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Sample records for 10b states analogue

  1. Analysis of T = 1 {sup 10}B States Analogue to {sup 10}Be Cluster States

    SciTech Connect

    Uroic, M.; Miljanic, D.; Blagus, S.; Bogovac, M.; Prepolec, L.; Skukan, N.; Soic, N.; Majer, M.; Milin, M.; Lattuada, M.; Musumarra, A.; Acosta, L.

    2009-08-26

    Current status of the search for T = 1 cluster states in {sup 10}Be, {sup 10}B and {sup 10}C is presented. The best known of the three, {sup 10}Be, has an established rotational band (6.18, 7.54 and 10.15 MeV) with unusually large moment of inertia. Search of their isobaric analogue in {sup 10}B is presented, with emphasis on {sup 3}He+{sup 11}B reaction.

  2. 10Bstates with chain-like structures in 14N

    NASA Astrophysics Data System (ADS)

    Kanada-En'yo, Yoshiko

    2015-12-01

    I investigate 10B+α -cluster states of 14N with a 10B+α -cluster model. Near the α -decay threshold energy, I obtain Kπ=3+ and Kπ=1+ rotational bands having 10B(3+) +α and 10B(1+) +α components, respectively. I assign the bandhead state of the Kπ=3+ band to the experimental 3+ at Ex=13.19 MeV of 14N observed in α scattering reactions by 10B and show that the calculated α -decay width is consistent with the experimental data. I discuss an α -cluster motion around the 10B cluster and show that the Kπ=3+ and Kπ=1+ rotational bands contain an enhanced component of a linear-chain 3 α configuration, in which an α cluster is localized in the longitudinal direction around the deformed 10B cluster.

  3. Radiative proton capture to low-lying T =0 and T =1 states in 10B

    NASA Astrophysics Data System (ADS)

    Chakrabarty, D. R.; Datar, V. M.; Kumar, Suresh; Mirgule, E. T.; Mishra, G.; Rout, P. C.; Ghosh, C.; Nanal, V.; Joshi, S.; Kujur, R.

    2017-01-01

    Cross sections of the radiative proton capture reaction 9Be(p ,γ ) , leading to the low-lying excited states in 10B with isospin T =0 and 1, have been measured over the proton energy range of 7 to 20 MeV. For this, the method of coincidence between the primary and the secondary γ rays has been used. These γ rays are emitted following, respectively, the proton capture to an excited state and the subsequent decay of that state. A direct-semidirect capture model calculation has been performed and compared with the experimental data. The experimental results do not show a strong isospin dependence of the GDR strength function built on the low-lying states. The derived photoproton cross sections on these states and the earlier-measured photoneutron cross sections on the ground state of 10B show a large difference.

  4. Transition States and transition state analogue interactions with enzymes.

    PubMed

    Schramm, Vern L

    2015-04-21

    Enzymatic transition states have lifetimes of a few femtoseconds (fs). Computational analysis of enzyme motions leading to transition state formation suggests that local catalytic site motions on the fs time scale provide the mechanism to locate transition states. An experimental test of protein fs motion and its relation to transition state formation can be provided by isotopically heavy proteins. Heavy enzymes have predictable mass-altered bond vibration states without altered electrostatic properties, according to the Born-Oppenheimer approximation. On-enzyme chemistry is slowed in most heavy proteins, consistent with altered protein bond frequencies slowing the search for the transition state. In other heavy enzymes, structural changes involved in reactant binding and release are also influenced. Slow protein motions associated with substrate binding and catalytic site preorganization are essential to allow the subsequent fs motions to locate the transition state and to facilitate the efficient release of products. In the catalytically competent geometry, local groups move in stochastic atomic motion on the fs time scale, within transition state-accessible conformations created by slower protein motions. The fs time scale for the transition state motions does not permit thermodynamic equilibrium between the transition state and stable enzyme states. Isotopically heavy enzymes provide a diagnostic tool for fast coupled protein motions to transition state formation and mass-dependent conformational changes. The binding of transition state analogue inhibitors is the opposite in catalytic time scale to formation of the transition state but is related by similar geometries of the enzyme-transition state and enzyme-inhibitor interactions. While enzymatic transition states have lifetimes as short as 10(-15) s, transition state analogues can bind tightly to enzymes with release rates greater than 10(3) s. Tight-binding transition state analogues stabilize the rare but

  5. Two-dimensional solid state gaseous detector based on 10B layer for thermal and cold neutrons

    NASA Astrophysics Data System (ADS)

    Potashev, S.; Burmistrov, Yu; Drachev, A.; Karaevsky, S.; Konobeevski, E.; Zuyev, S.

    2017-01-01

    Two-dimensional solid state gaseous detector for thermal and cold neutrons is created. The detector has active area of 128 x 128 mm2, 10B neutron converter, and gas chamber with thin windows. The resistive charge-division readout is applied to determine the neutron position. The detector was tested using W-Be photoneutron source at the Institute for Nuclear Research, Moscow. The detector efficiency is estimated as ∼4% at neutron wavelength λ = 1.82 Å and 8% at λ = 8 Å. The efficiency of the background detection was less than 10-5 of that for thermal neutrons. The resulting pulse height resolution and the spatial resolution are estimated as ∼15% and ∼2.5 mm, respectively.

  6. Isobaric Analogue States Studied in Mirrored Fragmentation and Knockout Reactions

    SciTech Connect

    Bentley, M.A.; Pritychenko, B.; Paterson,I.; Brown,J.R.; Taylor,M.J.; Digen,C.Aa.; Adrich,P.; Bazin,D.; Cook.J.M.; Gade,A.; Glasmacher,T.; McDaniel,S.; Ratkiewicz,A.; Siwek,K.; D.Weisshaar,D.; Pritychenko,B.; Lenzi,S.M.

    2010-05-21

    A Gamma-ray spectroscopic study of excited states of isobaric multiplets has been performed in recent years, with a view to gaining a quantitative understanding of energy differences between excited states in terms of a range of Coulomb and other isospin breaking phenomena. Recently, the experimental programme has been augmented by a study of isobaric analogue states of mirror nuclei populated in mirrored fragmentation reactions. In this presentation, recent results on the T = 3/2 analogue states in the T{sub z} = {+-} 3/2 mirror pair {sup 53}Ni/{sup 53}Mn will be summarised. In this work, further strong evidence is found for the need to include an anomalous isospin-breaking two-body matrix element for angular-momentum couplings of J = 2, in addition the expected Coulomb contribution, in order to account for the experimental data.

  7. OptZyme: Computational Enzyme Redesign Using Transition State Analogues

    PubMed Central

    Grisewood, Matthew J.; Gifford, Nathanael P.; Pantazes, Robert J.; Li, Ye; Cirino, Patrick C.; Janik, Michael J.; Maranas, Costas D.

    2013-01-01

    OptZyme is a new computational procedure for designing improved enzymatic activity (i.e., kcat or kcat/KM) with a novel substrate. The key concept is to use transition state analogue compounds, which are known for many reactions, as proxies for the typically unknown transition state structures. Mutations that minimize the interaction energy of the enzyme with its transition state analogue, rather than with its substrate, are identified that lower the transition state formation energy barrier. Using Escherichia coli β-glucuronidase as a benchmark system, we confirm that KM correlates (R2 = 0.960) with the computed interaction energy between the enzyme and the para-nitrophenyl- β, D-glucuronide substrate, kcat/KM correlates (R2 = 0.864) with the interaction energy of the transition state analogue, 1,5-glucarolactone, and kcat correlates (R2 = 0.854) with a weighted combination of interaction energies with the substrate and transition state analogue. OptZyme is subsequently used to identify mutants with improved KM, kcat, and kcat/KM for a new substrate, para-nitrophenyl- β, D-galactoside. Differences between the three libraries reveal structural differences that underpin improving KM, kcat, or kcat/KM. Mutants predicted to enhance the activity for para-nitrophenyl- β, D-galactoside directly or indirectly create hydrogen bonds with the altered sugar ring conformation or its substituents, namely H162S, L361G, W549R, and N550S. PMID:24116038

  8. Martin B-10B

    NASA Technical Reports Server (NTRS)

    1935-01-01

    Martin B-10B: Although the front turret looks like it may have bee too high, the drag of the Martin B-10 bomber was low enough for it to have been faster than any U. S. Fighter when it was first ordered in January 1933. The NACA flew one of these B-10Bs in 1937 at the Langley Memorial Aeronautical Laboratory.

  9. Superconducting analogue of the parafermion fractional quantum Hall states

    NASA Astrophysics Data System (ADS)

    Vaezi, Abolhassan

    2014-03-01

    Read and Rezayi Zk parafermion wavefunctions describe ν = 2 + k /(kM + 2) fractional quantum Hall (FQH) states. These states support non-Abelian excitations from which protected quantum gates can be designed. However, there is no experimental evidence for these non-Abelian anyons to date. In this talk, we discuss the ν = 2 / k FQH-superconductor heterostructure and through analytical and numerical calculations we argue that it can yield the superconducting analogue of the Zk parafermion FQH state. The resulting topological state has a gapless chiral edge state with Zk parafermion conformal field theory description. For instance, we find that a ν = 2 / 3 FQH in proximity to a superconductor produces a Z3 parafermion superconducting state. This state can host Fibonacci anyons capable of performing universal quantum computation through braiding operations. We finally discuss our experimental proposal for realizing parafermion superconductors. Reference: arXiv:1307.8069

  10. L-Enantiomers of Transition State Analogue Inhibitors Bound to Human Purine Nucleoside Phosphorylase

    SciTech Connect

    Rinaldo-Matthis,A.; Murkin, A.; Ramagopal, U.; Clinch, K.; Mee, S.; Evans, G.; Tyler, P.; Furneaux, R.; Almo, S.; Schramm, v.

    2008-01-01

    Human purine nucleoside phosphorylase (PNP) was crystallized with transition-state analogue inhibitors Immucillin-H and DADMe-Immucillin-H synthesized with ribosyl mimics of l-stereochemistry. The inhibitors demonstrate that major driving forces for tight binding of these analogues are the leaving group interaction and the cationic mimicry of the transition state, even though large geometric changes occur with d-Immucillins and l-Immucillins bound to human PNP.

  11. Anomalous transition in {sup 10}B

    SciTech Connect

    Kurath, D.

    1995-08-01

    The transitions between the J,T = 3,0 ground state of {sup 10}B and the 3,0 state at 4.77 MeV present some puzzling features. The gamma transition between the states is of unknown multipolarity and very weak, with a strength of only 0.1 WU even if it is a pure E2. The shell model with the Cohen-Kurath POT interaction predicts a nearly pure E2 transition but with a transition probability about 4 times too strong. Recent inelastic pion scattering experiments on {sup 10}B excited this state with a strength only one tenth the value predicted by the shell model. It was found that these weak transitions are very sensitive to the wave functions and that orthogonally mixing the states with an intensity of 2% can satisfy both the pion scattering and the {gamma} decay (60% E2, 40% M1).

  12. Specific recognition of a tetrahedral phosphonamidate transition state analogue group by a recombinant antibody Fab fragment.

    PubMed

    Hua, T D; Lamaty, F; Souriau, C; Rolland-Fulcrand, V; Lazaro, R; Viallefont, P; Lefranc, M P; Weill, M

    1996-06-01

    In order to obtain antibodies able to catalyse a peptide synthesis, a naive combinatorial library of human Fab antibody fragments was screened with the phosphonamidate transition state analogue of the reaction. Several Fab fragments were able to bind the analogue. Competitive binding studies performed with molecules containing representative parts of the hapten showed that two Fabs were able to recognize specifically the tetrahedral phosphorus present in the hapten.

  13. Heat Capacity Changes for Transition-State Analogue Binding and Catalysis with Human 5'-Methylthioadenosine Phosphorylase.

    PubMed

    Firestone, Ross S; Cameron, Scott A; Karp, Jerome M; Arcus, Vickery L; Schramm, Vern L

    2017-02-17

    Human 5'-methylthioadenosine phosphorylase (MTAP) catalyzes the phosphorolysis of 5'-methylthioadenosine (MTA). Its action regulates cellular MTA and links polyamine synthesis to S-adenosylmethionine (AdoMet) salvage. Transition state analogues with picomolar dissociation constants bind to MTAP in an entropically driven process at physiological temperatures, suggesting increased hydrophobic character or dynamic structure for the complexes. Inhibitor binding exhibits a negative heat capacity change (-ΔCp), and thus the changes in enthalpy and entropy upon binding are strongly temperature-dependent. The ΔCp of inhibitor binding by isothermal titration calorimetry does not follow conventional trends and is contrary to that expected from the hydrophobic effect. Thus, ligands of increasing hydrophobicity bind with increasing values of ΔCp. Crystal structures of MTAP complexed to transition-state analogues MT-DADMe-ImmA, BT-DADMe-ImmA, PrT-ImmA, and a substrate analogue, MT-tubercidin, reveal similar active site contacts and overall protein structural parameters, despite large differences in ΔCp for binding. In addition, ΔCp values are not correlated with Kd values. Temperature dependence of presteady state kinetics revealed the chemical step for the MTAP reaction to have a negative heat capacity for transition state formation (-ΔCp(‡)). A comparison of the ΔCp(‡) for MTAP presteady state chemistry and ΔCp for inhibitor binding revealed those transition-state analogues most structurally and thermodynamically similar to the transition state. Molecular dynamics simulations of MTAP apoenzyme and complexes with MT-DADMe-ImmA and MT-tubercidin show small, but increased dynamic motion in the inhibited complexes. Variable temperature CD spectroscopy studies for MTAP-inhibitor complexes indicate remarkable protein thermal stability (to Tm = 99 °C) in complexes with transition-state analogues.

  14. (10)B-NMR determination of (10)B-BPA, (10)B-BPA-fructose complex and total (10)B in blood for BNCT.

    PubMed

    Yoshino, K; Yabe, T; Hattori, T; Saito, K; Ishikawa, A; Ohki, H

    2014-06-01

    First spontaneous, noninvasive determination method of (10)B-BPA, (10)B-BPA-fructose complex, and total (10)B in blood is described. (10)B-NMR measurement with 100,000 FT accumulation enables us to obtain the result within 100min/sample. The detection limits for the simultaneous analysis were 3ppm, 3ppm and 6ppm for (10)B-BPA, (10)B-BPA-fructose complex and total (10)B respectively in this study. By this method, we can actually discuss behavior of the (10)B-BPA-fructose complex in blood.

  15. Classical analogues of Gilmore-Perelomov coherent states

    NASA Astrophysics Data System (ADS)

    Villanueva Vergara, Liliana; Rodríguez-Lara, B. M.

    2016-09-01

    We analyze the propagation of electromagnetic fields through tight-binding arrays of coupled photonic waveguides as a symmetry problem in the case of invariant properties of the propagation distance. We consider the Heisenberg-Weyl group and the photonic lattices with that underlying symmetry. Based on this, dispersion relations, impulse functions and normal states can be constructed from the point of view of Gilmore-Perelomov coherent state approach and different classes of propagation invariant input can be constructed.

  16. Precise Determination of 40Ti Mass by Measuring the 40Sc Isospin Analogue State

    NASA Astrophysics Data System (ADS)

    Liu, Wei-Ping; Hellström, M.; Collatz, R.; Benlliure, J.; Chulkov, L.; Cortina Gil, D.; Farget, F.; Grawe, H.; Z., Hu; Iwasa, N.; Pfützner, M.; Piechaczek, A.; Raabe, R.; Reusen, I.; Roeckl, E.; Vancraeynest, G.; Wöhr, A.

    2001-11-01

    The mass of 40Ti has been determined by using the isobaric multiplet mass equation method. The experimental data of the 40Ti β-decay were used to determine the level of the isospin analogue state of 40Sc. The ground-state mass excess and the QEC value for 40Ti were determined to be -9060+/-12 keV and 11 466 +/- 13 keV, respectively.

  17. Four Generations of Transition State Analogues for Human Purine Nucleoside Phosphorylase

    SciTech Connect

    Ho, M.; Shi, W; Rinaldo-Mathis, A; Tyler, P; Evans, G; Almo, S; Schramm, V

    2010-01-01

    Inhibition of human purine nucleoside phosphorylase (PNP) stops growth of activated T-cells and the formation of 6-oxypurine bases, making it a target for leukemia, autoimmune disorders, and gout. Four generations of ribocation transition-state mimics bound to PNP are structurally characterized. Immucillin-H (K*{sub i} = 58 pM, first-generation) contains an iminoribitol cation with four asymmetric carbons. DADMe-Immucillin-H (K*{sub i} = 9 pM, second-generation), uses a methylene-bridged dihydroxypyrrolidine cation with two asymmetric centers. DATMe-Immucillin-H (K*{sub i} = 9 pM, third-generation) contains an open-chain amino alcohol cation with two asymmetric carbons. SerMe-ImmH (K*{sub i} = 5 pM, fourth-generation) uses achiral dihydroxyaminoalcohol seramide as the ribocation mimic. Crystal structures of PNPs establish features of tight binding to be; (1) ion-pair formation between bound phosphate (or its mimic) and inhibitor cation, (2) leaving-group interactions to N1, O6, and N7 of 9-deazahypoxanthine, (3) interaction between phosphate and inhibitor hydroxyl groups, and (4) His257 interacting with the 5{prime}-hydroxyl group. The first generation analogue is an imperfect fit to the catalytic site with a long ion pair distance between the iminoribitol and bound phosphate and weaker interactions to the leaving group. Increasing the ribocation to leaving-group distance in the second- to fourth-generation analogues provides powerful binding interactions and a facile synthetic route to powerful inhibitors. Despite chemical diversity in the four generations of transition-state analogues, the catalytic site geometry is almost the same for all analogues. Multiple solutions in transition-state analogue design are available to convert the energy of catalytic rate enhancement to binding energy in human PNP.

  18. Nematic order-disorder state transition in a liquid crystal analogue formed by oriented and migrating amoeboid cells

    NASA Astrophysics Data System (ADS)

    Kemkemer, R.; Teichgräber, V.; Schrank-Kaufmann, S.; Kaufmann, D.; Gruler, H.

