l’âge de 12 ans pour une épilepsie avec la notion d'un retard mental depuis l'enfance, qui a présenté un syndrome confusionnel révélant un syndrome de Fahr avec la particularité de l'existence d'une hyperparathyroïdie. PMID:23734268

  11. Conformational readout of RNA by small ligands

    PubMed Central

    Kligun, Efrat; Mandel-Gutfreund, Yael

    2013-01-01

    RNA molecules have highly versatile structures that can fold into myriad conformations, providing many potential pockets for binding small molecules. The increasing number of available RNA structures, in complex with proteins, small ligands and in free form, enables the design of new therapeutically useful RNA-binding ligands. Here we studied RNA ligand complexes from 10 RNA groups extracted from the protein data bank (PDB), including adaptive and non-adaptive complexes. We analyzed the chemical, physical, structural and conformational properties of binding pockets around the ligand. Comparing the properties of ligand-binding pockets to the properties of computed pockets extracted from all available RNA structures and RNA-protein interfaces, revealed that ligand-binding pockets, mainly the adaptive pockets, are characterized by unique properties, specifically enriched in rare conformations of the nucleobase and the sugar pucker. Further, we demonstrate that nucleotides possessing the rare conformations are preferentially involved in direct interactions with the ligand. Overall, based on our comprehensive analysis of RNA-ligand complexes, we suggest that the unique conformations adopted by RNA nucleotides play an important role in RNA recognition by small ligands. We term the recognition of a binding site by a ligand via the unique RNA conformations “RNA conformational readout.” We propose that “conformational readout” is a general way by which RNA binding pockets are recognized and selected from an ensemble of different RNA states. PMID:23618839

  12. Conformational Sampling of Peptides in Cellular Environments☆

    PubMed Central

    Tanizaki, Seiichiro; Clifford, Jacob; Connelly, Brian D.; Feig, Michael

    2008-01-01

    Abstract Biological systems provide a complex environment that can be understood in terms of its dielectric properties. High concentrations of macromolecules and cosolvents effectively reduce the dielectric constant of cellular environments, thereby affecting the conformational sampling of biomolecules. To examine this effect in more detail, the conformational preference of alanine dipeptide, poly-alanine, and melittin in different dielectric environments is studied with computer simulations based on recently developed generalized Born methodology. Results from these simulations suggest that extended conformations are favored over α-helical conformations at the dipeptide level at and below dielectric constants of 5–10. Furthermore, lower-dielectric environments begin to significantly stabilize helical structures in poly-alanine at ɛ = 20. In the more complex peptide melittin, different dielectric environments shift the equilibrium between two main conformations: a nearly fully extended helix that is most stable in low dielectrics and a compact, V-shaped conformation consisting of two helices that is preferred in higher dielectric environments. An additional conformation is only found to be significantly populated at intermediate dielectric constants. Good agreement with previous studies of different peptides in specific, less-polar solvent environments, suggest that helix stabilization and shifts in conformational preferences in such environments are primarily due to a reduced dielectric environment rather than specific molecular details. The findings presented here make predictions of how peptide sampling may be altered in dense cellular environments with reduced dielectric response. PMID:17905846

  13. 40 CFR 52.938 - General conformity.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Implementation Plan (SIP). The Commonwealth of Kentucky incorporated by reference regulations 40 CFR part 51... 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...

  14. 14 CFR 17.45 - Conforming amendments.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Conforming amendments. 17.45 Section 17.45 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION PROCEDURAL RULES PROCEDURES FOR PROTESTS AND CONTRACTS DISPUTES Finality and Review § 17.45 Conforming amendments. The...

  15. Conformity to Peer Pressure in Preschool Children

    ERIC Educational Resources Information Center

    Haun, Daniel B. M.; Tomasello, Michael

    2011-01-01

    Both adults and adolescents often conform their behavior and opinions to peer groups, even when they themselves know better. The current study investigated this phenomenon in 24 groups of 4 children between 4;2 and 4;9 years of age. Children often made their judgments conform to those of 3 peers, who had made obviously erroneous but unanimous…

  16. Regulatory Conformance Checking: Logic and Logical Form

    ERIC Educational Resources Information Center

    Dinesh, Nikhil

    2010-01-01

    We consider the problem of checking whether an organization conforms to a body of regulation. Conformance is studied in a runtime verification setting. The regulation is translated to a logic, from which we synthesize monitors. The monitors are evaluated as the state of an organization evolves over time, raising an alarm if a violation is…

  17. CCProf: exploring conformational change profile of proteins

    PubMed Central

    Chang, Che-Wei; Chou, Chai-Wei; Chang, Darby Tien-Hao

    2016-01-01

    In many biological processes, proteins have important interactions with various molecules such as proteins, ions or ligands. Many proteins undergo conformational changes upon these interactions, where regions with large conformational changes are critical to the interactions. This work presents the CCProf platform, which provides conformational changes of entire proteins, named conformational change profile (CCP) in the context. CCProf aims to be a platform where users can study potential causes of novel conformational changes. It provides 10 biological features, including conformational change, potential binding target site, secondary structure, conservation, disorder propensity, hydropathy propensity, sequence domain, structural domain, phosphorylation site and catalytic site. All these information are integrated into a well-aligned view, so that researchers can capture important relevance between different biological features visually. The CCProf contains 986 187 protein structure pairs for 3123 proteins. In addition, CCProf provides a 3D view in which users can see the protein structures before and after conformational changes as well as binding targets that induce conformational changes. All information (e.g. CCP, binding targets and protein structures) shown in CCProf, including intermediate data are available for download to expedite further analyses. Database URL: http://zoro.ee.ncku.edu.tw/ccprof/ PMID:27016699

  18. Clinical Applications of Volumetric Modulated Arc Therapy

    SciTech Connect

    Matuszak, Martha M.; Yan Di; Grills, Inga; Martinez, Alvaro

    2010-06-01

    Purpose: To present treatment planning case studies for several treatment sites for which volumetric modulated arc therapy (VMAT) could have a positive impact; and to share an initial clinical experience with VMAT for stereotactic body radiotherapy (SBRT). Methods and Materials: Four case studies are presented to show the potential benefit of VMAT compared with conformal and intensity-modulated radiotherapy (IMRT) techniques in pediatric cancer, bone marrow-sparing whole-abdominopelvic irradiation (WAPI), and SBRT of the lung and spine. Details of clinical implementation of VMAT for SBRT are presented. The VMAT plans are compared with conventional techniques in terms of dosimetric quality and delivery efficiency. Results: Volumetric modulated arc therapy reduced the treatment time of spine SBRT by 37% and improved isodose conformality. Conformal and VMAT techniques for lung SBRT had similar dosimetric quality, but VMAT had improved target coverage and took 59% less time to deliver, although monitor units were increased by 5%. In a complex pediatric pelvic example, VMAT reduced treatment time by 78% and monitor units by 25% compared with IMRT. A double-isocenter VMAT technique for WAPI can spare bone marrow while maintaining good delivery efficiency. Conclusions: Volumetric modulated arc therapy is a new technology that may benefit different patient populations, including pediatric cancer patients and those undergoing concurrent chemotherapy and WAPI. Volumetric modulated arc therapy has been used and shown to be beneficial for significantly improving delivery efficiency of lung and spine SBRT.

  19. Technidilaton at the conformal edge

    SciTech Connect

    Hashimoto, Michio; Yamawaki, Koichi

    2011-01-01

    Technidilaton (TD) was proposed long ago in the technicolor near criticality/conformality. To reveal the critical behavior of TD, we explicitly compute the nonperturbative contributions to the scale anomaly <{theta}{sub {mu}}{sup {mu}>} and to the technigluon condensate <{alpha}G{sub {mu}{nu}}{sup 2}>, which are generated by the dynamical mass m of the technifermions. Our computation is based on the (improved) ladder Schwinger-Dyson equation, with the gauge coupling {alpha} replaced by the two-loop running coupling {alpha}({mu}) having the Caswell-Banks-Zaks infrared fixed point {alpha}{sub *}: {alpha}({mu}){approx_equal}{alpha}={alpha}{sub *} for the infrared region m<{mu}<{Lambda}{sub TC}, where {Lambda}{sub TC} is the intrinsic scale (analogue of {Lambda}{sub QCD} of QCD) relevant to the perturbative scale anomaly. We find that -<{theta}{sub {mu}}{sup {mu}}>/m{sup 4}{yields}const{ne}0 and <{alpha}G{sub {mu}}{nu}{sup 2}>/m{sup 4}{yields}({alpha}/{alpha}{sub cr}-1){sup -3/2}{yields}{infinity} in the criticality limit m/{Lambda}{sub TC}{approx}exp(-{pi}/({alpha}/{alpha}{sub cr}-1){sup 1/2}){yields}0 ({alpha}={alpha}{sub *}=>{alpha}{sub cr}, or N{sub f} approaches N{sub f}{sup cr}) ('conformal edge'). Our result precisely reproduces the formal identity <{theta}{sub {mu}}{sup {mu}>}=({beta}({alpha})/4{alpha}{sup 2})<{alpha}G{sub {mu}{nu}}{sup 2}>, where {beta}({alpha})={Lambda}{sub TC}({partial_derivative}{alpha}/{partial_derivative}{Lambda}{sub TC})=-(2{alpha}{sub cr}/{pi}){center_dot}({alpha}/{alpha}{sub cr}-1){sup 3/2} is the nonperturbative beta function corresponding to the above essential singularity scaling of m/{Lambda}{sub TC}. Accordingly, the partially conserved dilatation current implies (M{sub TD}/m){sup 2}(F{sub TD}/m){sup 2}=-4<{theta}{sub {mu}}{sup {mu}}>/m{sup 4}{yields}const{ne}0 at criticality limit, where M{sub TD} is the mass of TD and F{sub TD} the decay constant of TD. We thus conclude that at criticality limit the TD could become a ''true

  20. Technidilaton at the conformal edge

    NASA Astrophysics Data System (ADS)

    Hashimoto, Michio; Yamawaki, Koichi

    2011-01-01

    Technidilaton (TD) was proposed long ago in the technicolor near criticality/conformality. To reveal the critical behavior of TD, we explicitly compute the nonperturbative contributions to the scale anomaly ⟨θμμ⟩ and to the technigluon condensate ⟨αGμν2⟩, which are generated by the dynamical mass m of the technifermions. Our computation is based on the (improved) ladder Schwinger-Dyson equation, with the gauge coupling α replaced by the two-loop running coupling α(μ) having the Caswell-Banks-Zaks infrared fixed point α*: α(μ)≃α=α* for the infrared region m<μ<ΛTC, where ΛTC is the intrinsic scale (analogue of ΛQCD of QCD) relevant to the perturbative scale anomaly. We find that -⟨θμμ⟩/m4→const≠0 and ⟨αGμν2⟩/m4→(α/αcr-1)-3/2→∞ in the criticality limit m/ΛTC˜exp⁡(-π/(α/αcr-1)1/2)→0 (α=α*↘αcr, or Nf↗Nfcr) (“conformal edge”). Our result precisely reproduces the formal identity ⟨θμμ⟩=(β(α)/4α2)⟨αGμν2⟩, where β(α)=ΛTC(∂α)/(∂ΛTC)=-(2αcr/π)·(α/αcr-1)3/2 is the nonperturbative beta function corresponding to the above essential singularity scaling of m/ΛTC. Accordingly, the partially conserved dilatation current implies (MTD/m)2(FTD/m)2=-4⟨θμμ⟩/m4→const≠0 at criticality limit, where MTD is the mass of TD and FTD the decay constant of TD. We thus conclude that at criticality limit the TD could become a “true (massless) Nambu-Goldstone boson” MTD/m→0, only when m/FTD→0, namely, getting decoupled, as was the case of “holographic technidilaton” of Haba-Matsuzaki-Yamawaki. The decoupled TD can be a candidate of dark matter.

  1. Etude de la photosensibilite dans la silice implantee avec des ions de haute energie

    NASA Astrophysics Data System (ADS)

    Verhaegen, Marc

    La photosensibilite est la propriete par laquelle une materiau donne voit son indice de refraction changer sous l'effet d'une exposition lumineuse. Malgre le nombre croissant de dispositif base sur ce phenomene, les mecanismes a la base de la photosensibilite sont encore debattus. Nous apportons dans cette these un eclairage original sur ce sujet en etudiant la matrice de silice pure non dopee rendue photosensible par implantation d'ion de haute energie. L'implantation d'ions silicium de S MeV modifie l'indice de refraction principalement en densifiant une couche mince dont l'epaisseur est de l'ordre de quelques microns. Nos mesures montrent qu'un guide plan supportant les modes TEi et TMi (i = 0,1) est forme et que l'indice effectif du mode TE0 suit l'evolution de la densification en fonction de la dose de silicium implantee. Nous montrerons egalement que l'augmentation d'indice et la densification produites par implantation atteignent un palier pour une dose de 3 x 1014Si/cm 2, alors que la production de defauts par implantation atteint son palier pour une dose plus faible d'un ordre de grandeur soit 3 x 1013Si/cm2. Le profil d'indice longitudinal produit par l'implantation ionique est calcule a partir des mesures des indices effectifs des modes guides. Ce profil suggere que l'augmentation d'indice comprend une contribution dues collisions et une contribution dues aux pertes d'energie par ionisation. La contribution des pertes par ionisation influence significativement le profil d'indice pour des valeurs de pertes d'energie par unite de longueur (dE/dx) de l'ordre de 2 keV/nm. Lorsque la silice implantee est soumise a un rayonnement ultraviolet d'un laser a excimeres, il en resulte une diminution d'indice de refraction de l'ordre de 10-3 avec une efficacite plus grande si la longueur d'onde d'exposition est 193nm (ArF) plutot que 248nm (KrF). Deux regimes d'exposition lumineuse de la silice implantee a 193nm sont observes. Le premier regime produit une diminution

  2. Superintegrability of d-Dimensional Conformal Blocks.

    PubMed

    Isachenkov, Mikhail; Schomerus, Volker

    2016-08-12

    We observe that conformal blocks of scalar four-point functions in a d-dimensional conformal field theory can be mapped to eigenfunctions of a two-particle hyperbolic Calogero-Sutherland Hamiltonian. The latter describes two coupled Pöschl-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. We conclude with a short outlook, in particular, on the consequences of integrability for the theory of conformal blocks. PMID:27563949

  3. Performance of Conformable Ablators in Aerothermal Environments

    NASA Technical Reports Server (NTRS)

    Thornton, J.; Fan, W.; Skokova, K.; Stackpoole, M.; Beck, R.; Chavez-Garcia, J.

    2012-01-01

    Conformable Phenolic Impregnated Carbon Ablator, a cousin of Phenolic Impregnated Carbon Ablator (PICA), was developed at NASA Ames Research Center as a lightweight thermal protection system under the Fundamental Aeronautics Program. PICA is made using a brittle carbon substrate, which has a very low strain to failure. Conformable PICA is made using a flexible carbon substrate, a felt in this case. The flexible felt significantly increases the strain to failure of the ablator. PICA is limited by its thermal mechanical properties. Future NASA missions will require heatshields that are more fracture resistant than PICA and, as a result, NASA Ames is working to improve PICAs performance by developing conformable PICA to meet these needs. Research efforts include tailoring the chemistry of conformable PICA with varying amounts of additives to enhance mechanical properties and testing them in aerothermal environments. This poster shows the performance of conformable PICA variants in arc jets tests. Some mechanical and thermal properties will also be presented.

  4. Superintegrability of d -Dimensional Conformal Blocks

    NASA Astrophysics Data System (ADS)

    Isachenkov, Mikhail; Schomerus, Volker

    2016-08-01

    We observe that conformal blocks of scalar four-point functions in a d -dimensional conformal field theory can be mapped to eigenfunctions of a two-particle hyperbolic Calogero-Sutherland Hamiltonian. The latter describes two coupled Pöschl-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. We conclude with a short outlook, in particular, on the consequences of integrability for the theory of conformal blocks.

  5. Vibrational and vibronic spectra of tryptamine conformers

    NASA Astrophysics Data System (ADS)

    Mayorkas, Nitzan; Bernat, Amir; Izbitski, Shay; Bar, Ilana

    2013-03-01

    Conformation-specific ionization-detected stimulated Raman spectra, including both Raman loss and Raman gain lines, along with visible-visible-ultraviolet hole-burning spectra of tryptamine (TRA) conformers have been measured simultaneously, with the aim of obtaining new data for identifying them. The slightly different orientations of the ethylamine side chain relative to the indole lead to unique spectral signatures, pointing to the presence of seven TRA conformers in the molecular beam. Comparison of ionization-loss stimulated Raman spectra to computationally scaled harmonic Raman spectra, especially in the alkyl C-H and amine N-H stretch regions together with the retrieved information on the stabilities of the TRA conformers assisted their characterization and structural identification. The prospects and limitations of using these spectroscopic methods as potential conformational probes of flexible molecules are discussed.

  6. Dolastatin 11 conformations, analogues and pharmacophore.

    PubMed

    Ali, Md Ahad; Bates, Robert B; Crane, Zackary D; Dicus, Christopher W; Gramme, Michelle R; Hamel, Ernest; Marcischak, Jacob; Martinez, David S; McClure, Kelly J; Nakkiew, Pichaya; Pettit, George R; Stessman, Chad C; Sufi, Bilal A; Yarick, Gayle V

    2005-07-01

    Twenty analogues of the natural antitumor agent dolastatin 11, including majusculamide C, were synthesized and tested for cytotoxicity against human cancer cells and stimulation of actin polymerization. Only analogues containing the 30-membered ring were active. Molecular modeling and NMR evidence showed the low-energy conformations. The amide bonds are all trans except for the one between the Tyr and Val units, which is cis. Since an analogue restricted to negative 2-3-4-5 angles stimulated actin polymerization but was inactive in cells, the binding conformation (most likely the lowest-energy conformation in water) has a negative 2-3-4-5 angle, whereas a conformation with a positive 2-3-4-5 angle (most likely the lowest energy conformation in chloroform) goes through cell walls. The highly active R alcohol from borohydride reduction of dolastatin 11 is a candidate for conversion to prodrugs.

  7. Protein biosynthesis with conformationally restricted amino acids

    SciTech Connect

    Mendel, D. Lawrence Berkeley Lab., CA ); Ellman, J.; Schultz, P.G. )

    1993-05-19

    The incorporation of conformationally constrained amino acids into peptides is a powerful approach for generating structurally defined peptides as conformational probes and bioactive agents. The ability to site-specifically introduce constrained amino acids into large polypeptide chains would provide a similar opportunity to probe the flexibility, conformation, folding and stability of proteins. To this end, we have examined the competence of the Escherichia coli protein biosynthetic machinery to incorporate a number of these unnatural amino acids into the 164 residue protein T4 lysozyme (T4L). Results clearly demonstrate that the protein biosynthetic machinery can accommodate a wide variety of conformationally constrained amino acids. The expansion of structural motifs that can be biosynthetically incorporated into proteins to include a large number of conformationally constrained amino acids significantly increases the power of mutagenesis methods as probes of protein structure and function and provides additional insights into the steric requirements of the translational machinery. 13 refs., 2 figs.

  8. Conforming Morse-Smale Complexes

    SciTech Connect

    Gyulassy, Attila; Gunther, David; Levine, Joshua A.; Tierny, Julien; Pascucci, Valerio

    2014-08-11

    Morse-Smale (MS) complexes have been gaining popularity as a tool for feature-driven data analysis and visualization. However, the quality of their geometric embedding and the sole dependence on the input scalar field data can limit their applicability when expressing application-dependent features. In this paper we introduce a new combinatorial technique to compute an MS complex that conforms to both an input scalar field and an additional, prior segmentation of the domain. The segmentation constrains the MS complex computation guaranteeing that boundaries in the segmentation are captured as separatrices of the MS complex. We demonstrate the utility and versatility of our approach with two applications. First, we use streamline integration to determine numerically computed basins/mountains and use the resulting segmentation as an input to our algorithm. This strategy enables the incorporation of prior flow path knowledge, effectively resulting in an MS complex that is as geometrically accurate as the employed numerical integration. Our second use case is motivated by the observation that often the data itself does not explicitly contain features known to be present by a domain expert. We introduce edit operations for MS complexes so that a user can directly modify their features while maintaining all the advantages of a robust topology-based representation.

  9. Conforming Morse-Smale Complexes.

    PubMed

    Gyulassy, Attila; Günther, David; Levine, Joshua A; Tierny, Julien; Pascucci, Valerio

    2014-12-01

    Morse-Smale (MS) complexes have been gaining popularity as a tool for feature-driven data analysis and visualization. However, the quality of their geometric embedding and the sole dependence on the input scalar field data can limit their applicability when expressing application-dependent features. In this paper we introduce a new combinatorial technique to compute an MS complex that conforms to both an input scalar field and an additional, prior segmentation of the domain. The segmentation constrains the MS complex computation guaranteeing that boundaries in the segmentation are captured as separatrices of the MS complex. We demonstrate the utility and versatility of our approach with two applications. First, we use streamline integration to determine numerically computed basins/mountains and use the resulting segmentation as an input to our algorithm. This strategy enables the incorporation of prior flow path knowledge, effectively resulting in an MS complex that is as geometrically accurate as the employed numerical integration. Our second use case is motivated by the observation that often the data itself does not explicitly contain features known to be present by a domain expert. We introduce edit operations for MS complexes so that a user can directly modify their features while maintaining all the advantages of a robust topology-based representation.

  10. Conformal Higgs, or Techni-Dilaton -- Composite Higgs Near Conformality

    NASA Astrophysics Data System (ADS)

    Yamawaki, Koichi

    2011-01-01

    In contrast to the folklore that Technicolor (TC) is a "Higgsless theory", we shall discuss existence of a composite Higgs boson, Techni-Dilaton (TD), a pseudo-Nambu-Goldstone boson of the scale invariance in the Scale-invariant/Walking/Conformal TC (SWC TC) which generates a large anomalous dimension γm ≃ 1 in a wide region from the dynamical mass m = {O} ({TeV}) of the techni-fermion all the way up to the intrinsic scale ΛTC of the SWC TC (analogue of ΛQCD), where ΛTC is taken typically as the scale of the Extended TC scale ΛETC: ΛTC ≃ ΛETC 103 TeV (≫ m). All the techni-hadrons have mass on the same order {O}(m), which in SWC TC is extremely smaller than the intrinsic scale ΛTC ≃ ΛETC, in sharp contrast to QCD where both are of the same order. The mass of TD arises from the non-perturbative scale anomaly associated with the techni-fermion mass generation and is typically 500-600 GeV, even smaller than other techni-hadrons of the same order of {O}(m), in another contrast to QCD which is believed to have no scalar bar qq bound state lighter than other hadrons. We discuss the TD mass in various methods, Gauged NJL model via ladder Schwinger-Dyson (SD) equation, straightforward calculations in the ladder SD/ Bethe-Salpeter equation, and the holographic approach including techni-gluon condensate. The TD may be discovered in LHC.

