Sample records for vpr-importin alpha interactions

  1. Lectin interactions with alpha-galactosylated xenoantigens

    DEFF Research Database (Denmark)

    Kirkeby, Svend; Moe, Dennis


    alpha-Galactosylated xenoantigens (Galalpha1-3Galbeta1-4GlcNAcbeta1 and Galalpha1-3Galbeta1-4GlcNAcbeta1-3Galbeta1-4Glc) are often detected with the alpha-Gal specific lectin Griffonia simplicifolia 1 isolectin B4 (GS1 B4). However, this lectin exhibits a broad and variable specificity for carboh...

  2. Lambda alpha, Sigma alpha and Xi alpha potentials derived from the SU6 quark-model baryon-baryon interaction

    CERN Document Server

    Fujiwara, Y; Suzuki, Y


    We calculate Lambda alpha, Sigma alpha and Xi alpha potentials from the nuclear-matter G-matrices of the SU6 quark-model baryon-baryon interaction. The alpha-cluster wave function is assumed to be a simple harmonic-oscillator shell-model wave function. A new method is proposed to derive the direct and knock-on terms of the interaction Born kernel from the hyperon-nucleon G-matrices, with explicit treatments of the nonlocality and the center-of-mass motion between the hyperon and alpha. We find that the SU6 quark-model baryon-baryon interactions, FSS and fss2, yield a reasonable bound-state energy for 5 He Lambda, -3.18 -- -3.62 MeV, in spite of the fact that they give relatively large depths for the Lambda single-particle potentials, 46 -- 48 MeV, in symmetric nuclear matter. An equivalent local potential derived from the Wigner transform of the nonlocal Lambda alpha kernel shows a strong energy dependence for the incident Lambda-particle, indicating the importance of the strangeness-exchange process in the o...

  3. Plant alpha-amylase inhibitors and their interaction with insect alpha-amylases. (United States)

    Franco, Octávio L; Rigden, Daniel J; Melo, Francislete R; Grossi-De-Sá, Maria F


    Insect pests and pathogens (fungi, bacteria and viruses) are responsible for severe crop losses. Insects feed directly on the plant tissues, while the pathogens lead to damage or death of the plant. Plants have evolved a certain degree of resistance through the production of defence compounds, which may be aproteic, e.g. antibiotics, alkaloids, terpenes, cyanogenic glucosides or proteic, e.g. chitinases, beta-1,3-glucanases, lectins, arcelins, vicilins, systemins and enzyme inhibitors. The enzyme inhibitors impede digestion through their action on insect gut digestive alpha-amylases and proteinases, which play a key role in the digestion of plant starch and proteins. The natural defences of crop plants may be improved through the use of transgenic technology. Current research in the area focuses particularly on weevils as these are highly dependent on starch for their energy supply. Six different alpha-amylase inhibitor classes, lectin-like, knottin-like, cereal-type, Kunitz-like, gamma-purothionin-like and thaumatin-like could be used in pest control. These classes of inhibitors show remarkable structural variety leading to different modes of inhibition and different specificity profiles against diverse alpha-amylases. Specificity of inhibition is an important issue as the introduced inhibitor must not adversely affect the plant's own alpha-amylases, nor the nutritional value of the crop. Of particular interest are some bifunctional inhibitors with additional favourable properties, such as proteinase inhibitory activity or chitinase activity. The area has benefited from the recent determination of many structures of alpha-amylases, inhibitors and complexes. These structures highlight the remarkable variety in structural modes of alpha-amylase inhibition. The continuing discovery of new classes of alpha-amylase inhibitor ensures that exciting discoveries remain to be made. In this review, we summarize existing knowledge of insect alpha-amylases, plant alpha

  4. On the {\\alpha} formalism for the common envelope interaction

    CERN Document Server

    De Marco, Orsola; Moe, Maxwell; Herwig, Falk; Mac Low, Mordecai-Mark; Paxton, Bill


    The {\\alpha}-formalism is a common way to parametrize the common envelope interaction between a giant star and a more compact companion. The {\\alpha} parameter describes the fraction of orbital energy released by the companion that is available to eject the giant star's envelope. By using new, detailed stellar evolutionary calculations we derive a user-friendly prescription for the {\\lambda} parameter and an improved approximation for the envelope binding energy, thus revising the {\\alpha} equation. We then determine {\\alpha} both from simulations and observations in a self consistent manner. By using our own stellar structure models as well as population considerations to reconstruct the primary's parameters at the time of the common envelope interaction, we gain a deeper understanding of the uncertainties. We find that systems with very low values of q (the ratio of the companion's mass to the mass of the primary at the time of the common envelope interaction) have higher values of {\\alpha}. A fit to the da...

  5. Interaction of alphaVbeta3 and alphaVbeta6 integrins with human parechovirus 1. (United States)

    Seitsonen, Jani; Susi, Petri; Heikkilä, Outi; Sinkovits, Robert S; Laurinmäki, Pasi; Hyypiä, Timo; Butcher, Sarah J


    Human parechovirus (HPEV) infections are very common in early childhood and can be severe in neonates. It has been shown that integrins are important for cellular infectivity of HPEV1 through experiments using peptide blocking assays and function-blocking antibodies to alpha(V) integrins. The interaction of HPEV1 with alpha(V) integrins is presumably mediated by a C-terminal RGD motif in the capsid protein VP1. We characterized the binding of integrins alpha(V)beta(3) and alpha(V)beta(6) to HPEV1 by biochemical and structural studies. We showed that although HPEV1 bound efficiently to immobilized integrins, alpha(V)beta(6) bound more efficiently than alpha(V)beta(3) to immobilized HPEV1. Moreover, soluble alpha(V)beta(6), but not alpha(V)beta(3), blocked HPEV1 cellular infectivity, indicating that it is a high-affinity receptor for HPEV1. We also showed that HPEV1 binding to integrins in vitro could be partially blocked by RGD peptides. Using electron cryo-microscopy and image reconstruction, we showed that HPEV1 has the typical T=1 (pseudo T=3) organization of a picornavirus. Complexes of HPEV1 and integrins indicated that both integrin footprints reside between the 5-fold and 3-fold symmetry axes. This result does not match the RGD position predicted from the coxsackievirus A9 X-ray structure but is consistent with the predicted location of this motif in the shorter C terminus found in HPEV1. This first structural characterization of a parechovirus indicates that the differences in receptor binding are due to the amino acid differences in the integrins rather than to significantly different viral footprints.

  6. Amiloride interacts with renal. cap alpha. - and. beta. -adrenergic receptors

    Energy Technology Data Exchange (ETDEWEB)

    Howard, M.J.; Mullen, M.D.; Insel, P.A.


    The authors have used radioligand binding techniques to assess whether amiloride and certain analogues of amiloride (ethylisopropyl amiloride and benzamil) can bind to adrenergic receptors in the kidney. They found that amiloride could compete for (/sup 3/H)rauwolscine (..cap alpha../sub 2/-adrenergic receptors), (/sup 3/H)prazosin (..cap alpha../sub 1/-adrenergic receptors), and (/sup 125/I)iodocyanopindolol (..beta..-adrenergic receptors) binding in rat renal cortical membranes with inhibitor constants of 13.6 /plus minus/ 5.7, 24.4 /plus minus/ 7.4, and 8.36 /plus minus/ 13.5, respectively. Ethylisopropyl amiloride and benzamil were from 2- to 25-fold more potent than amiloride in competing for radioligand binding sites in studies with these membranes. In addition, amiloride and the two analogues competed for (/sup 3/H)prazosin sites on intact Madin-Darby canine kidney cells and amiloride blocked epinephrine-stimulated prostaglandin E/sub 2/ production in these cells. They conclude that amiloride competes for binding to several classes of renal adrenergic receptors with a rank order of potency of ..cap alpha../sub 2/ > ..cap alpha../sub 1/ > ..beta... Binding to, and antagonism of, adrenergic receptors occurs at concentrations of amiloride that are lower than previously observed nonspecific interactions of this agent.

  7. The interacting galaxy pair KPG 390: H$\\alpha$ kinematics

    CERN Document Server

    Repetto, P; Gabbasov, R; Fuentes-Carrera, I


    In this work we present scanning Fabry-Perot H$\\alpha$ observations of the isolated interacting galaxy pair NGC 5278/79 obtained with the PUMA Fabry-Perot interferometer. We derived velocity fields and rotation curves for both galaxies. For NGC 5278 we also obtained the residual velocity map to investigate the non-circular motions, and estimated its mass by fitting the rotation curve with a disk+halo components. We test three different types of halo (pseudo-isothermal, Hernquist and Navarro Frenk White) and obtain satisfactory fits to the rotation curve for all profiles. The amount of dark matter required by pseudo-isothermal profile is about ten times smaller than, that for the other two halo distributions. Finally, our kinematical results together with the analysis of dust lanes distribution and of surface brightness profiles along the minor axis allowed us to determine univocally that both components of the interacting pair are trailing spirals.

  8. Differential interaction of GRK2 with members of the G alpha q family. (United States)

    Day, Peter W; Carman, Christopher V; Sterne-Marr, Rachel; Benovic, Jeffrey L; Wedegaertner, Philip B


    Regulators of G protein signaling (RGS) proteins bind to active G alpha subunits and accelerate the rate of GTP hydrolysis and/or block interaction with effector molecules, thereby decreasing signal duration and strength. RGS proteins are defined by the presence of a conserved 120-residue region termed the RGS domain. Recently, it was shown that the G protein-coupled receptor kinase 2 (GRK2) contains an RGS domain that binds to the active form of G alpha(q). Here, the ability of GRK2 to interact with other members of the G alpha(q) family, G alpha(11), G alpha(14), and G alpha(16), was tested. The signaling of all members of the G alpha(q) family, with the exception of G alpha(16), was inhibited by GRK2. Immunoprecipitation of full-length GRK2 or pull down of GST-GRK2-(45-178) resulted in the detection of G alpha(q), but not G alpha(16), in an activation-dependent manner. Moreover, activated G alpha(16) failed to promote plasma membrane (PM) recruitment of a GRK2-(45-178)-GFP fusion protein. Assays with chimeric G alpha(q)(-)(16) subunits indicated that the C-terminus of G alpha(q) mediates binding to GRK2. Despite showing no interaction with GRK2, G alpha(16) does interact with RGS2, in both inositol phosphate and PM recruitment assays. Thus, GRK2 is the first identified RGS protein that discriminates between members of the G alpha(q) family, while another RGS protein, RGS2, binds to both G alpha(q) and G alpha(16).

  9. Quaternary organization of the goodpasture autoantigen, the alpha 3(IV) collagen chain. Sequestration of two cryptic autoepitopes by intrapromoter interactions with the alpha4 and alpha5 NC1 domains. (United States)

    Borza, Dorin-Bogdan; Bondar, Olga; Todd, Parvin; Sundaramoorthy, Munirathinam; Sado, Yoshikazu; Ninomiya, Yoshifumi; Hudson, Billy G


    Goodpasture's (GP) disease is caused by autoantibodies that target the alpha3(IV) collagen chain in the glomerular basement membrane (GBM). Goodpasture autoantibodies bind two conformational epitopes (E(A) and E(B)) located within the non-collagenous (NC1) domain of this chain, which are sequestered within the NC1 hexamer of the type IV collagen network containing the alpha3(IV), alpha4(IV), and alpha5(IV) chains. In this study, the quaternary organization of these chains and the molecular basis for the sequestration of the epitopes were investigated. This was accomplished by physicochemical and immunochemical characterization of the NC1 hexamers using chain-specific antibodies. The hexamers were found to have a molecular composition of (alpha3)(2)(alpha4)(2)(alpha5)(2) and to contain cross-linked alpha3-alpha5 heterodimers and alpha4-alpha4 homodimers. Together with association studies of individual NC1 domains, these findings indicate that the alpha3, alpha4, and alpha5 chains occur together in the same triple-helical protomer. In the GBM, this protomer dimerizes through NC1-NC1 domain interactions such that the alpha3, alpha4, and alpha5 chains of one protomer connect with the alpha5, alpha4, and alpha3 chains of the opposite protomer, respectively. The immunodominant Goodpasture autoepitope, located within the E(A) region, is sequestered within the alpha3alpha4alpha5 protomer near the triple-helical junction, at the interface between the alpha3NC1 and alpha5NC1 domains, whereas the E(B) epitope is sequestered at the interface between the alpha3NC1 and alpha4NC1 domains. The results also reveal the network distribution of the six chains of collagen IV in the renal glomerulus and provide a molecular explanation for the absence of the alpha3, alpha4, alpha5, and alpha6 chains in Alport syndrome.

  10. Interactive domains in the molecular chaperone human alphaB crystallin modulate microtubule assembly and disassembly.

    Directory of Open Access Journals (Sweden)

    Joy G Ghosh

    Full Text Available Small heat shock proteins regulate microtubule assembly during cell proliferation and in response to stress through interactions that are poorly understood.Novel functions for five interactive sequences in the small heat shock protein and molecular chaperone, human alphaB crystallin, were investigated in the assembly/disassembly of microtubules and aggregation of tubulin using synthetic peptides and mutants of human alphaB crystallin.The interactive sequence (113FISREFHR(120 exposed on the surface of alphaB crystallin decreased microtubule assembly by approximately 45%. In contrast, the interactive sequences, (131LTITSSLSSDGV(142 and (156ERTIPITRE(164, corresponding to the beta8 strand and the C-terminal extension respectively, which are involved in complex formation, increased microtubule assembly by approximately 34-45%. The alphaB crystallin peptides, (113FISREFHR(120 and (156ERTIPITRE(164, inhibited microtubule disassembly by approximately 26-36%, and the peptides (113FISREFHR(120 and (131LTITSSLSSDGV(142 decreased the thermal aggregation of tubulin by approximately 42-44%. The (131LTITSSLSSDGV(142 and (156ERTIPITRE(164 peptides were more effective than the widely used anti-cancer drug, Paclitaxel, in modulating tubulinmicrotubule dynamics. Mutagenesis of these interactive sequences in wt human alphaB crystallin confirmed the effects of the alphaB crystallin peptides on microtubule assembly/disassembly and tubulin aggregation. The regulation of microtubule assembly by alphaB crystallin varied over a narrow range of concentrations. The assembly of microtubules was maximal at alphaB crystallin to tubulin molar ratios between 1:4 and 2:1, while molar ratios >2:1 inhibited microtubule assembly.Interactive sequences on the surface of human alphaB crystallin collectively modulate microtubule assembly through a dynamic subunit exchange mechanism that depends on the concentration and ratio of alphaB crystallin to tubulin. These are the first

  11. Mutant and wild-type alpha-synuclein interact with mitochondrial cytochrome C oxidase. (United States)

    Elkon, Hanock; Don, Jermy; Melamed, Eldad; Ziv, Ilan; Shirvan, Anat; Offen, Daniel


    Alpha-synuclein, a presynaptic protein, was found to be the major component in the Lewy bodies (LB) in both inherited and sporadic Parkinson's disease (PD). Furthermore, rare mutations of alpha-synuclein cause autosomal-dominant PD. However, it is unknown how alpha-synuclein is involved in the pathogenesis of nigral degeneration in PD. In this study, we examine the protein-protein interactions of wild-type and mutant (A53T) a-synuclein with adult human brain cDNA expression library using the yeast two-hybrid technique. We found that both normal and mutant alpha-synuclein specifically interact with the mitochondrial complex IV enzyme, cytochrome C oxidase (COX). Wild-type and mutant alpha-synuclein genes were further fused with c-Myc tag and translated in rabbit reticulocyte lysate. Using anti-c-Myc antibody, we demonstrated that both wild-type and mutant alpha-synuclein, coimmunoprecipitated with COX. We also showed that potassium cyanide, a selective COX inhibitor, synergistically enhanced the sensitivity of SH-SY5Y neuroblastoma cells to dopamine-induced cell death. In conclusion, we found specific protein-protein interactions of alpha-synuclein, a major LB protein, to COX, a key enzyme of the mithochondrial respiratory system. This interaction suggests that alpha-synuclein aggregation may contribute to enhance the mitochondrial dysfunction, which might be a key factor in the pathogenesis of PD.

  12. Spectroscopic study on the interaction of Bacillus subtilis {alpha}-amylase with cetyltrimethylammonium bromide

    Energy Technology Data Exchange (ETDEWEB)

    Omidyan, R., E-mail: [Department of Chemistry, University of Isfahan, Isfahan 81746-73441 (Iran, Islamic Republic of); Department of Chemistry, Institute for Advanced Studies in Basic Sciences (IASBS), Zanjan 45137-66731 (Iran, Islamic Republic of); Kazemi, S.H. [Department of Chemistry, Institute for Advanced Studies in Basic Sciences (IASBS), Zanjan 45137-66731 (Iran, Islamic Republic of); Bordbar, A.K. [Department of Chemistry, University of Isfahan, Isfahan 81746-73441 (Iran, Islamic Republic of); Zaynalpour, S. [Department of Chemistry, Institute for Advanced Studies in Basic Sciences (IASBS), Zanjan 45137-66731 (Iran, Islamic Republic of)


    The interaction between {alpha}-amylase from Bacillus subtilis and cetyltrimethylammonium bromide (CTAB) has been investigated at various temperature conditions using fluorescence and circular dichroism (CD) spectroscopic methods. Fluorescence data revealed that the fluorescence quenching of {alpha}-amylase by CTAB is the result of complex formation between CTAB and {alpha}-amylase. The thermodynamic analysis on the binding interaction data shows that the interactions are strongly exothermic ({Delta}H{sup o}=-17.92 kJ mol{sup -1}) accompanied with increase in entropy ({Delta}S{sup o} between 109 to 135 J mol{sup -1} K{sup -1}). Thus the binding of CTAB to {alpha}-amylase is both enthalpic and entropic driven, which represent the predominate role of both electrostatic and hydrophobic interactions in complex formation process. The values of 2.17x10{sup -3} M{sup -1} and 1.30 have been obtained from associative binding constant (K{sub a}) and stoichiometry of binding number (n), from analysis of fluorescence data, respectively. Circular dichroism spectra showed the substantial conformational changes in secondary structure of {alpha}-amylase due to binding of CTAB, which represents the complete destruction of both secondary and tertiary structure of {alpha}-amylase by CTAB. - Research highlights: {yields} The Fluorescence quenching effect of {alpha}-amylase by CTAB is a consequence of formation {alpha}-amylase-CTAB complex. {yields} The {alpha}-helical analyzing from the CD spectra in the various concentration of CTAB shows strongly deformation of {alpha}-amylase. {yields} Thermodynamic analysis of quenching verify that the interactions are both enthalpy and entropic driven.

  13. {alpha}-{alpha} interaction reexamined in the context of the Sao Paulo potential: possible applications in astrophysics?

    Energy Technology Data Exchange (ETDEWEB)

    Gasques, L.R.; Chamon, L.C.; Botero, D.F.M. [Universidade de Sao Paulo (DFN/USP), SP (Brazil). Dept. de Fisica Nuclear; Alves, L.F.M. [Instituto Federal de Educacao, Ciencia e Tecnologia (Brazil); Carlson, B.V. [Instituto Tecnologico de Aeronautica (CTA/ITA), Sao Jose dos Campos, SP (Brazil). Dept. de Fisica Nuclear; Rossi Junior, E.S. [Centro Universitario FIEO(UNIFIEO), SP (Brazil)


    Full text: We have analyzed a large set of {alpha}-{alpha} elastic scattering data for bombarding energies ranging from 0.6 to 29.5 MeV. The complete lack of open reaction channels at these somehow low energies results in a vanishing imaginary part for the optical interaction. This characteristic makes the {alpha}-{alpha} reaction particularly interesting as the corresponding elastic scattering cross sections and phase shifts become very sensitive to the real part of the interaction. The data were analyzed within the context of the velocity-dependent Sao Paulo potential, which is a successful theoretical model for the description of heavy-ion reactions from sub-barrier to intermediate energies. We have shown that, even in this low energy region, the velocity dependence of the Sao Paulo potential model is a necessary ingredient for describing the data. Despite the reasonable description obtained with the Sao Paulo potential, the analyses indicate the necessity of an additional weak dependence of the interaction on the angular momentum. These important characteristics open the possibility for studying reactions with astrophysical interested. In particular, predictions of the astrophysical S-factor for the {sup 12}C({alpha},{gamma}) reaction will be presented. The understanding of the reaction rate for the {alpha}-capture process by a {sup 12}C nucleus is a crucial ingredient for predicting the stellar helium burning and the subsequent fate of stars as this reaction determines the ratio of carbon to oxygen towards the end of the Red Giants phase. It is well known that low mass stars evolve to White Dwarfs and this ratio determines the final abundance composition in White Dwarf matter and sets the trigger conditions for type Ia supernova explosions. The carbon-oxygen ratio also dictates the subsequent sequence of burning processes during the final stages of stellar evolution for massive stars. Thus, it has a key role in the determination of the abundance composition in

  14. Interaction of neutrons with alpha particles: A tribute to Heinz Barschall

    CERN Document Server

    Hoop, B


    As a tribute to our teacher and mentor on the occasion of his centennial celebration, we provide a brief historical overview and a summary of sustained interest in the topic of interaction of neutrons with alpha particles.

  15. The thermal structural transition of alpha-crystallin modulates subunit interactions and increases protein solubility.

    Directory of Open Access Journals (Sweden)

    Giuseppe Maulucci

    Full Text Available BACKGROUND: Alpha crystallin is an oligomer composed of two types of subunits, alpha-A and alpha-B crystallin, and is the major constituent of human lens. The temperature induced condensation of alpha-crystallin, the main cause for eye lens opacification (cataract, is a two step-process, a nucleation followed by an aggregation phase, and a protective effect towards the aggregation is exhibited over the alpha crystallin phase transition temperature (Tc = 318.16 K. METHODS/RESULTS: To investigate if a modulation of the subunit interactions over Tc could trigger the protective mechanism towards the aggregation, we followed, by using simultaneously static and dynamic light scattering, the temperature induced condensation of alpha-crystallin. By developing a mathematical model able to uncouple the nucleation and aggregation processes, we find a previously unobserved transition in the nucleation rate constant. Its temperature dependence allows to determine fundamental structural parameters, the chemical potential (Δμ and the interfacial tension (γ of the aggregating phase, that characterize subunit interactions. CONCLUSIONS/GENERAL SIGNIFICANCE: The decrease of both Δμ and γ at Tc, and a relative increase in solubility, reveal a significative decrease in the strenght of alpha-crystallin subunits interactions, which protects from supramolecolar condensation in hypertermic conditions. On the whole, we suggest a general approach able to understand the structural and kinetic mechanisms involved in aggregation-related diseases and in drugs development and testing.

  16. Interactions between alpha-latrotoxin and trivalent cations in rat striatal synaptosomal preparations

    Energy Technology Data Exchange (ETDEWEB)

    Scheer, H.W.


    The interactions between alpha-latrotoxin (alpha-LTx), a neurosecretagogue purified from the venom of the black widow spider, and the trivalent cations Al3+, Y3+, La3+, Gd3+, and Yb3+ were investigated in rat striatal synaptosomal preparations. All trivalent cations tested were inhibitors of alpha-LTx-induced (/sup 3/H)dopamine ((/sup 3/H)DA) release (order of potency: Yb3+ greater than Gd3+ approximately Y3+ greater than La3+ greater than Al3+). Only with Al3+ could inhibition of (/sup 3/H)DA release be attributed to a block of /sup 125/I-alpha-LTx specific binding to synaptosomal preparations. The inhibitory effect of trivalent ions was reversible provided synaptosomes were washed with buffer containing EDTA. Trivalent ions also inhibited alpha-LTx-induced (/sup 3/H)DA release at times when alpha-LTx-stimulated release was already evident. alpha-LTx-induced synaptosomal membrane depolarization was blocked by La3+, but not affected by Gd3+, Y3+, and Yb3+. alpha-LTx-stimulated uptake of /sup 45/Ca/sup 2 +/ was inhibited by all trivalent cations tested. These results demonstrate that there exist at least three means by which trivalent cations can inhibit alpha-LTx action in rat striatal synaptosomal preparations: (1) inhibition of alpha-LTx binding (Al3+); (2) inhibition of alpha-LTx-induced depolarization (La3+); and (3) inhibition of alpha-LTx-induced /sup 45/Ca/sup 2 +/ uptake (Gd3+, Y3+, Yb3+, La3+).

  17. Microwave-plasma interactions studied via mode diagnostics in ALPHA (United States)

    Friesen, T.; Andresen, G. B.; Ashkezari, M. D.; Baquero-Ruiz, M.; Bertsche, W.; Bowe, P. D.; Butler, E.; Cesar, C. L.; Chapman, S.; Charlton, M.; Eriksson, S.; Fajans, J.; Fujiwara, M. C.; Gill, D. R.; Gutierrez, A.; Hangst, J. S.; Hardy, W. N.; Hayano, R. S.; Hayden, M. E.; Humphries, A. J.; Hydomako, R.; Jonsell, S.; Kurchaninov, L.; Madsen, N.; Menary, S.; Nolan, P.; Olchanski, K.; Olin, A.; Povilus, A.; Pusa, P.; Robicheaux, F.; Sarid, E.; Silveira, D. M.; So, C.; Storey, J. W.; Thompson, R. I.; van der Werf, D. P.; Wurtele, J. S.; Yamazaki, Y.

    The goal of the ALPHA experiment is the production, trapping and spectroscopy of antihydrogen. A direct comparison of the ground state hyperfine spectra in hydrogen and antihydrogen has the potential to be a high-precision test of CPT symmetry. We present a novel method for measuring the strength of a microwave field for hyperfine spectroscopy in a Penning trap. This method incorporates a non-destructive plasma diagnostic system based on electrostatic modes within an electron plasma. We also show how this technique can be used to measure the cyclotron resonance of the electron plasma, which can potentially serve as a non-destructive measurement of plasma temperature.

  18. Magnetic interaction in oxygenated alpha Fe-phthalocyanines

    Energy Technology Data Exchange (ETDEWEB)

    Kuzmann, Ernő, E-mail:; Homonnay, Zoltán; Horváth, Attila [Institute of Chemistry, Eötvös Loránd University, P.O. Box 32, 1512 Budapest (Hungary); Pechousek, Jiri; Cuda, Jan; Machala, Libor; Zoppellaro, Giorgio; Zboril, Radek [Regional Centre of Advanced Technologies and Materials, Departments of Experimental Physics and Physical Chemistry, Faculty of Science Palacky University, 17. Listopadu 1192/12, 771 46 Olomouc (Czech Republic); Yin, Houping; Wei, Yen [Department of Chemistry, Drexel University, Philadelphia, PA 19104 (United States); Klencsár, Zoltán [Research Centre for Natural Sciences, Hungarian Academy of Sciences, Budapest, 1117 (Hungary); Kubuki, Shiro [Department of Chemistry, Graduate School of Science and Engineering, Tokyo Metropolitan University, 1-1 Minami-Osawa, Hachi-Oji, Tokyo 192-0397 (Japan); Nath, Amar [Department of Chemistry, University of North Carolina, Asheville, NC 28804 (United States)


    Alpha iron phthalocyanines (α-FePc) oxygenated at low temperatures were investigated with the help of {sup 57}Fe Mössbauer spectroscopy, magnetization measurements (SQUID) and X-ray diffractometry (XRD). Mössbauer spectroscopy revealed that upon oxygenation of α-FePc, new species were formed which could be associated with Fe{sup III}Pc oxygen adducts. Unexpectedly, magnetically split spectrum of oxygenated α-FePc was observed below 20 K. In-field Mössbauer spectra in a 5 T external magnetic field at 5K and magnetization measurements indicate antiferromagnetic coupling in oxygenated α-FePc.

  19. Interaction of berberine with human platelet. alpha. sub 2 adrenoceptors

    Energy Technology Data Exchange (ETDEWEB)

    Hui, Ka Kit; Yu, Jun Liang; Chan, Wai Fong A.; Tse, E. (UCLA School of Medicine, (USA))


    Berberine was found to inhibit competitively the specific binding of ({sup 3}H)-yohimbine. The displacement curve was parallel to those of clonidine, epinephrine, norepinephrine, with the rank order of potency (IC{sub 50}) being clonidine {gt} epinephrine {gt} norepinephrine (14.5 {mu}M) = berberine. Increasing concentrations of berberine from 0.1 {mu}M to 10 {mu}M inhibited ({sup 3}H)-yohimbine binding, shifting the saturation binding curve to the right without decreasing the maximum binding capacity. In platelet cyclic AMP accumulation experiments, berberine at concentrations of 0.1 {mu}M to 0.1 mM inhibited the cAMP accumulation induced by 10 {mu}M prostaglandin E{sub 1} in a dose dependent manner, acting as an {alpha}{sub 2} adrenoceptor agonist. In the presence of L-epinephrine, berberine blocked the inhibitory effect of L-epinephrine behaving as an {alpha}{sub 2} adrenoceptor antagonist.

  20. Description of alpha-nucleus interaction cross sections for cosmic ray shielding studies (United States)

    Cucinotta, Francis A.; Townsend, Lawrence W.; Wilson, John W.


    Nuclear interactions of high-energy alpha particles with target nuclei important for cosmic ray studies are discussed. Models for elastic, quasi-elastic, and breakup reactions are presented and compared with experimental data. Energy-dependent interaction cross sections and secondary spectra are presented based on theoretical models and the limited experimental data base.

  1. Accelerated healing of skin burns by anti-Gal/alpha-gal liposomes interaction. (United States)

    Galili, Uri; Wigglesworth, Kim; Abdel-Motal, Ussama M


    Topical application of alpha-gal liposomes on burns results in rapid local recruitment of neutrophils and macrophages. Recruited macrophages are pivotal for healing of burns because they secrete cytokines/growth factors that induce epidermis regeneration and tissue repair. alpha-Gal liposomes have glycolipids with alpha-gal epitopes (Galalpha1-3Galbeta1-4GlcNAc-R) which bind anti-Gal, the most abundant natural antibody in humans constituting approximately 1% of immunoglobulins. Interaction of alpha-gal liposomes with anti-Gal within the fluid film formed on burns, activates complement and generates chemotactic complement cleavage peptides which effectively recruit neutrophils and macrophages. Anti-Gal IgG coating alpha-gal liposomes further binds to Fcgamma receptors on macrophages and activates them to secrete cytokines/growth factors. Efficacy of alpha-gal liposomes treatment in accelerating burn healing is demonstrated in the experimental model of alpha1,3galactosyltransferase knockout mice. These mice are the only available nonprimate mammals that can produce anti-Gal in titers similar to those in humans. Pairs of burns in mice were covered either with a spot bandage coated with 10mg alpha-gal liposomes, or with a control spot bandage coated with saline. On Day 3 post-treatment, the alpha-gal liposomes treated burns contained approximately 5-fold as many neutrophils as control burns, whereas macrophages were found only in alpha-gal liposomes treated burns. On Day 6, 50-100% of the surface area of alpha-gal liposomes treated burns were covered with regenerating epidermis (re-epithelialization), whereas almost no epidermis was found in control burns. The extensive recruitment of macrophages by anti-Gal/alpha-gal liposomes interaction was further demonstrated in vivo with polyvinyl alcohol (PVA) sponge discs containing alpha-gal liposomes, implanted subcutaneously. Since anti-Gal is abundant in all humans, it is suggested that treatment with alpha-gal liposomes

  2. Alpha shape and Delaunay triangulation in studies of protein-related interactions. (United States)

    Zhou, Weiqiang; Yan, Hong


    In recent years, more 3D protein structures have become available, which has made the analysis of large molecular structures much easier. There is a strong demand for geometric models for the study of protein-related interactions. Alpha shape and Delaunay triangulation are powerful tools to represent protein structures and have advantages in characterizing the surface curvature and atom contacts. This review presents state-of-the-art applications of alpha shape and Delaunay triangulation in the studies on protein-DNA, protein-protein, protein-ligand interactions and protein structure analysis.

  3. Specific interaction of capsid protein and importin-{alpha}/{beta} influences West Nile virus production

    Energy Technology Data Exchange (ETDEWEB)

    Bhuvanakantham, Raghavan; Chong, Mun-Keat [Flavivirology Laboratory, Department of Microbiology, 5 Science Drive 2, National University of Singapore, Singapore 117597 (Singapore); Ng, Mah-Lee, E-mail: [Flavivirology Laboratory, Department of Microbiology, 5 Science Drive 2, National University of Singapore, Singapore 117597 (Singapore)


    West Nile virus (WNV) capsid (C) protein has been shown to enter the nucleus of infected cells. However, the mechanism by which C protein enters the nucleus is unknown. In this study, we have unveiled for the first time that nuclear transport of WNV and Dengue virus C protein is mediated by their direct association with importin-{alpha}. This interplay is mediated by the consensus sequences of bipartite nuclear localization signal located between amino acid residues 85-101 together with amino acid residues 42 and 43 of C protein. Elucidation of biological significance of importin-{alpha}/C protein interaction demonstrated that the binding efficiency of this association influenced the nuclear entry of C protein and virus production. Collectively, this study illustrated the molecular mechanism by which the C protein of arthropod-borne flavivirus enters the nucleus and showed the importance of importin-{alpha}/C protein interaction in the context of flavivirus life-cycle.

  4. De Sitter Space, Interacting Quantum Field Theory And Alpha Vacua

    CERN Document Server

    Goldstein, K


    Inspired by recent evidence for a positive cosmological constant, this thesis considers some of the implications of trying to incorporate approximately seventy percent of the universe, namely dark energy, consistently into quantum field theory on a curved background. Such considerations may have implications for inflation, the understanding of dark energy at the present time and finally the challenging topic of trying to incorporate a positive cosmological constant into string theory. We will mainly examine various aspects of the one parameter family of de Sitter invariant states—the so called α-vacua. On the phenomenological side, not only could such states provide a window into trans-planckian physics through their imprint on the cosmological microwave background (CMB), but they may also be a source of ultra-high energy cosmic rays (UHECR) at the present time. From a purely theoretical perspective, formulating interacting quantum field theory in these states is a challenging problem whic...

  5. Interaction between vitamin D receptor genotype and estrogen receptor alpha genotype influences vertebral fracture risk

    NARCIS (Netherlands)

    E.M. Colin (Edgar); A.G. Uitterlinden (André); A.P. Bergink (Arjan); M. van de Klift (Marjolein); Y. Fang (Yue); P.P. Arp (Pascal); H.A.P. Pols (Huib); J.P.T.M. van Leeuwen (Hans); J.B.J. van Meurs (Joyce); A. Hofman (Albert)


    textabstractIn view of the interactions of vitamin D and the estrogen endocrine system, we studied the combined influence of polymorphisms in the estrogen receptor (ER) alpha gene and the vitamin D receptor (VDR) gene on the susceptibility to osteoporotic vertebral fractures in 634

  6. Chiral Three-Nucleon Interactions in Light Nuclei, Neutron-$\\alpha$ Scattering, and Neutron Matter

    CERN Document Server

    Lynn, J E; Carlson, J; Gandolfi, S; Gezerlis, A; Schmidt, K E; Schwenk, A


    We present quantum Monte Carlo calculations of light nuclei, neutron-$\\alpha$ scattering, and neutron matter using local two- and three-nucleon (3N) interactions derived from chiral effective field theory up to next-to-next-to-leading order (N$^2$LO). The two undetermined 3N low-energy couplings are fit to the $^4$He binding energy and, for the first time, to the spin-orbit splitting in the neutron-$\\alpha$ $P$-wave phase shifts. Furthermore, we investigate different choices of local 3N operator structures and find that chiral interactions at N$^2$LO are able to simultaneously reproduce the properties of $A=4,5$ systems and of neutron matter, in contrast to commonly used phenomenological 3N interactions.

  7. Nucleon-alpha particle interactions from inversion of scattering phase shifts

    Energy Technology Data Exchange (ETDEWEB)

    Alexander, N.; Amos, K.; Apagyi, B.; Lun, D.R.


    Scattering amplitudes have been extracted from (elastic scattering) neutron-alpha (n-{alpha}) differential cross sections below threshold using the constraint that the scattering function is unitary. Real phase shifts have been obtained therefrom. A modification to the Newton iteration method has been used to solve the nonlinear equation that specifies the phase of the scattering amplitude in terms of the complete (0 to 180 deg) cross section since the condition for a unique and convergent solution by an exact iterated fixed point method, the `Martin` condition, is not satisfied. The results compare well with those found using standard optical model search procedures. Those optical model phase shifts, from both n - {alpha} and p - {alpha} (proton-alpha) calculations in which spin-orbit effects were included, were used in the second phase of this study, namely to determine the scattering potentials by inversion of that phase shift data. A modified Newton-Sabatier scheme to solve the inverse scattering problem has been used to obtain inversion potentials (both central and spin-orbit) for nucleon energies in the range 1 to 24 MeV. The inversion interactions differ noticeably from the Woods-Saxon forms used to give the input phase shifts. Not only do those inversion potentials when used in Schroedinger equations reproduce the starting phase shifts but they are also very smooth, decay rapidly, and are as feasible as the optical model potentials of others to be the local form for interactions deduced by folding realistic two-nucleon g matrices with the density matrix elements of the alpha particle. 23 refs., 8 tabs., 9 figs.

  8. n alpha RGM by the quark-model G-matrix NN interaction

    CERN Document Server

    Fujiwara, Y; Suzuki, Y


    We calculate n alpha phase-shifts in the resonating-group method (RGM), using the nuclear-matter G-matrix of the SU6 quark-model NN interaction. The interaction RGM kernels are evaluated in the center-of-mass system with explicit treatments of the nonlocality and momentum dependence of the partial-wave G-matrix components determined in symmetric nuclear matter. The momentum dependence of the G-matrix components is different for each of the nucleon-exchange and interaction types. The direct potential and the knock-on term are treated in a common framework in the present formalism. A simplified assumption of some G-matrix parameters makes the numerical calculation feasible. Without introducing any free parameters, the central and spin-orbit components of the n alpha Born kernel are found to have reasonable strengths under the assumption of the rigid translationally invariant shell-model wave function of the alpha-cluster. The phase-shift equivalent local potentials are examined in the WKB-RGM approximation, by ...

  9. Investigating a Possible Spectral Signature of the Wind-ISM Interaction Region of Alpha Tau

    CERN Document Server

    Wood, B E; Müller, H R; Zank, G P; Wood, Brian E.; Harper, Graham M.; Mueller, Hans-Reinhard; Zank, Gary P.


    Ultraviolet spectra from the GHRS instrument on board the Hubble Space Telescope reveal the presence of a mysterious absorption feature in the Mg II h & k lines of the nearby (d=20.0 pc) K5 III star Alpha Tau. The narrow absorption looks like an interstellar absorption feature but it is in the wrong location based on our knowledge of the local ISM flow vector. Since the absorption is close to the rest frame of the star, it has been interpreted as being from the interaction region between Alpha Tau's massive, cool wind and the interstellar medium, i.e., Alpha Tau's "astrosphere". We compute hydrodynamic models of the Alpha Tau astrosphere in order to see if the models can reproduce the Mg II absorption feature. These models do predict that stellar wind material heated, decelerated, and compressed after passing through a termination shock a few thousand AU from the star should produce a Mg II absorption feature with about the right width at roughly the right velocity. However, our first models underestimate...

  10. Interaction of plant chimeric calcium/calmodulin-dependent protein kinase with a homolog of eukaryotic elongation factor-1alpha (United States)

    Wang, W.; Poovaiah, B. W.


    A chimeric Ca2+/calmodulin-dependent protein kinase (CCaMK) was previously cloned and characterized in this laboratory. To investigate the biological functions of CCaMK, the yeast two-hybrid system was used to isolate genes encoding proteins that interact with CCaMK. One of the cDNA clones obtained from the screening (LlEF-1alpha1) has high similarity with the eukaryotic elongation factor-1alpha (EF-1alpha). CCaMK phosphorylated LlEF-1alpha1 in a Ca2+/calmodulin-dependent manner. The phosphorylation site for CCaMK (Thr-257) was identified by site-directed mutagenesis. Interestingly, Thr-257 is located in the putative tRNA-binding region of LlEF-1alpha1. An isoform of Ca2+-dependent protein kinase (CDPK) phosphorylated multiple sites of LlEF-1alpha1 in a Ca2+-dependent but calmodulin-independent manner. Unlike CDPK, CCaMK phosphorylated only one site, and this site is different from CDPK phosphorylation sites. This suggests that the phosphorylation of EF-1alpha by these two kinases may have different functional significance. Although the phosphorylation of LlEF-1alpha1 by CCaMK is Ca2+/calmodulin-dependent, in vitro binding assays revealed that CCaMK binds to LlEF-1alpha1 in a Ca2+-independent manner. This was further substantiated by coimmunoprecipitation of CCaMK and EF-1alpha using the protein extract from lily anthers. Dissociation of CCaMK from EF-1alpha by Ca2+ and phosphorylation of EF-1alpha by CCaMK in a Ca2+/calmodulin-dependent manner suggests that these interactions may play a role in regulating the biological functions of EF-1alpha.

  11. Interaction of plant chimeric calcium/calmodulin-dependent protein kinase with a homolog of eukaryotic elongation factor-1alpha (United States)

    Wang, W.; Poovaiah, B. W.


    A chimeric Ca2+/calmodulin-dependent protein kinase (CCaMK) was previously cloned and characterized in this laboratory. To investigate the biological functions of CCaMK, the yeast two-hybrid system was used to isolate genes encoding proteins that interact with CCaMK. One of the cDNA clones obtained from the screening (LlEF-1alpha1) has high similarity with the eukaryotic elongation factor-1alpha (EF-1alpha). CCaMK phosphorylated LlEF-1alpha1 in a Ca2+/calmodulin-dependent manner. The phosphorylation site for CCaMK (Thr-257) was identified by site-directed mutagenesis. Interestingly, Thr-257 is located in the putative tRNA-binding region of LlEF-1alpha1. An isoform of Ca2+-dependent protein kinase (CDPK) phosphorylated multiple sites of LlEF-1alpha1 in a Ca2+-dependent but calmodulin-independent manner. Unlike CDPK, CCaMK phosphorylated only one site, and this site is different from CDPK phosphorylation sites. This suggests that the phosphorylation of EF-1alpha by these two kinases may have different functional significance. Although the phosphorylation of LlEF-1alpha1 by CCaMK is Ca2+/calmodulin-dependent, in vitro binding assays revealed that CCaMK binds to LlEF-1alpha1 in a Ca2+-independent manner. This was further substantiated by coimmunoprecipitation of CCaMK and EF-1alpha using the protein extract from lily anthers. Dissociation of CCaMK from EF-1alpha by Ca2+ and phosphorylation of EF-1alpha by CCaMK in a Ca2+/calmodulin-dependent manner suggests that these interactions may play a role in regulating the biological functions of EF-1alpha.

  12. Free radical interaction between vitamin E (alpha-, beta-, gamma- and delta-tocopherol), ascorbate and flavonoids. (United States)

    Kadoma, Yoshinori; Ishihara, Mariko; Okada, Norihisa; Fujisawa, Seiichiro


    Despite a large number of previous studies, the mechanism of free radical interaction between vitamin E (VE) (alpha-, beta-, gamma- and delta-tocopherol) and ascorbate or flavonoids as coantioxidants remains unclear. VE, particularly alpha-tocopherol, shows less antioxidant activity against peroxyl radicals, suggesting that VE possesses functions that are independent of its antioxidant/radical-scavenging activity. The synergistic antioxidant effect of VE or L-ascorbyl 2,6-dibutyrate (ASDB, an ascorbate derivative) with the flavonoids (-)-epicatechin (EC) and (-)-epigallocatechin gallate (EGCG) was investigated using the induction period method in the polymerization of methyl methacrylate initiated by thermal decomposition of benzoyl peroxide (an oxygen-centered radical, PhCOO*) under nearly anaerobic conditions. For delta-tocopherol, a synergistic antioxidant effect was observed in the presence of both EC and EGCG, whereas antioxidant activity for alpha-, beta- and gamma-tocopherol was decreased by addition of EC and EGCG. This suggested that the partial regeneration between VE and flavonoids may depend on the chemical structure of VE, i.e., monomethyl, dimethyl, or trimethyl tocol. The regeneration of delta-tocopherol, a monomethyl tocol, by flavonoids may be due to the lower steric effect of tocol. For ASDB, regeneration of vitamin E, which is well-known for a VE/ascorbate mixture, was not observed, possibly due to the anaerobic experimental conditions. The radical interaction between VE and EC, EGCG or ASDB suggests reactivity of VE with biological systems.

  13. Efficient separation of homologous alpha-lactalbumin from transgenic bovine milk using optimized hydrophobic interaction chromatography. (United States)

    Zhang, Yan; Luo, Jian; Bi, Jingxiu; Wang, Jun; Sun, Lijing; Liu, Yongdong; Zhang, Guifeng; Ma, Guanghui; Su, Zhiguo


    Transgenic bovine milk could be a rich source of recombinant human proteins. However, the co-presence of bovine and human homologous proteins can be a challenge for product purification. In this study, the average surface hydrophobicity and electric potential of human alpha-lactalbumin (HLA) and bovine alpha-lactalbumin (BLA) were analyzed and compared through the exposure area calculation of different amino acids. Based on the analysis, calcium independent hydrophobic interaction chromatography was selected for separation of recombinant human alpha-lactalbumin (rHLA) from BLA in transgenic bovine milk. The operating conditions for the best separation of two proteins were predicted by fluorescence data. Three commercially available HIC resins (Butyl Sepharose 4 FF, Octyl Sepharose 4 FF, Phenyl Sepharose 6 FF) were compared. The transgenic milk was skimmed and treated by pH adjustment to remove a large quantity of casein protein. The supernatant was loaded on the hydrophobic interaction chromatographic matrix. The correct elution fraction was further treated with gel filtration chromatography. The overall recovery of rHLA was up to 67.1% with the purity greater than 95%. Circular dichroism spectroscopy (CD) and mass spectrogram (MS) confirmed the native state and glycosylated form of the purified rHLA.

  14. Periodic trends governing the interactions between impurity atoms [H-Ar] and (alpha)-U

    Energy Technology Data Exchange (ETDEWEB)

    Taylor, Christopher David [Los Alamos National Laboratory


    The binding energies, geometries, charges and electronic structures of a series of impurity atoms [H-Ar] interacting with the {alpha}-U lattice in various configurations were assessed by means of density functional theory calculations. Periodic trends governing the binding energy were highlighted and related to the electronic properties of the impurity atoms, with some consideration given to the band-structure of {alpha}-U. The strongest bound impurity atoms include [C, N, O] and [Si, P, S]. The general trends in the binding energy can be reproduced by a simple parameterisation in terms of the electronegativity (charge-transfer) and covalent radius (elasticity theory) of the impurity atom. The strongest bound atoms deviate from this model, due to their ability to bind with an optimum mixture of covalency and ionicity. This last point is evidenced by the partial overlap of the impurity atom p-band with the hybrid d-/f-band of {alpha}-U. It is expected that the trends and general behaviour reported in this work can be extended to the interactions of impurity atoms with other metallic systems.

  15. Functional discrepancies between tumor necrosis factor and lymphotoxin alpha explained by trimer stability and distinct receptor interactions

    DEFF Research Database (Denmark)

    Schuchmann, M; Hess, S; Bufler, P;


    interaction with the human p55TNFR. This was demonstrated in NIH 3T3 cells transfected with the human p55TNFR, where cytotoxicity is mediated exclusively by the transfected receptor. Although the p55ATNFR had virtually identical affinities for TNF and LT alpha, as defined by Scatchard analysis......Tumor necrosis factor (TNF) and lymphotoxin alpha (LT alpha) are closely related cytokines which bind with nearly identical affinities to the same pair of cell surface receptors, p55 and p75TNFR. Therefore it is assumed that TNF and LT alpha are redundant cytokines. This study, however...

  16. Glycoprotein VI but not alpha2beta1 integrin is essential for platelet interaction with collagen

    DEFF Research Database (Denmark)

    Nieswandt, B; Brakebusch, C; Bergmeier, W


    Platelet adhesion on and activation by components of the extracellular matrix are crucial to arrest post-traumatic bleeding, but can also harm tissue by occluding diseased vessels. Integrin alpha2beta1 is thought to be essential for platelet adhesion to subendothelial collagens, facilitating...... subsequent interactions with the activating platelet collagen receptor, glycoprotein VI (GPVI). Here we show that Cre/loxP-mediated loss of beta1 integrin on platelets has no significant effect on the bleeding time in mice. Aggregation of beta1-null platelets to native fibrillar collagen is delayed......, but not reduced, whereas aggregation to enzymatically digested soluble collagen is abolished. Furthermore, beta1-null platelets adhere to fibrillar, but not soluble collagen under static as well as low (150 s(-1)) and high (1000 s(-1)) shear flow conditions, probably through binding of alphaIIbbeta3 to von...

  17. Two-body interactions in the reaction {sup 9}Be(n,{alpha}{alpha}nn) at 14 MeV. 2. Cross-section measurements; Interactions a deux corps dans la reaction {sup 9}Be(n,{alpha}{alpha}nn) a 14 MeV. 2. Mesure des sections efficaces

    Energy Technology Data Exchange (ETDEWEB)

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


    We measure with a double time of flight spectrometer the momenta k{sub 1} and k{sub 2} of neutrons from the {sup 9}Be(n,nn){alpha}{alpha} reaction at E{sub n} = 14 MeV. After the analysis of corrections factors for the measurement of differential cross-sections, we appraise the importance of different interactions (nn,{sup 8}Be(0+): 1,8 {+-} 0.4 mb/sr{sup 2}, mn{sup 8}Be(2+): 2 {+-} 0,4 mb/sr{sup 2}, n{sup 9}Be, n{sup 8}Be, {alpha}-{alpha}) observed. Our results are compared with those In the literature. (author) [French] On mesure avec un spectrometre a double-temps-de-vol, les impulsions k{sub 1} et k{sub 2} des neutrons de la reaction {sup 9}Be (n,nn){alpha}{alpha} a E{sub n} = 14 MeV. Apres avoir analyse l'ensemble des facteurs de corrections a apporter aux mesures, pour determiner les sections efficaces differentielles, on estime l'importance des differentes interactions (nn{sup 8}Be(0+): 1,8 {+-} 0,4 mb/sr{sup 2}, nn{sup 8}Be(2+); 2 + 0,4 mb/sr{sup 2}, n{sup 9}Be, n{sup 8}Be, {alpha}-{alpha}) observees. Les valeurs obtenues sont ensuite comparees aux resultats anterieurs.

  18. Contribution of AmyA, an extracellular alpha-glucan degrading enzyme, to group A streptococcal host-pathogen interaction. (United States)

    Shelburne, Samuel A; Keith, David B; Davenport, Michael T; Beres, Stephen B; Carroll, Ronan K; Musser, James M


    alpha-Glucans such as starch and glycogen are abundant in the human oropharynx, the main site of group A Streptococcus (GAS) infection. However, the role in pathogenesis of GAS extracellular alpha-glucan binding and degrading enzymes is unknown. The serotype M1 GAS genome encodes two extracellular proteins putatively involved in alpha-glucan binding and degradation; pulA encodes a cell wall anchored pullulanase and amyA encodes a freely secreted putative cyclomaltodextrin alpha-glucanotransferase. Genetic inactivation of amyA, but not pulA, abolished GAS alpha-glucan degradation. The DeltaamyA strain had a slower rate of translocation across human pharyngeal epithelial cells. Consistent with this finding, the DeltaamyA strain was less virulent following mouse mucosal challenge. Recombinant AmyA degraded alpha-glucans into beta-cyclomaltodextrins that reduced pharyngeal cell transepithelial resistance, providing a physiologic explanation for the observed transepithelial migration phenotype. Higher amyA transcript levels were present in serotype M1 GAS strains causing invasive infection compared with strains causing pharyngitis. GAS proliferation in a defined alpha-glucan-containing medium was dependent on the presence of human salivary alpha-amylase. These data delineate the molecular mechanisms by which alpha-glucan degradation contributes to GAS host-pathogen interaction, including how GAS uses human salivary alpha-amylase for its own metabolic benefit.

  19. On RR Couplings, Singularity Structures and all order $\\alpha'$ contact interactions to BPS String Amplitudes

    CERN Document Server

    Hatefi, Ehsan


    We evaluate five point world-sheet string theory amplitudes of one transverse scalar field, two world volume gauge fields ( and two transverse scalars, a gauge field ) in the presence of a closed string Ramond-Ramond vertex operator in its symmetric picture. We carry out all the entire S-matrix elements of five point mixed RR-scalars/gauges $C^{-1}\\phi ^{0}A^{-1} A^{0}$,$C^{-1}\\phi ^{-1}A^{0} A^{0}$, $C^{-1}A^{0}\\phi ^{-1}\\phi^{0} $ and $C^{-1}A^{-1}\\phi ^{0}\\phi^{0} $ in detail and start comparing all order $\\alpha'$ contact interactions and singularities in both transverse and world volume directions. We explore the presence of various new couplings in string theory effective actions and find out their all order $\\alpha'$ higher derivative corrections in both type IIA and IIB. Ultimately we make various remarks for the singularities, contact terms whose RR momenta are embedded in transverse directions, also $\\alpha'$ corrections to some of Myers terms are addressed.

  20. A frequent kinase domain mutation that changes the interaction between PI3K[alpha] and the membrane

    Energy Technology Data Exchange (ETDEWEB)

    Mandelker, Diana; Gabelli, Sandra B.; Schmidt-Kittler, Oleg; Zhu, Jiuxiang; Cheong, Ian; Huang, Chuan-Hsiang; Kinzler, Kenneth W.; Vogelstein, Bert; Amzel, L. Mario; (JHU-MED); (HHMI)


    Mutations in oncogenes often promote tumorigenesis by changing the conformation of the encoded proteins, thereby altering enzymatic activity. The PIK3CA oncogene, which encodes p110{alpha}, the catalytic subunit of phosphatidylinositol 3-kinase alpha (PI3K{alpha}), is one of the two most frequently mutated oncogenes in human cancers. We report the structure of the most common mutant of p110{alpha} in complex with two interacting domains of its regulatory partner (p85{alpha}), both free and bound to an inhibitor (wortmannin). The N-terminal SH2 (nSH2) domain of p85{alpha} is shown to form a scaffold for the entire enzyme complex, strategically positioned to communicate extrinsic signals from phosphopeptides to three distinct regions of p110{alpha}. Moreover, we found that Arg-1047 points toward the cell membrane, perpendicular to the orientation of His-1047 in the WT enzyme. Surprisingly, two loops of the kinase domain that contact the cell membrane shift conformation in the oncogenic mutant. Biochemical assays revealed that the enzymatic activity of the p110{alpha} His1047Arg mutant is differentially regulated by lipid membrane composition. These structural and biochemical data suggest a previously undescribed mechanism for mutational activation of a kinase that involves perturbation of its interaction with the cellular membrane.

  1. Wandering in the Lyman-alpha forest: a study of dark matter-dark radiation interactions (United States)

    Krall, Rebecca; Cyr-Racine, Francis-Yan; Dvorkin, Cora


    The amplitude of large-scale matter fluctuations inferred from the observed Sunyaev-Zeldovich (SZ) cluster mass function and from weak gravitational lensing studies, when taken at face value, is in tension with measurements of the cosmic microwave background (CMB) and baryon acoustic oscillation (BAO). In this work, we revisit whether this possible discrepancy can be attributed to new interactions in the dark matter sector. Focusing on a cosmological model where dark matter interacts with a dark radiation species until the epoch of matter-radiation equality, we find that measurements of the Lyman-alpha flux power spectrum from the Sloan Digital Sky Survey provide no support to the hypothesis that new dark matter interactions can resolve the possible tension between CMB and large-scale structure (LSS). Indeed, while the addition of dark matter-dark radiation interactions leads to an improvement of 2Δ&ln;Script L=12 with respect to the standard Λ cold dark matter (ΛCDM) model when only CMB, BAO, and LSS data are considered, the inclusion of Lyman-alpha data reduces the improvement of the fit to 2Δ&ln;Script L=6 relative to ΛCDM . We thus conclude that the statistical evidence for new dark matter interactions (largely driven by the Planck SZ dataset) is marginal at best, and likely caused by systematics in the data. We also perform a Fisher forecast analysis for the reach of a future dataset composed of a CMB-S4 experiment combined with the Large Synoptic Survey Telescope galaxy survey. We find that the constraint on the effective number of fluid-like dark radiation species, Δ Nfluid, will be improved by an order of magnitude compared to current bounds.

  2. Interaction of alpha-lactalbumin with dimyristoyl phosphatidylcholine vesicles. II. A fluorescence polarization study. (United States)

    Herreman, W; van Tornout, P; van Cauwelaert, F H; Hanssens, I


    The interaction of alpha-lactalbumin with dimyristoyl phosphatidylcholine vesicles was studied as a function of temperature, pH and the molar ratio of phospholipid to protein. The method consisted of measuring the fluorescence polarization of 1,6-diphenyl-1,3,5-hexatriene used as a probe embedded in the vesicles. After incubation of the protein with the phospholipid for 2 h at 23 degrees C, the polarization of the light emitted by this probe shifted to higher values; the shift was greater at acidic pH than at neutral pH. After incubation at 37 degrees C, no shift in polarization was found at pH 7, 6 and 5 while a strong increase occurred at pH 4. Lowering the temperature, after incubation at 37 degrees C, had little effect on the polarization at neutral pH. At pH 5, however, and in the transition range of the phospholipid, the polarization increased greatly. A kinetic study of the interaction carried out around the transition temperature of dimyristoyl phosphatidylcholine as a function of pH shows that the speed of complex formation between alpha-lactalbumin and the lipid increases from neutral to acidic pH. From the present results and in agreement with our earlier calorimetric and fluorescence data (Hanssens, I., Houthuys, C., Herreman, W. and van Cauwelaert, F.H. (1980) Biochim. Biophys, Acta 602, 539--557), it is concluded that at neutral pH the interaction mechanism is probably different from that at acidic pH. At neutral pH and at all temperatures, alpha-lactalbumin is mainly absorbed electrostatically to the outer surface of the vesicle with little or no influence on the transition temperature of the phospholipid. At this pH, only around the transition temperature is penetration possible. At pH 4, however, the protein is able to penetrate the vesicle at all temperatures and to interact hydrophobically with the phospholipid fatty acid chains. As a result of this interaction, the transition temperature is increased by about 4 degrees C. This different

  3. Synergistic interaction of glycoalkaloids alpha-chaconine and alpha-solanine on developmental toxicity in Xenopus embryos. (United States)

    Rayburn, J R; Friedman, M; Bantle, J A


    The embryo toxicities of two major potato glycoalkaloids, alpha-chaconine and alpha-solanine, were examined individually and in mixtures using the frog embryo teratogenesis assay-Xenopus. Calculations of toxic units (TUs) were used to assess possible antagonism, synergism or response addition of several mixtures ranging from approximately 3:1 to 1:20 TUs of alpha-chaconine to alpha-solanine. Some combinations exhibited strong synergism in the following measures of developmental toxicity: (a) 96-hr LC50, defined as the median concentration causing 50% embryo lethality; (b) 96-hr EC50 (malformation), defined as the concentration causing 50% malformation of the surviving embryos; and (c) teratogenic index which is equal to LC50/EC50 (malformation). The results indicated that each of the mixtures caused synergistic mortality or malformation. Furthermore, these studies suggested that the synergism observed for a specific mixture cannot be used to predict possible synergism of other mixtures with different ratios of the two glycoalkaloids; toxicities observed for individual glycoalkaloids may not be able to predict toxicities of mixtures; and specific combinations found in different potato varieties need to be tested to assess the safety of a particular cultivar.

  4. Frontal alpha oscillations distinguish leaders from followers: Multivariate decoding of mutually interacting brains

    DEFF Research Database (Denmark)

    Konvalinka, Ivana; Bauer, Markus; Stahlhut, Carsten


    Successful social interactions rely upon the abilities of two or more people to mutually exchange information in real-time, while simultaneously adapting to one another. The neural basis of social cognition has mostly been investigated in isolated individuals, and more recently using two-person p......Successful social interactions rely upon the abilities of two or more people to mutually exchange information in real-time, while simultaneously adapting to one another. The neural basis of social cognition has mostly been investigated in isolated individuals, and more recently using two...... task anticipation and execution, such that only one member showed the frontal component. Analysis of the behavioral data showed that this distinction coincided with the leader–follower relationship in 8/9 pairs, with the leaders characterized by the stronger frontal alpha-suppression. This suggests...... that leaders invest more resources in prospective planning and control. Hence our results show that the spontaneous emergence of leader–follower relationships in dyadic interactions can be predicted from EEG recordings of brain activity prior to and during interaction. Furthermore, this emphasizes...

  5. Cytochrome c interaction with hematite ({alpha}-Fe{sub 2}O{sub 3}) surfaces

    Energy Technology Data Exchange (ETDEWEB)

    Eggleston, Carrick M. [Department of Geology and Geophysics, University of Wyoming, Laramie, WY 82071 (United States)]. E-mail:; Khare, Nidhi [Department of Geology and Geophysics, University of Wyoming, Laramie, WY 82071 (United States); Lovelace, David M. [Department of Geology and Geophysics, University of Wyoming, Laramie, WY 82071 (United States)


    The interaction of metalloproteins such as cytochromes with oxides is of interest for a number of reasons, including molecular catalysis of environmentally important mineral-solution electron transfer reactions (e.g., dehalogenations) and photovoltaic applications. Iron reduction by bacteria, thought to be cytochrome mediated, is of interest for geochemical and environmental remediation reasons. As a baseline for understanding cytochrome interaction with ferric oxide surfaces, we report on the interaction of mitochondrial cytochrome c (Mcc), a well-studied protein, with hematite ({alpha}-Fe{sub 2}O{sub 3}) surfaces. Mcc sorbs strongly to hematite from aqueous solution in a narrow pH range corresponding to opposite charge on Mcc and hematite (between pH 8.5 and 10, Mcc is positively charged and hematite surfaces are negatively charged). Cyclic voltammetry of Mcc using hematite electrodes gives redox potentials characteristic of Mcc in a native conformational state, with no evidence for unfolding on the hematite surface. Atomic force microscopy imaging is consistent with a loosely attached adsorbate that is easily deformed by the AFM tip. In phosphate-containing solution, Mcc adhers to the surface more strongly. These results establish hematite as a viable material for electrochemical and spectroscopic characterization of cytochrome-mineral interaction.

  6. Relativistic electron beam interaction and $K_{\\alpha}$-generation in solid targets

    CERN Document Server

    Fill, E; Eder, D; Eidmann, K; Saemann, A


    When fs laser pulses interact with solid surfaces at intensities I lambda /sup 2/ >10/sup 18/ W/cm/sup 2/ mu m/sup 2/, collimated relativistic electron beams are generated. These electrons can be used for producing intense X-radiation (bremsstrahlung or K/sub alpha /) for pumping an innershell X-ray laser. The basic concept of such a laser involves the propagation of the electron beam in a material which converts electron energy into appropriate pump photons. Using the ATLAS titanium-sapphire laser at Max-Planck-Institut fur Quantenoptik, we investigate the generation of hot electrons and of characteristic radiation in copper. The laser (200 mJ/130 fs) is focused by means of an off-axis parabola to a diameter of about 10 mu m. By varying the position of the focus, we measure the copper K/sub alpha /-yield as a function of intensity in a range from 10/sup 15/ to 2 x 10/sup 18/ W/cm/sup 2/ while keeping the laser pulse energy constant. Surprisingly, the highest emission is obtained at an intensity of about 10/s...

  7. On the interaction between radiation-induced defects and foreign interstitial atoms in {alpha}-iron

    Energy Technology Data Exchange (ETDEWEB)

    Nikolaev, Alexander L., E-mail: [Institute of Metal Physics, Russian Academy of Sciences Ural Branch 18, S. Kovalevskaya St., Ekaterinburg 620990 (Russian Federation); Kurennykh, Tatiana E. [Institute of Metal Physics, Russian Academy of Sciences Ural Branch 18, S. Kovalevskaya St., Ekaterinburg 620990 (Russian Federation)


    Interaction between Frenkel pair (FP) defects and nitrogen atoms in {alpha}-iron has been investigated by means of resistivity recovery method. Both FP defects are attracted to nitrogen atoms. Dissociation of self-interstitial atoms from nitrogen atoms is observed at 165 K while that of vacancies at 250 K. The binding energies of FP defects with nitrogen are both about 0.1-0.15 eV. A weak RR stage is observed at 340 K assigned to the presence of carbon in concentration of about 1 appm. Analysis of its features leads to a conclusion on a dissociation (binding) energy of vacancy-carbon atom pairs of about 0.9 (0.35) eV.

  8. TIP30 interacts with an estrogen receptor alpha-interacting coactivator CIA and regulates c-myc transcription. (United States)

    Jiang, Chao; Ito, Mitsuhiro; Piening, Valerie; Bruck, Kristy; Roeder, Robert G; Xiao, Hua


    Deregulation of c-myc expression is implicated in the pathogenesis of many neoplasias. Estrogen receptor alpha (ERalpha) can increase the rate of c-myc transcription through the recruitment of a variety of cofactors to the promoter, yet the precise roles of these cofactors in transcription and tumorigenesis are largely unknown. We show here that a putative tumor suppressor TIP30, also called CC3 or Htatip2, interacts with an ERalpha-interacting coactivator CIA. Using chromatin immunoprecipitation assays, we demonstrate that TIP30 and CIA are distinct cofactors that are dynamically associated with the promoter and downstream regions of the c-myc gene in response to estrogen. Both TIP30 and CIA are recruited to the c-myc gene promoter by liganded ERalpha in the second transcription cycle. TIP30 overexpression represses ERalpha-mediated c-myc transcription, whereas TIP30 deficiency enhances c-myc transcription in both the absence and presence of estrogen. Ectopic CIA cooperates with TIP30 to repress ERalpha-mediated c-myc transcription. Moreover, virgin TIP30 knockout mice exhibit increased c-myc expression in mammary glands. Together, these results reveal an important role for TIP30 in the regulation of ERalpha-mediated c-myc transcription and suggest a mechanism for tumorigenesis promoted by TIP30 deficiency.

  9. Two-source emission of relativistic alpha particles in 16O-Em interactions at 3.7 A GeV

    Institute of Scientific and Technical Information of China (English)

    Song Fu; Zhang Dong-Hai; Li Jun-Sheng


    The emission of alpha projectile fragments has been studied in 16O-emulsion interactions at 3.7 A GeV. The angular distributions of relativistic alphas cannot be explained by a clean-cut participant-spectator model. Therefore it is assumed that alphas originate from two distinct sources differing in their temperatures.

  10. Interaction of retinal guanylate cyclase with the alpha subunit of transducin: potential role in transducin localization. (United States)

    Rosenzweig, Derek H; Nair, K Saidas; Levay, Konstantin; Peshenko, Igor V; Crabb, John W; Dizhoor, Alexander M; Slepak, Vladlen Z


    Vertebrate phototransduction is mediated by cGMP, which is generated by retGC (retinal guanylate cyclase) and degraded by cGMP phosphodiesterase. Light stimulates cGMP hydrolysis via the G-protein transducin, which directly binds to and activates phosphodiesterase. Bright light also causes relocalization of transducin from the OS (outer segments) of the rod cells to the inner compartments. In the present study, we show experimental evidence for a previously unknown interaction between G(alphat) (the transducin alpha subunit) and retGC. G(alphat) co-immunoprecipitates with retGC from the retina or from co-transfected COS-7 cells. The retGC-G(alphat) complex is also present in cones. The interaction also occurs in mice lacking RGS9 (regulator of G-protein signalling 9), a protein previously shown to associate with both G(alphat) and retGC. The G(alphat)-retGC interaction is mediated primarily by the kinase homology domain of retGC, which binds GDP-bound G(alphat) stronger than the GTP[S] (GTPgammaS; guanosine 5'-[gamma-thio]triphosphate) form. Neither G(alphat) nor G(betagamma) affect retGC-mediated cGMP synthesis, regardless of the presence of GCAP (guanylate cyclase activating protein) and Ca2+. The rate of light-dependent transducin redistribution from the OS to the inner segments is markedly accelerated in the retGC-1-knockout mice, while the migration of transducin to the OS after the onset of darkness is delayed. Supplementation of permeabilized photoreceptors with cGMP does not affect transducin translocation. Taken together, these results suggest that the protein-protein interaction between G(alphat) and retGC represents a novel mechanism regulating light-dependent translocation of transducin in rod photoreceptors.

  11. Children's cortisol and salivary alpha-amylase interact to predict attention bias to threatening stimuli. (United States)

    Ursache, Alexandra; Blair, Clancy


    Physiological responses to threat occur through both the autonomic nervous system (ANS) and the hypothalamic pituitary adrenal (HPA) axis. Activity in these systems can be measured through salivary alpha-amylase (sAA) and salivary cortisol, respectively. Theoretical work and empirical studies have suggested the importance of examining the coordination of these systems in relation to cognitive functioning and behavior problems. Less is known, however, about whether these systems interactively predict more automatic aspects of attention processing such as attention toward emotionally salient threatening stimuli. We used a dot probe task to assess attention bias toward threatening stimuli in 347 kindergarten children. Cortisol and sAA were assayed from saliva samples collected prior to children's participation in assessments on a subsequent day. Using regression analyses, we examined relations of sAA and cortisol to attention bias. Results indicate that cortisol and sAA interact in predicting attention bias. Higher levels of cortisol predicted greater bias toward threat for children who had high levels of sAA, but predicted greater bias away from threat for children who had low levels of sAA. These results suggest that greater symmetry in HPA and ANS functioning is associated with greater reliance on automatic attention processes in the face of threat.

  12. DNA homologous recombination factor SFR1 physically and functionally interacts with estrogen receptor alpha.

    Directory of Open Access Journals (Sweden)

    Yuxin Feng

    Full Text Available Estrogen receptor alpha (ERα, a ligand-dependent transcription factor, mediates the expression of its target genes by interacting with corepressors and coactivators. Since the first cloning of SRC1, more than 280 nuclear receptor cofactors have been identified, which orchestrate target gene transcription. Aberrant activity of ER or its accessory proteins results in a number of diseases including breast cancer. Here we identified SFR1, a protein involved in DNA homologous recombination, as a novel binding partner of ERα. Initially isolated in a yeast two-hybrid screen, the interaction of SFR1 and ERα was confirmed in vivo by immunoprecipitation and mammalian one-hybrid assays. SFR1 co-localized with ERα in the nucleus, potentiated ER's ligand-dependent and ligand-independent transcriptional activity, and occupied the ER binding sites of its target gene promoters. Knockdown of SFR1 diminished ER's transcriptional activity. Manipulating SFR1 expression by knockdown and overexpression revealed a role for SFR1 in ER-dependent and -independent cancer cell proliferation. SFR1 differs from SRC1 by the lack of an intrinsic activation function. Taken together, we propose that SFR1 is a novel transcriptional modulator for ERα and a potential target in breast cancer therapy.

  13. Interaction of alpha-thrombin and prethrombin 2, with phosphatidylserine-containing monolayers. (United States)

    Lecompte, M F


    Prothrombin activation complex is located at a phospholipid surface on activated platelets. To see whether the thrombin domain of the molecule plays a role in the interaction with lipids, we investigated the direct interaction of human alpha-thrombin and its precursor prethrombin 2 with phospholipid monolayers of various compositions (PS/PC). Adsorption of the labeled proteins was determined by surface radioactivity measurements. Penetration of the proteins in the lipid layer was inferred from capacitance variation of the monolayer, measured by a.c. polarography. Disulfide bridges reduced at the electrode were determined by cyclic voltametry. In all the cases studied, although in different manners thrombin was found both to adsorb and penetrate the lipid layer, whereas prethrombin 2 did not penetrate pure phosphatidylcholine (PC). In the case of thrombin, but not of prethrombin 2, penetration is accompanied by S-S reduction which is maximum at 10 per cent of phosphatidylserine (PS). This indicates a different orientation for prethrombin 2 and thrombin in the lipid layer. This observation might be of importance for the comprehension of the architecture of the prothrombin activation complex and for the regulation of thrombin formation within the complex.

  14. The Effects of Pooling the Interaction and Within Components on the Alpha and Power for Main Effects Tests. (United States)

    Pohlmann, John T.

    The Monte Carlo method was used, and the factors considered were (1) level of main effects in the population; (2) level of interaction effects in the population; (3) alpha level used in determining whether to pool; and (4) number of degrees of freedom. The results indicated that when the ratio degrees of freedom (axb)/degrees of freedom (within)…


    The ability of several 4- and 5-ring polycyclic aromatic hydrocarbons (PAHs), heterocyclic PAHs, and their monohydroxy derivatives to interact with the estrogen receptor (ER) alpha and beta isoforms was examined. Only compounds possessing a hydroxyl group were able to compete wit...

  16. Molecular understanding of copper and iron interaction with alpha-synuclein by fluorescence analysis. (United States)

    Bharathi; Rao, K S J


    Alpha-synuclein aggregation is a hallmark pathological feature in Parkinson's disease (PD). The conversion of alpha-synuclein from a soluble monomer to an insoluble fibril may underlie the neurodegeneration associated with PD. Redox-active metal ions such as iron (Fe) and copper (Cu) are known to enhance alpha-synuclein fibrillogenesis. In the present investigation, we analyzed the binding efficiency of Cu and Fe to alpha-synuclein by fluorescence studies. It is interesting to note that Cu and Fe showed differential binding pattern toward alpha-synuclein (wild type and A30P, A53T, and E46K mutant forms) as revealed by intrinsic tyrosine fluorescence, thioflavin-T fluorescence, 1-anilino-8-naphthalenesulfonate-binding studies, and scatchard plot analysis. The experimental data might prove useful in understanding the hierarchy of metals binding to alpha-synuclein and its role in neurodegeneration.

  17. Trypanosoma cruzi: cruzipain and membrane-bound cysteine proteinase isoform(s) interacts with human alpha(2)-macroglobulin and pregnancy zone protein. (United States)

    Ramos, Adrián M; Duschak, Vilma G; Gerez de Burgos, Nelia M; Barboza, Mariana; Remedi, María S; Vides, Miguel A; Chiabrando, Gustavo A


    Plasmatic levels of pregnancy zone protein (PZP) increase in children with acute Chagas disease. PZP, as well as alpha2-macroglobulin (alpha2-M), are able to interact with Trypanosoma cruzi proteinases. The interaction of alpha2-M and PZP with cruzipain, the major cysteine proteinase of T. cruzi, was investigated. Several molecular changes on both alpha-M inhibitors under reaction with cruzipain were found. PAGE analysis showed: (i) formation of complexes of intermediate mobility and tetramerization of native alpha2-M and PZP, respectively; (ii) limited proteolysis of bait region in alpha2-M and PZP, and (iii) covalent binding of cruzipain to PZP and alpha2-M. Conformational and structural changes experimented by alpha-Ms correlate with modifications of the enzyme electrophoretic mobility and activity. Cruzipain-alpha-M complexes were also detected by gelatin SDS-PAGE and immunoblotting using polyclonal anti-cruzipain antibodies. Concomitantly, alpha2-M and PZP impaired the activity of cruzipain towards Bz-Pro-Phe-Arg-pNA substrate. In addition, alpha-Ms were able to form covalent complexes with membrane isoforms of cysteine proteinases cross-reacting with cruzipain. The present study suggests that both human alpha-macroglobulin inhibitors could prevent or minimize harmful action of cruzipain on host's molecules and hypothetically regulate parasite functions controlled by cruzipain.