    2000-10-01

    In cell culture, liquid crystal analogues are formed by elongated, migrating, and interacting amoeboid cells. An apolar nematic liquid crystal analogue is formed by different cell types like human melanocytes (=pigment cells of the skin), human fibroblasts (=connective tissue cells), human osteoblasts (=bone cells), human adipocytes (=fat cells), etc. The nematic analogue is quite well described by i) a stochastic machine equation responsible for cell orientation and ii) a self-organized extracellular guiding signal, E_2, which is proportional to the orientational order parameter as well as to the cell density. The investigations were mainly made with melanocytes. The transition to an isotropic state analogue can be accomplished either by changing the strength of interaction (e.g. variation of the cell density) or by influencing the cellular machinery by an externally applied signal: i) An isotropic gaseous state analogue is observed at low cell density (ρ < 110melanocytes/mm^2) and a nematic liquid crystal state analogue at higher cell density. ii) The nematic state analogue disappears if the bipolar shaped melanocytes are forced to become a star-like shape (induced by colchicine or staurosporine). The analogy between nematic liquid crystal state analogue formed by elongated, migrating and interacting cells and the nematic liquid crystal phase formed by interacting elongated molecules is discussed.

  19. Analogue scale modelling of extensional tectonic processes using a large state-of-the-art centrifuge

    NASA Astrophysics Data System (ADS)

    Park, Heon-Joon; Lee, Changyeol

    2017-04-01

    Analogue scale modelling of extensional tectonic processes such as rifting and basin opening has been numerously conducted. Among the controlling factors, gravitational acceleration (g) on the scale models was regarded as a constant (Earth's gravity) in the most of the analogue model studies, and only a few model studies considered larger gravitational acceleration by using a centrifuge (an apparatus generating large centrifugal force by rotating the model at a high speed). Although analogue models using a centrifuge allow large scale-down and accelerated deformation that is derived by density differences such as salt diapir, the possible model size is mostly limited up to 10 cm. A state-of-the-art centrifuge installed at the KOCED Geotechnical Centrifuge Testing Center, Korea Advanced Institute of Science and Technology (KAIST) allows a large surface area of the scale-models up to 70 by 70 cm under the maximum capacity of 240 g-tons. Using the centrifuge, we will conduct analogue scale modelling of the extensional tectonic processes such as opening of the back-arc basin. Acknowledgement This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (grant number 2014R1A6A3A04056405).

  20. The Analogue of the Aharonov-Bohm Effect for Bound States for Neutral Particles

    NASA Astrophysics Data System (ADS)

    Bakke, Knut; Furtado, C.

    We study the analogue of the Aharonov-Bohm effect for bound states for a neutral particle with a permanent magnetic dipole moment interacting with an external field. We consider a neutral particle confined to moving between two coaxial cylinders and show the dependence of the energy levels on the Aharonov-Casher quantum flux. Moreover, we show that the same flux dependence of the bound states can be found when the neutral particle is confined to a one-dimensional quantum ring and a quantum dot, and we also calculate the persistent currents in each case.

  1. Excited state properties of a short π-electron conjugated peridinin analogue

    PubMed Central

    Magdaong, Nikki M.; Niedzwiedzki, Dariusz M.; Greco, Jordan A.; Liu, Hongbin; Yano, Koki; Kajikawa, Takayuki; Sakaguchi, Kazuhiko; Katsumura, Shigeo; Birge, Robert R.; Frank, Harry A.

    2014-01-01

    C29-peridinin is a synthetic analogue of the important, naturally-occurring carotenoid, peridinin, found in several marine algal species. C29-peridinin has five conjugated carbon-carbon double bonds compared to eight possessed by peridinin and also lacks the methyl group functionalities typically present along the polyene chain of carotenoids. These structural modifications lead to unique excited state properties and important insights regarding the factors controlling the photophysics of peridinin and other carbonyl-containing carotenoids, which are critical components of the light-harvesting systems of many photosynthetic organisms. PMID:24678069

  2. Excited state properties of a short π-electron conjugated peridinin analogue

    NASA Astrophysics Data System (ADS)

    Magdaong, Nikki M.; Niedzwiedzki, Dariusz M.; Greco, Jordan A.; Liu, Hongbin; Yano, Koki; Kajikawa, Takayuki; Sakaguchi, Kazuhiko; Katsumura, Shigeo; Birge, Robert R.; Frank, Harry A.

    2014-02-01

    C29-peridinin is a synthetic analogue of the important, naturally-occurring carotenoid, peridinin, found in several marine algal species. C29-peridinin has five conjugated carbon-carbon double bonds compared to eight possessed by peridinin and also lacks the methyl group functionalities typically present along the polyene chain of carotenoids. These structural modifications lead to unique excited state properties and important insights regarding the factors controlling the photophysics of peridinin and other carbonyl-containing carotenoids, which are critical components of the light-harvesting systems of many photosynthetic organisms.

  3. Transition state analogues in structures of ricin and saporin ribosome-inactivating proteins

    SciTech Connect

    Ho, Meng-Chiao; Sturm, Matthew B.; Almo, Steven C.; Schramm, Vern L.

    2010-01-12

    Ricin A-chain (RTA) and saporin-L1 (SAP) catalyze adenosine depurination of 28S rRNA to inhibit protein synthesis and cause cell death. We present the crystal structures of RTA and SAP in complex with transition state analogue inhibitors. These tight-binding inhibitors mimic the sarcin-ricin recognition loop of 28S rRNA and the dissociative ribocation transition state established for RTA catalysis. RTA and SAP share unique purine-binding geometry with quadruple {pi}-stacking interactions between adjacent adenine and guanine bases and 2 conserved tyrosines. An arginine at one end of the {pi}-stack provides cationic polarization and enhanced leaving group ability to the susceptible adenine. Common features of these ribosome-inactivating proteins include adenine leaving group activation, a remarkable lack of ribocation stabilization, and conserved glutamates as general bases for activation of the H{sub 2}O nucleophile. Catalytic forces originate primarily from leaving group activation evident in both RTA and SAP in complex with transition state analogues.

  4. Transition State Analogues Rescue Ribosomes from Saporin-L1 Ribosome Inactivating Protein†

    PubMed Central

    Sturm, Matthew B.; Tyler, Peter C.; Evans, Gary B.; Schramm, Vern L.

    2009-01-01

    Ribosome-inactivating proteins (RIPs) catalyze the hydrolytic depurination of one or more adenosine residues from eukaryotic ribosomes. Depurination of the ribosomal sarcin-ricin tetraloop (GAGA) causes inhibition of protein synthesis and cellular death. We characterized the catalytic properties of saporin-L1 from Saponaria officinalis (soapwort) leaves and demonstrate robust activity against defined nucleic acid substrates and mammalian ribosomes. Transition state analogue mimics of small oligonucleotide substrates of saporin-L1 are powerful, slow-onset inhibitors when adenosine is replaced with the transition state mimic 9-deazaadenine-9-methylene-N-hydroxypyrrolidine (DADMeA). Linear, cyclic and stem-loop oligonucleotide inhibitors containing DADMeA and based on the GAGA sarcin-ricin tetraloop gave slow-onset tight-binding inhibition constants (Ki*) of 2.3 to 8.7 nM at physiological conditions and bind up to 40,000-fold tighter than RNA substrates. Saporin-L1 inhibition of rabbit reticulocyte translation was protected by these inhibitors. Transition state analogues of saporin-L1 have potential in cancer therapy that employs saporin-L1 linked immunotoxins. PMID:19764816

  5. Development of bacteriorhodopsin analogues and studies of charge separated excited states in the photoprocesses of linear polyenes.

    PubMed

    Singh, Anil K; Hota, Prasanta K

    2007-01-01

    Development of bacteriorhodopsin (bR) analogues employing chromophore substitution technique for the purpose of characterizing the binding site of bR and generating bR analogues with novel opto-electronic properties for applications as photoactive element in nanotechnical devices are described. Additionally, the photophysical and photochemical properties of variously substituted diarylpolyenes as models of photobiologically relevant linear polyenes are discussed. The role of charge separated dipolar excited states in the photoprocesses of linear polyenes is highlighted.

  6. MgF3(-) and AlF4(-) transition state analogue complexes of yeast phosphoglycerate kinase.

    PubMed

    McCormick, Nicole E; Forget, Stephanie M; Syvitski, Raymond T; Jakeman, David L

    2016-07-14

    The phospho-transfer mechanism of yeast phosphoglycerate kinase (PGK) has been probed through formation of trifluoromagnesate (MgF3(-)) and tetrafluoroaluminate (AlF4(-)) transition state analogue complexes and analyzed using (19)F, (1)H waterLOGSY and (1)H chemical shift perturbation NMR spectroscopy. We observed the first (19)F NMR spectroscopic evidence for the formation of metal fluoride transition state analogues of yeast PGK and also observed significant changes to proton chemical shifts of PGK in the presence, but not in the absence, of fluoride upon titration of ligands, providing indirect evidence of the formation of a closed ternary transition state. WaterLOGSY NMR spectroscopy experiments using an uncompetitive model were used in an attempt to measure ligand binding affinities within the transition state analogue complexes.

  7. LC-MS of palytoxin and its analogues: State of the art and future perspectives.

    PubMed

    Ciminiello, Patrizia; Dell'Aversano, Carmela; Dello Iacovo, Emma; Fattorusso, Ernesto; Forino, Martino; Tartaglione, Luciana

    2011-03-01

    The state of the art of LC-MS of palytoxin and its analogues is reported in the present review. MS data for palytoxin, 42-hydroxy-palytoxin, ostreocin-D, mascarenotoxins, and ovatoxins, obtained using different ionization techniques, namely fast-atom bombardment (FAB), matrix assisted laser desorption ionization (MALDI), and electrospray ionization (ESI), are summarized together with the LC-MS methods used for their detection. Application of the developed LC-MS methods to both plankton and seafood analysis is also reported, paying attention to the extraction procedures used and to limits of detection (LOD) and quantitation (LOQ) achieved. In a research setting, LC-MS has shown a good potential in determination of palytoxin and its analogues from various sources, but, in a regulatory setting, routine LC-MS analysis of palytoxins is still at a preliminary stage. The LOQ currently achieved in seafood analysis appears insufficient to detect palytoxins in shellfish extract at levels close to the tolerance limit for palytoxins (30 μg/kg) proposed by the European Food Safety Authority (EFSA, 2009). In addition, lacking of certified reference standard of palytoxins as well as of validation studies for the proposed LC-MS methods represent important issues that should be faced for future perspectives of LC-MS technique.

  8. WNT10B mutations in human obesity

    PubMed Central

    Christodoulides, C.; Scarda, A.; Granzotto, M.; Milan, G.; Dalla Nora, E.; Keogh, J.; De Pergola, G.; Stirling, H.; Pannacciulli, N.; Sethi, J. K.; Federspil, G.; Vidal-Puig, A.; Farooqi, I. S.; O’Rahilly, S.; Vettor, R.

    2015-01-01

    Aims/hypothesis Recent studies suggest that wingless-type MMTV integration site family, member 10B (WNT10B) may play a role in the negative regulation of adipocyte differentiation in vitro and in vivo. In order to determine whether mutations in WNT10B contribute to human obesity, we screened two independent populations of obese subjects for mutations in this gene. Subjects and methods We studied 96 subjects with severe obesity of early onset (less than 10 years of age) from the UK Genetics of Obesity Study and 115 obese Italian subjects of European origin. Results One proband with early-onset obesity was found to be heterozygous for a C256Y mutation, which abrogated the ability of WNT10B to activate canonical WNT signalling and block adipogenesis and was not found in 600 control alleles. All relatives of the proband who carried this allele were either overweight or obese. Three other rare missense variants were found in obese probands, but these did not clearly cosegregate with obesity in family studies and one (P301S), which was found in three unrelated subjects with early-onset obesity, had normal functional properties. Conclusions/interpretation These mutations represent the first naturally occurring missense variants of WNT10B. While the pedigree analysis in the case of C256Y WNT10B does not provide definitive proof of a causal link of this variant with obesity, the finding of a non-functioning WNT10B allele in a human family affected by obesity should encourage further study of this gene in other obese populations. PMID:16477437

  9. Slow Photoelectron Spectroscopy and State-Selected Unimolecular Decomposition of Ionized DNA Bases Analogues

    NASA Astrophysics Data System (ADS)

    Mahjoub, Ahmed; Hochlaf, Majdi; Poisson, Lionel; Garcia, Gustavo A.; Nahon, Laurent

    2013-06-01

    We studied the single-photon ionization of gas-phase 2-Piperidone (DNA basis analogue) and of its dimer using vacuum-ultraviolet (VUV) synchrotron radiation coupled to a velocity map imaging electron/ion coincidence spectrometer The slow photoelectron spectrum (SPES) of the monomer is dominated by the vibrational transitions to the ground state. These spectra are assigned with the help of theoretical calculations dealing with the equilibrium geometries, electronic-state patterns and evolutions, harmonic and anharmonic wavenumbers. After its formation, dimer is subject of intramolecular isomerization, H transfer and then unimolecular fragmentation processes. The near threshold photofragmentation pattern of the cationic 2-Piperidone cation and its dimer has been recorded. The experimental method yields the fragment intensity as a function of the internal energy deposited into the parent cation. In parallel, ab initio studies on ionic and neutral fragmentation products have been performed with the aim of determining the isomers of the ionic products observed experimentally as well as of their neutral counterparts. L. Nahon, N. De Oliveria,J. F. Gil,B. Pilette,O. Marcouillé, B. La garde and F. Polack Journal of Synchrotron Radiation {19}(4), 508-520; 2012

  10. Steady-state kinetics of horse-liver alcohol dehydrogenase with a covalently bound coenzyme analogue.

    PubMed

    Kovár, J; Simek, K; Kucera, I; Matyska, L

    1984-03-15

    The steady-state kinetics of the enzyme modified by affinity labelling with NAD analogue, nicotinamide-N6-[N-(6-aminohexyl)carbamoylmethyl]-adenine dinucleotide, has been investigated using a recycling reaction with p-nitrosodimethylaniline and n-butanol as substrates and compared to the kinetics of native alcohol dehydrogenase. The modified enzyme obeys a ping-pong mechanism involving two inactive enzyme forms (enzyme-NAD and enzyme-NADH complexes in the 'open' conformations, the nicotinamide moieties of the coenzymes being out of the active center). The rate of p-nitrosodimethylaniline reduction in the reaction catalyzed by the modified enzyme is comparable to that observed in the presence of the native enzyme. On the other hand, the oxidation of butanol by the modified enzyme is essentially slower under our experimental conditions (pH 8.5). The measurements in the presence of specific alcohol dehydrogenase inhibitors competing with substrates and coenzymes (isobutyramide, pyrazole and AMP) revealed that the relative portion of the inactive 'open' form of the enzyme-NADH complex is negligible, whereas the 'open' form of the enzyme-NAD complex seems to represent a more significant portion (about 30%) under the conditions used.

  11. Crystallization of a carbamatase catalytic antibody Fab fragment and its complex with a transition-state analogue.

    PubMed

    Muranova, Tatyana A; Ruzheinikov, Sergey N; Higginbottom, Adrian; Clipson, Jennifer A; Blackburn, G Michael; Wentworth, Paul; Datta, Anita; Rice, David W; Partridge, Lynda J

    2004-01-01

    Catalytic antibodies showing carbamatase activity have significant potential in antibody-directed prodrug therapy against tumours. The Fab fragment of an IgG1 mouse monoclonal carbamatase catalytic antibody JC1 raised against a transition-state analogue, ethyl N-(3,5-dicarboxyphenyl)-P-[N-[5'-(2",5"-dioxo-1"-pyrrolidinyl)oxy-1',5'-dioxopentyl]-4-aminophenylmethyl]phosphonamidate, was obtained by digestion of the whole antibody with papain and was purified by two-step ion-exchange chromatography. Using hanging-drop vapour-diffusion crystallization techniques, three different crystal forms of the Fab fragment were obtained in the presence and absence of the transition-state analogue. All crystals diffract X-rays to between 3.5 and 3.2 A resolution. The two crystal forms grown in the presence of the transition-state analogue contain up to four or eight copies of the Fab in the asymmetric unit and diffract to 3.5 and 3.2 A, respectively. The crystal of the Fab alone is most likely to contain only two copies of the Fab in the asymmetric unit and diffracts to beyond 3.5 A. Determination of the structure will provide insights into the active-site arrangement of this antibody and will help to increase our understanding of the molecular mechanisms by which the immune system can evolve catalytic function.

  12. Kepler's First Rocky Planet: Kepler-10b

    NASA Astrophysics Data System (ADS)

    Batalha, Natalie M.; Borucki, William J.; Bryson, Stephen T.; Buchhave, Lars A.; Caldwell, Douglas A.; Christensen-Dalsgaard, Jørgen; Ciardi, David; Dunham, Edward W.; Fressin, Francois; Gautier, Thomas N., III; Gilliland, Ronald L.; Haas, Michael R.; Howell, Steve B.; Jenkins, Jon M.; Kjeldsen, Hans; Koch, David G.; Latham, David W.; Lissauer, Jack J.; Marcy, Geoffrey W.; Rowe, Jason F.; Sasselov, Dimitar D.; Seager, Sara; Steffen, Jason H.; Torres, Guillermo; Basri, Gibor S.; Brown, Timothy M.; Charbonneau, David; Christiansen, Jessie; Clarke, Bruce; Cochran, William D.; Dupree, Andrea; Fabrycky, Daniel C.; Fischer, Debra; Ford, Eric B.; Fortney, Jonathan; Girouard, Forrest R.; Holman, Matthew J.; Johnson, John; Isaacson, Howard; Klaus, Todd C.; Machalek, Pavel; Moorehead, Althea V.; Morehead, Robert C.; Ragozzine, Darin; Tenenbaum, Peter; Twicken, Joseph; Quinn, Samuel; VanCleve, Jeffrey; Walkowicz, Lucianne M.; Welsh, William F.; Devore, Edna; Gould, Alan

    2011-03-01

    NASA's Kepler Mission uses transit photometry to determine the frequency of Earth-size planets in or near the habitable zone of Sun-like stars. The mission reached a milestone toward meeting that goal: the discovery of its first rocky planet, Kepler-10b. Two distinct sets of transit events were detected: (1) a 152 ± 4 ppm dimming lasting 1.811 ± 0.024 hr with ephemeris T [BJD] =2454964.57375+0.00060 -0.00082 + N*0.837495+0.000004 -0.000005 days and (2) a 376 ± 9 ppm dimming lasting 6.86 ± 0.07 hr with ephemeris T [BJD] =2454971.6761+0.0020 -0.0023 + N*45.29485+0.00065 -0.00076 days. Statistical tests on the photometric and pixel flux time series established the viability of the planet candidates triggering ground-based follow-up observations. Forty precision Doppler measurements were used to confirm that the short-period transit event is due to a planetary companion. The parent star is bright enough for asteroseismic analysis. Photometry was collected at 1 minute cadence for >4 months from which we detected 19 distinct pulsation frequencies. Modeling the frequencies resulted in precise knowledge of the fundamental stellar properties. Kepler-10 is a relatively old (11.9 ± 4.5 Gyr) but otherwise Sun-like main-sequence star with T eff = 5627 ± 44 K, M sstarf = 0.895 ± 0.060 M sun, and R sstarf = 1.056 ± 0.021 R sun. Physical models simultaneously fit to the transit light curves and the precision Doppler measurements yielded tight constraints on the properties of Kepler-10b that speak to its rocky composition: M P = 4.56+1.17 -1.29 M ⊕, R P = 1.416+0.033 -0.036 R ⊕, and ρP = 8.8+2.1 -2.9 g cm-3. Kepler-10b is the smallest transiting exoplanet discovered to date. Based in part on observations obtained at the W. M. Keck Observatory, which is operated by the University of California and the California Institute of Technology.

  13. Picomolar transition state analogue inhibitors of human 5'-methylthioadenosine phosphorylase and X-ray structure with MT-immucillin-A.

    PubMed

    Singh, Vipender; Shi, Wuxian; Evans, Gary B; Tyler, Peter C; Furneaux, Richard H; Almo, Steven C; Schramm, Vern L

    2004-01-13

    Methythioadenosine phosphorylase (MTAP) functions solely in the polyamine pathway of mammals to remove the methylthioadenosine (MTA) product from both spermidine synthase (2.5.1.16) and spermine synthase (2.5.1.22). Inhibition of polyamine synthesis is a validated anticancer target. We designed and synthesized chemically stable analogues for the proposed transition state of human MTAP on the basis of the known ribooxacarbenium character at all reported N-ribosyltransferase transition states [Schramm, V. L. (2003) Acc. Chem. Res. 36, 588-596]. Methylthio-immucillin-A (MT-ImmA) is an iminoribitol tight-binding transition state analogue inhibitor with an equilibrium dissociation constant of 1.0 nM. The immucillins resemble the ribooxacarbenium ion transition states of N-ribosyltransferases and are tightly bound as the N4' cations. An ion pair formed between the iminoribitol cation and phosphate anion mimics the ribooxacarbenium cation-phosphate anion pair formed at the transition state and is confirmed in the crystal structure. The X-ray crystal structure of human MTAP with bound MT-Imm-A also reveals that the 5'-methylthio group lies in a flexible hydrophobic pocket. Substitution of the 5'-methylthio group with a 5'-phenylthio group gives an equilibrium binding constant of 1.0 nM. Methylthio-DADMe-immucillin-A is a pyrrolidine analogue of the transition state with a methylene bridge between the 9-deazaadenine group and the pyrrolidine ribooxacarbenium mimic. It is a slow-onset inhibitor with a dissociation constant of 86 pM. Improved binding energy with DADMe-immucillin-A suggests that the transition state is more closely matched by increasing the distance between leaving group and ribooxacarbenium mimics, consistent with a more dissociative transition state. Increasing the hydrophobic volume near the 5'-position at the catalytic site with 5'-phenylthio-DADMe-immucillin-A gave a dissociation constant of 172 pM, slightly weaker than the 5'-methylthio group. p

  14. The spin-free analogue of Mukherjee's state-specific multireference coupled cluster theory.

    PubMed

    Datta, Dipayan; Mukherjee, Debashis

    2011-02-07

    spin-free analogues of the spin-orbital based Mk-MRCC theory. This leads to manifest size-extensivity and an intruder-free formulation. Our formalism provides a relaxed description of the nondynamical correlation in presence of dynamical correlation. Pilot numerical applications to doublet systems, e.g., potential energy surfaces for the first two excited (2)A' states of asymmetric H(2)S(+) ion and the ground (2)Σ(+)state of BeH radical are presented to assess the viability of our formalism over an wide range of nuclear geometries and the manifest avoidance of intruder state problem.

  15. Effects of Wnt-10b on proliferation and differentiation of murine melanoma cells

    SciTech Connect

    Misu, Masayasu; Ouji, Yukiteru; Kawai, Norikazu; Nishimura, Fumihiko; Nakamura-Uchiyama, Fukumi; Yoshikawa, Masahide

    2015-08-07

    In spite of the strong expression of Wnt-10b in melanomas, its role in melanoma cells has not been elucidated. In the present study, the biological effects of Wnt-10b on murine B16F10 (B16) melanoma cells were investigated using conditioned medium from Wnt-10b-producing COS cells (Wnt-CM). After 2 days of culture in the presence of Wnt-CM, proliferation of B16 melanoma cells was inhibited, whereas tyrosinase activity was increased. An in vitro wound healing assay demonstrated that migration of melanoma cells to the wound area was inhibited with the addition of Wnt-CM. Furthermore, evaluation of cellular senescence revealed prominent induction of SA-β-gal-positive senescent cells in cultures with Wnt-CM. Finally, the growth of B16 melanoma cell aggregates in collagen 3D-gel cultures was markedly suppressed in the presence of Wnt-CM. These results suggest that Wnt-10b represses tumor cell properties, such as proliferation and migration of B16 melanoma cells, driving them toward a more differentiated state along a melanocyte lineage. - Highlights: • Wnt-10b inhibited proliferation and migration of melanoma cells. • Wnt-10b induced tyrosinase activity and senescence of melanoma cells. • Wnt-10b suppressed growth of cell aggregates in collagen 3D-gel cultures. • Wnt-10b represses tumor cell properties, driving them toward a more differentiated state along a melanocyte lineage.

  16. An alpha autoradiographic technique for spatial quantification of sup 10 B concentrations in tissue

    SciTech Connect

    Woollard, J.E.; Blue, T.E.; Curran, J.F.; Dobelbower, M.C.; Busby, H.R. ); Barth, R.F. )

    1992-01-01

    This paper reports on boron neutron capture therapy (BNCT) which is an experimental radiation therapy that is being developed for the treatment of malignant tumors. One requirement for successful BNCT is that a sufficient amount of {sup 10}B concentrates in the tumor while clearing from normal tissues and blood. Many pharmaceuticals are currently being developed to selectively deliver {sup 10}B to a tumor. To evaluate the effectiveness of various {sup 10}B delivery agents, the concentrations of boron in blood, tumor, and normal tissues must be known. Using the solid-state nuclear track detector CR-39, a tissue assay technique has been developed to spatially determine {sup 10}B concentrations in tissue samples. The technique has been used to quantify {sup 10}B concentrations in tumor and normal tissue on lines across rat brain tissue sections. This was done by combining {sup 10}B concentrations measured on lines across the CR-39 with color digital images of the tissue section. Coupling the methodology that was developed for tissue samples with an existing analytical technique for blood-{sup 10}B concentration measurements allows for complete evaluation of {sup 10}B distributions in blood, tumor, and normal tissues and should be useful in evaluating various {sup 10}B delivery agents for use in BNCT.

  17. 17 CFR 260.10b-5 - Content.

    Code of Federal Regulations, 2010 CFR

    2011-04-01

    ... 17 Commodity and Securities Exchanges 3 2011-04-01 2011-04-01 false Content. 260.10b-5 Section 260.10b-5 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION (CONTINUED) GENERAL RULES AND REGULATIONS, TRUST INDENTURE ACT OF 1939 Rule Under Section 310 § 260.10b-5 Content. (a)...

  18. 17 CFR 260.10b-5 - Content.

    Code of Federal Regulations, 2010 CFR

    2000-04-01

    ... 17 Commodity and Securities Exchanges 3 2000-04-01 2000-04-01 false Content. 260.10b-5 Section 260.10b-5 Commodity and Securities Exchanges GENERAL RULES AND REGULATIONS, TRUST INDENTURE ACT OF 1939 Rule Under Section 310 § 260.10b-5 Content. (a) Each application for a stay of a trustee's duty...

  19. 17 CFR 260.10b-5 - Content.

    Code of Federal Regulations, 2010 CFR

    2012-04-01

    ... 17 Commodity and Securities Exchanges 3 2012-04-01 2012-04-01 false Content. 260.10b-5 Section 260.10b-5 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION (CONTINUED) GENERAL RULES AND REGULATIONS, TRUST INDENTURE ACT OF 1939 Rule Under Section 310 § 260.10b-5 Content. (a)...

  20. 17 CFR 260.10b-5 - Content.

    Code of Federal Regulations, 2010 CFR

    2005-04-01

    ... 17 Commodity and Securities Exchanges 3 2005-04-01 2005-04-01 false Content. 260.10b-5 Section 260.10b-5 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION (CONTINUED) GENERAL RULES AND REGULATIONS, TRUST INDENTURE ACT OF 1939 Rule Under Section 310 § 260.10b-5 Content. (a)...

  1. Analogue mouse pointer control via an online steady state visual evoked potential (SSVEP) brain-computer interface

    NASA Astrophysics Data System (ADS)

    Wilson, John J.; Palaniappan, Ramaswamy

    2011-04-01

    The steady state visual evoked protocol has recently become a popular paradigm in brain-computer interface (BCI) applications. Typically (regardless of function) these applications offer the user a binary selection of targets that perform correspondingly discrete actions. Such discrete control systems are appropriate for applications that are inherently isolated in nature, such as selecting numbers from a keypad to be dialled or letters from an alphabet to be spelled. However motivation exists for users to employ proportional control methods in intrinsically analogue tasks such as the movement of a mouse pointer. This paper introduces an online BCI in which control of a mouse pointer is directly proportional to a user's intent. Performance is measured over a series of pointer movement tasks and compared to the traditional discrete output approach. Analogue control allowed subjects to move the pointer faster to the cued target location compared to discrete output but suffers more undesired movements overall. Best performance is achieved when combining the threshold to movement of traditional discrete techniques with the range of movement offered by proportional control.

  2. Catalytic amidolysis of amino acid p-nitroanilides using transition state analogue imprinted artificial enzymes: Cooperative effect of pyridine moiety.

    PubMed

    Divya, Mathew; Benny, Thomas; Christy, Philip; Aparna, E P; Devaky, K S

    2017-10-01

    Enzyme-like polymer catalysts with the imprints of phosphonate transition state analogue (TSA) lined along with imidazole and pyridine moieties were synthesized using methacryloyl-l-histidine and 4-vinylpyridine as the functional monomers and phenyl-1-(N-benzyloxycarbonylamino)-2-(phenyl)ethyl phosphonate - the TSA of hydrolytic reaction as the template for the amidolysis of N-benzyloxycarbonyl-l-phenylalanine p-nitroanilide (Z-l-Phe-PNA). Polymers containing different functional groups can act together to provide catalytic activity and selectivity superior to what can be obtained from monofunctional analogues. The higher rate acceleration exhibited by the bifunctional polymer over the monofunctional polymers indicates cooperative catalysis of imidazole and pyridine moieties. The optimum catalytic competence is shown by the bifunctional polymer containing imidazole and pyridine moieties in 2:1M ratio which may be due to alignment of the functional groups in proper H-bond distance. In addition to the non-covalent interactions like hydrogen bonding or π-stacking interactions between the functional groups of the polymer and the template, 3D-microcavities complementary to the geometry of the template are necessary for effective shape selective binding. Michaelis-Menten kinetics implies that only the catalysts with imidazole moieties act as enzyme-like catalysts and imidazole is the key catalytic function of the enzyme mimics. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. NASA/ESMD Analogue Mission Plans

    NASA Technical Reports Server (NTRS)

    Hoffman, Stephen J.

    2007-01-01

    A viewgraph presentation exploring Earth and its analogues is shown. The topics include: 1) ESMD Goals for the Use of Earth Analogues; 2) Stakeholders Summary; 3) Issues with Current Analogue Situation; 4) Current state of Analogues; 5) External Implementation Plan (Second Step); 6) Recent Progress in Utilizing Analogues; 7) Website Layout Example-Home Page; 8) Website Layout Example-Analogue Site; 9) Website Layout Example-Analogue Mission; 10) Objectives of ARDIG Analog Initiatives; 11) Future Plans; 12) Example: Cold-Trap Sample Return; 13) Example: Site Characterization Matrix; 14) Integrated Analogue Studies-Prerequisites for Human Exploration; and 15) Rating Scale Definitions.

  4. Two active site divalent ions in the crystal structure of the hammerhead ribozyme bound to a transition state analogue

    DOE PAGES

    Mir, Aamir; Golden, Barbara L.

    2015-11-09

    The crystal structure of the hammerhead ribozyme bound to the pentavalent transition state analogue vanadate reveals significant rearrangements relative to the previously determined structures. The active site contracts, bringing G10.1 closer to the cleavage site and repositioning a divalent metal ion such that it could, ultimately, interact directly with the scissile phosphate. This ion could also position a water molecule to serve as a general acid in the cleavage reaction. A second divalent ion is observed coordinated to O6 of G12. This metal ion is well-placed to help tune the pKA of G12. Finally, on the basis of this crystalmore » structure as well as a wealth of biochemical studies, in this paper we propose a mechanism in which G12 serves as the general base and a magnesium-bound water serves as a general acid.« less

  5. Two active site divalent ions in the crystal structure of the hammerhead ribozyme bound to a transition state analogue

    SciTech Connect

    Mir, Aamir; Golden, Barbara L.

    2015-11-09

    The crystal structure of the hammerhead ribozyme bound to the pentavalent transition state analogue vanadate reveals significant rearrangements relative to the previously determined structures. The active site contracts, bringing G10.1 closer to the cleavage site and repositioning a divalent metal ion such that it could, ultimately, interact directly with the scissile phosphate. This ion could also position a water molecule to serve as a general acid in the cleavage reaction. A second divalent ion is observed coordinated to O6 of G12. This metal ion is well-placed to help tune the pKA of G12. Finally, on the basis of this crystal structure as well as a wealth of biochemical studies, in this paper we propose a mechanism in which G12 serves as the general base and a magnesium-bound water serves as a general acid.

  6. Analogue Gravity.

    PubMed

    Barceló, Carlos; Liberati, Stefano; Visser, Matt

    2011-01-01

    Analogue gravity is a research programme which investigates analogues of general relativistic gravitational fields within other physical systems, typically but not exclusively condensed matter systems, with the aim of gaining new insights into their corresponding problems. Analogue models of (and for) gravity have a long and distinguished history dating back to the earliest years of general relativity. In this review article we will discuss the history, aims, results, and future prospects for the various analogue models. We start the discussion by presenting a particularly simple example of an analogue model, before exploring the rich history and complex tapestry of models discussed in the literature. The last decade in particular has seen a remarkable and sustained development of analogue gravity ideas, leading to some hundreds of published articles, a workshop, two books, and this review article. Future prospects for the analogue gravity programme also look promising, both on the experimental front (where technology is rapidly advancing) and on the theoretical front (where variants of analogue models can be used as a springboard for radical attacks on the problem of quantum gravity).

  7. 17 CFR 260.10b-5 - Content.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Content. 260.10b-5 Section 260.10b-5 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION (CONTINUED) GENERAL RULES AND REGULATIONS, TRUST INDENTURE ACT OF 1939 Rule Under Section 310 § 260.10b-5 Content. (a) Each application for a stay of a trustee's duty...

  8. 17 CFR 260.10b-5 - Content.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 17 Commodity and Securities Exchanges 3 2013-04-01 2013-04-01 false Content. 260.10b-5 Section 260.10b-5 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION (CONTINUED) GENERAL RULES AND REGULATIONS, TRUST INDENTURE ACT OF 1939 Rule Under Section 310 § 260.10b-5 Content. (a) Each application for a stay of a trustee's duty...

  9. 17 CFR 260.10b-5 - Content.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 17 Commodity and Securities Exchanges 4 2014-04-01 2014-04-01 false Content. 260.10b-5 Section 260.10b-5 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION (CONTINUED) GENERAL RULES AND REGULATIONS, TRUST INDENTURE ACT OF 1939 Rule Under Section 310 § 260.10b-5 Content. (a) Each application for a stay of a trustee's duty...

  10. Intersections of potential energy surfaces of short-lived states: the complex analogue of conical intersections.

    PubMed

    Feuerbacher, Sven; Sommerfeld, Thomas; Cederbaum, Lorenz S

    2004-02-15

    Whereas conical intersections between potential energy surfaces of bound states are well known, the interaction of short-lived states has been investigated only rarely. Here, we present several systematically constructed model Hamiltonians to study the topology of intersecting complex potential energy surfaces describing short-lived states: We find the general phenomenon of doubly intersecting complex energy surfaces, i.e., there are two points instead of one as in the case of bound states where the potential energy surfaces coalesce. In addition, seams of intersections of the respective real and imaginary parts of the potential energy surfaces emanate from these two points. Using the Sigma* and Pi* resonance states of the chloroethene anion as a practical example, we demonstrate that our complete linear model Hamiltonian is able to reproduce all phenomena found in explicitly calculated ab initio complex potential energy surfaces.

  11. 18 CFR 35.10b - Electric Quarterly Reports.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 18 Conservation of Power and Water Resources 1 2013-04-01 2013-04-01 false Electric Quarterly Reports. 35.10b Section 35.10b Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY... energy or transmission services within the Electric Reliability Council of Texas or any entity...

  12. 18 CFR 35.10b - Electric Quarterly Reports.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 18 Conservation of Power and Water Resources 1 2014-04-01 2014-04-01 false Electric Quarterly Reports. 35.10b Section 35.10b Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY... energy or transmission services within the Electric Reliability Council of Texas or any entity...

  13. 17 CFR 260.10b-1 - Calculation of percentages.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Calculation of percentages. 260.10b-1 Section 260.10b-1 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION... Calculation of percentages. The percentages of voting securities and other securities specified in section...

  14. Population-Based Preference Weights for the EQ-5D Health States Using the Visual Analogue Scale (VAS) in Iran

    PubMed Central

    Goudarzi, Reza; Zeraati, Hojjat; Akbari Sari, Ali; Rashidian, Arash; Mohammad, Kazem

    2016-01-01

    Background Health-related quality of life (HRQoL) is used as a measure to valuate healthcare interventions and guide policy making. The EuroQol EQ-5D is a widely used generic preference-based instrument to measure Health-related quality of life. Objectives The objective of this study was to develop a value set of the EQ-5D health states for an Iranian population. Patients and Methods This study is a cross-sectional study of Iranian populations. Our sample from Iranian populations consists out of 869 participants, who were selected for this study using a stratified probability sampling method. The sample was taken from individuals living in the city of Tehran and was stratified by age and gender from July to November 2013. Respondents valued 13 health states using the visual analogue scale (VAS) of the EQ-5D. Several fixed effects regression models were tested to predict the full set of health states. We selected the final model based on the logical consistency of the estimates, the sign and magnitude of the regression coefficients, goodness of fit, and parsimony. We also compared predicted values with a value set from similar studies in the UK and other countries. Results Our results show that the HRQoL does not vary among socioeconomic groups. Models at the individual level resulted in an additive model with all coefficients being statistically significant, R2 = 0.55, a value of 0.75 for the best health state (11112), and a value of -0.074 for the worst health state (33333). The value set obtained for the study sample remarkably differs from those elicited in developed countries. Conclusions This study is the first estimate for the EQ-5D value set based on the VAS in Iran. Given the importance of locally adapted value set the use of this value set can be recommended for future studies in Iran and In the EMRO regions. PMID:27186384

  15. When a DNA triple helix melts: an analogue of the Efimov state

    NASA Astrophysics Data System (ADS)

    Maji, Jaya; Bhattacharjee, Somendra M.; Seno, Flavio; Trovato, Antonio

    2010-08-01

    The base sequences of DNA contain the genetic code, and, to decode it, a double helical DNA has to be unzipped to reveal the bases. Recent studies have shown that a third strand can be used to identify the base sequences, not by opening the double helix but rather by forming a triple helix. It is predicted here that a three-strand DNA exhibits the unusual behaviour of the existence of a three-chain bound state in the absence of any two being bound. Such a state can occur at or above the duplex melting point. This phenomenon is analogous to the Efimov state in three-particle quantum mechanics. A scaling theory is used to justify the Efimov connection. Real space renormalization group (RG) and exact numerical calculations are used to validate the prediction of a biological Efimov effect.

  16. Study of the 10B(p, αγ) 7Be and 10B (p,p‧ γ)10B reactions for PIGE purposes

    NASA Astrophysics Data System (ADS)

    Lagoyannis, A.; Preketes-Sigalas, K.; Axiotis, M.; Foteinou, V.; Harissopulos, S.; Kokkoris, M.; Misaelides, P.; Paneta, V.; Patronis, N.

    2015-01-01

    Differential cross sections were measured at 8 angles and at proton energies from 2 to 5 MeV for the 10B(p, αγ) 7Be and 10B (p,p‧ γ)10B reactions using two thin targets. The γ-rays emitted at Eγ = 429 and 718 keV respectively, were detected by four HPGe detectors placed on a motorized turntable. The overall systematic uncertainty of the measurements was estimated to be ∼8% while the statistical errors did not exceed 5%. The validity of the obtained cross sections was tested by performing a thick target benchmarking experiment. The results of the present work are compared with existing ones from literature and possible explanations for the observed differences are discussed.

  17. Specific killing effect of 10B1-para-boronophenylalanine in thermal neutron capture therapy of malignant melanoma: in vitro radiobiological evaluation

    SciTech Connect

    Ichihashi, M.; Nakanishi, T.; Mishima, Y.

    1982-03-01

    A 10B-dopa analogue, 10B1-para-boronophenylalanine (10B1-BPA) has been found to have a marked melanoma killing effect as expressed by the Do value, 0.9-1.2 X 10(12) n/cm2. The Do value of the neutron alone is 2.8 X 10(12) n/cm2. After the introduction of high LET irradiation into radiotherapy, its higher energy deposition in the target cancer cells is one of the major problems currently to be solved. This can be achieved by our thermal neutron capture therapy in the order of cellular dimensions when we have highly tumor-seeking 10B-compounds available. Our present evidence seems to indicate that our new 10B1-BPA can highly concentrate 10B into melanoma cells, to as much as 11 times the level of the medium in the in vitro system.

  18. B cell activating factor (BAFF) selects IL-10(-)B cells over IL-10(+)B cells during inflammatory responses.

    PubMed

    Ma, Ning; Zhang, Yu; Liu, Qilin; Wang, Zhiding; Liu, Xiaoling; Zhu, Gaizhi; Yu, Dandan; Han, Gencheng; Chen, Guojiang; Hou, Chunmei; Wang, Tianxiao; Ma, Yuanfang; Shen, Beifen; Li, Yan; Xiao, He; Wang, Renxi

    2017-05-01

    B cell activating factor (BAFF) regulates B cell maturation, survival, function, and plays a critical pathogenic role in autoimmune diseases. It remains unclear how BAFF affects IL-10(-)B cells versus regulatory B cells (Bregs) in inflammatory responses. In this study, we found that IL-10-expressing Bregs decreased in lupus-prone MRL/lpr mice and experimental allergic encephalomyelitis (EAE) mice. On blockade of the effects of BAFF with TACI-IgG, IL-10(+) Bregs were upregulated in MRL/lpr and EAE mice. In addition, BAFF expanded IL-10(+)B cells over IL-10(-)B cells under noninflammatory conditions in vitro, whereas it expanded IL-10(-)B cells over IL-10(+)B cells during inflammatory responses, such as stimulation with autoantigen and LPS. Finally, the selection of IL-10(-)B cells over IL-10(+)B cells by BAFF was dependent on BAFF receptors (BAFFR, TACI, and BCMA) that were upregulated by inflammatory responses. This study suggests that BAFF selects IL-10(-)B cells over IL-10(+) regulatory B cells via BAFF receptors in inflammatory responses.

  19. Three Hydrogen Bond Donor Catalysts: Oxyanion Hole Mimics and Transition State Analogues

    SciTech Connect

    Beletskiy, Evgeny V.; Schmidt, Jacob C.; Wang, Xue B.; Kass, Steven R.

    2012-11-14

    Enzymes and their mimics use hydrogen bonds to catalyze chemical transformations. Small molecule transition state analogs of oxyanion holes are characterized by gas phase IR and photoelectron spectroscopy and their binding constants in acetonitrile. As a result, a new class of hydrogen bond catalysts is proposed (OH donors that can contribute three hydrogen bonds to a single functional group) and demonstrated in a Friedel-Crafts reaction.

  20. Transient resonance Raman spectra of benzophenone and its four isotopic analogues in the lowest excited triplet state

    SciTech Connect

    Tahara, T.; Hamaguchi, H.; Tasumi, M.

    1987-11-05

    Transient resonance Raman spectra of T/sub 1/ benzophenone (T/sub 1/BP) and its four isotopic analogues in carbon tetrachloride solutions were measured. Vibrational assignments of eight T/sub 1/ bands have been made on the basis of the observed isotopic frequency shifts. The assignments clarified the following three points concerning the structure of T/sub 1/ BP in solution. (1) The CO bond order in T/sub 1/ BP is much lower than that in the ground-state benzophenone (S/sub 0/ BP). The CO stretching frequency in T/sub 1/ is found to be 1222 cm/sup -1/, whereas the corresponding value in S/sub 0/ is 1665 cm/sup -1/. The former frequency indicates a single-bond-like character of the CO bonding in the T/sub 1/ state. (2) Vibrational frequencies of several ring modes show marked downshifts in going from S/sub 0/ to T/sub 1/. This suggests the delocalization of the ..pi..* electron into the ring part. (3) The assignment (1302 cm/sup -1/) of the symmetric C-phenyl stretch mode in the T/sub 1/ withdraws S/sub 0/ absorption spectrum is questioned. According to the present assignment, the frequency of this mode (approx. 1100 cm/sup -1/) is slightly lower than that in the ground state (1150 cm/sup -1/). The simple quantum chemical picture of T/sub 1/ BP, which predicted the increase of the C-phenyl bond order with the ..pi..* withdraws n excitation, should therefore be reconsidered.

  1. Influence of long-term treatment with tuftsin analogue TP-7 on the anxiety-phobic states and body weight.

    PubMed

    Czabak-Garbacz, Róza; Cygan, Beata; Wolański, Lukasz; Kozlovsky, Igor

    2006-01-01

    TP-7 is a synthetic analogue of tuftsin. It has a structure of tuftsin, to which three natural L-amino-acids Pro-Gly-Pro are attached. This heptapeptide improves learning and memorization and causes antidepressant and anxiolytic effect. It is possible to use TP-7 in the future to optimize cognitive functions and as a potential new anxioselective, fast-acting and easy-dosed drug. Therefore, it was purposeful to study such properties of the heptapeptide as its influence on anxiety-fear and body weight under a long-term treatment regimen. The experiment was performed on 24 preselected Wistar rats with the use of Rodina's method. There were three experimental groups of animals with high initial emotional reactivity: passive control group (P), active control group (A, receiving distilled water) and group treated with TP-7 at the dose of 0.3 mg/kg (T). The rats of A and T groups received intraperitoneal injections every day. The experiments were conducted 15 min after the administration of the drug, one and two days after initial testing day, then 1, 2, 3 and 4 weeks after that. The heptapeptide reduced the anxiety-phobic states significantly starting from the second day of drug application. The observed effects persisted throughout four weeks of the experiment, which confirmed effective long-term anxiolytic properties of the heptapeptide. TP-7 did not cause any changes in the body mass by itself.

  2. Plasmodium falciparum Parasites Are Killed by a Transition State Analogue of Purine Nucleoside Phosphorylase in a Primate Animal Model

    PubMed Central

    Cassera, María B.; Hazleton, Keith Z.; Merino, Emilio F.; Obaldia, Nicanor; Ho, Meng-Chiao; Murkin, Andrew S.; DePinto, Richard; Gutierrez, Jemy A.; Almo, Steven C.; Evans, Gary B.; Babu, Yarlagadda S.; Schramm, Vern L.

    2011-01-01

    Plasmodium falciparum causes most of the one million annual deaths from malaria. Drug resistance is widespread and novel agents against new targets are needed to support combination-therapy approaches promoted by the World Health Organization. Plasmodium species are purine auxotrophs. Blocking purine nucleoside phosphorylase (PNP) kills cultured parasites by purine starvation. DADMe-Immucillin-G (BCX4945) is a transition state analogue of human and Plasmodium PNPs, binding with picomolar affinity. Here, we test BCX4945 in Aotus primates, an animal model for Plasmodium falciparum infections. Oral administration of BCX4945 for seven days results in parasite clearance and recrudescence in otherwise lethal infections of P. falciparum in Aotus monkeys. The molecular action of BCX4945 is demonstrated in crystal structures of human and P. falciparum PNPs. Metabolite analysis demonstrates that PNP blockade inhibits purine salvage and polyamine synthesis in the parasites. The efficacy, oral availability, chemical stability, unique mechanism of action and low toxicity of BCX4945 demonstrate potential for combination therapies with this novel antimalarial agent. PMID:22096507

  3. Inhibition and Structure of Trichomonas vaginalis Purine Nucleoside Phosphorylase with Picomolar Transition State Analogues

    SciTech Connect

    Rinaldo-Matthis,A.; Wing, C.; Ghanem, M.; Deng, H.; Wu, P.; Gupta, A.; Tyler, P.; Evans, G.; Furneaux, R.; et al.

    2007-01-01

    Trichomonas vaginalis is a parasitic protozoan purine auxotroph possessing a unique purine salvage pathway consisting of a bacterial type purine nucleoside phosphorylase (PNP) and a purine nucleoside kinase. Thus, T. vaginalis PNP (TvPNP) functions in the reverse direction relative to the PNPs in other organisms. Immucillin-A (ImmA) and DADMe-Immucillin-A (DADMe-ImmA) are transition stte mimics of adenosine with geometric and electrostatic features that resemble early and late transition states of adenosine at the transition state stabilized by TvPNP. ImmA demonstrates slow-onset tight-binding inhibition with TvPNP, to give an equilibrium dissociation constant of 87 pM, an inhibitor release half-time of 17.2 min, and a K{sub m}/K{sub d} ratio of 70,100. DADMe-ImmA resembles a late ribooxacarbenium ion transition state for TvPNP to give a dissociation constant of 30 pM, an inhibitor release half-time of 64 min, and a K{sub m}/K{sub d} ratio of 203,300. The tight binding of DADMe-ImmA supports a late S{sub N}1 transition state. Despite their tight binding to TvPNP, ImmA and DADMe-ImmA are weak inhibitors of human and P. falciparum PNPs. The crystal structures of the TvPNP-ImmA{center_dot}PO{sub 4} and TvPNP{center_dot}DADMe-ImmA{center_dot}PO{sub 4} ternary complexes differ from previous structures with substrate anologues. The tight binding with DADMe-ImmA is in part due to a 2.7 {angstrom} ionic interaction between a PO{sub 4} oxygen and the N1 cation of the hydroxypyrrolidine and is weaker in the TvPNP{center_dot}ImmA{center_dot}PO{sub 4} structure at 3.5 {angstrom}. However, the TvPNP{center_dot}ImmA{center_dot}PO{sub 4} structure includes hydrogen bonds between the 2'-hydroxyl and the protein that are not present in TvPNP{center_dot}DADMe-ImmA{center_dot}PO{sub 4}. These structures explain why DADMe-ImmA binds tighter than ImmA. Immucillin-H is a 12 nM inhibitor of TvPNP but a 56 pM inhibitor of human PNP. And this difference is explained by isotope

  4. The locus of microRNA-10b

    PubMed Central

    Biagioni, Francesca; Bossel Ben-Moshe, Noa; Fontemaggi, Giulia; Yarden, Yosef; Domany, Eytan; Blandino, Giovanni

    2013-01-01

    Contemporary microRNA research has led to significant advances in our understanding of the process of tumorigenesis. MicroRNAs participate in different events of a cancer cell’s life, through their ability to target hundreds of putative transcripts involved in almost every cellular function, including cell cycle, apoptosis, and differentiation. The relevance of these small molecules is even more evident in light of the emerging linkage between their expression and both prognosis and clinical outcome of many types of human cancers. This identifies microRNAs as potential therapeutic modifiers of cancer phenotypes. From this perspective, we overview here the miR-10b locus and its involvement in cancer, focusing on its role in the establishment (miR-10b*) and spreading (miR-10b) of breast cancer. We conclude that targeting the locus of microRNA 10b holds great potential for cancer treatment. PMID:23839045

  5. Excited-state intramolecular proton transfer molecules bearing o-hydroxy analogues of green fluorescent protein chromophore.

    PubMed

    Chuang, Wei-Ti; Hsieh, Cheng-Chih; Lai, Chin-Hung; Lai, Cheng-Hsuan; Shih, Chun-Wei; Chen, Kew-Yu; Hung, Wen-Yi; Hsu, Yu-Hsiang; Chou, Pi-Tai

    2011-10-21

    o-Hydroxy analogues, 1a-g, of the green fluorescent protein chromophore have been synthesized. Their structures and electronic properties were investigated by X-ray single-crystal analyses, electrochemistry, and luminescence properties. In solid and nonpolar solvents 1a-g exist mainly as Z conformers that possess a seven-membered-ring hydrogen bond and undergo excited-state intramolecular proton transfer (ESIPT) reactions, resulting in a proton-transfer tautomer emission. Fluorescence upconversion dynamics have revealed a coherent type of ESIPT, followed by a fast vibrational/solvent relaxation (<1 ps) to a twisted (regarding exo-C(5)-C(4)-C(3) bonds) conformation, from which a fast population decay of a few to several tens of picoseconds was resolved in cyclohexane. Accordingly, the proton-transfer tautomer emission intensity is moderate (0.08 in 1e) to weak (∼10(-4) in 1a) in cyclohexane. The stronger intramolecular hydrogen bonding in 1g suppresses the rotation of the aryl-alkene bond, resulting in a high yield of tautomer emission (Φ(f) ≈ 0.2). In the solid state, due to the inhibition of exo-C(5)-C(4)-C(3) rotation, intense tautomer emission with a quantum yield of 0.1-0.9 was obtained for 1a-g. Depending on the electronic donor or acceptor strength of the substituent in either the HOMO or LUMO site, a broad tuning range of the emission from 560 (1g) to 670 nm (1a) has been achieved.

  6. 33 CFR 157.10b - Segregated ballast tanks, dedicated clean ballast tanks, and special ballast arrangements for...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Continental Shelf oil. 157.10b Section 157.10b Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF... Continental Shelf oil. (a) Each tank vessel that is engaged in the transfer of crude oil from an offshore oil exploitation or production facility on the Outer Continental Shelf of the United States on or after June...

  7. Field investigation of dried lakes in western United States as an analogue to desiccation fractures on Mars

    NASA Astrophysics Data System (ADS)

    El-Maarry, M. R.; Watters, W. A.; Yoldi, Z.; Pommerol, A.; Fischer, D.; Eggenberger, U.; Thomas, N.

    2015-12-01

    Potential Desiccation Polygons (PDPs), tens to hundreds of meters in size, have been observed in numerous regions on Mars, particularly in ancient (>3 Gyr old) terrains of inferred paleolacustrine/playa geologic setting, and in association with hydrous minerals such as smectites. Therefore, a better understanding of the conditions in which large desiccation polygons form could yield unique insight into the ancient climate on Mars. Many dried lakebeds/playas in western United States display large (>50 m wide) desiccation polygons, which we consider to be analogues for PDPs on Mars. Therefore, we have carried out fieldwork in seven of these dried lakes in San Bernardino and the Death Valley National Park regions complemented with laboratory and spectral analysis of collected samples. Our study shows that the investigated lacustrine/playa sediments have (a) a soil matrix containing ~40-75% clays and fine silt (by volume) where the clay minerals are dominated by illite/muscovite followed by smectite, (b) carbonaceous mineralogy with variable amounts of chloride and sulfate salts, and significantly, (c) roughly similar spectral signatures in the visible-near-infrared (VIS-NIR) range. We conclude that the development of large desiccation fractures is consistent with water table retreat. In addition, the comparison of the mineralogical to the spectral observations further suggests that remote sensing VIS-NIR spectroscopy has its limitations for detailed characterization of lacustrine/playa deposits. Finally, our results imply that the widespread distribution of PDPs on Mars indicates global or regional climatic transitions from wet conditions to more arid ones making them important candidate sites for future in situ missions.

  8. Recent Findings in Relativistic Dissociation of {}^{10}B and {}^{12}C Nuclei

    NASA Astrophysics Data System (ADS)

    Artemenkov, D. A.; Mamatkulov, K. Z.; Kharlamov, S. P.; Zaitsev, A. A.; Zarubin, P. I.

    2017-03-01

    Recent findings related with the unstable nuclei ^8Be and ^9B in the coherent dissociation of relativistic nuclei ^{10}C, ^{10}B and ^{12}C in nuclear track emulsion ("white" stars) are highlighted The ^8Be_{g.s.} nucleus is manifested in the coherent dissociation ^{10}B → 2He + H with a probability of 25 ± 5% including 14 ± 3% of ^9B decays. A probability ratio of the mirror channels ^9B + n and ^9Be + p is estimated to be 6 ± 1. Reanalysis of relativistic ^{12}C dissociation in lead enriched emulsion revealed nine 3α -events corresponding to the Hoyle state.

  9. Absolute efficiency measurements with the 10B based Jalousie detector

    NASA Astrophysics Data System (ADS)

    Modzel, G.; Henske, M.; Houben, A.; Klein, M.; Köhli, M.; Lennert, P.; Meven, M.; Schmidt, C. J.; Schmidt, U.; Schweika, W.

    2014-04-01

    The 10B based Jalousie detector is a replacement for 3He counter tubes, which are nowadays less affordable for large area detectors due to the 3He crisis. In this paper we investigate and verify the performance of the new 10B based detector concept and its adoption for the POWTEX diffractometer, which is designed for the detection of thermal neutrons with predicted detection efficiencies of 75-50% for neutron energies of 10-100 meV, respectively. The predicted detection efficiency has been verified by absolute measurements using neutrons with a wavelength of 1.17 Å (59 meV).

  10. Radiosynthesis and evaluation of [11C]-(+)-4-propyl-3,4,4a,5,6,10b-hexahydro-2H-naphtho[1,2-b][1,4]oxazin-9-ol as a potential radiotracer for in vivo imaging of the dopamine D2 high-affinity state with positron emission tomography.

    PubMed

    Wilson, Alan A; McCormick, Patrick; Kapur, Shitij; Willeit, Matthaeus; Garcia, Armando; Hussey, Doug; Houle, Sylvain; Seeman, Philip; Ginovart, Nathalie

    2005-06-16

    In vivo imaging of dopamine D2 receptors with agonist (as opposed to the more commonly employed antagonist) radiotracers could provide important information on the high-affinity (functional) state of the D2 receptor in illnesses such as schizophrenia, movement disorders, and addictions. We report here the radiosynthesis and evaluation of the potent D2 agonist (+)-4-propyl-3,4,4a,5,6,10b-hexahydro-2H-naphtho[1,2-b][1,4]oxazin-9-ol, (+)-3, labeled with carbon-11, as a potential radiotracer for imaging the high-affinity state of dopamine D2 receptors with positron emission tomography (PET). [(11)C]-(+)-3 was reliably synthesized in the quantities and at the specific activities and radiochemical purities required for human PET studies. Ex vivo biodistribution studies in rat brain demonstrated that [(11)C]-(+)-3 crossed the blood-brain barrier readily and had an appropriate regional brain distribution for a radiotracer that maps dopamine D2 receptors. The binding of [(11)C]-(+)-3 was saturable and demonstrated an excellent signal-to-noise ratio as measured by its striatum-to-cerebellum ratio of 5.6, 60 min postinjection. The binding was highly stereospecific, and blocking and displacement studies were consistent with selective and specific binding to the dopamine D2 receptors. Further, [(11)C]-(+)-3 showed marked and appropriate sensitivity to both increases and decreases in the levels of endogenous dopamine. Brain radioactive metabolite and physicochemical measurements are in full accord with the desired properties of a neuroreceptor imaging agent for PET. All of the above, coupled with the documented full D2 agonistic properties of (+)-3, strongly indicate that [(11)C]-(+)-3 is a leading candidate radiotracer for the imaging of the dopamine D2 high-affinity state using PET in human subjects.

  11. Spectroscopic Investigation of Peridinin Analogues having Different π-electron Conjugated Chain Lengths: Exploring the Nature of the Intramolecular Charge Transfer State

    PubMed Central

    Niedzwiedzki, Dariusz M.; Chatterjee, Nirmalya; Enriquez, Miriam M.; Kajikawa, Takayuki; Hasegawa, Shinji; Katsumura, Shigeo; Frank, Harry A.

    2009-01-01

    The lifetime of the lowest excited singlet (S1) state of peridinin and many other carbonyl-containing carotenoids and polyenes has been reported depend on the polarity of the solvent. This effect has been attributed to the presence of an intramolecular charge transfer (ICT) state in the manifold of excited states for these molecules. The nature of this ICT state has yet to be elucidated. In the present work, steady-state and ultrafast time-resolved optical spectroscopy have been performed on peridinin and three synthetic analogues, C33-peridinin, C35-peridinin, and C39-peridinin which have different numbers of conjugated carbon-carbon double bonds. Otherwise, the molecules are structurally similar in that they posses the same functional groups. The trends in the positions of the steady-state and transient spectral profiles for this systematic series of molecules allow an assignment of the spectral features to transitions involving the S0, S1, S2 and ICT states. A kinetics analysis reveals the lifetimes of the excited states and the dynamics of their excited state deactivation pathways. The most striking observation in the data is that the lifetime of the ICT state converges to the same value of 10.0 ± 2.0 ps in the polar solvent, methanol, for all the peridinin analogues regardless of the extent of π-electron conjugation. This suggests that the ICT state is highly localized on the lactone ring which is a common structural feature in all the molecules. The data further suggest that the S1 and ICT states behave independently and that the ICT state is populated both from both S1 and S2, the rate and efficiency from S1 being dependent on the length of the π-electron chain of the carotenoid and the solvent polarity. PMID:19775150

  12. 18 CFR 35.10b - Electric Quarterly Reports.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Electric Quarterly... Application § 35.10b Electric Quarterly Reports. Each public utility shall file an updated Electric Quarterly..., file by January 31. Electric Quarterly Reports must be prepared in conformance with the Commission's...

  13. 18 CFR 35.10b - Electric Quarterly Reports.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 18 Conservation of Power and Water Resources 1 2011-04-01 2011-04-01 false Electric Quarterly... Application § 35.10b Electric Quarterly Reports. Each public utility shall file an updated Electric Quarterly..., file by January 31. Electric Quarterly Reports must be prepared in conformance with the Commission's...

  14. 18 CFR 35.10b - Electric Quarterly Reports.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 18 Conservation of Power and Water Resources 1 2012-04-01 2012-04-01 false Electric Quarterly... Application § 35.10b Electric Quarterly Reports. Each public utility shall file an updated Electric Quarterly..., file by January 31. Electric Quarterly Reports must be prepared in conformance with the...

  15. Study of the {sup 10}B(p,alpha){sup 7}Be Reaction through the Indirect Trojan Horse Method

    SciTech Connect

    Puglia, S. M. R.; Romano, S.; Lamia, L.; Spitaleri, C.; Cherubini, S.; Gulino, M.; La Cognata, M.; Pizzone, R. G.; Rapisarda, G. G.; Sergi, M. L.; Tudisco, S.; Del Santo, M. G.; Carlin, N.; Souza, F.; Szanto de Toledo, A.; Kroha, V.; Kubono, S.; Wakabayashi, Y.; Yamaguchi, H.; Li, C.

    2010-03-01

    The {sup 10}B(p,alpha){sup 7}Be reaction is the main responsible for {sup 10}B destruction in stellar interior. In such environments the process takes places mainly through a resonant state of the compound {sup 11}C nucleus. The {sup 10}B(p,alpha){sup 7}Be reaction has been studied by means of the Trojan Horse Method using the {sup 2}H({sup 10}B,alpha{sup 7}Be)n three-body reaction. The experiment was performed at the Laboratori Nazionali del Sud in Catania. The {sup 10}B(p,alpha){sup 7}Be reaction cross section has been extracted at low neutron momentum.

  16. Structures of ceftazidime and its transition-state analogue in complex with AmpC beta-lactamase: Implications for resistance mutations and inhibitor design

    SciTech Connect

    Powers, R.A.; Caselli, E.; Focia, P.J.; Prati, F.; Shoichet, B.K.

    2010-03-08

    Third-generation cephalosporins are widely used {beta}-lactam antibiotics that resist hydrolysis by {beta}-lactamases. Recently, mutant {beta}-lactamases that rapidly inactivate these drugs have emerged. To investigate why third-generation cephalosporins are relatively stable to wild-type class C {beta}-lactamases and how mutant enzymes might overcome this, the structures of the class C {beta}-lactamase AmpC in complex with the third-generation cephalosporin ceftazidime and with a transition-state analogue of ceftazidime were determined by X-ray crystallography to 2.0 and 2.3 {angstrom} resolution, respectively. Comparison of the acyl-enzyme structures of ceftazidime and loracarbef, a {beta}-lactam substrate, reveals that the conformation of ceftazidime in the active site differs from that of substrates. Comparison of the structures of the acyl-enzyme intermediate and the transition-state analogue suggests that ceftazidime blocks formation of the tetrahedral transition state, explaining why it is an inhibitor of AmpC. Ceftazidime cannot adopt a conformation competent for catalysis due to steric clashes that would occur with conserved residues Val211 and Tyr221. The X-ray crystal structure of the mutant {beta}-lactamase GC1, which has improved activity against third-generation cephalosporins, suggests that a tandem tripeptide insertion in the {Omega} loop, which contains Val211, has caused a shift of this residue and also of Tyr221 that would allow ceftazidime and other third-generation cephalosporins to adopt a more catalytically competent conformation. These structural differences may explain the extended spectrum activity of GC1 against this class of cephalosporins. In addition, the complexed structure of the transition-state analogue inhibitor (K{sub i} 20 nM) with AmpC reveals potential opportunities for further inhibitor design.

  17. Size-frequency analysis of petroleum accumulations in selected United States plays: potential analogues for frontier areas

    USGS Publications Warehouse

    Attanasi, E.D.; Freeman, P.A.

    2004-01-01

    This report presents the petroleum accumulation size-frequency relationships of selected mature plays assessed in the U.S. Geological Survey?s 1995 National Assessment of Oil and Gas Resources. The plays provide assessors with potential analogue models from which to estimate the numbers of undiscovered accumulations in medium and smaller size categories. Each play selected was required to have at least 50 discovered accumulations. Discovered accumulations plus the mean number of undiscovered accumulations equals the total accumulations assessed at the play level. There were 36 plays that met the criteria for oil accumulations and 25 plays that met the criteria for gas accumulations. Other properties of the plays such as primary trap type, lithology, depth, and hydrocarbon characteristics are also provided to assist the geologist in choosing an appropriate analogue. The text explains how the analogue size-frequency relationships can be used to estimate the number of small and medium size accumulations for frontier-area plays or partially explored plays in high cost areas. Although this document has been written in support of the Alaska North Slope Assessment, the basic size?frequency relationships provided are applicable elsewhere.

  18. Conformational states of Ras complexed with the GTP analogue GppNHp or GppCH2p: implications for the interaction with effector proteins.

    PubMed

    Spoerner, Michael; Nuehs, Andrea; Ganser, Petra; Herrmann, Christian; Wittinghofer, Alfred; Kalbitzer, Hans Robert

    2005-02-15

    The guanine nucleotide-binding protein Ras occurs in solution in two different states, state 1 and state 2, when the GTP analogue GppNHp is bound to the active center as detected by (31)P NMR spectroscopy. Here we show that Ras(wt).Mg(2+).GppCH(2)p also exists in two conformational states in dynamic equilibrium. The activation enthalpy DeltaH(++)(12) and the activation entropy DeltaS(++)(12) for the transition from state 1 to state 2 are 70 kJ mol(-1) and 102 J mol(-1) K(-1), within the limits of error identical to those determined for the Ras(wt).Mg(2+).GppNHp complex. The same is true for the equilibrium constants K(12) = [2]/[1] of 2.0 and the corresponding DeltaG(12) of -1.7 kJ mol(-1) at 278 K. This excludes a suggested specific effect of the NH group of GppNHp on the equilibrium. The assignment of the phosphorus resonance lines of the bound analogues has been done by two-dimensional (31)P-(31)P NOESY experiments which lead to a correction of the already reported assignments of bound GppNHp. Mutation of Thr35 in Ras.Mg(2+).GppCH(2)p to serine leads to a shift of the conformational equilibrium toward state 1. Interaction of the Ras binding domain (RBD) of Raf kinase or RalGDS with Ras(wt) or Ras(T35S) shifts the equilibrium completely to state 2. The (31)P NMR experiments suggest that, besides the type of the side chain of residue 35, a main contribution to the conformational equilibrium in Ras complexes with GTP and GTP analogues is the effective acidity of the gamma-phosphate group of the bound nucleotide. A reaction scheme for the Ras-effector interaction is presented which includes the existence of two conformations of the effector loop and a weak binding state.

  19. The preparation and crystallization of Fab fragments of a family of mouse esterolytic catalytic antibodies and their complexes with a transition-state analogue.

    PubMed

    Muranova, T A; Ruzheinikov, S N; Sedelnikova, S E; Moir, A; Partridge, L J; Kakinuma, H; Takahashi, N; Shimazaki, K; Sun, J; Nishi, Y; Rice, D W

    2001-08-01

    The Fab fragments of a family of mouse esterolytic monoclonal antibodies MS6-12, MS6-126 and MS6-164 have been obtained by digestion of whole antibodies with papain, purified and crystallized in a range of different forms either alone or in complex with a transition-state analogue. The crystals diffract X-rays to resolutions between 2.1 and 1.2 A and are suitable for structural studies. The determination of these structures could be important in understanding the different catalytic power of each of these related catalytic antibodies.

  20. Enhancing excited state intramolecular proton transfer in 2-(2'-hydroxyphenyl)benzimidazole and its nitrogen-substituted analogues by β-cyclodextrin: the effect of nitrogen substitution.

    PubMed

    Chipem, Francis A S; Behera, Santosh Kumar; Krishnamoorthy, G

    2013-05-23

    Excited state intramolecular proton transfer (ESIPT) in nitrogen-substituted analogues of 2-(2'-hydroxyphenyl)benzimidazole (HPBI), 2-(2'-hydroxyphenyl)-3H-imidazo[4,5-b]pyridine (HPIP-b), and 2-(2'-hydroxyphenyl)-3H-imidazo[4,5-c]pyridine (HPIP-c) have been investigated in a β-cyclodextrin (β-CD) nanocavity and compared with that of HPBI. The stoichiometry and the binding constants of the complexes were determined by tautomer emissions. Both pKa and NMR experiments were employed to determine the orientation of the molecules inside of the β-CD cavity. Huge enhancement in the tautomer emission of HPIP-b and HPIP-c compared to that of HPBI in β-CD suggests that not only is the ESIPT favored inside of the cavity, but also, the environment reduces the nonradiative decay through the formation of an intramolecular charge-transfer (ICT) state. Unlike HPBI, the tautomer emission to normal emission ratio of HPIP-b increases from 0.9 to 2.6, and that of HPIP-c increases from 4.9 to 7.4 in 15 mM β-CD. The effect of dimethylsulfoxide (DMSO) on complexation was also investigated for all three guest molecules. In DMSO, HPBI is present in neutral form, but the nitrogen-substituted analogues are present in both neutral and monoanionic forms. However, in DMSO upon encapsulation by β-CD, all three molecules are present in both neutral and monoanionic forms in the nanocavity. The monoanion is stabilized more inside of the β-CD cavity. The studies revealed that the ESIPT of nitrogen-substituted analogues is more susceptible to the environment than HPBI, and therefore, they are more promising probes.

  1. Conformational changes at the highly reactive cystein and lysine regions of skeletal muscle myosin induced by formation of transition state analogues.

    PubMed

    Maruta, S; Homma, K; Ohki, T

    1998-09-01

    Myosin forms stable ternary complexes with Mg2+-ADP and phosphate analogues of aluminum fluoride (AlF4-), beryllium fluoride (BeFn), and scandium fluoride (ScFn). These complexes are distinct from each other and may mimic different transient states in the ATPase cycle [Maruta et al. (1993) J. Biol. Chem. 268, 7093-7100]. Regions of skeletal muscle myosin containing the highly reactive residues Cys 707 (SH1), Cys 697 (SH2), and lysine 83 (RLR) dramatically alter their local conformation when myosin hydrolyzes ATP, and these changes may reflect formation of a series of transient intermediates during ATP hydrolysis. We used the fluorescent probes 4-fluoro-7-sulfamoylbezofurazan, 2-(4'-maleimidylanilino)naphthalene-6-sulfonic acid, and trinitrobenzene-sulfonate, which bind to SH1, SH2, and RLR, respectively, to examine differences in local conformations within myosin.ADP.phosphate analogue (BeFn, Vi, AlF4-, and ScFn) complexes. It was observed that the ternary complexes had SH1 conformations similar to those seen on S-1 in the presence of ATP. In contrast, local conformations in the SH2 and RLR regions of S-1.ADP.BeFn were different from those in corresponding regions of S-1.ADP.AlF4- or ScFn. These results suggest that SH1 and SH2 move distinctly during ATP hydrolysis and that the local conformations of the SH2 and RLR regions more sensitively reflect different transient states.

  2. Epinephrine analogues.

    PubMed

    Sneader, W

    2001-11-01

    Tyramine was the first epinephrine analogue to be introduced into medicine, in the early 1900s. It was followed by ephedrine and pseudoephedrine in the 1920s and by the amfetamines a decade later. The popularity of the amfetamines grew throughout the 1930s and 1940s; after that, there was a slowly dawning realization that they were being widely abused. Isoprenaline, introduced in the 1950s, was soon recognized as superior to epinephrine when used as an inhaler by asthmatics, and it remained the drug of choice for the relief of bronchospasm until around 1970. Orciprenaline, which featured an orcinol system, had a long duration of action and was active by mouth; Boehringer marketed it both as an inhaler and as a syrup for the prophylaxis of bronchospasm. The greatly superior bronchodilators salbutamol and terbutaline, launched in 1968 and 1970, respectively, incorporate further variation on the molecular theme that had led to the development of orciprenaline. (c) 2001 Prous Science. All rights reserved.

  3. Boron depletion: indirect measurement of the 10B(p,α)7Be S(E)-factor

    NASA Astrophysics Data System (ADS)

    Lamia, L.; Romano, S.; Carlin, N.; Cherubini, S.; Crucillà, V.; de Moura, M. M.; Del Santo, M. G.; Munhoz, M. G.; Gulino, M.; Liguori Neto, R.; La Cognata, M.; Mudò, F.; Pizzone, R. G.; Puglia, S. M. R.; Sergi, M. L.; Souza, F. A.; Spitaleri, C.; Suaide, A. A. P.; Szanto, E.; Szanto de Toledo, A.; Tudisco, S.; Tumino, A.

    2007-05-01

    The 10B(p,α)7Be reaction is the main responsible for 10B destruction in stellar interior. In such environments this p-capture process occurs at a Gamow energy of ˜10 keV, and takes places mainly through a resonant state (E=8.701 MeV) of the compound 11C nucleus. Thus, a resonance right in the region of the Gamow peak is expected to significantly influence the behaviour of the astrophysical S(E)-factor. The 10B(p,α)7Be reaction has been investigated by means of the Trojan Horse Method (THM) applied to the 2H(10B,α7Be)n three-body process. The experiment was performed at E=27 MeV at the Instituto de Fisica Nuclear de São Paulo. Preliminary results concerning the extraction of the bare-nucleus S(E)-factor will be presented.

  4. Vector Analyzing Power in ^9Be( p,γ)^10B

    NASA Astrophysics Data System (ADS)

    Wulf, E. A.; Godwin, M. A.; Guillemette, J. F.; Laymon, C. M.; Rice, B. J.; Weller, H. R.; Prior, R. M.; Spraker, M.; Tilley, D. R.

    1998-04-01

    Analyzing powers for the ^9Be( p,γ)^10B reaction were measured by stopping a 100 keV polarized proton beam in a ^9Be target. The measured vector analyzing power is A_y(90^circ) = 0.18 ± 0.03 for capture to the ground state, with smaller values at 90^circ for the first three excited states. The astrophysical S-factors were obtained for each of the final states using a direct capture-plus-resonance model calculation which fitted both the present analyzing power data and the previously reported cross-section data( D. Zahnow et al.), Nucl. Phys. A589, 95 (1995).. The S-factors at Ep = 0 keV for capture to the ground state and first three excited states were 0.25, 0.34, 0.27, and 0.10 keV\\cdotb, respectively, which are considerably smaller than previously reported(F. E. Cecil et al.), Nucl. Phys. A539, 75 (1992).. The tails of resonances in ^10B were observed to raise the extrapolated values of the astrophysical S-factors at Ep = 0 keV by 31% over a pure E1 direct capture model prediction for capture to the ground state and by a factor of 2.4, 9 and 5 for capture to the first three excited states respectively.

  5. Reaction mechanism for natural parity (p,p') transitions in 10B

    NASA Astrophysics Data System (ADS)

    Betker, A. C.; Chang, S.; Stephenson, E. J.; Bacher, A. D.; Bowyer, S. M.; Franklin, W. A.; Liu, J.; Olmer, C.; Prout, D. L.; Wells, S. P.; Wissink, S. W.; Yu, C.; Lindgren, R. A.; Baghaei, H.; Gladyshev, V.; Carr, J. A.; Yoon, S. K.; Petrovich, F.; Clausen, B. L.; Lisantti, J.

    2005-06-01

    We report angular distribution measurements of the cross section, analyzing power, induced polarization, and all polarization transfer coefficients for the natural parity transitions in 10B(p→,p→')10B at 197 MeV. All of the transitions closely follow the pattern for spin-1/2 scattering from spin-0, namely A=P,DSS'=DLL', and DSL'=-DLS'. Small deviations from DNN'=1 reflect spin-flip contributions to these transitions. Distorted wave impulse approximation calculations were generally successful, supporting the use of an empirical effective nucleon-nucleon interaction, the inclusion of channel-coupling in the ground state and the 3+↔4+ transition, and the procedure of increasing the L=2 strength of shell-model particle-hole matrix elements to match the collective contribution to these transitions.

  6. Combined quantum-mechanical molecular mechanics calculations with NWChem and AMBER: Excited state properties of green fluorescent protein chromophore analogue in aqueous solution.

    PubMed

    Pirojsirikul, Teerapong; Götz, Andreas W; Weare, John; Walker, Ross C; Kowalski, Karol; Valiev, Marat

    2017-07-05

    Combined quantum mechanical molecular mechanics (QM/MM) calculations have become a popular methodology for efficient and accurate description of large molecular systems. In this work we introduce our development of a QM/MM framework based on two well-known codes-NWChem and AMBER. As an initial application area we are focused on excited state properties of small molecules in an aqueous phase using an analogue of the green fluorescent protein (GFP) chromophore as a particular test case. Our approach incorporates high level coupled cluster theory for the analysis of excited states providing a reliable theoretical analysis of effects of an aqueous solvation environment on the photochemical properties of the GFP chromophore. Using a systematic approach, which involves comparison of gas phase and aqueous phase results for different protonation states and conformations, we resolve existing uncertainties regarding the theoretical interpretation of experimental data. We observe that the impact of aqueous environment on charged states generally results in blue shifts of the absorption spectra, but the magnitude of the effect is sensitive to both protonation state and conformation and can be rationalized based on charge movement into the area of higher/lower external electrostatic potentials. At neutral pH levels the experimentally observed absorption signal is most likely coming from the phenol protonated form. Our results also show that the high level electron correlated method is essential for a proper description of excited states of GFP. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  7. Reprocessing of 10B-contaminated 10Be AMS targets

    NASA Astrophysics Data System (ADS)

    Simon, K. J.; Pedro, J. B.; Smith, A. M.; Child, D. P.; Fink, D.

    2013-01-01

    10Be accelerator mass spectrometry (AMS) is an increasingly important tool in studies ranging from exposure age dating and palaeo-geomagnetism to the impact of solar variability on the Earth’s climate. High levels of boron in BeO AMS targets can adversely impact the quality of 10Be measurements through interference from the isobar 10B. Numerous methods in chemical sample preparation and AMS measurement have been employed in order to reduce the impact of excessive boron rates. We present details of a method developed to chemically reprocess a set of forty boron-contaminated BeO targets derived from modern Antarctic ice. Previously, the excessive boron levels in these samples, as measured in an argon-filled absorber cell preceding the ionisation detector, had precluded routine AMS measurement. The procedure involved removing the BeO + Nb mixture from the target holders and dissolving the BeO in hot concentrated H2SO4. The solution was then heated with HF to remove the boron as volatile BF3 before re-precipitating as Be(OH)2 and calcining to BeO. This was again mixed with niobium and pressed into fresh target holders. Following reprocessing, the samples gave boron rates reduced by 10-100×, which were sufficiently low and similar to previous successful batches of ice core, snow and associated blank samples, thus allowing a successful 10Be measurement in the absence of any boron correction. Overall recovery of the BeO for this process averaged 40%. Extensive testing of relevant processing equipment and reagents failed to determine the source of the boron. As a precautionary measure, a similar H2SO4 + HF step has been subsequently added to the standard ice processing method.

  8. Low-Luminosity AGN As Analogues of Galactic Black Holes in the Low/Hard State: Evidence from X-Ray Timing of NGC 4258

    NASA Technical Reports Server (NTRS)

    Markowitz, A.; Uttley, P.

    2005-01-01

    We present a broadband power spectral density function (PSD) measured from extensive RXTE monitoring data of the low-luminosity AGN NGC 4258, which has an accurate, maser-determined black hole mass of (3.9 plus or minus 0.1) x 10(exp 7) solar mass. We constrain the PSD break time scale to be greater than 4.5 d at greater than 90% confidence, which appears to rule out the possibility that NGC 4258 is an analogue of black hole X-ray binaries (BHXRBs) in the high/soft state. In this sense, the PSD of NGC 4258 is different to that of some more-luminous Seyferts, which appear similar to the PSDs of high/soft state X-ray binaries. This result supports previous analogies between LLAGN and X-ray binaries in the low/hard state based on spectral energy distributions, indicating that the AGN/BHXRB analogy is valid across a broad range of accretion rates.

  9. Low-lying excited states and nonradiative processes of the adenine analogues 7H- and 9H-2-aminopurine.

    PubMed

    Lobsiger, Simon; Sinha, Rajeev K; Trachsel, Maria; Leutwyler, Samuel

    2011-03-21

    We have investigated the UV vibronic spectra and excited-state nonradiative processes of the 7H- and 9H-tautomers of jet-cooled 2-aminopurine (2AP) and of the 9H-2AP-d(4) and -d(5) isotopomers, using two-color resonant two-photon ionization spectroscopy at 0.3 and 0.045  cm(-1) resolution. The S(1) ← S(0) transition of 7H-2AP was observed for the first time. It lies ∼1600  cm(-1) below that of 9H-2AP, is ∼1000 times weaker and exhibits only in-plane vibronic excitations. In contrast, the S(1) ← S(0) spectra of 9H-2AP, 9H-2AP-d(4), and 9H-2AP-d(5) show numerous low-frequency bands that can be systematically assigned to overtone and combinations of the out-of-plane vibrations ν(1)', ν(2)', and ν(3)'. The intensity of these out-of-plane bands reflects an out-of-plane deformation in the (1)ππ∗(L(a)) state. Approximate second-order coupled-cluster theory also predicts that 2-aminopurine undergoes a "butterfly" deformation in its lowest (1)ππ∗ state. The rotational contours of the 9H-2AP, 9H-2AP-d(4), and 9H-2AP-d(5) 0(0)(0) bands and of eight vibronic bands of 9H-2AP up to 0(0)(0) + 600 cm(-1) exhibit 75%-80% in-plane (a∕b) polarization, which is characteristic for a (1)ππ∗ excitation. A 20%-25% c-axis (perpendicular) transition dipole moment component may indicate coupling of the (1)ππ∗ bright state to the close-lying (1)nπ∗ dark state. However, no (1)nπ∗ vibronic bands were detected below or up to 500  cm(-1) above the (1)ππ∗ 0(0)(0) band. Following (1)ππ∗ excitation, 9H-2AP undergoes a rapid nonradiative transition to a lower-lying long-lived state with a lifetime ≥5 μs. The ionization potential of 9H-2AP was measured via the (1)ππ∗ state (IP = 8.020 eV) and the long-lived state (IP > 9.10 eV). The difference shows that the long-lived state lies ≥1.08 eV below the (1)ππ∗ state. Time-dependent B3LYP calculations predict the (3)ππ∗ (T(1)) state 1.12 eV below the (1)ππ∗ state, but place the (1)n

  10. Electrostatic contributions to binding of transition state analogues can be very different from the corresponding contributions to catalysis: phenolates binding to the oxyanion hole of ketosteroid isomerase.

    PubMed

    Warshel, Arieh; Sharma, Pankaz K; Chu, Zhen T; Aqvist, Johan

    2007-02-13

    The relationship between binding of transition state analogues (TSAs) and catalysis is an open problem. A recent study of the binding of phenolate TSAs to ketosteroid isomerase (KSI) found a small change in the binding energy with a change in charge delocalization of the TSAs. This has been taken as proof that electrostatic effects do not contribute in a major way to catalysis. Here we reanalyze the relationship between the binding of the TSAs and the chemical catalysis by KSI as well as the binding of the transition state (TS), by computer simulation approaches. Since the simulations reproduce the relevant experimental results, they can be used to quantify the different contributions to the observed effects. It is found that the binding of the TSA and the chemical catalysis represent different thermodynamic cycles with very different electrostatic contributions. While the binding of the TSA involves a small electrostatic contribution, the chemical catalysis involves a charge transfer process and a major electrostatic contribution due to the preorganization of the active site. Furthermore, it is found that the electrostatic preorganization contributions to the binding of the enolate intermediate of KSI and the TS are much larger than the corresponding effect for the binding of the TSAs. This reflects the dependence of the preorganization on the orientation of the nonpolar form of the TSAs relative to the oxyanion hole. It seems to us that this work provides an excellent example of the need for computational studies in analyzing key experimental findings about enzyme catalysis.

  11. Simultaneous removal of Cr(VI) and Amido black 10B (AB10B) from aqueous solutions using quaternized chitosan coated bentonite.

    PubMed

    Hu, Pan; Wang, Jing; Huang, Ruihua

    2016-11-01

    In this study, simultaneous removal of Cr(VI) and Amido Black 10B (AB10B) using quaternized chitosan coated bentonite was investigated by a batch method. The factors affecting adsorption process such as pH, adsorbent dosage, contact time and initial concentration and the interaction of two components in binary solutions have been studied. The results showed that the antagonism effect existed between Cr(VI) and AB10B in binary systems. The equilibrium time for Cr(VI) adsorption was less than the one for AB10B adsorption. The maximum adsorption capacities of the modified bentonite, according to the Langmuir isotherm model were 847.5mg/g for AB10B and 66.6mg/g for Cr(VI) at 298K. The experimental results demonstrated that both Cr(VI) and AB10B were well described by the pseudo-second-order model. Thermodynamic study depicted that the adsorption of Cr(VI) and AB10B onto the modified bentonite was both spontaneous. The adsorption for Cr(VI) was exothermic while the one for AB10B was endoth- ermic in nature. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. miR-10b promotes invasion by targeting KLF4 in osteosarcoma cells.

    PubMed

    Wang, Jing; Wang, Bing; Chen, Ling-Qiang; Yang, Jin; Gong, Zhi-Qiang; Zhao, Xue-Ling; Zhang, Chun-Qiang; Du, Kai-Li

    2016-12-01

    Osteosarcoma is a common malignancy with high rate of metastasis. miR-10b has been reported to be expressed in many types of tumors abnormally and be associated with cancer carcinogenesis and progression. But the function of miR-10b in osteosarcoma is still unknown. So this study was aimed to investigate the role of miR-10b in osteosarcoma development. miR-10b expression in osteosarcoma tissues and osteosarcoma cells were detected using real time PCR. The effects of miR-10b on osteosarcoma cells proliferation, apoptosis, migration and invasion were detected using CCK-8 assay, flow cytometry, wound-healing assay and transwell assay, respectively. The relationship between miR-10b and KLF4 was evaluated using dual-luciferase assay, correlation analysis. miR-10b was highly expressed in osteosarcoma tissues and osteosarcoma cells. Furthermore, inhibition of miR-10b in osteosarcoma cells depressed the cells proliferation, migration and invasion but promoted cells apoptosis. In addition, KLF4 was down-regulated by miR-10b and miR-10b expression was negatively related to KLF4 expression in osteosarcoma tissue, miR-10b participated in the process of osteosarcoma cells invasion by regulating KLF4 expression. miR-10b is overexpressed in osteosarcoma and KLF4 is the direct target gene of miR-10b. Furthermore, miR-10b promotes osteosarcoma cells progression by downregulating KLF4 expression. These results suggest that miR-10b functions as an oncomiR and play an important role in osteosarcoma cellular processes at least partially through regulating KLF4; miR-10b may be a therapeutic target for osteosarcoma treatment. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  13. 17 CFR 240.10b-5 - Employment of manipulative and deceptive devices.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... deceptive devices. 240.10b-5 Section 240.10b-5 Commodity and Securities Exchanges SECURITIES AND EXCHANGE... Under the Securities Exchange Act of 1934 Manipulative and Deceptive Devices and Contrivances § 240.10b-5 Employment of manipulative and deceptive devices. It shall be unlawful for any person, directly...

  14. 17 CFR 240.10b-5 - Employment of manipulative and deceptive devices.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... deceptive devices. 240.10b-5 Section 240.10b-5 Commodity and Securities Exchanges SECURITIES AND EXCHANGE... Under the Securities Exchange Act of 1934 Manipulative and Deceptive Devices and Contrivances § 240.10b-5 Employment of manipulative and deceptive devices. It shall be unlawful for any person, directly...

  15. 17 CFR 240.10b-5 - Employment of manipulative and deceptive devices.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... deceptive devices. 240.10b-5 Section 240.10b-5 Commodity and Securities Exchanges SECURITIES AND EXCHANGE... Under the Securities Exchange Act of 1934 Manipulative and Deceptive Devices and Contrivances § 240.10b-5 Employment of manipulative and deceptive devices. It shall be unlawful for any person, directly...

  16. 17 CFR 240.10b-5 - Employment of manipulative and deceptive devices.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... deceptive devices. 240.10b-5 Section 240.10b-5 Commodity and Securities Exchanges SECURITIES AND EXCHANGE... Under the Securities Exchange Act of 1934 Manipulative and Deceptive Devices and Contrivances § 240.10b-5 Employment of manipulative and deceptive devices. It shall be unlawful for any person, directly...

  17. 17 CFR 240.10b-5 - Employment of manipulative and deceptive devices.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... deceptive devices. 240.10b-5 Section 240.10b-5 Commodity and Securities Exchanges SECURITIES AND EXCHANGE... Under the Securities Exchange Act of 1934 Manipulative and Deceptive Devices and Contrivances § 240.10b-5 Employment of manipulative and deceptive devices. It shall be unlawful for any person, directly...

  18. Growth and Metastases of Human Lung Cancer Are Inhibited in Mouse Xenografts by a Transition State Analogue of 5′-Methylthioadenosine Phosphorylase*

    PubMed Central

    Basu, Indranil; Locker, Joseph; Cassera, Maria B.; Belbin, Thomas J.; Merino, Emilio F.; Dong, Xinyuan; Hemeon, Ivan; Evans, Gary B.; Guha, Chandan; Schramm, Vern L.

    2011-01-01

    The S-adenosylmethionine (AdoMet) salvage enzyme 5′-methylthioadenosine phosphorylase (MTAP) has been implicated as both a cancer target and a tumor suppressor. We tested these hypotheses in mouse xenografts of human lung cancers. AdoMet recycling from 5′-methylthioadenosine (MTA) was blocked by inhibition of MTAP with methylthio-DADMe-Immucillin-A (MTDIA), an orally available, nontoxic, picomolar transition state analogue. Blood, urine, and tumor levels of MTA increased in response to MTDIA treatment. MTDIA treatment inhibited A549 (human non-small cell lung carcinoma) and H358 (human bronchioloalveolar non-small cell lung carcinoma cells) xenograft tumor growth in immunodeficient Rag2−/−γC−/− and NCr-nu mice. Systemic MTA accumulation is implicated as the tumor-suppressive metabolite because MTDIA is effective for in vivo treatment of A549 MTAP−/− and H358 MTAP+/+ tumors. Tumors from treated mice showed increased MTA and decreased polyamines but little alteration in AdoMet, methionine, or adenine levels. Gene expression profiles of A549 tumors from treated and untreated mice revealed only modest alterations with 62 up-regulated and 63 down-regulated mRNAs (≥3-fold). MTDIA antitumor activity in xenografts supports MTAP as a target for lung cancer therapy. PMID:21135097

  19. Studies on yeast nucleoside triphosphate-nucleoside diphosphate transphosphorylase (nucleoside diphosphokinase). IV. Steady-state kinetic properties with thymidine nucleotides (including 3'-azido-3'-deoxythymidine analogues).

    PubMed

    Kuby, S A; Fleming, G; Alber, T; Richardson, D; Takenaka, H; Hamada, M

    1991-01-01

    A study of the steady-state kinetics of the crystalline brewer's yeast (Saccharomyces carlsbergensis) nucleoside diphosphokinase, with the magnesium complexes of the adenine and thymidine nucleotides as reactants, has led to a postulated kinetic mechanism which proceeds through a substituted enzyme. This agrees with the earlier conclusions of Garces and Cleland [Biochemistry 1969; 8:633-640] who characterized a reaction between the magnesium complexes of the adenine and uridine nucleotides. An advantage of using thymidine nucleotides as reactants is that they permit accurate, rapid and continuous assays of the enzymatic activity in coupled-enzymatic tests. Through measurements of the initial velocities and product inhibition studies, the Michaelis constants, maximum velocities, and inhibition constants could be evaluated for the individual substrates. Competitive substrate inhibition was encountered at relatively high substrate concentrations, which also permitted an evaluation of their ability to act as 'dead-end' inhibitors. The Michaelis constants for the 3'-azido-3'-deoxythymidine (AzT) analogues were also evaluated and, although these values were only somewhat higher than those of their natural substrates, the Km's for the adenine nucleotides as paired substrates were lower and the Vmax's were drastically reduced. The pharmacological implications of these observations are touched upon and extrapolated to the cases where therapeutic doses of AzT may be employed.

  20. Reaction mechanism for natural parity (p,p{sup '}) transitions in {sup 10}B

    SciTech Connect

    Betker, A.C.; Chang, S.; Stephenson, E.J.; Bacher, A.D.; Bowyer, S.M.; Franklin, W.A.; Liu, J.; Olmer, C.; Prout, D.L.; Wells, S.P.; Wissink, S.W.; Yu, C.; Lindgren, R.A.; Baghaei, H.; Gladyshev, V.; Carr, J.A.; Yoon, S.K.; Petrovich, F.; Clausen, B.L.; Lisantti, J.

    2005-06-01

    We report angular distribution measurements of the cross section, analyzing power, induced polarization, and all polarization transfer coefficients for the natural parity transitions in {sup 10}B(p{sup {yields}},p{sup {yields}}'){sup 10}B at 197 MeV. All of the transitions closely follow the pattern for spin-1/2 scattering from spin-0, namely A=P,D{sub SS{sup '}}=D{sub LL{sup '}}, and D{sub SL{sup '}}=-D{sub LS{sup '}}. Small deviations from D{sub NN{sup '}}=1 reflect spin-flip contributions to these transitions. Distorted wave impulse approximation calculations were generally successful, supporting the use of an empirical effective nucleon-nucleon interaction, the inclusion of channel-coupling in the ground state and the 3{sup +}{r_reversible}4{sup +} transition, and the procedure of increasing the L=2 strength of shell-model particle-hole matrix elements to match the collective contribution to these transitions.

  1. Immunohistochemical study of hair follicle stem cells in regenerated hair follicles induced by Wnt10b

    PubMed Central

    Zhang, Yiming; Xing, Yizhan; Guo, Haiying; Ma, Xiaogen; Li, Yuhong

    2016-01-01

    The regulation of the periodic regeneration of hair follicles is complicated. Although Wnt10b has been reported to induce hair follicle regeneration, the characteristics of induced hair follicles, especially the target cells of Wnt10b, have not yet been clearly elucidated. Thus, we systematically evaluated the expression and proliferation patterns of Wnt10b-induced hair follicles. We found that Wnt10b promoted the proliferation of hair follicle stem cells from 24 hours after AdWnt10b injection. Seventy-two hours after AdWnt10b injection, cells outside of bulge area began to proliferate. When the induced hair follicle entered full anagen, although the hair follicle stem cells were normal, canonical Wnt signaling was maintained in the hair precortex cells. Our results reveal that the target cells that overexpressed Wnt10b included hair follicle stem cells, hair precortex cells, and matrix cells. PMID:27766026

  2. Maxwell speed distribution and analogue Hawking-Unruh temperature in an ontological model of a Harmonic oscillator ground state

    NASA Astrophysics Data System (ADS)

    Budiyono, Agung; Gunara, Bobby Eka; Okamura, Makoto; Nakamura, Katsuhiro

    2015-03-01

    Within an ontological (hidden variable) model of quantum fluctuation, one can discuss the actual properties of a system regardless (independent) of measurement. Here we apply an ontological model proposed earlier to investigate a Harmonic oscillator in the quantum mechanical ground state. We first show that the actual speed of the oscillator fluctuates randomly following the Maxwell-Boltzmann distribution. On the other hand, the actual energy obeys a broad Gamma distribution with an average 3 ħ ω / 2, where ω is the classical angular frequency, so that one may conclude that the outcome of a single energy measurement reveals the average of the actual energy. The distribution of actual speed (energy) thus formally resembles the distribution of speed (energy) of an ideal gas in thermal equilibrium of temperature Tg = ħ ω / 2. We shall then argue that Tg can be written in a form analogous to the Hawking temperature for a Schwarzschild black hole in which the average distance of the oscillator from the origin plays the analogous role of the radius of the black hole event horizon. It can also be written in a form analogous to the Unruh temperature experienced by a body moving with a uniform acceleration. In the analogy, the oscillator suffers an effective acceleration which balances the attractive force of the trapping Harmonic potential, thus keeps its average position away from the origin.

  3. Physicochemical analyses of a bioactive 4-aminoantipyrine analogue - synthesis, crystal structure, solid state interactions, antibacterial, conformational and docking studies.

    PubMed

    Alam, Mohammad Sayed; Lee, Dong-Ung

    2016-01-01

    A novel Schiff base derivative of 4-aminoantipyrine, that is, (E)-4-(2-methoxybenzylideneamino)-1,5-dimethyl-2-phenyl-1H-pyrazol-3(2H)-one (MBA-dMPP), was synthesized and characterized by FT-IR, (1)H-NMR, and EI-MS. Single-crystal X-ray diffraction data revealed MBA-dMPP adopts a trans configuration around its central C=N double bond, and forms orthorhombic crystals. XRD revealed that MBA-dMPP possess two different planes, in which the pyrazolone and benzylidene groups attached to C9 of the pyrazolone ring are almost coplanar and the phenyl ring connected to the N1 atom of the pyrazolone moiety lies in another plane. The intermolecular, host-guest C-H…O, C-H…N, and C-H…C van der Waals interactions were found to form a 3D network and confer stability to the MBA-dMPP crystal structure. The quantitative and qualitative solid state behaviors of MBA-dMPP were subjected to 3D Hirshfeld surface analysis and 2D fingerprint plotting. Reciprocal H…H contacts contributed most (52.9 %) to the Hirshfeld surface, followed by C…H/H…C contacts (30.2 %), whereas, O…H/H…O and N…H/H…N interactions contributed 15.5 % to the Hirshfeld surface. Electrostatic potentials were mapped over the Hirshfeld surface to analyze electrostatic complementarities within the MBA-dMPP crystal. In addition, geometrical descriptors were also analyzed to the extent of surface interactions. MBA-dMPP was also investigated for in vitro antibacterial activity against Gram-positive and Gram-negative bacterial strains, and showed highest activity against Bacillus cereus (MIC = 12.5 μg mL(-1)) and Salmonellatythimurium (MIC = 50 μg mL(-1)). In silico screening was conducted by docking MBA-dMPP on the active site of S12 bacterial protein (an important therapeutic target of antibacterial agents) and its binding properties were compared with those of ciprofloxacin. Moreover, a field points map of MBA-dMPP ligand was studied to determine electrostatic and van der Waals forces, hydrophobic

  4. Physicochemical analyses of a bioactive 4-aminoantipyrine analogue - synthesis, crystal structure, solid state interactions, antibacterial, conformational and docking studies

    PubMed Central

    Alam, Mohammad Sayed; Lee, Dong-Ung

    2016-01-01

    A novel Schiff base derivative of 4-aminoantipyrine, that is, (E)-4-(2-methoxybenzylideneamino)-1,5-dimethyl-2-phenyl-1H-pyrazol-3(2H)-one (MBA-dMPP), was synthesized and characterized by FT-IR, 1H-NMR, and EI-MS. Single-crystal X-ray diffraction data revealed MBA-dMPP adopts a trans configuration around its central C=N double bond, and forms orthorhombic crystals. XRD revealed that MBA-dMPP possess two different planes, in which the pyrazolone and benzylidene groups attached to C9 of the pyrazolone ring are almost coplanar and the phenyl ring connected to the N1 atom of the pyrazolone moiety lies in another plane. The intermolecular, host-guest C-H…O, C-H…N, and C-H…C van der Waals interactions were found to form a 3D network and confer stability to the MBA-dMPP crystal structure. The quantitative and qualitative solid state behaviors of MBA-dMPP were subjected to 3D Hirshfeld surface analysis and 2D fingerprint plotting. Reciprocal H…H contacts contributed most (52.9 %) to the Hirshfeld surface, followed by C…H/H…C contacts (30.2 %), whereas, O…H/H…O and N…H/H…N interactions contributed 15.5 % to the Hirshfeld surface. Electrostatic potentials were mapped over the Hirshfeld surface to analyze electrostatic complementarities within the MBA-dMPP crystal. In addition, geometrical descriptors were also analyzed to the extent of surface interactions. MBA-dMPP was also investigated for in vitro antibacterial activity against Gram-positive and Gram-negative bacterial strains, and showed highest activity against Bacillus cereus (MIC = 12.5 μg mL-1) and Salmonella tythimurium (MIC = 50 μg mL-1). In silico screening was conducted by docking MBA-dMPP on the active site of S12 bacterial protein (an important therapeutic target of antibacterial agents) and its binding properties were compared with those of ciprofloxacin. Moreover, a field points map of MBA-dMPP ligand was studied to determine electrostatic and van der Waals forces, hydrophobic potentials

  5. Thermal-induced conformational changes in the product release area drive the enzymatic activity of xylanases 10B: Crystal structure, conformational stability and functional characterization of the xylanase 10B from Thermotoga petrophila RKU-1

    SciTech Connect

    Santos, Camila Ramos; Meza, Andreia Navarro; Hoffmam, Zaira Bruna; Silva, Junio Cota; Alvarez, Thabata Maria; Ruller, Roberto; Giesel, Guilherme Menegon; Verli, Hugo; Squina, Fabio Marcio; Prade, Rolf Alexander; Murakami, Mario Tyago

    2010-12-10

    Research highlights: {yields} The hyperthermostable xylanase 10B from Thermotoga petrophila RKU-1 produces exclusively xylobiose at the optimum temperature. {yields} Circular dichroism spectroscopy suggests a coupling effect of temperature-induced structural changes with its enzymatic behavior. {yields} Crystallographic and molecular dynamics studies indicate that conformational changes in the product release area modulate the enzyme action mode. -- Abstract: Endo-xylanases play a key role in the depolymerization of xylan and recently, they have attracted much attention owing to their potential applications on biofuels and paper industries. In this work, we have investigated the molecular basis for the action mode of xylanases 10B at high temperatures using biochemical, biophysical and crystallographic methods. The crystal structure of xylanase 10B from hyperthermophilic bacterium Thermotoga petrophila RKU-1 (TpXyl10B) has been solved in the native state and in complex with xylobiose. The complex crystal structure showed a classical binding mode shared among other xylanases, which encompasses the -1 and -2 subsites. Interestingly, TpXyl10B displayed a temperature-dependent action mode producing xylobiose and xylotriose at 20 {sup o}C, and exclusively xylobiose at 90 {sup o}C as assessed by capillary zone electrophoresis. Moreover, circular dichroism spectroscopy suggested a coupling effect of temperature-induced structural changes with this particular enzymatic behavior. Molecular dynamics simulations supported the CD analysis suggesting that an open conformational state adopted by the catalytic loop (Trp297-Lys326) provokes significant modifications in the product release area (+1,+2 and +3 subsites), which drives the enzymatic activity to the specific release of xylobiose at high temperatures.

  6. Specific killing of human melanoma cells with an efficient 10B-compound on monoclonal antibodies

    SciTech Connect

    Komura, A.; Tokuhisa, T.; Nakagawa, T.; Sasase, A.; Ichihashi, M.; Ferrone, S.; Mishima, Y. )

    1989-07-01

    We previously established methods which have enabled us to target a sufficient number of 10B atoms on human melanoma cells to destroy them by thermal neutron irradiation. Monoclonal antibodies were here used as vector of 10B atoms on the target cell. Thermal neutrons require at least 10(9) 10B atoms to destroy the cell. In order to accumulate an adequate number of 10B atoms on target cells, our first approach was to make an effective compound that contains 12 atoms of 10B in a molecule. The second step was to conjugate the compound with an avidin molecule (10B12-avidin). One molecule of the 10B12-avidin carries about 30 atoms of 10B. This 10B12-avidin can be specifically targeted on human melanoma cells by biotinated monoclonal antibodies specific for the cells. Furthermore, the number of 10B atoms on target cells can be augmented by a hapten-antihapten monoclonal antibody system. The cultured human melanoma cells treated with these methods were damaged by thermal neutron irradiation. This is the first study that indicates thermal neutrons do injure target cells boronated by monoclonal antibodies.

  7. Relation between the catalytic efficiency of the synthetic analogues of catechol oxidase with their electrochemical property in the free state and substrate-bound state.

    PubMed

    Chakraborty, Prateeti; Adhikary, Jaydeep; Ghosh, Bipinbihari; Sanyal, Ria; Chattopadhyay, Shyamal Kumar; Bauzá, Antonio; Frontera, Antonio; Zangrando, Ennio; Das, Debasis

    2014-08-18

    A library of 15 dicopper complexes as synthetic analogues of catechol oxidase has been synthesized with the aim to determine the relationship between the electrochemical behavior of the dicopper(II) species in the absence as well as in the presence of 3,5-di-tert-butylcatechol (3,5-DTBC) as model substrate and the catalytic activity, kcat, in DMSO medium. The complexes have been characterized by routine physicochemical techniques as well as by X-ray single-crystal structure analysis in some cases. Fifteen "end-off" compartmental ligands have been designed as 1 + 2 Schiff-base condensation product of 2,6-diformyl-4-R-phenol (R = Me, (t)Bu, and Cl) and five different amines, N-(2-aminoethyl)piperazine, N-(2-aminoethyl)pyrrolidine, N-(2-aminoethyl)morpholine, N-(3-aminopropyl)morpholine, and N-(2-aminoethyl)piperidine. Interestingly, in case of the combination of 2,6-diformyl-4-methylphenol and N-(2-aminoethyl)morpholine/N-(3-aminopropyl)morpholine/N-(2-aminoethyl)piperidine 1 + 1 condensation becomes the reality and the ligands are denoted as L2(1-3). On reaction of copper(II) nitrate with L2(1-3) in situ complexes 3, 12, and 13 are formed having general formula Cu2(L2(1-3))2(NO3)2. The remaining 12 ligands obtained as 1 + 2 condensation products are denoted as L1(1-12), which produce complexes having general formula Cu2(L1(1-12))(NO3)2. Catecholase activity of all 15 complexes has been investigated in DMSO medium using 3,5-DTBC as model substrate. Treatment on the basis of Michaelis-Menten model has been applied for kinetic study, and thereby turnover number, kcat, values have been evaluated. Cyclic voltametric (CV) and differential pulse voltametric (DPV) studies of the complexes in the presence as well as in the absence of 3,5-DTBC have been thoroughly investigated in DMSO medium. From those studies it is evident that oxidation of 3,5-DTBC catalyzed by dicopper(II) complexes proceed via two steps: first, semibenzoquinone followed by benzoquinone with concomitant

  8. Wnt-10b promotes differentiation of skin epithelial cells in vitro

    SciTech Connect

    Ouji, Yukiteru . E-mail: oujix@naramed-u.ac.jp; Yoshikawa, Masahide; Shiroi, Akira; Ishizaka, Shigeaki

    2006-03-31

    To evaluate the role of Wnt-10b in epithelial differentiation, we investigated the effects of Wnt-10b on adult mouse-derived primary skin epithelial cells (MPSEC). Recombinant Wnt-10b protein (rWnt-10b) was prepared using a gene engineering technique and MPSEC were cultured in its presence, which resulted in morphological changes from cuboidal to spindle-shaped and inhibited their proliferation. Further, involvement of the canonical Wnt signal pathway was also observed. MPSEC treated with rWnt-10b showed characteristics of the hair shaft and inner root sheath of the hair follicle, in results of Ayoub Shklar staining and immunocytochemistry. Further, the cells expressed mRNA for differentiated epithelial cells, including keratin 1, keratin 2, loricrin, mHa5, and mHb5, in association with a decreased expression of the basal cell marker keratin 5. These results suggest that Wnt-10b promotes the differentiation of MPSEC.

  9. Influence of the Charge State on the Structures and Interactions of Vancomycin Antibiotics with Cell-Wall Analogue Peptides: Experimental and Theoretical Studies

    SciTech Connect

    Yang, Zhibo; Vorpagel, Erich R.; Laskin, Julia

    2009-02-16

    In this study we examined the effect of the charge state on the energetics and dynamics of dissociation of the non-covalent complex between the vancomycin and the cell wall peptide analogue Nα,Nε-diacetyl-L-Lys-D-Ala-D-Ala (V-Ac2KDADA). The binding energies between the vancomycin and the peptide were obtained from the RRKM modeling of the time- and energy resolved surface-induced dissociation (SID) experiments. Our results demonstrate that the stability of the complex toward fragmentation increases in the order: [V+Ac2KDADA+H]+2 < [V+Ac2KDADA+H]+ < [V+Ac2KDADA-H]-. Dissociation of the singly protonated and singly deprotonated complex is characterized by very large entropy effects indicating substantial increase in the conformational flexibility of the resulting products. The experimental threshold energies of 1.75 eV and 1.34 eV obtained for the [V+Ac2KDADA-H]- and [V+Ac2KDADA+H]+ , respectively, are in excellent agreement with the results of density functional theory (DFT) calculations. The increased stability of the deprotonated complex observed experimentally is attributed to the presence of three charged sites in the deprotonated complex as compared to only one charged site in the singly protonated complex. The low binding energy of 0.93 eV obtained for the doubly protonated complex suggests that this ion is destabilized by Coulomb repulsion between the singly protonated vancomycin and the singly protonated peptide comprising the complex.

  10. Survey of Analogue Spacetimes

    NASA Astrophysics Data System (ADS)

    Visser, Matt

    Analogue spacetimes (and more boldly, analogue models both of and for gravity), have attracted significant and increasing attention over the last decade and a half. Perhaps the most straightforward physical example, which serves as a template for most of the others, is Bill Unruh's model for a dumb hole,(mute black hole, acoustic black hole), wherein sound is dragged along by a moving fluid—and can even be trapped behind an acoustic horizon. This and related analogue models for curved spacetimes are useful in many ways: analogue spacetimes provide general relativists with extremely concrete physical models to help focus their thinking, and conversely the techniques of curved spacetime can sometimes help improve our understanding of condensed matter and/or optical systems by providing an unexpected and countervailing viewpoint. In this chapter, I shall provide a few simple examples of analogue spacetimes as general background for the rest of the contributions.

  11. Treatment with intermittent PTH increases Wnt10b production by T cells in osteoporotic patients.

    PubMed

    D'Amelio, P; Sassi, F; Buondonno, I; Fornelli, G; Spertino, E; D'Amico, L; Marchetti, M; Lucchiari, M; Roato, I; Isaia, G C

    2015-12-01

    We evaluated the effect of parathyroid hormone (PTH) on Wnt10b production by immune system cells in humans. We showed that bone anabolic effect of intermittent PTH treatment may be amplified by T cells through increased production of Wnt10b. Chronic increase in PTH as in primary hyperparathyroidism does not increase Wnt10b expression. The aim of this study is to assess the effect of PTH on Wnt10b production by immune system cells in humans. We assessed both the effect of intermittent PTH administration (iPTH) and of chronic PTH hypersecretion in primary hyperparathyroidism (PHP). Eighty-two women affected by post-menopausal osteoporosis were randomly assigned to treatment with calcium and vitamin D alone (22) or plus 1-84 PTH (42), or intravenous ibandronate (18). Wnt10b production by unfractioned blood nucleated cells and by T, B cells and monocytes was assessed by real-time RT-PCR and ELISA at baseline, 3, 6, 12 and 18 months of treatment. The effect of chronic elevation of PTH was evaluated in 20 patients affected by PHP at diagnosis and after surgical removal of parathyroid adenoma. WNT10b from both osteoporotic and PHP patients was compared to healthy subjects matched for age and sex. iPTH increases Wnt10b production by T cells, whereas PHP does not. After surgical restoration of normal parathyroid function, WNT10b decreases, although it is still comparable with healthy subjects' level. Thus, chronic elevation of PTH does not significantly increase WNT10b production as respect to control. This is the first work showing the effect of both intermittent and chronic PTH increase on Wnt10b production by immune system cells. We suggest that, in humans, T cells amplified the anabolic effect of PTH on bone, by increasing Wnt10b production, which stimulates osteoblast activity.

  12. Genome Editing Reveals Glioblastoma Addiction to MicroRNA-10b.

    PubMed

    El Fatimy, Rachid; Subramanian, Shruthi; Uhlmann, Erik J; Krichevsky, Anna M

    2017-02-01

    Glioblastoma (GBM) brain tumor remains among the most lethal and incurable human diseases. Oncogenic microRNA-10b (miR-10b) is strongly and universally upregulated in GBM, and its inhibition by antisense oligonucleotides (ASOs) reduces the growth of heterogeneous glioma cells; therefore, miR-10b represents a unique therapeutic target for GBM. Here we explored the effects of miR-10b gene editing on GBM. Using the clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 system, we investigated effects of miR-10b gene editing on the growth of cultured human glioma cells, tumor-initiating stem-like cells, and mouse GBM xenografts, as well as the oncogene-induced transformation of normal astrocytes. We show that GBM is strictly "addicted" to miR-10b and that miR-10b gene ablation is lethal for glioma cell cultures and established intracranial tumors. miR-10b loss-of-function mutations lead to the death of glioma, but not other cancer cell lines. We have not detected escaped proliferative clones of GBM cells edited in the miR-10b locus. Finally, neoplastic transformation of normal astrocytes was abolished by the miR-10b-editing vectors. This study demonstrates the feasibility of gene editing for brain tumors in vivo and suggests virus-mediated miR-10b gene ablation as a promising therapeutic approach that permanently eliminates the key regulator essential for tumor growth and survival.

  13. Analogue of oscillation theorem for nonadiabatic diatomic states: application to the A (1)Sigma(+) and b (3)Pi states of KCs.

    PubMed

    Pupyshev, V I; Pazyuk, E A; Stolyarov, A V; Tamanis, M; Ferber, R

    2010-05-14

    Relative intensity measurements in the high resolution A (1)Sigma(+) approximately b (3)Pi--> X (1)Sigma(+) laser induced fluorescence spectra of the KCs molecule highlighted a breakdown of the conventional one-dimensional oscillation theorem (L. D. Landau and E. M. Lifshitz, Quantum Mechanics, Pergamon, New York, 1965). For strongly spin-orbit coupled A (1)Sigma(+) and b (3)Pi states the number of nodes n(A) and n(b) of the non-adiabatic vibrational eigenfunctions phi and phi corresponding to the v-th eigenstate differs essentially from their adiabatic counterparts. It is found, however, that in the general case of two-component states with wavefunctions phi and phi coupled by the sign-constant potential operator V(12) not equal 0: (1) the lowest state v = 0 is not degenerate; and (2) the arithmetic mean of the number of nodes n(1) and n(2) of phi and phi never exceeds the ordering number v of eigenstate: (n(1) + n(2))/2

  14. 17 CFR 240.10b-16 - Disclosure of credit terms in margin transactions.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Disclosure of credit terms in margin transactions. 240.10b-16 Section 240.10b-16 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION (CONTINUED) GENERAL RULES AND REGULATIONS, SECURITIES EXCHANGE ACT OF 1934 Rules...

  15. Tidal Dissipation in a Homogeneous Spherical Body. 2. Three Examples: Mercury, IO, and Kepler-10 b

    DTIC Science & Technology

    the previously used formulae, and noted the differences. Now we present case studies: Mercury, Kepler -10 b, and a triaxial Io. A sharp frequency...our calculation, Kepler -10 b could hardly survive the intensive tidal heating without being synchronized, circularized, and reshaped through a complete or partial melt-down.

  16. Silencing of Wnt10B reduces viability of heptocellular carcinoma HepG2 cells

    PubMed Central

    Wu, Guohui; Fan, Xiaoli; Sun, Li

    2015-01-01

    Dysregulation of Wnt-mediated β-catenin signaling is associated with carcinogenesis and progression of hepatocellular carcinoma (HCC). Our previous studies showed that the Wnt10B gene, a member of Wnt gene family, over-activated in HCC tissues and cells. Here we demonstrate that stable silencing of Wnt10B reduces the viability of HCC cells in culture. HepG2, a human HCC cell line, was cultured in vitro and Wnt10B gene in the cells stably silenced, as showed in Western blotting analysis, by the shRNA interference with lentivirus plasmid transfection. Compared to the control (HepG2 cells without Wnt10B silencing), the Wnt10B-silencing cells showed significant reductions in proliferation, colony formation, migration and invasion. Furthermore, serum deprivation-induced apoptotic death, assessed by Hoechst 33342 staining and fluorescent microscopy, increased significantly in the Wnt10B-silencing cells. FACScan analysis indicated an arrest of the cell cycle in the Wnt10B-silencing HCC cells, with significant increases in the number of cells in G0-G1 and S phases. Thus, we hypothesize that Wnt10B plays an oncogenic role in HCC and is a potential therapeutic target. PMID:26269753

  17. 40 CFR Appendix A-4 to Part 60 - Test Methods 6 through 10B

    Code of Federal Regulations, 2010 CFR

    2001-07-01

    ... 40 Protection of Environment 7 2001-07-01 2001-07-01 false Test Methods 6 through 10B A Appendix A-4 to Part 60 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY AIR PROGRAMS (CONTINUED) STANDARDS OF PERFORMANCE FOR NEW STATIONARY SOURCES (Continued) Appendix A-4 to Part 60—Test Methods 6 through 10B Method 6—Determination of...

  18. ATR LEU Monothlic and Dispersed with 10B Loading Minimization Design – Neutronics Performance Analysis

    SciTech Connect

    G. S. Chang

    2001-10-01

    The Advanced Test Reactor (ATR), currently operating in the United States, is used for material testing at very high neutron fluxes. Powered with highly enriched uranium (HEU), the ATR has a maximum thermal power rating of 250 MWth. Because of the large test volumes located in high flux areas, the ATR is an ideal candidate for assessing the feasibility of converting HEU driven reactor cores to low-enriched uranium (LEU) cores. The present work investigates the optimized LEU Monolithic and Dispersed fuel with 10B loading minimization design and evaluates the subsequent neutronics operating effects of these optimized fuel designs. The MCNP ATR 1/8th core model was used to optimize the 235U and minimize the 10B loading in the LEU core, such that the differences in K-eff and heat flux profiles between the HEU and LEU cores were minimized. The fuel depletion methodology MCWO was used to calculate K eff versus effective full power days (EFPD) in this paper. The MCWO-calculated results for the optimized LEU Monolithic and Dispersed fuel cases demonstrated adequate excess reactivity such that the K-eff versus EFPD plot is similar to the ATR reference HEU case study. Each HEU fuel element contains 19 fuel plates with a fuel meat thickness of 0.508 mm (20 mil). In this work, the proposed LEU Monolithic (U-10Mo) core conversion case with nominal fuel meat thickness of 0.330 mm (13 mil) and 235U enrichment of 19.7 wt% is used to optimize the radial heat flux profile by varying the fuel meat thickness. The proposed LEU fuel meat varies from 0.203 mm (8.0 mil) to 0.254 mm (10.0 mil) at the inner four fuel plates (1-4) and outer four fuel plates (16-19). In addition, an optimized LEU dispersed (U7Mo) case with all the fuel meat thickness of 0.635 mm (25 mil) was also proposed. Then, for both Monolithic and dispersed cases, a burnable absorber – 10B, was added in the inner and outer plates to reduce the initial excess reactivity, and the higher to average ratio of the inner

  19. The Vital Dye CDr10b Labels the Zebrafish Mid-Intestine and Lumen.

    PubMed

    Sander, Veronika; Patke, Shantanu; Lee, Jung Y; Chang, Young-Tae; Davidson, Alan J

    2017-03-13

    We describe the use of the fluorescent reporter compound CDr10b to label mid-intestinal structures in zebrafish larvae after simple immersion. CDr10b is deposited into the gut where it initially fills the lumen and is excreted. Using laser-mediated injury of the intestine, we show that CDr10b provides a useful readout of the integrity and repair of the epithelial cell barrier. In addition, CDr10b specifically labels the absorptive mid-intestine segment that is analogous to the mammalian small intestine. By perturbing retinoic acid signaling, which regulates the size of the mid-intestine segment, we show that CDr10b is a valuable tool to rapidly assess developmental malformations of the intestine in live animals.

  20. Oncogenic effects of miR-10b in glioblastoma stem cells

    PubMed Central

    Guessous, Fadila; Alvarado-Velez, Melissa; Marcinkiewicz, Lukasz; Zhang, Ying; Kim, Jungeun; Heister, Simon; Kefas, Benjamin; Godlewski, Jakub; Schiff, David; Purow, Benjamin

    2013-01-01

    MicroRNAs and cancer stem cells have emerged as critical players in glioblastoma, one of the deadliest human cancers. In this study, we investigated the expression and function of microRNA-10b in glioblastoma cells and stem cells. An analysis of The Cancer Genome Atlas data revealed a correlation between high miR-10b levels and poor prognosis in glioblastoma patients. We measured the levels of miR-10b and found that it is upregulated in human glioblastoma tissues, glioblastoma cell and stem cell lines as compared to normal human tissues or astrocytes. Inhibition of miR-10b with a specific antagomir inhibited the proliferation of glioblastoma established and stem cell lines. Inhibition of miR-10b strongly reduced cell invasion and migration in glioblastoma cell and stem cell lines while overexpression of miR-10b induced cell migration and invasion. We also investigated several predicted targets of miR-10b but could not verify any of them experimentally. Additionally, miR-10b inhibition significantly decreased the in vivo growth of stem cell-derived orthotopic GBM xenografts. Altogether, our findings confirm the oncogenic effects of miR-10b in GBM cells and show for the first time a role of this microRNA in GBM stem cells. Targeting miR-10b might therefore inhibit glioblastoma stem cells, which are thought to be at the origin of glioblastoma and to contribute its recurrence and resistance to therapy. PMID:23307328

  1. A Point Mutation in the Gene for Asparagine-Linked Glycosylation 10B (Alg10b) Causes Nonsyndromic Hearing Impairment in Mice (Mus musculus)

    PubMed Central

    Probst, Frank J.; Corrigan, Rebecca R.; del Gaudio, Daniela; Salinger, Andrew P.; Lorenzo, Isabel; Gao, Simon S.; Chiu, Ilene; Xia, Anping

    2013-01-01

    The study of mouse hearing impairment mutants has led to the identification of a number of human hearing impairment genes and has greatly furthered our understanding of the physiology of hearing. The novel mouse mutant neurological/sensory 5 (nse5) demonstrates a significantly reduced or absent startle response to sound and is therefore a potential murine model of human hearing impairment. Genetic analysis of 500 intercross progeny localized the mutant locus to a 524 kilobase (kb) interval on mouse chromosome 15. A missense mutation in a highly-conserved amino acid was found in the asparagine-linked glycosylation 10B gene (Alg10b), which is within the critical interval for the nse5 mutation. A 20.4 kb transgene containing a wildtype copy of the Alg10b gene rescued the mutant phenotype in nse5/nse5 homozygous animals, confirming that the mutation in Alg10b is responsible for the nse5/nse5 mutant phenotype. Homozygous nse5/nse5 mutants had abnormal auditory brainstem responses (ABRs), distortion product otoacoustic emissions (DPOAEs), and cochlear microphonics (CMs). Endocochlear potentials (EPs), on the other hand, were normal. ABRs and DPOAEs also confirmed the rescue of the mutant nse5/nse5 phenotype by the wildtype Alg10b transgene. These results suggested a defect in the outer hair cells of mutant animals, which was confirmed by histologic analysis. This is the first report of mutation in a gene involved in the asparagine (N)-linked glycosylation pathway causing nonsyndromic hearing impairment, and it suggests that the hearing apparatus, and the outer hair cells in particular, are exquisitely sensitive to perturbations of the N-linked glycosylation pathway. PMID:24303013

  2. A point mutation in the gene for asparagine-linked glycosylation 10B (Alg10b) causes nonsyndromic hearing impairment in mice (Mus musculus).

    PubMed

    Probst, Frank J; Corrigan, Rebecca R; Del Gaudio, Daniela; Salinger, Andrew P; Lorenzo, Isabel; Gao, Simon S; Chiu, Ilene; Xia, Anping; Oghalai, John S; Justice, Monica J

    2013-01-01

    The study of mouse hearing impairment mutants has led to the identification of a number of human hearing impairment genes and has greatly furthered our understanding of the physiology of hearing. The novel mouse mutant neurological/sensory 5 (nse5) demonstrates a significantly reduced or absent startle response to sound and is therefore a potential murine model of human hearing impairment. Genetic analysis of 500 intercross progeny localized the mutant locus to a 524 kilobase (kb) interval on mouse chromosome 15. A missense mutation in a highly-conserved amino acid was found in the asparagine-linked glycosylation 10B gene (Alg10b), which is within the critical interval for the nse5 mutation. A 20.4 kb transgene containing a wildtype copy of the Alg10b gene rescued the mutant phenotype in nse5/nse5 homozygous animals, confirming that the mutation in Alg10b is responsible for the nse5/nse5 mutant phenotype. Homozygous nse5/nse5 mutants had abnormal auditory brainstem responses (ABRs), distortion product otoacoustic emissions (DPOAEs), and cochlear microphonics (CMs). Endocochlear potentials (EPs), on the other hand, were normal. ABRs and DPOAEs also confirmed the rescue of the mutant nse5/nse5 phenotype by the wildtype Alg10b transgene. These results suggested a defect in the outer hair cells of mutant animals, which was confirmed by histologic analysis. This is the first report of mutation in a gene involved in the asparagine (N)-linked glycosylation pathway causing nonsyndromic hearing impairment, and it suggests that the hearing apparatus, and the outer hair cells in particular, are exquisitely sensitive to perturbations of the N-linked glycosylation pathway.

  3. 10B(n, Z) measurements in the energy range 0.7 to 5.0 MeV

    DOE PAGES

    Massey, T. N.; Ralston, J.; Grimes, S. M.; ...

    2014-09-03

    Four ΔE E telescopes were used at the WNR (n,Z) station to investigate the production of charged particles from 10B. The telescope consisted of a gas proportional detector and a silicon surface barrier detector. The flux was determined using a 238U fission chamber. A clear separation of the ground state alpha group and first excited state a was not achieved due to the target thickness. Proton emission was also observed. Furthermore, the proton branch was up to an order of magnitude larger than predicted in ENDF/B-VII A simple R-matrix analysis has been performed on the available data

  4. Effects of Wnt-10b on hair shaft growth in hair follicle cultures

    SciTech Connect

    Ouji, Yukiteru . E-mail: oujix@naramed-u.ac.jp; Yoshikawa, Masahide; Moriya, Kei; Ishizaka, Shigeaki

    2007-08-03

    Wnts are deeply involved in the proliferation and differentiation of skin epithelial cells. We previously reported the differentiation of cultured primary skin epithelial cells toward hair shaft and inner root sheath (IRS) of the hair follicle via {beta}-catenin stabilization caused by Wnt-10b, however, the effects of Wnt-10b on cultured hair follicles have not been reported. In the present study, we examined the effects of Wnt-10b on shaft growth using organ cultures of whisker hair follicles in serum-free conditions. No hair shaft growth was observed in the absence of Wnt-10b, whereas its addition to the culture promoted elongation of the hair shaft, intensive incorporation of BrdU in matrix cells flanking the dermal papilla (DP), and {beta}-catenin stabilization in DP and IRS cells. These results suggest a promoting effect of Wnt-10b on hair shaft growth that is involved with stimulation of the DP via Wnt-10b/{beta}-catenin signalling, proliferation of matrix cells next to the DP, and differentiation of IRS cells by Wnt-10b.

  5. miR-10b targets Tiam1: implications for Rac activation and carcinoma migration.

    PubMed

    Moriarty, Charlotte H; Pursell, Bryan; Mercurio, Arthur M

    2010-07-02

    Understanding the mechanisms by which specific microRNAs regulate cell migration and invasion is a timely and significant problem in cancer cell biology. miR-10b is of interest in this regard because its expression is altered in breast and other cancers. Our analysis of potential miR-10b targets identified Tiam1 (T lymphoma invasion and metastasis 1), a guanidine exchange factor for Rac. We demonstrate, using an miR-10b synthetic precursor, expression vector, and antisense oligonucleotide, that miR-10b represses Tiam1 expression in breast carcinoma cells and that it interacts with the 3'-UTR of Tiam1. Consistent with the involvement of Tiam1 in cell motility, we observed that miR-10b suppresses the ability of breast carcinoma cells to migrate and invade. