WorldWideScience

Sample records for strong oligomerization behavior

  1. <strong>Neuroeconomics and behavioral health economicsstrong>/>

    DEFF Research Database (Denmark)

    Larsen, Torben

    2009-01-01

    dissemination of relaxation procedures is evident in industrialized countries since about 1970 both inside the medical healthcare system and as NGO-settings in a market-alike competition. However, a serious barrier to the dissemination of meditative de-stressing is the lack of general knowledge of the action...... for explanation of the neural dynamics of normal decision making. Secondly, the literature is reviewed for evidence on hypothesized applications of NeM in behavioral health. Results I. The present bias as documented by neuroeconomic game-trials is explained by NeM as rooted in the basal activation of Amygdala...... - a key center in our emotional arousal (limbic system) - as shaped in the elder stone-age with many acute threats. II. In general, the Hawthorne-effect of human-relations management is explained as the result of supportive job-relations relaxing Amygdala for better emotional integration...

  2. Electron Microscopy Structural Insights into CPAP Oligomeric Behavior

    DEFF Research Database (Denmark)

    Alvarez-Cabrera, Ana L; Delgado, Sandra; Gil-Carton, David

    2017-01-01

    primary autosomal recessive microcephaly and Seckel syndrome. Despite of the biological/clinical relevance of CPAP, its mechanistic behavior remains unclear and its C-terminus (the G-box/TCP domain) is the only part whose structure has been solved. This situation is perhaps due in part to the challenges...

  3. Effect of polyhedral-oligomeric-sil-sesquioxanes on thermal and mechanical behavior of SC-15 epoxy

    Directory of Open Access Journals (Sweden)

    2008-07-01

    Full Text Available In this study, thermal and mechanical properties of nanocomposites containing SC-15 epoxy resin and polyhedral-oligomeric-sil-sesquioxanes (POSS have been studied. Dynamic Mechanical Analysis (DMA results show that the addition of 5 wt% of POSS yielded a 13% increase in the storage modulus and a 16°C enhancement in Tg. Thermo gravimetric Analysis (TGA results show that the thermal stability of epoxy increased with higher POSS content. Tension tests were used to evaluate the mechanical properties of materials. Both modulus and tensile strength are linear functions of POSS content. Scanning Electric Microscopy (SEM pictures of fracture surfaces show that the roughness of the fracture surfaces of epoxy increased after adding POSS. Based on experiment results, a three-parameter nonlinear constitutive equation was developed to describe the strain-softening stress-strain relationship behavior of materials. The parameters in this model are the elastic modulus, a strain exponent, m, and a compliance factor, β. Their relationships to the POSS weight fraction were obtained from the experiment results. The simulated stress-strain curves from the model agree with the test data. Analysis of the model shows that both the strain exponent, m, which controls the strain softening and hardening effect of the material, and the compliance parameter, β, which controls the flow stress level of the material, increase with higher POSS content.

  4. Universal behavior of strongly correlated Fermi systems

    Energy Technology Data Exchange (ETDEWEB)

    Shaginyan, Vasilii R [B.P. Konstantinov St. Petersburg Institute of Nuclear Physics, Russian Academy of Sciences, Gatchina, Leningrad region, Rusian Federation (Russian Federation); Amusia, M Ya [A.F. Ioffe Physico-Technical Institute, Russian Academy of Sciences, St. Petersburg (Russian Federation); Popov, Konstantin G [Komi Scientific Center, Ural Branch of the Russian Academy of Sciences, Syktyvkar (Russian Federation)

    2007-06-30

    This review discusses the construction of a theory and the analysis of phenomena occurring in strongly correlated Fermi systems such as high-T{sub c} superconductors, heavy-fermion metals, and quasi-two-dimensional Fermi systems. It is shown that the basic properties and the universal behavior of strongly correlated Fermi systems can be described in the framework of the Fermi-condensate quantum phase transition and the well-known Landau paradigm of quasiparticles and the order parameter. The concept of fermion condensation may be fruitful in studying neutron stars, finite Fermi systems, ultra-cold gases in traps, and quark plasma. (reviews of topical problems)

  5. Universal behavior of strongly correlated Fermi systems

    International Nuclear Information System (INIS)

    Shaginyan, Vasilii R; Amusia, M Ya; Popov, Konstantin G

    2007-01-01

    This review discusses the construction of a theory and the analysis of phenomena occurring in strongly correlated Fermi systems such as high-T c superconductors, heavy-fermion metals, and quasi-two-dimensional Fermi systems. It is shown that the basic properties and the universal behavior of strongly correlated Fermi systems can be described in the framework of the Fermi-condensate quantum phase transition and the well-known Landau paradigm of quasiparticles and the order parameter. The concept of fermion condensation may be fruitful in studying neutron stars, finite Fermi systems, ultra-cold gases in traps, and quark plasma. (reviews of topical problems)

  6. Synthesis, characterization and ethylene oligomerization behavior of 2-benzoimidazol-8-ethoxyquinolylnickel dihalides.

    Science.gov (United States)

    Liu, Hao; Zhang, Liping; Chen, Langqiu; Redshaw, Carl; Li, Yan; Sun, Wen-Hua

    2011-03-21

    A series of 2-benzoimidazol-8-ethoxyquinolines (L1-L6) and the nickel dihalides thereof (C1-C12) were synthesized and characterized by elemental analysis and infrared spectroscopy. The molecular structures of representative complexes were determined by single crystal X-ray diffraction which revealed a distorted pyramidal geometry at nickel. All complexes, when activated with Et(2)AlCl, showed high activities towards ethylene oligomerization and enhanced thermodynamic stability.

  7. Structure–Activity Relationship of Oligomeric Flavan-3-ols: Importance of the Upper-Unit B-ring Hydroxyl Groups in the Dimeric Structure for Strong Activities

    Directory of Open Access Journals (Sweden)

    Yoshitomo Hamada

    2015-10-01

    Full Text Available Proanthocyanidins, which are composed of oligomeric flavan-3-ol units, are contained in various foodstuffs (e.g., fruits, vegetables, and drinks and are strongly biologically active compounds. We investigated which element of the proanthocyanidin structure is primarily responsible for this functionality. In this study, we elucidate the importance of the upper-unit of 4–8 condensed dimeric flavan-3-ols for antimicrobial activity against Saccharomyces cerevisiae (S. cerevisiae and cervical epithelioid carcinoma cell line HeLa S3 proliferation inhibitory activity. To clarify the important constituent unit of proanthocyanidin, we synthesized four dimeric compounds, (−-epigallocatechin-[4,8]-(+-catechin, (−-epigallocatechin-[4,8]-(−-epigallocatechin, (−-epigallocatechin-[4,8]-(−-epigallocatechin-3-O-gallate, and (+-catechin-[4,8]-(−-epigallocatechin and performed structure–activity relationship (SAR studies. In addition to antimicrobial activity against S. cerevisiae and proliferation inhibitory activity on HeLa S3 cells, the correlation of 2,2-diphenyl-l-picrylhydrazyl radical scavenging activity with the number of phenolic hydroxyl groups was low. On the basis of the results of our SAR studies, we concluded that B-ring hydroxyl groups of the upper-unit of the dimer are crucially important for strong and effective activity.

  8. Isolation of a hexanuclear chromium cluster with a tetrahedral hydridic core and its catalytic behavior for ethylene oligomerization.

    Science.gov (United States)

    Alzamly, Ahmed; Gambarotta, Sandro; Korobkov, Ilia; Murugesu, Muralee; Le Roy, Jennifer J H; Budzelaar, Peter H M

    2014-06-16

    A chromium complex [2-(NHCH2PPh2)C5H4N]CrCl3·THF2 (1) of the ligand PyNHCH2PPh2 has been synthesized, characterized, and examined for its catalytic behavior toward ethylene oligomerization. When complex 1 was treated with (i-Bu)3Al, an unprecedented divalent polyhydride chromium cluster μ,κ(1),κ(2),κ(3)-N,N,P-{[2-(NCH2PPh2)C5H4N]Cr(μ-H)}4[(μ-Cl)Cr(μ-Cl)Al(i-Bu)2Cl]2 (2) was obtained. The complex contains a Cr4H4 core, which is expected to be diamagnetic, and which remains coordinated to two additional divalent high-spin Cr atoms via bridging interactions. Two aluminate residues remain bonded to the peripheral chromium atoms. The structure, magnetism, and electronic configuration are herein discussed.

  9. Fouling behaviors of polybenzimidazole (PBI)-polyhedral oligomeric silsesquioxane (POSS)/polyacrylonitrile (PAN) hollow fiber membranes for engineering osmosis processes

    KAUST Repository

    Chen, Sicong

    2014-02-01

    This paper investigated the individual effects of reverse salt flux and permeate flux on fouling behaviors of as-spun and annealed polybenzimidazole (PBI)-polyhedral oligomeric silsesquioxane (POSS)/polyacrylonitrile (PAN) hollow fiber membranes under forward osmosis (FO) and pressure retarded osmosis (PRO) processes. Two types of membrane fouling had been studied; namely, inorganic fouling (CaSO4·2H2O gypsum scaling) during FO operations and organic fouling (sodium alginate fouling) during PRO operations. It is found that gypsum scaling on the membrane surface may be inhibited and even eliminated with an increase in reverse MgCl2 flux due to competitive formations of MgSO4° and CaSO4·2H2O. In contrast, the increase of reverse NaCl flux exhibits a slight enhancement on alginate fouling in both FO and PRO processes. Comparing to the reverse salt flux, the permeate flux always plays a dominant role in fouling. Therefore, lesser fouling has been observed on the membrane surface under the pressurized PRO process than FO process because the reduced initial flux mitigates the fouling phenomena more significantly than the enhancement caused by an increase in reverse NaCl flux. © 2013 Elsevier B.V.

  10. Oligomerization process

    Science.gov (United States)

    Smith, L.A. Jr.; Hearn, D.; Jones, E.M. Jr.

    1991-03-26

    A liquid phase process is described for oligomerization of C[sub 4] and C[sub 5] isoolefins or the etherification thereof with C[sub 1] to C[sub 6] alcohols wherein the reactants are contacted in a reactor with a fixed bed acid cation exchange resin catalyst at an LHSV of 5 to 20, pressure of 0 to 400 psig and temperature of 120 to 300 F wherein the improvement is the operation of the reactor at a pressure to maintain the reaction mixture at its boiling point whereby at least a portion but less than all of the reaction mixture is vaporized. By operating at the boiling point and allowing a portion of the reaction mixture to vaporize, the exothermic heat of reaction is dissipated by the formation of more boil up and the temperature in the reactor is controlled. 2 figures.

  11. Understanding the Behavior of the Oligomeric Fractions During Pyrolysis Oils Upgrading

    Science.gov (United States)

    Stankovikj, Filip

    Fast pyrolysis oils represent most viable renewable sources for production of fuels and chemicals, and they could supplement significant portion of the depleting fossil fuels in near future. Progress on their utilization is impeded by their thermal and storage instability, lack of understanding of their complex composition and behavior during upgrading, including the poorly described water soluble fraction (WS). This work offers two new methodologies for simplified, and sensible description of the pyrolysis oils in terms of functional groups and chemical macro-families, augments our understanding of the composition of the WS, and the behavior of the heavy non-volatile fraction during pyrolysis oils stabilization. The concept of analyzing the volatile and non-volatile fraction in terms of functional groups has been introduced, and the quantification power of spectroscopic techniques (FTIR, 1H-NMR, UV fluorescence) for phenols, carbonyl and carboxyl groups was shown. The FT-ICR-MS van Krevelen diagram revealed the importance of dehydration reactions in pyrolysis oils and the presence of "pyrolytic humins" was hypothesized. For the first time the WS was analyzed with plethora of analytical techniques. This lead to proposition of a new characterization scheme based on functional groups, describing 90-100 wt.% of the bio-oils. The structure of idealized "pyrolytic humin" was further described as a random combination of 3-8 units of dehydrated sugars, coniferyl-type phenols, furans, and carboxylic acids attached on a 2,5-dioxo-6-hydroxyhexanal (DHH) backbone rich in carbonyl groups. TG-FTIR studies resulted in defining rules for fitting pyrolysis oils' DTG curves and assignment of TG residue. This second method is reliable for estimation of water content, light volatiles, WS and WIS. Finally, stabilization of two oils was analyzed through the prism of functional groups. Carbonyl and hydroxyl groups interconverted. The first attempt to follow silent 31P-NMR oxygen was

  12. Ideal gas behavior of a strongly coupled complex (dusty) plasma.

    Science.gov (United States)

    Oxtoby, Neil P; Griffith, Elias J; Durniak, Céline; Ralph, Jason F; Samsonov, Dmitry

    2013-07-05

    In a laboratory, a two-dimensional complex (dusty) plasma consists of a low-density ionized gas containing a confined suspension of Yukawa-coupled plastic microspheres. For an initial crystal-like form, we report ideal gas behavior in this strongly coupled system during shock-wave experiments. This evidence supports the use of the ideal gas law as the equation of state for soft crystals such as those formed by dusty plasmas.

  13. Sterically modulated binuclear bis-α-diimine Pd(II) complexes: Synthesis, characterization, DFT studies and catalytic behavior towards ethylene oligomerization

    Science.gov (United States)

    Netalkar, Sandeep P.; Budagumpi, Srinivasa; Abdallah, Hassan H.; Netalkar, Priya P.; Revankar, Vidyanand K.

    2014-10-01

    A series of Pd(II) complexes of bis-α-diimine derivatives with substituent at 2,6-positions of aniline increasing sterically from Me oligomerization of ethylene in combination with aluminum activators. Treatment of the bimetallic Pd(II) complexes with ethylaluminum sesquichloride (EASC) or Methylalluminooxane (MAO) in toluene generates active cationic catalyst in situ that oligomerize ethylene to α-olefins. All the Pd(II) complexes efficiently oligomerize ethylene to produce C4sbnd C20 fractions at activities of up to 1218.4 kg-oligomer mol-Pd-1 bar-1 h-1 at 30 °C in combination with EASC.

  14. Nanorheology of strongly confined oligomeric lubricants

    NARCIS (Netherlands)

    Manias, E.; Brinke, G. ten; Hadziioannou, G.

    1996-01-01

    Lubricant films confined in nanometric slit pores and subjected to shear flow are studied by non-equilibrium molecular dynamics in a planar Couette flow geometry. An inhomogeneous, layered density profile is developed near the confining surfaces and the shape of the velocity profile across the pore

  15. Anomalous behavior of the ionosphere before strong earthquakes

    Science.gov (United States)

    Peddi Naidu, P.; Madhavi Latha, T.; Madhusudhana Rao, D. N.; Indira Devi, M.

    2017-12-01

    In the recent years, the seismo-ionospheric coupling has been studied using various ionospheric parameters like Total Electron Content, Critical frequencies, Electron density and Phase and amplitude of Very Low Frequency waves. The present study deals with the behavior of the ionosphere in the pre-earthquake period of 3-4 days at various stations adopting the critical frequencies of Es and F2 layers. The relative phase measurements of 16 kHz VLF wave transmissions from Rugby (UK), received at Visakhapatnam (India) are utilized to study the D-region during the seismically active periods. The results show that, f0Es increases a few hours before the time of occurrence of the earthquake and day time values f0F2 are found to be high during the sunlit hours in the pre-earthquake period of 2-3 days. Anomalous VLF phase fluctuations are observed during the sunset hours before the earthquake event. The results are discussed in the light of the probable mechanism proposed by previous investigators.

  16. Muscarinic receptor oligomerization

    OpenAIRE

    Marsango, Sara; Ward, Richard J.; Alvarez-Curto, Elisa; Milligan, Graeme

    2017-01-01

    G protein-coupled receptors (GPCRs) have been classically described as monomeric entities that function by binding in a 1:1 stoichiometric ratio to both ligand and downstream signalling proteins. However, in recent years, a growing number of studies has supported the hypothesis that these receptors can interact to form dimers and higher order oligomers although the molecular basis for these interactions, the overall quaternary arrangements and the functional importance of GPCR oligomerization...

  17. Oligomerization in health and disease

    CERN Document Server

    Giraldo, Jesus

    2013-01-01

    This special volume of Progress in Molecular Biology and Translational Science focuses on oligomerization in health and disease. Contributions from leading authorities Informs and updates on all the latest developments in the field.

  18. Muscarinic receptor oligomerization.

    Science.gov (United States)

    Marsango, Sara; Ward, Richard J; Alvarez-Curto, Elisa; Milligan, Graeme

    2017-11-14

    G protein-coupled receptors (GPCRs) have been classically described as monomeric entities that function by binding in a 1:1 stoichiometric ratio to both ligand and downstream signalling proteins. However, in recent years, a growing number of studies has supported the hypothesis that these receptors can interact to form dimers and higher order oligomers although the molecular basis for these interactions, the overall quaternary arrangements and the functional importance of GPCR oligomerization remain topics of intense speculation. Muscarinic acetylcholine receptors belong to class A of the GPCR family. Each muscarinic receptor subtype has its own particular distribution throughout the central and peripheral nervous systems. In the central nervous system, muscarinic receptors regulate several sensory, cognitive, and motor functions while, in the peripheral nervous system, they are involved in the regulation of heart rate, stimulation of glandular secretion and smooth muscle contraction. Muscarinic acetylcholine receptors have long been used as a model for the study of GPCR structure and function and to address aspects of GPCR dimerization using a broad range of approaches. In this review, the prevailing knowledge regarding the quaternary arrangement for the various muscarinic acetylcholine receptors has been summarized by discussing work ranging from initial results obtained using more traditional biochemical approaches to those generated with more modern biophysical techniques. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  19. Generic strong coupling behavior of Cooper pairs in the surface of superfluid nuclei

    Energy Technology Data Exchange (ETDEWEB)

    Pillet, N. [DPTA/Service de Physique nucleaire, CEA/DAM Ile de France, BP12, F-91680 Bruyeres-le-Chatel (France); Sandulescu, N. [DPTA/Service de Physique nucleaire, CEA/DAM Ile de France, BP12, F-91680 Bruyeres-le-Chatel (France)]|[Institute of Physics and Nuclear Engineering, 76900 Bucharest (Romania)]|[Institut de Physique Nucleaire, CNRS, UMR 8608, Orsay, F-91406 (France); Schuck, P. [Institut de Physique Nucleaire, CNRS, UMR 8608, Orsay, F-91406 (France)]|[Universite Paris-Sud, Orsay, F-91505 (France)

    2007-01-15

    With realistic HFB calculations, using the D1S Gogny force, we reveal a generic behavior of concentration of small sized Cooper pairs (2-3 fm) in the surface of superfluid nuclei. This study confirms and extends previous results given in the literature that use more schematic approaches. It is shown that the strong concentration of pair probability of small Cooper pairs in the nuclear surface is a quite general and generic feature and that nuclear pairing is much closer to the strong coupling regime than previously assumed.

  20. Amelioration of behavioural toxicity of aluminium by oligomeric ...

    African Journals Online (AJOL)

    Despite its limited solubility at neutral pH, aluminium is significantly accumulated by the freshwater snail Lymnaea stagnalis, leading to behavioral toxicity. Both organic (humic acid) and non-organic (oligomeric silicic acid) ligands have been shown to reduce Al accumulation probably owing to their binding affinity for Al. This ...

  1. Ideal gas behavior of a strongly-coupled complex (dusty) plasma

    OpenAIRE

    Oxtoby, Neil P.; Griffith, Elias J.; Durniak, Céline; Ralph, Jason F.; Samsonov, Dmitry

    2012-01-01

    In a laboratory, a two-dimensional complex (dusty) plasma consists of a low-density ionized gas containing a confined suspension of Yukawa-coupled plastic microspheres. For an initial crystal-like form, we report ideal gas behavior in this strongly coupled system during shock-wave experiments. This evidence supports the use of the ideal gas law as the equation of state for soft crystals such as those formed by dusty plasmas.

  2. Biophysical characterization of GPCR oligomerization

    DEFF Research Database (Denmark)

    Mathiasen, Signe

    The biophysical characterization of the fundamental molecular mechanisms behind G-protein coupled receptors (GPCRs) oligomerization is proposed to be paramount for understanding the pharmacological consequence of receptor self-association. Here we developed an in vitro assay that allowed a quanti......The biophysical characterization of the fundamental molecular mechanisms behind G-protein coupled receptors (GPCRs) oligomerization is proposed to be paramount for understanding the pharmacological consequence of receptor self-association. Here we developed an in vitro assay that allowed...... a quantitative characterization of GPCR oligomerization. The assay provided the first quantification of the association energy of the β2 Adrenergic Receptor (β2AR), a prototypical GPCR. Furthermore we directly observed the time-dependent dimerization of β2AR and Cannabinoid receptor 1 at the single molecule...... level, and revealed the existence of several dimerization interfaces, each with specific kinetics. Finally we investigated how a property of the membrane solubilizing GPCRs affected oligomerization. We observed a dramatic decrease in oligomer stability with increasing geometrical membrane curvature. We...

  3. Strongly correlated Fermi-systems: Non-Fermi liquid behavior, quasiparticle effective mass and their interplay

    Energy Technology Data Exchange (ETDEWEB)

    Shaginyan, V.R. [Petersburg Nuclear Physics Institute, RAS, Gatchina 188300 (Russian Federation); Racah Institute of Physics, Hebrew University, Jerusalem 91904 (Israel)], E-mail: vrshag@thd.pnpi.spb.ru; Amusia, M.Ya. [Racah Institute of Physics, Hebrew University, Jerusalem 91904 (Israel); Popov, K.G. [Komi Science Center, Ural Division, RAS, Syktyvkar 167982 (Russian Federation)

    2009-06-15

    Basing on the density functional theory of fermion condensation, we analyze the non-Fermi liquid behavior of strongly correlated Fermi-systems such as heavy-fermion metals. When deriving equations for the effective mass of quasiparticles, we consider solids with a lattice and homogeneous systems. We show that the low-temperature thermodynamic and transport properties are formed by quasiparticles, while the dependence of the effective mass on temperature, number density, magnetic fields, etc., gives rise to the non-Fermi liquid behavior. Our theoretical study of the heat capacity, magnetization, energy scales, the longitudinal magnetoresistance and magnetic entropy are in good agreement with the remarkable recent facts collected on the heavy-fermion metal YbRh{sub 2}Si{sub 2}.

  4. Strongly correlated Fermi-systems: Non-Fermi liquid behavior, quasiparticle effective mass and their interplay

    International Nuclear Information System (INIS)

    Shaginyan, V.R.; Amusia, M.Ya.; Popov, K.G.

    2009-01-01

    Basing on the density functional theory of fermion condensation, we analyze the non-Fermi liquid behavior of strongly correlated Fermi-systems such as heavy-fermion metals. When deriving equations for the effective mass of quasiparticles, we consider solids with a lattice and homogeneous systems. We show that the low-temperature thermodynamic and transport properties are formed by quasiparticles, while the dependence of the effective mass on temperature, number density, magnetic fields, etc., gives rise to the non-Fermi liquid behavior. Our theoretical study of the heat capacity, magnetization, energy scales, the longitudinal magnetoresistance and magnetic entropy are in good agreement with the remarkable recent facts collected on the heavy-fermion metal YbRh 2 Si 2 .

  5. CFD modeling of particle behavior in supersonic flows with strong swirls for gas separation

    DEFF Research Database (Denmark)

    Yang, Yan; Wen, Chuang

    2017-01-01

    . The results showed that the gas flow was accelerated to supersonic velocity, and created the low pressure and temperature conditions for gas removal. Most of the particles collided with the walls or entered into the liquid-collection space directly, while only a few particles escaped together with the gas......The supersonic separator is a novel technique to remove the condensable components from gas mixtures. But the particle behavior is not well understood in this complex supersonic flow. The Discrete Particle Method was used here to study the particle motion in supersonic flows with a strong swirl...

  6. Strategies/Behaviors That Successful Superintendents Use to Build Strong Relationships and Trust during Their Entry Period

    Science.gov (United States)

    Green, C. K.

    2012-01-01

    The purpose of the study was to identify strategies/behaviors that successful superintendents used to build strong relationships and trust with their school boards within their entry period. The following research questions guided the study: (1) What strategies/behaviors are successful superintendents using to build strong relationships and trust…

  7. The effect of molecular shape on oligomerization of hydrophobic drugs: Molecular simulations of ciprofloxacin and nutlin

    Science.gov (United States)

    Li, Jianguo; Beuerman, Roger; Verma, Chandra

    2018-03-01

    Molecular aggregation plays a significant role in modulating the solubility, permeability, and bioactivity of drugs. The propensity to aggregate depends on hydrophobicity and on molecular shape. Molecular dynamics simulations coupled with enhanced sampling methods are used to explore the early stages of oligomerization of two drug molecules which have a strong aggregation propensity, but with contrasting molecule shapes: the antibiotic ciprofloxacin and the anticancer drug Nutlin-3A. The planar shape of ciprofloxacin induces the formation of stable oligomers at all cluster sizes. The aggregation of ciprofloxacin is driven by two-body interactions, and transferring one ciprofloxacin molecule to an existing cluster involves the desolvation of two faces and the concomitant hydrophobic interactions between the two faces; thus, the corresponding free energy of oligomerization weakly depends on the oligomer size. By contrast, Nutlin-3A has a star-shape and hence can only form stable oligomers when the cluster size is greater than 8. Free energy simulations further confirmed that the free energy of oligomer formation for Nutlin-3A becomes more favorable as the oligomer becomes larger. The aggregation of star-shaped Nutlin-3A results from many-body interactions and hence the free energy of cluster formation is strongly dependent on the size. The findings of this study provide atomistic insights into how molecular shape modulates the aggregation behavior of molecules and may be factored into the design of drugs or nano-particles.

  8. Spin quenching assisted by a strongly anisotropic compression behavior in MnP

    Energy Technology Data Exchange (ETDEWEB)

    Han, Fei; Wang, Di; Wang, Yonggang; Li, Nana; Bao, Jin-Ke; Li, Bing; Botana, Antia S.; Xiao, Yuming; Chow, Paul; Chung, Duck Young; Chen, Jiuhua; Wan, Xiangang; Kanatzidis, Mercouri G.; Yang, Wenge; Mao, Ho-Kwang

    2018-02-01

    We studied the crystal structure and spin state of MnP under high pressure with synchrotron X-ray diffraction and X-ray emission spectroscopy. MnP has an exceedingly strong anisotropy in compressibility, with the primary compressible direction along the b axis of the Pnma structure. X-ray emission spectroscopy reveals a pressure-driven quenching of the spin state in MnP. First-principles calculations suggest that the strongly anisotropic compression behavior significantly enhances the dispersion of the Mn d-orbitals and the splitting of the d-orbital levels compared to the hypothetical isotropic compression behavior. Thus, we propose spin quenching results mainly from the significant enhancement of the itinerancy of d electrons and partly from spin rearrangement occurring in the split d-orbital levels near the Fermi level. This explains the fast suppression of magnetic ordering in MnP under high pressure. The spin quenching lags behind the occurrence of superconductivity at ~8 GPa implying that spin fluctuations govern the electron pairing for superconductivity.

  9. Adsorption Behavior of Charge Isoforms of Monoclonal Antibodies on Strong Cation Exchangers.

    Science.gov (United States)

    Steinebach, Fabian; Wälchli, Ruben; Pfister, David; Morbidelli, Massimo

    2017-12-01

    In this work, the adsorption behavior of the different charge isoforms of the same monoclonal antibody (mAb) on strong cation-exchange resins is analyzed. While charge isoforms of the same antibody mainly differ in their effective charge, the similar structure and size allows developing a simplified model, which describes the adsorption behavior of mAb charge isoforms independently of the number of isoforms with only four parameters. In contrast to classical model-based descriptions of the adsorption isotherm, the proposed work enables retrieving some physical meaning in the definition of the model parameters. These model parameters are determined for several resin-antibody combinations. Thereby it is found that for mAbs on commercial cation exchangers an effective resin charge density of 0.22 ± 0.08 mmol mL -1 of solid phase is used for protein binding, which was found to be independent of the absolute resin charge density measured by titration. The presented results help to understand the adsorption behavior of mAbs on cation-exchangers, which is applicable both for the isolation of the main charge isoform or for preserving a certain charge isoform pattern during the polishing processes. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Phase transitions, nonequilibrium dynamics, and critical behavior of strongly interacting systems

    Energy Technology Data Exchange (ETDEWEB)

    Mottola, E.; Bhattacharya, T.; Cooper, F. [and others

    1998-12-31

    This is the final report of a three-year, Laboratory Directed Research and Development project at Los Alamos National Laboratory. In this effort, large-scale simulations of strongly interacting systems were performed and a variety of approaches to the nonequilibrium dynamics of phase transitions and critical behavior were investigated. Focus areas included (1) the finite-temperature quantum chromodynamics phase transition and nonequilibrium dynamics of a new phase of matter (the quark-gluon plasma) above the critical temperature, (2) nonequilibrium dynamics of a quantum fields using mean field theory, and (3) stochastic classical field theoretic models with applications to spinodal decomposition and structural phase transitions in a variety of systems, such as spin chains and shape memory alloys.

  11. Single-molecule diffusometry reveals the nucleotide-dependent oligomerization pathways of Nicotiana tabacum Rubisco activase

    Science.gov (United States)

    Wang, Quan; Serban, Andrew J.; Wachter, Rebekka M.; Moerner, W. E.

    2018-03-01

    Oligomerization plays an important role in the function of many proteins, but a quantitative picture of the oligomer distribution has been difficult to obtain using existing techniques. Here we describe a method that combines sub-stoichiometric labeling and recently developed single-molecule diffusometry to measure the size distribution of oligomers under equilibrium conditions in solution, one molecule at a time. We use this technique to characterize the oligomerization behavior of Nicotiana tabacum (Nt) Rubisco activase (Nt-Rca), a chaperone-like AAA-plus ATPase essential in regulating carbon fixation during photosynthesis. We directly observed monomers, dimers, and a tetramer/hexamer mixture and extracted their fractional abundance as a function of protein concentration. We show that the oligomerization pathway of Nt-Rca is nucleotide dependent: ATPγS binding strongly promotes tetramer/hexamer formation from dimers and results in a preferred tetramer/hexamer population for concentrations in the 1-10 μM range. Furthermore, we directly observed dynamic assembly and disassembly processes of single complexes in real time and from there estimated the rate of subunit exchange to be ˜0.1 s-1 with ATPγS. On the other hand, ADP binding destabilizes Rca complexes by enhancing the rate of subunit exchange by >2 fold. These observations provide a quantitative starting point to elucidate the structure-function relations of Nt-Rca complexes. We envision the method to fill a critical gap in defining and quantifying protein assembly pathways in the small-oligomer regime.

  12. Tuning smart microgel swelling and responsive behavior through strong and weak polyelectrolyte pair assembly.

    Science.gov (United States)

    Costa, Eunice; Lloyd, Margaret M; Chopko, Caroline; Aguiar-Ricardo, Ana; Hammond, Paula T

    2012-07-03

    The layer-by-layer (LbL) assembly of polyelectrolyte pairs on temperature and pH-sensitive cross-linked poly(N-isopropylacrylamide)-co-(methacrylic acid), poly(NIPAAm-co-MAA), microgels enabled a fine-tuning of the gel swelling and responsive behavior according to the mobility of the assembled polyelectrolyte (PE) pair and the composition of the outermost layer. Microbeads with well-defined morphology were initially prepared by synthesis in supercritical carbon dioxide. Upon LbL assembly of polyelectrolytes, interactions between the multilayers and the soft porous microgel led to differences in swelling and thermoresponsive behavior. For the weak PE pairs, namely poly(L-lysine)/poly(L-glutamic acid) and poly(allylamine hydrochloride)/poly(acrylic acid), polycation-terminated microgels were less swollen and more thermoresponsive than native microgel, whereas polyanion-terminated microgels were more swollen and not significantly responsive to temperature, in a quasi-reversible process with consecutive PE assembly. For the strong PE pair, poly(diallyldimethylammonium chloride)/poly(sodium styrene sulfonate), the differences among polycation and polyanion-terminated microgels are not sustained after the first PE bilayer due to extensive ionic cross-linking between the polyelectrolytes. The tendencies across the explored systems became less noteworthy in solutions with larger ionic strength due to overall charge shielding of the polyelectrolytes and microgel. ATR FT-IR studies correlated the swelling and responsive behavior after LbL assembly on the microgels with the extent of H-bonding and alternating charge distribution within the gel. Thus, the proposed LbL strategy may be a simple and flexible way to engineer smart microgels in terms of size, surface chemistry, overall charge and permeability.

  13. Modeling consequences of prolonged strong unpredictable stress in zebrafish: Complex effects on behavior and physiology.

    Science.gov (United States)

    Song, Cai; Liu, Bai-Ping; Zhang, Yong-Ping; Peng, Zhilan; Wang, JiaJia; Collier, Adam D; Echevarria, David J; Savelieva, Katerina V; Lawrence, Robert F; Rex, Christopher S; Meshalkina, Darya A; Kalueff, Allan V

    2018-02-02

    Chronic stress is the major pathogenetic factor of human anxiety and depression. Zebrafish (Danio rerio) have become a novel popular model species for neuroscience research and CNS drug discovery. The utility of zebrafish for mimicking human affective disorders is also rapidly growing. Here, we present a new zebrafish model of clinically relevant, prolonged unpredictable strong chronic stress (PUCS). The 5-week PUCS induced overt anxiety-like and motor retardation-like behaviors in adult zebrafish, also elevating whole-body cortisol and proinflammatory cytokines - interleukins IL-1β and IL-6. PUCS also elevated whole-body levels of the anti-inflammatory cytokine IL-10 and increased the density of dendritic spines in zebrafish telencephalic neurons. Chronic treatment of fish with an antidepressant fluoxetine (0.1mg/L for 8days) normalized their behavioral and endocrine phenotypes, as well as corrected stress-elevated IL-1β and IL-6 levels, similar to clinical and rodent data. The CNS expression of the bdnf gene, the two genes of its receptors (trkB, p75), and the gfap gene of glia biomarker, the glial fibrillary acidic protein, was unaltered in all three groups. However, PUCS elevated whole-body BDNF levels and the telencephalic dendritic spine density (which were corrected by fluoxetine), thereby somewhat differing from the effects of chronic stress in rodents. Together, these findings support zebrafish as a useful in-vivo model of chronic stress, also calling for further cross-species studies of both shared/overlapping and distinct neurobiological responses to chronic stress. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Critical Behavior of a Strongly-Interacting 2D Electron System

    Science.gov (United States)

    Sarachik, Myriam P.

    2013-03-01

    Two-dimensional (2D) electron systems that obey Fermi liquid theory at high electron densities are expected to undergo one or more transitions to spatially and/or spin-ordered phases as the density is decreased, ultimately forming a Wigner crystal in the dilute, strongly-interacting limit. Interesting, unexpected behavior is observed with decreasing electron density as the electrons' interactions become increasingly important relative to their kinetic energy: the resistivity undergoes a transition from metallic to insulating temperature dependence; the resistance increases sharply and then saturates abruptly with increasing in-plane magnetic field; a number of experiments indicate that the electrons' effective mass exhibits a substantial increase approaching a finite ``critical'' density. There has been a great deal of debate concerning the underlying physics in these systems, and many have questioned whether the change of the resistivity from metallic to insulating signals a phase transition or a crossover. In this talk, I will report measurements that show that with decreasing density ns, the thermopower S of a low-disorder 2D electron system in silicon exhibits a sharp increase by more than an order of magnitude, tending to a divergence at a finite, disorder-independent density nt, consistent with the critical form (- T / S) ~(ns -nt) x with x = 1 . 0 +/- 0 . 1 (T is the temperature). Unlike the resistivity which may not clearly distinguish between a transition and crossover behavior, the thermopower provides clear evidence that a true phase transition occurs with decreasing density to a new low-density phase. Work supported by DOE Grant DE-FG02-84ER45153, BSF grant 2006375, RFBR, RAS, and the Russian Ministry of Science.

  15. Heterogeneous Catalytic Oligomerization of Ethylene

    Science.gov (United States)

    Jan, Oliver Dennis

    Throughout this work, we report results for the oligomerization of ethylene over Ni-Hbeta in a packed bed reactor. We performed a parameterized study over temperature (30ºC-190ºC), pressure (8.5-25.6 bar), and weighted hourly space velocity (2.0-5.5 hr-1). We observed that the ethylene conversion increased with reaction pressure due primarily to the slower velocities at higher pressures. Increasing the temperature of the reactor led to the formation of larger oligomers and coke, but its effect on the conversion was small. The space velocity played an important role on ethylene conversion and product selectivity, with higher conversions observed at lower space velocities and higher selectivities to butene at higher space velocities. We also conducted a long experiment to determine the activity of the Ni-Hbeta catalyst over 72 hours-on-stream at 19.0 bar partial pressure of ethylene, 120ºC, and 3.1 hr-1 WHSV. We observed that catalyst deactivation occurred only during the startup period largely due to coke formation. Despite this initial deactivation, negligible coke formation occurred after 8 hours time-on-stream, as the conversion remained steady at 47% for the duration of the experiment. We also carried out oligomerization of ethylene using Ni-Hbeta in a laboratory-scale packed bed reactor for the synthesis of liquid hydrocarbons. We evaluated the effect of several process variables (temperature, pressure, weighted hourly space velocity, and nickel loading) on the liquid hydrocarbon/coke yield, ethylene conversion, and oligomeric product selectivity. Increases in pressure resulted in higher ethylene conversion, corresponding to a liquid yield of 12.4 wt.% with 5.7 wt.% coke. As the pressure increased, the selectivity towards octenes doubled alongside a decrease in butenes, which suggested that higher pressures promoted butene dimerization. Under the conditions studied, a minimum temperature of 120ºC was required to produce liquid hydrocarbons. The liquid yield

  16. Radiochemical study of Re/W adsorption behavior on a strongly basic anion exchange resin

    Energy Technology Data Exchange (ETDEWEB)

    Gott, Matthew D. [Los Alamos National Laboratory, Los Alamos, NM (United States). Chemistry Div.; Missouri Univ., Columbia, MO (United States). Dept. of Chemistry; Ballard, Beau D.; Redman, Lindsay N. [Los Alamos National Laboratory, Los Alamos, NM (United States). Chemistry Div.; and others

    2014-07-01

    Rhenium-186g is a radionuclide with a high potential for therapeutic applications. It emits therapeutic β{sup -} particles accompanied by low energy γ-rays, which allows for in-vivo tracking of the radiolabeled compound and dosimetry estimates. The current reactor production pathway {sup 185}Re(n,γ){sup 186g}Re produces low specific activity {sup 186g}Re, thereby limiting its therapeutic application. Work is underway to develop an accelerator-based, charged particle induced production method for high specific activity {sup 186g}Re from targets of enriched {sup 186}W. To optimize the chemical {sup 186g}Re recovery method, batch studies have been performed to characterize the adsorption behavior of Re and W on a strongly basic anion exchange resin. An in-depth physicochemical profile was developed for the interaction of Re with resin material, which showed the reaction to be endothermic and spontaneous. Basic (NaOH) and acidic (HNO{sub 3}) matrices were used to determine the equilibrium distribution coefficients for Re and W. The resin exhibits the best affinity for Re at slightly basic conditions and little affinity above moderately acidic concentrations. Tungsten has low affinity for the resin above moderately basic concentrations. A study was performed to examine the effect of W concentration on Re adsorption, which showed that even a high ionic WO{sub 4}{sup 2-} strength of up to 1.9 mol kg{sup -1} does not significantly compromise ReO{sub 4}{sup -} retention on the resin. (orig.)

  17. Dimerization and oligomerization of the chaperone calreticulin

    DEFF Research Database (Denmark)

    Jørgensen, Charlotte S; Ryder, L Rebekka; Steinø, Anne

    2003-01-01

    protein. Using PAGE, urea gradient gel electrophoresis, capillary electrophoresis and MS, we show that dimerization through the SH group can be induced by lowering the pH to 5-6, heating, or under conditions that favour partial unfolding such as urea concentrations above 2.6 m or SDS concentrations above...... that favour partial unfolding or an intramolecular local conformational change that allows oligomerization, resulting in a heterogeneous mixture of oligomers consisting of up to 10 calreticulin monomers. The oligomeric calreticulin was very stable, but oligomerization was partially reversed by addition of 8 m...

  18. Protein dimerization and oligomerization in biology

    National Research Council Canada - National Science Library

    Matthews, Jacqueline M

    2012-01-01

    .... However, protein function is so often linked to both homo- and hetero-oligomerization and many heterologous interactions likely evolved from homologous interaction, so this volume also covers many...

  19. Carbon Nanostructures Containing Polyhedral Oligomeric Silsesquioxanes (POSS)

    NARCIS (Netherlands)

    Potsi, Georgia; Rossos, Andreas; Kouloumpis, Antonios; Antoniou, Myrsini K.; Spyrou, Konstantinos; Karakassides, Michael A.; Gournis, Dimitrios; Rudolf, Petra

    2015-01-01

    This mini review describes the synthesis and properties of carbon nanostructures containing organic-inorganic cage-like polyhedral oligomeric silsesquioxane (POSS). The physical and chemical functionalization of carbon nanomaterials such as graphene, graphene oxide, carbon nanotubes, and fullerenes

  20. Reversible peptide oligomerization over nanoscale gold surfaces

    Directory of Open Access Journals (Sweden)

    Kazushige Yokoyama

    2015-11-01

    Full Text Available A selective oligomeric formation of amyloid beta 1-40 (Ab1-40 monomers over a nanogold colloidal surface was investigated. An unfolded Ab1-40 monomer is considered to construct a dimer or trimer based oligomeric form with its hydrophobic segment placing outward under an acidic condition. Under a basic condition, a conformation of Ab is expected to take a folded monomeric form with its hydrophilic segment folded inward, avoiding the networking with residual colloidal particles. The most probable oligomeric form constructed over a 20 nm gold colloidal surface within a 25 ℃ to 65 ℃ temperature range is a dimer based unit and that over 30 or 40 nm gold colloidal surface below 15 ℃ is concluded to be a trimer based unit. However, selective oligomerization was not successfully reproduced under the rest of the conditions. A dipole-induced dipole interaction must cause a flexible structural change between folded and unfolded forms.

  1. Activism: A Strong Predictor of Proactive Environmentally Friendly Buying Behavior in Turkey

    Directory of Open Access Journals (Sweden)

    Ahu Ergen

    2014-02-01

    Full Text Available The market for environmentally friendly products in Turkey is growing, and marketing experts are trying to understand the behavior of the consumers in this market with the help of variables such as demographic factors, information, attitudes, values and life styles. This study analyzes the effects of environmental activism, environmental knowledge and the perceived seriousness of environmental problems on green buying behavior. The study involved 516 Turkish consumers, over eighteen years of age. The results show that environmental activism, environmental knowledge and the perceived seriousness of environmental problems are all meaningful factors in environmentally friendly buying behavior. It was found that the most explanatory variables are environmental activism for proactive environmentally friendly buying behavior and the perceived seriousness of environmental problems for optional environmentally friendly buying behavior. The study is significant since it will offer insights for green marketing experts who especially target specific segments as activists, voluntary simplifiers or green consumers in Turkey.

  2. Activism: A Strong Predictor of Proactive Environmentally Friendly Buying Behavior in Turkey

    Directory of Open Access Journals (Sweden)

    Ahu Ergen

    2016-01-01

    Full Text Available The market for environmentally friendly products in Turkey is growing, and marketing experts are trying to understand the behavior of the consumers in this market with the help of variables such as demographic factors, information, attitudes, values and life styles. This study analyzes the effects of environmental activism, environmental knowledge and the perceived seriousness of environmental problems on green buying behavior. The study involved 516 Turkish consumers, over eighteen years of age. The results show that environmental activism, environmental knowledge and the perceived seriousness of environmental problems are all meaningful factors in environmentally friendly buying behavior. It was found that the most explanatory variables are environmental activism for proactive environmentally friendly buying behavior and the perceived seriousness of environmental problems for optional environmentally friendly buying behavior. The study is significant since it will offer insights for green marketing experts who especially target specific segments as activists, voluntary simplifiers or green consumers in Turkey.

  3. Synthesis of oligomeric boron-containing phospolyols

    International Nuclear Information System (INIS)

    Bondarenko, S.N.; Khokhlova, T.V.; Orlova, S.A.; Tuzhikov, O.I.

    2006-01-01

    Structure is investigated and reactivity of oligomeric boron-containing phospolyols is studied. Oligomeric boron-containing compound interacts with ethylene glycol, diethylene glycol, glycerol, 1,4-butandiol with formation of linear boron-containing phospolyols. Reactions proceed in noncatalytic conditions with stoichiometric quantities of reagents at 170-200 Deg C in inert gas media. Boron-containing phospolyols are viscous uncolored liquids, their physicochemical characteristics are represented [ru

  4. Departures from predicted type II behavior in dirty strong-coupling superconductors

    International Nuclear Information System (INIS)

    Park, J.C.; Neighbor, J.E.; Shiffman, C.A.

    1976-01-01

    Calorimetric measurements of the Ginsburg-Landau parameters for Pb-Sn and Pb-Bi alloys show good agreement with the calculations of Rainer and Bergmann for kappa 1 (t)/kappa 1 (1). However, the calculations of Rainer and Usadel for kappa 2 (t)/kappa 2 (1) substantially underestimate the enhancements due to strong-coupling. (Auth.)

  5. Echinococcus granulosus Antigen B Structure: Subunit Composition and Oligomeric States

    Science.gov (United States)

    Monteiro, Karina M.; Cardoso, Mateus B.; Follmer, Cristian; da Silveira, Nádya P.; Vargas, Daiani M.; Kitajima, Elliot W.; Zaha, Arnaldo; Ferreira, Henrique B.

    2012-01-01

    Background Antigen B (AgB) is the major protein secreted by the Echinococcus granulosus metacestode and is involved in key host-parasite interactions during infection. The full comprehension of AgB functions depends on the elucidation of several structural aspects that remain unknown, such as its subunit composition and oligomeric states. Methodology/Principal Findings The subunit composition of E. granulosus AgB oligomers from individual bovine and human cysts was assessed by mass spectrometry associated with electrophoretic analysis. AgB8/1, AgB8/2, AgB8/3 and AgB8/4 subunits were identified in all samples analyzed, and an AgB8/2 variant (AgB8/2v8) was found in one bovine sample. The exponentially modified protein abundance index (emPAI) was used to estimate the relative abundance of the AgB subunits, revealing that AgB8/1 subunit was relatively overrepresented in all samples. The abundance of AgB8/3 subunit varied between bovine and human cysts. The oligomeric states formed by E. granulosus AgB and recombinant subunits available, rAgB8/1, rAgB8/2 and rAgB8/3, were characterized by native PAGE, light scattering and microscopy. Recombinant subunits showed markedly distinct oligomerization behaviors, forming oligomers with a maximum size relation of rAgB8/3>rAgB8/2>rAgB8/1. Moreover, the oligomeric states formed by rAgB8/3 subunit were more similar to those observed for AgB purified from hydatid fluid. Pressure-induced dissociation experiments demonstrated that the molecular assemblies formed by the more aggregative subunits, rAgB8/2 and rAgB8/3, also display higher structural stability. Conclusions/Significance For the first time, AgB subunit composition was analyzed in samples from single hydatid cysts, revealing qualitative and quantitative differences between samples. We showed that AgB oligomers are formed by different subunits, which have distinct abundances and oligomerization properties. Overall, our findings have significantly contributed to increase the

  6. When a clear strong voice was needed: A retrospective review of Watson's (1924/1930) behaviorism.

    Science.gov (United States)

    Malone, John C; García-Penagos, Andrés

    2014-07-25

    Despite the attention given John B. Watson during the century since he introduced behaviorism, there remain questions about what he really contributed. He is still appropriately criticized for his arrogant self-promotion and especially for his perceived emphasis on a simple S-R reflexology. However, we argue that the former was necessary at the time and that criticism of Watson on the second count only diverts attention from the genuine contributions that he did make. In support of these contentions we examine several aspects of his contributions that warrant clarification, namely, his promotion of applied comparative psychology, his views on the nature of mind, his originality, criticism from and respect afforded by contemporaries, his relation to recent interest in "the embodiment of mind," his treatment of thinking, and his appreciation of Freud's work. We organize our discussion around specific chapters of the two editions of Behaviorism, but in support of our arguments we include publications of Watson that are less well known. Those works develop some important points that are only briefly treated in both editions of Behaviorism. © Society for the Experimental Analysis of Behavior.

  7. Serum MHPG Strongly Predicts Conversion to Alzheimer's Disease in Behaviorally Characterized Subjects with Down Syndrome

    NARCIS (Netherlands)

    Dekker, Alain D.; Coppus, Antonia M. W.; Vermeiren, Yannick; Aerts, Tony; van Duijn, Cornelia M.; Kremer, Berry P.; Naude, Pieter J. W.; Van Dam, Debby; De Deyn, Peter P.

    2015-01-01

    Background: Down syndrome (DS) is the most prevalent genetic cause of intellectual disability. Early-onset Alzheimer's disease (AD) frequently develops in DS and is characterized by progressive memory loss and behavioral and psychological signs and symptoms of dementia (BPSD). Predicting and

  8. Global Behavior for a Strongly Coupled Predator-Prey Model with One Resource and Two Consumers

    Directory of Open Access Journals (Sweden)

    Yujuan Jiao

    2012-01-01

    Full Text Available We consider a strongly coupled predator-prey model with one resource and two consumers, in which the first consumer species feeds on the resource according to the Holling II functional response, while the second consumer species feeds on the resource following the Beddington-DeAngelis functional response, and they compete for the common resource. Using the energy estimates and Gagliardo-Nirenberg-type inequalities, the existence and uniform boundedness of global solutions for the model are proved. Meanwhile, the sufficient conditions for global asymptotic stability of the positive equilibrium for this model are given by constructing a Lyapunov function.

  9. Behavior of Particle Depots in Molten Silicon During Float-Zone Growth in Strong Magnetic Fields

    Science.gov (United States)

    Jauss, T.; Croell, A.; SorgenFrei, T.; Azizi, M.; Reimann, C.; Friedrich, J.; Volz, M. P.

    2014-01-01

    Solar cells made from directionally solidified silicon cover 57% of the photovoltaic industry's market [1]. One major issue during directional solidification of silicon is the precipitation of foreign phase particles. These particles, mainly SiC and Si3N4, are precipitated from the dissolved crucible coating, which is made of silicon nitride, and the dissolution of carbon monoxide from the furnace atmosphere. Due to their hardness and size of several hundred micrometers, those particles can lead to severe problems during the wire sawing process for wafering the ingots. Additionally, SiC particles can act as a shunt, short circuiting the solar cell. Even if the particles are too small to disturb the wafering process, they can lead to a grit structure of silicon micro grains and serve as sources for dislocations. All of this lowers the yield of solar cells and reduces the performance of cells and modules. We studied the behaviour of SiC particle depots during float-zone growth under an oxide skin, and strong static magnetic fields. For high field strengths of 3T and above and an oxide layer on the sample surface, convection is sufficiently suppressed to create a diffusive like regime, with strongly dampened convection [2, 3]. To investigate the difference between atomically rough phase boundaries and facetted growth, samples with [100] and [111] orientation were processed.

  10. Describing nonequilibrium behavior in strongly correlated materials via dynamical mean-field theory

    Science.gov (United States)

    Freericks, James

    2010-03-01

    Dynamical mean-field theory was introduced in 1989 and has become one of the most successful methods for solving models of strongly correlated electrons in equilibrium (it becomes exact in the infinite-dimensional limit). In this talk, I show how to generalize dynamical mean-field theory to nonequilibrium situations. For transient response, one discretizes the Kadanoff-Baym-Keldysh contour then solves the discrete problem directly. For steady-state response, one can formulate a theory directly in the long-time limit for the retarded Green's functions. These techniques are applied to the problem of the quenching of Bloch oscillations due to electron-electron interactions and to the problem of time-resolved pump/probe photoemission spectroscopy of strongly correlated electrons when a system is driven to a nonequilibrium steady state and cannot be described by the quasiequilibrium approximation with an effective temperature. This work was completed in collaboration with Tom Devereaux, Sasha Joura, Hulikal Krishnamurthy, Brian Moritz, Thomas Pruschke, Volodomyr Turkowski, and Velko Zlati'c. Recent references include: J. K. Freericks, V. M. Turkowski, and V. Zlati'c, Phys. Rev. Lett. 97, 266408 (2006); J. K. Freericks, Phys. Rev. B 77, 075109 (2008); A. V.Joura, J. K. Freericks, and Th. Pruschke, Phys. Rev. Lett. 101, 196401 (2008); J. K. Freericks, H. R. Krishnamurthy and Th. Pruschke, Phys. Rev. Lett. 102, 136401 (2009); and B. Moritz, T. P. Devereaux, and J. K. Freericks, arXiv:0908.1807.

  11. Initial design for an experimental investigation of strongly coupled plasma behavior in the ATLAS facility

    CERN Document Server

    Munson, C P; Taylor, A J; Trainor, R J; Wood, B P; Wysocki, F J

    1999-01-01

    Summary form only given. Atlas is a high current (~30 MA peak, with a current risetime ~4.5 mu sec), high energy (E/sub stored/=24 MJ, E /sub load/=3-6 MJ), pulsed power facility which is being constructed at Los Alamos National Laboratory with a scheduled completion date in the year 2000. When operational, this facility will provide a platform for experiments in high pressure shocks (>20 Mbar), adiabatic compression ( rho / rho /sub 0/>5, P>10 Mbar), high magnetic fields (~2000 T), high strain and strain rates ( epsilon >200, d epsilon /dt~10/sup 4/ to 10/sup 6/ s/sup -1/), hydrodynamic instabilities of materials in turbulent regimes, magnetized target fusion, equation of state, and strongly coupled plasmas. For the strongly coupled plasma experiments, an auxiliary capacitor bank will be used to generate a moderate density (<0.1 solid), relatively cold (~1 eV) plasma by ohmic heating of a conducting material of interest such as titanium. This target plasma will be compressed against a central column conta...

  12. Transient oligomerization of the SARS-CoV N protein--implication for virus ribonucleoprotein packaging.

    Science.gov (United States)

    Chang, Chung-ke; Chen, Chia-Min Michael; Chiang, Ming-hui; Hsu, Yen-lan; Huang, Tai-huang

    2013-01-01

    The nucleocapsid (N) phosphoprotein of the severe acute respiratory syndrome coronavirus (SARS-CoV) packages the viral genome into a helical ribonucleocapsid and plays a fundamental role during viral self-assembly. The N protein consists of two structural domains interspersed between intrinsically disordered regions and dimerizes through the C-terminal structural domain (CTD). A key activity of the protein is the ability to oligomerize during capsid formation by utilizing the dimer as a building block, but the structural and mechanistic bases of this activity are not well understood. By disulfide trapping technique we measured the amount of transient oligomers of N protein mutants with strategically located cysteine residues and showed that CTD acts as a primary transient oligomerization domain in solution. The data is consistent with the helical oligomer packing model of N protein observed in crystal. A systematic study of the oligomerization behavior revealed that altering the intermolecular electrostatic repulsion through changes in solution salt concentration or phosphorylation-mimicking mutations affects oligomerization propensity. We propose a biophysical mechanism where electrostatic repulsion acts as a switch to regulate N protein oligomerization.

  13. Transient oligomerization of the SARS-CoV N protein--implication for virus ribonucleoprotein packaging.

    Directory of Open Access Journals (Sweden)

    Chung-ke Chang

    Full Text Available The nucleocapsid (N phosphoprotein of the severe acute respiratory syndrome coronavirus (SARS-CoV packages the viral genome into a helical ribonucleocapsid and plays a fundamental role during viral self-assembly. The N protein consists of two structural domains interspersed between intrinsically disordered regions and dimerizes through the C-terminal structural domain (CTD. A key activity of the protein is the ability to oligomerize during capsid formation by utilizing the dimer as a building block, but the structural and mechanistic bases of this activity are not well understood. By disulfide trapping technique we measured the amount of transient oligomers of N protein mutants with strategically located cysteine residues and showed that CTD acts as a primary transient oligomerization domain in solution. The data is consistent with the helical oligomer packing model of N protein observed in crystal. A systematic study of the oligomerization behavior revealed that altering the intermolecular electrostatic repulsion through changes in solution salt concentration or phosphorylation-mimicking mutations affects oligomerization propensity. We propose a biophysical mechanism where electrostatic repulsion acts as a switch to regulate N protein oligomerization.

  14. Synthesis and Characterization of CdS Nanoparticles with Strong Electrolyte Behavior

    International Nuclear Information System (INIS)

    Zhang Yu; Fu, Degang; Liu Juzheng

    2000-01-01

    The CdS nanoparticles whose structure is similar to a strong electrolyte were synthesized by the colloidal chemical method. The CdS nanoparticles with Cd 2+ -rich surface are capped by the electrically neutral ligand of 2,2'-bipyridine (bpy), and the counterion, BPh 4 - , is adsorbed around the particle as balance charge. The ω donation from 2,2'-bipyridine at 2-position to the Cd 2+ -rich surface of the CdS nanoparticles was characterized by X-ray photoelectron spectroscopy (XPS). These CdS nanoparticles can redisperse in pyridine (py) or DMF, and have high stability. The determination of electroconductivity and the electrophoresis deposition in dilute solution containing the CdS nanoparticles further prove the rationality of the above electrolyte structure of the CdS nanoparticles

  15. Absence of strong strain effects in behavioral analyses of Shank3-deficient mice

    Directory of Open Access Journals (Sweden)

    Elodie Drapeau

    2014-06-01

    Full Text Available Haploinsufficiency of SHANK3, caused by chromosomal abnormalities or mutations that disrupt one copy of the gene, leads to a neurodevelopmental syndrome called Phelan-McDermid syndrome, symptoms of which can include absent or delayed speech, intellectual disability, neurological changes and autism spectrum disorders. The SHANK3 protein forms a key structural part of the post-synaptic density. We previously generated and characterized mice with a targeted disruption of Shank3 in which exons coding for the ankyrin-repeat domain were deleted and expression of full-length Shank3 was disrupted. We documented specific deficits in synaptic function and plasticity, along with reduced reciprocal social interactions, in Shank3 heterozygous mice. Changes in phenotype owing to a mutation at a single locus are quite frequently modulated by other loci, most dramatically when the entire genetic background is changed. In mice, each strain of laboratory mouse represents a distinct genetic background and alterations in phenotype owing to gene knockout or transgenesis are frequently different across strains, which can lead to the identification of important modifier loci. We have investigated the effect of genetic background on phenotypes of Shank3 heterozygous, knockout and wild-type mice, using C57BL/6, 129SVE and FVB/Ntac strain backgrounds. We focused on observable behaviors with the goal of carrying out subsequent analyses to identify modifier loci. Surprisingly, there were very modest strain effects over a large battery of analyses. These results indicate that behavioral phenotypes associated with Shank3 haploinsufficiency are largely strain-independent.

  16. Star Poly(N-isopropylacrylamide Tethered to Polyhedral Oligomeric Silsesquioxane (POSS Nanoparticles by a Combination of ATRP and Click Chemistry

    Directory of Open Access Journals (Sweden)

    Shiao-Wei Kuo

    2012-01-01

    Full Text Available New star poly(N-isopropylacrylamide-b-polyhedral oligomeric silsesquioxane (PNIPAm-b-POSS copolymers were synthesized from octa-azido functionalized POSS (N3-POSS and alkyne-PNIPAm, which was prepared using an alkyne-functionalized atom transfer radical polymerization (ATRP initiator (propargyl 2-bromo-2-methylpropionamide, via click chemistry. These star PNIPAm-b-POSS copolymers undergo a sharp coil-globule transition in water at above 32°C changing from a hydrophilic state below this temperature to a hydrophobic state above it, which is similar to linear PNIPAm homopolymers. More interestingly, we found that these star polymers exhibited strong blue photoluminescence in water above a lower critical solution temperature (LCST. This photoluminescence was likely due to the constrained geometric freedom and relatively rigid structure caused by intramolecular hydrogen bonding within the star PNIPAm polymers, which exhibit an intrinsic fluorescent behavior.

  17. Strongly directional and differential swimming behavior of an adult female white shark, Carcharodon carcharias (Chondrichthyes: Lamnidae from Guadalupe Island, Mexico

    Directory of Open Access Journals (Sweden)

    Ramón Bonfil

    2015-03-01

    Full Text Available We report on an adult female white shark tracked for 288 days and 7,100 km in the NE Pacific Ocean. The shark, tagged with a real-time satellite tag off Guadalupe Island, Mexico in October 2006, remained around the island for 3.5 months but left in early February 2007 for a ca. 3,900 km westward migration. Heading and swimming speed data showed that: a the arc-like route followed by this shark during oceanic travel involved strongly directional rapid movement, and b once the shark arrived to a specific (ca. 680 km wide area located 790 km north-northeast of the Hawaiian Islands, it switched into a distinct roaming behavior. The shark remained in this roaming area from late March to at least late July 2007. We show that real-time satellite tags can provide unique and valuable information about the migratory behavior of white sharks.

  18. octamethyl-polyhedral oligomeric silsesquioxanes nanocomposites ...

    Indian Academy of Sciences (India)

    In this study, biodegradable poly(p-dioxanone) (PPDO)/octamethyl-polyhedral oligomeric silsesquioxanes (ome-POSS) nanocomposites were fabricated by the simple solution casting method with various ome-POSS loadings. Scanning electron microscopic observations indicate that ome-POSS is well dispersed in the ...

  19. Comparison of the Electrochemical Behavior of Ti and Nanostructured Ti-Coated AISI 304 Stainless Steel in Strongly Acidic Solutions

    Science.gov (United States)

    Attarzadeh, Farid Reza; Elmkhah, Hassan; Fattah-Alhosseini, Arash

    2017-02-01

    In this study, the electrochemical behaviors of pure titanium (Ti) and nanostructured (NS) Ti-coated AISI 304 stainless steel (SS) in strongly acidic solutions of H2SO4 were investigated and compared. A type of physical vapor deposition method, cathodic arc evaporation, was applied to deposit NS Ti on 304 SS. Scanning electron microscope and X-ray diffraction were used to characterize surface coating morphology. Potentiodynamic polarization, electrochemical impedance spectroscopy, and Mott-Schottky (M-S) analysis were used to evaluate the passive behavior of the samples. Electrochemical measurements revealed that the passive behavior of NS Ti coating was better than that of pure Ti in 0.1 and 0.01 M H2SO4 solutions. M-S analysis indicated that the passive films behaved as n-type semiconductors in H2SO4 solutions and the deposition method did not affect the semiconducting type of passive films formed on the coated samples. In addition, this analysis showed that the NS Ti coating had lower donor densities. Finally, all electrochemical tests showed that the passive behavior of the Ti-coated samples was superior, mainly due to the formation of thicker, yet less defective passive films.

  20. Oligomerization reaction of the Criegee intermediate leads to secondary organic aerosol formation in ethylene ozonolysis.

    Science.gov (United States)

    Sakamoto, Yosuke; Inomata, Satoshi; Hirokawa, Jun

    2013-12-05

    Ethylene ozonolysis was investigated in laboratory experiments using a Teflon bag reactor. A negative ion chemical ionization mass spectrometer (NI-CIMS) using SO2Cl(-) and Cl(-) as reagent ions was used for product analysis. In addition to the expected gas-phase products, such as formic acid and hydroperoxymethyl formate, oligomeric hydroperoxides composed of the Criegee intermediate (CH2OO) as a chain unit were observed. Furthermore, we observed secondary organic aerosol (SOA) formation from the ethylene ozonolysis, and the particle-phase products were also analyzed by NI-CIMS. The CH2OO oligomers were also observed as particle-phase components, suggesting that the oligomeric hydroperoxides formed in the gas phase partition into the particle phase. By adding methanol as a stabilized Criegee intermediate scavenger, both the gas-phase oligomer formation and SOA formation were strongly suppressed. This indicates that CH2OO plays a critical role in the formation of oligomeric hydroperoxides followed by SOA formation in ethylene ozonolysis. A new formation mechanism for the oligomeric hydroperoxides, which includes sequential addition of CH2OO to hydroperoxides, is proposed.

  1. Polymer Nanocomposites Designed with Polyhedral Oligomeric Silsesquioxanes (POSS) and Plastics

    National Research Council Canada - National Science Library

    Haddad, Timothy; Mabry, Joseph

    2005-01-01

    Polyhedral oligomeric silsesquioxanes (POSS) are nanoparticles that are used to enhance the thermal and mechanical properties of polymeric systems and are being examined for use in many applications...

  2. Deformation Behavior of Ultra-Strong and Ductile Mg-Gd-Y-Zn-Zr Alloy with Bimodal Microstructure

    Science.gov (United States)

    Xu, C.; Fan, G. H.; Nakata, T.; Liang, X.; Chi, Y. Q.; Qiao, X. G.; Cao, G. J.; Zhang, T. T.; Huang, M.; Miao, K. S.; Zheng, M. Y.; Kamado, S.; Xie, H. L.

    2018-02-01

    An ultra-strong and ductile Mg-8.2Gd-3.8Y-1Zn-0.4Zr (wt pct) alloy was developed by using hot extrusion to modify the microstructure via forced-air cooling and an artificial aging treatment. A superior strength-ductility balance was obtained that had a tensile yield strength of 466 MPa and an elongation to failure of 14.5 pct. The local strain evolution during the in situ testing of the ultra-strong and ductile alloy was quantitatively analyzed with high-resolution electron backscattered diffraction and digital image correlation. The fracture behavior during the tensile test was characterized by synchrotron X-ray tomography along with SEM and STEM observations. The alloy showed a bimodal microstructure, consisting of dynamically recrystallized (DRXed) grains with random orientations and elongated hot-worked grains with parallel to the extrusion direction. The DRXed grains were deformed by the basal slip and the hot-worked grains were deformed by the prismatic slip dominantly. The strain evolution analysis indicated that the multilayered structure relaxed the strain localization via strain transfer from the DRXed to the hot-worked regions, which led to the high ductility of the alloy. Precipitation of the γ' on basal planes and the β' phases on the prismatic planes of the α-Mg generated closed volumes, which enhanced the strength by pinning dislocations effectively, and contributed to the high ductility by impeding the propagation of micro-cracks inside the grains. The deformation incompatibility between the hot-worked grains and the arched block-shaped long-period stacking ordered (LPSO) phases induced the crack initiation and propagation, which fractured the alloy.

  3. Polybenzoxazine/Polyhedral Oligomeric Silsesquioxane (POSS Nanocomposites

    Directory of Open Access Journals (Sweden)

    Mohamed Gamal Mohamed

    2016-06-01

    Full Text Available The organic/inorganic hybrid materials from polyhedral oligomeric silsesquioxane (POSS, inorganic nanoparticles and polybenzoxazine (PBZ have received much interesting recently due to their excellent thermal and mechanical properties, flame retardance, low dielectric constant, well-defined inorganic framework at nanosized scale level, and higher performance relative to those of non-hybrid PBZs. This review describes the synthesis, dielectric constants, and thermal, rheological, and mechanical properties of covalently bonded mono- and multifunctionalized benzoxazine POSS hybrids, other functionalized benzoxazine POSS derivatives, and non-covalently (hydrogen bonded benzoxazine POSS composites.

  4. Heterogenization of Some PNP Ligands for the Oligomerization of ...

    African Journals Online (AJOL)

    NICO

    Full range linear alpha olefin (LAO) production is based on non-selective oligomerization catalysts and more selective systems are desireable.1 The oligomerization of ethylene to LAOs is an important process because the products are useful intermediates in the synthesis of polymers, lubricants and detergents. The.

  5. Endocytic pathways mediating oligomeric Aβ42 neurotoxicity

    Directory of Open Access Journals (Sweden)

    Laxton Kevin

    2010-05-01

    Full Text Available Abstract Background One pathological hallmark of Alzheimer's disease (AD is amyloid plaques, composed primarily of amyloid-β peptide (Aβ. Over-production or diminished clearance of the 42 amino acid form of Aβ (Aβ42 in the brain leads to accumulation of soluble Aβ and plaque formation. Soluble oligomeric Aβ (oAβ has recently emerged to be as a likely proximal cause of AD. Results Here we demonstrate that endocytosis is critical in mediating oAβ42-induced neurotoxicity and intraneuronal accumulation of Aβ. Inhibition of clathrin function either with a pharmacological inhibitor, knock-down of clathrin heavy chain expression, or expression of the dominant-negative mutant of clathrin-assembly protein AP180 did not block oAβ42-induced neurotoxicity or intraneuronal accumulation of Aβ. However, inhibition of dynamin and RhoA by expression of dominant negative mutants reduced neurotoxicity and intraneuronal Aβ accumulation. Pharmacologic inhibition of the dynamin-mediated endocytic pathway by genistein also reduced neurotoxicity. Conclusions These data suggest that dynamin-mediated and RhoA-regulated endocytosis are integral steps for oligomeric Aβ42-induced neurotoxicity and intraneuronal Aβ accumulation.

  6. Oligomerization of DHHC protein S-acyltransferases.

    Science.gov (United States)

    Lai, Jianbin; Linder, Maurine E

    2013-08-02

    The formation of dimers or higher-order oligomers is a property of numerous integral membrane proteins, including ion channels, transporters, and receptors. In this study, we examined whether members of the DHHC-S-acyltransferase family oligomerize in intact cells and in vitro. DHHC-S-acyltransferases are integral membrane proteins that catalyze the addition of palmitate to cysteine residues on proteins at the cytoplasmic face of cell membranes. Bioluminescence resonance energy transfer (BRET) experiments revealed that DHHC2 or DHHC3 (Golgi-specific DHHC zinc finger protein (GODZ)) self-associate when expressed in HEK-293 cells. Homomultimer formation was confirmed by coimmunoprecipitation. Purified DHHC3 resolved predominately as a monomer and dimer on blue native polyacrylamide gels. In intact cells and in vitro, catalytically inactive DHHC proteins displayed a greater propensity to form dimers. BRET signals were higher for the catalytically inactive DHHC2 or DHHC3 than their wild-type counterparts. DHHC3 BRET in cell membranes was decreased by the addition of its lipid substrate palmitoyl-CoA, a treatment that results in autoacylation of the enzyme. Enzyme activity of a covalently linked DHHC3 dimer was less than that of the monomeric form, suggesting that enzyme activity may be modulated by the oligomerization status of the protein.

  7. Oligomerization of DHHC Protein S-Acyltransferases*

    Science.gov (United States)

    Lai, Jianbin; Linder, Maurine E.

    2013-01-01

    The formation of dimers or higher-order oligomers is a property of numerous integral membrane proteins, including ion channels, transporters, and receptors. In this study, we examined whether members of the DHHC-S-acyltransferase family oligomerize in intact cells and in vitro. DHHC-S-acyltransferases are integral membrane proteins that catalyze the addition of palmitate to cysteine residues on proteins at the cytoplasmic face of cell membranes. Bioluminescence resonance energy transfer (BRET) experiments revealed that DHHC2 or DHHC3 (Golgi-specific DHHC zinc finger protein (GODZ)) self-associate when expressed in HEK-293 cells. Homomultimer formation was confirmed by coimmunoprecipitation. Purified DHHC3 resolved predominately as a monomer and dimer on blue native polyacrylamide gels. In intact cells and in vitro, catalytically inactive DHHC proteins displayed a greater propensity to form dimers. BRET signals were higher for the catalytically inactive DHHC2 or DHHC3 than their wild-type counterparts. DHHC3 BRET in cell membranes was decreased by the addition of its lipid substrate palmitoyl-CoA, a treatment that results in autoacylation of the enzyme. Enzyme activity of a covalently linked DHHC3 dimer was less than that of the monomeric form, suggesting that enzyme activity may be modulated by the oligomerization status of the protein. PMID:23793055

  8. Molecular basis of coiled-coil oligomerization-state specificity.

    Science.gov (United States)

    Ciani, Barbara; Bjelic, Saša; Honnappa, Srinivas; Jawhari, Hatim; Jaussi, Rolf; Payapilly, Aishwarya; Jowitt, Thomas; Steinmetz, Michel O; Kammerer, Richard A

    2010-11-16

    Coiled coils are extensively and successfully used nowadays to rationally design multistranded structures for applications, including basic research, biotechnology, nanotechnology, materials science, and medicine. The wide range of applications as well as the important functions these structures play in almost all biological processes highlight the need for a detailed understanding of the factors that control coiled-coil folding and oligomerization. Here, we address the important and unresolved question why the presence of particular oligomerization-state determinants within a coiled coil does frequently not correlate with its topology. We found an unexpected, general link between coiled-coil oligomerization-state specificity and trigger sequences, elements that are indispensable for coiled-coil formation. By using the archetype coiled-coil domain of the yeast transcriptional activator GCN4 as a model system, we show that well-established trimer-specific oligomerization-state determinants switch the peptide's topology from a dimer to a trimer only when inserted into the trigger sequence. We successfully confirmed our results in two other, unrelated coiled-coil dimers, ATF1 and cortexillin-1. We furthermore show that multiple topology determinants can coexist in the same trigger sequence, revealing a delicate balance of the resulting oligomerization state by position-dependent forces. Our experimental results should significantly improve the prediction of the oligomerization state of coiled coils. They therefore should have major implications for the rational design of coiled coils and consequently many applications using these popular oligomerization domains.

  9. Disruption of Bcr-Abl coiled coil oligomerization by design.

    Science.gov (United States)

    Dixon, Andrew S; Pendley, Scott S; Bruno, Benjamin J; Woessner, David W; Shimpi, Adrian A; Cheatham, Thomas E; Lim, Carol S

    2011-08-05

    Oligomerization is an important regulatory mechanism for many proteins, including oncoproteins and other pathogenic proteins. The oncoprotein Bcr-Abl relies on oligomerization via its coiled coil domain for its kinase activity, suggesting that a designed coiled coil domain with enhanced binding to Bcr-Abl and reduced self-oligomerization would be therapeutically useful. Key mutations in the coiled coil domain of Bcr-Abl were identified that reduce homo-oligomerization through intermolecular charge-charge repulsion yet increase interaction with the Bcr-Abl coiled coil through additional salt bridges, resulting in an enhanced ability to disrupt the oligomeric state of Bcr-Abl. The mutations were modeled computationally to optimize the design. Assays performed in vitro confirmed the validity and functionality of the optimal mutations, which were found to exhibit reduced homo-oligomerization and increased binding to the Bcr-Abl coiled coil domain. Introduction of the mutant coiled coil into K562 cells resulted in decreased phosphorylation of Bcr-Abl, reduced cell proliferation, and increased caspase-3/7 activity and DNA segmentation. Importantly, the mutant coiled coil domain was more efficacious than the wild type in all experiments performed. The improved inhibition of Bcr-Abl through oligomeric disruption resulting from this modified coiled coil domain represents a viable alternative to small molecule inhibitors for therapeutic intervention.