  11. Third and higher order NFPA twisted constructions of conformal field theories from lattices

    NASA Astrophysics Data System (ADS)

    Montague, P. S.

    1995-02-01

    We investigate orbifold constructions of conformal field theories from lattices by no-fixed-point automorphisms (NFPAs) Zp for p prime, p > 2, concentrating on the case p = 3. Explicit expressions are given for most of the relevant vertex operators, and we consider the locality relations necessary for these to define a consistent conformal field theory. A relation to constructions of lattices from codes, analogous to that found in earlier work in the p = 2 case which led to a generalisation of the triality structure of the Monster module, is also demonstrated.

  12. Atomic visualization of a flipped-back conformation of bisected glycans bound to specific lectins

    PubMed Central

    Nagae, Masamichi; Kanagawa, Mayumi; Morita-Matsumoto, Kana; Hanashima, Shinya; Kizuka, Yasuhiko; Taniguchi, Naoyuki; Yamaguchi, Yoshiki

    2016-01-01

    Glycans normally exist as a dynamic equilibrium of several conformations. A fundamental question concerns how such molecules bind lectins despite disadvantageous entropic loss upon binding. Bisected glycan, a glycan possessing bisecting N-acetylglucosamine (GlcNAc), is potentially a good model for investigating conformational dynamics and glycan-lectin interactions, owing to the unique ability of this sugar residue to alter conformer populations and thus modulate the biological activities. Here we analyzed bisected glycan in complex with two unrelated lectins, Calsepa and PHA-E. The crystal structures of the two complexes show a conspicuous flipped back glycan structure (designated ‘back-fold’ conformation), and solution NMR analysis also provides evidence of ‘back-fold’ glycan structure. Indeed, statistical conformational analysis of available bisected and non-bisected glycan structures suggests that bisecting GlcNAc restricts the conformations of branched structures. Restriction of glycan flexibility by certain sugar residues may be more common than previously thought and impinges on the mechanism of glycoform-dependent biological functions. PMID:26971576

  13. Cryptographie quantique avec des états cohérents à longueur d'onde télécom

    NASA Astrophysics Data System (ADS)

    Lodewyck, J.; Tualle-Brouri, R.; Debuisschert, T.; Grangier, P.

    2006-10-01

    Nous proposons un système de distribution quantique de clé avec des variables continues, implémenté avec des technologies télécom à 1550 nm. Le dispositif actuel nous a permis de transmettre une clé secrète brute au taux de 1 Mb/s sur une distance de quelques mètres. Une extension en cours de réalisation nous permettra de transmettre des clés sur des distances allant jusqu'à plusieurs dizaines dekilomètres.

  14. Perceived Symbols of Authority and Their Influence on Conformity.

    ERIC Educational Resources Information Center

    Bushman, Brad J.

    Although there are many variables that influence conformity, Bickman (1974) found that the apparel of the person making a request had a significant influence on conformity. To evaluate other factorswhicn may influence conformity (gender, age, status of the conforming subject, and altruism in conforming), 150 adult pedestrians (45% female, 71%…

  15. 47 CFR 2.1072 - Limitation on Declaration of Conformity.

    Code of Federal Regulations, 2010 CFR

    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...

  16. Representation of target-bound drugs by computed conformers: implications for conformational libraries

    PubMed Central

    Günther, Stefan; Senger, Christian; Michalsky, Elke; Goede, Andrean; Preissner, Robert

    2006-01-01

    Background The increasing number of known protein structures provides valuable information about pharmaceutical targets. Drug binding sites are identifiable and suitable lead compounds can be proposed. The flexibility of ligands is a critical point for the selection of potential drugs. Since computed 3D structures of millions of compounds are available, the knowledge of their binding conformations would be a great benefit for the development of efficient screening methods. Results Integration of two public databases allowed superposition of conformers for 193 approved drugs with 5507 crystallised target-bound counterparts. The generation of 9600 drug conformers using an atomic force field was carried out to obtain an optimal coverage of the conformational space. Bioactive conformations are best described by a conformational ensemble: half of all drugs exhibit multiple active states, distributed over the entire range of the reachable energy and conformational space. A number of up to 100 conformers per drug enabled us to reproduce the bound states within a similarity threshold of 1.0 Å in 70% of all cases. This fraction rises to about 90% for smaller or average sized drugs. Conclusion Single drugs adopt multiple bioactive conformations if they interact with different target proteins. Due to the structural diversity of binding sites they adopt conformations that are distributed over a broad conformational space and wide energy range. Since the majority of drugs is well represented by a predefined low number of conformers (up to 100) this procedure is a valuable method to compare compounds by three-dimensional features or for fast similarity searches starting with pharmacophores. The underlying 9600 generated drug conformers are downloadable from the Super Drug Web site [1]. All superpositions are visualised at the same source. Additional conformers (110,000) of 2400 classified WHO-drugs are also available. PMID:16764718

  17. The Principle of Maximum Conformality

    SciTech Connect

    Brodsky, Stanley J; Giustino, Di; /SLAC

    2011-04-05

    A key problem in making precise perturbative QCD predictions is the uncertainty in determining the renormalization scale of the running coupling {alpha}{sub s}({mu}{sup 2}). It is common practice to guess a physical scale {mu} = Q which is of order of a typical momentum transfer Q in the process, and then vary the scale over a range Q/2 and 2Q. This procedure is clearly problematic since the resulting fixed-order pQCD prediction will depend on the renormalization scheme, and it can even predict negative QCD cross sections at next-to-leading-order. Other heuristic methods to set the renormalization scale, such as the 'principle of minimal sensitivity', give unphysical results for jet physics, sum physics into the running coupling not associated with renormalization, and violate the transitivity property of the renormalization group. Such scale-setting methods also give incorrect results when applied to Abelian QED. Note that the factorization scale in QCD is introduced to match nonperturbative and perturbative aspects of the parton distributions in hadrons; it is present even in conformal theory and thus is a completely separate issue from renormalization scale setting. The PMC provides a consistent method for determining the renormalization scale in pQCD. The PMC scale-fixed prediction is independent of the choice of renormalization scheme, a key requirement of renormalization group invariance. The results avoid renormalon resummation and agree with QED scale-setting in the Abelian limit. The PMC global scale can be derived efficiently at NLO from basic properties of the PQCD cross section. The elimination of the renormalization scheme ambiguity using the PMC will not only increases the precision of QCD tests, but it will also increase the sensitivity of colliders to new physics beyond the Standard Model.

  18. Atomic levers control pyranose ring conformations

    PubMed Central

    Marszalek, Piotr E.; Pang, Yuan-Ping; Li, Hongbin; Yazal, Jamal El; Oberhauser, Andres F.; Fernandez, Julio M.

    1999-01-01

    Atomic force microscope manipulations of single polysaccharide molecules have recently expanded conformational chemistry to include force-driven transitions between the chair and boat conformers of the pyranose ring structure. We now expand these observations to include chair inversion, a common phenomenon in the conformational chemistry of six-membered ring molecules. We demonstrate that by stretching single pectin molecules (1 → 4-linked α-d-galactouronic acid polymer), we could change the pyranose ring conformation from a chair to a boat and then to an inverted chair in a clearly resolved two-step conversion: 4C1 ⇄ boat ⇄ 1C4. The two-step extension of the distance between the glycosidic oxygen atoms O1 and O4 determined by atomic force microscope manipulations is corroborated by ab initio calculations of the increase in length of the residue vector O1O4 on chair inversion. We postulate that this conformational change results from the torque generated by the glycosidic bonds when a force is applied to the pectin molecule. Hence, the glycosidic bonds act as mechanical levers, driving the conformational transitions of the pyranose ring. When the glycosidic bonds are equatorial (e), the torque is zero, causing no conformational change. However, when the glycosidic bond is axial (a), torque is generated, causing a rotation around C—C bonds and a conformational change. This hypothesis readily predicts the number of transitions observed in pyranose monomers with 1a-4a linkages (two), 1a-4e (one), and 1e-4e (none). Our results demonstrate single-molecule mechanochemistry with the capability of resolving complex conformational transitions. PMID:10393918

  19. Les astronomes européens auscultent les cieux avec le plus grand télescope du monde

    NASA Astrophysics Data System (ADS)

    Malbet, F.

    2008-09-01

    À l'heure des projets de télescopes extrêmement grands, l'Europe a déjà une longueur d'avance. Le télescope européen (VLT), en mode interférométrique avec l'instrument AMBER devient le plus grand télescope jamais utilisé dans le domaine optique aussi bien en surface de miroir (plus de 150 m2) qúen finesse de résolution qui atteint celle d'un télescope de 130 m de diamètre. Le journal professionnel Astronomy & Astrophysics a publié en 2007 un numéro spécial qui rapporte les premiers résultats obtenus avec l'instrument AMBER (Astronomical MultiBEam Recombiner) par le très grand télescope européen. Ces articles couvrent pratiquement tous les stades de l'évolution stellaire depuis la formation des étoiles et des planètes jusqu'a l'observation de l'explosion de type nova dans un système stellaire évolué. Ces résultats inédits ont été obtenus en utilisant simultanément 3 des 4 télescopes du VLT basés à l'Observatoire européen austral du mont Paranal au Chili. L'instrument AMBER équipant le VLTI (mode interférométrique du VLT) permet dâatteindre une résolution angulaire inégalée de l'ordre du millième de seconde d'angle autorisant l'observation des astres dans différentes longueurs d'onde, dans l'infrarouge proche. Les astronomes obtiennent donc des observations avec une finesse 13 fois plus importante que celle d'un télescope seul. Il devient alors possible de sonder les régions de formation de planètes, d'observer les vents des étoiles en rotation très rapide, d'étudier les différents types de matières éjectées par une étoile massive, de séparer les deux composantes d'une étoile double serrée et de voir en direct l'évolution d'une nova quelques jours seulement après son explosion.

  20. Conformation sensitive charge transport in conjugated polymers

    SciTech Connect

    Mattias Andersson, L.; Hedström, Svante; Persson, Petter

    2013-11-18

    Temperature dependent charge carrier mobility measurements using field effect transistors and density functional theory calculations are combined to show how the conformation dependent frontier orbital delocalization influences the hole- and electron mobilities in a donor-acceptor based polymer. A conformationally sensitive lowest unoccupied molecular orbital results in an electron mobility that decreases with increasing temperature above room temperature, while a conformationally stable highest occupied molecular orbital is consistent with a conventional hole mobility behavior and also proposed to be one of the reasons for why the material works well as a hole transporter in amorphous bulk heterojunction solar cells.

  1. The conformal window from the worldline formalism

    NASA Astrophysics Data System (ADS)

    Armoni, Adi

    2010-02-01

    We use the worldline formalism to derive a universal relation for the lower boundary of the conformal window in non-supersymmetric QCD-like theories. The derivation relies on the convergence of the expansion of the fermionic determinant in terms of Wilson loops. The expansion shares a similarity with the lattice strong coupling expansion and the genus expansion in string theory. Our result relates the lower boundary of the conformal window in theories with different representations and different gauge groups. Finally, we use SQCD to estimate the boundary of the conformal window in QCD-like theories and compare it with other approaches.

  2. Novel Approach to Conformal FINFET Extension Doping

    SciTech Connect

    Zschaetzsch, G.; Vandervorst, W.; Hoffmann, T. Y.; Horiguchi, N.; Hautala, J.; Shao, Y.

    2011-01-07

    This paper presents a novel strategy to achieve conformal FINFET extension doping with low tilt-angle beam-line ion implantation. The process relies on the self-aligned cap layer formation exclusively on top of the FIN to tune doping levels in this particular area by partial dopant trapping. The conformality itself is evaluated for n- and p-type dopants by a novel extraction method applied to FIN resistor test structures. Furthermore, the process was integrated into a full NMOS device flow and compared to a highly tilted and more conformal As implant condition.

  3. Conformational and Vibrational Studies of Triclosan

    NASA Astrophysics Data System (ADS)

    Özişik, Haci; Bayari, S. Haman; Saǧlam, Semran

    2010-01-01

    The conformational equilibrium of triclosan (5-chloro-2-(2, 4-dichlorophenoxy) phenol) have been calculated using density functional theory (DFTe/B3LYP/6-311++G(d, p)) method. Four different geometries were found to correspond to energy minimum conformations. The IR spectrum of triclosan was measured in the 4000-400 cm-1 region. We calculated the harmonic frequencies and intensities of the most stable conformers in order to assist in the assignment of the vibrational bands in the experimental spectrum. The fundamental vibrational modes were characterized depending on their total energy distribution (TED%) using scaled quantum mechanical (SQM) force field method.

  4. Conformable Fractional Nikiforov—Uvarov Method

    NASA Astrophysics Data System (ADS)

    Karayer, H.; Demirhan, D.; Büyükkılıç, F.

    2016-07-01

    We introduce conformable fractional Nikiforov—Uvarov (NU) method by means of conformable fractional derivative which is the most natural definition in non-integer calculus. Since, NU method gives exact eigenstate solutions of Schrödinger equation (SE) for certain potentials in quantum mechanics, this method is carried into the domain of fractional calculus to obtain the solutions of fractional SE. In order to demonstrate the applicability of the conformable fractional NU method, we solve fractional SE for harmonic oscillator potential, Woods—Saxon potential, and Hulthen potential.

  5. Anticholinergic substances: A single consistent conformation

    PubMed Central

    Pauling, Peter; Datta, Narayandas

    1980-01-01

    An interactive computer-graphics analysis of 24 antagonists of acetylcholine at peripheral autonomic post-ganglionic (muscarinic) nervous junctions and at similar junctions in the central nervous system, the crystal structures of which are known, has led to the determination of a single, consistent, energetically favorable conformation for all 24 substances, although their observed crystal structure conformations vary widely. The absolute configuration and the single, consistent (ideal) conformation of the chemical groups required for maximum anticholinergic activity are described quantitatively. Images PMID:16592775

  6. Conformity and Dissonance in Generalized Voter Models

    NASA Astrophysics Data System (ADS)

    Page, Scott E.; Sander, Leonard M.; Schneider-Mizell, Casey M.

    2007-09-01

    We generalize the voter model to include social forces that produce conformity among voters and avoidance of cognitive dissonance of opinions within a voter. The time for both conformity and consistency (which we call the exit time) is, in general, much longer than for either process alone. We show that our generalized model can be applied quite widely: it is a form of Wright's island model of population genetics, and is related to problems in the physical sciences. We give scaling arguments, numerical simulations, and analytic estimates for the exit time for a range of relative strengths in the tendency to conform and to avoid dissonance.

  7. Toward Focusing Conformational Ensembles on Bioactive Conformations: A Molecular Mechanics/Quantum Mechanics Study.

    PubMed

    Avgy-David, Hannah H; Senderowitz, Hanoch

    2015-10-26

    The identification of bound conformations, namely, conformations adopted by ligands when binding their target is critical for target-based and ligand-based drug design. Bound conformations could be obtained computationally from unbound conformational ensembles generated by conformational search tools. However, these tools also generate many nonrelevant conformations thus requiring a focusing mechanism. To identify such a mechanism, this work focuses on a comparison of energies and structural properties of bound and unbound conformations for a set of FDA approved drugs whose complexes are available in the PDB. Unbound conformational ensembles were initially obtained with three force fields. These were merged, clustered, and reminimized using the same force fields and four QM methods. Bound conformations of all ligands were represented by their crystal structures or by approximations to these structures. Energy differences were calculated between global minima of the unbound state or the Boltzmann averaged energies of the unbound ensemble and the approximated bound conformations. Ligand conformations which resemble the X-ray conformation (RMSD < 1.0 Å) were obtained in 91%-97% and 96%-98% of the cases using the ensembles generated by the individual force fields and the reminimized ensembles, respectively, yet only in 52%-56% (original ensembles) and 47%-65% (reminimized ensembles) as global energy minima. The energy window within which the different methods identified the bound conformation (approximated by its closest local energy minimum) was found to be at 4-6 kcal/mol with respect to the global minimum and marginally lower with respect to a Boltzmann averaged energy of the unbound ensemble. Better approximations to the bound conformation obtained with a constrained minimization using the crystallographic B-factors or with a newly developed Knee Point Detection (KPD) method gave lower values (2-5 kcal/mol). Overall, QM methods gave lower energy differences than

  8. Lipome du corps calleux: à propos d'un cas avec revue de littérature

    PubMed Central

    Zhari, Bouchra; Mattiche, Houda; Boumdine, Hassan; Amil, Touriya; Ennouali, Hassan

    2015-01-01

    Le lipome du corps calleux est une malformation congénitale très rare, qui peut être associée à des degrés divers de dysgénésie du corps calleux. Son extension dans le ventricule latéral est encore plus rare. Il est souvent asymptomatique, mais peut se présenter par une épilepsie, hémiplégie, démence ou de simples céphalées. La tomodensitométrie et l'imagerie par résonance magnétique permettent facilement le diagnostic. Nous rapportons le cas d'une jeune fille de 14 ans, souffrant de simples céphalées, chez qui on découvre un lipome du corps calleux avec extension au ventricule latéral. PMID:26526933

  9. Hyperemesis gravidarum avec troubles ioniques sévères: à propos d'un cas

    PubMed Central

    Jarraya, Anouar; Elleuch, Sahar; Zouari, Jawhar; Trigui, Khaled; Sofiene, Abidi; Smaoui, Mohamed; Kolsi, Kamel

    2015-01-01

    L'hyperemesis gravidarum s'accompagne habituellement d'une perte de poids, d'une acétonurie et de troubles hydro-électrolytiques comme il peut également s'accompagner d'anomalies du bilan hépatique. Nous rapportons un cas de vomissements gravidiques à 10 semaines d'aménorrhée non traité et vu tardivement avec des troubles ioniques sévères associés à des répercussions cliniques dans un contexte de cytolyse, de cholestase et d'insuffisance rénale aigue. Ce cas a bien répondu au traitement médical. PMID:26161187

  10. Impact Ft-Mw Spectroscopy of Organic Rings: Investigation of the Conformational Landscape

    NASA Astrophysics Data System (ADS)

    Wachsmuth, Dennis; Grabow, Jens-Uwe; Lesarri, Alberto

    2014-06-01

    Organic rings are common building blocks in biologically active molecules. In contrast to six-membered rings, cycloalkanes with seven or more ring atoms have a less rigid structure which allows for conformational diversity and complex internal dynamics. The broadband itshape in-phase/quadrature-phase-modulation passage-acquired-coherence technique \\upshape (IMPACT) FT-microwave spectroscopy is the ideal experimental method to gain insight into the conformational freedom and structure of these cyclic motifs. The combination of high spectral resolution (<10 kHz) and frequency accuracy with a 1 GHz wideband acquisition range per experimental pulse (over the entire 2 to 26.5 GHz range) makes the IMPACT spectrometer a time-saving tool when it comes to the investigation of fine or hyperfine effects and/or wide tunelling splittings. In this communication we will present the rotational spectra of several organic seven-membered rings, reporting on their conformational preferences and molecular structures.

  11. Calcineurin Undergoes a Conformational Switch Evoked via Peptidyl-Prolyl Isomerization

    PubMed Central

    Guasch, Alicia; Aranguren-Ibáñez, Álvaro; Pérez-Luque, Rosa; Aparicio, David; Martínez-Høyer, Sergio; Mulero, M. Carmen; Serrano-Candelas, Eva

    2015-01-01

    A limited repertoire of PPP family of serine/threonine phosphatases with a highly conserved catalytic domain acts on thousands of protein targets to orchestrate myriad central biological roles. A major structural reorganization of human calcineurin, a ubiquitous Ser/Thr PPP regulated by calcium and calmodulin and targeted by immunosuppressant drugs cyclosporin A and FK506, is unveiled here. The new conformation involves trans- to cis- isomerization of proline in the SAPNY sequence, highly conserved across PPPs, and remodels the main regulatory site where NFATc transcription factors bind. Transitions between cis- and trans- conformations may involve peptidyl prolyl isomerases such as cyclophilin A and FKBP12, which are known to physically interact with and modulate calcineurin even in the absence of immunosuppressant drugs. Alternative conformations in PPPs provide a new perspective on interactions with substrates and other protein partners and may foster development of more specific inhibitors as drug candidates. PMID:26248042

  12. Conformational dynamics of peptide T molecule

    NASA Astrophysics Data System (ADS)

    Akverdieva, Gulnare; Godjayev, Niftali; Akyuz, Sevim

    2002-05-01

    Using a method of the theoretical conformational analysis, a conformational dynamics of the side chains of the amino acid residues of peptide T, a competitor of the human immuno-deficiency virus in the binding to human T cells, was investigated. For this purpose, the conformational maps of the potential surfaces were constructed over the angles of the side chains for the preferable conformations of peptide T molecule. Permissible deviations of these angles from the optimal values were determined. It has been found that the angles of the side chains of the amino acid residues involved in physiologically active fragment Thr4-Thr8 are more rigid than in the other segment of the molecule. This fact confirms the existence of such a regular structure as β-turn revealed previously in studies of the spatial structure of the peptide T molecule.

  13. Energy maps for glycosidic linkage conformations.

    PubMed

    French, Alfred D

    2015-01-01

    Glycosidic linkage conformations are the main factors in determining the shapes of disaccharide, oligosaccharide, and polysaccharide molecules. The conformations are expressed in terms of the torsion angles about the bonds from each ring of the disaccharide moiety to its glycosidic oxygen atom, and the probability of a given conformation is often expressed in terms of its free or potential energy. The energy surface or map for a disaccharide is a display of the energy plotted against the two torsion angles. Successful mapping allows a particular kind of energy calculation to provide the energy values for each conformation and avoids possible pitfalls. Although different methods are discussed, the main emphasis of this chapter is on the technical production of the maps and their exploitation in further understanding the shape of the molecule in question.