  18. Remarks on Non-BPS String Amplitudes and their all Order $\\alpha'$ Contact Interactions

    CERN Document Server

    Hatefi, Ehsan


    We explore the entire form of S-Matrix elements of an antisymmetric potential $C_{n-1}$ Ramond-Ramond (RR) form field, a tachyon and two transverse scalar fields on both world volume and transverse directions of type IIB (IIA) superstring theory. Apart from $$, the other symmetric picture $$ is also revealed. We then start to compare all singularity structures of symmetric and asymmetric analysis, generating all infinite singularity structures as well as all order $\\alpha'$ contact interactions on the whole directions. This leads to deriving various new contact terms and several new restricted Bianchi identities. It is also shown that just some of the new couplings of type IIB (IIA) string theory can be re-verified in an Effective Field Theory (EFT) by pull-back of branes, while to construct the rest of S-matrix elements one needs to first derive restricted world volume (or bulk) Bianchi identities and then start discovering new EFT couplings. Finally the presence of commutator of scalar fields inside the exp...

  19. A quantitative approach to the free radical interaction between alpha-tocopherol or ascorbate and flavonoids. (United States)

    Fujisawa, Seiichiro; Ishihara, Mariko; Atsumi, Toshiko; Kadoma, Yoshinori


    Despite numerous previous studies, the mechanism of the free radical interaction between alpha-tocopherol (VE), or ascorbate and flavonoids, as coantioxidants remains unclear. The synergistic antioxidant effects of VE or L-ascorbyl 2,6-dibutyrate (ASDB, an ascorbate derivative) with the flavonoids (-)-epicatechin (EC), (-)-epigallocatechin (EGC), (-)-epicatechin gallate (ECG) and (-)-epigallocatechin gallate (EGCG) and methyl gallate (MG), were investigated by the induction period method in the polymerization of methyl methacrylate (MMA), initiated by thermal decomposition of 2,2'-azobis(isobutyronitrile) (an alkyl radical, R *), under nearly anaerobic conditions. For VE, a synergistic antioxidant effect was observed with MG, EC, EGC and ECG, whereas this activity was decreased by the addition of EGCG. For ASDB, a synergistic antioxidant effect was observed with EGC and ECG, whereas this activity was decreased by the addition of EGCG or MG. A synergistic antioxidant effect (regeneration of VE) appears to be feasible even though the BDE (phenolic O-H bond dissociation entropy) of the coantioxidants is significantly higher than that of VE. The driving force for the regeneration process may be the removal of the semiquinone radical from the flavonoids MG, EC, EGC and ECG by the VE radical. In the ASDB/flavonoid mixture, flavonoid radicals are scavenged by ASDB. The partial regeneration of flavonoids by ASDB may follow a similar recycling mechanism to that of the well-known VE/ascorbate mixture. The free radical interaction between EGCG and VE or ASDB decreased the antioxidant effect. Such enhancement of prooxidation in EGCG/VE or EGCG/ASDB mixtures oxidized by R * may increase their cytotoxic effects.

  20. No need to be HAMLET or BAMLET to interact with histones: binding of monomeric alpha-lactalbumin to histones and basic poly-amino acids. (United States)

    Permyakov, Serge E; Pershikova, Irina V; Khokhlova, Tatyana I; Uversky, Vladimir N; Permyakov, Eugene A


    The ability of a specific complex of human alpha-lactalbumin with oleic acid (HAMLET) to induce cell death with selectivity for tumor and undifferentiated cells was shown recently to be mediated by interaction of HAMLET with histone proteins irreversibly disrupting chromatin structure [Duringer, C., et al. (2003) J. Biol. Chem. 278, 42131-42135]. Here we show that monomeric alpha-lactalbumin (alpha-LA) in the absence of fatty acids is also able to bind efficiently to the primary target of HAMLET, histone HIII, regardless of Ca(2+) content. Thus, the modification of alpha-LA by oleic acid is not required for binding to histones. We suggest that interaction of negatively charged alpha-LA with the basic histone stabilizes apo-alpha-LA and destabilizes the Ca(2+)-bound protein due to compensation for excess negative charge of alpha-LA's Ca(2+)-binding loop by positively charged residues of the histone. Spectrofluorimetric curves of titration of alpha-LA by histone H3 were well approximated by a scheme of cooperative binding of four alpha-LA molecules per molecule of histone, with an equilibrium dissociation constant of 1.0 microM. Such a stoichiometry of binding implies that the binding process is not site-specific with respect to histone and likely is driven by just electrostatic interactions. Co-incubation of positively charged poly-amino acids (poly-Lys and poly-Arg) with alpha-LA resulted in effects which were similar to those caused by histone HIII, confirming the electrostatic nature of the alpha-LA-histone interaction. In all cases that were studied, the binding was accompanied by aggregation. The data indicate that alpha-lactalbumin can be used as a basis for the design of antitumor agents, acting through disorganization of chromatin structure due to interaction between alpha-LA and histone proteins.

  1. Interaction of iodine with 2-hydroxypropyl-alpha-cyclodextrin and its bactericidal activity. (United States)

    Tomono, K; Goto, H; Suzuki, T; Ueda, H; Nagai, T; Watanabe, J


    To obtain an effective iodine solution, the use of 2-hydroxypropyl-alpha-cyclodextrin (2-HP-alpha-CD) as solubilizer was examined in comparison with alpha-cyclodextrin (alpha-CD), beta-cyclodextrin (beta-CD), potassium iodide (KI), and polyvinylpyrrolidone (PVP). The stability constants for inclusion of iodine with cyclodextrin and KI were ascertained by the solubility method. The apparent stability constants increased in the following order: KI stabilization ability. The largest volatile depression effect was exhibited by 2HP-alpha-CD. The measurement of the minimum inhibitory concentration (MC) using Escherichia coli NIH-J-2 and Staphylococcus aureus FDA209P suggested that the bactericidal activity of the iodine/2-HP-alpha-CD system was the same as that of the iodine/alpha-CD, iodine/beta-CD, and iodine/PVP systems. The present results suggest that the combination of 2-HP-alpha-CD and iodine is useful for a stable and effective iodine solution.

  2. Interactions between different EEG frequency bands and their effect on alpha-fMRI correlations

    NARCIS (Netherlands)

    de Munck, J.C.; Gonçalves, S.I.; Mammoliti, R.; Heethaar, R.M.; Lopes da Silva, F.H.


    In EEG/fMRI correlation studies it is common to consider the fMRI BOLD as filtered version of the EEG alpha power. Here the question is addressed whether other EEG frequency components may affect the correlation between alpha and BOLD. This was done comparing the statistical parametric maps (SPMs)

  3. alpha-lactalbumin-AOT charge interactions tune phase structures in isooctane/brine mixtures. (United States)

    Kim, Jun Y; Dungan, Stephanie R


    Self-assembly of the anionic surfactant AOT with the protein alpha-lactalbumin in isooctane/brine mixtures results in phase structures whose type, size, and shape differ considerably from those formed by the surfactant alone. Small-angle X-ray scattering was used to determine the size and shape of these structures for 5.4 < pH < 11.2 and 0.25, 0.33, and 0.4 wt % NaCl. All pH values were above the reported isoelectric point for the protein. The composition of the system (except for salt) was fixed, with 2.5 wt % surfactant in equivolume mixtures of oil and water and either 0 or 0.4 wt % protein. Under these conditions, AOT in the absence of protein always formed spherical, water-in-oil (w/o) microemulsion droplets in the organic phase with no self-assembly in the aqueous phase. In the presence of alpha-lactalbumin, self-assembled structures were formed in both aqueous and organic phases, and the size and shape of these was tuned by both pH and [NaCl]. Protein-surfactant interaction was weakest at the most alkaline pH, with protein-free, spherical droplets forming in the organic phase and surfactant-decorated soluble protein clusters forming in the aqueous phase. As pH was decreased, protein increasingly partitioned to the organic phase and droplets became ellipsoidal and much larger in volume, with these effects enhanced at lower salt concentration. Aqueous structures were also strongly affected by pH, shifting from prolate protein/surfactant aggregates at alkaline pH to oil-in-water, oblate microemulsion droplets at neutral pH. At acidic pH and higher salt concentration, self-assembly shifted toward a third, anisotropic aqueous phase, which contained discoid bilayer structures. It is proposed that hydrophobic attraction causes association of the protein with the surfactant monolayer, and pH and [salt] tune the system via the protein by modifying electrostatic repulsion and monolayer curvature.

  4. Mannan-binding protein forms complexes with alpha-2-macroglobulin. A protein model for the interaction

    DEFF Research Database (Denmark)

    Storgaard, P; Holm Nielsen, E; Skriver, E;


    We report that alpha-2-macroglobulin (alpha 2M) can form complexes with a high molecular weight porcine mannan-binding protein (pMBP-28). The alpha 2M/pMBP-28 complexes was isolated by PEG-precipitation and affinity chromatography on mannan-Sepharose, protein A-Sepharose and anti-IgM Sepharose......-PAGE, which reacted with antibodies against alpha 2M and pMBP-28, respectively, in Western blotting. Furthermore, alpha 2M/pMBP-28 complexes were demonstrated by electron microscopy. Fractionation of pMBP-containing D-mannose eluate from mannan-Sepharose on Superose 6 showed two protein peaks which reacted...

  5. Transcription factors interacting with herpes simplex virus alpha gene promoters in sensory neurons. (United States)

    Hagmann, M; Georgiev, O; Schaffner, W; Douville, P


    Interference with VP16-mediated activation of herpes virus immediate-early (or alpha) genes is thought to be the major cause of establishing viral latency in sensory neurons. This could be brought about by lack of a key activating transcription factor(s) or active repression. In this study we find that sensory neurons express all important components for VP16-mediated alpha gene induction, such as the POU transcription factor Oct-1, host cell factor (HCF) and GABP alpha/beta. However, Oct-1 and GABP alpha/beta are only present at low levels and the VP16-induced complex (VIC) appears different. We do not find protein expression of the transcription factor Oct-2, implicated by others as an alpha gene repressor. The POU factor N-Oct3 (Brn 2 or POU3F2) is also present in sensory neurons and binds viral TAATGARAT motifs with higher affinity than Oct-1, indicating that it may be a candidate repressor for competitive binding to TAATGARAT motifs. When transfected into HeLa cells, where Oct-1 and GABP alpha/beta are highly abundant, N-Oct3 represses model promoters with multimerized TAATGARAT motifs, but fails to repress complete alpha gene promoters. Taken together our findings suggest that modulation of alpha gene promoters could contribute to viral latency when low concentrations of the activating transcription factors Oct-1 and GABP alpha/beta prevail. Our data, however, refute the notion that competing Oct factors are able to block alpha gene transcription to achieve viral latency. Images PMID:8559654

  6. Effect of alpha-lactalbumin on the phase behavior of AOT-brine-isooctane mixtures: role of charge interactions. (United States)

    Shimek, Justin W; Rohloff, Catherine M; Goldberg, Jessica; Dungan, Stephanie R


    We have found that both electrostatic and hydrophobic interactions are involved in the ability of the protein alpha-lactalbumin (alpha-LA) to affect the self-assembly of the anionic surfactant sodium bis(ethylhexyl) sulfosuccinate (AOT, 3.5 wt %) in equivolume mixtures of organic and aqueous solutions. The composition and size of AOT phase structures that form in the presence of 0.35 wt % protein were evaluated as a function of pH and ionic strength. In the absence of protein, AOT forms water-in-oil microemulsion droplets for all pH and salt concentrations studied here. The presence of the protein in the water-in-oil microemulsion phase boosts water solubilization and droplet size, as the spontaneous curvature of the surfactant interface becomes less negative. Aggregates of protein, surfactant, and oil also form in the water-continuous phase. The size and composition of structures in both phases can be tuned in the presence of protein by varying the pH and ionic strength. alpha-LA induces the appearance of an anisotropic surfactant phase at pH <5.8. At intermediate salt concentrations, a third isotropic, viscous aqueous phase appears that contains 55-60% of the protein, 10-14% of the surfactant, and significant amounts of oil. Circular dichroism and fluorescence spectroscopy indicate that the protein contains enhanced alpha-helical secondary structure when self-assembling with surfactant, and has a loosened tertiary structure. The protein does not interact with the surfactant as an unfolded random coil. Although the conformation of alpha-LA in aqueous salt solutions is known to depend on pH, when self-assembling with AOT the protein adopts a structure whose features are quite pH insensitive, and likely reflect an intrinsic interaction with the interface.

  7. Interaction of NGC 2276 with the NGC 2300 group - Fabry-Perot observations of the H-alpha velocity field (United States)

    Gruendl, Robert A.; Vogel, Stuart N.; Davis, David S.; Mulchaey, John S.


    We report kinematic observations of H-alpha emission from the spiral galaxy NGC 2276 obtained with a Fabry-Perot Camera. The 'bow shock' appearance and enhanced star formation in NGC 2276 have been attributed by Mulchaey et al. (1993) to a ram-pressure interaction with the dense IGM detected in ROSAT observations of the NGC 2300 group of galaxies. Along the 'bow shock' limb of the galaxy, we observe strong H-alpha emission and significant kinematic perturbations located immediately interior to an abrupt decrease in the scale length of the optical disk. Although ram-pressure forces may be important in the evolution of the outer gaseous disk, the peculiar kinematics and the truncation in the stellar disk are difficult to explain in a ram-pressure model; a more likely cause is tidal interaction, probably with the elliptical galaxy NGC 2300.

  8. Children’s cortisol and salivary alpha-amylase interact to predict attention bias to threatening stimuli


    Ursache, Alexandra; Blair, Clancy


    Physiological responses to threat occur through both the autonomic nervous system (ANS) and the hypothalamic pituitary adrenal (HPA) axis. Activity in these systems can be measured through salivary alpha-amylase (sAA) and salivary cortisol, respectively. Theoretical work and empirical studies have suggested the importance of examining the coordination of these systems in relation to cognitive functioning and behavior problems. Less is known, however, about whether these systems interactively ...

  9. The evaluation of the caveolin-1 and AT-rich interactive domain 1 alpha expressions in uterine smooth muscle tumors



    Objectives: This retrospective study was designed to evaluate the importance of tissue expressions of caveolin-1 (Cav-1) and AT-rich interactive domain 1 alpha (ARID-1A) which are known as signal regulator and tumor suppressor in differential diagnosis of uterine smooth muscle tumors (SMTs). Materials and Methods: Thirty patients recently diagnosed as uterine SMTs at the Tepecik Training and Research Hospital were identified using pathology databases. Immunohistochemical stains for Cav-1 and ...

  10. The Crystal Water Affect in the Interaction between the Tenebrio Molitor Alpha-Amylase and Its Inhibitor

    Directory of Open Access Journals (Sweden)

    Zhu Zhi-Fei


    Full Text Available Molecular dynamics simulation of the interaction between the Tenebrio molitor alpha-amylase and its inhibitor at different proportion of crystal water was carried out with OPLS force field by hyperchem 7.5 software. In the correlative study, the optimal temperature of wheat monomeric and dimeric protein inhibitors was from 273 K to 318 K. The the average temperature of experimentation is 289 K. (1 The optimal temperature of interaction between alpha-amylase and its inhibitors was 280 K without crystal water that was close to the results of experimentation. The forming of enzyme-water and inhibitor-water was easy, but incorporating third monomer was impossible. (2 Having analyzed the potential energy data, the optimal temperature of interaction energy between alpha-amylase and its inhibitors covering 9 : 1, 5 : 5, 4 : 6, and 1 : 9 proportion crystal water was 290 K. (3 We compared the correlative QSAR properties. The proportion of crystal water was close to the data of polarizability (12.4% in the QSAR properties. The optimal temperature was 280 K. This result was close to 289 K. These findings have theoretical and practical implications.

  11. Effect of peroxisome proliferator-activated receptor-alpha ligands in the interaction between adipocytes and macrophages in obese adipose tissue. (United States)

    Toyoda, Takuya; Kamei, Yasutomi; Kato, Hirotsugu; Sugita, Satoshi; Takeya, Motohiro; Suganami, Takayoshi; Ogawa, Yoshihiro


    This study was designed to examine the effect of peroxisome proliferator-activated receptor-alpha (PPAR-alpha) ligands on the inflammatory changes induced by the interaction between adipocytes and macrophages in obese adipose tissue. PPAR-alpha ligands (Wy-14,643 and fenofibrate) were added to 3T3-L1 adipocytes, RAW264 macrophages, or co-culture of 3T3-L1 adipocytes and RAW264 macrophages in vitro, and monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-alpha (TNF-alpha) mRNA expression and secretion were examined. PPAR-alpha ligands were administered to genetically obese ob/ob mice for 2 weeks. Moreover, the effect of PPAR-alpha ligands was also evaluated in the adipose tissue explants and peritoneal macrophages obtained from PPAR-alpha-deficient mice. In the co-culture of 3T3-L1 adipocytes and RAW264 macrophages, PPAR-alpha ligands reduced MCP-1 and TNF-alpha mRNA expression and secretion in vitro relative to vehicle-treated group. The anti-inflammatory effect of Wy-14,643 was observed in adipocytes treated with macrophage-conditioned media or mouse recombinant TNF-alpha and in macrophages treated with adipocyte-conditioned media or palmitate. Systemic administration of PPAR-alpha ligands inhibited the inflammatory changes in adipose tissue from ob/ob mice. Wy-14,643 also exerted an anti-inflammatory effect in the adipose tissue explants but not in peritoneal macrophages obtained from PPAR-alpha-deficient mice. This study provides evidence for the anti-inflammatory effect of PPAR-alpha ligands in the interaction between adipocytes and macrophages in obese adipose tissue, thereby improving the dysregulation of adipocytokine production and obesity-related metabolic syndrome.

  12. Alpha5beta1 integrin-fibronectin interactions specify liquid to solid phase transition of 3D cellular aggregates.

    Directory of Open Access Journals (Sweden)

    Carlos E Caicedo-Carvajal

    Full Text Available BACKGROUND: Tissue organization during embryonic development and wound healing depends on the ability of cells on the one hand to exchange adhesive bonds during active rearrangement and on the other to become fixed in place as tissue homeostasis is reached. Cells achieve these contradictory tasks by regulating either cell-cell adhesive bonds, mediated by cadherins, or cell-extracellular matrix (ECM connections, regulated by integrins. Integrin alpha5beta1 and soluble fibronectin (sFN are key players in cell-ECM force generation and in ECM polymerization. Here, we explore the interplay between integrin alpha5beta1 and sFN and its influence on tissue mechanical properties and cell sorting behavior. METHODOLOGY/PRINCIPAL FINDINGS: We generated a series of cell lines varying in alpha5beta1 receptor density. We then systematically explored the effects of different sFN concentrations on aggregate biomechanical properties using tissue surface tensiometry. We found previously unreported complex behaviors including the observation that interactions between fibronectin and integrin alpha5beta1 generates biphasic tissue cohesion profiles. Specifically, we show that at constant sFn concentration, aggregate cohesion increases linearly as alpha5beta1 receptor density is increased from low to moderate levels, producing a transition from viscoelastic-liquid to pseudo viscoelastic-solid behavior. However, further increase in receptor density causes an abrupt drop in tissue cohesion and a transition back to viscoelastic-liquid properties. We propose that this may be due to depletion of sFn below a critical value in the aggregate microenvironment at high alpha5beta1 levels. We also show that differential expression of alpha5beta1 integrin can promote phase-separation between cells. CONCLUSIONS/SIGNIFICANCE: The interplay between alpha5-integrin and sFn contributes significantly to tissue cohesion and, depending on their level of expression, can mediate a shift


    NARCIS (Netherlands)



    5-Fluorouracil (5-FU) activity has been improved by the use of leucovorin (LV) or alpha-2a interferon (alpha-IF). We investigated the feasibility and activity of addition of alpha-IF to a 5-FU/LV regimen. A phase I study with 26 patients (14 previously untreated, 12 previously treated) with dissemin

  14. Hard spectator interactions in B {yields} {pi}{pi} at order {alpha}{sup 2}{sub s}

    Energy Technology Data Exchange (ETDEWEB)

    Pilipp, V.


    In the present thesis I discuss the hard spectator interaction amplitude in B {yields} {pi}{pi} at NLO i.e. at O({alpha}{sup 2}{sub s}). This special part of the amplitude, whose LO starts at O({alpha}{sub s}), is defined in the framework of QCD factorization. QCD factorization allows to separate the short- and the long-distance physics in leading power in an expansion in {lambda}{sub QCD}/m{sub b}, where the short-distance physics can be calculated in a perturbative expansion in {alpha}{sub s}. Compared to other parts of the amplitude hard spectator interactions are formally enhanced by the hard collinear scale {radical}({lambda}{sub QCD}m{sub b}), which occurs next to the mb-scale and leads to an enhancement of {alpha}{sub s}. From a technical point of view the main challenges of this calculation are due to the fact that we have to deal with Feynman integrals that come with up to five external legs and with three independent ratios of scales. These Feynman integrals have to be expanded in powers of {delta}{sub QCD}/m{sub b}. I discuss integration by parts identities to reduce the number of master integrals and differential equations techniques to get their power expansions. A concrete implementation of integration by parts identities in a computer algebra system is given in the appendix. Finally I discuss numerical issues like scale dependence of the amplitudes and branching ratios. It turns out that the NLO contributions of the hard spectator interactions are important but small enough for perturbation theory to be valid. (orig.)

  15. Hard spectator interactions in B {yields} {pi}{pi} at order {alpha}{sup 2}{sub s}

    Energy Technology Data Exchange (ETDEWEB)

    Pilipp, V.


    In the present thesis I discuss the hard spectator interaction amplitude in B {yields} {pi}{pi} at NLO i.e. at O({alpha}{sup 2}{sub s}). This special part of the amplitude, whose LO starts at O({alpha}{sub s}), is defined in the framework of QCD factorization. QCD factorization allows to separate the short- and the long-distance physics in leading power in an expansion in {lambda}{sub QCD}/m{sub b}, where the short-distance physics can be calculated in a perturbative expansion in {alpha}{sub s}. Compared to other parts of the amplitude hard spectator interactions are formally enhanced by the hard collinear scale {radical}({lambda}{sub QCD}m{sub b}), which occurs next to the mb-scale and leads to an enhancement of {alpha}{sub s}. From a technical point of view the main challenges of this calculation are due to the fact that we have to deal with Feynman integrals that come with up to five external legs and with three independent ratios of scales. These Feynman integrals have to be expanded in powers of {delta}{sub QCD}/m{sub b}. I discuss integration by parts identities to reduce the number of master integrals and differential equations techniques to get their power expansions. A concrete implementation of integration by parts identities in a computer algebra system is given in the appendix. Finally I discuss numerical issues like scale dependence of the amplitudes and branching ratios. It turns out that the NLO contributions of the hard spectator interactions are important but small enough for perturbation theory to be valid. (orig.)

  16. Host-Pathogen Interactions: I. A Correlation Between alpha-Galactosidase Production and Virulence. (United States)

    English, P D; Albersheim, P


    Resistance or susceptibility of Red Kidney, Pinto and Small White beans (Phaseolus vulgaris) to the alpha, beta, and gamma strains of Colletotrichum lindemuthianum was either confirmed or established. These fungal strains secrete alpha-galactosidase, beta-galactosidase and beta-xylosidase when grown on cell walls isolated from the hypocotyls of any of the above bean varieties. These enzymes effectively degrade cell walls isolated from susceptible 5-day old hypocotyls but degrade only slightly the walls isolated from resistant 18-day old hypocotyls. The amounts of the beta-galactosidase and beta-xylosidase secreted by the 3 fungal strains are relatively low and are approximately equivalent. The secretion of these 2 enzymes is not dependent upon the bean variety from which the hypocotyl cell walls used as a carbon source were isolated. However, the fungal strains secrete greater amounts of alpha-galactosidase when grown on hypocotyl cell walls isolated from susceptible plants than when grown on walls from resistant plants. Virulent isolates of the fungus, when grown on hypocotyl cell walls isolated from a susceptible plant, secrete more alpha-galactosidase than do attenuated (avirulent) isolates of the same fungal strain grown under the same conditions. The alpha-galactosidase secreted by each of the fungal strains is capable of removing galactose from the hypocotyl cell walls of each bean variety tested. Galactose is removed from the cell walls of each variety at the same rate regardless of whether the cell walls were isolated from a susceptible or resistant plant.

  17. Spin reorientation in α-Fe2O3 nanoparticles induced by interparticle exchange interactions in alpha-Fe2O3/NiO nanocomposites

    DEFF Research Database (Denmark)

    Frandsen, Cathrine; Lefmann, Kim; Lebech, Bente


    We report that the spin structure of alpha-Fe2O3 nanoparticles rotates coherently out of the basal (001) plane at low temperatures when interacting with thin plate-shaped NiO nanoparticles. The observed spin reorientation (up to similar to 70 degrees) in alpha-Fe2O3 nanoparticles has, in appearan...

  18. Spin reorientation in α-Fe2O3 nanoparticles induced by interparticle exchange interactions in alpha-Fe2O3/NiO nanocomposites

    DEFF Research Database (Denmark)

    Frandsen, Cathrine; Lefmann, Kim; Lebech, Bente;


    We report that the spin structure of alpha-Fe2O3 nanoparticles rotates coherently out of the basal (001) plane at low temperatures when interacting with thin plate-shaped NiO nanoparticles. The observed spin reorientation (up to similar to 70 degrees) in alpha-Fe2O3 nanoparticles has, in appearan...

  19. Large- and small-scale interactions and quenching in an alpha2-dynamo. (United States)

    Frick, Peter; Stepanov, Rodion; Sokoloff, Dmitry


    The evolution of the large-scale magnetic field in a turbulent flow of conducting fluid is considered in the framework of a multiscale alpha2-dynamo model, which includes the poloidal and the toroidal components for the large-scale magnetic field and a shell model for the small-scale magnetohydrodynamical turbulence. The conjugation of the mean-field description for the large-scale field and the shell formalism for the small-scale turbulence is based on strict conformity to the conservation laws. The model displays a substantial magnetic contribution to the alpha effect. It was shown that a large-scale magnetic field can be generated by current helicity even solely. The alpha quenching and the role of the magnetic Prandtl number (Pm) are studied. We have determined the dynamic nature of the saturation mechanism of dynamo action. Any simultaneous cross correlation of alpha and large-scale magnetic field energy EB is negligible, whereas coupling between alpha and EB becomes substantial for moderate time lags. An unexpected result is the behavior of the large-scale magnetic energy with variation of the magnetic Prandtl number. Diminishing of Pm does not have an inevitable ill effect on the magnetic field generation. The most efficient large-scale dynamo operates under relatively low Prandtl numbers--then the small-scale dynamo is suppressed and the decrease of Pm can lead even to superequipartition of the large-scale magnetic field (i.e., EB>Eu). In contrast, the growth of Pm does not promote the large-scale magnetic field generation. A growing counteraction of the magnetic alpha effect reduces the level of mean large-scale magnetic energy at the saturated state.

  20. Interaction between AVP and sympathetic system in subtotal nephrectomy-saline hypertension: role of alpha and V1 receptors. (United States)

    Ozaykan, B; Doğan, A


    The development process of subtotal nephrectomy-salt hypertension is still unclear. The aim of the present study was to determine the role of the interaction between vasopressin and sympathetic system in the development of this hypertension by using AVP V1 antagonist and alpha blocker phentolamine under anesthesia condition. For this purpose, we carried out about 73% subtotal nephrectomy on male Wistar rats. One group of these rats (normotensive group) was given a low-salt diet and the other group (hypertensive group) was given a high-salt diet for 4 weeks. Finally, eight groups of rats were formed according to the kind(s) of the injected drug(s): (1) normotensive and hypertensive groups injected only V1 antagonist, (2) normotensive and hypertensive groups injected only phentolamine, (3) normotensive and hypertensive groups injected first V1 antagonist and then phentolamine, (4) normotensive and hypertensive groups injected first phentolamine and then V1 antagonist. Either V1 or alpha blockage separately led to a higher reduction in the mean blood pressure (MAP) of the hypertensives than, of the normotensives (p < 0.05). The combined blockage of V1 and alpha receptors, also caused a higher decrease in the MAP of hypertensive group than, of normotensive group, not depending on the order of the injections (p < 0.01). The heart rate increase recorded as a response to the phentolamine injection in normotensive group, did not develop in hypertensive group (p < 0.05). There was no significant difference between the two groups with regard to plasma electrolytes and osmolality. A positive correlation was found between systolic blood pressure and plasma osmolality in hypertensive group (r = 0.40, p < 0.05), but not in normotensive group. We conclude that the increase in V1 and alpha pressor activities contributes to the subtotal nephrectomy-saline hypertension and the augmentation of alpha pressor activity by vasopressin may participate in this contribution.

  1. Microcalorimetric and spectrographic studies on host-guest interactions of {alpha}-, {beta}-, {gamma}- and M{beta}-cyclodextrin with resveratrol

    Energy Technology Data Exchange (ETDEWEB)

    Li, Hui; Xu, Xiangyu; Liu, Min [College of Chemistry and Chemical Engineering, Liaocheng University, Liaocheng 252059, Shandong Province (China); Sun, Dezhi, E-mail: [College of Chemistry and Chemical Engineering, Liaocheng University, Liaocheng 252059, Shandong Province (China); Li, Linwei, E-mail: [College of Chemistry and Chemical Engineering, Liaocheng University, Liaocheng 252059, Shandong Province (China)


    Thermal effects of inclusion processes of {alpha}-, {beta}-, {gamma}- and M{beta}-cyclodextrin with resveratrol (RES) in aqueous solutions were determined by isothermal titration calorimetry (ITC) with nanowatt sensitivity at the temperature of 298.15 K. Standard enthalpy changes, stoichiometry and equilibrium constants of the inclusion complexes were derived from the direct calorimetric data utilizing nonlinear simulation. The thermodynamic parameters were discussed in the light of weak interactions between the host and the guest molecules combining with UV spectral message. The results indicate that all of the complexes formed in the aqueous solutions are in 1:1 stoichiometry. The binding processes of {alpha}-, {beta}- and M{beta}-cyclodextrin with the guest are mainly driven by enthalpy, while that of {gamma}-cyclodextrin with the drug is driven by both enthalpy and entropy.

  2. Structure and interactions of calcite spherulites with {alpha}-chitin in the brown shrimp (Penaeus aztecus) shell

    Energy Technology Data Exchange (ETDEWEB)

    Heredia, A. [Instituto de Ciencias Nucleares, Departamento de Quimica de Radiaciones y Radioquimica, UNAM, Circuito Exterior C.U. Apdo., Postal 70-543, 04510 Mexico, D.F. (Mexico); Physikalisches Institut and Center for Nanotechnology, Universitaet Muenster, Gievenbecker Weg 11, 48149 Muenster (Germany); Aguilar-Franco, M. [Instituto de Fisica, Depto de Fisicoquimica, UNAM, Circuito Exterior s/n, Ciudad Universitaria Apartado Postal 20-364 01000 Mexico D.F. (Mexico); Magana, C. [Instituto de Fisica, Depto de Estado Solido, UNAM, Circuito Exterior s/n, Ciudad Universitaria Apartado Postal 20-364 01000 Mexico D.F. (Mexico); Flores, C. [Instituto de Investigaciones en Materiales, Depto de Estado Solido, Laboratorio de Biomateriales, UNAM, Circuito Exterior C.U. S/N CP 04510 Mexico, D.F. (Mexico); Pina, C. [Instituto de Investigaciones en Materiales, Depto de Estado Solido, Laboratorio de Biomateriales, UNAM, Circuito Exterior C.U. S/N CP 04510 Mexico, D.F. (Mexico); Velazquez, R. [Centro de Fisica Aplicada Tecnologia Avanzada, UNAM, Km. 15 Carretera Queretaro-San Luis Potosi, C.P. 76230, Queretaro, Qro. (Mexico); Schaeffer, T.E. [Physikalisches Institut and Center for Nanotechnology, Universitaet Muenster, Gievenbecker Weg 11, 48149 Muenster (Germany); Bucio, L. [Instituto de Fisica, Depto de Estado Solido, UNAM, Circuito Exterior s/n, Ciudad Universitaria Apartado Postal 20-364 01000 Mexico D.F. (Mexico); Basiuk, V.A. [Instituto de Ciencias Nucleares, Departamento de Quimica de Radiaciones y Radioquimica, UNAM, Circuito Exterior C.U. Apdo., Postal 70-543, 04510 Mexico, D.F. (Mexico)


    White spots form in the brown shrimp (Penaeus aztecus, Decapoda) shell during frozen storage. The mineral formed consists of calcite incorporated into an amorphous {alpha}-chitin matrix. We studied mechanisms of interaction of amorphous {alpha}-chitin macromolecules with hkl crystal planes to form highly ordered structures, as well as the role of specific sites in the biopolymer, which can be related to nucleation and spheroidal crystal growth. We used low vacuum scanning electron microscopy (LVSEM), X-ray powder diffraction (XRD), atomic force microscopy (AFM), Fourier-transform infrared spectroscopy (FT-IR), and molecular mechanics modeling (MM+ method). AFM images showed fingerprint distances in the biopolymer and a highly layered structure in the crystalline material. The presence of {alpha}-chitin, with a specific spatial distribution of radicals, is thought to be responsible for nucleation and to thermodynamically stabilize ions to form the spherulite crystalline phase, which are usually oval to spherical (0.10 to 200 {mu}m in diameter). Our models of crystal-biopolymer interaction found high affinity of CO{sub 3} {sup 2-} anions in the (104) crystalline plane (the main plane in calcite monocrystals) to NH- groups of the biopolymer, as well as of the C=O in the biopolymer to Ca{sup 2+} cations in the crystalline structure. These interactions explain the spherical growth and inhibition in some planes. The specific physicochemical interactions (docking of groups depending on their geometrical distribution) suggest that the biomineral structure is controlled by the biopolymer on a local scale. This information is useful for further design and improvement of (hybrid) materials for versatile application, from nanotechnology to biomedicine and engineering.

  3. Factorization of the fragmentation cross sections in relativistic pA and. cap alpha. A interactions

    Energy Technology Data Exchange (ETDEWEB)

    Abashidze, L.I.; Avdeichikov, V.V.; Beznogikh, G.G.; Bogatin, V.I.; Budilov, V.A.; Gorshkov, N.L.; Zlomanchuk, Y.; Zhidkov, N.K.; Lozhkin, O.V.; Mruvchinski, S.


    We have experimentally demonstrated the factorization of the cross sections for production of the isotopes /sup 3//sup ,//sup 4/He with kinetic energy T> or approx. =100 MeV emitted at an angle 90/sup 0/ in the lab from the nuclei C, Cu, and Au in bombardment by ..cap alpha.. particles with energy 3.33 GeV/nucleon and by protons with energy 6.6 GeV.

  4. Interaction between fragile histamine triad and protein kinase C alpha in human non-small cell lung cancer tissues

    Institute of Scientific and Technical Information of China (English)


    Objective To investigate the interaction between fragile histamine triad (FHIT) and protein kinase C alpha (PKCα) in human non-small cell lung cancer tissues. Methods FHIT and PKCα double positive samples were screened by immunohistochemical staining from 13 human non-small cell lung cancer tissues. Co-immunoprecipitation was performed by using anti-FHIT and anti-PKCα. The immune precipitate was analyzed by SDS-PAGE and Western blot. Results Immune precipitate staining detection showed that 3 samples out of...

  5. Studies of alpha-helicity and intersegmental interactions in voltage-gated Na+ channels: S2D4.

    Directory of Open Access Journals (Sweden)

    Zhongming Ma

    Full Text Available Much data, including crystallographic, support structural models of sodium and potassium channels consisting of S1-S4 transmembrane segments (the "voltage-sensing domain" clustered around a central pore-forming region (S5-S6 segments and the intervening loop. Voltage gated sodium channels have four non-identical domains which differentiates them from the homotetrameric potassium channels that form the basis for current structural models. Since potassium and sodium channels also exhibit many different functional characteristics and the fourth domain (D4 of sodium channels differs in function from other domains (D1-D3, we have explored its structure in order to determine whether segments in D4 of sodium channels differ significantly from that determined for potassium channels. We have probed the secondary and tertiary structure and the role of the individual amino acid residues of the S2D4 of Na(v1.4 by employing cysteine-scanning mutagenesis (with tryptophan and glutamine substituted for native cysteine. A Fourier transform power spectrum of perturbations in free energy of steady-state inactivation gating (using midpoint potentials and slopes of Boltzmann equation fits of channel availability, h(infinity-V plots indicates a substantial amount of alpha-helical structure in S2D4 (peak at 106 degrees, alpha-Periodicity Index (alpha-PI of 3.10, This conclusion is supported by alpha-PI values of 3.28 and 2.84 for the perturbations in rate constants of entry into (beta and exit from (alpha fast inactivation at 0 mV for mutant channels relative to WT channels assuming a simple two-state model for transition from the open to inactivated state. The results of cysteine substitution at the two most sensitive sites of the S2D4 alpha-helix (N1382 and E1392C support the existence of electrostatic network interactions between S2 and other transmembrane segments within Na(v1.4D4 similar to but not identical to those proposed for K+ channels.

  6. Substrate-inhibitor interactions in the kinetics of alpha-amylase inhibition by ragi alpha-amylase/trypsin inhibitor (RATI) and its various N-terminal fragments. (United States)

    Alam, N; Gourinath, S; Dey, S; Srinivasan, A; Singh, T P


    The ragi alpha-amylase/trypsin bifunctional inhibitor (RATI) from Indian finger millet, Ragi (Eleucine coracana Gaertneri), represents a new class of cereal inhibitor family. It exhibits a completely new motif of trypsin inhibitory site and is not found in any known trypsin inhibitor structures. The alpha-amylase inhibitory site resides at the N-terminal region. These two sites are independent of each other and the inhibitor forms a ternary (1:1:1) complex with trypsin and alpha-amylase. The trypsin inhibition follows a simple competitive inhibition obeying the canonical serine protease inhibitor mechanism. However, the alpha-amylase inhibition kinetics is a complex one if larger (> or =7 glucose units) substrate is used. While a complete inhibition of trypsin activity can be achieved, the inhibition of amylase is not complete even at very high molar concentration. We have isolated the N-terminal fragment (10 amino acids long) by CNBr hydrolysis of RATI. This fragment shows a simple competitive inhibition of alpha-amylase activity. We have also synthesized various peptides homologous to the N-terminal sequence of RATI. These peptides also show a normal competitive inhibition of alpha-amylase with varying potencies. It has also been shown that RATI binds to the larger substrates of alpha-amylase. In light of these observations, we have reexamined the binding of proteinaceous inhibitors to alpha-amylase and its implications on the mechanism and kinetics of inhibition.

  7. p38 MAPK and beta-arrestin 2 mediate functional interactions between endogenous micro-opioid and alpha2A-adrenergic receptors in neurons. (United States)

    Tan, Miao; Walwyn, Wendy M; Evans, Christopher J; Xie, Cui-Wei


    Formation of receptor complexes between micro-opioid and alpha2A-adrenergic receptors has been demonstrated in transfected cells. The functional significance and underlying mechanisms of such receptor interactions remain to be determined in neuronal systems. We examined functional interactions between endogenous micro and alpha2A receptors in mouse dorsal root ganglion neurons. Acute application of the micro agonist [D-Ala2,N-MePhe4, Gly-ol5]enkephalin (DAMGO) or the alpha2 agonist clonidine inhibited voltage-gated Ca2+ currents in these neurons. Prolonged treatment with either DAMGO or clonidine induced a mutual cross-desensitization between micro and alpha2A receptor-mediated current inhibition. The cross-desensitization was closely associated with simultaneous internalization of micro and alpha2A receptors. Morphine, a mu agonist triggering little mu receptor endocytosis, induced neither cross-desensitization nor internalization of alpha2A receptors. Furthermore, inhibition of p38 MAPK prevented the cross-desensitization as well as cointernalization of micro and alpha2A receptors. Changes in receptor trafficking profiles suggested that p38 MAPK activity was required for initiating micro receptor internalization and maintaining possible micro-alpha2A association during their cointernalization. Finally, the micro-alpha2A cross-desensitization was absent in dorsal root ganglion neurons lacking beta-arrestin 2. These findings demonstrated p38 MAPK- and beta-arrestin 2-dependent cross-regulation between neuronal micro and alpha2A receptors. By promoting receptor cross-desensitization and cointernalization, such functional interactions may serve as negative feedback mechanisms triggered by prolonged agonist exposure to modulate the signaling of functionally related G protein-coupled receptors.

  8. Effects of clonidine and alpha-adrenoceptor antagonists on motor activity in DSP4-treated mice II: interactions with apomorphine. (United States)

    Fredriksson, A; Archer, T


    Adult mice were administered either the noradrenaline (NA) neurotoxin, N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4) or distilled water (control), 10-12 days before motor activity testing, and 6 h before testing all the mice were administered reserpine (10 mg/kg), the monoamine-depleting agent. The interactive effects of (I) clonidine, the alpha(2)-adrenoceptor agonist, with the dopamine (DA) agonist, apomorphine, and the alpha(2)-antagonist, yohimbine, and (II) with either yohimbine or the alpha(1)-antagonist, prazosin, upon motor behaviour in activity test chambers were studied in reserpinized DSP4-treated and control mice. It was shown that apomorphine (3 mg/kg) increased locomotor and total activity in both reserpinized DSP4-treated and control mice but the effect was attenuated in the DSP4 mice. Co-administration of clonidine (3 mg/kg) with apomorphine potentiated the effects of apomorphine on motor activity and this effect was enhanced markedly by DSP4 pretreatment. Yohimbine (10 mg/kg) antagonized the motor activity-stimulating effects of apomorphine in both DSP4-treated and control mice. Co-administration of clonidine with apomorphine, following yohimbine, restored motor activity levels to those obtained in the absence of yohimbine and this effect upon locomotor activity was enhanced by DSP4 pretreatment. The effects of clonidine on motor activity were enhanced by NA-denervation. Prazzosin (3 mg/kg) enhanced the locomotor activity of both reserpinized DSP4-treated and control mice after the initial 30-min period but was not affected by DSP4 treatment. Analysis of post-decapitation convulsions (PDCs) indicated loss of the reflex by DSP4 pretreatment. Reserpine pretreatment abolished the initial, exploratory phase (30 min) of motor activity. These results demonstrate interactions between NA and DA systems that may bear eventual relevance to neurologic disorders such as parkinsonism.

  9. Kinetic evidence for different mechanisms of interaction of black mamba toxins MT alpha and MT beta with muscarinic receptors. (United States)

    Jolkkonen, M; Oras, A; Toomela, T; Karlsson, E; Järv, J; Akerman, K E


    By studying the influence of two toxins from the black mamba Dendroaspis polylepis on the kinetics of [3H]-N-methylscopolamine binding to muscarinic acetylcholine receptors from rat cerebral cortex, it was revealed that these toxins, MT alpha and MT beta, interact with the receptors via kinetically distinct mechanisms. MT beta bound to receptors in a one-step, readily reversible process with the dissociation constant K(d)=5.3 microM. The binding mechanism of MTalpha was more complex, involving at least two consecutive steps. A fast receptor-toxin complex formation (K(T)=3.8 microM) was followed by a slow process of isomerisation of this complex (k(i)=1.8 x 10(-2) s(-1), half-time 39 s). A similar two-step interaction mechanism has been established for a related toxin, MT2 from the green mamba D. angusticeps (K(T)=1.4 microM, k(i)=8.3 x 10(-4) s(-1), half-time 840 s). The slow isomerisation process delays the effect of MT alpha and MT2, but increases their apparent potency compared to toxins unable to induce the isomerisation process.

  10. Interaction of 14-3-3 proteins with the Estrogen Receptor Alpha F domain provides a drug target interface (United States)

    De Vries-van Leeuwen, Ingrid J.; da Costa Pereira, Daniel; Flach, Koen D.; Piersma, Sander R.; Haase, Christian; Bier, David; Yalcin, Zeliha; Michalides, Rob; Feenstra, K. Anton; Jiménez, Connie R.; de Greef, Tom F. A.; Brunsveld, Luc; Ottmann, Christian; Zwart, Wilbert; de Boer, Albertus H.


    Estrogen receptor alpha (ERα) is involved in numerous physiological and pathological processes, including breast cancer. Breast cancer therapy is therefore currently directed at inhibiting the transcriptional potency of ERα, either by blocking estrogen production through aromatase inhibitors or antiestrogens that compete for hormone binding. Due to resistance, new treatment modalities are needed and as ERα dimerization is essential for its activity, interference with receptor dimerization offers a new opportunity to exploit in drug design. Here we describe a unique mechanism of how ERα dimerization is negatively controlled by interaction with 14-3-3 proteins at the extreme C terminus of the receptor. Moreover, the small-molecule fusicoccin (FC) stabilizes this ERα/14-3-3 interaction. Cocrystallization of the trimeric ERα/14-3-3/FC complex provides the structural basis for this stabilization and shows the importance of phosphorylation of the penultimate Threonine (ERα-T594) for high-affinity interaction. We confirm that T594 is a distinct ERα phosphorylation site in the breast cancer cell line MCF-7 using a phospho-T594–specific antibody and by mass spectrometry. In line with its ERα/14-3-3 interaction stabilizing effect, fusicoccin reduces the estradiol-stimulated ERα dimerization, inhibits ERα/chromatin interactions and downstream gene expression, resulting in decreased cell proliferation. Herewith, a unique functional phosphosite and an alternative regulation mechanism of ERα are provided, together with a small molecule that selectively targets this ERα/14-3-3 interface. PMID:23676274

  11. Ionic interaction of [11C]-N,alpha-dimethylbenzylamine (DMBA) in rodent brain. (United States)

    Inoue, Osamu; Hosoi, Rie; Momosaki, Sotaro; Kobayashi, Kaoru; Kida, Takayo; Suzuki, Kazutoshi; Gee, Antony


    The [S] enantiomer of [11C]-N,alpha-dimethylbenzylamine (DMBA) was synthesized by N-methylation of [S]-alpha-methylbenzylamine, and its biodistribution in mice was measured. [11C]-[S]-DMBA was rapidly distributed into the brain, heart and lungs, and considerable long-term retention in the brain was observed. The radioactive metabolites in the plasma were analyzed by liquid chromatography. Kinetic analysis using unmetabolized [11C]DMBA in the plasma as the input function was performed employing a simplified two-compartment model. The estimated distribution volumes (DV) of [11C]DMBA in the brain and heart were 6.05 and 3.95, respectively. The right striatum of the rat brain was lesioned with ibotenic acid 2 weeks before the tracer experiment. Both in vitro and in vivo autoragiographic studies were performed, and revealed significant reduction of the radioactivity levels in the lesioned striatum. On the other hand, the regional cerebral blood flow, as measured by [14C]iodoantipyrine, was not significantly altered in the lesioned striatum. These results indicate that the ionic binding component for DMBA exists mainly in neural cells rather than in glial cells. [11C]DMBA might be a useful radiotracer for detection of neural cell loss in the brain.

  12. The alpha-fetoprotein (AFP) third domain: a search for AFP interaction sites of cell cycle proteins. (United States)

    Mizejewski, G J


    The carboxy-terminal third domain of alpha-fetoprotein (AFP-3D) is known to harbor binding and/or interaction sites for hydrophobic ligands, receptors, and binding proteins. Such reports have established that AFP-3D consists of amino acid (AA) sequence stretches on the AFP polypeptide that engages in protein-to-protein interactions with various ligands and receptors. Using a computer software program specifically designed for such interactions, the present report identified AA sequence fragments on AFP-3D that could potentially interact with a variety of cell cycle proteins. The cell cycle proteins identified were (1) cyclins, (2) cyclin-dependent kinases, (3) cell cycle-associated proteins (inhibitors, checkpoints, initiators), and (4) ubiquitin ligases. Following detection of the AFP-3D to cell cycle protein interaction sites, the computer-derived AFP localization AA sequences were compared and aligned with previously reported hydrophobic ligand and receptor interaction sites on AFP-3D. A literature survey of the association of cell cycle proteins with AFP showed both positive relationships and correlations. Previous reports of experimental AFP-derived peptides effects on various cell cycle proteins served to confirm and verify the present computer cell cycle protein identifications. Cell cycle protein interactions with AFP-CD peptides have been reported in cultured MCF-7 breast cancer cells subjected to mRNA microarray analysis. After 7 days in culture with MCF-7 cells, the AFP-derived peptides were shown to downregulate cyclin E, SKP2, checkpoint suppressors, cyclin-dependent kinases, and ubiquitin ligases that modulate cyclin E/CdK2 transition from the G1 to the S-phase of the cell cycle. Thus, the experimental data on AFP-CD interaction with cell cycle proteins were consistent with the "in silico" findings.

  13. Retinoid X receptor alpha represses GATA-4-mediated transcription via a retinoid-dependent interaction with the cardiac-enriched repressor FOG-2. (United States)

    Clabby, Martha L; Robison, Trevor A; Quigley, Heather F; Wilson, David B; Kelly, Daniel P


    Dietary vitamin A and its derivatives, retinoids, regulate cardiac growth and development. To delineate mechanisms involved in retinoid-mediated control of cardiac gene expression, the regulatory effects of the retinoid X receptor alpha (RXR alpha) on atrial naturietic factor (ANF) gene transcription was investigated. The transcriptional activity of an ANF promoter-reporter in rat neonatal ventricular myocytes was repressed by RXR alpha in the presence of 9-cis-RA and by the constitutively active mutant RXR alpha F318A indicating that liganded RXR confers the regulatory effect. The RXR alpha-mediated repression mapped to the proximal 147 bp of the rat ANF promoter, a region lacking a consensus retinoid response element but containing several known cardiogenic cis elements including a well characterized GATA response element. Glutathione S-transferase "pull-down" assays revealed that RXR alpha interacts directly with GATA-4, in a ligand-independent manner, via the DNA binding domain of RXR alpha and the second zinc finger of GATA-4. Liganded RXR alpha repressed the activity of a heterologous promoter-reporter construct containing GATA-response element recognition sites in cardiac myocytes but not in several other cell types, suggesting that additional cardiac-enriched factors participate in the repression complex. Co-transfection of liganded RXR alpha and the known cardiac-enriched GATA-4 repressor, FOG-2, resulted in additive repression of GATA-4 activity in ventricular myocytes. In addition, RXR alpha was found to bind FOG-2, in a 9-cis-RA-dependent manner. These data reveal a novel mechanism by which retinoids regulate cardiogenic gene expression through direct interaction with GATA-4 and its co-repressor, FOG-2.

  14. Development of a high-throughput screening-compatible assay to identify inhibitors of the CK2alpha/CK2beta interaction

    DEFF Research Database (Denmark)

    Hochscherf, Jennifer; Lindenblatt, Dirk; Steinkrueger, Michaela;


    active site-directed approaches. The current article describes the development of a fluorescence anisotropy-based assay that mimics the principle of CK2 subunit interaction by using CK2alpha1-335 and the fluorescent probe CF-Ahx-Pc as a CK2beta analog. In addition, we identified new inhibitors able......Increased activity of protein kinase CK2 is associated with various types of cancer, neurodegenerative diseases, and chronic inflammation. In the search for CK2 inhibitors, attention has expanded toward compounds disturbing the interaction between CK2alpha and CK2beta in addition to established...... crystal structure of the Pc/CK2alpha1-335 complex. The dissociation constants obtained in the fluorescence anisotropy assay for binding of all compounds to human CK2alpha1-335 were validated by isothermal titration calorimetry. I-Pc was identified as the tightest binding ligand with a KD value of 240n...

  15. Primary and secondary interactions between CK2alpha and CK2beta lead to ring-like structures in the crystals of the CK2 holoenzyme

    DEFF Research Database (Denmark)

    Niefind, Karsten; Issinger, Olaf-Georg


    a distinct aggregation propensity of CK2. We demonstrate here that in the CK2 holoenzyme crystals contacts between different CK2 tetramers exists which provide structural details of the secondary CK2alpha/CK2beta interactions. These mainly ionic interactions lead to trimeric rings of CK2 holoenzymes...

  16. Faddeev calculation of 3 alpha and alpha alpha Lambda systems using alpha alpha resonating-group method kernel

    CERN Document Server

    Fujiwara, Y; Kohno, M; Suzuki, Y; Baye, D; Sparenberg, J M


    We carry out Faddeev calculations of three-alpha (3 alpha) and two-alpha plus Lambda (alpha alpha Lambda) systems, using two-cluster resonating-group method kernels. The input includes an effective two-nucleon force for the alpha alpha resonating-group method and a new effective Lambda N force for the Lambda alpha interaction. The latter force is a simple two-range Gaussian potential for each spin-singlet and triplet state, generated from the phase-shift behavior of the quark-model hyperon-nucleon interaction, fss2, by using an inversion method based on supersymmetric quantum mechanics. Owing to the exact treatment of the Pauli-forbidden states between the clusters, the present three-cluster Faddeev formalism can describe the mutually related, alpha alpha, 3 alpha and alpha alpha Lambda systems, in terms of a unique set of the baryon-baryon interactions. For the three-range Minnesota force which describes the alpha alpha phase shifts quite accurately, the ground-state and excitation energies of 9Be Lambda are...

  17. Who is Mr. HAMLET? Interaction of human alpha-lactalbumin with monomeric oleic acid. (United States)

    Knyazeva, Ekaterina L; Grishchenko, Valery M; Fadeev, Roman S; Akatov, Vladimir S; Permyakov, Sergei E; Permyakov, Eugene A


    A specific state of the human milk Ca(2+) binding protein alpha-lactalbumin (hLA) complexed with oleic acid (OA) prepared using an OA-pretreated ion-exchange column (HAMLET) triggers several cell death pathways in various tumor cells. The possibility of preparing a hLA-OA complex with structural and cytotoxic properties similar to those of the HAMLET but under solution conditions has been explored. The complex was formed by titration of hLA by OA at pH 8.3 up to OA critical micelle concentration. We have shown that complex formation strongly depends on calcium, ionic strength, and temperature; the optimal conditions were established. The spectrofluorimetrically estimated number of OA molecules irreversibly bound per hLA molecule (after dialysis of the OA-loaded preparation against water followed by lyophilization) depends upon temperature: 2.9 at 17 degrees C (native apo-hLA; resulting complex referred to as LA-OA-17 state) and 9 at 45 degrees C (thermally unfolded apo-hLA; LA-OA-45). Intrinsic tryptophan fluorescence measurements revealed substantially decreased thermal stability of Ca(2+)-free forms of HAMLET, LA-OA-45, and OA-saturated protein. The irreversibly bound OA does not affect the Ca(2+) association constant of the protein. Phase plot analysis of fluorimetric and CD data indicates that the OA binding process involves several hLA intermediates. The effective pseudoequilibrium OA association constants for Ca(2+)-free hLA were estimated. The far-UV CD spectra of Ca(2+)-free hLA show that all OA-bound forms of the protein are characterized by elevated content of alpha-helical structure. The various hLA-OA complexes possess similar cytotoxic activities against human epidermoid larynx carcinoma cells. Overall, the LA-OA-45 complex possesses physicochemical, structural, and cytotoxic properties closely resembling those of HAMLET. The fact that the HAMLET-like complex can be formed in aqueous solution makes the process of its preparation more transparent and

  18. Interaction with extracellular matrix proteins influences Lsh/Ity/Bcg (candidate Nramp) gene regulation of macrophage priming/activation for tumour necrosis factor-alpha and nitrite release. (United States)

    Formica, S; Roach, T I; Blackwell, J M


    The murine resistance gene Lsh/Ity/Bcg regulates activation of macrophages for tumour necrosis factor-alpha (TNF-alpha)-dependent production of nitric oxide mediating antimicrobial activity against Leishmania, Salmonella and Mycobacterium. As Lsh is differentially expressed in macrophages from different tissue sites, experiments were performed to determine whether interaction with extracellular matrix (ECM) proteins would influence the macrophage TNF-alpha response. Plating of bone marrow-derived macrophages onto purified fibrinogen or fibronectin-rich L929 cell-derived matrices, but not onto mannan, was itself sufficient to stimulate TNF-alpha release, with significantly higher levels released from congenic B10.L-Lshr compared to C57BL/10ScSn (Lshs) macrophages. Only macrophages plated onto fibrinogen also released measurable levels of nitrites, again higher in Lshr compared to Lshs macrophages. Addition of interferon-gamma (IFN-gamma), but not bacterial lipopolysaccharide or mycobacterial lipoarabinomannan, as a second signal enhanced the TNF-alpha and nitrite responses of macrophages plated onto fibrinogen, particularly in the Lshr macrophages. Interaction with fibrinogen and fibronectin also primed macrophages for an enhanced TNF-alpha response to leishmanial parasites, but this was only translated into enhanced nitrite responses in the presence of IFN-gamma. In these experiments, Lshr macrophages remained superior in their TNF-alpha responses throughout, but to a degree which reflected the magnitude of the difference observed on ECM alone. Hence, the specificity for the enhanced TNF-alpha responses of Lshr macrophages lay in their interaction with fibrinogen and fibronectin ECM, while a differential nitrite response was only observed with fibrinogen and/or IFN-gamma. The results are discussed in relation to the possible function of the recently cloned candidate gene Nramp, which has structural identity to eukaryote transporters and an N-terminal cytoplasmic

  19. Interaction between fragile histamine triad and protein kinase C alpha in human non-small cell lung cancer tissues

    Institute of Scientific and Technical Information of China (English)

    Peng-hui Zhuang; Zhao-hui Liu; Xiao-gang Jiang; Cheng-en Pan


    Objective To investigate the interaction between fragile histamine triad (FHIT) and protein kinase C alpha (PKCα) in human non-small cell lung cancer tissues. Methods FHIT and PKC伪 double positive samples were screened by immunohistochemical staining from 13 human non-small cell lung cancer tissues. Co-immunoprecipitation was performed by using anti-FHIT and anti-PKCα. The immune precipitate was analyzed by SDS-PAGE and Western blot. Results Immune precipitate staining detection showed that 3 samples out of the 13 cases were double positive for FHIT and PKCα. FHIT protein was present in the immune precipitate of anti-PKCα while there was PKCα in the immune precipitate of anti-FHITmAb. Conclusion FHIT and PKCα exist as a complex in human non-small cell lung cancer tissues, which will provide a new route for studying the pathogenesis and immunotherapy of human non-small cell lung cancer.

  20. Activation of Penile Proadipogenic Peroxisome Proliferator-Activated Receptor with an Estrogen: Interaction with Estrogen Receptor Alpha during Postnatal Development

    Directory of Open Access Journals (Sweden)

    Mahmoud M. Mansour


    Full Text Available Exposure to the estrogen receptor alpha (ER ligand diethylstilbesterol (DES between neonatal days 2 to 12 induces penile adipogenesis and adult infertility in rats. The objective of this study was to investigate the in vivo interaction between DES-activated ER and the proadipogenic transcription factor peroxisome proliferator-activated receptor gamma (PPAR. Transcripts for PPARs , , and and 1a splice variant were detected in Sprague-Dawley normal rat penis with PPAR predominating. In addition, PPAR1b and PPAR2 were newly induced by DES. The PPAR transcripts were significantly upregulated with DES and reduced by antiestrogen ICI 182, 780. At the cellular level, PPAR protein was detected in urethral transitional epithelium and stromal, endothelial, neuronal, and smooth muscular cells. Treatment with DES activated ER and induced adipocyte differentiation in corpus cavernosum penis. Those adipocytes exhibited strong nuclear PPAR expression. These results suggest a biological overlap between PPAR and ER and highlight a mechanism for endocrine disruption.


    NARCIS (Netherlands)

    Postma, J.; Bari, S.; Hoekstra, R.; Tielens, A. G. G. M.; Schlathoelter, T.


    The interaction of keV ions with polyaromatic hydrocarbons is dominated by charge exchange and electronic stopping. We have studied the response of the polyaromatic hydrocarbon anthracene (C(14)H(10)) upon keV H(+) and He(2+) impact using high-resolution time-of-flight mass spectrometry. Extensive f

  2. Interaction of alpha-latroinsectotoxin from Latrodectus mactans venom with bilayer lipid membranes. (United States)

    Shatursky OYa; Pashkov, V N; Bulgacov, O V; Grishin, E V


    alpha-Latroinsectotoxin (LIT) from Latrodectus mactans venom increased the conductance of bilayer lipid membranes (BLM) by inducing channel like activity. The channels formed had a maximal single channel conductance of 5 pS in 10 mM CaCl2 solution. This process occurred more rapidly in symmetrical 10 mM CaCl2 solution than in equimolar KCl or NaCl. The LIT induced conductance showed pronounced rectification, that was dependent upon the face of the BLM to which the LIT was applied. This suggests that the LIT molecules incorporate into the bilayer lipid membrane in an oriented manner. The ion channels formed in bilayer phospholipid membrane by LIT are cation selective. The permeability of divalent cations decreased in the order Ba2+ > Ca2+ > Mg2+ > Cd2+ > Zn2+ (Zn2+ and Cd2+ blocked effectively LIT channels with the ratio of Ca2+trans and Cd2+cis or Zn2+cis of 1:1). Selectivity of LIT to monovalent cations was not high and was Ca2+ sensitive. Our data suggest that LIT has at least two Ca(2+)-binding sites, a high affinity site and low one (pK of binding is 2.4). As a result, the binding kinetics of Ca2+ with the toxin shows a high positive cooperativity (Hill coefficient, (h) = 5.95) and that dimerization might be a prerequisite to channel formation. Temperature dependence of conductance of LIT treated lipid bilayers in 100 mM KCl and 10 mM CaCl2 solutions was also determined: 18.9 +/- 2.11 kJ/mol and 28.537 +/- 1.678 kJ/mol, respectively.

  3. Relativistic configuration-interaction calculation of $K\\alpha$ transition energies in beryllium-like argon

    CERN Document Server

    Yerokhin, V A; Fritzsche, S


    Relativistic configuration-interaction calculations have been performed for the energy levels of the low-lying and core-excited states of beryllium-like argon, Ar$^{14+}$. These calculations include the one-loop QED effects as obtained by two different methods, the screening-potential approach as well as the model QED operator approach. The calculations are supplemented by a systematic estimation of uncertainties of theoretical predictions.

  4. Plasminogen activator inhibitor type 1 interacts with alpha3 subunit of proteasome and modulates its activity. (United States)

    Boncela, Joanna; Przygodzka, Patrycja; Papiewska-Pajak, Izabela; Wyroba, Elzbieta; Osinska, Magdalena; Cierniewski, Czeslaw S


    Plasminogen activator inhibitor type-1 (PAI-1), a multifunctional protein, is an important physiological regulator of fibrinolysis, extracellular matrix homeostasis, and cell motility. Recent observations show that PAI-1 may also be implicated in maintaining integrity of cells, especially with respect to cellular proliferation or apoptosis. In the present study we provide evidence that PAI-1 interacts with proteasome and affects its activity. First, by using the yeast two-hybrid system, we found that the α3 subunit of proteasome directly interacts with PAI-1. Then, to ensure that the PAI-1-proteasome complex is formed in vivo, both proteins were coimmunoprecipitated from endothelial cells and identified with specific antibodies. The specificity of this interaction was evidenced after transfection of HeLa cells with pCMV-PAI-1 and coimmunoprecipitation of both proteins with anti-PAI-1 antibodies. Subsequently, cellular distribution of the PAI-1-proteasome complexes was established by immunogold staining and electron microscopy analyses. Both proteins appeared in a diffuse cytosolic pattern but also could be found in a dense perinuclear and nuclear location. Furthermore, PAI-1 induced formation of aggresomes freely located in endothelial cytoplasm. Increased PAI-1 expression abrogated degradation of degron analyzed after cotransfection of HeLa cells with pCMV-PAI-1 and pd2EGFP-N1 and prevented degradation of p53 as well as IκBα, as evidenced both by confocal microscopy and Western immunoblotting.

  5. Weak and saturable protein-surfactant interactions in the denaturation of apo-alpha-lactalbumin by acidic and lactonic sophorolipid

    Directory of Open Access Journals (Sweden)

    Kell K Andersen


    Full Text Available Biosurfactants are of growing interest as sustainable alternatives to fossil-fuel-derived chemical surfactants, particularly for the detergent industry. To realize this potential, it is necessary to understand how they affect proteins which they may encounter in their applications. However knowledge of such interactions is limited. Here we present a study of the interactions between the model protein apo-alpha-lactalbumin and the biosurfactant sophorolipid (SL produced by the yeast Starmerella bombicola. SL occurs both as an acidic and a lactonic form; the lactonic form (lactSL is sparingly soluble and has a lower critical micelle concentration than the acidic form (acidSL. We show that acidSL affects apo-aLA in a similar way to the related glycolipid biosurfactant rhamnolipid (RL, with the important difference that RL is also active below the cmc in contrast to acidSL. Using isothermal titration calorimetry data, we show that acidSL has weak and saturable interactions with apo-aLA at low concentrations; due to the relatively low cmc of acidSL (which means that the monomer concentration is limited to ca. 0-1 mM SL, it is only possible to observe interactions with monomeric acidSL at high apo-aLA concentrations. However, the denaturation kinetics of apo-aLA in the presence of acidSL are consistent with a collaboration between monomeric and micellar surfactant species, similar to RL and nonionic or zwitterionic surfactants. Inclusion of lactSL as mixed micelles with acidSL lowers the cmc and this effectively reduces the rate of unfolding, emphasizing that SL like other biosurfactants is a gentle anionic surfactant. Our data highlight the potential of these biosurfactants for future use in the detergent industry.

  6. Interaction of spermine with dimyristoyl-L-alpha-phosphatidyl-DL-glycerol multilamellar liposomes. (United States)

    Stevanato, R; Wisniewska, A; Momo, F


    Polycationic spermine interacts with the negative phosphate group of dimyristoylphosphatidylglycerol multilamellar liposomes, forming a positively charged shell around the vesicle surface. An association constant of (2.15+/-0.45) x 10(3) M(-1) between spermine and the phospholipid groups in liposomes has been evaluated by a new and rapid enzymatic method. ESR spectra show that the effects of this polycation on liposomes are substantially different from those of cations like Ca2+ and Mg2+ and confirm the ability of spermine to induce liposome aggregation and not fusion.

  7. Spectroscopic studies on ligand-enzyme interactions: complexation of alpha-chymotrypsin with 4',6-diamidino-2-phenylindole (DAPI). (United States)

    Banerjee, Debapriya; Srivastava, Sachin Kumar; Pal, Samir Kumar


    In the present study, the interaction of two structurally related proteolytic enzymes trypsin and alpha-chymotrypsin (CHT) with 4',6-Diamidino-2-phenylindole (DAPI) has been addressed. The binding of DAPI to CHT has been characterized by steady-state and picosecond time-resolved spectroscopic techniques. Enzymatic activity of CHT and simultaneous binding of the well-known inhibitor proflavin (PF) in the presence of DAPI clearly rule out the possibility of DAPI binding at the catalytic site of the enzyme. The spectral overlap between the emission of DAPI and absorption of PF offers the opportunity to explore the binding site of DAPI using Förster resonance energy transfer (FRET). FRET studies between DAPI and PF indicate that DAPI is bound to CHT with its transition dipole nearly perpendicular to that of PF. Competitive binding of DAPI with another fluorescent probe 2,6-p-toluidinonaphthalene sulfonate (TNS), having a well-defined binding site, indicates that DAPI and TNS bind at the same hydrophobic site of the enzyme CHT. The difference in the interactions of two well-studied, structurally similar enzymes with the same molecule may find its application in the design of specific substrate mimics or inhibitors of the enzymes.

  8. Atomic level simulations of interaction between edge dislocations and irradiation induced ellipsoidal voids in alpha-iron (United States)

    Zhu, Bida; Huang, Minsheng; Li, Zhenhuan


    High concentrations of vacancies tend to be formed inside the metal materials under irradiation, and then accumulate and cluster together gradually to promote the formation of nanovoids. Generally, these voids act as obstacles for dislocation glide and thereby change/degrade the mechanical behavior of irradiated materials. In this work, the interaction between ellipsoidal nanovoids with edge dislocations in alpha-iron has been studied by atomic simulations. The results illuminate that the ellipsoidal void's semi-major axis on the slip plane and parallel to the dislocation line is the dominant factor controlling the obstacle strength of ellipsoidal nanovoids. Two other semi-major axes, which are perpendicular to the glide plane and parallel to the Burgers vector, respectively, can also influence the critical resolved shear stress (CRSS) for dislocation shearing the ellipsoidal void. The intrinsic atomic mechanisms controlling above phenomena, such as nanovoid-geometry spatial constraint and nanovoid-surface curvature on dislocation evolution, have been discussed carefully. The classical continuum model has been amended to describe the dislocation-ellipsoidal nanovoid interaction base on current results. In addition, the influence of temperature on the CRSS of ellipsoidal nanovoids has also been investigated.

  9. Spectroscopic and thermodynamic studies on ferulic acid - Alpha-2-macroglobulin interaction (United States)

    Rehman, Ahmed Abdur; Sarwar, Tarique; Arif, Hussain; Ali, Syed Saqib; Ahsan, Haseeb; Tabish, Mohammad; Khan, Fahim Halim


    Ferulic acid is a major phenolic acid found in numerous plant species in conjugated form. It binds to enzymes and oligomeric proteins and modifies their structure and function. This study was designed to examine the interaction of ferulic acid, an active ingredient of some important medicines, with α2M, a key serum proteinase, under physiological conditions. The mechanism of interaction was studied by spectroscopic techniques such as, UV-visible absorption, fluorescence spectroscopy, circular dichroism along with isothermal titration calorimetry. Fluorescence quenching of α2M by ferulic acid demonstrated the formation of α2M-ferulic acid complex by static quenching mechanism. Binding parameters calculated by Stern-Volmer method showed that ferulic acid binds to α2M with moderate affinity of the order of ∼104 M-1. The thermodynamic signatures reveal that binding was enthalpy driven and hydrogen bonding played a major role in ferulic acid-α2M binding. CD spectra analysis suggests very little conformational changes in α2M on ferulic acid binding.

  10. PAK4 interacts with p85 alpha: implications for pancreatic cancer cell migration (United States)

    King, Helen; Thillai, Kiruthikah; Whale, Andrew; Arumugam, Prabhu; Eldaly, Hesham; Kocher, Hemant M.; Wells, Claire M.


    It has been reported that p21-activated kinase 4 (PAK4) is amplified in pancreatic cancer tissue. PAK4 is a member of the PAK family of serine/threonine kinases, which act as effectors for several small GTPases, and has been specifically identified to function downstream of HGF-mediated c-Met activation in a PI3K dependent manner. However, the functionality of PAK4 in pancreatic cancer and the contribution made by HGF signalling to pancreatic cancer cell motility remain to be elucidated. We now find that elevated PAK4 expression is coincident with increased expression levels of c-Met and the p85α subunit of PI3K. Furthermore, we demonstrate that pancreatic cancer cells have a specific motility response to HGF both in 2D and 3D physiomimetic organotypic assays; which can be suppressed by inhibition of PI3K. Significantly, we report a specific interaction between PAK4 and p85α and find that PAK4 deficient cells exhibit a reduction in Akt phosphorylation downstream of HGF signalling. These results implicate a novel role for PAK4 within the PI3K pathway via interaction with p85α. Thus, PAK4 could be an essential player in PDAC progression representing an interesting therapeutic opportunity. PMID:28205613

  11. Multiple interactions between the alpha2C- and beta1-adrenergic receptors influence heart failure survival

    Directory of Open Access Journals (Sweden)

    Case Karen L


    Full Text Available Abstract Background Persistent stimulation of cardiac β1-adrenergic receptors by endogenous norepinephrine promotes heart failure progression. Polymorphisms of this gene are known to alter receptor function or expression, as are polymorphisms of the α2C-adrenergic receptor, which regulates norepinephrine release from cardiac presynaptic nerves. The purpose of this study was to investigate possible synergistic effects of polymorphisms of these two intronless genes (ADRB1 and ADRA2C, respectively on the risk of death/transplant in heart failure patients. Methods Sixteen sequence variations in ADRA2C and 17 sequence variations in ADRB1 were genotyped in a longitudinal study of 655 white heart failure patients. Eleven sequence variations in each gene were polymorphic in the heart failure cohort. Cox proportional hazards modeling was used to identify polymorphisms and potential intra- or intergenic interactions that influenced risk of death or cardiac transplant. A leave-one-out cross-validation method was utilized for internal validation. Results Three polymorphisms in ADRA2C and five polymorphisms in ADRB1 were involved in eight cross-validated epistatic interactions identifying several two-locus genotype classes with significant relative risks ranging from 3.02 to 9.23. There was no evidence of intragenic epistasis. Combining high risk genotype classes across epistatic pairs to take into account linkage disequilibrium, the relative risk of death or transplant was 3.35 (1.82, 6.18 relative to all other genotype classes. Conclusion Multiple polymorphisms act synergistically between the ADRA2C and ADRB1 genes to increase risk of death or cardiac transplant in heart failure patients.

  12. Structural and protein interaction effects of hypertrophic and dilated cardiomyopathic mutations in alpha-tropomyosin

    Directory of Open Access Journals (Sweden)

    Audrey N. Chang


    Full Text Available The potential alterations to structure and associations with thin filament proteins caused by the dilated cardiomyopathy (DCM associated tropomyosin (Tm mutants E40K and E54K, and the hypertrophic cardiomyopathy (HCM associated Tm mutants E62Q and L185R, were investigated. In order to ascertain what the cause of the known functional effects may be, structural and protein-protein interaction studies were conducted utilizing actomyosin ATPase activity measurements and spectroscopy. In actomyosin ATPase measurements, both HCM mutants and the DCM mutant E54K caused increases in Ca2+-induced maximal activities, while E40K caused a decrease. Investigation of Tm’s ability to inhibit actomyosin ATPase in the absence of troponin showed that HCM-associated mutant Tms did not inhibit as well as wildtype, whereas the DCM associated mutant E40K inhibited better. E54K did not inhibit the actomyosin ATPase activity at any concentration of Tm tested. Thermal denaturation studies by circular dichroism and molecular modeling of the mutations in Tm showed that in general, the DCM mutants caused destabilization within the Tm, while the HCM mutants resulted in increased stability. These findings demonstrate that the structural alterations in Tm observed here may affect the regulatory function of Tm on actin, thereby directly altering the ATPase rates of myosin.