  10. Polymorphism and mesomorphism of oligomeric surfactants: effect of the degree of oligomerization.

    Science.gov (United States)

    Jurašin, D; Pustak, A; Habuš, I; Šmit, I; Filipović-Vinceković, N

    2011-12-06

    A series of cationic oligomeric surfactants (quaternary dodecyldimethylammonium ions with two, three, or four chains connected by an ethylene spacer at the headgroup level, abbreviated as dimer, trimer, and tetramer) were synthesized and characterized. The influence of the degree of oligomerization on their polymorphic and mesomorphic properties was investigated by means of X-ray diffraction, polarizing optical microscopy, thermogravimetry, and differential scanning calorimetry. All compounds display layered arrangements with interdigitated dodecyl chains. The increase in the degree of oligomerization increases the interlayer distance and decreases the ordering in the solid phase; whereas the dimer sample is fully crystalline with well-developed 3D ordering and the trimer and tetramer crystallize as highly ordered crystal smectic phases. The number of thermal phase transitions and sequence of phases are markedly affected by the number of dodecyl chains. Anhydrous samples exhibit polymorphism and thermotropic mesomorphism of the smectic type, with the exception of the tetramer that displays only transitions at higher temperature associated with decomposition and melting. All hydrated compounds form lyotropic mesophases showing reversible phase transitions upon heating and cooling. The sequence of liquid-crystalline phases for the dimer, typical of concentrated ionic surfactant systems, comprises a hexagonal phase at lower temperatures and a smectic phase at higher temperatures. In contrast, the trimer and tetramer reveal textures of the hexagonal phase. © 2011 American Chemical Society

  11. Genetic noise control via protein oligomerization

    Energy Technology Data Exchange (ETDEWEB)

    Ghim, C; Almaas, E

    2008-06-12

    Gene expression in a cell entails random reaction events occurring over disparate time scales. Thus, molecular noise that often results in phenotypic and population-dynamic consequences sets a fundamental limit to biochemical signaling. While there have been numerous studies correlating the architecture of cellular reaction networks with noise tolerance, only a limited effort has been made to understand the dynamical role of protein-protein associations. We have developed a fully stochastic model for the positive feedback control of a single gene, as well as a pair of genes (toggle switch), integrating quantitative results from previous in vivo and in vitro studies. In particular, we explicitly account for the fast protein binding-unbinding kinetics, RNA polymerases, and the promoter/operator sequences of DNA. We find that the overall noise-level is reduced and the frequency content of the noise is dramatically shifted to the physiologically irrelevant high-frequency regime in the presence of protein dimerization. This is independent of the choice of monomer or dimer as transcription factor and persists throughout the multiple model topologies considered. For the toggle switch, we additionally find that the presence of a protein dimer, either homodimer or heterodimer, may significantly reduce its intrinsic switching rate. Hence, the dimer promotes the robust function of bistable switches by preventing the uninduced (induced) state from randomly being induced (uninduced). The specific binding between regulatory proteins provides a buffer that may prevent the propagation of fluctuations in genetic activity. The capacity of the buffer is a non-monotonic function of association-dissociation rates. Since the protein oligomerization per se does not require extra protein components to be expressed, it provides a basis for the rapid control of intrinsic or extrinsic noise. The stabilization of phenotypically important toggle switches, and nested positive feedback loops in

  12. Cellular localization and detergent dependent oligomerization of rice allene oxide synthase-1.

    Science.gov (United States)

    Yoeun, Sereyvath; Kim, Jeong-Il; Han, Oksoo

    2015-01-01

    Allene oxide synthase-1 from Oryza sativa (OsAOS1) localizes to the chloroplast, but lacks a putative chloroplast targeting sequence typically found in dicot AOS. Here, kinetic parameters and the oligomerization state/subunit composition of OsAOS1 were characterized in vitro in the absence or presence of detergent micelles. The catalytic efficiency (k(cat)/K(m)) of OsAOS1 reached a maximum near the critical micelle concentration for polyoxyethylene 10 tridecyl ether. Native gel analysis showed that OsAOS1 exists as a multimer in the absence of detergent micelles. The multimeric form of OsAOS1 was stably cross-linked in the absence of detergents, while only monomeric OsAOS1 was detected in the presence of detergent micelles. Gel filtration analysis indicated that the oligomeric state of OsAOS1 depends strongly on the detergents and that the monomer becomes the predominant form in the presence of detergent micelles. These data suggest that the detergent-dependent oligomeric state of OsAOS1 is an important factor for the regulation of its catalytic efficiency.

  13. Strong photonic crystal behavior in regular arrays of core-shell and quantum disc InGaN/GaN nanorod light-emitting diodes

    International Nuclear Information System (INIS)

    Lewins, C. J.; Le Boulbar, E. D.; Lis, S. M.; Shields, P. A.; Allsopp, D. W. E.; Edwards, P. R.; Martin, R. W.

    2014-01-01

    We show that arrays of emissive nanorod structures can exhibit strong photonic crystal behavior, via observations of the far-field luminescence from core-shell and quantum disc InGaN/GaN nanorods. The conditions needed for the formation of directional Bloch modes characteristic of strong photonic behavior are found to depend critically upon the vertical shape of the nanorod sidewalls. Index guiding by a region of lower volume-averaged refractive index near the base of the nanorods creates a quasi-suspended photonic crystal slab at the top of the nanorods which supports Bloch modes. Only diffractive behavior could be observed without this region. Slab waveguide modelling of the vertical structure shows that the behavioral regime of the emissive nanorod arrays depends strongly upon the optical coupling between the nanorod region and the planar layers below. The controlled crossover between the two regimes of photonic crystal operation enables the design of photonic nanorod structures formed on planar substrates that exploit either behavior depending on device requirements.

  14. A Reanalysis of Polyhedral Oligomeric Silsesquioxane Ions and Salts

    National Research Council Canada - National Science Library

    Viers, Brent

    2003-01-01

    Polyhedral Oligomeric Silsesquioxanes (POSS) are of interest because the hydrolysis and condensation of the silane precursors can be controlled to form incompletely condensed "scaffolds" which can then be functionalized (via condensation...

  15. Protic Cationic Oligomeric Ionic Liquids of the Urethane Type

    DEFF Research Database (Denmark)

    Shevchenko, V. V.; Stryutsky, A. V.; Klymenko, N. S.

    2014-01-01

    temperature, but ethanesulfonate imidazolium and pyridinium oligomeric ionic liquids form a low melting crystalline phase. The proton conductivities of the oligomeric ionic liquids are determined by the type of cation in the temperature range 80-120 degrees C under anhydrous conditions and vary within five......Protic oligomeric cationic ionic liquids of the oligo(ether urethane) type are synthesized via the reaction of an isocyanate prepolymer based on oligo(oxy ethylene)glycol with M = 1000 with hexamethylene-diisocyanate followed by blocking of the terminal isocyanate groups with the use of amine...... derivatives of imidazole, pyridine, and 3-methylpyridine and neutralization of heterocycles with ethanesulfonic acid and p-toluenesulfonic acid. The structures and properties of the synthesized oligomeric ionic liquids substantially depend on the structures of the ionic groups. They are amorphous at room...

  16. Oligomeric protein structure networks: insights into protein-protein interactions

    Directory of Open Access Journals (Sweden)

    Brinda KV

    2005-12-01

    Full Text Available Abstract Background Protein-protein association is essential for a variety of cellular processes and hence a large number of investigations are being carried out to understand the principles of protein-protein interactions. In this study, oligomeric protein structures are viewed from a network perspective to obtain new insights into protein association. Structure graphs of proteins have been constructed from a non-redundant set of protein oligomer crystal structures by considering amino acid residues as nodes and the edges are based on the strength of the non-covalent interactions between the residues. The analysis of such networks has been carried out in terms of amino acid clusters and hubs (highly connected residues with special emphasis to protein interfaces. Results A variety of interactions such as hydrogen bond, salt bridges, aromatic and hydrophobic interactions, which occur at the interfaces are identified in a consolidated manner as amino acid clusters at the interface, from this study. Moreover, the characterization of the highly connected hub-forming residues at the interfaces and their comparison with the hubs from the non-interface regions and the non-hubs in the interface regions show that there is a predominance of charged interactions at the interfaces. Further, strong and weak interfaces are identified on the basis of the interaction strength between amino acid residues and the sizes of the interface clusters, which also show that many protein interfaces are stronger than their monomeric protein cores. The interface strengths evaluated based on the interface clusters and hubs also correlate well with experimentally determined dissociation constants for known complexes. Finally, the interface hubs identified using the present method correlate very well with experimentally determined hotspots in the interfaces of protein complexes obtained from the Alanine Scanning Energetics database (ASEdb. A few predictions of interface hot

  17. Theoretical Study of Ethylene Oligomerization by an Organometallic Nickel Catalyst.

    Science.gov (United States)

    Fan, L.; Krzywicki, A.; Somogyvari, A.; Ziegler, T.

    1996-06-19

    The mechanism for ethylene oligomerization by (acac)NiH has been studied using density functional theory (DFT). The transition states for chain propagation and chain termination were optimized and the related reaction barriers calculated. Several possible mechanisms were considered for the chain termination step. Chain termination by beta-hydrogen elimination was found to be energetically unfavorable, and is not likely to be important. Instead, beta-hydrogen transfer to the incoming ethylene unit seems to be operative. The most favorable beta-hydrogen transfer pathway has two transition states. The first leads from a weak pi-complex between an incoming ethylene unit and (acac)NiCH(2)CH(2)R to an intermediate in which the two olefins C(2)H(4) and H(2)CCHR both are strongly pi-complexed to the nickel hydride (acac)NiH. The second barrier takes the intermediate to another weak pi-complex between (acac)NiCH(2)CH(3) and H(2)C=CHR from which the oligomer H(2)C=CHR can be released and the catalyst (acac)NiCH(2)CH(3) regenerated. Due to the mechanism of chain termination, the actual catalyst is proposed to be (acac)NiCH(2)CH(3) whereas (acac)NiH serves as a precursor or precatalyst.

  18. <strong>Neuroeconomics and behavioral health economicsstrong>/>

    DEFF Research Database (Denmark)

    Larsen, Torben

    2009-01-01

    - a key center in our emotional arousal (limbic system) - as shaped in the elder stone-age with many acute threats. II. In general, the Hawthorne-effect of human-relations management is explained as the result of supportive job-relations relaxing Amygdala for better emotional integration...... some are rooted in the religious tradition while other aim to be post-religious. Medical meditation across settings combines savings on health care costs with de-stressing benefits as reduced anxiety, less use of stimulants and a reduction of blood pressure which in all increase life...... is met by a meso-strategy aiming the formation of an international, multidisciplinary network which might organize regional workshops for representatives for all involved parties in order to prepare local implementation projects.   Regarding de-stressing by medical meditation a relatively fast...

  19. Obesity is more strongly associated with inappropriate eating behaviors than with mental health in older adults receiving congregate meals.

    Science.gov (United States)

    Porter, Kathryn N; Johnson, Mary Ann

    2011-01-01

    This study explored the relationships of inappropriate eating behaviors and mental health with obesity in congregate meal participants in Georgia (N = 120, mean age = 75 years, 75% female, 43% African American). Inappropriate eating behaviors were evaluated with the Three-Factor Eating Questionnaire (18 questions); mental health was assessed with the Depression Anxiety Stress Scale (21 questions); history of depression was assessed with the Behavioral Risk Factor Surveillance Survey; and height and weight were measured to calculate body mass index (BMI) and obesity (52% ≥ 30 kg/m(2)). In bivariate analyses, obesity was associated with cognitive restraint (rho = 0.49, p eating (rho = 0.22; p emotional eating (rho = 0.32, p eating behavior and mental health indices, only cognitive restraint and emotional eating were consistently associated with obesity (p eating behaviors, particularly cognitive restraint and emotional eating, may be important targets for future research and intervention. Additional research is needed to better understand how cognitive restraint and emotional eating contribute to obesity in this population so that interdisciplinary research and health care teams can appropriately prevent and manage obesity in congregate meal participants.

  20. ROMP-derived Oligomeric Phosphates for Application in Facile Benzylation

    Science.gov (United States)

    Long, Toby R.; Maity, Pradip K.; Samarakoon, Thiwanka B.; Hanson, Paul R.

    2010-01-01

    The development of new ROMP-based oligomeric benzyl phosphates (OBPn) is reported for use as soluble, stable benzylating reagents. These oligomeric reagents are readily synthesized from commercially available materials and conveniently polymerized and purified in a one-pot process, affording bench stable, pure white, free-flowing solids on multi-gram scale. Utilization in benzylation reactions with a variety of nucleophiles is reported. PMID:20521800

  1. Interactions of Phospholipid Vesicles with Cationic and Anionic Oligomeric Surfactants.

    Science.gov (United States)

    Chen, Yao; Qiao, Fulin; Fan, Yaxun; Han, Yuchun; Wang, Yilin

    2017-07-27

    This work studied the interactions of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) with cationic ammonium surfactants and anionic sulfate or sulfonate surfactants of different oligomeric degrees, including cationic monomeric DTAB, dimeric C 12 C 3 C 12 Br 2 , and trimeric DDAD as well as anionic monomeric SDS, dimeric C 12 C 3 C 12 (SO 3 ) 2 , and trimeric TED-(C 10 SO 3 Na) 3 . The partition coefficient P of these surfactants between the DOPC vesicles and water was determined with isothermal titration microcalorimetry (ITC) by titrating concentrated DOPC solution into the monomer solution of these surfactants. It was found that the P value increases with the increase of the surfactant oligomeric degree. Moreover, the enthalpy change and the Gibbs free energy for the transition of these surfactants from water into the DOPC bilayer become more negative with increasing the oligomeric degree. Meanwhile, the calcein release experiment proves that the surfactant with a higher oligomeric degree shows stronger ability of changing the permeability of the DOPC vesicles. Furthermore, the solubilization of the DOPC vesicles by these oligomeric surfactants was studied by ITC, turbidity, and dynamic light scattering, and thus the phase boundaries for the surfactant/lipid mixtures have been determined. The critical surfactant to lipid ratios for the onset and end of the solubilization for the DOPC vesicles derived from the phase boundaries decrease remarkably with increasing the oligomeric degree. Overall, the surfactant with a larger oligomerization degree shows stronger ability in incorporating into the lipid bilayer, altering the membrane permeability and solubilizing lipid vesicles, which provides comprehensive understanding about the effects of structure and shape of oligomeric surfactant molecules on lipid-surfactant interactions.

  2. Depth investigation of rapid sand filters for drinking water production reveals strong stratification in nitrification biokinetic behavior

    DEFF Research Database (Denmark)

    Tatari, Karolina; Smets, Barth F.; Albrechtsen, Hans-Jørgen

    2016-01-01

    The biokinetic behavior of NH4 + removal was investigated at different depths of a rapid sand filter treating groundwater for drinking water preparation. Filter materials from the top, middle and bottom layers of a full-scale filter were exposed to various controlled NH4 + loadings in a continuous...

  3. Oligomeric forms of the metastasis-related Mts1 (S100A4) protein stimulate neuronal differentiation in cultures of rat hippocampal neurons

    DEFF Research Database (Denmark)

    Novitskaya, V; Grigorian, M; Kriajevska, M

    2000-01-01

    protein family. The oligomeric but not the dimeric form of Mts1 strongly induces differentiation of cultured hippocampal neurons. A mutant with a single Y75F amino acid substitution, which stabilizes the dimeric form of Mts1, is unable to promote neurite extension. Disulfide bonds do not play an essential...

  4. Cartilage oligomeric matrix protein enhances the vascularization of acellular nerves

    Directory of Open Access Journals (Sweden)

    Wei-ling Cui

    2016-01-01

    Full Text Available Vascularization of acellular nerves has been shown to contribute to nerve bridging. In this study, we used a 10-mm sciatic nerve defect model in rats to determine whether cartilage oligomeric matrix protein enhances the vascularization of injured acellular nerves. The rat nerve defects were treated with acellular nerve grafting (control group alone or acellular nerve grafting combined with intraperitoneal injection of cartilage oligomeric matrix protein (experimental group. As shown through two-dimensional imaging, the vessels began to invade into the acellular nerve graft from both anastomotic ends at day 7 post-operation, and gradually covered the entire graft at day 21. The vascular density, vascular area, and the velocity of revascularization in the experimental group were all higher than those in the control group. These results indicate that cartilage oligomeric matrix protein enhances the vascularization of acellular nerves.

  5. Behavior of Particle Depots in Molten Silicon During Float-Zone Growth in Strong Static Magnetic Fields

    Science.gov (United States)

    Jauss, T.; SorgenFrei, T.; Croell, A.; Azizi, M.; Reimann, C.; Friedrich, J.; Volz, M. P.

    2014-01-01

    In the photovoltaics industry, the largest market share is represented by solar cells made from multicrystalline silicon, which is grown by directional solidification. During the growth process, the silicon melt is in contact with the silicon nitride coated crucible walls and the furnace atmosphere which contains carbon monoxide. The dissolution of the crucible coating, the carbon bearing gas, and the carbon already present in the feedstock, lead to the precipitation of silicon carbide, and silicon nitride, at later stages of the growth process. The precipitation of Si3N4 and SiC particles of up to several hundred micrometers in diameter leads to severe problems during the wire sawing process for wafering the ingots. Furthermore the growth of the silicon grains can be negatively influenced by the presence of particles, which act as nucleation sources and lead to a grit structure of small grains and are sources for dislocations. If doped with Nitrogen from the dissolved crucible coating, SiC is a semi conductive material, and can act as a shunt, short circuiting parts of the solar cell. For these reasons, the incorporation of such particles needs to be avoided. In this contribution we performed model experiments in which the transport of intentionally added SiC particles and their interaction with the solid-liquid interface during float zone growth of silicon in strong steady magnetic fields was investigated. SiC particles of 7µm and 60µm size are placed in single crystal silicon [100] and [111] rods of 8mm diameter. This is achieved by drilling a hole of 2mm diameter, filling in the particles and closing the hole by melting the surface of the rod until a film of silicon covers the hole. The samples are processed under a vacuum of 1x10(exp -5) mbar or better, to prevent gas inclusions. An oxide layer to suppress Marangoni convection is applied by wet oxidation. Experiments without and with static magnetic field are carried out to investigate the influence of melt

  6. Genetic noise control via protein oligomerization

    Directory of Open Access Journals (Sweden)

    Almaas Eivind

    2008-11-01

    Full Text Available Abstract Background Gene expression in a cell entails random reaction events occurring over disparate time scales. Thus, molecular noise that often results in phenotypic and population-dynamic consequences sets a fundamental limit to biochemical signaling. While there have been numerous studies correlating the architecture of cellular reaction networks with noise tolerance, only a limited effort has been made to understand the dynamic role of protein-protein interactions. Results We have developed a fully stochastic model for the positive feedback control of a single gene, as well as a pair of genes (toggle switch, integrating quantitative results from previous in vivo and in vitro studies. In particular, we explicitly account for the fast binding-unbinding kinetics among proteins, RNA polymerases, and the promoter/operator sequences of DNA. We find that the overall noise-level is reduced and the frequency content of the noise is dramatically shifted to the physiologically irrelevant high-frequency regime in the presence of protein dimerization. This is independent of the choice of monomer or dimer as transcription factor and persists throughout the multiple model topologies considered. For the toggle switch, we additionally find that the presence of a protein dimer, either homodimer or heterodimer, may significantly reduce its random switching rate. Hence, the dimer promotes the robust function of bistable switches by preventing the uninduced (induced state from randomly being induced (uninduced. Conclusion The specific binding between regulatory proteins provides a buffer that may prevent the propagation of fluctuations in genetic activity. The capacity of the buffer is a non-monotonic function of association-dissociation rates. Since the protein oligomerization per se does not require extra protein components to be expressed, it provides a basis for the rapid control of intrinsic or extrinsic noise. The stabilization of regulatory circuits

  7. Experimental and Numerical Evaluation of the Mechanical Behavior of Strongly Anisotropic Light-Weight Metallic Fiber Structures under Static and Dynamic Compressive Loading

    Directory of Open Access Journals (Sweden)

    Olaf Andersen

    2016-05-01

    Full Text Available Rigid metallic fiber structures made from a variety of different metals and alloys have been investigated mainly with regard to their functional properties such as heat transfer, pressure drop, or filtration characteristics. With the recent advent of aluminum and magnesium-based fiber structures, the application of such structures in light-weight crash absorbers has become conceivable. The present paper therefore elucidates the mechanical behavior of rigid sintered fiber structures under quasi-static and dynamic loading. Special attention is paid to the strongly anisotropic properties observed for different directions of loading in relation to the main fiber orientation. Basically, the structures show an orthotropic behavior; however, a finite thickness of the fiber slabs results in moderate deviations from a purely orthotropic behavior. The morphology of the tested specimens is examined by computed tomography, and experimental results for different directions of loading as well as different relative densities are presented. Numerical calculations were carried out using real structural data derived from the computed tomography data. Depending on the direction of loading, the fiber structures show a distinctively different deformation behavior both experimentally and numerically. Based on these results, the prevalent modes of deformation are discussed and a first comparison with an established polymer foam and an assessment of the applicability of aluminum fiber structures in crash protection devices is attempted.

  8. Isolation and quantification of oligomeric and polymeric procyanidins in leaves and flowers of Hawthorn (Crataegus spp.).

    Science.gov (United States)

    Hellenbrand, N; Sendker, J; Lechtenberg, M; Petereit, F; Hensel, A

    2015-07-01

    Proanthocyanidins (PAs) constitute a class of polyphenols with flavan-3-ols as monomeric building blocks. These polyphenols are mostly quantified by colorimetric methods or by chromatographic determination of monomeric flavan-3-ols or low molecular oligomers as lead compounds. No reliable analytical methods are available for unambiguous identification of the homologues series of oligo- and polymeric PAs. For Hawthorn leaf and flower (Crataegi folium cum flore) from Crataegus spp. (Rosaceae) a protocol for preparative isolation of oligomeric and polymeric PAs from an acetone-water extract was developed, yielding procyanidin reference clusters with defined degree of polymerization (DP) from 2 to 10 besides a procyanidin-polymer. Identity and purity of these clusters were proven by HPLC, MS and in part NMR studies. For identification and quantification from Hawthorn an ICH-Q2 validated UHPLC method with fluorimetric detection and less than 10min runtime was developed. The method enabled quantification of procyanidin clusters with DP from 2 to 10 besides the polymer fraction. Batch analysis revealed procyanidin contents of about 20 to 45mg/g from a homologues series of oligomeric PAs and about 50% of polymer fraction. Monitoring of procyanidin distribution during seasonal growth of fresh plants of Crataegus monogyna showed more or less constant contents between 20 and 55mg/g dry weight of oligomeric procyanidins during the growing season in the different plant organs with strong accumulation in the flowers and fruits (55mg/g dry weight). From these data it can be speculated that procyanidins serve as part of the plants defense system in the reproductive organs of the plant. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. High Content Analysis of Compositional Heterogeneities to Study GPCR Oligomerization

    DEFF Research Database (Denmark)

    Walsh, Samuel McEwen

    In this thesis I demonstrate how the natural compositional heterogeneities of synthetic and living cell model systems can be used to quantitate the mechanics of G-protein coupled receptor (GPCR) oligomerization with Förster resonance energy transfer (FRET). The thesis is structured around three a...

  10. Receptor Oligomerization as a Process Modulating Cellular Semiotics

    DEFF Research Database (Denmark)

    Giorgi, Franco; Bruni, Luis Emilio; Maggio, Roberto

    2010-01-01

    The majority of G protein-coupled receptors (GPCRs) self-assemble in the form dimeric/oligomeric complexes along the plasma membrane. Due to the molecular interactions they participate, GPCRs can potentially provide the framework for discriminating a wide variety of intercellular signals, as base...

  11. Spa47 is an oligomerization-activated type three secretion system (T3SS) ATPase from Shigella flexneri.

    Science.gov (United States)

    Burgess, Jamie L; Jones, Heather B; Kumar, Prashant; Toth, Ronald T; Middaugh, C Russell; Antony, Edwin; Dickenson, Nicholas E

    2016-05-01

    Gram-negative pathogens often use conserved type three secretion systems (T3SS) for virulence. The Shigella type three secretion apparatus (T3SA) penetrates the host cell membrane and provides a unidirectional conduit for injection of effectors into host cells. The protein Spa47 localizes to the base of the apparatus and is speculated to be an ATPase that provides the energy for T3SA formation and secretion. Here, we developed an expression and purification protocol, producing active Spa47 and providing the first direct evidence that Spa47 is a bona fide ATPase. Additionally, size exclusion chromatography and analytical ultracentrifugation identified multiple oligomeric species of Spa47 with the largest greater than 8 fold more active for ATP hydrolysis than the monomer. An ATPase inactive Spa47 point mutant was then engineered by targeting a conserved Lysine within the predicted Walker A motif of Spa47. Interestingly, the mutant maintained a similar oligomerization pattern as active Spa47, but was unable to restore invasion phenotype when used to complement a spa47 null S. flexneri strain. Together, these results identify Spa47 as a Shigella T3SS ATPase and suggest that its activity is linked to oligomerization, perhaps as a regulatory mechanism as seen in some related pathogens. Additionally, Spa47 catalyzed ATP hydrolysis appears to be essential for host cell invasion, providing a strong platform for additional studies dissecting its role in virulence and providing an attractive target for anti-infective agents. © 2016 The Protein Society.

  12. Detergent-resistant oligomeric Leptosphaeria rhodopsin is a promising bio-nanomaterial and an alternative to bacteriorhodopsin.

    Science.gov (United States)

    Ji, Liangliang; Ma, Baofu; Meng, Qian; Li, Longjie; Liu, Ke; Chen, Deliang

    2017-11-04

    Bacteriorhodopsin has attracted remarkable attention as a photoactive bio-nanomaterial in the last decades. However, its instability in the presence of detergents has restricted the extent to which bacteriorhodopsin may be applied. In this study, we investigated the oligomerization of a eukaryotic light-driven H + -pump, Leptosphaeria rhodopsin, using circular dichroism spectroscopy and other biophysical and biochemical methods. Our findings revealed that Leptosphaeria rhodopsin assembled into oligomers in the cell membrane and also in 0.05% DDM detergent micelles. Moreover, unlike bacteriorhodopsin in purple membrane, Leptosphaeria rhodopsin retained its oligomeric structure in 1% Triton X-100 and demonstrated strong resistance to other common detergents. A maximal photocurrent density of ∼85 nA/cm 2 was consistently generated, which was substantially larger than that of solubilized bacteriorhodopsin (∼10 nA/cm 2 ). Therefore, oligomeric Leptosphaeria rhodopsin may be a promising bio-nanomaterial, and an alternative to bacteriorhodopsin, especially with the use of detergents. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. The semantic origin of unconscious priming: Behavioral and event-related potential evidence during category congruency priming from strongly and weakly related masked words.

    Science.gov (United States)

    Ortells, Juan J; Kiefer, Markus; Castillo, Alejandro; Megías, Montserrat; Morillas, Alejandro

    2016-01-01

    The mechanisms underlying masked congruency priming, semantic mechanisms such as semantic activation or non-semantic mechanisms, for example response activation, remain a matter of debate. In order to decide between these alternatives, reaction times (RTs) and event-related potentials (ERPs) were recorded in the present study, while participants performed a semantic categorization task on visible word targets that were preceded either 167 ms (Experiment 1) or 34 ms before (Experiment 2) by briefly presented (33 ms) novel (unpracticed) masked prime words. The primes and targets belonged to different categories (unrelated), or they were either strongly or weakly semantically related category co-exemplars. Behavioral (RT) and electrophysiological masked congruency priming effects were significantly greater for strongly related pairs than for weakly related pairs, indicating a semantic origin of effects. Priming in the latter condition was not statistically reliable. Furthermore, priming effects modulated the N400 event-related potential (ERP) component, an electrophysiological index of semantic processing, but not ERPs in the time range of the N200 component, associated with response conflict and visuo-motor response priming. The present results demonstrate that masked congruency priming from novel prime words also depends on semantic processing of the primes and is not exclusively driven by non-semantic mechanisms such as response activation. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Crystal Structure of the Marburg Virus VP35 Oligomerization Domain

    Energy Technology Data Exchange (ETDEWEB)

    Bruhn, Jessica F.; Kirchdoerfer, Robert N.; Urata, Sarah M.; Li, Sheng; Tickle, Ian J.; Bricogne, Gérard; Saphire, Erica Ollmann (Scripps); (Globel Phasing); (UCSD)

    2016-11-09

    ABSTRACT

    Marburg virus (MARV) is a highly pathogenic filovirus that is classified in a genus distinct from that of Ebola virus (EBOV) (generaMarburgvirusandEbolavirus, respectively). Both viruses produce a multifunctional protein termed VP35, which acts as a polymerase cofactor, a viral protein chaperone, and an antagonist of the innate immune response. VP35 contains a central oligomerization domain with a predicted coiled-coil motif. This domain has been shown to be essential for RNA polymerase function. Here we present crystal structures of the MARV VP35 oligomerization domain. These structures and accompanying biophysical characterization suggest that MARV VP35 is a trimer. In contrast, EBOV VP35 is likely a tetramer in solution. Differences in the oligomeric state of this protein may explain mechanistic differences in replication and immune evasion observed for MARV and EBOV.

    IMPORTANCEMarburg virus can cause severe disease, with up to 90% human lethality. Its genome is concise, only producing seven proteins. One of the proteins, VP35, is essential for replication of the viral genome and for evasion of host immune responses. VP35 oligomerizes (self-assembles) in order to function, yet the structure by which it assembles has not been visualized. Here we present two crystal structures of this oligomerization domain. In both structures, three copies of VP35 twist about each other to form a coiled coil. This trimeric assembly is in contrast to tetrameric predictions for VP35 of Ebola virus and to known structures of homologous proteins in the measles, mumps, and Nipah viruses. Distinct oligomeric states of the Marburg and Ebola virus VP35 proteins may explain differences between them in polymerase function and immune evasion. These findings may provide a more accurate understanding of the

  15. The Efficacy of “Parenting the Strong-Willed Child” Program for Mothers’ Parenting Practices and Children’s Behavioral Problems

    Directory of Open Access Journals (Sweden)

    حمیده حاجی سیدرضی

    2015-04-01

    Full Text Available The efficacy of a parent-training program based on “Strong Willed Children” for promoting mother’s parenting practices and decreasing childrenn’s behavioural problems was examined among families with 4-6 years old children. A sample of 25 volunteer mothers (mean age=30 and their children from play houses were collected and assigned into intervention (n=13 and comparison (n=12 groups. Parents completed measures of Children’s Reports of Parental Behavior Inventory (CRPBI; Margolies & Weintraub, 1977; including three dimensions of acceptance/rejection, psychological autonomy/ psychological control, firm control/ permissive control; and Eyberg Child Behavior Inventory (ECBI; Eyberg & Ross, 1978. Intervention group participated in a 6 -session of Parent training program weekly. The results showed that Parent training program significantly improved the parenting practices and firm control of mothers in experimental group. No significant differences was found in other dimensions of parenting practices and children’s behavioural problems among two groups. Explanations for obtaining different outcomes for behavioural problems and some dimensions of parenting based on cultural differences, measurements and length of the programme were discussed.

  16. Cyclic Tetrapyrrole Sulfonation, Metals, and Oligomerization in Antiprion Activity▿

    Science.gov (United States)

    Caughey, Winslow S.; Priola, Suzette A.; Kocisko, David A.; Raymond, Lynne D.; Ward, Anne; Caughey, Byron

    2007-01-01

    Cyclic tetrapyrroles are among the most potent compounds with activity against transmissible spongiform encephalopathies (TSEs; or prion diseases). Here the effects of differential sulfonation and metal binding to cyclic tetrapyrroles were investigated. Their potencies in inhibiting disease-associated protease-resistant prion protein were compared in several types of TSE-infected cell cultures. In addition, prophylactic antiscrapie activities were determined in scrapie-infected mice. The activity of phthalocyanine was relatively insensitive to the number of peripheral sulfonate groups but varied with the type of metal bound at the center of the molecule. The tendency of the various phthalocyanine sulfonates to oligomerize (i.e., stack) correlated with anti-TSE activity. Notably, aluminum(III) phthalocyanine tetrasulfonate was both the poorest anti-TSE compound and the least prone to oligomerization in aqueous media. Similar comparisons of iron- and manganese-bound porphyrin sulfonates confirmed that stacking ability correlates with anti-TSE activity among cyclic tetrapyrroles. PMID:17709470

  17. Cyclic tetrapyrrole sulfonation, metals, and oligomerization in antiprion activity.

    Science.gov (United States)

    Caughey, Winslow S; Priola, Suzette A; Kocisko, David A; Raymond, Lynne D; Ward, Anne; Caughey, Byron

    2007-11-01

    Cyclic tetrapyrroles are among the most potent compounds with activity against transmissible spongiform encephalopathies (TSEs; or prion diseases). Here the effects of differential sulfonation and metal binding to cyclic tetrapyrroles were investigated. Their potencies in inhibiting disease-associated protease-resistant prion protein were compared in several types of TSE-infected cell cultures. In addition, prophylactic antiscrapie activities were determined in scrapie-infected mice. The activity of phthalocyanine was relatively insensitive to the number of peripheral sulfonate groups but varied with the type of metal bound at the center of the molecule. The tendency of the various phthalocyanine sulfonates to oligomerize (i.e., stack) correlated with anti-TSE activity. Notably, aluminum(III) phthalocyanine tetrasulfonate was both the poorest anti-TSE compound and the least prone to oligomerization in aqueous media. Similar comparisons of iron- and manganese-bound porphyrin sulfonates confirmed that stacking ability correlates with anti-TSE activity among cyclic tetrapyrroles.

  18. Strong Cosmic Censorship

    Science.gov (United States)

    Isenberg, James

    2017-01-01

    The Hawking-Penrose theorems tell us that solutions of Einstein's equations are generally singular, in the sense of the incompleteness of causal geodesics (the paths of physical observers). These singularities might be marked by the blowup of curvature and therefore crushing tidal forces, or by the breakdown of physical determinism. Penrose has conjectured (in his `Strong Cosmic Censorship Conjecture`) that it is generically unbounded curvature that causes singularities, rather than causal breakdown. The verification that ``AVTD behavior'' (marked by the domination of time derivatives over space derivatives) is generically present in a family of solutions has proven to be a useful tool for studying model versions of Strong Cosmic Censorship in that family. I discuss some of the history of Strong Cosmic Censorship, and then discuss what is known about AVTD behavior and Strong Cosmic Censorship in families of solutions defined by varying degrees of isometry, and discuss recent results which we believe will extend this knowledge and provide new support for Strong Cosmic Censorship. I also comment on some of the recent work on ``Weak Null Singularities'', and how this relates to Strong Cosmic Censorship.

  19. Ethylene oligomerization promoted by chromium complexes bearing pyrrolide-imine-amine/ether tridentate ligands.

    Science.gov (United States)

    Pinheiro, A C; Roisnel, T; Kirillov, E; Carpentier, J-F; Casagrande, Osvaldo L

    2015-09-28

    Chromium(iii) complexes [CrCl2(L)(THF)] based on monoanionic tridentate ligands [, L = {2-(C4H3N-2'-CH[double bond, length as m-dash]N)C2H4NHPh}; , L = {5-tert-butyl-2-(C4H2N-2'-CH[double bond, length as m-dash]N)C2H3NHPh}; , L = {2-(C4H3N-2'-CH[double bond, length as m-dash]N)C2H4OPh}] have been prepared. Complexes and were converted into the monomeric acetonitrile adducts [CrCl2(L)(NCMe)] [, L = {2-(C4H3N-2'-CH[double bond, length as m-dash]N)C2H4NHPh}; , L = {5-tert-butyl-2-(C4H2N-2'-CH[double bond, length as m-dash]N)C2H3NHPh}] by reaction with acetonitrile at room temperature. All Cr complexes were characterized by IR spectroscopy, elemental analysis, magnetochemistry for , and by X-ray crystallography for and . Upon activation with methylaluminoxane (MAO), chromium precatalysts and showed good activity in ethylene oligomerization (TOF = 47.0-57.0 × 10(3) (mol ethylene)(mol Cr)(-1) h(-1) at 80 °C), producing mostly oligomers (93.0-95.6 wt% of total products). On the other hand, under identical oligomerization conditions, /MAO behaved as a polymerization catalyst generating predominantly polyethylene (73.0 wt%). However, the catalytic behavior of the precatalyst can be adjusted by varying the MAO-to-Cr ratio. Thus, the use of 500 equiv. causes a dramatic shift from polymerization to ethylene oligomerization, eventually producing mainly lighter α-olefin fractions [α-C4 (68.7 wt%) and α-C6 (19.2 wt%)]. A further increase in the amount of MAO (1000 equiv.) leads to a more balanced distribution of oligomers, with a drastic decrease in the α-C4 and increase in the α-C8 fractions.

  20. Oligomeric epoxide-amine adducts based on 2-amino-N-isopropylacetamide and α-amino-ε-caprolactam: Solubility in presence of cyclodextrin and curing properties.

    Science.gov (United States)

    Fischer, Julian; Ritter, Helmut

    2013-01-01

    2-Amino-N-isopropylacetamide and α-amino-ε-caprolactam were reacted with glycerol diglycidyl ether to give novel oligomeric thermoresponsive epoxide-amine adducts. These oligomers exhibit a lower critical solution temperature (LCST) behavior in water. The solubility properties were influenced with randomly methylated β-cyclodextrin (RAMEB-CD) and the curing properties of the amine-epoxide mixtures were analyzed by oscillatory rheology and differential scanning calorimetry, whereby significant differences in setting time, viscosity, and stiffness were observed.

  1. Discrete Pools of Oligomeric Amyloid-β Track with Spatial Learning Deficits in a Mouse Model of Alzheimer Amyloidosis.

    Science.gov (United States)

    Chiang, Angie C A; Fowler, Stephanie W; Reddy, Rohit; Pletnikova, Olga; Troncoso, Juan C; Sherman, Mathew A; Lesne, Sylvain E; Jankowsky, Joanna L

    2018-03-01

    Despite increasing appreciation that oligomeric amyloid-β (Aβ) may contribute to cognitive decline of Alzheimer disease, defining the most critical forms has been thwarted by the changeable nature of these aggregates and the varying methods used for detection. Herein, using a broad approach, we quantified Aβ oligomers during the evolution of cognitive deficits in an aggressive model of Aβ amyloidosis. Amyloid precursor protein/tetracycline transactivator mice underwent behavioral testing at 3, 6, 9, and 12 months of age to evaluate spatial learning and memory, followed by histologic assessment of amyloid burden and biochemical characterization of oligomeric Aβ species. Transgenic mice displayed progressive impairments in acquisition and immediate recall of the trained platform location. Biochemical analysis of cortical extracts from behaviorally tested mice revealed distinct age-dependent patterns of accumulation in multiple oligomeric species. Dot blot analysis demonstrated that nonfibrillar Aβ oligomers were highly soluble and extracted into a fraction enriched for extracellular proteins, whereas prefibrillar species required high-detergent conditions to retrieve, consistent with membrane localization. Low-detergent extracts tested by 82E1 enzyme-linked immunosorbent assay confirmed the presence of bona fide Aβ oligomers, whereas immunoprecipitation-Western blotting using high-detergent extracts revealed a variety of SDS-stable low-n species. These findings show that different Aβ oligomers vary in solubility, consistent with distinct localization, and identify nonfibrillar Aβ oligomer-positive aggregates as tracking most closely with cognitive decline in this model. Copyright © 2018 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  2. Polyhedral Oligomeric Silsesquioxane (POSS)-Containing Polymer Nanocomposites

    Science.gov (United States)

    Ayandele, Ebunoluwa; Sarkar, Biswajit; Alexandridis, Paschalis

    2012-01-01

    Hybrid materials with superior structural and functional properties can be obtained by incorporating nanofillers into polymer matrices. Polyhedral oligomeric silsesquioxane (POSS) nanoparticles have attracted much attention recently due to their nanometer size, the ease of which these particles can be incorporated into polymeric materials and the unique capability to reinforce polymers. We review here the state of POSS-containing polymer nanocomposites. We discuss the influence of the incorporation of POSS into polymer matrices via chemical cross-linking or physical blending on the structure of nanocomposites, as affected by surface functional groups, and the POSS concentration. PMID:28348318

  3. Oligomerizations of deoxyadenosine bis-phosphates and of their 3-prime-5-prime, 3-prime-3-prime, and 5-prime-5-prime dimers - Effects of a pyrophosphate-linked, poly(T) analog

    Science.gov (United States)

    Visscher, J.; Bakker, C. G.; Schwartz, Alan W.

    1990-01-01

    The effect of a 3-prime-5-prime pyrophosphate-linked oligomer of pTp on oligomerizations of pdAp and of its 3-prime-5-prime, 3-prime-3-prime, and 5-prime-5-prime dimers was investigated, using HPLC to separate the reaction mixtures; peak detection was by absorbance monitoring at 254 nm. It was expected that the dimers would form stable complexes with the template, with the degree of stability depending upon the internal linkage of each dimer. It was found that, although the isomers differ substantially in their oligomerization behavior in the absence of template, the analog-template catalyzes the oligomerization to about the same extent in all three cases.

  4. The oligomeric state of the active Vps4 AAA ATPase

    Science.gov (United States)

    Monroe, Nicole; Han, Han; Gonciarz, Malgorzata D.; Eckert, Debra M.; Karren, Mary Anne; Whitby, Frank G.; Sundquist, Wesley I.; Hill, Christopher P.

    2013-01-01

    The cellular ESCRT pathway drives membrane constriction toward the cytosol and effects membrane fission during cytokinesis, endosomal sorting, and the release of many enveloped viruses, including HIV. A component of this pathway, the AAA ATPase Vps4, provides energy for pathway progression. Although it is established that Vps4 functions as an oligomer, subunit stoichiometry and other fundamental features of the functional enzyme are unclear. Higher-order oligomers have thus far only been characterized for a Walker B mutant of Vps4 in the presence of ATP. Here, we report that although some mutant Vps4 proteins form dodecameric assemblies, active wild-type S. cerevisiae and S. solfataricus Vps4 enzymes can form hexamers in the presence of ATP and ADP, as assayed by size exclusion chromatography and equilibrium analytical ultracentifugation. The Vta1p activator binds hexameric yeast Vps4p without changing the oligomeric state of Vps4p, implying that the active Vta1p:Vps4p complex also contains a single hexameric ring. Additionally, we report crystal structures of two different archaeal Vps4 homologs, whose structures and lattice interactions suggest a conserved mode of oligomerization. Disruption of the proposed hexamerization interface by mutagenesis abolished the ATPase activity of archaeal Vps4 proteins and blocked Vps4p function in S. cerevisiae. These data challenge the prevailing model that active Vps4 is a double ring dodecamer, and argue that, like other type I AAA ATPases, Vps4 functions as a single ring with six subunits. PMID:24161953

  5. Oligomerization and polymerization of the filovirus matrix protein VP40

    International Nuclear Information System (INIS)

    Timmins, Joanna; Schoehn, Guy; Kohlhaas, Christine; Klenk, Hans-Dieter; Ruigrok, Rob W.H.; Weissenhorn, Winfried

    2003-01-01

    The matrix protein VP40 from Ebola virus plays an important role in the assembly process of virus particles by interacting with cellular factors, cellular membranes, and the ribonuclearprotein particle complex. Here we show that the N-terminal domain of VP40 folds into a mixture of two different oligomeric states in vitro, namely hexameric and octameric ringlike structures, as detected by gel filtration chromatography, chemical cross-linking, and electron microscopy. Octamer formation depends largely on the interaction with nucleic acids, which in turn confers in vitro SDS resistance. Refolding experiments with a nucleic acid free N-terminal domain preparation reveal a mostly dimeric form of VP40, which is transformed into an SDS resistant octamer upon incubation with E. coli nucleic acids. In addition, we demonstrate that the N-terminal domain of Marburg virus VP40 also folds into ringlike structures, similar to Ebola virus VP40. Interestingly, Marburg virus VP40 rings reveal a high tendency to polymerize into rods composed of stacked rings. These results may suggest distinct roles for different oligomeric forms of VP40 in the filovirus life cycle

  6. Bacterial flagellar capping proteins adopt diverse oligomeric states

    Energy Technology Data Exchange (ETDEWEB)

    Postel, Sandra; Deredge, Daniel; Bonsor, Daniel A.; Yu, Xiong; Diederichs, Kay; Helmsing, Saskia; Vromen, Aviv; Friedler, Assaf; Hust, Michael; Egelman, Edward H.; Beckett, Dorothy; Wintrode, Patrick L.; Sundberg, Eric J. (UV); (Braunschweig); (Maryland-MED); (Konstanz); (Maryland); (Hebrew)

    2016-09-24

    Flagella are crucial for bacterial motility and pathogenesis. The flagellar capping protein (FliD) regulates filament assembly by chaperoning and sorting flagellin (FliC) proteins after they traverse the hollow filament and exit the growing flagellum tip. In the absence of FliD, flagella are not formed, resulting in impaired motility and infectivity. Here, we report the 2.2 Å resolution X-ray crystal structure of FliD fromPseudomonas aeruginosa, the first high-resolution structure of any FliD protein from any bacterium. Using this evidence in combination with a multitude of biophysical and functional analyses, we find thatPseudomonasFliD exhibits unexpected structural similarity to other flagellar proteins at the domain level, adopts a unique hexameric oligomeric state, and depends on flexible determinants for oligomerization. Considering that the flagellin filaments on which FliD oligomers are affixed vary in protofilament number between bacteria, our results suggest that FliD oligomer stoichiometries vary across bacteria to complement their filament assemblies.

  7. Oligomerization and polymerization of the filovirus matrix protein VP40.

    Science.gov (United States)

    Timmins, Joanna; Schoehn, Guy; Kohlhaas, Christine; Klenk, Hans-Dieter; Ruigrok, Rob W H; Weissenhorn, Winfríed

    2003-08-01

    The matrix protein VP40 from Ebola virus plays an important role in the assembly process of virus particles by interacting with cellular factors, cellular membranes, and the ribonuclearprotein particle complex. Here we show that the N-terminal domain of VP40 folds into a mixture of two different oligomeric states in vitro, namely hexameric and octameric ringlike structures, as detected by gel filtration chromatography, chemical cross-linking, and electron microscopy. Octamer formation depends largely on the interaction with nucleic acids, which in turn confers in vitro SDS resistance. Refolding experiments with a nucleic acid free N-terminal domain preparation reveal a mostly dimeric form of VP40, which is transformed into an SDS resistant octamer upon incubation with E. coli nucleic acids. In addition, we demonstrate that the N-terminal domain of Marburg virus VP40 also folds into ringlike structures, similar to Ebola virus VP40. Interestingly, Marburg virus VP40 rings reveal a high tendency to polymerize into rods composed of stacked rings. These results may suggest distinct roles for different oligomeric forms of VP40 in the filovirus life cycle.

  8. Tailoring iron complexes for ethylene oligomerization and/or polymerization.

    Science.gov (United States)

    Zhang, Wenjuan; Sun, Wen-Hua; Redshaw, Carl

    2013-07-07

    Recent progress in the use of iron-based complex pre-catalysts for ethylene reactivity is reviewed, illustrating the current state-of-the-art and the potential usefulness of such systems for delivering solely ethylene oligomerization or polymerization products. The problems associated with the industrial use of late transition metal complex pre-catalysts are generally regarded as catalyst deactivation and the formation of more products of lower molecular weight at elevated temperature. These problems have been addressed for iron-based complex pre-catalysts via the fine tuning of substituents of existing ligands and/or the design of new ligand sets. Results revealed that modified bis(imino)pyridyliron dichlorides were capable of operating at elevated temperatures, and were capable of delivering highly linear polyethylene. Other new models of iron complexes have achieved high activity for ethylene oligomerization and/or polymerization. Particularly successful has been the use of the 2-iminophenanthrolyliron pre-catalyst, which have now been utilized in a 500 tonne pilot plant.

  9. Oligomerization interface of RAGE receptor revealed by MS-monitored hydrogen deuterium exchange.

    Directory of Open Access Journals (Sweden)

    Ewa Sitkiewicz

    Full Text Available Activation of the receptor for advanced glycation end products (RAGE leads to a chronic proinflammatory signal, affecting patients with a variety of diseases. Potentially beneficial modification of RAGE activity requires understanding the signal transduction mechanism at the molecular level. The ligand binding domain is structurally uncoupled from the cytoplasmic domain, suggesting receptor oligomerization is a requirement for receptor activation. In this study, we used hydrogen-deuterium exchange and mass spectrometry to map structural differences between the monomeric and oligomeric forms of RAGE. Our results indicated the presence of a region shielded from exchange in the oligomeric form of RAGE and led to the identification of a new oligomerization interface localized at the linker region between domains C1 and C2. Based on this finding, a model of a RAGE dimer and higher oligomeric state was constructed.

  10. Oligomerization interface of RAGE receptor revealed by MS-monitored hydrogen deuterium exchange.

    Science.gov (United States)

    Sitkiewicz, Ewa; Tarnowski, Krzysztof; Poznański, Jarosław; Kulma, Magdalena; Dadlez, Michal

    2013-01-01

    Activation of the receptor for advanced glycation end products (RAGE) leads to a chronic proinflammatory signal, affecting patients with a variety of diseases. Potentially beneficial modification of RAGE activity requires understanding the signal transduction mechanism at the molecular level. The ligand binding domain is structurally uncoupled from the cytoplasmic domain, suggesting receptor oligomerization is a requirement for receptor activation. In this study, we used hydrogen-deuterium exchange and mass spectrometry to map structural differences between the monomeric and oligomeric forms of RAGE. Our results indicated the presence of a region shielded from exchange in the oligomeric form of RAGE and led to the identification of a new oligomerization interface localized at the linker region between domains C1 and C2. Based on this finding, a model of a RAGE dimer and higher oligomeric state was constructed.

  11. DNA prime/protein boost vaccination elicits robust humoral response in rhesus macaques using oligomeric simian immunodeficiency virus envelope and Advax delta inulin adjuvant.

    Science.gov (United States)

    Menon, Veena; Ayala, Victor I; Rangaswamy, Sneha P; Kalisz, Irene; Whitney, Stephen; Galmin, Lindsey; Ashraf, Asma; LaBranche, Celia; Montefiori, David; Petrovsky, Nikolai; Kalyanaraman, Vaniambadi S; Pal, Ranajit

    2017-08-01

    The partial success of the RV144 trial underscores the importance of envelope-specific antibody responses for an effective HIV-1 vaccine. Oligomeric HIV-1 envelope proteins delivered with a potent adjuvant are expected to elicit strong antibody responses with broad neutralization specificity. To test this hypothesis, two SIV envelope proteins were formulated with delta inulin-based adjuvant (Advax) and used to immunize nonhuman primates. Oligomeric gp140-gp145 from SIVmac251 and SIVsmE660 was purified to homogeneity. Oligomers showed high-affinity interaction with CD4 and were highly immunogenic in rabbits, inducing Tier 2 SIV-neutralizing antibodies. The immunogenicity of an oligomeric Env DNA prime and protein boost together with Advax was evaluated in Chinese rhesus macaques. DNA administration elicited antibodies to both envelopes, and titres were markedly enhanced following homologous protein boosts via intranasal and intramuscular routes. Strong antibody responses were detected against the V1 and V2 domains of gp120. During peak immune responses, a low to moderate level of neutralizing activity was detected against Tier 1A/1B SIV isolates, with a moderate level noted against a Tier 2 isolate. Increased serum antibody affinity to SIVmac251 gp140 and generation of Env-specific memory B cells were observed in the immunized macaques. Animals were subjected to low-dose intravaginal challenge with SIVmac251 one week after the last protein boost. One out of three immunized animals was protected from infection. Although performed with a small number of macaques, this study demonstrates the utility of oligomeric envelopes formulated with Advax in eliciting broad antibody responses with the potential to provide protection against SIV transmission.

  12. Factors affecting the catalytic oligomerization of methane via microwave heating

    Science.gov (United States)

    Conde, Luis Daniel

    Catalytic microwave heating has been used as a method for the oligomerization of methane to higher hydrocarbons. Many catalysts were tested in this reaction. Nickel powder, raney nickel, iron powder and activated carbon were the most active and efficient catalysts for the production of higher hydrocarbons. When helium was used as a diluent gas and the applied power was optimized, the selectivities were controlled to the most desired products. In general, the most abundant products for all the experiments were C2s. Iron powder was active only at high power (1130 W). At these conditions acetylene was avoided and ethylene and ethane were produced in the same proportion. Activated carbon catalysts with helium as diluent led to a selectivity towards benzene up to 33%. Some manganese oxides such as OMS-1, OMS-2 and MnO2 (dielectric constant, epsilon ≈ 104) were not active in these reactions. These data suggest that the dielectric constant is not the most important factor in the oligomerization of methane via microwave heating. Conversion and activities of these materials are not proportionally related to the surface area of the catalysts. Higher catalytic activity was observed for Raney nickel than for regular nickel powder. The maximum conversion obtained was 24% at 400 W and 10 min of irradiation time. For regular nickel powder that conversion can be achieved only after 700 W of power and more than 20 min of reaction. BET surface area, Scanning Electron Microscopy, X-ray Photoelectron Spectroscopy, and Temperature-Programmed Desorption and Reduction analysis were performed to characterize the catalyst before and after reaction. Deactivation of Raney nickel by fouling and sintering was observed after 500 W and/or 15 min of reaction. The effect of microwave radiation frequency on activity and product distribution for methane oligomerization has been studied. Nickel, iron, and activated carbon catalysts were used in these studies. Experiments were done with pure methane

  13. Polypropylene containing Ti- and Al-polyhedral oligomeric silsesquioxanes: crystallization process and thermal properties

    Science.gov (United States)

    Carniato, Fabio; Fina, Alberto; Tabuani, Daniela; Boccaleri, Enrico

    2008-11-01

    This paper deals with the preparation and characterization of isotactic polypropylene (PP) containing different metal-polyhedral oligomeric silsesquioxanes (M-POSS). Two M-POSS, Ti(IV)- and Al(III)-isobutyl-POSS, defined by a monomeric structure, were selected for dispersion, and particular attention was paid to the assessment of the morphology, crystallization process and thermal behavior of M-POSS/PP composites, using SEM and TEM microscopy, x-ray diffraction (XRD), FTIR and Raman spectroscopy, differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and gas chromatography/mass spectrometry. The study of M-POSS/PP thermal degradation showed that Ti-POSS and Al-POSS induce different effects on the thermoxidative behavior of the polypropylene matrix, showing a clear specificity of the metal center on the PP degradation pathway. In particular, Ti-POSS showed a significant stabilization of PP when heating under air, whereas limited effects were observed with Al-POSS. Moreover, Ti-POSS was also found to affect PP crystallization, driving the crystallization process along specific crystallographic directions.

  14. Polypropylene containing Ti- and Al-polyhedral oligomeric silsesquioxanes: crystallization process and thermal properties.

    Science.gov (United States)

    Carniato, Fabio; Fina, Alberto; Tabuani, Daniela; Boccaleri, Enrico

    2008-11-26

    This paper deals with the preparation and characterization of isotactic polypropylene (PP) containing different metal-polyhedral oligomeric silsesquioxanes (M-POSS). Two M-POSS, Ti(IV)- and Al(III)-isobutyl-POSS, defined by a monomeric structure, were selected for dispersion, and particular attention was paid to the assessment of the morphology, crystallization process and thermal behavior of M-POSS/PP composites, using SEM and TEM microscopy, x-ray diffraction (XRD), FTIR and Raman spectroscopy, differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and gas chromatography/mass spectrometry. The study of M-POSS/PP thermal degradation showed that Ti-POSS and Al-POSS induce different effects on the thermoxidative behavior of the polypropylene matrix, showing a clear specificity of the metal center on the PP degradation pathway. In particular, Ti-POSS showed a significant stabilization of PP when heating under air, whereas limited effects were observed with Al-POSS. Moreover, Ti-POSS was also found to affect PP crystallization, driving the crystallization process along specific crystallographic directions.

  15. Receptor oligomerization in family B1 of G-protein-coupled receptors: focus on BRET investigations and the link between GPCR oligomerization and binding cooperativity.

    Science.gov (United States)

    Roed, Sarah Norklit; Orgaard, Anne; Jorgensen, Rasmus; De Meyts, Pierre

    2012-01-01

    The superfamily of the seven transmembrane G-protein-coupled receptors (7TM/GPCRs) is the largest family of membrane-associated receptors. GPCRs are involved in the pathophysiology of numerous human diseases, and they constitute an estimated 30-40% of all drug targets. During the last two decades, GPCR oligomerization has been extensively studied using methods like bioluminescence resonance energy transfer (BRET) and today, receptor-receptor interactions within the GPCR superfamily is a well-established phenomenon. Evidence of the impact of GPCR oligomerization on, e.g., ligand binding, receptor expression, and signal transduction indicates the physiological and pharmacological importance of these receptor interactions. In contrast to the larger and more thoroughly studied GPCR subfamilies A and C, the B1 subfamily is small and comprises only 15 members, including, e.g., the secretin receptor, the glucagon receptor, and the receptors for parathyroid hormone (PTHR1 and PTHR2). The dysregulation of several family B1 receptors is involved in diseases, such as diabetes, chronic inflammation, and osteoporosis which underlines the pathophysiological importance of this GPCR subfamily. In spite of this, investigation of family B1 receptor oligomerization and especially its pharmacological importance is still at an early stage. Even though GPCR oligomerization is a well-established phenomenon, there is a need for more investigations providing a direct link between these interactions and receptor functionality in family B1 GPCRs. One example of the functional effects of GPCR oligomerization is the facilitation of allosterism including cooperativity in ligand binding to GPCRs. Here, we review the currently available data on family B1 GPCR homo- and heteromerization, mainly based on BRET investigations. Furthermore, we cover the functional influence of oligomerization on ligand binding as well as the link between oligomerization and binding cooperativity.

  16. Lighting up multiprotein complexes: lessons from GPCR oligomerization

    Science.gov (United States)

    Ciruela, Francisco; Vilardaga, Jean-Pierre; Fernández-Dueñas, Víctor

    2011-01-01

    Spatiotemporal characterization of protein–protein interactions (PPIs) is essential in determining the molecular mechanisms of intracellular signaling processes. In this review, we discuss how new methodological strategies derived from non-invasive fluorescence- and luminescence-based approaches (FRET, BRET, BiFC and BiLC), when applied to the study of G protein-coupled receptor (GPCR) oligomerization, can be used to detect specific PPIs in live cells. These technologies alone or in concert with complementary methods (SRET, BRET or BiFC, and SNAP-tag or TR-FRET) can be extremely powerful approaches for PPI visualization, even between more than two proteins. Here we provide a comprehensive update on all the biotechnological aspects, including the strengths and weaknesses, of new fluorescence- and luminescence-based methodologies, with a specific focus on their application for studying PPIs. PMID:20542584

  17. Green Nanocomposites from Renewable Plant Oils and Polyhedral Oligomeric Silsesquioxanes

    Directory of Open Access Journals (Sweden)

    Takashi Tsujimoto

    2015-06-01

    Full Text Available Green nanocomposites based on renewable plant oils and polyhedral oligomeric silsesquioxanes (POSS have been developed. An acid-catalyzed curing of epoxidized plant oils with oxirane-containing POSS derivatives produced transparent nanocomposite coatings with high gloss surface, in which the organic and inorganic components were linked via covalent bonds. The hardness and mechanical strength were improved by the incorporation of the POSS unit into the organic polymer matrix. Nanostructural analyses of the nanocomposites showed the formation of homogeneous structures at the micrometer scale. On the other hand, such improvements of the coating and mechanical properties were not observed in the composite without covalent bonds between the plant oil-based polymer and POSS unit. The study demonstrates the correlation between the nanostructure of composites and macroscopic properties.

  18. Structural Determinants of Oligomerization of the Aquaporin-4 Channel*

    Science.gov (United States)

    Kitchen, Philip; Conner, Matthew T.; Bill, Roslyn M.; Conner, Alex C.

    2016-01-01

    The aquaporin (AQP) family of integral membrane protein channels mediate cellular water and solute flow. Although qualitative and quantitative differences in channel permeability, selectivity, subcellular localization, and trafficking responses have been observed for different members of the AQP family, the signature homotetrameric quaternary structure is conserved. Using a variety of biophysical techniques, we show that mutations to an intracellular loop (loop D) of human AQP4 reduce oligomerization. Non-tetrameric AQP4 mutants are unable to relocalize to the plasma membrane in response to changes in extracellular tonicity, despite equivalent constitutive surface expression levels and water permeability to wild-type AQP4. A network of AQP4 loop D hydrogen bonding interactions, identified using molecular dynamics simulations and based on a comparative mutagenic analysis of AQPs 1, 3, and 4, suggest that loop D interactions may provide a general structural framework for tetrameric assembly within the AQP family. PMID:26786101

  19. Structural Determinants of Oligomerization of the Aquaporin-4 Channel.

    Science.gov (United States)

    Kitchen, Philip; Conner, Matthew T; Bill, Roslyn M; Conner, Alex C

    2016-03-25

    The aquaporin (AQP) family of integral membrane protein channels mediate cellular water and solute flow. Although qualitative and quantitative differences in channel permeability, selectivity, subcellular localization, and trafficking responses have been observed for different members of the AQP family, the signature homotetrameric quaternary structure is conserved. Using a variety of biophysical techniques, we show that mutations to an intracellular loop (loop D) of human AQP4 reduce oligomerization. Non-tetrameric AQP4 mutants are unable to relocalize to the plasma membrane in response to changes in extracellular tonicity, despite equivalent constitutive surface expression levels and water permeability to wild-type AQP4. A network of AQP4 loop D hydrogen bonding interactions, identified using molecular dynamics simulations and based on a comparative mutagenic analysis of AQPs 1, 3, and 4, suggest that loop D interactions may provide a general structural framework for tetrameric assembly within the AQP family. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  20. Structural basis for oligomerization of auxin transcriptional regulators.

    Science.gov (United States)

    Nanao, Max H; Vinos-Poyo, Thomas; Brunoud, Géraldine; Thévenon, Emmanuel; Mazzoleni, Meryl; Mast, David; Lainé, Stéphanie; Wang, Shucai; Hagen, Gretchen; Li, Hanbing; Guilfoyle, Thomas J; Parcy, François; Vernoux, Teva; Dumas, Renaud

    2014-04-07

    The plant hormone auxin is a key morphogenetic regulator acting from embryogenesis onwards. Transcriptional events in response to auxin are mediated by the auxin response factor (ARF) transcription factors and the Aux/IAA (IAA) transcriptional repressors. At low auxin concentrations, IAA repressors associate with ARF proteins and recruit corepressors that prevent auxin-induced gene expression. At higher auxin concentrations, IAAs are degraded and ARFs become free to regulate auxin-responsive genes. The interaction between ARFs and IAAs is thus central to auxin signalling and occurs through the highly conserved domain III/IV present in both types of proteins. Here, we report the crystal structure of ARF5 domain III/IV and reveal the molecular determinants of ARF-IAA interactions. We further provide evidence that ARFs have the potential to oligomerize, a property that could be important for gene regulation in response to auxin.

  1. Effects of Glycine, Water, Ammonia, and Ammonium Bicarbonate on the Oligomerization of Methionine

    Science.gov (United States)

    Huang, Rui; Furukawa, Yoshihiro; Otake, Tsubasa; Kakegawa, Takeshi

    2017-06-01

    The abiotic oligomerization of amino acids may have created primordial, protein-like biological catalysts on the early Earth. Previous studies have proposed and evaluated the potential of diagenesis for the amino acid oligomerization, simulating the formation of peptides that include glycine, alanine, and valine, separately. However, whether such conditions can promote the formation of peptides composed of multiple amino acids remains unclear. Furthermore, the chemistry of pore water in sediments should affect the oligomerization and degradation of amino acids and oligomers, but these effects have not been studied extensively. In this study, we investigated the effects of water, ammonia, ammonium bicarbonate, pH, and glycine on the oligomerization and degradation of methionine under high pressure (150 MPa) and high temperature conditions (175 °C) for 96 h. Methionine is more difficult to oligomerize than glycine and methionine dimer was formed in the incubation of dry powder of methionine. Methionine oligomers as long as trimers, as well as methionylglycine and glycylmethionine, were formed under every condition with these additional compounds. Among the compounds tested, the oligomerization reaction rate was accelerated by the presence of water and by an increase in pH. Ammonia also increased the oligomerization rate but consumed methionine by side reactions and resulted in the rapid degradation of methionine and its peptides. Similarly, glycine accelerated the oligomerization rate of methionine and the degradation of methionine, producing water, ammonia, and bicarbonate through its decomposition. With Gly, heterogeneous dimers (methionylglycine and glycylmethionine) were formed in greater amounts than with other additional compounds although smaller amount of these heterogeneous dimers were formed with other additional compounds. These results suggest that accelerated reaction rates induced by water and co-existing reactive compounds promote the oligomerization

  2. Nanomolar oligomerization and selective co-aggregation of α-synuclein pathogenic mutants revealed by single-molecule fluorescence

    Science.gov (United States)

    Sierecki, Emma; Giles, Nichole; Bowden, Quill; Polinkovsky, Mark E.; Steinbeck, Janina; Arrioti, Nicholas; Rahman, Diya; Bhumkar, Akshay; Nicovich, Philip R.; Ross, Ian; Parton, Robert G.; Böcking, Till; Gambin, Yann

    2016-01-01

    Protein aggregation is a hallmark of many neurodegenerative diseases, notably Alzheimer’s and Parkinson’s disease. Parkinson’s disease is characterized by the presence of Lewy bodies, abnormal aggregates mainly composed of α-synuclein. Moreover, cases of familial Parkinson’s disease have been linked to mutations in α-synuclein. In this study, we compared the behavior of wild-type (WT) α-synuclein and five of its pathological mutants (A30P, E46K, H50Q, G51D and A53T). To this end, single-molecule fluorescence detection was coupled to cell-free protein expression to measure precisely the oligomerization of proteins without purification, denaturation or labelling steps. In these conditions, we could detect the formation of oligomeric and pre-fibrillar species at very short time scale and low micromolar concentrations. The pathogenic mutants surprisingly segregated into two classes: one group forming large aggregates and fibrils while the other tending to form mostly oligomers. Strikingly, co-expression experiments reveal that members from the different groups do not generally interact with each other, both at the fibril and monomer levels. Together, this data paints a completely different picture of α-synuclein aggregation, with two possible pathways leading to the development of fibrils. PMID:27892477

  3. Nanomolar oligomerization and selective co-aggregation of α-synuclein pathogenic mutants revealed by single-molecule fluorescence.

    Science.gov (United States)

    Sierecki, Emma; Giles, Nichole; Bowden, Quill; Polinkovsky, Mark E; Steinbeck, Janina; Arrioti, Nicholas; Rahman, Diya; Bhumkar, Akshay; Nicovich, Philip R; Ross, Ian; Parton, Robert G; Böcking, Till; Gambin, Yann

    2016-11-28

    Protein aggregation is a hallmark of many neurodegenerative diseases, notably Alzheimer's and Parkinson's disease. Parkinson's disease is characterized by the presence of Lewy bodies, abnormal aggregates mainly composed of α-synuclein. Moreover, cases of familial Parkinson's disease have been linked to mutations in α-synuclein. In this study, we compared the behavior of wild-type (WT) α-synuclein and five of its pathological mutants (A30P, E46K, H50Q, G51D and A53T). To this end, single-molecule fluorescence detection was coupled to cell-free protein expression to measure precisely the oligomerization of proteins without purification, denaturation or labelling steps. In these conditions, we could detect the formation of oligomeric and pre-fibrillar species at very short time scale and low micromolar concentrations. The pathogenic mutants surprisingly segregated into two classes: one group forming large aggregates and fibrils while the other tending to form mostly oligomers. Strikingly, co-expression experiments reveal that members from the different groups do not generally interact with each other, both at the fibril and monomer levels. Together, this data paints a completely different picture of α-synuclein aggregation, with two possible pathways leading to the development of fibrils.

  4. Thermal Degradation Mechanism of a Thermostable Polyester Stabilized with an Open-Cage Oligomeric Silsesquioxane

    Directory of Open Access Journals (Sweden)

    Yolanda Bautista

    2017-12-01

    Full Text Available A polyester composite was prepared through the polymerization of an unsaturated ester resin with styrene and an open-cage oligomeric silsesquioxane with methacrylate groups. The effect of the open-cage oligomeric silsesquioxane on the thermal stability of the thermostable polyester was studied using both thermogravimetric analysis and differential thermal analysis. The results showed that the methacryl oligomeric silsesquioxane improved the thermal stability of the polyester. The decomposition mechanism of the polyester/oligomer silsesquioxane composite was proposed by Fourier transform infrared spectroscopy (FTIR analysis of the volatiles.

  5. Thermal Degradation Mechanism of a Thermostable Polyester Stabilized with an Open-Cage Oligomeric Silsesquioxane

    Science.gov (United States)

    Gozalbo, Ana; Mestre, Sergio; Sanz, Vicente

    2017-01-01

    A polyester composite was prepared through the polymerization of an unsaturated ester resin with styrene and an open-cage oligomeric silsesquioxane with methacrylate groups. The effect of the open-cage oligomeric silsesquioxane on the thermal stability of the thermostable polyester was studied using both thermogravimetric analysis and differential thermal analysis. The results showed that the methacryl oligomeric silsesquioxane improved the thermal stability of the polyester. The decomposition mechanism of the polyester/oligomer silsesquioxane composite was proposed by Fourier transform infrared spectroscopy (FTIR) analysis of the volatiles. PMID:29295542

  6. Electron spin resonance and nuclear magnetic resonance of sodium macrostructures in strongly irradiated NaCl-K crystals: Manifestation of quasi-one-dimensional behavior of electrons

    NARCIS (Netherlands)

    Cherkasov, FG; Mustafin, RG; L'vov, SG; Denisenko, GA; den Hartog, HW; Vainshtein, D. I.

    1998-01-01

    Data from an investigation of electron spin resonance and nuclear magnetic resonance of NaCl-K (similar to 1 mole%) crystals strongly irradiated with electrons imply the observation of a metal-insulator transition with decreasing temperature and the manifestation of quasi-one-dimensional electron

  7. Zinc and the iron donor frataxin regulate oligomerization of the scaffold protein to form new Fe-S cluster assembly centers.

    Science.gov (United States)

    Galeano, B K; Ranatunga, W; Gakh, O; Smith, D Y; Thompson, J R; Isaya, G

    2017-06-21

    Early studies of the bacterial Fe-S cluster assembly system provided structural details for how the scaffold protein and the cysteine desulfurase interact. This work and additional work on the yeast and human systems elucidated a conserved mechanism for sulfur donation but did not provide any conclusive insights into the mechanism for iron delivery from the iron donor, frataxin, to the scaffold. We previously showed that oligomerization is a mechanism by which yeast frataxin (Yfh1) can promote assembly of the core machinery for Fe-S cluster synthesis both in vitro and in cells, in such a manner that the scaffold protein, Isu1, can bind to Yfh1 independent of the presence of the cysteine desulfurase, Nfs1. Here, in the absence of Yfh1, Isu1 was found to exist in two forms, one mostly monomeric with limited tendency to dimerize, and one with a strong propensity to oligomerize. Whereas the monomeric form is stabilized by zinc, the loss of zinc promotes formation of dimer and higher order oligomers. However, upon binding to oligomeric Yfh1, both forms take on a similar symmetrical trimeric configuration that places the Fe-S cluster coordinating residues of Isu1 in close proximity of iron-binding residues of Yfh1. This configuration is suitable for docking of Nfs1 in a manner that provides a structural context for coordinate iron and sulfur donation to the scaffold. Moreover, distinct structural features suggest that in physiological conditions the zinc-regulated abundance of monomeric vs. oligomeric Isu1 yields [Yfh1]·[Isu1] complexes with different Isu1 configurations that afford unique functional properties for Fe-S cluster assembly and delivery.

  8. Receptor oligomerization in family B1 of G-protein-coupled receptors

    DEFF Research Database (Denmark)

    Roed, Sarah Norklit; Ørgaard, Anne; Jørgensen, Rasmus

    2012-01-01

    , investigation of family B1 receptor oligomerization and especially its pharmacological importance is still at an early stage. Even though GPCR oligomerization is a well-established phenomenon, there is a need for more investigations providing a direct link between these interactions and receptor functionality......The superfamily of the seven transmembrane G-protein-coupled receptors (7TM/GPCRs) is the largest family of membrane-associated receptors. GPCRs are involved in the pathophysiology of numerous human diseases, and they constitute an estimated 30-40% of all drug targets. During the last two decades......, GPCR oligomerization has been extensively studied using methods like bioluminescence resonance energy transfer (BRET) and today, receptor-receptor interactions within the GPCR superfamily is a well-established phenomenon. Evidence of the impact of GPCR oligomerization on, e.g., ligand binding, receptor...

  9. Molecular cloning and functional characterization of duck nucleotide-binding oligomerization domain 1 (NOD1).

    Science.gov (United States)

    Li, Huilin; Jin, Hui; Li, Yaqian; Liu, Dejian; Foda, Mohamed Frahat; Jiang, Yunbo; Luo, Rui

    2017-09-01

    Nucleotide-binding oligomerization domain 1 (NOD1) is an imperative cytoplasmic pattern recognition receptor (PRR) and considered as a key member of the NOD-like receptor (NLR) family which plays a critical role in innate immunity through sensing microbial components derived from bacterial peptidoglycan. In the current study, the full-length of duck NOD1 (duNOD1) cDNA from duck embryo fibroblasts (DEFs) was cloned. Multiple sequence alignment and phylogenetic analysis demonstrated that duNOD1 exhibited a strong evolutionary relationship with chicken and rock pigeon NOD1. Tissue-specific expression analysis showed that duNOD1 was widely distributed in various organs, with the highest expression observed in the liver. Furthermore, duNOD1 overexpression induced NF-κB activation in DEFs and the CARD domain is crucial for duNOD1-mediated NF-κB activation. In addition, silencing the duNOD1 decreased the activity of NF-κB in DEFs stimulated by iE-DAP. Overexpression of duNOD1 significantly increased the expression of TNF-α, IL-6, and RANTES in DEFs. These findings highlight the crucial role of duNOD1 as an intracellular sensor in duck innate immune system. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Charged polyhedral oligomeric silsesquioxanes trigger in vitro METosis via both oxidative stress and autophagy.

    Science.gov (United States)

    Tonello, Stelvio; Carniato, Fabio; Rizzi, Manuela; Migliario, Mario; Rocchetti, Vincenzo; Marchese, Leonardo; Renò, Filippo

    2017-12-01

    Monocytes/macrophages are essential in innate immune response against pathogens also because their ability to release extracellular traps named METs (monocytes/macrophages extracellular traps). These structures are composed of DNA fibers decorated with nuclear and cytoplasmic proteins and their production process is called METosis. In this study attention has been focused on the ability of differently charged molecular systems (polyhedral oligomeric silsesquioxanes, POSS positively or negatively charged) to induce METosis. METs formation was induced by lipopolysaccharide (250μg/ml, positive control) and POSS positive and negative (0.05-1mg/ml) treatment. METs were visualized and quantified by confocal microscopy using Sytox green staining. Oxidative stress, autophagy, as well as endocytosis involvement in the POSS induced METosis was evaluated. Results obtained indicate a POSS positive or negative dose dependent ability in inducing MET release independently to their charge and that this phenomenon is a consequence of POSS +/- internalization. Moreover, studies using many reactive oxidative species (ROS) blockers and autophagy inhibitor showed a strong reduction in POSS induced METosis indicating their involvement. POSS +/- induce extracellular traps production in human monocytes/macrophages by oxidative and autophagic pathway. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Exploring alternate states and oligomerization preferences of coiled-coils by de novo structure modeling.