  14. The Conformational Behaviour of the Odorant Dihydrocarveol

    NASA Astrophysics Data System (ADS)

    Loru, Donatella; Jarman, Natasha; Sanz, M. Eugenia

    2016-06-01

    The odorant dihydrocarveol (C10H18O) has been investigated in the gas phase using a 2-8 GHz chirped-pulse Fourier transform microwave spectrometer. Dihydrocarveol was purchased as a mixture of n-, iso-, neo-, and neoiso- isomers. The sample was placed in a bespoke heating nozzle at about 85°C and seeded in Ne at 5 bar. Three conformers were observed and their rotational constants were determined. By comparing the experimental rotational constants with those calculated ab initio the three conformers were identified as belonging to n-dihydrocarveol. In all three conformers the isopropenyl group is in equatorial position with respect to the six-membered ring, and the OH group maintains the same configuration. The conformers differ in the orientation of the isopropenyl group.

  15. Conformational NMR Study of Bistriazolyl Anion Receptors.

    PubMed

    Makuc, Damjan; Merckx, Tamara; Dehaen, Wim; Plavec, Janez

    2016-01-01

    Conformational features of pyridine- and pyrimidine-based bistriazolyl anion receptors dissolved in acetonitrile-d3 were assessed by multidimensional, heteronuclear NMR spectroscopy. NOESY correlation signals suggested preorganization of both host molecules in solution in the absence of anions. In addition, only a single set of signals was observed in the 1H NMR spectra, which suggested a symmetrical conformation of anion receptors or their conformational exchange that is fast on the NMR time-scale. Furthermore, the predominant conformations of the pyridine- and pyrimidine-based anion receptors are preserved upon addition of chloride, bromide, and acetate anions. Chemical shift changes observed upon addition of anions showed that the NH (thio)urea and triazole protons are involved in anion-receptor interactions through hydrogen bonding. PMID:27640375

  16. Conformational Electroresistance and Hysteresis in Nanoclusters

    SciTech Connect

    Li, Xiangguo; Zhang, Xiaoguang; Cheng, Hai-Ping

    2014-07-02

    Among many mechanisms proposed for electroresistance, ones involving structural changes are the least understood because of challenges of controllability and repeatability. Yet structural changes can cause dramatic changes in electronic properties, leading to multiple ways in which conduction paths can be opened and closed, not limited to filament movement or variation in molecular conductance. Here we show at least another way: conformational dependence of the Coulomb charging energy of a nanocluster, where charging induced conformational distortion changes the blockade voltage, which in turn leads to a giant electroresistance. This intricate interplay between charging and conformation change is demonstrated in a nanocluster Zn3O4 by combining a first-principles calculation with a temperature dependent transport model. The predicted hysteretic Coulomb blockade staircase in the current-voltage curve adds another dimension to the rich phenomenon of tunneling electroresistance. The new mechanism also provides a better controlled and repeatable platform to study conformational electroresistance.

  17. Conformational Electroresistance and Hysteresis in Nanoclusters

    DOE PAGES

    Li, Xiangguo; Zhang, Xiaoguang; Cheng, Hai-Ping

    2014-07-02

    Among many mechanisms proposed for electroresistance, ones involving structural changes are the least understood because of challenges of controllability and repeatability. Yet structural changes can cause dramatic changes in electronic properties, leading to multiple ways in which conduction paths can be opened and closed, not limited to filament movement or variation in molecular conductance. Here we show at least another way: conformational dependence of the Coulomb charging energy of a nanocluster, where charging induced conformational distortion changes the blockade voltage, which in turn leads to a giant electroresistance. This intricate interplay between charging and conformation change is demonstrated in amore » nanocluster Zn3O4 by combining a first-principles calculation with a temperature dependent transport model. The predicted hysteretic Coulomb blockade staircase in the current-voltage curve adds another dimension to the rich phenomenon of tunneling electroresistance. The new mechanism also provides a better controlled and repeatable platform to study conformational electroresistance.« less

  18. Nanoporous films: From conventional to the conformal

    SciTech Connect

    Allendorf, Mark D.; Stavila, Vitalie

    2015-12-14

    Here, thin and continuous films of porous metal-organic frameworks can now be conformally deposited on various substrates using a vapor-phase synthesis approach that departs from conventional solution-based routes.

  19. Structure of The Planar Galilean Conformal Algebra

    NASA Astrophysics Data System (ADS)

    Gao, Shoulan; Liu, Dong; Pei, Yufeng

    2016-08-01

    In this paper, we compute the low-dimensional cohomology groups of the planar Galilean conformal algebra introduced by Bagchi and Goparkumar. Consequently we determine its derivations, central extensions, and automorphisms.

  20. Social conformity despite individual preferences for distinctiveness.

    PubMed

    Smaldino, Paul E; Epstein, Joshua M

    2015-03-01

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

  1. Theory of conformational transitions of viral shells

    NASA Astrophysics Data System (ADS)

    Guérin, Thomas; Bruinsma, Robijn

    2007-12-01

    We propose a continuum theory for the conformational transitions of viral shells. Conformational transitions of viral shells, as encountered during viral maturation, are associated with a soft mode instability of the capsid proteins [F. Tama and C. L. Brooks, J. Mol. Biol. 345(2), 299 (2005)]. The continuum theory presented here is an adaptation of the Ginzburg-Landau theory of soft-mode structural phase transitions of solids to viral shells. The theory predicts that the conformational transitions are characterized by a pronounced softening of the shell elasticity in the critical region. We demonstrate that the thermodynamics of the conformational transition can be probed quantitatively by a micromechanical atomic force microscope study. The external force can drive a capsid into a state of phase coexistence characterized by a highly nonlinear force deformation curve.

  2. Conformable apparatus in a drill string

    SciTech Connect

    Hall, David R.; Hall, Jr., H. Tracy; Pixton, David S.; Fox, Joe

    2007-08-28

    An apparatus in a drill string comprises an internally upset drill pipe. The drill pipe comprises a first end, a second end, and an elongate tube intermediate the first and second ends. The elongate tube and the ends comprising a continuous an inside surface with a plurality of diameters. A conformable metal tube is disposed within the drill pipe intermediate the ends thereof and terminating adjacent to the ends of the drill pipe. The conformable metal tube substantially conforms to the continuous inside surface of the metal tube. The metal tube may comprise a non-uniform section which is expanded to conform to the inside surface of the drill pipe. The non-uniform section may comprise protrusions selected from the group consisting of convolutions, corrugations, flutes, and dimples. The non-uniform section extends generally longitudinally along the length of the tube. The metal tube may be adapted to stretch as the drill pipes stretch.

  3. Présentation atypique d'une granulomatose avec polyangeite: à propos d'une observation pédiatrique

    PubMed Central

    Berriche, Olfa; Younes, Samia; Ammari, Wafa; Alaya, Wafa; Kessomtini, Wassia; Hammami, Sonia

    2015-01-01

    La granulomatose avec polyangéite (GPA) est une vascularite nécrosante systémique, caractérisée par une inflammation granulomateuse, une nécrose tissulaire et une vascularite touchant les vaisseaux de moyen et, surtout, de petit calibre, elle touche rarement l'enfant. PMID:26327978

  4. Scale-invariant breaking of conformal symmetry

    NASA Astrophysics Data System (ADS)

    Dymarsky, Anatoly; Zhiboedov, Alexander

    2015-10-01

    Known examples of unitary relativistic scale but not conformal-invariant field theories (SFTs) can be embedded into conventional conformal field theories (CFTs). We show that any SFT which is a subsector of a unitary CFT is a free theory. Our discussion applies to an arbitrary number of spacetime dimensions and explains triviality of known SFTs in four spacetime dimensions. We comment on examples of unitary SFTs which are not captured by our construction.

  5. On being loud and proud: non-conformity and counter-conformity to group norms.

    PubMed

    Hornsey, Matthew J; Majkut, Louise; Terry, Deborah J; McKimmie, Blake M

    2003-09-01

    Most experiments on conformity have been conducted in relation to judgments of physical reality; surprisingly few papers have experimentally examined the influence of group norms on social issues with a moral component. In response to this, participants were told that they were either in a minority or in a majority relative to their university group in terms of their attitudes toward recognition of gay couples in law (Expt 1: N = 205) and a government apology to Aborigines (Expt 2: N = 110). In both experiments, it was found that participants who had a weak moral basis for their attitude conformed to the group norm on private behaviours. In contrast, those who had a strong moral basis for their attitude showed non-conformity on private behaviours and counter-conformity on public behaviours. Incidences of non-conformity and counter-conformity are discussed with reference to theory and research on normative influence.

  6. Conformational properties of oxazoline-amino acids

    NASA Astrophysics Data System (ADS)

    Staś, Monika; Broda, Małgorzata A.; Siodłak, Dawid

    2016-04-01

    Oxazoline-amino acids (Xaa-Ozn) occur in natural peptides of potentially important bioactivity. The conformations of the model compounds: Ac-(S)-Ala-Ozn(4R-Me), Ac-(S)-Ala-Ozn(4S-Me), and (gauche+, gauche-, anti) Ac-(S)-Val-Ozn(4R-Me) were studied at meta-hybrid M06-2X/6-311++G(d,p) method including solvent effect. Boc-L-Ala-L-Ozn-4-COOMe and Boc-L-Val-L-Ozn-4-COOMe were synthesized and studied by FT-IR and NMR-NOE methods. The conformations in crystal state were gathered from the Cambridge Structural Data Base. The main conformational feature of the oxazoline amino acids is the conformation β2 (ϕ,ψ ∼ -161°, -6°), which predominates in weakly polar environment and still is accessible in polar surrounding. The changes of the conformational preferences towards the conformations αR (ϕ,ψ ∼ -70°, -15°) and then β (ϕ,ψ ∼ -57°, -155°) are observed with increase of the environment polarity.

  7. Controlling complex networks with conformity behavior

    NASA Astrophysics Data System (ADS)

    Wang, Xu-Wen; Nie, Sen; Wang, Wen-Xu; Wang, Bing-Hong

    2015-09-01

    Controlling complex networks accompanied by common conformity behavior is a fundamental problem in social and physical science. Conformity behavior that individuals tend to follow the majority in their neighborhood is common in human society and animal communities. Despite recent progress in understanding controllability of complex networks, the existent controllability theories cannot be directly applied to networks associated with conformity. Here we propose a simple model to incorporate conformity-based decision making into the evolution of a network system, which allows us to employ the exact controllability theory to explore the controllability of such systems. We offer rigorous theoretical results of controllability for representative regular networks. We also explore real networks in different fields and some typical model networks, finding some interesting results that are different from the predictions of structural and exact controllability theory in the absence of conformity. We finally present an example of steering a real social network to some target states to further validate our controllability theory and tools. Our work offers a more realistic understanding of network controllability with conformity behavior and can have potential applications in networked evolutionary games, opinion dynamics and many other complex networked systems.

  8. Measuring the mechanical properties of molecular conformers

    PubMed Central

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

    2015-01-01

    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. PMID:26388232

  9. Beyond conformity: Social influences on pain reports and physiology.

    PubMed

    Koban, Leonie; Wager, Tor D

    2016-02-01

    Social information can profoundly influence behavior, but its effects are often explained in terms of "conformity," implying effects on decision-making and communication rather than deeper sensory modulation. We examined whether information about other people's pain reports affected both participants' pain experience and skin conductance responses (SCR) during pain. Sixty volunteers experienced painful heat stimulation preceded by 2 kinds of informational cues: (a) nonreinforced social information indicating low or high pain ratings from previous participants; and (b) reinforced conditioned stimuli (CSlow, CShigh). Both high-pain social information and CShigh cues enhanced pain and SCRs relative to their respective controls, with particularly robust effects of social information. Effects of both manipulations on both pain and SCRs were mediated by trial-by-trial pain expectancies. These results demonstrate strong social influences on pain and autonomic responses, and suggest that expectations from multiple sources can influence pain physiology independent of reinforcement. PMID:26322566

  10. A Conformance Test Suite for Arden Syntax Compilers and Interpreters.

    PubMed

    Wolf, Klaus-Hendrik; Klimek, Mike

    2016-01-01

    The Arden Syntax for Medical Logic Modules is a standardized and well-established programming language to represent medical knowledge. To test the compliance level of existing compilers and interpreters no public test suite exists. This paper presents the research to transform the specification into a set of unit tests, represented in JUnit. It further reports on the utilization of the test suite testing four different Arden Syntax processors. The presented and compared results reveal the status conformance of the tested processors. How test driven development of Arden Syntax processors can help increasing the compliance with the standard is described with two examples. In the end some considerations how an open source test suite can improve the development and distribution of the Arden Syntax are presented. PMID:27577408

  11. Beyond conformity: Social influences on pain reports and physiology.

    PubMed

    Koban, Leonie; Wager, Tor D

    2016-02-01

    Social information can profoundly influence behavior, but its effects are often explained in terms of "conformity," implying effects on decision-making and communication rather than deeper sensory modulation. We examined whether information about other people's pain reports affected both participants' pain experience and skin conductance responses (SCR) during pain. Sixty volunteers experienced painful heat stimulation preceded by 2 kinds of informational cues: (a) nonreinforced social information indicating low or high pain ratings from previous participants; and (b) reinforced conditioned stimuli (CSlow, CShigh). Both high-pain social information and CShigh cues enhanced pain and SCRs relative to their respective controls, with particularly robust effects of social information. Effects of both manipulations on both pain and SCRs were mediated by trial-by-trial pain expectancies. These results demonstrate strong social influences on pain and autonomic responses, and suggest that expectations from multiple sources can influence pain physiology independent of reinforcement.

  12. Conformational mimicry in Alzheimer's disease. Role of apolipoproteins in amyloidogenesis.

    PubMed Central

    Wisniewski, T.; Golabek, A. A.; Kida, E.; Wisniewski, K. E.; Frangione, B.

    1995-01-01

    Several apolipoproteins are known to be closely associated with amyloid fibrillogenesis. Serum amyloid A, apolipoprotein (apo) AII and apo A1 are each deposited as biochemically distinct forms of amyloid. Late-onset Alzheimer's disease is linked to one isotype of apo E, apo E4. Apo E and apo E4 in particular have been shown to modulate amyloid fibril formation by amyloid-beta peptides in vitro. Furthermore, the carboxy terminus of apo E has been shown to be a constituent of plaque amyloid. We show immunohistochemically and electron microscopically the presence of apo A1 in senile plaques. The intact apo A1 can itself form amyloid-like fibrils in vitro that are Congo Red positive. We propose that some proteins when misfolded can propagate this misfolding to identical units, either autocatalytically or to other proteins that are induced to fold into the same abnormal conformation. This conformational mimicry may initiate and/or augment fibrillogenesis in Alzheimer's disease. Images Figure 1 Figure 3 Figure 2 PMID:7639323

  13. Probing the Conformation of the Fibronectin III1–2 Domain by Fluorescence Resonance Energy Transfer*S⃞

    PubMed Central

    Karuri, Nancy W.; Lin, Zong; Rye, Hays S.; Schwarzbauer, Jean E.

    2009-01-01

    Fibronectin (FN) matrix is crucial for cell and tissue functions during embryonic development, wound healing, and oncogenesis. Assembly of FN matrix fibrils requires FN domains that mediate interactions with integrin receptors and with other FN molecules. In addition, regulation of FN matrix assembly depends on the first two FN type III modules, III1 and III2, which harbor FN-binding sites. We propose that interactions between these two modules sequester FN-binding sites in soluble FN and that these sites become exposed by FN conformational changes during assembly. To test the idea that III1–2 has a compact conformation, we constructed CIIIY, a conformational sensor of III1–2 based on fluorescent resonance energy transfer between cyan and yellow fluorescent proteins conjugated at its N and C termini. We demonstrate energy transfer in CIIIY and show that fluorescent resonance energy transfer was eliminated by proteolysis and by treatment with mild denaturants that disrupted intramolecular interactions between the two modules. We also show that mutations of key charged residues resulted in conformational changes that exposed binding sites for the N-terminal 70-kDa FN fragment. Collectively, these results support a conformation-dependent mechanism for the regulation of FN matrix assembly by III1–2. PMID:19064996

  14. Stabilization of the conductive conformation of a voltage-gated K+ (Kv) channel: the lid mechanism.

    PubMed

    Santos, Jose S; Syeda, Ruhma; Montal, Mauricio

    2013-06-01

    Voltage-gated K(+) (Kv) channels are molecular switches that sense membrane potential and in response open to allow K(+) ions to diffuse out of the cell. In these proteins, sensor and pore belong to two distinct structural modules. We previously showed that the pore module alone is a robust yet dynamic structural unit in lipid membranes and that it senses potential and gates open to conduct K(+) with unchanged fidelity. The implication is that the voltage sensitivity of K(+) channels is not solely encoded in the sensor. Given that the coupling between sensor and pore remains elusive, we asked whether it is then possible to convert a pore module characterized by brief openings into a conductor with a prolonged lifetime in the open state. The strategy involves selected probes targeted to the filter gate of the channel aiming to modulate the probability of the channel being open assayed by single channel recordings from the sensorless pore module reconstituted in lipid bilayers. Here we show that the premature closing of the pore is bypassed by association of the filter gate with two novel open conformation stabilizers: an antidepressant and a peptide toxin known to act selectively on Kv channels. Such stabilization of the conductive conformation of the channel is faithfully mimicked by the covalent attachment of fluorescein at a cysteine residue selectively introduced near the filter gate. This modulation prolongs the occupancy of permeant ions at the gate. It is this longer embrace between ion and gate that we conjecture underlies the observed stabilization of the conductive conformation. This study provides a new way of thinking about gating.

  15. Conformal Radiotherapy in the Treatment of Advanced Juvenile Nasopharyngeal Angiofibroma With Intracranial Extension: An Institutional Experience

    SciTech Connect

    Chakraborty, Santam; Ghoshal, Sushmita; Patil, Vijay Maruti; Oinam, Arun Singh; Sharma, Suresh C.

    2011-08-01

    Purpose: To describe the results of conformal radiotherapy in advanced juvenile nasopharyngeal angiofibroma in a tertiary care institution. Methods and Materials: Retrospective chart review was conducted for 8 patients treated with conformal radiotherapy between 2006 and 2009. The median follow-up was 17 months. All patients had Stage IIIB disease with intracranial extension. Radiotherapy was considered as treatment because patients were deemed inoperable owing to extensive intracranial/intraorbital extension or proximity to optic nerve. All but 1 patient were treated with intensity-modulated radiotherapy using seven coplanar fields. Median (range) dose prescribed was 39.6 (30-46) Gy. Actuarial analysis of local control and descriptive analysis of toxicity profile was conducted. Results: Despite the large and complex target volume (median planning target volume, 292 cm{sup 3}), intensity-modulated radiotherapy achieved conformal dose distributions (median van't Reit index, 0.66). Significant sparing of the surrounding organs at risk was obtained. No significant Grade 3/4 toxicities were experienced during or after treatment. Actual local control at 2 years was 87.5%. One patient died 1 month after radiotherapy secondary to massive epistaxis. The remaining 7 patients had progressive resolution of disease and were symptom-free at last follow-up. Persistent rhinitis was the only significant toxicity, seen in 1 patient. Conclusions: Conformal radiotherapy results in good local control with minimal acute and late side effects in juvenile nasopharyngeal angiofibromas, even in the presence of advanced disease.

  16. Firefighting Module

    NASA Astrophysics Data System (ADS)

    1981-01-01

    Aviation Power Supply's mobile firefighting module called Firefly II is mounted on a trailer pulled by a pickup truck. Trailer unit has two three- inch water cannons, and the pickup carries a six inch cannon. Completely self contained, module pumps 3,000 gallons of water a minute from hydrants or open bodies of water. Stream can go as far as 400 feet or can be employed in a high-loft mode to reach the tops of tall refinery towers. Compact Firefly II weighs only 2,500 pounds when fully fueled. Key component is a specially designed two stage pump. Power for the pump is generated by a gas turbine engine. Module also includes an electronic/pump controller, multiple hose connections, up to 1,500 feet of hose and fuel for four hours operation. Firefly trailer can be backed onto specially-built large fireboat.

  17. Firefighting Module

    NASA Astrophysics Data System (ADS)

    1980-01-01

    Aviation Power Supply's mobile firefighting module called Firefly II is mounted on a trailer pulled by a pickup truck. Trailer unit has two three- inch water cannons, and the pickup carries a six inch cannon. Completely self contained, module pumps 3,000 gallons of water a minute from hydrants or open bodies of water. Stream can go as far as 400 feet or can be employed in a high-loft mode to reach the tops of tall refinery towers. Compact Firefly II weighs only 2,500 pounds when fully fueled. Key component is a specially designed two stage pump. Power for the pump is generated by a gas turbine engine. Module also includes an electronic/pump controller, multiple hose connections, up to 1,500 feet of hose and fuel for four hours operation. Firefly trailer can be backed onto specially-built large fireboat.

  18. Lightweight flexible rooftop PV module

    SciTech Connect

    Izu, M.; Ovshinsky, H.C.; Whelan, K.

    1994-12-31

    Energy Conversion Devices, Inc. (ECD) and United Solar Systems Corp. (United Solar) are developing lightweight, flexible photovoltaic modules that can replace conventional roofing materials and be economically and aesthetically integrated into residential and commercial buildings. The modules will be fabricated from high-efficiency multi-junction a-Si alloy solar cells developed by ECD and United Solar. These cells are produced on thin, flexible, stainless steel substrates. Two types of products 1 ft by 10 ft overlapping PV shingles and 1.3 ft by 20 ft PV roof panels are being developed by United Solar and ECD, respectively. United Solar`s shingle type design uses a roof mounting procedures similar to those used with conventional asphalt shingles, while ECD`s PV panel uses mounting procedures conforming to metal roof systems. Thus, they can be installed on roof sheathings, replacing ordinary shingles or metal roofing panels, on a standard wood roof construction.

  19. Thermionic modules

    DOEpatents

    King, Donald B.; Sadwick, Laurence P.; Wernsman, Bernard R.

    2002-06-18

    Modules of assembled microminiature thermionic converters (MTCs) having high energy-conversion efficiencies and variable operating temperatures manufactured using MEMS manufacturing techniques including chemical vapor deposition. The MTCs incorporate cathode to anode spacing of about 1 micron or less and use cathode and anode materials having work functions ranging from about 1 eV to about 3 eV. The MTCs also exhibit maximum efficiencies of just under 30%, and thousands of the devices and modules can be fabricated at modest costs.

  20. Quantum/molecular mechanics study of firefly bioluminescence on luciferase oxidative conformation

    NASA Astrophysics Data System (ADS)

    Pinto da Silva, Luís; Esteves da Silva, Joaquim C. G.

    2014-07-01

    This is the first report of a computational study of the color tuning mechanism of firefly bioluminescence, using the oxidative conformation of luciferase. The results of these calculations demonstrated that the electrostatic field generated by luciferase is fundamental both for the emission shift and efficiency. Further calculations indicated that a shift in emission is achieved by modulating the energy, at different degrees, of the emissive and ground states. These differences in energy modulation will then lead to changes in the energy gap between the states.

  1. The impact of N-terminal phosphorylation on LHCII conformation in state transition

    NASA Astrophysics Data System (ADS)

    Ding, Jin-Hong; Li, Ning; Wang, Man-Liu; Zhang, Yan; Lü, Shou-Qin; Long, Mian

    2014-06-01

    State transition is an important protection mechanism of plants for maintaining optimal efficiency through redistributing unbalanced excitation energy between photo-system II (PSII) and photosystem I (PSI). This process depends on the reversible phosphorylation/dephosphorylation of the major light-harvesting complex II (LHCII) and its bi-directional migration between PSII and PSI. But it remains unclear how phosphorylation/dephosphorylation modulates the LHCII conformation and further regulates its reversible migration. Here molecular dynamics simulations (MDS) were employed to elucidate the impact of phosphorylation on LHCII conformation. The results indicated that N-terminal phosphorylation loosened LHCII trimer with decreased hydrogen bond (H-bond) interactions and extended the distances between neighboring monomers, which stemmed from the conformational adjustment of each monomer itself. Global conformational change of LHCII monomer started from its stromal Nterminal (including the phosphorylation sites) by enhancing its interaction to lipid membrane and by adjusting the interaction network with surrounded inter-monomer and intra-monomer transmembrane helixes of B, C, and A, and finally triggered the reorientation of transmembrane helixes and transferred the conformational change to luminal side helixes and loops. These results further our understanding in molecular mechanism of LHCII migration during state transition from the phosphorylation-induced microstructural feature of LHCII.

  2. Spin labeling and Double Electron-Electron Resonance (DEER) to Deconstruct Conformational Ensembles of HIV Protease

    PubMed Central

    Casey, Thomas M.; Fanucci, Gail E.

    2016-01-01

    An understanding of macromolecular conformational equilibrium in biological systems is oftentimes essential to understand function, dysfunction, and disease. For the past few years, our lab has been utilizing site-directed spin labeling (SDSL), coupled with electron paramagnetic resonance (EPR) spectroscopy, to characterize the conformational ensemble and ligand-induced conformational shifts of HIV-1 protease (HIV-1PR). The biomedical importance of characterizing the fractional occupancy of states within the conformational ensemble critically impacts our hypothesis of a conformational selection mechanism of drug-resistance evolution in HIV-1PR. The purpose of the following chapter is to give a timeline perspective of our SDSL EPR approach to characterizing conformational sampling of HIV-1PR. We provide detailed instructions for the procedure utilized in analyzing distance profiles for HIV-1PR obtained from pulsed electron–electron double resonance (PELDOR). Specifically, we employ a version of PELDOR known as double electron–electron resonance (DEER). Data are processed with the software package “DeerAnalysis” (http://www.epr.ethz.ch/software), which implements Tikhonov regularization (TKR), to generate a distance profile from electron spin-echo amplitude modulations. We assign meaning to resultant distance profiles based upon a conformational sampling model, which is described herein. The TKR distance profiles are reconstructed with a linear combination of Gaussian functions, which is then statistically analyzed. In general, DEER has proven powerful for observing structural ensembles in proteins and, more recently, nucleic acids. Our goal is to present our advances in order to aid readers in similar applications. PMID:26477251

  3. Ion mobility-mass spectrometry of a rotary ATPase reveals ATP-induced reduction in conformational flexibility

    NASA Astrophysics Data System (ADS)

    Zhou, Min; Politis, Argyris; Davies, Roberta B.; Liko, Idlir; Wu, Kuan-Jung; Stewart, Alastair G.; Stock, Daniela; Robinson, Carol V.

    2014-03-01

    Rotary ATPases play fundamental roles in energy conversion as their catalytic rotation is associated with interdomain fluctuations and heterogeneity of conformational states. Using ion mobility mass spectrometry we compared the conformational dynamics of the intact ATPase from Thermus thermophilus with those of its membrane and soluble subcomplexes. Our results define regions with enhanced flexibility assigned to distinct subunits within the overall assembly. To provide a structural context for our experimental data we performed molecular dynamics simulations and observed conformational changes of the peripheral stalks that reflect their intrinsic flexibility. By isolating complexes at different phases of cell growth and manipulating nucleotides, metal ions and pH during isolation, we reveal differences that can be related to conformational changes in the Vo complex triggered by ATP binding. Together these results implicate nucleotides in modulating flexibility of the stator components and uncover mechanistic detail that underlies operation and regulation in the context of the holoenzyme.

  4. Ion mobility-mass spectrometry of a rotary ATPase reveals ATP-induced reduction in conformational flexibility.

    PubMed

    Zhou, Min; Politis, Argyris; Davies, Roberta B; Liko, Idlir; Wu, Kuan-Jung; Stewart, Alastair G; Stock, Daniela; Robinson, Carol V

    2014-03-01

    Rotary ATPases play fundamental roles in energy conversion as their catalytic rotation is associated with interdomain fluctuations and heterogeneity of conformational states. Using ion mobility mass spectrometry we compared the conformational dynamics of the intact ATPase from Thermus thermophilus with those of its membrane and soluble subcomplexes. Our results define regions with enhanced flexibility assigned to distinct subunits within the overall assembly. To provide a structural context for our experimental data we performed molecular dynamics simulations and observed conformational changes of the peripheral stalks that reflect their intrinsic flexibility. By isolating complexes at different phases of cell growth and manipulating nucleotides, metal ions and pH during isolation, we reveal differences that can be related to conformational changes in the Vo complex triggered by ATP binding. Together these results implicate nucleotides in modulating flexibility of the stator components and uncover mechanistic detail that underlies operation and regulation in the context of the holoenzyme.

  5. The Relationship between Creativity and Conformity among Preschool Children.

    ERIC Educational Resources Information Center

    Van Hook, Cheryl W.; Tegano, Deborah W.

    2002-01-01

    This study investigated the relationship between creativity and conformity (social conformity and impersonal conformity) with 45 preschool children. Findings support the hypothesis that highly conforming and highly nonconforming children do not score as highly on creativity measurements as children in the freedom of expression group (i.e., not…

  6. 47 CFR 2.906 - Declaration of Conformity.

    Code of Federal Regulations, 2010 CFR

    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...

  7. Fluorine Substitution in Neurotransmitters: Microwave Spectroscopy and Modelling of the Conformational Space and Non Bonding Interactions

    NASA Astrophysics Data System (ADS)

    Melandri, S.; Maris, A.; Merloni, A.

    2011-06-01

    Fluorine substitution in molecules is a common practice in bio-organic chemistry in order to modulate physicochemical properties and biological activity of molecules and an increasing number of drugs on the market contain fluorine, the presence of which is often of major importance to modify pharmacokinetics properties and molecular activity. The rationale for such a strategy is that fluorine is generally a stronger electron acceptor than the other halogen atoms and its size is intermediate between that of hydrogen and oxygen. We have studied two fluorinated analogs of 2-phenylethylamine (PEA), the prototype molecule for adrenergic neurotransmitters, namely: 4-Fluoro (4FPEA) and 2-Fluoro-2-phenylethylamine (2FPEA) by Molecular Beam Fourier Transform Microwave Spectroscopy in the frequency range 6-18 GHz and ab initio calculations at the MP2/6311++G** level. The aim is to obtain information on the spatial arrangement of the ethylamine side chain and the effects of fluorination on the energy landscape. The conformational space is dominated by low energy gauche conformations stabilized by weak interactions between the aminic hydrogens and the electron cloud of the benzene ring and anti conformations higher in energy. In 2FPEA the presence of the fluorine atom almost duplicate the number of possible conformation with respect to 4FPEA. We observed two conformers of 4FPEA and five conformers of 2FPEA which have been classified with the guide provided by accurate ab initio calculations. The identification of the conformational species was helped by the analysis of the quadrupole hyperfine pattern which is greatly influenced by the orientation of the amino group and acts as a fingerprint for each conformation. The orientation of the dipole moment within the principal axis frame and the order of stability of the different conformations are other independent pieces of evidence for the unambiguous assignment and identification of the conformers. The order of stability was

  8. Arcjet Testing of Advanced Conformal Ablative TPS

    NASA Technical Reports Server (NTRS)

    Gasch, Matthew; Beck, Robin; Agrawal, Parul

    2014-01-01

    A conformable TPS over a rigid aeroshell has the potential to solve a number of challenges faced by traditional rigid TPS materials (such as tiled Phenolic Impregnated Carbon Ablator (PICA) system on MSL. The compliant (high strain to failure) nature of the conformable ablative materials will allow integration of the TPS with the underlying aeroshell structure much easier and enable monolithic-like configuration and larger segments (or parts) to be used. In May of 2013 the CA250 project executed an arcjet test series in the Ames IHF facility to evaluate a phenolic-based conformal system (named Conformal-PICA) over a range of test conditions from 40-400Wcm2. The test series consisted of four runs in the 13-inch diameter nozzle. Test models were based on SPRITE configuration (a 55-deg sphere cone), as it was able to provide a combination of required heat flux, pressure and shear within a single entry. The preliminary in-depth TC data acquired during that test series allowed a mid-fidelity thermal response model for conformal-PICA to be created while testing of seam models began to address TPS attachment and joining of multiple segments for future fabrication of large-scale aeroshells. Discussed in this paper are the results.

  9. Conformational phases of membrane bound cytoskeletal filaments

    NASA Astrophysics Data System (ADS)

    Quint, David A.; Grason, Gregory; Gopinathan, Ajay

    2013-03-01

    Membrane bound cytoskeletal filaments found in living cells are employed to carry out many types of activities including cellular division, rigidity and transport. When these biopolymers are bound to a membrane surface they may take on highly non-trivial conformations as compared to when they are not bound. This leads to the natural question; What are the important interactions which drive these polymers to particular conformations when they are bound to a surface? Assuming that there are binding domains along the polymer which follow a periodic helical structure set by the natural monomeric handedness, these bound conformations must arise from the interplay of the intrinsic monomeric helicity and membrane binding. To probe this question, we study a continuous model of an elastic filament with intrinsic helicity and map out the conformational phases of this filament for various mechanical and structural parameters in our model, such as elastic stiffness and intrinsic twist of the filament. Our model allows us to gain insight into the possible mechanisms which drive real biopolymers such as actin and tubulin in eukaryotes and their prokaryotic cousins MreB and FtsZ to take on their functional conformations within living cells.

  10. Seed conformal blocks in 4D CFT

    NASA Astrophysics Data System (ADS)

    Echeverri, Alejandro Castedo; Elkhidir, Emtinan; Karateev, Denis; Serone, Marco

    2016-02-01

    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, overline{ℓ} ) of the Lorentz group in four dimensional conformal field theories. These blocks arise from 4-point functions involving two scalars, one (0, | ℓ - overline{7ell;} |) and one (| ℓ - overline{ℓ} |, 0) spinors or tensors. We directly solve the set of Casimir equations, that can elegantly be written in a compact form for any ( ℓ, overline{ℓ} ), 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 - overline{ℓ} | 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.

  11. Global attractors of complete conformal foliations

    SciTech Connect

    Zhukova, Nina I

    2012-03-31

    We prove that every complete conformal foliation (M,F) of codimension q{>=}3 is either Riemannian or a (Conf(S{sup q}), S{sup q})-foliation. We further prove that if (M,F) is not Riemannian, it has a global attractor which is either a nontrivial minimal set or a closed leaf or a union of two closed leaves. In this theorem we do not assume that the manifold M is compact. In particular, every proper conformal non-Riemannian foliation (M,F) has a global attractor which is either a closed leaf or a union of two closed leaves, and the space of all nonclosed leaves is a connected q-dimensional orbifold. We show that every countable group of conformal transformations of the sphere S{sup q} can be realized as the global holonomy group of a complete conformal foliation. Examples of complete conformal foliations with exceptional and exotic minimal sets as global attractors are constructed. Bibliography: 20 titles.

  12. Evolution of Conformity in Social Dilemmas.

    PubMed

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

    2015-01-01

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

  13. Predicting order of conformational changes during protein conformational transitions using an interpolated elastic network model.

    PubMed

    Tekpinar, Mustafa; Zheng, Wenjun

    2010-08-15

    The decryption of sequence of structural events during protein conformational transitions is essential to a detailed understanding of molecular functions of various biological nanomachines. Coarse-grained models have proven useful by allowing highly efficient simulations of protein conformational dynamics. By combining two coarse-grained elastic network models constructed based on the beginning and end conformations of a transition, we have developed an interpolated elastic network model to generate a transition pathway between the two protein conformations. For validation, we have predicted the order of local and global conformational changes during key ATP-driven transitions in three important biological nanomachines (myosin, F(1) ATPase and chaperonin GroEL). We have found that the local conformational change associated with the closing of active site precedes the global conformational change leading to mechanical motions. Our finding is in good agreement with the distribution of intermediate experimental structures, and it supports the importance of local motions at active site to drive or gate various conformational transitions underlying the workings of a diverse range of biological nanomachines.

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

    NASA Astrophysics Data System (ADS)

    Maxwell, David

    2014-07-01

    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.

  15. Conformation and hydrogen ion titration of proteins: a continuum electrostatic model with conformational flexibility.

    PubMed Central

    You, T J; Bashford, D

    1995-01-01

    A new method for including local conformational flexibility in calculations of the hydrogen ion titration of proteins using macroscopic electrostatic models is presented. Intrinsic pKa values and electrostatic interactions between titrating sites are calculated from an ensemble of conformers in which the positions of titrating side chains are systematically varied. The method is applied to the Asp, Glu, and Tyr residues of hen lysozyme. The effects of different minimization and/or sampling protocols for both single-conformer and multi-conformer calculations are studied. For single-conformer calculations it is found that the results are sensitive to the choice of all-hydrogen versus polar-hydrogen-only atomic models and to the minimization protocol chosen. The best overall agreement of single-conformer calculations with experiment is obtained with an all-hydrogen model and either a two-step minimization process or minimization using a high dielectric constant. Multi-conformational calculations give significantly improved agreement with experiment, slightly smaller shifts between model compound pKa values and calculated intrinsic pKa values, and reduced sensitivity of the intrinsic pKa calculations to the initial details of the structure compared to single-conformer calculations. The extent of these improvements depends on the type of minimization used during the generation of conformers, with more extensive minimization giving greater improvements. The ordering of the titrations of the active-site residues, Glu-35 and Asp-52, is particularly sensitive to the minimization and sampling protocols used. The balance of strong site-site interactions in the active site suggests a need for including site-site conformational correlations. Images FIGURE 1 PMID:8580316

  16. Supersymmetric extension of Galilean conformal algebras

    SciTech Connect

    Bagchi, Arjun; Mandal, Ipsita

    2009-10-15

    The Galilean conformal algebra has recently been realized in the study of the nonrelativistic limit of the AdS/CFT conjecture. This was obtained by a systematic parametric group contraction of the parent relativistic conformal field theory. In this paper, we extend the analysis to include supersymmetry. We work at the level of the coordinates in superspace to construct the N=1 super-Galilean conformal algebra. One of the interesting outcomes of the analysis is that one is able to naturally extend the finite algebra to an infinite one. This looks structurally similar to the N=1 superconformal algebra in two dimensions, but is different. We also comment on the extension of our construction to cases of higher N.

  17. Causality constraints in conformal field theory

    NASA Astrophysics Data System (ADS)

    Hartman, Thomas; Jain, Sachin; Kundu, Sandipan

    2016-05-01

    Causality places nontrivial constraints on QFT in Lorentzian signature, for example fixing the signs of certain terms in the low energy Lagrangian. In d dimensional conformal field theory, we show how such constraints are encoded in crossing symmetry of Euclidean correlators, and derive analogous constraints directly from the conformal bootstrap (analytically). The bootstrap setup is a Lorentzian four-point function corresponding to propagation through a shockwave. Crossing symmetry fixes the signs of certain log terms that appear in the conformal block expansion, which constrains the interactions of low-lying operators. As an application, we use the bootstrap to rederive the well known sign constraint on the (∂ ϕ)4 coupling in effective field theory, from a dual CFT. We also find constraints on theories with higher spin conserved currents. Our analysis is restricted to scalar correlators, but we argue that similar methods should also impose nontrivial constraints on the interactions of spinning operators.

  18. Spectral Analysis of a Protein Conformational Switch

    NASA Astrophysics Data System (ADS)

    Rackovsky, S.

    2011-06-01

    The existence of conformational switching in proteins, induced by single amino acid mutations, presents an important challenge to our understanding of the physics of protein folding. Sequence-local methods, commonly used to detect structural homology, are incapable of accounting for this phenomenon. We examine a set of proteins, derived from the GA and GB domains of Streptococcus protein G, which are known to show a dramatic conformational change as a result of single-residue replacement. It is shown that these sequences, which are almost identical locally, can have very different global patterns of physical properties. These differences are consistent with the observed complete change in conformation. These results suggest that sequence-local methods for identifying structural homology can be misleading. They point to the importance of global sequence analysis in understanding sequence-structure relationships.

  19. Conformal coatings : challenging environments lead to growth.

    SciTech Connect

    Challener, Cynthia A.

    2005-08-01

    Advances in technology have resulted in the need for electronic devices to continue functioning even when placed in harsh environments. Widespread use of cell phones, laptop computers, and other personal electronic devices, the increased number of electronic controls in home appliances, and the ever more extensive utilization of digital technology in the automotive industry have led to a growing demand for printed circuit boards (PCBs) that can perform under difficult conditions. Conformal coatings provide a protective barrier that enables the PCBs to function in these demanding environments. This growth in demand comes despite the cost and numerous difficulties associated with the application of these coatings. Many conformal coatings manufacturers are investing in the development of new technologies that minimize these difficulties. Others are involved in developing disruptive technologies that will serve as alternatives to traditional conformal coatings processes.

  20. Understanding Modern Magnets through Conformal Mapping

    SciTech Connect

    Halbach, K.

    1989-10-27

    When I had to choose, within some narrow range, the topic of this paper, I received great help from a colleague in Berkeley and from Prof. Little when it was suggested that I should pick among the possible subjects of my talk the subject that Prof. Bloch would have enjoyed most. Since Prof. Bloch would prefer a scalpel over a sword every time, I hope and think that most people will approve my choice. When one intends to talk about a subject that is as old as conformal mapping and one does not want to lose the audience in a very short time, it is advisable to start by explaining both the motivation for the talk as well as the goals one has in mind when giving the talk. This particular talk has been motivated by the increasing frequency with which one hears, from people that ought to know better, statements like: 'Conformal mapping is really a thing of the past because of all the marvelous computer programs that we now have'. Even though, or more likely because, I have been intimately involved in the development of some large and widely used computer codes, I am deeply disturbed by such statements since they indicate a severe lack of understanding of the purpose of conformal mapping techniques, computers, and computer codes. In my view, conformal mapping can be an extremely powerful computational technique, and the easy availability of computers has made that aspect even more important now than it has been in the past. Additionally, and more importantly, conformal mapping can give very deep and unique insight into problems, giving often solutions to problems that can not be obtained with any other method, in particular not with computers. Wanting to demonstrate in particular the latter part, I set myself two goals for this talk: (1) 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

  1. Logarithm conformal mapping brings the cloaking effect

    PubMed Central

    Xu, Lin; Chen, Huanyang

    2014-01-01

    Over the past years, invisibility cloaks have been extensively discussed since transformation optics emerges. Generally, the electromagnetic parameters of invisibility cloaks are complicated tensors, yet difficult to realize. As a special method of transformation optics, conformal mapping helps us design invisibility cloak with isotropic materials of a refractive index distribution. However, for all proposed isotropic cloaks, the refractive index range is at such a breadth that challenges current experimental fabrication. In this work, we propose two new kinds of logarithm conformal mappings for invisible device designs. For one of the mappings, the refractive index distribution of conformal cloak varies from 0 to 9.839, which is more feasible for future implementation. Numerical simulations by using finite element method are performed to confirm the theoretical analysis. PMID:25359138

  2. Logarithm conformal mapping brings the cloaking effect.

    PubMed

    Xu, Lin; Chen, Huanyang

    2014-01-01

    Over the past years, invisibility cloaks have been extensively discussed since transformation optics emerges. Generally, the electromagnetic parameters of invisibility cloaks are complicated tensors, yet difficult to realize. As a special method of transformation optics, conformal mapping helps us design invisibility cloak with isotropic materials of a refractive index distribution. However, for all proposed isotropic cloaks, the refractive index range is at such a breadth that challenges current experimental fabrication. In this work, we propose two new kinds of logarithm conformal mappings for invisible device designs. For one of the mappings, the refractive index distribution of conformal cloak varies from 0 to 9.839, which is more feasible for future implementation. Numerical simulations by using finite element method are performed to confirm the theoretical analysis. PMID:25359138

  3. Marginal breaking of conformal SUSY QCD

    NASA Astrophysics Data System (ADS)

    Cleary, Kevin F.; Terning, John

    2016-07-01

    We provide an example of a 4D theory that exhibits the Contino-Pomarol-Rattazzi mechanism, where breaking conformal symmetry by an almost marginal operator leads to a light pseudo-Goldstone boson, the dilaton, and a parametrically suppressed contribution to vacuum energy. We consider SUSY QCD at the edge of the conformal window and break conformal symmetry by weakly gauging a subgroup of the flavor symmetry. Using Seiberg duality we show that for a range of parameters the singlet meson in the dual theory reaches the unitarity bound, however, this theory does not have a stable vacuum. We stabilize the vacuum with soft breaking terms, compute the mass of the dilaton, and determine the range of parameters where the leading contribution to the dilaton mass is from the almost marginal coupling.

  4. The conforming brain and deontological resolve.

    PubMed

    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.

  5. Logarithm conformal mapping brings the cloaking effect

    NASA Astrophysics Data System (ADS)

    Xu, Lin; Chen, Huanyang

    2014-10-01

    Over the past years, invisibility cloaks have been extensively discussed since transformation optics emerges. Generally, the electromagnetic parameters of invisibility cloaks are complicated tensors, yet difficult to realize. As a special method of transformation optics, conformal mapping helps us design invisibility cloak with isotropic materials of a refractive index distribution. However, for all proposed isotropic cloaks, the refractive index range is at such a breadth that challenges current experimental fabrication. In this work, we propose two new kinds of logarithm conformal mappings for invisible device designs. For one of the mappings, the refractive index distribution of conformal cloak varies from 0 to 9.839, which is more feasible for future implementation. Numerical simulations by using finite element method are performed to confirm the theoretical analysis.