  13. Functional interactions of phospholemman (PLM) (FXYD1) with Na+,K+-ATPase. Purification of alpha1/beta1/PLM complexes expressed in Pichia pastoris. (United States)

    Lifshitz, Yael; Lindzen, Moshit; Garty, Haim; Karlish, Steven J D


    Human FXYD1 (phospholemman, PLM) has been expressed in Pichia pastoris with porcine alpha1/His10-beta1 subunits of Na+,K+-ATPase or alone. Dodecyl-beta-maltoside-soluble complexes of alpha1/beta1/PLM have been purified by metal chelate chromatography, either from membranes co-expressing alpha1,His10-beta1, and PLM or by in vitro reconstitution of PLM with alpha1/His10-beta1 subunits. Comparison of functional properties of purified alpha1/His10-beta1 and alpha1/His10-beta1/PLM complexes show that PLM lowered K0.5 for Na+ ions moderately (approximately 30%) but did not affect the turnover rate or Km of ATP for activating Na+,K+-ATPase activity. PLM also stabilized the alpha1/His10-beta1 complex. In addition, PLM markedly (>3-fold) reduced the K0.5 of Na+ ions for activating Na+-ATPase activity. In membranes co-expressing alpha1/His10-beta1 with PLM the K0.5 of Na+ ions was also reduced, compared with the control, excluding the possibility that detergent or lipid in purified complexes compromise functional interactions. When expressed in HeLa cells with rat alpha1, rat PLM significantly raised the K0.5 of Na+ ions, whereas for a chimeric molecule consisting of transmembranes segments of PLM and extramembrane segments of FXYD4, the K0.5 of Na+ ions was significantly reduced, compared with the control. The opposite functional effects in P. pastoris and HeLa cells are correlated with endogenous phosphorylation of PLM at Ser68 or unphosphorylated PLM, respectively, as detected with antibodies, which recognize PLM phosphorylated at Ser68 (protein kinase A site) or unphosphorylated PLM. We hypothesize that PLM interacts with alpha1/His10-beta1 subunits at multiple locations, the different functional effects depending on the degree of phosphorylation at Ser68. We discuss the role of PLM in regulation of Na+,K+-ATPase in cardiac or skeletal muscle cells.

  14. Impact of Interaction Between PPAR Alpha and PPAR Gamma on Breast Cancer Risk in the Chinese Han Population. (United States)

    Lianggeng, Xiong; Baiwu, Liang; Maoshu, Bai; Jiming, Liu; Youshan, Li


    Several studies have been conducted to investigate the association of the peroxisome proliferator-activated receptor (PPAR) alpha (PPAR A) and PPAR gamma (PPAR G) polymorphism and breast cancer (BC) risk, but the results were inconsistent, and, until now, no study focused on the impact of gene-gene interactions between PPAR A and PPAR G on BC risk; thus, the aim of this study was to investigate the impact of interaction between PPAR A and PPAR G on BC risk in the Chinese Han population. A total of 862 participants with a mean age of 63.0 ± 15.7 years were selected, including 432 patients with BC and 430 controls. A logistic regression model was used to examine the association between single-nucleotide polymorphisms and BC risk. The odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. Generalized multifactor dimensionality reduction was employed to analyze the gene-gene interaction. Logistic regression analysis showed that BC risk was significantly higher in carriers of G allele of rs1800206 polymorphism than those with CC (CG + GG vs. CC) (adjusted OR, 1.50; 95% CI, 1.20-1.93). In addition, we found that BC risk was also significantly higher in carriers of the G allele of the rs1805192 polymorphism than those with the CC genotype (CG + GG vs. CC) (adjusted OR, 1.78; 95% CI, 1.34-2.26). There was a significant gene-gene interaction between rs1805192 and rs1800206. Overall, the 2-locus models had a cross-validation consistency of 10 of 10, and had a testing accuracy of 60.11%. Patients with CG or GG of rs1805192 and CG or GG of rs1800206 genotype have the highest BC risk, compared with patients with CC of rs1805192 and CC of rs1800206 genotype (OR, 2.59; 95% CI, 1.70-3.48, after covariates adjustment for gender, age, age at menarche, number of children, body mass index, and waist circumference). The minor allele of rs1800206 and rs1805192 and its interaction were associated with increased BC risk. Copyright © 2016 Elsevier Inc. All rights

  15. Neuroimmune Interactions in Schizophrenia: Focus on Vagus Nerve Stimulation and Activation of the Alpha-7 Nicotinic Acetylcholine Receptor

    Directory of Open Access Journals (Sweden)

    Fabiana Maria das Graças Corsi-Zuelli


    Full Text Available Schizophrenia is one of the most debilitating mental disorders and is aggravated by the lack of efficacious treatment. Although its etiology is unclear, epidemiological studies indicate that infection and inflammation during development induces behavioral, morphological, neurochemical, and cognitive impairments, increasing the risk of developing schizophrenia. The inflammatory hypothesis of schizophrenia is also supported by clinical studies demonstrating systemic inflammation and microglia activation in schizophrenic patients. Although elucidating the mechanism that induces this inflammatory profile remains a challenge, mounting evidence suggests that neuroimmune interactions may provide therapeutic advantages to control inflammation and hence schizophrenia. Recent studies have indicated that vagus nerve stimulation controls both peripheral and central inflammation via alpha-7 nicotinic acetylcholine receptor (α7nAChR. Other findings have indicated that vagal stimulation and α7nAChR-agonists can provide therapeutic advantages for neuropsychiatric disorders, such as depression and epilepsy. This review analyzes the latest results regarding: (I the immune-to-brain pathogenesis of schizophrenia; (II the regulation of inflammation by the autonomic nervous system in psychiatric disorders; and (III the role of the vagus nerve and α7nAChR in schizophrenia.

  16. Neuroimmune Interactions in Schizophrenia: Focus on Vagus Nerve Stimulation and Activation of the Alpha-7 Nicotinic Acetylcholine Receptor (United States)

    Corsi-Zuelli, Fabiana Maria das Graças; Brognara, Fernanda; Quirino, Gustavo Fernando da Silva; Hiroki, Carlos Hiroji; Fais, Rafael Sobrano; Del-Ben, Cristina Marta; Ulloa, Luis; Salgado, Helio Cesar; Kanashiro, Alexandre; Loureiro, Camila Marcelino


    Schizophrenia is one of the most debilitating mental disorders and is aggravated by the lack of efficacious treatment. Although its etiology is unclear, epidemiological studies indicate that infection and inflammation during development induces behavioral, morphological, neurochemical, and cognitive impairments, increasing the risk of developing schizophrenia. The inflammatory hypothesis of schizophrenia is also supported by clinical studies demonstrating systemic inflammation and microglia activation in schizophrenic patients. Although elucidating the mechanism that induces this inflammatory profile remains a challenge, mounting evidence suggests that neuroimmune interactions may provide therapeutic advantages to control inflammation and hence schizophrenia. Recent studies have indicated that vagus nerve stimulation controls both peripheral and central inflammation via alpha-7 nicotinic acetylcholine receptor (α7nAChR). Other findings have indicated that vagal stimulation and α7nAChR-agonists can provide therapeutic advantages for neuropsychiatric disorders, such as depression and epilepsy. This review analyzes the latest results regarding: (I) the immune-to-brain pathogenesis of schizophrenia; (II) the regulation of inflammation by the autonomic nervous system in psychiatric disorders; and (III) the role of the vagus nerve and α7nAChR in schizophrenia. PMID:28620379

  17. Junctional adhesion molecule (JAM)-B supports lymphocyte rolling and adhesion through interaction with alpha4beta1 integrin. (United States)

    Ludwig, Ralf J; Hardt, Katja; Hatting, Max; Bistrian, Roxana; Diehl, Sandra; Radeke, Heinfried H; Podda, Maurizio; Schön, Michael P; Kaufmann, Roland; Henschler, Reinhard; Pfeilschifter, Josef M; Santoso, Sentot; Boehncke, Wolf-Henning


    Junctional adhesion molecule-A (JAM-A), JAM-B and JAM-C have been implicated in leucocyte transmigration. As JAM-B binds to very late activation antigen (VLA)-4, a leucocyte integrin that contributes to rolling and firm adhesion of lymphocytes to endothelial cells through binding to vascular cell adhesion molecule (VCAM)-1, we hypothesized that JAM-B is also involved in leucocyte rolling and firm adhesion. To test this hypothesis, intravital microscopy of murine skin microvasculature was performed. Rolling interactions of murine leucocytes were significantly affected by blockade of JAM-B [which reduced rolling interactions from 9.1 +/- 2.6% to 3.2 +/- 1.2% (mean +/- standard deviation)]. To identify putative ligands, T lymphocytes were perfused over JAM-B-coated slides in a dynamic flow chamber system. JAM-B-dependent rolling and sticking interactions were observed at low shear stress [0.3 dyn/cm(2): 220 +/- 71 (mean +/- standard deviation) versus 165 +/- 88 rolling (P JAM-B- compared with baseline], but not at higher shear forces (1.0 dyn/cm(2)). As demonstrated by antibody blocking experiments, JAM-B-mediated rolling and sticking of T lymphocytes was dependent on alpha4 and beta1 integrin, but not JAM-C expression. To investigate whether JAM-B-mediated leucocyte-endothelium interactions are involved in a disease-relevant in vivo model, adoptive transfer experiments in 2,4,-dinitrofluorobenzene (DNFB)-induced contact hypersensitivity reactions were performed in mice in the absence or in the presence of a function-blocking JAM-B antibody. In this model, JAM-B blockade during the sensitization phase impaired the generation of the immune response to DNFB, which was assessed as the increase in ear swelling in untreated, DNFB-challenged mice, by close to 40% [P = 0.037; analysis of variance (anova)]. Overall, JAM-B appears to contribute to leucocyte extravasation by facilitating not only transmigration but also rolling and adhesion.

  18. Structural Basis of the CD8[alpha beta]/MHC Class I Interaction: Focused Recognition Orients CD8[beta] to a T Cell Proximal Position[superscript 1,2

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Rui; Natarajan, Kannan; Margulies, David H.; (NIH)


    In the immune system, B cells, dendritic cells, NK cells, and T lymphocytes all respond to signals received via ligand binding to receptors and coreceptors. Although the specificity of T cell recognition is determined by the interaction of T cell receptors with MHC/peptide complexes, the development of T cells in the thymus and their sensitivity to Ag are also dependent on coreceptor molecules CD8 (for MHC class I (MHCI)) and CD4 (for MHCII). The CD8{alpha}{beta} heterodimer is a potent coreceptor for T cell activation, but efforts to understand its function fully have been hampered by ignorance of the structural details of its interactions with MHCI. In this study we describe the structure of CD8{alpha}{beta} in complex with the murine MHCI molecule H-2D{sup d} at 2.6 {angstrom} resolution. The focus of the CD8{alpha}{beta} interaction is the acidic loop (residues 222-228) of the {alpha}3 domain of H-2D{sup d}. The {beta} subunit occupies a T cell membrane proximal position, defining the relative positions of the CD8{alpha} and CD8{beta} subunits. Unlike the CD8{alpha}{alpha} homodimer, CD8{alpha}{beta} does not contact the MHCI {alpha}{sub 2}- or {beta}{sub 2}-microglobulin domains. Movements of the CD8{alpha} CDR2 and CD8{beta} CDR1 and CDR2 loops as well as the flexibility of the H-2D{sup d} CD loop facilitate the monovalent interaction. The structure resolves inconclusive data on the topology of the CD8{alpha}{beta}/MHCI interaction, indicates that CD8{beta} is crucial in orienting the CD8{alpha}{beta} heterodimer, provides a framework for understanding the mechanistic role of CD8{alpha}{beta} in lymphoid cell signaling, and offers a tangible context for design of structurally altered coreceptors for tumor and viral immunotherapy.


    NARCIS (Netherlands)



    The role of high temperature resistance in the world-wide cline of Adh and alpha-Gpdh allele frequencies of Drosophila melanogaster was investigated. Experimental strains were used with different combinations of Adh and alpha-Gpdh alleles but with similar genetic background. The survival time of adu

  20. Immunohistochemical localization of integrin alpha V beta 3 and osteopontin suggests that they do not interact during embryo implantation in ruminants

    Directory of Open Access Journals (Sweden)

    MacLaren Leslie A


    Full Text Available Abstract Background It has been suggested that trophoblast attachment requires co-expression of integrin alpha V beta 3 and its ligand osteopontin at the fetal-maternal interface. Until now the expression patterns of integrin alpha V beta 3 and osteopontin in the pregnant bovine uterus were unknown. The objectives of this study were to localize integrin alpha V beta 3 and osteopontin in bovine and sheep endometrium during the periimplantation period and to compare the distribution patterns using antibodies that had not yet been tested in sheep. Methods Cell compartments within endometrial tissue sections were scored for immunohistochemical staining intensity and data were analyzed to determine the effects of day of pregnancy or cycle. Results In pregnant bovine endometrium, integrin alpha V beta 3 was detected in luminal epithelium, stroma, myometrium and smooth muscle. A strong band of immunoreactivity was observed in the subepithelial stroma of intercaruncular regions, but there was reduced reactivity in the caruncles and glands. Bovine trophoblast did not express integrin alpha V beta 3 at any stage of pregnancy. In ovine endometrium a different pattern of staining for integrin alpha V beta 3 was observed. Reactivity was not present in the luminal epithelium or trophoblast. There was strong staining of the deep glands and no reactivity in the superficial glands. Osteopontin distribution was similar for sheep and cattle. For both species, apical staining was present on the luminal epithelium and glands and on embryonic tissues. Conclusion In ruminants, integrin alpha V beta 3 and osteopontin do not co-localize at the fetal-maternal interface indicating that these proteins could not interact to facilitate embryo attachment as has been proposed in other species.

  1. Ab initio alpha-alpha scattering

    CERN Document Server

    Elhatisari, Serdar; Rupak, Gautam; Epelbaum, Evgeny; Krebs, Hermann; Lähde, Timo A; Luu, Thomas; Meißner, Ulf-G


    Processes involving alpha particles and alpha-like nuclei comprise a major part of stellar nucleosynthesis and hypothesized mechanisms for thermonuclear supernovae. In an effort towards understanding alpha processes from first principles, we describe in this letter the first ab initio calculation of alpha-alpha scattering. We use lattice effective field theory to describe the low-energy interactions of nucleons and apply a technique called the adiabatic projection method to reduce the eight-body system to an effective two-cluster system. We find good agreement between lattice results and experimental phase shifts for S-wave and D-wave scattering. The computational scaling with particle number suggests that alpha processes involving heavier nuclei are also within reach in the near future.

  2. TNF{alpha} induced FOXP3-NF{kappa}B interaction dampens the tumor suppressor role of FOXP3 in gastric cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Hao, Qiang; Li, Weina; Zhang, Cun; Qin, Xin; Xue, Xiaochang; Li, Meng; Shu, Zhen; Xu, Tianjiao; Xu, Yujin; Wang, Weihua [The State Key Laboratory of Cancer Biology, School of Pharmacy, Department of Biopharmaceutics, Fourth Military Medical University, Xi' an 710032 (China); Zhang, Wei, E-mail: [The State Key Laboratory of Cancer Biology, School of Pharmacy, Department of Biopharmaceutics, Fourth Military Medical University, Xi' an 710032 (China); Zhang, Yingqi, E-mail: [The State Key Laboratory of Cancer Biology, School of Pharmacy, Department of Biopharmaceutics, Fourth Military Medical University, Xi' an 710032 (China)


    Highlights: Black-Right-Pointing-Pointer FOXP3 inhibition of cell proliferation is p21-dependent under basal conditions. Black-Right-Pointing-Pointer Inflammation induced by TNF{alpha} inhibits the tumor suppressor role of FOXP3. Black-Right-Pointing-Pointer Interaction between p65 and FOXP3 inhibits p21 transcription activation. -- Abstract: Controversial roles of FOXP3 in different cancers have been reported previously, while its role in gastric cancer is largely unknown. Here we found that FOXP3 is unexpectedly upregulated in some gastric cancer cells. To test whether increased FOXP3 remains the tumor suppressor role in gastric cancer as seen in other cancers, we test its function in cell proliferation both at basal and TNF{alpha} mimicked inflammatory condition. Compared with the proliferation inhibitory role observed in basal condition, FOXP3 is insufficient to inhibit the cell proliferation under TNF{alpha} treatment. Molecularly, we found that TNF{alpha} induced an interaction between FOXP3 and p65, which in turn drive the FOXP3 away from the promoter of the well known target p21. Our data here suggest that although FOXP3 is upregulated in gastric cancer, its tumor suppressor role has been dampened due to the inflammation environment.

  3. A doppel alpha-helix peptide fragment mimics the copper(II) interactions with the whole protein. (United States)

    La Mendola, Diego; Magrì, Antonio; Campagna, Tiziana; Campitiello, Maria Anna; Raiola, Luca; Isernia, Carla; Hansson, Orjan; Bonomo, Raffaele P; Rizzarelli, Enrico


    The doppel protein (Dpl) is the first homologue of the prion protein (PrP(C)) to be discovered; it is overexpressed in transgenic mice that lack the prion gene, resulting in neurotoxicity. The whole prion protein is able to inhibit Dpl neurotoxicity, and its N-terminal domain is the determinant part of the protein function. This region represents the main copper(II) binding site of PrP(C). Dpl is able to bind at least one copper ion, and the specific metal-binding site has been identified as the histidine residue at the beginning of the third helical region. However, a reliable characterization of copper(II) coordination features has not been reported. In a previous paper, we studied the copper(II) interaction with a peptide that encompasses only the loop region potentially involved in metal binding. Nevertheless, we did not find a complete match between the EPR spectroscopic parameters of the copper(II) complexes formed with the synthesized peptide and those reported for the copper(II) binding sites of the whole protein. Herein, the synthesis of the human Dpl peptide fragment hDpl(122-139) (Ac-KPDNKLHQQVLWRLVQEL-NH(2)) and its copper(II) complex species are reported. This peptide encompasses the third alpha helix and part of the loop linking the second and the third helix of human doppel protein. The single-point-mutated peptide, hDpl(122-139)D124N, in which aspartate 124 replaces an asparagine residue, was also synthesized. This peptide was used to highlight the role of the carboxylate group on both the conformation preference of the Dpl fragment and its copper(II) coordination features. NMR spectroscopic measurements show that the hDpl(122-139) peptide fragment is in the prevailing alpha-helix conformation. It is localized within the 127-137 amino acid residue region that represents a reliable conformational mimic of the related protein domain. A comparison with the single-point-mutated hDpl(122-139)D124N reveals the significant role played by the aspartic

  4. Tumor Necrosis Factor-alpha Induced Protein 3 Interacting Protein 1 Gene Polymorphisms and Pustular Psoriasis in Chinese Han Population

    Institute of Scientific and Technical Information of China (English)

    Jian-Wen Han; Yong Wang; Chulu Alateng; Hong-Bin Li; Yun-Hua Bai; Xin-Xiang Lyu; Rina Wu


    Background:Psoriasis is a common immune-mediated inflammatory dermatosis.Generalized pustular psoriasis (GPP) is the severe and rare type of psoriasis.The association between tumor necrosis factor-alpha induced protein 3 interacting protein 1 (TNIP1) gene and psoriasis was confirmed in people with multiple ethnicities.This study was to investigate the association between TNIP1 gene polymorphisms and pustular psoriasis in Chinese Han population.Methods:Seventy-three patients with GPP,67 patients with palmoplantar pustulosis (PPP),and 476 healthy controls were collected from Chinese Han population.Six single nucleotide polymorphisms (SNPs) of the TNIP1 gene,namely rs3805435,rs3792798,rs3792797,rs869976,rs17728338,and rs999011 were genotyped by using polymerase chain reaction-ligase detection reaction.Statistical analyses were performed using the PLINK 1.07 package.Allele frequencies and genotyping frequencies for six SNPs were compared by using Chi-square test,odd ratio (OR) (including 95% confidence interval) were calculated.The haplotype analysis was conducted by Haploview software.Results:The frequencies of alleles of five SNPs were significantly different between the GPP group and the control group (P≤ 7.22 × 10-3),especially in the GPP patients without psoriasis vulgaris (PsV).In the haplotype analysis,the most significantly different haplotype was H4:ACGAAC,with 13.1% frequency in the GPP group but only 3.4% in the control group (OR =4.16,P =4.459 × 10-7).However,no significant difference in the allele frequencies was found between the PPP group and control group for each of the six SNPs (P > 0.05).Conclusions:Polymorphisms in TNIP1 are associated with GPP in Chinese Han population.However,no association with PPP was found.These findings suggest that TNIP1 might be a susceptibility gene for GPP.

  5. The evaluation of the caveolin-1 and AT-rich interactive domain 1 alpha expressions in uterine smooth muscle tumors

    Directory of Open Access Journals (Sweden)

    Duygu Ayaz


    Full Text Available Objectives: This retrospective study was designed to evaluate the importance of tissue expressions of caveolin-1 (Cav-1 and AT-rich interactive domain 1 alpha (ARID-1A which are known as signal regulator and tumor suppressor in differential diagnosis of uterine smooth muscle tumors (SMTs. Materials and Methods: Thirty patients recently diagnosed as uterine SMTs at the Tepecik Training and Research Hospital were identified using pathology databases. Immunohistochemical stains for Cav-1 and ARID-1A were performed. Results: In this series, there were 10 leiomyosarcomas (LMSs, 10 uterine smooth muscle tumors of uncertain malignant potentials (STUMPs, and 10 leiomyomas (LMs. Cav-1 expression located cytoplasmic or perivascular area. Cytoplasmic Cav-1 expression was determined in 5 LMSs and 2 STUMPs while perivascular Cav-1 expression was determined in 9 LMSs and 2 STUMPs. Statistically, it was determined that if the tumor becomes malignant and more invasive, it gains the perivascular Cav-1 expression (P = 0.029. On the other hand, the mean nuclear staining rate for ARID-1A in LMSs (63 ± 23.4% was higher than both STUMPs (60 ± 18.5% and LMs (34.5 ± 16.5%. Statistically, it was determined that the expression of ARID-1A was significantly downregulated in LMs when compared with STUMPs and LMSs (P = 0.004. Conclusions: Our findings were demonstrated that perivascular Cav-1 expression was seen to be a marker for malignancy of uterine SMTs. Similarly, we found to link of ARID-1A expression and the aggressiveness of SMTs. Therefore, it may be suggested that Cav-1 and ARID-1A may act as predictive biomarkers in uterine SMTs.

  6. Interaction between retinoid acid receptor-related orphan receptor alpha (RORA and neuropeptide S receptor 1 (NPSR1 in asthma.

    Directory of Open Access Journals (Sweden)

    Nathalie Acevedo

    Full Text Available Retinoid acid receptor-related Orphan Receptor Alpha (RORA was recently identified as a susceptibility gene for asthma in a genome-wide association study. To investigate the impact of RORA on asthma susceptibility, we performed a genetic association study between RORA single nucleotide polymorphisms (SNPs in the vicinity of the asthma-associated SNP (rs11071559 and asthma-related traits. Because the regulatory region of a previously implicated asthma susceptibility gene, Neuropeptide S receptor 1 (NPSR1, has predicted elements for RORA binding, we hypothesized that RORA may interact biologically and genetically with NPSR1. 37 RORA SNPs and eight NPSR1 SNPs were genotyped in the Swedish birth cohort BAMSE (2033 children and the European cross-sectional PARSIFAL study (1120 children. Seven RORA SNPs confined into a 49 kb region were significantly associated with physician-diagnosed childhood asthma. The most significant association with rs7164773 (T/C was driven by the CC genotype in asthma cases (OR = 2.0, 95%CI 1.36-2.93, p = 0.0003 in BAMSE; and 1.61, 1.18-2.19, p = 0.002 in the combined BAMSE-PARSIFAL datasets, respectively, and strikingly, the risk effect was dependent on the Gln344Arg mutation in NPSR1. In cell models, stimulation of NPSR1 activated a pathway including RORA and other circadian clock genes. Over-expression of RORA decreased NPSR1 promoter activity further suggesting a regulatory loop between these genes. In addition, Rora mRNA expression was lower in the lung tissue of Npsr1 deficient mice compared to wildtype littermates during the early hours of the light period. We conclude that RORA SNPs are associated with childhood asthma and show epistasis with NPSR1, and the interaction between RORA and NPSR1 may be of biological relevance. Combinations of common susceptibility alleles and less common functional polymorphisms may modify the joint risk effects on asthma susceptibility.

  7. Interaction between obesity and the Hypoxia Inducible Factor 3 Alpha Subunit rs3826795 polymorphism in relation with plasma alanine aminotransferase. (United States)

    Wang, Shuo; Song, Jieyun; Yang, Yide; Zhang, Yining; Chawla, Nitesh V; Ma, Jun; Wang, Haijun


    Hypoxia Inducible Factor 3 Alpha Subunit (HIF3A) DNA has been demonstrated to be associated with obesity in the methylation level, and it also has a Body Mass Index (BMI)-independent association with plasma alanine aminotransferase (ALT). However, the relation among obesity, plasma ALT, HIF3A polymorphism and methylation remains unclear. This study aims to identify the association between HIF3A polymorphism and plasma ALT, and further to determine whether the effect of HIF3A polymorphism on ALT could be modified by obesity or mediated by DNA methylation. The HIF3A rs3826795 polymorphism was genotyped in a case-control study including 2030 Chinese children aged 7-18 years (705 obese cases and 1325 non-obese controls). Furthermore, the HIF3A DNA methylation of the peripheral blood was measured in 110 severely obese children and 110 age- and gender- matched normal-weight controls. There was no overall association between the HIF3A rs3826795 polymorphism and ALT. A significant interaction between obesity and rs3826795 in relation with ALT was found (P inter = 0.042), with rs3826795 G-allele number elevating ALT significantly only in obese children (β' = 0.075, P = 0.037), but not in non-obese children (β' = -0.009, P = 0.741). Additionally, a mediation effect of HIF3A methylation was found in the association between the HIF3A rs3826795 polymorphism and ALT among obese children (β' = 0.242, P = 0.014). This is the first study to report the interaction between obesity and HIF3A gene in relation with ALT, and also to reveal a mediation effect among the HIF3A polymorphism, methylation and ALT. This study provides new evidence to the function of HIF3A gene, which would be helpful for future risk assessment and personalized treatment of liver diseases.

  8. Interaction of transforming growth factor-beta-1 with alpha-2-macroglobulin from normal and inflamed equine joints.


    Coté, N; Trout, D R; Hayes, M. A.


    Binding between equine plasma alpha-2-macroglobulin (alpha 2M) and several cytokines known to participate in inflammatory reactions in other species was initially examined. Plasma was obtained from 5 horses with various abnormalities. Samples, both untreated and after reaction with methylamine, were incubated with exogenous, radiolabeled, porcine-derived transforming growth factor-beta-1 (125I-TGF-beta 1), recombinant human interleukin-1-beta (125I-IL-1 beta), and recombinant human tumor necr...

  9. Structural and mutational analyses of the interaction between the barley alpha-amylase/subtilisin inhibitor and the subtilisin savinase reveal a novel mode of inhibition. (United States)

    Micheelsen, Pernille Ollendorff; Vévodová, Jitka; De Maria, Leonardo; Ostergaard, Peter Rahbek; Friis, Esben Peter; Wilson, Keith; Skjøt, Michael


    Subtilisins represent a large class of microbial serine proteases. To date, there are three-dimensional structures of proteinaceous inhibitors from three families in complex with subtilisins in the Protein Data Bank. All interact with subtilisin via an exposed loop covering six interacting residues. Here we present the crystal structure of the complex between the Bacillus lentus subtilisin Savinase and the barley alpha-amylase/subtilisin inhibitor (BASI). This is the first reported structure of a cereal Kunitz-P family inhibitor in complex with a subtilisin. Structural analysis revealed that BASI inhibits Savinase in a novel way, as the interacting loop is shorter than loops previously reported. Mutational analysis showed that Thr88 is crucial for the inhibition, as it stabilises the interacting loop through intramolecular interactions with the BASI backbone.

  10. Biosensor analysis of dynamics of interleukin 5 receptor subunit beta(c) interaction with IL5:IL5R(alpha) complexes. (United States)

    Scibek, Jeffery J; Evergren, Emma; Zahn, Stefan; Canziani, Gabriela A; Van Ryk, Donald; Chaiken, Irwin M


    To gain insight into IL5 receptor subunit recruitment mechanism, and in particular the experimentally elusive pathway for assembly of signaling subunit beta(c), we constructed a soluble beta(c) ectodomain (s(beta)(c)) and developed an optical biosensor assay to measure its binding kinetics. Functionally active s(beta)(c) was anchored via a C-terminal His tag to immobilized anti-His monoclonal antibodies on the sensor surface. Using this surface, we quantitated for the first time direct binding of s(beta)(c) to IL5R(alpha) complexed to either wild-type or single-chain IL5. Binding was much weaker if at all with either R(alpha) or IL5 alone. Kinetic evaluation revealed a moderate affinity (0.2-1 microM) and relatively fast off rate for the s(beta)(c) interaction with IL5:R(alpha) complexes. The data support a model in which beta(c) recruitment occurs with preformed IL5:R(alpha) complex. Dissociation kinetics analysis suggests that the IL5-alpha-beta(c) complex is relatively short-lived. Overall, this study solidifies a model of sequential recruitment of receptor subunits by IL5, provides a novel biosensor binding assay of beta(c) recruitment dynamics, and sets the stage for more advanced characterization of the roles of structural elements within R(alpha), beta(c), and cytokines of the IL5/IL3/GM-CSF family in receptor recruitment and activation.

  11. The host-dependent interaction of alpha-importins with influenza PB2 polymerase subunit is required for virus RNA replication.

    Directory of Open Access Journals (Sweden)

    Patricia Resa-Infante

    Full Text Available The influenza virus polymerase is formed by the PB1, PB2 and PA subunits and is required for virus transcription and replication in the nucleus of infected cells. As PB2 is a relevant host-range determinant we expressed a TAP-tagged PB2 in human cells and isolated intracellular complexes. Alpha-importin was identified as a PB2-associated factor by proteomic analyses. To study the relevance of this interaction for virus replication we mutated the PB2 NLS and analysed the phenotype of mutant subunits, polymerase complexes and RNPs. While mutant PB2 proteins showed reduced nuclear accumulation, they formed polymerase complexes normally when co expressed with PB1 and PA. However, mutant RNPs generated with a viral CAT replicon showed up to hundred-fold reduced CAT accumulation. Rescue of nuclear localisation of mutant PB2 by insertion of an additional SV40 TAg-derived NLS did not revert the mutant phenotype of RNPs. Furthermore, determination of recombinant RNP accumulation in vivo indicated that PB2 NLS mutations drastically reduced virus RNA replication. These results indicate that, above and beyond its role in nuclear accumulation, PB2 interaction with alpha-importins is required for virus RNA replication. To ascertain whether PB2-alpha-importin binding could contribute to the adaptation of H5N1 avian viruses to man, their association in vivo was determined. Human alpha importin isoforms associated efficiently to PB2 protein of an H3N2 human virus but bound to diminished and variable extents to PB2 from H5N1 avian or human strains, suggesting that the function of alpha importin during RNA replication is important for the adaptation of avian viruses to the human host.

  12. Alpha Thalassemia (United States)

    Alpha Thalassemia Physicians often mistake alpha thalassemia trait for iron deficiency anemia and incorrectly prescribe iron supplements that have no effect 1 on the anemia. αα αα Normal alpha ...

  13. Phase space trajectories and Lyapunov exponents in the dynamics of an alpha-helical protein lattice with intra- and inter-spine interactions

    Energy Technology Data Exchange (ETDEWEB)

    Angelin Jeba, K.; Latha, M. M., E-mail: [Department of Physics, Women' s Christian College, Nagercoil 629 001 (India); Jain, Sudhir R. [Nuclear Physics Division, Bhabha Atomic Research Centre, Mumbai 400085 (India)


    The nonlinear dynamics of intra- and inter-spine interaction models of alpha-helical proteins is investigated by proposing a Hamiltonian using the first quantized operators. Hamilton's equations of motion are derived, and the dynamics is studied by constructing the trajectories and phase space plots in both cases. The phase space plots display a chaotic behaviour in the dynamics, which opens questions about the relationship between the chaos and exciton-exciton and exciton-phonon interactions. This is verified by plotting the Lyapunov characteristic exponent curves.

  14. Tumor necrosis factor alpha modulates the dynamics of the plasminogen-mediated early interaction between Bifidobacterium animalis subsp. lactis and human enterocytes. (United States)

    Centanni, Manuela; Bergmann, Simone; Turroni, Silvia; Hammerschmidt, Sven; Chhatwal, Gursharan Singh; Brigidi, Patrizia; Candela, Marco


    The capacity to intervene with the host plasminogen system has recently been considered an important component in the interaction process between Bifidobacterium animalis subsp. lactis and the human host. However, its significance in the bifidobacterial microecology within the human gastrointestinal tract is still an open question. Here we demonstrate that human plasminogen favors the B. animalis subsp. lactis BI07 adhesion to HT29 cells. Prompting the HT29 cell capacity to activate plasminogen, tumor necrosis factor alpha (TNF-α) modulated the plasminogen-mediated bacterium-enterocyte interaction, reducing the bacterial adhesion to the enterocytes and enhancing migration to the luminal compartment.

  15. Phase space trajectories and Lyapunov exponents in the dynamics of an alpha-helical protein lattice with intra- and inter-spine interactions. (United States)

    Angelin Jeba, K; Latha, M M; Jain, Sudhir R


    The nonlinear dynamics of intra- and inter-spine interaction models of alpha-helical proteins is investigated by proposing a Hamiltonian using the first quantized operators. Hamilton's equations of motion are derived, and the dynamics is studied by constructing the trajectories and phase space plots in both cases. The phase space plots display a chaotic behaviour in the dynamics, which opens questions about the relationship between the chaos and exciton-exciton and exciton-phonon interactions. This is verified by plotting the Lyapunov characteristic exponent curves.

  16. Formation of the isomeric pair 194Irm,g in interactions of [alpha] particles with 192Os


    Uddin, M. S.; Sudár Sándor (1946-) (fizikus); Qaim, Syed M.


    Cross sections were measured by the activation technique for the nuclear processes Os-192(alpha,d+pn+np)Ir-194(m,g) up to alpha-particle energies of 39 MeV. From the measured data the isomeric cross-section ratio was deduced as a function of projectile energy. The present experimental data as well as those for the Pt-194(n,p)Ir-194(m,g) reaction, given in the literature, were compared with the results of nuclear model calculations using the code TALYS, which combines the statistical, precompo...

  17. Designing a Site to Embed and to Interact with Wolfram Alpha Widgets in Math and Sciences Courses (United States)

    Cepeda, Francisco Javier Delgado; Acosta, Ruben Dario Santiago


    This paper reports design and implementation outcomes at middle development advance of an educative program based on use and construction of widgets on Wolfram Alpha platform at higher education level for engineering and sciences areas. Widgets were based on Physics and Mathematics curricula under Project Oriented Learning and Blended Learning…

  18. Dynamic retention of Ero1alpha and Ero1beta in the endoplasmic reticulum by interactions with PDI and ERp44. (United States)

    Otsu, Mieko; Bertoli, Gloria; Fagioli, Claudio; Guerini-Rocco, Elena; Nerini-Molteni, Silvia; Ruffato, Elena; Sitia, Roberto


    Disulfide bonds are formed in the endoplasmic reticulum (ER) by sequential interchange reactions: Ero1alpha and Ero1beta transfer oxidative equivalents to protein disulfide isomerase (PDI), which in turn oxidizes cargo proteins. Neither Ero1alpha nor Ero1beta contains known ER localization motif(s), raising the question of how they are retained in this organelle. Here the authors show that, unlike endogenous molecules, overexpressed Ero1alpha and Ero1beta are secreted by HeLa transfectants, suggesting saturation of their normal retention mechanism(s). Co-expression of either PDI or ERp44 prevents Ero1 secretion in a KDEL/RDEL dependent way. Covalent interactions between ERp44 and Ero1 are essential for retention. In contrast, a mutant PDI lacking the four cysteines in the two active sites still inhibits secretion, albeit less efficiently. PDI and ERp44 compete for Ero1 binding. PDI also prevents Ero1 aggregation and dimerization, thus chaperoning its own oxidase. This dynamic retention mechanism of Ero1 may be important for fine-tuning the regulation of ER redox homeostasis and quality control.

  19. Modeling of creep-fatigue interaction of zirconium {alpha} under cyclic loading at 200 C; Modelisation du comportement et de l`endommagement en fatigue-fluage du zirconium {alpha} a 200C

    Energy Technology Data Exchange (ETDEWEB)

    Vogel, C.


    The present work deals with mechanical behaviour of zirconium alpha at 200 deg. C and crack initiation prediction methods, particularly when loading conditions lead to interaction of fatigue and creep phenomena. A classical approach used to study interaction between cyclic effects and constant loading effects does not give easy understanding of experimental results. Therefore, a new approach has been developed, which allow to determine a number of cycles for crack initiation for complex structures under large loading conditions. To study influence of fatigue and creep interaction on crack initiation, a model was chosen, using a scalar variable, giving representation of the material deterioration state. The model uses a non linear cumulating effect between the damage corresponding to cyclic loads and the damage correlated to time influence. The model belongs to uncoupled approaches between damage and behaviour, which is described here by a two inelastic deformations model. This mechanical behaviour model is chosen because it allows distinction between a plastic and a viscous part in inelastic flow. Cyclic damage is function of stress amplitude and mean stress. For the peculiar sensitivity of the material to creep, a special parameter bas been defined to be critical toward creep damage. It is the kinematic term associated to state variables describing this type of hardening in the viscous mechanism. (author).

  20. Chronic immune activation in HIV-1 infection contributes to reduced interferon alpha production via enhanced CD40:CD40 ligand interaction.

    Directory of Open Access Journals (Sweden)

    Norbert Donhauser

    Full Text Available Although a signature of increased interferon (IFN-alpha production is observed in HIV-1 infection, the response of circulating plasmacytoid dendritic cells (PDC to Toll-like receptor ligand stimulation is substantially impaired. This functional PDC deficit, which we specifically observed in HIV-1 infected individuals with less than 500 CD4+ T cells/µl, is not well understood. We provide evidence that the peripheral IFN-alpha production in HIV-1 infection is actively suppressed by the enhanced interaction of CD40 ligand (CD40L, a member of the tumor necrosis factor family, and its receptor CD40, which are both upregulated upon immune activation. Plasma levels of soluble CD40L were significantly higher in untreated HIV-1 infected individuals (n = 52 than in subjects on long-term antiretroviral therapy (n = 62, p<0.03 and in uninfected control donors (n = 16, p<0.001. Concomitantly, cell-associated CD40L and the expression of the receptor CD40 on the PDC were significantly upregulated in HIV-1 infection (p<0.05. Soluble and cell-associated CD40L inhibited the PDC-derived IFN-alpha production by CpG oligodeoxynucleotides dose-dependently. This suppressive effect was observed at much lower, physiological CD40L concentrations in peripheral blood mononuclear cells (PBMC of HIV-1 infected individuals compared to controls (p<0.05. The CpG-induced IFN-alpha production in PBMC of HIV-1 infected donors was directly correlated with PDC and CD4+ T cell counts, and inversely correlated with the viral loads (p<0.001. In HIV-1 infected donors with less than 500 CD4+ T cells/µl, the CpG-induced IFN-alpha production was significantly correlated with the percentage of CD40-expressing PDC and the level of CD40 expression on these cells (p<0.05, whereas CD40L plasma levels played a minor role. In addition, low-dose CD40L contributed to the enhanced production of interleukin 6 and 8 in PBMC of HIV-1 infected donors compared to controls. Our data support

  1. Magnetoencephalographic alpha band connectivity reveals differential Default Mode Network interactions during focused attention and open monitoring meditation

    Directory of Open Access Journals (Sweden)

    Laura eMarzetti


    Full Text Available According to several conceptualizations of meditation, the interplay between brain systems associated to self-related processing, attention and executive control is crucial for meditative states and related traits. We used magnetoencephalography to investigate such interplay in a highly selected group of virtuoso meditators (Theravada Buddhist monks, with long-term training in the two main meditation styles: focused attention (FA and open monitoring (OM meditation. Specifically, we investigated the differences between FA meditation, OM meditation and resting state in the coupling between the posterior cingulate cortex, core node of the Default Mode Network (DMN implicated in mind wandering and self-related processing, and the whole brain, with a recently developed phase coherence approach. Our findings showed a state dependent coupling of PCC to nodes of the DMN and of the executive control brain network in the alpha frequency band (8-12 Hz, related to different attentional and cognitive control processes in FA and OM meditation, consistently with the putative role of alpha band synchronization in the functional mechanisms for attention and consciousness. The coupling of posterior cingulate cortex with left medial prefrontal cortex and superior frontal gyrus characterized the contrast between the two meditation styles in a way that correlated with meditation expertise. These correlations may be related to a higher mindful observing ability and a reduced identification with ongoing mental activity in more expert meditators. Notably, different styles of meditation and different meditation expertise appeared to modulate the dynamic balance between fronto-parietal and DMN networks. Our results support the idea that the interplay between the DMN and the fronto-parietal network in the alpha band is crucial for the transition from resting state to different meditative states.

  2. Magnetoencephalographic alpha band connectivity reveals differential default mode network interactions during focused attention and open monitoring meditation. (United States)

    Marzetti, Laura; Di Lanzo, Claudia; Zappasodi, Filippo; Chella, Federico; Raffone, Antonino; Pizzella, Vittorio


    According to several conceptualizations of meditation, the interplay between brain systems associated to self-related processing, attention and executive control is crucial for meditative states and related traits. We used magnetoencephalography (MEG) to investigate such interplay in a highly selected group of "virtuoso" meditators (Theravada Buddhist monks), with long-term training in the two main meditation styles: focused attention (FA) and open monitoring (OM) meditation. Specifically, we investigated the differences between FA meditation, OM meditation and resting state in the coupling between the posterior cingulate cortex, core node of the Default Mode Network (DMN) implicated in mind wandering and self-related processing, and the whole brain, with a recently developed phase coherence approach. Our findings showed a state dependent coupling of posterior cingulate cortex (PCC) to nodes of the DMN and of the executive control brain network in the alpha frequency band (8-12 Hz), related to different attentional and cognitive control processes in FA and OM meditation, consistently with the putative role of alpha band synchronization in the functional mechanisms for attention and consciousness. The coupling of PCC with left medial prefrontal cortex (lmPFC) and superior frontal gyrus characterized the contrast between the two meditation styles in a way that correlated with meditation expertise. These correlations may be related to a higher mindful observing ability and a reduced identification with ongoing mental activity in more expert meditators. Notably, different styles of meditation and different meditation expertise appeared to modulate the dynamic balance between fronto-parietal (FP) and DMN networks. Our results support the idea that the interplay between the DMN and the FP network in the alpha band is crucial for the transition from resting state to different meditative states.

  3. Interaction of Salivary alpha-Amylase and Amylase-Binding-Protein A (AbpA of Streptococcus gordonii with Glucosyltransferase of S. gordonii and Streptococcus mutans

    Directory of Open Access Journals (Sweden)

    Tanzer Jason M


    Full Text Available Abstract Background Glucosyltransferases (Gtfs, enzymes that produce extracellular glucans from dietary sucrose, contribute to dental plaque formation by Streptococcus gordonii and Streptococcus mutans. The alpha-amylase-binding protein A (AbpA of S. gordonii, an early colonizing bacterium in dental plaque, interacts with salivary amylase and may influence dental plaque formation by this organism. We examined the interaction of amylase and recombinant AbpA (rAbpA, together with Gtfs of S. gordonii and S. mutans. Results The addition of salivary alpha-amylase to culture supernatants of S. gordonii precipitated a protein complex containing amylase, AbpA, amylase-binding protein B (AbpB, and the glucosyltransferase produced by S. gordonii (Gtf-G. rAbpA was expressed from an inducible plasmid, purified from Escherichia coli and characterized. Purified rAbpA, along with purified amylase, interacted with and precipitated Gtfs from culture supernatants of both S. gordonii and S. mutans. The presence of amylase and/or rAbpA increased both the sucrase and transferase component activities of S. mutans Gtf-B. Enzyme-linked immunosorbent assay (ELISA using anti-Gtf-B antibody verified the interaction of rAbpA and amylase with Gtf-B. A S. gordonii abpA-deficient mutant showed greater biofilm growth under static conditions than wild-type in the presence of sucrose. Interestingly, biofilm formation by every strain was inhibited in the presence of saliva. Conclusion The results suggest that an extracellular protein network of AbpA-amylase-Gtf may influence the ecology of oral biofilms, likely during initial phases of colonization.

  4. Characterizing alpha helical properties of Ebola viral proteins as potential targets for inhibition of alpha-helix mediated protein-protein interactions [v3; ref status: indexed,

    Directory of Open Access Journals (Sweden)

    Sandeep Chakraborty


    Full Text Available Ebola, considered till recently as a rare and endemic disease, has dramatically transformed into a potentially global humanitarian crisis. The genome of Ebola, a member of the Filoviridae family, encodes seven proteins. Based on the recently implemented software (PAGAL for analyzing the hydrophobicity and amphipathicity properties of alpha helices (AH in proteins, we characterize the helices in the Ebola proteome. We demonstrate that AHs with characteristically unique features are involved in critical interactions with the host proteins. For example, the Ebola virus membrane fusion subunit, GP2, from the envelope glycoprotein ectodomain has an AH with a large hydrophobic moment. The neutralizing antibody (KZ52 derived from a human survivor of the 1995 Kikwit outbreak recognizes a protein epitope on this AH, emphasizing the critical nature of this secondary structure in the virulence of the Ebola virus. Our method ensures a comprehensive list of such `hotspots'. These helices probably are or can be the target of molecules designed to inhibit AH mediated protein-protein interactions. Further, by comparing the AHs in proteins of the related Marburg viruses, we are able to elicit subtle changes in the proteins that might render them ineffective to previously successful drugs. Such differences are difficult to identify by a simple sequence or structural alignment. Thus, analyzing AHs in the small Ebola proteome can aid rational design aimed at countering the `largest Ebola epidemic, affecting multiple countries in West Africa' (

  5. A Non-Nuclear Role of the Estrogen Receptor Alpha in the Regulation of Cell-Cell Interactions (United States)


    the absence of E2, staining for E-cadherin/j3-catenin and ERu did not overlap, suggesting that ERu does not interact with these junctions (Fig. 5...vitro expressed ERa. As shown in figure 7 A, ERa interacted preferably with the a-catenin homodimer. A role of ERu in F-actin cytoskeleton remodeling

  6. Hyperfine interaction of {sup 25}Al in {alpha}-Al{sub 2}O{sub 3} and its quadrupole moment

    Energy Technology Data Exchange (ETDEWEB)

    Matsuta, K., E-mail:; Mihara, M. [Osaka University, Department of Physics (Japan); Nagatomo, T. [RIKEN (Japan); Matsumiya, R. [Osaka University, Department of Physics (Japan); Momota, S. [Kochi University of Technology (Japan); Ohtsubo, T. [Niigata University, Department of Physics (Japan); Izumikawa, T. [Niigata University, Radioisotope Center (Japan); Hirano, H.; Takahashi, S. [Niigata University, Department of Physics (Japan); Nishimura, D.; Komurasaki, J. [Osaka University, Department of Physics (Japan); Kitagawa, A.; Kanazawa, M.; Torikoshi, M.; Sato, S. [National Institute of Radiological Sciences (Japan); Fukuda, M. [Osaka University, Department of Physics (Japan); Minamisono, T. [Fukui University of Technology (Japan); Sumikama, T. [Tokyo University of Science (Japan); Tanaka, K.; Takechi, M. [RIKEN (Japan)


    The electric quadrupole (Q) moment of short-lived nucleus {sup 25}Al (I{sup {pi}} = 5/2{sup +}, T{sub 1/2} = 7.18 s) has been measured for the first time, by means of the {beta}-NQR technique. The spin polarization of {sup 25}Al was produced in heavy ion collisions and was kept in a {alpha}-Al{sub 2}O{sub 3} single crystal for as long as 2 s and the quadrupole coupling frequency was obtained as vertical bar eqQ / h({sup 25}Al in Al{sub 2}O{sub 3}) vertical bar = (4.05 {+-}0.30) MHz. From the result, the Q moment was determined as |Q({sup 25}Al)| = (240 {+-}20) mb. The present Q moment is larger by 30% than the shell model value of 184 mb, calculated by OXBASH code, which may show additional deformation of the nucleus.

  7. $\\rm{H}\\alpha$ Velocity Fields and Galaxy Interaction in the Quartet of Galaxies NGC 7769, 7770, 7771 and 7771A

    Indian Academy of Sciences (India)

    A. A. Yeghiazaryan; T. A. Nazaryan; A. A. Hakobyan


    The quartet of galaxies NGC 7769, 7770, 7771 and 7771A is a system of interacting galaxies. Close interaction between galaxies caused characteristic morphological features: tidal arms and bars, as well as an induced star formation. In this study, we performed the Fabry–Perot scanning interferometry of the system in $\\rm{H}\\alpha$ line and studied the velocity fields of the galaxies. We found that the rotation curve of NGC 7769 is weakly distorted. The rotation curve of NGC 7771 is strongly distorted with the tidal arms caused by direct flyby of NGC 7769 and flyby of a smaller neighbor NGC 7770. The rotation curve of NGC 7770 is significantly skewed because of the interaction with the much massive NGC 7771. The rotation curves and morphological disturbances suggest that the NGC 7769 and NGC 7771 have passed the first pericenter stage, however, probably the second encounter has not happened yet. Profiles of surface brightness of NGC 7769 have a characteristic break, and profiles of color indices have a minimum at a radius of intensive star formation induced by the interaction with NGC 7771.

  8. Visualization by BiFC of different C/EBP{beta} dimers and their interaction with HP1{alpha} reveals a differential subnuclear distribution of complexes in living cells

    Energy Technology Data Exchange (ETDEWEB)

    Susperreguy, Sebastian; Prendes, Luciana P.; Desbats, Maria A.; Charo, Nancy L. [Instituto de Biologia y Medicina Experimental, CONICET, Buenos Aires (Argentina); Brown, Karen [Chromosome Biology Group, Imperial College of London, London (United Kingdom); MacDougald, Ormond A. [Dept. of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI (United States); Kerppola, Tom [Dept. of Biological Chemistry, University of Michigan Medical School, Ann Arbor, MI (United States); Schwartz, Jessica [Dept. of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI (United States); Piwien-Pilipuk, Graciela, E-mail: [Instituto de Biologia y Medicina Experimental, CONICET, Buenos Aires (Argentina)


    How the co-ordinated events of gene activation and silencing during cellular differentiation are influenced by spatial organization of the cell nucleus is still poorly understood. Little is known about the molecular mechanisms controlling subnuclear distribution of transcription factors, and their interplay with nuclear proteins that shape chromatin structure. Here we show that C/EBP{beta} not only associates with pericentromeric heterochromatin but also interacts with the nucleoskeleton upon induction of adipocyte differentiation of 3T3-L1 cells. Different C/EBP{beta} dimers localize in different nuclear domains. Using BiFC in living cells, we show that LAP (Liver Activating Protein) homodimers localize in euchromatin and heterochromatin. In contrast, LIP (Liver Inhibitory Protein) homodimers localize exclusively in heterochromatin. Importantly, their differential subnuclear distribution mirrors the site for interaction with HP1{alpha}. HP1{alpha} inhibits LAP transcriptional capacity and occupies the promoter of the C/EBP{beta}-dependent gene c/ebp{alpha} in 3T3-L1 preadipocytes. When adipogenesis is induced, HP1{alpha} binding decreases from c/ebp{alpha} promoter, allowing transcription. Thus, the equilibrium among different pools of C/EBP{beta} associated with chromatin or nucleoskeleton, and dynamic changes in their interaction with HP1{alpha}, play key roles in the regulation of C/EBP target genes during adipogenesis.

  9. Homology modeling of lanosterol 14alpha-demethylase of Candida albicans and Aspergillus fumigatus and insights into the enzyme-substrate Interactions

    Institute of Scientific and Technical Information of China (English)

    Sheng C; Zhou Y; Zhu J; Lu J; Zhang W; Zhang M; Song Y; Ji H; Zhu J; Yao J; Yu J; Yang S


    The crystal structure of 14alpha-sterol demethylase from Mycobacterium tuberculosis (MT_14DM) provides a good template for modeling the three dimensional structure of lanosterol 14alpha-demethylase, which is the target of azole antifungal agents. Homologous 3D models of lanosterol 14alpha-demethylase from Candida albicans (CA_14DM) and Aspergillus fumigatus (AF_14DM) were built on the basis of the crystal coordinates of MT_14DM in complex with 4-phenylimidazole and fluconazole. The reliability of the two models was assessed by Ramachandran plots, Profile-3D analysis, and by analyzing the consistency of the two models with the experimental data on the P450(14DM). The overall structures of the resulting CA_14DM model and AF_14DM model are similar to those of the template structures. The two models remain the core structure characteristic for cytochrome P450s and most of the insertions and deletions expose the molecular surface. The structurally and functionally important residues such as the heme binding residues, the residues lining the substrate access channel, and residues in active site were identified from the model. To explore the binding mode of the substrate with the two models, 24(28)-methylene-24,25-dihydrolanosterol was docked into the active site of the two models and hydrophobic interaction and hydrogen-bonding were found to play an important role in substrate recognition and orientation. These results provided a basis for experiments to probe structure-function relationships in the P450(14DM). Although CA_14DM and AF_14DM shared similar core structural character, the active site of the two models were quite different, thus allowing the rational design of specific inhibitors to the target enzyme and the discovery of novel antifungal agents with broad spectrum.

  10. Atomic-scale Modeling of Interactions of Helium, Vacancies and Helium-vacancy Clusters with Screw Dislocations in Alpha-Iron

    Energy Technology Data Exchange (ETDEWEB)

    Heinisch, Howard L.; Gao, Fei; Kurtz, Richard J.


    The interactions of He and vacancy defects with <111> screw dislocations in alpha-Fe are modeled using molecular statics, molecular dynamics and transition state energy determinations. The formation energies and binding energies of interstitial He atoms, vacancies and He-vacancy clusters near and within dislocations in alpha-Fe are determined at various locations relative to the dislocation core. Using the dimer transition state method the migration energies and trajectories of the He and vacancy defects near and within the screw dislocation are also determined. Both interstitial He atoms and single vacancies are attracted to and trapped in the dislocation core region, and they both migrate along the dislocation line with a migration energy of about 0.4 eV, which is about half the migration energy of vacancies in the perfect crystal and about five times the migration energy for interstitial He in the perfect crystal. Divacancies and He-divacancy complexes have migration properties within the dislocation core that are similar to those in the perfect crystal, although the stability of these defects within the dislocation may be somewhat less than in the perfect crystal.

  11. Coat proteins of Rice tungro bacilliform virus and Mungbean yellow mosaic virus contain multiple nuclear-localization signals and interact with importin alpha. (United States)

    Guerra-Peraza, O; Kirk, D; Seltzer, V; Veluthambi, K; Schmit, A C; Hohn, T; Herzog, E


    Transport of the viral genome into the nucleus is an obligatory step in the replication cycle of plant pararetro- and geminiviruses. In both these virus types, the multifunctional coat protein (CP) is thought to be involved in this process. Here, a green fluorescent protein tagging approach was used to demonstrate nuclear import of the CPs of Rice tungro bacilliform virus (RTBV) and Mungbean yellow mosaic virus--Vigna (MYMV) in Nicotiana plumbaginifolia protoplasts. In both cases, at least two nuclear localization signals (NLSs) were identified and characterized. The NLSs of RTBV CP are located within both N- and C-terminal regions (residues 479KRPK/497KRK and 744KRK/758RRK), and those of MYMV CP within the N-terminal part (residues 3KR and 41KRRR). The MYMV and RTBV CP NLSs resemble classic mono- and bipartite NLSs, respectively. However, the N-terminal MYMV CP NLS and both RTBV CP NLSs show peculiarities in the number and position of basic residues. In vitro pull-down assays revealed interaction of RTBV and MYMV CPs with the nuclear import factor importin alpha, suggesting that both CPs are imported into the nucleus via an importin alpha-dependent pathway. The possibility that this pathway could serve for docking of virions to the nucleus is discussed.

  12. Deuteron - $\\alpha$ interaction by inversion of RGM S-matrix determination of spin-orbit potential for spin-1 projectile

    CERN Document Server

    MacIntosh, R S


    The iterative-perturbative (IP) procedure for S-matrix to potential inversion is applied to spin-one projectiles for the restricted case of vector spin-orbit interaction only. In order to evaluate this extension of IP inversion we have inverted the multi-channel RGM $S_{lj}$ of Kanada et al for deuterons scattering from $^4$He with deuteron distortion and then compared the central components with those derived from RGM with spin set to zero. Attention is given to the question of how well the resulting potentials are established. Reliable spin-1 inversion is demonstrated. Results relating to inversion, to deuteron-nucleus interactions and to RGM are presented and suggest the range of nuclear interaction information which the procedure makes possible. Unusual non-locality and parity dependence effects are found; these are of possible relevance to generic properties of nuclear potentials.

  13. Comparative characteristics of protons and alpha particles interactions with C, Fe, Pb nuclei in different models at high energies

    CERN Document Server

    Rapoport, I D; Shestoperov, V Y


    The main parameters of hadron interaction models FLUKA, GHEISHA, QGSM are compared with each other and with some experimental data. The differences of hadron cascades in lead and iron absorbers caused by the models are explored. Possibility to use these codes at high energies (> 1 TeV) is studied

  14. Alpha Blockers (United States)

    ... positive side, alpha blockers might decrease low-density lipoprotein (LDL) cholesterol (the "bad" cholesterol). Alpha blockers can ... PreventionTreatmentofHighBloodPressure/Types-of-Blood-Pressure-Medications_UCM_303247_Article.jsp. Accessed June 4, 2016. Kaplan NM, et ...

  15. Interaction of 2C T cells with a hybrid Ld molecule bearing an alpha 3 domain derived from the class IB molecule, Qa-2. (United States)

    Ungchusri, T; Kettman, J R; Forman, J


    The CD8 co-receptor interacts with nonpolymorphic residues on class I molecules. LQ3, a laboratory engineered Ld molecule bearing an alpha 3 domain derived from Q7 (Qa-2), interacts poorly with anti-Ld CD8-dependent T cells. 2C TCR transgenic mice bear a receptor specific for the p2Ca peptide bound to Ld. The authors show that although this peptide interacts with LQ3, LQ3 APC fail to activate splenic 2C CD8 T cells in vitro in the absence of IL-2, while control Ld APC do. The authors have used this receptor ligand pair to examine negative selection within the thymus of (B6 x C3H.Ld)F1 versus (B6 x C3H.LQ3)F1 radiation chimeras repopulated with 2C bone marrow cells. While positive selection occurs normally in (B6 x C3H)F1 chimeras, animals expressing either Ld or LQ3 fail to generate 2C CD8+ cells. Thus, either CD8 is not required for negative selection of this TCR or a weak interaction of CD8 with LQ3 is sufficient. TSA-1, a developmentally regulated marker, was used to follow the process of negative selection. The results show that deletion of 2C T cells does not occur until thymocytes reach the double positive (DP) stage. Furthermore, the authors noted a small population of DP TSA-1hi cells remains, while DP TSA-1int and TSA-1lo cells are absent. These data support the notion that thymocytes either reach a particular stage of development or locate in an appropriate intrathymic compartment before they undergo negative selection.

  16. Kinetic interaction analysis of human interleukin 5 receptor alpha mutants reveals a unique binding topology and charge distribution for cytokine recognition. (United States)

    Ishino, Tetsuya; Pasut, Gianfranco; Scibek, Jeffery; Chaiken, Irwin


    Human interleukin 5 receptor alpha (IL5Ralpha) comprises three fibronectin type III domains (D1, D2, and D3) in the extracellular region. Previous results have indicated that residues in the D1D2 domains are crucial for high affinity interaction with human interleukin 5 (IL5). Yet, it is the D2D3 domains that have sequence homology with the classic cytokine recognition motif that is generally assumed to be the minimum cytokine-recognizing unit. In the present study, we used kinetic interaction analysis of alanine-scanning mutational variants of IL5Ralpha to define the residues involved in IL5 recognition. Soluble forms of IL5Ralpha variants were expressed in S2 cells, selectively captured via their C-terminal V5 tag by anti-V5 tag antibody immobilized onto the sensor chip and examined for IL5 interaction by using a sandwich surface plasmon resonance biosensor method. Marked effects on the interaction kinetics were observed not only in D1 (Asp(55), Asp(56), and Glu(58)) and D2 (Lys(186) and Arg(188)) domains, but also in the D3 (Arg(297)) domain. Modeling of the tertiary structure of IL5Ralpha indicated that these binding residues fell into two clusters. The first cluster consists of D1 domain residues that form a negatively charged patch, whereas the second cluster consists of residues that form a positively charged patch at the interface of D2 and D3 domains. These results suggest that the IL5 x IL5Ralpha system adopts a unique binding topology, in which the cytokine is recognized by a D2D3 tandem domain combined with a D1 domain, to form an extended cytokine recognition interface.

  17. Drosophila sperm surface alpha-L-fucosidase interacts with the egg coats through its core fucose residues. (United States)

    Intra, Jari; Concetta, Veltri; Daniela, De Caro; Perotti, Maria Elisa; Pasini, Maria Enrica


    Sperm-oocyte interaction during fertilization is multiphasic, with multicomponent events, taking place between egg's glycoproteins and sperm surface receptors. Protein-carbohydrate complementarities in gamete recognition have observed in cases throughout the whole evolutionary scale. Sperm-associated α-L-fucosidases have been identified in various organisms. Their wide distribution and known properties reflect the hypothesis that fucose and α-L-fucosidases have fundamental function(s) during gamete interactions. An α-L-fucosidase has been detected as transmembrane protein on the surface of spermatozoa of eleven species across the genus Drosophila. Immunofluorescence labeling showed that the protein is localized in the sperm plasma membrane over the acrosome and the tail, in Drosophila melanogaster. In the present study, efforts were made to analyze with solid phase assays the oligosaccharide recognition ability of fruit fly sperm α-L-fucosidase with defined carbohydrate chains that can functionally mimic egg glycoconjugates. Our results showed that α-L-fucosidase bound to fucose residue and in particular it prefers N-glycans carrying core α1,6-linked fucose and core α1,3-linked fucose in N-glycans carrying only a terminal mannose residue. The ability of sperm α-L-fucosidase to bind to the micropylar chorion and to the vitelline envelope was examined in in vitro assays in presence of α-L-fucosidase, either alone or in combination with molecules containing fucose residues. No binding was detected when α-L-fucosidase was pre-incubated with fucoidan, a polymer of α-L-fucose and the monosaccharide fucose. Furthermore, egg labeling with anti-horseradish peroxidase, that recognized only core α1,3-linked fucose, correlates with α-L-fucosidase micropylar binding. Collectively, these data support the hypothesis of the potential role of this glycosidase in sperm-egg interactions in Drosophila.

  18. INCURVATA2 encodes the catalytic subunit of DNA Polymerase alpha and interacts with genes involved in chromatin-mediated cellular memory in Arabidopsis thaliana. (United States)

    Barrero, José María; González-Bayón, Rebeca; del Pozo, Juan Carlos; Ponce, María Rosa; Micol, José Luis


    Cell type-specific gene expression patterns are maintained by the stable inheritance of transcriptional states through mitosis, requiring the action of multiprotein complexes that remodel chromatin structure. Genetic and molecular interactions between chromatin remodeling factors and components of the DNA replication machinery have been identified in Schizosaccharomyces pombe, indicating that some epigenetic marks are replicated simultaneously to DNA with the participation of the DNA replication complexes. This model of epigenetic inheritance might be extended to the plant kingdom, as we report here with the positional cloning and characterization of INCURVATA2 (ICU2), which encodes the putative catalytic subunit of the DNA polymerase alpha of Arabidopsis thaliana. The strong icu2-2 and icu2-3 insertional alleles caused fully penetrant zygotic lethality when homozygous and incompletely penetrant gametophytic lethality, probably because of loss of DNA polymerase activity. The weak icu2-1 allele carried a point mutation and caused early flowering, leaf incurvature, and homeotic transformations of sepals into carpels and of petals into stamens. Further genetic analyses indicated that ICU2 interacts with TERMINAL FLOWER2, the ortholog of HETEROCHROMATIN PROTEIN1 of animals and yeasts, and with the Polycomb group (PcG) gene CURLY LEAF. Another PcG gene, EMBRYONIC FLOWER2, was found to be epistatic to ICU2. Quantitative RT-PCR analyses indicated that a number of regulatory genes were derepressed in the icu2-1 mutant, including genes associated with flowering time, floral meristem, and floral organ identity.

  19. Structural bases of dimerization of yeast telomere protein Cdc13 and its interaction with the catalytic subunit of DNA polymerase [alpha

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Jia; Yang, Yuting; Wan, Ke; Mao, Ninghui; Yu, Tai-Yuan; Lin, Yi-Chien; DeZwaan, Diane C.; Freeman, Brian C.; Lin, Jing-Jer; Lue, Neal F.; Lei, Ming


    Budding yeast Cdc13-Stn1-Ten1 (CST) complex plays an essential role in telomere protection and maintenance, and has been proposed to be a telomere-specific replication protein A (RPA)-like complex. Previous genetic and structural studies revealed a close resemblance between Stn1-Ten1 and RPA32-RPA14. However, the relationship between Cdc13 and RPA70, the largest subunit of RPA, has remained unclear. Here, we report the crystal structure of the N-terminal OB (oligonucleotide/oligosaccharide binding) fold of Cdc13. Although Cdc13 has an RPA70-like domain organization, the structures of Cdc13 OB folds are significantly different from their counterparts in RPA70, suggesting that they have distinct evolutionary origins. Furthermore, our structural and biochemical analyses revealed unexpected dimerization by the N-terminal OB fold and showed that homodimerization is probably a conserved feature of all Cdc13 proteins. We also uncovered the structural basis of the interaction between the Cdc13 N-terminal OB fold and the catalytic subunit of DNA polymerase {alpha} (Pol1), and demonstrated a role for Cdc13 dimerization in Pol1 binding. Analysis of the phenotypes of mutants defective in Cdc13 dimerization and Cdc13-Pol1 interaction revealed multiple mechanisms by which dimerization regulates telomere lengths in vivo. Collectively, our findings provide novel insights into the mechanisms and evolution of Cdc13.

  20. Functional interaction of hepatic nuclear factor-4 and peroxisome proliferator-activated receptor-gamma coactivator 1alpha in CYP7A1 regulation is inhibited by a key lipogenic activator, sterol regulatory element-binding protein-1c. (United States)

    Ponugoti, Bhaskar; Fang, Sungsoon; Kemper, Jongsook Kim


    Insulin inhibits transcription of cholesterol 7alpha-hydroxylase (Cyp7a1), a key gene in bile acid synthesis, and the hepatic nuclear factor-4 (HNF-4) site in the promoter was identified as a negative insulin response sequence. Using a fasting/feeding protocol in mice and insulin treatment in HepG2 cells, we explored the inhibition mechanisms. Expression of sterol regulatory element-binding protein-1c (SREBP-1c), an insulin-induced lipogenic factor, inversely correlated with Cyp7a1 expression in mouse liver. Interaction of HNF-4 with its coactivator, peroxisome proliferator-activated receptor-gamma coactivator 1alpha (PGC-1alpha), was observed in livers of fasted mice and was reduced after feeding. Conversely, HNF-4 interaction with SREBP-1c was increased after feeding. In vitro studies suggested that SREBP-1c competed with PGC-1alpha for direct interaction with the AF2 domain of HNF-4. Reporter assays showed that SREBP-1c, but not of a SREBP-1c mutant lacking the HNF-4 interacting domain, inhibited HNF-4/PGC-1alpha transactivation of Cyp7a1. SREBP-1c also inhibited PGC-1alpha-coactivation of estrogen receptor, constitutive androstane receptor, pregnane X receptor, and farnesoid X receptor, implying inhibition of HNF-4 by SREBP-1c could extend to other nuclear receptors. In chromatin immunoprecipitation studies, HNF-4 binding to the promoter was not altered, but PGC-1alpha was dissociated, SREBP-1c and histone deacetylase-2 (HDAC2) were recruited, and acetylation of histone H3 was decreased upon feeding. Adenovirus-mediated expression of a SREBP-1c dominant-negative mutant, which blocks the interaction of SREBP-1c and HNF-4, partially but significantly reversed the inhibition of Cyp7a1 after feeding. Our data show that SREBP-1c functions as a non-DNA-binding inhibitor and mediates, in part, suppression of Cyp7a1 by blocking functional interaction of HNF-4 and PGC-1alpha. This mechanism may be relevant to known repression of many other HNF-4 target genes upon

  1. A quantitative approach to the free radical interaction between alpha-tocopherol and the coantioxidants eugenol, resveratrol or ascorbate. (United States)

    Kadoma, Yoshinori; Ishihara, Mariko; Fujisawa, Seiichiro


    The regeneration of alpha-tocopherol (vitamin E; VE) by coantioxidants such as phenolics and ascorbate has been studied in homogeneous hydrocarbon solution and in biological systems. However, VE phenoxyl radicals (VE*) may be sufficiently reactive to cooxidize phenolic compounds and ascorbates. The coantioxidant behavior of some relevant phenols such as eugenol (EUG), isoeugenol (IsoEUG), 2,6-di-tert-butyl-4-methoxyphenol (DTBMP), trans-resveratrol (RES) and L-ascorbyl-2,6-dibutyrate (ASDB; an ascorbate derivative) with the antioxidant VE at a molar ratio of 1:1 was investigated by the induction period (IP) method in the kinetics of polymerization of methyl methacrylate (MMA) initiated by the thermal decomposition of 2,2'-azobis(isobutyronitrile) (AIBN; a source of alkyl radicals, R*) or benzoyl peroxide (BPO; a source of peroxy radicals, PhCOO*) under nearly anaerobic conditions. Synergism, implying regeneration of VE by the coantioxidant, was observed with only two of these combinations, VE/EUG with PhCOO* and VE/DTBMP with R*. For other mixtures of VE with a phenolic coantioxidant, VE was able to cooxidize the phenolic. Regeneration can only be observed if the bond dissociation energy (BDE) of the coantioxidant is lower than, or at least close to, that of VE. The driving force for regeneration of VE by EUG may be removal of the semiquinone radical of EUG by VE, leading to the formation of VE and EUG-quinonemethide, even though the BDE value of EUG is greater by 5.8 kcal/mol than that of VE. Further evidence for this mechanism of regeneration is provided by the value of approximately 2 for the stoichiometric factor (n) of EUG induced by PhCOO*, but not by R*, again implying the formation of EUG-quinonemethide. The regeneration of VE by DTBMP in the R* system may result from their much smaller difference in BDE (0.1-1.3 kcal/mol). Since VE is rapidly oxidized by PhCOO*, regeneration of VE by DTBMP was not found in this system. The observed IP for the VE

  2. Immunoassay for Visualization of Protein-Protein Interactions on Ni-Nitrilotriacetate Support: Example of a Laboratory Exercise with Recombinant Heterotrimeric G[alpha][subscript i2][beta][subscript 1[gamma]2] Tagged by Hexahistidine from sf9 Cells (United States)

    Bavec, Aljosa


    We have developed an "in vitro assay" for following the interaction between the [alpha][subscript i2] subunit and [beta][subscript 1[gamma]2] dimer from sf9 cells. This method is suitable for education purposes because it is easy, reliable, nonexpensive, can be applied for a big class of 20 students, and avoid the commonly used kinetic approach,…

  3. Disruption of estrogen receptor alpha-p53 interaction in breast tumors: a novel mechanism underlying the anti-tumor effect of radiation therapy. (United States)

    Liu, Wensheng; Ip, Margot M; Podgorsak, Matthew B; Das, Gokul M


    Inactivation of tumor suppressor p53 is one of the most frequent events in cancer. Unlike many other cancers, however, p53 gene mutations are infrequent in breast cancers, as about 80% of breast tumors contain wild type p53. The mechanisms underlying functional inactivation of wild type p53 in breast cancer have remained elusive. Besides, how p53 gets activated in breast tumors subjected to radiation therapy remains unknown. We recently reported that in MCF-7 breast cancer cells, estrogen receptor alpha (ERalpha) directly binds to p53 and represses its function. Furthermore, the ERalpha-p53 interaction was disrupted by ionizing radiation. These observations have important translational implications especially as there are no reliable cellular or molecular criteria for rational radiotherapy for breast cancer. Here we report our studies towards addressing this important issue, using an MCF-7 breast cancer xenograft model in mice. Radiation effectively inhibits growth of these tumors and stabilizes p53, but has no observable effect on ERalpha protein level. Importantly, chromatin immunoprecipitation (ChIP) assays demonstrated that ERalpha interacts with p53 bound to endogenous target gene promoters in tumors in vivo, and this interaction is considerably reduced in response to radiotherapy although p53 level is increased. Concomitant with its effect on ERalpha-p53 interaction, radiation increases p53-mediated transcriptional activation of several target genes and increases p53-mediated transcriptional repression of survivin. Our studies show that disruption of ERalpha-p53 interaction in vivo resulting in restoration of functional p53 is a cellular response to radiation. Radiation could be affecting ERalpha and/or p53 directly or it could be influencing other proteins associated with the ERalpha-p53 complex. To the best of our knowledge, this is the first report on analysis of DNA-protein-protein interaction occurring on endogenous gene promoters in vivo in breast tumor

  4. Alpha fetoprotein (United States)

    Fetal alpha globulin; AFP ... Greater than normal levels of AFP may be due to: Cancer in testes , ovaries, biliary (liver secretion) tract, stomach, or pancreas Cirrhosis of the liver Liver cancer ...

  5. Inhibin alpha gene expression in human trophoblasts is regulated by interactions between TFAP2 and cAMP signaling pathways. (United States)

    Depoix, Christophe L; Debiève, Frédéric; Hubinont, Corinne


    Inhibin α (Inha) gene expression is regulated, in rat granulosa cells, via a cyclic 3',5'-adenosine monophosphate (AMP)-response element (CRE) found in a region of the promoter that is homologous to the human INHA promoter. We previously found that during in vitro cytotrophoblast differentiation, human INHA gene expression was regulated by TFAP2A via association with an AP-2 site located upstream of this CRE. The aim of this study was to evaluate if the human INHA gene was also regulated by cAMP in trophoblasts, and to investigate the possible crosstalk between TFAP2 and cAMP signaling pathways in the regulation of INHA gene expression. Treatment with cAMP or forskolin increased INHA mRNA expression by 7- and 2-fold in primary cytotrophoblasts and choriocarcinoma-derived BeWo cells, respectively. Treatment with the protein kinase A inhibitor H-89 reduced forskolin-induced luciferase activity by ∼40% in BeWo cells transfected with an INHA promoter-driven luciferase reporter vector. TFAP2 overexpression increased basal luciferase activity, whereas the dominant repressor KCREB abolished it. Surprisingly, mutation of the CRE also eliminated the TFAP2-induced transcription, although TFAP2 overexpression was still able to increase forskolin-induced luciferase activity when the AP-2 binding site, but not the CRE site, was mutated. Thus, INHA gene expression is upregulated by cAMP via CRE in human trophoblasts, and TFAP2 regulates this expression by interacting with CRE.