    Science.gov (United States)

    Rämisch, Sebastian; Lizatović, Robert; André, Ingemar

    2015-02-01

    Homomeric coiled-coils can self-assemble into a wide range of structural states with different helix topologies and oligomeric states. In this study, we have combined de novo structure modeling with stability calculations to simultaneously predict structure and oligomeric states of homomeric coiled-coils. For dimers an asymmetric modeling protocol was developed. Modeling without symmetry constraints showed that backbone asymmetry is important for the formation of parallel dimeric coiled-coils. Collectively, our results demonstrate that high-resolution structure of coiled-coils, as well as parallel and antiparallel orientations of dimers and tetramers, can be accurately predicted from sequence. De novo modeling was also used to generate models of competing oligomeric states, which were used to compare stabilities and thus predict the native stoichiometry from sequence. In a benchmark set of 33 coiled-coil sequences, forming dimers to pentamers, up to 70% of the oligomeric states could be correctly predicted. The calculations demonstrated that the free energy of helix folding could be an important factor for determining stability and oligomeric state of homomeric coiled-coils. The computational methods developed here should be broadly applicable to studies of sequence-structure relationships in coiled-coils and the design of higher order assemblies with improved oligomerization specificity. © 2014 Wiley Periodicals, Inc.

  12. Oligomeric state of hypoxanthine-guanine phosphoribosyltransferase from Mycobacterium tuberculosis.

    Science.gov (United States)

    Eng, Wai Soon; Keough, Dianne T; Hockova, Dana; Winzor, Donald J; Guddat, Luke W

    2017-04-01

    Sedimentation equilibrium and size-exclusion chromatography experiments on Mycobacterium tuberculosis hypoxanthine-guanine phosphoribosyltransferase (MtHGPRT) have established the existence of this enzyme as a reversibly associating mixture of dimeric and tetrameric species in 0.1 M Tris-HCl-0.012 M MgCl 2 , pH 7.4. Displacement of the equilibrium position towards the larger oligomer by phosphate signifies the probable existence of MtHGPRT as a tetramer in the biological environment. These data thus add credibility to the relevance of considering enzyme function in the light of a published tetrameric structure deduced from X-ray crystallography. Failure of 5-phospho-α-d-ribosyl-1-pyrophosphate (PRib-PP) to perturb the dimer-tetramer equilibrium position indicates the equivalence and independence of binding for this substrate (the first to bind in an ordered sequential mechanism) to the two oligomers. By virtue of the displacement of the equilibrium position towards dimer that is affected by removing MgCl 2 from the Tris-HCl buffer, it can be concluded that divalent metal ions, as well as phosphate, can affect the oligomerization. These characteristics of MtHGPRT in solution are correlated with published crystal structures of four enzyme-ligand complexes. Copyright © 2017 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

  13. Free-energy landscape of protein oligomerization from atomistic simulations

    Science.gov (United States)

    Barducci, Alessandro; Bonomi, Massimiliano; Prakash, Meher K.; Parrinello, Michele

    2013-01-01

    In the realm of protein–protein interactions, the assembly process of homooligomers plays a fundamental role because the majority of proteins fall into this category. A comprehensive understanding of this multistep process requires the characterization of the driving molecular interactions and the transient intermediate species. The latter are often short-lived and thus remain elusive to most experimental investigations. Molecular simulations provide a unique tool to shed light onto these complex processes complementing experimental data. Here we combine advanced sampling techniques, such as metadynamics and parallel tempering, to characterize the oligomerization landscape of fibritin foldon domain. This system is an evolutionarily optimized trimerization motif that represents an ideal model for experimental and computational mechanistic studies. Our results are fully consistent with previous experimental nuclear magnetic resonance and kinetic data, but they provide a unique insight into fibritin foldon assembly. In particular, our simulations unveil the role of nonspecific interactions and suggest that an interplay between thermodynamic bias toward native structure and residual conformational disorder may provide a kinetic advantage. PMID:24248370

  14. Oligomerization and toxicity of A{beta} fusion proteins

    Energy Technology Data Exchange (ETDEWEB)

    Caine, Joanne M., E-mail: Jo.Caine@csiro.au [CSIRO Materials Science and Engineering and the Preventive Health Flagship, Parkville, Victoria (Australia); Bharadwaj, Prashant R. [CSIRO Materials Science and Engineering and the Preventive Health Flagship, Parkville, Victoria (Australia); Centre for Excellence for Alzheimer' s Disease Research and Care, School of Exercise, Biomedical and Health Sciences, Edith Cowan University, Western Australia (Australia); Sankovich, Sonia E. [CSIRO Materials Science and Engineering and the Preventive Health Flagship, Parkville, Victoria (Australia); Ciccotosto, Giuseppe D. [The Department of Pathology and Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Victoria 3010 (Australia); Streltsov, Victor A.; Varghese, Jose [CSIRO Materials Science and Engineering and the Preventive Health Flagship, Parkville, Victoria (Australia)

    2011-06-10

    Highlights: {yields} We expressed amyloid-{beta} (A{beta}) peptide as a soluble maltose binding protein fusion (MBP-A{beta}42 and MBP-A{beta}16). {yields} The full length A{beta} peptide fusion, MBP-A{beta}42, forms oligomeric species as determined by SDS-PAGE gels, gel filtration and DLS. {yields} The MBP-A{beta}42, but not MBP-A{beta}16 or MBP alone, is toxic to both yeast and mammalian cells as determined by toxicity assays. -- Abstract: This study has found that the Maltose binding protein A{beta}42 fusion protein (MBP-A{beta}42) forms soluble oligomers while the shorter MBP-A{beta}16 fusion and control MBP did not. MBP-A{beta}42, but neither MBP-A{beta}16 nor control MBP, was toxic in a dose-dependent manner in both yeast and primary cortical neuronal cells. This study demonstrates the potential utility of MBP-A{beta}42 as a reagent for drug screening assays in yeast and neuronal cell cultures and as a candidate for further A{beta}42 characterization.

  15. Oligomerization of mouse alpha 1-syntrophin and self-association of its pleckstrin homology domain 1 containing sequences.

    Science.gov (United States)

    Oak, S A; Jarrett, H W

    2000-08-01

    Syntrophins are known to self-associate to form oligomers. Mouse alpha 1-syntrophin sequences were produced as chimeric fusion proteins in bacteria and were found to also oligomerize and in a micromolar Ca(2+)-dependent manner. The oligomerization was localized to the N-terminal pleckstrin homology domain (PH1) or adjacent sequences; the second, C-terminal PH2 domain did not show oligomerization. PH1 was found to self-associate, and calmodulin or Ca(2+)-chelating agents such as ethylene glycol bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) could effectively prevent this oligomerization. A single calmodulin bound per syntrophin to cause inhibition of the precipitation. Since calmodulin inhibited syntrophin oligomerization in the presence or absence of Ca(2+), Ca(2+) binding to syntrophin is responsible for the inhibition by EGTA of syntrophin oligomerization.

  16. Bioactivity and properties of a dental adhesive functionalized with polyhedral oligomeric silsesquioxanes (POSS) and bioactive glass.

    Science.gov (United States)

    Rizk, Marta; Hohlfeld, Lisa; Thanh, Loan Tao; Biehl, Ralf; Lühmann, Nicole; Mohn, Dirk; Wiegand, Annette

    2017-09-01

    This study aimed to analyze the effect of infiltrating a commercial adhesive with nanosized bioactive glass (BG-Bi) particles or methacryl-functionalized polyhedral oligomeric silsesquioxanes (POSS) on material properties and bioactivity. An acetone-based dental adhesive (Solobond Plus adhesive, VOCO GmbH, Cuxhaven, Germany) was infiltrated with nanosized bioactive glass particles (0.1 or 1wt%), or with monofunctional or multifunctional POSS particles (10 or 20wt%). Unfilled adhesive served as control. Dispersion and hydrodynamic radius of the nanoparticles were studied by dynamic light scattering. Set specimens were immersed for 28days in artificial saliva at 37°C, and surfaces were mapped for the formation of calcium phospate (Ca/P) precipitates (scanning electron microscopy/energy-dispersive X-ray spectroscopy). Viscosity (rheometry) and the structural characteristic of the networks were studied, such as degree of conversion (FTIR spectroscopy), sol fraction and water sorption. POSS particles showed a good dispersion of the particles for both types of particles being smaller than 3nm, while the bioactive glass particles had a strong tendency to agglomerate. All nanoparticles induced the formation of Ca/P precipitates. The viscosity of the adhesive was not or only slightly increased by POSS particle addition but strongly increased by the bioactive glass particles. The degree of conversion, water sorption and sol fraction showed a maintained or improved network structure and properties when filled with BG-Bi and multifunctional POSS, however, less polymerization was found when loading a monofunctional POSS. Multifunctional POSS may be incorporated into dental adhesives to provide a bioactive potential without changing material properties adversely. Copyright © 2017 The Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

  17. Oligomerization of optically active N-(4-hydroxyphenylmandelamide in the presence of β-cyclodextrin and the minor role of chirality

    Directory of Open Access Journals (Sweden)

    Helmut Ritter

    2014-10-01

    Full Text Available The oxidative oligomerization of a chiral mandelamide derivative (N-(4-hydroxyphenylmandelamide, 1 was performed in the presence of horseradish peroxidase, laccase and N,N'-bis(salicylideneethylenediamine-iron(II to obtain chiral oligophenols 2. The low enantioselectivity of the enzymatic catalyzed asymmetric enantiomer-differentiating oligomerizations was investigated. In addition, the poor influence of cyclodextrin on the enantioselectivity of enzymatic catalyzed asymmetric enantiomer-differentiating oligomerizations was studied.

  18. Hydrogen/Deuterium Exchange Mass Spectrometry Reveals Mechanistic Details of Activation of Nucleoside Diphosphate Kinases by Oligomerization

    OpenAIRE

    Dautant , Alain; Meyer , Philippe; Georgescauld , Florian

    2017-01-01

    International audience; Most oligomeric proteins become active only after assembly, but why oligomerization is required to support function is not well understood. Here, we address this question using the WT and a destabilized mutant (D93N) of the hexameric nucleoside diphosphate kinase from the pathogen Mycobacterium tuberculosis (Mt-NDPK). The conformational dynamics and oligomeric states of each were analyzed during unfolding/folding by Hydrogen/Deuterium exchange mass spectrometry (HDX-MS...

  19. Oligomeric epoxide–amine adducts based on 2-amino-N-isopropylacetamide and α-amino-ε-caprolactam: Solubility in presence of cyclodextrin and curing properties

    Science.gov (United States)

    Fischer, Julian

    2013-01-01

    Summary 2-Amino-N-isopropylacetamide and α-amino-ε-caprolactam were reacted with glycerol diglycidyl ether to give novel oligomeric thermoresponsive epoxide–amine adducts. These oligomers exhibit a lower critical solution temperature (LCST) behavior in water. The solubility properties were influenced with randomly methylated β-cyclodextrin (RAMEB-CD) and the curing properties of the amine–epoxide mixtures were analyzed by oscillatory rheology and differential scanning calorimetry, whereby significant differences in setting time, viscosity, and stiffness were observed. PMID:24367444

  20. Oligomeric epoxide–amine adducts based on 2-amino-N-isopropylacetamide and α-amino-ε-caprolactam: Solubility in presence of cyclodextrin and curing properties

    Directory of Open Access Journals (Sweden)

    Julian Fischer

    2013-12-01

    Full Text Available 2-Amino-N-isopropylacetamide and α-amino-ε-caprolactam were reacted with glycerol diglycidyl ether to give novel oligomeric thermoresponsive epoxide–amine adducts. These oligomers exhibit a lower critical solution temperature (LCST behavior in water. The solubility properties were influenced with randomly methylated β-cyclodextrin (RAMEB-CD and the curing properties of the amine–epoxide mixtures were analyzed by oscillatory rheology and differential scanning calorimetry, whereby significant differences in setting time, viscosity, and stiffness were observed.

  1. Morphology and Phase Transitions in Styrene-Butadiene-Styrene Triblock Copolymer Grafted with Isobutyl Substituted Polyhedral Oligomeric Silsesquioxanes (Postprint)

    National Research Council Canada - National Science Library

    Drazowski, Daniel B; Lee, Andre; Haddad, Timothy S

    2007-01-01

    Two symmetric triblock polystyrene-butadiene-polystyrene (SBS) copolymers with different styrene content were grafted with varying amounts of isobutyl-substituted polyhedral oligomeric silsesquioxane (POSS) molecules...

  2. Morphology and Phase Transitions in Styrene-Butadiene-Styrene Triblock Copolymer Grafted with Isobutyl Substituted Polyhedral Oligomeric Silsesquioxanes (preprint)

    National Research Council Canada - National Science Library

    Drazkowski, Daniel B; Lee, Andre; Haddad, Timothy S

    2006-01-01

    Two symmetric triblock polystyrene-butadiene-polystyrene (SBS) copolymers with different styrene content were grafted with varying amounts of isobutyl-substituted polyhedral oligomeric silsesquioxane (POSS) molecules...

  3. Mixed-potential Behavior of Nanostructured RuO2 Sensing Electrode of Water Quality Sensors in Strong Alkaline Solutions at a Temperature Range of 9-30° C

    Science.gov (United States)

    Zhuiykov, Serge

    2009-05-01

    Mixed-potential behavior of the water quality monitoring sensors using nanostructured RuO2 sensing electrode (SE) has been observed in strong alkaline solutions at dissolved oxygen (DO) measurements in the temperature range of 9-30° C. This behavior indicated that a Faradaic oxygen reduction reaction becomes not only a one-electron process, which is typical for DO measurements at a neutral pH, but rather multi-step process with superoxide oxygen ions (O2-), OH- and RuO42- ions involvement. The DO sensing characteristics were examined in the pH range of 2.0-13.0. The measured emf at strong alkaline solutions is a mixed potential from the reactions involved RuO42- and OH- ions and DO. Impedance spectroscopy was employed for confirmation the mixed-potential behavior of the sensor. It was also found during experiments that OH- ions influence the response/recovery rate of the SE reactions as the pH of water increases.

  4. Membrane-Mediated Oligomerization of G Protein Coupled Receptors and Its Implications for GPCR Function.

    Science.gov (United States)

    Gahbauer, Stefan; Böckmann, Rainer A

    2016-01-01

    The dimerization or even oligomerization of G protein coupled receptors (GPCRs) causes ongoing, controversial debates about its functional role and the coupled biophysical, biochemical or biomedical implications. A continously growing number of studies hints to a relation between oligomerization and function of GPCRs and strengthens the assumption that receptor assembly plays a key role in the regulation of protein function. Additionally, progress in the structural analysis of GPCR-G protein and GPCR-ligand interactions allows to distinguish between actively functional and non-signaling complexes. Recent findings further suggest that the surrounding membrane, i.e., its lipid composition may modulate the preferred dimerization interface and as a result the abundance of distinct dimeric conformations. In this review, the association of GPCRs and the role of the membrane in oligomerization will be discussed. An overview of the different reported oligomeric interfaces is provided and their capability for signaling discussed. The currently available data is summarized with regard to the formation of GPCR oligomers, their structures and dependency on the membrane microenvironment as well as the coupling of oligomerization to receptor function.

  5. Oligomerization of Baculovirus LEF-11 Is Involved in Viral DNA Replication.

    Science.gov (United States)

    Dong, Zhan-Qi; Hu, Nan; Zhang, Jun; Chen, Ting-Ting; Cao, Ming-Ya; Li, Hai-Qing; Lei, Xue-Jiao; Chen, Peng; Lu, Cheng; Pan, Min-Hui

    2015-01-01

    We have previously reported that baculovirus Bombyx mori nucleopolyhedrovirus (BmNPV) late expression factor 11 (lef-11) is associated with viral DNA replication and have demonstrated that it potentially interacts with itself; however, whether LEF-11 forms oligomers and the impact of LEF-11 oligomerization on viral function have not been substantiated. In this study, we first demonstrated that LEF-11 is capable of forming oligomers. Additionally, a series of analyses using BmNPV LEF-11 truncation mutants indicated that two distinct domains control LEF-11 oligomerization (aa 42-61 and aa 72-101). LEF-11 truncation constructs were inserted into a lef-11-knockout BmNPV bacmid, which was used to demonstrate that truncated LEF-11 lacking either oligomerization domain abrogates viral DNA replication. Finally, site-directed mutagenesis was used to determine that the conserved hydrophobic residues Y58&I59 (representing Y58 and I59), I85 and L88&L89 (representing L88 and L89) are required for LEF-11 oligomerization and viral DNA replication. Collectively, these data indicate that BmNPV LEF-11 oligomerization influences viral DNA replication.

  6. Strongly correlated systems experimental techniques

    CERN Document Server

    Mancini, Ferdinando

    2015-01-01

    The continuous evolution and development of experimental techniques is at the basis of any fundamental achievement in modern physics. Strongly correlated systems (SCS), more than any other, need to be investigated through the greatest variety of experimental techniques in order to unveil and crosscheck the numerous and puzzling anomalous behaviors characterizing them. The study of SCS fostered the improvement of many old experimental techniques, but also the advent of many new ones just invented in order to analyze the complex behaviors of these systems. Many novel materials, with functional properties emerging from macroscopic quantum behaviors at the frontier of modern research in physics, chemistry and materials science, belong to this class of systems. The volume presents a representative collection of the modern experimental techniques specifically tailored for the analysis of strongly correlated systems. Any technique is presented in great detail by its own inventor or by one of the world-wide recognize...

  7. Cartilage oligomeric matrix protein enhances matrix assembly during chondrogenesis of human mesenchymal stem cells.

    Science.gov (United States)

    Haleem-Smith, Hana; Calderon, Raul; Song, Yingjie; Tuan, Rocky S; Chen, Faye H

    2012-04-01

    Cartilage oligomeric matrix protein/thrombospondin-5 (COMP/TSP5) is an abundant cartilage extracellular matrix (ECM) protein that interacts with major cartilage ECM components, including aggrecan and collagens. To test our hypothesis that COMP/TSP5 functions in the assembly of the ECM during cartilage morphogenesis, we have employed mesenchymal stem cell (MSC) chondrogenesis in vitro as a model to examine the effects of COMP over-expression on neo-cartilage formation. Human bone marrow-derived MSCs were transfected with either full-length COMP cDNA or control plasmid, followed by chondrogenic induction in three-dimensional pellet or alginate hydrogel culture. MSC chondrogenesis and ECM production was estimated based on quantitation of sulfated glycosaminoglycan (sGAG) accumulation, immunohistochemistry of the presence and distribution of cartilage ECM proteins, and real-time RT-PCR analyis of mRNA expression of cartilage markers. Our results showed that COMP over-expression resulted in increased total sGAG content during the early phase of MSC chondrogenesis, and increased immuno-detectable levels of aggrecan and collagen type II in the ECM of COMP-transfected pellet and alginate cultures, indicating more abundant cartilaginous matrix. COMP transfection did not significantly increase the transcript levels of the early chondrogenic marker, Sox9, or aggrecan, suggesting that enhancement of MSC cartilage ECM was effected at post-transcriptional levels. These findings strongly suggest that COMP functions in mesenchymal chondrogenesis by enhancing cartilage ECM organization and assembly. The action of COMP is most likely mediated not via direct changes in cartilage matrix gene expression but via interactions of COMP with other cartilage ECM proteins, such as aggrecan and collagens, that result in enhanced assembly and retention.

  8. Marginal integrity of restorations produced with a model composite based on polyhedral oligomeric silsesquioxane (POSS

    Directory of Open Access Journals (Sweden)

    Luciano Ribeiro CORREA NETTO

    2015-10-01

    Full Text Available Marginal integrity is one of the most crucial aspects involved in the clinical longevity of resin composite restorations.Objective To analyze the marginal integrity of restorations produced with a model composite based on polyhedral oligomeric silsesquioxane (POSS.Material and Methods A base composite (B was produced with an organic matrix with UDMA/TEGDMA and 70 wt.% of barium borosilicate glass particles. To produce the model composite, 25 wt.% of UDMA were replaced by POSS (P25. The composites P90 and TPH3 (TP3 were used as positive and negative controls, respectively. Marginal integrity (%MI was analyzed in bonded class I cavities. The volumetric polymerization shrinkage (%VS and the polymerization shrinkage stress (Pss - MPa were also evaluated.Results The values for %MI were as follows: P90 (100% = TP3 (98.3% = B (96.9% > P25 (93.2%, (p<0.05. The %VS ranged from 1.4% (P90 to 4.9% (P25, while Pss ranged from 2.3 MPa (P90 to 3.9 MPa (B. For both properties, the composite P25 presented the worst results (4.9% and 3.6 MPa. Linear regression analysis showed a strong positive correlation between %VS and Pss (r=0.97, whereas the correlation between Pss and %MI was found to be moderate (r=0.76.Conclusions The addition of 25 wt.% of POSS in methacrylate organic matrix did not improve the marginal integrity of class I restorations. Filtek P90 showed lower polymerization shrinkage and shrinkage stress when compared to the experimental and commercial methacrylate composite.

  9. Reversibility and two state behaviour in the thermal unfolding of oligomeric TIM barrel proteins.

    Science.gov (United States)

    Romero-Romero, Sergio; Costas, Miguel; Rodríguez-Romero, Adela; Alejandro Fernández-Velasco, D

    2015-08-28

    Temperature is one of the main variables that modulate protein function and stability. Thermodynamic studies of oligomeric proteins, the dominant protein natural form, have been often hampered because irreversible aggregation and/or slow reactions are common. There are no reports on the reversible equilibrium thermal unfolding of proteins composed of (β/α)8 barrel subunits, albeit this "TIM barrel" topology is one of the most abundant and versatile in nature. We studied the eponymous TIM barrel, triosephosphate isomerase (TIM), belonging to five species of different bacterial taxa. All of them were found to be catalytically efficient dimers. The three-dimensional structure of four enzymes was solved at high/medium resolution. Irreversibility and kinetic control were observed in the thermal unfolding of two TIMs, while for the other three the thermal unfolding was found to follow a two-state equilibrium reversible process. Shifts in the global stability curves of these three proteins are related to the organismal temperature range of optimal growth and modulated by variations in maximum stability temperature and in the enthalpy change at that temperature. Reversibility appears to correlate with the low isoelectric point, the absence of a residual structure in the unfolded state, small cavity volume in the native state, low conformational stability and a low melting temperature. Furthermore, the strong coupling between dimer dissociation and monomer unfolding may reduce aggregation and favour reversibility. It is therefore very thought-provoking to find that a common topological ensemble, such as the TIM barrel, can unfold/refold in the Anfinsen way, i.e. without the help of the cellular machinery.

  10. Zn(2+) site engineering at the oligomeric interface of the dopamine transporter

    DEFF Research Database (Denmark)

    Norgaard-Nielsen, Kristine; Norregaard, Lene; Hastrup, Hanne

    2002-01-01

    Increasing evidence suggests that Na(+)/Cl(-)-dependent neurotransmitter transporters exist as homo-oligomeric proteins. However, the functional implication of this oligomerization remains unclear. Here we demonstrate the engineering of a Zn(2+) binding site at the predicted dimeric interface...... of the dopamine transporter (DAT) corresponding to the external end of transmembrane segment 6. Upon binding to this site, which involves a histidine inserted in position 310 (V310H) and the endogenous Cys306 within the same DAT molecule, Zn(2+) potently inhibits [(3)H]dopamine uptake. These data provide indirect...... evidence that conformational changes critical for the translocation process may occur at the interface between two transporter molecules in the oligomeric structure....

  11. N-(1-Pyrenyl Maleimide Induces Bak Oligomerization and Mitochondrial Dysfunction in Jurkat Cells

    Directory of Open Access Journals (Sweden)

    Pei-Rong Huang

    2015-01-01

    Full Text Available N-(1-pyrenyl maleimide (NPM is a fluorescent reagent that is frequently used as a derivatization agent for the detection of thio-containing compounds. NPM has been shown to display a great differential cytotoxicity against hematopoietic cancer cells. In this study, the molecular mechanism by which NPM induces apoptosis was examined. Here, we show that treatment of Jurkat cells with NPM leads to Bak oligomerization, loss of mitochondrial membrane potential (Δψm, and release of cytochrome C from mitochondria to cytosol. Induction of Bak oligomerization appears to play a critical role in NPM-induced apoptosis, as downregulation of Bak by shRNA significantly prevented NPM-induced apoptosis. Inhibition of caspase 8 by Z-IETD-FMK and/or depletion of Bid did not affect NPM-induced oligomerization of Bak. Taken together, these results suggest that NPM-induced apoptosis is mediated through a pathway that is independent of caspase-8 activation.

  12. Zn(2+) site engineering at the oligomeric interface of the dopamine transporter.

    Science.gov (United States)

    Norgaard-Nielsen, Kristine; Norregaard, Lene; Hastrup, Hanne; Javitch, Jonathan A; Gether, Ulrik

    2002-07-31

    Increasing evidence suggests that Na(+)/Cl(-)-dependent neurotransmitter transporters exist as homo-oligomeric proteins. However, the functional implication of this oligomerization remains unclear. Here we demonstrate the engineering of a Zn(2+) binding site at the predicted dimeric interface of the dopamine transporter (DAT) corresponding to the external end of transmembrane segment 6. Upon binding to this site, which involves a histidine inserted in position 310 (V310H) and the endogenous Cys306 within the same DAT molecule, Zn(2+) potently inhibits [(3)H]dopamine uptake. These data provide indirect evidence that conformational changes critical for the translocation process may occur at the interface between two transporter molecules in the oligomeric structure.

  13. Catalyst-controlled oligomerization for the collective synthesis of polypyrroloindoline natural products

    Science.gov (United States)

    Jamison, Christopher R.; Badillo, Joseph J.; Lipshultz, Jeffrey M.; Comito, Robert J.; MacMillan, David W. C.

    2017-12-01

    In nature, many organisms generate large families of natural product metabolites that have related molecular structures as a means to increase functional diversity and gain an evolutionary advantage against competing systems within the same environment. One pathway commonly employed by living systems to generate these large classes of structurally related families is oligomerization, wherein a series of enzymatically catalysed reactions is employed to generate secondary metabolites by iteratively appending monomers to a growing serial oligomer chain. The polypyrroloindolines are an interesting class of oligomeric natural products that consist of multiple cyclotryptamine subunits. Herein we describe an iterative application of asymmetric copper catalysis towards the synthesis of six distinct oligomeric polypyrroloindoline natural products: hodgkinsine, hodgkinsine B, idiospermuline, quadrigemine H and isopsychotridine B and C. Given the customizable nature of the small-molecule catalysts employed, we demonstrate that this strategy is further amenable to the construction of quadrigemine H-type alkaloids not isolated previously from natural sources.

  14. Reactive bay functionalized perylene monoimide-polyhedral oligomeric silsesquioxane organic electronic dye

    Directory of Open Access Journals (Sweden)

    Wangatia Lodrick Makokha

    2015-03-01

    Full Text Available Aggregation-induced quenching is particularly detrimental in perylene diimides, which are characterized by a near-unity fluorescence quantum yield in solution but are far less emissive in the solid state. Previously, perylene diimide has been improved by linking it to the inorganic cage of polyhedral oligomeric silsesquioxanes. As a further study on perylene diimidepolyhedral oligomeric silsesquioxanes, we report on a double functionalized molecular structure, which can be used for substitution at the bay area and as a side group in other materials. Typical solution absorption and emission features of the perylene diimide fragment have been observed in this new reactive perylene diimide-polyhedral oligomeric silsesquioxane. Moreover, reduced stacking during aggregation and spherical particles exhibiting solid fluorescence have been obtained. Organic semiconducting material with enhanced solid state photophysical properties, like solid fluorescence is a subject of great interest owing to its possible high-tech applications in optoelectronic devices.

  15. Methyl methacrylate oligomerically-modified clay and its poly(methyl methacrylate) nanocomposites

    International Nuclear Information System (INIS)

    Zheng Xiaoxia; Jiang, David D.; Wilkie, Charles A.

    2005-01-01

    A methyl methacrylate oligomerically-modified clay was used to prepare poly(methyl methacrylate) clay nanocomposites by melt blending and the effect of the clay loading level on the modified clay and corresponding nanocomposite was studied. These nanocomposites were characterized by X-ray diffraction, transmission electron microscopy, thermogravimetric analysis and cone calorimetry. The results show a mixed intercalated/delaminated morphology with good nanodispersion. The compatibility between the methylacrylate-subsituted clay and poly(methyl methacrylate) (PMMA) are greatly improved compared to other oligomerically-modified clays

  16. Mechanistic Insights into Oxidative Oligomerization of p-Phenylenediamine and Resorcinol.

    Science.gov (United States)

    Bailey, Aaron D; Murphy, Bryan P; Guan, Hairong

    2016-11-03

    An efficient synthesis of a green dye from oxidative coupling of p-phenylenediamine (PPD) and resorcinol (in a 2:1 ratio) has been developed. Reactivity studies of this dye molecule with a variety of reagents (PPD, resorcinol, the oxidized form of the green dye itself, and a dinuclear indo dye) demonstrate that it cannot be the key reactive intermediate in reported oxidative oligomerization of PPD and resorcinol. However, the trinuclear species does form large aggregates. At least one viable pathway of oligomerization has been demonstrated with the dinuclear indo dye.

  17. Catalytic ethylene dimerization and oligomerization: recent developments with nickel complexes containing P,N-chelating ligands.

    Science.gov (United States)

    Speiser, Fredy; Braunstein, Pierre; Saussine, Lucien

    2005-10-01

    Catalytic ethylene oligomerization represents a topic of considerable current academic and industrial interest, in particular for the production of linear alpha-olefins in the C4-C10 range, whose demand is growing fast. Identifying and fine-tuning the parameters that influence the activity and selectivity of metal catalysts constitute major challenges at the interface between ligand design, coordination/organometallic chemistry, and homogeneous catalysis. In this Account, we show how comparative studies aiming at modulating the coordinating properties of functional ligands for a metal, such as nickel, which is used in industrial processes, lead to beneficial effects in catalytic ethylene oligomerization.

  18. Substituted tridentate pyrazolyl ligands for chromium and nickel-catalyzed ethylene oligomerization reactions: effect of auxiliary ligand on activity and selectivity

    International Nuclear Information System (INIS)

    Oliveira, Lucilene L. de; Campedelli, Roberta R.; Bergamo, Adao L.; Santos, Ana H.D.P dos; Casagrande, Osvaldo L.

    2010-01-01

    Two new chromium(III) complexes [CrCl 3 (L)] based on tridentate ligands (1a, L = bis[2-(3-phenyl-1-pyrazolyl)ethyl)]amine; 2a, L bis[2-(3-methyl-5-phenyl-l-pyrazolyl)ethyl]sulfide) have been prepared and characterized by elemental analysis. Upon activation with methylaluminoxane (MAO), these pre-catalysts showed high turnover frequencies for ethylene oligomerization under optimized conditions (TOFs = 22.9-36.4 x 103 mol C 2 H 4 (mol Cr III ) -1 h -1 , [Cr] = 10.0 μmol, 80 deg C, 20 bar ethylene, MAO: Cr = 300, oligomerization time = 20 min), producing alpha-olefins in the range C 4 -C 14+ with high selectively (67.71-73.47%). The catalytic performances are substantially affected by the ligand environment, especially the substituents at the 3- and 5-positions of the pyrazolyl rings. In parallel, the use of nickel complexes such as NiCl 2 {bis[2-(3,5-dimethyl-1-pyrazolyl)methyl]benzylamine} (3) and NiCl 2 {bis[2-(3,5-dimethyl-1-pyrazolyl)ethyl)]ether} (5) in oligomerization reactions carried out in the presence of triphenylphosphine (PPh 3 ) afforded highly active catalytic systems with turnover frequencies (TOFs) varying from 36.4 to 154.2 x 10 3 mol C 2 H 4 (mol Ni II ) -1 h -1 . The presence of this auxiliary ligand has a strong impact on the selectivity towards the production of a-olefins, decreasing substantially the amount of 1-butene with a concomitant increase of the 2-butene fractions. Attempts to crystallize the nickel complex 3 afforded the tetrametallic [{ (L)(μ 3 -Cl)NiCl} 4 ] (4, L 1-anilinomethyl-3,5-dimethylpyrazole) which was characterized by X-ray diffraction analysis. (author)

  19. <strong>Robert Aumannstrong>

    DEFF Research Database (Denmark)

    Hansen, Pelle Guldborg

    2007-01-01

    In this interview Nobel Prize Winner Robert Aumann talks about how he was initially drawn into game theory, when he came to think of formalizing the folk-theorem, the proper role of game theory in relation to other disciplines and why behavioral game theory probably won't last long.......In this interview Nobel Prize Winner Robert Aumann talks about how he was initially drawn into game theory, when he came to think of formalizing the folk-theorem, the proper role of game theory in relation to other disciplines and why behavioral game theory probably won't last long....

  20. Behaviorism

    Science.gov (United States)

    Moore, J.

    2011-01-01

    Early forms of psychology assumed that mental life was the appropriate subject matter for psychology, and introspection was an appropriate method to engage that subject matter. In 1913, John B. Watson proposed an alternative: classical S-R behaviorism. According to Watson, behavior was a subject matter in its own right, to be studied by the…

  1. Behavior

    NARCIS (Netherlands)

    Bouwman, L.I.

    2014-01-01

    Health behaviors are people’s actions, some purposefully deployed to promote or protect health; some thoughtlessly undertaken without concern for their potential risk to health; some consciously, even defiantly, deployed regardless of consequences to health. Risk behaviors are specific forms of

  2. Testing strong interaction theories

    International Nuclear Information System (INIS)

    Ellis, J.

    1979-01-01

    The author discusses possible tests of the current theories of the strong interaction, in particular, quantum chromodynamics. High energy e + e - interactions should provide an excellent means of studying the strong force. (W.D.L.)

  3. Cobalt Oxide on N-Doped Carbon for 1-Butene Oligomerization to Produce Linear Octenes

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Dongting [Department; Xu, Zhuoran [Department; Chada, Joseph P. [Department; Carrero, Carlos A. [Department; Rosenfeld, Devon C. [The Dow Chemical Company, 2301 N. Brazosport Boulevard, Freeport, Texas 77541-3257, United States; Rogers, Jessica L. [The Dow Chemical Company, 2301 N. Brazosport Boulevard, Freeport, Texas 77541-3257, United States; Hermans, Ive [Department; Huber, George W. [Department

    2017-10-02

    Cobalt oxide supported on N-doped carbon catalysts were investigated for 1-butene oligomerization. The materials were synthesized by treating activated carbon with nitric acid and subsequently with NH3 at 200, 400, 600, and 800 °C, followed by impregnation with cobalt. The 1-butene oligomerization selectivity increased with ammonia treatment temperature of the carbon support. The oligomerization selectivity of cobalt oxide on N-doped carbon synthesized at 800 °C (800A-CoOx/N-C) is 2.6 times higher than previously reported cobalt oxide on N-doped carbon synthesized with NH4OH (2A-CoOx/N-C). Over 70% of the butene dimers were linear C8 olefins for all catalysts. The oligomerization selectivity increased with 1-butene conversion. The catalysts were characterized by elemental analysis, N2 adsorption, X-ray diffraction (XRD), X-ray absorption spectroscopy (XAS), and X-ray photoelectron spectroscopy (XPS). The nitrogen content of the catalysts increases with ammonia treatment temperature as confirmed by elemental analysis. The surface content of pyridinic nitrogen with a binding energy of 398.4 ± 0.1 eV increased with ammonia treatment temperature as evidenced by deconvolution of N 1s XPS spectra.

  4. Influence of oligomeric resins on traction and rolling resistance of silica tire treads

    NARCIS (Netherlands)

    Vleugels, N.; Pille-Wolf, W.; Dierkes, Wilma K.; Noordermeer, Jacobus W.M.

    2016-01-01

    This study concerns the silica-reinforcement of synthetic rubber compounds for passenger tire treads with the objective to gain insight into the beneficial effects of oligomeric resins, derived from natural and synthetic monomers, on the major tire performance factors: rolling resistance and (wet)

  5. Influence of oligomeric resins on traction and rolling resistance of silica tire treads

    NARCIS (Netherlands)

    Vleugels, N.; Pille-Wolf, W.; Dierkes, Wilma K.; Noordermeer, Jacobus W.M.

    2013-01-01

    This study concerns the silica-reinforcement of synthetic rubber compounds for passenger tire treads with the objective to gain insight into the beneficial effects of oligomeric resins, derived from natural and synthetic monomers, on the major tire performance factors: Rolling Resistance and (Wet)

  6. Understanding the Influence of oligomeric resins on traction and rolling resistance of silica tire treads

    NARCIS (Netherlands)

    Vleugels, N.; Pille-Wolf, W.; Dierkes, Wilma K.; Noordermeer, Jacobus W.M.

    2015-01-01

    This study concerns the silica reinforcement of styrene–butadiene rubber compounds for passenger car tire treads, with the objective of gaining greater insight into the beneficial effects of oligomeric resins. The major tire performance factors predicted are rolling resistance and (wet) skid

  7. Styrene oligomerization as a molecular probe reaction for Brønsted acidity at the nanoscale

    NARCIS (Netherlands)

    Aramburo Corrales, Luis; Wirick, Sue; Miedema, P.S.; Buurmans, I.L.C.; de Groot, F.M.F.; Weckhuysen, B.M.

    2012-01-01

    The Brønsted acid-catalyzed oligomerization of 4-fluorostyrene has been studied on a series ofH-ZSM-5 zeolite powders, steamed under different conditions, with a combination of UV-Vismicro-spectroscopy and Scanning Transmission X-ray Microscopy (STXM). UV-Vis microspectroscopyand STXM have been used

  8. Oligomerization of a Glucagon-like Peptide 1 Analog: Bridging Experiment and Simulations

    DEFF Research Database (Denmark)

    Frederiksen, Tine Maja; Sønderby, Pernille; Ryberg, Line A.

    2015-01-01

    The glucagon-like peptide 1 (GLP-1) analog, liraglutide, is a GLP-1 agonist and is used in the treatment of type-2 diabetes mellitus and obesity. From a pharmaceutical perspective, it is important to know the oligomerization state of liraglutide with respect to stability. Compared to GLP-1...

  9. Mechanics of the mannitol transporter from Escherichia coli : substrate-probing and oligomeric structure

    NARCIS (Netherlands)

    Veldhuis, Gertjan

    2006-01-01

    Gertjan Veldhuis bestudeerde de mannitoltransporter van Escherichia coli, EnzymeIImtl (EIImtl), om meer inzicht te krijgen in het bindingsmechanisme en de oligomere toestand van dit membraaneiwit. Hij concludeerde onder andere dat dimeer EIImtl één mannitol bindt, de dimeer zeer stabiel is en dat

  10. Development and validation of a yeast high-throughput screen for inhibitors of Aβ42 oligomerization

    Directory of Open Access Journals (Sweden)

    Sei-Kyoung Park

    2011-11-01

    Recent reports point to small soluble oligomers, rather than insoluble fibrils, of amyloid β (Aβ, as the primary toxic species in Alzheimer’s disease. Previously, we developed a low-throughput assay in yeast that is capable of detecting small Aβ42 oligomer formation. Specifically, Aβ42 fused to the functional release factor domain of yeast translational termination factor, Sup35p, formed sodium dodecyl sulfate (SDS-stable low-n oligomers in living yeast, which impaired release factor activity. As a result, the assay for oligomer formation uses yeast growth to indicate restored release factor activity and presumably reduced oligomer formation. We now describe our translation of this assay into a high-throughput screen (HTS for anti-oligomeric compounds. By doing so, we also identified two presumptive anti-oligomeric compounds from a sub-library of 12,800 drug-like small molecules. Subsequent biochemical analysis confirmed their anti-oligomeric activity, suggesting that this form of HTS is an efficient, sensitive and cost-effective approach to identify new inhibitors of Aβ42 oligomerization.

  11. Implications of lipid moiety in oligomerization and immunoreactivities of GPI-anchored proteins

    Science.gov (United States)

    Seong, Jihyoun; Wang, Yetao; Kinoshita, Taroh; Maeda, Yusuke

    2013-01-01

    Glycosylphosphatidylinositol (GPI) enriches GPI-anchored proteins (GPI-AP) in lipid rafts by intimate interaction of its lipid moiety with sphingolipids and cholesterol. In addition to such lipid-lipid interactions, it has been reported that GPI may interact with protein moiety linked to GPI and affect protein conformations because GPI delipidation reduced immunoreactivities of protein. Here, we report that GPI-APs that have not undergone fatty acid remodeling exhibit reduced immunoreactivities in Western blotting, similar to delipidated proteins, compared with normal remodeled GPI-APs. In contrast, immunostaining in flow cytometry and immunoprecipitation did not show significant differences between remodeled and unremodeled GPI-APs. Moreover, detection with premixed primary/secondary antibody complexes or Fab fragments eliminated this difference in Western blotting. These results indicate that normally remodeled GPI enhanced oligomerization of GPI-APs and that inefficient oligomerization of unremodeled GPI-APs was responsible for reduced immunoreactivities. Moreover, the reduction in immunoreactivities of delipidated GPI-APs was most likely caused by the same effect. Finally, by chemical cross-linking of surface proteins in living cells and cell killing assay using a pore-forming bacterial toxin, we showed that enhanced oligomerization by GPI-remodeling occurs under a physiological membrane environment. Thus, this study clarifies the significance of GPI fatty acid remodeling in oligomerization of GPI-APs and provides useful information for technical studies of these cell components. PMID:23378600

  12. Antitumor-promoting activity of oligomeric proanthocyanidins in mouse epidermis in vivo

    Science.gov (United States)

    Mei Xiao Gao; Elisabeth M. Perchellet; Hala U. Gali; Limarie Rodriguez; Richard W. Hemingway; Jean-Pierre Perchellet

    1994-01-01

    The flavanoid catechin and heterogenous samples of oligomeric proanthocyanidins extracted from various sources were compared for their ability to inhibit the biochemical and biological effects of 12-o-tertra-decanoylphorbol-13-acetate (TPA) in mouse epidermis in vivo. Topical applications of catechin fail to alter the hydroperoxide response to TPA but inhibit the...

  13. Selective Antimicrobial Activities and Action Mechanism of Micelles Self-Assembled by Cationic Oligomeric Surfactants.

    Science.gov (United States)

    Zhou, Chengcheng; Wang, Fengyan; Chen, Hui; Li, Meng; Qiao, Fulin; Liu, Zhang; Hou, Yanbo; Wu, Chunxian; Fan, Yaxun; Liu, Libing; Wang, Shu; Wang, Yilin

    2016-02-17

    This work reports that cationic micelles formed by cationic trimeric, tetrameric, and hexameric surfactants bearing amide moieties in spacers can efficiently kill Gram-negative E. coli with a very low minimum inhibitory concentration (1.70-0.93 μM), and do not cause obvious toxicity to mammalian cells at the concentrations used. With the increase of the oligomerization degree, the antibacterial activity of the oligomeric surfactants increases, i.e., hexameric surfactant > tetrameric surfactant > trimeric surfactant. Isothermal titration microcalorimetry, scanning electron microscopy, and zeta potential results reveal that the cationic micelles interact with the cell membrane of E. coli through two processes. First, the integrity of outer membrane of E. coli is disrupted by the electrostatic interaction of the cationic ammonium groups of the surfactants with anionic groups of E. coli, resulting in loss of the barrier function of the outer membrane. The inner membrane then is disintegrated by the hydrophobic interaction of the surfactant hydrocarbon chains with the hydrophobic domains of the inner membrane, leading to the cytoplast leakage. The formation of micelles of these cationic oligomeric surfactants at very low concentration enables more efficient interaction with bacterial cell membrane, which endows the oligomeric surfactants with high antibacterial activity.

  14. Concentration Dependent Ion-Protein Interaction Patterns Underlying Protein Oligomerization Behaviours

    Science.gov (United States)

    Batoulis, Helena; Schmidt, Thomas H.; Weber, Pascal; Schloetel, Jan-Gero; Kandt, Christian; Lang, Thorsten

    2016-04-01

    Salts and proteins comprise two of the basic molecular components of biological materials. Kosmotropic/chaotropic co-solvation and matching ion water affinities explain basic ionic effects on protein aggregation observed in simple solutions. However, it is unclear how these theories apply to proteins in complex biological environments and what the underlying ionic binding patterns are. Using the positive ion Ca2+ and the negatively charged membrane protein SNAP25, we studied ion effects on protein oligomerization in solution, in native membranes and in molecular dynamics (MD) simulations. We find that concentration-dependent ion-induced protein oligomerization is a fundamental chemico-physical principle applying not only to soluble but also to membrane-anchored proteins in their native environment. Oligomerization is driven by the interaction of Ca2+ ions with the carboxylate groups of aspartate and glutamate. From low up to middle concentrations, salt bridges between Ca2+ ions and two or more protein residues lead to increasingly larger oligomers, while at high concentrations oligomers disperse due to overcharging effects. The insights provide a conceptual framework at the interface of physics, chemistry and biology to explain binding of ions to charged protein surfaces on an atomistic scale, as occurring during protein solubilisation, aggregation and oligomerization both in simple solutions and membrane systems.

  15. A structurally characterized Ni-Al methyl-bridged complex with catalytic ethylene oligomerization activity.

    Science.gov (United States)

    Weng, Zhiqiang; Teo, Shihui; Koh, Lip Lin; Hor, T S Andy

    2006-03-28

    A bimetallic Ni-Al (2.5087(15) A) complex with an agostic alpha-C-H, [eta-C5H4CH=N(C6F5)]Fe[eta-C5H4PPh2]Ni(AlMe3), has been isolated and crystallographically established. The complex is active towards ethylene oligomerization/polymerization under moderate conditions.

  16. Early-transition-metal catalysts with phenoxy-imine-type ligands for the oligomerization of ethylene.

    Science.gov (United States)

    Kinoshita, Shinsuke; Kawamura, Kazumori; Fujita, Terunori

    2011-02-01

    Early-transition-metal complexes incorporating phenoxy-imine-type bidentate and tridentate ligands, after activation, can achieve selective as well as nonselective ethylene oligomerization to produce 1-hexene, linear α-olefins, and vinyl-terminated low-molecular-weight polyethylenes, all with high efficiency. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Understanding the role of aluminum-based activators in single site iron catalysts for ethylene oligomerization.

    OpenAIRE

    Boudene , Zoubeyr; Boudier , Adrien; Breuil , Pierre-Alain; Olivier-Bourbigou , Hélène; Raybaud , Pascal; Toulhoat , Hervé; De Bruin , Theodorus

    2014-01-01

    International audience; In a combined experimental and theoretical study, the activation process of a single site ethylene oligomerization catalyst with aluminum-based activators has been studied. The results put forward a plausible deactivation reaction path of the catalyst for trimethylaluminum, while for methylaluminoxane and a novel phenoxyaluminum-based activator, the experimental catalyst's activity correlates with the energy barrier for the ethylene insertion.

  18. Cobalt and Nickel Complexes Bearing 2-(2-pyridyl-Benzimidazole: Synthesis and Ethylene Oligomerization

    Directory of Open Access Journals (Sweden)

    Jian-Long Du

    2005-01-01

    Full Text Available A series of cobalt and nickel complexes MLX2 (M=Co or Ni, X=Cl bearing 2-(2-pyridylbenzimidazole ligands were synthesized. Treatment of the complexes with methylaluminoxane (MAO leads to active catalysts for ethylene oligomerization. The oligomers were olefins from C2 to C6.

  19. Cobalt and Nickel Complexes Bearing 2-(2-pyridyl)-Benzimidazole: Synthesis and Ethylene Oligomerization

    OpenAIRE

    Du, Jian-Long; Li-Jun-Li

    2005-01-01

    A series of cobalt and nickel complexes MLX2 (M=Co or Ni, X=Cl) bearing 2-(2-pyridyl)benzimidazole ligands were synthesized. Treatment of the complexes with methylaluminoxane (MAO) leads to active catalysts for ethylene oligomerization. The oligomers were olefins from C2 to C6.

  20. Oligomeric state of membrane transport proteins analyzed with blue native electrophoresis and analytical ultracentrifugation

    NARCIS (Netherlands)

    Heuberger, E.H M L; Veenhoff, L.M.; Duurkens, R.H.T.; Friesen, R.H.E.; Poolman, B.

    2002-01-01

    Blue native electrophoresis is used widely for the analysis of non-dissociated protein complexes with respect to composition, oligomeric state and molecular mass. However, the effects of detergent or dye binding on the mass and stability of the integral membrane proteins have not been studied. By

  1. Dispersion states and surface characteristics of physically blended polyhedral oligomeric silsesquioxane/polymer hybrid nanocomposites

    Science.gov (United States)

    Misra, Rahul

    Control of dispersion and segregation states of nanostructured additives is one of the biggest challenges in realizing the optimum potential of high performance hybrid polymer nanocomposites. Polyhedral oligomeric silsesquioxane (POSS) nanostructured chemicals, with their hybrid organic-inorganic nature and flexible functionalization with a variety of organic substituents, yield possibilities to control dispersion and tune compatibility in a wide range of polymer systems. The overall goal of this research is to investigate the fundamental parameters that influence the dispersion and segregation states of POSS nanostructured chemicals, and to understand chain dynamics and conformations in physically blended POSS hybrid polymer nanocomposites (HPNC's). Multiple structural and mechanical factors influencing macro to nano scale surface and bulk properties were successfully investigated and correlated. A strategy based on thermodynamic principles for selective control of POSS dispersion states in a given polymer matrix is developed and discussed. This dissertation consists of eight chapters. Chapter 1 provides a detailed introduction about the development and current research interest in POSS/polymer nanocomposites. This chapter also discusses limitations of current advanced nanoprobe techniques. Chapter 2 establishes the overall goal of this research and specific research ii objectives. Chapter 3 establishes the preferential surface migration behavior of physically dispersed, non-reactive, closed cage octaisobutyl POSS (Oib-POSS) in a non-polar polypropylene matrix. Furthermore, influence of POSS surface segregation on the surface properties, especially nano-tribomechanical behavior is also discussed. Chapter 4 expands the studies by melt blending two different types of POSS molecules, a non-reactive, closed cage Oib-POSS and an open cage trisilanolphenyl POSS (Tsp-POSS), in a nylon 6 matrix. This chapter discusses the morphology, nano-dispersion and macro- to

  2. Development of Biodegradable Poly(citrate)-Polyhedral Oligomeric Silsesquioxanes Hybrid Elastomers with High Mechanical Properties and Osteogenic Differentiation Activity.

    Science.gov (United States)

    Du, Yuzhang; Yu, Meng; Chen, Xiaofeng; Ma, Peter X; Lei, Bo

    2016-02-10

    Biodegradable elastomeric biomaterials have attracted much attention in tissue engineering due to their biomimetic viscoelastic behavior and biocompatibility. However, the low mechanical stability at hydrated state, fast biodegradation in vivo, and poor osteogenic activity greatly limited bioelastomers applications in bone tissue regeneration. Herein, we develop a series of poly(octanediol citrate)-polyhedral oligomeric silsesquioxanes (POC-POSS) hybrids with highly tunable elastomeric behavior (hydrated state) and biodegradation and osteoblasts biocompatibility through a facile one-pot thermal polymerization strategy. POC-POSS hybrids show significantly improved stiffness and ductility in either dry or hydrated conditions, as well as good antibiodegradation ability (20-50% weight loss in 3 months). POC-POSS hybrids exhibit significantly enhanced osteogenic differentiation through upregulating alkaline phosphatase (ALP) activity, calcium deposition, and expression of osteogenic markers (ALPL, BGLAP, and Runx2). The high mechanical stability at hydrated state and enhanced osteogenic activity make POC-POSS hybrid elastomers promising as scaffolds and nanoscale vehicles for bone tissue regeneration and drug delivery. This study may also provide a new strategy (controlling the stiffness under hydrated condition) to design advanced hybrid biomaterials with high mechanical properties under physiological condition for tissue regeneration applications.

  3. DOPAL is transmissible to and oligomerizes alpha-synuclein in human glial cells.

    Science.gov (United States)

    Jinsmaa, Yunden; Sullivan, Patricia; Sharabi, Yehonatan; Goldstein, David S

    2016-01-01

    Glial cytoplasmic inclusions (GCIs) containing alpha-synuclein (AS) are a neuropathologic hallmark of multiple system atrophy (MSA). Oligomerized AS is thought to be the pathogenic form of the protein. Glial cells normally express little AS, but they can take up AS from the extracellular fluid. 3,4-Dihydroxyphenylacetaldehyde (DOPAL), an obligate intermediate in the intra-neuronal metabolism of dopamine (DA), potently oligomerizes AS. In this study we tested whether DOPAL is taken up by human glial cells and augments intracellular oligomerization of AS. DOPAL (exogenous or endogenous from co-incubation with PC12 cells) and AS (native or A53T mutant form) were added to the incubation medium of glial cells (glioblastoma or MO3.13 oligodendrocytes). Glial cellular contents of DOPAL and its intracellular metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) were measured at up to 180 min of incubation. Glial cellular AS oligomers were quantified by Western blotting. Neither glioblastoma nor MO3.13 cells contained endogenous catecholamines or AS. Co-incubation of the cells with DA-producing PC12 cells produced time-related increases in DOPAL and DOPAC contents. Similarly, glial cellular DOPAL and DOPAC contents increased rapidly after addition of DOPAL to the medium. After addition of native or A53T-AS, intracellular AS also increased. Incubation of glial cells with both DOPAL and AS enhanced the intracellular oligomerization of native and A53T-AS. DOPAL is transmissible to glial cells and enhances intracellular oligomerization of AS. An interaction of DOPAL with AS might help explain the formation of CGIs in MSA. Published by Elsevier B.V.

  4. Discovery and Development of Pyridine-bis(imine) and Related Catalysts for Olefin Polymerization and Oligomerization.

    Science.gov (United States)

    Small, Brooke L

    2015-09-15

    For over 40 years following the polyolefin catalyst discoveries of Hogan and Banks (Phillips) and Ziegler (Max Planck Institute), chemists traversed the periodic table searching for new transition metal and lanthanide-based olefin polymerization systems. Remarkably, none of these "hits" employed iron, that is, until three groups independently reported iron catalysts for olefin polymerization in the late 1990's. The history surrounding the discovery of these catalysts was only the beginning of their uniqueness, as the ensuing years have proven these systems remarkable in several regards. Of primary importance are the pyridine-bis(imine) ligands (herein referred to as PDI), which produced iron catalysts that are among the world's most active for ethylene polymerization, demonstrated "staying power" despite over 15 years of ligand improvement efforts, and generated highly active polymerization systems with cobalt, chromium, and vanadium. Although many ligands have been employed in iron-catalyzed polymerization, the PDI family has thus far provided the most information about iron's capabilities and tendencies. For example, iron systems tend to be highly selective for ethylene over higher olefins, making them strong candidates for producing highly crystalline polyethylene, or highly linear α-olefins. Iron PDI polymerizes propylene with 2,1-regiochemistry via a predominantly isotactic, chain end control mechanism. Because the first insertion proceeds via 1,2-regiochemistry, iron (and cobalt) PDI systems can be tailored to make highly linear dimers of α-olefins by "head-to-head" coupling, resulting from a switch in regiochemistry after the first insertion. Finally, PDI ligands, while not being surpassed in activity, have inspired the development of related ligand families and complexes, such as pendant donor diimines (PDD), which are also highly efficient at producing linear α-olefins. This Account will detail a variety of oligomerization and polymerization results

  5. DNA structure modulates the oligomerization properties of the AAV initiator protein Rep68.

    Directory of Open Access Journals (Sweden)

    Jorge Mansilla-Soto

    2009-07-01

    Full Text Available Rep68 is a multifunctional protein of the adeno-associated virus (AAV, a parvovirus that is mostly known for its promise as a gene therapy vector. In addition to its role as initiator in viral DNA replication, Rep68 is essential for site-specific integration of the AAV genome into human chromosome 19. Rep68 is a member of the superfamily 3 (SF3 helicases, along with the well-studied initiator proteins simian virus 40 large T antigen (SV40-LTag and bovine papillomavirus (BPV E1. Structurally, SF3 helicases share two domains, a DNA origin interaction domain (OID and an AAA(+ motor domain. The AAA(+ motor domain is also a structural feature of cellular initiators and it functions as a platform for initiator oligomerization. Here, we studied Rep68 oligomerization in vitro in the presence of different DNA substrates using a variety of biophysical techniques and cryo-EM. We found that a dsDNA region of the AAV origin promotes the formation of a complex containing five Rep68 subunits. Interestingly, non-specific ssDNA promotes the formation of a double-ring Rep68, a known structure formed by the LTag and E1 initiator proteins. The Rep68 ring symmetry is 8-fold, thus differing from the hexameric rings formed by the other SF3 helicases. However, similiar to LTag and E1, Rep68 rings are oriented head-to-head, suggesting that DNA unwinding by the complex proceeds bidirectionally. This novel Rep68 quaternary structure requires both the DNA binding and AAA(+ domains, indicating cooperativity between these regions during oligomerization in vitro. Our study clearly demonstrates that Rep68 can oligomerize through two distinct oligomerization pathways, which depend on both the DNA structure and cooperativity of Rep68 domains. These findings provide insight into the dynamics and oligomeric adaptability of Rep68 and serve as a step towards understanding the role of this multifunctional protein during AAV DNA replication and site-specific integration.

  6. Imaging amyloid beta peptide oligomeric particles in solution.

    Science.gov (United States)

    Dong, Jijun; Apkarian, Robert P; Lynn, David G

    2005-09-01

    While all protein misfolding diseases are characterized by fibrous amyloid deposits, the favorable free energy and strongly cooperative nature of the self-assembly have complicated the development of therapeutic strategies aimed at preventing their formation. As structural models for the amyloid fibrils approach atomic resolution, increasing evidence suggests that early folding intermediates, rather than the final structure, are more strongly associated with the loss of neuronal function. For that reason we now demonstrate the use of cryo-etch high-resolution scanning electron microscopy (cryo-HRSEM) for the direct observation of pathway intermediates in amyloid assembly. A congener of the Abeta peptide of Alzheimer's disease, Abeta(13-21), samples a variety of time-dependent self-assembles in a manner similar to those seen for larger proteins. A morphological description of these intermediates is the first step towards their structural characterization and the definition of their role in both amyloid assembly and neurotoxicity.

  7. Screening of drugs inhibiting in vitro oligomerization of Cu/Zn-superoxide dismutase with a mutation causing amyotrophic lateral sclerosis

    Directory of Open Access Journals (Sweden)

    Itsuki Anzai

    2016-08-01

    Full Text Available Dominant mutations in Cu/Zn-superoxide dismutase (SOD1 gene have been shown to cause a familial form of amyotrophic lateral sclerosis (SOD1-ALS. A major pathological hallmark of this disease is abnormal accumulation of mutant SOD1 oligomers in the affected spinal motor neurons. While no effective therapeutics for SOD1-ALS is currently available, SOD1 oligomerization will be a good target for developing cures of this disease. Recently, we have reproduced the formation of SOD1 oligomers abnormally cross-linked via disulfide bonds in a test tube. Using our in vitro model of SOD1 oligomerization, therefore, we screened 640 FDA-approved drugs for inhibiting the oligomerization of SOD1 proteins, and three effective classes of chemical compounds were identified. Those hit compounds will provide valuable information on the chemical structures for developing a novel drug candidate suppressing the abnormal oligomerization of mutant SOD1 and possibly curing the disease.

  8. Pacemaker reed switch behavior in 0.5, 1.5, and 3.0 Tesla magnetic resonance imaging units: are reed switches always closed in strong magnetic fields?

    Science.gov (United States)

    Luechinger, Roger; Duru, Firat; Zeijlemaker, Volkert A; Scheidegger, Markus B; Boesiger, Peter; Candinas, Reto

    2002-10-01

    MRI is established as an important diagnostic tool in medicine. However, the presence of a cardiac pacemaker is usually regarded as a contraindication for MRI due to safety reasons. The aim of this study was to investigate the state of a pacemaker reed switch in different orientations and positions in the main magnetic field of 0.5-, 1.5-, and 3.0-T MRI scanners. Reed switches used in current pacemakers and ICDs were tested in 0.5-, 1.5-, and 3.0-T MRI scanners. The closure of isolated reed switches was evaluated for different orientations and positions relative to the main magnetic field. The field strengths to close and open the reed switch and the orientation dependency of the closed state inside the main magnetic field were investigated. The measurements were repeated using two intact pacemakers to evaluate the potential influence of the other magnetic components, like the battery. If the reed switches were oriented parallel to the magnetic fields, they closed at 1.0 +/- 0.2 mT and opened at 0.7 +/- 0.2 mT. Two different reed switch behaviors were observed at different magnetic field strengths. In low magnetic fields ( 200 mT), the reed switches opened in 50% of all tested orientations. No difference between the three scanners could be demonstrated. The reed switches showed the same behavior whether they were isolated or an integral part of the pacemakers. The reed switch in a pacemaker or an ICD does not necessarily remain closed in strong magnetic fields at 0.5, 1.5, or 3.0 T and the state of the reed switch may not be predictable with certainty in clinical situations.

  9. Unusual Emission of Polystyrene-Based Alternating Copolymers Incorporating Aminobutyl Maleimide Fluorophore-Containing Polyhedral Oligomeric Silsesquioxane Nanoparticles

    Directory of Open Access Journals (Sweden)

    Mohamed Gamal Mohamed

    2017-03-01

    Full Text Available In this study, we synthesized an unusual 2-aminobutyl maleimide isobutyl polyhedral oligomeric silsesquioxane (MIPOSS-NHBu monomer lacking conventional fluorescent groups. We then prepared poly(styrene-alt-2-aminobutyl maleimide isobutyl POSS [poly(S-alt-MIPOSS-NHBu] and poly(4-acetoxystyrene-alt-2-aminobutyl maleimide isobutyl POSS [poly(AS-alt-MIPOSS-NHBu] copolymers through facile free radical copolymerizations using azobisisobutyronitrile as the initiator and tetrahydrofuran as the solvent. A poly(4-hydroxystyrene-alt-2-aminobutyl maleimide isobutyl POSS [poly(HS-alt-MIPOSS-NHBu] copolymer was prepared through acetoxyl hydrazinolysis of poly(AS-alt-MIPOSS-NHBu. We employed 1H, 13C, and 29Si nuclear magnetic resonance spectroscopy; Fourier transform infrared spectroscopy; differential scanning calorimetry; and photoluminescence spectroscopy to investigate the structures and the thermal and optical properties of the monomers and novel POSS-containing alternating copolymers. Intramolecular hydrogen bonding between the amino and dihydrofuran-2,5-dione group and clustering of the locked C=O groups from the POSS nanoparticles in the MIPOSS-NHBu units restricted the intramolecular motion of the polymer chain, causing it to exhibit strong light emission. As a result, the MIPOSS-NHBu monomer and the poly(AS-alt-MIPOSS-NHBu copolymer both have potential applicability in the detection of metal ions with good selectivity.

  10. Mechanistic Studies of Ethylene and α-Olefin Co-oligomerization Catalyzed by Chromium-PNP Complexes.

    Science.gov (United States)

    Do, Loi H; Labinger, Jay A; Bercaw, John E

    2012-07-23

    To explore the possibility of producing a narrow distribution of mid- to long-chain hydrocarbons from ethylene as a chemical feedstock, co-oligomerization of ethylene and linear α-olefins (LAOs) was investigated, using a previously reported chromium complex, [CrCl(3)(PNP(OMe))] (1, where PNP(OMe) = N,N-bis(bis(o-methoxyphenyl)phosphino)methylamine). Activation of 1 by treatment with modified methylaluminoxane (MMAO) in the presence of ethylene and 1-hexene afforded mostly C(6) and C(10) alkene products. The identities of the C(10) isomers, assigned by detailed gas chromatographic and mass spectrometric analyses, strongly support a mechanism that involves five- and seven-membered metallacyclic intermediates comprising of ethylene and LAO units. Using 1-heptene as a mechanistic probe, it was established that 1-hexene formation from ethylene is competitive with formation of ethylene/LAO co-trimers, and that co-trimers derived from one ethylene and two LAO molecules are also generated. Complex 1/MMAO is also capable of converting 1-hexene to C(12) dimers and C(18) trimers, albeit with poor efficiency. The mechanistic implications of these studies are discussed and compared to previous reports of olefin co-trimerization.

  11. Continued biological investigations of boron-rich oligomeric phosphate diesters (OPDs). Tumor-selective boron agents for BNCT

    International Nuclear Information System (INIS)

    Lee, Mark W.; Shelly, Kenneth; Kane, Robert R.; Hawthorne, M. Frederick

    2006-01-01

    Clinical success of Boron Neutron Capture Therapy will rely on the selective intracellular delivery of high concentrations of boron-10 to tumor tissue. In order for a boron agent to facilitate clinical success, the simultaneous needs of obtaining a high tumor dose, high tumor selectivity, and low systemic toxicity must be realized. Boron-rich oligomeric phosphate diesters (OPDs) are a class of highly water-soluble compounds containing up to 40% boron by weight. Previous work in our groups demonstrated that once placed in the cytoplasm of tumor cells, OPDs quickly accumulate within the cell nucleus. The objective of the current study was to determine the biodistribution of seven different free OPDs in BALB/c mice bearing EMT6 tumors. Fructose solutions containing between 1.4 and 6.4 micrograms of boron per gram of tissue were interveinously injected in mice seven to ten days after tumor implantation. At intervals during the study, animals were euthanized and samples of tumor, blood, liver, kidney, brain and skin were collected and analyzed for boron content using ICP-AES. Tumor boron concentrations of between 5 and 29 ppm were achieved and maintained over the 72-hour time course of each experiment. Several OPDs demonstrated high tumor selectivity with one oligomer exhibiting a tumor to blood ratio of 35:1. The apparent toxicity of each oligomer was assessed through animal behavior during the experiment and necropsy of each animal upon sacrifice. (author)

  12. Prebiotic nucleotide oligomerization in a fluctuating environment - Effects of kaolinite and cyanamide

    Science.gov (United States)

    Odom, D. G.; Lahav, N.; Chang, S.

    1979-01-01

    The clay kaolinite was tested for its ability to promote nucleotide oligomerization in model prebiotic systems. Heterogeneous mixtures of clay, water and nucleotide were repeatedly evaporated to dryness at 60 C and redissolved in water in cyclic fashion in the presence or absence of cyanamide and/or ammonium chloride. With or without cycling, kaolinite alone did not promote the oligomerization of nucleotides at detectable levels. Cycling of clay in combination with cyanamide, however, promoted high levels of condensation to a mixture of oligonucleotides and dinucleotide pyrophosphate without requiring ammonium chloride. Although cycling with clay favored synthesis of dinucleotide pyrophosphate, cycling without clay enhanced formation of oligonucleotides. These results support the hypothesis that the presence of clays in fluctuating environments would have influenced the course of prebiotic condensation reactions.

  13. Fusion to a homo-oligomeric scaffold allows cryo-EM analysis of a small protein.

    Science.gov (United States)

    Coscia, Francesca; Estrozi, Leandro F; Hans, Fabienne; Malet, Hélène; Noirclerc-Savoye, Marjolaine; Schoehn, Guy; Petosa, Carlo

    2016-08-03

    Recent technical advances have revolutionized the field of cryo-electron microscopy (cryo-EM). However, most monomeric proteins remain too small (protein is genetically fused to a homo-oligomeric scaffold protein and the junction optimized to allow the target to adopt the scaffold symmetry, thereby generating a chimeric particle suitable for cryo-EM. To demonstrate the concept, we fused maltose-binding protein (MBP), a 40 kDa monomer, to glutamine synthetase, a dodecamer formed by two hexameric rings. Chimeric constructs with different junction lengths were screened by biophysical analysis and negative-stain EM. The optimal construct yielded a cryo-EM reconstruction that revealed the MBP structure at sub-nanometre resolution. These findings illustrate the feasibility of using homo-oligomeric scaffolds to enable cryo-EM analysis of monomeric proteins, paving the way for applying this strategy to challenging structures resistant to crystallographic and NMR analysis.

  14. Photocatalytically Active Oligomeric Graphitic Carbon Nitride: Conformational Flexibility, Electronic Levels, Carrier Localization

    Science.gov (United States)

    Blum, Volker; Lau, Vincent; Botari, Tiago; Huhn, William; Lotsch, Bettina V.

    2015-03-01

    Polymers consisting of bridged heptazine units (often called ``graphitic carbon nitride'' or ``g-C3N4'') show considerable promise as photocatalysts for solar hydrogen evolution. Recent experimental evidence suggests that oligomeric rather than fully polymerized ``g-C3N4'' exhibits increased intrinsic photocatalytic activity. Using density-functional theory (DFT; van der Waals corrected PBE functional for conformers, hybrid DFT and GW for electronic levels), we show that considerable conformational flexibility exists for the heptazine trimers and tetramers. Analysis of HOMO and LUMO locations as well as trends in photocatalytic activity among heptazine oligomers and polymers reveals the NH2 groups of the oligomers as potential charge-transfer sites. We show that conformational variations of the oligomers can lead to significant, electrostatically motivated carrier localization effects. We suggest that NH2 side groups and the intrinsic conformational variations of the oligomeric species lead to the observed enhanced catalytic activity.

  15. Ethylene oligomerization using iron complexes: beyond the discovery of bis(imino)pyridine ligands.

    Science.gov (United States)

    Boudier, Adrien; Breuil, Pierre-Alain R; Magna, Lionel; Olivier-Bourbigou, Hélène; Braunstein, Pierre

    2014-02-11

    Since the discovery that bis(imino)pyridine ligands are able to confer high activities in ethylene oligomerization and polymerization to their iron complexes, considerable attention has been focused on catalyst design for these reactions and this research constitutes an ever-growing area in molecular catalysis. The tuning of the ligand structures and properties, and thus of catalysts, generally represents the basis for subsequent work contributing to process development and industrialization. Significant effort is therefore devoted to generate structural diversity in order to access the required catalyst stability and selectivity. This feature article outlines nitrogen-containing ligands that have been developed for the iron-catalyzed oligomerization of ethylene since the seminal discovery of the properties of bis(imino)pyridine ligands.

  16. Domain architecture and oligomerization properties of the paramyxovirus PIV 5 hemagglutinin-neuraminidase (HN) protein.

    Science.gov (United States)

    Yuan, Ping; Leser, George P; Demeler, Borries; Lamb, Robert A; Jardetzky, Theodore S

    2008-09-01

    The mechanism by which the paramyxovirus hemagglutinin-neuraminidase (HN) protein couples receptor binding to activation of virus entry remains to be fully understood, but the HN stalk is thought to play an important role in the process. We have characterized ectodomain constructs of the parainfluenza virus 5 HN to understand better the underlying architecture and oligomerization properties that may influence HN functions. The PIV 5 neuraminidase (NA) domain is monomeric whereas the ectodomain forms a well-defined tetramer. The HN stalk also forms tetramers and higher order oligomers with high alpha-helical content. Together, the data indicate that the globular NA domains form weak intersubunit interactions at the end of the HN stalk tetramer, while stabilizing the stalk and overall oligomeric state of the ectodomain. Electron microscopy of the HN ectodomain reveals flexible arrangements of the NA and stalk domains, which may be important for understanding how these two HN domains impact virus entry.

  17. Strongly Correlated Systems Theoretical Methods

    CERN Document Server

    Avella, Adolfo

    2012-01-01

    The volume presents, for the very first time, an exhaustive collection of those modern theoretical methods specifically tailored for the analysis of Strongly Correlated Systems. Many novel materials, with functional properties emerging from macroscopic quantum behaviors at the frontier of modern research in physics, chemistry and materials science, belong to this class of systems. Any technique is presented in great detail by its own inventor or by one of the world-wide recognized main contributors. The exposition has a clear pedagogical cut and fully reports on the most relevant case study where the specific technique showed to be very successful in describing and enlightening the puzzling physics of a particular strongly correlated system. The book is intended for advanced graduate students and post-docs in the field as textbook and/or main reference, but also for other researchers in the field who appreciates consulting a single, but comprehensive, source or wishes to get acquainted, in a as painless as po...

  18. Strongly correlated systems numerical methods

    CERN Document Server

    Mancini, Ferdinando

    2013-01-01

    This volume presents, for the very first time, an exhaustive collection of those modern numerical methods specifically tailored for the analysis of Strongly Correlated Systems. Many novel materials, with functional properties emerging from macroscopic quantum behaviors at the frontier of modern research in physics, chemistry and material science, belong to this class of systems. Any technique is presented in great detail by its own inventor or by one of the world-wide recognized main contributors. The exposition has a clear pedagogical cut and fully reports on the most relevant case study where the specific technique showed to be very successful in describing and enlightening the puzzling physics of a particular strongly correlated system. The book is intended for advanced graduate students and post-docs in the field as textbook and/or main reference, but also for other researchers in the field who appreciate consulting a single, but comprehensive, source or wishes to get acquainted, in a as painless as possi...

  19. Strongly Correlated Topological Insulators

    Science.gov (United States)

    2016-02-03

    Strongly Correlated Topological Insulators In the past year, the grant was used for work in the field of topological phases, with emphasis on finding...surface of topological insulators. In the past 3 years, we have started a new direction, that of fractional topological insulators. These are materials...in which a topologically nontrivial quasi-flat band is fractionally filled and then subject to strong interactions. The views, opinions and/or

  20. Structural Determinants of Oligomerization of !1-Pyrroline-5-Carboxylate Dehydrogenase: Identification of a Hexamerization Hot Spot

    Science.gov (United States)

    Luo, Min; Singh, Ranjan K.; Tanner, John J.

    2013-01-01

    The aldehyde dehydrogenase (ALDH) superfamily member !1-pyrroline-5-carboxylate dehydrogenase (P5CDH) catalyzes the NAD+-dependent oxidation of glutamate semialdehyde to glutamate, which is the final step of proline catabolism. Defects in P5CDH activity lead to the metabolic disorder type II hyperprolinemia, P5CDH is essential for virulence of the fungal pathogen Cryptococcus neoformans, and bacterial P5CDHs have been targeted for vaccine development. Although the enzyme oligomeric state is known to be important for ALDH function, the oligomerization of P5CDH has remained relatively unstudied. Here we determine the oligomeric states and quaternary structures of four bacterial P5CDHs using a combination of small-angle X-ray scattering, X-ray crystallography, and dynamic light scattering. The P5CDHs from Thermus thermophilus and Deinococcus radiodurans form trimer-of-dimers hexamers in solution, which is the first observation of a hexameric ALDH in solution. In contrast, two Bacillus P5CDHs form dimers in solution but do not assemble into a higher order oligomer. Site-directed mutagenesis was used to identify a hexamerization hot spot that is centered on an arginine residue in the NAD+-binding domain. Mutation of this critical Arg residue to Ala in either of the hexameric enzymes prevents hexamer formation in solution. Paradoxically, the dimeric Arg-to-Ala T. thermophilus mutant enzyme packs as a hexamer in the crystal state, which illustrates the challenges associated with predicting the biological assembly in solution from crystal structures. The observation of different oligomeric states among P5CDHs suggests potential differences in cooperativity and protein-protein interactions. PMID:23747974

  1. Aqueous phase oligomerization of methyl vinyl ketone through photooxidation - Part 1: Aging processes of oligomers

    Science.gov (United States)

    Renard, P.; Siekmann, F.; Salque, G.; Smaani, A.; Demelas, C.; Coulomb, B.; Vassalo, L.; Ravier, S.; Temime-Roussel, B.; Voisin, D.; Monod, A.