  6. Hidden conformal symmetry and quasinormal modes

    NASA Astrophysics Data System (ADS)

    Chen, Bin; Long, Jiang

    2010-12-01

    We provide an algebraic way to calculate the quasinormal modes of a black hole, which possesses a hidden conformal symmetry. We construct an infinite tower of quasinormal modes from the highest-weight mode, in a simple and elegant way. For the scalar, the hidden conformal symmetry manifests itself in the fact that the scalar Laplacian could be rewritten in terms of the SL(2,R) quadratic Casimir. For the vector and the tensor, the hidden conformal symmetry acts on them through Lie derivatives. We show that for three-dimensional black holes, with an appropriate combination of the components, the radial equations of the vector and the tensor could be written in terms of the Lie-induced quadratic Casimir. This makes the algebraic construction of the quasinormal modes feasible. Our results are in good agreement with the previous study.

  7. Infrared modification of gravity from conformal symmetry

    NASA Astrophysics Data System (ADS)

    Gegenberg, Jack; Rahmati, Shohreh; Seahra, Sanjeev S.

    2016-03-01

    We reconsider a gauge theory of gravity in which the gauge group is the conformal group SO(4,2), and the action is of the Yang-Mills form, quadratic in the curvature. The resulting gravitational theory exhibits local conformal symmetry and reduces to Weyl-squared gravity under certain conditions. When the theory is linearized about flat spacetime, we find that matter which couples to the generators of special conformal transformations reproduces Newton's inverse square law. Conversely, matter which couples to generators of translations induces a constant and possibly repulsive force far from the source, which may be relevant for explaining the late-time acceleration of the Universe. The coupling constant of the theory is dimensionless, which means that it is potentially renormalizable.

  8. Silence et divulgation dans des familles d’adolescents vivant avec le VIH depuis la naissance : une exploration qualitative

    PubMed Central

    Proulx-Boucher, Karène; Blais, Martin; Fernet, Mylène; Richard, Marie-Ève; Otis, Joanne; Josy Lévy, Joseph; Samson, Johanne; Lapointe, Normand; Morin, Guylaine; Thériault, Jocelyne; Trottier, Germain

    2011-01-01

    OBJECTIF : Les études ciblant les enfants nés avec le VIH se sont principalement intéressées à la période précédant l’annonce du diagnostic à l’enfant. L’objectif de cette étude est d’explorer les dynamiques de communication intrafamiliale suivant l’annonce du diagnostic. MÉTHODOLOGIE : Vingt-neuf jeunes (de dix à 18 ans) vivant avec le VIH depuis la naissance ont accordé des entrevues individuelles semi-dirigées portant sur : 1) le dévoilement du statut sérologique, 2) leurs relations familiales et 3) l’éducation sexuelle en milieu familial. Les témoignages ont fait l’objet d’une analyse de contenu. RÉSULTATS : Les jeunes ont appris en moyenne à l’âge de 11 ans leur diagnostic VIH+. La dynamique qui s’installe après cette annonce apparaît régie par le silence : les échanges qui s’ensuivent portent en majorité sur des questions relatives à la médication et à la prévention d’une transmission sexuelle du virus. Ce silence préserverait l’équilibre familial en occupant trois fonctions : protéger la mère d’un sentiment de culpabilité à l’égard de la transmission, assurer l’harmonie familiale, se sentir normal face aux autres. Le diagnostic de l’adolescent n’est généralement pas révélé à la famille élargie, préservant ainsi leur intégration au sein de la famille en les protégeant du rejet, de la trahison et du jugement. EXPOSÉ : Les fonctions du silence et du secret occupent une place stabilisatrice importante au sein de la famille. Toutefois, elles contribuent à isoler les adolescents d’une forme de soutien affectif dont ils ont pourtant besoin. Des pistes d’intervention sont suggérées. PMID:22851894

  9. Phosphorylation of Cysteine String Protein Triggers a Major Conformational Switch.

    PubMed

    Patel, Pryank; Prescott, Gerald R; Burgoyne, Robert D; Lian, Lu-Yun; Morgan, Alan

    2016-08-01

    Cysteine string protein (CSP) is a member of the DnaJ/Hsp40 chaperone family that localizes to neuronal synaptic vesicles. Impaired CSP function leads to neurodegeneration in humans and model organisms as a result of misfolding of client proteins involved in neurotransmission. Mammalian CSP is phosphorylated in vivo on Ser10, and this modulates its protein interactions and effects on neurotransmitter release. However, there are no data on the structural consequences of CSP phosphorylation to explain these functional effects. We show that Ser10 phosphorylation causes an order-to-disorder transition that disrupts CSP's extreme N-terminal α helix. This triggers the concomitant formation of a hairpin loop stabilized by ionic interactions between phosphoSer10 and the highly conserved J-domain residue, Lys58. These phosphorylation-induced effects result in significant changes to CSP conformation and surface charge distribution. The phospho-switch revealed here provides structural insight into how Ser10 phosphorylation modulates CSP function and also has potential implications for other DnaJ phosphoproteins.

  10. Phosphorylation of Cysteine String Protein Triggers a Major Conformational Switch.

    PubMed

    Patel, Pryank; Prescott, Gerald R; Burgoyne, Robert D; Lian, Lu-Yun; Morgan, Alan

    2016-08-01

    Cysteine string protein (CSP) is a member of the DnaJ/Hsp40 chaperone family that localizes to neuronal synaptic vesicles. Impaired CSP function leads to neurodegeneration in humans and model organisms as a result of misfolding of client proteins involved in neurotransmission. Mammalian CSP is phosphorylated in vivo on Ser10, and this modulates its protein interactions and effects on neurotransmitter release. However, there are no data on the structural consequences of CSP phosphorylation to explain these functional effects. We show that Ser10 phosphorylation causes an order-to-disorder transition that disrupts CSP's extreme N-terminal α helix. This triggers the concomitant formation of a hairpin loop stabilized by ionic interactions between phosphoSer10 and the highly conserved J-domain residue, Lys58. These phosphorylation-induced effects result in significant changes to CSP conformation and surface charge distribution. The phospho-switch revealed here provides structural insight into how Ser10 phosphorylation modulates CSP function and also has potential implications for other DnaJ phosphoproteins. PMID:27452402

  11. Conformational Interconversions of Amino Acid Derivatives.

    PubMed

    Kaminský, Jakub; Jensen, Frank

    2016-02-01

    Exhaustive conformational interconversions including transition structure analyses of N-acetyl-l-glycine-N-methylamide as well as its alanine, serine, and cysteine analogues have been investigated at the MP2/6-31G** level, yielding a total of 142 transition states. Improved estimates of relative energies were obtained by separately extrapolating the Hartree-Fock and MP2 energies to the basis set limit and adding the difference between CCSD(T) and MP2 results with the cc-pVDZ basis set to the extrapolated MP2 results. The performance of eight empirical force fields (AMBER94, AMBER14SB, MM2, MM3, MMFFs, CHARMM22_CMAP, OPLS_2005, and AMOEBAPRO13) in reproducing ab initio energies of transition states was tested. Our results indicate that commonly used class I force fields employing a fixed partial charge model for the electrostatic interaction provide mean errors in the ∼10 kJ/mol range for energies of conformational transition states for amino acid conformers. Modern reparametrized versions, such as CHARMM22_CMAP, and polarizable force fields, such as AMOEBAPRO13, have slightly lower mean errors, but maximal errors are still in the 35 kJ/mol range. There are differences between the force fields in their ability for reproducing conformational transitions classified according to backbone/side-chain or regions in the Ramachandran angles, but the data set is likely too small to draw any general conclusions. Errors in conformational interconversion barriers by ∼10 kJ/mol suggest that the commonly used force field may bias certain types of transitions by several orders of magnitude in rate and thus lead to incorrect dynamics in simulations. It is therefore suggested that information for conformational transition states should be included in parametrizations of new force fields. PMID:26691979

  12. Correct light deflection in Weyl conformal gravity

    NASA Astrophysics Data System (ADS)

    Cattani, Carlo; Scalia, Massimo; Laserra, Ettore; Bochicchio, Ivana; Nandi, Kamal K.

    2013-02-01

    The conformal gravity fit to observed galactic rotation curves requires γ>0. On the other hand, the conventional method for light deflection by galaxies gives a negative contribution to the Schwarzschild value for γ>0, which is contrary to observation. Thus, it is very important that the contribution to bending should in principle be positive, no matter how small its magnitude is. Here we show that the Rindler-Ishak method gives a positive contribution to Schwarzschild deflection for γ>0, as desired. We also obtain the exact local coupling term derived earlier by Sereno. These results indicate that conformal gravity can potentially test well against all astrophysical observations to date.

  13. The conformal anomaly of k-strings

    NASA Astrophysics Data System (ADS)

    Giudice, Pietro; Gliozzi, Ferdinando; Lottini, Stefano

    2007-05-01

    Simple scaling properties of correlation functions of a confining gauge theory in d-dimensions lead to the conclusion that k-string dynamics is described, in the infrared limit, by a two-dimensional conformal field theory with conformal anomaly c = (d-2)σk/σ, where σk is the k-string tension and σ that of the fundamental representation. This result applies to any gauge theory with stable k-strings. We check it in a 3D Bbb Z4 gauge model at finite temperature, where a string effect directly related to c can be clearly identified.

  14. Vacuum energy sequestering and conformal symmetry

    NASA Astrophysics Data System (ADS)

    Ben-Dayan, Ido; Richter, Robert; Ruehle, Fabian; Westphal, Alexander

    2016-05-01

    In a series of recent papers Kaloper and Padilla proposed a mechanism to sequester standard model vacuum contributions to the cosmological constant. We study the consequences of embedding their proposal into a fully local quantum theory. In the original work, the bare cosmological constant Λ and a scaling parameter λ are introduced as global fields. We find that in the local case the resulting Lagrangian is that of a spontaneously broken conformal field theory where λ plays the role of the dilaton. A vanishing or a small cosmological constant is thus a consequence of the underlying conformal field theory structure.

  15. Game Theory and Social Psychology: Conformity Games

    NASA Astrophysics Data System (ADS)

    Alessio, Danielle; Kilgour, D. Marc

    2011-11-01

    Game models can contribute to understanding of how social biases and pressures to conform can lead to puzzling behaviour in social groups. A model of the psychological biases false uniqueness and false consensus is set out. The model predicts the phenomenon of pluralistic ignorance, which is well-studied in social psychology, showing how it arises as a result of the prevalence of false uniqueness and the desire to conform. An efficient method is developed for finding Nash equilibria of the model under certain restrictions.

  16. Consistency relations for the conformal mechanism

    SciTech Connect

    Creminelli, Paolo; Joyce, Austin; Khoury, Justin; Simonović, Marko E-mail: joyceau@sas.upenn.edu E-mail: marko.simonovic@sissa.it

    2013-04-01

    We systematically derive the consistency relations associated to the non-linearly realized symmetries of theories with spontaneously broken conformal symmetry but with a linearly-realized de Sitter subalgebra. These identities relate (N+1)-point correlation functions with a soft external Goldstone to N-point functions. These relations have direct implications for the recently proposed conformal mechanism for generating density perturbations in the early universe. We study the observational consequences, in particular a novel one-loop contribution to the four-point function, relevant for the stochastic scale-dependent bias and CMB μ-distortion.

  17. Raising a gender non-conforming child.

    PubMed

    Wisnowski, Deborah L

    2011-10-01

    This article overviews the challenges parents face raising gender non-conforming children. The author is the mother of a fifteen year old gender non-conforming (GNC) child and co-founder of Stepping Stones Support Group which organizes support programs for families of GNC. The article discusses social challenges, educational challenges and internal conflicts the author has experienced while raising her child. The author also discusses the process of founding Stepping Stones and the importance having support has played in her and her child's life.

  18. Simulating Massive Conformation Changes within Polypeptide Systems

    NASA Astrophysics Data System (ADS)

    Singh, Jaspinder Paul

    In this dissertation I employ all-atom structure based models with stable energy basins to several existing and novel polypeptide systems (postulated conformation changes of the mammalian prion protein and structurally dual proteins). The common themes are finding unfolding and refolding pathways between highly dissimilar protein structures as a means of understanding exactly how and why a protein may misfold. The modeling is based on the energy funnel landscape theory of protein conformation space. The principle of minimal frustration is considered as the model includes parameters which vary the roughness of the landscape and give rise to off-pathway misfoldings. The dual basin model is applied to the C-terminal (residues 166-226) of the mammalian prion protein. One basin represents the known alpha-helical (aH) structure while the other represents the same residues in a lefthanded beta-helical (LHBH) conformation. The LHBH structure has been proposed to help describe one class of in vitro grown fibrils, as well as possibly self-templating the conversion of normal cellular prion protein to the infectious form. Yet, it is unclear how the protein may make this global rearrangement. Our results demonstrate that the conformation changes are not strongly limited by large-scale geometry modification and that there may exist an overall preference for the LHBH conformation. Furthermore, our model presents novel intermediate trapping conformations with twisted LHBH structure. Polypeptides that display structural duality have primary structures that can give rise to different potential native conformations. We apply the structure-based all-atom model to a leucine zipper protein template with a stable aH structure that has been shown in experiment to switch to a β hairpin structure when exposed to a low-pH environment. We show that the model can be used to perform large-scale temperature-dependent conformational switching by simulating this switching behavior. We augmented

  19. Comparative conformational analysis of peptide T analogs

    NASA Astrophysics Data System (ADS)

    Akverdieva, Gulnare; Godjayev, Niftali; Akyuz, Sevim

    2009-01-01

    A series of peptide T analogs were investigated within the molecular mechanics framework. In order to determine the role of the aminoacid residues in spatial formation of peptide T the conformational peculiarities of the glycine-substituted analogs were investigated. The conformational profiles of some biologically tested analogs of this peptide were determined independently. The received data permit to assess the active form of this peptide. It is characterized by β-turn at the C-terminal physiologically active pentapeptide fragment of peptide molecule. The received results are important for the investigation of the structure-activity relationship and may be used at design of a rigid-molecule drug against HIV.

  20. Isoperimetric inequality on conformally hyperbolic manifolds

    SciTech Connect

    Kesel'man, V M

    2003-04-30

    It is shown that on an arbitrary non-compact Riemannian manifold of conformally hyperbolic type the isoperimetric inequality can be taken by a conformal change of the metric to the same canonical linear form as in the case of the standard hyperbolic Lobachevskii space. Both the absolute isoperimetric inequality and the relative one (for manifolds with boundary) are obtained. This work develops the results and methods of a joint paper with Zorich, in which the absolute isoperimetric inequality was obtained under a certain additional condition; the resulting statements are definitive in a certain sense.

  1. Firefighting Module

    NASA Astrophysics Data System (ADS)

    1984-01-01

    Firefly II pump module is NASA's Marshall Space Flight Center's commercial offshoot of a NASA/US Coast Guard program involving development of a lightweight, helicopter-transportable firefighting module for a quick response in combating shipboard or harbor fires. Operable on land or water, the Amphib One is equipped with 3 water cannons. When all 3 are operating, unit pumps more than 3,000 gallons a minute. Newly developed model used by U.S. Coast Guard can pump 5,000 gallons per minute. It was designed for applications such as firefighting onboard ship fires, emergency dockside water pumping, dewatering ships in danger of sinking, flood control, and emergency water supply at remote locations.

  2. Thermoelectric module

    DOEpatents

    Kortier, William E.; Mueller, John J.; Eggers, Philip E.

    1980-07-08

    A thermoelectric module containing lead telluride as the thermoelectric mrial is encapsulated as tightly as possible in a stainless steel canister to provide minimum void volume in the canister. The lead telluride thermoelectric elements are pressure-contacted to a tungsten hot strap and metallurgically bonded at the cold junction to iron shoes with a barrier layer of tin telluride between the iron shoe and the p-type lead telluride element.

  3. Linear modulator

    NASA Technical Reports Server (NTRS)

    1972-01-01

    A study of frequency division multiplexing (FDM) systems was made for the purpose of determining the system performance that can be obtained with available state of the art components. System performance was evaluated on the basis of past experience, system analysis, and component evaluation. The system study was specifically directed to the area of FDM systems using subcarrier channel frequencies from 4 kHz to 200 kHz and channel information bandwidths of dc to 1, 2, 4, 8, and 16 kHz. The evaluation also assumes that the demodulation will be from a tape recorder which produces frequency modulation of + or - 1% on the signal due to the tape recorder wow and flutter. For the modulation system it is assumed that the pilot and carrier channel frequencies are stable to within + or - .005% and that the FM on the channel carriers is negligible. The modulator system was evaluated for the temperature range of -20 degree to +85 degree while the demodulator system was evaluated for operation at room temperature.

  4. Cancer bronchique à petites cellules et grossesse: à propos d'un cas avec revue de la literature

    PubMed Central

    Safini, Fatima; Jjouhadi, Hassan; Chehal, Asmaa; Mernissi, Farida; Wilfried, Akpoo; Bouchbika, Zineb; Taleb, Amina; Benchakroun, Nadia; Tawfiq, Nezha; Sahraoui, Souha; Benider, Abdellatif

    2016-01-01

    Le cancer broncho-pulmonaire (CBP) de la femme enceinte est une entité rare, d’évolution péjorative. Cette situation devient de plus en plus fréquente, du fait de l'augmentation du tabagisme chez la femme. La transmission tumorale trans-placentaire avec atteinte fœtale est décrite surtout chez les femmes non traitées. Le traitement est multidisciplinaire et n'est pas bien codifié. Nous rapportons le cas d'une patiente de 23 ans chez qui le diagnostic d'un carcinome bronchique à petites cellules a été fait au cours de sa grossesse. Elle avait bénéficié d'une chimiothérapie pendant la grossesse, bien tolérée. L’évaluation radiologique a objectivé une stabilisation du processus pulmonaire. Le traitement a été complété par une association radio-chimiothérapie concomitante après l'accouchement. PMID:27279957

  5. Photovoltaic module and module arrays

    DOEpatents

    Botkin, Jonathan; Graves, Simon; Lenox, Carl J. S.; Culligan, Matthew; Danning, Matt

    2013-08-27

    A photovoltaic (PV) module including a PV device and a frame, The PV device has a PV laminate defining a perimeter and a major plane. The frame is assembled to and encases the laminate perimeter, and includes leading, trailing, and side frame members, and an arm that forms a support face opposite the laminate. The support face is adapted for placement against a horizontal installation surface, to support and orient the laminate in a non-parallel or tilted arrangement. Upon final assembly, the laminate and the frame combine to define a unitary structure. The frame can orient the laminate at an angle in the range of 3.degree.-7.degree. from horizontal, and can be entirely formed of a polymeric material. Optionally, the arm incorporates integral feature(s) that facilitate interconnection with corresponding features of a second, identically formed PV module.

  6. Photovoltaic module and module arrays

    DOEpatents

    Botkin, Jonathan; Graves, Simon; Lenox, Carl J. S.; Culligan, Matthew; Danning, Matt

    2012-07-17

    A photovoltaic (PV) module including a PV device and a frame. The PV device has a PV laminate defining a perimeter and a major plane. The frame is assembled to and encases the laminate perimeter, and includes leading, trailing, and side frame members, and an arm that forms a support face opposite the laminate. The support face is adapted for placement against a horizontal installation surface, to support and orient the laminate in a non-parallel or tilted arrangement. Upon final assembly, the laminate and the frame combine to define a unitary structure. The frame can orient the laminate at an angle in the range of 3.degree.-7.degree. from horizontal, and can be entirely formed of a polymeric material. Optionally, the arm incorporates integral feature(s) that facilitate interconnection with corresponding features of a second, identically formed PV module.

  7. [Conformation theory of polymers and biopolymers].

    PubMed

    Volkenstein, M V

    1977-01-01

    A short review is given of the Soviet investigations in the field of physics of polymers and biopolymers based on the concept of conformational motility of macromolecules. It is shown that the ideas originally used for the treatment of the properties of the synthetic polymers and, in particular, of the rubber elasticity, have found broad applications in molecular biophysics.

  8. Conformity Behavior and Self-Consciousness.

    ERIC Educational Resources Information Center

    Froming, William J.

    Compliance, conforming behavior as a response to social influences, is affected by a variety of factors within the self. Some of these factors pertain to one's perceived place in the social context; others pertain to the salience of one's immediate affective and perceptual experience. The self-aspect chosen as the object of one's attention can…

  9. Surveillance and Conformity in Competitive Youth Swimming

    ERIC Educational Resources Information Center

    Lang, Melanie

    2010-01-01

    Underpinned by a Foucauldian analysis of sporting practices, this paper identifies the disciplinary mechanism of surveillance at work in competitive youth swimming. It highlights the ways in which swimmers and their coaches are subject to and apply this mechanism to produce embodied conformity to normative behaviour and obedient, docile bodies.…

  10. On the physical origin of galactic conformity

    NASA Astrophysics Data System (ADS)

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

    2016-09-01

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

  11. Role Conflict and Conformity in Dress.

    ERIC Educational Resources Information Center

    Jasper, Cynthia R.; Roach-Higgins, Mary Ellen

    1988-01-01

    Examined conflict regarding what form of dress is appropriate for Roman Catholic priest. Data from 5,475 American Catholic priests revealed that priests who conformed to church regulations regarding dress differed from nonconformists in beliefs about their roles as priests and in their opinions of church reform, commitment to the priesthood,…

  12. Conformally flat polytropes for anisotropic matter

    NASA Astrophysics Data System (ADS)

    Herrera, L.; Di Prisco, A.; Barreto, W.; Ospino, J.

    2014-12-01

    We analyze in detail conformally flat spherically symmetric fluid distributions, satisfying a polytropic equation of state. Among the two possible families of relativistic polytropes, only one contains models which satisfy all the required physical conditions. The ensuing configurations are necessarily anisotropic and show interesting physical properties. Prospective applications of the presented models to the study of super-Chandrasekhar white dwarfs, are discussed.

  13. The conformational specificity of viral epitopes.

    PubMed

    Van Regenmortel, M H

    1992-12-15

    Four types of antigenic sites found in viruses are discussed: cryptotopes, neotopes, metatopes and neutralization epitopes. The role played by conformation on the specificity of viral epitopes is illustrated in the case of tobacco mosaic virus and influenza virus. It appears that mechanisms reminiscent of induced fit contribute to the recognition of viral epitopes by antibodies.

  14. Conformal Visualization for Partially-Immersive Platforms

    PubMed Central

    Petkov, Kaloian; Papadopoulos, Charilaos; Zhang, Min; Kaufman, Arie E.; Gu, Xianfeng

    2010-01-01

    Current immersive VR systems such as the CAVE provide an effective platform for the immersive exploration of large 3D data. A major limitation is that in most cases at least one display surface is missing due to space, access or cost constraints. This partially-immersive visualization results in a substantial loss of visual information that may be acceptable for some applications, however it becomes a major obstacle for critical tasks, such as the analysis of medical data. We propose a conformal deformation rendering pipeline for the visualization of datasets on partially-immersive platforms. The angle-preserving conformal mapping approach is used to map the 360°3D view volume to arbitrary display configurations. It has the desirable property of preserving shapes under distortion, which is important for identifying features, especially in medical data. The conformal mapping is used for rasterization, realtime raytracing and volume rendering of the datasets. Since the technique is applied during the rendering, we can construct stereoscopic images from the data, which is usually not true for image-based distortion approaches. We demonstrate the stereo conformal mapping rendering pipeline in the partially-immersive 5-wall Immersive Cabin (IC) for virtual colonoscopy and architectural review. PMID:26279083

  15. A Ratio Scale Measurement of Conformity.

    ERIC Educational Resources Information Center

    Beins, Bernard C.; Porter, J. William

    A sensitive technique for assessing conformity on a ratio scale was designed and tested in one group of 18 naive subjects and one group of 20 volunteer subjects, 10 of whom were naive and 10 of whom were informed. All subjects were undergraduates from Thomas More College (New York). The experiment required subjects to observe a line briefly…

  16. Computing the conformational entropy for RNA folds

    NASA Astrophysics Data System (ADS)

    Liu, Liang; Chen, Shi-Jie

    2010-06-01

    We develop a polymer physics-based method to compute the conformational entropy for RNA tertiary folds, namely, conformations consisting of multiple helices connected through (cross-linked) loops. The theory is based on a virtual bond conformational model for the nucleotide chain. A key issue in the calculation of the entropy is how to treat the excluded volume interactions. The weak excluded volume interference between the different loops leads to the decomposition of the whole structure into a number of three-body building blocks, each consisting of a loop and two helices connected to the two ends of the loop. The simple construct of the three-body system allows an accurate computation for the conformational entropy for each building block. The assembly of the building blocks gives the entropy of the whole structure. This approach enables treatment of molten globule-like folds (partially unfolded tertiary structures) for RNAs. Extensive tests against experiments and exact computer enumerations indicate that the method can give accurate results for the entropy. The method developed here provides a solid first step toward a systematic development of a theory for the entropy and free energy landscape for complex tertiary folds for RNAs and proteins.

  17. Conformational maturation of measles virus nucleocapsid protein.

    PubMed Central

    Gombart, A F; Hirano, A; Wong, T C

    1993-01-01

    We have obtained a polyclonal antiserum, N-BE, against the denatured, amino-terminal half of the measles virus (MV) nucleocapsid (N) protein and a monoclonal antibody (MAb), N46, which recognizes a conformation-dependent epitope in the same region. Amino acid residues 23 to 239 were required and sufficient for the formation of the conformational epitope. Using these antibodies, we show that the N protein of MV is synthesized as a relatively unfolded protein which first appears in the free-protein pool. This nascent N protein undergoes a conformational change into a more folded mature form. This change does not require the participation of other viral proteins or genomic RNA. The mature N protein does not accumulate in the free-protein pool but is quickly and selectively incorporated into the viral nucleocapsids. The mature N protein is a target for interaction with the phosphoprotein (P protein) of MV. This interaction interferes with the recognition of the N protein by the N46 MAb. This suggests that the association with the P protein may mask the binding site for the N46 MAb or that it induces a conformational change in the N protein. Images PMID:7685410

  18. Harrison-Zeldovich spectrum from conformal invariance

    SciTech Connect

    Rubakov, V.A.

    2009-09-01

    We show that flat spectrum of small perturbations of field(s) is generated in a simple way in a theory of multi-component scalar field provided this theory is conformally invariant, it has some global symmetry and the quartic potential is negative. We suggest a mechanism of converting these field perturbations into adiabatic scalar perturbations with flat spectrum.

  19. 40 CFR 52.2133 - General conformity.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... were submitted on November 8, 1996. South Carolina incorporated by reference regulations 40 CFR part 51... 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...

  20. Enhancing Moral Conformity and Enhancing Moral Worth.

    PubMed

    Douglas, Thomas

    2014-01-01

    It is plausible that we have moral reasons to become better at conforming to our moral reasons. However, it is not always clear what means to greater moral conformity we should adopt. John Harris has recently argued that we have reason to adopt traditional, deliberative means in preference to means that alter our affective or conative states directly-that is, without engaging our deliberative faculties. One of Harris' concerns about direct means is that they would produce only a superficial kind of moral improvement. Though they might increase our moral conformity, there is some deeper kind of moral improvement that they would fail to produce, or would produce to a lesser degree than more traditional means. I consider whether this concern might be justified by appeal to the concept of moral worth. I assess three attempts to show that, even where they were equally effective at increasing one's moral conformity, direct interventions would be less conducive to moral worth than typical deliberative alternatives. Each of these attempts is inspired by Kant's views on moral worth. Each, I argue, fails.

  1. Piston ring conformability in a distorted bore

    SciTech Connect

    Tomanik, E.

    1996-09-01

    Some different equations to calculate the maximum deformation that a given ring can conform to, are found in the bibliography. These equations do not consider the ring end gap and ovality, gas pressure acting on it, nor the actual bore shape, but only the maximum amplitude for a given term (from a fourier Series that describes the bore shape). A more exact prediction can be done with Finite Element tools or specific codes for piston ring simulation; those approaches are not usually carried out, except in special cases or in more fundamental studies. Experimental measurements were carried out to verify the simple conformability criteria. Deformed shapes were produced in a static jig and areas of non contact, between ring and the deformed bore shapes, were measured. Based on these measurements, a semi-empirical equation is proposed to calculate the limit of piston ring conformability. The proposed equation is simple enough to be calculated in the initial engine design phases (where the required inputs to more detailed methods are not available) or on a day-by-day basis. If bore deformation surpasses the ring conformability, the percentage of ring periphery contacting the bore can be estimated, in a first approximation, by the linear regression empirically found in the experiments.

  2. Conformal symmetry of brane world effective actions

    SciTech Connect

    McFadden, Paul L.; Turok, Neil

    2005-01-15

    A simple derivation of the low-energy effective action for brane worlds is given, highlighting the role of conformal invariance. We show how to improve the effective action for a positive- and negative-tension brane pair using the AdS/CFT correspondence.

  3. NMR Studies of Dynamic Biomolecular Conformational Ensembles

    PubMed Central

    Torchia, Dennis A.

    2015-01-01

    Multidimensional heteronuclear NMR approaches can provide nearly complete sequential signal assignments of isotopically enriched biomolecules. The availability of assignments together with measurements of spin relaxation rates, residual spin interactions, J-couplings and chemical shifts provides information at atomic resolution about internal dynamics on timescales ranging from ps to ms, both in solution and in the solid state. However, due to the complexity of biomolecules, it is not possible to extract a unique atomic-resolution description of biomolecular motions even from extensive NMR data when many conformations are sampled on multiple timescales. For this reason, powerful computational approaches are increasingly applied to large NMR data sets to elucidate conformational ensembles sampled by biomolecules. In the past decade, considerable attention has been directed at an important class of biomolecules that function by binding to a wide variety of target molecules. Questions of current interest are: “Does the free biomolecule sample a conformational ensemble that encompasses the conformations found when it binds to various targets; and if so, on what time scale is the ensemble sampled?” This article reviews recent efforts to answer these questions, with a focus on comparing ensembles obtained for the same biomolecules by different investigators. A detailed comparison of results obtained is provided for three biomolecules: ubiquitin, calmodulin and the HIV-1 trans-activation response RNA. PMID:25669739

  4. Design of conformal lens by drilling holes materials using quasi-conformal transformation optics.

    PubMed

    Li, Shouliang; Zhang, Zhan; Wang, Junhong; He, Xianshi

    2014-10-20

    In this paper, based on quasi-conformal transformation optics, a 3D conformal lens made of isotropic and non-resonant metamaterial is designed, which can make a cylindrical conformal array behave similarly to a uniform linear array. After discussion and simplification in the two-dimensional model, we realize the proposed lens by utilizing drilling-hole material in the three-dimensional structure. The ring-like shape and forward-only radiation make it possible to equip the lens on a cylindrical device.

  5. A disulfide-stabilized conformer of methionine synthase reveals an unexpected role for the histidine ligand of the cobalamin cofactor

    SciTech Connect

    Datta, Supratim; Koutmos, Markos; Pattridge, Katherine A.; Ludwig, Martha L.; Matthews, Rowena G.

    2008-07-08

    B{sub 12}-dependent methionine synthase (MetH) from Escherichia coli is a large modular protein that is alternately methylated by methyltetrahydrofolate to form methylcobalamin and demethylated by homocysteine to form cob(I)alamin. Major domain rearrangements are required to allow cobalamin to react with three different substrates: homocysteine, methyltetrahydrofolate, and S-adenosyl-l-methionine (AdoMet). These same rearrangements appear to preclude crystallization of the wild-type enzyme. Disulfide cross-linking was used to lock a C-terminal fragment of the enzyme into a unique conformation. Cysteine point mutations were introduced at Ile-690 and Gly-743. These cysteine residues span the cap and the cobalamin-binding module and form a cross-link that reduces the conformational space accessed by the enzyme, facilitating protein crystallization. Here, we describe an x-ray structure of the mutant fragment in the reactivation conformation; this conformation enables the transfer of a methyl group from AdoMet to the cobalamin cofactor. In the structure, the axial ligand to the cobalamin, His-759, dissociates from the cobalamin and forms intermodular contacts with residues in the AdoMet-binding module. This unanticipated intermodular interaction is expected to play a major role in controlling the distribution of conformers required for the catalytic and the reactivation cycles of the enzyme.

  6. Testing of Advanced Conformal Ablative TPS

    NASA Technical Reports Server (NTRS)

    Gasch, Matthew; Agrawal, Parul; Beck, Robin

    2013-01-01

    In support of the CA250 project, this paper details the results of a test campaign that was conducted at the Ames Arcjet Facility, wherein several novel low density thermal protection (TPS) materials were evaluated in an entry like environment. The motivation for these tests was to investigate whether novel conformal ablative TPS materials can perform under high heat flux and shear environment as a viable alternative to rigid ablators like PICA or Avcoat for missions like MSL and beyond. A conformable TPS over a rigid aeroshell has the potential to solve a number of challenges faced by traditional rigid TPS materials (such as tiled Phenolic Impregnated Carbon Ablator (PICA) system on MSL, and honeycomb-based Avcoat on the Orion Multi Purpose Crew Vehicle (MPCV)). The compliant (high strain to failure) nature of the conformable ablative materials will allow better integration of the TPS with the underlying aeroshell structure and enable monolithic-like configuration and larger segments to be used in fabrication.A novel SPRITE1 architecture, developed by the researchers at NASA Ames was used for arcjet testing. This small probe like configuration with 450 spherecone, enabled us to test the materials in a combination of high heat flux, pressure and shear environment. The heat flux near the nose were in the range of 500-1000 W/sq cm whereas in the flank section of the test article the magnitudes were about 50 of the nose, 250-500W/sq cm range. There were two candidate conformable materials under consideration for this test series. Both test materials are low density (0.28 g/cu cm) similar to Phenolic Impregnated Carbon Ablator (PICA) or Silicone Impregnated Refractory Ceramic Ablator (SIRCA) and are comprised of: A flexible carbon substrate (Carbon felt) infiltrated with an ablative resin system: phenolic (Conformal-PICA) or silicone (Conformal-SICA). The test demonstrated a successful performance of both the conformable ablators for heat flux conditions between 50

  7. Coexisting conformations of fibronectin in cell culture imaged using fluorescence resonance energy transfer

    PubMed Central

    Baneyx, Gretchen; Baugh, Loren; Vogel, Viola

    2001-01-01

    Fluorescence resonance energy transfer (FRET) between fluorophores attached to single proteins provides a tool to study the conformation of proteins in solution and in cell culture. As a protein unfolds, nanometer-scale increases in distance between donor and acceptor fluorophores cause decreases in FRET. Here we demonstrate the application of FRET to imaging coexisting conformations of fibronectin (Fn) in cell culture. Fn is a flexible 440-kDa extracellular matrix protein, with functional sites that are regulated by unfolding events. Fn was labeled with multiple donor and acceptor fluorophores such that intramolecular FRET could be used to distinguish a range of Fn conformations. The sensitivity of FRET to unfolding was tested by progressively denaturing labeled Fn using guanidium chloride. To investigate Fn conformation changes during cell binding and matrix assembly, we added labeled Fn to the culture medium of NIH 3T3 fibroblasts. Coexisting conformations of Fn were visualized using fluorescence microscopy, and spectra from specific features were measured with an attached spectrometer. Using FRET as an indicator of Fn conformation, Fn diffusely bound to cells was in a compact state, whereas Fn in matrix fibrils was highly extended. Matrix fibrils exhibited a range of FRET that suggested some degree of unfolding of Fn's globular modules. Fn in cell-associated clusters that preceded fibril formation appeared more extended than diffuse cell-bound Fn but less extended than fibrillar Fn, suggesting that Fn undergoes extension after cell binding and before polymerization. FRET thus provides an approach to gain insight into the integrin-mediated pathway of Fn fibrillogenesis. PMID:11717404

  8. Lie algebra of conformal Killing–Yano forms

    NASA Astrophysics Data System (ADS)

    Ertem, Ümit

    2016-06-01

    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.

  9. Black hole temperature: Minimal coupling vs conformal coupling

    SciTech Connect

    Fazel, Mohamadreza; Mirza, Behrouz; Mansoori, Seyed Ali Hosseini

    2014-05-15

    In this article, we discuss the propagation of scalar fields in conformally transformed spacetimes with either minimal or conformal coupling. The conformally coupled equation of motion is transformed into a one-dimensional Schrödinger-like equation with an invariant potential under conformal transformation. In a second stage, we argue that calculations based on conformal coupling yield the same Hawking temperature as those based on minimal coupling. Finally, it is conjectured that the quasi normal modes of black holes are invariant under conformal transformation.

  10. Calcul couple fluide/structure avec ANSYS : étude numérique et expérimentale d'une plaque élastique en contact avec un fluide lourd compressible

    NASA Astrophysics Data System (ADS)

    Sigrist, J. F.; Laine, C.; Peseux, B.

    2002-12-01

    Une préoccupation constante de tout industriel est la maîtrise des marges de dimensionnement de ses structures. Le recours aux techniques de calcul scientifique permet en phase de conception détaillée un dimensionnement au plus juste des structures, tout en respectant les différentes contraintes de conception (exigences fonctionnelles, conditions d'environnement, aspects réglementaires). Une meilleure maîtrise des marges passe donc par une meilleure connaissance de l'outil de calcul (précision intrinsèque, mise en œuvre de techniques de calcul plus ou moins élaborées) et la prise en compte d'une réalité physique plus complexe (avec par exemple un couplage entre différents phénomènes physiques) pour une meilleure représentativité du calcul. Une démarche globale de recherche et développement a été mise en place au sein du Service Scientifique et Technique de l'établissement DCN de Nantes Indret pour répondre à ce besoin. Nous présentons ici un exemple d'application pour le calcul de structures en présence de fluide. Cette étude numérique et expérimentale nous permet de valider conjointement le processus de calcul en bureau d'étude et les méthodes de mesure sur site dans le domaine de l'analyse fréquentielle de structures mouillées.

  11. Internal switches modulating electron tunneling currents in respiratory complex III.

    PubMed

    Hagras, Muhammad A; Stuchebrukhov, Alexei A

    2016-06-01

    In different X-ray crystal structures of bc1 complex, some of the key residues of electron tunneling pathways are observed in different conformations; here we examine their relative importance in modulating electron transfer and propose their possible gating function in the Q-cycle. The study includes inter-monomeric electron transfer; here we provide atomistic details of the reaction, and discuss the possible roles of inter-monomeric electronic communication in bc(1) complex. Binding of natural ligands or inhibitors leads to local conformational changes which propagate through protein and control the conformation of key residues involved in the electron tunneling pathways. Aromatic-aromatic interactions are highly utilized in the communication network since the key residues are aromatic in nature. The calculations show that there is a substantial change of the electron transfer rates between different redox pairs depending on the different conformations acquired by the key residues of the complex.

  12. Mediastinal irradiation in a patient affected by lung carcinoma after heart transplantation: Helical tomotherapy versus three dimensional conformal radiotherapy

    PubMed Central

    Iorio, Vincenzo; Cammarota, Fabrizio; Toledo, Diego; Senese, Rossana; Francomacaro, Ferdinando; Muto, Matteo; Muto, Paolo

    2016-01-01

    Abstract Patients who have undergone solid organ transplants are known to have an increased risk of neoplasia compared with the general population. We report our experience using mediastinal irradiation with helical tomotherapy versus three‐dimensional conformal radiation therapy to treat a patient with lung carcinoma 15 years after heart transplantation. Our dosimetric evaluation showed no particular difference between the techniques, with the exception of some organs. Mediastinal irradiation after heart transplantation is feasible and should be considered after evaluation of the risk. Conformal radiotherapy or intensity‐modulated radiotherapy appears to be the appropriate treatment in heart‐transplanted oncologic patients. PMID:27148425

  13. Mediastinal irradiation in a patient affected by lung carcinoma after heart transplantation: Helical tomotherapy versus three dimensional conformal radiotherapy.

    PubMed

    Giugliano, Francesca M; Iorio, Vincenzo; Cammarota, Fabrizio; Toledo, Diego; Senese, Rossana; Francomacaro, Ferdinando; Muto, Matteo; Muto, Paolo

    2016-04-26

    Patients who have undergone solid organ transplants are known to have an increased risk of neoplasia compared with the general population. We report our experience using mediastinal irradiation with helical tomotherapy versus three-dimensional conformal radiation therapy to treat a patient with lung carcinoma 15 years after heart transplantation. Our dosimetric evaluation showed no particular difference between the techniques, with the exception of some organs. Mediastinal irradiation after heart transplantation is feasible and should be considered after evaluation of the risk. Conformal radiotherapy or intensity-modulated radiotherapy appears to be the appropriate treatment in heart-transplanted oncologic patients.

  14. Redox-linked conformational changes of a multiheme cytochrome from Geobacter sulfurreducens

    SciTech Connect

    Morgado, Leonor; Bruix, Marta; Londer, Yuri Y.; Pokkuluri, P. Raj; Schiffer, Marianne; Salgueiro, Carlos A. . E-mail: csalgueiro@dq.fct.unl.pt

    2007-08-17

    Multiheme c-type cytochromes from members of the Desulfovibrionacea and Geobactereacea families play crucial roles in the bioenergetics of these microorganisms. Thermodynamic studies using NMR and visible spectroscopic techniques on tetraheme cytochromes c {sub 3} isolated from Desulfovibrio spp. and more recently on a triheme cytochrome from Geobacter sulfurreducens showed that the properties of each redox centre are modulated by the neighbouring redox centres enabling these proteins to perform energy transduction and thus contributing to cellular energy conservation. Electron/proton transfer coupling relies on redox-linked conformational changes that were addressed for some multiheme cytochromes from the comparison of protein structure of fully reduced and fully oxidised forms. In this work, we identify for the first time in a multiheme cytochrome the simultaneous presence of two different conformations in solution. This was achieved by probing the different oxidation stages of a triheme cytochrome isolated from G. sulfurreducens using 2D-NMR techniques. The results presented here will be the foundations to evaluate the modulation of the redox centres properties by conformational changes that occur during the reoxidation of a multiheme protein.

  15. Identification and isolation of a hyperphosphorylated, conformationally changed intermediate of human protein tau expressed in yeast.

    PubMed

    Vandebroek, Tom; Vanhelmont, Thomas; Terwel, Dick; Borghgraef, Peter; Lemaire, Katleen; Snauwaert, Johan; Wera, Stefaan; Van Leuven, Fred; Winderickx, Joris

    2005-08-30

    Hyperphosphorylation and aggregation of protein tau are typical for neurodegenerative tauopathies, including Alzheimer's disease (AD). We demonstrate here that human tau expressed in yeast acquired pathological phosphoepitopes, assumed a pathological conformation, and formed aggregates. These processes were modulated by yeast kinases Mds1 and Pho85, orthologues of GSK-3beta and cdk5, respectively. Surprisingly, inactivation of Pho85 increased phosphorylation of tau-4R, concomitant with increased conformational change defined by antibody MC1 and a 40-fold increase in aggregation. Soluble protein tau, purified from yeast lacking PHO85, spontaneously and rapidly formed tau filaments in vitro. Further fractionation of tau by anion-exchange chromatography yielded a hyperphosphorylated monomeric subfraction, termed hP-tau/MC1, with slow electrophoretic mobility and enriched with all major epitopes, including MC1. Isolated hP-tau/MC1 vastly accelerated in vitro aggregation of wild-type tau-4R, demonstrating its functional capacity to initiate aggregation, as well as its structural stability. Combined, this novel yeast model recapitulates hyperphosphorylation, conformation, and aggregation of protein tau, provides insight in molecular changes crucial in tauopathies, offers a source for isolation of modified protein tau, and has potential for identification of modulating compounds and genes.

  16. Conformational switching explains the intrinsic multifunctionality of plant light-harvesting complexes.

    PubMed

    Krüger, Tjaart P J; Wientjes, Emilie; Croce, Roberta; van Grondelle, Rienk

    2011-08-16

    The light-harvesting complexes of photosystem I and II (Lhcas and Lhcbs) of plants display a high structural homology and similar pigment content and organization. Yet, the spectroscopic properties of these complexes, and accordingly their functionality, differ substantially. This difference is primarily due to the charge-transfer (CT) character of a chlorophyll dimer in all Lhcas, which mixes with the excitonic states of these complexes, whereas this CT character is generally absent in Lhcbs. By means of single-molecule spectroscopy near room temperature, we demonstrate that the presence or absence of such a CT state in Lhcas and Lhcbs can occasionally be reversed; i.e., these complexes are able to interconvert conformationally to quasi-stable spectral states that resemble the Lhcs of the other photosystem. The high structural similarity of all the Lhca and Lhcb proteins suggests that the stable conformational states that give rise to the mixed CT-excitonic state are similar for all these proteins, and similarly for the conformations that involve no CT state. This indicates that the specific functions related to Lhca and Lhcb complexes are realized by different stable conformations of a single generic protein structure. We propose that this functionality is modulated and controlled by the protein environment.

  17. Conformational flexibility of BECN1: Essential to its key role in autophagy and beyond.

    PubMed

    Mei, Yang; Glover, Karen; Su, Minfei; Sinha, Sangita C

    2016-10-01

    BECN1 (Beclin 1), a highly conserved eukaryotic protein, is a key regulator of autophagy, a cellular homeostasis pathway, and also participates in vacuolar protein sorting, endocytic trafficking, and apoptosis. BECN1 is important for embryonic development, the innate immune response, tumor suppression, and protection against neurodegenerative disorders, diabetes, and heart disease. BECN1 mediates autophagy as a core component of the class III phosphatidylinositol 3-kinase complexes. However, the exact mechanism by which it regulates the activity of these complexes, or mediates its other diverse functions is unclear. BECN1 interacts with several diverse protein partners, perhaps serving as a scaffold or interaction hub for autophagy. Based on extensive structural, biophysical and bioinformatics analyses, BECN1 consists of an intrinsically disordered region (IDR), which includes a BH3 homology domain (BH3D); a flexible helical domain (FHD); a coiled-coil domain (CCD); and a β-α-repeated autophagy-specific domain (BARAD). Each of these BECN1 domains mediates multiple diverse interactions that involve concomitant conformational changes. Thus, BECN1 conformational flexibility likely plays a key role in facilitating diverse protein interactions. Further, BECN1 conformation and interactions are also modulated by numerous post-translational modifications. A better structure-based understanding of the interplay between different BECN1 conformational and binding states, and the impact of post-translational modifications will be essential to elucidating the mechanism of its multiple biological roles.

  18. Protonation-dependent conformational dynamics of the multidrug transporter EmrE

    PubMed Central

    Dastvan, Reza; Mishra, Smriti; Meiler, Jens; Mchaourab, Hassane S.

    2016-01-01

    The small multidrug transporter from Escherichia coli, EmrE, couples the energetically uphill extrusion of hydrophobic cations out of the cell to the transport of two protons down their electrochemical gradient. Although principal mechanistic elements of proton/substrate antiport have been described, the structural record is limited to the conformation of the substrate-bound state, which has been shown to undergo isoenergetic alternating access. A central but missing link in the structure/mechanism relationship is a description of the proton-bound state, which is an obligatory intermediate in the transport cycle. Here we report a systematic spin labeling and double electron electron resonance (DEER) study that uncovers the conformational changes of EmrE subsequent to protonation of critical acidic residues in the context of a global description of ligand-induced structural rearrangements. We find that protonation of E14 leads to extensive rotation and tilt of transmembrane helices 1–3 in conjunction with repacking of loops, conformational changes that alter the coordination of the bound substrate and modulate its access to the binding site from the lipid bilayer. The transport model that emerges from our data posits a proton-bound, but occluded, resting state. Substrate binding from the inner leaflet of the bilayer releases the protons and triggers alternating access between inward- and outward-facing conformations of the substrate-loaded transporter, thus enabling antiport without dissipation of the proton gradient. PMID:26787875

  19. Etude de la Production des Mesons d* Sur le PIC de Resonance du Boson Z Observes AU Lep avec le Detecteur Opal

    NASA Astrophysics Data System (ADS)

    Przysiezniak, Helenka

    L'etude de la production des mesons D* est effectuee a partir d'evenements multihadroniques rm Z^0to q| q, avec des donnees prises en 1990, 1991 et 1992 avec le detecteur OPAL au LEP. La notation q definit les quarks des cinq saveurs pouvant etre observees au LEP: up (u), down (d), strange (s), charme (c), beaute (b). Les D* et les correlations D*-leptons sont identifiees et ces dernieres servent a effecteur une separation claire entre les evenements rm Z^0to b| b et Z^0to c| c. On mesure la distribution de la variable de fragmentation x_{rm D^ *}=E_{rm D^*}/E _{rm faisceau} pour les D* produits dans les evenements rm Z^0 to c| c. Elle est notee f _{rm cto D^*}. Ce resultat est a la base d'une publication OPAL (1), avec trois autres methodes de separation etudiees en parallele, donnat la premiere mesure OPAL de f _{rm cto D^*} qui soit independante de toute modelisation de la fragmentation des quarks lourds, ainsi qu'une mesure de Gamma_{rm c| c} parmi les plus precises effectuees a ce jour, ou Gamma_{rm c| c} est la largeur partielle de la desintegration du Z^0 en une paire cc. En ce qui concerne les resultats obtenus dans le cadre de cette these, la valeur moyenne de la distribution f_ {rm cto D^*}, notee < x_{rm cto D^*}>, est donnee par:< x_{rm cto D^*}>=0.530+/-0.027 +/-0.022ou la premiere erreur est statistique, et la seconde est systematique. On mesure aussi le taux de production des mesons D*, donnee par: {Gamma({rm Z^0to D^ *}X)overGamma_{rm hadrons}}=0.207+/-0.007+/-0.017 ou Gamma_{rm hadrons } est la largeur totale de la desintegration du Z^0 en paires de qq des cinq saveurs. La separation entre evenements rm Z^0to b| b et Z^0 to c| c, dans lesquels sont produits des D* se desintegrant selon rm D^ *to D^0pito (Kpi)pi, nous donne:(DIAGRAM, TABLE OR GRAPHIC OMITTED...PLEASE SEE DAI)La variable de fragmentation x_ {rm cto D^*} est utilisee pour tester les modeles des processes perturbatifs et non-perturbatifs qui entrent en jeu lors de la fragmentation des

  20. Les carcinomes epidermoïdes du scrotum: à propos de 7 cas avec revue de la litterature

    PubMed Central

    Halfya, Ayoub; Elmortaji, Khalid; Redouane, Rabii; fethi, Meziane; Rafik, Amine; Mohamed, Ezzoubi; Abdessamad, Chlihi

    2015-01-01

    Quoique rare le carcinome épidermoïde du scrotum a un mauvais pronostic. Les Carcinomes du scrotum induite et - liées au travail sont moins fréquentes en raison d'une meilleure hygiène, vêtements de protection, et la sensibilisation de la cancérogénicité des huiles industrielles. L’épidémie à l'HPV a induit une augmentation de l'incidence. Le traitement de dépend toujours exérèse locale de la lésion primaire. La radiothérapie a peu de bénéfice thérapeutique dans le traitement d'un carcinome épidermoïde du scrotum. La bléomycine peut être utile comme traitement adjuvant pour les maladies ilio-inguinal généralisée avant la tentative exérèse, même si cela n'a pas encore été prouvé. Entre janvier 2011 au 1er janvier 2013, 7 patients atteints de carcinome épidermoïde ont été pris en charge, Trois patients ont présenté une localisation ganglionnaire. Les sept patients ont eu un traitement chirurgical par exérèse large avec reconstruction, Deux patients ont été adressé pour chimiothérapie.2 patients ont présenté une récidive, dont un est décédé. PMID:26113906

  1. 40 CFR 93.157 - Reevaluation of conformity.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... determination is not required for the action at the time NEPA analysis is completed, the date of the finding of... the conformity determination date. (b) The conformity status of a Federal action automatically...

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

    PubMed

    Tormena, Cláudio F

    2016-08-01

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

  3. 40 CFR 91.106 - Certificate of conformity.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Provisions § 91.106 Certificate of conformity. (a) Every manufacturer of a new marine SI engine produced... importing into the United States the new marine SI engine. (b) The certificate of conformity is valid...

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

    PubMed

    Tormena, Cláudio F

    2016-08-01

    This review deals with conformational analysis in small organic molecules, and describes the stereoelectronic interactions responsible for conformational stability. Conformational analysis is usually performed using NMR spectroscopy through measurement of coupling constants at room or low temperature in different solvents to determine the populations of conformers in solution. Quantum mechanical calculations are used to address the interactions responsible for conformer stability. The conformational analysis of a large number of small molecules is described, using coupling constant measurements in different solvents and at low temperature, as well as recent applications of through-space and through-hydrogen bond coupling constants JFH as tools for the conformational analysis of fluorinated molecules. Besides NMR parameters, stereoelectronic interactions such as conjugative, hyperconjugative, steric and intramolecular hydrogen bond interactions involved in conformational preferences are discussed. PMID:27573182

  5. Conformal invariance and Hamilton Jacobi theory for dissipative systems

    NASA Technical Reports Server (NTRS)

    Kiehn, R. M.

    1975-01-01

    For certain dissipative systems, a comparison can be made between the Hamilton-Jacobi theory and the conformal invariance of action theory. The two concepts are not identical, but the conformal action theory covers the Hamilton-Jacobi theory.

  6. Covariant Conformal Decomposition of Einstein Equations

    NASA Astrophysics Data System (ADS)

    Gourgoulhon, E.; Novak, J.

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

  7. Conformal linear gravity in de Sitter space

    SciTech Connect

    Takook, M. V.; Tanhayi, M. R.; Fatemi, S.

    2010-03-15

    It has been shown that the theory of linear conformal quantum gravity must include a tensor field of rank-3 and mixed symmetry [Binegar et al., Phys. Rev. D 27, 2249 (1983)]. In this paper, we obtain the corresponding field equation in de Sitter space. Then, in order to relate this field with the symmetric tensor field of rank-2, K{sub {alpha}}{sub {beta}} related to graviton, we will define homomorphisms between them. Our main result is that if one insists K{sub {alpha}}{sub {beta}} to be a unitary irreducible representation of de Sitter and conformal groups, it must satisfy a field equation of order of 6, which is obtained.

  8. Radial expansion for spinning conformal blocks

    NASA Astrophysics Data System (ADS)

    Costa, Miguel S.; Hansen, Tobias; Penedones, João; Trevisani, Emilio

    2016-07-01

    This paper develops a method to compute any bosonic conformal block as a series expansion in the optimal radial coordinate introduced by Hogervorst and Rychkov. The method reduces to the known result when the external operators are all the same scalar operator, but it allows to compute conformal blocks for external operators with spin. Moreover, we explain how to write closed form recursion relations for the coefficients of the expansions. We study three examples of four point functions in detail: one vector and three scalars; two vectors and two scalars; two spin 2 tensors and two scalars. Finally, for the case of two external vectors, we also provide a more efficient way to generate the series expansion using the analytic structure of the blocks as a function of the scaling dimension of the exchanged operator.

  9. Scale without conformal invariance at three loops

    NASA Astrophysics Data System (ADS)

    Fortin, Jean-François; Grinstein, Benjamín; Stergiou, Andreas

    2012-08-01

    We carry out a three-loop computation that establishes the existence of scale without conformal invariance in dimensional regularization with the MS scheme in unitary theories in d = 4 - ɛ spacetime dimensions. We also comment on the effects of scheme changes in theories with many couplings, as well as in theories that live on non-conformal scale-invariant renormalization group trajectories. Stability properties of such trajectories are analyzed, revealing both attractive and repulsive directions in a specific example. We explain how our results are in accord with those of Jack & Osborn on a c-theorem in d = 4 (and d = 4 - ɛ) dimensions. Finally, we point out that limit cycles with turning points are unlike limit cycles with continuous scale invariance.

  10. Chromosome Conformation Capture in Primary Human Cells.

    PubMed

    Cortesi, Alice; Bodega, Beatrice

    2016-01-01

    3D organization of the genome, its structural and regulatory function of cell identity, is acquiring prominent features in epigenetics studies; more efforts have been done to develop techniques that allow studying nuclear structure. Chromosome conformation capture (3C) has been set up in 2002 from Dekker and from that moment great investments were made to develop genomics variants of 3C technology (4C, 5C, Hi-C) providing new tools to investigate the shape of the genome in a more systematic and unbiased manner. 3C method allows scientists to fix dynamic and variable 3D interactions in nuclear space, and consequently to study which sequences interact, how a gene is regulated by different and distant enhancer, or how a set of enhancer could regulate transcriptional units; to follow the conformation that mediates regulation change in development; and to evaluate if this fine epigenetic mechanism is impaired in disease condition. PMID:27659988

  11. Conformational selection in trypsin-like proteases

    PubMed Central

    Pozzi, Nicola; Vogt, Austin D.; Gohara, David W.; Di Cera, Enrico

    2012-01-01

    For over four decades, two competing mechanisms of ligand recognition – conformational selection and induced-fit - have dominated our interpretation of protein allostery. Defining the mechanism broadens our understanding of the system and impacts our ability to design effective drugs and new therapeutics. Recent kinetics studies demonstrate that trypsin-like proteases exist in equilibrium between two forms: one fully accessible to substrate (E) and the other with the active site occluded (E*). Analysis of the structural database confirms existence of the E* and E forms and vouches for the allosteric nature of the trypsin fold. Allostery in terms of conformational selection establishes an important paradigm in the protease field and enables protein engineers to expand the repertoire of proteases as therapeutics. PMID:22664096

  12. Conformation-controlled binding kinetics of antibodies

    NASA Astrophysics Data System (ADS)

    Galanti, Marta; Fanelli, Duccio; Piazza, Francesco

    2016-01-01

    Antibodies are large, extremely flexible molecules, whose internal dynamics is certainly key to their astounding ability to bind antigens of all sizes, from small hormones to giant viruses. In this paper, we build a shape-based coarse-grained model of IgG molecules and show that it can be used to generate 3D conformations in agreement with single-molecule Cryo-Electron Tomography data. Furthermore, we elaborate a theoretical model that can be solved exactly to compute the binding rate constant of a small antigen to an IgG in a prescribed 3D conformation. Our model shows that the antigen binding process is tightly related to the internal dynamics of the IgG. Our findings pave the way for further investigation of the subtle connection between the dynamics and the function of large, flexible multi-valent molecular machines.

  13. Impacts of Conformational Geometries in Fluorinated Alkanes.

    PubMed

    Brandenburg, Tim; Golnak, Ronny; Nagasaka, Masanari; Atak, Kaan; Sreekantan Nair Lalithambika, Sreeju; Kosugi, Nobuhiro; Aziz, Emad F

    2016-01-01

    Research of blood substitute formulations and their base materials is of high scientific interest. Especially fluorinated microemulsions based on perfluorocarbons, with their interesting chemical properties, offer opportunities for applications in biomedicine and physical chemistry. In this work, carbon K-edge absorption spectra of liquid perfluoroalkanes and their parent hydrocarbons are presented and compared. Based on soft X-ray absorption, a comprehensive picture of the electronic structure is provided with the aid of time dependent density functional theory. We have observed that conformational geometries mainly influence the chemical and electronic interactions in the presented liquid materials, leading to a direct association of conformational geometries to the dissolving capacity of the presented perfluorocarbons with other solvents like water and possibly gases like oxygen. PMID:27527753

  14. Tuning Riboswitch Regulation through Conformational Selection

    PubMed Central

    Wilson, Ross C.; Smith, Angela M.; Fuchs, Ryan T.; Kleckner, Ian R.; Henkin, Tina M.; Foster, Mark P.

    2010-01-01

    SUMMARY The SMK box riboswitch, which represents one of three known classes of S-adenosylmethionine (SAM)-responsive riboswitches, regulates gene expression in bacteria at the level of translation initiation. In contrast to most riboswitches, which contain separate domains responsible for ligand recognition and gene regulation, the ligand-binding and regulatory domains of the SMK box riboswitch are coincident. This property was exploited to allow the first atomic-level characterization of a functionally intact riboswitch in both the ligand-bound and ligand-free states. NMR spectroscopy revealed distinct mutually exclusive RNA conformations that are differentially populated in the presence or absence of the effector metabolite. Isothermal titration calorimetry and in vivo reporter assay results revealed the thermodynamic and functional consequences of this conformational equilibrium. We present a comprehensive model of the structural, thermodynamic, and functional properties of this compact RNA regulatory element. PMID:21075119

  15. Conformational Flexibility in the Transmembrane Protein TSPO.

    PubMed

    Jaremko, Łukasz; Jaremko, Mariusz; Giller, Karin; Becker, Stefan; Zweckstetter, Markus

    2015-11-01

    The translocator protein (TSPO) is an integral membrane protein that interacts with a wide variety of endogenous ligands, such as cholesterol and porphyrins, and is also the target for several small molecules with substantial in vivo efficacy. When complexed with the TSPO-specific radioligand (R)-PK11195, TSPO folds into a rigid five-helix bundle. However, little is known about the structure and dynamics of TSPO in the absence of high-affinity ligands. By means of NMR spectroscopy, we show that TSPO exchanges between multiple conformations in the absence of (R)-PK11195. Extensive motions on time scales from pico- to microseconds occur all along the primary sequence of the protein, leading to a loss of stable tertiary interactions and local unfolding of the helical structure in the vicinity of the ligand-binding site. The flexible nature of TSPO highlights the importance of conformational plasticity in integral membrane proteins.

  16. Conformation-controlled binding kinetics of antibodies

    PubMed Central

    Galanti, Marta; Fanelli, Duccio; Piazza, Francesco

    2016-01-01

    Antibodies are large, extremely flexible molecules, whose internal dynamics is certainly key to their astounding ability to bind antigens of all sizes, from small hormones to giant viruses. In this paper, we build a shape-based coarse-grained model of IgG molecules and show that it can be used to generate 3D conformations in agreement with single-molecule Cryo-Electron Tomography data. Furthermore, we elaborate a theoretical model that can be solved exactly to compute the binding rate constant of a small antigen to an IgG in a prescribed 3D conformation. Our model shows that the antigen binding process is tightly related to the internal dynamics of the IgG. Our findings pave the way for further investigation of the subtle connection between the dynamics and the function of large, flexible multi-valent molecular machines. PMID:26755272

  17. Impacts of Conformational Geometries in Fluorinated Alkanes

    PubMed Central

    Brandenburg, Tim; Golnak, Ronny; Nagasaka, Masanari; Atak, Kaan; Sreekantan Nair Lalithambika, Sreeju; Kosugi, Nobuhiro; Aziz, Emad F.

    2016-01-01

    Research of blood substitute formulations and their base materials is of high scientific interest. Especially fluorinated microemulsions based on perfluorocarbons, with their interesting chemical properties, offer opportunities for applications in biomedicine and physical chemistry. In this work, carbon K-edge absorption spectra of liquid perfluoroalkanes and their parent hydrocarbons are presented and compared. Based on soft X-ray absorption, a comprehensive picture of the electronic structure is provided with the aid of time dependent density functional theory. We have observed that conformational geometries mainly influence the chemical and electronic interactions in the presented liquid materials, leading to a direct association of conformational geometries to the dissolving capacity of the presented perfluorocarbons with other solvents like water and possibly gases like oxygen. PMID:27527753

  18. Impacts of Conformational Geometries in Fluorinated Alkanes

    NASA Astrophysics Data System (ADS)

    Brandenburg, Tim; Golnak, Ronny; Nagasaka, Masanari; Atak, Kaan; Sreekantan Nair Lalithambika, Sreeju; Kosugi, Nobuhiro; Aziz, Emad F.

    2016-08-01

    Research of blood substitute formulations and their base materials is of high scientific interest. Especially fluorinated microemulsions based on perfluorocarbons, with their interesting chemical properties, offer opportunities for applications in biomedicine and physical chemistry. In this work, carbon K-edge absorption spectra of liquid perfluoroalkanes and their parent hydrocarbons are presented and compared. Based on soft X-ray absorption, a comprehensive picture of the electronic structure is provided with the aid of time dependent density functional theory. We have observed that conformational geometries mainly influence the chemical and electronic interactions in the presented liquid materials, leading to a direct association of conformational geometries to the dissolving capacity of the presented perfluorocarbons with other solvents like water and possibly gases like oxygen.

  19. Conformal field theory of critical Casimir forces

    NASA Astrophysics Data System (ADS)

    Emig, Thorsten; Bimonte, Giuseppe; Kardar, Mehran

    2015-03-01

    Thermal fluctuations of a critical system induce long-ranged Casimir forces between objects that couple to the underlying field. For two dimensional conformal field theories (CFT) we derive exact results for the Casimir interaction for a deformed strip and for two compact objects of arbitrary shape in terms of the free energy of a standard region (circular ring or flat strip) whose dimension is determined by the mutual capacitance of two conductors with the objects' shape; and a purely geometric energy that is proportional to conformal charge of the CFT, but otherwise super-universal in that it depends only on the shapes and is independent of boundary conditions and other details. The effect of inhomogenous boundary conditions is also discussed.

  20. Conformation of the C1 phorbol-ester-binding domain participates in the activating conformational change of protein kinase C.

    PubMed Central

    Ho, C; Slater, S J; Stagliano, B A; Stubbs, C D

    1999-01-01

    The fluorescent phorbol ester 12-N-methylanthraniloylphorbol 13-acetate [sapintoxin D (SAPD)] was used as both the activator and the probe for the activating conformational change of the C1 domain of recombinant protein kinase C (PKC)alpha. Fluorescence emission spectra and steady-state anisotropy measurements of SAPD in fully active membrane-associated PKC show that there is a relatively hydrophobic environment and restricted motional freedom characterizing the phorbol-ester-binding site. SAPD also interacts with the membrane lipids so that it was necessary to resort to time-resolved anisotropy measurements to resolve the signals corresponding to PKC-bound SAPD from that associated with buffer and lipid. In the presence of membrane lipids (unilamellar vesicles of phosphatidylcholine and phosphatidylserine, 4:1 molar ratio) and Ca(2+), at a concentration sufficient to activate the enzyme fully, a long correlation time characteristic of highly restricted motion was observed for PKC-associated SAPD. The fraction of SAPD molecules displaying this restricted motion, in comparison with the total SAPD including that in lipids and in buffer, increased with increasing concentrations of Ca(2+) and paralleled the appearance of enzyme activity, whereas the rotational correlation time remained constant. This could be rationalized as an increase in the number of active PKC conformers in the total population of PKC molecules. It therefore seems that there is a distinct conformation of the C1 activator-binding domain associated with the active form of PKC. The addition of SAPD and dioleoyl-sn-glycerol together produced an activity higher than that achievable by either activator alone both at concentrations that alone induced maximal activity for the respective activator; this higher activity was associated with a further restriction in SAPD motion. Increasing the cholesterol concentration, the phosphatidylethanolamine concentration, the sn-2 unsaturation in phosphatidylcholine

  1. Conformational Dynamics and Allostery in Pyruvate Kinase.

    PubMed

    Donovan, Katherine A; Zhu, Shaolong; Liuni, Peter; Peng, Fen; Kessans, Sarah A; Wilson, Derek J; Dobson, Renwick C J

    2016-04-22

    Pyruvate kinase catalyzes the final step in glycolysis and is allosterically regulated to control flux through the pathway. Two models are proposed to explain how Escherichia coli pyruvate kinase type 1 is allosterically regulated: the "domain rotation model" suggests that both the domains within the monomer and the monomers within the tetramer reorient with respect to one another; the "rigid body reorientation model" proposes only a reorientation of the monomers within the tetramer causing rigidification of the active site. To test these hypotheses and elucidate the conformational and dynamic changes that drive allostery, we performed time-resolved electrospray ionization mass spectrometry coupled to hydrogen-deuterium exchange studies followed by mutagenic analysis to test the activation mechanism. Global exchange experiments, supported by thermostability studies, demonstrate that fructose 1,6-bisphosphate binding to the allosteric domain causes a shift toward a globally more dynamic ensemble of conformations. Mapping deuterium exchange to peptides within the enzyme highlight site-specific regions with altered conformational dynamics, many of which increase in conformational flexibility. Based upon these and mutagenic studies, we propose an allosteric mechanism whereby the binding of fructose 1,6-bisphosphate destabilizes an α-helix that bridges the allosteric and active site domains within the monomeric unit. This destabilizes the β-strands within the (β/α)8-barrel domain and the linked active site loops that are responsible for substrate binding. Our data are consistent with the domain rotation model but inconsistent with the rigid body reorientation model given the increased flexibility at the interdomain interface, and we can for the first time explain how fructose 1,6-bisphosphate affects the active site. PMID:26879751

  2. Protein Conformational Switches: From Nature to Design

    PubMed Central

    Ha, Jeung-Hoi

    2012-01-01

    Protein conformational switches alter their shape upon receiving an input signal, such as ligand binding, chemical modification, or change in environment. The apparent simplicity of this transformation—which can be carried out by a molecule as small as a thousand atoms or so—belies its critical importance to the life of the cell as well as its capacity for engineering by humans. In the realm of molecular switches, proteins are unique because they are capable of performing a variety of biological functions. Switchable proteins are therefore of high interest to the fields of biology, bio-technology, and medicine. These molecules are beginning to be exploited as the core machinery behind a new generation of biosensors, functionally regulated enzymes, and “smart” biomaterials that react to their surroundings. As inspirations for these designs, researchers continue to analyze existing examples of allosteric proteins. Recent years have also witnessed the development of new methodologies for introducing conformational change into proteins that previously had none. Herein we review examples of both natural and engineered protein switches in the context of four basic modes of conformational change: rigid-body domain movement, limited structural rearrangement, global fold switching, and folding–unfolding. Our purpose is to highlight examples that can potentially serve as platforms for the design of custom switches. Accordingly, we focus on inducible conformational changes that are substantial enough to produce a functional response (e.g., in a second protein to which it is fused), yet are relatively simple, structurally well-characterized, and amenable to protein engineering efforts. PMID:22688954

  3. Scoring docking conformations using predicted protein interfaces

    PubMed Central

    2014-01-01

    Background Since proteins function by interacting with other molecules, analysis of protein-protein interactions is essential for comprehending biological processes. Whereas understanding of atomic interactions within a complex is especially useful for drug design, limitations of experimental techniques have restricted their practical use. Despite progress in docking predictions, there is still room for improvement. In this study, we contribute to this topic by proposing T-PioDock, a framework for detection of a native-like docked complex 3D structure. T-PioDock supports the identification of near-native conformations from 3D models that docking software produced by scoring those models using binding interfaces predicted by the interface predictor, Template based Protein Interface Prediction (T-PIP). Results First, exhaustive evaluation of interface predictors demonstrates that T-PIP, whose predictions are customised to target complexity, is a state-of-the-art method. Second, comparative study between T-PioDock and other state-of-the-art scoring methods establishes T-PioDock as the best performing approach. Moreover, there is good correlation between T-PioDock performance and quality of docking models, which suggests that progress in docking will lead to even better results at recognising near-native conformations. Conclusion Accurate identification of near-native conformations remains a challenging task. Although availability of 3D complexes will benefit from template-based methods such as T-PioDock, we have identified specific limitations which need to be addressed. First, docking software are still not able to produce native like models for every target. Second, current interface predictors do not explicitly consider pairwise residue interactions between proteins and their interacting partners which leaves ambiguity when assessing quality of complex conformations. PMID:24906633

  4. Mapping L1 Ligase ribozyme conformational switch

    PubMed Central

    Giambaşu, George M.; Lee, Tai-Sung; Scott, William G.; York, Darrin M.

    2012-01-01

    L1 Ligase (L1L)molecular switch is an in vitro optimized synthetic allosteric ribozyme that catalyzes the regioselective formation of a 5’-to-3’ phosphodiester bond, a reaction for which there is no known naturally occurring RNA catalyst. L1L serves as a proof of principle that RNA can catalyze a critical reaction for prebiotic RNA self-replication according to the RNA World hypothesis. L1L crystal structure captures two distinct conformations that differ by a re-orientation of one of the stems by around 80 Å and are presumed to correspond to the active and inactive state, respectively. It is of great interest to understand the nature of these two states in solution, and the pathway for their interconversion. In this study, we use explicit solvent molecular simulation together with a novel enhanced sampling method that utilizes concepts from network theory to map out the conformational transition between active and inactive states of L1L. We find that the overall switching mechanism can be described as a 3-state/2-step process. The first step involves a large-amplitude swing that re-orients stem C. The second step involves the allosteric activation of the catalytic site through distant contacts with stem C. Using a conformational space network representation of the L1L switch transition, it is shown that the connection between the three states follows different topographical patterns: the stem C swing step passes through a narrow region of the conformational space network, whereas the allosteric activation step covers a much wider region and a more diverse set of pathways through the network. PMID:22771572

  5. Sealing apparatus utilizing a conformable member

    DOEpatents

    Neef, William S.; Lambert, Donald R.

    1988-01-01

    Sealing apparatus and method, comprising first and second surfaces or membranes, at least one of which surfaces is deformable, placed in proximity to one another. Urging means cause these surfaces to contact one another in a manner such that the deformable surface "deforms" to conform to the geometry of the other surface, thereby creating a seal. The seal is capable of undergoing multiple cycles of sealing and unsealing.

  6. Marginally Relevant Topics in Conformal Field Theories

    NASA Astrophysics Data System (ADS)

    Cleary, Kevin Francis

    We consider a set of topics in conformal field theory. We provide an example of a 4D theory that exhibits the Contino-Pomarol-Rattazzi mechanism, where breaking conformal symmetry by an almost marginal operator leads to a light pseudo-Goldstone boson, the dilaton, and a parametrically suppressed contribution to vacuum energy. We consider SUSY QCD at the edge of the conformal window and break conformal symmetry by weakly gauging a subgroup of the flavor symmetry. Using Seiberg duality we show that for a range of parameters the singlet meson in the dual theory reaches the unitarity bound, however, this theory does not have a stable vacuum. We stabilize the vacuum with soft breaking terms, compute the mass of the dilaton, and determine the range of parameters where the leading contribution to the dilaton mass is from the almost marginal coupling. We also weigh in on a widely held belief that increasing bounds on the gluino mass, which feeds down to the stop mass through renormalization group running, are making a light stop increasingly unlikely. Here we present a counter-example. We examine the case of the Minimal Composite Supersymmetric Standard Model which has a light composite stop. The large anomalous dimension of the stop from strong dynamics pushes the stop mass toward a quasi-fixed point in the infrared, which is smaller than standard estimates by a factor of a large logarithm. The gluino can be about three times heavier than the stop, which is comparable to hierarchy achieved with supersoft Dirac gluino masses. Thus, in this class of models, a heavy gluino is not necessarily indicative of a heavy stop.

  7. Conformational Recognition of an Intrinsically Disordered Protein

    PubMed Central

    Krieger, James M.; Fusco, Giuliana; Lewitzky, Marc; Simister, Philip C.; Marchant, Jan; Camilloni, Carlo; Feller, Stephan M.; De Simone, Alfonso

    2014-01-01

    There is a growing interest in understanding the properties of intrinsically disordered proteins (IDPs); however, the characterization of these states remains an open challenge. IDPs appear to have functional roles that diverge from those of folded proteins and revolve around their ability to act as hubs for protein-protein interactions. To gain a better understanding of the modes of binding of IDPs, we combined statistical mechanics, calorimetry, and NMR spectroscopy to investigate the recognition and binding of a fragment from the disordered protein Gab2 by the growth factor receptor-bound protein 2 (Grb2), a key interaction for normal cell signaling and cancer development. Structural ensemble refinement by NMR chemical shifts, thermodynamics measurements, and analysis of point mutations indicated that the population of preexisting bound conformations in the free-state ensemble of Gab2 is an essential determinant for recognition and binding by Grb2. A key role was found for transient polyproline II (PPII) structures and extended conformations. Our findings are likely to have very general implications for the biological behavior of IDPs in light of the evidence that a large fraction of these proteins possess a specific propensity to form PPII and to adopt conformations that are more extended than the typical random-coil states. PMID:24739176

  8. Spherically symmetric conformal gravity and ''gravitational bubbles''

    SciTech Connect

    Berezin, V.A.; Dokuchaev, V.I.; Eroshenko, Yu.N. E-mail: dokuchaev@inr.ac.ru

    2016-01-01

    The general structure of the spherically symmetric solutions in the Weyl conformal gravity is described. The corresponding Bach equations are derived for the special type of metrics, which can be considered as the representative of the general class. The complete set of the pure vacuum solutions is found. It consists of two classes. The first one contains the solutions with constant two-dimensional curvature scalar of our specific metrics, and the representatives are the famous Robertson-Walker metrics. One of them we called the ''gravitational bubbles'', which is compact and with zero Weyl tensor. Thus, we obtained the pure vacuum curved space-times (without any material sources, including the cosmological constant) what is absolutely impossible in General Relativity. Such a phenomenon makes it easier to create the universe from ''nothing''. The second class consists of the solutions with varying curvature scalar. We found its representative as the one-parameter family. It appears that it can be conformally covered by the thee-parameter Mannheim-Kazanas solution. We also investigated the general structure of the energy-momentum tensor in the spherical conformal gravity and constructed the vectorial equation that reveals clearly some features of non-vacuum solutions. Two of them are explicitly written, namely, the metrics à la Vaidya, and the electrovacuum space-time metrics.

  9. Spatial Separation of Molecular Conformers and Clusters

    PubMed Central

    Horke, Daniel; Trippel, Sebastian; Chang, Yuan-Pin; Stern, Stephan; Mullins, Terry; Kierspel, Thomas; Küpper, Jochen

    2014-01-01

    Gas-phase molecular physics and physical chemistry experiments commonly use supersonic expansions through pulsed valves for the production of cold molecular beams. However, these beams often contain multiple conformers and clusters, even at low rotational temperatures. We present an experimental methodology that allows the spatial separation of these constituent parts of a molecular beam expansion. Using an electric deflector the beam is separated by its mass-to-dipole moment ratio, analogous to a bender or an electric sector mass spectrometer spatially dispersing charged molecules on the basis of their mass-to-charge ratio. This deflector exploits the Stark effect in an inhomogeneous electric field and allows the separation of individual species of polar neutral molecules and clusters. It furthermore allows the selection of the coldest part of a molecular beam, as low-energy rotational quantum states generally experience the largest deflection. Different structural isomers (conformers) of a species can be separated due to the different arrangement of functional groups, which leads to distinct dipole moments. These are exploited by the electrostatic deflector for the production of a conformationally pure sample from a molecular beam. Similarly, specific cluster stoichiometries can be selected, as the mass and dipole moment of a given cluster depends on the degree of solvation around the parent molecule. This allows experiments on specific cluster sizes and structures, enabling the systematic study of solvation of neutral molecules. PMID:24457426

  10. Conformable, Low Level Light Therapy platform

    NASA Astrophysics Data System (ADS)

    Jablonski, Michal; Bossuyt, Frederick; Vanfleteren, Jan; Vervust, Thomas; De Smet, Herbert

    2014-05-01

    Well-being applications demand unobtrusive treatment methods in order to reach user acceptance. In the field of light therapy this needs to be carefully addressed because, in most cases, light treatment system size has to be significant with respect to human body scale. At the same time we observe the push to make wearable devices that deliver the treatment on the go. Once scaled up, standard flexible electronics (FPC) fail to conform to body curvatures leading to decrease in comfort. A solution to this problem demands new or modified methods for fabrication of the electronic circuits that fulfill the conformability demand (flexing, but also stretching). Application of Stretchable Molded Interconnect (SMI) technology, that attempts to address these demands, will be discussed. The unique property of SMI is that its manufacturing draws mainly from standard PCB and FCB technologies to inherit the reliability and conductivity. At the same time, however, it allows soft, flexible and stretchable circuits with biomimetic haptics and high optical efficiency. In this work a demonstrator device for blue light therapy of RSI is presented that illustrates the strengths as well as challenges ahead of conformable light circuits. We report system electro-optical efficiency, possible irradiance levels within skin thermal comfort and efficiency under cyclic, tensile stretching deformation.

  11. Spatial separation of molecular conformers and clusters.

    PubMed

    Horke, Daniel; Trippel, Sebastian; Chang, Yuan-Pin; Stern, Stephan; Mullins, Terry; Kierspel, Thomas; Küpper, Jochen

    2014-01-09

    Gas-phase molecular physics and physical chemistry experiments commonly use supersonic expansions through pulsed valves for the production of cold molecular beams. However, these beams often contain multiple conformers and clusters, even at low rotational temperatures. We present an experimental methodology that allows the spatial separation of these constituent parts of a molecular beam expansion. Using an electric deflector the beam is separated by its mass-to-dipole moment ratio, analogous to a bender or an electric sector mass spectrometer spatially dispersing charged molecules on the basis of their mass-to-charge ratio. This deflector exploits the Stark effect in an inhomogeneous electric field and allows the separation of individual species of polar neutral molecules and clusters. It furthermore allows the selection of the coldest part of a molecular beam, as low-energy rotational quantum states generally experience the largest deflection. Different structural isomers (conformers) of a species can be separated due to the different arrangement of functional groups, which leads to distinct dipole moments. These are exploited by the electrostatic deflector for the production of a conformationally pure sample from a molecular beam. Similarly, specific cluster stoichiometries can be selected, as the mass and dipole moment of a given cluster depends on the degree of solvation around the parent molecule. This allows experiments on specific cluster sizes and structures, enabling the systematic study of solvation of neutral molecules.

  12. Scattering and radiation from cylindrically conformal antennas

    NASA Astrophysics Data System (ADS)

    Kempel, Leo Charles

    Microstrip patch antennas offer considerable advantages in terms of weight, aerodynamic drag, cost, flexibility, and observability over more conventional protruding antennas. Two hybrid finite element methods are presented and are used to examine the scattering and radiation behavior of cylindrically conformal patches. In conjunction with a new divergence-free cylindrical shell element, the finite element-boundary integral method is shown to have low computational and memory requirements when compared with competing approaches. This method uses an efficient creeping wave series for the computation of the dyadic Green's function and a uniform surface mesh so that a fast Fourier transform may be used to reduce the computational and memory burden of the method. An alternative finite element-absorbing boundary condition approach incorporates a new conformal vector condition which minimizes the computational domain. The latter method is more flexible than the former because it can incorporate surface coatings and protruding antennas. Guidelines are established for minimal ABC displacement from the aperture. These two hybrid finite element methods are used to study the scattering, radiation, and input impedance of typical conformal antenna arrays. In particular, the effect of curvature and cavity size is examined for both discrete and wraparound antenna arrays.

  13. Rényi entropy and conformal defects

    NASA Astrophysics Data System (ADS)

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

    2016-07-01

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

  14. Causality constraints in conformal field theory

    DOE PAGES

    Hartman, Thomas; Jain, Sachin; Kundu, Sandipan

    2016-05-17

    Causality places nontrivial constraints on QFT in Lorentzian signature, for example fixing the signs of certain terms in the low energy Lagrangian. In d dimensional conformal field theory, we show how such constraints are encoded in crossing symmetry of Euclidean correlators, and derive analogous constraints directly from the conformal bootstrap (analytically). The bootstrap setup is a Lorentzian four-point function corresponding to propagation through a shockwave. Crossing symmetry fixes the signs of certain log terms that appear in the conformal block expansion, which constrains the interactions of low-lying operators. As an application, we use the bootstrap to rederive the well knownmore » sign constraint on the (Φ)4 coupling in effective field theory, from a dual CFT. We also find constraints on theories with higher spin conserved currents. As a result, our analysis is restricted to scalar correlators, but we argue that similar methods should also impose nontrivial constraints on the interactions of spinning operators« less

  15. Pyranose sulfamates: conformation and hydrogen bonding

    NASA Astrophysics Data System (ADS)

    Kubicki, Maciej; Codding, Penelope W.; Litster, Stephen A.; Szkaradziñska, Maria B.; Bassyouni, Hanan A. R.

    1999-01-01

    The crystal structure of a new anticonvulsant drug, topiramate — 2,3:4,5-bis- O-(1-methylethylidene)- β-D-fructopyranose sulfamate ( 1), together with those of three similar but biologically almost inactive sugar sulfamates: 4,5- O-cyclohexylidene-2,3- O-(1-methyl-ethylidene)- β-D-fructopyranose sulfamate ( 2), 2,3:- O-(1-methylethylidene)- β-D-fructo-pyranose sulfamate ( 3), and 1,2:3,4-bis- O-(1-methylethylidene)- α-D-galactopyranose sulfamate ( 4), have been determined by X-rays. The pyranose rings adopt distorted twist-boat 2S O conformations as a result of flattening of the chair conformation, observed in free pyranoses, by the fused five-membered ring(s). In 3 an unfavourable gauche-trans conformation about C1-C2 bond is observed. The active compound, topiramate ( 1), shows, in comparison with the other three compounds, a different disposition of nitrogen and oxygen atoms from the sulfamate group with respect to the O1-S1 bond. As a result, the nitrogen atom in 1 is ca. 1 Å farther from the O6 pyranose ring oxygen atom than in the other three compounds. This difference describes the mutual disposition of the hydrophilic and hydrophobic parts of the molecule, and can be related to the difference in biological activity. In all compounds, hydrogen bonds connect molecules into three-dimensional networks; simple chains and more complicated rings are found and described using the graph set notation.

  16. An event-based account of conformity.

    PubMed

    Kim, Diana; Hommel, Bernhard

    2015-04-01

    People often change their behavior and beliefs when confronted with deviating behavior and beliefs of others, but the mechanisms underlying such phenomena of conformity are not well understood. Here we suggest that people cognitively represent their own actions and others' actions in comparable ways (theory of event coding), so that they may fail to distinguish these two categories of actions. If so, other people's actions that have no social meaning should induce conformity effects, especially if those actions are similar to one's own actions. We found that female participants adjusted their manual judgments of the beauty of female faces in the direction consistent with distracting information without any social meaning (numbers falling within the range of the judgment scale) and that this effect was enhanced when the distracting information was presented in movies showing the actual manual decision-making acts. These results confirm that similarity between an observed action and one's own action matters. We also found that the magnitude of the standard conformity effect was statistically equivalent to the movie-induced effect.

  17. Multi-field conformal cosmological attractors

    SciTech Connect

    Kallosh, Renata; Linde, Andrei E-mail: alinde@stanford.edu

    2013-12-01

    We describe a broad class of multi-field inflationary models with spontaneously broken conformal invariance. It generalizes the recently discovered class of cosmological attractors with a single inflaton field [1]. In the new multi-field theories, just as in the single-field models of [1], the moduli space has a boundary (Kähler cone) in terms of the original homogeneous conformal variables. Upon spontaneous breaking of the conformal invariance and switching to the Einstein frame, this boundary moves to infinity in terms of the canonically normalized inflaton field. This results in the exponential stretching and flattening of scalar potentials in the vicinity of the boundary of the moduli space, which makes even very steep potentials perfectly suitable for the slow-roll inflation. These theories, just like their single-field versions, typically lead to inflationary perturbations with n{sub s} = 1−2/N and r = 12/N{sup 2}, where N is the number of e-foldings.

  18. Correlation functions in conformal invariant stochastic processes

    NASA Astrophysics Data System (ADS)

    Alcaraz, Francisco C.; Rittenberg, Vladimir

    2015-11-01

    We consider the problem of correlation functions in the stationary states of one-dimensional stochastic models having conformal invariance. If one considers the space dependence of the correlators, the novel aspect is that although one considers systems with periodic boundary conditions, the observables are described by boundary operators. From our experience with equilibrium problems one would have expected bulk operators. Boundary operators have correlators having critical exponents being half of those of bulk operators. If one studies the space-time dependence of the two-point function, one has to consider one boundary and one bulk operators. The Raise and Peel model has conformal invariance as can be shown in the spin 1/2 basis of the Hamiltonian which gives the time evolution of the system. This is an XXZ quantum chain with twisted boundary condition and local interactions. This Hamiltonian is integrable and the spectrum is known in the finite-size scaling limit. In the stochastic base in which the process is defined, the Hamiltonian is not local anymore. The mapping into an SOS model, helps to define new local operators. As a byproduct some new properties of the SOS model are conjectured. The predictions of conformal invariance are discussed in the new framework and compared with Monte Carlo simulations.

  19. 21 CFR 26.69 - Monitoring of conformity assessment bodies.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 1 2011-04-01 2011-04-01 false Monitoring of conformity assessment bodies. 26.69... COMMUNITY âFrameworkâ Provisions § 26.69 Monitoring of conformity assessment bodies. The following shall apply with regard to the monitoring of conformity assessment bodies (CAB's) listed in subpart B of...

  20. 21 CFR 26.70 - Conformity assessment bodies.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 1 2011-04-01 2011-04-01 false Conformity assessment bodies. 26.70 Section 26.70...Frameworkâ Provisions § 26.70 Conformity assessment bodies. Each party recognizes that the conformity assessment bodies (CAB's) listed in subpart B of this part fulfill the conditions of eligibility to...