  6. Structural variation of alpha-synuclein with temperature by a coarse-grained approach with knowledge-based interactions

    Directory of Open Access Journals (Sweden)

    Peter Mirau


    Full Text Available Despite enormous efforts, our understanding the structure and dynamics of α-synuclein (ASN, a disordered protein (that plays a key role in neurodegenerative disease is far from complete. In order to better understand sequence-structure-property relationships in α-SYNUCLEIN we have developed a coarse-grained model using knowledge-based residue-residue interactions and used it to study the structure of free ASN as a function of temperature (T with a large-scale Monte Carlo simulation. Snapshots of the simulation and contour contact maps show changes in structure formation due to self-assembly as a function of temperature. Variations in the residue mobility profiles reveal clear distinction among three segments along the protein sequence. The N-terminal (1-60 and C-terminal (96-140 regions contain the least mobile residues, which are separated by the higher mobility non-amyloid component (NAC (61-95. Our analysis of the intra-protein contact profile shows a higher frequency of residue aggregation (clumping in the N-terminal region relative to that in the C-terminal region, with little or no aggregation in the NAC region. The radius of gyration (Rg of ASN decays monotonically with decreasing the temperature, consistent with the finding of Allison et al. (JACS, 2009. Our analysis of the structure function provides an insight into the mass (N distribution of ASN, and the dimensionality (D of the structure as a function of temperature. We find that the globular structure with D ≈ 3 at low T, a random coil, D ≈ 2 at high T and in between (2 ≤ D ≤ 3 at the intermediate temperatures. The magnitudes of D are in agreement with experimental estimates (J. Biological Chem 2002.

  7. Structural variation of alpha-synuclein with temperature by a coarse-grained approach with knowledge-based interactions (United States)

    Mirau, Peter; Farmer, B. L.; Pandey, R. B.


    Despite enormous efforts, our understanding the structure and dynamics of α-synuclein (ASN), a disordered protein (that plays a key role in neurodegenerative disease) is far from complete. In order to better understand sequence-structure-property relationships in α-SYNUCLEIN we have developed a coarse-grained model using knowledge-based residue-residue interactions and used it to study the structure of free ASN as a function of temperature (T) with a large-scale Monte Carlo simulation. Snapshots of the simulation and contour contact maps show changes in structure formation due to self-assembly as a function of temperature. Variations in the residue mobility profiles reveal clear distinction among three segments along the protein sequence. The N-terminal (1-60) and C-terminal (96-140) regions contain the least mobile residues, which are separated by the higher mobility non-amyloid component (NAC) (61-95). Our analysis of the intra-protein contact profile shows a higher frequency of residue aggregation (clumping) in the N-terminal region relative to that in the C-terminal region, with little or no aggregation in the NAC region. The radius of gyration (Rg) of ASN decays monotonically with decreasing the temperature, consistent with the finding of Allison et al. (JACS, 2009). Our analysis of the structure function provides an insight into the mass (N) distribution of ASN, and the dimensionality (D) of the structure as a function of temperature. We find that the globular structure with D ≈ 3 at low T, a random coil, D ≈ 2 at high T and in between (2 ≤ D ≤ 3) at the intermediate temperatures. The magnitudes of D are in agreement with experimental estimates (J. Biological Chem 2002).

  8. Interaction of the heterotrimeric G protein alpha subunit SSG-1 of Sporothrix schenckii with proteins related to stress response and fungal pathogenicity using a yeast two-hybrid assay

    Directory of Open Access Journals (Sweden)

    González-Méndez Ricardo


    Full Text Available Abstract Background Important biological processes require selective and orderly protein-protein interactions at every level of the signalling cascades. G proteins are a family of heterotrimeric GTPases that effect eukaryotic signal transduction through the coupling of cell surface receptors to cytoplasmic effector proteins. They have been associated with growth and pathogenicity in many fungi through gene knock-out studies. In Sporothrix schenckii, a pathogenic, dimorphic fungus, we previously identified a pertussis sensitive G alpha subunit, SSG-1. In this work we inquire into its interactions with other proteins. Results Using the yeast two-hybrid technique, we identified protein-protein interactions between SSG-1 and other important cellular proteins. The interactions were corroborated using co-immuneprecipitation. Using these techniques we identified a Fe/Mn superoxide dismutase (SOD, a glyceraldehyde-3-P dehydrogenase (GAPDH and two ion transport proteins, a siderophore-iron transporter belonging to the Major Facilitator Superfamily (MFS and a divalent-cation transporter of the Nramp (natural resistance-associated macrophage protein family as interacting with SSG-1. The cDNA's encoding these proteins were sequenced and bioinformatic macromolecular sequence analyses were used for the correct classification and functional assignment. Conclusions This study constitutes the first report of the interaction of a fungal G alpha inhibitory subunit with SOD, GAPDH, and two metal ion transporters. The identification of such important proteins as partners of a G alpha subunit in this fungus suggests possible mechanisms through which this G protein can affect pathogenicity and survival under conditions of environmental stress or inside the human host. The two ion transporters identified in this work are the first to be reported in S. schenckii and the first time they are identified as interacting with fungal G protein alpha subunits. The association

  9. Folding model study of the elastic $\\alpha + \\alpha$ scattering at low energies

    CERN Document Server

    Tan, Ngo Hai; Khoa, Dao T


    The folding model analysis of the elastic $\\alpha + \\alpha$ scattering at the incident energies below the reaction threshold of 34.7 MeV (in the lab system) has been done using the well-tested density dependent versions of the M3Y interaction and realistic choices for the $^4$He density. Because the absorption is negligible at the energies below the reaction threshold, we were able to probe the $\\alpha + \\alpha$ optical potential at low energies quite unambiguously and found that the $\\alpha + \\alpha$ overlap density used to construct the density dependence of the M3Y interaction is strongly distorted by the Pauli blocking. This result gives possible explanation of a long-standing inconsistency of the double-folding model in its study of the elastic $\\alpha + \\alpha$ and $\\alpha$-nucleus scattering at low energies using the same realistic density dependent M3Y interaction.

  10. Comparison of the interactions of a specific neurotoxin (alpha-bungarotoxin) with the acetylcholine receptor in Torpedo californica and Electrophorus electricus membrane preparations. (United States)

    Leprince, P; Noble, R L; Hess, G P


    alpha-Bungarotoxin, a snake neurotoxin, binds irreversibly and specifically to the acetylcholine receptor isolated from the electroplax of Electrophorus electricus and Torpedo species and has been an important tool in the study of the receptor-ligand binding mechanism. Two distinct kinetic processes have been observed in studies with membranes from E. electricus. A minimum mechanism for the toxin reaction involves (i) the reversible binding of two toxin molecules to the receptor prior to the irreversible formation of toxin receptor complexes and (ii) a toxin-induced conformational change of the receptor which leads to an increase in the affinity of the receptor binding sites for toxin [Hess, G. P., Bulger, J. E., Fu, J.-j. L., Hindy, E. F., & Silberstein, R. J. (1975) Biochem. Biophys. Res. Commun. 64, 1018-1027]. Only one process has been detected in Torpedo membranes. Here, we determine whether the receptors in Torpedo californica and E. electricus membranes have different properties or whether the measurements and their interpretation were responsible for the different results. Two methods which are frequently used in binding studies to separate free and bound toxin, a CM-52 cellulose minicolumn assay and DE-81 filter disk assay, have been compared. The results obtained indicate that the interaction of toxin with receptor from T. californica is similar to that observed with receptor from E. electricus. The apparent differences which have been reported in the literature are shown to have arisen from the design of the experiments in which T. californica membranes were used.

  11. A peptide mimic of an antigenic loop of alpha-human chorionic gonadotropin hormone: solution structure and interaction with a llama V-HH domain

    NARCIS (Netherlands)

    Ferrat, G.; Renisio, J.G.; Morelli, X.; Slootstra, J.W.; Meloen, R.; Cambillau, C.; Darbon, H.


    The X-ray structure of a ternary complex between human chorionic gonadotropin hormone (hCG) and two Fvs recognizing its alpha and beta subunits has been recently determined. The Fvs recognize the elongated hCG molecule by its two ends, one being the Leu-12-Cys-29 loop of the alpha subunit. We have d

  12. $\\alpha_s$ review (2016)

    CERN Document Server

    d'Enterria, David


    The current world-average of the strong coupling at the Z pole mass, $\\alpha_s(m^2_{Z}) = 0.1181 \\pm 0.0013$, is obtained from a comparison of perturbative QCD calculations computed, at least, at next-to-next-to-leading-order accuracy, to a set of 6 groups of experimental observables: (i) lattice QCD "data", (ii) $\\tau$ hadronic decays, (iii) proton structure functions, (iv) event shapes and jet rates in $e^+e^-$ collisions, (v) Z boson hadronic decays, and (vi) top-quark cross sections in p-p collisions. In addition, at least 8 other $\\alpha_s$ extractions, usually with a lower level of theoretical and/or experimental precision today, have been proposed: pion, $\\Upsilon$, W hadronic decays; soft and hard fragmentation functions; jets cross sections in pp, e-p and $\\gamma$-p collisions; and photon F$_2$ structure function in $\\gamma\\,\\gamma$ collisions. These 14 $\\alpha_s$ determinations are reviewed, and the perspectives of reduction of their present uncertainties are discussed.

  13. Raman micro-spectroscopic investigation of the interaction of cultured HCT116 colon cancer cells with alpha-difluoromethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase (United States)

    Akyuz, S.; Ozel, A. E.; Balci, K.; Akyuz, T.; Coker, A.; Arisan, E. D.; Palavan-Unsal, N.; Ozalpan, A.


    The interaction of cultured colon cancer cells with alpha-difluoromethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase, has been investigated, using Raman micro-spectroscopy, in order to investigate DFMO induced effects. Raman spectra of the cultured HCT116 colon cancer cells treated with DFMO at different concentrations (0, 1, 2.5, 5, and 7.5 mM) were recorded in the range 550-2300 cm -1. It has been shown that second derivative profile of the raw Raman spectrum of the colon cancer cells (i.e., the original experimental spectrum without any computational corrections) discriminates the weak but sharp bands from the strong, broad fluorescence background, and gives information about the position of the peaks and their band widths. The relative integrated intensities of the 781 cm -1 and 788 cm -1 DNA/RNA marker bands to that of 1451 cm -1 band are found to decrease by addition of DFMO. Up to 65% reduction in the magnitude of the 1003 cm -1 band, the characteristic phenylalanine ring breathing mode, in comparison to that of 1451 band, is observed. The results indicate DFMO induced apoptosis. On the other hand the intensity ratio of the tyrosine Fermi doubled around 830 cm -1 and 850 cm -1, which is a marker of hydrogen-bonding state of phenolic OH, is changed. The addition of DFMO may alter the tyrosine environment in cells, and parts of tyrosine residues are exposed. We also observed some modifications in amide I band, pointing out the alterations of the secondary structure of cell proteins by the presence of DFMO.

  14. Interaction between TNF and BmooMP-Alpha-I, a Zinc Metalloprotease Derived from Bothrops moojeni Snake Venom, Promotes Direct Proteolysis of This Cytokine: Molecular Modeling and Docking at a Glance (United States)

    Silva, Maraisa Cristina; Lopes Silva, Tamires; Silva, Murilo Vieira; Mota, Caroline Martins; Santiago, Fernanda Maria; Fonseca, Kelly Cortes; Oliveira, Fábio; Mineo, Tiago Wilson Patriarca; Mineo, José Roberto


    Tumor necrosis factor (TNF) is a major cytokine in inflammatory processes and its deregulation plays a pivotal role in several diseases. Here, we report that a zinc metalloprotease extracted from Bothrops moojeni venom (BmooMP-alpha-I) inhibits TNF directly by promoting its degradation. This inhibition was demonstrated by both in vitro and in vivo assays, using known TLR ligands. These findings are supported by molecular docking results, which reveal interaction between BmooMP-alpha-I and TNF. The major cluster of interaction between BmooMP-alpha-I and TNF was confirmed by the structural alignment presenting Ligand Root Mean Square Deviation LRMS = 1.05 Å and Interactive Root Mean Square Deviation IRMS = 1.01 Å, this result being compatible with an accurate complex. Additionally, we demonstrated that the effect of this metalloprotease on TNF is independent of cell cytotoxicity and it does not affect other TLR-triggered cytokines, such as IL-12. Together, these results indicate that this zinc metalloprotease is a potential tool to be further investigated for the treatment of inflammatory disorders involving TNF deregulation. PMID:27447669

  15. HSP72 protects cells from ER stress-induced apoptosis via enhancement of IRE1alpha-XBP1 signaling through a physical interaction.

    Directory of Open Access Journals (Sweden)

    Sanjeev Gupta

    Full Text Available Endoplasmic reticulum (ER stress is a feature of secretory cells and of many diseases including cancer, neurodegeneration, and diabetes. Adaptation to ER stress depends on the activation of a signal transduction pathway known as the unfolded protein response (UPR. Enhanced expression of Hsp72 has been shown to reduce tissue injury in response to stress stimuli and improve cell survival in experimental models of stroke, sepsis, renal failure, and myocardial ischemia. Hsp72 inhibits several features of the intrinsic apoptotic pathway. However, the molecular mechanisms by which Hsp72 expression inhibits ER stress-induced apoptosis are not clearly understood. Here we show that Hsp72 enhances cell survival under ER stress conditions. The UPR signals through the sensor IRE1alpha, which controls the splicing of the mRNA encoding the transcription factor XBP1. We show that Hsp72 enhances XBP1 mRNA splicing and expression of its target genes, associated with attenuated apoptosis under ER stress conditions. Inhibition of XBP1 mRNA splicing either by dominant negative IRE1alpha or by knocking down XBP1 specifically abrogated the inhibition of ER stress-induced apoptosis by Hsp72. Regulation of the UPR was associated with the formation of a stable protein complex between Hsp72 and the cytosolic domain of IRE1alpha. Finally, Hsp72 enhanced the RNase activity of recombinant IRE1alpha in vitro, suggesting a direct regulation. Our data show that binding of Hsp72 to IRE1alpha enhances IRE1alpha/XBP1 signaling at the ER and inhibits ER stress-induced apoptosis. These results provide a physical connection between cytosolic chaperones and the ER stress response.

  16. HSP72 protects cells from ER stress-induced apoptosis via enhancement of IRE1alpha-XBP1 signaling through a physical interaction.

    LENUS (Irish Health Repository)

    Gupta, Sanjeev


    Endoplasmic reticulum (ER) stress is a feature of secretory cells and of many diseases including cancer, neurodegeneration, and diabetes. Adaptation to ER stress depends on the activation of a signal transduction pathway known as the unfolded protein response (UPR). Enhanced expression of Hsp72 has been shown to reduce tissue injury in response to stress stimuli and improve cell survival in experimental models of stroke, sepsis, renal failure, and myocardial ischemia. Hsp72 inhibits several features of the intrinsic apoptotic pathway. However, the molecular mechanisms by which Hsp72 expression inhibits ER stress-induced apoptosis are not clearly understood. Here we show that Hsp72 enhances cell survival under ER stress conditions. The UPR signals through the sensor IRE1alpha, which controls the splicing of the mRNA encoding the transcription factor XBP1. We show that Hsp72 enhances XBP1 mRNA splicing and expression of its target genes, associated with attenuated apoptosis under ER stress conditions. Inhibition of XBP1 mRNA splicing either by dominant negative IRE1alpha or by knocking down XBP1 specifically abrogated the inhibition of ER stress-induced apoptosis by Hsp72. Regulation of the UPR was associated with the formation of a stable protein complex between Hsp72 and the cytosolic domain of IRE1alpha. Finally, Hsp72 enhanced the RNase activity of recombinant IRE1alpha in vitro, suggesting a direct regulation. Our data show that binding of Hsp72 to IRE1alpha enhances IRE1alpha\\/XBP1 signaling at the ER and inhibits ER stress-induced apoptosis. These results provide a physical connection between cytosolic chaperones and the ER stress response.

  17. Detailed analysis of the IL-5-IL-5R alpha interaction: characterization of crucial residues on the ligand and the receptor.


    S; Cornelis; Plaetinck, G; Devos, R; Van der Heyden, J; Tavernier, J.; Sanderson, C. J.; Guisez, Y; Fiers, W


    The receptor for interleukin-5 (IL-5) is composed of two different subunits. The IL-5 receptor alpha (IL-5R alpha) is required for ligand-specific binding while association with the beta-chain results in increased binding affinity. Murine IL-5 (mIL-5) has similar activity on human and murine cells, whereas human IL-5 (hIL-5) has marginal activity on murine cells. We found that the combined substitution of K84 and N108 on hIL-5 by their respective murine counterpart yields a molecule which is ...

  18. Hyperekplexia mutation R271L of alpha1 glycine receptors potentiates allosteric interactions of nortropeines, propofol and glycine with [3H]strychnine binding. (United States)

    Maksay, Gábor; Bíró, Tímea; Laube, Bodo; Nemes, Péter


    Human alpha1 and hyperekplexia mutant alpha1(R271L) glycine receptors (GlyRs) were transiently expressed in human embryonic kidney 293 cells for [3H]strychnine binding. Binding parameters were determined using a ternary allosteric model. The hyperekplexia mutation increased the positive cooperativity of 0.3 mM propofol and glycine binding by about six times: the cooperativity factor beta was 0.26 for alpha1 GlyRs and 0.04 for alpha1(R271L) GlyRs. Thus, propofol restored the potency of glycine impaired by the mutation. Five nortropeines, i.e. substituted benzoates of nortropine and a new compound, nortropisetron were prepared and also examined on [3H]strychnine binding. They showed nanomolar displacing potencies amplified by the hyperekplexia mutation. The affinity of nor-O-zatosetron (2.6 nM) is one of the highest reported for GlyRs. This binding test offers an in vitro method to evaluate agents against neurological disorders associated with inherited mutations of GlyRs.

  19. Acyl-CoA esters antagonize the effects of ligands on peroxisome proliferator-activated receptor alpha conformation, DNA binding, and interaction with Co-factors

    DEFF Research Database (Denmark)

    Elholm, M; Dam, I; Jorgensen, C;


    The peroxisome proliferator-activated receptor alpha (PPARalpha) is a ligand-activated transcription factor and a key regulator of lipid homeostasis. Numerous fatty acids and eicosanoids serve as ligands and activators for PPARalpha. Here we demonstrate that S-hexadecyl-CoA, a nonhydrolyzable...

  20. Recognition of interaction interface residues in low-resolution structures of protein assemblies solely from the positions of C(alpha atoms.

    Directory of Open Access Journals (Sweden)

    Rupali A Gadkari

    Full Text Available BACKGROUND: The number of available structures of large multi-protein assemblies is quite small. Such structures provide phenomenal insights on the organization, mechanism of formation and functional properties of the assembly. Hence detailed analysis of such structures is highly rewarding. However, the common problem in such analyses is the low resolution of these structures. In the recent times a number of attempts that combine low resolution cryo-EM data with higher resolution structures determined using X-ray analysis or NMR or generated using comparative modeling have been reported. Even in such attempts the best result one arrives at is the very course idea about the assembly structure in terms of trace of the C(alpha atoms which are modeled with modest accuracy. METHODOLOGY/PRINCIPAL FINDINGS: In this paper first we present an objective approach to identify potentially solvent exposed and buried residues solely from the position of C(alpha atoms and amino acid sequence using residue type-dependent thresholds for accessible surface areas of C(alpha. We extend the method further to recognize potential protein-protein interface residues. CONCLUSION/ SIGNIFICANCE: Our approach to identify buried and exposed residues solely from the positions of C(alpha atoms resulted in an accuracy of 84%, sensitivity of 83-89% and specificity of 67-94% while recognition of interfacial residues corresponded to an accuracy of 94%, sensitivity of 70-96% and specificity of 58-94%. Interestingly, detailed analysis of cases of mismatch between recognition of interface residues from C(alpha positions and all-atom models suggested that, recognition of interfacial residues using C(alpha atoms only correspond better with intuitive notion of what is an interfacial residue. Our method should be useful in the objective analysis of structures of protein assemblies when positions of only (alpha positions are available as, for example, in the cases of integration of cryo

  1. TNF-alpha and 9-cis-retinoic acid synergistically induce ICAM-1 expression: evidence for interaction of retinoid receptors with NF-kappa B. (United States)

    Chadwick, C C; Shaw, L J; Winneker, R C


    TNF-alpha and 9-cis-retinoic acid (9-cis-R) synergistically enhance ICAM-1 protein expression in immortalized human aortic endothelial cells (HAECTs). At a TNF-alpha concentration of 0.1 ng/ml, 1 microM 9-cis-R enhanced ICAM-1 protein expression 4-fold. Treatment with 1 microM 9-cis-R alone caused no induction of ICAM-1 expression. Functional analysis of human ICAM-1 promoter-luciferase constructs revealed that the synergism was attributable to transcriptional regulation. Expression of a luciferase reporter vector containing a 311-bp fragment of the ICAM-1 promoter (-252 to + 59 bp relative to the transcriptional start site) was increased 2.9- and 4.9-fold by treatment with 9-cis-R and TNF-alpha, respectively, while cotreatment with 9-cis-R and TNF-alpha induced expression to 19.9-fold. Mutation studies revealed that RARE and NF-kappa B sites located respectively at -226 and -188 bp relative to the transcription start site are essential for the synergistic control of promoter activity. Mutation of either the RARE or the NF-kappa B site eliminated the synergistic enhancement of promoter activity. Moreover, mutation of the RARE abrogated promoter activity induced by treatment with TNF-alpha alone and mutation of the NF-kappa B site eliminated promoter activity induced by treatment with 9-cis-R alone. We conclude that retinoid receptors and NF-kappa B act in concert at the promoter level to facilitate ICAM-1 expression in endothelial cells.

  2. Direct binding of syndecan-4 cytoplasmic domain to the catalytic domain of protein kinase C alpha (PKC alpha) increases focal adhesion localization of PKC alpha

    DEFF Research Database (Denmark)

    Lim, Ssang-Taek; Longley, Robert L; Couchman, John R


    Syndecan-4 is a transmembrane heparan sulfate proteoglycan that acts as a coreceptor with integrins in focal adhesion formation. The central region of syndecan-4 cytoplasmic domain (4V; LGKKPIYKK) binds phosphatidylinositol 4,5-bisphosphate, and together they regulate protein kinase C alpha (PKC...... alpha) activity. Syndecan 4V peptide directly potentiates PKC alpha activity, leading to "superactivation" of the enzyme, apparently through an interaction with its catalytic domain. We now have performed yeast two-hybrid and in vitro binding assays to determine the interaction sites between 4V and PKC...... alpha. Full-length PKC alpha weakly interacted with 4V by yeast two-hybrid assays, but PKC alpha constructs that lack the pseudosubstrate region or constructs of the whole catalytic domain interacted more strongly. A mutated 4V sequence (4V(YF): LGKKPIFKK) did not interact with PKC alpha, indicating...

  3. A reassessment of the potential for an alpha-mode containment failure and a review of the current understanding of broader fuel-coolant interaction issues. Second steam explosion review group workshop

    Energy Technology Data Exchange (ETDEWEB)

    Basu, S. [Nuclear Regulatory Commission, Washington, DC (United States); Ginsberg, T. [Brookhaven National Lab., Upton, NY (United States)


    This report summarizes the review and evaluation by experts of the current understanding of the molten fuel-coolant interaction (FCI) issues covering the complete spectrum of interactions, i.e., from mild quenching to very energetic interactions including those that could lead to the alpha-mode containment failure. Of the eleven experts polled, all but two concluded that the alpha-mode failure issue was resolved from a risk perspective, meaning that this mode of failure is of very low probability, that it is of little or no significance to the overall risk from a nuclear power plant, and that any further reduction in residual uncertainties is not likely to change the probability in an appreciable manner. To a lesser degree, discussions also took place on the broader FCI issues such as mild quenching of core melt during non-explosive FCI, and shock loading of lower head and ex-vessel support structures arising from explosive localized FCIs. These latter issues are relevant with regard to determining the efficacy of certain accident management strategies for operating reactors as well as for advanced light water reactors. The experts reviewed the status of understanding of the FCI phenomena in the context of these broader issues, identified residual uncertainties in the understanding, and recommended future research (both experimental and analytical) to reduce the uncertainties.

  4. Interaction between wheat alpha-amylase/trypsin bi-functional inhibitor and mammalian digestive enzymes: Kinetic, equilibrium and structural characterization of binding. (United States)

    Cuccioloni, Massimiliano; Mozzicafreddo, Matteo; Ali, Ishtiaq; Bonfili, Laura; Cecarini, Valentina; Eleuteri, Anna Maria; Angeletti, Mauro


    Alpha-amylase/trypsin bi-functional inhibitors (ATIs) are non-gluten protein components of wheat and other cereals that can hypersensitise the human gastrointestinal tract, eventually causing enteropathies in predisposed individuals. These inhibitory proteins can act both directly by targeting specific pro-inflammatory receptors, and indirectly by impairing the activity of digestive enzymes, the latter event causing the accumulation of undigested peptides with potential immunogenic properties. Herein, according to a concerted approach based on in vitro and in silico methods we characterized kinetics, equilibrium parameters and modes of binding of the complexes formed between wheat ATI and two representative mammalian digestive enzymes, namely trypsin and alpha-amylase. Interestingly, we demonstrated ATI to target both enzymes with independent binding sites and with moderately high affinity.

  5. Interaction between {alpha}5{beta}1 integrin and secreted fibronectin is involved in macrophage differentiation of human HL-60 myeloid leukemia cells.

    Energy Technology Data Exchange (ETDEWEB)

    Laouar, A.; Collart, F. R.; Chubb, C. B. H.; Xie, B.; Huberman, E.; Center for Mechanistic Biology and Biotechnology; anl-cmb


    We examined the role of fibronectin (FN) and FN-binding integrins in macrophage differentiation. Increased FN and {alpha}5{beta}1 integrin gene expression was observed in phorbol 12-myristate 13-acetate PMA-treated HL-60 cells and PMA- or macrophage-CSF-treated blood monocytes before the manifestation of macrophage markers. After treatment of HL-60 cells and monocytes, newly synthesized FN was released and deposited on the dishes. An HL-60 cell variant, HL-525, which is deficient in the protein kinase C{beta} (PKC-{beta}) and resistant to PMA-induced differentiation, failed to express FN after PMA treatment. Transfecting HL-525 cells with a PKC-{beta} expression plasmid restored PMA-induced FN gene expression and macrophage differentiation. Untreated HL-525 cells (which have a high level of the {alpha}5{beta}1 integrin) incubated on FN differentiated into macrophages. The percentage of cells having a macrophage phenotype induced by PMA in HL-60 cells, by FN in HL-525 cells, or by either PMA or macrophage-CSF in monocytes was reduced in the presence of mAbs to FN and {alpha}5{beta}1 integrin. The integrin-signaling nonreceptor tyrosine kinase, p72{sup Syk}, was activated in PMA-treated HL-60 and FN-treated HL-525 cells. We suggest that macrophage differentiation involves the activation of PKC-{beta} and expression of extracellular matrix proteins such as FN and the corresponding integrins, {alpha}5{beta}1 integrin in particular. The stimulated cells, through the integrins, attach to substrates by binding to the deposited FN. This attachment, in turn, may through integrin signaling activate nonreceptor tyrosine kinases, including p72{sup Syk}, and later lead to expression of other genes involved in evoking the macrophage phenotype.

  6. Recent advances in the discovery of alpha1-adrenoceptor agonists. (United States)

    Bishop, Michael J


    The alpha(1) adrenoceptors are three of nine well-characterized receptors that are activated by epinephrine and norepinephrine. Agonists acting at the alpha(1) adrenoceptors produce numerous physiological effects, and are used therapeutically for several indications. Many known alpha(1) adrenoceptor agonists are alpha(1A) selective, but the discovery of highly selective alpha(1B) and alpha(1D) adrenoceptor agonists has proven to be an extremely difficult goal to achieve. This review will focus on recent advances in the discovery, development and clinical utility of subtype-specific alpha(1) agonists as well as contributions to our understanding of agonist-receptor interactions.

  7. Atypical Alpha Asymmetry in Adults with ADHD (United States)

    Hale, T. Sigi; Smalley, Susan L.; Hanada, Grant; Macion, James; McCracken, James T.; McGough, James J.; Loo, Sandra K.


    Introduction: A growing body of literature suggests atypical cerebral asymmetry and interhemispheric interaction in ADHD. A common means of assessing lateralized brain function in clinical populations has been to examine the relative proportion of EEG alpha activity (8-12 Hz) in each hemisphere (i.e., alpha asymmetry). Increased rightward alpha…

  8. Atypical Alpha Asymmetry in Adults with ADHD (United States)

    Hale, T. Sigi; Smalley, Susan L.; Hanada, Grant; Macion, James; McCracken, James T.; McGough, James J.; Loo, Sandra K.


    Introduction: A growing body of literature suggests atypical cerebral asymmetry and interhemispheric interaction in ADHD. A common means of assessing lateralized brain function in clinical populations has been to examine the relative proportion of EEG alpha activity (8-12 Hz) in each hemisphere (i.e., alpha asymmetry). Increased rightward alpha…

  9. Modeling the interactions of a peptide-major histocompatibility class I ligand with its receptors. I. Recognition by two alpha beta T cell receptors

    DEFF Research Database (Denmark)

    Rognan, D; Stryhn, A; Fugger, L


    dynamics. Next, three-dimensional models of two different T cell receptors (TCRs) both specific for the Ha255-262/Kk complex were generated based on previously published TCR X-ray structures. Finally, guided by the recently published X-ray structures of ternary TCR/peptide/MHC-I complexes, the TCR models...... the models. They were found to account well for the experimentally obtained data, lending considerable support to the proposed models and suggesting a universal docking mode for alpha beta TCRs to MHC-peptide complexes. Such models may also be useful in guiding future rational experimentation....

  10. Rapid, Automated, and Specific Immunoassay to Directly Measure Matrix Metalloproteinase-9–Tissue Inhibitor of Metalloproteinase-1 Interactions in Human Plasma Using AlphaLISA Technology: A New Alternative to Classical ELISA

    Directory of Open Access Journals (Sweden)

    Helena Pulido-Olmo


    Full Text Available The protocol describes a novel, rapid, and no-wash one-step immunoassay for highly sensitive and direct detection of the complexes between matrix metalloproteinases (MMPs and their tissue inhibitor of metalloproteinases (TIMPs based on AlphaLISA® technology. We describe two procedures: (i one approach is used to analyze MMP-9–TIMP-1 interactions using recombinant human MMP-9 with its corresponding recombinant human TIMP-1 inhibitor and (ii the second approach is used to analyze native or endogenous MMP-9–TIMP-1 protein interactions in samples of human plasma. Evaluating native MMP-9–TIMP-1 complexes using this approach avoids the use of indirect calculations of the MMP-9/TIMP-1 ratio for which independent MMP-9 and TIMP-1 quantifications by two conventional ELISAs are needed. The MMP-9–TIMP-1 AlphaLISA® assay is quick, highly simplified, and cost-effective and can be completed in less than 3 h. Moreover, the assay has great potential for use in basic and preclinical research as it allows direct determination of native MMP-9–TIMP-1 complexes in circulating blood as biofluid.

  11. The interaction between menstrual cycle, Tumour Necrosis Factor alpha receptors and sex hormones in healthy non-obese women – results from an observational study

    Directory of Open Access Journals (Sweden)

    Paweł Rzymski


    Full Text Available There is growing evidence that TNF-alpha and its two receptors play an important role in hormonal regulation, metabolism, inflammation and cancer. The biological effects of TNF-alpha are mediated by two receptors, p55 and p75. The aim of this study was to analyze serum concentrations of p55 and p75 and hormonal status in healthy women during the normal menstrual cycle. Eight women aged 20–22 with regular menstrual cycles were scheduled for examination on 3[sup]rd[/sup] , 8[sup]th[/sup] , 14[sup]th[/sup] and 25[sup]th [/sup] day of their menstrual cycle. We only observed a positive correlation of p75 subunit with prolactin level (correlation coefficient 0.417; p=0.0116 and negative correlation with insulin level (correlation coefficient -0.35; p=0.032 and HOMA[sub]IR[/sub] insulin resistance index correlation coefficient 0.39; p=0.0185. Furthermore, a negative correlation of p55/p75 ratio with prolactin (correlation coefficient -0.42; p=0.0101 and a positive correlations of p55/p75 ratio with insulin level (correlation coefficient 0.43; p=0.008 and HOMA[sub]IR[/sub] insulin resistance factor correlation coefficient 0.45; p=0.0065 were found.

  12. Interaction of a novel Tn (GalNAc alpha 1-->Ser/Thr) glycoprotein with Gal, GalNAc and GlcNAc specific lectins. (United States)

    Wu, A M; Wu, J H; Shen, F


    A naturally occurring Tn glycoprotein (Native ASG-Tn) with GalNAc alpha 1-->Ser/Thr as the only carbohydrate side chains, has been prepared from armadillo submandibular glands. In a quantitative precipitin assay, this glycoprotein completely precipitated Maclura pomifera (MPA), Vicia villosa B4 (VVL-B4) and Artocarpus integrifolia (Jacalin, AIL). It also reacted well with Helix pomatia (HPL) and Wistaria floribunda (WFL) and precipitated over 75% of the lectin nitrogen added, but poorly with Ricinus communis agglutinin (RCA1), ricin, peanut (Arachis hypogaea, PNA), Abrus precatorius agglutinin (APA) and Triticum vulgaris (WGA). This finding suggests that this novel Tn-glycoprotein may serve as a useful reagent for differentiating Tn and T specific monoclonal antibodies and lectins.

  13. Studies on the subsite structure of amylases. II. Difference-spectrophotometric studies on the interaction of maltotriose with liquefying alpha-amylase from Bacillus subtilis. (United States)

    Ohnishi, M; Kegai, H; Hiromi, K


    The difference spectra of liquefying alpha-amylase (EC from B. subtilis upon the addition of a slowly reacting substrate, maltotriose, were measured to investigate specific binding of the substrate to the enzyme. The spectra produced by maltotriose were attributed to one tryptophan and one tyrosine residues on the basis of analysis of their shape and magnitude. From the dependence of the difference absorption upon the concentration of maltotriose, the dissociation constant of the maltotriose-enzyme complex was determined to be 170(+/- 20) mM, which is in good agreement with the Michaelis constant, Km obtained from the steady-state kinetics. The difference spectrum characteristic of a tryptophan residue was significantly decreased by the chemical modification of a trytophan residue with N-bromosuccinimide.

  14. Interaction Study of an Amorphous Solid Dispersion of Cyclosporin A in Poly-Alpha-Cyclodextrin with Model Membranes by 1H-, 2H-, 31P-NMR and Electron Spin Resonance

    Directory of Open Access Journals (Sweden)

    Jean-Claude Debouzy


    Full Text Available The properties of an amorphous solid dispersion of cyclosporine A (ASD prepared with the copolymer alpha cyclodextrin (POLYA and cyclosporine A (CYSP were investigated by 1H-NMR in solution and its membrane interactions were studied by 1H-NMR in small unilamellar vesicles and by 31P 2H NMR in phospholipidic dispersions of DMPC (dimyristoylphosphatidylcholine in comparison with those of POLYA and CYSP alone. 1H-NMR chemical shift variations showed that CYSP really interacts with POLYA, with possible adduct formation, dispersion in the solid matrix of the POLYA, and also complex formation. A coarse approach to the latter mechanism was tested using the continuous variations method, indicating an apparent 1 : 1 stoichiometry. Calculations gave an apparent association constant of log Ka = 4.5. A study of the interactions with phospholipidic dispersions of DMPC showed that only limited interactions occurred at the polar head group level (31P. Conversely, by comparison with the expected chain rigidification induced by CYSP, POLYA induced an increase in the fluidity of the layer while ASD formation led to these effects almost being overcome at 298 K. At higher temperature, while the effect of CYSP seems to vanish, a resulting global increase in chain fluidity was found in the presence of ASD.

  15. Characteristic interaction of Ca2+ ions with elastin coacervate: ion transport study across coacervate layers of alpha-elastin and elastin model polypeptide, (Val-Pro-Gly-Val-Gly)n. (United States)

    Kaibara, K; Akinari, Y; Okamoto, K; Uemura, Y; Yamamoto, S; Kodama, H; Kondo, M


    Ion transport characteristics across a macrocoacervate layer membrane composed of aqueous elastin model polypeptides with a specific repeating pentapeptide sequence, H-(Val-Pro-Gly-Val-Gly)n-Val-OMe (n > or = 40), were investigated. Transmembrane potential responses for NaCl. MgCl2, and CaCl2 concentration-cell systems were measured and examined systematically by comparing with those across a coacervate membrane composed of bovine neck ligamental alpha-elastin. In the case of the NaCl and MgCl2 systems, potential responses across these protein liquid membranes were different noticeably from each other depending upon the molecular structure with and without charged peptide side chains, whereas in the CaCl2 systems the transmembrane potential responses across the noncharged polypentapeptide coacervate membrane were comparable with those across the alpha-elastin coacervate membrane carrying both the positively and negatively charged amino acid residues as an amphoteric ion-exchange membrane. These results indicated that mechanisms of major Ca2+ ion transport are based on the specific and selective interactions with electrically neutral sites of elastin, such as the polypentapeptide backbone chain.

  16. NapA and NapB are the Aspergillus nidulans Nap/SET family members and NapB is a nuclear protein specifically interacting with importin alpha. (United States)

    Araújo-Bazán, Lidia; Fernández-Martínez, Javier; Ríos, Vivian Maythe de Los; Etxebeste, Oier; Albar, Juan Pablo; Peñalva, Miguel Angel; Espeso, Eduardo Antonio


    In eukaryotic cells, importin alpha is the major carrier for transport protein cargoes into the nucleus. We characterize here kapA, the single Aspergillus nidulans gene encoding an importin alpha. Using an affinity approach, we identify six potential interactors of KapA(50), a deleted version of KapA lacking the autoinhibitory importin-beta-binding domain. One such interactor is NapB, the A. nidulans orthologue of Saccharomyces cerevisiae Vps75p, a histone chaperone member of the Nap/SET family of proteins that additionally plays a cytosolic role in vacuolar protein sorting. NapB, but not its close relative NapA (the A. nidulans orthologue of yeast Nap1p) interacts directly with KapA(50) in pull down assays, despite the fact that NapB does not contain a classical nuclear localization sequence. NapB is a nuclear protein which exits nuclei at the onset of mitosis when two simultaneous mechanisms might be acting, the partial disassembly of the nuclear pore complexes and as yet unidentified posttranslational modification of NapB. The mitotic cytosolic localization of NapB might facilitate its putative role in the sorting of protein cargoes to the vacuole. In addition, we show that NapB and the mitotic B-type cyclin NimE compete for in vitro binding to KapA.

  17. alpha-cluster states of sup 2 sup 1 sup 2 Po nucleus and realistic alpha-particle potential

    CERN Document Server

    Baktybaev, K


    The alpha-nuclear potential is obtained from a double-folding procedure and boson interacting model is investigated in this article. Half-life and alpha-branching ratios for the member of the ground state band in sup 2 sup 1 sup 2 Po are deduced using an alpha-cluster model. (author)

  18. Alpha Particle Physics Experiments in the Tokamak Fusion Test Reactor

    Energy Technology Data Exchange (ETDEWEB)

    Budny, R.V.; Darrow, D.S.; Medley, S.S.; Nazikian, R.; Zweben, S.J.; et al.


    Alpha particle physics experiments were done on the Tokamak Fusion Test Reactor (TFTR) during its deuterium-tritium (DT) run from 1993-1997. These experiments utilized several new alpha particle diagnostics and hundreds of DT discharges to characterize the alpha particle confinement and wave-particle interactions. In general, the results from the alpha particle diagnostics agreed with the classical single-particle confinement model in magnetohydrodynamic (MHD) quiescent discharges. Also, the observed alpha particle interactions with sawteeth, toroidal Alfvén eigenmodes (TAE), and ion cyclotron resonant frequency (ICRF) waves were roughly consistent with theoretical modeling. This paper reviews what was learned and identifies what remains to be understood.

  19. Infusions of 3alpha,5alpha-THP to the VTA enhance exploratory, anti-anxiety, social, and sexual behavior and increase levels of 3alpha,5alpha-THP in midbrain, hippocampus, diencephalon, and cortex of female rats. (United States)

    Frye, Cheryl A; Rhodes, Madeline E


    17beta-Estradiol (E2) and progesterone (P4) influence the onset and duration of sexual behavior and are also associated with changes in behaviors that may contribute to mating, such as exploration, anxiety, and social behaviors (socio-sexual behaviors). In the midbrain ventral tegmental area (VTA), the P4 metabolite, 5alpha-pregnan-3alpha-ol-20-one (3alpha,5alpha-THP), modulates lordosis of E2-primed rodents; 3alpha,5alpha-THP can also influence anxiety and social behaviors. To examine if 3alpha,5alpha-THP in the VTA mediates socio-sexual behaviors, we infused 3alpha,5alpha-THP to the VTA of diestrous and proestrous rats. As expected, proestrous, compared to diestrous, rats showed more exploratory (open field), anxiolytic (elevated plus maze), pro-social (partner preference, social interaction), and sexual (paced mating) behavior and had increased E2, P4, dihydroprogesterone (DHP), and 3alpha,5alpha-THP in serum, midbrain, hippocampus, diencephalon, and cortex. Infusions of 3alpha,5alpha-THP to the VTA, but not control sites, such as the substantia nigra (SN) or central grey (CG), of diestrous rats produced behavioral and endocrine effects akin to that of proestrous rats and increased DHP and 3alpha,5alpha-THP levels in midbrain, hippocampus, and diencephalon. Levels of DHP and 3alpha,5alpha-THP, but neither E2 nor P4 concentrations, in midbrain, hippocampus, diencephalon, and/or cortex were positively correlated with socio-sexual behaviors. Thus, 3alpha,5alpha-THP infusions to the VTA, but not SN or CG, can enhance socio-sexual behaviors and increase levels in midbrain, hippocampus, and diencephalon.

  20. A highly conserved glycine within linker I and the extreme C terminus of G protein alpha subunits interact cooperatively in switching G protein-coupled receptor-to-effector specificity

    DEFF Research Database (Denmark)

    Kostenis, Evi; Martini, Lene; Ellis, James;


    Numerous studies have attested to the importance of the extreme C terminus of G protein alpha subunits in determining their selectivity of receptor recognition. We have previously reported that a highly conserved glycine residue within linker I is important for constraining the fidelity of receptor...... recognition by Galpha(q) proteins. Herein, we explored whether both modules (linker I and extreme C terminus) interact cooperatively in switching G protein-coupled receptor (GPCR)-to-effector specificity and created as models mutant Galpha(q) proteins in which glycine was replaced with various amino acids...... and the C-terminal five Galpha(q) residues with the corresponding Galpha(i) or Galpha(s) sequence. Coupling properties of the mutated Galpha(q) proteins were determined after coexpression with a panel of 13 G(i)-and G(s) -selective receptors and compared with those of Galpha proteins modified in only one...

  1. In Vivo Clearance of Alpha-1 Acid Glycoprotein Is Influenced by the Extent of Its N-Linked Glycosylation and by Its Interaction with the Vessel Wall

    Directory of Open Access Journals (Sweden)

    Teresa R. McCurdy


    Full Text Available Alpha-1 acid glycoprotein (AGP is a highly glycosylated plasma protein that exerts vasoprotective effects. We hypothesized that AGP’s N-linked glycans govern its rate of clearance from the circulation, and followed the disappearance of different forms of radiolabeled human AGP from the plasma of rabbits and mice. Enzymatic deglycosylation of human plasma-derived AGP (pdAGP by Peptide: N-Glycosidase F yielded a mixture of differentially deglycosylated forms (PNGase-AGP, while the introduction of five Asn to Gln mutations in recombinant Pichia pastoris-derived AGP (rAGP-N(5Q eliminated N-linked glycosylation. PNGase-AGP was cleared from the rabbit circulation 9-fold, and rAGP-N(5Q, 46-fold more rapidly than pdAGP, primarily via a renal route. Pichia pastoris-derived wild-type rAGP differed from pdAGP in expressing mannose-terminated glycans, and, like neuraminidase-treated pdAGP, was more rapidly removed from the rabbit circulation than rAGP-N(5Q. Systemic hyaluronidase treatment of mice transiently decreased pdAGP clearance. AGP administration to mice reduced vascular binding of hyaluronic acid binding protein in the liver microcirculation and increased its plasma levels. Our results support a critical role of N-linked glycosylation of AGP in regulating its in vivo clearance and an influence of a hyaluronidase-sensitive component of the vessel wall on its transendothelial passage.

  2. The Schmidt-Kennicutt Law of Matched-Age Star Forming Regions; Pa-alpha Observations of the Early-Phase Interacting Galaxy Taffy I

    CERN Document Server

    Komugi, S; Motohara, K; Takagi, T; Iono, D; Kaneko, H; Ueda, J; Saitoh, T R; Kato, N; Konishi, M; Koshida, S; Morokuma, T; Takahashi, H; Tanabe, T; Yoshii, Y


    In order to test a recent hypothesis that the dispersion in the Schmidt-Kennicutt law arises from variations in the evolutionary stage of star forming molecular clouds, we compared molecular gas and recent star formation in an early-phase merger galaxy pair, Taffy I (UGC\\ 12915/UGC\\ 12914, VV\\ 254) which went through a direct collision 20 Myr ago and whose star forming regions are expected to have similar ages. Narrow-band Pa-alpha image is obtained using the ANIR near-infrared camera on the mini-TAO 1m telescope. The image enables us to derive accurate star formation rates within the galaxy directly. The total star formation rate, 22.2 M_sun/yr, was found to be much higher than previous estimates. Ages of individual star forming blobs estimated from equivalent widths indicate that most star forming regions are ~7 Myr old, except for a giant HII region at the bridge which is much younger. Comparison between star formation rates and molecular gas masses for the regions with the same age exhibits a surprisingly...


    DEFF Research Database (Denmark)

    Jochum, Elizabeth; Borggreen, Gunhild; Murphey, TD

    This paper considers the impact of visual art and performance on robotics and human-computer interaction and outlines a research project that combines puppetry and live performance with robotics. Kinesics—communication through movement—is the foundation of many theatre and performance traditions...... interaction between a human operator and an artificial actor or agent. We can apply insights from puppetry to develop culturally-aware robots. Here we describe the development of a robotic marionette theatre wherein robotic controllers assume the role of human puppeteers. The system has been built, tested...

  4. Interaction of carbon with vacancy and self-interstitial atom clusters in {alpha}-iron studied using metallic-covalent interatomic potential

    Energy Technology Data Exchange (ETDEWEB)

    Terentyev, Dmitry, E-mail: dterenty@sckcen.b [SCK-CEN, Nuclear Materials Science Institute, Boeretang 200, B-2400 Mol (Belgium); Anento, Napoleon; Serra, Anna [Department Matematica Aplicada III, E.T.S. Enginyeria de Camins, Universitat Politecnica de Catalunya, Jordi Girona 1-3, 08034 Barcelona (Spain); Jansson, Ville [SCK-CEN, Nuclear Materials Science Institute, Boeretang 200, B-2400 Mol (Belgium); Department of Physics, University of Helsinki, P.O. Box 43, FI-00014, Helsinki 00014 (Finland); Khater, Hassan [Department Matematica Aplicada III, E.T.S. Enginyeria de Camins, Universitat Politecnica de Catalunya, Jordi Girona 1-3, 08034 Barcelona (Spain); Bonny, Giovanni [SCK-CEN, Nuclear Materials Science Institute, Boeretang 200, B-2400 Mol (Belgium)


    The presence of even small amount of carbon interstitial impurity affects properties of Fe and Fe-based ferritic alloys. From earlier experiments it follows that carbon exhibits considerably strong interaction with lattice defects and therefore influences their mobility, hence affecting the evolution of the microstructure under irradiation. This work is dedicated to understanding the interaction of carbon-vacancy complexes with glissile dislocation loops, which form in Fe, Fe-based alloys and ferritic steels under irradiation. We apply large scale atomistic simulations coupled with the so-called 'metallic-covalent bonding' interatomic model for the Fe-C system, known to be the most consistent interatomic model available today. With these techniques we have studied (i) the stability of vacancy-carbon clusters; (ii) the interaction of octahedral carbon with 1/2<1 1 1> loops; (iii) possibility of the dynamic drag of carbon by 1/2<1 1 1> loops and (iv) the interaction of 1/2<1 1 1> loops with the most stable vacancy-carbon clusters expected to occur under irradiation. Finally, we have shown that carbon-vacancy complexes act as strong traps for 1/2<1 1 1> loops.

  5. Phylogenetic divergence of CD47 interactions with human signal regulatory protein alpha reveals locus of species specificity. Implications for the binding site. (United States)

    Subramanian, Shyamsundar; Boder, Eric T; Discher, Dennis E


    Cell-cell interactions between ubiquitously expressed integrin-associated protein (CD47) and its counterreceptor signal regulatory protein (SIRPalpha) on phagocytes regulate a wide range of adhesive signaling processes, including the inhibition of phagocytosis as documented in mice. We show that CD47-SIRPalpha binding interactions are different between mice and humans, and we exploit phylogenetic divergence to identify the species-specific binding locus on the immunoglobulin domain of human CD47. All of the studies are conducted in the physiological context of membrane protein display on Chinese hamster ovary (CHO) cells. Novel quantitative flow cytometry analyses with CD47-green fluorescent protein and soluble human SIRPalpha as a probe show that neither human CD47 nor SIRPalpha requires glycosylation for interaction. Human CD47-expressing CHO cells spread rapidly on SIRPalpha-coated glass surfaces, correlating well with the spreading of primary human T cells. In contrast, CHO cells expressing mouse CD47 spread minimally and show equally weak binding to soluble human SIRPalpha. Further phylogenetic analyses and multisite substitutions of the CD47 Ig domain show that human to cow mutation of a cluster of seven residues on adjacent strands near the middle of the domain decreases the association constant for human SIRPalpha to about one-third that of human CD47. Direct tests of cell-cell adhesion between human monocytes and CD47-displaying CHO cells affirm the species specificity as well as the importance of the newly identified binding locus in cell-cell interactions.

  6. Alpha Thalassemia (For Parents) (United States)

    ... Kids to Be Smart About Social Media Alpha Thalassemia KidsHealth > For Parents > Alpha Thalassemia Print A A ... Complications Symptoms Diagnosis Treatment en español Alfa talasemia Thalassemias Thalassemias are a group of blood disorders that ...

  7. Analysis of the interaction between the dendritic conductance density and activated area in modulating alpha-motoneuron EPSP: statistical computer model. (United States)

    Gradwohl, Gideon; Grossman, Yoram


    Five reconstructed alpha-motoneurons (MNs) are simulated under physiological and morphological realistic parameters. We compare the resulting excitatory postsynaptic potential (EPSP) of models, containing voltage-dependent channels on the dendrites, with the EPSP of a passive MN and an active soma and axon model. In our simulations, we apply three different distribution functions of the voltage-dependent channels on the dendrites: a step function (ST) with uniform spatial dispersion; an exponential decay (ED) function, with proximal to the soma high-density location; and an exponential rise (ER) with distally located conductance density. In all cases, the synaptic inputs are located as a gaussian function on the dendrites. Our simulations lead to eight key observations. (1) The presence of the voltage-dependent channels conductance (g(Active)) in the dendrites is vital for obtaining EPSP peak boosting. (2) The mean EPSP peaks of the ST, ER, and ED distributions are similar when the ranges of G (total conductance) are equal. (3) EPSP peak increases monotonically when the magnitude of g(Na_step) (maximal g(Na) at a particular run) is increased. (4) EPSP kinetics parameters were differentially affected; time integral was decreased monotonically with increased g(Na_step), but the rate of rise (the decay time was not analyzed) does not show clear relations. (5) The total G can be elevated by increasing the number of active dendrites; however, only a small active area of the dendritic tree is sufficient to get the maximal boosting. (6) The sometimes large variations in the parameters values for identical G depend on the g(Na_step) and active dendritic area. (7) High g(Na_step) in a few dendrites is more efficient in amplifying the EPSP peak than low g(Na_step) in many dendrites. (8) The EPSP peak is approximately linear with respect to the MNs' R(N) (input resistance).

  8. Application of Circular Dichroism Spectroscopy to the Analysis of the Interaction Between the Estrogen Receptor Alpha and Coactivators: The Case of Calmodulin. (United States)

    Miclet, Emeric; Bourgoin-Voillard, Sandrine; Byrne, Cillian; Jacquot, Yves


    The estrogen receptor α ligand-binding domain (ERα-LBD) binds the natural hormone 17β-estradiol (E2) to induce transcription and cell proliferation. This process occurs with the contribution of protein and peptide partners (also called coactivators) that can modulate the structure of ERα, and therefore its specificity of action. As with most transcription factors, ERα exhibits a high content of α helix, making it difficult to routinely run spectroscopic studies capable of deciphering the secondary structure of the different partners under binding conditions. Ca(2+)-calmodulin, a protein also highly structured in α-helix, is a key coactivator for ERα activity. Here, we show how circular dichroism can be used to study the interaction of ERα with Ca(2+)-calmodulin. Our approach allows the determination not only of the conformational changes induced upon complex formation but also the dissociation constant (K d) of this interaction.

  9. The Alpha Antihydrogen Experiment (United States)

    Madsen, N.; Andresen, G.; Bertsche, W.; Boston, A.; Bowe, P. D.; Butler, E.; Cesar, C. L.; Chapman, S.; Charlton, M.; Chartier, M.; Fajans, J.; Funakoshi, R.; Gill, D. R.; Hangst, J. S.; Hardy, W. N.; Hayano, R. S.; Hayden, M.; Hydomako, R.; Jenkins, M. J.; Jørgensen, L. V.; Kurchaninov, L.; Nolan, P.; Olchanski, K.; Olin, A.; Page, R. D.; Povilus, A.; Robicheaux, F.; Sarid, E.; Seif El Nasr, S.; Silveira, D. M.; Storey, J. W.; Thompson, R. I.; van der Werf, D. P.; Wurtele, J. S.; Yamazaki, Y.


    ALPHA is a new experiment at the CERN Antiproton Decelerator (AD). The short term goal of ALPHA is trapping of cold antihydrogen, with the long term goal of conducting precise spectroscopic comparisons of hydrogen and antihydrogen. Here we present the current status of ALPHA and the physics considerations and results leading to its design as well as recent progress towards trapping.

  10. The mechanism of interactions between tea polyphenols and porcine pancreatic alpha-amylase: Analysis by inhibition kinetics, fluorescence quenching, differential scanning calorimetry and isothermal titration calorimetry. (United States)

    Sun, Lijun; Gidley, Michael J; Warren, Frederick J


    This study aims to use a combination of biochemical and biophysical methods to derive greater mechanistic understanding of the interactions between tea polyphenols and porcine pancreatic α-amylase (PPA). The interaction mechanism was studied through fluorescence quenching (FQ), differential scanning calorimetry (DSC) and isothermal titration calorimetry (ITC) and compared with inhibition kinetics. The results showed that a higher quenching effect of polyphenols corresponded to a stronger inhibitory activity against PPA. The red-shift of maximum emission wavelength of PPA bound with some polyphenols indicated a potential structural unfolding of PPA. This was also suggested by the decreased thermostability of PPA with these polyphenols in DSC thermograms. Through thermodynamic binding analysis of ITC and inhibition kinetics, the equilibrium of competitive inhibition was shown to result from the binding of particularly galloylated polyphenols with specific sites on PPA. There were positive linear correlations between the reciprocal of competitive inhibition constant (1/Kic ), quenching constant (KFQ ) and binding constant (Kitc ). The combination of inhibition kinetics, FQ, DSC and ITC can reasonably characterize the interactions between tea polyphenols and PPA. The galloyl moiety is an important group in catechins and theaflavins in terms of binding with and inhibiting the activity of PPA. © 2017 The Authors. Molecular Nutrition & Food Research Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Cnr interferes with dimerization of the replication protein alpha in phage-plasmid P4. (United States)

    Tocchetti, A; Serina, S; Oliva, I; Dehò, G; Ghisotti, D


    DNA replication of phage-plasmid P4 in its host Escherichia coli depends on its replication protein alpha. In the plasmid state, P4 copy number is controlled by the regulator protein Cnr (copy number regulation). Mutations in alpha (alpha(cr)) that prevent regulation by Cnr cause P4 over-replication and cell death. Using the two-hybrid system in Saccharomyces cerevisiae and a system based on lambda immunity in E.coli for in vivo detection of protein-protein interactions, we found that (i) alpha protein interacts with Cnr, whereas alpha(cr) proteins do not; (ii) both alpha-alpha and alpha(cr)-alpha(cr) interactions occur and the interaction domain is located within the C-terminal of alpha; (iii) Cnr-Cnr interaction also occurs. Using an in vivo competition assay, we found that Cnr interferes with both alpha-alpha and alpha(cr)-alpha(cr) dimerization. Our data suggest that Cnr and alpha interact in at least two ways, which may have different functional roles in P4 replication control.

  12. Structure-function of proteins interacting with the alpha1 pore-forming subunit of high voltage-activated calcium channel

    Directory of Open Access Journals (Sweden)

    Alan eNeely


    Full Text Available Openings of high-voltage-activated calcium channels lead to a transient increase in calcium concentration that in turn activate a plethora of cellular functions, including muscle contraction, secretion and gene transcription. To coordinate all these responses calcium channels form supramolecular assemblies containing effectors and regulatory proteins that couple calcium influx to the downstream signal cascades and to feedback elements. According to the original biochemical characterization of skeletal muscle Dihydropyridine receptors, high-voltage-activated calcium channels are multi-subunit protein complexes consisting of a pore-forming subunit (α1 associated with four additional polypeptide chains β, α2, δ and γ, often referred to as accessory subunits. Twenty-five years after the first purification of a high-voltage calcium channel, the concept of a flexible stoichiometry to expand the repertoire of mechanisms that regulate calcium channel influx has emerged. Several other proteins have been identified that associate directly with the α1-subunit, including calmodulin and multiple members of the small and large GTPase family. Some of these proteins only interact with a subset of α1-subunits and during specific stages of biogenesis. More strikingly, most of the α1-subunit interacting proteins, such as the β-subunit and small GTPases, regulate both gating and trafficking through a variety of mechanisms. Modulation of channel activity covers almost all biophysical properties of the channel. Likewise, regulation of the number of channels in the plasma membrane is performed by altering the release of the α1-subunit from the endoplasmic reticulum, by reducing its degradation or enhancing its recycling back to the cell surface. In this review, we discuss the structural basis, interplay and functional role of selected proteins that interact with the central pore-forming subunit of high-voltage-activated calcium channels.

  13. Non-Gaussian polymers described by alpha-stable chain statistics: Model, effective interactions in binary mixtures, and application to on-surface separation (United States)

    Majka, M.; Góra, P. F.


    The Gaussian chain model is the classical description of a polymeric chain, which provides analytical results regarding end-to-end distance, the distribution of segments around the mass center of a chain, coarse-grained interactions between two chains and effective interactions in binary mixtures. This hierarchy of results can be calculated thanks to the α stability of the Gaussian distribution. In this paper we show that it is possible to generalize the model of Gaussian chain to the entire class of α -stable distributions, obtaining the analogous hierarchy of results expressed by the analytical closed-form formulas in the Fourier space. This allows us to establish the α -stable chain model. We begin with reviewing the applications of Levy flights in the context of polymer sciences, which include: chains described by the heavy-tailed distributions of persistence length; polymers adsorbed to the surface; and the chains driven by a noise with power-law spatial correlations. Further, we derive the distribution of segments around the mass center of the α -stable chain and construct the coarse-grained interaction potential between two chains. These results are employed to discuss the model of binary mixture consisting of the α -stable chains. In what follows, we establish the spinodal decomposition condition generalized to the mixtures of the α -stable polymers. This condition is further applied to compare the on-surface phase separation of adsorbed polymers (which are known to be described with heavy-tailed statistics) with the phase separation condition in the bulk. Finally, we predict the four different scenarios of simultaneous mixing and demixing in the two- and three-dimensional systems.

  14. Interactions

    DEFF Research Database (Denmark)

    The main theme of this anthology is the unique interaction between mathematics, physics and philosophy during the beginning of the 20th century. Seminal theories of modern physics and new fundamental mathematical structures were discovered or formed in this period. Significant physicists...... such as Lorentz and Einstein as well as mathematicians such as Poincare, Minkowski, Hilbert and Weyl contributed to this development. They created the new physical theories and the mathematical disciplines that play such paramount roles in their mathematical formulations. These physicists and mathematicians were...

  15. Elucidation of the molecular basis of selective recognition uncovers the interaction site for the core domain of scorpion alpha-toxins on sodium channels. (United States)

    Gur, Maya; Kahn, Roy; Karbat, Izhar; Regev, Noa; Wang, Jinti; Catterall, William A; Gordon, Dalia; Gurevitz, Michael


    Neurotoxin receptor site-3 at voltage-gated Na(+) channels is recognized by various peptide toxin inhibitors of channel inactivation. Despite extensive studies of the effects of these toxins, their mode of interaction with the channel remained to be described at the molecular level. To identify channel constituents that interact with the toxins, we exploited the opposing preferences of LqhαIT and Lqh2 scorpion α-toxins for insect and mammalian brain Na(+) channels. Construction of the DIV/S1-S2, DIV/S3-S4, DI/S5-SS1, and DI/SS2-S6 external loops of the rat brain rNa(v)1.2a channel (highly sensitive to Lqh2) in the background of the Drosophila DmNa(v)1 channel (highly sensitive to LqhαIT), and examination of toxin activity on the channel chimera expressed in Xenopus oocytes revealed a substantial decrease in LqhαIT effect, whereas Lqh2 was as effective as at rNa(v)1.2a. Further substitutions of individual loops and specific residues followed by examination of gain or loss in Lqh2 and LqhαIT activities highlighted the importance of DI/S5-S6 (pore module) and the C-terminal region of DIV/S3 (gating module) of rNa(v)1.2a for Lqh2 action and selectivity. In contrast, a single substitution of Glu-1613 to Asp at DIV/S3-S4 converted rNa(v)1.2a to high sensitivity toward LqhαIT. Comparison of depolarization-driven dissociation of Lqh2 and mutant derivatives off their binding site at rNa(v)1.2a mutant channels has suggested that the toxin core domain interacts with the gating module of DIV. These results constitute the first step in better understanding of the way scorpion α-toxins interact with voltage-gated Na(+)-channels at the molecular level.

  16. The LSD1-Type Zinc Finger Motifs of Pisum sativa LSD1 Are a Novel Nuclear Localization Signal and Interact with Importin Alpha


    Shanping He; Kuowei Huang; Xu Zhang; Xiangchun Yu; Ping Huang; Chengcai An


    BACKGROUND: Genetic studies of the Arabidopsis mutant lsd1 highlight the important role of LSD1 in the negative regulation of plant programmed cell death (PCD). Arabidopsis thaliana LSD1 (AtLSD1) contains three LSD1-type zinc finger motifs, which are involved in the protein-protein interaction. METHODOLOGY/PRINCIPAL FINDINGS: To further understand the function of LSD1, we have analyzed cellular localization and functional localization domains of Pisum sativa LSD1 (PsLSD1), which is a homolog ...

  17. Alpha particle nonionizing energy loss (NIEL) for device applications (United States)

    Jun, Insoo; Xapsos, Michael A.; Messenger, Scott R.; Burke, Edward A.; Walters, Robert J.; Summers, Geoff; Jordan, Thomas


    A method developed for the proton NIEL calculation previously is extended to incident alpha particles in this study: ZBL screened potential for Coulomb interactions and MCNPX 'thin target approximation' for nuclear interactions.

  18. Development of a novel high-throughput screen and identification of small-molecule inhibitors of the Gα-RGS17 protein-protein interaction using AlphaScreen. (United States)

    Mackie, Duncan I; Roman, David L


    In this study, the authors used AlphaScreen technology to develop a high-throughput screening method for interrogating small-molecule libraries for inhibitors of the Gα(o)-RGS17 interaction. RGS17 is implicated in the growth, proliferation, metastasis, and the migration of prostate and lung cancers. RGS17 is upregulated in lung and prostate tumors up to a 13-fold increase over patient-matched normal tissues. Studies show RGS17 knockdown inhibits colony formation and decreases tumorigenesis in nude mice. The screen in this study uses a measurement of the Gα(o)-RGS17 protein-protein interaction, with an excellent Z score exceeding 0.73, a signal-to-noise ratio >70, and a screening time of 1100 compounds per hour. The authors screened the NCI Diversity Set II and determined 35 initial hits, of which 16 were confirmed after screening against controls. The 16 compounds exhibited IC(50) 50% when compared to a biotinylated glutathione-S-transferase control. This report describes the first high-throughput screen for RGS17 inhibitors, as well as a novel paradigm adaptable to many other RGS proteins, which are emerging as attractive drug targets for modulating G-protein-coupled receptor signaling.

  19. A multilevel prediction of physiological response to challenge: Interactions among child maltreatment, neighborhood crime, endothelial nitric oxide synthase gene (eNOS), and GABA(A) receptor subunit alpha-6 gene (GABRA6). (United States)

    Lynch, Michael; Manly, Jody Todd; Cicchetti, Dante


    Physiological response to stress has been linked to a variety of healthy and pathological conditions. The current study conducted a multilevel examination of interactions among environmental toxins (i.e., neighborhood crime and child maltreatment) and specific genetic polymorphisms of the endothelial nitric oxide synthase gene (eNOS) and GABA(A) receptor subunit alpha-6 gene (GABRA6). One hundred eighty-six children were recruited at age 4. The presence or absence of child maltreatment as well as the amount of crime that occurred in their neighborhood during the previous year were determined at that time. At age 9, the children were brought to the lab, where their physiological response to a cognitive challenge (i.e., change in the amplitude of the respiratory sinus arrhythmia) was assessed and DNA samples were collected for subsequent genotyping. The results confirmed that complex Gene × Gene, Environment × Environment, and Gene × Environment interactions were associated with different patterns of respiratory sinus arrhythmia reactivity. The implications for future research and evidence-based intervention are discussed.

  20. Specificity and mechanism of action of alpha-helical membrane-active peptides interacting with model and biological membranes by single-molecule force spectroscopy. (United States)

    Sun, Shiyu; Zhao, Guangxu; Huang, Yibing; Cai, Mingjun; Shan, Yuping; Wang, Hongda; Chen, Yuxin


    In this study, to systematically investigate the targeting specificity of membrane-active peptides on different types of cell membranes, we evaluated the effects of peptides on different large unilamellar vesicles mimicking prokaryotic, normal eukaryotic, and cancer cell membranes by single-molecule force spectroscopy and spectrum technology. We revealed that cationic membrane-active peptides can exclusively target negatively charged prokaryotic and cancer cell model membranes rather than normal eukaryotic cell model membranes. Using Acholeplasma laidlawii, 3T3-L1, and HeLa cells to represent prokaryotic cells, normal eukaryotic cells, and cancer cells in atomic force microscopy experiments, respectively, we further studied that the single-molecule targeting interaction between peptides and biological membranes. Antimicrobial and anticancer activities of peptides exhibited strong correlations with the interaction probability determined by single-molecule force spectroscopy, which illustrates strong correlations of peptide biological activities and peptide hydrophobicity and charge. Peptide specificity significantly depends on the lipid compositions of different cell membranes, which validates the de novo design of peptide therapeutics against bacteria and cancers.

  1. The determination of $\\alpha_s$ by the ALPHA collaboration

    CERN Document Server

    Bruno, Mattia


    We review the ALPHA collaboration strategy for obtaining the QCD coupling at high scale. In the three-flavor effective theory it avoids the use of perturbation theory at $\\alpha > 0.2$ and at the same time has the physical scales small compared to the cutoff $1/a$ in all stages of the computation. The result $\\Lambda_\\overline{MS}^{(3)}=332(14)$~MeV is translated to $\\alpha_\\overline{MS}(m_Z)=0.1179(10)(2)$ by use of (high order) perturbative relations between the effective theory couplings at the charm and beauty quark "thresholds". The error of this perturbative step is discussed and estimated as $0.0002$.

  2. Diet-induced muscle insulin resistance is associated with extracellular matrix remodeling and interaction with integrin alpha2beta1 in mice. (United States)

    Kang, Li; Ayala, Julio E; Lee-Young, Robert S; Zhang, Zhonghua; James, Freyja D; Neufer, P Darrell; Pozzi, Ambra; Zutter, Mary M; Wasserman, David H


    The hypothesis that high-fat (HF) feeding causes skeletal muscle extracellular matrix (ECM) remodeling in C57BL/6J mice and that this remodeling contributes to diet-induced muscle insulin resistance (IR) through the collagen receptor integrin α(2)β(1) was tested. The association between IR and ECM remodeling was studied in mice fed chow or HF diet. Specific genetic and pharmacological murine models were used to study effects of HF feeding on ECM in the absence of IR. The role of ECM-integrin interaction in IR was studied using hyperinsulinemic-euglycemic clamps on integrin α(2)β(1)-null (itga2(-/-)), integrin α(1)β(1)-null (itga1(-/-)), and wild-type littermate mice fed chow or HF. Integrin α(2)β(1) and integrin α(1)β(1) signaling pathways have opposing actions. HF-fed mice had IR and increased muscle collagen (Col) III and ColIV protein; the former was associated with increased transcript, whereas the latter was associated with reduced matrix metalloproteinase 9 activity. Rescue of muscle IR by genetic muscle-specific mitochondria-targeted catalase overexpression or by the phosphodiesterase 5a inhibitor, sildenafil, reversed HF feeding effects on ECM remodeling and increased muscle vascularity. Collagen remained elevated in HF-fed itga2(-/-) mice. Nevertheless, muscle insulin action and vascularity were increased. Muscle IR in HF-fed itga1(-/-) mice was unchanged. Insulin sensitivity in chow-fed itga1(-/-) and itga2(-/-) mice was not different from wild-type littermates. ECM collagen expansion is tightly associated with muscle IR. Studies with itga2(-/-) mice provide mechanistic insight for this association by showing that the link between muscle IR and increased collagen can be uncoupled by the absence of collagen-integrin α(2)β(1) interaction.

  3. Insights into interactions between the alpha-helical region of the salmon calcitonin antagonists and the human calcitonin receptor using photoaffinity labeling. (United States)

    Pham, Vi; Dong, Maoqing; Wade, John D; Miller, Laurence J; Morton, Craig J; Ng, Hooi-Ling; Parker, Michael W; Sexton, Patrick M


    Fish-like calcitonins (CTs), such as salmon CT (sCT), are widely used clinically in the treatment of bone-related disorders; however, the molecular basis for CT binding to its receptor, a class II G protein-coupled receptor, is not well defined. In this study we have used photoaffinity labeling to identify proximity sites between CT and its receptor. Two analogues of the antagonist sCT(8-32) containing a single photolabile p-benzoyl-l-phenylalanine (Bpa) residue in position 8 or 19 were used. Both analogues retained high affinity for the CT receptor and potently inhibited agonist-induced cAMP production. The [Bpa(19)]sCT(8-32) analogue cross-linked to the receptor at or near the equivalent cross-linking site of the full-length peptide, within the fragment Cys(134)-Lys(141) (within the amino terminus of the receptor, adjacent to transmembrane 1) (Pham, V., Wade, J. D., Purdue, B. W., and Sexton, P. M. (2004) J. Biol. Chem. 279, 6720-6729). In contrast, proteolytic mapping and mutational analysis identified Met(49) as the cross-linking site for [Bpa(8)]sCT(8-32). This site differed from the previously identified cross-linking site of the agonist [Bpa(8)]human CT (Dong, M., Pinon, D. I., Cox, R. F., and Miller, L. J. (2004) J. Biol. Chem. 279, 31177-31182) and may provide evidence for conformational differences between interaction with active and inactive state receptors. Molecular modeling suggests that the difference in cross-linking between the two Bpa(8) analogues can be accounted for by a relatively small change in peptide orientation. The model was also consistent with cooperative interaction between the receptor amino terminus and the receptor core.

  4. Aspergillus nidulans alpha-galactosidase of glycoside hydrolase family 36 catalyses the formation of alpha-galacto-oligosaccharides by transglycosylation. (United States)

    Nakai, Hiroyuki; Baumann, Martin J; Petersen, Bent O; Westphal, Yvonne; Hachem, Maher Abou; Dilokpimol, Adiphol; Duus, Jens Ø; Schols, Henk A; Svensson, Birte


    The alpha-galactosidase from Aspergillus nidulans (AglC) belongs to a phylogenetic cluster containing eukaryotic alpha-galactosidases and alpha-galacto-oligosaccharide synthases of glycoside hydrolase family 36 (GH36). The recombinant AglC, produced in high yield (0.65 g.L(-1) culture) as His-tag fusion in Escherichia coli, catalysed efficient transglycosylation with alpha-(1-->6) regioselectivity from 40 mm 4-nitrophenol alpha-d-galactopyranoside, melibiose or raffinose, resulting in a 37-74% yield of 4-nitrophenol alpha-D-Galp-(1-->6)-D-Galp, alpha-D-Galp-(1-->6)-alpha-D-Galp-(1-->6)-D-Glcp and alpha-D-Galp-(1-->6)-alpha-D-Galp-(1-->6)-D-Glcp-(alpha1-->beta2)-d-Fruf (stachyose), respectively. Furthermore, among 10 monosaccharide acceptor candidates (400 mm) and the donor 4-nitrophenol alpha-D-galactopyranoside (40 mm), alpha-(1-->6) linked galactodisaccharides were also obtained with galactose, glucose and mannose in high yields of 39-58%. AglC did not transglycosylate monosaccharides without the 6-hydroxymethyl group, i.e. xylose, L-arabinose, L-fucose and L-rhamnose, or with axial 3-OH, i.e. gulose, allose, altrose and L-rhamnose. Structural modelling using Thermotoga maritima GH36 alpha-galactosidase as the template and superimposition of melibiose from the complex with human GH27 alpha-galactosidase supported that recognition at subsite +1 in AglC presumably requires a hydrogen bond between 3-OH and Trp358 and a hydrophobic environment around the C-6 hydroxymethyl group. In addition, successful transglycosylation of eight of 10 disaccharides (400 mm), except xylobiose and arabinobiose, indicated broad specificity for interaction with the +2 subsite. AglC thus transferred alpha-galactosyl to 6-OH of the terminal residue in the alpha-linked melibiose, maltose, trehalose, sucrose and turanose in 6-46% yield and the beta-linked lactose, lactulose and cellobiose in 28-38% yield. The product structures were identified using NMR and ESI-MS and five of the 13

  5. New ALPHA-2 magnet

    CERN Multimedia

    Anaïs Schaeffer


    On 21 June, members of the ALPHA collaboration celebrated the handover of the first solenoid designed for the ALPHA-2 experiment. The magnet has since been successfully installed and is working well.   Khalid Mansoor, Sumera Yamin and Jeffrey Hangst in front of the new ALPHA-2 solenoid. “This was the first of three identical solenoids that will be installed between now and September, as the rest of the ALPHA-2 device is installed and commissioned,” explains ALPHA spokesperson Jeffrey Hangst. “These magnets are designed to allow us to transfer particles - antiprotons, electrons and positrons - between various parts of the new ALPHA-2 device by controlling the transverse size of the particle bunch that is being transferred.” Sumera Yamin and Khalid Mansoor, two Pakistani scientists from the National Centre for Physics in Islamabad, came to CERN in February specifically to design and manufacture these magnets. “We had the chance to work on act...

  6. Lyman Alpha Control

    CERN Document Server

    Nielsen, Daniel Stefaniak


    This document gives an overview of how to operate the Lyman Alpha Control application written in LabVIEW along with things to watch out for. Overview of the LabVIEW code itself as well as the physical wiring of and connections from/to the NI PCI-6229 DAQ box is also included. The Lyman Alpha Control application is the interface between the ALPHA sequencer and the HighFinesse Wavelength Meter as well as the Lyman Alpha laser setup. The application measures the wavelength of the output light from the Lyman Alpha cavity through the Wavelength Meter. The application can use the Wavelength Meter’s PID capabilities to stabilize the Lyman Alpha laser output as well as switch between up to three frequencies.

  7. Alpha Shapes and Proteins

    DEFF Research Database (Denmark)

    Winter, Pawel; Sterner, Henrik; Sterner, Peter


    We provide a unified description of (weighted) alpha shapes, beta shapes and the corresponding simplicialcomplexes. We discuss their applicability to various protein-related problems. We also discuss filtrations of alpha shapes and touch upon related persistence issues.We claim that the full...... potential of alpha-shapes and related geometrical constructs in protein-related problems yet remains to be realized and verified. We suggest parallel algorithms for (weighted) alpha shapes, and we argue that future use of filtrations and kinetic variants for larger proteins will need such implementation....

  8. Interpreting EEG alpha activity. (United States)

    Bazanova, O M; Vernon, D


    Exploring EEG alpha oscillations has generated considerable interest, in particular with regards to the role they play in cognitive, psychomotor, psycho-emotional and physiological aspects of human life. However, there is no clearly agreed upon definition of what constitutes 'alpha activity' or which of the many indices should be used to characterize it. To address these issues this review attempts to delineate EEG alpha-activity, its physical, molecular and morphological nature, and examine the following indices: (1) the individual alpha peak frequency; (2) activation magnitude, as measured by alpha amplitude suppression across the individual alpha bandwidth in response to eyes opening, and (3) alpha "auto-rhythmicity" indices: which include intra-spindle amplitude variability, spindle length and steepness. Throughout, the article offers a number of suggestions regarding the mechanism(s) of alpha activity related to inter and intra-individual variability. In addition, it provides some insights into the various psychophysiological indices of alpha activity and highlights their role in optimal functioning and behavior.

  9. Buffett’s Alpha

    DEFF Research Database (Denmark)

    Frazzini, Andrea; Kabiller, David; Heje Pedersen, Lasse

    Berkshire Hathaway has realized a Sharpe ratio of 0.76, higher than any other stock or mutual fund with a history of more than 30 years, and Berkshire has a significant alpha to traditional risk factors. However, we find that the alpha becomes insignificant when controlling for exposures to Betting...

  10. Testing the ability of rhodanine and 2, 4-thiazolidinedione to interact with the human pancreatic alpha-amylase: electron-density descriptors complement molecular docking, QM, and QM/MM dynamics calculations. (United States)

    Devi, Rajendran Niranjana; Khrenova, Maria G; Israel, Samuel; Anzline, Chellam; Astakhov, Andrey A; Tsirelson, Vladimir G


    A combined molecular docking, QM, and QM/MM dynamics modeling complemented with electron-density based descriptors computed at the B3LYP/6-311G++(d,p) level of theory have been carried out in order to understand the ability of the drugs rhodanine (RD) and 2,4-thiazolidinedione (TZD) in the effective treatment of type 2 diabetes mellitus. The global HOMO/LUMO descriptors provided just a very rough estimate of the chemical reactivity of both molecules, while the features of electron density studied in terms of its Laplacian and electrostatic potential allowed identifying the local electron rich/poor sites which were associated with the regions of electrophilic/nucleophilic attacks in RD and TZD. These results were thoroughly checked using the novel physically-grounded functional descriptors such as the phase-space Fisher information density and the internal kinetic electronic pressure density, which confirmed the information on bonding and lone electron pair details. The molecular docking, QM, and QM/MM dynamics analyses revealed the detailed picture of interactions of the drugs with the amino acid residues of the active site of the human pancreatic alpha-amylase protein (hPAA). The main difference in behavior of RD and TZD molecules is related to the hydrogen bond between the NH group of the ligand and Asp197. In hPAA complex with RD the proton from the NH group, which carries large positive charge (~ +0.45 e), spontaneously transfers to the carboxyl group of Asp197 and stays there, while in complex with TZD this proton frequently changes its position with the more preferable formation of covalent bond with the N atom. Upon deprotonation of the ligand, its hydrogen bonds with Arg195 and His299 become stronger. This process influences the binding with the difference of the binding constants of RD and TZD about 200 times with the higher value corresponding to the RD molecule. Thus, the cumulative results lead to the conclusion that rhodanine would have a higher

  11. Laser assisted {alpha} decay

    Energy Technology Data Exchange (ETDEWEB)

    Castaneda Cortes, Hector Mauricio


    Excited or short-lived nuclei often decay by emitting alpha particles that are assumed to be preformed inside the nucleus and confined in the nuclear potential well. In this picture, {alpha} decay refers to the tunneling of the alpha particle through the potential barrier. In this thesis we investigate for the first time how strong laser fields can assist the tunneling of the alpha particle and thus influence the nuclear decay. Generally speaking, laser-assisted {alpha} decay can be described as laser-assisted tunneling of a quasistationary state, i.e, a slowly decaying state. Our theoretical treatment is developed starting from the complex trajectory formulation of the well-known strong-field approximation used to describe laser-induced ionization. We extend this formulation and develop a method to treat the decay of quasistationary states. The effect of both static and optical and X-ray monochromatic fields on the lifetimes and {alpha}-particle emission spectra are investigated for a number of {alpha}-emitting nuclei. We find that even at strong intensities, the laser-induced acceleration of the {alpha} decay is negligible, ranging from a relative modification in the decay rate of 10{sup -3} for static fields of electric field strengths of 10{sup 15} V/m, to 10{sup -8} for strong optical fields with intensities of 10{sup 22} W/cm{sup 2}, and to 10{sup -6} for strong X-ray fields with laser intensities around 10{sup 24} W/cm{sup 2}. However, the effect of the external field is visible in the spectrum of emitted alpha particles, leading in the case of optical fields even to rescattering phenomena for intensities approaching 6 x 10{sup 22} W/cm{sup 2}. The dynamics of the alpha particle in laser fields of intensities below the rescattering limit is investigated.

  12. alpha-synuclein and LRRK2: partners in crime. (United States)

    Tong, Youren; Shen, Jie


    In this issue of Neuron, Lin et al. report that LRRK2 modulates age-related neurodegeneration caused by overexpression of alpha-synuclein in the forebrain of transgenic mice. Overexpression of LRRK2 accelerates the progression of alpha-synuclein-mediated neuropathological changes, whereas deletion of LRRK2 alleviates these alterations. The results reveal an interesting interaction between alpha-synuclein and LRRK2, two gene products linked to dominantly inherited Parkinson's disease.

  13. Changes in vascular alpha 1- and alpha 2-adrenoceptor responsiveness by selegiline treatment. (United States)

    Pelat, M; Verwaerde, P; Tran, M A; Berlan, M; Senard, J M; Montastruc, J L


    Pharmacoepidemiological studies have reported an excess of mortality with selegiline, a MAO B inhibitor used in the treatment of Parkinson's disease. The mechanism of this putative adverse effect remains unknown but an interaction with the sympathetic nervous system was suggested. The aim of the present study was to investigate the influence of selegiline (10 mg/daily, orally during one week) on vascular alpha1- and alpha2-adrenoceptor responsiveness in conscious unrestrained dogs. Selegiline significantly increased resting values of both systolic and diastolic blood pressures and noradrenaline plasma levels (HPLC) without changing heart rate. Moreover, spectral analysis of systolic blood pressure (Fast Fourier Transformation) showed that selegiline increased the relative energy of a low frequency band without modifying the total spectrum. ED 50 calculated from dose-pressor response curves with phenylephrine (after beta-blockade by propranolol), an index of alpha1-adrenoceptor response or with noradrenaline (after alpha1- and beta blockade by prazosin plus propranolol), an index of alpha2-adrenoceptor response, were significantly higher after selegiline. Selegiline failed to modify the number of platelet alpha2-adrenoceptors measured by [(3)H] RX 821002 binding. Yohimbine-induced increase in noradrenaline release was significantly more marked after selegiline. These results support the evidence that selegiline induces a vascular alpha1- and alpha2-adrenoceptor-hyposensitivity that can be explained by the increase in noradrenaline release elicited by the drug.

  14. Genetics Home Reference: alpha thalassemia (United States)

    ... Facebook Twitter Home Health Conditions alpha thalassemia alpha thalassemia Printable PDF Open All Close All Enable Javascript to view the expand/collapse boxes. Description Alpha thalassemia is a blood disorder that reduces the production ...

  15. Existence of six-$\\alpha$ linear structure

    CERN Document Server

    Iwata, Yoritaka; Itagaki, Naoyuki; Maruhn, Joachim A; Otsuka, Takaharu


    The stable existence of a six-$\\alpha$ linear structure in highly excited states of $^{24}$Mg is studied based on a systematic Cranked Hartree-Fock calculation with various Skyrme-type interactions. Its stability is examined by allowing the transition of the cluster structure to the shell-model like structure. Especially, the six-$\\alpha$ linear state is exposed to two major instabilities: the bending motion, which is the main path for the transition to low-lying states, and the spin-orbit interaction, which is the driving force to break the $\\alpha$ clusters and enhance the independent motion of the nucleons. The linear structure with large angular momentum is obtained as a meta-stable stationary state.

  16. Syndecan-4 associates with alpha-actinin

    DEFF Research Database (Denmark)

    Greene, Daniel K; Tumova, Sarka; Couchman, John R;


    during the formation of focal adhesions. To date, a direct link between syndecan-4 and the cytoskeleton has remained elusive. We now demonstrate by Triton X-100 extraction immunoprecipitation and in vitro binding assays that the focal adhesion component alpha-actinin interacts with syndecan-4 in a beta...

  17. alpha_s from tau decays revisited

    CERN Document Server

    Boito, D; Golterman, M; Jamin, M; Maltman, K; Osborne, J; Peris, S


    Being a determination at low energies, the analysis of hadronic tau decay data provides a rather precise determination of the strong coupling alpha_s after evolving the result to M_Z. At such a level of precision, even small non-perturbative effects become relevant for the central value and error. While those effects had been taken into account in the framework of the operator product expansion, contributions going beyond it, so-called duality violations, have previously been neglected. The following investigation fills this gap through a finite-energy sum rule analysis of tau decay spectra from the OPAL experiment, including duality violations and performing a consistent fit of all appearing QCD parameters. The resulting values for alpha_s(M_tau) are 0.307(19) in fixed-order perturbation theory and 0.322(26) in contour-improved perturbation theory, which translates to the n_f=5 values 0.1169(25) and 0.1187(32) at M_Z, respectively.

  18. Alpha-1 Antitrypsin Deficiency (United States)

    ... by blood tests showing the low levels of alpha-1 antitrypsin and abnormal liver tests. Other tests such as ultrasound imaging or tests using specialized X-ray techniques may be necessary. A liver biopsy may ...

  19. Increasing 3alpha,5alpha-THP following inhibition of neurosteroid biosynthesis in the ventral tegmental area reinstates anti-anxiety, social, and sexual behavior of naturally receptive rats. (United States)

    Frye, Cheryl A; Paris, Jason J; Rhodes, Madeline E


    The progesterone metabolite and neurosteroid, 5alpha-pregnan-3alpha-ol-20-one (3alpha,5alpha-THP), has actions in the midbrain ventral tegmental area (VTA) to modulate lordosis, but its effects on other reproductively relevant behaviors are not well understood. Effects on exploration, anxiety, and social behavior resulting from inhibition of 3alpha,5alpha-THP formation, as well as 3alpha,5alpha-THP enhancement, were investigated in the midbrain VTA. Naturally sexually receptive, female rats (n=8-10/group) received infusions aimed at the midbrain VTA of vehicle, PK11195 (an inhibitor of neurosteroidogenesis), and/or indomethacin (an inhibitor of 3alpha,5alpha-THP formation from prohormones), and were subsequently infused with vehicle or FGIN 1-27 (a neurosteroidogenesis enhancer). The rats were then assessed in a behavioral battery that examined exploration (open field), anxiety (elevated plus maze), social (social interaction), and sexual (paced mating) behavior. Inhibition of 3alpha,5alpha-THP formation decreased exploratory, anti-anxiety, social, and sexual behavior, as well as midbrain 3alpha,5alpha-THP levels. Infusions of FGIN 1-27 following 3alpha,5alpha-THP inhibition restored these behaviors and midbrain 3alpha,5alpha-THP levels to those commensurate with control rats that had not been administered inhibitors. These findings suggest that 3alpha,5alpha-THP formation in the midbrain VTA may influence appetitive, as well as consummatory, aspects of mating behavior.

  20. ALPHA-2: the sequel

    CERN Multimedia

    Katarina Anthony


    While many experiments are methodically planning for intense works over the long shutdown, there is one experiment that is already working at full steam: ALPHA-2. Its final components arrived last month and will completely replace the previous ALPHA set-up. Unlike its predecessor, this next generation experiment has been specifically designed to measure the properties of antimatter.   The ALPHA team lower the new superconducting solenoid magnet into place. The ALPHA collaboration is working at full speed to complete the ALPHA-2 set-up for mid-November – this will give them a few weeks of running before the AD shutdown on 17 December. “We really want to get some experience with this device this year so that, if we need to make any changes, we will have time during the long shutdown in which to make them,” says Jeffrey Hangst, ALPHA spokesperson. “Rather than starting the 2014 run in the commissioning stage, we will be up and running from the get go.&...

  1. Expression and functional importance of collagen-binding integrins, alpha 1 beta 1 and alpha 2 beta 1, on virus-activated T cells

    DEFF Research Database (Denmark)

    Andreasen, Susanne Ø; Thomsen, Allan R; Koteliansky, Victor E


    Adhesive interactions are crucial to cell migration into inflammatory sites. Using murine lymphocytic choriomeningitis virus as an Ag model system, we have investigated expression and function of collagen-binding integrins, alpha(1)beta(1) and alpha(2)beta(1), on activated and memory T cells. Using...... this system and MHC tetramers to define Ag-specific T cells, we demonstrate that contrary to being VLAs, expression of alpha(1)beta(1) and alpha(2)beta(1) can be rapidly induced on acutely activated T cells, that expression of alpha(1)beta(1) remains elevated on memory T cells, and that expression of alpha(1...... decreased responses were seen upon transfer of alpha(1)-deficient activated/memory T cells. Thus, expression of alpha(1)beta(1) and alpha(2)beta(1) integrins on activated T cells is directly functionally important for generation of inflammatory responses within tissues. Finally, the inhibitory effect...

  2. [Bifunctional inhibitor of alpha-amylase/trypsin from wheat grain]. (United States)

    Islamov, R A; Furusov, O V


    A trypsin inhibitor, isolated from whole-wheat grain (Triticum aestivum L.) by the method of bio-specific chromatography on trypsin-Sepharose, was potent in inhibiting human salivary alpha-amylase. The bi-functional alpha-amylase/trypsin inhibitor was characterized by a narrow specificity for other alpha-amylases and proteinases. The high thermostability of the inhibitor was lost in the presence of SH group-reducing agents. The inhibitor-trypsin complex retained its activity against alpha-amylase. The inhibitor-alpha-amylase complex was active against trypsin. Studies of the enzyme kinetics demonstrated that the inhibition of alpha-amylase and trypsin was noncompetitive. Our results suggest the existence of two independent active sites responsible for the interaction with the enzymes.

  3. Does \\Sigma -\\Sigma -\\alpha Form a Quasi-Bound State?

    CERN Document Server

    Htun Oo, H; Kamada, H; Glöckle, W


    We have investigated the possible existence of a quasi-bound state for the \\Sigma -\\Sigma -\\alpha system in the framework of Faddeev calculations. We are particularly interested in the state of total iso-spin T=2, since for an inert \\alpha particle there is no strong conversion to \\Xi -N-\\alpha or \\Lambda -\\Lambda -\\alpha possible. A \\Sigma -\\alpha optical potential based on Nijmegen model D and original \\Sigma -\\Sigma interactions of the series of Nijmegen potentials NSC97 as well a simulated Gaussian type versions thereof are used. Our investigation of the \\Sigma -\\Sigma -\\alpha system leads to a quasi bound state where, depending on the potential parameters, the energy ranges between -1.4 and -2.4 MeV and the level width is about 0.2MeV.

  4. Synthesis of stabilized alpha-helical peptides. (United States)

    Bernal, Federico; Katz, Samuel G


    Stabilized alpha-helical (SAH) peptides are valuable laboratory tools to explore important protein-protein interactions. Whereas most peptides lose their secondary structure when isolated from the host protein, stapled peptides incorporate an all-hydrocarbon "staple" that reinforces their natural alpha-helical structure. Thus, stapled peptides retain their functional ability to bind their native protein targets and serve multiple experimental uses. First, they are useful for structural studies such as NMR or crystal structures that map and better define binding sites. Second, they can be used to identify small molecules that specifically target that interaction site. Third, stapled peptides can be used to test the importance of specific amino acid residues or posttranslational modifications to the binding. Fourth, they can serve as structurally competent bait to identify novel binding partners to specific alpha-helical motifs. In addition to markedly improved alpha-helicity, stapled peptides also display resistance to protease cleavage and enhanced cell permeability. Most importantly, they are useful for intracellular experiments that explore the functional consequences of blocking particular protein interactions. Because of their remarkable stability, stapled peptides can be applied to whole-animal, in vivo studies. Here we describe a protocol for the synthesis of a peptide that incorporates an all-hydrocarbon "staple" employing a ring-closing olefin metathesis reaction. With proper optimization, stapled peptides can be a fundamental, accurate laboratory tool in the modern chemical biologist's armory.

  5. Expression Analysis of cPLA2 Alpha Interacting TIP60 in Diabetic KKAy and Non-Diabetic C57BL Wild-Type Mice: No Impact of Transient and Stable TIP60 Overexpression on Glucose-Stimulated Insulin Secretion in Pancreatic Beta-Cells

    DEFF Research Database (Denmark)

    Nordentoft, Iver; Jeppesen, Per B; Nielsen, Anders L;


    In the present study we investigate the expression levels of cytosolic phospholipase A2 alpha (cPLA2alpha) interacting histone acetyl transferase proteins TIP60alpha and TIP60beta in non-diabetic C57BL wild-type mice and obese type 2 diabetic KKAy model mice. The aim was to test our hypothesis...... that TIP60 plays a regulatory role in glucose-stimulated insulin secretion from pancreatic beta-cells. MATERIAL AND METHODS: Ten obese diabetic KKAy mice and ten non-diabetic C57BL mice were fed a standard chow diet. After nine weeks, islet RNA was purified and used to measure TIP60 expression. We...... investigated the effect of TIP60alpha and TIP60beta on glucose-stimulated insulin secretion by transient and stable overexpression in the pancreatic mouse beta-cell line MIN6 and the rat beta-cell line INS-1E. RESULTS: We found that non-diabetic C57BL mice and diabetic KKAy mice have the same level of both...

  6. Interaction of a nondiffracting high-order Bessel (vortex) beam of fractional type alpha and integer order m with a rigid sphere: linear acoustic scattering and net instantaneous axial force. (United States)

    Mitri, Farid G


    Closed-form analytical solutions for the acoustic scattering and net axial force of a new class of Bessel beams, termed nondiffracting Bessel vortex beams of fractional type alpha, are derived. This new class of Bessel beams preserves the same nondiffracting feature of conventional high-order Bessel beams of integer order. The far-field acoustic scattering field by a rigid sphere centered on the beam axis is expressed as a partial wave series involving the real number alpha, the scattering angle relative to the beam axis theta, and the half-conical angle beta of the wave number components of the beam. Unlike the acoustic scattering properties of conventional high-order Bessel beams, the acoustic forward scattering (theta = 0 degrees) and backscattering (theta = 180 degrees) of Bessel vortex beams of fractional type alpha by a rigid sphere do not vanish unless alpha becomes an integer number. Furthermore, an expression for the net instantaneous axial force is derived for the case of progressive, stationary, and quasi-stationary waves. These results provide new insights into the acoustic scattering theory in the context of nondiffracting beams. The properties of nondiffracting Bessel vortex beams of fractional type alpha may lead to the development of an "acoustic blender" with possible applications in particle rotation, mixing, and manipulation. Imaging and other related applications may also benefit from this new type of acoustic beams.

  7. In cellulo examination of a beta-alpha hybrid construct of beta-hexosaminidase A subunits, reported to interact with the GM2 activator protein and hydrolyze GM2 ganglioside.

    Directory of Open Access Journals (Sweden)

    Incilay Sinici

    Full Text Available The hydrolysis in lysosomes of GM2 ganglioside to GM3 ganglioside requires the correct synthesis, intracellular assembly and transport of three separate gene products; i.e., the alpha and beta subunits of heterodimeric beta-hexosaminidase A, E.C. # (encoded by the HEXA and HEXB genes, respectively, and the GM2-activator protein (GM2AP, encoded by the GM2A gene. Mutations in any one of these genes can result in one of three neurodegenerative diseases collectively known as GM2 gangliosidosis (HEXA, Tay-Sachs disease, MIM # 272800; HEXB, Sandhoff disease, MIM # 268800; and GM2A, AB-variant form, MIM # 272750. Elements of both of the hexosaminidase A subunits are needed to productively interact with the GM2 ganglioside-GM2AP complex in the lysosome. Some of these elements have been predicted from the crystal structures of hexosaminidase and the activator. Recently a hybrid of the two subunits has been constructed and reported to be capable of forming homodimers that can perform this reaction in vivo, which could greatly simplify vector-mediated gene transfer approaches for Tay-Sachs or Sandhoff diseases. A cDNA encoding a hybrid hexosaminidase subunit capable of dimerizing and hydrolyzing GM2 ganglioside could be incorporated into a single vector, whereas packaging both subunits of hexosaminidase A into vectors, such as adeno-associated virus, would be impractical due to size constraints. In this report we examine the previously published hybrid construct (H1 and a new more extensive hybrid (H2, with our documented in cellulo (live cell- based assay utilizing a fluorescent GM2 ganglioside derivative. Unfortunately when Tay-Sachs cells were transfected with either the H1 or H2 hybrid construct and then were fed the GM2 derivative, no significant increase in its turnover was detected. In vitro assays with the isolated H1 or H2 homodimers confirmed that neither was capable of human GM2AP-dependent hydrolysis of GM2 ganglioside.

  8. Interaction of C/EBP-beta and NF-Y factors constrains activity levels of the nutritionally controlled promoter IA expressing the acetyl-CoA carboxylase-alpha gene in cattle

    Directory of Open Access Journals (Sweden)

    Shi Xuanming


    Full Text Available Abstract Background The enzyme acetyl-CoA carboxylase-alpha (ACC-α is rate limiting for de novo fatty acid synthesis. Among the four promoters expressing the bovine gene, promoter IA (PIA is dominantly active in lipogenic tissues. This promoter is in principal repressed but activated under favorable nutritional conditions. Previous analyses already coarsely delineated the repressive elements on the distal promoter but did not resolve the molecular nature of the repressor. Knowledge about the molecular functioning of this repressor is fundamental to understanding the nutrition mediated regulation of PIA activity. We analyzed here the molecular mechanism calibrating PIA activity. Results We finely mapped the repressor binding sites in reporter gene assays and demonstrate together with Electrophoretic Mobility Shift Assays that nuclear factor-Y (NF-Y and CCAAT/enhancer binding protein-β(C/EBPβ each separately repress PIA activity by binding to their cognate low affinity sites, located on distal elements of the promoter. Simultaneous binding of both factors results in strongest repression. Paradoxically, over expression of NFY factors, but also - and even more so - of C/EBPβ significantly activated the promoter when bound to high affinity sites on the proximal promoter. However, co-transfection experiments revealed that NF-Y may eventually diminish the strong stimulatory effect of C/EBPβ at the proximal PIA in a dose dependent fashion. We validated by chromatin immunoprecipitation, that NF-Y and C/EBP factors may physically interact. Conclusion The proximal promoter segment of PIA appears to be principally in an active state, since even minute concentrations of both, NF-Y and C/EBPβ factors can saturate the high affinity activator sites. Higher factor concentrations will saturate the low affinity repressive sites on the distal promoter resulting in reduced and calibrated promoter activity. Based on measurements of the mRNA concentrations of

  9. The vaccinia virus 14-kilodalton (A27L) fusion protein forms a triple coiled-coil structure and interacts with the 21-kilodalton (A17L) virus membrane protein through a C-terminal alpha-helix. (United States)

    Vázquez, M I; Rivas, G; Cregut, D; Serrano, L; Esteban, M


    The vaccinia virus 14-kDa protein (encoded by the A27L gene) plays an important role in the biology of the virus, acting in virus-to-cell and cell-to-cell fusions. The protein is located on the surface of the intracellular mature virus form and is essential for both the release of extracellular enveloped virus from the cells and virus spread. Sequence analysis predicts the existence of four regions in this protein: a structureless region from amino acids 1 to 28, a helical region from residues 29 to 37, a triple coiled-coil helical region from residues 44 to 72, and a Leu zipper motif at the C terminus. Circular dichroism spectroscopy, analytical ultracentrifugation, and chemical cross-linking studies of the purified wild-type protein and several mutant forms, lacking one or more of the above regions or with point mutations, support the above-described structural division of the 14-kDa protein. The two contiguous cysteine residues at positions 71 and 72 are not responsible for the formation of 14-kDa protein trimers. The location of hydrophobic residues at the a and d positions on a helical wheel and of charged amino acids in adjacent positions, e and g, suggests that the hydrophobic and ionic interactions in the triple coiled-coil helical region are involved in oligomer formation. This conjecture was supported by the construction of a three-helix bundle model and molecular dynamics. Binding assays with purified proteins expressed in Escherichia coli and cytoplasmic extracts from cells infected with a virus that does not produce the 14-kDa protein during infection (VVindA27L) show that the 21-kDa protein (encoded by the A17L gene) is the specific viral binding partner and identify the putative Leu zipper, the predicted third alpha-helix on the C terminus of the 14-kDa protein, as the region involved in protein binding. These findings were confirmed in vivo, following transfection of animal cells with plasmid vectors expressing mutant forms of the 14-kDa protein and

  10. Iron modulates the alpha chain of fibrinogen. (United States)

    Nielsen, Vance G; Jacobsen, Wayne K


    Iron-bound fibrinogen has been noted to accelerate plasmatic coagulation in patients with divergent conditions involving upregulation of heme oxygenase activity, including hemodialysis, Alzheimer's disease, sickle cell anemia, and chronic migraine. Our goal was to determine if a site of iron-fibrinogen interaction was on the alpha chain. Using thrombelastography, we compared the coagulation kinetic profiles of plasma exposed to 0-10 µM ferric chloride after activation of coagulation with thrombin generated by contact activation of plasma with the plastic sample cup or by exposure to 1 µg/ml of Calloselasma rhodostoma venom (rich in ancrod activity), which causes coagulation via polymerization of alpha chain monomers. Venom mediated coagulation always occurred before thrombin activated thrombus formation, and ferric chloride always diminished the time of onset of coagulation and increased the velocity of clot growth. Iron enhances plasmatic coagulation kinetics by modulating the alpha chain of fibrinogen.

  11. ALPHA MIS: Reference manual

    Energy Technology Data Exchange (ETDEWEB)

    Lovin, J.K.; Haese, R.L.; Heatherly, R.D.; Hughes, S.E.; Ishee, J.S.; Pratt, S.M.; Smith, D.W.


    ALPHA is a powerful and versatile management information system (MIS) initiated and sponsored and by the Finance and Business Management Division of Oak Ridge National Laboratory, who maintain and develop it in concert with the Business Systems Division for its Information Center. A general-purpose MIS, ALPHA allows users to access System 1022 and System 1032 databases to obtain and manage information. From a personal computer or a data terminal, Energy Systems employees can use ALPHA to control their own report reprocessing. Using four general commands (Database, Select, Sort, and Report) they can (1) choose a mainframe database, (2) define subsets within it, (3) sequentially order a subset by one or more variables, and (4) generate a report with their own or a canned format.

  12. Engagement of SIRP alpha Inhibits Growth and Induces Programmed Cell Death in Acute Myeloid Leukemia Cells

    NARCIS (Netherlands)

    Irandoust, Mahban; Zarate, Julian Alvarez; Hubeek, Isabelle; van Beek, Ellen M.; Schornagel, Karin; Broekhuizen, Aart J. F.; Akyuz, Mercan; van de Loosdrecht, Arjan A.; Delwel, Ruud; Valk, Peter J.; Sonneveld, Edwin; Kearns, Pamela; Creutzig, Ursula; Reinhardt, Dirk; de Bont, Eveline S. J. M.; Coenen, Eva A.; van den Heuvel-Eibrink, Marry M.; Zwaan, C. Michel; Kaspers, Gertjan J. L.; Cloos, Jacqueline; van den Berg, Timo K.


    Background: Recent studies show the importance of interactions between CD47 expressed on acute myeloid leukemia (AML) cells and the inhibitory immunoreceptor, signal regulatory protein-alpha (SIRP alpha) on macrophages. Although AML cells express SIRP alpha, its function has not been investigated in

  13. AlphaSphere


    Place, A.; Lacey, L.; Mitchell, T.


    The AlphaSphere is an electronic musical instrument featuring a series of tactile, pressure sensitive touch pads arranged in a spherical form. It is designed to offer a new playing style, while allowing for the expressive real-time modulation of sound available in electronic-based music. It is also designed to be programmable, enabling the flexibility to map a series of different notational arrangements to the pad-based interface.\\ud \\ud The AlphaSphere functions as an HID, MIDI and OSC devic...

  14. Alpha-mannosidosis

    DEFF Research Database (Denmark)

    Borgwardt, Line; Stensland, Hilde Monica Frostad Riise; Olsen, Klaus Juul;


    of the three subgroups of genotype/subcellular localisation and the clinical and biochemical data were done to investigate the potential relationship between genotype and phenotype in alpha-mannosidosis. Statistical analyses were performed using the SPSS software. Analyses of covariance were performed...

  15. Alpha Antihydrogen Experiment (United States)

    Fujiwara, M. C.; Andresen, G. B.; Ashkezari, M. D.; Baquero-Ruiz, M.; Bertsche, W.; Bray, C. C.; Butler, E.; Cesar, C. L.; Chapman, S.; Charlton, M.; Cesar, C. L.; Fajans, J.; Friesen, T.; Gill, D. R.; Hangst, J. S.; Hardy, W. N.; Hayano, R. S.; Hayden, M. E.; Humphries, A. J.; Hydomako, R.; Jonsell, S.; Kurchaninov, L.; Lambo, R.; Madsen, N.; Menary, S.; Nolan, P.; Olchanski, K.; Olin, A.; Povilus, A.; Pusa, P.; Robicheaux, F.; Sarid, E.; Silveira, D. M.; So, C.; Storey, J. W.; Thompson, R. I.; van der Werf, D. P.; Wilding, D.; Wurtele, J. S.; Yamazaki, Y.


    ALPHA is an experiment at CERN, whose ultimate goal is to perform a precise test of CPT symmetry with trapped antihydrogen atoms. After reviewing the motivations, we discuss our recent progress toward the initial goal of stable trapping of antihydrogen, with some emphasis on particle detection techniques.

  16. Case Study - Alpha

    Directory of Open Access Journals (Sweden)

    Stephen Leybourne


    Full Text Available This case study was developed from an actual scenario by Dr. Steve Leybourne of Boston University.  The case documents the historical evolution of an organization, and has been used successfully in courses dealing with organizational and cultural change, and the utilization of ‘soft skills’ in project-based management. This is a short case, ideal for classroom use and discussion.  The issues are easily accessible to students, and there is a single wide ranging question that allows for the inclusion of many issues surrounding strategic decision-making, and behavioural and cultural change. Alpha was one of the earlier companies in the USA to invest in large, edge-of-town superstores, with plentiful free vehicle parking, selling food and related household products. Alpha was created in the 1950s as a subsidiary of a major publicly quoted retail group.  It started business by opening a string of very large discount stores in converted industrial and warehouse premises in the south of the United States. In the early days shoppers were offered a limited range of very competitively priced products. When Alpha went public in 1981 it was the fourth largest food retailer in the US, selling an ever-widening range of food and non-food products.  Its success continued to be based on high volume, low margins and good value for money, under the slogan of ‘Alpha Price.’

  17. Alpha Antihydrogen Experiment

    CERN Document Server

    Fujiwara, M C; Ashkezari, M D; Baquero-Ruiz, M; Bertsche, W; Bray, C C; Butler, E; Cesar, C L; Chapman, S; Charlton, M; Cesar, C L; Fajans, J; Friesen, T; Gill, D R; Hangst, J S; Hardy, W N; Hayano, R S; Hayden, M E; Humphries, A J; Hydomako, R; Jonsell, S; Kurchaninov, L; Lambo, R; Madsen, N; Menary, S; Nolan, P; Olchanski, K; Olin, A; Povilus, A; Pusa, P; Robicheaux, F; Sarid, E; Silveira, D M; So, C; Storey, J W; Thompson, R I; van der Werf, D P; Wilding, D; Wurtele, J S; Yamazaki, Y


    ALPHA is an experiment at CERN, whose ultimate goal is to perform a precise test of CPT symmetry with trapped antihydrogen atoms. After reviewing the motivations, we discuss our recent progress toward the initial goal of stable trapping of antihydrogen, with some emphasis on particle detection techniques.

  18. Stereoselective Synthesis of [alpha, alpha][superscript ']-Biprolines

    Energy Technology Data Exchange (ETDEWEB)

    Vartak, Ashish P.; Young, Jr., Victor G.; Johnson, Rodney L. (Minnesota)


    A means to induce dehydrodimerization of Seebach's oxazolidinone (5), the stereochemical outcome of which is entirely temperature dependent, is described. The resultant dimers 3 and 4 are precursors to (R,R)-alpha,alpha'-biproline (1) and meso-alpha,alpha'-biproline (2), respectively. An organohypobromite and an iminium halide are proposed to serve as electrophiles in the reaction with the enolate of 5 to give 3 and 4, respectively.

  19. Genetic evidence that HNF-1alpha-dependent transcriptional control of HNF-4alpha is essential for human pancreatic beta cell function

    DEFF Research Database (Denmark)

    Hansen, Sara K; Párrizas, Marcelina; Jensen, Maria L;


    , and consequently in reduced HNF-1alpha-dependent activation. These findings provide genetic evidence that HNF-1alpha serves as an upstream regulator of HNF-4alpha and interacts directly with the P2 promoter in human pancreatic cells. Furthermore, they indicate that this regulation is essential to maintain normal...... in human islets and exocrine cells is primarily mediated by the P2 promoter. Furthermore, we describe a G --> A mutation in a conserved nucleotide position of the HNF-1alpha binding site of the P2 promoter, which cosegregates with MODY. The mutation results in decreased affinity for HNF-1alpha...

  20. Karyopherin alpha7 (KPNA7), a divergent member of the importin alpha family of nuclear import receptors. (United States)

    Kelley, Joshua B; Talley, Ashley M; Spencer, Adam; Gioeli, Daniel; Paschal, Bryce M


    Classical nuclear localization signal (NLS) dependent nuclear import is carried out by a heterodimer of importin alpha and importin beta. NLS cargo is recognized by importin alpha, which is bound by importin beta. Importin beta mediates translocation of the complex through the central channel of the nuclear pore, and upon reaching the nucleus, RanGTP binding to importin beta triggers disassembly of the complex. To date, six importin alpha family members, encoded by separate genes, have been described in humans. We sequenced and characterized a seventh member of the importin alpha family of transport factors, karyopherin alpha 7 (KPNA7), which is most closely related to KPNA2. The domain of KPNA7 that binds Importin beta (IBB) is divergent, and shows stronger binding to importin beta than the IBB domains from of other importin alpha family members. With regard to NLS recognition, KPNA7 binds to the retinoblastoma (RB) NLS to a similar degree as KPNA2, but it fails to bind the SV40-NLS and the human nucleoplasmin (NPM) NLS. KPNA7 shows a predominantly nuclear distribution under steady state conditions, which contrasts with KPNA2 which is primarily cytoplasmic. KPNA7 is a novel importin alpha family member in humans that belongs to the importin alpha2 subfamily. KPNA7 shows different subcellular localization and NLS binding characteristics compared to other members of the importin alpha family. These properties suggest that KPNA7 could be specialized for interactions with select NLS-containing proteins, potentially impacting developmental regulation.

  1. HB Hillingdon [alpha46(CE4)Phe-->Val (alpha1 Or alpha2)]: a new alpha chain hemoglobin variant. (United States)

    Babb, Anna; Solaiman, Susannah; Green, Brian N; Mantio, Debbie; Patel, Ketan


    Routine antenatal hemoglobinopathy screening detected a new alpha chain variant that eluted with Hb A(2) on cation exchange high performance liquid chromatography (HPLC) in a lady of Sri Lankan origin who had normal hematological indices. The mutation was identified by electrospray ionization mass spectrometry (ESI-MS) as alpha46(CE4)Phe-->Val, inferring that the variant was due to a single base change at codon 46 (TTC>GTC) of the alpha1- or alpha2-globin genes.

  2. $\\alpha$-Representation for QCD


    Tuan, Richard Hong


    An $\\alpha$-parameter representation is derived for gauge field theories.It involves, relative to a scalar field theory, only constants and derivatives with respect to the $\\alpha$-parameters. Simple rules are given to obtain the $\\alpha$-representation for a Feynman graph with an arbitrary number of loops in gauge theories in the Feynman gauge.

  3. Alpha and Beta Determinations

    CERN Document Server

    Dunietz, Isard


    Because the Bd -> J/psi Ks asymmetry determines only sin(2 beta), a discrete ambiguity in the true value of beta remains. This note reviews how the ambiguity can be removed. Extractions of the CKM angle alpha are discussed next. Some of the methods require very large data samples and will not be feasible in the near future. In the near future, semi-inclusive CP-violating searches could be undertaken, which are reviewed last.

  4. Low-energy direct photon production in p p and alpha alpha collisions at the cern intersecting storage rings

    CERN Document Server

    Choi, Young-il


    High transverse momentum (p(,T)) direct photons have given us some of our best evidence for low order perturbative QCD proces- ses in hadron collisions. It is also important to examine hadronic collisions with a weakly interacting probe in the low p(,T) region, where hadron interactions involve very complicated phenomena. A previous experiment at SQRT.(s) = 12 GeV has observed an excess of low p(,T) direct photons. The present experiment has studied direct soft photons in pp interactions at SQRT.(s) = 63 GeV and alpha-alpha interactions at SQRT.(s(,NN)) = 31.5 GeV at the CERN ISR. Comparisons of photon production with respect to track production in pp minimum bias events with that in pp events with high transverse energy (E(,T)) and with alpha-alpha minimum bias events are investigated. For alpha-alpha minimum bias data, within experimental errors there was no excess of photons with respect to tracks, compared with pp minimum bias data. But for pp high E(,T) data, we observed an interesting effect: as p(,T) i...

  5. Combining Alphas via Bounded Regression

    Directory of Open Access Journals (Sweden)

    Zura Kakushadze


    Full Text Available We give an explicit algorithm and source code for combining alpha streams via bounded regression. In practical applications, typically, there is insufficient history to compute a sample covariance matrix (SCM for a large number of alphas. To compute alpha allocation weights, one then resorts to (weighted regression over SCM principal components. Regression often produces alpha weights with insufficient diversification and/or skewed distribution against, e.g., turnover. This can be rectified by imposing bounds on alpha weights within the regression procedure. Bounded regression can also be applied to stock and other asset portfolio construction. We discuss illustrative examples.

  6. Orthopositronium lifetime. Analytic results in O ({alpha}) and O ({alpha}{sup 3} ln {alpha})

    Energy Technology Data Exchange (ETDEWEB)

    Kniehl, B.A.; Kotikov, A.V.; Veretin, O.L. [Hamburg Univ. (Germany). 2. Inst. fuer Theoretische Physik


    We present the O({alpha}) and O({alpha}{sup 3}ln {alpha}) corrections to the total decay width of orthopositronium in closed analytic form, in terms of basic transcendental numbers, which can be evaluated numerically to arbitrary precision. (orig.)

  7. H$\\alpha$ kinematics of KPG 390

    CERN Document Server

    Repetto, P; Fuentes-Carrera, R Gabbasov I


    In this work we present scanning Fabry-Perot H$\\alpha$ observations of the isolated interacting galaxy pair NGC 5278/79 obtained with the PUMA Fabry-Perot interferometer. We derived velocity fields, various kinematic parameters and rotation curves for both galaxies. Our kinematical results together with the fact that dust lanes have been detected in both galaxies, as well as the analysis of surface brightness profiles along the minor axis, allowed us to determine that both components of the interacting pair are trailing spirals.

  8. EEG, alpha waves and coherence (United States)

    Ascolani, Gianluca

    This thesis addresses some theoretical issues generated by the results of recent analysis of EEG time series proving the brain dynamics are driven by abrupt changes making them depart from the ordinary Poisson condition. These changes are renewal, unpredictable and non-ergodic. We refer to them as crucial events. How is it possible that this form of randomness be compatible with the generation of waves, for instance alpha waves, whose observation seems to suggest the opposite view the brain is characterized by surprisingly extended coherence? To shed light into this apparently irretrievable contradiction we propose a model based on a generalized form of Langevin equation under the influence of a periodic stimulus. We assume that there exist two different forms of time, a subjective form compatible with Poisson statistical physical and an objective form that is accessible to experimental observation. The transition from the former to the latter form is determined by the brain dynamics interpreted as emerging from the cooperative interaction among many units that, in the absence of cooperation would generate Poisson fluctuations. We call natural time the brain internal time and we make the assumption that in the natural time representation the time evolution of the EEG variable y(t) is determined by a Langevin equation perturbed by a periodic process that in this time representation is hardly distinguishable from an erratic process. We show that the representation of this random process in the experimental time scale is characterized by a surprisingly extended coherence. We show that this model generates a sequence of damped oscillations with a time behavior that is remarkably similar to that derived from the analysis of real EEG's. The main result of this research work is that the existence of crucial events is not incompatible with the alpha wave coherence. In addition to this important result, we find another result that may help our group, or any other research

  9. [alpha-Latrotoxin as an instrument for studying neurosecretions]. (United States)

    Himmel'reĭkh, N H


    alpha-Latrotoxin, a presynaptic toxin from black widow spider venom Latrodectus mactans tredecimguttatus, triggers exocytosis in a variety of neurosecretory cells both in the presence and absence of calcium in the medium. The toxin interacts with two types of membrane the receptors which belong to different families of neuronal proteins and have different structures. Calcium-dependent receptor of alpha-latrotoxin is identified as neurexin I alpha and belongs to the family of neurexins. This family is selectively expressed in nerve tissue. The calcium-independent receptor of alpha-latrotoxin belongs to the family of G-protein-coupled receptors and proteins which homologous to it are found in heart, lung, kidney and spleen tissues. As a result of alpha-latrotoxin interaction with membrane receptor in the calcium medium the toxin forms the ionic channels in plasmalemma and enhances its calcium permeability. The effects of alpha-latrotoxin on exocytosis in the calcium and calcium-free media and question concerning coupling of channel-forming and secretogenic properties of alpha-latrotoxin are discussed.

  10. The role of TNF-alpha in amygdala kindled rats. (United States)

    Shandra, A A; Godlevsky, L S; Vastyanov, R S; Oleinik, A A; Konovalenko, V L; Rapoport, E N; Korobka, N N


    In the present study, the interaction between epileptogenesis and the immune system were studied in a kindling model. First, the effects of a single administration of TNF-alpha (5.0 microg/kg, i.p.) on seizure and EEG activity were investigated in amygdala-kindled rats. TNF-alpha treated rats showed more prolonged epileptiformic discharges than control rats. TNF-alpha also induced a decrease in the power of delta band and an increase in theta and alpha activity. In addition, a marked increase in the power of beta and gamma band was observed. The EEG changes were most numerous in the frontal cortex and amygdala. All effects were registered 24 h after TNF-alpha administration. Finally, electrical stimulation enhanced the level of TNF-alpha in blood serum from 1.9 +/- 1.5 to 12.7 +/- 3.8 pg/ml and in brain tissue 56.8 +/- 6.0 to 109.2 +/- 6.0 pg/mg, as was determined via the ELISA method. It can be concluded that there is a mutual facilitative interaction of both epileptogenic and cytokine-derived mechanisms on this type of seizure. The changes in the power spectrum of the EEG after TNF-alpha might contribute to intensify thalamic-derived facilitation of epileptic discharge in cortical structures.

  11. Role of TNF-alpha and its receptors in pericoronitis. (United States)

    Beklen, A; Laine, M; Ventä, I; Hyrkäs, T; Konttinen, Y T


    The classic stimulus for cellular cytokine production is bacterial lipopolysaccharide (endotoxin). It was therefore hypothesized that tumor necrosis factor-alpha (TNF-alpha) may be responsible for pericoronitis. TNF-alpha and its receptors were detected by immunohistochemical staining in third molar pericoronitis in ten patients and ten healthy control samples. The percentage of TNF-alpha positive cells was high in pericoronitis (p = 0.0317). TNF receptors TNF-R1 and TNF-R2 were found in macrophage- and fibroblast-like cells, vascular endothelial cells in post-capillary venules, and basal epithelial cells in pericoronitis, but were only weakly expressed in controls. Increased expression of interleukin-1beta and vascular cell adhesion molecule-1 was found as a biological indicator of TNF-alpha ligand-receptor interaction. Explanted tissues acquired destructive potential upon TNF-alpha stimulation, whereas TNF-alpha blockers controlled it in inflamed tissues. These findings suggest that, in pericoronitis, inflammatory and resident cells produce and respond to potent pro-inflammatory cytokine TNF-alpha, with pathogenic and potential therapeutic relevance.

  12. Alpha-tocopherol inhibits pore formation in the oxidized bilayers

    CERN Document Server

    Boonnoy, Phansiri; Wong-ekkabut, Jirasak


    In biological membranes, alpha-tocopherols ({\\alpha}-toc; vitamin E) protect polyunsaturated lipids from free radicals. Although the interactions of {\\alpha}-toc with non-oxidized lipid bilayers have been studied, their on oxidized bilayers remain unknown. In this study, atomistic molecular dynamics (MD) simulations of oxidized lipid bilayers were performed with varying concentrations of {\\alpha}-toc. Bilayers with 1-palmitoyl-2-lauroyl-sn-glycero-3-phosphocholine (PLPC) lipids and its aldehyde derivatives at 1:1 ratio were studied. Our simulations show that oxidized lipids self-assemble into aggregates with a water pore rapidly developing across the lipid bilayer. The free energy of transporting an {\\alpha}-toc molecule in a lipid bilayer suggests that {\\alpha}-tocs can passively adsorb into the bilayer. When {\\alpha}-toc molecules were present at low concentrations in bilayers containing oxidized lipids, the formation of water pores was slowed down. At high {\\alpha}-toc concentra-tions, no pores were observ...

  13. A simple approach to $\\alpha$-decay fine structure

    CERN Document Server

    Delion, D S; Liotta, R J; Wyss, R


    We propose a simple method to evaluate $\\alpha$-transition rates to low-lying excited states in even-even nuclei. For this a realistic $\\alpha$-daughter double folding interaction is approximated by a parabola in the region where the decay process takes place. This allows us to evaluate the penetration probability analytically. The main experimental features of branching ratios to excited states are reproduced by this simple approach.

  14. Biased mutagenesis in the N-terminal region by degenerate oligonucleotide gene shuffling enhances secretory expression of barley alpha-amylase 2 in yeast

    DEFF Research Database (Denmark)

    Fukuda, Kenji; Jensen, Malene Hillerup; Aghajari, Nushin


    Recombinant barley alpha-amylase 1 (rAMY1) and 2 (rAMY2), despite 80% sequence identity, are produced in very different amounts of 1.1 and alpha loop 2 that interacts with domain B (beta-->alpha loop 3) protruding from the catalytic (beta/alpha)(8)-barrel. Most remarkably Pichia pastoris strain GS...

  15. Biased mutagenesis in the N-terminal region by degenerate oligonucleotide gene shuffling enhances secretory expression of barley alpha-amylase 2 in yeast

    DEFF Research Database (Denmark)

    Fukuda, Kenji; Jensen, Malene Hillerup; Aghajari, Nushin


    Recombinant barley alpha-amylase 1 (rAMY1) and 2 (rAMY2), despite 80% sequence identity, are produced in very different amounts of 1.1 and alpha loop 2 that interacts with domain B (beta-->alpha loop 3) protruding from the catalytic (beta/alpha)(8)-barrel. Most remarkably Pichia pastoris strain GS...

  16. alpha-Globin genes: thalassemic and structural alterations in a Brazilian population

    Directory of Open Access Journals (Sweden)

    M.R.S.C. Wenning


    Full Text Available Seven unrelated patients with hemoglobin (Hb H disease and 27 individuals with alpha-chain structural alterations were studied to identify the alpha-globin gene mutations present in the population of Southeast Brazil. The -alpha3.7, --MED and -(alpha20.5 deletions were investigated by PCR, whereas non-deletional alpha-thalassemia (alphaHphalpha, alphaNcoIalpha, aaNcoI, alphaIcalpha and alphaTSaudialpha was screened with restriction enzymes and by nested PCR. Structural alterations were identified by direct DNA sequencing. Of the seven patients with Hb H disease, all of Italian descent, two had the -(alpha20.5/-alpha3.7 genotype, one had the --MED/-alpha3.7 genotype, one had the --MED/alphaHphalpha genotype and three showed interaction of the -alpha3.7 deletion with an unusual, unidentified form of non-deletional alpha-thalassemia [-alpha3.7/(aaT]. Among the 27 patients with structural alterations, 15 (of Italian descent had Hb Hasharon (alpha47Asp->His associated with the -alpha3.7 deletion, 4 (of Italian descent were heterozygous for Hb J-Rovigo (alpha53Ala->Asp, 4 (3 Blacks and 1 Caucasian were heterozygous for Hb Stanleyville-II (alpha78Asn->Lys associated with the alpha+-thalassemia, 1 (Black was heterozygous for Hb G-Pest (alpha74Asp->Asn, 1 (Caucasian was heterozygous for Hb Kurosaki (alpha7Lys->Glu, 1 (Caucasian was heterozygous for Hb Westmead (alpha122His->Gln, and 1 (Caucasian was the carrier of a novel silent variant (Hb Campinas, alpha26Ala->Val. Most of the mutations found reflected the Mediterranean and African origins of the population. Hbs G-Pest and Kurosaki, very rare, and Hb Westmead, common in southern China, were initially described in individuals of ethnic origin differing from those of the carriers reported in the present study and are the first cases to be reported in the Brazilian population.

  17. Activity of alpha-amylase inhibitors from Phaseolus coccineus on digestive alpha-amylases of the coffee berry borer. (United States)

    Valencia-Jiménez, Arnubio; Arboleda Valencia, Jorge W; Grossi-De-Sá, Maria Fátima


    Seeds of scarlet runner bean ( Phaseolus coccineus L.) were analyzed for alpha-amylase inhibitor (alpha-AI) activity. Through the use of polyclonal antibodies raised against pure alpha-AI-1 from common bean ( Phaseolus vulgaris L.), typical alpha-AlphaIota polypeptides (Mr 14-18 kDa) as well as a large polypeptide of Mr 32000 Da, usually referred to as "amylase inhibitor like", were detected. The inhibitor activity present in four accessions of P. coccineus was examined, both in semiquantitative zymograms allowing the separation of different isoforms and in quantitative assays against human salivary amylase, porcine pancreatic amylase, and coffee berry borer, Hypothenemus hampei Ferrari (Coleoptera: Scolytidae) amylase. Differential inhibition curves lead to the suggestion that the gene encoding one of the inhibitors in P. coccineus (in accession G35590) would be a good candidate for genetic engineering of coffee resistance toward the coffee berry borer. An in vitro proteolytic digestion treatment of pure alpha-AlphaIota-1 resulted in a rapid loss of the inhibitory activity, seriously affecting its natural capacity to interact with mammalian alpha-amylases.

  18. Alpha-mannosidosis

    Directory of Open Access Journals (Sweden)

    Nilssen Øivind


    Full Text Available Abstract Alpha-mannosidosis is an inherited lysosomal storage disorder characterized by immune deficiency, facial and skeletal abnormalities, hearing impairment, and intellectual disability. It occurs in approximately 1 of 500,000 live births. The children are often born apparently normal, and their condition worsens progressively. Some children are born with ankle equinus or develop hydrocephalus in the first year of life. Main features are immune deficiency (manifested by recurrent infections, especially in the first decade of life, skeletal abnormalities (mild-to-moderate dysostosis multiplex, scoliosis and deformation of the sternum, hearing impairment (moderate-to-severe sensorineural hearing loss, gradual impairment of mental functions and speech, and often, periods of psychosis. Associated motor function disturbances include muscular weakness, joint abnormalities and ataxia. The facial trait include large head with prominent forehead, rounded eyebrows, flattened nasal bridge, macroglossia, widely spaced teeth, and prognathism. Slight strabismus is common. The clinical variability is significant, representing a continuum in severity. The disorder is caused by lysosomal alpha-mannosidase deficiency. Alpha-mannosidosis is inherited in an autosomal recessive fashion and is caused by mutations in the MAN2B1 gene located on chromosome 19 (19 p13.2-q12. Diagnosis is made by measuring acid alpha-mannosidase activity in leukocytes or other nucleated cells and can be confirmed by genetic testing. Elevated urinary secretion of mannose-rich oligosaccharides is suggestive, but not diagnostic. Differential diagnoses are mainly the other lysosomal storage diseases like the mucopolysaccharidoses. Genetic counseling should be given to explain the nature of the disease and to detect carriers. Antenatal diagnosis is possible, based on both biochemical and genetic methods. The management should be pro-active, preventing complications and treating

  19. Alpha phoenix公司

    Institute of Scientific and Technical Information of China (English)


    德国Alpha phoenix公司成立于2009年.专注于制药领域清洗机器的研发和生产,产品符合cGMP的要求。公司的人员是制药领域清洗机器研发和生产的专家,他们具有20多年的全自动清洗机器的设计和生产经验。

  20. Robust estimation of Cronbach's alpha



    Cronbach’s alpha is a popular method to measure reliability, e.g. in quantifying the reliability of a score to summarize the information of several items in questionnaires. The alpha coefficient is known to be non-robust. We study the behavior of this coefficient in different settings to identify situations, which can easily occur in practice, but under which the Cronbach’s alpha coefficient is extremely sensitive to violations of the classical model assumptions. Furthermore, we construct a r...

  1. Are alpha-gliadins glycosylated? (United States)

    Turner, J B; Garner, G V; Gordon, D B; Brookes, S J; Smith, C A


    Alpha-gliadins isolated by carboxymethylcellulose chromatography contain noncovalently bound glucose probably due to contaminating proteoglycans and to material shed from the column. Traces of carbohydrate remain strongly bound to alpha-gliadins even after harsh denaturation, but our results indicate alpha-gliadins are not glycoproteins. Suggestions that gliadins are glycoproteins are probably due to contamination with this glucose and the presence of these proteoglycans.

  2. The Lyman alpha reference sample

    DEFF Research Database (Denmark)

    Hayes, M.; Östlin, G.; Schaerer, D.


    We report on new imaging observations of the Lyman alpha emission line (Lyα), performed with the Hubble Space Telescope, that comprise the backbone of the Lyman alpha Reference Sample. We present images of 14 starburst galaxies at redshifts 0.028 alpha emission line (Lyα), performed with the Hubble Space Telescope, that comprise the backbone of the Lyman alpha Reference Sample. We present images of 14 starburst galaxies at redshifts 0.028

  3. Molecular characterization of alpha 1- and alpha 2-adrenoceptors. (United States)

    Harrison, J K; Pearson, W R; Lynch, K R


    Three 'alpha 1-adrenoceptors' and three 'alpha 2-adrenoceptors' have now been cloned. How closely do these receptors match the native receptors that have been identified pharmacologically? What are the properties of these receptors, and how do they relate to other members of the cationic amine receptor family? Kevin Lynch and his colleagues discuss these questions in this review.

  4. PDFs, $\\alpha_s$, and quark masses from global fits

    CERN Document Server

    Alekhin, S; Moch, S; Placakyte, R


    The strong coupling constant $\\alpha_s$ and the heavy-quark masses, $m_c$, $m_b$, $m_t$ are extracted simultaneosly with the parton distribution functions (PDFs) in the updated ABM12 fit including recent data from CERN-SPS, HERA, Tevatron, and the LHC. The values of \\begin{eqnarray} \

  5. Alpha-mannosidosis

    DEFF Research Database (Denmark)

    Borgwardt, Line Gutte; Danielsen, E R; Thomsen, Carsten;


    Alpha-mannosidosis (AM) (OMIM 248500) is a rare lysosomal storage disease. The understanding of the central nervous system (CNS) pathology is limited. This study is the first describing the CNS pathology and the correlation between the CNS pathology and intellectual disabilities in human AM. Thirty......-protein, glial fibrillary acidic protein and neurofilament light protein in 97 patients, 74% and 41% of CSF samples, respectively. A negative correlation between CSF-biomarkers and cognitive function and CSF-oligosaccharides and cognitive function was found. The combination of MRS/MRI changes, elevated...... concentrations of CSF-biomarkers and CSF-oligosaccharides suggests gliosis and reduced myelination, as part of the CNS pathology in AM. Our data demonstrate early neuropathological changes, which may be taken into consideration when planning initiation of treatment....

  6. Molecular Mechanism of AHSP-Mediated Stabilization of Alpha-Hemoglobin

    Energy Technology Data Exchange (ETDEWEB)

    Feng,L.; Gell, D.; Zhou, S.; Gu, L.; Kong, Y.; Li, J.; Hu, M.; Yan, N.; Lee, C.; et al.


    Hemoglobin A (HbA), the oxygen delivery system in humans, comprises two alpha and two beta subunits. Free alpha-hemoglobin (alphaHb) is unstable, and its precipitation contributes to the pathophysiology of beta thalassemia. In erythrocytes, the alpha-hemoglobin stabilizing protein (AHSP) binds alphaHb and inhibits its precipitation. The crystal structure of AHSP bound to Fe(II)-alphaHb reveals that AHSP specifically recognizes the G and H helices of alphaHb through a hydrophobic interface that largely recapitulates the alpha1-beta1 interface of hemoglobin. The AHSP-alphaHb interactions are extensive but suboptimal, explaining why beta-hemoglobin can competitively displace AHSP to form HbA. Remarkably, the Fe(II)-heme group in AHSP bound alphaHb is coordinated by the distal but not the proximal histidine. Importantly, binding to AHSP facilitates the conversion of oxy-alphaHb to a deoxygenated, oxidized [Fe(III)], nonreactive form in which all six coordinate positions are occupied. These observations reveal the molecular mechanisms by which AHSP stabilizes free alphaHb.

  7. The ALPHA antihydrogen trapping apparatus (United States)

    Amole, C.; Andresen, G. B.; Ashkezari, M. D.; Baquero-Ruiz, M.; Bertsche, W.; Bowe, P. D.; Butler, E.; Capra, A.; Carpenter, P. T.; Cesar, C. L.; Chapman, S.; Charlton, M.; Deller, A.; Eriksson, S.; Escallier, J.; Fajans, J.; Friesen, T.; Fujiwara, M. C.; Gill, D. R.; Gutierrez, A.; Hangst, J. S.; Hardy, W. N.; Hayano, R. S.; Hayden, M. E.; Humphries, A. J.; Hurt, J. L.; Hydomako, R.; Isaac, C. A.; Jenkins, M. J.; Jonsell, S.; Jørgensen, L. V.; Kerrigan, S. J.; Kurchaninov, L.; Madsen, N.; Marone, A.; McKenna, J. T. K.; Menary, S.; Nolan, P.; Olchanski, K.; Olin, A.; Parker, B.; Povilus, A.; Pusa, P.; Robicheaux, F.; Sarid, E.; Seddon, D.; Seif El Nasr, S.; Silveira, D. M.; So, C.; Storey, J. W.; Thompson, R. I.; Thornhill, J.; Wells, D.; van der Werf, D. P.; Wurtele, J. S.; Yamazaki, Y.


    The ALPHA collaboration, based at CERN, has recently succeeded in confining cold antihydrogen atoms in a magnetic minimum neutral atom trap and has performed the first study of a resonant transition of the anti-atoms. The ALPHA apparatus will be described herein, with emphasis on the structural aspects, diagnostic methods and techniques that have enabled antihydrogen trapping and experimentation to be achieved.

  8. The ALPHA antihydrogen trapping apparatus

    Energy Technology Data Exchange (ETDEWEB)

    Amole, C. [Department of Physics and Astronomy, York University, Toronto ON Canada, M3J 1P3 (Canada); Andresen, G.B. [Department of Physics and Astronomy, Aarhus University, DK-8000 Aarhus C (Denmark); Ashkezari, M.D. [Department of Physics, Simon Fraser University, Burnaby, BC Canada, V5A 1S6 (Canada); Baquero-Ruiz, M. [Department of Physics, University of California at Berkeley, Berkeley, CA 94720-7300 (United States); Bertsche, W. [Department of Physics, College of Science, Swansea University, Swansea SA2 8PP (United Kingdom); School of Physics and Astronomy, University of Manchester, Manchester M13 9PL (United Kingdom); The Cockcroft Institute, Warrington WA4 4AD (United Kingdom); Bowe, P.D. [Department of Physics and Astronomy, Aarhus University, DK-8000 Aarhus C (Denmark); Butler, E. [Physics Department, CERN, CH-1211 Geneva 23 (Switzerland); Capra, A. [Department of Physics and Astronomy, York University, Toronto ON Canada, M3J 1P3 (Canada); Carpenter, P.T. [Department of Physics, Auburn University, Auburn, AL 36849-5311 (United States); Cesar, C.L. [Instituto de Física, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-972 (Brazil); Chapman, S. [Department of Physics, University of California at Berkeley, Berkeley, CA 94720-7300 (United States); Charlton, M.; Deller, A.; Eriksson, S. [Department of Physics, College of Science, Swansea University, Swansea SA2 8PP (United Kingdom); Escallier, J. [Brookhaven National Laboratory, Upton, NY 11973 (United States); Fajans, J. [Department of Physics, University of California at Berkeley, Berkeley, CA 94720-7300 (United States); Friesen, T. [Department of Physics and Astronomy, University of Calgary, Calgary AB, Canada, T2N 1N4 (Canada); Fujiwara, M.C.; Gill, D.R. [TRIUMF, 4004 Wesbrook Mall, Vancouver BC, Canada V6T 2A3 (Canada); Gutierrez, A. [Department of Physics and Astronomy, University of British Columbia, Vancouver BC, Canada V6T 1Z4 (Canada); and others


    The ALPHA collaboration, based at CERN, has recently succeeded in confining cold antihydrogen atoms in a magnetic minimum neutral atom trap and has performed the first study of a resonant transition of the anti-atoms. The ALPHA apparatus will be described herein, with emphasis on the structural aspects, diagnostic methods and techniques that have enabled antihydrogen trapping and experimentation to be achieved.

  9. Alpha particle emitters in medicine

    Energy Technology Data Exchange (ETDEWEB)

    Fisher, D.R.


    Radiation-induced cancer of bone, liver and lung has been a prominent harmful side-effect of medical applications of alpha emitters. In recent years, however, the potential use of antibodies labeled with alpha emitting radionuclides against cancer has seemed promising because alpha particles are highly effective in cell killing. High dose rates at high LET, effectiveness under hypoxic conditions, and minimal expectancy of repair are additional advantages of alpha emitters over antibodies labeled with beta emitting radionuclides for cancer therapy. Cyclotron-produced astatine-211 ({sup 211}At) and natural bismuth-212 ({sup 212}Bi) have been proposed and are under extensive study in the United States and Europe. Radium-223 ({sup 223}Ra) also has favorable properties as a potential alpha emitting label, including a short-lived daughter chain with four alpha emissions. The radiation dosimetry of internal alpha emitters is complex due to nonuniformly distributed sources, short particle tracks, and high relative specific ionization. The variations in dose at the cellular level may be extreme. Alpha-particle radiation dosimetry, therefore, must involve analysis of statistical energy deposition probabilities for cellular level targets. It must also account fully for nonuniform distributions of sources in tissues, source-target geometries, and particle-track physics. 18 refs., 4 figs.


    Recent DFT optimization studies on alpha-maltose improved our understanding of the preferred conformations of alpha-maltose and the present study extends these studies to alpha-maltotriose with three alpha-D-glucopyranose residues linked by two alpha-[1-4] bridges, denoted herein as DP-3's. Combina...

  11. Formation of visual memories controlled by gamma power phase-locked to alpha oscillations (United States)

    Park, Hyojin; Lee, Dong Soo; Kang, Eunjoo; Kang, Hyejin; Hahm, Jarang; Kim, June Sic; Chung, Chun Kee; Jiang, Haiteng; Gross, Joachim; Jensen, Ole


    Neuronal oscillations provide a window for understanding the brain dynamics that organize the flow of information from sensory to memory areas. While it has been suggested that gamma power reflects feedforward processing and alpha oscillations feedback control, it remains unknown how these oscillations dynamically interact. Magnetoencephalography (MEG) data was acquired from healthy subjects who were cued to either remember or not remember presented pictures. Our analysis revealed that in anticipation of a picture to be remembered, alpha power decreased while the cross-frequency coupling between gamma power and alpha phase increased. A measure of directionality between alpha phase and gamma power predicted individual ability to encode memory: stronger control of alpha phase over gamma power was associated with better memory. These findings demonstrate that encoding of visual information is reflected by a state determined by the interaction between alpha and gamma activity.

  12. Proteinaceous alpha-araylase inhibitors

    DEFF Research Database (Denmark)

    Svensson, Birte; Fukuda, Kenji; Nielsen, P.K.


    Proteins that inhibit alpha-amylases have been isolated from plants and microorganisms. These inhibitors can have natural roles in the control of endogenous a-amylase activity or in defence against pathogens and pests; certain inhibitors are reported to be antinutritional factors. The alpha-amylase...... inhibitors belong to seven different protein structural families, most of which also contain evolutionary related proteins without inhibitory activity. Two families include bifunctional inhibitors acting both on alpha-amylases and proteases. High-resolution structures are available of target alpha-amylases...... in complex with inhibitors from five families. These structures indicate major diversity but also some similarity in the structural basis of alpha-amylase inhibition. Mutational analysis of the mechanism of inhibition was performed in a few cases and various protein engineering and biotechnological...

  13. An alpha particle instrument with alpha, proton, and X-ray modes for planetary chemical analyses (United States)

    Economou, T. E.; Turkevich, A. L.


    The interaction of alpha particles with matter is employed in a compact instrument that could provide rather complete in-situ chemical analyses of surfaces and thin atmospheres of extraterrestrial bodies. The instrument is a miniaturized and improved version of the Surveyor lunar instrument. The backscattering of alpha particles and (alpha, p) reactions provide analytical data on the light elements (carbon-iron). An X-ray mode that detects the photons produced by the alpha sources provides sensitivity and resolution for the chemical elements heavier than about silicon. The X-rays are detected by semiconductor detectors having a resolution between 150 and 250 eV at 5.9 keV. Such an instrument can identify and determine with good accuracy 99 percent of the atoms (except hydrogen) in rocks. For many trace elements, the detecting sensitivity is a few ppm. Auxiliary sources could be used to enhance the sensitivities for elements of special interest. The instrument could probably withstand the acceleration involved in semi-hard landings.

  14. Simultaneous quantification of GABAergic 3alpha,5alpha/3alpha,5beta neuroactive steroids in human and rat serum. (United States)

    Porcu, Patrizia; O'Buckley, Todd K; Alward, Sarah E; Marx, Christine E; Shampine, Lawrence J; Girdler, Susan S; Morrow, A Leslie


    The 3alpha,5alpha- and 3alpha,5beta-reduced derivatives of progesterone, deoxycorticosterone, dehydroepiandrosterone and testosterone enhance GABAergic neurotransmission and produce inhibitory neurobehavioral and anti-inflammatory effects. Despite substantial information on the progesterone derivative (3alpha,5alpha)-3-hydroxypregnan-20-one (3alpha,5alpha-THP, allopregnanolone), the physiological significance of the other endogenous GABAergic neuroactive steroids has remained elusive. Here, we describe the validation of a method using gas chromatography-mass spectrometry to simultaneously identify serum levels of the eight 3alpha,5alpha- and 3alpha,5beta-reduced derivatives of progesterone, deoxycorticosterone, dehydroepiandrosterone and testosterone. The method shows specificity, sensitivity and enhanced throughput compared to other methods already available for neuroactive steroid quantification. Administration of pregnenolone to rats and progesterone to women produced selective effects on the 3alpha,5alpha- and 3alpha,5beta-reduced neuroactive steroids, indicating differential regulation of their biosynthetic pathways. Pregnenolone administration increased serum levels of 3alpha,5alpha-THP (+1488%, psteroid was detected only in 3/16 control subjects. Levels of 3alpha,5alpha-A, 3alpha,5beta-A and pregnenolone were not altered. This method can be used to investigate the physiological and pathological role of neuroactive steroids and to develop biomarkers and new therapeutics for neurological and psychiatric disorders.

  15. Genetics Home Reference: alpha-mannosidosis (United States)

    ... Email Facebook Twitter Home Health Conditions alpha-mannosidosis alpha-mannosidosis Enable Javascript to view the expand/collapse boxes. Download PDF Open All Close All Description Alpha-mannosidosis is a rare inherited disorder that causes ...

  16. ALPHA freezes antiprotons

    CERN Multimedia

    CERN Bulletin


    Laboratories like CERN can routinely produce many different types of antiparticles. In 1995, the PS210 experiment formed the first antihydrogen atoms and a few years later, in 2002, ATRAP and ATHENA were already able to produce several thousand of them. However, no experiment in the world has succeeded in ‘trapping’ these anti-atoms in order to study them. This is the goal of the ALPHA experiment, which has recently managed to cool down the antiprotons to just a few Kelvin. This represents a major step towards trapping the anti-atom, thus opening a new avenue into the investigation of antimatter properties.   Members of the ALPHA collaboration working on the apparatus in the Antiproton Decelerator experimental hall at CERN. Just like the atom, the anti-atom is neutral. Unlike the atom, the anti-atom is made up of antiprotons (as opposed to protons in the atom) and positrons (as opposed to electrons). In order to thoroughly study the properties of the anti-atoms, scien...

  17. Venus - Alpha Regio (United States)


    The eastern edge of Alpha Regio is shown in this image centered at 30 degrees south latitude and 11.8 degrees east longitude (longitude on Venus is measured from 0 degrees to 360 degrees east). Seven circular, dome-like hills, averaging 25 kilometers (15 miles) in diameter with maximum heights of 750 meters (2,475 feet) dominate the scene. These features are interpreted as very thick lava flows that came from an opening on the relatively level ground, which allowed the lava to flow in an even pattern outward from the opening. The complex fractures on top of the domes suggest that if the domes were created by lava flows, a cooled outer layer formed and then further lava flowing in the interior stretched the surface. The domes may be similar to volcanic domes on Earth. Another interpretation is that the domes are the result of molten rock or magma in the interior that pushed the surface layer upward. The near-surface magma then withdrew to deeper levels, causing the collapse and fracturing of the dome surface. The bright margins possibly indicate the presence of rock debris on the slopes of the domes. Some of the fractures on the plains cut through the domes, while others appear to be covered by the domes. This indicates that active processes pre date and post date the dome-like hills. The prominent black area in the northeast corner of the image is a data gap. North is at the top of the image.

  18. In vitro and in vivo estrogenic effects of 17alpha-estradiol in medaka (Oryzias latipes). (United States)

    Huang, Chong; Zhang, Zhaobin; Wu, Shimin; Zhao, Yanbin; Hu, Jianying


    17alpha-Estradiol (17alpha-E2), the stereoisomer of 17beta-estradiol (17beta-E2), is considered a weak estrogen in mammals. However, little is known about its estrogenic potency in teleost fish, even though 17alpha-E2 has been frequently detected in aquatic environment. To investigate the estrogenic activity of 17alpha-E2, an in vitro assay based on the ligand-dependent interaction between medaka estrogen receptor alpha (med-ERalpha) and coactivator was conducted. Japanese medaka (Oryziaslatipes) were exposed to 1, 10, 100, 1000 and 10000ng L(-1) 17alpha-E2 (actual concentrations of 1.91, 12.81, 96.24, 1045.15, and 9320.81ng L(-1), respectively) for 3 weeks, and expression for vitellogenins (VTG-I), Choriogenin H (CHG-H) and estrogen receptor alpha (ERalpha) mRNA in the livers was analyzed by quantitative real-time RT-PCR (Q-RT-PCR). The in vitro study showed that the EC(50) of 17alpha-E2 was 114.10nM, which was 30 times less potent than that of 17beta-E2 (3.80nM). Dose-dependent induction of gene expression of VTG-I, CHG-H and ERalpha were observed. The benchmark dose (BMD) values for VTG-I, CHG-H and ERalpha were 44.16ng L(-1), 15.25ng L(-1) and 66.03ng L(-1), which were about 11-, 17- and 14-times less potent than that of 17beta-E2, respectively. Comparing this study with those reported previously in mammals, it is suggested that fish species may be more susceptive to 17alpha-E2 than mammals.

  19. Measurement of $\\alpha_{s}$ with Radiative Hadronic Events

    CERN Document Server

    Abbiendi, G; Åkesson, P F; Alexander, G; Anagnostou, G; Anderson, K J; Asai, S; Axen, D; Bailey, I; Barberio, E; Barillari, T; Barlow, R J; Batley, R J; Bechtle, P; Behnke, T; Bell, K W; Bell, P J; Bella, G; Bellerive, A; Benelli, G; Bethke, S; Biebel, O; Boeriu, O; Bock, P; Boutemeur, M; Braibant, S; Brown, R M; Burckhart, H J; Campana, S; Capiluppi, P; Carnegie, R K; Carter, A A; Carter, J R; Chang, C Y; Charlton, D G; Ciocca, C; Csilling, A; Cuffiani, M; Dado, S; Dallavalle, M; de Roeck, A; De Wolf, E A; Desch, K; Dienes, B; Dubbert, J; Duchovni, E; Duckeck, G; Duerdoth, I P; Etzion, E; Fabbri, F; Ferrari, P; Fiedler, F; Fleck, I; Ford, M; Frey, A; Gagnon, P; Gary, J W; Geich-Gimbel, C; Giacomelli, G; Giacomelli, P; Giunta, M; Goldberg, J; Gross, E; Grunhaus, J; Gruwé, M; Sen-Gupta, A; Hajdu, C; Hamann, M; Hanson, G G; Harel, A; Hauschild, M; Hawkes, C M; Hawkings, R; Herten, G; Heuer, R D; Hill, J C; Horváth, D; Igo-Kemenes, P; Ishii, K; Jeremie, H; Jovanovic, P; Junk, T R; Kanzaki, J; Karlen, D; Kawagoe, K; Kawamoto, T; Keeler, R K; Kellogg, R G; Kennedy, B W; Kluth, S; Kobayashi, T; Kobel, M; Komamiya, S; Kramer, T; Krasznahorkays, A Jr; Krieger, P; Von Krogh, J; Kühl, T; Kupper, M; Lafferty, G D; Landsman, H; Lanske, D; Lellouch, D; Letts, J; Levinson, L; Lillich, J; Lloyd, S L; Loebinger, F K; Lü, J; Ludwig, A; Ludwig, J; Mader, W; Marcellini, S; Martin, A J; Mashimo, T; Mättig, P; McKenna, J; McPherson, R A; Meijers, F; Menges, W; Merritt, F S; Mes, H; Meyer, N; Michelini, A; Mihara, S; Mikenberg, G; Miller, D J; Mohr, W; Mori, T; Mutter, A; Nagai, K; Nakamura, I; Nanjo, H; Neal, H A; O'Neale, S W; Oh, A; Oreglia, M J; Orito, S; Pahl, C; Pásztor, G; Pater, J R; Pilcher, J E; Pinfold, J L; Plane, D E; Pooth, O; Przybycien, M; Quadt, A; Rabbertz, K; Rembser, C; Renkel, P; Roney, J M; Rossi, A M; Rozen, Y; Runge, K; Sachs, K; Saeki, T; Sarkisyan-Grinbaum, E; Schaile, A D; Schaile, O; Scharff-Hansen, P; Schiecks, J; Schörner-Sadenius, T; Schröder, M; Schumacher, M; Seuster, R; Shears, T G; Shen, B C; Sherwood, P; Skuja, A; Smith, A M; Sobie, R J; Söldner-Rembold, S; Spanó, F; Stahl, A; Strom, D; Ströhmer, R; Tarem, S; Tasevsky, M; Teuscher, R; Thomson, M A; Torrence, E; Toya, D; Trigger, I; Trócsányi, Z L; Tsur, E; Turner-Watson, M F; Ueda, I; Ujvári, B; Vollmer, C F; Vannerem, P; Vertesi, R; Verzocchi, M; Voss, H; Vossebeld, J; Ward, C P; Ward, D R; Watkins, P M; Watson, A T; Watson, N K; Wells, P S; Wengler, T; Wermes, N; Wilson, G W; Wilson, J A; Wolf, G; Wyatt, T R; Yamashita, S; Zer-Zion, D; Zivkovic, L


    Hadronic final states with a hard isolated photon are studied using data taken at centre-of-mass energies around the mass of the Z0 boson with the OPAL detector at LEP. The strong coupling alpha S is extracted by comparing data and QCD predictions for event shape observables at average reduced centre-of-mass energies ranging from 24 GeV to 78 GeV, and the energy dependence of alpha S is studied. Our results are consistent with the running of alpha S as predicted by QCD and show that within the uncertainties of our analysis event shapes in hadronic Z0 decays with hard and isolated photon radiation can be described by QCD at reduced centre-of-mass energies. Combining all values from different event shape observables and energies gives alpha S (Mz)=0.1182 pm 0.0015(stat.) pm 0.0101(syst.).

  20. Two alpha, three alpha and multiple heavy-ion radioactivities

    Energy Technology Data Exchange (ETDEWEB)

    Poenaru, D.N.; Ivascu, M. (Institute for Physics and Nuclear Engineering, Bucharest (Romania))


    New decay modes by spontaneous emission of two and three ..cap alpha.. particles and two identical or different heavy ions, are predicted. The analytical variant of the superasymmetric fission model is used to estimate the half lives.

  1. Radiative Corrections to the Muonium Hyperfine Structure; 2, The $\\alpha (Z\\alpha)^2$ Correction

    CERN Document Server

    Nio, M


    This is the second of a series of papers on the radiative corrections of order $\\alpha^2 (Z\\alpha)$, $\\alpha (Z\\alpha )^2$, and various logarithmic terms of order $\\alpha^4$, to the hyperfine structure of the muonium ground state. This paper deals with the $\\alpha (Z\\alpha)^2$ correction. Based on the NRQED bound state theory, we isolated the term of order $\\alpha(Z\\alpha)^2$ exactly. Our result $+16.904~2~(11) \\alpha(Z\\alpha)^2 E_F / \\pi$ for the non-logarithmic part is consistent with the $\\alpha (Z\\alpha)^2$ part of Sapirstein's calculation and the recent result of Pachucki, and reduces the numerical uncertainty in the $\\alpha (Z\\alpha)^2$ term by two orders of magnitude.

  2. Alpha heating in toroidal devices

    Energy Technology Data Exchange (ETDEWEB)

    Miley, G.H.


    Ignition (or near-ignition) by alpha heating is a key objective for the achievement of economic fusion reactors. While good confinement of high-energy alphas appears possible in larger reactors, near-term tokamak-type ignition experiments as well as some concepts for small reactors (e.g., the Field-Reversed Mirror or FRM) potentially face marginal situations. Consequently, there is a strong motivation to develop methods to evaluate alpha losses and heating profiles in some detail. Such studies for a TFTR-size tokamak and for a small FRM are described here.

  3. Binding of [alpha, alpha]-Disubstituted Amino Acids to Arginase Suggests New Avenues for Inhibitor Design

    Energy Technology Data Exchange (ETDEWEB)

    Ilies, Monica; Di Costanzo, Luigi; Dowling, Daniel P.; Thorn, Katherine J.; Christianson, David W. (MIT); (Episcopal U); (Rutgers); (Drexel); (Penn)


    Arginase is a binuclear manganese metalloenzyme that hydrolyzes L-arginine to form L-ornithine and urea, and aberrant arginase activity is implicated in various diseases such as erectile dysfunction, asthma, atherosclerosis, and cerebral malaria. Accordingly, arginase inhibitors may be therapeutically useful. Continuing our efforts to expand the chemical space of arginase inhibitor design and inspired by the binding of 2-(difluoromethyl)-L-ornithine to human arginase I, we now report the first study of the binding of {alpha},{alpha}-disubstituted amino acids to arginase. Specifically, we report the design, synthesis, and assay of racemic 2-amino-6-borono-2-methylhexanoic acid and racemic 2-amino-6-borono-2-(difluoromethyl)hexanoic acid. X-ray crystal structures of human arginase I and Plasmodium falciparum arginase complexed with these inhibitors reveal the exclusive binding of the L-stereoisomer; the additional {alpha}-substituent of each inhibitor is readily accommodated and makes new intermolecular interactions in the outer active site of each enzyme. Therefore, this work highlights a new region of the protein surface that can be targeted for additional affinity interactions, as well as the first comparative structural insights on inhibitor discrimination between a human and a parasitic arginase.

  4. Binding of carbohydrates and protein inhibitors to the surface of alpha-amylases

    DEFF Research Database (Denmark)

    Bozonnet, Sophie; Bønsager, Birgit Christine; Kramhoft, B.


    This review on barley alpha-amylases 1 (AMY1) and 2 (AMY2) addresses rational mutations at distal subsites to the catalytic site, polysaccharide hydrolysis, and interactions with proteinaceous inhibitors. Subsite mapping of barley alpha-amylases revealed 6 glycone and 4 aglycone substrate subsite...

  5. Hemoglobin alpha 2 gene +861 G>A polymorphism in Turkish ...

    African Journals Online (AJOL)

    Dilay Ciglidag Dungul

    Abstract Thalassemia is an inherited blood disorder which is divided into two groups: alpha and beta. HBA1 and HBA2 are the two genes associated with alpha thalassemia. The aim of this ... that affects a patient's ability to produce hemoglobin, resulting ..... interaction of a deletional o-thalassemia-1 and a newly discovered.

  6. DNA Repair, Redox Regulation and Modulation of Estrogen Receptor Alpha Mediated Transcription (United States)

    Curtis-Ducey, Carol Dianne


    Interaction of estrogen receptor [alpha] (ER[alpha]) with 17[beta]-estradiol (E[subscript 2]) facilitates binding of the receptor to estrogen response elements (EREs) in target genes, which in turn leads to recruitment of coregulatory proteins. To better understand how estrogen-responsive genes are regulated, our laboratory identified a number of…

  7. Binding of carbohydrates and protein inhibitors to the surface of alpha-amylases

    DEFF Research Database (Denmark)

    Bozonnet, Sophie; Bønsager, Birgit Christine; Kramhoft, B.


    This review on barley alpha-amylases 1 (AMY1) and 2 (AMY2) addresses rational mutations at distal subsites to the catalytic site, polysaccharide hydrolysis, and interactions with proteinaceous inhibitors. Subsite mapping of barley alpha-amylases revealed 6 glycone and 4 aglycone substrate subsite...

  8. IPHAS : Surveying the North Galactic Plane in H-alpha

    NARCIS (Netherlands)

    Drew, J.E.; Groot, P.J.; Morales-Rueda, L.; Roelofs, G.H.A.


    H-alpha emission is ubiquitous in our Galaxy. It traces ionised gas of assorted nebulae such as HII regions, planetary nebulae, Wolf-Rayet nebulae, and supernova remnants. It is a strong signature of active stars, interacting binaries, very massive stars (especially supergiants, Luminous Blue Variab

  9. Erythromycin increases plasma concentrations of alpha-dihydroergocryptine in humans

    NARCIS (Netherlands)

    de Mey, C; Althaus, M; Ezan, E; Retzow, A


    Objective. Our objective was to investigate the potential for relevant pharmacotherapeutic interaction between cytochrome P4503A4 (CYP3A4)-inhibiting agents such as erythromycin and the dopamine agonist alpha -dihydroergocryptine (DHEC). Methods. The study was carried out as a single-center, control

  10. Characterization of salivary alpha-amylase binding to Streptococcus sanguis

    Energy Technology Data Exchange (ETDEWEB)

    Scannapieco, F.A.; Bergey, E.J.; Reddy, M.S.; Levine, M.J. (State Univ. of New York, Buffalo (USA))


    The purpose of this study was to identify the major salivary components which interact with oral bacteria and to determine the mechanism(s) responsible for their binding to the bacterial surface. Strains of Streptococcus sanguis, Streptococcus mitis, Streptococcus mutans, and Actinomyces viscosus were incubated for 2 h in freshly collected human submandibular-sublingual saliva (HSMSL) or parotid saliva (HPS), and bound salivary components were eluted with 2% sodium dodecyl sulfate. By sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western transfer, alpha-amylase was the prominent salivary component eluted from S. sanguis. Studies with {sup 125}I-labeled HSMSL or {sup 125}I-labeled HPS also demonstrated a component with an electrophoretic mobility identical to that of alpha-amylase which bound to S. sanguis. Purified alpha-amylase from human parotid saliva was radiolabeled and found to bind to strains of S. sanguis genotypes 1 and 3 and S. mitis genotype 2, but not to strains of other species of oral bacteria. Binding of ({sup 125}I)alpha-amylase to streptococci was saturable, calcium independent, and inhibitable by excess unlabeled alpha-amylases from a variety of sources, but not by secretory immunoglobulin A and the proline-rich glycoprotein from HPS. Reduced and alkylated alpha-amylase lost enzymatic and bacterial binding activities. Binding was inhibited by incubation with maltotriose, maltooligosaccharides, limit dextrins, and starch.

  11. The Lyman-$\\alpha$ signature of the first galaxies

    CERN Document Server

    Smith, Aaron; Bromm, Volker; Milosavljević, Miloš


    We present the Cosmic Lyman-$\\alpha$ Transfer code (COLT), a new massively parallel Monte-Carlo radiative transfer code, to simulate Lyman-$\\alpha$ (Ly$\\alpha$) resonant scattering through neutral hydrogen as a probe of the first galaxies. We explore the interaction of centrally produced Ly$\\alpha$ radiation with the host galactic environment. The Ly$\\alpha$ photons emitted from the luminous starburst region escape with characteristic features in the line profile depending on the density distribution, ionization structure, and bulk velocity fields. For example, the presence of anisotropic ionization exhibits a tall peak close to line centre with a skewed tail that drops off gradually. Furthermore, moderate (~10 km/s) outflow produces an amplified peak redward of line centre. Idealized models of first galaxies explore the effect of mass, anisotropic H II regions, and radiation pressure driven winds on Ly$\\alpha$ observables. We employ mesh refinement to resolve critical structures. We also post-process an ab i...

  12. Stability against $\\alpha$ decay of some recently observed superheavy elements

    CERN Document Server

    Chowdhury, Partha Roy; Bhattacharyya, Abhijit


    The probability of $\\alpha$ particle emission for some recently observed superheavy nuclei (SHN) are investigated. The $\\alpha$-decay half lives of SHN are calculated in a quantum tunneling model with density dependent M3Y (DDM3Y) effective nuclear interaction using theoretical and measured $Q_\\alpha$ values. We determine the density distribution of $\\alpha$ and daughter nuclei from the relativistic mean field theory (RMF) using FSUGold force, NL3 and TM1 parameter sets. The double folded nuclear potential is numerically calculated in a more microscopic manner using these density distributions. The estimated values of $\\alpha$-decay half-lives are in good agreement with the recent data. We compare our results with recently detected $\\alpha$-decay chains from new element with atomic number Z=117 reported by JINR, Dubna. Finally, we determine the half-lives of superheavy elements with Z=108-120 and neutron number N=152-190 to explore the long-standing predictions on the existence of an "island of stability" due...

  13. Alpha Theta Meditation: Phenomenological, neurophysiologic ...

    African Journals Online (AJOL)

    African Journal for Physical Activity and Health Sciences ... neurophysiologic, mindfulness, mood, health and sport implications ... Integrated findings are in line with other studies which support the psychological value of alpha theta training.

  14. Alpha Decay in the Complex Energy Shell Model

    CERN Document Server

    Betan, R Id


    Alpha emission from a nucleus is a fundamental decay process in which the alpha particle formed inside the nucleus tunnels out through the potential barrier. We describe alpha decay of $^{212}$Po and $^{104}$Te by means of the configuration interaction approach. To compute the preformation factor and penetrability, we use the complex-energy shell model with a separable T=1 interaction. The single-particle space is expanded in a Woods-Saxon basis that consists of bound and unbound resonant states. Special attention is paid to the treatment of the norm kernel appearing in the definition of the formation amplitude that guarantees the normalization of the channel function. Without explicitly considering the alpha-cluster component in the wave function of the parent nucleus, we reproduce the experimental alpha-decay width of $^{212}$Po and predict an upper limit of T_{1/2}=5.5x10^{-7} sec for the half-life of $^{104}$Te. The complex-energy shell model in a large valence configuration space is capable of providing ...

  15. Almost Redundant Components in the 3 alpha Faddeev Equation for the Buck, Friedlich and Wheatly alpha alpha Potential

    CERN Document Server

    Fujiwara, Y; Kohno, M


    The 3 alpha orthogonality condition model using the Pauli-forbidden bound states of the Buck, Friedlich and Wheatly alpha alpha potential can yield a compact 3 alpha ground state with a large binding energy, in which a small admixture of the redundant components can never be eliminated.

  16. Transgenic up-regulation of alpha-CaMKII in forebrain leads to increased anxiety-like behaviors and aggression

    Directory of Open Access Journals (Sweden)

    Hasegawa Shunsuke


    Full Text Available Abstract Background Previous studies have demonstrated essential roles for alpha-calcium/calmodulin-dependent protein kinase II (alpha-CaMKII in learning, memory and long-term potentiation (LTP. However, previous studies have also shown that alpha-CaMKII (+/- heterozygous knockout mice display a dramatic decrease in anxiety-like and fearful behaviors, and an increase in defensive aggression. These findings indicated that alpha-CaMKII is important not only for learning and memory but also for emotional behaviors. In this study, to understand the roles of alpha-CaMKII in emotional behavior, we generated transgenic mice overexpressing alpha-CaMKII in the forebrain and analyzed their behavioral phenotypes. Results We generated transgenic mice overexpressing alpha-CaMKII in the forebrain under the control of the alpha-CaMKII promoter. In contrast to alpha-CaMKII (+/- heterozygous knockout mice, alpha-CaMKII overexpressing mice display an increase in anxiety-like behaviors in open field, elevated zero maze, light-dark transition and social interaction tests, and a decrease in locomotor activity in their home cages and novel environments; these phenotypes were the opposite to those observed in alpha-CaMKII (+/- heterozygous knockout mice. In addition, similarly with alpha-CaMKII (+/- heterozygous knockout mice, alpha-CaMKII overexpressing mice display an increase in aggression. However, in contrast to the increase in defensive aggression observed in alpha-CaMKII (+/- heterozygous knockout mice, alpha-CaMKII overexpressing mice display an increase in offensive aggression. Conclusion Up-regulation of alpha-CaMKII expression in the forebrain leads to an increase in anxiety-like behaviors and offensive aggression. From the comparisons with previous findings, we suggest that the expression levels of alpha-CaMKII are associated with the state of emotion; the expression level of alpha-CaMKII positively correlates with the anxiety state and strongly affects

  17. p25alpha relocalizes in oligodendroglia from myelin to cytoplasmic inclusions in multiple system atrophy

    DEFF Research Database (Denmark)

    Song, Yun Ju C; Lundvig, Ditte M S; Huang, Yue


    was revealed by immunoblotting along with the presence of immunoreactivity for MBP degradation products in oligodendroglia. The oligodendroglial cell bodies in MSA displayed an enlargement along with the relocalization of p25alpha, and this was enhanced after the deposition of alpha-synuclein in the glial...... cytoplasmic inclusions. Overall, the data indicate that changes in the cellular interactions between MBP and p25alpha occur early in MSA and contribute to abnormalities in myelin and subsequent alpha-synuclein aggregation and the ensuing neuronal degeneration that characterizes this disease....

  18. Automated docking of {alpha}-(1,4)- and {alpha}-(1,6)-linked glucosyl trisaccharides in the glucoamylase active site

    Energy Technology Data Exchange (ETDEWEB)

    Countinho, P.M.; Reilly, P.J. [Iowa State Univ., Ames, IA (United States). Dept. of Chemical Engineering; Dowd, M.K. [Dept. of Agriculture, New Orleans, LA (United States). Southern Regional Research Center


    Low-energy conformers of five {alpha}-(1,4)- and {alpha}-(1,6)-linked glucosyl trisaccharides were flexibly docked into the glucoamylase active site using AutoDock 2.2. To ensure that all significant conformational space was searched, the starting trisaccharide conformers for docking were all possible combinations of the corresponding disaccharide low-energy conformers. All docked trisaccharides occupied subsites {minus}1 and +1 in very similar modes to those of corresponding nonreducing-end disaccharides. For linear substrates, full binding at subsite +2 occurred only when the substrate reducing end was {alpha}-(1,4)-linked, with hydrogen-bonding with the hydroxy-methyl group being the only polar interaction there. Given the absence of other important interactions at this subsite, multiple substrate conformations are allowed. For the one docked branched substrate, steric hindrance in the {alpha}-(1,6)-glycosidic oxygen suggests that the active-site residues have to change position for hydrolysis to occur. Subsite +1 of the glucoamylase active site allows flexibility in binding but, at least in Aspergillus glucoamylases, subsite +2 selectively binds substrates {alpha}-(1,4)-linked between subsites +1 and +2. Enzyme engineering to limit substrate flexibility at subsite +2 could improve glucoamylase industrial properties.

  19. Cytoplasmic polyadenylation-element-binding protein (CPEB)1 and 2 bind to the HIF-1alpha mRNA 3'-UTR and modulate HIF-1alpha protein expression. (United States)

    Hägele, Sonja; Kühn, Uwe; Böning, Melanie; Katschinski, Dörthe M


    The heterodimeric HIF (hypoxia-inducible factor)-1 is a transcriptional master regulator of several genes involved in mammalian oxygen homoeostasis. Besides the well described regulation of the HIF-1alpha subunit via hydroxylation-mediated protein stability in hypoxia, there are several indications of an additional translational control of the HIF-1alpha mRNA, especially after growth factor stimulation. We identified an interaction of CPEB (cytoplasmic polyadenylation-element-binding protein) 1 and CPEB2 with the 3'-UTR (untranslated region) of HIF-1alpha mRNA. Overexpression of CPEB1 and CPEB2 affected HIF-1alpha protein levels mediated by the 3'-UTR of HIF-1alpha mRNA. Stimulation of neuroblastoma SK-N-MC cells with insulin and thus activation of endogenous CPEBs increased the expression of a luciferase reporter gene fused to the 3'-UTR of HIF-1alpha as well as endogenous HIF-1alpha protein levels. This could be abrogated by treating the cells with CPEB1 or CPEB2 siRNAs (short interfering RNAs). Injection of HIF-1alpha cRNA into Xenopus oocytes verified the elongation of the poly(A)+ (polyadenylated) tail by cytoplasmic polyadenylation. Thus CPEB1 and CPEB2 are involved in the regulation of HIF-1alpha following insulin stimulation.

  20. Modeling the interactions of a peptide-major histocompatibility class I ligand with its receptors. II. Cross-reaction between a monoclonal antibody and two alpha beta T cell receptors

    DEFF Research Database (Denmark)

    Rognan, D; Engberg, J; Stryhn, A;


    but is more deeply anchored to the peptide-MHC (pep/MHC) ligand than TCRs, notably through numerous interactions of its heavy chain. The present model accounts well for the experimentally determined binding affinity of a set of 144 single amino acid substituted Ha analogues and the observed shared specificity......-restricted T cell hybridomas has supported this contention. A three-dimensional model of pSAN13.4.1 has been derived by homology modeling techniques. Subsequently, the structure of the pSAN13.4.1 antibody in complex with the antigenic Ha-Kk ligand was derived after a flexible and automated docking of the MHC...

  1. Shared receptor components but distinct complexes for alpha and beta interferons. (United States)

    Lewerenz, M; Mogensen, K E; Uzé, G


    The type I interferon family includes 13 alpha, one omega and one beta subtypes recognized by a complex containing the receptor subunits ifnar1 and ifnar2 and their associated Janus tyrosine kinases, Tyk2 and Jak1. To investigate the reported differences in the way that alpha and beta interferons signal through the receptor, we introduced alanine-substitutions in the ifnar2 extracellular domain, and expressed the mutants in U5A cells, lacking endogenous ifnar2. A selection, designed to recover mutants that responded preferentially to alpha or beta interferon yielded three groups: I, neutral; II, sensitive to alpha interferon, partially resistant to beta interferon; III, resistant to alpha interferon, partially sensitive to beta interferon. A mutant clone, TMK, fully resistant to alpha interferon with good sensitivity to beta interferon, was characterized in detail and compared with U5A cells complemented with wild-type ifnar2 and also with Tyk2-deficient 11.1 cells, which exhibit a similar alpha-unresponsive phenotype with a partial beta interferon response. Using anti-receptor antibodies and mutant forms of beta interferon, three distinct modes of ligand interaction could be discerned: (i) alpha interferon with ifnar1 and ifnar2; (ii) beta interferon with ifnar1 and ifnar2; (iii) beta interferon with ifnar2 alone. We conclude that alpha and beta interferons signal differently through their receptors because the two ligand subtypes interact with the receptor subunits ifnar 1 and ifnar2 in entirely different ways.

  2. Functional Cortical Network in Alpha Band Correlates with Social Bargaining (United States)

    Billeke, Pablo; Zamorano, Francisco; Chavez, Mario; Cosmelli, Diego; Aboitiz, Francisco


    Solving demanding tasks requires fast and flexible coordination among different brain areas. Everyday examples of this are the social dilemmas in which goals tend to clash, requiring one to weigh alternative courses of action in limited time. In spite of this fact, there are few studies that directly address the dynamics of flexible brain network integration during social interaction. To study the preceding, we carried out EEG recordings while subjects played a repeated version of the Ultimatum Game in both human (social) and computer (non-social) conditions. We found phase synchrony (inter-site-phase-clustering) modulation in alpha band that was specific to the human condition and independent of power modulation. The strength and patterns of the inter-site-phase-clustering of the cortical networks were also modulated, and these modulations were mainly in frontal and parietal regions. Moreover, changes in the individuals’ alpha network structure correlated with the risk of the offers made only in social conditions. This correlation was independent of changes in power and inter-site-phase-clustering strength. Our results indicate that, when subjects believe they are participating in a social interaction, a specific modulation of functional cortical networks in alpha band takes place, suggesting that phase synchrony of alpha oscillations could serve as a mechanism by which different brain areas flexibly interact in order to adapt ongoing behavior in socially demanding contexts. PMID:25286240

  3. Barley alpha-amylase/subtilisin inhibitor: structure, biophysics and protein engineering

    DEFF Research Database (Denmark)

    Nielsen, P.K.; Bønsager, Birgit Christine; Fukuda, Kenji;


    Bifunctional alpha-amylase/subtilisin inhibitors have been implicated in plant defence and regulation of endogenous alpha-amylase action. The barley alpha-amylase/subtilisin inhibitor (BASI) inhibits the barley alpha-amylase 2 (AMY2) and subtilisin-type serine proteases. BASI belongs to the Kunitz...... Ca2+-modulated kinetics of the AMY2/BASl interaction and found that the complex formation involves minimal structural changes. The modulation of the interaction by calcium ions makes it unique among the currently known binding mechanisms of proteinaceous alpha-amylase inhibitors.......-type trypsin inhibitor family of the beta-trefoil fold proteins. Diverse approaches including site-directed mutagenesis, hybrid constructions, and crystallography have been used to characterise the structures and contact residues in the AMY2/BASI complex. The three-dimensional structure of the AMY2/BASI...

  4. An X11alpha/FSBP complex represses transcription of the GSK3beta gene promoter.

    LENUS (Irish Health Repository)

    Lau, Kwok-Fai


    X11alpha is a neuronal adaptor protein that interacts with the amyloid precursor protein (APP) through a centrally located phosphotyrosine binding domain to inhibit the production of Abeta peptide that is deposited in Alzheimer\\'s disease brains. X11alpha also contains two C-terminal postsynaptic density-95, large discs, zona occludens 1 (PDZ) domains, and we show here that through its PDZ domains, X11alpha interacts with a novel transcription factor, fibrinogen silencer binding protein. Moreover, we show that an X11alpha\\/fibrinogen silencer binding protein complex signals to the nucleus to repress glycogen synthase kinase-3beta promoter activity. Glycogen synthase kinase-3beta is a favoured candidate kinase for phosphorylating tau in Alzheimer\\'s disease. Our findings show a new function for X11alpha that may impact on Alzheimer\\'s disease pathogenesis.

  5. Microscopic calculations of elastic scattering between light nuclei based on a realistic nuclear interaction

    Energy Technology Data Exchange (ETDEWEB)

    Dohet-Eraly, Jeremy [F.R.S.-FNRS (Belgium); Sparenberg, Jean-Marc; Baye, Daniel, E-mail:, E-mail:, E-mail: [Physique Nucleaire et Physique Quantique, CP229, Universite Libre de Bruxelles (ULB), B-1050 Brussels (Belgium)


    The elastic phase shifts for the {alpha} + {alpha} and {alpha} + {sup 3}He collisions are calculated in a cluster approach by the Generator Coordinate Method coupled with the Microscopic R-matrix Method. Two interactions are derived from the realistic Argonne potentials AV8' and AV18 with the Unitary Correlation Operator Method. With a specific adjustment of correlations on the {alpha} + {alpha} collision, the phase shifts for the {alpha} + {alpha} and {alpha} + {sup 3}He collisions agree rather well with experimental data.

  6. Investigation of the Pygmy Dipole Resonance in (alpha, alpha 'gamma) coincidence experiments

    NARCIS (Netherlands)

    Savran, D.; Babilon, M.; van den Berg, A. M.; Harakeh, M. N.; Hasper, J.; Wortche, H. J.; Zilges, A.


    We report on first results from experiments using the (alpha, alpha'gamma) reaction at E alpha = 136 MeV to investigate bound electric dipole (El) excitations building the so-called Pygmy Dipole Resonance (PDR) in the semi-magic nucleus Ce-140. The method of (alpha, alpha'gamma) allows the separatio

  7. Contribution of mucosal maltase-glucoamylase activities to mouse small intestinal starch alpha-glucogenesis. (United States)

    Quezada-Calvillo, Roberto; Robayo-Torres, Claudia C; Opekun, Antone R; Sen, Partha; Ao, Zihua; Hamaker, Bruce R; Quaroni, Andrea; Brayer, Gary D; Wattler, Sigrid; Nehls, Michael C; Sterchi, Erwin E; Nichols, Buford L


    Digestion of starch requires activities provided by 6 interactive small intestinal enzymes. Two of these are luminal endo-glucosidases named alpha-amylases. Four are exo-glucosidases bound to the luminal surface of enterocytes. These mucosal activities were identified as 4 different maltases. Two maltase activities were associated with sucrase-isomaltase. Two remaining maltases, lacking other identifying activities, were named maltase-glucoamylase. These 4 activities are better described as alpha-glucosidases because they digest all linear starch oligosaccharides to glucose. Because confusion persists about the relative roles of these 6 enzymes, we ablated maltase-glucoamylase gene expression by homologous recombination in Sv/129 mice. We assayed the alpha-glucogenic activities of the jejunal mucosa with and without added recombinant pancreatic alpha-amylase, using a range of food starch substrates. Compared with wild-type mucosa, null mucosa or alpha-amylase alone had little alpha-glucogenic activity. alpha-Amylase amplified wild-type and null mucosal alpha-glucogenesis. alpha-Amylase amplification was most potent against amylose and model resistant starches but was inactive against its final product limit-dextrin and its constituent glucosides. Both sucrase-isomaltase and maltase-glucoamylase were active with limit-dextrin substrate. These mucosal assays were corroborated by a 13C-limit-dextrin breath test. In conclusion, the global effect of maltase-glucoamylase ablation was a slowing of rates of mucosal alpha-glucogenesis. Maltase-glucoamylase determined rates of digestion of starch in normal mice and alpha-amylase served as an amplifier for mucosal starch digestion. Acarbose inhibition was most potent against maltase-glucoamylase activities of the wild-type mouse. The consortium of 6 interactive enzymes appears to be a mechanism for adaptation of alpha-glucogenesis to a wide range of food starches.

  8. Workshop on Precision Measurements of $\\alpha_s$

    Energy Technology Data Exchange (ETDEWEB)

    Bethke, Siegfried; /Munich, Max Planck Inst.; Hoang, Andre H.; /Vienna U.; Kluth, Stefan; /Munich, Max Planck Inst.; Schieck, Jochen; /Munich U.; Stewart, Iain W.; Aoki, S.; Beneke, M.; Bethke, S.; Blumlein, J.; Brambilla, N.; Brodsky, S.; /MIT, LNS


    These are the proceedings of the Workshop on Precision Measurements of {alpha}{sub s} held at the Max-Planck-Institute for Physics, Munich, February 9-11, 2011. The workshop explored in depth the determination of {alpha}{sub s}(m{sub Z}) in the {ovr MS} scheme from the key categories where high precision measurements are currently being made, including DIS and global PDF fits, {tau}-decays, electro-weak precision observables and Z-decays, event-shapes, and lattice QCD. These proceedings contain a short summary contribution from the speakers, as well as the lists of authors, conveners, participants, and talks.

  9. Scale Setting for $\\alpha_{s}$ Beyond Leading Order

    CERN Document Server

    Hornbostel, K; Morningstar, C J


    We present a general procedure for applying the scale-setting prescription of Brodsky, Lepage and Mackenzie to higher orders in the strong coupling constant $\\alphas$. In particular, we show how to apply this prescription when the leading coefficient or coefficients in a series in $\\alphas$ are anomalously small. We give a general method for computing an optimum scale numerically, within dimensional regularization, and in cases when the coefficients of a series are known. We find significant corrections to the scales for $R_{e^+ e^-}$, $\\Gamma(B \\to X_u e \\bar{\

  10. Proxima's orbit around Alpha Centauri

    CERN Document Server

    Kervella, P


    Proxima and Alpha Centauri AB have almost identical distances and proper motions with respect to the Sun. Although the probability of such similar parameters is in principle very low, the question whether they actually form a single gravitationally bound triple system has been open since the discovery of Proxima one century ago. Owing to recent high precision radial velocity measurements and the revision of the parameters of the Alpha Cen pair, we show that Proxima and Alpha Cen are gravitationally bound with a high degree of confidence. The orbital period of Proxima is approximately 600 000 years, with a moderate excentricity of 0.42 +0.07 -0.08. Proxima comes within 5.3 -0.9 +1.2 kAU of Alpha Cen at periastron, and the apastron occurs at 12.9 +0.3 -0.1 kAU. This orbital motion may have influenced the formation or evolution of the recently discovered planet orbiting Proxima as well as circumbinary planet formation around Alpha Cen.

  11. Sensitive bioassay for detection of PPAR{alpha} potentially hazardous ligands with gold nanoparticle probe

    Energy Technology Data Exchange (ETDEWEB)

    Xia, Wei; Wan, Yan-Jian [Minister of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, Hubei Province 430030 (China); Wang, Xianliang [Division of Environmental Pollution and Human Health, Chinese Research Academy of Environmental Sciences, Beijing 100012 (China); Li, Yuan-yuan; Yang, Wen-Jie; Wang, Chun-Xiang [Minister of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, Hubei Province 430030 (China); Xu, Shun-qing, E-mail: [Minister of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, Hubei Province 430030 (China)


    Highlights: {yields} We develop a sensitive and high throughput method to screen PPAR{alpha} ligands. {yields} This method is based on the ligand-receptor interaction on microplate. {yields} The sensitivity is increased through sliver enhancement on captured gold nanoparticle probes. {yields} There is a significant correlation between the bioassay and LC-MS for water spiked samples. - Abstract: There are so many kinds of peroxisome proliferator-activated receptor {alpha} (PPAR{alpha}) ligands with hazardous effect for human health in the environment, such as certain herbicides, plasticizers and drugs. Among these agonists, perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), and mono-(2-ethylhexyl) phthalate (MEHP) are mostly investigated due to their persistence and accumulation in environment and their potential toxicity via PPAR{alpha}. This investigation aims at developing a bioassay method to detect PPAR{alpha} ligands based on the ligand-receptor interaction on microplate. PPAR{alpha}, which formed heterodimers with retinoid X receptor-{alpha} (RXR{alpha}), were activated by PPAR{alpha} ligands to form ligands-PPAR{alpha}-RXR{alpha} complexes. Then the complexes were transferred into a microplate and captured via monoclonal anti-PPAR{alpha} antibody. The PPAR{alpha} responsive elements (PPRE) modified-gold nanoparticle probes were captured by the ligand-PPAR{alpha}-RXR{alpha} complexes immobilized on the microplate, and then could be quantified through measuring the optical density after silver enhancement. The results showed that PFOS was quantified with a linear range from 100 pM to 1 {mu}M and the detection limit was 10 pM. In addition to PFOS, PFOA and MEHP were also quantified within a proper range through the proposed bioassay. This bioassay was compared with that of liquid chromatography tandem-mass spectrometry (LC-MS) for water spiked samples with a significant correlation (r = 0.9893). This study provides a high-throughput detection

  12. Space Station alpha joint bearing (United States)

    Everman, Michael R.; Jones, P. Alan; Spencer, Porter A.


    Perhaps the most critical structural system aboard the Space Station is the Solar Alpha Rotary Joint which helps align the power generation system with the sun. The joint must provide structural support and controlled rotation to the outboard transverse booms as well as power and data transfer across the joint. The Solar Alpha Rotary Joint is composed of two transition sections and an integral, large diameter bearing. Alpha joint bearing design presents a particularly interesting problem because of its large size and need for high reliability, stiffness, and on orbit maintability. The discrete roller bearing developed is a novel refinement to cam follower technology. It offers thermal compensation and ease of on-orbit maintenance that are not found in conventional rolling element bearings. How the bearing design evolved is summarized. Driving requirements are reviewed, alternative concepts assessed, and the selected design is described.

  13. Bioisosteric phentolamine analogs as selective human alpha(2)- versus alpha(1)-adrenoceptor ligands. (United States)

    Bavadekar, Supriya A; Hong, Seoung-Soo; Lee, Sang-Ii; Miller, Duane D; Feller, Dennis R


    Phentolamine is known to act as a competitive, non-subtype-selective alpha-adrenoceptor antagonist. In an attempt to improve alpha(2)- versus alpha(1)-adrenoceptor selectivity and alpha(2)-adrenoceptor subtype-selectivity, two new chemical series of bioisosteric phentolamine analogs were prepared and evaluated. These compounds were evaluated for binding affinities on alpha(1)- (alpha(1A)-, alpha(1B)-, alpha(1D)-) and alpha(2)- (alpha(2A)-, alpha(2B)-, alpha(2C)-) adrenoceptor subtypes that had been stably expressed in human embryonic kidney and Chinese hamster ovary cell lines, respectively. Methylation of the phenolic hydroxy group and replacement of the 4-methyl group of phentolamine with varying lipophilic substituents yielded bioisosteric analogs selective for the alpha(2)- versus alpha(1)-adrenoceptors. Within the alpha(2)-adrenoceptors, these analogs bound with higher affinity at the alpha(2A)- and alpha(2C)-subtypes as compared to the alpha(2B)-subtype. In particular, the t-butyl analog was found to be the most selective, its binding at the alpha(2C)-adrenoceptor (Ki=3.6 nM) being 37- to 173-fold higher than that at the alpha(1)-adrenoceptors, and around 2- and 19-fold higher than at the alpha(2A)- and alpha(2B)-adrenoceptors, respectively. Data from luciferase reporter gene assays confirmed the functional antagonist activities of selected compounds from the bioisosteric series on human alpha(1A)- and alpha(2C)-adrenoceptors. Thus, the results with these bioisosteric analogs of phentolamine provide a lead to the rational design of potent and selective alpha(2)-adrenoceptor ligands that may be useful in improving the therapeutic profile of this drug class for human disorders.

  14. Simulating the Lyman Alpha Forest

    CERN Document Server

    Machacek, M E; Anninos, P; Meiksin, A; Norman, M L; Machacek, Marie E.; Bryan, Greg L.; Anninos, Peter; Meiksin, Avery; Norman, Michael L.


    In this paper we review the importance of the Lyman alpha forest as a probe of structure formation in the universe. We first discuss the statistics used to describe the Lyman alpha forest and the numerical techniques used to produce simulated spectra of the forest from a given cosmological model. We then discuss the physical picture of the absorbing structures that emerges from these numerical simulations. Finally, we comment on how two of the statistics, the slope of the column density distribution and the b parameter distribution, may be used to constrain competing cosmologies.

  15. NACA Physicist Studying Alpha Rays (United States)


    NACA Physicits studying Alpha Rays in a continuous cloud chamber. A cloud chamber is used by Lewis scientists to obtain information aimed at minimizing undesirable effects of radiation on nuclear-powered aircraft components. Here, alpha particles from a polonium source emit in a flower-like pattern at the cloud chamber's center. The particles are made visible by means of alcohol vapor diffusing from an area at room temperature to an area at minus -78 deg. Centigrade. Nuclear-powered aircraft were never developed and aircraft nuclear propulsion systems were canceled in the early 1960s.

  16. GHRS Observations of the Lyman $\\alpha$ Forest

    CERN Document Server

    Morris, S L


    I review the results obtained using the GHRS on low redshift Lyman alpha absorbers. Until the advent of HST and the GHRS, the existence of such absorbers was doubted. The confirmation of their existence, in one of the first GHRS GTO team results to be published, must rank as one of the HSTs most interesting results. The GHRS resolution allows us to probe equivalent widths well below those detectable with the FOS, and has led to a number of interesting new questions. One example is the apparent disagreement between the GHRS result that there are many Lyman alpha absorbers which are not associated with luminous galaxies, and FOS studies which suggest that all such absorbers have a nearby galaxy causing them. This almost certainly shows that the equivalent width (or column density) range reachable by the GHRS includes gas from a wide range of causes, and not only the halos of luminous galaxies. With these data, we are seeing the debris left over from Galaxy formation, material flung out from galaxy interactions ...

  17. Helicobacter pylori HP(2-20) induces eosinophil activation and accumulation in superficial gastric mucosa and stimulates VEGF-alpha and TGF-beta release by interacting with formyl-peptide receptors. (United States)

    Prevete, N; Rossi, F W; Rivellese, F; Lamacchia, D; Pelosi, C; Lobasso, A; Necchi, V; Solcia, E; Fiocca, R; Ceppa, P; Staibano, S; Mascolo, M; D'Argenio, G; Romano, M; Ricci, V; Marone, G; De Paulis, A


    Eosinophils participate in the immune response against Helicobacter pylori, but little is known about their role in the gastritis associated to the infection. We recently demonstrated that the Hp(2-20) peptide derived from H. pylori accelerates wound healing of gastric mucosa by interacting with N-formyl peptide receptors (FPRs) expressed on gastric epithelial cells. The aim of the present study was to investigate whether eosinophils play a role in the repair of gastric mucosa tissue during H. pylori infection. Immuno-histochemistry and transmission electron microscopy were used to detect eosinophils in gastric mucosal biopsies. Eosinophil re-distribution occurred in the gastric mucosa of H. pylori-infected patients: their density did not change in the deep mucosal layer, whereas it increased in the superficial lamina propria just below the foveolar epithelium; eosinophils entered the epithelium itself as well as the lumen of foveolae located close to the area harboring bacteria, which in turn were also engulfed by eosinophils. The H. pylori-derived peptide Hp(2-20) stimulated eosinophil migration through the engagement of FPR2 and FPR3, and also induced production of VEGF-A and TGF-beta, two key mediators of tissue remodelling. We also demonstrate that Hp(2-20) in vivo induced eosinophil infiltration in rat gastric mucosa after injury brought about by indomethacin. This study suggests that eosinophil infiltrate could modulate the capacity of gastric mucosa to maintain or recover its integrity thereby shedding light on the role of eosinophils in H. pylori infection.

  18. THE MEANING OF ALPHA FEMALE IN FEMALE LIBRARIAN: Building a Positive Image of Libraries through Female Librarians as Alpha Female

    Directory of Open Access Journals (Sweden)

    Yunus Winoto


    Full Text Available MAKNA DIRI ALPHA FEMALE PADA PUSTAKAWAN PEREMPUAN: Membangun Citra Positif Perpustakaan Melalui Kiprah Pustakawan Perempuan Sebagai Alpha Female Abstract The profession of librarians is often associated with women. This can be justified if we refer to data and research results that have been done in several countries. However, many women who work in the library, this does not necessarily describe that library work is a simple and easy job. However, on the contrary, work in the field of library is increasingly complex and demands the competence and mastery of information technology. Moreover, the expectations of some users who demand a fast and quality service. Therefore to answer this problem required a female librarian who has the competence, intelligent and able to become a leader for his group and can show the characteristics as a professional. As for the description of people like this people call it with the term alpha female. With the birth of alpha female figures among female librarians is expected to change the positive image of librarians and library institutions. This is because the female alpha figure in the female librarian is a figure of women who are considered "perfect" are still rare today. Keywords: library, librarian, symbolic interaction, alpha female. Abstrak Profesi pustakawan kerapkali dikaitkan dengan kaum perempuan. Hal ini dapat dibenarkan jika kita merujuk pada data dan hasil riset yang telah dilakukan di beberapa negara. Namun demikian banyaknya kaum perempuan yang bekerja di perpustakaan, ini tidak serta merta menggambarkan bahwa pekerjaaan perpustakaan merupakan pekerjaan yang sederhana dan mudah. Namun justru sebaliknya pekerjaaan di bidang perpustakaan saat ini semakin kompleks dan menuntut kompetensi dan penguasaan teknologi informasi. Apalagi harapan sebagian pengguna yang menuntut suatu pelayanan ayang cepat dan berkualitas. Oleh karena demikian untuk menjawab permasalahan ini diperlukan sosok pustakawan

  19. Inflaton Decay in an Alpha Vacuum

    CERN Document Server

    Naidu, S; Naidu, Siddartha; Holman, Richard


    We study the alpha vacua of de Sitter space by considering the decay rate of the inflaton field coupled to a scalar field placed in an alpha vacuum. We find an {\\em alpha dependent} Bose enhancement relative to the Bunch-Davies vacuum and, surprisingly, no non-renormalizable divergences. We also consider a modified alpha dependent time ordering prescription for the Feynman propagator and show that it leads to an alpha independent result. This result suggests that it may be possible to calculate in any alpha vacuum if we employ the appropriate causality preserving prescription.

  20. Alpha-nucleus potential for alpha-decay and sub-barrier fusion

    CERN Document Server

    Denisov, V Y


    The set of parameters for alpha-nucleus potential is derived by using the data for both the alpha-decay half-lives and the fusion cross-sections around the barrier for reactions alpha+40Ca, alpha+59Co, alpha+208Pb. The alpha-decay half-lives are obtained in the framework of a cluster model using the WKB approximation. The evaluated alpha-decay half-lives and the fusion cross-sections agreed well with the data. Fusion reactions between alpha-particle and heavy nuclei can be used for both the formation of very heavy nuclei and spectroscopic studies of the formed compound nuclei.

  1. Alpha-nucleus potential for alpha-decay and sub-barrier fusion


    Denisov, V. Yu.; Ikezoe, H.


    The set of parameters for alpha-nucleus potential is derived by using the data for both the alpha-decay half-lives and the fusion cross-sections around the barrier for reactions alpha+40Ca, alpha+59Co, alpha+208Pb. The alpha-decay half-lives are obtained in the framework of a cluster model using the WKB approximation. The evaluated alpha-decay half-lives and the fusion cross-sections agreed well with the data. Fusion reactions between alpha-particle and heavy nuclei can be used for both the f...

  2. Alpha-cluster model of atomic nuclei

    Energy Technology Data Exchange (ETDEWEB)

    Sosin, Zbigniew; Kallunkathariyil, Jinesh [Jagiellonian University, M. Smoluchowski Institute of Physics, Krakow (Poland); Blocki, Jan [NCBJ, Theoretical Physics Division (BP2), Swierk (Poland); Lukasik, Jerzy; Pawlowski, Piotr [IFJ PAN, Krakow (Poland)


    The description of a nuclear system in its ground state and at low excitations based on the equation of state (EoS) around normal density is presented. In the expansion of the EoS around the saturation point, additional spin polarization terms are taken into account. These terms, together with the standard symmetry term, are responsible for the appearance of the α-like clusters in the ground-state configurations of the N=Z even-even nuclei. At the nuclear surface these clusters can be identified as alpha particles. A correction for the surface effects is introduced for atomic nuclei. Taking into account an additional interaction between clusters the binding energies and sizes of the considered nuclei are very accurately described. The limits of the EoS parameters are established from the properties of the α, {sup 3}He and t particles. (orig.)

  3. Substitutional and Interstitial Diffusion in alpha2-Ti3Al(O) (United States)

    Copland, Evan; Young, David J.; Gleeson, Brian; Jacobson, Nathan


    The reaction between Al2O3 and alpha2-Ti3Al was studied with a series of Al2O3/alpha2-Ti3Al multiphase diffusion couples annealed at 900, 1000 and 1100 C. The diffusion-paths were found to strongly depend on alpha2- Ti3Al(O) composition. For alloys with low oxygen concentrations the reaction involved the reduction of Al2O3, the formation of a gamma-TiAl reaction-layer and diffusion of Al and O into the alpha2-Ti3Al substrate. Measured concentration profiles across the interaction-zone showed "up-hill" diffusion of O in alpha2-Ti3Al(O) indicating a significant thermodynamic interaction between O and Al, Ti or both. Diffusion coefficients for the interstitial O in alpha2-Ti3Al(O) were determined independently from the interdiffusion of Ti and Al on the substitutional lattice. Diffusion coefficients are reported for alpha2-Ti3Al(O) as well as gamma-TiAl. Interpretation of the results were aided with the subsequent measurement of the activities of Al, Ti and O in alpha 2-Ti3Al(O) by Knudsen effusion-cell mass spectrometry.

  4. Modulation of separation distress by alpha-MSH. (United States)

    Panksepp, J; Abbott, B B


    The effects of centrally administered alpha-MSH on separation-induced distress vocalizations (DVs) and squatting were evaluated in domestic chicks for dose-response, time course, and interactions with peripheral naloxone and both peripheral and central morphine. Some of the tests were conducted in both the presence and absence of social stimuli (mirrors or a conspecific). Doses of 0.04 microgram of alpha-MSH or greater eliminated the usual suppression of DVs produced by mirrors or conspecifics. This effect lasted 10-15 minutes and was followed by inhibition of DVs, accompanied by a dose-dependent vigilant squatting posture, that lasted about one hour. These effects showed no development of tolerance to repeated alpha-MSH injections over a six-day period, and no apparent interaction with the effects of peripherally injected naloxone or either peripherally or centrally injected morphine. It is suggested that, in keeping with its role in defensive camouflage in amphibians, alpha-MSH in chicks may activate a central state akin to fear to adaptively modulate DVs and defensive hiding.

  5. What Powers Lyman alpha Blobs?

    CERN Document Server

    Ao, Y; Beelen, A; Henkel, C; Cen, R; De Breuck, C; Francis, P; Kovacs, A; Lagache, G; Lehnert, M; Mao, M; Menten, K M; Norris, R; Omont, A; Tatemastu, K; Weiss, A; Zheng, Z


    Lyman alpha blobs (LABs) are spatially extended lyman alpha nebulae seen at high redshift. The origin of Lyman alpha emission in the LABs is still unclear and under debate. To study their heating mechanism(s), we present Australia Telescope Compact Array (ATCA) observations of the 20 cm radio emission and Herschel PACS and SPIRE measurements of the far-infrared (FIR) emission towards the four LABs in the protocluster J2143-4423 at z=2.38. Among the four LABs, B6 and B7 are detected in the radio with fluxes of 67+/-17 microJy and 77+/-16 microJy, respectively, and B5 is marginally detected at 3 sigma (51+/-16 microJy). For all detected sources, their radio positions are consistent with the central positions of the LABs. B6 and B7 are obviously also detected in the FIR. By fitting the data with different templates, we obtained redshifts of 2.20$^{+0.30}_{-0.35}$ for B6 and 2.20$^{+0.45}_{-0.30}$ for B7 which are consistent with the redshift of the lyman alpha emission within uncertainties, indicating that both ...

  6. Alpha proton x ray spectrometer (United States)

    Rieder, Rudi; Waeke, H.; Economou, T.


    Mars Pathfinder will carry an alpha-proton x ray spectrometer (APX) for the determination of the elemental chemical composition of Martian rocks and soils. The instrument will measure the concentration of all major and some minor elements, including C, N, and O at levels above typically 1 percent.

  7. Sparse Coding for Alpha Matting. (United States)

    Johnson, Jubin; Varnousfaderani, Ehsan; Cholakkal, Hisham; Rajan, Deepu


    Existing color sampling based alpha matting methods use the compositing equation to estimate alpha at a pixel from pairs of foreground (F) and background (B) samples. The quality of the matte depends on the selected (F,B) pairs. In this paper, the matting problem is reinterpreted as a sparse coding of pixel features, wherein the sum of the codes gives the estimate of the alpha matte from a set of unpaired F and B samples. A non-parametric probabilistic segmentation provides a certainty measure on the pixel belonging to foreground or background, based on which a dictionary is formed for use in sparse coding. By removing the restriction to conform to (F,B) pairs, this method allows for better alpha estimation from multiple F and B samples. The same framework is extended to videos, where the requirement of temporal coherence is handled effectively. Here, the dictionary is formed by samples from multiple frames. A multi-frame graph model, as opposed to a single image as for image matting, is proposed that can be solved efficiently in closed form. Quantitative and qualitative evaluations on a benchmark dataset are provided to show that the proposed method outperforms current state-of-the-art in image and video matting.

  8. Two source emission behaviour of alpha fragments of projectile having energy around 1 GeV per nucleon

    CERN Document Server

    Singh, V; Pathak, Ramji


    The emission of projectile fragments alpha has been studied in ^{84}Kr interactions with nuclei of the nuclear emulsion detector composition at relativistic energy below 2 GeV per nucleon. The angular distribution of projectile fragments alpha in terms of transverse momentum could not be explained by a straight and clean-cut collision geometry hypothesis of Participant - Spectator (PS) Model. Therefore, it is assumed that projectile fragments alpha were produced from two separate sources that belong to the projectile spectator region differing drastically in their temperatures. It has been clearly observed that the emission of projectile fragments alpha are from two different sources. The contribution of projectile fragments alpha from contact layer or hot source is a few percent of the total emission of projectile fragments alphas. Most of the projectile fragments alphas are emitted from the cold source. It has been noticed that the temperature of hot and cold regions are dependent on the projectile mass num...

  9. Induction of Endothelial Cell Apoptosis by Anti-alpha-enolase Antibody

    Institute of Scientific and Technical Information of China (English)

    Hong-bo Yang; Wen-jie Zheng; Xuan Zhang; Fu-lin Tang


    Objective To assess the prevalence of anti-alpha-enolase antibody in systemic autoimmune diseases in Chinese patients and its role in endothelial cell apoptosis.Methods The reactivity of anti-alpha-enolase antibody in a variety of autoimmune disorders in Chinese patients was evaluated by dot blot assay. Endothelial cell apoptosis was investigated by in vitro incubation of endothelial cells with IgG purified from anti-alpha-enolase antibody-positive sera, with or without pre-incubation with recombinant alpha-enolase.Results Anti-alpha-enolase antibody was prevalent in different systemic autoimmune diseases with relatively high reactivity in Chinese patients. In vitro incubation of endothelial cells with IgG containing anti-alpha-enolase antibody induced apoptosis in a time- and dose-dependent manner. Apoptosis was partly inhibited by pre-incubation of the endothelial cells with recombinant alpha-enolase.Conclusions Our data suggest that alpha-enolase is a common auto-antigen recognized by antiendothelial cell antibodies in connective tissue disease. Interaction between alpha-enolase and its autoantibody plays a role in endothelial cell apoptosis. Changes other than cell killing may contribute to the pathogenesis of endothelial damage and microvascular lesions.

  10. Integrin alphaVbeta6 is a high-affinity receptor for coxsackievirus A9. (United States)

    Heikkilä, Outi; Susi, Petri; Stanway, Glyn; Hyypiä, Timo


    Coxsackievirus A9 (CAV9), a member of the genus Enterovirus in the family Picornaviridae, possesses an integrin-binding arginine-glycine-aspartic acid (RGD) motif in the C terminus of VP1 capsid protein. CAV9 has been shown to utilize integrins alphaVbeta3 and alphaVbeta6 as primary receptors for cell attachment. While CAV9 RGD-mutants (RGE and RGDdel) are capable of infecting rhabdomyosarcoma (RD) cell line, they grow very poorly in an epithelial lung carcinoma cell line (A549). In this study, the relationships between CAV9 infectivity in A549 and RD cells, receptor expression and integrin binding were analysed. A549 cells were shown to express both integrins alphaVbeta3 and alphaVbeta6, whereas alphaVbeta6 expression was not detected on the RD cells. Native CAV9 but not RGE and RGDdel mutants bound efficiently to immobilized alphaVbeta3 and alphaVbeta6. Adhesion of CAV9 but not RGE/RGDdel to A549 cells was also significantly higher than to RD cells. In contrast, no affinity or adhesion of bacterially produced VP1 proteins to the integrins or to the cells was detected. Function-blocking antibodies against alphaV-integrins blocked CAV9 but not CAV9-RGDdel infectivity, indicating that the viruses use different internalization routes; this may explain the differential infection kinetics of CAV9 and RGDdel. In an affinity assay, soluble alphaVbeta6, but not alphaVbeta3, bound to immobilized CAV9. Similarly, only soluble alphaVbeta6 blocked virus infectivity. These data suggest that CAV9 binding to alphaVbeta6 is a high-affinity interaction, which may indicate its importance in clinical infections; this remains to be determined.

  11. Modulation of gene expression by alpha-tocopherol and alpha-tocopheryl phosphate in thp-1 monocytes (United States)

    The naturally occurring vitamin E analogue, alpha-tocopheryl phosphate (alphaTP), has been reported to be more potent than the un-phosphorylated alpha alpha-tocopherol (alphaT). We have now measured plasma levels of alphaTP and compared the cellular effects of alphaTP and gamma-tocopheryl phosphate ...

  12. Alpha-clustered hypernuclei and chiral SU(3) dynamics

    CERN Document Server

    Hiyama, Emiko; Kaiser, Norbert; Weise, Wolfram


    Light hypernuclei with an $\\alpha$ cluster substructure of the core nucleus are studied using an accurate cluster approach (the Hyper-THSR wave function) in combination with a density-dependent $\\Lambda$ hyperon-nuclear interaction derived from chiral SU(3) effective field theory. This interaction includes important two-pion exchange processes involving $\\Sigma N$ intermediate states and associated three-body mechanisms as well as effective mass and surface terms arising in a derivative expansion of the in-medium $\\Lambda$ self-energy. Applications and calculated results are presented and discussed for $_\\Lambda^9$Be and $^{13}_\\Lambda$C. Furthermore, the result of the lightest $\\alpha$ clustered hypernucleus, $^5_{\\Lambda}$He using realistic $ab initio$ four nucleon density is shown.

  13. Constraining PCP Violating Varying Alpha Theory through Laboratory Experiments

    Energy Technology Data Exchange (ETDEWEB)

    Maity, Debaprasad; /NCTS, Taipei /Taiwan, Natl. Taiwan U.; Chen, Pisin; /NCTS, Taipei /Taiwan, Natl. Taiwan U. /KIPAC, Menlo Park /SLAC


    In this report we have studied the implication of a parity and charge-parity (PCP) violating interaction in varying alpha theory. Due to this interaction, the state of photon polarization can change when it passes through a strong background magnetic field. We have calculated the optical rotation and ellipticity of the plane of polarization of an electromagnetic wave and tested our results against different laboratory experiments. Our model contains a PCP violating parameter {beta} and a scale of alpha variation {omega}. By analyzing the laboratory experimental data, we found the most stringent constraints on our model parameters to be 1 {le} {omega} {le} 10{sup 13} GeV{sup 2} and -0.5 {le} {beta} {le} 0.5. We also found that with the existing experimental input parameters it is very difficult to detect the ellipticity in the near future.

  14. Astrophysical reaction rate for $\\alpha(\\alpha n,\\gamma)$

    CERN Document Server

    Sumiyoshi, K; Goko, S; Kajino, T


    We study the astrophysical reaction rate for the formation of $^{9}$Be through the three body reaction $\\alpha(\\alpha n,\\gamma)$. This reaction is one of the key reactions which could bridge the mass gap at A = 8 nuclear systems to produce intermediate-to-heavy mass elements in alpha- and neutron-rich environments such as r-process nucleosynthesis in supernova explosions, s-process nucleosynthesis in asymptotic giant branch (AGB) stars, and primordial nucleosynthesis in baryon inhomogeneous cosmological models. To calculate the thermonuclear reaction rate in a wide range of temperatures, we numerically integrate the thermal average of cross sections assuming a two-steps formation through a metastable $^{8}$Be. Off-resonant and on-resonant contributions from the ground state in $^{8}$Be are taken into account. As input cross section, we adopt the latest experimental data by photodisintegration of $^{9}$Be with laser-electron photon beams, which covers all relevant resonances in $^{9}$Be. We provide the reactio...

  15. Evolution and seismology of alpha Centauri

    CERN Document Server

    Montalban, J; Montalban, Josefina; Miglio, Andrea


    Solar-like oscillations detected in both components of the binary system alpha Centauri provide strong constraints on the fundamental parameters of the stellar system. We model alpha Centauri by means of a Levenberg-Marquardt minimization algorithm including seismic and classical constraints. Computations, that were perfomed decreasing significanly the weight of alpha Cen B seismic data in the calibration procedure, predict small separations in good agreement with new observations of solar-like oscillations in alpha Cen B by Bedding (these proceedings).

  16. Massless correlators of vector, scalar and tensor currents in position space at orders alpha_s^3 and alpha_s^4: explicit analytical results


    Chetyrkin, K. G.; Maier, A


    We present analytical results both in momentum and position space for the massless correlators of the vector and scalar currents to order alpha_s^4 as well as for the tensor currents to order alpha_s^3. The evolution equations for the correlators together with all relevant anomalous dimensions are discussed in detail. As an application we present explicit conversion formulas relating the MSbar-renormalized vector, scalar and tensor currents to their counterparts renormalized in the X-space re...

  17. Statistical convergence of order $\\alpha$ in probability


    Pratulananda Das; Sanjoy Ghosal; Sumit Som


    In this paper ideas of different types of convergence of a sequence of random variables in probability, namely, statistical convergence of order $\\alpha$ in probability, strong $p$-Ces$\\grave{\\mbox{a}}$ro summability of order $\\alpha$ in probability, lacunary statistical convergence or $S_{\\theta}$-convergence of order $\\alpha$ in probability, ${N_{\\theta}}$-convergence of order $\\alpha$ in probability have been introduced and their certain basic properties have been studied.

  18. NF-{kappa}B suppresses HIF-1{alpha} response by competing for P300 binding

    Energy Technology Data Exchange (ETDEWEB)

    Mendonca, Daniela B.S., E-mail: [Universidade Catolica de Brasilia, Pos-Graduacao em Ciencias Genomicas e Biotecnologia, SGAN Quadra 916, Av. W5 Norte, 70790-160 Brasilia, DF (Brazil); Bone Biology and Implant Therapy Laboratory, Department of Prosthodontics, University of North Carolina at Chapel Hill, 330 Brauer Hall, CB 7450, Chapel Hill, NC 27599 (United States); Mendonca, Gustavo [Universidade Catolica de Brasilia, Pos-Graduacao em Ciencias Genomicas e Biotecnologia, SGAN Quadra 916, Av. W5 Norte, 70790-160 Brasilia, DF (Brazil); Bone Biology and Implant Therapy Laboratory, Department of Prosthodontics, University of North Carolina at Chapel Hill, 330 Brauer Hall, CB 7450, Chapel Hill, NC 27599 (United States); Aragao, Francisco J.L. [Universidade Catolica de Brasilia, Pos-Graduacao em Ciencias Genomicas e Biotecnologia, SGAN Quadra 916, Av. W5 Norte, 70790-160 Brasilia, DF (Brazil); Embrapa Recursos Geneticos e Biotecnologia, Laboratorio de Introducao e Expressao de Genes, PqEB W5 Norte, 70770-900 Brasilia, DF (Brazil); Cooper, Lyndon F., E-mail: [Bone Biology and Implant Therapy Laboratory, Department of Prosthodontics, University of North Carolina at Chapel Hill, 330 Brauer Hall, CB 7450, Chapel Hill, NC 27599 (United States)


    Research highlights: {yields} p65 completely blocked HIF-1{alpha} activity at the HRE on different cell lines. {yields} p65 caused minor changes in HIF-1{alpha} and HIF-1{alpha} target genes mRNA expression. {yields} p65 reduced transcription of VEGF promoter. {yields} p65 competes with HIF-1{alpha} for p300. -- Abstract: Hypoxia has emerged as a key determinant of osteogenesis. HIF-1{alpha} is the transcription factor mediating hypoxia responses that include induction of VEGF and related bone induction. Inflammatory signals antagonize bone repair via the NF-{kappa}B pathway. The present investigation explored the functional relationship of hypoxia (HIF-1{alpha} function) and inflammatory signaling (NF-{kappa}B) in stem like and osteoprogenitor cell lines. The potential interaction between HIF-1{alpha} and NF-{kappa}B signaling was explored by co-transfection studies in hFOB with p65, HIF-1{alpha} and 9x-HRE-luc or HIF-1{alpha} target genes reporter plasmids. Nuclear cross-talk was directly tested using the mammalian Gal4/VP16 two-hybrid, and confirmed by co-immunoprecipitation/western blotting assays. The results show that inflammatory stimulation (TNF-{alpha} treatment) causes a marked inhibition of HIF-1{alpha} function at the HRE in all cell lines studied. Also, co-transfection with p65 expression vector leads to reduced hVEGFp transcription after DFO-induced hypoxia. However, TNF-{alpha} treatment had little effect on HIF-1{alpha} mRNA levels. The functional interaction of Gal4-HIF-1{alpha} and VP16-p300 fusion proteins is effectively blocked by expression of p65 in a dose dependent manner. It was concluded that NF-{kappa}B-mediated inflammatory signaling is able to block HIF-1{alpha} transactivation at HRE-encoding genes by direct competition for p300 binding at the promoter. Inflammation may influence the stem cell niche and tissue regeneration by influencing cellular responses to hypoxia.

  19. Structural and Biochemical Basis for the Binding Selectivity of Peroxisome Proliferator-activated Receptor [gamma] to PGC-1[alpha

    Energy Technology Data Exchange (ETDEWEB)

    Li, Yong; Kovach, Amanda; Suino-Powell, Kelly; Martynowski, Dariusz; Xu, H. Eric (Pitt); (Van Andel)


    The functional interaction between the peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}) and its coactivator PGC-1{alpha} is crucial for the normal physiology of PPAR{gamma} and its pharmacological response to antidiabetic treatment with rosiglitazone. Here we report the crystal structure of the PPAR{gamma} ligand-binding domain bound to rosiglitazone and to a large PGC-1{alpha} fragment that contains two LXXLL-related motifs. The structure reveals critical contacts mediated through the first LXXLL motif of PGC-1{alpha} and the PPAR{gamma} coactivator binding site. Through a combination of biochemical and structural studies, we demonstrate that the first LXXLL motif is the most potent among all nuclear receptor coactivator motifs tested, and only this motif of the two LXXLL-related motifs in PGC-1{alpha} is capable of binding to PPAR{gamma}. Our studies reveal that the strong interaction of PGC-1{alpha} and PPAR{gamma} is mediated through both hydrophobic and specific polar interactions. Mutations within the context of the full-length PGC-1{alpha} indicate that the first PGC-1{alpha} motif is necessary and sufficient for PGC-1{alpha} to coactivate PPAR{gamma} in the presence or absence of rosiglitazone. These results provide a molecular basis for specific recruitment and functional interplay between PPAR{gamma} and PGC-1{alpha} in glucose homeostasis and adipocyte differentiation.

  20. Effectiveness of Alpha Biofeedback Therapy: Negative Results. (United States)

    Watson, Charles G.; Herder, Joseph


    Assessed the utility of alpha biofeedback training in the treatment of patients (N=66). Biofeedback and placebo biofeedback groups were given alpha or mock-alpha training sessions. Improvement on 54 variables was compared to that of no-treatment controls. Only a chance number of significant changes appeared among the groups. (Author)


    NARCIS (Netherlands)



    We have identified a new protein fold-the alpha/beta-hydrolase fold-that is common to several hydrolytic enzymes of widely differing phylogenetic origin and catalytic function. The core of each enzyme is similar: an alpha/beta-sheet, not barrel, of eight beta-sheets connected by alpha-helices. These


    NARCIS (Netherlands)



    We have identified a new protein fold-the alpha/beta-hydrolase fold-that is common to several hydrolytic enzymes of widely differing phylogenetic origin and catalytic function. The core of each enzyme is similar: an alpha/beta-sheet, not barrel, of eight beta-sheets connected by alpha-helices. These

  3. 21 CFR 882.1610 - Alpha monitor. (United States)


    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Alpha monitor. 882.1610 Section 882.1610 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES NEUROLOGICAL DEVICES Neurological Diagnostic Devices § 882.1610 Alpha monitor. (a) Identification. An alpha monitor is a device with electrodes...

  4. Interferon-alpha induced Raynaud's syndrome. (United States)

    Kruit, W H; Eggermont, A M; Stoter, G


    The cytokine interferon-alpha (IFN-alpha) is increasingly prescribed for a number of indications, especially viral hepatitis and several malignancies. Two patients are described who developed Raynaud's syndrome during treatment with IFN-alpha as adjuvant therapy for high-risk melanoma. With a review of the available literature the symptomatology, possible pathophysiologic mechanisms and treatment options are discussed.

  5. Enzyme replacement therapy for alpha-mannosidosis

    DEFF Research Database (Denmark)

    Borgwardt, Line Gutte; Dali, Christine I.; Fogh, J


    Alpha-mannosidosis (OMIM 248500) is a rare lysosomal storage disease (LSD) caused by alpha-mannosidase deficiency. Manifestations include intellectual disabilities, facial characteristics and hearing impairment. A recombinant human alpha-mannosidase (rhLAMAN) has been developed for weekly intrave...... intravenous enzyme replacement therapy (ERT). We present the preliminary data after 12 months of treatment....

  6. TNF-alpha in tuberculosis: a cytokine with a split personality. (United States)

    Mootoo, Amanda; Stylianou, Elena; Arias, Mauricio A; Reljic, Rajko


    TNF-alpha is an essential component of the innate defence mechanism of the host against pathogenic challenge. Unfortunately, it can also play a major role in the pathology of certain diseases, such as tuberculosis. This disease is a striking example of the role of TNF-alpha as a 'double-edged sword', because apart from its role in controlling the Mycobacterium tuberculosis infection, it can also cause severe tissue damage. TNF-alpha exhibits a very complex network of interactions and many of its activities are still not fully understood. This report aims to review the pivotal role of TNF-alpha in controlling the mycobacterial infection, with a particular emphasis on its influence on chemokine expression and cell movement during granuloma formation, and the issues surrounding the use of TNF-alpha inhibitors for therapeutic use in inflammatory diseases.

  7. Recent $\\alpha$ decay half-lives and analytic expression predictions including superheavy nuclei

    CERN Document Server

    Royer, G


    New recent experimental $\\alpha$ decay half-lives have been compared with the results obtained from previously proposed formulas depending only on the mass and charge numbers of the $\\alpha$ emitter and the Q$\\alpha$ value. For the heaviest nuclei they are also compared with calculations using the Density-Dependent M3Y (DDM3Y) effective interaction and the Viola-Seaborg-Sobiczewski (VSS) formulas. The correct agreement allows us to make predictions for the $\\alpha$ decay half-lives of other still unknown superheavy nuclei from these analytic formulas using the extrapolated Q$\\alpha$ of G. Audi, A. H. Wapstra, and C. Thibault [Nucl. Phys. A729, 337 (2003)].

  8. A specific domain in alpha-catenin mediates binding to beta-catenin or plakoglobin. (United States)

    Huber, O; Krohn, M; Kemler, R


    The E-cadherin-catenin adhesion complex has been the subject of many structural and functional studies because of its importance in development, normal tissue function and carcinogenesis. It is well established that the cytoplasmic domain of E-cadherin binds either beta-catenin or plakoglobin, which both can assemble alpha-catenin into the complex. Recently we have identified an alpha-catenin binding site in beta-catenin and plakoglobin and postulated, based on sequence analysis, that these protein-protein interactions are mediated by a hydrophobic interaction mechanism. Here we have now identified the reciprocal complementary binding site in alpha-catenin which mediates its interaction with beta-catenin and plakoglobin. Using in vitro association assays with C-terminal truncations of alpha-catenin expressed as recombinant fusion proteins, we found that the N-terminal 146 amino acids are required for this interaction. We then identified a peptide of 27 amino acids within this sequence (amino acid positions 117-143) which is necessary and sufficient to bind beta-catenin or plakoglobin. As shown by mutational analysis, hydrophobic amino acids within this binding site are important for the interaction. The results described here, together with our previous work, give strong support for the idea that these proteins associate by hydrophobic interactions of two alpha-helices.

  9. Nature of the pygmy dipole resonance in Ce-140 studied in (alpha, alpha 'gamma) experiments

    NARCIS (Netherlands)

    Savran, D.; Babilon, M.; van den Berg, A. M.; Harakeh, M. N.; Hasper, J.; Matic, A.; Wortche, H. J.; Zilges, A.


    A concentration of electric-dipole excitations below the particle threshold, which is frequently denoted as the pygmy dipole resonance, has been studied in the semimagic nucleus Ce-140 in (alpha, alpha(')gamma) experiments at E-alpha=136 MeV. The technique of alpha-gamma coincidence experiments allo

  10. Refinement of the $n-\\alpha$ and $p-\\alpha$ fish-bone potential

    CERN Document Server

    Smith, E; Papp, Z


    The fishbone potential of composite particles simulates the Pauli effect by nonlocal terms. We determine the $n-\\alpha$ and $p-\\alpha$ fish-bone potential by simultaneously fitting to the experimental phase shifts. We found that with a double Gaussian parametrization of the local potential can describe the $n-\\alpha$ and $p-\\alpha$ phase shifts for all partial waves.

  11. Stereoselective synthesis of Z-alpha-aryl-alpha,beta-unsaturated esters. (United States)

    Mani, Neelakandha S; Mapes, Christopher M; Wu, Jiejun; Deng, Xiaohu; Jones, Todd K


    An efficient method for the stereoselective synthesis of (Z)-alpha-arylacrylates is described. Treatment of alpha-hydroxyesters with triflic anhydride and pyridine at 0 degrees C followed by warming to room temperature afforded the corresponding (Z)-alpha-aryl-alpha,beta-unsaturated esters in very good yields and excellent stereoselectivity.

  12. Separation of the subtypes of type V collagen molecules, [alpha 1(V)]2 alpha 2(V) and alpha 1(V) alpha 2(V) alpha 3(V), by chain composition-dependent affinity for heparin: single alpha 1(V) chain shows intermediate heparin affinity between those of the type V collagen subtypes composed of [alpha 1(V)]2 alpha 2(V) and of alpha 1(V) alpha 2(V) alpha 3(V). (United States)

    Mizuno, K; Hayashi, T


    The heparin affinities of heat-treated type V collagen alpha-chains and the triple-helical molecules were evaluated in terms of the NaCl concentration required for prevention of binding to a heparin-Sepharose column. After heat treatment, alpha 1(V) chain required approximately two-fold higher NaCl concentration to pass through the column than the other two chains, alpha 2(V) and alpha 3(V). Thus, the heparin affinity of alpha 1(V) may be approximately two-fold higher than those of the other alpha (V)-chains. The type V collagen molecules in triple-helical conformation were separated into two fractions at 170 mM NaCl in 20 mM phosphate buffer, pH 7.2, containing 2 M urea; bound and non-bound. The ratio of the three alpha-chains, alpha 1(V): alpha 2(V): alpha 3(V) was 2 : 1 : 0 and 1 : 1 : 1 in the bound and flow-through fractions, respectively, on analysis by SDS-PAGE. The differential affinity of the two fractions could be accounted for by the number of alpha 1(V) chains in the triple-helical molecule, if these fractions contained triple-helical subtypes with the chain compositions of [alpha 1(V)]2 alpha 2(V) and alpha 1(V) alpha 2(V) alpha 3(V), respectively. From the comparison of the NaCl concentration required for prevention of the binding, [alpha 1(V)]2, alpha 2(V) had about two-fold higher affinity than alpha 1(V) alpha 2(V) alpha 3(V), and the separated alpha 1(V) chain showed an intermediate affinity. A possible explanation for difference in heparin affinity among the subtypes of molecules and the separated alpha-chains is that the heparin affinity of type V collagen molecule is governed by the number of alpha 1(V) chains contained in the molecule and that steric restraint in a triple-helical conformation weakens the binding of alpha 1(V) chain to heparin.

  13. Functional effect of point mutations in the alpha-folate receptor gene of CABA I ovarian carcinoma cells. (United States)

    Mangiarotti, F; Miotti, S; Galmozzi, E; Mazzi, M; Sforzini, S; Canevari, S; Tomassetti, A


    The alpha-folate receptor (alpha FR) is overexpressed in 90% of nonmucinous ovarian carcinomas. In addition to the known role of alpha FR binding and mediating the internalization of folates, functional interaction of alpha FR with signaling molecules was recently shown. To identify a model to study the role of alpha FR in ovarian carcinoma, we characterized the alpha FR gene in the ovarian carcinoma cell line CABA I in comparison to a reference line, IGROV1. In CABA I cells, Northern blot analysis revealed an alpha FR transcript of the expected length and FACS analysis indicated receptor expression on the cell membrane; however, RNase protection assay revealed no specific signals. Southern blot and genomic PCR analysis suggested the presence of a rearrangement(s) involving the 5' region of the gene in CABA I cells as compared to IGROV1 cells. Cloning and sequencing of CABA I alpha FR cDNA revealed several point mutations. The partitioning of alpha FR in membrane microdomains from CABA I cells and its association with regulatory molecules was comparable to that of IGROV1 cells. By contrast, the alpha FR expressed on the CABA I cell membrane bound folic acid with lower affinity, and ectopic expression of the corresponding cDNA in CHO cells confirmed impaired folic acid binding. Thus, CABA I cells may provide a tool to delineate functional domains of the alpha FR. Copyright 2001 Wiley-Liss, Inc.

  14. Crystalline anhydrous {alpha},{alpha}-trehalose (polymorph {beta}) and crystalline dihydrate {alpha},{alpha}-trehalose: A calorimetric study

    Energy Technology Data Exchange (ETDEWEB)

    Pinto, Susana S. [Centro de Quimica Estrutural, Complexo Interdisciplinar, Instituto Superior Tecnico, 1049-001 Lisbon (Portugal)]. E-mail:; Diogo, Herminio P. [Centro de Quimica Estrutural, Complexo Interdisciplinar, Instituto Superior Tecnico, 1049-001 Lisbon (Portugal)]. E-mail:; Moura-Ramos, Joaquim J. [Centro de Quimica-Fisica Molecular, Complexo Interdisciplinar, Instituto Superior Tecnico, 1049-001 Lisbon (Portugal)]. E-mail:


    The mean values of the standard massic energy of combustion of crystalline anhydrous {alpha},{alpha}-trehalose (C{sub 12}H{sub 22}O{sub 11}, polymorph {beta}) and crystalline dihydrate {alpha},{alpha}-trehalose (C{sub 12}H{sub 26}O{sub 13}) measured by static-bomb combustion calorimetry in oxygen, at the temperature T=298.15K, are {delta}{sub c}u{sup o}=-(16434.05+/-4.50)J.g{sup -1} and {delta}{sub c}u{sup o}=-(14816.05+/-3.52)J.g{sup -1}, respectively. The standard (p{sup o}=0.1MPa) molar enthalpy of formation of these compounds were derived from the corresponding standard molar enthalpies of combustion, respectively, {delta}{sub f}H{sub m}{sup o} (C{sub 12}H{sub 22}O{sub 11},cr)=-(2240.9+/-3.9)kJ.mol{sup -1}, and {delta}{sub f}H{sub m}{sup o} (C{sub 12}H{sub 26}O{sub 13},cr)=-(2832.6+/-3.6)kJ.mol{sup -1}. The values of the standard enthalpies of formation obtained in this work, together with data on enthalpies of solution at infinite dilution ({delta}{sub sol}H{sup {approx}}) for crystalline dihydrate and amorphous anhydrous trehalose, allow a better insight on the thermodynamic description of the trehalose system which can provide, together with the future research on the subject, a contribution for understanding the metabolism in several organisms, as well as the phase transition between the different polymorphs.

  15. Alpha voltaic batteries and methods thereof (United States)

    Raffaelle, Ryne P. (Inventor); Jenkins, Phillip (Inventor); Wilt, David (Inventor); Scheiman, David (Inventor); Chubb, Donald (Inventor); Castro, Stephanie (Inventor)


    An alpha voltaic battery includes at least one layer of a semiconductor material comprising at least one p/n junction, at least one absorption and conversion layer on the at least one layer of semiconductor layer, and at least one alpha particle emitter. The absorption and conversion layer prevents at least a portion of alpha particles from the alpha particle emitter from damaging the p/n junction in the layer of semiconductor material. The absorption and conversion layer also converts at least a portion of energy from the alpha particles into electron-hole pairs for collection by the one p/n junction in the layer of semiconductor material.

  16. TIF1alpha: a possible link between KRAB zinc finger proteins and nuclear receptors

    DEFF Research Database (Denmark)

    Le Douarin, B; You, J; Nielsen, Anders Lade


    Ligand-induced gene activation by nuclear receptors (NRs) is thought to be mediated by transcriptional intermediary factors (TIFs), that interact with their ligand-dependent AF-2 activating domain. Included in the group of the putative AF-2 TIFs identified so far is TIF1alpha, a member of a new...... family of proteins which contains an N-terminal RBCC (RING finger-B boxes-coiled coil) motif and a C-terminal bromodomain preceded by a PHD finger. In addition to these conserved domains present in a number of transcriptional regulatory proteins, TIF1alpha was found to contain several protein......-protein interaction sites. Of these, one specifically interacts with NRs bound to their agonistic ligand and not with NR mutants that are defective in the AF-2 activity. Immediately adjacent to this 'NR box', TIF1alpha contains an interaction site for members of the chromatin organization modifier (chromo) family, HP...

  17. Interaction of europium and curium with alpha-amylase

    Energy Technology Data Exchange (ETDEWEB)

    Barkleit, Astrid [Helmholtz-Zentrum Dresden-Rossendorf e.V., Dresden (Germany). Div. Chemistry of the F-Elements; Heller, Anne [Technische Univ. Dresden (Germany). Inst. for Zoology, Molecular Cell Physiology and Endocrinology; Helmholtz-Zentrum Dresden-Rossendorf e.V., Dresden (Germany). Div. Biogeochemistry


    Time-resolved laser-induced fluorescence spectroscopy (TRLFS) revealed that Eu(III) and Cm(III) form two dominant species with the protein α-amylase (Amy): one with the coordination of a single carboxylate group of the protein and the other with three coordinating carboxylate groups.

  18. Interactions between Calcium and Alpha-Synuclein in Neurodegeneration (United States)

    Rcom-H’cheo-Gauthier, Alex; Goodwin, Jacob; Pountney, Dean L.


    In Parkinson’s disease and some atypical Parkinson’s syndromes, aggregation of the α-synuclein protein (α-syn) has been linked to neurodegeneration. Many triggers for pathological α-syn aggregation have been identified, including port-translational modifications, oxidative stress and raised metal ions, such as Ca2+. Recently, it has been found using cell culture models that transient increases of intracellular Ca2+ induce cytoplasmic α-syn aggregates. Ca2+-dependent α-syn aggregation could be blocked by the Ca2+ buffering agent, BAPTA-AM, or by the Ca2+ channel blocker, Trimethadione. Furthermore, a greater proportion of cells positive for aggregates occurred when both raised Ca2+ and oxidative stress were combined, indicating that Ca2+ and oxidative stress cooperatively promote α-syn aggregation. Current on-going work using a unilateral mouse lesion model of Parkinson’s disease shows a greater proportion of calbindin-positive neurons survive the lesion, with intracellular α-syn aggregates almost exclusively occurring in calbindin-negative neurons. These and other recent findings are reviewed in the context of neurodegenerative pathologies and suggest an association between raised Ca2+, α-syn aggregation and neurotoxicity. PMID:25256602

  19. Interactions between Calcium and Alpha-Synuclein in Neurodegeneration

    Directory of Open Access Journals (Sweden)

    Alex Rcom-H'cheo-Gauthier


    Full Text Available In Parkinson’s disease and some atypical Parkinson’s syndromes, aggregation of the α-synuclein protein (α-syn has been linked to neurodegeneration. Many triggers for pathological α-syn aggregation have been identified, including port-translational modifications, oxidative stress and raised metal ions, such as Ca2+. Recently, it has been found using cell culture models that transient increases of intracellular Ca2+ induce cytoplasmic α-syn aggregates. Ca2+-dependent α-syn aggregation could be blocked by the Ca2+ buffering agent, BAPTA-AM, or by the Ca2+ channel blocker, Trimethadione. Furthermore, a greater proportion of cells positive for aggregates occurred when both raised Ca2+ and oxidative stress were combined, indicating that Ca2+ and oxidative stress cooperatively promote α-syn aggregation. Current on-going work using a unilateral mouse lesion model of Parkinson’s disease shows a greater proportion of calbindin-positive neurons survive the lesion, with intracellular α-syn aggregates almost exclusively occurring in calbindin-negative neurons. These and other recent findings are reviewed in the context of neurodegenerative pathologies and suggest an association between raised Ca2+, α-syn aggregation and neurotoxicity.

  20. A novel human scFv fragment against TNF-alpha from de novo design method. (United States)

    Chang, Hong; Qin, Weisong; Li, Yan; Zhang, Jiyan; Lin, Zhou; Lv, Ming; Sun, Yingxun; Feng, Jiannan; Shen, Beifen


    Anti-TNF antibody has been an effective therapeutic strategy for the diseases related to aberrant production of TNF-alpha, such as rheumatoid arthritis (RA) and Crohn's disease. The limitations of large molecule inhibitors in the therapy of these diseases prompted the search for other potent novel TNF-alpha antagonists. Antagonistic peptides, derived directly or designed rationally from complementarity-determining regions (CDRs) of neutralizing antibodies against TNF-alpha, have been demonstrated for their ability of inhibiting TNF-alpha. However, their activity is very low. In this study, to increase the affinity and bioactivity, human antibody variable region was used as scaffold to display antagonistic peptides, which were designed on the interaction between TNF-alpha and its neutralizing monoclonal antibody (mAb Z12). Based on the previously designed domain antibody (framework V(H)5), framework V(kappa)1 was used as light chain scaffold. On the basis of computer-guided molecular design method, a novel human scFv fragment (named as TSA1) was designed. Theoretical analysis showed that TSA1 could bind to TNF-alpha with more hydrogen bonds and lower binding free energy than the designed domain antibody. The biological experiments demonstrated that TSA1 could directly bind with TNF-alpha, competitively inhibit the binding of mAb Z12 to TNF-alpha and block the binding of TNF-alpha to TNFR I and TNFR II. TSA1 could also inhibit TNF-induced cytotoxicity on L929 cells and TNF-mediated NF-kappaB activation on HEK-293T cells. The bioactivity of TSA1 was significantly increased over the domain antibody. This study indicated that the framework of antibody variable region could serve as an ideal scaffold for displaying the peptides and provides a novel strategy to design TNF-alpha inhibitors with the ability to block the deleterious biological effects of TNF-alpha.

  1. Collagen IV alpha 3, alpha 4, and alpha 5 chains in rodent basal laminae: sequence, distribution, association with laminins, and developmental switches



    Collagen IV is a major component of vertebrate basal laminae (BLs). Studies in humans have revealed a family of genes encoding alpha 1- alpha 6 collagen IV chains and implicated alpha 3-alpha 6 in disease processes (Goodpasture and Alport syndromes and diffuse leiomyomatosis). To extend studies of these components to an experimentally accessible animal, we cloned cDNAs encoding partial collagen alpha 3, alpha 4, and alpha 5(IV) chains from the mouse. Ribonuclease protection assays showed that...

  2. Inhibitory effects of human alpha 2-macroglobulin on Trypanosoma cruzi epimastigote proteinases. (United States)

    Ramos, A; Remedi, M S; Sánchez, C; Bonacci, G; Vides, M A; Chiabrando, G


    The inactivation of Trypanosoma cruzi proteinases by human alpha 2-macroglobulin (alpha 2-M), a major plasma proteinase inhibitor was studied. Evidences regarding the interaction between alpha 2-M and proteolytic enzymes contained in crude cell-free extracts of T. cruzi were derived from electrophoretic and enzymatic assays. The former showed conformational and structural changes occurring in alpha 2-M, as judged by the appearance of transformed 'fast' form on native PAGE; generation of bands of approximately 90 kDa on reduced SDS-PAGE and formation of covalent complexes enzyme-inhibitor on SDS-PAGE. On the other hand, the total proteolytic activity on azocasein dropped significantly in the presence of alpha 2-M, although partial activity was still maintained. The proteinases detected as a double band of 44 and 53 kDa on gelatin SDS-PAGE were also inhibited by alpha 2-M. Results suggest that the study of specific interactions between alpha 2-M and T. cruzi-proteinases, probably with cruzipain, could be biologically important in the fate of T. cruzi-infection and Chagas' disease.

  3. Flicker regularity is crucial for entrainment of alpha oscillations

    Directory of Open Access Journals (Sweden)

    Annika Notbohm


    are compared to those presented during the maximum.In the second experiment stimulation with higher light intensity during both rhythmic and arrhythmic stimulation lead to an increased behavioral modulation depth, supposedly as a consequence of stronger entrainment during rhythmic stimulation.Altogether, our results reveal evidence for rhythmic and arrhythmic visual stimulation to induce fundamentally different processes in the brain: we suggest that rhythmic but not arrhythmic stimulation interacts with ongoing alpha oscillations

  4. Alpha-event and surface characterisation in segmented true-coaxial HPGe detectors

    CERN Document Server

    Abt, Iris; Gooch, Chris; Irlbeck, Sabine; Liu, Xiang; Palermo, Matteo; Schulz, Oliver


    A detailed study of alpha interactions on the passivation layer on the end-plate of a true-coaxial high-purity germanium detector is presented. The observation of alpha events on such a surface indicates an unexpectedly thin so-called "dead layer" of less than 20 {\\mu}m thickness. In addition, the influence of the metalisation close to the end-plate on the time evolution of the output pulses is discussed. The results indicate that alpha contamination can result in events which could be mistaken as signals for neutrinoless double beta decay and provide some guidance on how to prevent this.

  5. A synthetic peptide derived from A1 module in CRD4 of human TNF receptor-1 inhibits binding and proinflammatory effect of human TNF-alpha. (United States)

    Cao, Yingnan; Wang, Zhaohe; Bu, Xianzhang; Tang, Shu; Mei, Zhengrong; Liu, Peiqing


    Tumour necrosis factor alpha (TNF-alpha) is a proinflammatory cytokine, which has been shown to be a causative factor in rheumatoid arthritis, inflammatory bowel disease and septic shock. Proinflammatory effect of TNF-alpha is activated mainly through human TNF receptor-1 (TNF-R1). However, the role of the fourth cystein-rich domain (CRD4) of TNF-R1 extracellular portion in the interaction of TNF-alpha with TNF-R1 is still unclear. In the present study, binding activity of TNF-alpha to TNF-R1 and protein levels of IkappaB-alpha and nuclear transcription factor kappa B (NF-kappaB) p65 subunit in HeLa cells were measured using enzyme-linked immunosorbent assay (ELISA) and western-blot analysis. Pep 3 (LRENECVS) which was derived from the hydrophilic region of A1 module in CRD4 remarkably inhibited the binding of TNF-alpha to TNF-R1, and also reversed TNF-alpha-induced degradation of IkappaB-alpha and nuclear translocation of NF-kappaB p65 subunit in HeLa cells. Our results confirmed that the hydrophilic region of A1 module in CRD4 participated in the interaction of TNF-alpha with TNF-R1, and demonstrated the potential of small-molecule TNF-alpha extracellular inhibitors targeting at A1 module in CRD4 of TNF-R1 in suppressing proinflammatory effect of TNF-alpha.

  6. Identification and characterization of an alternative promoter of the human PGC-1{alpha} gene

    Energy Technology Data Exchange (ETDEWEB)

    Yoshioka, Toyo; Inagaki, Kenjiro [Division of Diabetes, Metabolism, and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017 (Japan); Noguchi, Tetsuya, E-mail: [Division of Diabetes, Metabolism, and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017 (Japan); Sakai, Mashito; Ogawa, Wataru; Hosooka, Tetsuya [Division of Diabetes, Metabolism, and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017 (Japan); Iguchi, Haruhisa; Watanabe, Eijiro; Matsuki, Yasushi; Hiramatsu, Ryuji [Genomic Science Laboratories, DainipponSumitomo Pharma Co. Ltd., 4-2-1 Takatsukasa, Takarazuka 665-8555 (Japan); Kasuga, Masato [Division of Diabetes, Metabolism, and Endocrinology, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017 (Japan); Research Institute, International Medical Center of Japan, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655 (Japan)


    The transcriptional regulator peroxisome proliferator-activated receptor-{gamma} coactivator-1{alpha} (PGC-1{alpha}) controls mitochondrial biogenesis and energy homeostasis. Although physical exercise induces PGC-1{alpha} expression in muscle, the underlying mechanism of this effect has remained incompletely understood. We recently identified a novel muscle-enriched isoform of PGC-1{alpha} transcript (designated PGC-1{alpha}-b) that is derived from a previously unidentified first exon. We have now cloned and characterized the human PGC-1{alpha}-b promoter. The muscle-specific transcription factors MyoD and MRF4 transactivated this promoter through interaction with a proximal E-box motif. Furthermore, either forced expression of Ca{sup 2+}- and calmodulin-dependent protein kinase IV (CaMKIV), calcineurin A, or the p38 mitogen-activated protein kinase (p38 MAPK) kinase MKK6 or the intracellular accumulation of cAMP activated the PGC-1{alpha}-b promoter in cultured myoblasts through recruitment of cAMP response element (CRE)-binding protein (CREB) to a putative CRE located downstream of the E-box. Our results thus reveal a potential molecular basis for isoform-specific regulation of PGC-1{alpha} expression in contracting muscle.

  7. Suppression of estrogen receptor-alpha transactivation by thyroid transcription factor-2 in breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Park, Eunsook; Gong, Eun-Yeung [Hormone Research Center, School of Biological Sciences and Technology, Chonnam National University, Gwangju 500-757 (Korea, Republic of); Romanelli, Maria Grazia [Department of Life and Reproduction Sciences, University of Verona, Strada le Grazie 8, 37134 Verona (Italy); Lee, Keesook, E-mail: [Hormone Research Center, School of Biological Sciences and Technology, Chonnam National University, Gwangju 500-757 (Korea, Republic of)


    Highlights: Black-Right-Pointing-Pointer TTF-2 was expressed in mammary glands and breast cancer cells. Black-Right-Pointing-Pointer TTF-2 repressed ER{alpha} transactivation. Black-Right-Pointing-Pointer TTF-2 inhibited the proliferation of breast cancer cells. -- Abstract: Estrogen receptors (ERs), which mediate estrogen actions, regulate cell growth and differentiation of a variety of normal tissues and hormone-responsive tumors through interaction with cellular factors. In this study, we show that thyroid transcription factor-2 (TTF-2) is expressed in mammary gland and acts as ER{alpha} co-repressor. TTF-2 inhibited ER{alpha} transactivation in a dose-dependent manner in MCF-7 breast cancer cells. In addition, TTF-2 directly bound to and formed a complex with ER{alpha}, colocalizing with ER{alpha} in the nucleus. In MCF-7/TTF-2 stable cell lines, TTF-2 repressed the expression of endogenous ER{alpha} target genes such as pS2 and cyclin D1 by interrupting ER{alpha} binding to target promoters and also significantly decreased cell proliferation. Taken together, these data suggest that TTF-2 may modulate the function of ER{alpha} as a corepressor and play a role in ER-dependent proliferation of mammary cells.

  8. Electron acceptors based on alpha-position substituted PDI for OPV solar cells.

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Donglin; Wu, Qinghe; Cai, Zhengxu; Zheng, T; Chen, Wei; Lu, Jessica; Yu, L


    The ortho-position functionalized perylene diimide derivatives (alphaPPID, alphaPBDT) were synthesized and used as the electron acceptors in nonfullerene organic photovoltaics. Due to the good planarity of ortho-position functionalized PDI, the alphaPPID and alphaPBDT show strong tendency to form aggregate because of their enhanced intermolecular pie-pie interaction. Moreover, they maintain the pure domains and the same packing order as in the pure film if they are blended with PBT7-TH and the SCLC measurement also shows the high electron mobility. The inverted OPVs employing alphaPDI-based compounds as acceptor and PBT7-TH as the donor give the highest PCE of 4.92 % for alphaPBDT based device and 3.61 % for alphaPPID based device, which is 39 % and 4 % higher than that for their counterpart betaPBDT and betaPPID. The charge separation study shows the more efficient exciton dissociation at interfaces between PDI based compounds and PBT7-TH. The results suggest that compared to beta-substituted ones, alpha-substituted PDI derivatives are more promising electron acceptors for OPV.

  9. Further Precise Determinations of $\\alpha_s$ from Lattice QCD

    CERN Document Server

    Davies, C T H; Lepage, G P; McCallum, P; Shigemitsu, J; Sloan, J


    We present a new determination of the strong coupling constant from lattice QCD simulations. We use four different short-distance quantities to obtain the coupling, three different (infrared) meson splittings to tune the simulation parameters, and a wide range of lattice spacings, quark masses, and lattice volumes to test for systematic errors. Our final result consists of ten different determinations of $\\alpha^{(3)}_{P}(8.2 GeV)$, which agree well with each other and with our previous results. The most accurate of these, when evolved perturbatively to the $Z^0$ mass, gives obtained from other recent lattice simulations.

  10. Double-real corrections at O(alpha alpha_s) to single gauge boson production

    CERN Document Server

    Bonciani, Roberto; Mondini, Roberto; Vicini, Alessandro


    We consider the O(alpha alpha_s) corrections to single on-shell gauge boson production at hadron colliders. We concentrate on the contribution of all the subprocesses where the gauge boson is accompanied by the emission of two additional real partons and we evaluate the corresponding total cross sections. The latter are divergent quantities, because of soft and collinear emissions, and are expressed as Laurent series in the dimensional regularization parameter. The total cross sections are evaluated by means of reverse unitarity, i.e. expressing the phase-space integrals in terms of two-loop forward box integrals with cuts on the final state particles. The results are reduced to a combination of Master Integrals, which eventually are evaluated in terms of Generalized Polylogarithms. The presence of internal massive lines in the Feynman diagrams, due to the exchange of electroweak gauge bosons, causes the appearance of 14 Master Integrals which were not previously known in the literature and have been evaluate...

  11. Single universal curve for Alpha decay derived from semi-microscopic calculations


    Ismail, M.; Seif, W. M.; Ellithi, A. Y.; Abdurrahman, A


    The universal curve is one of the simple ways to get preliminary information about the Alpha-decay half-life times of heavy nuclei. We try to find parameterization for the universal curve of Alpha decay based on semi-microscopic calculations, starting from the realistic M3Y-Reid nucleon-nucleon interaction. Within the deformed density-dependent cluster model, the penetration probability and the assault frequency are calculated using the WKB penetration probability. The deformations of daughte...

  12. Absence of genotoxicity of potato alkaloids alpha-chaconine, alpha-solanine and solanidine in the Ames Salmonella and adult and foetal erythrocyte micronucleus assays. (United States)

    Friedman, M; Henika, P R


    To assess whether reported toxicities of potato-derived glycoalkaloids could be the result of interactions with cellular DNA, the genotoxic effects of alpha-solanine, alpha-chaconine and solanidine were studied, using the Ames test (Salmonella strains TA98 and TA100), the mouse peripheral blood micronucleus test and the mouse transplacental micronucleus test. The Ames test for mutagenicity with alpha-solanine was weakly positive in TA100 with S-9 activation (29 revertants per millimole per plate). However, pooled data from duplicate tests gave a negative effect. Pooled data from two experiments with alpha-chaconine gave a weak positive response in TA98 without microsomes (17 revertants per millimole per plate). The micronucleus tests for clastogenicity using male mouse and foetal blood were negative. The absence of mutagenicity and clastogenicity suggests lack of damage to intracellular DNA for potato alkaloid toxicity.

  13. Na/H exchanger regulatory factors control parathyroid hormone receptor signaling by facilitating differential activation of G(alpha) protein subunits. (United States)

    Wang, Bin; Ardura, Juan A; Romero, Guillermo; Yang, Yanmei; Hall, Randy A; Friedman, Peter A


    The Na/H exchanger regulatory factors, NHERF1 and NHERF2, are adapter proteins involved in targeting and assembly of protein complexes. The parathyroid hormone receptor (PTHR) interacts with both NHERF1 and NHERF2. The NHERF proteins toggle PTHR signaling from predominantly activation of adenylyl cyclase in the absence of NHERF to principally stimulation of phospholipase C when the NHERF proteins are expressed. We hypothesized that this signaling switch occurs at the level of the G protein. We measured G protein activation by [(35)S]GTPgammaS binding and G(alpha) subtype-specific immunoprecipitation using three different cellular models of PTHR signaling. These studies revealed that PTHR interactions with NHERF1 enhance receptor-mediated stimulation of G(alpha)(q) but have no effect on stimulation of G(alpha)(i) or G(alpha)(s). In contrast, PTHR associations with NHERF2 enhance receptor-mediated stimulation of both G(alpha)(q) and G(alpha)(i) but decrease stimulation of G(alpha)(s). Consistent with these functional data, NHERF2 formed cellular complexes with both G(alpha)(q) and G(alpha)(i), whereas NHERF1 was found to interact only with G(alpha)(q). These findings demonstrate that NHERF interactions regulate PTHR signaling at the level of G proteins and that NHERF1 and NHERF2 exhibit isotype-specific effects on G protein activation.

  14. Scale setting for alpha_s beyond leading order

    CERN Document Server

    Hornbostel, K; Morningstar, C J


    We present a general procedure for incorporating higher-order information into the scale-setting prescription of Brodsky, Lepage and Mackenzie. In particular, we show how to apply this prescription when the leading coefficient or coefficients in a series in the strong coupling alpha_s are anomalously small and the original prescription can give an unphysical scale. We give a general method for computing an optimum scale numerically, within dimensional regularization, and in cases when the coefficients of a series are known. We apply it to the heavy quark mass and energy renormalization in lattice NRQCD, and to a variety of known series. Among the latter, we find significant corrections to the scales for the ratio of e+e- to hadrons over muons, the ratio of the quark pole to MSbar mass, the semi-leptonic B-meson decay width, and the top decay width. Scales for the latter two decay widths, expressed in terms of MSbar masses, increase by factors of five and thirteen, respectively, substantially reducing the size...

  15. Recoil-alpha-fission and recoil-alpha-alpha-fission events observed in the reaction Ca-48 + Am-243

    CERN Document Server

    Forsberg, U; Andersson, L -L; Di Nitto, A; Düllmann, Ch E; Gates, J M; Golubev, P; Gregorich, K E; Gross, C J; Herzberg, R -D; Hessberger, F P; Khuyagbaatar, J; Kratz, J V; Rykaczewski, K; Sarmiento, L G; Schädel, M; Yakushev, A; Åberg, S; Ackermann, D; Block, M; Brand, H; Carlsson, B G; Cox, D; Derkx, X; Dobaczewski, J; Eberhardt, K; Even, J; Fahlander, C; Gerl, J; Jäger, E; Kindler, B; Krier, J; Kojouharov, I; Kurz, N; Lommel, B; Mistry, A; Mokry, C; Nazarewicz, W; Nitsche, H; Omtvedt, J P; Papadakis, P; Ragnarsson, I; Runke, J; Schaffner, H; Schausten, B; Shi, Y; Thörle-Pospiech, P; Torres, T; Traut, T; Trautmann, N; Türler, A; Ward, A; Ward, D E; Wiehl, N


    Products of the fusion-evaporation reaction Ca-48 + Am-243 were studied with the TASISpec set-up at the gas-filled separator TASCA at the GSI Helmholtzzentrum f\\"ur Schwerionenforschung. Amongst the detected thirty correlated alpha-decay chains associated with the production of element Z=115, two recoil-alpha-fission and five recoil-alpha-alpha-fission events were observed. The latter are similar to four such events reported from experiments performed at the Dubna gas-filled separator. Contrary to their interpretation, we propose an alternative view, namely to assign eight of these eleven decay chains of recoil-alpha(-alpha)-fission type to start from the 3n-evaporation channel 115-288. The other three decay chains remain viable candidates for the 2n-evaporation channel 115-289.

  16. The Alpha Magnetic Spectrometer (AMS)

    Energy Technology Data Exchange (ETDEWEB)

    Alcaraz, J.; Alpat, B.; Ambrosi, G.; Anderhub, H.; Ao, L.; Arefiev, A.; Azzarello, P.; Babucci, E.; Baldini, L.; Basile, M.; Barancourt, D.; Barao, F.; Barbier, G.; Barreira, G.; Battiston, R.; Becker, R.; Becker, U.; Bellagamba, L.; Bene, P.; Berdugo, J.; Berges, P.; Bertucci, B.; Biland, A.; Bizzaglia, S.; Blasko, S.; Boella, G.; Boschini, M.; Bourquin, M.; Brocco, L.; Bruni, G.; Buenerd, M.; Burger, J.D.; Burger, W.J.; Cai, X.D.; Camps, C.; Cannarsa, P.; Capell, M.; Casadei, D.; Casaus, J.; Castellini, G.; Cecchi, C.; Chang, Y.H.; Chen, H.F.; Chen, H.S.; Chen, Z.G.; Chernoplekov, N.A.; Chiueh, T.H.; Chuang, Y.L.; Cindolo, F.; Commichau, V.; Contin, A. E-mail:; Crespo, P.; Cristinziani, M.; Cunha, J.P. da; Dai, T.S.; Deus, J.D.; Dinu, N.; Djambazov, L.; DAntone, I.; Dong, Z.R.; Emonet, P.; Engelberg, J.; Eppling, F.J.; Eronen, T.; Esposito, G.; Extermann, P.; Favier, J.; Fiandrini, E.; Fisher, P.H.; Fluegge, G.; Fouque, N.; Galaktionov, Yu.; Gervasi, M.; Giusti, P.; Grandi, D.; Grimm, O.; Gu, W.Q.; Hangarter, K.; Hasan, A.; Hermel, V.; Hofer, H.; Huang, M.A.; Hungerford, W.; Ionica, M.; Ionica, R.; Jongmanns, M.; Karlamaa, K.; Karpinski, W.; Kenney, G.; Kenny, J.; Kim, W.; Klimentov, A.; Kossakowski, R.; Koutsenko, V.; Kraeber, M.; Laborie, G.; Laitinen, T.; Lamanna, G.; Laurenti, G.; Lebedev, A.; Lee, S.C.; Levi, G.; Levtchenko, P.; Liu, C.L.; Liu, H.T.; Lopes, I.; Lu, G.; Lu, Y.S.; Luebelsmeyer, K.; Luckey, D.; Lustermann, W.; Mana, C.; Margotti, A.; Mayet, F.; McNeil, R.R.; Meillon, B.; Menichelli, M.; Mihul, A.; Mourao, A.; Mujunen, A.; Palmonari, F.; Papi, A.; Park, I.H.; Pauluzzi, M.; Pauss, F.; Perrin, E.; Pesci, A.; Pevsner, A.; Pimenta, M.; Plyaskin, V.; Pojidaev, V.; Postolache, V.; Produit, N.; Rancoita, P.G.; Rapin, D.; Raupach, F.; Ren, D.; Ren, Z.; Ribordy, M.; Richeux, J.P.; Riihonen, E.; Ritakari, J.; Roeser, U.; Roissin, C.; Sagdeev, R.; Sartorelli, G.; Schultz von Dratzig, A.; Schwering, G.; Scolieri, G.; Seo, E.S.; Shoutko, V.


    The Alpha Magnetic Spectrometer (AMS) is a large acceptance (0.65 sr m{sup 2}) detector designed to operate in the International Space Station (ISS) for three years. The purposes of the experiment are to search for cosmic antimatter and dark matter and to study the composition and energy spectrum of the primary cosmic rays. A 'scaled-down' version has been flown on the Space Shuttle Discovery for 10 days in June 1998. The complete AMS is programmed for installation on the ISS in October 2003 for an operational period of 3 yr. This contribution reports on the experimental configuration that will be installed on the ISS.

  17. The Alpha Magnetic Spectrometer (AMS)

    CERN Document Server

    Alcaraz, J; Ambrosi, G; Anderhub, H; Ao, L; Arefev, A; Azzarello, P; Babucci, E; Baldini, L; Basile, M; Barancourt, D; Barão, F; Barbier, G; Barreira, G; Battiston, R; Becker, R; Becker, U; Bellagamba, L; Bene, P; Berdugo, J; Berges, P; Bertucci, B; Biland, A; Bizzaglia, S; Blasko, S; Bölla, G; Boschini, M; Bourquin, Maurice; Brocco, L; Bruni, G; Buénerd, M; Burger, J D; Burger, W J; Cai, X D; Camps, C; Cannarsa, P; Capell, M; Casadei, D; Casaus, J; Castellini, G; Cecchi, C; Chang, Y H; Chen, H F; Chen, H S; Chen, Z G; Chernoplekov, N A; Tzi Hong Chiueh; Chuang, Y L; Cindolo, F; Commichau, V; Contin, A; Crespo, P; Cristinziani, M; Cunha, J P D; Dai, T S; Deus, J D; Dinu, N; Djambazov, L; Dantone, I; Dong, Z R; Emonet, P; Engelberg, J; Eppling, F J; Eronen, T; Esposito, G; Extermann, P; Favier, Jean; Fiandrini, E; Fisher, P H; Flügge, G; Fouque, N; Galaktionov, Yu; Gervasi, M; Giusti, P; Grandi, D; Grimm, O; Gu, W Q; Hangarter, K; Hasan, A; Hermel, V; Hofer, H; Huang, M A; Hungerford, W; Ionica, M; Ionica, R; Jongmanns, M; Karlamaa, K; Karpinski, W; Kenney, G; Kenny, J; Kim, W; Klimentov, A; Kossakowski, R; Koutsenko, V F; Kraeber, M; Laborie, G; Laitinen, T; Lamanna, G; Laurenti, G; Lebedev, A; Lee, S C; Levi, G; Levchenko, P M; Liu, C L; Liu, H T; Lopes, I; Lu, G; Lü, Y S; Lübelsmeyer, K; Luckey, D; Lustermann, W; Maña, C; Margotti, A; Mayet, F; McNeil, R R; Meillon, B; Menichelli, M; Mihul, A; Mourao, A; Mujunen, A; Palmonari, F; Papi, A; Park, I H; Pauluzzi, M; Pauss, Felicitas; Perrin, E; Pesci, A; Pevsner, A; Pimenta, M; Plyaskin, V; Pozhidaev, V; Postolache, V; Produit, N; Rancoita, P G; Rapin, D; Raupach, F; Ren, D; Ren, Z; Ribordy, M; Richeux, J P; Riihonen, E; Ritakari, J; Röser, U; Roissin, C; Sagdeev, R; Sartorelli, G; Schwering, G; Scolieri, G; Seo, E S; Shoutko, V; Shoumilov, E; Siedling, R; Son, D; Song, T; Steuer, M; Sun, G S; Suter, H; Tang, X W; Ting, Samuel C C; Ting, S M; Tornikoski, M; Torsti, J; Ulbricht, J; Urpo, S; Usoskin, I; Valtonen, E; Vandenhirtz, J; Velcea, F; Velikhov, E P; Verlaat, B; Vetlitskii, I; Vezzu, F; Vialle, J P; Viertel, Gert M; Vitè, Davide F; Gunten, H V; Wallraff, W; Wang, B C; Wang, J Z; Wang, Y H; Wiik, K; Williams, C; Wu, S X; Xia, P C; Yan, J L; Yan, L G; Yang, C G; Yang, M; Ye, S W; Yeh, P; Xu, Z Z; Zhang, H Y; Zhang, Z P; Zhao, D X; Zhu, G Y; Zhu, W Z; Zhuang, H L; Zichichi, A; Zimmermann, B


    The Alpha Magnetic Spectrometer (AMS) is a large acceptance (0.65 sr m sup 2) detector designed to operate in the International Space Station (ISS) for three years. The purposes of the experiment are to search for cosmic antimatter and dark matter and to study the composition and energy spectrum of the primary cosmic rays. A 'scaled-down' version has been flown on the Space Shuttle Discovery for 10 days in June 1998. The complete AMS is programmed for installation on the ISS in October 2003 for an operational period of 3 yr. This contribution reports on the experimental configuration that will be installed on the ISS.

  18. Targeted alpha therapy for cancer

    Energy Technology Data Exchange (ETDEWEB)

    Allen, Barry J [Centre for Experimental Radiation Oncology, St George Cancer Care Centre, Gray St, Kogarah 2217, NSW (Australia); Raja, Chand [Centre for Experimental Radiation Oncology, St George Cancer Care Centre, Gray St, Kogarah 2217, NSW (Australia); Rizvi, Syed [Centre for Experimental Radiation Oncology, St George Cancer Care Centre, Gray St, Kogarah 2217, NSW (Australia); Li Yong [Centre for Experimental Radiation Oncology, St George Cancer Care Centre, Gray St, Kogarah 2217, NSW (Australia); Tsui, Wendy [Centre for Experimental Radiation Oncology, St George Cancer Care Centre, Gray St, Kogarah 2217, NSW (Australia); Zhang, David [Centre for Experimental Radiation Oncology, St George Cancer Care Centre, Gray St, Kogarah 2217, NSW (Australia); Song, Emma [Centre for Experimental Radiation Oncology, St George Cancer Care Centre, Gray St, Kogarah 2217, NSW (Australia); Qu, C F [Centre for Experimental Radiation Oncology, St George Cancer Care Centre, Gray St, Kogarah 2217, NSW (Australia); Kearsley, John [Centre for Experimental Radiation Oncology, St George Cancer Care Centre, Gray St, Kogarah 2217, NSW (Australia); Graham, Peter [Centre for Experimental Radiation Oncology, St George Cancer Care Centre, Gray St, Kogarah 2217, NSW (Australia); Thompson, John [Sydney Melanoma Unit, Royal Prince Alfred Hospital, Camperdown 2050 NSW (Australia)


    Targeted alpha therapy (TAT) offers the potential to inhibit the growth of micrometastases by selectively killing isolated and preangiogenic clusters of cancer cells. The practicality and efficacy of TAT is tested by in vitro and in vivo studies in melanoma, leukaemia, colorectal, breast and prostate cancers, and by a phase 1 trial of intralesional TAT for melanoma. The alpha-emitting radioisotope used is Bi-213, which is eluted from the Ac-225 generator and chelated to a cancer specific monoclonal antibody (mab) or protein (e.g. plasminogen activator inhibitor-2 PAI2) to form the alpha-conjugate (AC). Stable alpha-ACs have been produced which have been tested for specificity and cytotoxicity in vitro against melanoma (9.2.27 mab), leukaemia (WM60), colorectal (C30.6), breast (PAI2, herceptin), ovarian (PAI2, herceptin, C595), prostate (PAI2, J591) and pancreatic (PAI2, C595) cancers. Subcutaneous inoculation of 1-1.5 million human cancer cells into the flanks of nude mice causes tumours to grow in all mice. Tumour growth is compared for untreated controls, nonspecific AC and specific AC, for local (subcutaneous) and systemic (tail vein or intraperitoneal) injection models. The {sup 213}Bi-9.2.27 AC is injected into secondary skin melanomas in stage 4 patients in a dose escalation study to determine the effective tolerance dose, and to measure kinematics to obtain the equivalent dose to organs. In vitro studies show that TAT is one to two orders of magnitude more cytotoxic to targeted cells than non-specific ACs, specific beta emitting conjugates or free isotopes. In vivo local TAT at 2 days post-inoculation completely prevents tumour formation for all cancers tested so far. Intra-lesional TAT can completely regress advanced sc melanoma but is less successful for breast and prostate cancers. Systemic TAT inhibits the growth of sc melanoma xenografts and gives almost complete control of breast and prostate cancer tumour growth. Intralesional doses up to 450 {mu

  19. Crossing symmetry in Alpha space

    CERN Document Server

    CERN. Geneva


    The conformal bootstrap program aims to catalog all conformal field theories (second-order phase transitions) in D dimensions. Despite its ambitious scope much progress has been made over the past decade, e.g. in computing critical exponents for the 3D O(N) models to high precision. At this stage, analytic methods to explore the CFT landscape are not as well developed. In this talk I will describe a new mathematical framework for the bootstrap known as "alpha space", which reduces crossing symmetry to a set of integral equations. Based on arXiv:1702.08471 (with Balt van Rees) and arXiv:1703.08159.

  20. Linearized Bekenstein Varying Alpha Models

    CERN Document Server

    Pina-Avelino, P; Oliveira, J C


    We study the simplest class of Bekenstein-type, varying $\\alpha$ models, in which the two available free functions (potential and gauge kinetic function) are Taylor-expanded up to linear order. Any realistic model of this type reduces to a model in this class for a certain time interval around the present day. Nevertheless, we show that no such model is consistent with all existing observational results. We discuss possible implications of these findings, and in particular clarify the ambiguous statement (often found in the literature) that ``the Webb results are inconsistent with Oklo''.

  1. Patterns of secretion of transforming growth factor-alpha (TGF-alpha) in experimental silicosis. Acute and subacute effects of cristobalite exposure in the rat. (United States)

    Absher, M; Sjöstrand, M; Baldor, L C; Hemenway, D R; Kelley, J


    Transforming growth factor-alpha (TGF-alpha) a cytokine having potent mitogenic activity for epithelial and mesenchymal cells, may play a role in the lung remodeling of silicosis. Lung macrophages are among the major cells producing TGF-alpha in a lung tissue. A pivotal event in the cascade of pathologic events leading to pulmonary silicosis is the interaction between inhaled silica and macrophages. TGF-alpha may be critical in directing the proliferation of type II pneumocytes that characterize silicosis. An inhalation model of brief exposure of pathogen-restricted male rats to 25 mg/M3 cristobalite, a highly reactive form of silicon dioxide was used to study experimental silicosis. This model is characterized by a rapid, intense, and sustained increase in macrophages, neutrophils, and lymphocytes in both alveolar and interstitial compartments of the lung. TGF-alpha was measured in an A431 cell proliferation assay made specific with the use of anti-TGF-alpha neutralizing antiserum in epithelial lining fluid (ELF) and conditioned media harvested from cultured alveolar and interstitial macrophages. Soluble TGF-alpha levels found in ELF were slightly elevated above control values during the exposure period, then increased 5-fold during the 20 weeks after the 8-day exposure period. Secretion of TGF-alpha by macrophages was elevated during exposure to cristobalite but then fell during the early post exposure period. Marked elevations in TGF-alpha secretion from both interstitial and alveolar macrophages (10- and 12-fold, respectively) occurred 8-16 weeks after cessation of exposure.(ABSTRACT TRUNCATED AT 250 WORDS)

  2. Study of the Alpha-Decay Chain for7753 194Rn with Relativistic Mean-Field Theory

    Institute of Scientific and Technical Information of China (English)

    SHENG Zong-Qiang; GUO Jian-You


    The structures of the nuclei on the alpha-decay chain of 194Rn are investigated in the deformed relativistic mean-field theory with the effective interaction TMA. We put an emphasis on the ground state properties of 194Rn. The calculated alpha-decay energies and lifetimes are both very close to the experimental data for 186pb and 190po. For 194 Rn, the deviations are a little large on both the alpha-decay energy and the lifetime. We also calculate the alpha-decay energies for the isotopes 192~208Rn. The tendency for the change of the alpha-decay energies with neutron number is correctly reproduced in the relativistic mean-field theory (RMF). In general, the RMF theory can give a good description of the alpha decay chain of 194Rn.

  3. Orthopositronium lifetime at O({alpha}) and O({alpha}{sup 3} ln {alpha}) in closed form

    Energy Technology Data Exchange (ETDEWEB)

    Kniehl, B.A.; Kotikov, A.V.; Veretin, O.L. [Hamburg Univ. (Germany). 2. Inst. fuer Theoretische Physik


    Recently, the O({alpha}) and O({alpha}{sup 3} ln{alpha}) radiative corrections to the orthopositronium lifetime have been presented in closed analytical form, in terms of basic irrational numbers that can be evaluated numerically to arbitrary precision [Phys. Rev. Lett. 101, 193401 (2008)]. Here, we present the details of this calculation and reveal the nature of these new constants. We also list explicit transformation formulas for generalized polylogarithms of weight four, which may be useful for other applications. (orig.)

  4. Identification of alpha 2-adrenergic receptor sites in human retinoblastoma (Y-79) and neuroblastoma (SH-SY5Y) cells

    Energy Technology Data Exchange (ETDEWEB)

    Kazmi, S.M.; Mishra, R.K.


    The existence of specific alpha 2-adrenergic receptor sites has been shown in human retinoblastoma (Y-79) and neuroblastoma (SH-SH5Y) cells using direct radioligand binding. (/sup 3/H)Rauwolscine, a selective alpha 2-adrenergic receptor antagonist, exhibited high affinity, saturable binding to both Y-79 and SH-SY5Y cell membranes. The binding of alpha 1 specific antagonist, (/sup 3/H)Prazocine, was not detectable in either cell type. Competition studies with antagonists yielded pharmacological characteristics typical of alpha 2-adrenergic receptors: rauwolscine greater than yohimbine greater than phentolamine greater than prazocine. Based on the affinity constants of prazocine and oxymetazoline, it appears that Y-79 cells contain alpha 2A receptor, whereas SH-SY5Y cells probably represent a mixture of alpha 2A and alpha 2B receptors. alpha 2-agonists clonidine and (-)epinephrine inhibition curves yielded high and low affinity states of the receptor in SH-SY5Y cells. Gpp(NH)p and sodium ions reduced the proportion of high affinity sites of alpha 2 receptors. These two neuronal cell lines of human origin would prove useful in elucidating the action and regulation of human alpha 2-adrenergic receptors and their interaction with other receptor systems.

  5. Karyopherin alpha2: a control step of glucose-sensitive gene expression in hepatic cells. (United States)

    Guillemain, Ghislaine; Muñoz-Alonso, Maria J; Cassany, Aurélia; Loizeau, Martine; Faussat, Anne-Marie; Burnol, Anne-Françoise; Leturque, Armelle


    Glucose is required for an efficient expression of the glucose transporter GLUT2 and other genes. We have shown previously that the intracytoplasmic loop of GLUT2 can divert a signal, resulting in the stimulation of glucose-sensitive gene transcription. In the present study, by interaction with the GLUT2 loop, we have cloned the rat karyopherin alpha2, a receptor involved in nuclear import. The specificity of the binding was restricted to GLUT2, and not GLUT1 or GLUT4, and to karyopherin alpha2, not alpha1. When rendered irreversible by a cross-linking agent, this transitory interaction was detected in vivo in hepatocytes. A role for karyopherin alpha2 in the transcription of two glucose-sensitive genes was investigated by transfection of native and inactive green fluorescent protein-karyopherin alpha2 in GLUT2-expressing hepatoma cells. The amount of inactive karyopherin alpha2 receptor reduced, in a dose-dependent manner, the GLUT2 and liver pyruvate kinase mRNA levels by competition with endogenous active receptor. In contrast, the overexpression of karyopherin alpha2 did not significantly stimulate GLUT2 and liver pyruvate kinase mRNA accumulation in green fluorescent protein-sorted cells. The present study suggests that, in concert with glucose metabolism, karyopherin alpha2 transmits a signal to the nucleus to regulate glucose-sensitive gene expression. The transitory tethering of karyopherin alpha2 to GLUT2 at the plasma membrane might indicate that the receptor can load the cargo to be imported locally.

  6. Alpha radioactivity in tobacco leaves: Effect of fertilizers

    Energy Technology Data Exchange (ETDEWEB)

    Nain, Mahabir [Department of Physics, Government College Karnal, Haryana 132001 (India)], E-mail:; Chauhan, R.P. [Department of Physics, National Institute of Technology, Kurukshetra 136119 (India); Chakarvarti, S.K. [Department of Applied Physics, NIT, Kurukshetra 136119 (India)


    The link between cigarette smoke and cancer has long been established. Smokers are 10 times at a greater risk of developing lung cancer than that of non-smokers. The toxicity in tobacco is considered mainly due to the presence of chemi-toxins like nicotine, tar, aromatic hydrocarbons, sterols and many other materials leading to mutagenicity and carcinogenicity. There are many reports on the presence of naturally occurring radionuclides viz., {sup 210}Po and {sup 210}Pb in tobacco. Investigations on alpha-emitting radionuclides, especially on {sup 210}Po have gained significant importance as alpha interactions with chromosomes of cells may contribute to early arteriosclerosis developments in tobacco smokers. Due to relatively high activity concentration of {sup 210}Po and {sup 210}Pb that are found in tobacco and its product cigarette can increase the internal intake of both the radionuclides and their concentrations in lung tissues. This causes an increase in the internal radiation dose which enhances the instances of lung cancer. Many workers have tried to explain the role of {sup 210}Po in tobacco in the epidemiological investigation of cancer and tumour formation. In the present work, the estimation of alpha radioactivity in tobacco leaves taken from tobacco plants grown using different types of chemical fertilizers like diammonium phosphate (DAP), zinc sulphate, potash, super phosphate, urea etc. in varying amounts before the plantation of the seedlings has been made. For these measurements we used {alpha}-sensitive LR-115 type II plastic track detectors. The results indicate an increase in alpha radioactivity with the use of some fertilizers.

  7. Selective sorting of alpha-granule proteins. (United States)

    Italiano, J E; Battinelli, E M


    One of the main functions of blood platelets is to secrete a variety of substances that can modify a developing thrombus, regulate the growth of the vasculature, promote wound repair, and contribute to cell-adhesive events. A majority of this vast array of secreted proteins are stored in alpha-granules. Until recently, it was assumed that platelets contained one homogeneous population of alpha-granules that undergo complete de-granulation during platelet activation. This review focuses on the mechanisms of alpha-granule biogenesis and secretion, with a particular emphasis on recent findings that clearly demonstrate that platelets contain distinct subpopulations of alpha-granules that undergo differential release during activation. We consider the implications of this new paradigm of platelet secretion, discuss mechanisms of alpha-granule biogenesis, and review the molecular basis of transport and delivery of alpha-granules to assembling platelets.

  8. GTP synthases. Proton pumping and phosphorylation in ligand-receptor-G alpha-protein complexes. (United States)

    Nederkoorn, P H; Timmerman, H; Donné-Op Den Kelder, G M; Timms, D; Wilkinson, A J; Kelly, D R; Broadley, K J; Davies, R H


    A structural model for a ligand-receptor-Gs alpha-protein complex to function as a GTP synthase is presented. The mechanism which is dependent on the movement and rotation of the G alpha-protein alpha 2-helix is seen to involve the delivery of, at least, one proton to the phosphorylation site in the rotation of this helix. The cycle is driven by a ligand-mediated proton pump through the alpha-helices of the receptor, attachment of the conserved Tyr-Arg-Tyr receptor proton shuttle being made to an aspartate group on the Gs alpha-protein terminal sidechain, which is itself linked to the Asn-Gln interaction known to control movement and rotation of the alpha 2-helix between .GDP and .GTP structures. The energetics of proton transfer through the shuttle mechanism and delivery of a proton to the aspartate group are shown to be sufficient to rupture this controlling interaction and its associated backbone bond. The complex leads to full spatial and energetic definition of the receptor proton shuttle mechanism, while there is a striking association of further Tyrosine and Arginine residues in the vicinity of the Gs alpha-protein Asn-Gln interaction. Calculations at the HF 6-31G** level confirm that a critical balance between ion pair and neutral forms of Tyr-Arg interactions under multiply hydrogen bonded conditions in a hydrophobic environment controls proton transfer and recovery mechanisms. The intrinsic preference of the neutral Tyr-Arg form over the ion-pair is 14.0 kcal/mol. Activation of the Tyrosine oxygen atom in the neutral form by single-NH or -OH groups reduces this difference by some 6.4-8.6 kcal/mol but the dominance of the neutral form is maintained. The expected slight overestimates are consistent with the maximum activation enthalpy of 11.0-12.0 kcal/ mol required to initiate proton transfer through the shuttle. The extended form of the shuttle with the Arginine acting competitively between the two Tyrosine residues allows interpretation of observed

  9. Alpha-synuclein association with phosphatidylglycerol probed by lipid spin labels. (United States)

    Ramakrishnan, Muthu; Jensen, Poul H; Marsh, Derek


    Alpha-synuclein is a small presynaptic protein, which is linked to the development of Parkinson's disease. Alpha-synuclein partitions between cytosolic and vesicle-bound states, where membrane binding is accompanied by the formation of an amphipathic helix in the N-terminal section of the otherwise unstructured protein. The impact on alpha-synuclein of binding to vesicle-like liposomes has been studied extensively, but far less is known about the impact of alpha-synuclein on the membrane. The interactions of alpha-synuclein with phosphatidylglycerol membranes are studied here by using spin-labeled lipid species and electron spin resonance (ESR) spectroscopy to allow a detailed analysis of the effect on the membrane lipids. Membrane association of alpha-synuclein perturbs the ESR spectra of spin-labeled lipids in bilayers of phosphatidylglycerol but not of phosphatidylcholine. The interaction is inhibited at high ionic strength. The segmental motion is hindered at all positions of spin labeling in the phosphatidylglycerol sn-2 chain, while still preserving the chain flexibility gradient characteristic of fluid phospholipid membranes. Direct motional restriction of the lipid chains, resulting from penetration of the protein into the hydrophobic interior of the membrane, is not observed. Saturation occurs at a protein/lipid ratio corresponding to approximately 36 lipids/protein added. Alpha-synuclein exhibits a selectivity of interaction with different phospholipid spin labels when bound to phosphatidylglycerol membranes in the following order: stearic acid > cardiolipin > phosphatidylcholine > phosphatidylglycerol approximately phosphatidylethanolamine > phosphatidic acid approximately phosphatidylserine > N-acyl phosphatidylethanolamine > diglyceride. Accordingly, membrane-bound alpha-synuclein associates at the interfacial region of the bilayer where it may favor a local concentration of certain phospholipids.

  10. Morphological characterization of the AlphaA- and AlphaB-crystallin double knockout mouse lens

    Directory of Open Access Journals (Sweden)

    Brady James P


    Full Text Available Abstract Background One approach to resolving some of the in vivo functions of alpha-crystallin is to generate animal models where one or both of the alpha-crystallin gene products have been eliminated. In the single alpha-crystallin knockout mice, the remaining alpha-crystallin may fully or partially compensate for some of the functions of the missing protein, especially in the lens, where both alphaA and alphaB are normally expressed at high levels. The purpose of this study was to characterize gross lenticular morphology in normal mice and mice with the targeted disruption of alphaA- and alphaB-crystallin genes (alphaA/BKO. Methods Lenses from 129SvEvTac mice and alphaA/BKO mice were examined by standard scanning electron microscopy and confocal microscopy methodologies. Results Equatorial and axial (sagittal dimensions of lenses for alphaA/BKO mice were significantly smaller than age-matched wild type lenses. No posterior sutures or fiber cells extending to the posterior capsule of the lens were found in alphaA/BKO lenses. Ectopical nucleic acid staining was observed in the posterior subcapsular region of 5 wk and anterior subcapsular cortex of 54 wk alphaA/BKO lenses. Gross morphological differences were also observed in the equatorial/bow, posterior and anterior regions of lenses from alphaA/BKO mice as compared to wild mice. Conclusion These results indicated that both alphaA- and alphaB-crystallin are necessary for proper fiber cell formation, and that the absence of alpha-crystallin can lead to cataract formation.

  11. The alpha,alpha-(1-->1) linkage of trehalose is key to anhydrobiotic preservation. (United States)

    Albertorio, Fernando; Chapa, Vanessa A; Chen, Xin; Diaz, Arnaldo J; Cremer, Paul S


    This study compares the efficacy of six disaccharides and glucose for the preservation of solid supported lipid bilayers (SLBs) upon exposure to air. Disaccharide molecules containing an alpha,alpha-(1-->1) linkage, such as alpha,alpha-trehalose and alpha,alpha-galacto-trehalose, were found to be effective at retaining bilayer structure in the absence of water. These sugars are known to crystallize in a clam shell conformation. Other saccharides, which are found to crystallize in more open structures, did not preserve the SLB structure during the drying process. These included the nonreducing sugar, sucrose, as well as maltose, lactose, and the monosaccharide, glucose. In fact, even close analogs to alpha,alpha-trehalose, such as alpha,beta-trehalose, which connects its glucopyranose rings via a (1-->1) linkage in an axial, equatorial fashion, permitted nearly complete delamination and destruction of supported bilayers upon exposure to air. Lipids with covalently attached sugar molecules such as ganglioside GM1, lactosyl phosphatidylethanolamine, and glucosylcerebroside were also ineffective at preserving bilayer structure. The liquid crystalline-to-gel phase transition temperature of supported phospholipid bilayers was tested in the presence of sugars in a final set of experiments. Only alpha,alpha-trehalose and alpha,alpha-galacto-trehalose depressed the phase transition temperature, whereas the introduction of other sugar molecules into the bulk solution caused the phase transition temperature of the bilayer to increase. These results point to the importance of the axial-axial linkage of disaccharides for preserving SLB structure.

  12. Quantum Estimates of Alpha Emitter Life Time

    Directory of Open Access Journals (Sweden)

    B. Santoso


    Full Text Available Quantum estimates of several alpha radioactive life time have been made using the probability of quantum tunneling through the nuclear potential barrier. It is assumed that for a given nucleus with mass number A and isotopic number Z, there exists an alpha particle moving freely back and forth in the nucleus with mass and isotopic numbers A -4 and Z-2. If the probability of penetrating the nuclear potential barrier is Τ, then after N times (N=1/Τ hitting the barrier an alpha particle is emitted. To obtain the elapsed time for emitting an alpha particle requires N times τ0, where τ0 is the time travel for alpha across the nuclear diameter, which is dependent on alpha energy. It is assumed here that this kinetic energy is the same as the emitted energy. The emitting alpha kinetic energies here are calculated by the difference of the masses of the parent and daughter nuclei and the alpha particles. They are in closed agreement with the experimental observations. While the alpha radioactive life time are not the same order of magnitudes but give the same linearity on the logarithmic scale as function of the inverse square root of energy.

  13. Inhibition of MAP kinase promotes the recruitment of corepressor SMRT by tamoxifen-bound estrogen receptor alpha and potentiates tamoxifen action in MCF-7 cells

    Energy Technology Data Exchange (ETDEWEB)

    Hong, Wei, E-mail: [Department of Immunology, Tianjin Medical University, 300070 Tianjin (China); Department of Laboratory Medicine, Tianjin Medical University, 300070 Tianjin (China); Chen, Linfeng [Department of Medical Oncology, Harvard Medical School, Dana Farber Cancer Institute, Boston, 02115 MA (United States); Li, Juan [Department of Laboratory Medicine, Tianjin Medical University, 300070 Tianjin (China); Yao, Zhi [Department of Immunology, Tianjin Medical University, 300070 Tianjin (China)


    Estrogen receptor alpha (ER{alpha}), a ligand controlled transcription factor, plays an important role in breast cancer growth and endocrine therapy. Tamoxifen (TAM) antagonizes ER{alpha} activity and has been applied in breast cancer treatment. TAM-bound ER{alpha} associates with nuclear receptor-corepressors. Mitogen-activated protein kinase (MAPK) has been elucidated to result in cross-talk between growth factor and ER{alpha} mediated signaling. We show that activated MAPK represses interaction of TAM-bound ER{alpha} with silencing mediator for retinoid and thyroid hormone receptors (SMRT) and inhibits the recruitment of SMRT by ER{alpha} to certain estrogen target genes. Blockade of MAPK signaling cascade with MEK inhibitor U0126 promotes the interaction and subsequently inhibits ER{alpha} activity via enhanced recruitment of SMRT, leading to reduced expression of ER{alpha} target genes. The growth rate of MCF-7 cells was decelerated when treated with both TAM and U0126. Moreover, the growth of MCF-7 cells stably expressing SMRT showed a robust repression in the presence of TAM and U0126. These results suggest that activated MAPK signaling cascade attenuates antagonist-induced recruitment of SMRT to ER{alpha}, suggesting corepressor mediates inhibition of ER{alpha} transactivation and breast cancer cell growth by antagonist. Taken together, our finding indicates combination of antagonist and MAPK inhibitor could be a helpful approach for breast cancer therapy.

  14. $\\alpha_{s}$ from the (revised) ALEPH data for $\\tau$ decay

    CERN Document Server

    Boito, Diogo; Maltman, Kim; Osborne, James; Peris, Santiago


    We present a new analysis of $\\alpha_s$ from hadronic $\\tau$ decays based on the recently revised ALEPH data. The analysis is based on a strategy which we previously applied to the OPAL data. We critically compare our strategy to the one traditionally used and comment on the main differences. Our analysis yields the values $\\alpha_s(m_\\tau^2)=0.296\\pm 0.010$ using fixed-order perturbation theory, and $\\alpha_s(m_\\tau^2)=0.310\\pm 0.014$ using contour-improved perturbation theory. Averaging these values with our previously obtained values from the OPAL data, we find $\\alpha_s(m_\\tau^2)=0.303\\pm 0.009$, respectively, $\\alpha_s(m_\\tau^2)=0.319\\pm 0.012$, as the most reliable results for $\\alpha_s$ from $\\tau$ decays currently available.

  15. Role of macrophage inflammatory protein-1 alpha (MIP-1 alpha) in acute lung injury in rats

    DEFF Research Database (Denmark)

    Shanley, T P; Schmal, H; Friedl, H P


    The role of macrophage inflammatory protein-1 alpha (MIP-1 alpha) in the pathogenesis of acute lung injury in rats after intrapulmonary deposition of IgG immune complexes or intratracheal administration of LPS has been assessed. Critical to these studies was the cloning and functional expression...... of rat MIP-1 alpha. The resulting product shared 92% and 90% homology with the known murine sequence at the cDNA level and protein level, respectively. Recombinant rat MIP-1 alpha exhibited dose-dependent chemotactic activity for both rat and human monocytes and neutrophils, which could be blocked...... by anti-murine MIP-1 alpha Ab. Rat MIP-1 alpha mRNA and protein expression were determined as a function of time in both injury models. A time-dependent increase in MIP-1 alpha mRNA in lung extracts was observed in both models. In the LPS model, MIP-1 alpha protein could also be detected...

  16. Synergism between the potato glycoalkaloids alpha-chaconine and alpha-solanine in inhibition of snail feeding. (United States)

    Smith, D B; Roddick, J G; Jones, J L


    Snails (Helix aspersa L.) were fed filter paper treated with the potato glycoalkaloids, alpha-solanine and alpha-chaconine, singly or together. In pure form, both glycoalkaloids deterred feeding, with chaconine being the more active compound. In combination, authentic solanine and chaconine interacted synergistically in their inhibition of feeding. The antifeedant activities of methanolic extracts of tuber peel of the potato varieties Majestic and Sharpe's Express presented via filter paper discs did not differ significantly from those of authentic glycoalkaloid solutions of comparable concentration and ratio. In contrast, feeding inhibition by diluted tuber peel extracts of the variety Homeguard was greater than that elicited by comparable authentic glycoalkaloid solutions suggesting additional inhibitory compound(s) in the peel of this variety. Comparison of data from peel extracts of all three potato varieties and authentic glycoalkaloids indicated that the level of feeding inhibition by the extracts was, at least in part, a consequence of a synergism between solanine and chaconine.

  17. Carbohydrate composition of the alpha-subunit of human choriogonadotropin (hCG alpha) and the free alpha molecules produced in pregnancy: most free alpha and some combined hCG alpha molecules are fucosylated. (United States)

    Blithe, D L


    The carbohydrate compositions of pregnancy-derived hCG alpha (dissociated from intact hCG) and free alpha-subunit were analyzed using a combination of chemical analysis, lectin affinity chromatography, and glycosidase sensitivity. For direct compositional analysis, parallel samples were hydrolyzed in trifluoroacetic acid and analyzed for sialic acid and neutral sugars without prior derivatization. Separation of the monosaccharides was achieved by HPLC on a Dionex CarboPac column eluted at high pH, and the resolved monosaccharides were quantified by pulsed amperometric detection. The amounts of sugar that were found relative to peptide indicated the presence of two N-linked oligosaccharides per molecule on both hCG alpha and free alpha. Free alpha contained 2.5-fold higher amounts of sialic acid and galactose as well as a higher amount of N-acetylglucosamine than did hCG alpha. Free alpha also contained a 6-fold higher amount of fucose than did hCG alpha (1.2 vs. 0.2 residues of fucose/molecule). Serial fractionation of intact hCG alpha and free alpha molecules by lectin affinity chromatography indicated that virtually all of the hCG alpha-subunits contained at least one Concanavalin-A (Con-A)-binding site, whereas as many as 32% of the free alpha molecules could not bind to Con-A. Chromatography on Lens culinaris (Lch) resulted in 12% binding of hCG alpha and approximately 72% binding of free alpha (80-85% of the Con-A-bound free alpha and 47-48% of the Con-A-nonbound free alpha bound to Lch). Endoglycosidase-H (endo-H) treatment of hCG alpha released a portion of the oligosaccharides. The endo-H-released material appeared to be a monoantennary hybrid based on DEAE-binding properties and carbohydrate composition. In contrast to hCG alpha, free alpha was completely resistant to endo-H treatment. Incubation of endo-H-resistant hCG alpha with glycopeptidase-A resulted in the release of two components, which could be separated into monoantennary and biantennary

  18. Inhibitory effects of amiloride on alpha adrenoceptors in canine vascular smooth muscle

    Energy Technology Data Exchange (ETDEWEB)

    Shi, A.G.; Wang, Z.L.; Kwan, C.Y.; Daniel, E.E. (McMaster Univ., Hamilton, Ontario (Canada))


    Amiloride inhibits vascular smooth muscle contractions from canine aorta and saphenous vein. The mechanisms were studied using radioligand binding and functional techniques. Amiloride inhibited ({sup 3}H)prazosin and ({sup 3}H)rauwolscine binding to alpha-1 and alpha-2 adrenoceptors in a concentration-dependent manner. Amiloride increased Kd values for ({sup 3}H)rauwolscine without affecting the maximum binding of ({sup 3}H)prazosin. These results suggest that the drug interacts with the alpha-1 adrenoceptor binding sites in a competitive manner and with the alpha-2 adrenoceptor binding sites in a noncompetitive manner. Amiloride reduced maximal contractile responses to agonists selective for both alpha adrenoceptors and to elevated K+, the EC50 values were increased by about 10-fold in the presence of amiloride. In Ca+(+)-free Krebs' solution, contractions induced in saphenous vein after addition of Ca++ in saphenous vein in the presence of adrenoceptor agonists were inhibited by amiloride. Our results suggest that amiloride reduced alpha-1 and alpha-2 adrenoceptor-mediated responses and inhibited Ca++ influx.

  19. The Structure of Neurexin 1[alpha] Reveals Features Promoting a Role as Synaptic Organizer

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Fang; Venugopal, Vandavasi; Murray, Beverly; Rudenko, Gabby (Michigan)


    {alpha}-Neurexins are essential synaptic adhesion molecules implicated in autism spectrum disorder and schizophrenia. The {alpha}-neurexin extracellular domain consists of six LNS domains interspersed by three EGF-like repeats and interacts with many different proteins in the synaptic cleft. To understand how {alpha}-neurexins might function as synaptic organizers, we solved the structure of the neurexin 1{alpha} extracellular domain (n1{alpha}) to 2.65 {angstrom}. The L-shaped molecule can be divided into a flexible repeat I (LNS1-EGF-A-LNS2), a rigid horseshoe-shaped repeat II (LNS3-EGF-B-LNS4) with structural similarity to so-called reelin repeats, and an extended repeat III (LNS5-EGF-B-LNS6) with controlled flexibility. A 2.95 {angstrom} structure of n1{alpha} carrying splice insert SS3 in LNS4 reveals that SS3 protrudes as a loop and does not alter the rigid arrangement of repeat II. The global architecture imposed by conserved structural features enables {alpha}-neurexins to recruit and organize proteins in distinct and variable ways, influenced by splicing, thereby promoting synaptic function.

  20. Structural and biological mimicry of protein surface recognition by [alpha/beta]-peptide foldamers

    Energy Technology Data Exchange (ETDEWEB)

    Horne, W. Seth; Johnson, Lisa M.; Ketas, Thomas J.; Klasse, Per Johan; Lu, Min; Moore, John P.; Gellman, Samuel H.; (Cornell); (UW)


    Unnatural oligomers that can mimic protein surfaces offer a potentially useful strategy for blocking biomedically important protein-protein interactions. Here we evaluate an approach based on combining {alpha}- and {beta}-amino acid residues in the context of a polypeptide sequence from the HIV protein gp41, which represents an excellent testbed because of the wealth of available structural and biological information. We show that {alpha}/{beta}-peptides can mimic structural and functional properties of a critical gp41 subunit. Physical studies in solution, crystallographic data, and results from cell-fusion and virus-infectivity assays collectively indicate that the gp41-mimetic {alpha}/{beta}-peptides effectively block HIV-cell fusion via a mechanism comparable to that of gp41-derived {alpha}-peptides. An optimized {alpha}/{beta}-peptide is far less susceptible to proteolytic degradation than is an analogous {alpha}-peptide. Our findings show how a two-stage design approach, in which sequence-based {alpha} {yields} {beta} replacements are followed by site-specific backbone rigidification, can lead to physical and biological mimicry of a natural biorecognition process.

  1. Overproduction and purification of biologically active native fungal alpha-sarcin in Escherichia coli. (United States)

    Lacadena, J; Martínez del Pozo, A; Barbero, J L; Mancheño, J M; Gasset, M; Oñaderra, M; López-Otín, C; Ortega, S; García, J; Gavilanes, J G


    An efficient system was developed to produce, in Escherichia coli, large amounts of native alpha-sarcin (alpha Sar), a cytotoxin from the mold Aspergillus giganteus. The protein has been purified to homogeneity with a yield of 1.5 micrograms/ml of original culture. The constructed expression vector (pINPG alpha S) is based on the synthesis of a fusion protein between alpha Sar and a modified version of the OmpA signal peptide. This peptide seems to favour the postranslational processing of the fusion protein. The purified recombinant alpha-sarcin (re-alpha Sar) is structurally identical to the mature fungal protein according to the following criteria: N-terminal amino acid (aa) sequence, aa composition, electrophoretic mobility, chromatographic behaviour, immunoreactivity and spectroscopic features. Indeed, the recombinant protein recovered is completely functional, since it cleaves, in vitro, eukaryotic rRNA and it is able to interact with phospholipid vesicles with the same specificity as the native fungal alpha Sar.

  2. Local Varying-Alpha Theories

    CERN Document Server

    Barrow, John D


    In a recent paper we demonstrated how the simplest model for varying alpha may be interpreted as the effect of a dielectric material, generalized to be consistent with Lorentz invariance. Unlike normal dielectrics, such a medium cannot change the speed of light, and its dynamics obey a Klein-Gordon equation. This work immediately suggests an extension of the standard theory, even if we require compliance with Lorentz invariance. Instead of a wave equation, the dynamics may satisfy a local algebraic relation involving the permittivity and the properties of the electromagnetic field, in analogy with more conventional dielectric (but still preserving Lorentz invariance). We develop the formalism for such theories and investigate some phenomenological implications. The problem of the divergence of the classical self-energy can be solved, or at least softened, in this framework. Some interesting new cosmological solutions for the very early universe are found, including the possibility of a bounce, inflation and e...

  3. Matching coefficients for alpha_s and m_b to O(alpha_s^2) in the MSSM

    CERN Document Server

    Bauer, A; Salomon, J


    We compute the exact two-loop matching coefficients for the strong coupling constant alpha_s and the bottom-quark mass m_b within the Minimal Supersymmetric Standard Model (MSSM), taking into account O(alpha_s^2) contributions from Supersymmetric Quantum Chromodynamics (SQCD). We find that the explicit mass pattern of the supersymmetric particles has a significant impact on the predictions of alpha_s and m_b at high energies. Further on, the three-loop corrections exceed the uncertainty due to the current experimental accuracy. In case of the the running bottom-quark mass, they can reach in the large tan(beta) regime up to 30% from the tree-level value.

  4. Resting-State Alpha in Autism Spectrum Disorder and Alpha Associations with Thalamic Volume (United States)

    Edgar, J. Christopher; Heiken, Kory; Chen, Yu-Han; Herrington, John D.; Chow, Vivian; Liu, Song; Bloy, Luke; Huang, Mingxiong; Pandey, Juhi; Cannon, Katelyn M.; Qasmieh, Saba; Levy, Susan E.; Schultz, Robert T.; Roberts, Timothy P. L.


    Alpha circuits (8-12 Hz), necessary for basic and complex brain processes, are abnormal in autism spectrum disorder (ASD). The present study obtained estimates of resting-state (RS) alpha activity in children with ASD and examined associations between alpha activity, age, and clinical symptoms. Given that the thalamus modulates cortical RS alpha…


    NARCIS (Netherlands)



    The enzymatic hydrolyses of a variety of alpha-substituted mandelic and lactic esters using pig liver esterase (PLE) have been investigated. High to moderate enantioselectivity was found for various alpha-substituted mandelic esters, whereas PLE showed low to no enantioselectivity for alpha-substitu

  6. Alpha Virginis: line-profile variations and orbital elements

    CERN Document Server

    Harrington, David; Olguín, Enrique; Ilyin, Ilya; Berdyugina, Svetlana V; Lara, Bruno; Moreno, Edmundo


    Abridged: Alpha Virginis is a binary system whose proximity and brightness allow detailed investigations of the internal structure and evolution of stars undergoing time-variable tidal interactions. Previous studies have led to the conclusion that the internal structure of Spica's primary star may be more centrally condensed than predicted by theoretical models of single stars, raising the possibility that the interactions could lead to effects that are currently neglected in structure and evolution calculations. The key parameters in confirming this result are the values of the orbital eccentricity $e$, the apsidal period $U$, and the primary star's radius, R_1. We analyze the impact that line profile variability has on the derivation of its orbital elements and R_1. We use high SNR observations obtained in 2000, 2008, and 2013 to derive the orbital elements from fits to the radial velocity curves. We produce synthetic line profiles using an ab initio tidal interaction model. Results: The variations in the l...