    2014-06-01

    Secondary organic aerosol (SOA) represents a substantial part of organic aerosol, which affects climate and human health. It is now accepted that one of the important pathways of SOA formation occurs via aqueous phase chemistry in the atmosphere. Recently, we have shown in a previous study (Renard et al., 2013) the mechanism of oligomerization of MVK (methyl vinyl ketone), and suggested that unsaturated water soluble organic compounds (UWSOC) might efficiently form SOA in wet aerosol particles, even for weakly soluble ones like MVK. The atmospheric relevance of these processes is explored by means of process model studies (in a companion paper). In the present study we investigate the aging of these aqueous phase MVK-oligomers (Part 1). We compared aqueous phase composition and SOA composition after nebulization, mainly by means of UPLC-ESI-MS and AMS, respectively. Both instruments match and show similar trend of oligomer formation and aging. The SMPS analysis performed on the nebulized solutions allow to quantify these SOA and to measure their mass yields. We have highlighted in the current study that MVK •OH-oxidation undergoes kinetic competition between functionalization and oligomerization. The SOA composition and its evolution highly depend on the precursor initial concentration. We determined the threshold of MVK concentration, i.e. 2 mM, from which oligomerization prevails over functionalization. Hence, at these concentrations, •OH-oxidation of MVK forms oligomers that are SV-OOA, with low O / C and high f43. Oligomers are then fragmented, via unidentified intermediates that have the properties of LV-OOA which then end into succinic, malonic and oxalic diacids. For lower initial MVK concentrations, the oligomerization is not the major process, and functionalization dominates, resulting in small carbonyls, dicarbonyls and mainly monoacids. The aging of these oligomers could be an explanation for the presence of a part of the diacids observed in aerosol.

  2. An Investigation of Chemical Landscapes in Aqueous Electrosprays by Tracking Oligomerization of Isoprene

    KAUST Repository

    Junior, Adair Gallo

    2017-12-01

    Electrospray ionization mass spectrometry (ESIMS) is widely used to characterize neutral and ionic species in solvents. Typically, electrical, thermal, and pneumatic potentials are applied to create electrosprays from which charged ionic species are ejected for downstream analysis by mass spectrometry. Most recently, ESIMS has been exploited to investigate ambient proton transfer reactions at air-water interfaces in real time. We assessed the validity of these experiments via complementary laboratory experiments. Specifically, we characterized the products of two reaction scenarios via ESIMS and proton nuclear magnetic resonance (1H-NMR): (i) emulsions of pH-adjusted water and isoprene (C5H8) that were mechanically agitated, and (ii) electrosprays of pH-adjusted water that were collided with gas-phase isoprene. Our experiments unambiguously demonstrate that, while isoprene does not oligomerize in emulsions, it does undergo protonation and oligomerization in electrosprays, both with and without pH-adjusted water, confirming that C-C bonds form along myriad high-energy pathways during electrospray ionization. We also compared our experimental results with some quantum mechanics simulations of isoprene molecules interacting with hydronium at different hydration levels (gas versus liquid phase). In agreement with our experiments, the kinetic barriers to protonation and oligomerization of isoprene were inaccessible under ambient conditions. Rather, the gas-phase chemistries during electrospray ionization drove the oligomerization of isoprene. Therefore, we consider that ESIMS could induce artifacts in interfacial reactions. These findings warrant a reassessment of previous reports on tracking chemistries under ambient conditions at liquid-vapor interfaces via ESIMS. Further, we took some high-speed images of electrosprays where it was possible to observe the main characteristics of the phenomena, i.e. Taylor cone, charge separation, and Coulomb fission. Finally, we took

  3. “Click”-Capture, ROMP, Release: Facile Triazolation Utilizing ROMP-derived Oligomeric Phosphates

    Science.gov (United States)

    Long, Toby R.; Faisal, Saqib; Maity, Pradip K.; Rolfe, Alan; Kurtz, Ryan; Klimberg, Sarra V.; Najjar, Muhammad-Rabbie; Basha, Fatima Z.; Hanson, Paul R.

    2011-01-01

    Soluble, high-load ROMP-derived oligomeric triazole phosphates (OTP) are reported for application as efficient triazolating reagents of nucleophilic species. Utilizing a “Click”-capture, ROMP, release protocol, the efficient and purification free, direct triazolation of N-, O- and S-nucleophilic species was successfully achieved. A variety of OTP derivatives were rapidly synthesized as free-flowing solids on multi-gram scale from commercially available materials. PMID:21434675

  4. Alternative aluminum-based cocatalysts for the iron-catalyzed oligomerization of ethylene.

    Science.gov (United States)

    Boudier, Adrien; Breuil, Pierre-Alain R; Magna, Lionel; Olivier-Bourbigou, Hélène; Braunstein, Pierre

    2015-08-07

    Multinuclear aluminum cocatalysts have been obtained by the reaction of various phenols, alcohols or diols with trimethylaluminum and were used in situ or as isolated, well-defined species, for the activation of an iron(ii) or an iron(iii) pre-catalyst for the oligomerization of ethylene. The best cocatalyst candidate involves 2,2'-biphenol () in a /AlMe3 ratio of 2/3.

  5. Alternative aluminum-based cocatalysts for the iron-catalyzed oligomerization of ethylene.

    OpenAIRE

    Boudier , Adrien; Breuil , Pierre-Alain; Magna , Lionel; Olivier-Bourbigou , Hélène; Braunstein , Pierre

    2015-01-01

    International audience; Multinuclear aluminum cocatalysts have been obtained by the reaction of various phenols, alcohols or diois with trimethylaluminum and were used in situ or as isolated, welldefined species, for the activation of an iron(ll) or an iron(lll) precatalyst for the oligomerization of ethylene. The best cocatalyst candidate involves 2,2'-biphenol (10) in a 10/AIMe3 ratio of 2/3.

  6. Oligomerization and phase transitions in aqueous solutions of native and truncated human beta B1-crystallin.

    Science.gov (United States)

    Annunziata, Onofrio; Pande, Ajay; Pande, Jayanti; Ogun, Olutayo; Lubsen, Nicolette H; Benedek, George B

    2005-02-01

    Human betaB1-crystallin is a major eye-lens protein that undergoes in vivo truncation at the N-terminus with aging. By studying native betaB1 and truncated betaB1DeltaN41, which mimics an age-related in vivo truncation, we have determined quantitatively the effect of truncation on the oligomerization and phase transition properties of betaB1 aqueous solutions. The oligomerization studies show that the energy of attraction between the betaB1DeltaN41 proteins is about 10% greater than that of the betaB1 proteins. We have found that betaB1DeltaN41 aqueous solutions undergo two distinct types of phase transitions. The first phase transition involves an initial formation of thin rodlike assemblies, which then evolve to form crystals. The induction time for the formation of rodlike assemblies is sensitive to oligomerization. The second phase transition can be described as liquid-liquid phase separation (LLPS) accompanied by gelation within the protein-rich phase. We refer to this process as heterogeneous gelation. These two phase transitions are not observed in the case of betaB1 aqueous solutions. However, upon the addition of poly(ethylene glycol) (PEG), we observe heterogeneous gelation also for betaB1. Our PEG experiments allow us to estimate the difference in phase separation temperatures between betaB1 and betaB1DeltaN41. This difference is consistent with the increase in energy of attraction found in our oligomerization studies. Our work suggests that truncation is a cataractogenic modification since it favors protein condensation and the consequent formation of light scattering elements, and highlights the importance of the N-terminus of betaB1 in maintaining lens transparency.

  7. An unprecedented alpha-olefin distribution arising from a homogeneous ethylene oligomerization catalyst.

    Science.gov (United States)

    Tomov, Atanas K; Chirinos, Juan J; Long, Richard J; Gibson, Vernon C; Elsegood, Mark R J

    2006-06-21

    Treatment of the bis(benzimidazolyl)amine chromium complex 2 with ethylene in the presence of MAO affords an exceptionally active oligomerization catalyst and an unprecedented distribution of 1-olefin products in which the C4n series is much more abundant than the C4n+2 series. Deuterium labeling studies are consistent with a metallacyclic chain growth mechanism in which the unusual product distribution arises from the interplay of two sites.

  8. Assessing the Structure and Stability of Transmembrane Oligomeric Intermediates of an α-Helical Toxin.

    Science.gov (United States)

    Desikan, Rajat; Maiti, Prabal K; Ayappa, K Ganapathy

    2017-10-24

    Protein membrane interactions play an important role in our understanding of diverse phenomena ranging from membrane-assisted protein aggregation to oligomerization and folding. Pore-forming toxins (PFTs) are the primary vehicle for infection by several strains of bacteria. These proteins which are expressed in a water-soluble form (monomers) bind to the target membrane and conformationally transform (protomers) and self-assemble to form a multimer transmembrane pore complex through a process of oligomerization. On the basis of the structure of the transmembrane domains, PFTs are broadly classified into β or α toxins. In contrast to β-PFTs, the paucity of available crystal structures coupled with the amphipathic nature of the transmembrane domains has hindered our understanding of α-PFT pore formation. In this article, we use molecular dynamics (MD) simulations to examine the process of pore formation of the bacterial α-PFT, cytolysin A from Escherichia coli (ClyA) in lipid bilayer membranes. Using atomistic MD simulations ranging from 50 to 500 ns, we show that transmembrane oligomeric intermediates or "arcs" form stable proteolipidic complexes consisting of protein arcs with toroidal lipids lining the free edges. By creating initial conditions where the lipids are contained within the arcs, we study the dynamics of spontaneous lipid evacuation and toroidal edge formation. This process occurs on the time scale of tens of nanoseconds, suggesting that once protomers oligomerize, transmembrane arcs are rapidly stabilized to form functional water channels capable of leakage. Using umbrella sampling with a coarse-grained molecular model, we obtain the free energy of insertion of a single protomer into the membrane. A single inserted protomer has a stabilization free energy of -52.9 ± 1.2 kJ/mol and forms a stable transmembrane water channel capable of leakage. Our simulations reveal that arcs are stable and viable intermediates that can occur during the pore

  9. Recursive directional ligation by plasmid reconstruction allows rapid and seamless cloning of oligomeric genes.

    Science.gov (United States)

    McDaniel, Jonathan R; Mackay, J Andrew; Quiroz, Felipe García; Chilkoti, Ashutosh

    2010-04-12

    This paper reports a new strategy, recursive directional ligation by plasmid reconstruction (PRe-RDL), to rapidly clone highly repetitive polypeptides of any sequence and specified length over a large range of molecular weights. In a single cycle of PRe-RDL, two halves of a parent plasmid, each containing a copy of an oligomer, are ligated together, thereby dimerizing the oligomer and reconstituting a functional plasmid. This process is carried out recursively to assemble an oligomeric gene with the desired number of repeats. PRe-RDL has several unique features that stem from the use of type IIs restriction endonucleases: first, PRe-RDL is a seamless cloning method that leaves no extraneous nucleotides at the ligation junction. Because it uses type IIs endonucleases to ligate the two halves of the plasmid, PRe-RDL also addresses the major limitation of RDL in that it abolishes any restriction on the gene sequence that can be oligomerized. The reconstitution of a functional plasmid only upon successful ligation in PRe-RDL also addresses two other limitations of RDL: the significant background from self-ligation of the vector observed in RDL, and the decreased efficiency of ligation due to nonproductive circularization of the insert. PRe-RDL can also be used to assemble genes that encode different sequences in a predetermined order to encode block copolymers or append leader and trailer peptide sequences to the oligomerized gene.

  10. Effect Of Oligomeric Enteral Nutrition On Symptoms Of Acute Radiation Enteritis

    International Nuclear Information System (INIS)

    Dubinsky, P.

    2008-01-01

    Radiotherapy of abdominal and pelvic tumours is frequently associated with acute radiation enteritis. Predominant symptoms include diarrhea, watery stools, abdominal pain, nausea and vomiting. There are very few effective interventions available for this condition. Enteral oligomeric nutrition has been used in bowel diseases with functional failure similar to radiation enteritis. The aim of presented work was to observe occurrence of symptoms of radiation enteritis in patients undergoing abdominal or pelvic radiotherapy. Apart from diet and pharmacological therapy, oral oligomeric enteral nutrition (Peptisorb Powder Nutricia) at the dose of 1000 - 2000 ml per day was administered for minimum of 4 days. Planned period of administration was 14 days and longer. Symptoms of radiation enteritis were evaluated at the beginning and in the end of administration. Prevalence of all evaluated symptoms of radiation enteritis was decreased and difference was statistically significant for diarrhea, watery stools, abdominal pain, nausea and vomiting. The use of evaluated oligomeric nutritional support might, in conjunction with pharmacotherapy and diet, alleviate symptoms of acute radiation enteritis and maintain nutritional status of patients. (author)

  11. Single-Molecule characterization of oligomerization kinetics and equilibria of the tumor suppressor p53.

    Science.gov (United States)

    Rajagopalan, Sridharan; Huang, Fang; Fersht, Alan R

    2011-03-01

    The state of oligomerization of the tumor suppressor p53 is an important factor in its various biological functions. It has a well-defined tetramerization domain, and the protein exists as monomers, dimers and tetramers in equilibrium. The dissociation constants between oligomeric forms are so low that they are at the limits of measurement by conventional methods in vitro. Here, we have used the high sensitivity of single-molecule methods to measure the equilibria and kinetics of oligomerization of full-length p53 and its isolated tetramerization domain, p53tet, at physiological temperature, pH and ionic strength using fluorescence correlation spectroscopy (FCS) in vitro. The dissociation constant at 37 °C for tetramers dissociating into dimers for full-length p53 was 50 ± 7 nM, and the corresponding value for dimers into monomers was 0.55 ± 0.08 nM. The half-lives for the two processes were 20 and 50 min, respectively. The equivalent quantities for p53tet were 150 ± 10 nM, 1.0 ± 0.14 nM, 2.5 ± 0.4 min and 13 ± 2 min. The data suggest that unligated p53 in unstressed cells should be predominantly dimeric. Single-molecule FCS is a useful procedure for measuring dissociation equilibria, kinetics and aggregation at extreme sensitivity.

  12. Strong Arcwise Connectedness

    OpenAIRE

    Espinoza, Benjamin; Gartside, Paul; Kovan-Bakan, Merve; Mamatelashvili, Ana

    2012-01-01

    A space is `n-strong arc connected' (n-sac) if for any n points in the space there is an arc in the space visiting them in order. A space is omega-strong arc connected (omega-sac) if it is n-sac for all n. We study these properties in finite graphs, regular continua, and rational continua. There are no 4-sac graphs, but there are 3-sac graphs and graphs which are 2-sac but not 3-sac. For every n there is an n-sac regular continuum, but no regular continuum is omega-sac. There is an omega-sac ...

  13. Abortion: Strong's counterexamples fail

    DEFF Research Database (Denmark)

    Di Nucci, Ezio

    2009-01-01

    This paper shows that the counterexamples proposed by Strong in 2008 in the Journal of Medical Ethics to Marquis's argument against abortion fail. Strong's basic idea is that there are cases--for example, terminally ill patients--where killing an adult human being is prima facie seriously morally......'s scenarios have some valuable future or admitted that killing them is not seriously morally wrong. Finally, if "valuable future" is interpreted as referring to objective standards, one ends up with implausible and unpalatable moral claims....

  14. A strong comeback

    International Nuclear Information System (INIS)

    Marier, D.

    1992-01-01

    This article presents the results of a financial rankings survey which show a strong economic activity in the independent energy industry. The topics of the article include advisor turnover, overseas banks, and the increase in public offerings. The article identifies the top project finance investors for new projects and restructurings and rankings for lenders

  15. Strong Electroweak Symmetry Breaking

    CERN Document Server

    Grinstein, Benjamin

    2011-01-01

    Models of spontaneous breaking of electroweak symmetry by a strong interaction do not have fine tuning/hierarchy problem. They are conceptually elegant and use the only mechanism of spontaneous breaking of a gauge symmetry that is known to occur in nature. The simplest model, minimal technicolor with extended technicolor interactions, is appealing because one can calculate by scaling up from QCD. But it is ruled out on many counts: inappropriately low quark and lepton masses (or excessive FCNC), bad electroweak data fits, light scalar and vector states, etc. However, nature may not choose the minimal model and then we are stuck: except possibly through lattice simulations, we are unable to compute and test the models. In the LHC era it therefore makes sense to abandon specific models (of strong EW breaking) and concentrate on generic features that may indicate discovery. The Technicolor Straw Man is not a model but a parametrized search strategy inspired by a remarkable generic feature of walking technicolor,...

  16. Substituted tridentate pyrazolyl ligands for chromium and nickel-catalyzed ethylene oligomerization reactions: effect of auxiliary ligand on activity and selectivity

    Energy Technology Data Exchange (ETDEWEB)

    Oliveira, Lucilene L. de; Campedelli, Roberta R.; Bergamo, Adao L.; Santos, Ana H.D.P dos; Casagrande, Osvaldo L., E-mail: osvaldo.casagrande@ufrgs.b [Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS (Brazil). Inst. de Quimica. Lab. de Catalise Molecular

    2010-07-01

    Two new chromium(III) complexes [CrCl{sub 3}(L)] based on tridentate ligands (1a, L = bis[2-(3-phenyl-1-pyrazolyl)ethyl)]amine; 2a, L bis[2-(3-methyl-5-phenyl-l-pyrazolyl)ethyl]sulfide) have been prepared and characterized by elemental analysis. Upon activation with methylaluminoxane (MAO), these pre-catalysts showed high turnover frequencies for ethylene oligomerization under optimized conditions (TOFs = 22.9-36.4 x 103 mol C{sub 2}H{sub 4} (mol Cr{sup III}){sup -1} h{sup -1}, [Cr] = 10.0 mumol, 80 deg C, 20 bar ethylene, MAO: Cr = 300, oligomerization time = 20 min), producing alpha-olefins in the range C{sub 4}-C{sub 14+} with high selectively (67.71-73.47%). The catalytic performances are substantially affected by the ligand environment, especially the substituents at the 3- and 5-positions of the pyrazolyl rings. In parallel, the use of nickel complexes such as NiCl{sub 2}{l_brace}bis[2-(3,5-dimethyl-1-pyrazolyl)methyl]benzylamine{r_brace} (3) and NiCl{sub 2}{l_brace}bis[2-(3,5-dimethyl-1-pyrazolyl)ethyl)]ether{r_brace} (5) in oligomerization reactions carried out in the presence of triphenylphosphine (PPh{sub 3}) afforded highly active catalytic systems with turnover frequencies (TOFs) varying from 36.4 to 154.2 x 10{sup 3} mol C{sub 2}H{sub 4} (mol Ni{sup II}){sup -1} h{sup -1}. The presence of this auxiliary ligand has a strong impact on the selectivity towards the production of a-olefins, decreasing substantially the amount of 1-butene with a concomitant increase of the 2-butene fractions. Attempts to crystallize the nickel complex 3 afforded the tetrametallic [{l_brace} (L)(mu{sub 3}-Cl)NiCl{r_brace}{sub 4}] (4, L 1-anilinomethyl-3,5-dimethylpyrazole) which was characterized by X-ray diffraction analysis. (author)

  17. Plasmons in strong superconductors

    International Nuclear Information System (INIS)

    Baldo, M.; Ducoin, C.

    2011-01-01

    We present a study of the possible plasmon excitations that can occur in systems where strong superconductivity is present. In these systems the plasmon energy is comparable to or smaller than the pairing gap. As a prototype of these systems we consider the proton component of Neutron Star matter just below the crust when electron screening is not taken into account. For the realistic case we consider in detail the different aspects of the elementary excitations when the proton, electron components are considered within the Random-Phase Approximation generalized to the superfluid case, while the influence of the neutron component is considered only at qualitative level. Electron screening plays a major role in modifying the proton spectrum and spectral function. At the same time the electron plasmon is strongly modified and damped by the indirect coupling with the superfluid proton component, even at moderately low values of the gap. The excitation spectrum shows the interplay of the different components and their relevance for each excitation modes. The results are relevant for neutrino physics and thermodynamical processes in neutron stars. If electron screening is neglected, the spectral properties of the proton component show some resemblance with the physical situation in high-T c superconductors, and we briefly discuss similarities and differences in this connection. In a general prospect, the results of the study emphasize the role of Coulomb interaction in strong superconductors.

  18. Hsp70 oligomerization is mediated by an interaction between the interdomain linker and the substrate-binding domain.

    Directory of Open Access Journals (Sweden)

    Francesco A Aprile

    Full Text Available Oligomerization in the heat shock protein (Hsp 70 family has been extensively documented both in vitro and in vivo, although the mechanism, the identity of the specific protein regions involved and the physiological relevance of this process are still unclear. We have studied the oligomeric properties of a series of human Hsp70 variants by means of nanoelectrospray ionization mass spectrometry, optical spectroscopy and quantitative size exclusion chromatography. Our results show that Hsp70 oligomerization takes place through a specific interaction between the interdomain linker of one molecule and the substrate-binding domain of a different molecule, generating dimers and higher-order oligomers. We have found that substrate binding shifts the oligomerization equilibrium towards the accumulation of functional monomeric protein, probably by sequestering the helical lid sub-domain needed to stabilize the chaperone: substrate complex. Taken together, these findings suggest a possible role of chaperone oligomerization as a mechanism for regulating the availability of the active monomeric form of the chaperone and for the control of substrate binding and release.

  19. Small-angle neutron scattering reveals the assembly mode and oligomeric architecture of TET, a large, dodecameric aminopeptidase.

    Science.gov (United States)

    Appolaire, Alexandre; Girard, Eric; Colombo, Matteo; Durá, M Asunción; Moulin, Martine; Härtlein, Michael; Franzetti, Bruno; Gabel, Frank

    2014-11-01

    The specific self-association of proteins into oligomeric complexes is a common phenomenon in biological systems to optimize and regulate their function. However, de novo structure determination of these important complexes is often very challenging for atomic-resolution techniques. Furthermore, in the case of homo-oligomeric complexes, or complexes with very similar building blocks, the respective positions of subunits and their assembly pathways are difficult to determine using many structural biology techniques. Here, an elegant and powerful approach based on small-angle neutron scattering is applied, in combination with deuterium labelling and contrast variation, to elucidate the oligomeric organization of the quaternary structure and the assembly pathways of 468 kDa, hetero-oligomeric and symmetric Pyrococcus horikoshii TET2-TET3 aminopeptidase complexes. The results reveal that the topology of the PhTET2 and PhTET3 dimeric building blocks within the complexes is not casual but rather suggests that their quaternary arrangement optimizes the catalytic efficiency towards peptide substrates. This approach bears important potential for the determination of quaternary structures and assembly pathways of large oligomeric and symmetric complexes in biological systems.

  20. N-Glycosylation instead of cholesterol mediates oligomerization and apical sorting of GPI-APs in FRT cells.

    Science.gov (United States)

    Imjeti, Naga Salaija; Lebreton, Stéphanie; Paladino, Simona; de la Fuente, Erwin; Gonzalez, Alfonso; Zurzolo, Chiara

    2011-12-01

    Sorting of glycosylphosphatidyl-inositol--anchored proteins (GPI-APs) in polarized epithelial cells is not fully understood. Oligomerization in the Golgi complex has emerged as the crucial event driving apical segregation of GPI-APs in two different kind of epithelial cells, Madin-Darby canine kidney (MDCK) and Fisher rat thyroid (FRT) cells, but whether the mechanism is conserved is unknown. In MDCK cells cholesterol promotes GPI-AP oligomerization, as well as apical sorting of GPI-APs. Here we show that FRT cells lack this cholesterol-driven oligomerization as apical sorting mechanism. In these cells both apical and basolateral GPI-APs display restricted diffusion in the Golgi likely due to a cholesterol-enriched membrane environment. It is striking that N-glycosylation is the critical event for oligomerization and apical sorting of GPI-APs in FRT cells but not in MDCK cells. Our data indicate that at least two mechanisms exist to determine oligomerization in the Golgi leading to apical sorting of GPI-APs. One depends on cholesterol, and the other depends on N-glycosylation and is insensitive to cholesterol addition or depletion.

  1. Strong-coupling approximations

    International Nuclear Information System (INIS)

    Abbott, R.B.

    1984-03-01

    Standard path-integral techniques such as instanton calculations give good answers for weak-coupling problems, but become unreliable for strong-coupling. Here we consider a method of replacing the original potential by a suitably chosen harmonic oscillator potential. Physically this is motivated by the fact that potential barriers below the level of the ground-state energy of a quantum-mechanical system have little effect. Numerically, results are good, both for quantum-mechanical problems and for massive phi 4 field theory in 1 + 1 dimensions. 9 references, 6 figures

  2. Strong interaction and QFD

    International Nuclear Information System (INIS)

    Ebata, T.

    1981-01-01

    With an assumed weak multiplet structure for bosonic hadrons, which is consistent with the ΔI = 1/2 rule, it is shown that the strong interaction effective hamiltonian is compatible with the weak SU(2) x U(1) gauge transformation. Especially the rho-meson transforms as a triplet under SU(2)sub(w), and this is the origin of the rho-photon analogy. It is also shown that the existence of the non-vanishing Cabibbo angle is a necessary condition for the absence of the exotic hadrons. (orig.)

  3. Involvement of C-Terminal Histidines in Soybean PM1 Protein Oligomerization and Cu2+ Binding.

    Science.gov (United States)

    Liu, Guobao; Liu, Ke; Gao, Yang; Zheng, Yizhi

    2017-06-01

    Late embryogenesis abundant (LEA) proteins are widely distributed among plant species, where they contribute to abiotic stress tolerance. LEA proteins can be classified into seven groups according to conserved sequence motifs. The PM1 protein from soybean, which belongs to the Pfam LEA_1 group, has been shown previously to be at least partially natively unfolded, to bind metal ions and potentially to stabilize proteins and membranes. Here, we investigated the role of the PM1 C-terminal domain and in particular the multiple histidine residues in this half of the protein. We constructed recombinant plasmids expressing full-length PM1 and two truncated forms, PM1-N and PM1-C, which represent the N- and C-terminal halves of the protein, respectively. Immunoblotting and cross-linking experiments showed that full-length PM1 forms oligomers and high molecular weight (HMW) complexes in vitro and in vivo, while PM1-C, but not PM1-N, also formed oligomers and HMW complexes in vitro. When the histidine residues in PM1 and PM1-C were chemically modified, oligomerization was abolished, suggesting that histidines play a key role in this process. Furthermore, we demonstrated that high Cu2+ concentrations promote oligomerization and induce PM1 and PM1-C to form HMW complexes. Therefore, we speculate that PM1 proteins not only maintain ion homeostasis in the cytoplasm, but also potentially stabilize and protect other proteins during abiotic stress by forming a large, oligomeric molecular shield around biological targets. © The Author 2017. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  4. Crystal structures from the Plasmodium peroxiredoxins: new insights into oligomerization and product binding.

    Science.gov (United States)

    Qiu, Wei; Dong, Aiping; Pizarro, Juan C; Botchkarsev, Alexei; Min, Jinrong; Wernimont, Amy K; Hills, Tanya; Hui, Raymond; Artz, Jennifer D

    2012-03-19

    Plasmodium falciparum is the protozoan parasite primarily responsible for more than one million malarial deaths, annually, and is developing resistance to current therapies. Throughout its lifespan, the parasite is subjected to oxidative attack, so Plasmodium antioxidant defences are essential for its survival and are targets for disease control. To further understand the molecular aspects of the Plasmodium redox system, we solved 4 structures of Plasmodium peroxiredoxins (Prx). Our study has confirmed PvTrx-Px1 to be a hydrogen peroxide (H2O2)-sensitive peroxiredoxin. We have identified and characterized the novel toroid octameric oligomer of PyTrx-Px1, which may be attributed to the interplay of several factors including: (1) the orientation of the conserved surface/buried arginine of the NNLA(I/L)GRS-loop; and (2) the C-terminal tail positioning (also associated with the aforementioned conserved loop) which facilitates the intermolecular hydrogen bond between dimers (in an A-C fashion). In addition, a notable feature of the disulfide bonds in some of the Prx crystal structures is discussed. Finally, insight into the latter stages of the peroxiredoxin reaction coordinate is gained. Our structure of PyPrx6 is not only in the sulfinic acid (RSO2H) form, but it is also with glycerol bound in a way (not previously observed) indicative of product binding. The structural characterization of Plasmodium peroxiredoxins provided herein provides insight into their oligomerization and product binding which may facilitate the targeting of these antioxidant defences. Although the structural basis for the octameric oligomerization is further understood, the results yield more questions about the biological implications of the peroxiredoxin oligomerization, as multiple toroid configurations are now known. The crystal structure depicting the product bound active site gives insight into the overoxidation of the active site and allows further characterization of the leaving group

  5. The effects of oligomerization on Saccharomyces cerevisiae Mcm4/6/7 function

    Directory of Open Access Journals (Sweden)

    Davey Megan J

    2010-09-01

    Full Text Available Abstract Background Minichromosome maintenance proteins (Mcm 2, 3, 4, 5, 6 and 7 are related by sequence and form a variety of complexes that unwind DNA, including Mcm4/6/7. A Mcm4/6/7 trimer forms one half of the Mcm2-7 hexameric ring and can be thought of as the catalytic core of Mcm2-7, the replicative helicase in eukaryotic cells. Oligomeric analysis of Mcm4/6/7 suggests that it forms a hexamer containing two Mcm4/6/7 trimers, however, under certain conditions trimeric Mcm4/6/7 has also been observed. The functional significance of the different Mcm4/6/7 oligomeric states has not been assessed. The results of such an assessment would have implications for studies of both Mcm4/6/7 and Mcm2-7. Results Here, we show that Saccharomyces cerevisiae Mcm4/6/7 reconstituted from individual subunits exists in an equilibrium of oligomeric forms in which smaller oligomers predominate in the absence of ATP. In addition, we found that ATP, which is required for Mcm4/6/7 activity, shifts the equilibrium towards larger oligomers, likely hexamers of Mcm4/6/7. ATPγS and to a lesser extent ADP also shift the equilibrium towards hexamers. Study of Mcm4/6/7 complexes containing mutations that interfere with the formation of inter-subunit ATP sites (arginine finger mutants indicates that full activity of Mcm4/6/7 requires all of its ATP sites, which are formed in a hexamer and not a trimer. In keeping with this observation, Mcm4/6/7 binds DNA as a hexamer. Conclusions The minimal functional unit of Mcm4/6/7 is a hexamer. One of the roles of ATP binding by Mcm4/6/7 may be to stabilize formation of hexamers.

  6. Strongly coupled dust coulomb clusters

    International Nuclear Information System (INIS)

    Juan Wentau; Lai Yingju; Chen Mingheng; I Lin

    1999-01-01

    The structures and motions of quasi-2-dimensional strongly coupled dust Coulomb clusters with particle number N from few to hundreds in a cylindrical rf plasma trap are studied and compared with the results from the molecular dynamic simulation using more ideal models. Shell structures with periodic packing in different shells and intershell rotational motion dominated excitations are observed at small N. As N increases, the boundary has less effect, the system recovers to the triangular lattice with isotropic vortex type cooperative excitations similar to an infinite N system except the outer shell region. The above generic behaviors are mainly determined by the system symmetry and agree with the simulation results. The detailed interaction form causes minor effect such as the fine structure of packing

  7. Multi-PAS domain-mediated protein oligomerization of PpsR from Rhodobacter sphaeroides

    Energy Technology Data Exchange (ETDEWEB)

    Heintz, Udo; Meinhart, Anton; Winkler, Andreas, E-mail: andreas.winkler@mpimf-heidelberg.mpg.de [Max Planck Institute for Medical Research, Heidelberg (Germany)

    2014-03-01

    Crystal structures of two truncated variants of the transcription factor PpsR from R. sphaeroides are presented that enabled the phasing of a triple PAS domain construct. Together, these structures reveal the importance of α-helical PAS extensions for multi-PAS domain-mediated protein oligomerization and function. Per–ARNT–Sim (PAS) domains are essential modules of many multi-domain signalling proteins that mediate protein interaction and/or sense environmental stimuli. Frequently, multiple PAS domains are present within single polypeptide chains, where their interplay is required for protein function. Although many isolated PAS domain structures have been reported over the last decades, only a few structures of multi-PAS proteins are known. Therefore, the molecular mechanism of multi-PAS domain-mediated protein oligomerization and function is poorly understood. The transcription factor PpsR from Rhodobacter sphaeroides is such a multi-PAS domain protein that, in addition to its three PAS domains, contains a glutamine-rich linker and a C-terminal helix–turn–helix DNA-binding motif. Here, crystal structures of two N-terminally and C-terminally truncated PpsR variants that comprise a single (PpsR{sub Q-PAS1}) and two (PpsR{sub N-Q-PAS1}) PAS domains, respectively, are presented and the multi-step strategy required for the phasing of a triple PAS domain construct (PpsR{sub ΔHTH}) is illustrated. While parts of the biologically relevant dimerization interface can already be observed in the two shorter constructs, the PpsR{sub ΔHTH} structure reveals how three PAS domains enable the formation of multiple oligomeric states (dimer, tetramer and octamer), highlighting that not only the PAS cores but also their α-helical extensions are essential for protein oligomerization. The results demonstrate that the long helical glutamine-rich linker of PpsR results from a direct fusion of the N-cap of the PAS1 domain with the C-terminal extension of the N-domain that

  8. Polyhedral oligomeric silsequioxane monolayer as a nanoporous interlayer for preparation of low-k dielectric films

    International Nuclear Information System (INIS)

    Liu, Y-L; Liu, C-S; Cho, C-I; Hwu, M-J

    2007-01-01

    Polyhedral oligomeric silsequioxane (POSS) monomer was fixed to a silicon surface by reacting octakis(glycidyldimethylsiloxy)octasilsesquioxane (OG-POSS) with the OH-terminated silicon surface in the presence of tin (II) chloride. The POSS cage layer then served as a nanoporous interlayer to reduce the dielectric constants of polyimide films on silicon surfaces. The chemical structure and surface morphology of OG-POSS modified silicon surfaces were characterized with XPS. With the introduction of a POSS nanopored interlayer, the dielectric constants of polyimide films were reduced

  9. Icosahedron oligomerization and condensation in intermetallic compounds. Bonding and electronic requirements.

    Science.gov (United States)

    Tillard-Charbonnel, M; Manteghetti, A; Belin, C

    2000-04-17

    Icosahedron-based clustering has been found to be very common in intermetallics, particularly for group 13 and early p-block icosogen elements. Linking of the icosahedral building blocks depends on the valence electron concentrations. Vertex-, edge-, or face-sharing icosahedra occur as the structure compensates for electron deficiency. Some examples of icosahedron-based clusters have been selected for an analysis of the relationships between the structural features (icosahedron oligomerization, atomic defects, etc.) and the bonding and electronic requirements. The extended Hückel method has been used with either a molecular approach or an electronic band structure calculation to rationalize bonding in the intermetallic framework.

  10. Porphinogen Formation from the Co-Oligomerization of Formaldehyde and Pyrrole: Free Energy Pathways.

    Science.gov (United States)

    Kua, Jeremy; Loli, Helen

    2017-10-26

    We have investigated the nonoxidative stepwise co-oligomerization of formaldehyde and pyrrole to form porphinogen using density functional theory calculations that include free energy corrections. While the addition of formaldehyde to the pyrrole nitrogen is kinetically favored, thermodynamics suggest that this reaction is reversible in aqueous solution. The more thermodynamically favorable addition of formaldehyde to the ortho-carbon of pyrrole begins a stepwise process, forming dipyrromethane via an azafulvene intermediate. Subsequent additions of formaldehyde and pyrrole lead to bilanes (linear tetrapyrroles), which favorably cyclize to form porphinogen. Porphinogen is a precursor to porphin, the simplest unsubstituted porphyrin that could have played a role in primitive metabolism at the origin of life.

  11. Thermo-mechanical characterization of a monochlorophenyl, hepta isobutyl polyhedral oligomeric silsesquioxane/polystyrene composite

    International Nuclear Information System (INIS)

    Blanco, Ignazio; Bottino, Francesco A.; Cicala, Gianluca; Cozzo, Giulia; Latteri, Alberta; Recca, Antonino

    2014-01-01

    The thermal and mechanical properties of a monochlorophenyl, hepta isobutyl Polyhedral Oligomeric Silsesquioxane/Polystyrene (ph,hib-POSS/PS) composite were studied and compared with those of pristine polymer. ph,hib-POSS/PS system was prepared by solubilization and precipitation of Polystyrene (PS) in the presence of POSS. Scanning Electron Microscopy (SEM) was performed to check the distribution of the filler in the polymer matrix. Dynamic Mechanical Analysis (DMA) was carried out to measure viscoelastic properties of solid samples. Degradations were carried out into a thermobalance and the obtained thermogravimetric (TG) and differential thermogravimetric (DTG) curves were discussed and interpreted

  12. PCNCP ligands in the chromium-catalyzed oligomerization of ethylene: tri- versus tetramerization.

    Science.gov (United States)

    Klemps, Christian; Payet, Elina; Magna, Lionel; Saussine, Lucien; Le Goff, Xavier F; Le Floch, Pascal

    2009-08-17

    Chromium(III) complexes bearing R'N(CH2PR2)2 (PCNCP) ligands have been prepared. Upon activation with methylaluminoxane, these complexes proved to be effective in the selective tri- and tetramerization of ethylene. The formation of either 1-hexene or 1-octene was found to be highly dependent on the steric bulk of the substituents R on the phosphine moieties. This observation was rationalized by using density functional theory calculations on selected steps of the metallacyclic mechanism of the ethylene oligomerization reaction.

  13. Characteristics of ethylene oligomerization on a gel-immobilized catalyst system

    Energy Technology Data Exchange (ETDEWEB)

    Popov, V.G.; Vasil' chenko, S.V.

    1989-02-01

    The characteristics of the oligomerization of ethylene in the presence of a gel-immobilized catalyst system (GCS) based on dicyclopentadienyltitanium dichloride and an alkylaluminum chloride was investigated. 1,2-Polybutadiene was used as support. The reaction rate on the GCS is constant for a long period of time, in contrast to homogeneous catalyst systems. The activity of the GCS is retained when unpurified ethylene is used. The MWD of normal olefins when the GCS is used differs from Schulz-Flory distribution by an increase of the share of the middle fraction. The process takes place in the internal diffusion region.

  14. Transient structural distortion of metal-free Cu/Zn superoxide dismutase triggers aberrant oligomerization

    DEFF Research Database (Denmark)

    Teilum, Kaare; Smith, Melanie H; Schulz, Eike

    2009-01-01

    remained enigmatic, however, as is the case in other protein-misfolding diseases. Here, we target the critical conformational change that defines the earliest step toward aggregation. Using nuclear spin relaxation dispersion experiments, we identified a short-lived (0.4 ms) and weakly populated (0.......7%) conformation of metal-depleted SOD1 that triggers aberrant oligomerization. This excited state emanates from the folded ground state and is suppressed by metal binding, but is present in both the disulfide-oxidized and disulfide-reduced forms of the protein. Our results pinpoint a perturbed region...

  15. Strong Coupling Holography

    CERN Document Server

    Dvali, Gia

    2009-01-01

    We show that whenever a 4-dimensional theory with N particle species emerges as a consistent low energy description of a 3-brane embedded in an asymptotically-flat (4+d)-dimensional space, the holographic scale of high-dimensional gravity sets the strong coupling scale of the 4D theory. This connection persists in the limit in which gravity can be consistently decoupled. We demonstrate this effect for orbifold planes, as well as for the solitonic branes and string theoretic D-branes. In all cases the emergence of a 4D strong coupling scale from bulk holography is a persistent phenomenon. The effect turns out to be insensitive even to such extreme deformations of the brane action that seemingly shield 4D theory from the bulk gravity effects. A well understood example of such deformation is given by large 4D Einstein term in the 3-brane action, which is known to suppress the strength of 5D gravity at short distances and change the 5D Newton's law into the four-dimensional one. Nevertheless, we observe that the ...

  16. Pleiotropic benefit of monomeric and oligomeric flavanols on vascular health--a randomized controlled clinical pilot study.

    Directory of Open Access Journals (Sweden)

    Antje R Weseler

    Full Text Available BACKGROUND: Cardiovascular diseases are expanding to a major social-economic burden in the Western World and undermine man's deep desire for healthy ageing. Epidemiological studies suggest that flavanol-rich foods (e.g. grapes, wine, chocolate sustain cardiovascular health. For an evidenced-based application, however, sound clinical data on their efficacy are strongly demanded. METHODS: In a double-blind, randomized, placebo-controlled intervention study we supplemented 28 male smokers with 200 mg per day of monomeric and oligomeric flavanols (MOF from grape seeds. At baseline, after 4 and 8 weeks we measured macro- and microvascular function and a cluster of systemic biomarkers for major pathological processes occurring in the vasculature: disturbances in lipid metabolism and cellular redox balance, and activation of inflammatory cells and platelets. RESULTS: In the MOF group serum total cholesterol and LDL decreased significantly (P ≤ 0.05 by 5% (n = 11 and 7% (n = 9, respectively in volunteers with elevated baseline levels. Additionally, after 8 weeks the ratio of glutathione to glutathione disulphide in erythrocytes rose from baseline by 22% (n = 15, P<0.05 in MOF supplemented subjects. We also observed that MOF supplementation exerts anti-inflammatory effects in blood towards ex vivo added bacterial endotoxin and significantly reduces expression of inflammatory genes in leukocytes. Conversely, alterations in macro- and microvascular function, platelet aggregation, plasma levels of nitric oxide surrogates, endothelin-1, C-reactive protein, fibrinogen, prostaglandin F2alpha, plasma antioxidant capacity and gene expression levels of antioxidant defense enzymes did not reach statistical significance after 8 weeks MOF supplementation. However, integrating all measured effects into a global, so-called vascular health index revealed a significant improvement of overall vascular health by MOF compared to placebo (P ≤ 0.05. CONCLUSION: Our

  17. Interaction of polyhedral oligomeric silsesquioxanes and dipalmitoylphosphatidylcholine at the air/water interface: Thermodynamic and rheological study.

    Science.gov (United States)

    Skrzypiec, M; Georgiev, G As; Rojewska, M; Prochaska, K

    2017-10-01

    Polyhedral oligomeric silsesquioxanes (POSS) derivatives containing open silsesquioxane cage bear great potential for biomedical applications and therefore their lateral interactions with phospholipids, major biomembranes and drug vehicles constituent, should be studied in detail. That is why the properties of surface films by two POSS-derivatives, POSS-polyethylene glycol (POSS-PEG) and POSS-perfluoroalkyl (POSS-OFP), pure and in presence of 1,2-dipalmitoyl-sn-glycerol-3-phosphocholine (DPPC) were studied using Langmuir surface balance. Side chains of opposite nature (PEG is hydrophilic; OFP is hydrophobic) were selected, so that to evaluate their impact on polymers' surface properties. Two types of measurements were performed: (i) the miscibility of POSS-derivatives with DPPC was evaluated via thermodynamic analysis of the surface pressure (π)-area (A) isotherms and (ii) the dilatational rheology of selected POSS-polymer containing films was studied by the stress relaxation method. Fourier transformation analysis of the relaxation transients allows to access films' dynamic interfacial properties in broad frequency range (10 -5 -1Hz). Film morphology was monitored with Brewster Angle Microscopy. PEG moiety enabled POSS-PEG to stably incorporate in DPPC films, modifying their equilibrium and dynamic properties. In contrast OFP chains excluded from interactions with other molecules and diminished PEG-OFP amphiphilicity. Therefore at high packing densities (π≥25mN/m) PEG-OFP was expelled from the air/water interface in DPPC/PEG-OFP mixtures, and the binary films equilibrium and dynamic surface properties were determined primarily by DPPC. Thus the choice of POSS side chains can play key role in biomedical applications depending on whether strong or weak incorporation of POSS-polymers in lipid environment is aimed for. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Discovery and optimization of new chromium catalysts for ethylene oligomerization and polymerization aided by high-throughput screening.

    Science.gov (United States)

    Jones, David J; Gibson, Vernon C; Green, Simon M; Maddox, Peter J; White, Andrew J P; Williams, David J

    2005-08-10

    High throughput screening (HTS) of a 205 member Schiff base salicylaldimine ligand library derived from salicylaldehydes bearing bulky ortho-substituents, i.e., 9-anthracenyl, 1,4,5,8-tetramethylanthracenyl or triptycenyl, reacted in-situ with (p-tolyl)CrCl2(thf)3, identified two new classes of highly active chromium based systems for the oligomerization and polymerization of ethylene, respectively. The polymerization system comprises bidentate ortho-substituted anthracenyl Schiff bases bearing small primary or secondary alkyl imine substituents. The oligomerization catalysts are based upon tridentate ortho-triptycenyl-substituted Schiff bases with pyridylmethyl or quinolyl substituents. Validation tests confirmed polymerization productivities of up to 3000 g x mmol(-1)h(-1)bar(-1) for the polymerization catalyst systems while the oligomerization catalysts gave productivities up to 10 000 g x mmol(-1)h(-1)bar(-1). Key catalyst precursors have been characterized by X-ray crystallography.

  19. Mutations in BIN1 associated with centronuclear myopathy disrupt membrane remodeling by affecting protein density and oligomerization.

    Directory of Open Access Journals (Sweden)

    Tingting Wu

    Full Text Available The regulation of membrane shapes is central to many cellular phenomena. Bin/Amphiphysin/Rvs (BAR domain-containing proteins are key players for membrane remodeling during endocytosis, cell migration, and endosomal sorting. BIN1, which contains an N-BAR domain, is assumed to be essential for biogenesis of plasma membrane invaginations (T-tubules in muscle tissues. Three mutations, K35N, D151N and R154Q, have been discovered so far in the BAR domain of BIN1 in patients with centronuclear myopathy (CNM, where impaired organization of T-tubules has been reported. However, molecular mechanisms behind this malfunction have remained elusive. None of the BIN1 disease mutants displayed a significantly compromised curvature sensing ability. However, two mutants showed impaired membrane tubulation both in vivo and in vitro, and displayed characteristically different behaviors. R154Q generated smaller membrane curvature compared to WT N-BAR. Quantification of protein density on membranes revealed a lower membrane-bound density for R154Q compared to WT and the other mutants, which appeared to be the primary reason for the observation of impaired deformation capacity. The D151N mutant was unable to tubulate liposomes under certain experimental conditions. At medium protein concentrations we found 'budding' structures on liposomes that we hypothesized to be intermediates during the tubulation process except for the D151N mutant. Chemical crosslinking assays suggested that the D151N mutation impaired protein oligomerization upon membrane binding. Although we found an insignificant difference between WT and K35N N-BAR in in vitro assays, depolymerizing actin in live cells allowed tubulation of plasma membranes through the K35N mutant. Our results provide insights into the membrane-involved pathophysiological mechanisms leading to human disease.

  20. LIGO: The strong belief

    CERN Multimedia

    Antonella Del Rosso

    2016-01-01

    Twenty years of designing, building and testing a number of innovative technologies, with the strong belief that the endeavour would lead to a historic breakthrough. The Bulletin publishes an abstract of the Courier’s interview with Barry Barish, one of the founding fathers of LIGO.   The plots show the signals of gravitational waves detected by the twin LIGO observatories at Livingston, Louisiana, and Hanford, Washington. (Image: Caltech/MIT/LIGO Lab) On 11 February, the Laser Interferometer Gravitational-Wave Observatory (LIGO) and Virgo collaborations published a historic paper in which they showed a gravitational signal emitted by the merger of two black holes. These results come after 20 years of hard work by a large collaboration of scientists operating the two LIGO observatories in the US. Barry Barish, Linde Professor of Physics, Emeritus at the California Institute of Technology and former Director of the Global Design Effort for the Internat...

  1. The Agrobacterium tumefaciens Transcription Factor BlcR Is Regulated via Oligomerization

    Energy Technology Data Exchange (ETDEWEB)

    Pan, Yi; Fiscus, Valena; Meng, Wuyi; Zheng, Zhida; Zhang, Lian-Hui; Fuqua, Clay; Chen, Lingling (IMCB-Singapore); (Indiana)

    2012-02-08

    The Agrobacterium tumefaciens BlcR is a member of the emerging isocitrate lyase transcription regulators that negatively regulates metabolism of {gamma}-butyrolactone, and its repressing function is relieved by succinate semialdehyde (SSA). Our crystal structure showed that BlcR folded into the DNA- and SSA-binding domains and dimerized via the DNA-binding domains. Mutational analysis identified residues, including Phe{sup 147}, that are important for SSA association; BlcR{sup F147A} existed as tetramer. Two BlcR dimers bound to target DNA and in a cooperative manner, and the distance between the two BlcR-binding sequences in DNA was critical for BlcR-DNA association. Tetrameric BlcR{sup F147A} retained DNA binding activity, and importantly, this activity was not affected by the distance separating the BlcR-binding sequences in DNA. SSA did not dissociate tetrameric BlcR{sup F147A} or BlcR{sup F147A}-DNA. As well as in the SSA-binding site, Phe{sup 147} is located in a structurally flexible loop that may be involved in BlcR oligomerization. We propose that SSA regulates BlcR DNA-binding function via oligomerization.

  2. An Asymmetric Deuterium Labeling Strategy to Identify Interprotomer and Intraprotomer NOEs in Oligomeric Proteins

    International Nuclear Information System (INIS)

    Jasanoff, Alan

    1998-01-01

    A major difficulty in determining the structure of an oligomeric protein by NMR is the problem of distinguishing inter- from intraprotomer NOEs. In order to address this issue in studies of the 27 kD compact trimeric domain of the MHC class II-associated invariant chain, we compared the 13C NOESY-HSQC spectrum of a uniformly 13C-labeled trimer with the spectrum of the same trimer labeled with 13C in only one protomer, and with deuterium in the other two protomers. The spectrum of the unmixed trimer included both inter- and intraprotomer NOEs while the spectrum of the mixed trimer included only intraprotomer peaks. NOEs clearly absent from the spectrum of the mixed trimer could be confidently assigned to interprotomer interactions. Asymmetrically labeled trimers were isolated by refolding a 13C-labeled shorter form of the protein with a 2H-labeled longer form, chromatographically purifying trimers with only one short chain, and then processing with trypsin to yield only protomers with the desired N- and C-termini. In contrast to earlier studies, in which statistical mixtures of differently labeled protomers were analyzed, our procedure generated only a well-defined 1:2 oligomer, and no other mixed oligomers were present. This increased the maximum possible concentration of NMR-active protomers and thus the sensitivity of the experiments. Related methods should be applicable to many oligomeric proteins, particularly those with slow protomer exchange rates

  3. Cartilage oligomeric matrix protein in patients with juvenile idiopathic arthritis: relation to growth and disease activity

    DEFF Research Database (Denmark)

    Bjørnhart, Birgitte; Juul, Anders; Nielsen, Susan

    2009-01-01

    OBJECTIVE: Cartilage oligomeric matrix protein (COMP) has been identified as a prognostic marker of progressive joint destruction in rheumatoid arthritis. In this population based study we evaluated associations between plasma concentrations of COMP, disease activity, and growth velocity in patie......OBJECTIVE: Cartilage oligomeric matrix protein (COMP) has been identified as a prognostic marker of progressive joint destruction in rheumatoid arthritis. In this population based study we evaluated associations between plasma concentrations of COMP, disease activity, and growth velocity...... significantly reduced compared to healthy children (p correlated negatively with C-reactive protein (CRP; r = -0.29, p = 0.01) and thrombocyte count (r = -0.28, p = 0.02). COMP levels in the JIA patients correlated positively with growth velocity (cm/yr) (r = 0.38, p = 0.0003) and growth velocity...... (SDS) (r = 0.29, p = 0.007). CONCLUSION: We found reduced COMP levels in children with JIA compared with healthy children. COMP levels in JIA correlated negatively with inflammatory activity as evaluated by CRP and the thrombocyte counts, and were associated with reduced growth rate....

  4. Phosphate and HEPES buffers potently affect the fibrillation and oligomerization mechanism of Alzheimer's Aβ peptide

    International Nuclear Information System (INIS)

    Garvey, Megan; Tepper, Katharina; Haupt, Caroline; Knuepfer, Uwe; Klement, Karolin; Meinhardt, Jessica; Horn, Uwe; Balbach, Jochen; Faendrich, Marcus

    2011-01-01

    Highlights: → Sodium phosphate buffer accelerated Aβ(1-40) nucleation relative to HEPES. → Aβ(1-40) fibrils formed in the two buffers show only minor structural differences. → NMR revealed that Aβ(1-40) histidine residues mediate buffer dependent changes. -- Abstract: The oligomerization of Aβ peptide into amyloid fibrils is a hallmark of Alzheimer's disease. Due to its biological relevance, phosphate is the most commonly used buffer system for studying the formation of Aβ and other amyloid fibrils. Investigation into the characteristics and formation of amyloid fibrils frequently relies upon material formed in vitro, predominantly in phosphate buffers. Herein, we examine the effects on the fibrillation and oligomerization mechanism of Aβ peptide that occur due solely to the influence of phosphate buffer. We reveal that significant differences in amyloid fibrillation are observed due to fibrillation being initiated in phosphate or HEPES buffer (at physiological pH and temperature). Except for the differing buffer ions, all experimental parameters were kept constant. Fibril formation was assessed using fluorescently monitored kinetic studies, microscopy, X-ray fiber diffraction and infrared and nuclear magnetic resonance spectroscopies. Based on this set up, we herein reveal profound effects on the mechanism and speed of Aβ fibrillation. The three histidine residues at positions 6, 13 and 14 of Aβ(1-40) are instrumental in these mechanistic changes. We conclude that buffer plays a more significant role in fibril formation than has been generally acknowledged.

  5. Amyloid β Oligomeric Species Present in the Lag Phase of Amyloid Formation.

    Directory of Open Access Journals (Sweden)

    Martin Wolff

    Full Text Available Alzheimer's disease (AD-associated amyloid β peptide (Aβ is one of the main actors in AD pathogenesis. Aβ is characterized by its high tendency to self-associate, leading to the generation of oligomers and amyloid fibrils. The elucidation of pathways and intermediates is crucial for the understanding of protein assembly mechanisms in general and in conjunction with neurodegenerative diseases, e.g., for the identification of new therapeutic targets. Our study focused on Aβ42 and its oligomeric assemblies in the lag phase of amyloid formation, as studied by sedimentation velocity (SV centrifugation. The assembly state of Aβ during the lag phase, the time required by an Aβ solution to reach the exponential growth phase of aggregation, was characterized by a dominant monomer fraction below 1 S and a population of oligomeric species between 4 and 16 S. From the oligomer population, two major species close to a 12-mer and an 18-mer with a globular shape were identified. The recurrence of these two species at different initial concentrations and experimental conditions as the smallest assemblies present in solution supports the existence of distinct, energetically favored assemblies in solution. The sizes of the two species suggest an Aβ42 aggregation pathway that is based on a basic hexameric building block. The study demonstrates the potential of SV analysis for the evaluation of protein aggregation pathways.

  6. Mic10 oligomerizes to bend mitochondrial inner membranes at cristae junctions.

    Science.gov (United States)

    Barbot, Mariam; Jans, Daniel C; Schulz, Christian; Denkert, Niels; Kroppen, Benjamin; Hoppert, Michael; Jakobs, Stefan; Meinecke, Michael

    2015-05-05

    The mitochondrial inner membrane is highly folded and displays a complex molecular architecture. Cristae junctions are highly curved tubular openings that separate cristae membrane invaginations from the surrounding boundary membrane. Despite their central role in many vital cellular processes like apoptosis, the details of cristae junction formation remain elusive. Here we identify Mic10, a core subunit of the recently discovered MICOS complex, as an inner mitochondrial membrane protein with the ability to change membrane morphology in vitro and in vivo. We show that Mic10 spans the inner membrane in a hairpin topology and that its ability to sculpt membranes depends on oligomerization through a glycine-rich motif. Oligomerization mutants fail to induce curvature in model membranes, and when expressed in yeast, mitochondria display an altered inner membrane architecture characterized by drastically decreased numbers of cristae junctions. Thus, we demonstrate that membrane sculpting by Mic10 is essential for cristae junction formation. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Unusual Enhancement of Doxorubicin Activity on Co-Delivery with Polyhedral Oligomeric Silsesquioxane (POSS

    Directory of Open Access Journals (Sweden)

    Ewelina Sobierajska

    2017-05-01

    Full Text Available Polyhedral oligomeric silsesquioxane (POSS, bearing eight 3-chloroammoniumpropyl substituents, was studied as a potential nanocarrier in co-delivery systems with doxorubicin (DOX. The toxicity of doxorubicin and POSS:DOX complexes at four different molar ratios (1:1; 1:2, 1:4, 1:8 towards microvascular endothelial cells (HMEC-1, breast cancer cells (MCF-7, and human cervical cancer endothelial cells (HeLa was determined. The rate of penetration of the components into the cells, their cellular localization and the hydrodynamic diameter of the complexes was also determined. A cytotoxicity profile of POSS:DOX complexes indicated that the POSS:DOX system at the molar ratio of 1:8 was more effective than free DOX. Confocal images showed that DOX co-delivery with POSS allowed for more effective penetration of doxorubicin through the cell membrane. Taking all the results into account, it can be claimed that the polyhedral oligomeric silsesquioxane (T8-POSS is a promising, complex nanocarrier for doxorubicin delivery.

  8. Dry Deposition of Biogenic Terpenes via Cationic Oligomerization on Environmental Aqueous Surfaces.

    Science.gov (United States)

    Enami, Shinichi; Hoffmann, Michael R; Colussi, Agustín J

    2012-11-01

    Unraveling the complex interactions between the atmosphere and the biosphere is critical for predicting climate changes. Although it is well-recognized that the large amounts of biogenic volatile organic compounds (BVOCs) emitted by plants must play important roles in this regard, current atmospheric models fail to account for their fate due to missing chemical sinks. Here, we applied online electrospray mass spectrometry to monitor aqueous microjets exposed to gaseous monoterpenes (α-pinene, β-pinene, and d-limonene) and found that these BVOCs are readily protonated (to C10H17(+)) and undergo oligomerization (to C20H33(+) and C30H49(+)) upon colliding with the surface of pH < 4 microjets. By considering that the yields of all products show inflection points at pH ≈ 3.5 and display solvent kinetic hydrogen isotope effects larger than 2, we conclude that the oligomerization process is initiated by weakly hydrated hydronium ions, H3O(+), present at the gas-water interface. Present results provide a universal mechanism for the dry deposition of unsaturated BVOCs and may account for recent observations on the uptake of terpenes in forest canopies and over grassland.

  9. Multicoil2: Predicting Coiled Coils and Their Oligomerization States from Sequence in the Twilight Zone

    Science.gov (United States)

    Trigg, Jason; Gutwin, Karl; Keating, Amy E.; Berger, Bonnie

    2011-01-01

    The alpha-helical coiled coil can adopt a variety of topologies, among the most common of which are parallel and antiparallel dimers and trimers. We present Multicoil2, an algorithm that predicts both the location and oligomerization state (two versus three helices) of coiled coils in protein sequences. Multicoil2 combines the pairwise correlations of the previous Multicoil method with the flexibility of Hidden Markov Models (HMMs) in a Markov Random Field (MRF). The resulting algorithm integrates sequence features, including pairwise interactions, through multinomial logistic regression to devise an optimized scoring function for distinguishing dimer, trimer and non-coiled-coil oligomerization states; this scoring function is used to produce Markov Random Field potentials that incorporate pairwise correlations localized in sequence. Multicoil2 significantly improves both coiled-coil detection and dimer versus trimer state prediction over the original Multicoil algorithm retrained on a newly-constructed database of coiled-coil sequences. The new database, comprised of 2,105 sequences containing 124,088 residues, includes reliable structural annotations based on experimental data in the literature. Notably, the enhanced performance of Multicoil2 is evident when tested in stringent leave-family-out cross-validation on the new database, reflecting expected performance on challenging new prediction targets that have minimal sequence similarity to known coiled-coil families. The Multicoil2 program and training database are available for download from http://multicoil2.csail.mit.edu. PMID:21901122

  10. Site-isolation effects in a dendritic nickel catalyst for the oligomerization of ethylene.

    Science.gov (United States)

    Müller, Christian; Ackerman, Lily J; Reek, Joost N H; Kamer, Paul C J; van Leeuwen, Piet W N M

    2004-11-17

    Dendrimers, specifically suited to construct site-isolated groups due to their well-defined hyperbranched structure, have been used as a ligand design element for the construction of nickel catalysts for ethylene oligomerization. The dendritic P,O ligand indeed suppresses the formation of inactive bis(P,O)Ni complexes in toluene, as is evident from NMR studies, and, as a consequence, outperforms the parent ligand in catalysis in this solvent. The dendritic effect observed in methanol is more subtle because both the dendritic ligand 1 and the parent 2 form bis(P,O)nickel complexes in solution according to NMR spectroscopy. Unlike the parent complex 8, the dendritic bis(P,O)Ni complex 7 derived from dendrimer ligand 1 is able to dissociate to a mono-ligated species under catalytic conditions, that is, 40 bar ethylene and 80 degrees C, which can enter the catalytic cycle. Indeed, dendritic ligand 1 gives much more active nickel catalysts for the oligomerization in methanol than does 2.

  11. Solvent Oligomerization during SEI Formation on Model Systems for Li-Ion Battery Anodes

    Energy Technology Data Exchange (ETDEWEB)

    Tavassol, Hadi; Buthker, Joseph W.; Ferguson, Glen A.; Curtiss, Larry A.; Gewirth, Andrew A.

    2012-01-01

    We report the results of electrochemical quartz crystal microbalance (EQCM), and matrix assisted laser desorption ionization (MALDI) time of flight (TOF) mass spectrometry (MS) measurements along with detailed calculations examining the formation of the solid electrolyte interphase (SEI) on battery anode electrodes. EQCM analysis of Au and Sn surfaces in propylene carbonate (PC) and a 1:1 mixture of ethylene carbonate and dimethyl carbonate (EC:DMC) showed major irreversible mass uptake by the electrode surface especially during the first five cycles between +2 and 0.1 V vs. Li/Li+. MALDI-MS on emersed electrodes showed that long chain (m/z = 3000 on PC) oligomerized species were present on Au surfaces in PC and EC:DMC solvents, where oligomerized species formed in PC solutions showed higher mass ratios. The repeating units of the oligomer, visible as oscillations in the MALDI-MS, vary with the type of the solvent and electrode material. Sn surfaces initially showed formation of long chain polymers, but this material was not in evidence on electrode emersed after five cycles, which likely arises as a consequence of the catalytic involvement of Sn in decomposition of initially formed species. Density functional theory (DFT) calculations of cyclic solvent molecules suggested a radical initiated polymerization mechanism and predict oligomer subunits consistent with the experimental results.

  12. Study of the kinetics and equilibria of the oligomerization reactions of 2-methylglyceric acid

    Directory of Open Access Journals (Sweden)

    A. W. Birdsall

    2013-03-01

    Full Text Available The presence of a variety of chemical species related to the gaseous precursor isoprene in ambient secondary organic aerosol (SOA has stimulated investigations of the nature of SOA-phase chemical processing. Recent work has demonstrated that 2-methylglyceric acid (2-MG is an important isoprene-derived ambient SOA component and atmospheric chamber experiments have suggested that 2-MG may exist in oligomeric form (as oligoesters under conditions of low SOA water content. In order to better understand the thermodynamic and kinetic parameters of such oligomerization reactions, nuclear magnetic resonance techniques were used to study the bulk phase acid-catalyzed aqueous reactions (Fischer esterification of 2-MG. While the present results indicate that 2-MG oligoesters are formed in the bulk phase with similar water content equilibrium dependences as observed in atmospheric chamber SOA experiments, the acid-catalyzed rate of the Fischer esterification mechanism may be too slow to rationalize the 2-MG oligoester production timescales observed in the atmospheric chamber experiments. Furthermore, it appears that unrealistically high ambient SOA acidities would also be required for significant 2-MG oligoester content to arise via Fischer esterification. Therefore, the present results suggest that other, more kinetically facile, esterification mechanisms may be necessary to rationalize the existence of 2-MG oligomers in atmospheric chamber-generated and ambient SOA.

  13. Multicoil2: predicting coiled coils and their oligomerization states from sequence in the twilight zone.

    Directory of Open Access Journals (Sweden)

    Jason Trigg

    Full Text Available The alpha-helical coiled coil can adopt a variety of topologies, among the most common of which are parallel and antiparallel dimers and trimers. We present Multicoil2, an algorithm that predicts both the location and oligomerization state (two versus three helices of coiled coils in protein sequences. Multicoil2 combines the pairwise correlations of the previous Multicoil method with the flexibility of Hidden Markov Models (HMMs in a Markov Random Field (MRF. The resulting algorithm integrates sequence features, including pairwise interactions, through multinomial logistic regression to devise an optimized scoring function for distinguishing dimer, trimer and non-coiled-coil oligomerization states; this scoring function is used to produce Markov Random Field potentials that incorporate pairwise correlations localized in sequence. Multicoil2 significantly improves both coiled-coil detection and dimer versus trimer state prediction over the original Multicoil algorithm retrained on a newly-constructed database of coiled-coil sequences. The new database, comprised of 2,105 sequences containing 124,088 residues, includes reliable structural annotations based on experimental data in the literature. Notably, the enhanced performance of Multicoil2 is evident when tested in stringent leave-family-out cross-validation on the new database, reflecting expected performance on challenging new prediction targets that have minimal sequence similarity to known coiled-coil families. The Multicoil2 program and training database are available for download from http://multicoil2.csail.mit.edu.

  14. John Strong (1941 - 2006)

    CERN Multimedia

    Wickens, F

    Our friend and colleague John Strong was cruelly taken from us by a brain tumour on Monday 31st July, a few days before his 65th birthday John started his career working with a group from Westfield College, under the leadership of Ted Bellamy. He obtained his PhD and spent the early part of his career on experiments at Rutherford Appleton Laboratory (RAL), but after the early 1970s his research was focussed on experiments in CERN. Over the years he made a number of notable contributions to experiments in CERN: The Omega spectrometer adopted a system John had originally developed for experiments at RAL using vidicon cameras to record the sparks in the spark chambers; He contributed to the success of NA1 and NA7, where he became heavily involved in the electronic trigger systems; He was responsible for the second level trigger system for the ALEPH detector and spent five years leading a team that designed and built the system, which ran for twelve years with only minor interventions. Following ALEPH he tur...

  15. Stirring Strongly Coupled Plasma

    CERN Document Server

    Fadafan, Kazem Bitaghsir; Rajagopal, Krishna; Wiedemann, Urs Achim

    2009-01-01

    We determine the energy it takes to move a test quark along a circle of radius L with angular frequency w through the strongly coupled plasma of N=4 supersymmetric Yang-Mills (SYM) theory. We find that for most values of L and w the energy deposited by stirring the plasma in this way is governed either by the drag force acting on a test quark moving through the plasma in a straight line with speed v=Lw or by the energy radiated by a quark in circular motion in the absence of any plasma, whichever is larger. There is a continuous crossover from the drag-dominated regime to the radiation-dominated regime. In the crossover regime we find evidence for significant destructive interference between energy loss due to drag and that due to radiation as if in vacuum. The rotating quark thus serves as a model system in which the relative strength of, and interplay between, two different mechanisms of parton energy loss is accessible via a controlled classical gravity calculation. We close by speculating on the implicati...

  16. Strong-interaction nonuniversality

    International Nuclear Information System (INIS)

    Volkas, R.R.; Foot, R.; He, X.; Joshi, G.C.

    1989-01-01

    The universal QCD color theory is extended to an SU(3) 1 direct product SU(3) 2 direct product SU(3) 3 gauge theory, where quarks of the ith generation transform as triplets under SU(3)/sub i/ and singlets under the other two factors. The usual color group is then identified with the diagonal subgroup, which remains exact after symmetry breaking. The gauge bosons associated with the 16 broken generators then form two massive octets under ordinary color. The interactions between quarks and these heavy gluonlike particles are explicitly nonuniversal and thus an exploration of their physical implications allows us to shed light on the fundamental issue of strong-interaction universality. Nonuniversality and weak flavor mixing are shown to generate heavy-gluon-induced flavor-changing neutral currents. The phenomenology of these processes is studied, as they provide the major experimental constraint on the extended theory. Three symmetry-breaking scenarios are presented. The first has color breaking occurring at the weak scale, while the second and third divorce the two scales. The third model has the interesting feature of radiatively induced off-diagonal Kobayashi-Maskawa matrix elements

  17. Kinetic model and mathematical description of oligomerization of ethylene to higher linear alpha-olefins, catalyzed by the system Zr(OCOiso-C3H7)-(C2H5)3AL2CL3

    International Nuclear Information System (INIS)

    Byrikhina, N.A.; Brikenstein, K.M.; Gerasina, M.P.; Matkovskii, P.E.; Pechatnikov, E L.

    1986-01-01

    The authors have formulated a mathematical model of ethylene oligomerization in the presence of the system Zr (OCOR) 4 - (C 2 H 5 ) 3 AL 2 CL 3 , worked out an approximate analytical description of the kinetic relationships of ethylene consumption in the course of its oligomerization in presence of this system, and estimated the effective rate constants of the principal oligomerization stages

  18. Controlling Josephson dynamics by strong microwave fields

    NARCIS (Netherlands)

    Chesca, B.; Savel'ev, E.; Rakhmanov, A.L.; Smilde, H.J.H.; Hilgenkamp, Johannes W.M.

    2008-01-01

    We observe several sharp changes in the slope of the current-voltage characteristics (CVCs) of thin-film ramp-edge Josephson junctions between YBa2Cu3O7−delta and Nb when applying strong microwave fields. Such behavior indicates an intriguing Josephson dynamics associated with the switching from a

  19. Strongly interacting photons and atoms

    International Nuclear Information System (INIS)

    Alge, W.

    1999-05-01

    This thesis contains the main results of the research topics I have pursued during the my PhD studies at the University of Innsbruck and partly in collaboration with the Institut d' Optique in Orsay, France. It is divided into three parts. The first and largest part discusses the possibility of using strong standing waves as a tool to cool and trap neutral atoms in optical cavities. This is very important in the field of nonlinear optics where several successful experiments with cold atoms in cavities have been performed recently. A discussion of the optical parametric oscillator in a regime where the nonlinearity dominates the evolution is the topic of the second part. We investigated mainly the statistical properties of the cavity output of the three interactive cavity modes. Very recently a system has been proposed which promises fantastic properties. It should exhibit a giant Kerr nonlinearity with negligible absorption thus leading to a photonic turnstile device based on cold atoms in cavity. We have shown that this model suffers from overly simplistic assumptions and developed several more comprehensive approaches to study the behavior of this system. Apart from the division into three parts of different contents the thesis is divided into publications, supplements and invisible stuff. The intention of the supplements is to reach researchers which work in related areas and provide them with more detailed information about the concepts and the numerical tools we used. It is written especially for diploma and PhD students to give them a chance to use the third part of our work which is actually the largest one. They consist of a large number of computer programs we wrote to investigate the behavior of the systems in parameter regions where no hope exists to solve the equations analytically. (author)

  20. A Small-Molecule Inhibitor of Bax and Bak Oligomerization Prevents Genotoxic Cell Death and Promotes Neuroprotection.

    Science.gov (United States)

    Niu, Xin; Brahmbhatt, Hetal; Mergenthaler, Philipp; Zhang, Zhi; Sang, Jing; Daude, Michael; Ehlert, Fabian G R; Diederich, Wibke E; Wong, Eve; Zhu, Weijia; Pogmore, Justin; Nandy, Jyoti P; Satyanarayana, Maragani; Jimmidi, Ravi K; Arya, Prabhat; Leber, Brian; Lin, Jialing; Culmsee, Carsten; Yi, Jing; Andrews, David W

    2017-04-20

    Aberrant apoptosis can lead to acute or chronic degenerative diseases. Mitochondrial outer membrane permeabilization (MOMP) triggered by the oligomerization of the Bcl-2 family proteins Bax/Bak is an irreversible step leading to execution of apoptosis. Here, we describe the discovery of small-molecule inhibitors of Bax/Bak oligomerization that prevent MOMP. We demonstrate that these molecules disrupt multiple, but not all, interactions between Bax dimer interfaces thereby interfering with the formation of higher-order oligomers in the MOM, but not recruitment of Bax to the MOM. Small-molecule inhibition of Bax/Bak oligomerization allowed cells to evade apoptotic stimuli and rescued neurons from death after excitotoxicity, demonstrating that oligomerization of Bax is essential for MOMP. Our discovery of small-molecule Bax/Bak inhibitors provides novel tools for the investigation of the mechanisms leading to MOMP and will ultimately facilitate development of compounds inhibiting Bax/Bak in acute and chronic degenerative diseases. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Effect of the cross-talk between autophagy and endoplasmic reticulum stress on Mn-induced alpha-synuclein oligomerization.

    Science.gov (United States)

    Liu, Chang; Yan, Dong-Ying; Tan, Xuan; Ma, Zhuo; Wang, Can; Deng, Yu; Liu, Wei; Yang, Tian-Yao; Xu, Zhao-Fa; Xu, Bin

    2018-03-01

    Overexposure to manganese (Mn) has been known to induce alpha-synuclein (α-Syn) oligomerization, which is degraded mainly depending on endoplasmic reticulum stress (ER stress) and autophagy pathways. However, little data reported the cross-talk between ER stress and autophagy on Mn-induced α-Syn oligomerization. To explore the relationship between ER stress and autophagy, we used 4-phenylbutyric acid (4-PBA, the ER stress inhibitor), rapamycin (Rap, autophagy activator) and 3-methyladenine (3-MA, autophagy inhibitor) in mice model of manganism. After 4 weeks of treatment with Mn, both ER stress and autophagy were activated. Exposed to Mn also resulted in α-Syn oligomerization and neuronal cell damage in the brain tissue of mice, which could be relieved by 4-PBA pretreatment. Moreover, when the ER stress was inhibited, the activation of autophagy was also inhibited. Rap pretreatment significantly activated autophagy and decreased α-Syn oligomers. However, 3-MA pretreatment inhibited autophagy resulting in increase of α-Syn oligomers, and compensatorily activated PERK signaling pathway. Our results also demonstrated that the inhibition of autophagy by 3-MA aggravated neuronal cell damage. The findings clearly demonstrated that the cross-talking between autophagy and ER stress might play an important role in the α-Syn oligomerization and neurotoxicity by Mn. © 2017 Wiley Periodicals, Inc.

  2. Human immunodeficiency virus type 1 Vpr: oligomerization is an essential feature for its incorporation into virus particles

    Directory of Open Access Journals (Sweden)

    Klein-Seetharaman Judith

    2010-06-01

    Full Text Available Abstract HIV-1 Vpr, a nonstructural viral protein associated with virus particles, has a positive role in the efficient transport of PIC into the nucleus of non-dividing target cells and enhances virus replication in primary T cells. Vpr is a 96 amino acid protein and the structure by NMR shows three helical domains. Vpr has been shown to exist as dimers and higher order oligomers. Considering the multifunctional nature of Vpr, the contribution of distinct helical domains to the dimer/oligomer structure of Vpr and the relevance of this feature to its functions are not clear. To address this, we have utilized molecular modeling approaches to identify putative models of oligomerization. The predicted interface residues were subjected to site-directed mutagenesis and evaluated their role in intermolecular interaction and virion incorporation. The interaction between Vpr molecules was monitored by Bimolecular Fluorescence complementation (BiFC method. The results show that Vpr forms oligomers in live cells and residues in helical domains play critical roles in oligomerization. Interestingly, Vpr molecules defective in oligomerization also fail to incorporate into the virus particles. Based on the data, we suggest that oligomerization of Vpr is essential for virion incorporation property and may also have a role in the events associated with virus infection.

  3. Hydrogen/Deuterium Exchange Mass Spectrometry Reveals Mechanistic Details of Activation of Nucleoside Diphosphate Kinases by Oligomerization.

    Science.gov (United States)

    Dautant, Alain; Meyer, Philippe; Georgescauld, Florian

    2017-06-13

    Most oligomeric proteins become active only after assembly, but why oligomerization is required to support function is not well understood. Here, we address this question using the wild type (WT) and a destabilized mutant (D93N) of the hexameric nucleoside diphosphate kinase from the pathogen Mycobacterium tuberculosis (Mt-NDPK). The conformational dynamics and oligomeric states of each were analyzed during unfolding and/or folding by hydrogen/deuterium exchange mass spectrometry (HDX-MS) at peptide resolution and by additional biochemical techniques. We found that WT and D93N native hexamers present a stable core and a flexible periphery, the latter being more flexible for the destabilized mutant. Stable but inactive species formed during unfolding of D93N and folding of WT were characterized. For the first time, we show that both of these species are nativelike dimers, each of its monomers having a major subdomain folded, while a minor subdomain (Kpn/α 0 ) remains unfolded. The Kpn/α 0 subdomain, which belongs to the catalytic site, becomes structured only upon hexamerization, explaining why oligomerization is required for NDPK activity. Further HDX-MS studies are necessary to establish the general activation mechanism for other homo-oligomers.

  4. Regulation of complement by cartilage oligomeric matrix protein allows for a novel molecular diagnostic principle in rheumatoid arthritis

    DEFF Research Database (Denmark)

    Happonen, Kaisa E; Saxne, Tore; Aspberg, Anders

    2010-01-01

    Cartilage oligomeric matrix protein (COMP) is a structural component of cartilage, where it catalyzes collagen fibrillogenesis. Elevated amounts of COMP are found in serum during increased turnover of cartilage associated with active joint disease, such as rheumatoid arthritis (RA) and osteoarthr...

  5. Lipid bilayer disruption by oligomeric α-synuclein depends on bilayer charge and accessibility of the hydrophobic core

    NARCIS (Netherlands)

    van Rooijen, Bart; Claessens, Mireille Maria Anna Elisabeth; Subramaniam, Vinod

    2009-01-01

    Soluble oligomeric aggregates of α-synuclein have been implicated to play a central role in the pathogenesis of Parkinson's disease. Disruption and permeabilization of lipid bilayers by α-synuclein oligomers is postulated as a toxic mechanism, but the molecular details controlling the

  6. Cobalt and Nickel Complexes Bearing 2,6-Bis(imino)phenoxy Ligands:Synthesis and Ethylene Oligomerization Study

    OpenAIRE

    Du, Jian-Long; Li, Li-Jun

    2006-01-01

    A series of new cobalt and nickel complexes MLX2 (M = Co or Ni, X = Cl) bearing 2,6-bis(imino)phenoxy ligands have been synthesized. Treatment of the complexes with methylaluminoxane (MAO) leads to active catalysts for ethylene oligomerization. The oligomers are olefins from C4 to C6.

  7. Cobalt and Nickel Complexes Bearing 2,6-Bis(iminophenoxy Ligands:Synthesis and Ethylene Oligomerization Study

    Directory of Open Access Journals (Sweden)

    Jian-Long Du

    2006-01-01

    Full Text Available A series of new cobalt and nickel complexes MLX2 (M = Co or Ni, X = Cl bearing 2,6-bis(iminophenoxy ligands have been synthesized. Treatment of the complexes with methylaluminoxane (MAO leads to active catalysts for ethylene oligomerization. The oligomers are olefins from C4 to C6.

  8. Bis(carbene)pyridine complexes of Cr(III): exceptionally active catalysts for the oligomerization of ethylene.

    Science.gov (United States)

    McGuinness, David S; Gibson, Vernon C; Wass, Duncan F; Steed, Jonathan W

    2003-10-22

    Pincer-heterocyclic carbene complexes of Cr(III), of the form [2,6-(1-alkylimidazol-2-ylidene)pyridine]CrCl3, have been prepared and evaluated as catalysts for the oligomerization of ethylene to alpha-olefins. In combination with methylaluminoxane cocatalyst, exceptionally high activities are obtained, ranging up to ca. 40 000 g mmol-1 bar-1 h-1.

  9. The extended reciprocity: Strong belief outperforms persistence.

    Science.gov (United States)

    Kurokawa, Shun

    2017-05-21

    The existence of cooperation is a mysterious phenomenon and demands explanation, and direct reciprocity is one key potential explanation for the evolution of cooperation. Direct reciprocity allows cooperation to evolve for cooperators who switch their behavior on the basis of information about the opponent's behavior. Here, relevant to direct reciprocity is information deficiency. When the opponent's last move is unknown, how should players behave? One possibility is to choose cooperation with some default probability without using any further information. In fact, our previous paper (Kurokawa, 2016a) examined this strategy. However, there might be beneficial information other than the opponent's last move. A subsequent study of ours (Kurokawa, 2017) examined the strategy which uses the own last move when the opponent's last move is unknown, and revealed that referring to the own move and trying to imitate it when information is absent is beneficial. Is there any other beneficial information else? How about strong belief (i.e., have infinite memory and believe that the opponent's behavior is unchanged)? Here, we examine the evolution of strategies with strong belief. Analyzing the repeated prisoner's dilemma game and using evolutionarily stable strategy (ESS) analysis against an invasion by unconditional defectors, we find the strategy with strong belief is more likely to evolve than the strategy which does not use information other than the opponent player's last move and more likely to evolve than the strategy which uses not only the opponent player's last move but also the own last move. Strong belief produces the extended reciprocity and facilitates the evolution of cooperation. Additionally, we consider the two strategies game between strategies with strong belief and any strategy, and we consider the four strategies game in which unconditional cooperators, unconditional defectors, pessimistic reciprocators with strong belief, and optimistic reciprocators with

  10. Chaperonin of Group I: Oligomeric Spectrum and Biochemical and Biological Implications

    Directory of Open Access Journals (Sweden)

    Silvia Vilasi

    2018-01-01

    Full Text Available Chaperonins play various physiological roles and can also be pathogenic. Elucidation of their structure, e.g., oligomeric status and post-translational modifications (PTM, is necessary to understand their functions and mechanisms of action in health and disease. Group I chaperonins form tetradecamers with two stacked heptameric rings. The tetradecamer is considered the typical functional complex for folding of client polypeptides. However, other forms such as the monomer and oligomers with smaller number of subunits than the classical tetradecamer, also occur in cells. The properties and functions of the monomer and oligomers, and their roles in chaperonin-associated diseases are still incompletely understood. Chaperonin I in eukaryotes occurs in various locations, not just the mitochondrion, which is its canonical place of residence and function. Eukaryotic Chaperonin I, namely Hsp60 (designated HSP60 or HSPD1 in humans has, indeed, been found in the cytosol; the plasma-cell membrane; on the outer surface of cells; in the intercellular space; in biological liquids such as lymph, blood, and cerebrospinal fluid; and in secretions, for instance saliva and urine. Hsp60 has also been found in cell-derived vesicles such as exosomes. The functions of Hsp60 in all these non-canonical locales are still poorly characterized and one of the questions not yet answered is in what form, i.e., monomer or oligomer, is the chaperonin present in these non-canonical locations. In view of the steady increase in interest on chaperonopathies over the last several years, we have studied human HSP60 to determine its role in various diseases, its locations in cells and tissues and migrations in the body, and its post-translational modifications that might have an impact on its location and function. We also carried out experiments to characterize the oligomeric status of extramitochondrial of HSP60 in solution. Here, we provide an overview of our results, focusing on

  11. Human α4β2 nicotinic acetylcholine receptor as a novel target of oligomeric α-synuclein.

    Directory of Open Access Journals (Sweden)

    Qiang Liu

    Full Text Available Cigarette smoking is associated with a decreased incidence of Parkinson disease (PD through unknown mechanisms. Interestingly, a decrease in the numbers of α4β2 nicotinic acetylcholine receptors (α4β2-nAChRs in PD patients suggests an α4β2-nAChR-mediated cholinergic deficit in PD. Although oligomeric forms of α-synuclein have been recognized to be toxic and involved in the pathogenesis of PD, their direct effects on nAChR-mediated cholinergic signaling remains undefined. Here, we report for the first time that oligomeric α-synuclein selectively inhibits human α4β2-nAChR-mediated currents in a dose-dependent, non-competitive and use-independent manner. We show that pre-loading cells with guanyl-5'-yl thiophosphate fails to prevent this inhibition, suggesting that the α-synuclein-induced inhibition of α4β2-nAChR function is not mediated by nAChR internalization. By using a pharmacological approach and cultures expressing transfected human nAChRs, we have shown a clear effect of oligomeric α-synuclein on α4β2-nAChRs, but not on α4β4- or α7-nAChRs, suggesting nAChR subunit selectivity of oligomeric α-synuclein-induced inhibition. In addition, by combining the size exclusion chromatography and atomic force microscopy (AFM analyses, we find that only large (>4 nm oligomeric α-synuclein aggregates (but not monomeric, small oligomeric or fibrillar α-synuclein aggregates exhibit the inhibitory effect on human α4β2-nAChRs. Collectively, we have provided direct evidence that α4β2-nAChR is a sensitive target to mediate oligomeric α-synuclein-induced modulation of cholinergic signaling, and our data imply that therapeutic strategies targeted toward α4β2-nAChRs may have potential for developing new treatments for PD.

  12. Oligomeric recombinant H5 HA1 vaccine produced in bacteria protects ferrets from homologous and heterologous wild-type H5N1 influenza challenge and controls viral loads better than subunit H5N1 vaccine by eliciting high-affinity antibodies.

    Science.gov (United States)

    Verma, Swati; Dimitrova, Milena; Munjal, Ashok; Fontana, Juan; Crevar, Corey J; Carter, Donald M; Ross, Ted M; Khurana, Surender; Golding, Hana

    2012-11-01

    Recombinant hemagglutinin from influenza viruses with pandemic potential can be produced rapidly in various cell substrates. In this study, we compared the functionality and immunogenicity of bacterially produced oligomeric or monomeric HA1 proteins from H5N1 (A/Vietnam/1203/04) with those of the egg-based licensed subunit H5N1 (SU-H5N1) vaccine in ferrets challenged with homologous or heterologous H5N1 highly pathogenic influenza strains. Ferrets were vaccinated twice with the oligomeric or monomeric rHA1 or with SU-H5N1 (Sanofi Pasteur) emulsified with Titermax adjuvant and were challenged with wild-type homologous (A/Vietnam/1203/04; clade 1) or heterologous (A/Whooperswan/Mongolia/244/2005; clade 2.2) virus. Only the oligomeric rHA1 (not the monomeric rHA1) immunogen and the SU-H5N1 vaccine provided protection against the lethality and morbidity of homologous and heterologous highly pathogenic H5N1. Oligomeric rHA1 generated more cross-neutralizing antibodies and higher levels of serum antibody binding to HA1, with stronger avidity and a better IgG/IgM ratio, than monomeric HA1 and SU-H5N1 vaccines, as determined by surface plasmon resonance (SPR). Importantly, viral loads after heterologous H5N1 challenge were more efficiently controlled in ferrets vaccinated with the oligomeric rHA1 immunogen than in SU-H5N1-vaccinated ferrets. The reduction of viral loads in the nasal washes correlated strongly with higher-avidity antibodies to oligomeric rHA1 derived from H5N1 clade 1 and clade 2.2 viruses, as measured by SPR. This is the first study to show the role of antibody avidity for the HA1 globular head domain in reduction of viral loads in the upper respiratory tract, which could significantly reduce viral transmission.

  13. Small-angle neutron scattering reveals the assembly mode and oligomeric architecture of TET, a large, dodecameric aminopeptidase

    Energy Technology Data Exchange (ETDEWEB)

    Appolaire, Alexandre; Girard, Eric; Colombo, Matteo; Durá, M. Asunción [Université Grenoble Alpes, IBS, 38044 Grenoble (France); CNRS, IBS, 38044 Grenoble (France); CEA, IBS, 38044 Grenoble (France); Moulin, Martine; Härtlein, Michael [Institut Laue–Langevin, 38042 Grenoble CEDEX 9 (France); Franzetti, Bruno [Université Grenoble Alpes, IBS, 38044 Grenoble (France); CNRS, IBS, 38044 Grenoble (France); CEA, IBS, 38044 Grenoble (France); Gabel, Frank, E-mail: frank.gabel@ibs.fr [Université Grenoble Alpes, IBS, 38044 Grenoble (France); CNRS, IBS, 38044 Grenoble (France); CEA, IBS, 38044 Grenoble (France); Institut Laue–Langevin, 38042 Grenoble CEDEX 9 (France)

    2014-11-01

    The present work illustrates that small-angle neutron scattering, deuteration and contrast variation, combined with in vitro particle reconstruction, constitutes a very efficient approach to determine subunit architectures in large, symmetric protein complexes. In the case of the 468 kDa heterododecameric TET peptidase machine, it was demonstrated that the assembly of the 12 subunits is a highly controlled process and represents a way to optimize the catalytic efficiency of the enzyme. The specific self-association of proteins into oligomeric complexes is a common phenomenon in biological systems to optimize and regulate their function. However, de novo structure determination of these important complexes is often very challenging for atomic-resolution techniques. Furthermore, in the case of homo-oligomeric complexes, or complexes with very similar building blocks, the respective positions of subunits and their assembly pathways are difficult to determine using many structural biology techniques. Here, an elegant and powerful approach based on small-angle neutron scattering is applied, in combination with deuterium labelling and contrast variation, to elucidate the oligomeric organization of the quaternary structure and the assembly pathways of 468 kDa, hetero-oligomeric and symmetric Pyrococcus horikoshii TET2–TET3 aminopeptidase complexes. The results reveal that the topology of the PhTET2 and PhTET3 dimeric building blocks within the complexes is not casual but rather suggests that their quaternary arrangement optimizes the catalytic efficiency towards peptide substrates. This approach bears important potential for the determination of quaternary structures and assembly pathways of large oligomeric and symmetric complexes in biological systems.

  14. Inhibition of listeriolysin O oligomerization by lutein prevents Listeria monocytogenes infection.

    Science.gov (United States)

    Liu, Bowen; Teng, Zihao; Wang, Jianfeng; Lu, Gejin; Deng, Xuming; Li, Li

    2017-01-01

    The foodborne pathogenic bacterial species Listeria monocytogenes (L. monocytogenes) has caused incalculable damages to public health, and its successful infection requires various virulence factors, including Listeriolysin O (LLO). By forming pores in phagosomal membranes and even in some organelles, LLO plays an indispensable role in the ability of L. monocytogenes to escape from host immune attacks. Because of its critical role, LLO offers an appropriate therapeutic target against L. monocytogenes infection. Here, lutein, a natural small molecule existing widely in fruits and vegetables, is demonstrated as an effective inhibitor of LLO that works by blocking its oligomerization during invasion without showing significant bacteriostatic activity. Further assays applying lutein in cell culture models of invasion and in animal models showed that lutein could effectively inhibit L. monocytogenes infection. Overall, our results indicate that lutein may represent a promising and novel therapeutic agent against L. monocytogenes infection. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Synthesis, and Micro-Phase Separation of Hybrid Organic-Inorganic Polyhedral Oligomeric Silsesquioxane Block Copolymers

    Science.gov (United States)

    Intasanta, Narupol; Russell, Thomas P.; Coughlin, E. Bryan

    2004-03-01

    Hybrid organic-inorganic di- and triblock copolymers containing Polyhedral Oligomeric Silsesquioxane (POSS) nanoparticles have been synthesized using Atom Transfer Radical Polymerization (ATRP). Chemical compositions and molecular weight distributions were determined by 1H NMR, and GPC, thermal properties were obtained by Differential Scanning Calorimetry (DSC) and Thermal Gravimetric Analysis (TGA). The block copolymers include either Methyl methacrylate (MMA), Styrene, or n-Butyl Acrylate (nBuA) as the organic block. Bulk morphologies and order-disorder transition phenomenon have been studied using Small Angle X-ray Scattering (SAXS). Thin film morphologies and interfacial interactions were investigated utilizing Atomic Force Microscopy (AFM). Fundamental studies on the dynamics of the polymers with, and without, applied external field have also been conducted. For PMMA containing block copolymers, the MMA blocks have been selectively degraded using UV irradiation and consequentially transformed into glass-like nano-patterned array utilizing oxygen plasma oxidation.

  16. Menthols as Chiral Auxiliaries for Asymmetric Cycloadditive Oligomerization: Syntheses and Studies of β-Proline Hexamers.

    Science.gov (United States)

    Kudryavtsev, Konstantin V; Ivantcova, Polina M; Muhle-Goll, Claudia; Churakov, Andrei V; Sokolov, Mikhail N; Dyuba, Artem V; Arutyunyan, Alexander M; Howard, Judith A K; Yu, Chia-Chun; Guh, Jih-Hwa; Zefirov, Nikolay S; Bräse, Stefan

    2015-12-18

    To produce a novel class of structurally ordered poly-β-prolines, an emergent method for synthesizing chiral β-peptide molecular frameworks was developed based on 1,3-dipolar cycloaddition chemistry of azomethine ylides. Functionalized short β-peptides with up to six monomeric residues were efficiently synthesized in homochiral forms using a cycloadditive oligomerization approach. X-ray, NMR, and CD structural analyses of the novel β-peptides revealed secondary structure features that were generated primarily by Z/E-β-peptide bond isomerism. Anticancer in cellulo activity of the new β-peptides toward hormone-refractory prostate cancer cells was observed and was dependent on the absolute configuration of the stereogenic centers and the chain length of the β-proline oligomers.

  17. Tunable Gravimetric and Volumetric Hydrogen Storage Capacities in Polyhedral Oligomeric Silsesquioxane Frameworks.

    Science.gov (United States)

    Deshmukh, Amol; Chiu, Cheng-Chau; Chen, Yun-Wen; Kuo, Jer-Lai

    2016-09-28

    We study the hydrogen adsorption in porous frameworks composed of silsesquioxane cages linked via boron substituted aromatic structures by first-principles modeling. Such polyhedral oligomeric silsesquioxane (POSS) frameworks can be further modified by decorating them with metal atoms binding to the ring structures of the linkers. We have considered Sc- and Ti-doped frameworks which bind H2 via so-called Kubas interaction between hydrogen molecules and transition metal atoms. It will be demonstrated that the maximum H2 gravimetric capacity can be improved to more than 7.5 wt % by using longer linkers with more ring structures. However, the maximum H2 volumetric capacity can be tuned to more than 70 g/L by varying the size of silsesquioxane cages. We are optimistic that by varying the building blocks, POSS frameworks can be modified to meet the targets for the gravimetric and volumetric capacities set by the U.S. Department of Energy.

  18. Flow cytometry evidence of human granulocytes interaction with polyhedral oligomeric silsesquioxanes: effect of nanoparticle charge

    Science.gov (United States)

    Renò, Filippo; Carniato, Fabio; Rizzi, Manuela; Olivero, Francesco; Pittarella, Pamela; Marchese, Leonardo

    2013-05-01

    Nanoparticles (NPs) entering the human body are immediately confronted with the innate part of human immune system. In particular, monocyte and neutrophil granulocytes readily clear particles by phagocytosis, even if in the case of NPs the uptake mechanism may be classified as macropinocytosis. Among engineered nanoparticles, in the last years, siliceous materials have emerged as promising materials for several applications ranging from catalysis to biomedical. The polyhedral oligomeric silsesquioxanes (POSS) are nanodimensional, easily synthesizable molecular compounds and POSS-based systems are promising carriers for biological molecules. In this work, the ability of human granulocytes to uptake positively and negatively charged POSS was measured using a simple flow cytometry analysis based on cell size modifications. The data obtained showed that after a 30 min exposure only positive NPs were uptaken by human granulocyte using both macropinocytosis and clathrin-mediated mechanisms as demonstrated by uptake inhibition mediated by amiloride and chlorpromazine.

  19. Efficient light-emitting devices based on platinum-complexes-anchored polyhedral oligomeric silsesquioxane materials

    KAUST Repository

    Yang, Xiaohui

    2010-08-24

    The synthesis, photophysical, and electrochemical characterization of macromolecules, consisting of an emissive platinum complex and carbazole moieties covalently attached to a polyhedral oligomeric silsesquioxane (POSS) core, is reported. Organic light-emitting devices based on these POSS materials exhibit a peak external quantum efficiency of ca. 8%, which is significantly higher than that of the analogous devices with a physical blend of the platinum complexes and a polymer matrix, and they represent noticeable improvement in the device efficiency of solution-processable phosphorescent excimer devices. Furthermore, the ratio of monomer and excimer/aggregate electroluminescent emission intensity, as well as the device efficiency, increases as the platinum complex moiety presence on the POSS macromolecules decreases. © 2010 American Chemical Society.

  20. Ni-exchanged AlSBA-15 mesoporous materials as outstanding catalysts for ethylene oligomerization

    Science.gov (United States)

    Andrei, R. D.; Mureseanu, M.; Popa, M. I.; Cammarano, C.; Fajula, F.; Hulea, V.

    2015-07-01

    Ni-exchanged mesoporous materials with SBA-15 topology were prepared by post-synthesis alumination of SBA-15 silica with sodium aluminate at room temperature, followed by ion exchange with nickel. Exploration of various parameters resulted in a simple preparation method for catalysts with perfect pore system and aluminium tetrahedrally coordinated in the silica framework for Si/Al > 6. These properties were proved by using appropriate characterisation techniques, including powder X-ray diffraction, N2 sorption, TEM, and 27Al MAS NMR. Ni-AlSBA-15 exhibited outstanding catalytic properties in the oligomerization reaction of ethylene performed at 150 ∘C and 3.5 MPa. Activity up to 175 g of oligomers per gram of catalyst per hour was the highest reported to date with Ni-based solid catalysts.

  1. Evolutionarily conserved domain of heat shock transcription factor negatively regulates oligomerization and DNA binding.

    Science.gov (United States)

    Ota, Azumi; Enoki, Yasuaki; Yamamoto, Noritaka; Sawai, Maki; Sakurai, Hiroshi

    2013-09-01

    Heat shock transcription factor (HSF) regulates the expression of genes encoding molecular chaperones and stress-responsive proteins. Conversion of HSF from a monomer to a homotrimer or heterotrimer is essential for its binding to heat shock elements (HSEs) comprised of inverted repeats of the pentamer nGAAn. Here, we constructed various human HSF1 derivatives and analyzed their transcriptional activity through the continuously and discontinuously arranged nGAAn units. We identified a short stretch of amino acids that inhibits the activation ability of HSF1, especially through discontinuous HSEs. This stretch is conserved in HSFs of various organisms, interacts with the hydrophobic repeat regions that mediate HSF oligomerization, and impedes homotrimer formation and DNA binding. This conserved domain plays an important role in maintaining HSF in an inactive monomeric form. Copyright © 2013 Elsevier B.V. All rights reserved.

  2. An Intramolecular Salt Bridge in Bacillus thuringiensis Cry4Ba Toxin Is Involved in the Stability of Helix α-3, Which Is Needed for Oligomerization and Insecticidal Activity.

    Science.gov (United States)

    Pacheco, Sabino; Gómez, Isabel; Sánchez, Jorge; García-Gómez, Blanca-Ines; Soberón, Mario; Bravo, Alejandra

    2017-10-15

    Bacillus thuringiensis three-domain Cry toxins kill insects by forming pores in the apical membrane of larval midgut cells. Oligomerization of the toxin is an important step for pore formation. Domain I helix α-3 participates in toxin oligomerization. Here we identify an intramolecular salt bridge within helix α-3 of Cry4Ba (D111-K115) that is conserved in many members of the family of three-domain Cry toxins. Single point mutations such as D111K or K115D resulted in proteins severely affected in toxicity. These mutants were also altered in oligomerization, and the mutant K115D was more sensitive to protease digestion. The double point mutant with reversed charges, D111K-K115D, recovered both oligomerization and toxicity, suggesting that this salt bridge is highly important for conservation of the structure of helix α-3 and necessary to promote the correct oligomerization of the toxin. IMPORTANCE Domain I has been shown to be involved in oligomerization through helix α-3 in different Cry toxins, and mutations affecting oligomerization also elicit changes in toxicity. The three-dimensional structure of the Cry4Ba toxin reveals an intramolecular salt bridge in helix α-3 of domain I. Mutations that disrupt this salt bridge resulted in changes in Cry4Ba oligomerization and toxicity, while a double point reciprocal mutation that restored the salt bridge resulted in recovery of toxin oligomerization and toxicity. These data highlight the role of oligomer formation as a key step in Cry4Ba toxicity. Copyright © 2017 American Society for Microbiology.

  3. Core-6 fucose and the oligomerization of the 1918 pandemic influenza viral neuraminidase

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Zhengliang L., E-mail: Leon.wu@bio-techne.com [Bio-Techne Inc., 614 McKinley Place NE, Minneapolis, MN 55413 (United States); Zhou, Hui [Gregg Hall, UNH Glycomics Center, University of New Hampshire (United States); Ethen, Cheryl M. [Bio-Techne Inc., 614 McKinley Place NE, Minneapolis, MN 55413 (United States); Reinhold, Vernon N., E-mail: Vernon.Reinhold@unh.edu [Gregg Hall, UNH Glycomics Center, University of New Hampshire (United States)

    2016-04-29

    The 1918 H1N1 influenza virus was responsible for one of the most deadly pandemics in human history. Yet to date, the structure component responsible for its virulence is still a mystery. In order to search for such a component, the neuraminidase (NA) antigen of the virus was expressed, which led to the discovery of an active form (tetramer) and an inactive form (dimer and monomer) of the protein due to different glycosylation. In this report, the N-glycans from both forms were released and characterized by mass spectrometry. It was found that the glycans from the active form had 26% core-6 fucosylated, while the glycans from the inactive form had 82% core-6 fucosylated. Even more surprisingly, the stalk region of the active form was almost completely devoid of core-6-linked fucose. These findings were further supported by the results obtained from in vitro incorporation of azido fucose and {sup 3}H-labeled fucose using core-6 fucosyltransferase, FUT8. In addition, the incorporation of fucose did not change the enzymatic activity of the active form, implying that core-6 fucose is not directly involved in the enzymatic activity. It is postulated that core-6 fucose prohibits the oligomerization and subsequent activation of the enzyme. - Graphical abstract: Proposed mechanism for how core-fucose prohibits the tetramerization of the 1918 pandemic viral neuraminidase. Only the cross section of the stalk region with two N-linked glycans are depicted for clarity. (A) Carbohydrate–carbohydrate interaction on non-fucosylated monomer allows tetramerization. (B) Core-fucosylation disrupts the interaction and prevents the tetramerization. - Highlights: • Expressed 1918 pandemic influenza viral neuraminidase has inactive and active forms. • The inactive form contains high level of core-6 fucose, while the active form lacks such modification. • Core fucose could interfere the oligomerization of the neuraminidase and thus its activation. • This discovery may explain

  4. Core-6 fucose and the oligomerization of the 1918 pandemic influenza viral neuraminidase

    International Nuclear Information System (INIS)

    Wu, Zhengliang L.; Zhou, Hui; Ethen, Cheryl M.; Reinhold, Vernon N.

    2016-01-01

    The 1918 H1N1 influenza virus was responsible for one of the most deadly pandemics in human history. Yet to date, the structure component responsible for its virulence is still a mystery. In order to search for such a component, the neuraminidase (NA) antigen of the virus was expressed, which led to the discovery of an active form (tetramer) and an inactive form (dimer and monomer) of the protein due to different glycosylation. In this report, the N-glycans from both forms were released and characterized by mass spectrometry. It was found that the glycans from the active form had 26% core-6 fucosylated, while the glycans from the inactive form had 82% core-6 fucosylated. Even more surprisingly, the stalk region of the active form was almost completely devoid of core-6-linked fucose. These findings were further supported by the results obtained from in vitro incorporation of azido fucose and 3 H-labeled fucose using core-6 fucosyltransferase, FUT8. In addition, the incorporation of fucose did not change the enzymatic activity of the active form, implying that core-6 fucose is not directly involved in the enzymatic activity. It is postulated that core-6 fucose prohibits the oligomerization and subsequent activation of the enzyme. - Graphical abstract: Proposed mechanism for how core-fucose prohibits the tetramerization of the 1918 pandemic viral neuraminidase. Only the cross section of the stalk region with two N-linked glycans are depicted for clarity. (A) Carbohydrate–carbohydrate interaction on non-fucosylated monomer allows tetramerization. (B) Core-fucosylation disrupts the interaction and prevents the tetramerization. - Highlights: • Expressed 1918 pandemic influenza viral neuraminidase has inactive and active forms. • The inactive form contains high level of core-6 fucose, while the active form lacks such modification. • Core fucose could interfere the oligomerization of the neuraminidase and thus its activation. • This discovery may explain why

  5. EDITORIAL: Strongly correlated electron systems Strongly correlated electron systems

    Science.gov (United States)

    Ronning, Filip; Batista, Cristian

    2011-03-01

    Strongly correlated electrons is an exciting and diverse field in condensed matter physics. This special issue aims to capture some of that excitement and recent developments in the field. Given that this issue was inspired by the 2010 International Conference on Strongly Correlated Electron Systems (SCES 2010), we briefly give some history in order to place this issue in context. The 2010 International Conference on Strongly Correlated Electron Systems was held in Santa Fe, New Mexico, a reunion of sorts from the 1989 International Conference on the Physics of Highly Correlated Electron Systems that also convened in Santa Fe. SCES 2010—co-chaired by John Sarrao and Joe Thompson—followed the tradition of earlier conferences, in this century, hosted by Buzios (2008), Houston (2007), Vienna (2005), Karlsruhe (2004), Krakow (2002) and Ann Arbor (2001). Every three years since 1997, SCES has joined the International Conference on Magnetism (ICM), held in Recife (2000), Rome (2003), Kyoto (2006) and Karlsruhe (2009). Like its predecessors, SCES 2010 topics included strongly correlated f- and d-electron systems, heavy-fermion behaviors, quantum-phase transitions, non-Fermi liquid phenomena, unconventional superconductivity, and emergent states that arise from electronic correlations. Recent developments from studies of quantum magnetism and cold atoms complemented the traditional subjects and were included in SCES 2010. 2010 celebrated the 400th anniversary of Santa Fe as well as the birth of astronomy. So what's the connection to SCES? The Dutch invention of the first practical telescope and its use by Galileo in 1610 and subsequent years overturned dogma that the sun revolved about the earth. This revolutionary, and at the time heretical, conclusion required innovative combinations of new instrumentation, observation and mathematics. These same combinations are just as important 400 years later and are the foundation of scientific discoveries that were discussed

  6. The role of surface electrostatics on the stability, function and regulation of human cystathionine β-synthase, a complex multidomain and oligomeric protein.

    Science.gov (United States)

    Pey, Angel L; Majtan, Tomas; Kraus, Jan P

    2014-09-01

    Human cystathionine β-synthase (hCBS) is a key enzyme of sulfur amino acid metabolism, controlling the commitment of homocysteine to the transsulfuration pathway and antioxidant defense. Mutations in hCBS cause inherited homocystinuria (HCU), a rare inborn error of metabolism characterized by accumulation of toxic homocysteine in blood and urine. hCBS is a complex multidomain and oligomeric protein whose activity and stability are independently regulated by the binding of S-adenosyl-methionine (SAM) to two different types of sites at its C-terminal regulatory domain. Here we study the role of surface electrostatics on the complex regulation and stability of hCBS using biophysical and biochemical procedures. We show that the kinetic stability of the catalytic and regulatory domains is significantly affected by the modulation of surface electrostatics through noticeable structural and energetic changes along their denaturation pathways. We also show that surface electrostatics strongly affect SAM binding properties to those sites responsible for either enzyme activation or kinetic stabilization. Our results provide new insight into the regulation of hCBS activity and stability in vivo with implications for understanding HCU as a conformational disease. We also lend experimental support to the role of electrostatic interactions in the recently proposed binding modes of SAM leading to hCBS activation and kinetic stabilization. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. Development of the optical sensor for discriminating isomers of fatty acids based on emissive network polymers composed of polyhedral oligomeric silsesquioxane.

    Science.gov (United States)

    Narikiyo, Hayato; Kakuta, Takahiro; Matsuyama, Hiroki; Gon, Masayuki; Tanaka, Kazuo; Chujo, Yoshiki

    2017-07-01

    It was shown that water-soluble network polymers composed of polyhedral oligomeric silsesquioxane (POSS) had hydrophobic spaces inside the network because of strong hydrophobicity of the cubic silica cage. In this study, the water-soluble POSS network polymers connected with triphenylamine derivatives (TPA-POSS) were synthesized, and their functions as a sensor for discriminating the geometric isomers of fatty acids were investigated. Accordingly, in the photoluminescence spectra, different time-courses of intensity and peak wavelengths of the emission bands were detected from the TPA-POSS-containing solution in the presence of cis- or trans-fatty acids during incubation. Furthermore, variable time-dependent changes were obtained by changing coexisting ratios between two geometric isomers. From the mechanistic investigation, it was implied that these changes could be originated from the difference in the degree of interaction between the POSS networks and each fatty acid. Our data could be applicable for constructing a sensing material for generation and proportion of trans-fatty acids in the oil. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. An important role of temperature dependent scattering time in understanding the high temperature thermoelectric behavior of strongly correlated system: La0.75Ba0.25CoO3.

    Science.gov (United States)

    Singh, Saurabh; Kumar, Devendra; Pandey, Sudhir K

    2017-03-15

    In the present work, we report the temperature dependent thermopower (α) behavior of La 0.75 Ba 0.25 CoO 3 compound in the temperature range 300-600 K. Using the Heikes formula, the estimated value of α corresponding to high-spin configuration of Co 3+ and Co 4+ ions is found to be  ∼16 [Formula: see text], which is close to the experimental value, ∼13 [Formula: see text], observed at  ∼600 K. The temperature dependent TE behavior of the compound is studied by combining the WIEN2K and BoltzTrap code. The self consistency field calculations show that the compound have ferromagnetic ground state structure. The electronic structure calculations give half metallic characteristic with a small gap of  ∼50 meV for down spin channel. The large and positive value for down spin channel is obtained due to the unique band structure shown by this spin channel. The temperature dependent relaxation time for both the spin-channel charge carriers is considered to study the thermopower data in temperature range 300-600 K. For evaluation of α, almost linear values of [Formula: see text] and a non-linear values of [Formula: see text] are taken into account. By taking the temperature dependent values of relaxation time for both the spin channels, the calculated values of α using two current model are found to be in good agreement with experimental values in the temperature range 300-600 K. At 300 K, the calculated value of electrical conductivity by using the same value of relaxation time, i.e. 0.1 [Formula: see text] 10 -14 seconds for spin-up and [Formula: see text] seconds for spin-dn channel, is found to be equal to the experimentally reported value.

  9. Inhibiting α-synuclein oligomerization by stable cell-penetrating β-synuclein fragments recovers phenotype of Parkinson's disease model flies.

    Directory of Open Access Journals (Sweden)

    Ronit Shaltiel-Karyo

    Full Text Available The intracellular oligomerization of α-synuclein is associated with Parkinson's disease and appears to be an important target for disease-modifying treatment. Yet, to date, there is no specific inhibitor for this aggregation process. Using unbiased systematic peptide array analysis, we identified molecular interaction domains within the β-synuclein polypeptide that specifically binds α-synuclein. Adding such peptide fragments to α-synuclein significantly reduced both amyloid fibrils and soluble oligomer formation in vitro. A retro-inverso analogue of the best peptide inhibitor was designed to develop the identified molecular recognition module into a drug candidate. While this peptide shows indistinguishable activity as compared to the native peptide, it is stable in mouse serum and penetrates α-synuclein over-expressing cells. The interaction interface between the D-amino acid peptide and α-synuclein was mapped by Nuclear Magnetic Resonance spectroscopy. Finally, administering the retro-inverso peptide to a Drosophila model expressing mutant A53T α-synuclein in the nervous system, resulted in a significant recovery of the behavioral abnormalities of the treated flies and in a significant reduction in α-synuclein accumulation in the brains of the flies. The engineered retro-inverso peptide can serve as a lead for developing a novel class of therapeutic agents to treat Parkinson's disease.

  10. Purification, crystallization and preliminary crystallographic analysis of Est-Y29: a novel oligomeric β-lactamase

    International Nuclear Information System (INIS)

    Kim, SeungBum; Joo, Sangbum; Yoon, Sangyoung; Kim, Sungsoo; Moon, Jongkook; Ryu, Yeonwoo; Kim, Kyeong Kyu; Kim, T. Doohun

    2009-01-01

    Est-Y29, a novel oligomeric class C β-lactamase from a metagenomic library, was crystallized in space group I4 1 and diffraction data were collected to 1.49 Å resolution. β-Lactam antibiotics such as penicillins and cephalosporins have a four-atom ring as a common element in their structure. The β-lactamases, which catalyze the inactivation of these antibiotics, are of great interest because of their high incidence in pathogenic bacteria. A novel oligomeric class C β-lactamase (Est-Y29) from a metagenomic library was expressed, purified and crystallized. The recombinant protein was expressed in Escherichia coli with an N-terminal 6×His tag and purified to homogeneity. EstY-29 was crystallized and X-ray intensity data were collected to 1.49 Å resolution using synchrotron radiation

  11. Characterization of oligomerization of a peptide from the ebola virus glycoprotein by small-angle neutron scattering

    International Nuclear Information System (INIS)

    Egorov, V. V.; Gorshkov, A. N.; Murugova, T. N.; Vasin, A. V.; Lebedev, D. V.; Isaev-Ivanov, V. V.; Kiselev, O. I.

    2016-01-01

    Transmission electron microscopy (TEM) and small-angle neutron scattering (SANS) studies showed that model peptides QNALVCGLRQ (G33) and QNALVCGLRG (G31) corresponding to region 551–560 of the GP protein of the Sudan Ebola virus are prone to oligomerization in solution. Both peptides can form amyloid-like fibrills. The G33 peptide forms fibrils within one day of incubation, whereas the fibrillogenesis of the G31 peptide is observed only after incubation for several months. The possible role of the observed processes in the pathogenesis and the possibility of applying a combination of the TEM and SANS techniques to search for new compounds that are able to influence the protein oligomerization are discussed

  12. Characterization of oligomerization of a peptide from the ebola virus glycoprotein by small-angle neutron scattering

    Energy Technology Data Exchange (ETDEWEB)

    Egorov, V. V., E-mail: vlaegur@omrb.pnpi.spb.ru [National Research Center “Kurchatov Institute”, Konstantinov Petersburg Nuclear Physics Institute (Russian Federation); Gorshkov, A. N. [Ministry of Health of the Russian Federation, Research Institute of Influenza (Russian Federation); Murugova, T. N. [Joint Institute for Nuclear Research (Russian Federation); Vasin, A. V. [Ministry of Health of the Russian Federation, Research Institute of Influenza (Russian Federation); Lebedev, D. V.; Isaev-Ivanov, V. V. [National Research Center “Kurchatov Institute”, Konstantinov Petersburg Nuclear Physics Institute (Russian Federation); Kiselev, O. I. [Ministry of Health of the Russian Federation, Research Institute of Influenza (Russian Federation)

    2016-01-15

    Transmission electron microscopy (TEM) and small-angle neutron scattering (SANS) studies showed that model peptides QNALVCGLRQ (G33) and QNALVCGLRG (G31) corresponding to region 551–560 of the GP protein of the Sudan Ebola virus are prone to oligomerization in solution. Both peptides can form amyloid-like fibrills. The G33 peptide forms fibrils within one day of incubation, whereas the fibrillogenesis of the G31 peptide is observed only after incubation for several months. The possible role of the observed processes in the pathogenesis and the possibility of applying a combination of the TEM and SANS techniques to search for new compounds that are able to influence the protein oligomerization are discussed.

  13. Characterization of oligomerization of a peptide from the ebola virus glycoprotein by small-angle neutron scattering

    Science.gov (United States)

    Egorov, V. V.; Gorshkov, A. N.; Murugova, T. N.; Vasin, A. V.; Lebedev, D. V.; Isaev-Ivanov, V. V.; Kiselev, O. I.

    2016-01-01

    Transmission electron microscopy (TEM) and small-angle neutron scattering (SANS) studies showed that model peptides QNALVCGLRQ (G33) and QNALVCGLRG (G31) corresponding to region 551-560 of the GP protein of the Sudan Ebola virus are prone to oligomerization in solution. Both peptides can form amyloid-like fibrills. The G33 peptide forms fibrils within one day of incubation, whereas the fibrillogenesis of the G31 peptide is observed only after incubation for several months. The possible role of the observed processes in the pathogenesis and the possibility of applying a combination of the TEM and SANS techniques to search for new compounds that are able to influence the protein oligomerization are discussed.

  14. Thermally induced disintegration of the oligomeric structure of alphaB-crystallin mutant F28S is associated with diminished chaperone activity.

    Science.gov (United States)

    Kelley, Patrick B; Abraham, Edathara C

    2003-10-01

    alphaB-crystallin, a member of the small heat-shock protein (hsp) family of proteins, is able to function as a molecular chaperone by protecting other proteins from stress-induced aggregation by recognizing and binding to partially unfolded species of damaged proteins. The present work has investigated the role of phenylalanine-28 (F28) of the 22RLFDQFF28 region of alphaB-crystallin in maintaining chaperone function and oligomeric structure under physiological condition and under thermal stress. Bovine alphaB-crystallin was cloned for the first time and the cDNA sequence revealed greater than 90% homology to that of human, rat and mouse alphaB-crystallins. F28 was mutated to a serine followed by expression of the mutant F28S and the wild-type alphaB (alphaB-wt) in E. coli and subsequent purification of the protein by size-exclusion chromatography. Secondary and tertiary structure analyses showed some structural changes in the mutant. Chaperone activity and oligomeric size of the mutant was unchanged at 37 degrees C whereas at 58 degrees C the chaperone activity was significantly decreased and the oligomeric size ranged from low molecular weight to high molecular weight showing disintegration of the oligomeric structure. The data support the idea that the participation of large oligomeric structure rather than smaller units is required to have optimal chaperone activity and the hydrophobic F28 residue is needed for maintaining the native oligomeric structure under thermal stress.

  15. Structural determinants of oligomerization of δ(1)-pyrroline-5-carboxylate dehydrogenase: identification of a hexamerization hot spot.

    Science.gov (United States)

    Luo, Min; Singh, Ranjan K; Tanner, John J

    2013-09-09

    The aldehyde dehydrogenase (ALDH) superfamily member Δ(1)-pyrroline-5-carboxylate dehydrogenase (P5CDH) catalyzes the NAD(+)-dependent oxidation of glutamate semialdehyde to glutamate, which is the final step of proline catabolism. Defects in P5CDH activity lead to the metabolic disorder type II hyperprolinemia, P5CDH is essential for virulence of the fungal pathogen Cryptococcus neoformans, and bacterial P5CDHs have been targeted for vaccine development. Although the enzyme oligomeric state is known to be important for ALDH function, the oligomerization of P5CDH has remained relatively unstudied. Here we determine the oligomeric states and quaternary structures of four bacterial P5CDHs using a combination of small-angle X-ray scattering, X-ray crystallography, and dynamic light scattering. The P5CDHs from Thermus thermophilus and Deinococcus radiodurans form trimer-of-dimers hexamers in solution, which is the first observation of a hexameric ALDH in solution. In contrast, two Bacillus P5CDHs form dimers in solution but do not assemble into a higher-order oligomer. Site-directed mutagenesis was used to identify a hexamerization hot spot that is centered on an arginine residue in the NAD(+)-binding domain. Mutation of this critical Arg residue to Ala in either of the hexameric enzymes prevents hexamer formation in solution. Paradoxically, the dimeric Arg-to-Ala T. thermophilus mutant enzyme packs as a hexamer in the crystal state, which illustrates the challenges associated with predicting the biological assembly in solution from crystal structures. The observation of different oligomeric states among P5CDHs suggests potential differences in cooperativity and protein-protein interactions. Copyright © 2013 Elsevier Ltd. All rights reserved.

  16. Synthesis and Catalytic Performances of a Novel Zn-MOF Catalyst Bearing Nickel Chelating Diimine Carboxylate Ligands for Ethylene Oligomerization

    Directory of Open Access Journals (Sweden)

    Suyan Liu

    2015-01-01

    Full Text Available A novel Zn-MOF[Zn3(OH2L2] was synthesized from dicarboxylate ligands with diimine groups (1,4-bis(4-CO2HC6H4-2,3-dimethyl-1,4-diazabutadiene. The physicochemical properties of the material were characterized by a series of technologies including XRD, SEM, and ICP. In order to adapt to the ethylene oligomerization process, a catalyst [Zn3OH2L1Ni2] (denoted as Cat.A possessing active Ni2+ centers was prepared by a postsynthetic treatment method using dichloride nickel as a nickel source in this work. For comparison, α-diimine ligands with/without dicarboxylic acid groups reacted with dichloride nickel to obtain homogenous Cat.B and Cat.C, respectively. The effects of reaction parameters, including n(Al/n(Ni, temperature, and pressure on the oligomerization activities and oligomers distribution were investigated. The results demonstrated that all of catalysts used with diethylaluminum chloride were active for the ethylene oligomerization. Among them, Cat.A and Cat.B showed higher catalytic activities and higher selectivities to low-carbon α-olefins at atmospheric pressure. The Cat.A exhibited the optimal catalytic activity [6.7 × 105 g/(mol·Ni·h·atm] for C4 (91.8% under the conditions of Al/Ni = 1500, P = 1.0 atm, T = 20°C. In addition, Cat.A and Cat.B presented large amount of ethylene polymer, while Cat.C had a higher catalytic activity of ethylene oligomerization at high pressure.

  17. Mechanistic Studies of Ethylene and α-Olefin Co-Oligomerization Catalyzed by Chromium−PNP Complexes

    OpenAIRE

    Do, Loi H.; Labinger, Jay A.; Bercaw, John E.

    2012-01-01

    To explore the possibility of producing a narrow distribution of mid- to long-chain hydrocarbons from ethylene as a chemical feedstock, co-oligomerization of ethylene and linear α-olefins (LAOs) was investigated, using a previously reported chromium complex, [CrCl_3(PNP^(OMe))] (1, where PNP^(OMe) = N,N-bis(bis(o-methoxyphenyl)- phosphino)methylamine). Activation of 1 by treatment with modified methylaluminoxane (MMAO) in the presence of ethylene and 1-hexene afforded mos...

  18. Quantum electrodynamics of strong fields

    International Nuclear Information System (INIS)

    Greiner, W.

    1983-01-01

    Quantum Electrodynamics of Strong Fields provides a broad survey of the theoretical and experimental work accomplished, presenting papers by a group of international researchers who have made significant contributions to this developing area. Exploring the quantum theory of strong fields, the volume focuses on the phase transition to a charged vacuum in strong electric fields. The contributors also discuss such related topics as QED at short distances, precision tests of QED, nonperturbative QCD and confinement, pion condensation, and strong gravitational fields In addition, the volume features a historical paper on the roots of quantum field theory in the history of quantum physics by noted researcher Friedrich Hund

  19. Oligomeric adiponectin forms and their complexes in the blood of healthy donors and patients with type 2 diabetes mellitus.

    Science.gov (United States)

    Kogan, Alexander E; Filatov, Vladimir L; Kolosova, Olga V; Katrukha, Ivan A; Mironova, Ekaterina V; Zhuravleva, Natalya S; Nagibin, Oleg A; Kara, Andrei N; Bereznikova, Anastasiya V; Katrukha, Alexey G

    2013-01-01

    Adiponectin (Adn) is a protein that circulates in the blood in several oligomeric forms, namely low-, medium-, and high-molecular-weight forms. Adn may serve as a risk factor for type 2 diabetes mellitus (T2DM). The aims of this work were (1) to produce monoclonal antibodies (MAbs) specific to different Adn oligomeric forms, (2) to design immunoassays suitable for measuring the Adn forms present in human blood, and (3) to investigate the changes in Adn forms that occur in patients with T2DM. Gel filtration, fluoroimmunoassays, and Western blotting were utilized as major techniques in this study. MAbs recognizing various oligomeric forms of Adn were obtained. Complexes between Adn and complement component C1q and between the low molecular weight form of Adn and albumin were described in human blood. A decrease in the total Adn and Adn-albumin complex levels in the blood of patients with T2DM and no difference in the levels of the Adn-C1q complex in comparison with healthy volunteers were demonstrated. An Adn94-Adn63 fluoroimmunoassay was selected as the technique that most accurately measured the mass ratio of Adn oligomers in blood samples, and an Adn214-Adn27 assay that measured the low-molecular-weight form of Adn only.

  20. The Pseudo signal peptide of the corticotropin-releasing factor receptor type 2A prevents receptor oligomerization.

    Science.gov (United States)

    Teichmann, Anke; Rutz, Claudia; Kreuchwig, Annika; Krause, Gerd; Wiesner, Burkhard; Schülein, Ralf

    2012-08-03

    N-terminal signal peptides mediate the interaction of native proteins with the translocon complex of the endoplasmic reticulum membrane and are cleaved off during early protein biogenesis. The corticotropin-releasing factor receptor type 2a (CRF(2(a))R) possesses an N-terminal pseudo signal peptide, which represents a so far unique domain within the large protein family of G protein-coupled receptors (GPCRs). In contrast to a conventional signal peptide, the pseudo signal peptide remains uncleaved and consequently forms a hydrophobic extension at the N terminus of the receptor. The functional consequence of the presence of the pseudo signal peptide is not understood. Here, we have analyzed the significance of this domain for receptor dimerization/oligomerization in detail. To this end, we took the CRF(2(a))R and the homologous corticotropin-releasing factor receptor type 1 (CRF(1)R) possessing a conventional cleaved signal peptide and conducted signal peptide exchange experiments. Using single cell and single molecule imaging methods (fluorescence resonance energy transfer and fluorescence cross-correlation spectroscopy, respectively) as well as biochemical experiments, we obtained two novel findings; we could show that (i) the CRF(2(a))R is expressed exclusively as a monomer, and (ii) the presence of the pseudo signal peptide prevents its oligomerization. Thus, we have identified a novel functional domain within the GPCR protein family, which plays a role in receptor oligomerization and which may be useful to study the functional significance of this process in general.

  1. Strong WW Interaction at LHC

    Energy Technology Data Exchange (ETDEWEB)

    Pelaez, Jose R

    1998-12-14

    We present a brief pedagogical introduction to the Effective Electroweak Chiral Lagrangians, which provide a model independent description of the WW interactions in the strong regime. When it is complemented with some unitarization or a dispersive approach, this formalism allows the study of the general strong scenario expected at the LHC, including resonances.

  2. Reversible unfolding of infectious prion assemblies reveals the existence of an oligomeric elementary brick.

    Directory of Open Access Journals (Sweden)

    Angélique Igel-Egalon

    2017-09-01

    Full Text Available Mammalian prions, the pathogens that cause transmissible spongiform encephalopathies, propagate by self-perpetuating the structural information stored in the abnormally folded, aggregated conformer (PrPSc of the host-encoded prion protein (PrPC. To date, no structural model related to prion assembly organization satisfactorily describes how strain-specified structural information is encoded and by which mechanism this information is transferred to PrPC. To achieve progress on this issue, we correlated the PrPSc quaternary structural transition from three distinct prion strains during unfolding and refolding with their templating activity. We reveal the existence of a mesoscopic organization in PrPSc through the packing of a highly stable oligomeric elementary subunit (suPrP, in which the strain structural determinant (SSD is encoded. Once kinetically trapped, this elementary subunit reversibly loses all replicative information. We demonstrate that acquisition of the templating interface and infectivity requires structural rearrangement of suPrP, in concert with its condensation. The existence of such an elementary brick scales down the SSD support to a small oligomer and provide a basis of reflexion for prion templating process and propagation.

  3. MAK33 antibody light chain amyloid fibrils are similar to oligomeric precursors.

    Directory of Open Access Journals (Sweden)

    Manuel Hora

    Full Text Available Little structural information is available so far on amyloid fibrils consisting of immunoglobulin light chains. It is not understood which features of the primary sequence of the protein result in fibril formation. We report here MAS solid-state NMR studies to identify the structured core of κ-type variable domain light chain fibrils. The core contains residues of the CDR2 and the β-strands D, E, F and G of the native immunoglobulin fold. The assigned core region of the fibril is distinct in comparison to the core identified in a previous solid-state NMR study on AL-09 by Piehl at. al, suggesting that VL fibrils can adopt different topologies. In addition, we investigated a soluble oligomeric intermediate state, previously termed the alternatively folded state (AFS, using NMR and FTIR spectroscopy. The NMR oligomer spectra display a high degree of similarity when compared to the fibril spectra, indicating a high structural similarity of the two aggregation states. Based on comparison to the native state NMR chemical shifts, we suggest that fibril formation via domain-swapping seems unlikely. Moreover, we used our results to test the quality of different amyloid prediction algorithms.

  4. Surface modification of polyhedral oligomeric silsesquioxane block copolymer films by 157 nm laser light

    Science.gov (United States)

    Sarantopoulou, Evangelia; Kollia, Zoe; Cefalas, Alkiviadis Constantinos; Siokou, Ageliki Elina; Argitis, Panagiotis; Bellas, Vassilios; Kobe, Spomenka

    2009-06-01

    Thin films of ethyl polyhedral oligomeric silsesquioxane (ethyl-POSS) containing polymers at different compositions were chemically modified using laser irradiation at 157 nm. The irradiation caused photodissociation of C-O and C-H bonds followed by the formation of new chemical bonds. The content of Si-O and C-O bonds increased, as did the surface hardness. Vacuum ultraviolet (VUV) absorption, mass spectrometry, x-ray photoelectron spectroscopy, and atomic force microscopy imaging and indentation were used to evaluate the effects of the 157 nm irradiation. The chemical modification was restricted to a thin surface layer. The layer depth was determined by the penetration depth of the 157 nm VUV photons inside the thin copolymer layer. With prolonged VUV irradiation, the absorbance of the polymers increased, eventually becoming saturated. The chemical changes were accompanied by surface hardening, as evidenced by the increase in the Young's modulus from 4 to 24 GPa due to glassification of the irradiated parts. The chemically modified layer acts as a shield against photodissociation and degradation of the deeper portion of the POSS polymer by VUV radiation. Applications include the protection of solar cells on low orbit satellites from solar VUV photons.

  5. Oligomerization of 10,16-Dihydroxyhexadecanoic Acid and Methyl 10,16-Dihydroxyhexadecanoate Catalyzed by Lipases

    Directory of Open Access Journals (Sweden)

    Daniel Arrieta-Baez

    2013-08-01

    Full Text Available The main monomer of tomato cuticle, 10,16-dihydroxyhexadecanoic acid (10,16-DHPA and its methyl ester derivative (methyl-10,16-dihydroxyhexadecanote; methyl-10,16-DHHD, were used to study their oligomerization reactions catalyzed by five lipases: Candida antarctica lipase B (CAL-B, Rhizomucor miehei lipase (RM, Thermomyces lanuginosus lipase (TL, Pseudomonas cepacia lipase (PCL and porcine pancreatic lipase (PPL. For 10,16-DHPA, optimum yields were obtained at 60 °C using toluene and 2-methyl-2-butanol (2M2B as solvent, while for methyl-10,16-DHHD the bests yields were obtained in toluene and acetonitrile. Both reactions leaded to linear polyesters according to the NMR and FT-IR analysis, and there was no data indicating the presence of branched polymers. Using optimized conditions, poly(10,16-DHPA and poly(methyl-10,16-DHHD with Mw = 814 and Mn = 1,206 Da, and Mw = 982 and Mn = 860 Da, respectively, were formed according to their MALDI-TOF MS and ESI-MS data. The self-assembly of the polyesters obtained were analyzed by AFM.

  6. Protein oligomerization equilibria and kinetics investigated by fluorescence correlation spectroscopy: a mathematical treatment.

    Science.gov (United States)

    Kanno, David M; Levitus, Marcia

    2014-10-30

    Fluorescence correlation spectroscopy (FCS) is a technique that is increasingly being used to investigate protein oligomerization equilibria and dynamics. Each individual FCS decay is characterized by its amplitude and a characteristic diffusion time, both of which are sensitive to the degree of dissociation of the protein. Here, we provide a mathematical treatment that relates these observables with the parameters of interest: the equilibrium constants of the different protein dissociation steps and their corresponding dissociation and association kinetic rate constants. We focused on the two most common types of protein homooligomers (dimers and tetramers) and on the experimental variables relevant for the design of the experiment (protein concentration, fractional concentration of labeled protein). The analysis of the theoretical expectations for proteins with different dissociation constants is a key aspect of experiment design and data analysis and cannot be performed without a physically accurate treatment of the system. In particular, we show that the analysis of FCS data using some commonly used empirical models may result in a serious misinterpretation of the experimental results.

  7. Dielectric properties of polyhedral oligomeric silsesquioxane (POSS)-based nanocomposites at 77k

    International Nuclear Information System (INIS)

    Pan, Ming-Jen; Gorzkowski, Edward; McAllister, Kelly

    2011-01-01

    The goal of this study is to develop dielectric nanocomposites for high energy density applications at liquid nitrogen temperature by utilizing a unique nano-material polyhedral oligomeric silsesquioxanes (POSS). A POSS molecule is consisted of a silica cage core with 8 silicon and 12 oxygen atoms and organic functional groups attached to the corners of the cage. In this study, we utilize POSS for the fabrication of nanocomposites both as a silica nanoparticle filler to enhance the breakdown strength and as a surfactant for effective dispersion of high permittivity ceramic nanoparticles in a polymer matrix. The matrix materials selected for the study are polyvinylidene fluoride (PVDF) and poly(methyl methacrylate) (PMMA). The ceramic nanoparticles are barium strontium titanate (BST 50/50) and strontium titanate. The dielectric properties of the solution-cast nanocomposites films were correlated to the composition and processing conditions. We determined that the addition of POSS did not provide enhanced dielectric performance in PVDF- and PMMA-based materials at either room temperature or 77K. In addition, we found that the dielectric breakdown strength of PMMA is lower at 77K than at room temperature, contradicting literature data.

  8. Structure-properties relationships of polyhedral oligomeric silsesquioxane (POSS filled PS nanocomposites

    Directory of Open Access Journals (Sweden)

    J. J. Schwab

    2012-07-01

    Full Text Available The polyhedral oligomeric silsesquioxane (POSS additivated polystyrene (PS based nanocomposites were prepared by melt processing and the structure-properties relationships of the POSS-PS systems were compared to those of the neat PS. In order to investigate the effect of these structural parameters on the final properties of the polymer nanocomposites, five different kinds of POSS samples were used, in particular, POSS with different inorganic cage and with different organic pendent groups. The rheological investigation suggests clearly that the POSS acts as a plasticizer and that the processability of the PS was positively modified. The affinity between the POSS samples and the PS matrix was estimated by the calculated theoretical solubility parameters, considering the Hoy’s method and by morphology analysis. Minor difference between the solubility parameter of POSS and the matrix means better compatibility and no aggregation tendency. Furthermore, the POSS loading leads to a decrease of the rigidity, of the glass transition temperature and of the damping factor of the nanocomposite systems. The loading of different POSS molecules with open cage leads to a more pronounced effect on all the investigated properties that the loading of the POSS molecules with closed cage. Moreover, the melt properties are significantly influenced by the type of inorganic framework, by the type of the pendent organic groups and by the interaction between the POSS organic groups and the host matrix, while, the solid state properties appears to be influenced more by the kind of cage.

  9. IntraGolgi distribution of the Conserved Oligomeric Golgi (COG) complex

    International Nuclear Information System (INIS)

    Vasile, Eliza; Oka, Toshihiko; Ericsson, Maria; Nakamura, Nobuhiro; Krieger, Monty

    2006-01-01

    The Conserved Oligomeric Golgi (COG) complex is an eight-subunit (Cog1-8) peripheral Golgi protein involved in membrane trafficking and glycoconjugate synthesis. COG appears to participate in retrograde vesicular transport and is required to maintain normal Golgi structure and function. COG mutations interfere with normal transport, distribution, and/or stability of Golgi proteins associated with glycoconjugate synthesis and trafficking, and lead to failure of spermatogenesis in Drosophila melanogaster, misdirected migration of gonadal distal tip cells in Caenorhabditis elegans, and type II congenital disorders of glycosylation in humans. The mechanism by which COG influences Golgi structure and function is unclear. Immunogold electron microscopy was used to visualize the intraGolgi distribution of a functional, hemagglutinin epitope-labeled COG subunit, Cog1-HA, that complements the Cog1-deficiency in Cog1-null Chinese hamster ovary cells. COG was found to be localized primarily on or in close proximity to the tips and rims of the Golgi's cisternae and their associated vesicles and on vesicles and vesiculo-tubular structures seen on both the cis and trans-Golgi Network faces of the cisternal stacks, in some cases on COPI containing vesicles. These findings support the proposal that COG is directly involved in controlling vesicular retrograde transport of Golgi resident proteins throughout the Golgi apparatus

  10. Internal lipid architecture of the hetero-oligomeric cytochrome b6f complex.

    Science.gov (United States)

    Hasan, S Saif; Cramer, William A

    2014-07-08

    The role of lipids in the assembly, structure, and function of hetero-oligomeric membrane protein complexes is poorly understood. The dimeric photosynthetic cytochrome b6f complex, a 16-mer of eight distinct subunits and 26 transmembrane helices, catalyzes transmembrane proton-coupled electron transfer for energy storage. Using a 2.5 Å crystal structure of the dimeric complex, we identified 23 distinct lipid-binding sites per monomer. Annular lipids are proposed to provide a connection for super-complex formation with the photosystem-I reaction center and the LHCII kinase enzyme for transmembrane signaling. Internal lipids mediate crosslinking to stabilize the domain-swapped iron-sulfur protein subunit, dielectric heterogeneity within intermonomer and intramonomer electron transfer pathways, and dimer stabilization through lipid-mediated intermonomer interactions. This study provides a complete structure analysis of lipid-mediated functions in a multi-subunit membrane protein complex and reveals lipid sites at positions essential for assembly and function. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Mitochonic Acid 5 (MA-5 Facilitates ATP Synthase Oligomerization and Cell Survival in Various Mitochondrial Diseases

    Directory of Open Access Journals (Sweden)

    Tetsuro Matsuhashi

    2017-06-01

    Full Text Available Mitochondrial dysfunction increases oxidative stress and depletes ATP in a variety of disorders. Several antioxidant therapies and drugs affecting mitochondrial biogenesis are undergoing investigation, although not all of them have demonstrated favorable effects in the clinic. We recently reported a therapeutic mitochondrial drug mitochonic acid MA-5 (Tohoku J. Exp. Med., 2015. MA-5 increased ATP, rescued mitochondrial disease fibroblasts and prolonged the life span of the disease model “Mitomouse” (JASN, 2016. To investigate the potential of MA-5 on various mitochondrial diseases, we collected 25 cases of fibroblasts from various genetic mutations and cell protective effect of MA-5 and the ATP producing mechanism was examined. 24 out of the 25 patient fibroblasts (96% were responded to MA-5. Under oxidative stress condition, the GDF-15 was increased and this increase was significantly abrogated by MA-5. The serum GDF-15 elevated in Mitomouse was likewise reduced by MA-5. MA-5 facilitates mitochondrial ATP production and reduces ROS independent of ETC by facilitating ATP synthase oligomerization and supercomplex formation with mitofilin/Mic60. MA-5 reduced mitochondria fragmentation, restores crista shape and dynamics. MA-5 has potential as a drug for the treatment of various mitochondrial diseases. The diagnostic use of GDF-15 will be also useful in a forthcoming MA-5 clinical trial.

  12. Formation of semisolid, oligomerized aqueous SOA: lab simulations of cloud processing.

    Science.gov (United States)

    Hawkins, Lelia N; Baril, Molly J; Sedehi, Nahzaneen; Galloway, Melissa M; De Haan, David O; Schill, Gregory P; Tolbert, Margaret A

    2014-02-18

    Glyoxal, methylglyoxal, glycolaldehyde, and hydroxyacetone form N-containing and oligomeric compounds during simulated cloud processing with small amines. Using a novel hygroscopicity tandem differential mobility analysis (HTDMA) system that allows varied humidification times, the hygroscopic growth (HG) of each of the resulting products of simulated cloud processing was measured. Continuous water uptake (gradual deliquescence) was observed beginning at ∼ 40% RH for all aldehyde-methylamine products. Particles containing ionic reaction products of either glyoxal or glycine were most hygroscopic, with HG between 1.16 and 1.20 at 80% RH. Longer humidification times (up to 20 min) produced an increase in growth factors for glyoxal-methylamine (19% by vol) and methylglyoxal-methylamine (8% by vol) aerosol, indicating that unusually long equilibration times can be required for HTDMA measurements of such particles. Glyoxal- and methylglyoxal-methylamine aerosol particles shattered in Raman microscopy impact-flow experiments, revealing that the particles were semisolid. Similar experiments on glycolaldehyde- and hydroxyacetone-methylamine aerosol found that the aerosol particles were liquid when dried for glyoxal > glycolaldehyde = hydroxyacetone, likely caused by the speed of oligomer formation in each system.

  13. Dielectric properties of polyhedral oligomeric silsesquioxane (POSS)-based nanocomposites at 77k

    Energy Technology Data Exchange (ETDEWEB)

    Pan, Ming-Jen; Gorzkowski, Edward; McAllister, Kelly, E-mail: pan@anvil.nrl.navy.mi [Multifunctional Materials Branch, Code 6350 U.S. Naval Research Laboratory 4555 Overlook Avenue SW, Washington, DC 20375 (United States)

    2011-10-29

    The goal of this study is to develop dielectric nanocomposites for high energy density applications at liquid nitrogen temperature by utilizing a unique nano-material polyhedral oligomeric silsesquioxanes (POSS). A POSS molecule is consisted of a silica cage core with 8 silicon and 12 oxygen atoms and organic functional groups attached to the corners of the cage. In this study, we utilize POSS for the fabrication of nanocomposites both as a silica nanoparticle filler to enhance the breakdown strength and as a surfactant for effective dispersion of high permittivity ceramic nanoparticles in a polymer matrix. The matrix materials selected for the study are polyvinylidene fluoride (PVDF) and poly(methyl methacrylate) (PMMA). The ceramic nanoparticles are barium strontium titanate (BST 50/50) and strontium titanate. The dielectric properties of the solution-cast nanocomposites films were correlated to the composition and processing conditions. We determined that the addition of POSS did not provide enhanced dielectric performance in PVDF- and PMMA-based materials at either room temperature or 77K. In addition, we found that the dielectric breakdown strength of PMMA is lower at 77K than at room temperature, contradicting literature data.

  14. Protective effect of oligomeric proanthocyanidins against alcohol-induced liver steatosis and injury in mice.

    Science.gov (United States)

    Wang, Zhiguo; Su, Bo; Fan, Sumei; Fei, Haixia; Zhao, Wei

    2015-03-20

    The long-term consumption of alcohol has been associated with multiple pathologies at all levels, such as alcoholism, chronic pancreatitis, malnutrition, alcoholic liver disease (ALD) and cancer. In the current study, we investigated the protective effect of oligomeric proanthocyanidins (OPC) against alcohol-induced liver steatosis and injury and the possible mechanisms using ethanol-induced chronic liver damage mouse models. The results showed that OPC significantly improved alcohol-induced dyslipidemia and alleviated liver steatosis by reducing levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), total triglyceride (TG), total cholesterol (TC), low-density cholesterol (LDL-c) and liver malondialdehyde (MDA), and increasing levels of serum high-density lipoprotein (HDL-c), liver superoxide dismutase (SOD). Further investigation indicated that OPC markedly decreased the expressions of lipid synthesis genes and inflammation genes such as sterol regulatory element-binding protein-1c (Srebp-1c), protein-2 (Srebp2), interleukin IL-1β, IL-6 and TNF-α. Furthermore, AML-12 cells line was used to investigate the possible mechanisms which indicated that OPC might alleviate liver steatosis and damage through AMP-activated protein kinase (AMPK) activation involving oxidative stress. In conclusion, our study demonstrated excellent protective effect of OPC against alcohol-induced liver steatosis and injury, which could a potential drug for the treatment of alcohol-induced liver injury in the future. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Effects of pressure on the dynamics of an oligomeric protein from deep-sea hyperthermophile

    Science.gov (United States)

    Shrestha, Utsab R.; Bhowmik, Debsindhu; Copley, John R. D.; Tyagi, Madhusudan; Leão, Juscelino B.; Chu, Xiang-qiang

    2015-01-01

    Inorganic pyrophosphatase (IPPase) from Thermococcus thioreducens is a large oligomeric protein derived from a hyperthermophilic microorganism that is found near hydrothermal vents deep under the sea, where the pressure is up to 100 MPa (1 kbar). It has attracted great interest in biophysical research because of its high activity under extreme conditions in the seabed. In this study, we use the quasielastic neutron scattering (QENS) technique to investigate the effects of pressure on the conformational flexibility and relaxation dynamics of IPPase over a wide temperature range. The β-relaxation dynamics of proteins was studied in the time ranges from 2 to 25 ps, and from 100 ps to 2 ns, using two spectrometers. Our results indicate that, under a pressure of 100 MPa, close to that of the native environment deep under the sea, IPPase displays much faster relaxation dynamics than a mesophilic model protein, hen egg white lysozyme (HEWL), at all measured temperatures, opposite to what we observed previously under ambient pressure. This contradictory observation provides evidence that the protein energy landscape is distorted by high pressure, which is significantly different for hyperthermophilic (IPPase) and mesophilic (HEWL) proteins. We further derive from our observations a schematic denaturation phase diagram together with energy landscapes for the two very different proteins, which can be used as a general picture to understand the dynamical properties of thermophilic proteins under pressure. PMID:26504206

  16. The LisH motif of muskelin is crucial for oligomerization and governs intracellular localization.

    Science.gov (United States)

    Delto, Carolyn F; Heisler, Frank F; Kuper, Jochen; Sander, Bodo; Kneussel, Matthias; Schindelin, Hermann

    2015-02-03

    Neurons regulate the number of surface receptors by balancing the transport to and from the plasma membrane to adjust their signaling properties. The protein muskelin was recently identified as a key factor guiding the transport of α1 subunit-containing GABAA receptors. Here we present the crystal structure of muskelin, comprising its N-terminal discoidin domain and Lis1-homology (LisH) motif. The molecule crystallized as a dimer with the LisH motif exclusively mediating oligomerization. Our subsequent biochemical analyses confirmed that the LisH motif acts as a dimerization element in muskelin. Together with an intermolecular head-to-tail interaction, the LisH-dependent dimerization is required to assemble a muskelin tetramer. Intriguingly, our cellular studies revealed that the loss of this dimerization results in a complete redistribution of muskelin from the cytoplasm to the nucleus and impairs muskelin's function in GABAA receptor transport. These studies demonstrate that the LisH-dependent dimerization is a crucial factor for muskelin function. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Oil Palm Phenolics Inhibit the In Vitro Aggregation of β-Amyloid Peptide into Oligomeric Complexes

    Directory of Open Access Journals (Sweden)

    Robert P. Weinberg

    2018-01-01

    Full Text Available Alzheimer’s disease is a severe neurodegenerative disease characterized by the aggregation of amyloid-β peptide (Aβ into toxic oligomers which activate microglia and astrocytes causing acute neuroinflammation. Multiple studies show that the soluble oligomers of Aβ42 are neurotoxic and proinflammatory, whereas the monomers and insoluble fibrils are relatively nontoxic. We show that Aβ42 aggregation is inhibited in vitro by oil palm phenolics (OPP, an aqueous extract from the oil palm tree (Elaeis guineensis. The data shows that OPP inhibits stacking of β-pleated sheets, which is essential for oligomerization. We demonstrate the inhibition of Aβ42 aggregation by (1 mass spectrometry; (2 Congo Red dye binding; (3 2D-IR spectroscopy; (4 dynamic light scattering; (5 transmission electron microscopy; and (6 transgenic yeast rescue assay. In the yeast rescue assay, OPP significantly reduces the cytotoxicity of aggregating neuropeptides in yeast genetically engineered to overexpress these peptides. The data shows that OPP inhibits (1 the aggregation of Aβ into oligomers; (2 stacking of β-pleated sheets; and (3 fibrillar growth and coalescence. These inhibitory effects prevent the formation of neurotoxic oligomers and hold potential as a means to reduce neuroinflammation and neuronal death and thereby may play some role in the prevention or treatment of Alzheimer’s disease.

  18. Design of a minimal protein oligomerization domain by a structural approach.

    Science.gov (United States)

    Burkhard, P; Meier, M; Lustig, A

    2000-12-01

    Because of the simplicity and regularity of the alpha-helical coiled coil relative to other structural motifs, it can be conveniently used to clarify the molecular interactions responsible for protein folding and stability. Here we describe the de novo design and characterization of a two heptad-repeat peptide stabilized by a complex network of inter- and intrahelical salt bridges. Circular dichroism spectroscopy and analytical ultracentrifugation show that this peptide is highly alpha-helical and 100% dimeric tinder physiological buffer conditions. Interestingly, the peptide was shown to switch its oligomerization state from a dimer to a trimer upon increasing ionic strength. The correctness of the rational design principles used here is supported by details of the atomic structure of the peptide deduced from X-ray crystallography. The structure of the peptide shows that it is not a molten globule but assumes a unique, native-like conformation. This de novo peptide thus represents an attractive model system for the design of a molecular recognition system.

  19. The Oligomeric Form of the Escherichia coli Dps Protein Depends on the Availability of Iron Ions

    Directory of Open Access Journals (Sweden)

    Sergey Antipov

    2017-11-01

    Full Text Available The Dps protein of Escherichia coli, which combines ferroxidase activity and the ability to bind DNA, is effectively used by bacteria to protect their genomes from damage. Both activities depend on the integrity of this multi-subunit protein, which has an inner cavity for iron oxides; however, the diversity of its oligomeric forms has only been studied fragmentarily. Here, we show that iron ions stabilize the dodecameric form of Dps. This was found by electrophoretic fractionation and size exclusion chromatography, which revealed several oligomers in highly purified protein samples and demonstrated their conversion to dodecamers in the presence of 1 mM Mohr’s salt. The transmission electron microscopy data contradicted the assumption that the stabilizing effect is given by the optimal core size formed in the inner cavity of Dps. The charge state of iron ions was evaluated using Mössbauer spectroscopy, which showed the presence of Fe3O4, rather than the expected Fe2O3, in the sample. Assuming that Fe2+ can form additional inter-subunit contacts, we modeled the interaction of FeO and Fe2O3 with Dps, but the binding sites with putative functionality were predicted only for Fe2O3. The question of how the dodecameric form can be stabilized by ferric oxides is discussed.

  20. Cooperative Binding in a Phosphine Oxide-Based Halogen Bonded Dimer Drives Supramolecular Oligomerization.

    Science.gov (United States)

    Maugeri, Leonardo; Lébl, Tomáš; Cordes, David B; Slawin, Alexandra M Z; Philp, Douglas

    2017-02-17

    Triphenylphosphine oxide forms halogen-bonded (XB) complexes with pentafluoroiodobenzene and a 1,4-diaryl-5-iodotriazole. The stability of these complexes is assessed computationally and by 31 P NMR spectroscopy in toluene-d 8 solution, where both complexes are weakly associated. This knowledge is applied to the design and synthesis of two self-complementary phosphine oxide-iodotriazole hybrids that incorporate a phosphine oxide XB acceptor and a 1,4-diphenyl-5-iodotriazole XB donor within the same molecule. The self-complementary design of these modules facilitates their assembly in both toluene-d 8 and, surprisingly, DCM-d 2 into dimers, with significant stabilities, through the formation of halogen-bonded diads. The stability of these assemblies is a result of significant levels of cooperative binding that is present in both solvents. The connection of two of these hybrid units together, using a flexible spacer, facilitates the aggregation of these modules in DCM-d 2 solution, through halogen bonding, forming oligomeric assemblies.

  1. LOGICOIL--multi-state prediction of coiled-coil oligomeric state.

    Science.gov (United States)

    Vincent, Thomas L; Green, Peter J; Woolfson, Derek N

    2013-01-01

    The coiled coil is a ubiquitous α-helical protein-structure domain that directs and facilitates protein-protein interactions in a wide variety of biological processes. At the protein-sequence level, the coiled coil is readily recognized via a conspicuous heptad repeat of hydrophobic and polar residues. However, structurally coiled coils are more complicated, existing in a wide range of oligomer states and topologies. As a consequence, predicting these various states from sequence remains an unmet challenge. This work introduces LOGICOIL, the first algorithm to address the problem of predicting multiple coiled-coil oligomeric states from protein-sequence information alone. By covering >90% of the known coiled-coil structures, LOGICOIL is a net improvement compared with other existing methods, which achieve a predictive coverage of ∼31% of this population. This leap in predictive power offers better opportunities for genome-scale analysis, and analyses of coiled-coil containing protein assemblies. LOGICOIL is available via a web-interface at http://coiledcoils.chm.bris.ac.uk/LOGICOIL. Source code, training sets and supporting information can be downloaded from the same site.

  2. Polyhedral oligomeric silsesquioxane (POSS)–poly(ethylene glycol) (PEG) hybrids as injectable biomaterials

    International Nuclear Information System (INIS)

    Engstrand, Johanna; López, Alejandro; Engqvist, Håkan; Persson, Cecilia

    2012-01-01

    One of the major issues with the currently available injectable biomaterials for hard tissue replacement is the mismatch between their mechanical properties and those of the surrounding bone. Hybrid bone cements that combine the benefits of tough polymeric and bioactive ceramic materials could become a good alternative. In this work, polyhedral oligomeric silsesquioxane (POSS) was copolymerized with poly(ethylene glycol) (PEG) to form injectable in situ cross-linkable hybrid cements. The hybrids were characterized in terms of their mechanical, rheological, handling and in vitro bioactive properties. The results indicated that hybridization improves the mechanical and bioactive properties of POSS and PEG. The Young moduli of the hybrids were lower than those of commercial cements and more similar to those of cancellous bone. Furthermore, the strength of the hybrids was similar to that of commercial cements. Calcium deficient hydroxyapatite grew on the surface of the hybrids after 28 days in PBS, indicating bioactivity. The study showed that PEG–POSS-based hybrid materials are a promising alternative to commercial bone cements. (paper)

  3. Detection of Cartilage Oligomeric Matrix Protein Using a Quartz Crystal Microbalance

    Directory of Open Access Journals (Sweden)

    Chih-Hsin Hung

    2010-12-01

    Full Text Available Current methods for diagnosing early stage osteoarthritis (OA based on the magnetic resonance imaging and enzyme-linked immunosorbent assay methods are specific, but require specialized laboratory facilities and highly trained personal to obtain a definitive result. In this work, a user friendly and non-invasive quartz crystal microbalance (QCM immunosensor method has been developed to detect Cartilage Oligomeric Matrix Protein (COMP for early stage OA diagnosis. This QCM immunosensor was fabricated to immobilize COMP antibodies utilizing the self-assembled monolayer technique. The surface properties of the immunosensor were characterized by its FTIR and electrochemical impedance spectra (EIS. The feasibility study was based on urine samples obtained from 41 volunteers. Experiments were carried out in a flow system and the reproducibility of the electrodes was evaluated by the impedance measured by EIS. Its potential dynamically monitored the immunoreaction processes and could increase the efficiency and sensitivity of COMP detection in laboratory-cultured preparations and clinical samples. The frequency responses of the QCM immunosensor changed from 6 kHz when testing 50 ng/mL COMP concentration. The linear regression equation of frequency shift and COMP concentration was determined as: y = 0.0872 x + 1.2138 (R2 = 0.9957. The COMP in urine was also determined by both QCM and EIS for comparison. A highly sensitive, user friendly and cost effective analytical method for the early stage OA diagnosis has thus been successfully developed.

  4. Esters of oligo-(glycerol carbonate-glycerol): New biobased oligomeric surfactants.

    Science.gov (United States)

    Holmiere, Sébastien; Valentin, Romain; Maréchal, Philippe; Mouloungui, Zéphirin

    2017-02-01

    Glycerol carbonate is one of the most potentially multifunction glycerol-derived compounds. Glycerol is an important by-product of the oleochemical industry. The oligomerization of glycerol carbonate, assisted by the glycerol, results in the production of polyhydroxylated oligomers rich in linear carbonate groups. The polar moieties of these oligomers (M w ethylene oxide as in most commercial surfactants. The insertion of linear carbonate groups into the glycerol-based skeleton rendered the oligomers amphiphilic, resulting in a decrease in air/water surface tension to 57mN/m. We improved the physical and chemical properties of the oligomers, by altering the type of acylation reaction and the nature of the acyl donor. The polar head is constituted of homo-oligomers and hetero-oligomers. Homo-oligomers are oligoglycerol and/or oligocarbonate, hetero-oligomers are oligo(glycerol-glycerol carbonate). Coprah oligoesters had the best surfactant properties (CMCethylene glycol monododecyl ether, glycol ethers and fatty acid esters of sorbitan polyethoxylates. The self-assembling properties of oligocarbonate esters were highlighted by their ability to stabilize inverse and multiple emulsions. The oligo-(glycerol carbonate-glycerol ether) with relatively low molecular weights showed properties of relatively high-molecular weight molecules, and constitute a viable "green" alternative to ethoxylated surfactants. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. A well-defined model system for the chromium-catalyzed selective oligomerization of ethylene.

    Science.gov (United States)

    Monillas, Wesley H; Young, John F; Yap, Glenn P A; Theopold, Klaus H

    2013-07-07

    The chromium(I) dinitrogen complex [(i-Pr2Ph)2nacnacCr]2(μ-η(2):η(2)-N2) catalyzes the selective trimerization of ethylene to 1-hexene at ambient pressure and temperature, and in the absence of any cocatalyst. After the conversion of the substrate, the catalyst cleanly converts to another chromium(I) species, namely [(i-Pr2Ph)2nacnacCr]2(μ-η(2):η(2)-C2H4), which is not catalytically active. Binuclear metallacycles containing Cr(II) have been prepared as candidates for catalytically active intermediates; however they are not kinetically competent to explain the catalysis. Turning thus to mononuclear metallacycles featuring Cr(III), a chromacyclopentane, chromacyclopentene and chromacyclopentadiene have been prepared as models of catalytic intermediates. Of these, the latter also catalyzes the trimerization of ethylene. These results support the proposal that selective ethylene oligomerization catalysis involves an interplay between Cr(I) ethylene complexes and mononuclear Cr(III) metallacycles.

  6. Dinuclear nickel complexes with bidentate N,O ligands: synthesis, structure, and catalytic oligomerization of ethylene.

    Science.gov (United States)

    Speiser, Fredy; Braunstein, Pierre; Saussine, Lucien

    2004-07-12

    The new dicationic dinuclear complexes [Ni(micro-Cl)(2)(N,OH)(2)]Cl(2) (11, N,OH = 2-(4,4-dimethyl-4,5-dihydrooxazol-2-yl)-propan-2-ol; 12, N,OH = 2-pyridin-2-yl-propan-2-ol) were prepared in good yields and evaluated as precatalyts in the oligomerization of ethylene, using MAO or AlEtCl(2) as cocatalyst. These paramagnetic complexes were characterized by single-crystal X-ray diffraction in the solid state and in solution with the help of the Evans method, which revealed agreement between the octahedral coordination spheres found in solution and in the solid state. The N donor atoms of each chelating ligand are in mutual cis position, and the OH donors are mutually trans situated. Selectivities for 1-butene within the C(4) fraction of 61% (11) and 58% (12) were observed in the presence of 200 equiv of MAO, but better turnover frequencies (28 300 (11) and 20 400 (12) mol of C(2)H(4)/(mol of Ni.h)) were obtained when 800 equiv of MAO was used. In the presence of 6 equiv of AlEtCl(2), the activities were considerably increased, up to 174 300 (11) and 97 100 (12) mol of C(2)H(4)/(mol of Ni.h), and the selectivity for C(4) olefins was 70% and 64%, respectively.

  7. Strong-back safety latch

    International Nuclear Information System (INIS)

    DeSantis, G.N.

    1995-01-01

    The calculation decides the integrity of the safety latch that will hold the strong-back to the pump during lifting. The safety latch will be welded to the strong-back and will latch to a 1.5-in. dia cantilever rod welded to the pump baseplate. The static and dynamic analysis shows that the safety latch will hold the strong-back to the pump if the friction clamps fail and the pump become free from the strong-back. Thus, the safety latch will meet the requirements of the Lifting and Rigging Manual for under the hook lifting for static loading; it can withstand shock loads from the strong-back falling 0.25 inch

  8. Strong-back safety latch

    Energy Technology Data Exchange (ETDEWEB)

    DeSantis, G.N.

    1995-03-06

    The calculation decides the integrity of the safety latch that will hold the strong-back to the pump during lifting. The safety latch will be welded to the strong-back and will latch to a 1.5-in. dia cantilever rod welded to the pump baseplate. The static and dynamic analysis shows that the safety latch will hold the strong-back to the pump if the friction clamps fail and the pump become free from the strong-back. Thus, the safety latch will meet the requirements of the Lifting and Rigging Manual for under the hook lifting for static loading; it can withstand shock loads from the strong-back falling 0.25 inch.

  9. Titanium: light, strong, and white

    Science.gov (United States)

    Woodruff, Laurel; Bedinger, George

    2013-01-01

    Titanium (Ti) is a strong silver-gray metal that is highly resistant to corrosion and is chemically inert. It is as strong as steel but 45 percent lighter, and it is twice as strong as aluminum but only 60 percent heavier. Titanium dioxide (TiO2) has a very high refractive index, which means that it has high light-scattering ability. As a result, TiO2 imparts whiteness, opacity, and brightness to many products. ...Because of the unique physical properties of titanium metal and the whiteness provided by TiO2, titanium is now used widely in modern industrial societies.

  10. Radical mechanisms of methyl vinyl ketone oligomerization through aqueous phase OH-oxidation: on the paradoxical role of dissolved molecular oxygen

    Directory of Open Access Journals (Sweden)

    P. Renard

    2013-07-01

    Full Text Available It is now accepted that one of the important pathways of secondary organic aerosol (SOA formation occurs through aqueous phase chemistry in the atmosphere. However, the chemical mechanisms leading to macromolecules are still not well understood. It was recently shown that oligomer production by OH radical oxidation in the aerosol aqueous phase from α-dicarbonyl precursors, such as methylglyoxal and glyoxal, is irreversible and fast. Methyl vinyl ketone (MVK was chosen in the present study as it is an α,β-unsaturated carbonyl that can undergo radical oligomerization in the aerosol aqueous phase. We present here experiments on the aqueous phase OH-oxidation of MVK, performed under various conditions. Using NMR and UV absorption spectroscopy, high and ultra-high resolution mass spectrometry, we show that the fast formation of oligomers up to 1800 Da is due to radical oligomerization of MVK, and 13 series of oligomers (out of a total of 26 series are identified. The influence of atmospherically relevant parameters such as temperature, initial concentrations of MVK and dissolved oxygen are presented and discussed. In agreement with the experimental observations, we propose a chemical mechanism of OH-oxidation of MVK in the aqueous phase that proceeds via radical oligomerization of MVK on the olefin part of the molecule. This mechanism highlights in our experiments the paradoxical role of dissolved O2: while it inhibits oligomerization reactions, it contributes to produce oligomerization initiator radicals, which rapidly consume O2, thus leading to the dominance of oligomerization reactions after several minutes of reaction. These processes, together with the large range of initial concentrations investigated show the fundamental role that radical oligomerization processes likely play in polluted fogs and atmospheric aerosol.

  11. Oligomerization of Bacillus subtilis DesR is required for fine tuning regulation of membrane fluidity.

    Science.gov (United States)

    Najle, Sebastián R; Inda, María E; de Mendoza, Diego; Cybulski, Larisa E

    2009-10-01

    The DesK-DesR two-component system regulates the order of membrane lipids in the bacterium Bacillus subtilis by controlling the expression of the des gene coding for the delta 5-acyl-lipid desaturase. To activate des transcription, the membrane-bound histidine kinase DesK phosphorylates the response regulator DesR. This covalent modification of the regulatory domain of dimeric DesR promotes, in a cooperative fashion, the hierarchical occupation of two adjacent, non-identical, DesR-P binding sites, so that there is a shift in the equilibrium toward the tetrameric active form of the response regulator. However, the mechanism of regulation of DesR activity by phosphorylation and oligomerization is not well understood. We employed deletion analysis and reporter fusions to study the role of the N-terminal domain on DesR activity. In addition, electromobility shift assays were used to analyze the binding capacity of the transcription factor to deletion mutants of the des promoter. We show that DesR lacking the N-terminal domain is still able to bind to the des promoter. We also demonstrate that if the RA site is moved closer to the -35 region of Pdes, the adjacent site RB is dispensable for activation. Our results indicate that the unphosphorylated regulatory domain of DesR obstructs the access of the recognition helix of DesR to its DNA target. In addition, we present evidence showing that RB is physiologically relevant to control the activation of the des gene when the levels of DesR-P reach a critical threshold.

  12. Binding and Oligomerization of Modified and Native Bt Toxins in Resistant and Susceptible Pink Bollworm.

    Directory of Open Access Journals (Sweden)

    Josue Ocelotl

    Full Text Available Insecticidal proteins from Bacillus thuringiensis (Bt are used extensively in sprays and transgenic crops for pest control, but their efficacy is reduced when pests evolve resistance. Better understanding of the mode of action of Bt toxins and the mechanisms of insect resistance is needed to enhance the durability of these important alternatives to conventional insecticides. Mode of action models agree that binding of Bt toxins to midgut proteins such as cadherin is essential for toxicity, but some details remain unresolved, such as the role of toxin oligomers. In this study, we evaluated how Bt toxin Cry1Ac and its genetically engineered counterpart Cry1AcMod interact with brush border membrane vesicles (BBMV from resistant and susceptible larvae of Pectinophora gossypiella (pink bollworm, a global pest of cotton. Compared with Cry1Ac, Cry1AcMod lacks 56 amino acids at the amino-terminus including helix α-1; previous work showed that Cry1AcMod formed oligomers in vitro without cadherin and killed P. gossypiella larvae harboring cadherin mutations linked with >1000-fold resistance to Cry1Ac. Here we found that resistance to Cry1Ac was associated with reduced oligomer formation and insertion. In contrast, Cry1AcMod formed oligomers in BBMV from resistant larvae. These results confirm the role of cadherin in oligomerization of Cry1Ac in susceptible larvae and imply that forming oligomers without cadherin promotes toxicity of Cry1AcMod against resistant P. gossypiella larvae that have cadherin mutations.

  13. Degradation studies on biodegradable nanocomposite based on polycaprolactone/polycarbonate (80:20%) polyhedral oligomeric silsesquioxane.

    Science.gov (United States)

    Raghunath, Joanne; Georgiou, George; Armitage, David; Nazhat, Showan N; Sales, Kevin M; Butler, Peter E; Seifalian, Alexander M

    2009-12-01

    The development of biocompatible polymers has greatly advanced the field of tissue engineering. Some tissues can be propagated on a nondegradable scaffold. Tissue such as cartilage, however, is a complex tissue in which the chondrocytes require their own synthesized extracellular matrix (ECM) to function. Suitable scaffolds for tissue engineering cartilage should provide mechanical strength and degrade at a similar rate to that of cell growth and ECM production. We have developed a biodegradable nanocomposite based on polycaprolactone and polycarbonate polyurethane (PCU) with an incorporated polyhedral oligomeric silsesquioxane (POSS) (POSS modified Poly(caprolactone/carbonate) urethane/urea). Previous work on POSS incorporated into PCU (POSS-PCU) has been shown to possess good mechanical strength, elasticity and resistance to degradation. This series of experiments involved exposing this polymer to a selection of accelerated degradative solutions for up to 8 weeks. The samples were analyzed by infra-red spectroscopy, scanning electron microscopy, X-ray microanalysis, contact angle analysis, and stress-strain mechanical analysis. Degradation of hard and soft segments of the nanocomposite was evident by infra-red spectroscopy in all conditioned samples. POSS nanocage degradation was evident in some oxidative/peroxidative systems accompanied by gross changes in surface topography and significant changes in mechanical properties. The hydrophobic polymer became more hydrophilic in all conditions. This biodegradable nanocomposite demonstrated steady degradation with protection of mechanical properties when exposed to hydrolytic enzymes and plasma protein fractions and exhibited more dramatic degradation by oxidation.This pattern may be potentially employed in tissue engineering scaffolds where controlled degradation and retained structural stability of the scaffold is required. Copyright 2008 Wiley Periodicals, Inc.

  14. A chemical analog of curcumin as an improved inhibitor of amyloid Abeta oligomerization.

    Science.gov (United States)

    Orlando, Robert A; Gonzales, Amanda M; Royer, Robert E; Deck, Lorraine M; Vander Jagt, David L

    2012-01-01

    Amyloid-like plaques are characteristic lesions defining the neuropathology of Alzheimer's disease (AD). The size and density of these plaques are closely associated with cognitive decline. To combat this disease, the few therapies that are available rely on drugs that increase neurotransmission; however, this approach has had limited success as it has simply slowed an imminent decline and failed to target the root cause of AD. Amyloid-like deposits result from aggregation of the Aβ peptide, and thus, reducing amyloid burden by preventing Aβ aggregation represents an attractive approach to improve the therapeutic arsenal for AD. Recent studies have shown that the natural product curcumin is capable of crossing the blood-brain barrier in the CNS in sufficient quantities so as to reduce amyloid plaque burden. Based upon this bioactivity, we hypothesized that curcumin presents molecular features that make it an excellent lead compound for the development of more effective inhibitors of Aβ aggregation. To explore this hypothesis, we screened a library of curcumin analogs and identified structural features that contribute to the anti-oligomerization activity of curcumin and its analogs. First, at least one enone group in the spacer between aryl rings is necessary for measureable anti-Aβ aggregation activity. Second, an unsaturated carbon spacer between aryl rings is essential for inhibitory activity, as none of the saturated carbon spacers showed any margin of improvement over that of native curcumin. Third, methoxyl and hydroxyl substitutions in the meta- and para-positions on the aryl rings appear necessary for some measure of improved inhibitory activity. The best lead inhibitors have either their meta- and para-substituted methoxyl and hydroxyl groups reversed from that of curcumin or methoxyl or hydroxyl groups placed in both positions. The simple substitution of the para-hydroxy group on curcumin with a methoxy substitution improved inhibitor function by 6

  15. LPS-Induced Galectin-3 Oligomerization Results in Enhancement of Neutrophil Activation

    Science.gov (United States)

    Fermino, Marise Lopes; Polli, Claudia Danella; Toledo, Karina Alves; Liu, Fu-Tong; Hsu, Dan K.; Roque-Barreira, Maria Cristina; Pereira-da-Silva, Gabriela

    2011-01-01

    Galectin-3 (Gal 3) is a glycan-binding protein that can be secreted by activated macrophages and mast cells at inflammation sites and plays an important role in inflammatory diseases caused by Bacteria and their products, such as lipopolysaccharides (LPS). Although it is well established that Gal 3 can interact with LPS, the pathophysiological importance of LPS/Gal 3 interactions is not fully understood. Data presented herein demonstrate for the first time that the interaction of Gal 3, either via its carbohydrate binding C-terminal domain or via its N-terminal part, with LPS from different bacterial strains, enhances the LPS-mediated neutrophil activation in vitro. Gal 3 allowed low LPS concentrations (1 µg/mL without serum, 1 ng/mL with serum) to upregulate CD11b expression and reactive oxygen species (ROS) generation on human neutrophils in vitro and drastically enhanced the binding efficiency of LPS to the neutrophil surface. These effects required LPS preincubation with Gal 3, before neutrophil stimulation and involved specific Gal 3/LPS interaction. A C-terminal Gal-3 fragment, which retains the lectin domain but lacks the N-terminal part, was still able to bind both to Escherichia coli LPS and to neutrophils, but had lost the ability to enhance neutrophil response to LPS. This result emphasizes the importance of an N-terminus-mediated Gal 3 oligomerization induced by its interaction with LPS. Finally we demonstrated that Balb/C mice were more susceptible to LPS-mediated shock when LPS was pretreated with Gal 3. Altogether, these results suggest that multimeric interactions between Gal 3 oligomers and LPS potentiate its pro-inflammatory effects on neutrophils. PMID:22031821

  16. Abnormal Salivary Total and Oligomeric Alpha-Synuclein in Parkinson's Disease.

    Directory of Open Access Journals (Sweden)

    Giorgio Vivacqua

    Full Text Available In Parkinson's disease (PD, alpha-synuclein (a-syn can be detected in biological fluids including saliva. Although previous studies found reduced a-syn total (a-syntotal concentration in saliva of PD patients, no studies have previously examined salivary a-syn oligomers (a-synolig concentrations or assessed the correlation between salivary a-syntotal, a-synolig and clinical features in a large cohort of PD patients. Is well known that a-synolig exerts a crucial neurotoxic effect in PD. We collected salivary samples from 60 PD patients and 40 age- and sex-comparable healthy subjects. PD was diagnosed according to the United Kingdom Brain Bank Criteria. Samples of saliva were analyzed by specific anti-a-syn and anti-oligomeric a-syn ELISA kits. A complete clinical evaluation of each patient was performed using MDS-Unified Parkinson's Disease Rating Scale, Beck Depression Inventory, Montreal Cognitive Assessment and Frontal Assessment Battery. Salivary a-syntotal was lower, whereas a-synolig was higher in PD patients than healthy subjects. The a-synolig/a-syntotal ratio was also higher in patients than in healthy subjects. Salivary a-syntotal concentration negatively correlated with that of a-synolig and correlated with several patients' clinical features. In PD, decreased salivary concentration of a-syntotal may reflect the reduction of a-syn monomers (a-synmon, as well as the formation of insoluble intracellular inclusions and soluble oligomers. The combined detection of a-syntotal and a-synolig in the saliva might help the early diagnosis of PD.

  17. Biophysical investigation of type A PutAs reveals a conserved core oligomeric structure

    Energy Technology Data Exchange (ETDEWEB)

    Korasick, David A. [Department of Biochemistry, University of Missouri, Columbia MO USA; Singh, Harkewal [Department of Chemistry, University of Missouri, Columbia MO USA; Pemberton, Travis A. [Department of Chemistry, University of Missouri, Columbia MO USA; Luo, Min [Department of Chemistry, University of Missouri, Columbia MO USA; Dhatwalia, Richa [Department of Chemistry, University of Missouri, Columbia MO USA; Tanner, John J. [Department of Biochemistry, University of Missouri, Columbia MO USA; Department of Chemistry, University of Missouri, Columbia MO USA

    2017-08-01

    Many enzymes form homooligomers, yet the functional significance of self-association is seldom obvious. Herein, we examine the connection between oligomerization and catalytic function for proline utilization A (PutA) enzymes. PutAs are bifunctional enzymes that catalyze both reactions of proline catabolism. Type A PutAs are the smallest members of the family, possessing a minimal domain architecture consisting of N-terminal proline dehydrogenase and C-terminal l-glutamate-γ-semialdehyde dehydrogenase modules. Type A PutAs form domain-swapped dimers, and in one case (Bradyrhizobium japonicum PutA), two of the dimers assemble into a ring-shaped tetramer. Whereas the dimer has a clear role in substrate channeling, the functional significance of the tetramer is unknown. To address this question, we performed structural studies of four-type A PutAs from two clades of the PutA tree. The crystal structure of Bdellovibrio bacteriovorus PutA covalently inactivated by N-propargylglycine revealed a fold and substrate-channeling tunnel similar to other PutAs. Small-angle X-ray scattering (SAXS) and analytical ultracentrifugation indicated that Bdellovibrio PutA is dimeric in solution, in contrast to the prediction from crystal packing of a stable tetrameric assembly. SAXS studies of two other type A PutAs from separate clades also suggested that the dimer predominates in solution. To assess whether the tetramer of B. japonicum PutA is necessary for catalytic function, a hot spot disruption mutant that cleanly produces dimeric protein was generated. The dimeric variant exhibited kinetic parameters similar to the wild-type enzyme. These results implicate the domain-swapped dimer as the core structural and functional unit of type A PutAs.

  18. High-Performance Oligomeric Catholytes for Effective Macromolecular Separation in Nonaqueous Redox Flow Batteries

    Science.gov (United States)

    2018-01-01

    Nonaqueous redox flow batteries (NRFBs) represent an attractive technology for energy storage from intermittent renewable sources. In these batteries, electrical energy is stored in and extracted from electrolyte solutions of redox-active molecules (termed catholytes and anolytes) that are passed through an electrochemical flow cell. To avoid battery self-discharge, the anolyte and catholyte solutions must be separated by a membrane in the flow cell. This membrane prevents crossover of the redox active molecules, while simultaneously allowing facile transport of charge-balancing ions. A key unmet challenge for the field is the design of redox-active molecule/membrane pairs that enable effective electrolyte separation while maintaining optimal battery properties. Herein, we demonstrate the development of oligomeric catholytes based on tris(dialkylamino)cyclopropenium (CP) salts that are specifically tailored for pairing with size-exclusion membranes composed of polymers of intrinsic microporosity (PIMs). Systematic studies were conducted to evaluate the impact of oligomer size/structure on properties that are crucial for flow battery performance, including cycling stability, charge capacity, solubility, electron transfer kinetics, and crossover rates. These studies have led to the identification of a CP-derived tetramer in which these properties are all comparable, or significantly improved, relative to the monomeric counterpart. Finally, a proof-of-concept flow battery is demonstrated by pairing this tetrameric catholyte with a PIM membrane. After 6 days of cycling, no crossover is detected, demonstrating the promise of this approach. These studies provide a template for the future design of other redox-active oligomers for this application. PMID:29532018

  19. Ethylene oligomerization in metal-organic frameworks bearing nickel(ii) 2,2'-bipyridine complexes.

    Science.gov (United States)

    Gonzalez, Miguel I; Oktawiec, Julia; Long, Jeffrey R

    2017-09-08

    The metal-organic frameworks Zr 6 O 4 (OH) 4 (bpydc) 6 (1; bpydc 2- = 2,2'-bipyridine-5,5'-dicarboxylate) and Zr 6 O 4 (OH) 4 (bpydc) 0.84 (bpdc) 5.16 (2; bpdc 2- = biphenyl-4,4'-dicarboxylate) were readily metalated with Ni(DME)Br 2 (DME = dimethoxyethane) to produce the corresponding metalated frameworks 1(NiBr 2 ) 6 and 2(NiBr 2 ) 0.84 . Both nickel(ii)-containing frameworks catalyze the oligomerization of ethylene in the presence of Et 2 AlCl. In these systems, the pore environment around the active nickel sites significantly influences their selectivity for formation of oligomers over polymer. Specifically, the single-crystal structure of 1(NiBr 2 ) 5.64 reveals that surrounding metal-linker complexes enforce a steric environment on each nickel site that causes polymer formation to become favorable. Minimizing this steric congestion by isolating the nickel(ii) bipyridine complexes in the mixed-linker framework 2(NiBr 2 ) 0.84 markedly improves both the catalytic activity and selectivity for oligomers. Furthermore, both frameworks give product mixtures that are enriched in shorter olefins (C 4-10 ), leading to deviations from the expected Schulz-Flory distribution of oligomers. Although these deviations indicate possible pore confinement effects on selectivity, control experiments using the nickel-treated biphenyl framework Zr 6 O 4 (OH) 4 (bpdc) 6 (NiBr 2 ) 0.14 (3(NiBr 2 ) 0.14 ) reveal that they likely arise at least in part from the presence of nickel species that are not ligated by bipyridine within 1(NiBr 2 ) 5.64 and 2(NiBr 2 ) 0.84 .

  20. Oligomerization state of photosynthetic core complexes is correlated with the dimerization affinity of a transmembrane helix.

    Science.gov (United States)

    Hsin, Jen; LaPointe, Loren M; Kazy, Alla; Chipot, Christophe; Senes, Alessandro; Schulten, Klaus

    2011-09-07

    In the Rhodobacter (Rba.) species of photosynthetic purple bacteria, a single transmembrane α-helix, PufX, is found within the core complex, an essential photosynthetic macromolecular assembly that performs the absorption and the initial processing of light energy. Despite its structural simplicity, many unresolved questions surround PufX, the most important of which is its location within the photosynthetic core complex. One proposed placement of PufX is at the center of a core complex dimer, where two PufX helices associate in the membrane and form a homodimer. Inability for PufX of certain Rba. species to form a homodimer is thought to lead to monomeric core complexes. In the present study, we employ a combination of computational and experimental techniques to test the hypothesized homodimerization of PufX. We carry out a systematic investigation to measure the dimerization affinity of PufX from four Rba. species, Rba. blasticus , Rba. capsulatus , Rba. sphaeroides , and Rba. veldkampii , using a molecular dynamics-based free-energy method, as well as experimental TOXCAT assays. We found that the four PufX helices have substantially different dimerization affinities. Both computational and experimental techniques demonstrate that species with dimeric core complexes have PufX that can potentially form a homodimer, whereas the one species with monomeric core complexes has a PufX with little to no dimerization propensity. Our analysis of the helix-helix interface revealed a number of positions that may be important for PufX dimerization and the formation of a hydrogen-bond network between these GxxxG-containing helices. Our results suggest that the different oligomerization states of core complexes in various Rba. species can be attributed, among other factors, to the different propensity of its PufX helix to homodimerize.

  1. Oligomerization of the E. coli Core RNA Polymerase: Formation of (α2ββ'ω)2–DNA Complexes and Regulation of the Oligomerization by Auxiliary Subunits

    Science.gov (United States)

    Kansara, Seema G.; Sukhodolets, Maxim V.

    2011-01-01

    In this work, using multiple, dissimilar physico-chemical techniques, we demonstrate that the Escherichia coli RNA polymerase core enzyme obtained through a classic purification procedure forms stable (α2ββ'ω)2 complexes in the presence or absence of short DNA probes. Multiple control experiments indicate that this self-association is unlikely to be mediated by RNA polymerase-associated non-protein molecules. We show that the formation of (α2ββ'ω)2 complexes is subject to regulation by known RNA polymerase interactors, such as the auxiliary SWI/SNF subunit of RNA polymerase RapA, as well as NusA and σ70. We also demonstrate that the separation of the core RNA polymerase and RNA polymerase holoenzyme species during Mono Q chromatography is likely due to oligomerization of the core enzyme. We have analyzed the oligomeric state of the polymerase in the presence or absence of DNA, an aspect that was missing from previous studies. Importantly, our work demonstrates that RNA polymerase oligomerization is compatible with DNA binding. Through in vitro transcription and in vivo experiments (utilizing a RapAR599/Q602 mutant lacking transcription-stimulatory function), we demonstrate that the formation of tandem (α2ββ'ω)2–DNA complexes is likely functionally significant and beneficial for the transcriptional activity of the polymerase. Taken together, our findings suggest a novel structural aspect of the E. coli elongation complex. We hypothesize that transcription by tandem RNA polymerase complexes initiated at hypothetical bidirectional “origins of transcription” may explain recurring switches of the direction of transcription in bacterial genomes. PMID:21533049

  2. The SNAP Strong Lens Survey

    Energy Technology Data Exchange (ETDEWEB)

    Marshall, P.

    2005-01-03

    Basic considerations of lens detection and identification indicate that a wide field survey of the types planned for weak lensing and Type Ia SNe with SNAP are close to optimal for the optical detection of strong lenses. Such a ''piggy-back'' survey might be expected even pessimistically to provide a catalogue of a few thousand new strong lenses, with the numbers dominated by systems of faint blue galaxies lensed by foreground ellipticals. After sketching out our strategy for detecting and measuring these galaxy lenses using the SNAP images, we discuss some of the scientific applications of such a large sample of gravitational lenses: in particular we comment on the partition of information between lens structure, the source population properties and cosmology. Understanding this partitioning is key to assessing strong lens cosmography's value as a cosmological probe.

  3. Strong coupling phase in QED

    International Nuclear Information System (INIS)

    Aoki, Ken-ichi

    1988-01-01

    Existence of a strong coupling phase in QED has been suggested in solutions of the Schwinger-Dyson equation and in Monte Carlo simulation of lattice QED. In this article we recapitulate the previous arguments, and formulate the problem in the modern framework of the renormalization theory, Wilsonian renormalization. This scheme of renormalization gives the best understanding of the basic structure of a field theory especially when it has a multi-phase structure. We resolve some misleading arguments in the previous literature. Then we set up a strategy to attack the strong phase, if any. We describe a trial; a coupled Schwinger-Dyson equation. Possible picture of the strong coupling phase QED is presented. (author)

  4. Synthesis and characterization of polyhedral oligomeric titanized silsesquioxane: A new biocompatible cage like molecule for biomedical application

    Energy Technology Data Exchange (ETDEWEB)

    Yahyaei, Hossein [Department of Polymer Engineering and Color Technology, Amirkabir University of Technology, P.O. Box 15875-4413, Tehran (Iran, Islamic Republic of); Mohseni, Mohsen, E-mail: mmohseni@aut.ac.ir [Department of Polymer Engineering and Color Technology, Amirkabir University of Technology, P.O. Box 15875-4413, Tehran (Iran, Islamic Republic of); Ghanbari, Hossein [Department of Medical Nanotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences (TUMS), Tehran (Iran, Islamic Republic of); Messori, Massimo [Dipartimento di Ingegneria ‘Enzo Ferrari’, Università di Modena e Reggio Emilia, Modena (Italy)

    2016-04-01

    Organic–inorganic hybrid materials have shown improved properties to be used as biocompatible coating in biomedical applications. Polyhedral oligomeric silsesquioxane (POSS) containing coatings are among hybrid materials showing promising properties for these applications. In this work an open cage POSS has been reacted with a titanium alkoxide to end cap the POSS molecule with titanium atom to obtain a so called polyhedral oligomeric metalized silsesquioxane (POMS). The synthesized POMS was characterized by FTIR, RAMAN and UV–visible spectroscopy as well as {sup 29}Si NMR and matrix assisted laser desorption/ionization time-of-flight (MALDI-TOF) techniques. Appearance of peaks at 920 cm{sup −1} in FTIR and 491 cm{sup −1} and 1083 cm{sup −1} in Raman spectra confirmed Si–O–Ti linkage formation. It was also demonstrated that POMS was in a monomeric form. To evaluate the biocompatibility of hybrids films, pristine POSS and synthesized POMS were used in synthesis of a polycarbonate urethane polymer. Results revealed that POMS containing hybrid, not only had notable thermal and mechanical stability compared to POSS containing one, as demonstrated by DSC and DMTA analysis, they also showed controlled surface properties in such a manner that hydrophobicity and biocompatibility were both reachable to give rise to improved cell viability in presence of human umbilical vein endothelial cells (HUVEC) and MRC-5 cells. - Highlight: • Polyhedral Oligomeric Metalized Silsesquioxane (POMS) based on titanium was synthesized. • POMS can improve mechanical properties of polyurethane. • POMS increases hydrophobicity of polyurethane. • POMS is a unique nanocage to enhance biocompatibility of polyurethane.

  5. Oligomerization of adenosin-5´-O-ylmethylphosphonate, an isopolar AMP analogue: Evaluation of the route to short oligoadenylates

    Czech Academy of Sciences Publication Activity Database

    Pressová, Martina; Buděšínský, Miloš; Kóšiová, Ivana; Kopecký, V. Jr.; Cvačka, Josef; Kašička, Václav; Šimák, Ondřej; Točík, Zdeněk; Rosenberg, Ivan

    2010-01-01

    Roč. 93, č. 3 (2010), s. 277-289 ISSN 0006-3525 R&D Projects: GA MŠk(CZ) LC06077; GA MŠk(CZ) LC06061; GA AV ČR KAN200520801; GA ČR GA203/09/0820; GA ČR GA202/09/0193 Grant - others:EMIL-FW6(XE) 503569 Institutional research plan: CEZ:AV0Z40550506 Keywords : spontaneous oligomerization * oligoadenylates * phosphonate linkage Subject RIV: CC - Organic Chemistry Impact factor: 2.572, year: 2010

  6. Outer-Sphere Reactivity Shift of Secondary Phosphine Oxide-Based Nickel Complexes: From Ethylene Hydrophosphinylation to Oligomerization.

    Science.gov (United States)

    Lhermet, Rudy; Moser, Emile; Jeanneau, Erwann; Olivier-Bourbigou, Hélène; Breuil, Pierre-Alain R

    2017-06-01

    A new dimension for secondary phosphine oxide (SPOs) ligands is described in this article. Demonstrated on original π-allylic nickel structures, these self-assembled complexes trigger catalytic hydrophosphinylation reactions. Addition of a Lewis acid B(C 6 F 5 ) 3 switches the reactivity towards migratory insertion and thus ethylene oligomerization through an unprecedented outer-sphere interaction with the coordinated SPO ligand. NMR experiments and X-ray analyses allowed for the observation of the formation of zwitterionic active species as well as their degradation pathway. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Mad2 binding to Mad1 and Cdc20, rather than oligomerization, is required for the spindle checkpoint

    DEFF Research Database (Denmark)

    Sironi, L; Melixetian, M; Faretta, M

    2001-01-01

    Mad2 is a key component of the spindle checkpoint, a device that controls the fidelity of chromosome segregation in mitosis. The ability of Mad2 to form oligomers in vitro has been correlated with its ability to block the cell cycle upon injection into Xenopus embryos. Here we show that Mad2 forms...... incompatible complexes with Mad1 and Cdc20, neither of which requires Mad2 oligomerization. A monomeric point mutant of Mad2 can sustain a cell cycle arrest of comparable strength to that of the wild-type protein. We show that the interaction of Mad2 with Mad1 is crucial for the localization of Mad2...

  8. Effect of Walker A mutation (K86M) on oligomerization and surface targeting of the multidrug resistance transporter ABCG2

    DEFF Research Database (Denmark)

    Henriksen, Ulla Birk; Gether, Ulrik; Litman, Thomas

    2005-01-01

    of the nucleotide binding domain (NBD) known to be critical for ATP binding and/or hydrolysis in ABC transporters. The mutant (ABCG2-K86M) was inactive as expected but was expressed at similar levels as the wild-type (wt) protein. The mutation did not affect the predicted oligomerization properties......The ATP binding cassette (ABC) half-transporter ABCG2 (MXR/BCRP/ABCP) is associated with mitoxantrone resistance accompanied by cross-resistance to a broad spectrum of cytotoxic drugs. Here we investigate the functional consequences of mutating a highly conserved lysine in the Walker A motif...... of the NBDs in assisting proper surface targeting of ABC transporters....

  9. In situ oligomerization of 2-(thiophen-3-yl)acetate intercalated into Zn{sub 2}Al layered double hydroxide

    Energy Technology Data Exchange (ETDEWEB)

    Tronto, Jairo, E-mail: jairotronto@ufv.br [Universidade Federal de Viçosa, Instituto de Ciências Exatas e Tecnológicas, Campus de Rio Parsanaíba, Rodovia BR 354 km 310, Cx. Postal 22, CEP, 38.810-000 Rio Paranaíba, MG (Brazil); Pinto, Frederico G.; Costa, Liovando M. da [Universidade Federal de Viçosa, Instituto de Ciências Exatas e Tecnológicas, Campus de Rio Parsanaíba, Rodovia BR 354 km 310, Cx. Postal 22, CEP, 38.810-000 Rio Paranaíba, MG (Brazil); Leroux, Fabrice; Dubois, Marc [Clermont Université, Université Blaise Pascal, Institut de Chimie de Clermont-Ferrand, BP 10448, F-63000 Clermont-Ferrand (France); CNRS, UMR 6296, ICCF, BP 80026, F-6317 Clermont-Ferrand (France); Valim, João B. [Universidade de São Paulo, Faculdade de Filosofia Ciências e Letras de Ribeirão Preto, Departamento de Química, Av. dos Bandeirantes 3900, CEP 14.040-901, Ribeirão Preto, SP (Brazil)

    2015-01-15

    A layered double hydroxide (LDH) with cation composition Zn{sub 2}Al was intercalated with 2-(thiophen-3-yl)acetate (3-TA) monomers. To achieve in situ polymerization and/or oligomerization of the intercalated monomers, soft thermal treatments were carried out, and subsequent hybrid LDH materials were analyzed by means of several characterization techniques using powder X-ray diffraction (PXRD), Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), {sup 13}C CP–MAS nuclear magnetic resonance (NMR), electron spin resonance (EPR), scanning electron microscopy (SEM), and transmission electron microscopy (TEM), inductively coupled plasma optical emission spectroscopy (ICP–OES), and elemental analysis. PXRD analysis suggested that the intercalated monomers formed a bilayer. Thermal treatment of the hybrid LDH assembly above 120 °C provokes partially the breakdown of the layered structure, generating the phase zincite. EPR results indicated that vicinal monomers (oligomerization) were bound to each other after hydrothermal or thermal treatment, leading to a polaron response characteristic of electron conductivity localized on a restricted number of thiophene-based monomer segments. Localized unpaired electrons exist in the material and interact with the {sup 27}Al nuclei of the LDH layers by superhyperfine coupling. These unpaired electrons also interact with the surface of ZnO (O{sup 2−} vacancies), formed during the thermal treatments. - Graphical abstract: We synthesized a layered double hydroxide (LDH) with cation composition Zn{sub 2}Al, intercalated with 2-(thiophen-3-yl)acetate (3-TA) monomers, by coprecipitation at constant pH. We thermally treated the material, to achieve in situ polymerization and/or oligomerization of the intercalated monomers. - Highlights: • A Zn{sub 2}Al–LDH was intercalated with 2-(thiophen-3-yl)acetate monomers. • To achieve in situ oligomerization of the monomers, thermal treatments were made.

  10. Strong Decomposition of Random Variables

    DEFF Research Database (Denmark)

    Hoffmann-Jørgensen, Jørgen; Kagan, Abram M.; Pitt, Loren D.

    2007-01-01

    A random variable X is stongly decomposable if X=Y+Z where Y=Φ(X) and Z=X-Φ(X) are independent non-degenerated random variables (called the components). It is shown that at least one of the components is singular, and we derive a necessary and sufficient condition for strong decomposability...

  11. Strong interaction at finite temperature

    Indian Academy of Sciences (India)

    Abstract. We review two methods discussed in the literature to determine the effective parameters of strongly interacting particles as they move through a heat bath. The first one is the general method of chiral perturbation theory, which may be readily applied to this problem. The other is the method of thermal QCD sum rules ...

  12. Strong-strong beam-beam simulation on parallel computer

    Energy Technology Data Exchange (ETDEWEB)

    Qiang, Ji

    2004-08-02

    The beam-beam interaction puts a strong limit on the luminosity of the high energy storage ring colliders. At the interaction points, the electromagnetic fields generated by one beam focus or defocus the opposite beam. This can cause beam blowup and a reduction of luminosity. An accurate simulation of the beam-beam interaction is needed to help optimize the luminosity in high energy colliders.

  13. Strong-strong beam-beam simulation on parallel computer

    International Nuclear Information System (INIS)

    Qiang, Ji

    2004-01-01

    The beam-beam interaction puts a strong limit on the luminosity of the high energy storage ring colliders. At the interaction points, the electromagnetic fields generated by one beam focus or defocus the opposite beam. This can cause beam blowup and a reduction of luminosity. An accurate simulation of the beam-beam interaction is needed to help optimize the luminosity in high energy colliders

  14. Coating of Carbon Fiber with Polyhedral Oligomeric Silsesquioxane (POSS to Enhance Mechanical Properties and Durability of Carbon/Vinyl Ester Composites

    Directory of Open Access Journals (Sweden)

    Mujib Khan

    2011-09-01

    Full Text Available Our continuing quest to improve the performance of polymer composites under moist and saltwater environments has gained momentum in recent years with the reinforcement of inorganic nanoparticles into the polymer. The key to mitigate degradation of composites under such environments is to maintain the integrity of the fiber/matrix (F/M interface. In this study, the F/M interface of carbon/vinyl ester composites has been modified by coating the carbon fiber with polyhedral oligomeric silsesquioxane (POSS. POSS is a nanostructured inorganic-organic hybrid particle with a cubic structure having silicon atoms at the core and linked to oxygen atoms. The advantage of using POSS is that the silicon atoms can be linked to a substituent that can be almost any chemical group known in organic chemistry. Cubic silica cores are ‘hard particles’ and are about 0.53 nm in diameter. The peripheral organic unit is a sphere of about 1–3 nm in diameter. Further, cubic structure of POSS remains intact during the polymerization process and therefore with appropriate functional groups, if installed on the fiber surface, would provide a stable and strong F/M interface. Two POSS systems with two different functional groups; namely, octaisobutyl and trisilanolphenyl have been investigated. A set of chemical and mechanical procedures has been developed to coat carbon fibers with POSS, and to fabricate layered composites with vinyl ester resin. Interlaminar shear and low velocity impact tests have indicated around 17–38% improvement in mechanical properties with respect to control samples made without the POSS coating. Saltwater and hygrothermal tests at various environmental conditions have revealed that coating with POSS reduces water absorption by 20–30% and retains the composite properties.

  15. Renormalization in theories with strong vector forces

    International Nuclear Information System (INIS)

    Kocic, A.

    1991-01-01

    There are not many field theories in four dimensions that have sensible ultraviolet and interesting (non-trivial) infrared behavior. At present, asymptotically free theories seem to have deserved their legitimacy and there is a strong prejudice that they might be the only ones to have such a distinction. This belief stems mostly from the fact that most of the knowledge of field theory in four dimensions comes from perturbation theory. However, nonperturbative studies of the lower dimensional theories reveal a host of interesting phenomena that are perturbative studies of the lower dimensional theories reveal a host of interesting phenomena that perturbatively inaccessible. The lack of asymptotic freedom implies that the coupling constant grows at short distances and perturbation theory breaks down. Thus, in such theories, ultraviolet behavior requires nonperturbative treatment. Recently, the interest in strongly coupled gauge theories has been revived. In particularly, four dimensional quantum electrodynamics has received considerable attention. This was motivated by the discovery of an ultraviolet stable fixed point at strong couplings. If this fixed point would turn out to be non-gaussian, then QED would be the first nontrivial nonasymptotically free theory in four dimensions. The importance of such a result would be twofold. First, the old question of the existence of QED could be settled. Of course, this would be the case provided that the low energy limit of the theory actually describes photons and electrons; apriori, there is no reason to assume this. Second, the discovery of a nontrivial nonasymptotically free theory would be of great paradigmatic value. The theories which quenched QED resembles the most are nonabelian gauge theories with many flavors with beta-function positive or vanishing at weak couplings. These theories are at present considered as viable candidates for technicolor unification schemes

  16. PREFACE: Strongly correlated electron systems Strongly correlated electron systems

    Science.gov (United States)

    Saxena, Siddharth S.; Littlewood, P. B.

    2012-07-01

    This special section is dedicated to the Strongly Correlated Electron Systems Conference (SCES) 2011, which was held from 29 August-3 September 2011, in Cambridge, UK. SCES'2011 is dedicated to 100 years of superconductivity and covers a range of topics in the area of strongly correlated systems. The correlated electronic and magnetic materials featured include f-electron based heavy fermion intermetallics and d-electron based transition metal compounds. The selected papers derived from invited presentations seek to deepen our understanding of the rich physical phenomena that arise from correlation effects. The focus is on quantum phase transitions, non-Fermi liquid phenomena, quantum magnetism, unconventional superconductivity and metal-insulator transitions. Both experimental and theoretical work is presented. Based on fundamental advances in the understanding of electronic materials, much of 20th century materials physics was driven by miniaturisation and integration in the electronics industry to the current generation of nanometre scale devices. The achievements of this industry have brought unprecedented advances to society and well-being, and no doubt there is much further to go—note that this progress is founded on investments and studies in the fundamentals of condensed matter physics from more than 50 years ago. Nevertheless, the defining challenges for the 21st century will lie in the discovery in science, and deployment through engineering, of technologies that can deliver the scale needed to have an impact on the sustainability agenda. Thus the big developments in nanotechnology may lie not in the pursuit of yet smaller transistors, but in the design of new structures that can revolutionise the performance of solar cells, batteries, fuel cells, light-weight structural materials, refrigeration, water purification, etc. The science presented in the papers of this special section also highlights the underlying interest in energy-dense materials, which

  17. Shape memory and actuation behavior of semicrystalline polymer networks

    International Nuclear Information System (INIS)

    Bothe, Martin

    2014-01-01

    Shape memory polymers (SMPs) can change their shape on application of a suitable stimulus. To enable such behavior, a 'programming' procedure fixes a deformation, yielding a stable temporary shape. In thermoresponsive SMPs, subsequent heating triggers entropy-elastic recovery of the initial shape. An additional shape change on cooling, i.e. thermoreversible two-way actuation, can be stimulated by a crystallization phenomenon. In this thesis, cyclic thermomechanical measurements systematically determined (1) the shape memory and (2) the actuation behavior under constant load as well as under stress-free conditions. Chemically cross-linked, star-shaped polyhedral oligomeric silsesquioxane polyurethane (SPOSS-PU) hybrid polymer networks and physically cross-linked poly(ester urethane) (PEU) block copolymers were investigated around the melting and crystallization temperatures of their polyester soft segments. (1) The SPOSS-PUs showed excellent shape fixities and recoverabilities of almost 100% at high cross-linking density, while PEUs exhibited pronounced shape memory properties at increased soft segment content. Furthermore, two-fold programmed SPOSS-PU specimens were able to recover their initial shape in two thermally separated events. Even a neck, which formed during deformation of SPOSS-PUs with high soft segment content, was reversed. (2) In PEUs, globally oriented crystallization on cooling drove expansion of the sample, in particular at high soft segment content and after application of a strong deformation. Melting reversed that orientation; the PEU sample contracted and thereby completed the thermoreversible actuation cycle. Under load, multiple polymorphic phase transitions enabled two successive expansion and contraction steps, while under stress-free conditions various geometric shape changes, including the increase and decrease of PEU sample length and thickness as well as twisting and untwisting could be experimentally witnessed. Such actuation

  18. Novel dendritic light-emitting materials containing polyhedral oligomeric silsesquioxanes core

    International Nuclear Information System (INIS)

    Chen, K.-B.; Chang, Y.-P.; Yang, S.-H.; Hsu, C.-S.

    2006-01-01

    A new series of star-like light-emitting materials (POSS1, POSS2 and POSS3) were synthesized by hydrosilylation of the polyhedral oligomeric silsesquioxane with 4,4'-bis(4-(di-(4-methylphenyl)amino)styryl)-2-(hexan-1-yloxy) -5-(10-undecen-1-yloxy)benzene (C1), 4,4'-bis[(E)-2-(N-ethylcarbazoyl)ethenyl]-2-(hexan-1-yloxy)-5- (10-undecen-1-yoxy)benzene (C2), and Iridium(III) bis(2-phenylpyridine-C 2 -N') (13-teradecenyl acetonate) (C3), respectively. All synthesized materials are soluble in common organic solvents, such as chloroform, toluene and 1,2-dichloroethane, and exhibit good film-forming properties. Therefore, they can be used to fabricate devices by spin-coating. The aggregation of peripheral chromophores can be prevented by the rigid POSS core. A double-layer, light-emitting diode with the configuration of indium-tin oxide/poly(ethylene 3,4-dioxythiophene)/POSS1/Ca/Al was fabricated using POSS1 as the active layer. The device emitted green light with a maximum brightness of 115 cd/m 2 and a current yield of 0.07 cd/A. When the light-emitting layer is blended with 0.8% electron-transport material, 2-(4'-tert-butylphenyl)-5-(4'-diphenyl)-1,3,4-oxadiazole, the maximum brightness and current yield of the device can reach 1469 cd/m 2 and 0.8 cd/A, respectively. The performance of a POSS2 device with the same device structure can reach 1102 cd/m 2 and 0.88 cd/A. POSS3 is a kind of triplet material and blended with 4,4-N,N'-dicarbazole-biphenyl as host material, to fabricate the light-emitting device. The maximum brightness and current yield reach 1008 cd/m 2 and 1.04 cd/A, respectively. Blending with 1,3,5-tris(2-N-phenylbenzimi dazolyl)benzene as the hole-blocking material yields a maximum brightness and current yield of 1172 cd/m 2 and 3.99 cd/A

  19. SHOP-type nickel complexes with alkyl substituents on phosphorus, synthesis and catalytic ethylene oligomerization.

    Science.gov (United States)

    Kermagoret, Anthony; Braunstein, Pierre

    2008-02-14

    The beta-keto phosphorus ylides (n-Bu)3P=CHC(O)Ph 6, (t-Bu)2PhP=CHC(O)Ph 7, (t-Bu)Ph2P=CHC(O)Ph 8, (n-Bu)2PhP=CHC(O)Ph 9, (n-Bu)Ph2P=CHC(O)Ph 10, Me2PhP=CHC(O)Ph 11 and Ph3P=CHC(O)(o-OMe-C6H4) 12 have been synthesized in 80-96% yields. The Ni(II) complexes [NiPh{Ph2PCH...C(...O)(o-OMeC6H4)}(PPh3)] 13, [NiPh{Ph(t-Bu)PCHC(O)Ph}(PPh3)] 15, [NiPh{(n-Bu)2PCH...C(...O)Ph}(PPh3)] 16 and [NiPh{Ph(n-Bu)PCH...C(...O)Ph}(PPh3)] 17 have been prepared by reaction of equimolar amounts of [Ni(COD)2] and PPh3 with the beta-keto phosphorus ylides 12 or 8-10, respectively, and characterized by 1H and 31P{1H} NMR spectroscopy. NMR studies and the crystal structure determination of 13 indicated an interaction between the hydrogen atom of the C-H group alpha to phosphorus and the ether function. The complexes [NiPh{Ph2PCHC(O)Ph}(Py)] 18, [NiPh{Ph(t-Bu)PCHC(O)Ph}(Py)] 19, [NiPh{(n-Bu)2PCH...C(...O)Ph}(Py)] 20, [NiPh{Ph(n-Bu)PCH...C(...O)Ph}(Py)] 21 and [NiPh{Me2PCH...C(...O)Ph}(Py)] 22 have been isolated from the reactions of [Ni(COD)2] and an excess of pyridine with the -keto phosphorus ylides Ph3PCH=C(O)Ph 3 or 8-11, respectively, and characterized by 1H and 31P{1H} NMR spectroscopy. Ligands 3, 8, 10 and 12 have been used to prepare in situ oligomerization catalysts by reaction with one equiv. of [Ni(COD)2] and PPh3 under an ethylene pressure of 30 or 60 bar. The catalyst prepared in situ from 12, [Ni(COD)2] and PPh3 was the most active of the series with a TON of 12700 mol C2H4 (mol Ni)-1 under 30 bar ethylene. When the beta-keto phosphorus ylide 8 was reacted in situ with three equiv. of [Ni(COD)2] and one equiv. of PPh3 under 30 bar of ethylene, ethylene polymerization was observed with a TON of 5500 mol C2H4 (mol Ni)-1.

  20. Predicting success of oligomerized pool engineering (OPEN for zinc finger target site sequences

    Directory of Open Access Journals (Sweden)

    Goodwin Mathew J

    2010-11-01

    Full Text Available Abstract Background Precise and efficient methods for gene targeting are critical for detailed functional analysis of genomes and regulatory networks and for potentially improving the efficacy and safety of gene therapies. Oligomerized Pool ENgineering (OPEN is a recently developed method for engineering C2H2 zinc finger proteins (ZFPs designed to bind specific DNA sequences with high affinity and specificity in vivo. Because generation of ZFPs using OPEN requires considerable effort, a computational method for identifying the sites in any given gene that are most likely to be successfully targeted by this method is desirable. Results Analysis of the base composition of experimentally validated ZFP target sites identified important constraints on the DNA sequence space that can be effectively targeted using OPEN. Using alternate encodings to represent ZFP target sites, we implemented Naïve Bayes and Support Vector Machine classifiers capable of distinguishing "active" targets, i.e., ZFP binding sites that can be targeted with a high rate of success, from those that are "inactive" or poor targets for ZFPs generated using current OPEN technologies. When evaluated using leave-one-out cross-validation on a dataset of 135 experimentally validated ZFP target sites, the best Naïve Bayes classifier, designated ZiFOpT, achieved overall accuracy of 87% and specificity+ of 90%, with an ROC AUC of 0.89. When challenged with a completely independent test set of 140 newly validated ZFP target sites, ZiFOpT performance was comparable in terms of overall accuracy (88% and specificity+ (92%, but with reduced ROC AUC (0.77. Users can rank potentially active ZFP target sites using a confidence score derived from the posterior probability returned by ZiFOpT. Conclusion ZiFOpT, a machine learning classifier trained to identify DNA sequences amenable for targeting by OPEN-generated zinc finger arrays, can guide users to target sites that are most likely to function

  1. Strongly nonlinear oscillators analytical solutions

    CERN Document Server

    Cveticanin, Livija

    2014-01-01

    This book provides the presentation of the motion of pure nonlinear oscillatory systems and various solution procedures which give the approximate solutions of the strong nonlinear oscillator equations. The book presents the original author’s method for the analytical solution procedure of the pure nonlinear oscillator system. After an introduction, the physical explanation of the pure nonlinearity and of the pure nonlinear oscillator is given. The analytical solution for free and forced vibrations of the one-degree-of-freedom strong nonlinear system with constant and time variable parameter is considered. Special attention is given to the one and two mass oscillatory systems with two-degrees-of-freedom. The criteria for the deterministic chaos in ideal and non-ideal pure nonlinear oscillators are derived analytically. The method for suppressing chaos is developed. Important problems are discussed in didactic exercises. The book is self-consistent and suitable as a textbook for students and also for profess...

  2. Flavour Democracy in Strong Unification

    CERN Document Server

    Abel, S A; Abel, Steven; King, Steven

    1998-01-01

    We show that the fermion mass spectrum may naturally be understood in terms of flavour democratic fixed points in supersymmetric theories which have a large domain of attraction in the presence of "strong unification". Our approach provides an alternative to the approximate Yukawa texture zeroes of the Froggatt-Nielsen mechanism. We discuss a particular model based on a broken gauged $SU(3)_L\\times SU(3)_R$ family symmetry which illustrates our approach.

  3. Protective Effects of Testosterone on Presynaptic Terminals against Oligomeric β-Amyloid Peptide in Primary Culture of Hippocampal Neurons

    Directory of Open Access Journals (Sweden)

    Chi-Fai Lau

    2014-01-01

    Full Text Available Increasing lines of evidence support that testosterone may have neuroprotective effects. While observational studies reported an association between higher bioavailable testosterone or brain testosterone levels and reduced risk of Alzheimer’s disease (AD, there is limited understanding of the underlying neuroprotective mechanisms. Previous studies demonstrated that testosterone could alleviate neurotoxicity induced by β-amyloid (Aβ, but these findings mainly focused on neuronal apoptosis. Since synaptic dysfunction and degeneration are early events during the pathogenesis of AD, we aim to investigate the effects of testosterone on oligomeric Aβ-induced synaptic changes. Our data suggested that exposure of primary cultured hippocampal neurons to oligomeric Aβ could reduce the length of neurites and decrease the expression of presynaptic proteins including synaptophysin, synaptotagmin, and synapsin-1. Aβ also disrupted synaptic vesicle recycling and protein folding machinery. Testosterone preserved the integrity of neurites and the expression of presynaptic proteins. It also attenuated Aβ-induced impairment of synaptic exocytosis. By using letrozole as an aromatase antagonist, we further demonstrated that the effects of testosterone on exocytosis were unlikely to be mediated through the estrogen receptor pathway. Furthermore, we showed that testosterone could attenuate Aβ-induced reduction of HSP70, which suggests a novel mechanism that links testosterone and its protective function on Aβ-induced synaptic damage. Taken together, our data provide further evidence on the beneficial effects of testosterone, which may be useful for future drug development for AD.

  4. Fingolimod phosphate attenuates oligomeric amyloid β-induced neurotoxicity via increased brain-derived neurotrophic factor expression in neurons.

    Directory of Open Access Journals (Sweden)

    Yukiko Doi

    Full Text Available The neurodegenerative processes that underlie Alzheimer's disease are mediated, in part, by soluble oligomeric amyloid β, a neurotoxic protein that inhibits hippocampal long-term potentiation, disrupts synaptic plasticity, and induces the production of reactive oxygen species. Here we show that the sphingosine-1-phosphate (S1P receptor (S1PR agonist fingolimod phosphate (FTY720-P-a new oral drug for multiple sclerosis-protects neurons against oligomeric amyloid β-induced neurotoxicity. We confirmed that primary mouse cortical neurons express all of the S1P receptor subtypes and FTY720-P directly affects the neurons. Treatment with FTY720-P enhanced the expression of brain-derived neurotrophic factor (BDNF in neurons. Moreover, blocking BDNF-TrkB signaling with a BDNF scavenger, TrkB inhibitor, or ERK1/2 inhibitor almost completely ablated these neuroprotective effects. These results suggested that the neuroprotective effects of FTY720-P are mediated by upregulated neuronal BDNF levels. Therefore, FTY720-P may be a promising therapeutic agent for neurodegenerative diseases, such as Alzheimer's disease.

  5. Highly efficient phosphorescent materials based on Ir(iii) complexes-grafted on a polyhedral oligomeric silsesquioxane core.

    Science.gov (United States)

    Yu, Tianzhi; Xu, Zixuan; Su, Wenming; Zhao, Yuling; Zhang, Hui; Bao, Yanjun

    2016-09-14

    A new iridium(iii) complex containing a coumarin derivative as the cyclometalated ligand (L) and a carbazole-functionalized β-diketonate (Cz-acac-allyl) as the ancillary ligand, namely, Ir(iii) bis(3-(pyridin-2-yl)coumarinato-N,C(4))(1-(9-butyl-9H-carbazol-3-yl)hept-6-ene-1,3-dionato-O,O) [Ir(L)2(Cz-acac-allyl)], was firstly synthesized as the emissive iridium(iii) complex. Then three new phosphorescent polyhedral oligomeric silsesquioxane (POSS) materials, consisting of the emissive Ir(iii) complex and carbazole moieties covalently attached to a polyhedral oligomeric silsesquioxane (POSS) core were successfully synthesized by hydrosilylation reaction in the presence of platinum(0)-1,3-divinyl-1,1,3,3-tetramethyldisiloxane (Pt-dvs) as the catalyst. These phosphorescent POSS materials offer many advantages including amorphous properties, good thermal stabilities, and good solubility in common solvents, and high purity via column chromatography. The photoluminescence spectra of the POSS materials in solution and in the solid state indicate a reduction in the degrees of interactions among the Ir(iii) complex units and concentration quenching due to the bulky POSS core. Solution processed light-emitting devices based on these phosphorescent POSS materials exhibit a maximum external quantum efficiency (EQE) of 9.77%.

  6. Early diagnostic and prognostic values of anti-cyclic citrullinated peptide antibody and cartilage oligomeric matrix protein in rheumatoid arthritis.

    Science.gov (United States)

    Algergawy, Shereen A; Abd El-Sabour, M; Osman, Ahmed S; Emam, Sherin M; Elham, N

    2013-01-01

    This study aimed to evaluate the role of Anti-Cyclic Citrullinated Peptide (anti-CCP) antibody in comparison to Cartilage oligomeric matrix protein (COMP) in Rheumatoid Arthritis (RA) patients as predictors of the disease activity and cartilage destruction. The study included 60 patients &10 apparently healthy subjects. They were divided into 4 groups. Group 1: consisted of 20 patients with established rheumatoid arthritis( and positive rheumatoid factor). Group 2: 20 suspected (rheumatoid factor negative) patients Group 3: 20 patients with other autoimmune inflammatory diseases (15 with psoaritic arthritis, 5 with systemic lupus erthromatosis).and Group 4: 10 age and sex matched controls. For each patient medical examination and disease activity evaluation using Disease Activity Score (DAS) was performed Anti cyclic citrullinated peptide (anti CCP) level was measured by ELISA method and cartilage oligomeric matrix protein (COMP) was determined by indirect immune fluorescent method. Serum level of anti CCP antibodies and COMP were Significantly related to DAS (disease activity score) and cartilage destruction, the serum presence of COMP was highly significant in rheumatoid arthritis patients than those with other autoimmune disease, the sensitivity of anti CCP in diagnosis of RA was 77.5% and specificity was96.6%. It is concluded that anti CCP, and COMP may be a useful noninvasive markers for disease activity and cartilage destruction.

  7. Humanin decreases mitochondrial membrane permeability by inhibiting the membrane association and oligomerization of Bax and Bid proteins.

    Science.gov (United States)

    Ma, Ze-Wei; Liu, Dong-Xiang

    2017-12-21

    Humanin (HN) is a 24-residue peptide identified from the brain of a patient with Alzheimer's disease (AD). HN has been found to protect against neuronal insult caused by Aβ peptides or transfection of familial AD mutant genes. In order to elucidate the molecular mechanisms of HN neuroprotection, we explored the effects of HN on the association of Bax or Bid with lipid bilayers and their oligomerization in the membrane. By using single-molecule fluorescence and Förster resonance energy transfer techniques, we showed that Bax was mainly present as monomers, dimers and tetramers in lipid bilayers, while truncated Bid (tBid) enhanced the membrane association and tetramerization of Bax. HN (100 nmol/L) inhibited the self-association and tBid-activated association of Bax with the bilayers, and significantly decreased the proportion of Bax in tetramers. Furthermore, HN inhibited Bid translocation to lipid bilayers. HN could bind with Bax and Bid either in solution or in the membrane. However, HN could not pull the proteins out of the membrane. Based on these results, we propose that HN binds to Bax and cBid in solution and inhibits their translocation to the membrane. Meanwhile, HN interacts with the membrane-bound Bax and tBid, preventing the recruitment of cytosolic Bax and its oligomerization in the membrane. In this way, HN inhibits Bax pore formation in mitochondrial outer membrane and suppresses cytochrome c release and mitochondria-dependent apoptosis.

  8. Synthesis and ion-binding properties of polymeric pseudocrown ethers II: Template ion induced cyclization of oligomeric ethylene glycol diacrylates

    Energy Technology Data Exchange (ETDEWEB)

    Mathur, A.M.; Scranton, A.B. [Michigan State Univ., East Lansing, MI (United States)

    1997-01-01

    Inexpensive polymeric pseudocrown ethers have been synthesized based upon a {open_quotes}template ion{close_quotes} effect in which oligomeric ethylene glycol diacrylates are induced to assume a circular conformation in which the unsaturated end-groups are in proximity. This synthetic scheme has considerable potential for the development of inexpensive materials for binding of target cations. In this contribution, the authors report a spectroscopic study of the induced cyclization caused by ion-dipole interactions between the templating cation and the electron lone pairs of the ethylene glycol ether linkages. Fluorescence spectroscopy was used to provide insight into the templatization process by examining excimer formation in pyrene end-labeled oligomeric ethylene glycol both in the absence and in the presence of the templating ion. Pyrene end-labeled tetraethylene glycol and pentaethylene glycol were synthesized and excimer fluorescence enhancement was studied with the introduction of cations such as nickel, chromium and tin in solvents such as tetrahydrofuran and chloroform. An increase in excimer fluorescence indicated enhanced excimer formation due to the templating effect of the cation which results in the end groups being close to each other. Molecular dynamics simulations of pyrene end-labeled ligands were performed to elucidate the effect of the large fluorescent chromophores on the chain conformations.

  9. A D53 repression motif induces oligomerization of TOPLESS corepressors and promotes assembly of a corepressor-nucleosome complex.

    Science.gov (United States)

    Ma, Honglei; Duan, Jingbo; Ke, Jiyuan; He, Yuanzheng; Gu, Xin; Xu, Ting-Hai; Yu, Hong; Wang, Yonghong; Brunzelle, Joseph S; Jiang, Yi; Rothbart, Scott B; Xu, H Eric; Li, Jiayang; Melcher, Karsten

    2017-06-01

    TOPLESS are tetrameric plant corepressors of the conserved Tup1/Groucho/TLE (transducin-like enhancer of split) family. We show that they interact through their TOPLESS domains (TPDs) with two functionally important ethylene response factor-associated amphiphilic repression (EAR) motifs of the rice strigolactone signaling repressor D53: the universally conserved EAR-3 and the monocot-specific EAR-2. We present the crystal structure of the monocot-specific EAR-2 peptide in complex with the TOPLESS-related protein 2 (TPR2) TPD, in which the EAR-2 motif binds the same TPD groove as jasmonate and auxin signaling repressors but makes additional contacts with a second TPD site to mediate TPD tetramer-tetramer interaction. We validated the functional relevance of the two TPD binding sites in reporter gene assays and in transgenic rice and demonstrate that EAR-2 binding induces TPD oligomerization. Moreover, we demonstrate that the TPD directly binds nucleosomes and the tails of histones H3 and H4. Higher-order assembly of TPD complexes induced by EAR-2 binding markedly stabilizes the nucleosome-TPD interaction. These results establish a new TPD-repressor binding mode that promotes TPD oligomerization and TPD-nucleosome interaction, thus illustrating the initial assembly of a repressor-corepressor-nucleosome complex.

  10. Crystal Structure of FadA Adhesin from Fusobacterium nucleatum Reveals a Novel Oligomerization Motif, the Leucine Chain

    Energy Technology Data Exchange (ETDEWEB)

    Nithianantham, Stanley; Xu, Minghua; Yamada, Mitsunori; Ikegami, Akihiko; Shoham, Menachem; Han, Yiping W.; (Case Western)

    2009-04-07

    Many bacterial appendages have filamentous structures, often composed of repeating monomers assembled in a head-to-tail manner. The mechanisms of such linkages vary. We report here a novel protein oligomerization motif identified in the FadA adhesin from the Gram-negative bacterium Fusobacterium nucleatum. The 2.0 {angstrom} crystal structure of the secreted form of FadA (mFadA) reveals two antiparallel {alpha}-helices connected by an intervening 8-residue hairpin loop. Leucine-leucine contacts play a prominent dual intra- and intermolecular role in the structure and function of FadA. First, they comprise the main association between the two helical arms of the monomer; second, they mediate the head-to-tail association of monomers to form the elongated polymers. This leucine-mediated filamentous assembly of FadA molecules constitutes a novel structural motif termed the 'leucine chain.' The essential role of these residues in FadA is corroborated by mutagenesis of selected leucine residues, which leads to the abrogation of oligomerization, filament formation, and binding to host cells.

  11. Atoms in strong laser fields

    International Nuclear Information System (INIS)

    L'Huillier, A.

    2002-01-01

    When a high-power laser focuses into a gas of atoms, the electromagnetic field becomes of the same magnitude as the Coulomb field which binds a 1s electron in a hydrogen atom. 3 highly non-linear phenomena can happen: 1) ATI (above threshold ionization): electrons initially in the ground state absorb a large number of photons, many more than the minimum number required for ionization; 2) multiple ionization: many electrons can be emitted one at a time, in a sequential process, or simultaneously in a mechanism called direct or non-sequential; and 3) high order harmonic generation (HHG): efficient photon emission in the extreme ultraviolet range, in the form of high-order harmonics of the fundamental laser field can occur. The theoretical problem consists in solving the time dependent Schroedinger equation (TDSE) that describes the interaction of a many-electron atom with a laser field. A number of methods have been proposed to solve this problem in the case of a hydrogen atom or a single-active electron atom in a strong laser field. A large effort is presently being devoted to go beyond the single-active approximation. The understanding of the physics of the interaction between atoms and strong laser fields has been provided by a very simple model called ''simple man's theory''. A unified view of HHG, ATI, and non-sequential ionization, originating from the simple man's model and the strong field approximation, expressed in terms of electrons trajectories or quantum paths is slowly emerging. (A.C.)

  12. Strongly Interacting Light Dark Matter

    Directory of Open Access Journals (Sweden)

    Sebastian Bruggisser, Francesco Riva, Alfredo Urbano

    2017-09-01

    Full Text Available In the presence of approximate global symmetries that forbid relevant interactions, strongly coupled light Dark Matter (DM can appear weakly coupled at small energy and generate a sizable relic abundance. Fundamental principles like unitarity restrict these symmetries to a small class, where the leading interactions are captured by effective operators up to dimension-8. Chiral symmetry, spontaneously broken global symmetries and non-linearly realized supersymmetry are examples of this. Their DM candidates (composite fermions, pseudo Nambu-Goldstone Bosons and Goldstini are interesting targets for LHC missing-energy searches.

  13. Strongly interacting light dark matter

    International Nuclear Information System (INIS)

    Bruggisser, Sebastian; Riva, Francesco; Urbano, Alfredo

    2016-07-01

    In the presence of approximate global symmetries that forbid relevant interactions, strongly coupled light Dark Matter (DM) can appear weakly coupled at small-energy and generate a sizable relic abundance. Fundamental principles like unitarity restrict these symmetries to a small class, where the leading interactions are captured by effective operators up to dimension-8. Chiral symmetry, spontaneously broken global symmetries and non-linearly realized supersymmetry are examples of this. Their DM candidates (composite fermions, pseudo-Nambu-Goldstone Bosons and Goldstini) are interesting targets for LHC missing-energy searches.

  14. Rydberg atoms in strong fields

    International Nuclear Information System (INIS)

    Kleppner, D.; Tsimmerman, M.

    1985-01-01

    Experimental and theoretical achievements in studying Rydberg atoms in external fields are considered. Only static (or quasistatic) fields and ''one-electron'' atoms, i.e. atoms that are well described by one-electron states, are discussed. Mainly behaviour of alkali metal atoms in electric field is considered. The state of theoretical investigations for hydrogen atom in magnetic field is described, but experimental data for atoms of alkali metals are presented as an illustration. Results of the latest experimental and theoretical investigations into the structure of Rydberg atoms in strong fields are presented

  15. Scalar strong interaction hadron theory

    CERN Document Server

    Hoh, Fang Chao

    2015-01-01

    The scalar strong interaction hadron theory, SSI, is a first principles' and nonlocal theory at quantum mechanical level that provides an alternative to low energy QCD and Higgs related part of the standard model. The quark-quark interaction is scalar rather than color-vectorial. A set of equations of motion for mesons and another set for baryons have been constructed. This book provides an account of the present state of a theory supposedly still at its early stage of development. This work will facilitate researchers interested in entering into this field and serve as a basis for possible future development of this theory.

  16. Strong Plate, Weak Slab Dichotomy

    Science.gov (United States)

    Petersen, R. I.; Stegman, D. R.; Tackley, P.

    2015-12-01

    Models of mantle convection on Earth produce styles of convection that are not observed on Earth.Moreover non-Earth-like modes, such as two-sided downwellings, are the de facto mode of convection in such models.To recreate Earth style subduction, i.e. one-sided asymmetric recycling of the lithosphere, proper treatment of the plates and plate interface are required. Previous work has identified several model features that promote subduction. A free surface or pseudo-free surface and a layer of material with a relatively low strength material (weak crust) allow downgoing plates to bend and slide past overriding without creating undue stress at the plate interface. (Crameri, et al. 2012, GRL)A low viscosity mantle wedge, possibly a result of slab dehydration, decouples the plates in the system. (Gerya et al. 2007, Geo)Plates must be composed of material which, in the case of the overriding plate, are is strong enough to resist bending stresses imposed by the subducting plate and yet, as in the case of the subducting plate, be weak enough to bend and subduct when pulled by the already subducted slab. (Petersen et al. 2015, PEPI) Though strong surface plates are required for subduction such plates may present a problem when they encounter the lower mantle.As the subducting slab approaches the higher viscosity, lower mantle stresses are imposed on the tip.Strong slabs transmit this stress to the surface.There the stress field at the plate interface is modified and potentially modifies the style of convection. In addition to modifying the stress at the plate interface, the strength of the slab affects the morphology of the slab at the base of the upper mantle. (Stegman, et al 2010, Tectonophysics)Slabs that maintain a sufficient portion of their strength after being bent require high stresses to unbend or otherwise change their shape.On the other hand slabs that are weakened though the bending process are more amenable to changes in morphology. We present the results of

  17. Physics of Strongly Coupled Plasma

    Energy Technology Data Exchange (ETDEWEB)

    Kraeft, Wolf-Dietrich [Universitat Rostock (Germany)

    2007-07-15

    Strongly coupled plasmas (or non-ideal plasmas) are multi-component charged many-particle systems, in which the mean value of the potential energy of the system is of the same order as or even higher than the mean value of the kinetic energy. The constituents are electrons, ions, atoms and molecules. Dusty (or complex) plasmas contain still mesoscopic (multiply charged) particles. In such systems, the effects of strong coupling (non-ideality) lead to considerable deviations of physical properties from the corresponding properties of ideal plasmas, i.e., of plasmas in which the mean kinetic energy is essentially larger than the mean potential energy. For instance, bound state energies become density dependent and vanish at higher densities (Mott effect) due to the interaction of the pair with the surrounding particles. Non-ideal plasmas are of interest both for general scientific reasons (including, for example, astrophysical questions), and for technical applications such as inertially confined fusion. In spite of great efforts both experimentally and theoretically, satisfactory information on the physical properties of strongly coupled plasmas is not at hand for any temperature and density. For example, the theoretical description of non-ideal plasmas is possible only at low densities/high temperatures and at extremely high densities (high degeneracy). For intermediate degeneracy, however, numerical experiments have to fill the gap. Experiments are difficult in the region of 'warm dense matter'. The monograph tries to present the state of the art concerning both theoretical and experimental attempts. It mainly includes results of the work performed in famous Russian laboratories in recent decades. After outlining basic concepts (chapter 1), the generation of plasmas is considered (chapter 2, chapter 3). Questions of partial (chapter 4) and full ionization (chapter 5) are discussed including Mott transition and Wigner crystallization. Electrical and

  18. Strong earthquakes can be predicted: a multidisciplinary method for strong earthquake prediction

    Directory of Open Access Journals (Sweden)

    J. Z. Li

    2003-01-01

    Full Text Available The imminent prediction on a group of strong earthquakes that occurred in Xinjiang, China in April 1997 is introduced in detail. The prediction was made on the basis of comprehensive analyses on the results obtained by multiple innovative methods including measurements of crustal stress, observation of infrasonic wave in an ultra low frequency range, and recording of abnormal behavior of certain animals. Other successful examples of prediction are also enumerated. The statistics shows that above 40% of 20 total predictions jointly presented by J. Z. Li, Z. Q. Ren and others since 1995 can be regarded as effective. With the above methods, precursors of almost every strong earthquake around the world that occurred in recent years were recorded in our laboratory. However, the physical mechanisms of the observed precursors are yet impossible to explain at this stage.

  19. Relativistically strong electromagnetic radiation in a plasma

    Science.gov (United States)

    Bulanov, S. V.; Esirkepov, T. Zh.; Kando, M.; Kiriyama, H.; Kondo, K.

    2016-03-01

    Physical processes in a plasma under the action of relativistically strong electromagnetic waves generated by high-power lasers have been briefly reviewed. These processes are of interest in view of the development of new methods for acceleration of charged particles, creation of sources of bright hard electromagnetic radiation, and investigation of macroscopic quantum-electrodynamical processes. Attention is focused on nonlinear waves in a laser plasma for the creation of compact electron accelerators. The acceleration of plasma bunches by the radiation pressure of light is the most efficient regime of ion acceleration. Coherent hard electromagnetic radiation in the relativistic plasma is generated in the form of higher harmonics and/or electromagnetic pulses, which are compressed and intensified after reflection from relativistic mirrors created by nonlinear waves. In the limit of extremely strong electromagnetic waves, radiation friction, which accompanies the conversion of radiation from the optical range to the gamma range, fundamentally changes the behavior of the plasma. This process is accompanied by the production of electron-positron pairs, which is described within quantum electrodynamics theory.

  20. Biophysical investigation of type A PutAs reveals a conserved core oligomeric structure.

    Science.gov (United States)

    Korasick, David A; Singh, Harkewal; Pemberton, Travis A; Luo, Min; Dhatwalia, Richa; Tanner, John J

    2017-09-01

    Many enzymes form homooligomers, yet the functional significance of self-association is seldom obvious. Herein, we examine the connection between oligomerization and catalytic function for proline utilization A (PutA) enzymes. PutAs are bifunctional enzymes that catalyze both reactions of proline catabolism. Type A PutAs are the smallest members of the family, possessing a minimal domain architecture consisting of N-terminal proline dehydrogenase and C-terminal l-glutamate-γ-semialdehyde dehydrogenase modules. Type A PutAs form domain-swapped dimers, and in one case (Bradyrhizobium japonicum PutA), two of the dimers assemble into a ring-shaped tetramer. Whereas the dimer has a clear role in substrate channeling, the functional significance of the tetramer is unknown. To address this question, we performed structural studies of four-type A PutAs from two clades of the PutA tree. The crystal structure of Bdellovibrio bacteriovorus PutA covalently inactivated by N-propargylglycine revealed a fold and substrate-channeling tunnel similar to other PutAs. Small-angle X-ray scattering (SAXS) and analytical ultracentrifugation indicated that Bdellovibrio PutA is dimeric in solution, in contrast to the prediction from crystal packing of a stable tetrameric assembly. SAXS studies of two other type A PutAs from separate clades also suggested that the dimer predominates in solution. To assess whether the tetramer of B. japonicum PutA is necessary for catalytic function, a hot spot disruption mutant that cleanly produces dimeric protein was generated. The dimeric variant exhibited kinetic parameters similar to the wild-type enzyme. These results implicate the domain-swapped dimer as the core structural and functional unit of type A PutAs. Proline dehydrogenase (EC 1.5.5.2); l-glutamate-γ-semialdehyde dehydrogenase (EC 1.2.1.88). The atomic coordinates and structure factor amplitudes have been deposited in the Protein Data Bank under accession number 5UR2. The SAXS data have

  1. Stable states in a strong IR field

    Science.gov (United States)

    Zhong, Changchun; Robicheaux, Francis

    2015-05-01

    It is found that 10% of atoms stay in the quasi-stable states after being exposed to intense laser or microwave (MW) pulses, even though the pulses' intensity is much stronger than that needed for static fields ionization. The reason why atoms survive those strong pulses has attracted growing attentions. A. Arakelyan et al. have observed the optical spectra of the surviving Lithium atoms after interaction with intense 38-GHz MW fields for more than 1000 cycles, and the spectra exhibit a periodic train of peaks 38 GHz apart. It suggests that those weakly bound Rydberg electrons seldom go back to the ionic core, where the cycle average energy exchange happens. In this study, we are interested in the electron behavior in the presence of intense infrared fields with a much shorter wavelength (1000 nm). By solving the full 3D time dependent Schrodinger equation, we calculate the spectra of the surviving atoms under intense IR fields. Our numerical calculations show atoms survive the intense field in quasi-stable states for a long time, and the optical spectra are obviously modulated by the IR frequency. Through tuning the ponderomotive energy, we see how field parameters affect the behavior of electrons. Different atoms, such as Hydrogen, Helium, Lithium, and Sodium, are tested to see how atom's energy structures influence the results.

  2. Tri(pyridylmethyl)phosphine: the elusive congener of TPA shows surprisingly different coordination behavior.

    Science.gov (United States)

    Whiteoak, Christopher J; Nobbs, James D; Kiryushchenkov, Evgeny; Pagano, Sandro; White, Andrew J P; Britovsek, George J P

    2013-06-17

    Tri(pyridylmethyl)phosphine (TPPh), the remarkably elusive congener of tri(pyridylmethyl)amine (TPA), has been prepared, as well as the relative tri(N-methyl-pyridylamino)phosphine (TPAMP). The coordination properties of these new ligands have been evaluated for chromium(III), iron(II), and ruthenium(II) complexes and compared with the related TPA complexes. In all cases, a different coordination behavior has been observed whereby TPPh and TPAMP always act as tridentate ligands. A chromium(III) complex [Cr(TPPh)Cl3] has been prepared, which has shown low ethylene oligomerization activity. Octahedral low spin iron(II) complexes [Fe(TPPh)2](2+) and [Fe(TPAMP)2](2+) were obtained with two ligands bound to the metal center. Ruthenium(II) chloro complexes of TPA and TPPh undergo ligand exchange reactions in acetonitrile, and the ruthenium(II) complex [Ru(MeCN)2(TPA)](2+) can be oxidized by m-CPBA in acetonitrile to give a transient ruthenium(IV) oxo complex [Ru(O)(MeCN)(TPA)](2+). Attempts to generate high valent ruthenium(IV) oxo TPPh or TPAMP complexes could not be achieved, probably due to insufficient stabilization by these strong field ligands.

  3. Probability densities in strong turbulence

    Science.gov (United States)

    Yakhot, Victor

    2006-03-01

    In this work we, using Mellin’s transform combined with the Gaussian large-scale boundary condition, calculate probability densities (PDFs) of velocity increments P(δu,r), velocity derivatives P(u,r) and the PDF of the fluctuating dissipation scales Q(η,Re), where Re is the large-scale Reynolds number. The resulting expressions strongly deviate from the Log-normal PDF P(δu,r) often quoted in the literature. It is shown that the probability density of the small-scale velocity fluctuations includes information about the large (integral) scale dynamics which is responsible for the deviation of P(δu,r) from P(δu,r). An expression for the function D(h) of the multifractal theory, free from spurious logarithms recently discussed in [U. Frisch, M. Martins Afonso, A. Mazzino, V. Yakhot, J. Fluid Mech. 542 (2005) 97] is also obtained.

  4. Oxidation and oligomerization of ethyl linoleate under the influence of the combination of ascorbic acid 6-palmitate/iron-2-ethylhexanoate

    NARCIS (Netherlands)

    Micciche, F.; Haveren, van J.; Oostveen, E.A.; Ming, W.; Linde, van der R.

    2006-01-01

    In this paper we report the oxidation and oligomerization of ethyl linoleate (EL), a model compound for alkyd resins, under the influence of iron-2-ethylhexanoate (Fe-eh) in combination with ascorbic acid 6-palmitate (AsA6p) at different AsA6p/Fe-eh molar ratios (0/1¿4/1). Reactions were studied in

  5. Constitutive homo- and hetero-oligomerization of TbetaRII-B, an alternatively spliced variant of the mouse TGF-beta type II receptor

    DEFF Research Database (Denmark)

    Krishnaveni, Manda S; Hansen, Jakob Lerche; Seeger, Werner

    2006-01-01

    , but the oligomerization pattern and dynamics of TbetaRII splice variants in live cells has not been demonstrated thus far. Using co-immunoprecipitation and bioluminescence resonance energy transfer (BRET), we demonstrate that the mouse TbetaRII receptor splice variant TbetaRII-B is capable of forming ligand...

  6. Back to the oligomeric state pH-induced dissolution of concanavalin A amyloid-like fibrils into non-native oligomers

    DEFF Research Database (Denmark)

    Santangelo, M. G.; Foderà, V.; Militello, V.

    2016-01-01

    ) or they are promptly dissolved leaving in solution non-native oligomers (pH > 10). The latter result can be ascribed to the change of the charge state for the ConA amino acid side chain with high pKa values. Our results support the idea of fibrils as a reservoir of oligomeric species that can be released if changes...

  7. Direct evidence for a coordination-insertion mechanism of ethylene oligomerization catalysed by neutral 2,6-bisiminopyridine iron monoalkyl complexes

    OpenAIRE

    Cartes, M. Ángeles; Rodríguez-Delgado, Antonio; Palma, Pilar; Sánchez, Luis J.; Cámpora, Juan; CSIC - Unidad de Recursos de Información Científica para la Investigación (URICI)

    2014-01-01

    1H NMR studies on ethylene oligomerization catalysed by the neutral monoalkyl complex [Fe(Me)(iPrBIP)] allow direct observation of alkyl iron intermediates as well as reversible ethylene coordination to the metal center, providing for the first time experimental evidence for a coordination-insertion mechanism of iron-catalysed ethylene upgrade reactions. © 2014 the Partner Organisations.

  8. The effect of immobilization/mobilization processes on the temperature onset of a catalyst bed production studied with ethylene oligomerization on HZSM-5 zeolites

    Czech Academy of Sciences Publication Activity Database

    Zikánová, Arlette; Derewinski, M.; Sarv, P.; Hudec, P.; Hrabánek, Pavel; Kočiřík, Milan

    2006-01-01

    Roč. 114, 2-3 (2006), s. 248-256 ISSN 0920-5861 R&D Projects: GA AV ČR IAA400400501 Institutional research plan: CEZ:AV0Z40400503 Keywords : HZSM-5 * ethylene * oligomeration * sorption and reaction dynamics Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 2.148, year: 2006

  9. Strong-Superstrong Transition in Glass Transition of Metallic Glass

    International Nuclear Information System (INIS)

    Dan, Wang; Hong-Yan, Peng; Xiao-Yu, Xu; Bao-Ling, Chen; Chun-Lei, Wu; Min-Hua, Sun

    2010-01-01

    Dynamic fragility of bulk metallic glass (BMG) of Zr 64 Cu 16 Ni 10 Al 10 alloy is studied by three-point beam bending methods. The fragility parameter mfor Zr 64 Cu 16 Ni 10 Al 10 BMG is calculated to be 24.5 at high temperature, which means that the liquid is a 'strong' liquid, while to be 13.4 at low temperature which means that the liquid is a 'super-strong' liquid. The dynamical behavior of Zr 64 Cu 16 Ni 10 Al 10 BMG in the supercooled region undergoes a strong to super-strong transition. To our knowledge, it is the first time that a strong-to-superstrong transition is found in the metallic glass. Using small angle x-ray scattering experiments, we find that this transition is assumed to be related to a phase separation process in supercooled liquid. (condensed matter: structure, mechanical and thermal properties)

  10. Strong Ideal Convergence in Probabilistic Metric Spaces

    Indian Academy of Sciences (India)

    In the present paper we introduce the concepts of strongly ideal convergent sequence and strong ideal Cauchy sequence in a probabilistic metric (PM) space endowed with the strong topology, and establish some basic facts. Next, we define the strong ideal limit points and the strong ideal cluster points of a sequence in this ...

  11. Strong ideal convergence in probabilistic metric spaces

    Indian Academy of Sciences (India)

    In the present paper we introduce the concepts of strongly ideal convergent sequence and strong ideal Cauchy sequence in a probabilistic metric (PM) space endowed with the strong topology, and establish some basic facts. Next, we define the strong ideal limit points and the strong ideal cluster points of a sequence in this ...

  12. Remnants of strong tidal interactions

    International Nuclear Information System (INIS)

    Mcglynn, T.A.

    1990-01-01

    This paper examines the properties of stellar systems that have recently undergone a strong tidal shock, i.e., a shock which removes a significant fraction of the particles in the system, and where the shocked system has a much smaller mass than the producer of the tidal field. N-body calculations of King models shocked in a variety of ways are performed, and the consequences of the shocks are investigated. The results confirm the prediction of Jaffe for shocked systems. Several models are also run where the tidal forces on the system are constant, simulating a circular orbit around a primary, and the development of tidal radii under these static conditions appears to be a mild process which does not dramatically affect material that is not stripped. The tidal radii are about twice as large as classical formulas would predict. Remnant density profiles are compared with a sample of elliptical galaxies, and the implications of the results for the development of stellar populations and galaxies are considered. 38 refs

  13. John Strong - 1941-2006

    CERN Document Server

    2006-01-01

    Our friend and colleague John Strong was cruelly taken from us by a brain tumour on 31 July, a few days before his 65th birthday. John started his career and obtained his PhD in a group from Westfield College, initially working on experiments at Rutherford Appleton Laboratory (RAL). From the early 1970s onwards, however, his research was focused on experiments in CERN, with several particularly notable contributions. The Omega spectrometer adopted a system John had originally developed for experiments at RAL using vidicon cameras (a type of television camera) to record the sparks in the spark chambers. This highly automated system allowed Omega to be used in a similar way to bubble chambers. He contributed to the success of NA1 and NA7, where he became heavily involved in the electronic trigger systems. In these experiments the Westfield group joined forces with Italian colleagues to measure the form factors of the pion and the kaon, and the lifetime of some of the newly discovered charm particles. Such h...

  14. Strong seismic ground motion propagation

    International Nuclear Information System (INIS)

    Seale, S.; Archuleta, R.; Pecker, A.; Bouchon, M.; Mohammadioun, G.; Murphy, A.; Mohammadioun, B.

    1988-10-01

    At the McGee Creek, California, site, 3-component strong-motion accelerometers are located at depths of 166 m, 35 m and 0 m. The surface material is glacial moraine, to a depth of 30.5 m, overlying homfels. Accelerations were recorded from two California earthquakes: Round Valley, M L 5.8, November 23, 1984, 18:08 UTC and Chalfant Valley, M L 6.4, July 21, 1986, 14:42 UTC. By separating out the SH components of acceleration, we were able to determine the orientations of the downhole instruments. By separating out the SV component of acceleration, we were able to determine the approximate angle of incidence of the signal at 166 m. A constant phase velocity Haskell-Thomson model was applied to generate synthetic SH seismograms at the surface using the accelerations recorded at 166 m. In the frequency band 0.0 - 10.0 Hz, we compared the filtered synthetic records to the filtered surface data. The onset of the SH pulse is clearly seen, as are the reflections from the interface at 30.5 m. The synthetic record closely matches the data in amplitude and phase. The fit between the synthetic accelerogram and the data shows that the seismic amplification at the surface is a result of the contrast of the impedances (shear stiffnesses) of the near surface materials

  15. Cartilage oligomeric matrix protein deficiency promotes early onset and the chronic development of collagen-induced arthritis

    DEFF Research Database (Denmark)

    Geng, Hui; Carlsen, Stefan; Nandakumar, Kutty

    2008-01-01

    ABSTRACT: INTRODUCTION: Cartilage oligomeric matrix protein (COMP) is a homopentameric protein in cartilage. The development of arthritis, like collagen-induced arthritis (CIA), involves cartilage as a target tissue. We have investigated the development of CIA in COMP-deficient mice. METHODS: COMP......-deficient mice in the 129/Sv background were backcrossed for 10 generations against B10.Q mice, which are susceptible to chronic CIA. COMP-deficient and wild-type mice were tested for onset, incidence, and severity of arthritis in both the collagen and collagen antibody-induced arthritis models. Serum anti......-collagen II and anti-COMP antibodies as well as serum COMP levels in arthritic and wild-type mice were measured by enzyme-linked immunosorbent assay. RESULTS: COMP-deficient mice showed a significant early onset and increase in the severity of CIA in the chronic phase, whereas collagen II-antibody titers were...

  16. Effects of Bentonite on p-Methoxybenzyl Acetate: A Theoretical Model for Oligomerization via an Electrophilic-Substitution Mechanism

    Directory of Open Access Journals (Sweden)

    Manuel Salmón

    2011-02-01

    Full Text Available Tonsil Actisil FF, a commercial bentonitic clay, promotes the formation of a series of electrophilic-aromatic-substitution products from para-methoxybenzyl acetate in carbon disulfide. The molecules obtained correspond to linear isomeric dimers, trimers, tetramers and a pentamer, according to their spectroscopic data. A clear indication of the title mechanistic pathway for the oligomerization growth was obtained from the analysis of a set of computational-chemistry calculations using the density-functional-theory level B3LYP/6-311++G(d,p. The corresponding conclusions were based on the computed dipole moments, the HOMO/LUMO distributions, and a natural-populations analysis of the studied molecules.

  17. DFT study on the impact of the methylaluminoxane cocatalyst in ethylene oligomerization using a titanium-based catalyst

    KAUST Repository

    Pasha, Farhan Ahmad

    2015-01-26

    A computational study within the framework of density functional theory is presented on the oligomerization of ethylene to yield 1-hexene using [(η5-C5H4CMe2C6H5)]TiCl3/MAO] catalyst. This study explicitly takes into account a methylaluminoxane (MAO) cocatalyst model, where the MAO cluster has become an anionic species after having abstracted one chloride anion, yielding a cationic activated catalyst. Hence, the reaction profile was calculated using the zwitterionic system, and the potential energy surface has been compared to the cationic catalytic system. Modest differences were found between the two free energy profiles. However, we show for the first time that the use of a realistic zwitterionic model is required to obtain a Brønsted-Evans-Polanyi relationship between the energy barriers and reaction energies.

  18. N-(2,2-Dimethyl-1-(quinolin-2-yl)propylidene) arylaminonickel Complexes and Their Ethylene Oligomerization.

    Science.gov (United States)

    Suo, Hongyi; Zhao, Tong; Wang, Yiqing; Ban, Qing; Sun, Wen-Hua

    2017-04-13

    A series of N -(2,2-dimethyl-1-(quinolin-2-yl)propylidene) arylamines was sophisticatedly synthesized and reacted with nickel(II) bromine for the formation of the corresponding nickel complexes. All the organic compounds were characterized by IR, NMR spectra and elemental analysis, while all the nickel complexes were characterized by IR spectra and elemental analysis. On activation with ethylaluminium sesquichloride (EASC) and modified methylaluminoxane (MMAO), all nickel precatalysts exhibited good activities toward ethylene oligomerization, indicating the positive efficiency of gem-dimethyl substitutents; in which major hexenes were obtained with MMAO. The catalytic parameters were verified, and the steric and electronic influences of substituents with ligands were observed, with a slight change of activities under different ethylene pressures.

  19. Highly active chromium(III) complexes based on tridentate pyrazolyl pyridyl ligands for ethylene polymerization and oligomerization.

    Science.gov (United States)

    Park, Jong-Eun; Kang, Sung Kwon; Woo, Jeong Oh; Son, Kyung-sun

    2015-06-07

    A set of new chromium(III) [Cr(III)] complexes based on the tridentate ligand HC(Pz)2Py (Pz = pyrazole; Py = pyridine) and its derivatives were prepared, characterized, and evaluated for ethylene polymerization/oligomerization. X-ray single-crystal analyses of the Cr(III) complexes showed tridentate coordination on the fac-octahedral Cr sphere. Upon activation with methylaluminoxane (MAO), the precatalysts and the ligands L1-L3 mixed in situ with Cr(acac)3 were highly active and generally produced polyethylene as a major product. Their catalytic performances were markedly affected by the substituents on the methine carbon atom of the ligands and reaction conditions.

  20. Multiwalled carbon nanotubes@octavinyl polyhedral oligomeric silsesquioxanes nanocomposite preparation via cross-linking reaction in acidic media

    Energy Technology Data Exchange (ETDEWEB)

    Somasekharan, Lakshmipriya; Thomas, Sabu [Mahatma Gandhi University, International and Interuniversity Centre for Nanoscience and Nanotechnology (India); Comoy, Corinne [Université de Lorraine, SRSMC, UMR 7565 (France); Sivasankarapillai, Anilkumar [NSS Hindu College (India); Kalarikkal, Nandakumar [Mahatma Gandhi University, International and Interuniversity Centre for Nanoscience and Nanotechnology (India); Lamouroux, Emmanuel, E-mail: Emmanuel.Lamouroux@univ-lorraine.fr [Université de Lorraine, SRSMC, UMR 7565 (France)

    2016-11-15

    Multiwalled carbon nanotubes have unique properties allowing their use in a wide range of applications—from microelectronics to biomedical and polymer fields. Nevertheless, a crucial aspect for their use resides in the ease of handling them during the process. Here, we report a facile route to prepare multiwalled carbon nanotubes@octavinyl polyhedral oligomeric silsesquioxanes (MWCNT@POSS) nanocomposite. The method involves the formation of a covalent bond between carboxylated MWCNTs and OV-POSS using acid-catalyzed electrophilic addition reaction. The resulting nanocomposite have been characterized by Fourier transform infrared spectroscopy (FTIR), powder X-Ray diffraction (PXRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and thermogravimetric analysis (TGA). The results confirmed that the formation of MWCNT@POSS nanocomposite did not deteriorate MWCNT structure or morphology. Here, we used a 1:1 ratio of carboxylated MWCNTs and OV-POSS and the POSS content in the nanocomposite was 39.5 wt%.

  1. The role of entropy in initializing the aggregation of peptides: a first principle study on oligopeptide oligomerization.

    Science.gov (United States)

    Pohl, Gábor; Jákli, Imre; Csizmadia, Imre G; Papp, Dóra; Matías, Garibotto Francisco; Perczel, András

    2012-01-28

    The initiation and progression of Alzheimer's disease is coupled to the oligo- and polymerization of amyloid peptides in the brain. Amyloid like aggregates of protein domains were found practically independent of their primary sequences. Thus, the driving force of the transformation from the original to a disordered amyloid fold is expected to lie in the protein backbone common to all proteins. In order to investigate the thermodynamics of oligomerization, full geometry optimizations and frequency calculations were performed both on parallel and antiparallel β-pleated sheet model structures of [HCO-(Ala)(1-6)-NH(2)](2) and (For-Ala(1-2)-NH(2))(1-6) peptides, both at the B3LYP and M05-2X/6-311++G(d,p)//M05-2X/6-31G(d) levels of theory, both in vacuum and in water. Our results show that relative entropy and enthalpy both show a hyperbolic decrease with increasing residue number and with increasing number of strands as well. Thus, di- and oligomerization are always thermodynamically favored. Antiparallel arrangements were found to have greater stability than parallel arrangements of the polypeptide backbones. During our study the relative changes in thermodynamic functions are found to be constant for long enough peptides, indicating that stability and entropy terms are predictable. All thermodynamic functions of antiparallel di- and oligomers show a staggered nature along the increasing residue number. By identifying and analyzing the 6 newly emerging dimer vibrational modes of the 10- and 14-membered building units, the staggered nature of the entropy function can be rationalized. Thus, the vanishing rotational and translational modes with respect to single strands are converted into entropy terms "holding tight" the dimers and oligomers formed, rationalizing the intrinsic adherence of natural polypeptide backbones to aggregate.

  2. Preparation of flame-retardant polyethylene terephthalate fabrics by electron beam-induced grafting of oligomeric vinyl phosphonate

    International Nuclear Information System (INIS)

    Kaji, Kanako; Ohkura, Hiroshi; Okada, Toshio.

    1979-01-01

    For the purpose of making polyethylene terephthalate (polyester) fabric, flame-retardant grafting of oligomeric vinyl phosphonate was carried out using electron-beams either from a Van de Graaff or a Transformer-Rectifier type accelerator at a dose rate of up to 3.3 x 10 6 rad/sec. The fabric impregnated with a selected amount of oligomer was irradiated for the grafting. In the present report ''grafting'' means only an apparent one and it is very probable that most of the oligomer is deposited on the surface of the fibers as insoluble polymer due to cross-linking. When 20% methanol solution of the oligomer was used, an average amount of oligomer take up was about 25% and an add-on by grafting up to 20% was obtained at a dose of 20 Mrad with oligomer utilization higher than 75%. Flame retardance of the fabric is much improved by the grafting. Limiting oxygen index (LOI) increases from 18.5 of original fabric to 26.0 of the fabric containing 12% phosphorus. The fabric of 10% add-on (phosphorus content 2.2%) was proved to be self-extinguishing when it was exposed to open flame according to a netting basket flame-retardance test. The flame-retardance is obtained at LOI of 23.0. The graft fabric exhibited much improved anti-static property. At about 3% add-on the frictional electric charge was lowered to the same level as that cotton fabric. Thermal stability of the graft fabric tested by thermogravimetric analysis shows that it is far better than the chlorinated fabrics. No or a very little change in tensile properties of the fabric was observed upon grafting oligomeric vinyl phosphonate. The graft fabric has an excellent hand. (author)

  3. Structural basis for TatA oligomerization: an NMR study of Escherichia coli TatA dimeric structure.

    Science.gov (United States)

    Zhang, Yi; Hu, Yunfei; Li, Hongwei; Jin, Changwen

    2014-01-01

    Many proteins are transported across lipid membranes by protein translocation systems in living cells. The twin-arginine transport (Tat) system identified in bacteria and plant chloroplasts is a unique system that transports proteins across membranes in their fully-folded states. Up to date, the detailed molecular mechanism of this process remains largely unclear. The Escherichia coli Tat system consists of three essential transmembrane proteins: TatA, TatB and TatC. Among them, TatB and TatC form a tight complex and function in substrate recognition. The major component TatA contains a single transmembrane helix followed by an amphipathic helix, and is suggested to form the translocation pore via self-oligomerization. Since the TatA oligomer has to accommodate substrate proteins of various sizes and shapes, the process of its assembly stands essential for understanding the translocation mechanism. A structure model of TatA oligomer was recently proposed based on NMR and EPR observations, revealing contacts between the transmembrane helices from adjacent subunits. Herein we report the construction and stabilization of a dimeric TatA, as well as the structure determination by solution NMR spectroscopy. In addition to more extensive inter-subunit contacts between the transmembrane helices, we were also able to observe interactions between neighbouring amphipathic helices. The side-by-side packing of the amphipathic helices extends the solvent-exposed hydrophilic surface of the protein, which might be favourable for interactions with substrate proteins. The dimeric TatA structure offers more detailed information of TatA oligomeric interface and provides new insights on Tat translocation mechanism.

  4. Ethylene oligomerization studies by nickel(ii) complexes chelated by (amino)pyridine ligands: experimental and density functional theory studies.

    Science.gov (United States)

    Nyamato, George S; Ojwach, Stephen O; Akerman, Matthew P

    2016-02-28

    Reductions of imine compounds 2-methoxy-N-(1-(pyridin-2-yl)ethylidene)ethanamine (L1), 2-methoxy-N-((pyridin-2-yl)methylene)ethanamine (L2), N,N-diethyl-N-((pyridin-2-yl)methylene)ethane-1,2-diamine (L3) and 2-((pyridin-2-yl)methyleneamino)ethanol (L4) using NABH4 produced their corresponding amine analogues N-(2-methoxyethyl)-1-(pyridin-2-yl)ethanamine (L1a), 2-methoxy-N-((pyridin-2-yl)methyl)-ethanamine (L2a), N,N-diethyl-N-((pyridin-2-yl)methyl)ethane-1,2-diamine (L3a) and 2-((pyridin-2-yl)methylamino)ethanol (L4a) in good yields. Reactions of the (amino)pyridine ligands L1a–L4a with [NiBr2(DME)] afforded nickel(II) complexes, [NiBr2(L1a)2] (1), [NiBr2(L2a)2] (2), [NiBr2(L3a)2] (3) and [NiBr2(L4a)2] (4), respectively in quantitative yields. Molecular structures of complexes 2 and 4 confirmed the formation of the bis(chelated)nickel(II) complexes. Activation of complexes 1–4 with either EtAlCl2 or methylaluminoxane (MAO), produced active ethylene oligomerization catalysts to afford mostly ethylene dimers (C4), in addition to trimmers (C6) and tetramers (C8). Density functional theory studies provided valuable insight into the reactivity trends and influence of complex structure on the ethylene oligomerization reactions.

  5. Charge frustration and quantum criticality for strongly correlated fermions

    NARCIS (Netherlands)

    Huijse, L.; Halverson, J.; Fendley, P.; Schoutens, K.

    2008-01-01

    We study a model of strongly correlated electrons on the square lattice which exhibits charge frustration and quantum critical behavior. The potential is tuned to make the interactions supersymmetric. We establish a rigorous mathematical result which relates quantum ground states to certain tiling

  6. Topics in strong Langmuir turbulence

    International Nuclear Information System (INIS)

    Skoric, M.M.

    1981-01-01

    This thesis discusses certain aspects of the turbulence of a fully ionised non-isothermal plasma dominated by the Langmuir mode. Some of the basic properties of strongly turbulent plasmas are reviewed. In particular, interest is focused on the state of Langmuir turbulence, that is the turbulence of a simple externally unmagnetized plasma. The problem of the existence and dynamics of Langmuir collapse is discussed, often met as a non-linear stage of the modulational instability in the framework of the Zakharov equations (i.e. simple time-averaged dynamical equations). Possible macroscopic consequences of such dynamical turbulent models are investigated. In order to study highly non-linear collapse dynamics in its advanced stage, a set of generalized Zakharov equations are derived. Going beyond the original approximation, the author includes the effects of higher electron non-linearities and a breakdown of slow-timescale quasi-neutrality. He investigates how these corrections may influence the collapse stabilisation. Recently, it has been realised that the modulational instability in a Langmuir plasma will be accompanied by the collisionless-generation of a slow-timescale magnetic field. Accordingly, a novel physical situation has emerged which is investigated in detail. The stability of monochromatic Langmuir waves in a self-magnetized Langmuir plasma, is discussed, and the existence of a novel magneto-modulational instability shown. The wave collapse dynamics is investigated and a physical interpretation of the basic results is given. A problem of the transient analysis of an interaction of time-dependent electromagnetic pulses with linear cold plasma media is investigated. (Auth.)

  7. Promoting Strong Written Communication Skills

    Science.gov (United States)

    Narayanan, M.

    2015-12-01

    The reason that an improvement in the quality of technical writing is still needed in the classroom is due to the fact that universities are facing challenging problems not only on the technological front but also on the socio-economic front. The universities are actively responding to the changes that are taking place in the global consumer marketplace. Obviously, there are numerous benefits of promoting strong written communication skills. They can be summarized into the following six categories. First, and perhaps the most important: The University achieves learner satisfaction. The learner has documented verbally, that the necessary knowledge has been successfully acquired. This results in learner loyalty that in turn will attract more qualified learners.Second, quality communication lowers the cost per pupil, consequently resulting in increased productivity backed by a stronger economic structure and forecast. Third, quality communications help to improve the cash flow and cash reserves of the university. Fourth, having high quality communication enables the university to justify the need for high costs of tuition and fees. Fifth, better quality in written communication skills result in attracting top-quality learners. This will lead to happier and satisfied learners, not to mention greater prosperity for the university as a whole. Sixth, quality written communication skills result in reduced complaints, thus meaning fewer hours spent on answering or correcting the situation. The University faculty and staff are thus able to devote more time on scholarly activities, meaningful research and productive community service. References Boyer, Ernest L. (1990). Scholarship reconsidered: Priorities of the Professorate.Princeton, NJ: Carnegie Foundation for the Advancement of Teaching. Hawkins, P., & Winter, J. (1997). Mastering change: Learning the lessons of the enterprise.London: Department for Education and Employment. Buzzel, Robert D., and Bradley T. Gale. (1987

  8. Inhomogeneities in a strongly correlated d-wave superconductors in the limit of strong disorder

    Science.gov (United States)

    Chakraborty, Debmalya; Sensarma, Rajdeep; Ghosal, Amit

    2015-03-01

    The complex interplay of the strong correlations and impurities in a high temperature superconductor is analyzed within a Hartree-Fock-Bogoliubov theory, augmented with Gutzwiller approximation for taking care of the strong electronic repulsion. The inclusion of such correlations is found to play a crucial role in reducing inhomogeneities in both qualitative and quantitative manner. This difference is comprehended by investigating the underlying one-particle ``normal states'' that includes the order parameters in the Hartree and Fock channels in the absence of superconductivity. This amounts to the renormalization of disorder both on the lattice sites and also on links. These two components of disorder turn out to be spatially anti-correlated through self-consistency. Interestingly, a simple pairing theory in terms of these normal states is found to describe the complex behaviors of dirty cuprates with reasonable accuracy. However, this framework needs modifications in the limit where disorder strengths are comparable to the band width. We will discuss appropriate updates in the formalism to describe physics of inhomogeneities with strong disorder.

  9. Starting Strong: A School-Based Indicated Prevention Program during the Transition to Kindergarten

    Science.gov (United States)

    Eisenhower, Abbey; Taylor, Heather; Baker, Bruce L.

    2016-01-01

    Starting Strong in Kindergarten (Starting Strong) is a school-based indicated prevention targeting behavior problems, student-teacher relationships, and parent-school connectedness for children with or at risk for disruptive behavior problems during the transition to kindergarten. By use of a block-randomized, controlled trial to test program…

  10. Is It Possible to Predict Strong Earthquakes?

    Science.gov (United States)

    Polyakov, Y. S.; Ryabinin, G. V.; Solovyeva, A. B.; Timashev, S. F.

    2015-07-01

    The possibility of earthquake prediction is one of the key open questions in modern geophysics. We propose an approach based on the analysis of common short-term candidate precursors (2 weeks to 3 months prior to strong earthquake) with the subsequent processing of brain activity signals generated in specific types of rats (kept in laboratory settings) who reportedly sense an impending earthquake a few days prior to the event. We illustrate the identification of short-term precursors using the groundwater sodium-ion concentration data in the time frame from 2010 to 2014 (a major earthquake occurred on 28 February 2013) recorded at two different sites in the southeastern part of the Kamchatka Peninsula, Russia. The candidate precursors are observed as synchronized peaks in the nonstationarity factors, introduced within the flicker-noise spectroscopy framework for signal processing, for the high-frequency component of both time series. These peaks correspond to the local reorganizations of the underlying geophysical system that are believed to precede strong earthquakes. The rodent brain activity signals are selected as potential "immediate" (up to 2 weeks) deterministic precursors because of the recent scientific reports confirming that rodents sense imminent earthquakes and the population-genetic model of K irshvink (Soc Am 90, 312-323, 2000) showing how a reliable genetic seismic escape response system may have developed over the period of several hundred million years in certain animals. The use of brain activity signals, such as electroencephalograms, in contrast to conventional abnormal animal behavior observations, enables one to apply the standard "input-sensor-response" approach to determine what input signals trigger specific seismic escape brain activity responses.

  11. Attention to Intentions--How to Stimulate Strong Intentions to Change

    Science.gov (United States)

    Dam, M.; Janssen, F. J. J. M.; van Driel, J. H.

    2018-01-01

    The implementation of educational reforms requires behavioral changes from the teachers involved. Theories on successful behavioral change prescribe the following conditions: teachers need to possess the necessary knowledge and skills, form strong positive intentions to perform the new behavior, and have a supporting environment for change.…

  12. Age- and brain region-dependent α-synuclein oligomerization is attributed to alterations in intrinsic enzymes regulating α-synuclein phosphorylation in aging monkey brains.

    Science.gov (United States)

    Chen, Min; Yang, Weiwei; Li, Xin; Li, Xuran; Wang, Peng; Yue, Feng; Yang, Hui; Chan, Piu; Yu, Shun

    2016-02-23

    We previously reported that the levels of α-syn oligomers, which play pivotal pathogenic roles in age-related Parkinson's disease (PD) and dementia with Lewy bodies, increase heterogeneously in the aging brain. Here, we show that exogenous α-syn incubated with brain extracts from older cynomolgus monkeys and in Lewy body pathology (LBP)-susceptible brain regions (striatum and hippocampus) forms higher amounts of phosphorylated and oligomeric α-syn than that in extracts from younger monkeys and LBP-insusceptible brain regions (cerebellum and occipital cortex). The increased α-syn phosphorylation and oligomerization in the brain extracts from older monkeys and in LBP-susceptible brain regions were associated with higher levels of polo-like kinase 2 (PLK2), an enzyme promoting α-syn phosphorylation, and lower activity of protein phosphatase 2A (PP2A), an enzyme inhibiting α-syn phosphorylation, in these brain extracts. Further, the extent of the age- and brain-dependent increase in α-syn phosphorylation and oligomerization was reduced by inhibition of PLK2 and activation of PP2A. Inversely, phosphorylated α-syn oligomers reduced the activity of PP2A and showed potent cytotoxicity. In addition, the activity of GCase and the levels of ceramide, a product of GCase shown to activate PP2A, were lower in brain extracts from older monkeys and in LBP-susceptible brain regions. Our results suggest a role for altered intrinsic metabolic enzymes in age- and brain region-dependent α-syn oligomerization in aging brains.

  13. Dominant negative mutants of Bacillus thuringiensis Cry1Ab toxin function as anti-toxins: demonstration of the role of oligomerization in toxicity.

    Directory of Open Access Journals (Sweden)

    Claudia Rodríguez-Almazán

    Full Text Available Bacillus thuringiensis Cry toxins, that are used worldwide in insect control, kill insects by a mechanism that depends on their ability to form oligomeric pores that insert into the insect-midgut cells. These toxins are being used worldwide in transgenic plants or spray to control insect pests in agriculture. However, a major concern has been the possible effects of these insecticidal proteins on non-target organisms mainly in ecosystems adjacent to agricultural fields.We isolated and characterized 11 non-toxic mutants of Cry1Ab toxin affected in different steps of the mechanism of action namely binding to receptors, oligomerization and pore-formation. These mutant toxins were analyzed for their capacity to block wild type toxin activity, presenting a dominant negative phenotype. The dominant negative phenotype was analyzed at two levels, in vivo by toxicity bioassays against susceptible Manduca sexta larvae and in vitro by pore formation activity in black lipid bilayers. We demonstrate that some mutations located in helix alpha-4 completely block the wild type toxin activity at sub-stoichiometric level confirming a dominant negative phenotype, thereby functioning as potent antitoxins.This is the first reported case of a Cry toxin dominant inhibitor. These data demonstrate that oligomerization is a fundamental step in Cry toxin action and represent a potential mechanism to protect special ecosystems from the possible effect of Cry toxins on non-target organisms.

  14. Molecular basis of the STIL coiled coil oligomerization explains its requirement for de-novo formation of centrosomes in mammalian cells.

    Science.gov (United States)

    David, Ahuvit; Amartely, Hadar; Rabinowicz, Noa; Shamir, Mai; Friedler, Assaf; Izraeli, Shai

    2016-04-14

    The STIL protein is essential for centriole replication and for the non-templated, de novo centriole biogenesis that is required for mammalian embryogenesis. Here we performed quantitative biophysical and structural analysis of the central short coiled coil domain (CCD) of STIL that is critical for its function. Using biophysical, biochemical and cell biology approaches, we identified the specific residues in the CCD that mediate the oligomerization, centrosomal localization and protein interactions of STIL. We characterized the structural properties of the coiled coil peptide using circular dichroism spectroscopy and size exclusion chromatography. We identified two regions in this domain, containing eight hydrophobic residues, which mediate the coiled coil oligomerization. Mutations in these residues destabilized the coiled coil thermodynamically but in most cases did not affect its secondary structure. Reconstituting mouse embryonic fibroblasts lacking endogenous Stil, we show that STIL oligomerization mediated by these residues is not only important for the centrosomal functions of STIL during the canonical duplication process but also for de-novo formation of centrosomes.

  15. Atoms and clusters in strong laser fields

    NARCIS (Netherlands)

    Marchenko, T.

    2008-01-01

    This thesis describes experimental and theoretical studies on the interaction of strong infrared laser fields with atoms and atomic clusters. Part I provides an overview of the main strong-field phenomena in atoms, molecules and clusters and describes the state-of-the-art in strong-field science.

  16. Strong Bisimilarity of Simple Process Algebras

    DEFF Research Database (Denmark)

    Srba, Jirí

    2003-01-01

    We study bisimilarity and regularity problems of simple process algebras. In particular, we show PSPACE-hardness of the following problems: (i) strong bisimilarity of Basic Parallel Processes (BPP), (ii) strong bisimilarity of Basic Process Algebra (BPA), (iii) strong regularity of BPP, and (iv) ...

  17. 78 FR 15710 - Strong Sensitizer Guidance

    Science.gov (United States)

    2013-03-12

    ... definition of ``strong sensitizer'' found at 16 CFR 1500.3(c)(5). The Commission is proposing to revise the supplemental definition of ``strong sensitizer'' due to advancements in the science of sensitization that have... document is intended to clarify the ``strong sensitizer'' definition, assist manufacturers in understanding...

  18. Social and Emotional Learning in the Classroom: Evaluation of "Strong Kids" and "Strong Teens" on Students' Social-Emotional Knowledge and Symptoms

    Science.gov (United States)

    Merrell, Kenneth W.; Juskelis, Michael P.; Tran, Oanh K.; Buchanan, Rohanna

    2008-01-01

    This article describes the results of three pilot studies that were conducted to evaluate the recently developed "Strong Kids" and "Strong Teens" social-emotional learning programs in increasing students' knowledge of healthy social-emotional behavior and decreasing their symptoms of negative affect and emotional distress. The first study included…

  19. Functional significance of the oligomeric structure of the Na,K-pump from radiation inactivation and ligand binding

    International Nuclear Information System (INIS)

    Norby, J.G.; Jensen, J.

    1991-01-01

    The present article is concerned with the oligomeric structure and function of the Na,K-pump (Na,K-ATPase). The questions we have addressed, using radiation inactivation and target size analysis as well as ligand binding, are whether the minimal structural unit and the functional unit have more than one molecule of the catalytic subunit, alpha. The authors first discuss the fundamentals of the radiation inactivation method and emphasize the necessity for rigorous internal standardization with enzymes of known molecular mass. They then demonstrate that the radiation inactivation of Na,K-ATPase is a stepwise process which leads to intermediary fragments of the alpha-subunit with partial catalytic activity. From the target size analysis it is most likely that the membrane-bound Na,K-ATPase is structurally organized as a diprotomer containing two alpha-subunits. Determination of ADP- and ouabain-binding site stoichiometry favors a theory with one substrate site per (alpha beta) 2. 47 references

  20. Supplementary Material for: A new mode of SAM domain mediated oligomerization observed in the CASKIN2 neuronal scaffolding protein

    KAUST Repository

    Smirnova, Ekaterina

    2016-01-01

    Abstract Background CASKIN2 is a homolog of CASKIN1, a scaffolding protein that participates in a signaling network with CASK (calcium/calmodulin-dependent serine kinase). Despite a high level of homology between CASKIN2 and CASKIN1, CASKIN2 cannot bind CASK due to the absence of a CASK Interaction Domain and consequently, may have evolved undiscovered structural and functional distinctions. Results We demonstrate that the crystal structure of the Sterile Alpha Motif (SAM) domain tandem (SAM1-SAM2) oligomer from CASKIN2 is different than CASKIN1, with the minimal repeating unit being a dimer, rather than a monomer. Analytical ultracentrifugation sedimentation velocity methods revealed differences in monomer/dimer equilibria across a range of concentrations and ionic strengths for the wild type CASKIN2 SAM tandem and a structure-directed double mutant that could not oligomerize. Further distinguishing CASKIN2 from CASKIN1, EGFP-tagged SAM tandem proteins expressed in Neuro2a cells produced punctae that were distinct both in shape and size. Conclusions This study illustrates a new way in which neuronal SAM domains can assemble into large macromolecular assemblies that might concentrate and amplify synaptic responses.

  1. Cloning, expression, purification and characterization of oligomeric states of the native 5HT2A G-Protein-Coupled Receptor.

    Science.gov (United States)

    Mahesh, Gopa; Jaiswal, Priyank; Dey, Sandip; Sengupta, Jayati; Mukherjee, Sujoy

    2018-02-06

    The serotonin 5HT2A G-protein coupled receptor (GPCR) is involved in a plethora of neuromodulatory functions and its dysregulation is linked to psychiatric disorders. However, there is insufficient, direct structural evidence of the structure, dynamics and the mechanism of function of this receptor. Cholesterol plays an important role in the function of many GPCRs and reduced cholesterol levels may be linked to serotonergic pathway disruptions. But cholesterol's effect on the structure, especially the oligomeric states of the 5HT2A receptor is not well understood. Structural studies on most GPCRs typically require the substitution of the dynamic intracellular loop 3 along with other mutations and truncations for stability and hence, structural characterization of native receptor sequence is relatively rare. Here we have cloned, over-expressed and purified native sequence of rat serotonin 5HT2A GPCR using baculoviral expression system. Subsequently, we used cryo-electron microscopy to show that the 5HT2A GPCR forms a dimer in presence of cholesterol but converts to a monomer when cholesterol is depleted. Since dimer formation is necessary for signaling by 5HT2A receptors, our results also indicate the importance of cholesterol in serotonin 5HT2A receptor's function. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  2. Nuclear Envelope Retention of LINC Complexes Is Promoted by SUN-1 Oligomerization in the Caenorhabditis elegans Germ Line.

    Science.gov (United States)

    Daryabeigi, Anahita; Woglar, Alexander; Baudrimont, Antoine; Silva, Nicola; Paouneskou, Dimitra; Vesely, Cornelia; Rauter, Manuel; Penkner, Alexandra; Jantsch, Michael; Jantsch, Verena

    2016-06-01

    SUN (Sad1 and UNC-84) and KASH (Klarsicht, ANC-1, and Syne homology) proteins are constituents of the inner and outer nuclear membranes. They interact in the perinuclear space via C-terminal SUN-KASH domains to form the linker of nucleoskeleton and cytoskeleton (LINC) complex thereby bridging the nuclear envelope. LINC complexes mediate numerous biological processes by connecting chromatin with the cytoplasmic force-generating machinery. Here we show that the coiled-coil domains of SUN-1 are required for oligomerization and retention of the protein in the nuclear envelope, especially at later stages of female gametogenesis. Consistently, deletion of the coiled-coil domain makes SUN-1 sensitive to unilateral force exposure across the nuclear membrane. Premature loss of SUN-1 from the nuclear envelope leads to embryonic death due to loss of centrosome-nuclear envelope attachment. However, in contrast to previous notions we can show that the coiled-coil domain is dispensable for functional LINC complex formation, exemplified by successful chromosome sorting and synapsis in meiotic prophase I in its absence. Copyright © 2016 by the Genetics Society of America.

  3. Morphology and Phase Transitions in Styrene-Butadiene-Styrene Triblock Copolymer Grafted with Isobutyl-Substituted Polyhedral Oligomeric Silsesquioxanes

    Energy Technology Data Exchange (ETDEWEB)

    Drazkowski, Daniel B.; Lee, Andre; Haddad, Timothy S. (ERC, Inc.); (MSU)

    2008-10-03

    Two symmetric triblock polystyrene-butadiene-polystyrene (SBS) copolymers with different initial morphologies were grafted with varying amounts of isobutyl-substituted polyhedral oligomeric silsesquioxane (POSS) molecules. The POSS octamers, R{prime}R{sub 7}Si{sub 8}O{sub 12}, were designed to contain a single silane functional group, R{prime}, which was used to graft onto the dangling 1,2-butadienes in the polybutadiene block and seven identical organic groups, R = isobutyl (iBu). Morphology and phase transitions of these iBu-POSS-modified SBS were investigated using small-angle X-ray scattering and rheological methods. It was observed that when iBu-POSS was grafted to the butadiene segment, the long-range and local order of the morphology were preserved, and the d-spacing showed a small, systematic increase with increasing POSS content. These observations suggest that grafted iBu-POSS were well-distributed within the butadiene domains and did not interact with the styrene domains; effectively, grafting of iBu-POSS to butadiene did not affect the segregation between butadiene and styrene domains. However, addition of iBu-POSS reduces the overall polystyrene volume. Consequently, from a morphology standpoint, this modification effectively shifts the phase diagram to lower styrene content. This was supported with SAXS and transition temperatures measurements made from the different host morphologies.

  4. Collagen XII and XIV, New Partners of Cartilage Oligomeric Matrix Protein in the Skin Extracellular Matrix Suprastructure*

    Science.gov (United States)

    Agarwal, Pallavi; Zwolanek, Daniela; Keene, Douglas R.; Schulz, Jan-Niklas; Blumbach, Katrin; Heinegård, Dick; Zaucke, Frank; Paulsson, Mats; Krieg, Thomas; Koch, Manuel; Eckes, Beate

    2012-01-01

    The tensile and scaffolding properties of skin rely on the complex extracellular matrix (ECM) that surrounds cells, vasculature, nerves, and adnexus structures and supports the epidermis. In the skin, collagen I fibrils are the major structural component of the dermal ECM, decorated by proteoglycans and by fibril-associated collagens with interrupted triple helices such as collagens XII and XIV. Here we show that the cartilage oligomeric matrix protein (COMP), an abundant component of cartilage ECM, is expressed in healthy human skin. COMP expression is detected in the dermal compartment of skin and in cultured fibroblasts, whereas epidermis and HaCaT cells are negative. In addition to binding collagen I, COMP binds to collagens XII and XIV via their C-terminal collagenous domains. All three proteins codistribute in a characteristic narrow zone in the superficial papillary dermis of healthy human skin. Ultrastructural analysis by immunogold labeling confirmed colocalization and further revealed the presence of COMP along with collagens XII and XIV in anchoring plaques. On the basis of these observations, we postulate that COMP functions as an adapter protein in human skin, similar to its function in cartilage ECM, by organizing collagen I fibrils into a suprastructure, mainly in the vicinity of anchoring plaques that stabilize the cohesion between the upper dermis and the basement membrane zone. PMID:22573329

  5. Role of Nucleotide-Binding Oligomerization Domain-Containing (NOD 2 in Host Defense during Pneumococcal Pneumonia.

    Directory of Open Access Journals (Sweden)

    Tijmen J Hommes

    Full Text Available Streptococcus (S. pneumoniae is the most common causative pathogen in community-acquired pneumonia. Nucleotide-binding oligomerization domain-containing (NOD 2 is a pattern recognition receptor located in the cytosol of myeloid cells that is able to detect peptidoglycan fragments of S. pneumoniae. We here aimed to investigate the role of NOD2 in the host response during pneumococcal pneumonia. Phagocytosis of S. pneumoniae was studied in NOD2 deficient (Nod2-/- and wild-type (Wt alveolar macrophages and neutrophils in vitro. In subsequent in vivo experiments Nod2-/- and Wt mice were inoculated with serotype 2 S. pneumoniae (D39, an isogenic capsule locus deletion mutant (D39Δcps or serotype 3 S. pneumoniae (6303 via the airways, and bacterial growth and dissemination and the lung inflammatory response were evaluated. Nod2-/- alveolar macrophages and blood neutrophils displayed a reduced capacity to internalize pneumococci in vitro. During pneumonia caused by S. pneumoniae D39 Nod2-/- mice were indistinguishable from Wt mice with regard to bacterial loads in lungs and distant organs, lung pathology and neutrophil recruitment. While Nod2-/- and Wt mice also had similar bacterial loads after infection with the more virulent S. pneumoniae 6303 strain, Nod2-/- mice displayed a reduced bacterial clearance of the normally avirulent unencapsulated D39Δcps strain. These results suggest that NOD2 does not contribute to host defense during pneumococcal pneumonia and that the pneumococcal capsule impairs recognition of S. pneumoniae by NOD2.

  6. Non-transferrin-bound iron (NTBI uptake by T lymphocytes: evidence for the selective acquisition of oligomeric ferric citrate species.

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    Joao Arezes

    Full Text Available Iron is an essential nutrient in several biological processes such as oxygen transport, DNA replication and erythropoiesis. Plasma iron normally circulates bound to transferrin. In iron overload disorders, however, iron concentrations exceed transferrin binding capacity and iron appears complexed with low molecular weight molecules, known as non-transferrin-bound iron (NTBI. NTBI is responsible for the toxicity associated with iron-overload pathologies but the mechanisms leading to NTBI uptake are not fully understood. Here we show for the first time that T lymphocytes are able to take up and accumulate NTBI in a manner that resembles that of hepatocytes. Moreover, we show that both hepatocytes and T lymphocytes take up the oligomeric Fe3Cit3 preferentially to other iron-citrate species, suggesting the existence of a selective NTBI carrier. These results provide a tool for the identification of the still elusive ferric-citrate cellular carrier and may also open a new pathway towards the design of more efficient iron chelators for the treatment of iron overload disorders.

  7. Structure of the large terminase from a hyperthermophilic virus reveals a unique mechanism for oligomerization and ATP hydrolysis.

    Science.gov (United States)

    Xu, Rui-Gang; Jenkins, Huw T; Antson, Alfred A; Greive, Sandra J

    2017-12-15

    The crystal structure of the large terminase from the Geobacillus stearothermophilus bacteriophage D6E shows a unique relative orientation of the N-terminal adenosine triphosphatase (ATPase) and C-terminal nuclease domains. This monomeric 'initiation' state with the two domains 'locked' together is stabilized via a conserved C-terminal arm, which may interact with the portal protein during motor assembly, as predicted for several bacteriophages. Further work supports the formation of an active oligomeric state: (i) AUC data demonstrate the presence of oligomers; (ii) mutational analysis reveals a trans-arginine finger, R158, indispensable for ATP hydrolysis; (iii) the location of this arginine is conserved with the HerA/FtsK ATPase superfamily; (iv) a molecular docking model of the pentamer is compatible with the location of the identified arginine finger. However, this pentameric model is structurally incompatible with the monomeric 'initiation' state and is supported by the observed increase in kcat of ATP hydrolysis, from 7.8 ± 0.1 min-1 to 457.7 ± 9.2 min-1 upon removal of the C-terminal nuclease domain. Taken together, these structural, biophysical and biochemical data suggest a model where transition from the 'initiation' state into a catalytically competent pentameric state, is accompanied by substantial domain rearrangements, triggered by the removal of the C-terminal arm from the ATPase active site. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  8. Observing Changes in the Structure and Oligomerization State of a Helical Protein Dimer Using Solid-State Nanopores.

    Science.gov (United States)

    Niedzwiecki, David J; Lanci, Christopher J; Shemer, Gabriel; Cheng, Phillip S; Saven, Jeffery G; Drndić, Marija

    2015-09-22

    Protein analysis using solid-state nanopores is challenging due to limitations in bandwidth and signal-to-noise ratio. Recent improvements of those two aspects have made feasible the study of small peptides using solid-state nanopores, which have an advantage over biological counterparts in tunability of the pore diameter. Here, we report on the detection and characterization of peptides as small as 33 amino acids. Silicon nitride nanopores with thicknesses less than 10 nm are used to provide signal-to-noise (S/N) levels up to S/N ∼ 10 at 100 kHz. We demonstrate differentiation of monomer and dimer forms of the GCN4-p1 leucine zipper, a coiled-coil structure well studied in molecular biology, and compare with the unstructured 33-residue monomer. GCN4-p1 is sequence segment associated with homodimerization of the transcription factor General Control Nonderepressible 4 (GCN4), which is involved in the control of amino acid synthesis in yeast. The differentiation between two oligomeric forms demonstrates the capabilities of improved solid-state nanopore platforms to extract structural information involving short peptide structures.

  9. Nucleotide-Binding Oligomerization Domain-1 and -2 Play No Role in Controlling Brucella abortus Infection in Mice

    Directory of Open Access Journals (Sweden)

    Fernanda S. Oliveira

    2012-01-01

    Full Text Available Nucleotide-binding oligomerization domain proteins (NODs are modular cytoplasmic proteins implicated in the recognition of peptidoglycan-derived molecules. Further, several in vivo studies have demonstrated a role for Nod1 and Nod2 in host defense against bacterial pathogens. Here, we demonstrated that macrophages from NOD1-, NOD2-, and Rip2-deficient mice produced lower levels of TNF-α following infection with live Brucella abortus compared to wild-type mice. Similar reduction on cytokine synthesis was not observed for IL-12 and IL-6. However, NOD1, NOD2, and Rip2 knockout mice were no more susceptible to infection with virulent B. abortus than wild-type mice. Additionally, spleen cells from NOD1-, NOD2-, and Rip2-deficient mice showed unaltered production of IFN-γ compared to C57BL/6 mice. Taken together, this study demonstrates that NOD1, NOD2 and Rip2 are dispensable for the control of B. abortus during in vivo infection.

  10. Polyhedral oligomeric silsesquioxane poly(carbonate-urea) urethane (POSS-PCU): applications in nanotechnology and regenerative medicine.

    Science.gov (United States)

    Tan, Aaron; Farhatnia, Yasmin; Seifalian, Alexander M

    2013-01-01

    The field of nanotechnology and regenerative medicine has been progressing at a rapid pace. From theranostic nanoparticles to biomaterials, the possibilities seem endless. Researchers at the University College London have developed and patented a technology to manufacture a new breed of novel nanocomposite material called polyhedral oligomeric silsesquioxane poly(carbonate-urea) urethane (POSS-PCU). The enhanced biocompatibility, superior mechanical engineering properties, and augmented degradative resistance of POSS-PCU render it capable of functioning as a scaffold for bioartificial organs, nanoparticles for biomedical applications, and a coating for medical devices. Indeed, POSS-PCU has been used in 3 first-in-man studies as a bypass graft, lacrimal duct, and, most notably, the world's first synthetic trachea. Our group has a vested interest in the development of next-generation smart biomaterials that use nano-inspired technologies and mobilize the regenerative capacity of biological systems. Herein we provide a concise and authoritative account of the evolution of biomaterials research within a University College London and POSS-PCU context, with further emphasis on the prospects and challenges involved in driving the future of bioartificial organs in tandem with advanced drug delivery systems in the realm of nanotechnology and regenerative medicine.

  11. The cholesterol-binding motif of the HIV-1 glycoprotein gp41 regulates lateral sorting and oligomerization.

    Science.gov (United States)

    Schwarzer, Roland; Levental, Ilya; Gramatica, Andrea; Scolari, Silvia; Buschmann, Volker; Veit, Michael; Herrmann, Andreas

    2014-10-01

    Enveloped viruses often use membrane lipid rafts to assemble and bud, augment infection and spread efficiently. However, the molecular bases and functional consequences of the partitioning of viral glycoproteins into microdomains remain intriguing questions in virus biology. Here, we measured Foerster resonance energy transfer by fluorescence lifetime imaging microscopy (FLIM-FRET) to study the role of distinct membrane proximal regions of the human immunodeficiency virus glycoprotein gp41 for lipid raft partitioning in living Chinese hamster ovary cells (CHO-K1). Gp41 was labelled with a fluorescent protein at the exoplasmic face of the membrane, preventing any interference of the fluorophore with the proposed role of the transmembrane and cytoplasmic domains in lateral organization of gp41. Raft localization was deduced from interaction with an established raft marker, a fluorescently tagged glycophosphatidylinositol anchor and the cholesterol recognition amino acid consensus (CRAC) was identified as the crucial lateral sorting determinant in CHO-K1 cells. Interestingly, the raft association of gp41 indicates a substantial cell-to-cell heterogeneity of the plasma membrane microdomains. In complementary fluorescence polarization microscopy, a distinct CRAC requirement was found for the oligomerization of the gp41 variants. Our data provide further insight into the molecular basis and biological implications of the cholesterol dependent lateral sorting of viral glycoproteins for virus assembly at cellular membranes. © 2014 John Wiley & Sons Ltd.

  12. Higher Order Oligomerization of the Licensing ORC4 Protein Is Required for Polar Body Extrusion in Murine Meiosis.

    Science.gov (United States)

    Nguyen, Hieu; James, Nicholas G; Nguyen, Lynn; Nguyen, Thien P; Vuong, Cindy; Ortega, Michael A; Jameson, David M; Ward, W Steven

    2017-09-01

    We have previously shown that the DNA replication licensing factor ORC4 forms a cage around the chromosomes that are extruded in both polar bodies during murine oogenesis, but not around the chromosomes that are retained in the oocyte or around the sperm chromatin. We termed this structure the ORC4 cage. Here, we tested whether the formation of the ORC4 cage is necessary for polar body extrusion (PBE). We first experimentally forced oocytes to extrude sperm chromatin as a pseudo-polar body and found that under these conditions the sperm chromatin did become enclosed in an ORC4 cage. Next, we attempted to prevent the formation of the ORC4 cage by injecting peptides that contained sequences of different domains of the ORC4 protein into metaphase II (MII) oocytes just before the cage normally forms. Our rationale was that the ORC4 peptides would block protein-protein interactions required for cage formation. Two out of six tested peptides prevented the ORC4 cage formation and simultaneously inhibited PBE, resulting in the formation of two pronuclei (2 PN) that were retained in the oocyte. Together, these data demonstrate that ORC4 oligomerization is required to form the ORC4 cage and that it is required for PBE. J. Cell. Biochem. 118: 2941-2949, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  13. Nickel(II) Complexes Bearing 4-Arylimino-1,2,3-trihydroacridines: Synthesis, Characterization, and Ethylene Oligomerization.

    Science.gov (United States)

    Wang, Shengdong; Du, Shizhen; Zhang, Wenjuan; Asuha, Sin; Sun, Wen-Hua

    2015-06-01

    Nickel(II) complexes have attracted much attention as a new generation of olefin catalysts since the α-diiminonickel complex was discovered as a highly efficient procatalyst for ethylene polymerization. A series of novel 4-arylimino-1,2,3-trihydroacridylnickel(II) dihalide complexes was synthesized in a one-pot reaction of 2,3-dihydroacridine-4-one and different anilines with nickel(II) chloride or nickel(II) bromide 1,2-dimethoxyethane complex. The complexes were characterized by infrared spectroscopy and elemental analysis. The molecular structures of the representative complexes 4-(2,6-diisopropylphenylimino)-1,2,3-trihydroacridylnickel(II) dichloride (C3), 4-(2,4,6-trimethylphenylimino)-1,2,3-trihydroacridylnickel dichloride(II) (C4), and 4-(2,4,6-trimethylphenylimino)-1,2,3-trihydroacridylnickel(II) dibromide (C9) were confirmed by single-crystal X-ray crystallography, revealing a distorted tetrahedral geometry around the nickel(II) of C3 and distorted trigonal bipyramidal geometry for C4 and C9. With the activation of trimethylaluminium (TMA), all nickel(II) complexes exhibited good activity for ethylene oligomerization, and oligomer products ranged from butene (C4) to hexadecene (C16).

  14. Chromium(III) complexes bearing 2-benzazole-1,10-phenanthrolines: synthesis, molecular structures and ethylene oligomerization and polymerization.

    Science.gov (United States)

    Zhang, Min; Wang, Kefeng; Sun, Wen-Hua

    2009-08-28

    The 2-benzazole-1,10-phenanthrolines and their chromium(III) complexes were synthesized and characterized by elemental and spectroscopic analyses as well as by single-crystal X-ray crystallography. X-Ray crystallographic analyses of C6 and C8 reveal an octahedral geometry around both chromium centers. The electronic spectra of the chromium complexes exhibit d-d transitions typically of a pseudo-octahedral coordinated d(3) ion, falling into the region nu(1)(4)A(2g)-->(4)T(2g) 600-700 nm,nu(2)(4)A(2g)-->(4)T(1g)(F) 430-470 nm, and the 10Dq values between 15674 and 16529 cm(-1). The variation of the heteroatoms (X = N, O, S) in benzazole group shows regular influence on the 10Dq values as 10Dq (O) > 10Dq (N) > 10Dq (S), which reflects the sigma-donor/pi-acceptor properties of these benzazole ligands. Upon activation with modified methylaluminoxane (MMAO), these complexes exhibited high activities for ethylene oligomerization (up to 7.36 x 10(6) g mol(-1) (Cr) h(-1)) and ethylene polymerization (up to 1.28 x 10(6) g mol(-1) (Cr) h(-1)). The effects of non-coordinated N, O or S heteroatoms in the ligands have been examined, and interestingly catalytic activities also strictly adhered to the trend O > N > S under various ethylene pressures. Reaction conditions significantly influenced the catalytic properties of the complexes.

  15. Benchmark, DFT assessments, cooperativity, and energy decomposition analysis of the hydrogen bonds in HCN/HNC oligomeric complexes.

    Science.gov (United States)

    de Oliveira, Paulo McMiller C; Silva, Juliana A B; Longo, Ricardo L

    2017-02-01

    Hydrogen cyanide (HCN) and its tautomer hydrogen isocyanide (HNC) are relevant for extraterrestrial chemistry and possible relation to the origin of biomolecules. Several processes and reactions involving these molecules depend on their intermolecular interactions that can lead to aggregates and liquids especially due to the hydrogen bonds. It is thus important to comprehend, to describe, and to quantify their hydrogen bonds, mainly their nature and the cooperativity effects. A systematic study of all linear complexes up to pentamers of HCN and HNC is presented. CCSD(T)/CBS energy calculations, with and without basis set superposition error (BSSE) corrections for energies and geometries, provided a suitable set of benchmarks. Approximated methods based on the density functional theory (DFT) such as BP86, PBE, TPSS, B3LYP, CAM-B3LYP with and without dispersion corrections and long-range corrections, were assessed to describe the interaction energies and cooperativity effects. These assessments are relevant to select DFT functionals for liquid simulations. Energy decomposition analysis was performed at the PBE/STO-TZ2P level and provided insights into the nature of the hydrogen bonds, which are dominated by the electrostatic component. In addition, several linear relationships between the various energy components and the interaction energy were obtained. The cooperativity energy was also found to be practically linear with respect to the interaction energy, which may be relevant for designing and/or correcting empirical force fields. Graphical Abstract Hydrogen bonds in HCN/HNC oligomeric complexesᅟ.

  16. Theoretical Study on the Second Hyperpolarizailities of Oligomeric Systems Composed of Carbon and Silicon π-Structures.

    Science.gov (United States)

    Matsui, Hiroshi; Nagami, Takanori; Takamuku, Shota; Ito, Soichi; Kitagawa, Yasutaka; Nakano, Masayoshi

    2016-11-15

    To explore the prospect of molecules involving silicon-silicon multiple bonds as nonlinear optical molecular systems, the relationship between the structure and the second hyperpolarizabilities γ of the oligomeric systems composed of carbon and silicon π-structures is investigated using the density functional theory method. It is found that these compounds indicate intramolecular charge transfer (ICT) from the silicon units to the carbon units together with nonzero diradical characters. The γ values of these compounds are shown to be 2-13 times as large as those of the carbon analogs. Although asymmetric carbon and silicon π-systems exhibit comparable enhancement to the corresponding symmetric systems, donor-π-donor structures exhibit remarkable enhancement of γ despite of their both-end short silicon π-chain moieties (donor units). Further analysis using the odd electron and γ densities clarifies that the intermediate diradical character also contributes to the enhancement of γ. These results predict that even short π-conjugated silicone moieties can cause remarkable enhancement of γ by introducing them into π-conjugated hydrocarbon structures.

  17. CCR5/CD4/CXCR4 oligomerization prevents HIV-1 gp120IIIB binding to the cell surface.

    Science.gov (United States)

    Martínez-Muñoz, Laura; Barroso, Rubén; Dyrhaug, Sunniva Y; Navarro, Gemma; Lucas, Pilar; Soriano, Silvia F; Vega, Beatriz; Costas, Coloma; Muñoz-Fernández, M Ángeles; Santiago, César; Rodríguez Frade, José Miguel; Franco, Rafael; Mellado, Mario

    2014-05-13

    CCR5 and CXCR4, the respective cell surface coreceptors of R5 and X4 HIV-1 strains, both form heterodimers with CD4, the principal HIV-1 receptor. Using several resonance energy transfer techniques, we determined that CD4, CXCR4, and CCR5 formed heterotrimers, and that CCR5 coexpression altered the conformation of both CXCR4/CXCR4 homodimers and CD4/CXCR4 heterodimers. As a result, binding of the HIV-1 envelope protein gp120IIIB to the CD4/CXCR4/CCR5 heterooligomer was negligible, and the gp120-induced cytoskeletal rearrangements necessary for HIV-1 entry were prevented. CCR5 reduced HIV-1 envelope-induced CD4/CXCR4-mediated cell-cell fusion. In nucleofected Jurkat CD4 cells and primary human CD4(+) T cells, CCR5 expression led to a reduction in X4 HIV-1 infectivity. These findings can help to understand why X4 HIV-1 strains infection affect T-cell types differently during AIDS development and indicate that receptor oligomerization might be a target for previously unidentified therapeutic approaches for AIDS intervention.

  18. Immobilization of homogeneous monomeric, oligomeric and fibrillar Aβ species for reliable SPR measurements.

    Directory of Open Access Journals (Sweden)

    Daniel Frenzel

    Full Text Available There is strong evidence that the amyloid-beta peptide (Aβ plays a central role in the pathogenesis of Alzheimer's disease (AD. In this context, a detailed quantitative description of the interactions with different Aβ species is essential for characterization of physiological and artificial ligands. However, the high aggregation propensity of Aβ in concert with its susceptibility to structural changes due to even slight changes in solution conditions has impeded surface plasmon resonance (SPR studies with homogeneous Aβ conformer species. Here, we have adapted the experimental procedures to state-of-the-art techniques and established novel approaches to reliably overcome the aforementioned challenges. We show that the application of density gradient centrifugation (DGC for sample purification and the use of a single chain variable fragment (scFv of a monoclonal antibody directed against the amino-terminus of Aβ allows reliable SPR measurements and quality control of the immobilized Aβ aggregate species at any step throughout the experiment.

  19. Noise Spectroscopy in Strongly Correlated Oxides

    Science.gov (United States)

    Alsaqqa, Ali M.

    Strongly correlated materials are an interesting class of materials, thanks to the novel electronic and magnetic phenomena they exhibit as a result of the interplay of various degrees of freedom. This gives rise to an array of potential applications, from Mott-FET to magnetic storage. Many experimental probes have been used to study phase transitions in strongly correlated oxides. Among these, resistance noise spectroscopy, together with conventional transport measurements, provides a unique viewpoint to understand the microscopic dynamics near the phase transitions in these oxides. In this thesis, utilizing noise spectroscopy and transport measurements, four different strongly correlated materials were studied: (1) neodymium nickel oxide (NdNiO 3) ultrathin films, (2) vanadium dioxide (VO2) microribbons, (3) copper vanadium bronze (CuxV2O 5) microribbons and (4) niobium triselenide (NbSe3) microribbons. Ultra thin films of rare-earth nickelates exhibit several temperature-driven phase transitions. In this thesis, we studied the metal-insulator and Neel transitions in a series of NdNiO3 films with different lattice mismatches. Upon colling down, the metal-insulator phase transition is accompanied by a structural (orthorohombic to monoclinic) and magnetic (paramagnetic to antiferromagnetic) transitions as well, making the problem more interesting and complex at the same time. The noise is of the 1/f type and is Gaussian in the high temperature phase, however deviations are seen in the low temperature phases. Below the metal-insulator transition, noise magnitude increases by orders of magnitude: a sign of inhomogeneous electrical conduction as result of phase separation. This is further assured by the non-Gaussian noise signature. At very low temperatures (T thesis, we tried to answer this question by utilizing three different tuning parameters: temperature, voltage bias and strain. Our results point to an unusual noise behavior in the high-temperature metallic phase

  20. Structural basis for the oligomerization-state switch from a dimer to a trimer of an engineered cortexillin-1 coiled-coil variant.

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    Saša Bjelić

    Full Text Available Coiled coils are well suited to drive subunit oligomerization and are widely used in applications ranging from basic research to medicine. The optimization of these applications requires a detailed understanding of the molecular determinants that control of coiled-coil formation. Although many of these determinants have been identified and characterized in great detail, a puzzling observation is that their presence does not necessarily correlate with the oligomerization state of a given coiled-coil structure. Thus, other determinants must play a key role. To address this issue, we recently investigated the unrelated coiled-coil domains from GCN4, ATF1 and cortexillin-1 as model systems. We found that well-known trimer-specific oligomerization-state determinants, such as the distribution of isoleucine residues at heptad-repeat core positions or the trimerization motif Arg-h-x-x-h-Glu (where h = hydrophobic amino acid; x = any amino acid, switch the peptide's topology from a dimer to a trimer only when inserted into the trigger sequence, a site indispensable for coiled-coil formation. Because high-resolution structural information could not be obtained for the full-length, three-stranded cortexillin-1 coiled coil, we here report the detailed biophysical and structural characterization of a shorter variant spanning the trigger sequence using circular dichroism, anatytical ultracentrifugation and x-ray crystallography. We show that the peptide forms a stable α-helical trimer in solution. We further determined the crystal structure of an optimised variant at a resolution of 1.65 Å, revealing that the peptide folds into a parallel, three-stranded coiled coil. The two complemented R-IxxIE trimerization motifs and the additional hydrophobic core isoleucine residue adopt the conformations seen in other extensively characterized parallel, three-stranded coiled coils. These findings not only confirm the structural basis for the switch in

  1. Structural basis for the oligomerization-state switch from a dimer to a trimer of an engineered cortexillin-1 coiled-coil variant.

    Science.gov (United States)

    Bjelić, Saša; Wieser, Mara; Frey, Daniel; Stirnimann, Christian U; Chance, Mark R; Jaussi, Rolf; Steinmetz, Michel O; Kammerer, Richard A

    2013-01-01

    Coiled coils are well suited to drive subunit oligomerization and are widely used in applications ranging from basic research to medicine. The optimization of these applications requires a detailed understanding of the molecular determinants that control of coiled-coil formation. Although many of these determinants have been identified and characterized in great detail, a puzzling observation is that their presence does not necessarily correlate with the oligomerization state of a given coiled-coil structure. Thus, other determinants must play a key role. To address this issue, we recently investigated the unrelated coiled-coil domains from GCN4, ATF1 and cortexillin-1 as model systems. We found that well-known trimer-specific oligomerization-state determinants, such as the distribution of isoleucine residues at heptad-repeat core positions or the trimerization motif Arg-h-x-x-h-Glu (where h = hydrophobic amino acid; x = any amino acid), switch the peptide's topology from a dimer to a trimer only when inserted into the trigger sequence, a site indispensable for coiled-coil formation. Because high-resolution structural information could not be obtained for the full-length, three-stranded cortexillin-1 coiled coil, we here report the detailed biophysical and structural characterization of a shorter variant spanning the trigger sequence using circular dichroism, anatytical ultracentrifugation and x-ray crystallography. We show that the peptide forms a stable α-helical trimer in solution. We further determined the crystal structure of an optimised variant at a resolution of 1.65 Å, revealing that the peptide folds into a parallel, three-stranded coiled coil. The two complemented R-IxxIE trimerization motifs and the additional hydrophobic core isoleucine residue adopt the conformations seen in other extensively characterized parallel, three-stranded coiled coils. These findings not only confirm the structural basis for the switch in oligomerization state from

  2. Structural insights into the unusually strong ATPase activity of the AAA domain of the Caenorhabditis elegans fidgetin-like 1 (FIGL-1) protein.

    Science.gov (United States)

    Peng, Wentao; Lin, Zhijie; Li, Weirong; Lu, Jing; Shen, Yuequan; Wang, Chunguang

    2013-10-11

    The FIGL-1 (fidgetin like-1) protein is a homolog of fidgetin, a protein whose mutation leads to multiple developmental defects. The FIGL-1 protein contains an AAA (ATPase associated with various activities) domain and belongs to the AAA superfamily. However, the biological functions and developmental implications of this protein remain unknown. Here, we show that the AAA domain of the Caenorhabditis elegans FIGL-1 protein (CeFIGL-1-AAA), in clear contrast to homologous AAA domains, has an unusually high ATPase activity and forms a hexamer in solution. By determining the crystal structure of CeFIGL-1-AAA, we found that the loop linking helices α9 and α10 folds into the short helix α9a, which has an acidic surface and interacts with a positively charged surface of the neighboring subunit. Disruption of this charge interaction by mutagenesis diminishes both the ATPase activity and oligomerization capacity of the protein. Interestingly, the acidic residues in helix α9a of CeFIGL-1-AAA are not conserved in other homologous AAA domains that have relatively low ATPase activities. These results demonstrate that the sequence of CeFIGL-1-AAA has adapted to establish an intersubunit charge interaction, which contributes to its strong oligomerization and ATPase activity. These unique properties of CeFIGL-1-AAA distinguish it from other homologous proteins, suggesting that CeFIGL-1 may have a distinct biological function.

  3. Application of strong phosphoric acid to radiochemistry

    International Nuclear Information System (INIS)

    Terada, Kikuo

    1977-01-01

    Not only inorganic and organic compounds but also natural substrances, such as accumulations in soil, are completely decomposed and distilled by heating with strong phosphoric acid for 30 to 50 minutes. As applications of strong phosphoric acid to radiochemistry, determination of uranium and boron by use of solubilization effect of this substance, titration of uranyl ion by use of sulfuric iron (II) contained in this substance, application to tracer experiment, and determination of radioactive ruthenium in environmental samples are reviewed. Strong phosphoric acid is also applied to activation analysis, for example, determination of N in pyrographite with iodate potassium-strong phosphoric acid method, separation of Os and Ru with sulfuric cerium (IV) - strong phosphoric acid method or potassium dechromate-strong phosphoric acid method, analysis of Se, As and Sb rocks and accumulations with ammonium bromide, sodium chloride and sodium bromide-strong phosphoric acid method. (Kanao, N.)

  4. Dynamic polarizability of a complex atom in strong laser fields

    International Nuclear Information System (INIS)

    Rapoport, L.P.; Klinskikh, A.F.; Mordvinov, V.V.

    1997-01-01

    An asymptotic expansion of the dynamic polarizability of a complex atom in a strong circularly polarized light field is found for the case of high frequencies. The self-consistent approximation of the Hartree-Fock type for the ''atom+field'' system is developed, within the framework of which a numerical calculation of the dynamic polarizability of Ne, Kr, and Ar atoms in a strong radiation field is performed. The strong field effect is shown to manifest itself not only in a change of the energy spectrum and the character of behavior of the wave functions of atomic electrons, but also in a modification of the one-electron self-consistent potential for the atom in the field

  5. Interplay of Anderson localization and strong interaction in disordered systems

    Energy Technology Data Exchange (ETDEWEB)

    Henseler, Peter

    2010-01-15

    We study the interplay of disorder localization and strong local interactions within the Anderson-Hubbard model. Taking into account local Mott-Hubbard physics and static screening of the disorder potential, the system is mapped onto an effective single-particle Anderson model, which is studied within the self-consistent theory of electron localization. For fermions, we find rich nonmonotonic behavior of the localization length {xi}, particularly in two-dimensional systems, including an interaction-induced exponential enhancement of {xi} for small and intermediate disorders and a strong reduction of {xi} due to hopping suppression by strong interactions. In three dimensions, we identify for half filling a Mott-Hubbard-assisted Anderson localized phase existing between the metallic and the Mott-Hubbard-gapped phases. For small U there is re-entrant behavior from the Anderson localized phase to the metallic phase. For bosons, the unrestricted particle occupation number per lattice site yields a monotonic enhancement of {xi} as a function of decreasing interaction, which we assume to persist until the superfluid Bose-Einstein condensate phase is entered. Besides, we study cold atomic gases expanding, by a diffusion process, in a weak random potential. We show that the density-density correlation function of the expanding gas is strongly affected by disorder and we estimate the typical size of a speckle spot, i.e., a region of enhanced or depleted density. Both a Fermi gas and a Bose-Einstein condensate (in a mean-field approach) are considered. (orig.)

  6. Interplay of Anderson localization and strong interaction in disordered systems

    International Nuclear Information System (INIS)

    Henseler, Peter

    2010-01-01

    We study the interplay of disorder localization and strong local interactions within the Anderson-Hubbard model. Taking into account local Mott-Hubbard physics and static screening of the disorder potential, the system is mapped onto an effective single-particle Anderson model, which is studied within the self-consistent theory of electron localization. For fermions, we find rich nonmonotonic behavior of the localization length ξ, particularly in two-dimensional systems, including an interaction-induced exponential enhancement of ξ for small and intermediate disorders and a strong reduction of ξ due to hopping suppression by strong interactions. In three dimensions, we identify for half filling a Mott-Hubbard-assisted Anderson localized phase existing between the metallic and the Mott-Hubbard-gapped phases. For small U there is re-entrant behavior from the Anderson localized phase to the metallic phase. For bosons, the unrestricted particle occupation number per lattice site yields a monotonic enhancement of ξ as a function of decreasing interaction, which we assume to persist until the superfluid Bose-Einstein condensate phase is entered. Besides, we study cold atomic gases expanding, by a diffusion process, in a weak random potential. We show that the density-density correlation function of the expanding gas is strongly affected by disorder and we estimate the typical size of a speckle spot, i.e., a region of enhanced or depleted density. Both a Fermi gas and a Bose-Einstein condensate (in a mean-field approach) are considered. (orig.)

  7. Diagnosing a Strong-Fault Model by Conflict and Consistency.

    Science.gov (United States)

    Zhang, Wenfeng; Zhao, Qi; Zhao, Hongbo; Zhou, Gan; Feng, Wenquan

    2018-03-29

    The diagnosis method for a weak-fault model with only normal behaviors of each component has evolved over decades. However, many systems now demand a strong-fault models, the fault modes of which have specific behaviors as well. It is difficult to diagnose a strong-fault model due to its non-monotonicity. Currently, diagnosis methods usually employ conflicts to isolate possible fault and the process can be expedited when some observed output is consistent with the model's prediction where the consistency indicates probably normal components. This paper solves the problem of efficiently diagnosing a strong-fault model by proposing a novel Logic-based Truth Maintenance System (LTMS) with two search approaches based on conflict and consistency. At the beginning, the original a strong-fault model is encoded by Boolean variables and converted into Conjunctive Normal Form (CNF). Then the proposed LTMS is employed to reason over CNF and find multiple minimal conflicts and maximal consistencies when there exists fault. The search approaches offer the best candidate efficiency based on the reasoning result until the diagnosis results are obtained. The completeness, coverage, correctness and complexity of the proposals are analyzed theoretically to show their strength and weakness. Finally, the proposed approaches are demonstrated by applying them to a real-world domain-the heat control unit of a spacecraft-where the proposed methods are significantly better than best first and conflict directly with A* search methods.

  8. Seeking a Mechanism for the Toxicity of Oligomeric α-Synuclein

    Directory of Open Access Journals (Sweden)

    Hazel L. Roberts

    2015-03-01

    Full Text Available In a number of neurological diseases including Parkinson’s disease (PD, α‑synuclein is aberrantly folded, forming abnormal oligomers, and amyloid fibrils within nerve cells. Strong evidence exists for the toxicity of increased production and aggregation of α-synuclein in vivo. The toxicity of α-synuclein is popularly attributed to the formation of “toxic oligomers”: a heterogenous and poorly characterized group of conformers that may share common molecular features. This review presents the available evidence on the properties of α-synuclein oligomers and the potential molecular mechanisms of their cellular disruption. Toxic α-synuclein oligomers may impact cells in a number of ways, including the disruption of membranes, mitochondrial depolarization, cytoskeleton changes, impairment of protein clearance pathways, and enhanced oxidative stress. We also examine the relationship between α-synuclein toxic oligomers and amyloid fibrils, in the light of recent studies that paint a more complex picture of α-synuclein toxicity. Finally, methods of studying and manipulating oligomers within cells are described.

  9. Oligomerized backbone pilin helps piliated Lactococcus lactis to withstand shear flow.

    Science.gov (United States)

    Castelain, Mickaël; Duviau, Marie-Pierre; Oxaran, Virginie; Schmitz, Philippe; Cocaign-Bousquet, Muriel; Loubière, Pascal; Piard, Jean-Christophe; Mercier-Bonin, Muriel

    2016-09-01

    The present work focuses on the role of pili present at the cell surface of Lactococcus lactis in bacterial adhesion to abiotic (hydrophobic polystyrene) and biotic (mucin-coated polystyrene) surfaces. Native pili-displaying strains and isogenic derivatives in which pilins or sortase C structural genes had been modified were used. Surface physico-chemistry, morphology and shear-flow-induced detachment of lactococcal cells were evaluated. The involvement of pili in L. lactis adhesion was clearly demonstrated, irrespective of the surface characteristics (hydrophobic/hydrophilic, presence or not of specific binding sites). The accessory pilin, PilC, and the backbone pilin, PilB, were revealed to play a major role in adhesion, provided that the PilB was present in its polymerized form. Within the population fraction that remained attached to the surface under increasing shear flow, different association behaviors were observed, showing that pili could serve as anchoring sites thus hampering the effect of shear flow on cell orientation and detachment.

  10. Melting processes of oligomeric α and β isotactic polypropylene crystals at ultrafast heating rates

    Energy Technology Data Exchange (ETDEWEB)

    Ji, Xiaojing [School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072 (China); He, Xuehao, E-mail: xhhe@tju.edu.cn, E-mail: scjiang@tju.edu.cn [Department of Chemistry, School of Science, Tianjin University, and Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin 300072 (China); Jiang, Shichun, E-mail: xhhe@tju.edu.cn, E-mail: scjiang@tju.edu.cn [School of Material, Tianjin University, Tianjin 300072 (China)

    2014-02-07

    The melting behaviors of α (stable) and β (metastable) isotactic polypropylene (iPP) crystals at ultrafast heating rates are simulated with atomistic molecular dynamics method. Quantitative information about the melting processes of α- and β-iPP crystals at atomistic level is achieved. The result shows that the melting process starts from the interfaces of lamellar crystal through random dislocation of iPP chains along the perpendicular direction of lamellar crystal structure. In the melting process, the lamellar crystal gradually expands but the corresponding thickness decreases. The analysis shows that the system expansion lags behind the crystallinity decreasing and the lagging extents for α- and β-iPP are significantly different. The apparent melting points of α- and β-iPP crystals rise with the increase of the heating rate and lamellar crystal thickness. The apparent melting point of α-iPP crystal is always higher than that of β-iPP at differently heating rates. Applying the Gibbs-Thomson rule and the scaling property of the melting kinetics, the equilibrium melting points of perfect α- and β-iPP crystals are finally predicted and it shows a good agreement with experimental result.

  11. Strongly correlating liquids and their isomorphs

    OpenAIRE

    Pedersen, Ulf R.; Gnan, Nicoletta; Bailey, Nicholas P.; Schröder, Thomas B.; Dyre, Jeppe C.

    2010-01-01

    This paper summarizes the properties of strongly correlating liquids, i.e., liquids with strong correlations between virial and potential energy equilibrium fluctuations at constant volume. We proceed to focus on the experimental predictions for strongly correlating glass-forming liquids. These predictions include i) density scaling, ii) isochronal superposition, iii) that there is a single function from which all frequency-dependent viscoelastic response functions may be calculated, iv) that...

  12. Atom collisions in a strong electromagnetic field

    International Nuclear Information System (INIS)

    Smirnov, V.S.; Chaplik, A.V.

    1976-01-01

    It is shown that the long-range part of interatomic interaction is considerably altered in a strong electromagnetic field. Instead of the van der Waals law the potential asymptote can best be described by a dipole-dipole R -3 law. Impact broadening and the line shift in a strong nonresonant field are calculated. The possibility of bound states of two atoms being formed in a strong light field is discussed

  13. Aβ(39–42) Modulates Aβ Oligomerization but Not Fibril Formation

    Science.gov (United States)

    Gessel, Megan Murray; Wu, Chun; Li, Huiyuan; Bitan, Gal; Shea, Joan-Emma; Bowers, Michael T.

    2012-01-01

    Recently, certain C-terminal fragments (CTFs) of Aβ42 have been shown to be effective inhibitors of Aβ42 toxicity. Here, we examine the interactions between the shortest CTF in the original series, Aβ(39–42) and full-length Aβ. Mass spectrometry results indicate that Aβ(39–42) binds directly to Aβ monomers and to the n=2,4, and 6 oligomers. The Aβ42:Aβ(39–42) complex is further probed using in molecular dynamics simulations. Although the CTF was expected to bind to the hydrophobic C-terminus of Aβ42, the simulations show that Aβ(39–42) binds at several locations on Aβ42, including the C-terminus, other hydrophobic regions, and preferentially in the N-terminus. Ion mobility-mass spectrometry (IM-MS) and electron microscopy experiments indicate that Aβ(39–42) disrupts the early assembly of full-length Aβ. Specifically, the ion-mobility results show that Aβ(39–42) prevents the formation of large decamer/dodecamer Aβ42 species and, moreover, can remove these structures from solution. At the same time, thioflavin T fluorescence and electron microscopy results show that the CTF does not inhibit fibril formation, lending strong support to the hypothesis that oligomers and not amyloid fibrils are the Aβ form responsible for toxicity. The results emphasize the role of small, soluble assemblies in Aβ-induced toxicity and suggest that Aβ(39–42) inhibits Aβ-induced toxicity by a unique mechanism, modulating early assembly into non-toxic heterooligomers, without preventing fibril formation. PMID:22129303

  14. Strong Coupling Gauge Theories in LHC ERA

    Science.gov (United States)

    Fukaya, H.; Harada, M.; Tanabashi, M.; Yamawaki, K.

    2011-01-01

    AdS/QCD, light-front holography, and the nonperturbative running coupling / Stanley J. Brodsky, Guy de Teramond and Alexandre Deur -- New results on non-abelian vortices - Further insights into monopole, vortex and confinement / K. Konishi -- Study on exotic hadrons at B-factories / Toru Iijima -- Cold compressed baryonic matter with hidden local symmetry and holography / Mannque Rho -- Aspects of baryons in holographic QCD / T. Sakai -- Nuclear force from string theory / K. Hashimoto -- Integrating out holographic QCD back to hidden local symmetry / Masayasu Harada, Shinya Matsuzaki and Koichi Yamawaki -- Holographic heavy quarks and the giant Polyakov loop / Gianluca Grignani, Joanna Karczmarek and Gordon W. Semenoff -- Effect of vector-axial-vector mixing to dilepton spectrum in hot and/or dense matter / Masayasu Harada and Chihiro Sasaki -- Infrared behavior of ghost and gluon propagators compatible with color confinement in Yang-Mills theory with the Gribov horizon / Kei-Ichi Kondo -- Chiral symmetry breaking on the lattice / Hidenori Fukaya [for JLQCD and TWQCD collaborations] -- Gauge-Higgs unification: Stable Higgs bosons as cold dark matter / Yutaka Hosotani -- The limits of custodial symmetry / R. Sekhar Chivukula ... [et al.] -- Higgs searches at the tevatron / Kazuhiro Yamamoto [for the CDF and D[symbol] collaborations] -- The top triangle moose / R. S. Chivukula ... [et al.] -- Conformal phase transition in QCD like theories and beyond / V. A. Miransky -- Gauge-Higgs unification at LHC / Nobuhito Maru and Nobuchika Okada -- W[symbol]W[symbol] scattering in Higgsless models: Identifying better effective theories / Alexander S. Belyaev ... [et al.] -- Holographic estimate of Muon g - 2 / Deog Ki Hong -- Gauge-Higgs dark matter / T. Yamashita -- Topological and curvature effects in a multi-fermion interaction model / T. Inagaki and M. Hayashi -- A model of soft mass generation / J. Hosek -- TeV physics and conformality / Thomas Appelquist -- Conformal

  15. Cyclosporine A Impairs Nucleotide Binding Oligomerization Domain (Nod1)-Mediated Innate Antibacterial Renal Defenses in Mice and Human Transplant Recipients

    Science.gov (United States)

    Tourneur, Emilie; Ben Mkaddem, Sanae; Chassin, Cécilia; Bens, Marcelle; Goujon, Jean-Michel; Charles, Nicolas; Pellefigues, Christophe; Aloulou, Meryem; Hertig, Alexandre; Monteiro, Renato C.; Girardin, Stephen E.; Philpott, Dana J.; Rondeau, Eric

    2013-01-01

    Acute pyelonephritis (APN), which is mainly caused by uropathogenic Escherichia coli (UPEC), is the most common bacterial complication in renal transplant recipients receiving immunosuppressive treatment. However, it remains unclear how immunosuppressive drugs, such as the calcineurin inhibitor cyclosporine A (CsA), decrease renal resistance to UPEC. Here, we investigated the effects of CsA in host defense against UPEC in an experimental model of APN. We show that CsA-treated mice exhibit impaired production of the chemoattractant chemokines CXCL2 and CXCL1, decreased intrarenal recruitment of neutrophils, and greater susceptibility to UPEC than vehicle-treated mice. Strikingly, renal expression of Toll-like receptor 4 (Tlr4) and nucleotide-binding oligomerization domain 1 (Nod1), neutrophil migration capacity, and phagocytic killing of E. coli were significantly reduced in CsA-treated mice. CsA inhibited lipopolysaccharide (LPS)-induced, Tlr4-mediated production of CXCL2 by epithelial collecting duct cells. In addition, CsA markedly inhibited Nod1 expression in neutrophils, macrophages, and renal dendritic cells. CsA, acting through inhibition of the nuclear factor of activated T-cells (NFATs), also markedly downregulated Nod1 in neutrophils and macrophages. Silencing the NFATc1 isoform mRNA, similar to CsA, downregulated Nod1 expression in macrophages, and administration of the 11R-VIVIT peptide inhibitor of NFATs to mice also reduced neutrophil bacterial phagocytosis and renal resistance to UPEC. Conversely, synthetic Nod1 stimulating agonists given to CsA-treated mice significantly increased renal resistance to UPEC. Renal transplant recipients receiving CsA exhibited similar decrease in NOD1 expression and neutrophil phagocytosis of E. coli. The findings suggest that such mechanism of NFATc1-dependent inhibition of Nod1-mediated innate immune response together with the decrease in Tlr4-mediated production of chemoattractant chemokines caused by CsA may

  16. Cyclosporine A impairs nucleotide binding oligomerization domain (Nod1-mediated innate antibacterial renal defenses in mice and human transplant recipients.

    Directory of Open Access Journals (Sweden)

    Emilie Tourneur

    2013-01-01

    Full Text Available Acute pyelonephritis (APN, which is mainly caused by uropathogenic Escherichia coli (UPEC, is the most common bacterial complication in renal transplant recipients receiving immunosuppressive treatment. However, it remains unclear how immunosuppressive drugs, such as the calcineurin inhibitor cyclosporine A (CsA, decrease renal resistance to UPEC. Here, we investigated the effects of CsA in host defense against UPEC in an experimental model of APN. We show that CsA-treated mice exhibit impaired production of the chemoattractant chemokines CXCL2 and CXCL1, decreased intrarenal recruitment of neutrophils, and greater susceptibility to UPEC than vehicle-treated mice. Strikingly, renal expression of Toll-like receptor 4 (Tlr4 and nucleotide-binding oligomerization domain 1 (Nod1, neutrophil migration capacity, and phagocytic killing of E. coli were significantly reduced in CsA-treated mice. CsA inhibited lipopolysaccharide (LPS-induced, Tlr4-mediated production of CXCL2 by epithelial collecting duct cells. In addition, CsA markedly inhibited Nod1 expression in neutrophils, macrophages, and renal dendritic cells. CsA, acting through inhibition of the nuclear factor of activated T-cells (NFATs, also markedly downregulated Nod1 in neutrophils and macrophages. Silencing the NFATc1 isoform mRNA, similar to CsA, downregulated Nod1 expression in macrophages, and administration of the 11R-VIVIT peptide inhibitor of NFATs to mice also reduced neutrophil bacterial phagocytosis and renal resistance to UPEC. Conversely, synthetic Nod1 stimulating agonists given to CsA-treated mice significantly increased renal resistance to UPEC. Renal transplant recipients receiving CsA exhibited similar decrease in NOD1 expression and neutrophil phagocytosis of E. coli. The findings suggest that such mechanism of NFATc1-dependent inhibition of Nod1-mediated innate immune response together with the decrease in Tlr4-mediated production of chemoattractant chemokines caused by Cs

  17. Nucleotide-oligomerization-domain-2 affects commensal gut microbiota composition and intracerebral immunopathology in acute Toxoplasma gondii induced murine ileitis.

    Directory of Open Access Journals (Sweden)

    Markus M Heimesaat

    Full Text Available Within one week following peroral high dose infection with Toxoplasma (T. gondii, susceptible mice develop non-selflimiting acute ileitis due to an underlying Th1-type immunopathology. The role of the innate immune receptor nucleotide-oligomerization-domain-2 (NOD2 in mediating potential extra-intestinal inflammatory sequelae including the brain, however, has not been investigated so far.Following peroral infection with 100 cysts of T. gondii strain ME49, NOD2-/- mice displayed more severe ileitis and higher small intestinal parasitic loads as compared to wildtype (WT mice. However, systemic (i.e. splenic levels of pro-inflammatory cytokines such as TNF-α and IFN-γ were lower in NOD2-/- mice versus WT controls at day 7 p.i. Given that the immunopathological outcome might be influenced by the intestinal microbiota composition, which is shaped by NOD2, we performed a quantitative survey of main intestinal bacterial groups by 16S rRNA analysis. Interestingly, Bifidobacteria were virtually absent in NOD2-/- but not WT mice, whereas differences in remaining bacterial species were rather subtle. Interestingly, more distinct intestinal inflammation was accompanied by higher bacterial translocation rates to extra-intestinal tissue sites such as liver, spleen, and kidneys in T. gondii infected NOD2-/- mice. Strikingly, intracerebral inflammatory foci could be observed as early as seven days following T. gondii infection irrespective of the genotype of animals, whereas NOD2-/- mice exhibited higher intracerebral parasitic loads, higher F4/80 positive macrophage and microglia numbers as well as higher IFN-γ mRNA expression levels as compared to WT control animals.NOD2 signaling is involved in protection of mice from T. gondii induced acute ileitis. The parasite-induced Th1-type immunopathology at intestinal as well as extra-intestinal sites including the brain is modulated in a NOD2-dependent manner.

  18. Oligomeric proanthocyanidins protects A549 cells against H2O2-induced oxidative stress via the Nrf2-ARE pathway.

    Science.gov (United States)

    Sun, Chao; Jin, Weiguo; Shi, Hongcan

    2017-06-01

    Oxidative signaling and oxidative stress contribute to aging, cancer and diseases resulting from lung fibrosis. In this study, we explored the anti-oxidative potential of oligomeric proanthocyanidins (OPCs), natural flavonoid compounds. We examined the protective effects of OPCs against hydrogen peroxide (H2O2)-induced oxidative stress in non-small cell lung cancer cells (A549). We demonstrated that OPC markedly attenuated H2O2-induced A549 cell viability, as shown by by 3-[4,5-dimethylthiazol-2-yl)]-2,5-diphenyl-tetrazolium bromide (MTT) assay. At the same time, OPC inhibited H2O2-induced oxidative stress by significantly increasing the activities of superoxide dismutase, catalase and glutathione, and reducing the levels of reactive oxygen species (ROS) and malondialdehyde (MDA). Treatment of the A549 cells with OPC significantly promoted the nuclear translocation of NF-E2-related factor 2 (Nrf2) and significantly enhanced the expression of its target genes [heme oxygenase-1 (HO-1), NAD(P)H quinone dehydrogenase 1 (NQO1) and thioredoxin reductase 1 (TXNRD1)] with different fold change values at both the mRNA and protein level. The knockout of Nrf2 using CRISPR/Cas9 technology attenuated OPC-mediated ARE gene transcription, and almost abolished the OPC-mediated protective effects against H2O2-induced oxidative stress. On the whole, our study suggests that OPC plays an important role in controlling the antioxidant response of A549 cells via the Nrf2-ARE pathway.

  19. Cartilage oligomeric matrix protein (COMP) in rheumatoid arthritis and its correlation with sonographic knee cartilage thickness and disease activity.

    Science.gov (United States)

    Sakthiswary, Rajalingham; Rajalingam, Shamala; Hussein, Heselynn; Sridharan, Radhika; Asrul, Abdul Wahab

    2017-12-01

    The aim of the study is to investigate the correlation of serum cartilage oligomeric matrix protein (COMP) levels with articular cartilage damage based on sonographic knee cartilage thickness (KCT) and disease activity in rheumatoid arthritis (RA). A total of 61 RA patients and 27 healthy controls were recruited in this study. Serum samples were obtained from all subjects to determine the serum COMP levels. All subjects had bilateral ultrasound scan of their knees. The KCT was based on the mean of measurements at three sites: the medial condyle, lateral condyle and intercondylar notch. Besides, the RA patients were assessed for their disease activity based on 28-joint-based Disease Activity Score (DAS 28). Serum COMP concentrations were significantly elevated in the RA patients compared to the controls (p = 0.001). The serum COMP levels had an inverse relationship with bilateral KCT in RA subjects and the healthy controls. COMP correlated significantly with disease activity based on DAS 28 (r = 0.299, p = 0.010), disease duration (r = 0.439, p = correlation between serum COMP and DAS 28 scores was comparable to the traditional markers of inflammation: erythrocyte sedimentation rate (ESR) (r = 0.372, p = 0.003) and C-reactive protein (CRP) (r = 0.305, p = 0.017). The serum COMP is a promising biomarker in RA which reflects disease activity and damage to the articular cartilage.

  20. Insights into Basal Signaling Regulation, Oligomerization, and Structural Organization of the Human G-Protein Coupled Receptor 83.

    Directory of Open Access Journals (Sweden)

    Anne Müller

    Full Text Available The murine G-protein coupled receptor 83 (mGPR83 is expressed in the hypothalamus and was previously suggested to be involved in the regulation of metabolism. The neuropeptide PEN has been recently identified as a potent GPR83 ligand. Moreover, GPR83 constitutes functionally relevant hetero-oligomers with other G-protein coupled receptors (GPCR such as the ghrelin receptor (GHSR or GPR171. Previous deletion studies also revealed that the long N-terminal extracellular receptor domain (eNDo of mGPR83 may act as an intra-molecular ligand, which participates in the regulation of basal signaling activity, which is a key feature of GPCR function. Here, we investigated particular amino acids at the eNDo of human GPR83 (hGPR83 by side-directed mutagenesis to identify determinants of the internal ligand. These studies were accompanied by structure homology modeling to combine functional insights with structural information. The capacity for hetero-oligomer formation of hGPR83 with diverse family A GPCRs such as the melanocortin-4 receptor (MC4R was also investigated, with a specific emphasis on the impact of the eNDo on oligomerization and basal signaling properties. Finally, we demonstrate that hGPR83 exhibits an unusual basal signaling for different effectors, which also supports signaling promiscuity. hGPR83 interacts with a variety of hypothalamic GPCRs such as the MC4R or GHSR. These interactions are not dependent on the ectodomain and most likely occur at interfaces constituted in the transmembrane regions. Moreover, several amino acids at the transition between the eNDo and transmembrane helix 1 were identified, where mutations lead also to biased basal signaling modulation.

  1. Oligomeric proanthocyanidins (OPCs) modulating radiation-induced oxidative stress on functional and structural performance of eye in male rats

    International Nuclear Information System (INIS)

    Said, U.Z.; Soliman, S.M.; Azab, Kh.Sh.; El-Tahawy, N.A.

    2005-01-01

    Eye oxidative stress may play a major role in the etiology and pathogenesis of eye disorders such as macular degeneration and photic injury of retinal degeneration that lead to vision loss. Proanthocyanidins derived from pine bark and from grape seeds have various anti pathophysiological functions. This study was performed to evaluate the role of oligomeric proanthocyanidins (OPCs) on the radiation-induced changes in rat eye tissues. OPCs were supplemented to rats (100 mg /kg body weight/ day) for 14 successive days before and 7 successive days after exposure to 7 Gy (single dose) of whole body gamma irradiation. The results revealed radiation-induced depletion in the activities of eye endogenous antioxidant enzymes and rise in pro-oxidant levels. Supplementation of OPCs pre- and post-irradiation has significantly reduced the levels of thiobarbituric acid reactive substances, xanthine oxidase, and significantly ameliorated the activities of xanthine dehydrogenase and reactive oxygen scavenging enzymes such as superoxide dismutase, glutathione peroxidase and catalase activities in eye tissues. OPCs significantly ameliorated the radiation-induced changes in levels of insulin and glucose in the serum. The oxidative stress induced cellular damage as indicated by retardation in the responses of eye to photo stimulation as well as histopathological changes in the eye tissues. Severe intra-retinal hemorrhages, cornea swelling, disruption of photoreceptor layer of the retina and epithelial necrosis were seen. The eye tissues of rats that received OPCs supplement showed significant less severe histological damage and remarkable improvement in photo stimulation responses when compared to irradiated rats on the 7 T h and 21 s t days after exposure to gamma irradiation. According to the results obtained, it could be concluded that OPCs might protect the eye tissues from the oxidative stress possibly by virtue of its anti oxidative activity through augmentation of antioxidant

  2. Tempol modulates changes in xenobiotic permeability and occludin oligomeric assemblies at the blood-brain barrier during inflammatory pain

    Science.gov (United States)

    Lochhead, Jeffrey J.; McCaffrey, Gwen; Sanchez-Covarrubias, Lucy; Finch, Jessica D.; DeMarco, Kristin M.; Quigley, Colleen E.; Davis, Thomas P.

    2012-01-01

    Our laboratory has shown that λ-carrageenan-induced peripheral inflammatory pain (CIP) can alter tight junction (TJ) protein expression and/or assembly leading to changes in blood-brain barrier xenobiotic permeability. However, the role of reactive oxygen species (ROS) and subsequent oxidative stress during CIP is unknown. ROS (i.e., superoxide) are known to cause cellular damage in response to pain/inflammation. Therefore, we examined oxidative stress-associated effects at the blood-brain barrier (BBB) in CIP rats. During CIP, increased staining of nitrosylated proteins was detected in hind paw tissue and enhanced presence of protein adducts containing 3-nitrotyrosine occurred at two molecular weights (i.e., 85 and 44 kDa) in brain microvessels. Tempol, a pharmacological ROS scavenger, attenuated formation of 3-nitrotyrosine-containing proteins in both the hind paw and in brain microvessels when administered 10 min before footpad injection of λ-carrageenan. Similarly, CIP increased 4-hydroxynoneal staining in brain microvessels and this effect was reduced by tempol. Brain permeability to [14C]sucrose and [3H]codeine was increased, and oligomeric assemblies of occludin, a critical TJ protein, were altered after 3 h CIP. Tempol attenuated both [14C]sucrose and [3H]codeine brain uptake as well as protected occludin oligomers from disruption in CIP animals, suggesting that ROS production/oxidative stress is involved in modulating BBB functional integrity during pain/inflammation. Interestingly, tempol administration reduced codeine analgesia in CIP animals, indicating that oxidative stress during pain/inflammation may affect opioid delivery to the brain and subsequent efficacy. Taken together, our data show for the first time that ROS pharmacological scavenging is a viable approach for maintaining BBB integrity and controlling central nervous system drug delivery during acute inflammatory pain. PMID:22081706

  3. Activation of nucleotide oligomerization domain 2 (NOD2 by human cytomegalovirus initiates innate immune responses and restricts virus replication.

    Directory of Open Access Journals (Sweden)

    Arun Kapoor

    Full Text Available Nucleotide-binding oligomerization domain 2 (NOD2 is an important innate immune sensor of bacterial pathogens. Its induction results in activation of the classic NF-κB pathway and alternative pathways including type I IFN and autophagy. Although the importance of NOD2 in recognizing RNA viruses has recently been identified, its role in sensing DNA viruses has not been studied. We report that infection with human cytomegalovirus (HCMV results in significant induction of NOD2 expression, beginning as early as 2 hours post infection and increasing steadily 24 hours post infection and afterwards. Infection with human herpesvirus 1 and 2 does not induce NOD2 expression. While the HCMV-encoded glycoprotein B is not required for NOD2 induction, a replication competent virion is necessary. Lentivirus-based NOD2 knockdown in human foreskin fibroblasts (HFFs and U373 glioma cells leads to enhanced HCMV replication along with decreased levels of interferon beta (IFN-β and the pro-inflammatory cytokine, IL8. NOD2 induction in HCMV-infected cells activates downstream NF-κB and interferon pathways supported by reduced nuclear localization of NF-κB and pIRF3 in NOD2 knockdown HFFs. Stable overexpression of NOD2 in HFFs restricts HCMV replication in association with increased levels of IFN-β and IL8. Similarly, transient overexpression of NOD2 in U373 cells or its downstream kinase, RIPK2, results in decreased HCMV replication and enhanced cytokine responses. However, overexpression of a mutant NOD2, 3020insC, associated with severe Crohn's disease, results in enhanced HCMV replication and decreased levels of IFN-β in U373 cells. These results show for the first time that NOD2 plays a significant role in HCMV replication and may provide a model for studies of HCMV recognition by the host cell and HCMV colitis in Crohn's disease.

  4. Crystal engineering of giant molecules based on perylene diimide conjugated polyhedral oligomeric silsesquioxane nano-atom

    Science.gov (United States)

    Ren, He

    Molecular architectures and topologies are found contributing to the formation of supramolecular structures of giant molecules. Dr. Cheng's research group developed a diverse of giant molecules via precisely controlled chemistry synthetic routes. These giant molecules can be categorized into several different families, namely giant surfactants, giant shape amphiphiles and giant polyhedron. By analyzing the hierarchical structures of these carefully designed and precisely synthesized giant molecules, the structural factors which affect, or even dominates, in some cases, the formation of supramolecular structures are revealed in these intensive researches. The results will further contribute to the understanding of dependence of supramolecular structures on molecular designs as well as molecular topology, and providing a practical solution to the scaling up of microscopic molecular functionalities to macroscopic material properties. Molecular Nano Particles (MNPs), including fullerene (C60), POSS, Polyoxometalate (POM) and proteins etc., is defined and applied as a specific type of building blocks in the design and synthesis of giant molecules. The persistence in shape and symmetry is considered as one of the major properties of MNPs. This persistence will support the construction of giant molecules for further supramolecular structures' study by introducing specific shapes, or precisely located side groups which will facilitate self-assembling behaviors with pre-programmed secondary interactions. Dictating material physical properties by its chemical composition is an attractive yet currently failed approach in the study of materials. However, the pursuit of determining material properties by microscopic molecular level properties is never seized, and found its solution when the idea of crystal engineering is raised: should each atom in the material is located exactly where it is designed to be and is properly bonded, the property of the material is hence determined

  5. Strong ideal convergence in probabilistic metric spaces

    Indian Academy of Sciences (India)

    sequence and strong ideal Cauchy sequence in a probabilistic metric (PM) space endowed with the strong topology, and ... also important applications in nonlinear analysis [2]. The theory was brought to ..... for each t > 0 since each set on the right-hand side of the relation (3.1) belongs to I. Thus, by Definition 2.11 and the ...

  6. Large N baryons, strong coupling theory, quarks

    International Nuclear Information System (INIS)

    Sakita, B.

    1984-01-01

    It is shown that in QCD the large N limit is the same as the static strong coupling limit. By using the static strong coupling techniques some of the results of large N baryons are derived. The results are consistent with the large N SU(6) static quark model. (author)

  7. Optimization of strong and weak coordinates

    NARCIS (Netherlands)

    Swart, M.; Bickelhaupt, F.M.

    2006-01-01

    We present a new scheme for the geometry optimization of equilibrium and transition state structures that can be used for both strong and weak coordinates. We use a screening function that depends on atom-pair distances to differentiate strong coordinates from weak coordinates. This differentiation

  8. Strong decays of nucleon and delta resonances

    International Nuclear Information System (INIS)

    Bijker, R.; Leviatan, A.

    1996-01-01

    We study the strong couplings of the nucleon and delta resonances in a collective model. In the ensuing algebraic treatment we derive closed expressions for decay widths which are used to analyze the experimental data for strong decays into the pion and eta channels. (Author)

  9. Theoretical studies of strongly correlated fermions

    Energy Technology Data Exchange (ETDEWEB)

    Logan, D. [Institut Max von Laue - Paul Langevin (ILL), 38 - Grenoble (France)

    1997-04-01

    Strongly correlated fermions are investigated. An understanding of strongly correlated fermions underpins a diverse range of phenomena such as metal-insulator transitions, high-temperature superconductivity, magnetic impurity problems and the properties of heavy-fermion systems, in all of which local moments play an important role. (author).

  10. Seismic switch for strong motion measurement

    Science.gov (United States)

    Harben, P.E.; Rodgers, P.W.; Ewert, D.W.

    1995-05-30

    A seismic switching device is described that has an input signal from an existing microseismic station seismometer and a signal from a strong motion measuring instrument. The seismic switch monitors the signal level of the strong motion instrument and passes the seismometer signal to the station data telemetry and recording systems. When the strong motion instrument signal level exceeds a user set threshold level, the seismometer signal is switched out and the strong motion signal is passed to the telemetry system. The amount of time the strong motion signal is passed before switching back to the seismometer signal is user controlled between 1 and 15 seconds. If the threshold level is exceeded during a switch time period, the length of time is extended from that instant by one user set time period. 11 figs.

  11. Association behavior of native beta-lactoglobulin

    DEFF Research Database (Denmark)

    Verheul, M.; Pedersen, J.S.; Roefs, S.P.F.M.

    1999-01-01

    The association behavior of beta-lactoglobulin has been studied by small-angle neutron scattering as a function of protein concentration, temperature, pH, and NaCl concentration of the solution. By indirect Fourier transformation of the spectra, pair-distance distribution functions for the various...... samples were obtained. These functions provided information on the maximum size, the weight-averaged molecular mass, and the z-averaged radius of gyration oo the the beta-lactoglobulin particles. Al room temperature and pH values below 4 and above IZ the protein consists predominantly of monomers...... and dimers, consistent with literature. In these pH regimes the formation of dimers is favored upon increasing ionic strength and decreasing protein charge (pH values closer to the isoelectric point of the protein). Around pH 4.7 larger oligomeric structures ape formed enhanced by a decrease in temperature...

  12. Strong saturable absorption of black titanium oxide nanoparticle films

    Science.gov (United States)

    Zhang, Rong-Fang; Guo, Deng-Zhu; Zhang, Geng-Min

    2017-12-01

    Nonlinear optical materials with strong saturable absorption (SA) properties play an essential role in passive mode-locking generation of ultrafast lasers. Here we report black TiO2-x nanoparticles are promising candidate for such an application. Black TiO2-x nanoparticles are synthesized by using cathodic plasma electrolysis, and nanoparticle films are deposited on optical glass plates via natural sedimentation and post annealing. Characterization of the samples with TEM, SEM, XRD and XPS reveal that nanoparticles have diameters of 8-70 nm, and are in polycrystalline structure and co-existence of anatase, rutile and abundant oxygen-deficient phases. Optical transmittance and reflectance measurements with a UV/VIS/NIR spectrophotometer evidence an excellent wide-spectral optical absorption property. The nonlinear optical properties of the samples were measured by using open-aperture Z-scan technique with picosecond 532-nm laser, and verified by direct transmission measurements using nanosecond 1064-nm laser. Strong SA behavior was detected, and the nonlinear absorption coefficient is as high as β = - 4.9 × 10-8 m/W, at least two orders larger than most previous reports on ordinary TiO2. The strong SA behaviors are ascribed to the existence of plenty surface states and defect states within bandgap, and the relaxation rates of electrons from upper energy levels to lower ones are much slower than excitation rates.

  13. Hydrolyzable Tannins of Tamaricaceous Plants. 7.1 Structures and Cytotoxic Properties of Oligomeric Ellagitannins from Leaves of Tamarix nilotica and Cultured Tissues of Tamarix tetrandra.

    Science.gov (United States)

    Orabi, Mohamed A A; Taniguchi, Shoko; Sakagami, Hiroshi; Yoshimura, Morio; Amakura, Yoshiaki; Hatano, Tsutomu

    2016-04-22

    Partially unacylated new oligomeric hydrolyzable tannins, nilotinin T2 (1, trimer) and nilotinin Q1 (2, tetramer), together with four known trimers, nilotinin T1 (3) and hirtellins T1-T3 (4-6), and a dimer, tamarixinin B (7), were isolated from the aqueous acetone extracts of leaves of Tamarix nilotica. Among them, the new trimer 1 and the known trimers 4 and 6, in addition to the partially unacylated new trimer nilotinin T3 (8), the known dimers nilotinin D3 (9) and tamarixinin C (10), and the monomer tellimagrandin I (11), were isolated from the cultured shoots of Tamarix tetrandra. The structures of the new hydrolyzable tannins were established by chromatographic analyses and extensive 1D and 2D NMR, HRESI-TOFMS, and ECD spectroscopic experiments. Among the new oligomeric tannins, the particular unacylated position of a glucose core is attributed to a possible biosynthetic route. Isolation of the same oligomeric tannins from cultured shoots of T. tetrandra emphasizes the unique biogenetic ability of the obtained cultures on production of the structurally and biologically characteristic tamaricaceous tannins commonly produced by the intact Tamarix plants. Additionally, tannins obtained in the present study together with gemin D (12) and 1,3-di-O-galloyl-4,6-O-(aS)-hexahydroxydiphenoyl-β-d-glucose (13), from our previous investigation of the leaves of T. nilotica, exhibited variable tumor-specific cytotoxic effects. The ellagitannin trimers 4, 6, and 8 and the dimer 9 exerted predominant tumor-selective cytotoxic effects with high specificity toward human promyelocytic leukemia cells.

  14. Aqueous phase oligomerization of α,β-unsaturated carbonyls and acids investigated using ion mobility spectrometry coupled to mass spectrometry (IMS-MS)

    Science.gov (United States)

    Renard, Pascal; Tlili, Sabrine; Ravier, Sylvain; Quivet, Etienne; Monod, Anne

    2016-04-01

    One of the current essential issues to unravel our ability to forecast future climate change and air quality, implies a better understanding of natural processes leading to secondary organic aerosol (SOA) formation, and in particular the formation and fate of oligomers. The difficulty in characterizing macromolecules is to discern between large oxygenated molecules from series of oligomers containing repeated small monomers of diverse structures. In the present study, taking advantage from previously established radical vinyl oligomerization of methyl vinylketone (MVK) in the aqueous phase, where relatively simple oligomers containing up to 14 monomers were observed, we have investigated the same reactivity on several other unsaturated water soluble organic compounds (UWSOCs) and on a few mixtures of these precursor compounds. The technique used to characterize the formed oligomers was a traveling wave ion mobility spectrometry coupled to a hybrid quadrupole - time of flight mass spectrometer (IMS-MS) fitted with an electrospray source and ultra-high performance liquid chromatography (UPLC). The technique allows for an additional separation, especially for large ions, containing long carbon chains. We have shown the efficiency of the IMS-mass spectrometry technique to detect oligomers derived from MVK photooxidation in the aqueous phase. The results were then compared to other oligomers, derived from ten other individual biogenic UWSOCs. The technique allowed distinguishing between different oligomers arising from different precursors. It also clearly showed that compounds bearing a non-conjugated unsaturation did not provide oligomerization. Finally, it was shown that the IMS-mass spectrometry technique, applied to mixtures of unsaturated conjugated precursors, exhibited the ability of these precursors to co-oligomerize, i.e. forming only one complex oligomer system bearing monomers of different structures. The results are discussed in terms of atmospheric

  15. Structure-based design of a disulfide-linked oligomeric form of the simian virus 40 (SV40) large T antigen DNA-binding domain

    International Nuclear Information System (INIS)

    Meinke, Gretchen; Phelan, Paul; Fradet-Turcotte, Amélie; Archambault, Jacques; Bullock, Peter A.

    2011-01-01

    With the aim of forming the ‘lock-washer’ conformation of the origin-binding domain of SV40 large T antigen in solution, using structure-based analysis an intermolecular disulfide bridge was engineered into the origin-binding domain to generate higher order oligomers in solution. The 1.7 Å resolution structure shows that the mutant forms a spiral in the crystal and has the de novo disulfide bond at the protein interface, although structural rearrangements at the interface are observed relative to the wild type. The modular multifunctional protein large T antigen (T-ag) from simian virus 40 orchestrates many of the events needed for replication of the viral double-stranded DNA genome. This protein assembles into single and double hexamers on specific DNA sequences located at the origin of replication. This complicated process begins when the origin-binding domain of large T antigen (T-ag ODB) binds the GAGGC sequences in the central region (site II) of the viral origin of replication. While many of the functions of purified T-ag OBD can be studied in isolation, it is primarily monomeric in solution and cannot assemble into hexamers. To overcome this limitation, the possibility of engineering intermolecular disulfide bonds in the origin-binding domain which could oligomerize in solution was investigated. A recent crystal structure of the wild-type T-ag OBD showed that this domain forms a left-handed spiral in the crystal with six subunits per turn. Therefore, we analyzed the protein interface of this structure and identified two residues that could potentially support an intermolecular disulfide bond if changed to cysteines. SDS–PAGE analysis established that the mutant T-ag OBD formed higher oligomeric products in a redox-dependent manner. In addition, the 1.7 Å resolution crystal structure of the engineered disulfide-linked T-ag OBD is reported, which establishes that oligomerization took place in the expected manner

  16. Insight into the template effect of vesicles on the laccase-catalyzed oligomerization of N-phenyl-1,4-phenylenediamine from Raman spectroscopy and cyclic voltammetry measurements

    Science.gov (United States)

    Ležaić, Aleksandra Janoševic; Luginbühl, Sandra; Bajuk-Bogdanović, Danica; Pašti, Igor; Kissner, Reinhard; Rakvin, Boris; Walde, Peter; Ćirić-Marjanović, Gordana

    2016-08-01

    We report about the first Raman spectroscopy study of a vesicle-assisted enzyme-catalyzed oligomerization reaction. The aniline dimer N-phenyl-1,4-phenylenediamine (= p-aminodiphenylamine, PADPA) was oxidized and oligomerized with Trametes versicolor laccase and dissolved O2 in the presence of sodium bis(2-ethylhexyl)sulfosuccinate (AOT) vesicles (80-100 nm diameter) as templates. The conversion of PADPA into oligomeric products, poly(PADPA), was monitored during the reaction by in situ Raman spectroscopy. The results obtained are compared with UV/vis/NIR and EPR measurements. All three complementary methods indicate that at least some of the poly(PADPA) products, formed in the presence of AOT vesicles, resemble the conductive emeraldine salt form of polyaniline (PANI-ES). The Raman measurements also show that structural units different from those of “ordinary” PANI-ES are present too. Without vesicles PANI-ES-like products are not obtained. For the first time, the as-prepared stable poly(PADPA)-AOT vesicle suspension was used directly to coat electrodes (without product isolation) for investigating redox activities of poly(PADPA) by cyclic voltammetry (CV). CV showed that poly(PADPA) produced with vesicles is redox active not only at pH 1.1-as expected for PANI-ES-but also at pH 6.0, unlike PANI-ES and poly(PADPA) synthesized without vesicles. This extended pH range of the redox activity of poly(PADPA) is important for applications.

  17. A Free Energy Barrier Caused by the Refolding of an Oligomeric Intermediate Controls the Lag Time of Amyloid Formation by hIAPP.

    Science.gov (United States)

    Serrano, Arnaldo L; Lomont, Justin P; Tu, Ling-Hsien; Raleigh, Daniel P; Zanni, Martin T

    2017-11-22

    Transiently populated oligomers formed en route to amyloid fibrils may constitute the most toxic aggregates associated with many amyloid-associated diseases. Most nucleation theories used to describe amyloid aggregation predict low oligomer concentrations and do not take into account free energy costs that may be associated with structural rearrangements between the oligomer and fiber states. We have used isotope labeling and two-dimensional infrared spectroscopy to spectrally resolve an oligomeric intermediate during the aggregation of the human islet amyloid protein (hIAPP or amylin), the protein associated with type II diabetes. A structural rearrangement includes the F 23 G 24 A 25 I 26 L 27 region of hIAPP, which starts from a random coil structure, evolves into ordered β-sheet oligomers containing at least 5 strands, and then partially disorders in the fibril structure. The supercritical concentration is measured to be between 150 and 250 μM, which is the thermodynamic parameter that sets the free energy of the oligomers. A 3-state kinetic model fits the experimental data, but only if it includes a concentration independent free energy barrier >3 kcal/mol that represents the free energy cost of refolding the oligomeric intermediate into the structure of the amyloid fibril; i.e., "oligomer activation" is required. The barrier creates a transition state in the free energy landscape that slows fibril formation and creates a stable population of oligomers during the lag phase, even at concentrations below the supercritical concentration. Largely missing in current kinetic models is a link between structure and kinetics. Our experiments and modeling provide evidence that protein structural rearrangements during aggregation impact the populations and kinetics of toxic oligomeric species.

  18. The Role of Co-Activation and Ligand Functionalization in Neutral Methallyl Nickel(II) Catalysts for Ethylene Oligomerization and Polymerization.

    Science.gov (United States)

    Ortega, Daniela E; Cortés-Arriagada, Diego; Trofymchuk, Oleksandra S; Yepes, Diana; Gutiérrez-Oliva, Soledad; Rojas, René S; Toro-Labbé, Alejandro

    2017-07-26

    A detailed quantum chemical study that analyzed the mechanism of ethylene oligomerization and polymerization by means of a family of four neutral methallyl Ni II catalysts is presented. The role of the boron co-activators, BF 3 and B(C 6 F 5 ) 3 , and the position of ligand functionalization (ortho or para position of the N-arylcyano moiety of the catalysts) were investigated to explain the chain length of the obtained polymers. The chain initialization proceeded with higher activation barriers for the ortho-functionalized complexes (≈19 kcal mol -1 ) than the para-substituted isomers (17-18 kcal mol -1 ). Two main pathways were revealed for the chain propagation: The first pathway was favored when using the B(C 6 F 5 ) 3 co-activated catalyst, and it produced long-chain polymers. A second pathway led to the β-hydrogen complexes, which resulted in chain oligomerization; this pathway was preferred when the BF 3 co-activated catalysts were used. Otherwise, the termination of longer chains occurred via a stable hydride intermediate, which was formed with an energy barrier of about 14 kcal mol -1 for the B(C 6 F 5 ) 3 co-activated catalysts. Significant new insights were made into the reaction mechanism, whereby neutral methallyl Ni II catalysts act in oligomerization and polymerization processes. Specifically, the role of co-activation and ligand functionalization, which are key information for the further design of related catalysts, were revealed. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. De novo polymerase activity and oligomerization of hepatitis C virus RNA-dependent RNA-polymerases from genotypes 1 to 5.

    Directory of Open Access Journals (Sweden)

    Pilar Clemente-Casares

    Full Text Available Hepatitis C virus (HCV shows a great geographical diversity reflected in the high number of circulating genotypes and subtypes. The response to HCV treatment is genotype specific, with the predominant genotype 1 showing the lowest rate of sustained virological response. Virally encoded enzymes are candidate targets for intervention. In particular, promising antiviral molecules are being developed to target the viral NS3/4A protease and NS5B polymerase. Most of the studies with the NS5B polymerase have been done with genotypes 1b and 2a, whilst information about other genotypes is scarce. Here, we have characterized the de novo activity of NS5B from genotypes 1 to 5, with emphasis on conditions for optimum activity and kinetic constants. Polymerase cooperativity was determined by calculating the Hill coefficient and oligomerization through a new FRET-based method. The V(max/K(m ratios were statistically different between genotype 1 and the other genotypes (p<0.001, mainly due to differences in V(max values, but differences in the Hill coefficient and NS5B oligomerization were noted. Analysis of sequence changes among the studied polymerases and crystal structures show the αF helix as a structural component probably involved in NS5B-NS5B interactions. The viability of the interaction of αF and αT helixes was confirmed by docking studies and calculation of electrostatic surface potentials for genotype 1 and point mutants corresponding to mutations from different genotypes. Results presented in this study reveal the existence of genotypic differences in NS5B de novo activity and oligomerization. Furthermore, these results allow us to define two regions, one consisting of residues Glu128, Asp129, and Glu248, and the other consisting of residues of αT helix possibly involved in NS5B-NS5B interactions.

  20. Strong and superstrong pulsed magnetic fields generation

    CERN Document Server

    Shneerson, German A; Krivosheev, Sergey I

    2014-01-01

    Strong pulsed magnetic fields are important for several fields in physics and engineering, such as power generation and accelerator facilities. Basic aspects of the generation of strong and superstrong pulsed magnetic fields technique are given, including the physics and hydrodynamics of the conductors interacting with the field as well as an account of the significant progress in generation of strong magnetic fields using the magnetic accumulation technique. Results of computer simulations as well as a survey of available field technology are completing the volume.

  1. Impurity screening in strongly coupled plasma systems

    CERN Document Server

    Kyrkos, S

    2003-01-01

    We present an overview of the problem of screening of an impurity in a strongly coupled one-component plasma within the framework of the linear response (LR) theory. We consider 3D, 2D and quasi-2D layered systems. For a strongly coupled plasma the LR can be determined by way of the known S(k) structure functions. In general, an oscillating screening potential with local overscreening and antiscreening regions emerges. In the case of the bilayer, this phenomenon becomes global, as overscreening develops in the layer of the impurity and antiscreening in the adjacent layer. We comment on the limitations of the LR theory in the strong coupling situation.

  2. The lambda sigma calculus and strong normalization

    DEFF Research Database (Denmark)

    Schack-Nielsen, Anders; Schürmann, Carsten

    Explicit substitution calculi can be classified into several dis- tinct categories depending on whether they are confluent, meta-confluent, strong normalization preserving, strongly normalizing, simulating, fully compositional, and/or local. In this paper we present a variant of the λσ-calculus......, which satisfies all seven conditions. In particular, we show how to circumvent Mellies counter-example to strong normalization by a slight restriction of the congruence rules. The calculus is implemented as the core data structure of the Celf logical framework. All meta-theoretic aspects of this work...

  3. [Ni0]-catalyzed Co-oligomerization of 1,3-butadiene and ethylene: a theoretical mechanistic investigation of competing routes for generation of linear and cyclic C10-olefins.

    Science.gov (United States)

    Tobisch, Sven

    2004-01-14

    A detailed theoretical investigation of the mechanism for the [Ni(0)]-catalyzed co-oligomerization of 1,3-butadiene and ethylene to afford linear and cyclic C(10)-olefins is presented. Crucial elementary processes have been carefully explored for a tentative catalytic cycle, employing a gradient-corrected density functional theory (DFT) method. The favorable route for oxidative coupling starts from the prevalent [Ni(0)(eta(2)-butadiene)(2)(ethylene)] form of the active catalyst through oxidative coupling between the two eta(2)-butadienes. The initial eta(3),eta(1)(C(1))-octadienediyl-Ni(II) product is the active precursor for ethylene insertion, which preferably takes place into the syn-eta(3)-allyl-Ni(II) bond of the prevalent eta(3)-syn,eta(1)(C(1)),Delta-cis isomer. The insertion is driven by a strong thermodynamic force, giving rise entirely to eta(3),eta(1),Delta-trans-decatrienyl-Ni(II) forms, with the eta(3)-anti,eta(1),Delta-trans isomer almost exclusively generated. Occurrence of allyl,eta(1),Delta-cis isomers, however, is precluded on both kinetic and thermodynamic grounds, thereby rationalizing the observation that cis-DT and cis,cis-CDD are never formed. Linear and cyclic C(10)-olefins are generated in a highly stereoselective fashion, with trans-DT and cis,trans-CDD as the only isomers, along competing routes of stepwise transition-metal-assisted H-transfer (DT) and reductive CC elimination under ring closure (CDD), respectively, that start from the prevalent eta(3)-anti,eta(1),Delta-trans-decatrienyl-Ni(II) species. The role of allylic conversion in the octadienediyl-Ni(II) and decatrienyl-Ni(II) complexes has been analyzed. As a result of the detailed exploration of all important elementary steps, a theoretically verified, refined catalytic cycle is proposed and the regulation of the selectivity for formation of linear and cyclic C(10)-olefins is elucidated.

  4. Strong Coupling Corrections in Quantum Thermodynamics

    Science.gov (United States)

    Perarnau-Llobet, M.; Wilming, H.; Riera, A.; Gallego, R.; Eisert, J.

    2018-03-01

    Quantum systems strongly coupled to many-body systems equilibrate to the reduced state of a global thermal state, deviating from the local thermal state of the system as it occurs in the weak-coupling limit. Taking this insight as a starting point, we study the thermodynamics of systems strongly coupled to thermal baths. First, we provide strong-coupling corrections to the second law applicable to general systems in three of its different readings: As a statement of maximal extractable work, on heat dissipation, and bound to the Carnot efficiency. These corrections become relevant for small quantum systems and vanish in first order in the interaction strength. We then move to the question of power of heat engines, obtaining a bound on the power enhancement due to strong coupling. Our results are exemplified on the paradigmatic non-Markovian quantum Brownian motion.

  5. Finding quantum effects in strong classical potentials

    Science.gov (United States)

    Hegelich, B. Manuel; Labun, Lance; Labun, Ou Z.

    2017-06-01

    The long-standing challenge to describing charged particle dynamics in strong classical electromagnetic fields is how to incorporate classical radiation, classical radiation reaction and quantized photon emission into a consistent unified framework. The current, semiclassical methods to describe the dynamics of quantum particles in strong classical fields also provide the theoretical framework for fundamental questions in gravity and hadron-hadron collisions, including Hawking radiation, cosmological particle production and thermalization of particles created in heavy-ion collisions. However, as we show, these methods break down for highly relativistic particles propagating in strong fields. They must therefore be improved and adapted for the description of laser-plasma experiments that typically involve the acceleration of electrons. Theory developed from quantum electrodynamics, together with dedicated experimental efforts, offer the best controllable context to establish a robust, experimentally validated foundation for the fundamental theory of quantum effects in strong classical potentials.

  6. The Charm and Beauty of Strong Interactions

    Science.gov (United States)

    El-Bennich, Bruno

    2018-01-01

    We briefly review common features and overlapping issues in hadron and flavor physics focussing on continuum QCD approaches to heavy bound states, their mass spectrum and weak decay constants in different strong interaction models.

  7. Atomica ionization by strong coherent radiation

    International Nuclear Information System (INIS)

    Brandi, H.S.; Davidovich, L.

    1979-07-01

    The relation among the three most frequently used non-perturbative methods proposed to study the ionization of atoms by strong electromagnetic fields is established. Their range of validity is also determined. (Author) [pt

  8. Perturbation of an exact strong gravity solution

    International Nuclear Information System (INIS)

    Baran, S.A.

    1982-10-01

    Perturbations of an exact strong gravity solution are investigated. It is shown, by using the new multipole expansions previously presented, that this exact and static spherically symmetric solution is stable under odd parity perturbations. (author)

  9. Strong-force theorists scoop Noble Prize

    CERN Multimedia

    Durrani, Matin

    2004-01-01

    Three US theorists have shared the 2004 Nobel Prize in Physics "for the discovery of asymptotic freedom in the theory of the strong interaction". Their theoretical work explains why quarks behave almost as free particles at high energies (½ page)

  10. Calculating hadronic properties in strong QCD

    International Nuclear Information System (INIS)

    Pennington, M.R.

    1996-01-01

    This talk gives a brief review of the progress that has been made in calculating the properties of hadrons in strong QCD. In keeping with this meeting I will concentrate on those properties that can be studied with electromagnetic probes. Though perturbative QCD is highly successful, it only applies in a limited kinematic regime, where hard scattering occur, and the quarks move in the interaction region as if they are free, pointlike objects. However, the bulk of strong interactions are governed by the long distance regime, where the strong interaction is strong. It is this regime of length scales of the order of a Fermi, that determines the spectrum of light hadrons and their properties. The calculation of these properties requires an understanding of non-perturbative QCD, of confinement and chiral symmetry breaking. (author)

  11. Rydberg-atom formation in strongly correlated ultracold plasmas

    International Nuclear Information System (INIS)

    Bannasch, G.; Pohl, T.

    2011-01-01

    In plasmas at very low temperatures, the formation of neutral atoms is dominated by collisional three-body recombination, owing to the strong ∼T -9/2 scaling of the corresponding recombination rate with the electron temperature T. While this law is well established at high temperatures, the unphysical divergence as T→0 clearly suggests a breakdown in the low-temperature regime. Here, we present a combined molecular dynamics Monte Carlo study of electron-ion recombination over a wide range of temperatures and densities. Our results reproduce the known behavior of the recombination rate at high temperatures, but reveal significant deviations with decreasing temperature. We discuss the fate of the kinetic bottleneck and resolve the divergence problem as the plasma enters the ultracold, strongly coupled domain.

  12. Jet quenching parameters in strongly coupled nonconformal gauge theories

    International Nuclear Information System (INIS)

    Buchel, Alex

    2006-01-01

    Recently Liu, Rajagopal, and Wiedemann (LRW) [H. Liu, K. Rajagopal, and U. A. Wiedemann, hep-ph/0605178.] proposed a first principle, nonperturbative quantum field theoretic definition of 'jet quenching parameter' q-circumflex used in models of medium-induced radiative parton energy loss in nucleus-nucleus collisions at RHIC. Relating q-circumflex to a short-distance behavior of a certain lightlike Wilson loop, they used gauge theory-string theory correspondence to evaluate q-circumflex for the strongly coupled N=4 SU(N c ) gauge theory plasma. We generalize analysis of LRW to strongly coupled nonconformal gauge theory plasma. We find that a jet quenching parameter is gauge theory specific (not universal). Furthermore, it appears its value increases as the number of effective adjoint degrees of freedom of a gauge theory plasma increases

  13. Building strong brands – does it matter?

    OpenAIRE

    Aure, Kristin Gaaseide; Nervik, Kristine Dybvik

    2014-01-01

    Brand equity has proven, through several decades of research, to be a primary source of competitive advantage and future earnings (Yoo & Donthu, 2001). Building strong brands has therefore become a priority for many organizations, with the presumption that building strong brands yields these advantages (Yasin et al., 2007). A quantitative survey was conducted at Sunnmøre in Norway in order to answer the two developed research questions. - Does the brand equity dimensions; brand...

  14. Algebra of strong and electroweak interactions

    International Nuclear Information System (INIS)

    Bolokhov, S.V.; Vladimirov, Yu.S.

    2004-01-01

    The algebraic approach to describing the electroweak and strong interactions is considered within the frames of the binary geometrophysics, based on the principles of the Fokker-Feynman direct interparticle interaction theories of the Kaluza-Klein multidimensional geometrical models and the physical structures theory. It is shown that in this approach the electroweak and strong elementary particles interaction through the intermediate vector bosons, are characterized by the subtypes of the algebraic classification of the complex 3 x 3-matrices [ru

  15. Emerging signs of strong reciprocity in human ontogeny

    Directory of Open Access Journals (Sweden)

    Erin eRobbins

    2011-12-01

    Full Text Available Strong reciprocity is considered here as the propensity to sacrifice resources to be kind or to punish in response to prior acts, a behavior not simply reducible to self-interest and a likely force behind human cooperation and sociality. The aim was to capture emerging signs of strong reciprocity in human ontogeny. Three- and five-year-old middle class American children (N=162 were tested in a simple, multiple round, three-way sharing game involving the child, a generous puppet, and a stingy puppet. At the end of the game, the child was offered an opportunity to sacrifice some of her personal gains to punish one of the puppets. By three years, American children demonstrate a willingness to engage in costly punishment. However, only five-year-olds show some evidence of strong reciprocity by orienting their punishment systematically toward the stingy puppet. Further analyses and 3 additional control conditions demonstrate that such propensity is not simply reducible to a straight imitation, or b inequity aversion. To assess the relative universality of such development, a group of five- to six-year-old children from rural Samoa (N=14 were tested and compared to age and gender matched American children. Samoan children did not manifest the same propensity toward strong reciprocity. The results are interpreted as pointing to 1 the developmental emergence of an ethical stance between three and five years of age, and 2 that the expression of such stance by young children could depend on culture.

  16. OPEC behavior

    Science.gov (United States)

    Yang, Bo

    This thesis aims to contribute to a further understanding of the real dynamics of OPEC production behavior and its impacts on the world oil market. A literature review in this area shows that the existing studies on OPEC still have some major deficiencies in theoretical interpretation and empirical estimation technique. After a brief background review in chapter 1, chapter 2 tests Griffin's market-sharing cartel model on the post-Griffin time horizon with a simultaneous system of equations, and an innovative hypothesis of OPEC's behavior (Saudi Arabia in particular) is then proposed based on the estimation results. Chapter 3 first provides a conceptual analysis of OPEC behavior under the framework of non-cooperative collusion with imperfect information. An empirical model is then constructed and estimated. The results of the empirical studies in this thesis strongly support the hypothesis that OPEC has operated as a market-sharing cartel since the early 1980s. In addition, the results also provide some support of the theory of non-cooperative collusion under imperfect information. OPEC members collude under normal circumstances and behave competitively at times in response to imperfect market signals of cartel compliance and some internal attributes. Periodic joint competition conduct plays an important role in sustaining the collusion in the long run. Saudi Arabia acts as the leader of the cartel, accommodating intermediate unfavorable market development and punishing others with a tit-for-tat strategy in extreme circumstances.

  17. Manipulating light with strongly modulated photonic crystals

    International Nuclear Information System (INIS)

    Notomi, Masaya

    2010-01-01

    Recently, strongly modulated photonic crystals, fabricated by the state-of-the-art semiconductor nanofabrication process, have realized various novel optical properties. This paper describes the way in which they differ from other optical media, and clarifies what they can do. In particular, three important issues are considered: light confinement, frequency dispersion and spatial dispersion. First, I describe the latest status and impact of ultra-strong light confinement in a wavelength-cubic volume achieved in photonic crystals. Second, the extreme reduction in the speed of light is reported, which was achieved as a result of frequency dispersion management. Third, strange negative refraction in photonic crystals is introduced, which results from their unique spatial dispersion, and it is clarified how this leads to perfect imaging. The last two sections are devoted to applications of these novel properties. First, I report the fact that strong light confinement and huge light-matter interaction enhancement make strongly modulated photonic crystals promising for on-chip all-optical processing, and present several examples including all-optical switches/memories and optical logics. As a second application, it is shown that the strong light confinement and slow light in strongly modulated photonic crystals enable the adiabatic tuning of light, which leads to various novel ways of controlling light, such as adiabatic frequency conversion, efficient optomechanics systems, photon memories and photons pinning.

  18. Kondo memory in driven strongly correlated quantum dots.

    Science.gov (United States)

    Zheng, Xiao; Yan, YiJing; Di Ventra, Massimiliano

    2013-08-23

    We investigate the real-time current response of strongly correlated quantum dot systems under sinusoidal driving voltages. By means of an accurate hierarchical equations of motion approach, we demonstrate the presence of prominent memory effects induced by the Kondo resonance on the real-time current response. These memory effects appear as distinctive hysteresis line shapes and self-crossing features in the dynamic current-voltage characteristics, with concomitant excitation of odd-number overtones. They emerge as a cooperative effect of quantum coherence-due to inductive behavior-and electron correlations-due to the Kondo resonance. We also show the suppression of memory effects and the transition to classical behavior as a function of temperature. All these phenomena can be observed in experiments and may lead to novel quantum memory applications.

  19. Behavioral Immunity in Insects

    Directory of Open Access Journals (Sweden)

    Thierry Lefèvre

    2012-08-01

    Full Text Available Parasites can dramatically reduce the fitness of their hosts, and natural selection should favor defense mechanisms that can protect hosts against disease. Much work has focused on understanding genetic and physiological immunity against parasites, but hosts can also use behaviors to avoid infection, reduce parasite growth or alleviate disease symptoms. It is increasingly recognized that such behaviors are common in insects, providing strong protection against parasites and parasitoids. We review the current evidence for behavioral immunity in insects, present a framework for investigating such behavior, and emphasize that behavioral immunity may act through indirect rather than direct fitness benefits. We also discuss the implications for host-parasite co-evolution, local adaptation, and the evolution of non-behavioral physiological immune systems. Finally, we argue that the study of behavioral immunity in insects has much to offer for investigations in vertebrates, in which this topic has traditionally been studied.

  20. Molecular transformations of phenolic SOA during photochemical aging in the aqueous phase: competition among oligomerization, functionalization, and fragmentation

    Directory of Open Access Journals (Sweden)

    L. Yu

    2016-04-01

    Full Text Available Organic aerosol is formed and transformed in atmospheric aqueous phases (e.g., cloud and fog droplets and deliquesced airborne particles containing small amounts of water through a multitude of chemical reactions. Understanding these reactions is important for a predictive understanding of atmospheric aging of aerosols and their impacts on climate, air quality, and human health. In this study, we investigate the chemical evolution of aqueous secondary organic aerosol (aqSOA formed during reactions of phenolic compounds with two oxidants – the triplet excited state of an aromatic carbonyl (3C∗ and hydroxyl radical (•OH. Changes in the molecular composition of aqSOA as a function of aging time are characterized using an offline nanospray desorption electrospray ionization mass spectrometer (nano-DESI MS whereas the real-time evolution of SOA mass, elemental ratios, and average carbon oxidation state (OSC are monitored using an online aerosol mass spectrometer (AMS. Our results indicate that oligomerization is an important aqueous reaction pathway for phenols, especially during the initial stage of photooxidation equivalent to  ∼  2 h irradiation under midday winter solstice sunlight in Northern California. At later reaction times functionalization (i.e., adding polar oxygenated functional groups to the molecule and fragmentation (i.e., breaking of covalent bonds become more important processes, forming a large variety of functionalized aromatic and open-ring products with higher OSC values. Fragmentation reactions eventually dominate the photochemical evolution of phenolic aqSOA, forming a large number of highly oxygenated ring-opening molecules with carbon numbers (nC below 6. The average nC of phenolic aqSOA decreases while average OSC increases over the course of photochemical aging. In addition, the saturation vapor pressures (C∗ of dozens of the most abundant phenolic aqSOA molecules are estimated. A wide range of C