  7. Analysis of radiation risk from alpha particle component of solar particle events (United States)

    Cucinotta, F. A.; Townsend, L. W.; Wilson, J. W.; Golightly, M. J.; Weyland, M.


    The solar particle events (SPE) will contain a primary alpha particle component, representing a possible increase in the potential risk to astronauts during an SPE over the often studied proton component. We discuss the physical interactions of alpha particles important in describing the transport of these particles through spacecraft and body shielding. Models of light ion reactions are presented and their effects on energy and linear energy transfer (LET) spectra in shielding discussed. We present predictions of particle spectra, dose, and dose equivalent in organs of interest for SPE spectra typical of those occurring in recent solar cycles. The large events of solar cycle 19 are found to have substantial increase in biological risk from alpha particles, including a large increase in secondary neutron production from alpha particle breakup.

  8. Relation of central alpha-adrenoceptor and other receptors to the control of renin secretion. (United States)

    Ganong, W F


    The location and nature of the receptors in the brain on which clonidine acts to decrease renin secretion have been investigated in dogs. Clonidine was injected into the vertebral and carotid arteries, and its effects were compared with those of norepinephrine and epinephrine when injected into the third ventricle. It was also injected intravenously (IV) after transection of the brain stem and following treatment with intraventricular 6-hydroxydopamine. The results suggest that the renin-regulating receptors are located in the brain stem in a region different from the receptors mediating the depressor response, that they are alpha 2-adrenoceptors, and that they are postsynaptic in location. Central alpha 1-adrenoceptors appear to mediate increased renin secretion. Central serotonergic receptors also mediate increased renin secretion, but it is not known how the alpha 1- and alpha 2-adrenoceptors interact with the serotonergic systems.

  9. Identification of a karyopherin alpha 2 recognition site in PLAG1, which functions as a nuclear localization signal. (United States)

    Braem, Caroline V; Kas, Koen; Meyen, Eva; Debiec-Rychter, Maria; Van De Ven, Wim J M; Voz, Marianne L


    The activation of the pleomorphic adenoma gene 1 (PLAG1) is the most frequent gain-of-function mutation found in pleomorphic adenomas of the salivary glands. To gain more insight into the regulation of PLAG1 function, we searched for PLAG1-interacting proteins. Using the yeast two-hybrid system, we identified karyopherin alpha2 as a PLAG1-interacting protein. Physical interaction between PLAG1 and karyopherin alpha2 was confirmed by an in vitro glutathione S-transferase pull-down assay. Karyopherin alpha2 escorts proteins into the nucleus via interaction with a nuclear localization sequence (NLS) composed of short stretches of basic amino acids. Two putative NLSs were identified in PLAG1. The predicted NLS1 (KRKR) was essential for physical interaction with karyopherin alpha2 in glutathione S-transferase pull-down assay, and its mutation resulted in decreased nuclear import of PLAG1. Moreover, NLS1 was able to drive the nuclear import of the cytoplasmic protein beta-galactosidase. In contrast, predicted NLS2 of PLAG1 (KPRK) was not involved in karyopherin alpha2 binding nor in its nuclear import. The residual nuclear import of PLAG1 after mutation of the NLS1 was assigned to the zinc finger domain of PLAG1. These observations indicate that the nuclear import of PLAG1 is governed by its zinc finger domain and by NLS1, a karyopherin alpha2 recognition site.

  10. Acute exercise modulates the Foxo1/PGC-1alpha pathway in the liver of diet-induced obesity rats. (United States)

    Ropelle, Eduardo R; Pauli, José R; Cintra, Dennys E; Frederico, Marisa J S; de Pinho, Ricardo A; Velloso, Lício A; De Souza, Cláudio T


    PGC-1alpha expression is a tissue-specific regulatory feature that is extremely relevant to diabetes. Several studies have shown that PGC-1alpha activity is atypically activated in the liver of diabetic rodents and contributes to hepatic glucose production. PGC-1alpha and Foxo1 can physically interact with one another and represent an important signal transduction pathway that governs the synthesis of glucose in the liver. However, the effect of physical activity on PGC-1alpha/Foxo1 association is unknown. Here we investigate the expression of PGC-1alpha and the association of PGC-1alpha/Foxo1 in the liver of diet-induced obese rats after acute exercise. Wistar rats swam for two 3 h-long bouts, separated by a 45 min rest period. Eight hours after the acute exercise protocol, the rats were submitted to an insulin tolerance test (ITT) and biochemical and molecular analysis. Results demonstrate that acute exercise improved insulin signalling, increasing insulin-stimulated Akt and Foxo1 phosphorylation and decreasing PGC-1alpha expression and PGC-1alpha/Foxo1 interaction in the liver of diet-induced obesity rats under fasting conditions. These phenomena are accompanied by a reduction in the expression of gluconeogenesis genes, such as phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphate (G6Pase). Thus, these results provide new insights into the mechanism by which exercise could improve fasting hyperglycaemia.

  11. Confidence Intervals for Cronbach's Coefficient Alpha Values

    NARCIS (Netherlands)

    A.J. Koning (Alex); Ph.H.B.F. Franses (Philip Hans)


    textabstractCoefficient Alpha, which is widely used in empirical research, estimates the reliability of a test consisting of parallel items. In practice it is difficult to compare values of alpha across studies as it depends on the number of items used. In this paper we provide a simple solution, wh

  12. Alpha Shape Topology of the Cosmic Web

    NARCIS (Netherlands)

    Weygaert, Rien van de; Platen, Erwin; Vegter, Gert; Eldering, Bob; Kruithof, Nico


    We study the topology of the Megaparsec Cosmic Web on the basis of the Alpha Shapes of the galaxy distribution. The simplicial complexes of the alpha shapes are used to determine the set of Betti numbers (βk, k = 1, . . . , D), which represent a complete characterization of the topology of a manifol

  13. The ALPHA detector : Module Production and Assembly

    CERN Document Server

    Andresen, G; Bowe, P D; Cesar, C L; Chapman, S; Charlton, M; Fajans, J; Fujiwara, M C; Gill, D R; Hangst, J S; Hydomako, R; Jenkins, M J; Kurchaninov, L; Madsen, N; Nolan, P; Olchanski, K; Olin, A; Povilus, A; Robicheaux, F; Sarid, E; Silveira, D M; Storey, J W; Thompson, R I; van der Werf, D P; Wurtele, J S; Yamazaki, Y; Ashkezari, M D; Baquero-Ruiz, M; Butler, E; Deller, A; Eriksson, S; Friesen, T; Gutierrez, A; Hardy, W N; Hayden, M E; Humphries, A J; Jonsell, S; McKenna, J T K; Menary, S; Pusa, P; Sampson, J; Seddon, D; Seif el Nasr, S; So, C; Thornhill, J; Wells, D; Jorgensen, L V


    ALPHA is one of the experiments situated at CERN's Antiproton Decelerator (AD). A Silicon Vertex Detector (SVD) is placed to surround the ALPHA atom trap. The main purpose of the SVD is to detect and locate antiproton annihilation events by means of the emitted charged pions. The SVD system is presented with special focus given to the design, fabrication and performance of the modules.

  14. Psychiatric Symptoms in Alpha-Mannosidosis (United States)

    Malm, D.; Pantel, J.; Linaker, O. M.


    Alpha-mannosidosis is characterized by mild to moderate intellectual disability (ID), moderate to severe neurosensory hearing loss, frequent infections, psychomotor disturbances and skeletal dysmorphism. For the first time, a panel of nine alpha-mannosidosis patients with psychiatric symptoms is presented. The clinical picture has several…

  15. The ALPHA - detector: Module Production and Assembly (United States)

    Andresen, G. B.; Ashkezari, M. D.; Baquero-Ruiz, M.; Bertsche, W.; Bowe, P. D.; Butler, E.; Cesar, C. L.; Chapman, S.; Charlton, M.; Deller, A.; Eriksson, S.; Fajans, J.; Friesen, T.; Fujiwara, M. C.; Gill, D. R.; Gutierrez, A.; Hangst, J. S.; Hardy, W. N.; Hayden, M. E.; Humphries, A. J.; Hydomako, R.; Jenkins, M. J.; Jonsell, S.; JØrgensen, L. V.; Kurchaninov, L.; Madsen, N.; McKenna, J. T. K.; Menary, S.; Nolan, P.; Olchanski, K.; Olin, A.; Povilus, A.; Pusa, P.; Robicheaux, F.; Sampson, J.; Sarid, E.; Seddon, D.; Seif el Nasr, S.; Silveira, D. M.; So, C.; Storey, J. W.; Thompson, R. I.; Thornhill, J.; Wells, D.; van der Werf, D. P.; Wurtele, J. S.; Yamazaki, Y.


    ALPHA is one of the experiments situated at CERN's Antiproton Decelerator (AD). A Silicon Vertex Detector (SVD) is placed to surround the ALPHA atom trap. The main purpose of the SVD is to detect and locate antiproton annihilation events by means of the emitted charged pions. The SVD system is presented with special focus given to the design, fabrication and performance of the modules.

  16. Teaching Calculus with Wolfram|Alpha (United States)

    Dimiceli, Vincent E.; Lang, Andrew S. I. D.; Locke, LeighAnne


    This article describes the benefits and drawbacks of using Wolfram|Alpha as the platform for teaching calculus concepts in the lab setting. It is a result of our experiences designing and creating an entirely new set of labs using Wolfram|Alpha. We present the reasoning behind our transition from using a standard computer algebra system (CAS) to…

  17. Remote Associates Test and Alpha Brain Waves (United States)

    Haarmann, Henk J.; George, Timothy; Smaliy, Alexei; Dien, Joseph


    Previous studies found that performance on the remote associates test (RAT) improves after a period of incubation and that increased alpha brain waves over the right posterior brain predict the emergence of RAT insight solutions. We report an experiment that tested whether increased alpha brain waves during incubation improve RAT performance.…

  18. Measurement of the angle alpha at BABAR

    CERN Document Server

    Pérez, A


    We present recent measurements of the CKM angle alpha using data collected by the BABAR detector at the PEP-II asymmetric-energy e^+e^- collider at the SLAC National Accelerator Laboratory, operating at the Upsilon(4S) resonance. We present constraints on alpha from B->pipi, B->rhorho and B->rhopi decays.

  19. Remote Associates Test and Alpha Brain Waves (United States)

    Haarmann, Henk J.; George, Timothy; Smaliy, Alexei; Dien, Joseph


    Previous studies found that performance on the remote associates test (RAT) improves after a period of incubation and that increased alpha brain waves over the right posterior brain predict the emergence of RAT insight solutions. We report an experiment that tested whether increased alpha brain waves during incubation improve RAT performance.…

  20. Teaching Calculus with Wolfram|Alpha (United States)

    Dimiceli, Vincent E.; Lang, Andrew S. I. D.; Locke, LeighAnne


    This article describes the benefits and drawbacks of using Wolfram|Alpha as the platform for teaching calculus concepts in the lab setting. It is a result of our experiences designing and creating an entirely new set of labs using Wolfram|Alpha. We present the reasoning behind our transition from using a standard computer algebra system (CAS) to…

  1. 27 CFR 21.95 - Alpha terpineol. (United States)


    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Alpha terpineol. 21.95 Section 21.95 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS FORMULAS FOR DENATURED ALCOHOL AND RUM Specifications for Denaturants § 21.95 Alpha terpineol. (a) Boiling point at 752mm...

  2. Commentary on Coefficient Alpha: A Cautionary Tale (United States)

    Green, Samuel B.; Yang, Yanyun


    The general use of coefficient alpha to assess reliability should be discouraged on a number of grounds. The assumptions underlying coefficient alpha are unlikely to hold in practice, and violation of these assumptions can result in nontrivial negative or positive bias. Structural equation modeling was discussed as an informative process both to…

  3. Bayesian Meta-Analysis of Coefficient Alpha (United States)

    Brannick, Michael T.; Zhang, Nanhua


    The current paper describes and illustrates a Bayesian approach to the meta-analysis of coefficient alpha. Alpha is the most commonly used estimate of the reliability or consistency (freedom from measurement error) for educational and psychological measures. The conventional approach to meta-analysis uses inverse variance weights to combine…

  4. Bayesian Meta-Analysis of Coefficient Alpha (United States)

    Brannick, Michael T.; Zhang, Nanhua


    The current paper describes and illustrates a Bayesian approach to the meta-analysis of coefficient alpha. Alpha is the most commonly used estimate of the reliability or consistency (freedom from measurement error) for educational and psychological measures. The conventional approach to meta-analysis uses inverse variance weights to combine…

  5. Anomalous atomic volume of alpha-Pu

    DEFF Research Database (Denmark)

    Kollar, J.; Vitos, Levente; Skriver, Hans Lomholt


    .3%. The comparison between the LDA and GGA results show that the anomalously large atomic volume of alpha-Pu relative to alpha-Np can be ascribed to exchange-correlation effects connected with the presence of low coordinated sites in the structure where the f electrons are close to the onset of localization...

  6. On the thermalization of the $\\alpha$-Fermi-Pasta-Ulam system

    CERN Document Server

    Onorato, Miguel; Proment, Davide; Lvov, Yuri V


    We study theoretically the original $\\alpha$-Fermi-Pasta-Ulam (FPU) system with $N=16,32$ and $64$ masses connected by a nonlinear quadratic spring. Our approach is based on resonant wave-wave interaction theory. We show that the route to thermalization consists of three stages. The first one is associated with non-resonant three-wave interactions. At this short time scale, the dynamics is reversible; this stage coincides with the observation of recurrent phenomena in numerical simulations of the $\\alpha$-FPU. On a larger time scale, exact four-wave resonant interactions start to take place; however, we find that all quartets are isolated, preventing a full mixing of energy in the spectrum and thermalization. The last stage corresponds to six-wave resonant interactions. Those are responsible for the energy equipartition recently observed in numerical simulations. A key role in our finding is played by the {\\it Umklapp} (flip over) resonant interactions, typical of discrete systems.

  7. Real-time imaging of HIF-1alpha stabilization and degradation.

    Directory of Open Access Journals (Sweden)

    Ekaterina Moroz

    Full Text Available HIF-1alpha is overexpressed in many human cancers compared to normal tissues due to the interaction of a multiplicity of factors and pathways that reflect specific genetic alterations and extracellular stimuli. We developed two HIF-1alpha chimeric reporter systems, HIF-1alpha/FLuc and HIF-1alpha(DeltaODDD/FLuc, to investigate the tightly controlled level of HIF-1alpha protein in normal (NIH3T3 and HEK293 and glioma (U87 cells. These reporter systems provided an opportunity to investigate the degradation of HIF-1alpha in different cell lines, both in culture and in xenografts. Using immunofluorescence microscopy, we observed different patterns of subcellular localization of HIF-1alpha/FLuc fusion protein between normal cells and cancer cells; similar differences were observed for HIF-1alpha in non-transduced, wild-type cells. A dynamic cytoplasmic-nuclear exchange of the fusion protein and HIF-1alpha was observed in NIH3T3 and HEK293 cells under different conditions (normoxia, CoCl2 treatment and hypoxia. In contrast, U87 cells showed a more persistent nuclear localization pattern that was less affected by different growing conditions. Employing a kinetic model for protein degradation, we were able to distinguish two components of HIF-1alpha/FLuc protein degradation and quantify the half-life of HIF-1alpha fusion proteins. The rapid clearance component (t(1/2 approximately 4-6 min was abolished by the hypoxia-mimetic CoCl2 MG132 treatment and deletion of ODD domain, and reflects the oxygen/VHL-dependent degradation pathway. The slow clearance component (t(1/2 approximately 200 min is consistent with other unidentified non-oxygen/VHL-dependent degradation pathways. Overall, the continuous bioluminescence readout of HIF-1alpha/FLuc stabilization in vitro and in vivo will facilitate the development and validation of therapeutics that affect the stability and accumulation of HIF-1alpha.

  8. Similarity and divergence between the RNA polymerase alpha subunits from hyperthermophilic Thermotoga maritima and mesophilic Escherichia coli bacteria. (United States)

    Braun, Frederique; Marhuenda, Fanny B; Morin, Amelie; Guevel, Laetitia; Fleury, Fabrice; Takahashi, Masayuki; Sakanyan, Vehary


    The alpha subunit (alphaTm) of Thermotoga maritima RNA polymerase has been characterized to investigate its role in transcriptional regulation in one of the few known anaerobic hyperthermophilic bacteria. The highly thermostable alphaTm shares 54% similarity with its Escherichia coli analogue (alphaEc). The T. maritima rpoA gene coding the alpha subunit does not complement the thermosensitive rpoA112 mutation of E. coli. However, alphaTm and alphaEc show similar folding patterns as determined by circular dichroism. Purified alphaTm binds to the T. maritima PargGo promoter region (probably to a UP-element) and Arg282 appears to be crucial for DNA binding. The thermostable protein is also able to interact with transcription regulatory proteins, like ArgR from T. neapolitana or CRP from E. coli. These data indicate that the RNA polymerase alpha subunit might play a crucial role in the modulation of gene expression in hyperthermophiles.

  9. Structure, stability and folding of the alpha-helix. (United States)

    Doig, A J; Andrew, C D; Cochran, D A; Hughes, E; Penel, S; Sun, J K; Stapley, B J; Clarke, D T; Jones, G R


    Pauling first described the alpha-helix nearly 50 years ago, yet new features of its structure continue to be discovered, using peptide model systems, site-directed mutagenesis, advances in theory, the expansion of the Protein Data Bank and new experimental techniques. Helical peptides in solution form a vast number of structures, including fully helical, fully coiled and partly helical. To interpret peptide results quantitatively it is essential to use a helix/coil model that includes the stabilities of all these conformations. Our models now include terms for helix interiors, capping, side-chain interactions, N-termini and 3(10)-helices. The first three amino acids in a helix (N1, N2 and N3) and the preceding N-cap are unique, as their amide NH groups do not participate in backbone hydrogen bonding. We surveyed their structures in proteins and measured their amino acid preferences. The results are predominantly rationalized by hydrogen bonding to the free NH groups. Stabilizing side-chain-side-chain energies, including hydrophobic interactions, hydrogen bonding and polar/non-polar interactions, were measured accurately in helical peptides. Helices in proteins show a preference for having approximately an integral number of turns so that their N- and C-caps lie on the same side. There are also strong periodic trends in the likelihood of terminating a helix with a Schellman or alpha L C-cap motif. The kinetics of alpha-helix folding have been studied with stopped-flow deep ultraviolet circular dichroism using synchrotron radiation as the light source; this gives a far superior signal-to-noise ratio than a conventional instrument. We find that poly(Glu), poly(Lys) and alanine-based peptides fold in milliseconds, with longer peptides showing a transient overshoot in helix content.

  10. Catalytic Mechanism of Human Alpha-galactosidase

    Energy Technology Data Exchange (ETDEWEB)

    Guce, A.; Clark, N; Salgado, E; Ivanen, D; Kulinskaya, A; Brumer, H; Garman, S


    The enzyme {alpha}-galactosidase ({alpha}-GAL, also known as {alpha}-GAL A; E.C. is responsible for the breakdown of {alpha}-galactosides in the lysosome. Defects in human {alpha}-GAL lead to the development of Fabry disease, a lysosomal storage disorder characterized by the buildup of {alpha}-galactosylated substrates in the tissues. {alpha}-GAL is an active target of clinical research: there are currently two treatment options for Fabry disease, recombinant enzyme replacement therapy (approved in the United States in 2003) and pharmacological chaperone therapy (currently in clinical trials). Previously, we have reported the structure of human {alpha}-GAL, which revealed the overall structure of the enzyme and established the locations of hundreds of mutations that lead to the development of Fabry disease. Here, we describe the catalytic mechanism of the enzyme derived from x-ray crystal structures of each of the four stages of the double displacement reaction mechanism. Use of a difluoro-{alpha}-galactopyranoside allowed trapping of a covalent intermediate. The ensemble of structures reveals distortion of the ligand into a {sup 1}S{sub 3} skew (or twist) boat conformation in the middle of the reaction cycle. The high resolution structures of each step in the catalytic cycle will allow for improved drug design efforts on {alpha}-GAL and other glycoside hydrolase family 27 enzymes by developing ligands that specifically target different states of the catalytic cycle. Additionally, the structures revealed a second ligand-binding site suitable for targeting by novel pharmacological chaperones.

  11. Alpha-2-Macroglobulin Is Acutely Sensitive to Freezing and Lyophilization: Implications for Structural and Functional Studies.

    Directory of Open Access Journals (Sweden)

    Amy R Wyatt

    Full Text Available Alpha-2-macroglobulin is an abundant secreted protein that is of particular interest because of its diverse ligand binding profile and multifunctional nature, which includes roles as a protease inhibitor and as a molecular chaperone. The activities of alpha-2-macroglobulin are typically dependent on whether its conformation is native or transformed (i.e. adopts a more compact conformation after interactions with proteases or small nucleophiles, and are also influenced by dissociation of the native alpha-2-macroglobulin tetramer into stable dimers. Alpha-2-macroglobulin is predominately present as the native tetramer in vivo; once purified from human blood plasma, however, alpha-2-macroglobulin can undergo a number of conformational changes during storage, including transformation, aggregation or dissociation. We demonstrate that, particularly in the presence of sodium chloride or amine containing compounds, freezing and/or lyophilization of alpha-2-macroglobulin induces conformational changes with functional consequences. These conformational changes in alpha-2-macroglobulin are not always detected by standard native polyacrylamide gel electrophoresis, but can be measured using bisANS fluorescence assays. Increased surface hydrophobicity of alpha-2-macroglobulin, as assessed by bisANS fluorescence measurements, is accompanied by (i reduced trypsin binding activity, (ii increased chaperone activity, and (iii increased binding to the surfaces of SH-SY5Y neurons, in part, via lipoprotein receptors. We show that sucrose (but not glycine effectively protects native alpha-2-macroglobulin from denaturation during freezing and/or lyophilization, thereby providing a reproducible method for the handling and long-term storage of this protein.

  12. The Role of Alpha Activity in Spatial and Feature-Based Attention (United States)

    Miller, Lee M.


    Abstract Modulations in alpha oscillations (∼10 Hz) are typically studied in the context of anticipating upcoming stimuli. Alpha power decreases in sensory regions processing upcoming targets compared to regions processing distracting input, thereby likely facilitating processing of relevant information while suppressing irrelevant. In this electroencephalography study using healthy human volunteers, we examined whether modulations in alpha power also occur after the onset of a bilaterally presented target and distractor. Spatial attention was manipulated through spatial cues and feature-based attention through adjusting the color-similarity of distractors to the target. Consistent with previous studies, we found that informative spatial cues induced a relative decrease of pretarget alpha power at occipital electrodes contralateral to the expected target location. Interestingly, this pattern reemerged relatively late (300–750 ms) after stimulus onset, suggesting that lateralized alpha reflects not only preparatory attention, but also ongoing attentive stimulus processing. Uninformative cues (i.e., conveying no information about the spatial location of the target) resulted in an interaction between spatial attention and feature-based attention in post-target alpha lateralization. When the target was paired with a low-similarity distractor, post-target alpha was lateralized (500–900 ms). Crucially, the lateralization was absent when target selection was ambiguous because the distractor was highly similar to the target. Instead, during this condition, midfrontal theta was increased, indicative of reactive conflict resolution. Behaviorally, the degree of alpha lateralization was negatively correlated with the reaction time distraction cost induced by target–distractor similarity. These results suggest a pivotal role for poststimulus alpha lateralization in protecting sensory processing of target information. PMID:27822505

  13. Folate receptor {alpha} regulates cell proliferation in mouse gonadotroph {alpha}T3-1 cells

    Energy Technology Data Exchange (ETDEWEB)

    Yao, Congjun; Evans, Chheng-Orn [Department of Neurosurgery and Laboratory of Molecular Neurosurgery and Biotechnology, Emory University, School of Medicine, Atlanta, Georgia (United States); Stevens, Victoria L. [Epidemiology and Surveillance Research, American Cancer Society, Atlanta, Georgia (United States); Owens, Timothy R. [Emory University, School of Medicine, Atlanta, Georgia (United States); Oyesiku, Nelson M., E-mail: [Department of Neurosurgery and Laboratory of Molecular Neurosurgery and Biotechnology, Emory University, School of Medicine, Atlanta, Georgia (United States)


    We have previously found that the mRNA and protein levels of the folate receptor alpha (FR{alpha}) are uniquely over-expressed in clinically human nonfunctional (NF) pituitary adenomas, but the mechanistic role of FR{alpha} has not fully been determined. We investigated the effect of FR{alpha} over-expression in the mouse gonadotroph {alpha}T3-1 cell line as a model for NF pituitary adenomas. We found that the expression and function of FR{alpha} were strongly up-regulated, by Western blotting and folic acid binding assay. Furthermore, we found a higher cell growth rate, an enhanced percentage of cells in S-phase by BrdU assay, and a higher PCNA staining. These observations indicate that over-expression of FR{alpha} promotes cell proliferation. These effects were abrogated in the same {alpha}T3-1 cells when transfected with a mutant FR{alpha} cDNA that confers a dominant-negative phenotype by inhibiting folic acid binding. Finally, by real-time quantitative PCR, we found that mRNA expression of NOTCH3 was up-regulated in FR{alpha} over-expressing cells. In summary, our data suggests that FR{alpha} regulates pituitary tumor cell proliferation and mechanistically may involve the NOTCH pathway. Potentially, this finding could be exploited to develop new, innovative molecular targeted treatment for human NF pituitary adenomas.

  14. Light nuclear charge measurement with Alpha Magnetic Spectrometer Electromagnetic Calorimeter

    Energy Technology Data Exchange (ETDEWEB)

    Basara, Laurent [Trento Institute for Fundamental Physics and Applications, Povo 38123 (Italy); Choutko, Vitaly [Massachusetts Institute of Technology, Cambridge, MA 02139 (United States); Li, Qiang, E-mail: [Harbin Institute of Technology, Harbin, 150001 (China)


    The Alpha Magnetic Spectrometer (AMS) is a high energy particle detector installed and operating on board of the International Space Station (ISS) since May 2011. So far more than 70 billion cosmic ray events have been recorded by AMS. In the present paper the Electromagnetic Calorimeter (ECAL) detector of AMS is used to measure cosmic ray nuclear charge magnitudes up to Z=10. The obtained charge magnitude resolution is about 0.1 and 0.3 charge unit for Helium and Carbon, respectively. These measurements are important for an accurate determination of the interaction probabilities of various nuclei with the AMS materials. The ECAL charge calibration and measurement procedures are presented.

  15. Transformation plasticity in titanium alpha double prime martensite

    Energy Technology Data Exchange (ETDEWEB)

    Ivasishin, O.M.; Teliovich, R.V. [Institute of Metal Physics, Kiev (Ukraine)


    In this paper, explanation of an exceptionally low yield strength and high plasticity of {alpha}{sup ''}-martensite is given using the experimental data on martensite crystal structure of Ti-7%Mo (wt). It is supposed that as-quenched martensite microstructure is a highly nonuniform set of distorted due to compositional modulation microvolumes. Interaction between internal stresses generated in martensite modulated microstructure and external applied stresses modifies crystal lattice in a specific way, leading to a transformation induced plasticity. (orig.)

  16. Anomalous variation of electric field gradient in {alpha}-Ti

    Energy Technology Data Exchange (ETDEWEB)

    Govindaraj, R., E-mail: [Materials Science Group, Indira Gandhi Centre for Atomic Research, Kalpakkam 603102 (India); Sundar, C.S. [Materials Science Group, Indira Gandhi Centre for Atomic Research, Kalpakkam 603102 (India)


    Variation of electric field gradient (EFG) at {sup 181}Ta occupying substitutional sites in {alpha}-Ti matrix has been studied in the temperature interval from 10 to 300 K using time differential perturbed angular correlation spectroscopy. Among the main sources of EFG such as conduction electrons and lattice ions, the present study shows that in {alpha}-Ti, the temperature dependence of EFG is predominantly due to conduction electrons. The variation of EFG could not be fitted with either as the linear dependence of temperature (T) or T{sup 3/2} over the whole temperature interval 10-300 K. Existence of two different slopes with a change of slope occurring around 150 K is observed while the EFG is fitted with T or T{sup 3/2}. The above change of slopes of EFG in {alpha}-Ti, which is understood to be due to a slight modification in conduction electron-phonon interactions based on this work, is possibly caused by the electronic topological transitions below 150 K as has been reported.

  17. Measurements of the CKM Angle Alpha at BaBar

    Energy Technology Data Exchange (ETDEWEB)

    Stracka, Simone; /Milan U. /INFN, Milan


    The authors present improved measurements of the branching fractions and CP-asymmetries fin the B{sup 0} {yields} {pi}{sup +}{pi}{sup -}, B{sup 0} {yields} {pi}{sup 0}{pi}{sup 0}, and B{sup +} {yields} {rho}{sup +}{rho}{sup 0} decays, which impact the determination of {alpha}. The combined branching fractions of B {yields} K{sub 1}(1270){pi} and B {yields} K{sub 1}(1400){pi} decays are measured for the first time and allow a novel determination of {alpha} in the B{sup 0} {yields} {alpha}{sub 1}(1260){sup {+-}}{pi}{sup {-+}} decay channel. These measurements are performed using the final dataset collected by the BaBar detector at the PEP-II B-factory. The primary goal of the experiments based at the B factories is to test the Cabibbo-Kobayashi-Maskawa (CKM) picture of CP violation in the standard model of electroweak interactions. This can be achieved by measuring the angles and sides of the Unitarity Triangle in a redundant way.

  18. TFTR 60 GHz alpha particle collective Thomson Scattering diagnostic

    Energy Technology Data Exchange (ETDEWEB)

    Machuzak, J.S.; Woskov, P.P.; Gilmore, J. [Massachusetts Inst. of Tech., Cambridge, MA (United States); Bretz, N.L.; Park, H.K. [Princeton Univ., NJ (United States). Plasma Physics Lab.; Aamodt, R.E.; Cheung, P.Y.; Russell, D.A. [Lodestar Research Corp., Boulder, CO (United States); Bindslev, H. [JET Joint Undertaking, Abingdon (United Kingdom)


    A 60 GHz gyrotron collective Thomson Scattering alpha particle diagnostic has been implemented for the D-T period on TFM. Gyrotron power of 0.1-1 kW in pulses of up to 1 second can be launched in X-mode. Efficient corrugated waveguides are used with antennaes and vacuum windows of the TFTR Microwave Scattering system. A multichannel synchronous detector receiver system and spectrum analyzer acquire the scattered signals. A 200 Megasample/sec digitizer is used to resolve fine structure in the frequency spectrum. By scattering nearly perpendicular to the magnetic field, this experiment will take advantage of an enhancement of the scattered signal which results from the interaction of the alpha particles with plasma resonances in the lower hybrid frequency range. Significant enhancements are expected, which will make these measurements possible with gyrotron power less than 1 kW, while maintaining an acceptable signal to noise ratio. We hope to extract alpha particle density and velocity distribution functions from the data. The D and T fuel densities and temperatures may also be obtainable by measurement of the respective ion cyclotron harmonic frequencies.

  19. Measurements of the CKM Angle Alpha at BaBar

    Energy Technology Data Exchange (ETDEWEB)

    Stracka, Simone; /Milan U. /INFN, Milan


    The authors present improved measurements of the branching fractions and CP-asymmetries fin the B{sup 0} {yields} {pi}{sup +}{pi}{sup -}, B{sup 0} {yields} {pi}{sup 0}{pi}{sup 0}, and B{sup +} {yields} {rho}{sup +}{rho}{sup 0} decays, which impact the determination of {alpha}. The combined branching fractions of B {yields} K{sub 1}(1270){pi} and B {yields} K{sub 1}(1400){pi} decays are measured for the first time and allow a novel determination of {alpha} in the B{sup 0} {yields} {alpha}{sub 1}(1260){sup {+-}}{pi}{sup {-+}} decay channel. These measurements are performed using the final dataset collected by the BaBar detector at the PEP-II B-factory. The primary goal of the experiments based at the B factories is to test the Cabibbo-Kobayashi-Maskawa (CKM) picture of CP violation in the standard model of electroweak interactions. This can be achieved by measuring the angles and sides of the Unitarity Triangle in a redundant way.

  20. Peginterferon alpha-2a versus peginterferon alpha-2b for chronic hepatitis C

    DEFF Research Database (Denmark)

    Hauser, Goran; Awad, Tahany; Thorlund, Kristian


    BACKGROUND: A combination of weekly pegylated interferon (peginterferon) alpha and daily ribavirin still represents standard treatment of chronic hepatitis C infection in the majority of patients. However, it is not established which of the two licensed peginterferon products, peginterferon alpha-2......a or peginterferon alpha-2b, is the most effective and has a better safety profile. OBJECTIVES: To systematically evaluate the benefits and harms of peginterferon alpha-2a versus peginterferon alpha-2b in head-to-head randomised clinical trials in patients with chronic hepatitis C. SEARCH METHODS...... literature. SELECTION CRITERIA: We included randomised clinical trials comparing peginterferon alpha-2a versus peginterferon alpha-2b given with or without co-intervention(s) (for example, ribavirin) for chronic hepatitis C. Quasi-randomised studies and observational studies as identified by the searches...

  1. Radiative corrections to the muonium hyperfine structure; 1, the $\\alpha^{2}$ (Z$\\alpha$) correction

    CERN Document Server

    Kinoshita, T


    This is the first of a series of papers on a systematic application of the NRQED bound state theory of Caswell and Lepage to higher-order radiative corrections to the hyperfine structure of the muonium ground state. This paper describes the calculation of the \\alpha^2 (Z\\alpha) radiative correction. Our result for the complete \\alpha^2 (Z\\alpha) correction is 0.424(4) kHz, which reduces the theoretical uncertainty significantly. The remaining uncertainty is dominated by that of the numerical evaluation of the nonlogarithmic part of the \\alpha (Z\\alpha )^2 term and logarithmic terms of order \\alpha^4. These terms will be treated in the subsequent papers.

  2. The fratricide of alpha-Omega dynamos by their alpha-squared siblings

    CERN Document Server

    Hubbard, Alexander; Brandenburg, Axel


    Context. Helically forced magneto-hydrodynamic shearing-sheet turbulence can support different large-scale dynamo modes, although the {\\alpha} - {\\Omega} mode is generally expected to dominate because it is the fastest growing. In an {\\alpha} - {\\Omega} dynamo, most of the field amplification is produced by the shear. As differential rotation is an ubiquitous source of shear in astrophysics, such dynamos are believed to be the source of most astrophysical large-scale magnetic fields. Aims. We study the stability of oscillatory migratory {\\alpha} - {\\Omega} type dynamos in turbulence simulations. Methods. We use shearing-sheet simulations of hydromagnetic turbulence that is helically forced at a wavenumber that is about three times larger than the lowest wavenumber in the domain so that both {\\alpha} - {\\Omega} and {\\alpha}2 dynamo action is possible. Results. After initial dominance and saturation, the {\\alpha} - {\\Omega} mode is found to be destroyed by an orthogonal {\\alpha}2 mode sustained by the helical t...

  3. Alpha macroglobulins and the low-density-lipoprotein-related protein alpha-2-macroglobulin receptor in experimental renal fibrosis

    NARCIS (Netherlands)

    van Goor, H; Diamond, [No Value; Ding, GH; Kaysen, GA


    In this study, we evaluated the location of non-specific proteinase inhibitors and their receptor in experimental glomerular and interstitial fibrosis. The alpha macroglobulins alpha-2-macroglobulin (alpha 2M) and alpha-1-inhibitor 3 (alpha 1I3) are proteinase inhibitors, including metalloproteinase

  4. Alpha1 and Alpha2 Integrins Mediate Invasive Activity of Mouse Mammary Carcinoma Cells through Regulation of Stromelysin-1 Expression

    Energy Technology Data Exchange (ETDEWEB)

    Lochter, Andre; Navre, Marc; Werb, Zena; Bissell, Mina J


    Tumor cell invasion relies on cell migration and extracellular matrix proteolysis. We investigated the contribution of different integrins to the invasive activity of mouse mammary carcinoma cells. Antibodies against integrin subunits {alpha}6 and {beta}1, but not against {alpha}1 and {alpha}2, inhibited cell locomotion on a reconstituted basement membrane in two-dimensional cell migration assays, whereas antibodies against {beta}1, but not against a6 or {alpha}2, interfered with cell adhesion to basement membrane constituents. Blocking antibodies against {alpha}1 integrins impaired only cell adhesion to type IV collagen. Antibodies against {alpha}1, {alpha}2, {alpha}6, and {beta}1, but not {alpha}5, integrin subunits reduced invasion of a reconstituted basement membrane. Integrins {alpha}1 and {alpha}2, which contributed only marginally to motility and adhesion, regulated proteinase production. Antibodies against {alpha}1 and {alpha}2, but not {alpha}6 and {beta}1, integrin subunits inhibited both transcription and protein expression of the matrix metalloproteinase stromelysin-1. Inhibition of tumor cell invasion by antibodies against {alpha}1 and {alpha}2 was reversed by addition of recombinant stromelysin-1. In contrast, stromelysin-1 could not rescue invasion inhibited by anti-{alpha}6 antibodies. Our data indicate that {alpha}1 and {alpha}2 integrins confer invasive behavior by regulating stromelysin-1 expression, whereas {alpha}6 integrins regulate cell motility. These results provide new insights into the specific functions of integrins during tumor cell invasion.

  5. Peroxisome proliferator-activated receptor-gamma coactivator-1alpha activation of CYP7A1 during food restriction and diabetes is still inhibited by small heterodimer partner. (United States)

    Shin, Dong-Ju; Osborne, Timothy F


    Cholesterol 7alpha-hydroxylase (CYP7A1) catalyzes the rate-limiting step in the classic pathway of hepatic bile acid biosynthesis from cholesterol. During fasting and in type I diabetes, elevated levels of peroxisome proliferator-activated receptor gamma-coactivator-1alpha (PGC-1alpha) induce expression of the Cyp7A1 gene and overexpression of PGC-1alpha in hepatoma cells stimulates bile acid synthesis. Using Ad-PGC-1alpha-RNA interference to induce acute disruption of PGC-1alpha in mice, here we show that PGC-1alpha is necessary for fasting-mediated induction of CYP7A1. Co-immunoprecipitation and promoter activation studies reveal that the induction of CYP7A1 is mediated by direct interaction between PGC-1alpha and the AF2 domain of liver receptor homolog-1 (LRH-1). In contrast, the very similar PGC-1beta could not substitute for PGC-1alpha. We also show that transactivation of PGC-1alpha and LRH-1 is repressed by the small heterodimer partner (SHP). Treatment of mice with GW4064, a synthetic agonist for farnesoid X receptor, induced SHP expression and decreased both the recruitment of PGC-1alpha to the Cyp7A1 promoter and the fasting-induced expression of CYP7A1 mRNA. These data suggest that PGC-1alpha is an important co-activator for LRH-1 and that SHP targets the interaction between LRH-1 and PGC-1alpha to inhibit CYP7A1 expression. Overall, these studies provide further evidence for the important role of PGC-1alpha in bile acid homeostasis and suggest that pharmacological targeting of farnesoid X receptor in vivo can be used to reverse the increase in CYP7A1 associated with adverse metabolic conditions.

  6. Radiative nonrecoil nuclear finite size corrections of order $\\alpha(Z\\alpha)^5$ to the hyperfine splitting of S-states in muonic hydrogen

    CERN Document Server

    Faustov, R N; Martynenko, G A; Sorokin, V V


    On the basis of quasipotential method in quantum electrodynamics we calculate nuclear finite size radiative corrections of order $\\alpha(Z\\alpha)^5$ to the hyperfine structure of S-wave energy levels in muonic hydrogen and muonic deuterium. For the construction of the particle interaction operator we employ the projection operators on the particle bound states with definite spins. The calculation is performed in the infrared safe Fried-Yennie gauge. Modern experimental data on the electromagnetic form factors of the proton and deuteron are used.

  7. Mapping High-Velocity H-alpha and Lyman-alpha Emission from Supernova 1987A (United States)

    France, Kevin; McCray, Richard; Fransson, Claes; Larsson, Josefin; Frank, Kari A.; Burrows, David N.; Challis, Peter; Kirshner, Robert P.; Chevalier, Roger A.; Garnavich, Peter; Heng, Kevin; Lawrence, Stephen S.; Lundqvist, Peter; Smith, Nathan; Sonneborn, George


    We present new Hubble Space Telescope images of high-velocity H-alpha and Lyman-alpha emission in the outer debris of SN 1987A. The H-alpha images are dominated by emission from hydrogen atoms crossing the reverse shock. For the first time we observe emission from the reverse shock surface well above and below the equatorial ring, suggesting a bipolar or conical structure perpendicular to the ring plane. Using the H-alpha imaging, we measure the mass flux of hydrogen atoms crossing the reverse shock front, in the velocity intervals (-7,500 < V(sub obs) < -2,800 km/s) and (1,000 < V(sub obs) < 7,500 km/s), ?M(sub H) = 1.2 × 10(exp -3) M/ y. We also present the first Lyman-alpha imaging of the whole remnant and new Chandra X-ray observations. Comparing the spatial distribution of the Lyman-alpha and X-ray emission, we observe that the majority of the high-velocity Lyman-alpha emission originates interior to the equatorial ring. The observed Lyman-alpha/H-alpha photon ratio, R(L-alpha/H-alpha) approx. = 17, is significantly higher than the theoretically predicted ratio of approx. = 5 for neutral atoms crossing the reverse shock front. We attribute this excess to Lyman-alpha emission produced by X-ray heating of the outer debris. The spatial orientation of the Lyman-alpha and X-ray emission suggests that X-ray heating of the outer debris is the dominant Lyman-alpha production mechanism in SN 1987A at this phase in its evolution.

  8. Involvement of central alpha1-adrenoceptors on renal responses to central moxonidine and alpha-methylnoradrenaline. (United States)

    de Andrade, Carina A F; de Andrade, Glaucia M F; De Paula, Patricia M; De Luca, Laurival A; Menani, José V


    Moxonidine (alpha2-adrenoceptor/imidazoline receptor agonist) injected into the lateral ventricle induces diuresis, natriuresis and renal vasodilation. Moxonidine-induced diuresis and natriuresis depend on central imidazoline receptors, while central alpha1-adrenoceptors are involved in renal vasodilation. However, the involvement of central alpha1-adrenoceptors on diuresis and natriuresis to central moxonidine was not investigated yet. In the present study, the effects of moxonidine, alpha-methylnoradrenaline (alpha2-adrenoceptor agonist) or phenylephrine (alpha1-adrenoceptor agonist) alone or combined with previous injections of prazosin (alpha1-adrenoceptor antagonist), yohimbine or RX 821002 (alpha2-adrenoceptor antagonists) intracerebroventricularly (i.c.v.) on urinary sodium, potassium and volume were investigated. Male Holtzman rats (n = 5-18/group) with stainless steel cannula implanted into the lateral ventricle and submitted to gastric water load (10% of body weight) were used. Injections of moxonidine (20 nmol) or alpha-methylnoradrenaline (80 nmol) i.c.v. induced natriuresis (196 +/- 25 and 171 +/- 30, respectively, vs. vehicle: 101 +/- 9 microEq/2 h) and diuresis (9.0 +/- 0.4 and 12.3 +/- 1.6, respectively, vs. vehicle: 5.2 +/- 0.5 ml/2 h). Pre-treatment with prazosin (320 nmol) i.c.v. abolished the natriuresis (23 +/- 4 and 76 +/- 11 microEq/2 h, respectively) and diuresis (5 +/- 1 and 7.6 +/- 0.8 ml/2 h, respectively) produced by i.c.v. moxonidine or alpha-methylnoradrenaline. RX 821002 (320 nmol) i.c.v. abolished the natriuretic effect of alpha-methylnoradrenaline, however, yohimbine (320 nmol) did not change renal responses to moxonidine. Phenylephrine (80 nmol) i.c.v. induced natriuresis and kaliuresis that were blocked by prazosin. Therefore, the present data suggest that moxonidine and alpha-methylnoradrenaline acting on central imidazoline receptors and alpha2-adrenoceptors, respectively, activate central alpha1-adrenergic mechanisms to

  9. [Contents and its change during storage of alpha-solanine and alpha-chaconine in potatoes]. (United States)

    Shindo, Tetsuya; Ushiyama, Hirofumi; Kan, Kimiko; Yasuda, Kazuo; Saito, Kazuo


    Contents of alpha-solanine and alpha-chaconine in native species of potato (May Queen, Danshaku and Waseshiro), and in species (Jagakids Red '90 (Red) and Jagakids Purple '90 (Purple)) on the market, and their change during storage at room temparature were investigated. alpha-Solanine and alpha-chaconine were extracted from potatoes with methanol, cleaned up by using a Sep-Pak Plus C18 cartridge, and then subjected to HPLC. The recoveries of alpha-solanine and alpha-chaconine from potatoes were both more than 96%, and the quantitation limits were both 2 microg/g. alpha-Solanine and alpha-chaconine were detected in periderm in all samples at the levels of 260-320 microg/g in May Queen,190-240 microg/g in Danshaku, 43-63 microg/g in Waseshiro, 140-200 microg/g in Red and 84-130 microg/g in Purple, respectively. alpha-Solanine and alpha-chaconine were detected in the cortex in all samples of May Queen and Danshaku at the levels of 2.7-12 microg/g and 5.8-31 microg/g, respectively. Contents of alpha-solanine and alpha-chaconine in the cortex of May Queen and Danshaku were less than 10% of those in the periderm. When potatoes were stored for 90 days at room temparature in a dark place, no marked change in the contents of alpha-solanine and alpha-chaconine was observed in any of the potato samples.

  10. A new alpha chain hemoglobin variant: Hb Al-Hammadi Riyadh [alpha75(EF4)Asp-->Val (alpha2)]. (United States)

    Burnichon, Nelly; Lacan, Philippe; Becchi, Michel; Zanella-Cleon, Isabelle; Aubry, Martine; Mowafy, Mohammed; Couprie, Nicole; Francina, Alain


    A new hemoglobin (Hb) variant in the heterozygous state, Hb Al-Hammadi Riyadh [codon 75 (GAC-->GTC); alpha75(EF4)Asp-->Val (alpha2)] corresponding to an A-->T transversion on the second exon of the alpha2-globin gene, is described. The variant was characterized by DNA sequencing and mass spectrometry (MS). The variant was found during a routine Hb analysis for anemia in a 16-month-old boy who lived in Riyadh, Kingdom of Saudi Arabia.

  11. $Q_{\\alpha}$-Normal Families and entire functions

    CERN Document Server

    Gul, Shai


    For every countable ordinal number $\\alpha$ we construct an entire function $f=f_\\alpha$ such that the family $\\left\\{f(nz):n\\in\\mathbb{N}\\right\\}$ is exactly $Q_\\alpha$-normal in the unit disk.

  12. Genetics Home Reference: mucolipidosis III alpha/beta (United States)

    ... Health Conditions mucolipidosis III alpha/beta mucolipidosis III alpha/beta Enable Javascript to view the expand/collapse ... PDF Open All Close All Description Mucolipidosis III alpha/beta is a disorder that affects many parts ...

  13. Genetics Home Reference: mucolipidosis II alpha/beta (United States)

    ... Health Conditions mucolipidosis II alpha/beta mucolipidosis II alpha/beta Enable Javascript to view the expand/collapse ... PDF Open All Close All Description Mucolipidosis II alpha/beta (also known as I-cell disease) is ...

  14. [Study of the interaction of main potato glycoalkaloids in inhibition of immobilized butyryl cholinesterase]. (United States)

    Arkhypova, V M; Dziadevych, S V; Jaffrezic-Renault, N; Martelet, C; Soldatkin, O P


    The interaction of main potato glycoalkaloids alpha-solanine and alpha-chaconine in inhibition of horse serum butyryl cholinesterases immobilized on the pH-sensitive field-effect transistors has been investigated. The method of isobol diagram of Loewe and Muishnek has been used for interpretation of results. It has been shown the alpha-chaconine inhibits the immobilized bytyryl cholinesterases more strongly than alpha-solanine, and their mixture has the addition effect.

  15. Increased virulence and competitive advantage of a/alpha over a/a or alpha/alpha offspring conserves the mating system of Candida albicans. (United States)

    Lockhart, Shawn R; Wu, Wei; Radke, Joshua B; Zhao, Rui; Soll, David R


    The majority of Candida albicans strains in nature are a/alpha and must undergo homozygosis to a/a or alpha/alpha to mate. Here we have used a mouse model for systemic infection to test the hypothesis that a/alpha strains predominate in nature because they have a competitive advantage over a/a and alpha/alpha offspring in colonizing hosts. Single-strain injection experiments revealed that a/alpha strains were far more virulent than either their a/a or alpha/alpha offspring. When equal numbers of parent a/alpha and offspring a/a or alpha/alpha cells were co-injected, a/alpha always exhibited a competitive advantage at the time of extreme host morbidity or death. When equal numbers of an engineered a/a/alpha2 strain and its isogenic a/a parent strain were co-injected, the a/a/alpha2 strain exhibited a competitive advantage at the time of host morbidity or death, suggesting that the genotype of the mating-type (MTL) locus, not associated genes on chromosome 5, provides a competitive advantage. We therefore propose that heterozygosity at the MTL locus not only represses white-opaque switching and genes involved in the mating process, but also affects virulence, providing a competitive advantage to the a/alpha genotype that conserves the mating system of C. albicans in nature.

  16. Does Occipital Alpha Neurofeedback Require Critical Branching to Causally Influence LTRCs and Deterministic ERPs?

    CERN Document Server

    Campbell, Tom


    Critical branching is a form of theoretical interaction between simple units, which, in the case of the human brain are assumed to be neuronal elements. Zhigalov, Kaplan, & Palva (Clin Neurophysiol 2016;127:288-89) revealed that neurofeedback flash stimulation phase-locked to high-amplitude occipital alpha influences the stimulus-locked occipital alpha-band averages and the power scaling of long-range temporal correlations of alpha-band amplitude fluctuations. At first, it might seem that neurofeedback influenced critical branching alongside there being an interaction between ongoing neuronal activity and evoked responses. However, the causal relations between these neuronal Long Range Temporal Correlations, sustained attention, and any avalanche dynamics are called into question, as is the assertion of Zhigalov et al. that the neurofeedback flashes are unconsciously processed rather than capturing attention. Uncorrected concerns about false discovery rate and an objective mathematical error in the cited ...

  17. Assessment of Loads and Performance of a Containment in a Hypothetical Accident (ALPHA). Facility design report

    Energy Technology Data Exchange (ETDEWEB)

    Yamano, Norihiro; Maruyama, Yu; Kudo, Tamotsu; Moriyama, Kiyofumi; Ito, Hideo; Komori, Keiichi; Sonobe, Hisao; Sugimoto, Jun [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment


    In the ALPHA (Assessment of Loads and Performance of Containment in Hypothetical Accident) program, several tests have been performed to quantitatively evaluate loads to and performance of a containment vessel during a severe accident of a light water reactor. The ALPHA program focuses on investigating leak behavior through the containment vessel, fuel-coolant interaction, molten core-concrete interaction and FP aerosol behavior, which are generally recognized as significant phenomena considered to occur in the containment. In designing the experimental facility, it was considered to simulate appropriately the phenomena mentioned above, and to cover experimental conditions not covered by previous works involving high pressure and temperature. Experiments from the viewpoint of accident management were also included in the scope. The present report describes design specifications, dimensions, instrumentation of the ALPHA facility based on the specific test objectives and procedures. (author)

  18. Lyman Alpha Spicule Observatory (LASO) (United States)

    Chamberlin, P. C.; Allred, J. C.; Airapetian, V.; Gong, Q.; Mcintosh, S. W.; De Pontieu, B.; Fontenla, J. M.


    The Lyman Alpha Spicule Observatory (LASO) sounding rocket will observe small-scale eruptive events called "Rapid Blue-shifted Events" (RBEs) [Rouppe van der Voort et al., 2009], the on-disk equivalent of Type-II spicules, and extend observations that explore their role in the solar coronal heating problem [De Pontieu et al., 2011]. LASO utilizes a new and novel optical design to simultaneously observe two spatial dimensions at 4.2" spatial resolution (2.1" pixels) over a 2'x2' field of view with high spectral resolution of 66mÅ (33mÅ pixels) across a broad 20Å spectral window. This spectral window contains three strong chromospheric and transition region emissions and is centered on the strong Hydrogen Lyman-α emission at 1216Å. This instrument makes it possible to obtain new data crucial to the physical understanding of these phenomena and their role in the overall energy and momentum balance from the upper chromosphere to lower corona. LASO was submitted March 2011 in response to the ROSES SHP-LCAS call.

  19. Diagnostics for PLX-alpha (United States)

    Gilmore, Mark; Hsu, Scott


    The goal of the Plasma Liner eXperiment PLX-alpha at Los Alamos National Laboratory is to establish the viability of creating a spherically imploding plasma liner for MIF and HED applications, using a spherical array of supersonic plasma jets launched by innovative contoured-gap coaxial plasma guns. PLX- α experiments will focus in particular on establishing the ram pressure and uniformity scalings of partial and fully spherical plasma liners. In order to characterize these parameters experimentally, a suite of diagnostics is planned, including multi-camera fast imaging, a 16-channel visible interferometer (upgraded from 8 channels) with reconfigurable, fiber-coupled front end, and visible and VUV high-resolution and survey spectroscopy. Tomographic reconstruction and data fusion techniques will be used in conjunction with interferometry, imaging, and synthetic diagnostics from modeling to characterize liner uniformity in 3D. Diagnostic and data analysis design, implementation, and status will be presented. Supported by the Advanced Research Projects Agency - Energy - U.S. Department of Energy.

  20. Lyman alpha emission in starburst galaxies (United States)

    Kunth, Daniel


    We propose to perform a deep study of Ly-alpha emission and destruction in 3 star-forming galaxies. These objects have been already observed with the GHRS and exhibit a variety of situations, with Ly-alpha showing P Cyg profiles, secondary emissions or even a deep damped absorption line with no emission. They also span a range of intrinsic properties: IZW18 is a gas-rich, metal deficient dust free dwarf galaxy, Haro 2 has a simple morphology while IRAS 08339+6517 is a luminous IRAS starburst galaxy with more dust and complex Ly- alpha profile. The use of STIS will allow for the first time to study the geometrical/kinematical configuration of the ionized and neutral gas across the galaxies nuclear regions and pin point the effects of porosity and the kinematical structure of the ISM, that may play the key roles {in addition to dust} in the detectability of the line. This study will have important impact for cosmology since Ly-alpha emitters are nowaday found at high-re dshift. We strongly emphasize that since Ly-alpha is primarely a diagnostic of the ISM, a full understanding of how the ISM and Ly-alpha are related is a necessary step before we can hope to correlate Ly-alpha to the cosmic star-formation rate. Our results will be interpreted against the model of superbubble evolution developed with G. Tenorio Tagle.

  1. Lucid dreaming and alpha activity: a preliminary report. (United States)

    Ogilvie, R D; Hunt, H T; Tyson, P D; Lucescu, M L; Jeakins, D B


    10 good dream recallers spent 2 nights in the sleep lab during which they were awakened 4 times per night from REM sleep, twice during their highest alpha activity in REM, and twice during low REM alpha. 5 were given alpha feedback training prior to sleep onset. Arousals from high alpha REM sleep yielded significantly higher lucidity ratings. Alpha feedback had no effect upon lucidity or REM alpha levels. Similarities between lucid dreams and meditative phenomena are discussed.

  2. Structural and dynamic study of the tetramerization region of non-erythroid alpha-spectrin: a frayed helix revealed by site-directed spin labeling electron paramagnetic resonance. (United States)

    Li, Qufei; Fung, L W-M


    The N-terminal region of alpha-spectrin is responsible for its association with beta-spectrin in a heterodimer, forming functional tetramers. Non-erythroid alpha-spectrin (alphaII-spectrin) has a significantly higher association affinity for beta-spectrin than the homologous erythroid alpha-spectrin (alphaI-spectrin). We have previously determined the solution structure of the N-terminal region of alphaI-spectrin by NMR methods, but currently no structural information is available for alphaII-spectrin. We have used cysteine scanning, spin labeling electron paramagnetic resonance (EPR), and isothermal titration calorimetry (ITC) methods to study the tetramerization region of alphaII-spectrin. EPR data clearly show that, in alphaII-spectrin, the first nine N-terminal residues were unstructured, followed by an irregular helix (helix C'), frayed at the N-terminal end, but rigid at the C-terminal end, which merges into the putative triple-helical structural domain. The region corresponding to the important unstructured junction region linking helix C' to the first structural domain in alphaI-spectrin was clearly structured. On the basis of the published model for aligning helices A', B', and C', important interactions among residues in helix C' of alphaI- and alphaII-spectrin and helices A' and B' of betaI- and betaII-spectrin are identified, suggesting similar coiled coil helical bundling for spectrin I and II in forming tetramers. The differences in affinity are likely due to the differences in the conformation of the junction regions. Equilibrium dissociation constants of spin-labeled alphaII and betaI complexes from ITC measurements indicate that residues 15, 19, 37, and 40 are functionally important residues in alphaII-spectrin. Interestingly, all four corresponding homologous residues in alphaI-spectrin (residues 24, 28, 46, and 49) have been reported to be clinically significant residues involved in hematological diseases.

  3. Variable displacement alpha-type Stirling engine (United States)

    Homutescu, V. M.; Bălănescu, D. T.; Panaite, C. E.; Atanasiu, M. V.


    The basic design and construction of an alpha-type Stirling engine with on load variable displacement is presented. The variable displacement is obtained through a planar quadrilateral linkage with one on load movable ground link. The physico-mathematical model used for analyzing the variable displacement alpha-type Stirling engine behavior is an isothermal model that takes into account the real movement of the pistons. Performances and power adjustment capabilities of such alpha-type Stirling engine are calculated and analyzed. An exemplification through the use of the numerical simulation was performed in this regard.

  4. Alpha decay chains from superheavy nuclei

    CERN Document Server

    Samanta, C


    Magic islands for extra-stable nuclei in the midst of the sea of fission-instability were predicted to be around Z=114, 124 or, 126 with N=184, and Z=120, with N=172. Whether these fission-survived superheavy nuclei with high Z and N would live long enough for detection or, undergo alpha-decay in a very short time remains an open question. Alpha-decay half lives of nuclei with 130 118 are found to have alpha-decay half lives of the order of microseconds or, less.

  5. First Attempts at Antihydrogen Trapping in ALPHA

    CERN Document Server

    Andresen, G B; Bowe, P D; Bray, C C; Butler, E; Cesar, C L; Chapman, S; Charlton, M; Fajans, J; Funakoshi, R; Gill, D R; Hangst, J S; Hardy, W N; Hayano, R S; Hayden, M E; Humphries, A J; Hydomako, R; Jenkins, M J; Jørgensen, L V; Kurchaninov, L; Lambo, R; Madsen, N; Nolan, P; Olchanski, K; Olin, A; Page, R D; Povilus, A; Pusa, P; Robicheaux, F; Sarid, E; Seif El Nasr, S; Silveira, D M; Storey, J W; Thompson, R I; Van der Werf, D P; Wasilenko, L; Wurtele, J S; Yamazaki, Y; Fujiwara, M C


    We discuss aspects of antihydrogen studies, that relate to particle physics ideas and techniques, within the context of the ALPHA experiment at CERN's Antiproton Decelerator facility. We review the fundamental physics motivations for antihydrogen studies, and their potential physics reach. We argue that initial spectroscopy measurements, once antihydrogen is trapped, could provide competitive tests of CPT, possibly probing physics at the Planck Scale. We discuss some of the particle detection techniques used in ALPHA. Preliminary results from commissioning studies of a partial system of the ALPHA Si vertex detector are presented, the results of which highlight the power of annihilation vertex detection capability in antihydrogen studies.

  6. On $\\alpha$-roughly weighted games

    CERN Document Server

    Freixas, Josep


    Very recently Gvozdeva, Hemaspaandra, and Slinko (2011) have introduced three hierarchies for simple games in order to measure the distance of a given simple game to the class of weighted voting games or roughly weighted voting games. Their third class $\\mathcal{C}_\\alpha$ consists of all simple games permitting a weighted representation such that each winning coalition has a weight of at least 1 and each losing coalition a weight of at most $\\alpha$. We continue their work and contribute some new results on the possible values of $\\alpha$ for a given number of voters.

  7. Generalized dual symmetry of nonabelian theories and the freezing of \\alpha_s

    CERN Document Server

    Das, C R; Nielsen, H B


    The quantum Yang-Mills theory, describing a system of fields with non-dual (chromo-electric g) and dual (chromo-magnetic \\tilde g) charges and revealing the generalized dual symmetry, is developed by analogy with the Zwanziger formalism in QED. The renormalization group equations (RGEs) for pure nonabelian theories are analysed for both constants, \\alpha = g^2 / 4\\pi and \\tilde\\alpha = {\\tilde g}^2 / 4\\pi. The pure SU(3) \\times \\widetilde{SU(3)} gauge theory is investigated as an example. We consider not only monopoles, but also dyons. The behaviour of the total SU(3) \\beta-function is investigated in the whole region of \\alpha \\equiv \\alpha_s: 0 \\le \\alpha < \\infty. It is shown that this \\beta-function is antisymmetric under the interchange \\alpha \\leftrightarrow 1/\\alpha and is given by the well-known perturbative expansion not only for \\alpha \\ll 1, but also for \\alpha \\gg 1. Using an idea of the Maximal Abelian Projection by t' Hooft, we considered the formation of strings - the ANO flux tubes - in the...

  8. Measurements of $\\alpha_s$ in $pp$ Collisions at the LHC

    CERN Document Server

    Warburton, Andreas; The ATLAS collaboration


    The coupling of the strong force, $\\alpha_s$, is deemed to be a fundamental parameter of Nature, and, beyond the quark masses, constitutes the only free parameter in the QCD Lagrangian. Provided is an overview of CERN Large Hadron Collider (LHC) measurements of $\\alpha_s(M_Z)$ evaluated at the $Z$-boson mass and of the running of $\\alpha_s(Q)$ as a function of energy-momentum transfer $Q$. The measurements were performed by the ATLAS and CMS Collaborations using proton-proton ($pp$) collisions with centre-of-mass energies of 7 TeV and data samples with time-integrated luminosities of up to 5 fb$^{-1}$. Four different categories of observable were used in the described extractions of $\\alpha_s$: inclusive jet cross sections, 3-jet to 2-jet inclusive cross-section ratios, 3-jet mass cross sections, and top-quark pair production cross sections. These results, which include the first NNLO measurement of $\\alpha_s$ at a hadron collider and the first determinations of $\\alpha_s$ at energy scales above 1 TeV, are co...

  9. Collagen alpha5 and alpha2(IV) chain coexpression: analysis of skin biopsies of Alport patients. (United States)

    Patey-Mariaud de Serre, N; Garfa, M; Bessiéres, B; Noël, L H; Knebelmann, B


    Alport syndrome is a collagen type IV disease caused by mutations in the COL4A5 gene with the X-linked form being most prevalent. The resultant alpha5(IV) collagen chain is a component of the glomerular and skin basement membranes (SBMs). Immunofluorescent determination of the alpha5(IV) chain in skin biopsies is the procedure of choice to identify patients. In 30% of patients, however, the mutant protein is still found in the SBM resulting in a normal staining pattern. In order to minimize or eliminate false results, we compared the distribution of the alpha2(IV) chain (another SBM component) and the alpha5(IV) chain by standard double label immunofluorescence (IF) and by confocal laser scanning microscopy. The study was performed on 55 skin biopsies of patients suspected of Alports and five normal control specimens. In normal skin, IF showed the classical linear pattern for both collagens along the basement membrane. Additionally, decreased alpha5(IV) was found in the bottom of the dermal papillary basement membrane. Confocal analysis confirmed the results and show alpha5(IV) focal interruptions. In suspected patients, both techniques showed the same rate of abnormal alpha5(IV) expression: segmental in women and absent in men. Our results show a physiological variation of alpha5(IV) location with focal interruptions and decreased expression in the bottom of the dermal basement membrane. Comparison of alpha5(IV) with alpha2(IV) expression is simple and eliminates technical artifacts.

  10. Alpha-Synuclein to the Rescue: Immune Cell Recruitment by Alpha-Synuclein during Gastrointestinal Infection. (United States)

    Labrie, Viviane; Brundin, Patrik


    Intraneuronal accumulation of misfolded alpha-synuclein in the central and peripheral nervous systems is strongly linked to Parkinson disease (PD) and other related synucleinopathies. In rare inherited forms of PD, point mutations or gene multiplications mediate the formation of alpha-synuclein protein aggregates. However, in most PD cases it is presumed that the combined effects of ageing and environmental factors drive the formation of alpha-synuclein aggregates. Despite advances regarding alpha-synuclein pathobiology, the normal functions of this protein and factors that regulate its expression are not well understood. We discuss a recent study reporting that viral infection induces alpha-synuclein expression in neurons of the gastrointestinal tract. Alpha-synuclein levels increased during norovirus infection in the duodenum of children. In an in vitro paradigm, monomeric and oligomeric alpha-synuclein acted as chemoattractants for neutrophils and monocytes, and promoted the maturation of dendritic cells. This suggests that alpha-synuclein facilitates immune responses to infection. We explore the possibility that intestinal infections, and associated inflammation, place individuals at increased risk of PD by increasing alpha-synuclein levels and promoting the formation of alpha-synuclein aggregates that propagate in a prion-like fashion via the vagal nerve to the brainstem. © 2017 S. Karger AG, Basel.

  11. High precision $^{89}$Y($\\alpha$,$\\alpha$)$^{89}$Y scattering at low energies

    CERN Document Server

    Kiss, G G; \\, Zs; Fülöp,; Galaviz, D; Gyürky, Gy; Elekes, Z; Somorjai, E; Kretschmer, A; Sonnabend, K; Zilges, A; Avrigeanu, M


    Elastic scattering cross sections of the $^{89}$Y($\\alpha$,$\\alpha$)$^{89}$Y reaction have been measured at energies E$_{c.m.}$ = 15.51 and 18.63 MeV. The high precision data for the semi-magic $N = 50$ nucleus $^{89}$Y are used to derive a local potential and to evaluate the predictions of global and regional $\\alpha$-nucleus potentials. The variation of the elastic alpha scattering cross sections along the $N = 50$ isotonic chain is investigated by a study of the ratios of angular distributions for $^{89}$Y($\\alpha$,$\\alpha$)$^{89}$Y and $^{92}$Mo($\\alpha$,$\\alpha$)$^{92}$Mo at E$_{c.m.} \\approx$ 15.51 and 18.63 MeV. This ratio is a very sensitive probe at energies close to the Coulomb barrier, where scattering data alone is usually not enough to characterize the different potentials. Furthermore, $\\alpha$-cluster states in $^{93}$Nb = $^{89}$Y $\\otimes$ $\\alpha$ are investigated.

  12. $\\alpha_s$ from the updated ALEPH data for hadronic $\\tau$ decays

    CERN Document Server

    Boito, Diogo; Maltman, Kim; Osborne, James; Peris, Santiago


    We extract the strong coupling $\\alpha_s(m_\\tau^2)$ from the recently updated ALEPH non-strange spectral functions obtained from hadronic $\\tau$ decays. We apply a self-consistent analysis method, first tested in the analysis of OPAL data, to extract $\\alpha_s(m_\\tau^2)$ and non-perturbative contributions. The analysis yields $\\alpha_s^{\\rm FO}(m_\\tau^2)=0.296\\pm0.010 $, using Fixed Order Perturbation Theory (FOPT), and $\\alpha^{\\rm CI}_s(m_\\tau^2)= 0.310\\pm0.014$, using Contour Improved Perturbation Theory (CIPT). The weighted average of these results with those previously obtained from OPAL data give $\\alpha_s^{\\rm FO}(m_\\tau^2)=0.303\\pm 0.009$ and $\\alpha_s^{\\rm CI}(m_\\tau^2)=0.319\\pm 0.012$, which gives, after evolution to the $Z$ boson mass scale, $\\alpha^{\\rm FO}_s(m_Z^2)=0.1165\\pm0.0012 $ and $\\alpha_s^{\\rm CI}(m_Z^2)=0.1185\\pm0.0015 $, respectively. We observe that non-perturbative effects limit the accuracy with which $\\alpha_s$ can be extracted from $\\tau$ decay data.

  13. Validity test of the Trojan Horse Method applied to the {sup 7}Li+p{yields} {alpha}+{alpha} reaction via the {sup 3}He break-up

    Energy Technology Data Exchange (ETDEWEB)

    Tumino, A.; Spitaleri, C.; Sergi, M.L.; Cherubini, S.; La Cognata, M.; Lamia, L.; Romano, S.; Tudisco, S. [Universita di Catania, Dipartimento di Metodologie Fisiche e Chimiche per l' Ingegneria, Catania (Italy); INFN Laboratori Nazionali del Sud, Catania (Italy); Kroha, V.; Burjan, V.; Novac, J.; Vincour, J. [Nuclear Physics Institute of ASCR, Rez, Prague (Czech Republic); Fueloep, Z.; Somorjai, E. [Institute of Nuclear Research of Hungarian Academy of Sciences (ATOMKI), Debrecen (Hungary); Pizzone, R.G. [INFN Laboratori Nazionali del Sud, Catania (Italy)


    The Trojan Horse Method (THM) was applied to the {sup 3}He+{sup 7}Li interaction in order to investigate the quasi-free {sup 7}Li(p,{alpha}){sup 4}He reaction. The three-body experiment was performed at 33 MeV corresponding to a {sup 7}Li-p relative energy ranging from 50 keV to 7 MeV. The extracted {sup 7}Li(p,{alpha}){sup 4}He quasi-free cross-section was compared with the behavior of direct data, as well as with the result of a previous THM investigation on the {sup 7}Li(p,{alpha}){sup 4}He reaction off the neutron in {sup 2}H. A good agreement between data sets shows up throughout the energy range investigated, providing a very important validity test of the pole approximation for the THM. (orig.)

  14. Synthesis of alpha-phosphorylated alpha,beta-unsaturated imines and their selective reduction to vinylogous and saturated alpha-aminophosphonates. (United States)

    Palacios, Francisco; Vicario, Javier; Maliszewska, Agnieszka; Aparicio, Domitila


    An efficient synthesis of alpha,beta-unsaturated imines derived from alpha-aminophosphonates is achieved through aza-Wittig reaction of P-trimethyl phosphazenes with beta,gamma-unsaturated alpha-ketophosphonates. Selective 1,2-reduction of such 1-azadienes affords beta,gamma-unsaturated alpha-aminophosphonates, phosphorylated analogs of vinylglycines, which are hydrogenated to yield saturated alpha-aminophosphonate derivatives.

  15. Nickel doping effect on resistance to movement of edge dislocations in. cap alpha. -Fe

    Energy Technology Data Exchange (ETDEWEB)

    Brovkov, V.A.; Dudarev, E.F. (Tomskij Gosudarstvennyj Univ. (USSR). Sibirskij Fiziko-Tekhnicheskij Inst.)


    Microplastic deformation of ..cap alpha..-Fe polycrystals and Fe-Ni solid solutions is studied. Data on the concentration and temperature dependences of resistance to movement of edge dislocation at the expense of elastic interaction with atoms of the doping element are obtained.

  16. Fragmentation of alpha- and beta-alanine molecules by ions at Bragg-peak energies

    NARCIS (Netherlands)

    Bari, S.; Sobocinski, P.; Postma, J.; Alvarado, F.; Hoekstra, R.; Bernigaud, V.; Manil, B.; Rangama, J.; Huber, B.; Schlathoelter, T.


    The interaction of keV He(+), He(2+), and O(5+) ions with isolated alpha and beta isomers of the amino acid alanine was studied by means of high resolution coincidence time-of-flight mass spectrometry. We observed a strong isomer dependence of characteristic fragmentation channels which manifests in

  17. Complete $\\alpha^6\\,m$ corrections to the ground state of H$_2$

    CERN Document Server

    Puchalski, Mariusz; Czachorowski, Pawel; Pachucki, Krzysztof


    We perform the calculation of all relativistic and quantum electrodynamic corrections of the order of $\\alpha^6\\,m$ to the ground electronic state of a hydrogen molecule and present improved results for the dissociation and the fundamental transitions energies. These results open the window for the high-precision spectroscopy of H$_2$ and related low-energy tests of fundamental interactions.

  18. Cysteine-rich domain of human ADAM 12 (meltrin alpha) supports tumor cell adhesion

    DEFF Research Database (Denmark)

    Iba, K; Albrechtsen, R; Gilpin, B J;


    The ADAMs (A disintegrin and metalloprotease) comprise a family of membrane-anchored cell surface proteins with a putative role in cell-cell and/or cell-matrix interactions. By immunostaining, ADAM 12 (meltrin alpha) was up-regulated in several human carcinomas and could be detected along the tum...

  19. Structural Basis for Iloprost as a Dual Peroxisome Proliferator-activated Receptor [alpha/delta] Agonist

    Energy Technology Data Exchange (ETDEWEB)

    Jin, Lihua; Lin, Shengchen; Rong, Hui; Zheng, Songyang; Jin, Shikan; Wang, Rui; Li, Yong (Pitt); (Xiamen)


    Iloprost is a prostacyclin analog that has been used to treat many vascular conditions. Peroxisome proliferator-activated receptors (PPARs) are ligand-regulated transcription factors with various important biological effects such as metabolic and cardiovascular physiology. Here, we report the crystal structures of the PPAR{alpha} ligand-binding domain and PPAR{delta} ligand-binding domain bound to iloprost, thus providing unambiguous evidence for the direct interaction between iloprost and PPARs and a structural basis for the recognition of PPAR{alpha}/{delta} by this prostacyclin analog. In addition to conserved contacts for all PPAR{alpha} ligands, iloprost also initiates several specific interactions with PPARs using its unique structural groups. Structural and functional studies of receptor-ligand interactions reveal strong functional correlations of the iloprost-PPAR{alpha}/{delta} interactions as well as the molecular basis of PPAR subtype selectivity toward iloprost ligand. As such, the structural mechanism may provide a more rational template for designing novel compounds targeting PPARs with more favorable pharmacologic impact based on existing iloprost drugs.

  20. Determination of alpha_s and W boson leptonic branching ratio from the W and Z cross sections

    CERN Document Server

    Xiao, Weichen


    We try to determine the strong coupling alpha_s and the W boson leptonic branching ratio from the W and Z boson production cross section through pp collisions in the LHC. We run the MCFM program together with LHAPDF or HERAPDF les to extract the theoretical prediction of cross sections at different alpha_s in different experiments. We compare the predicted values and the experimental results to do a precise measurement of alpha_s and the branching ratio.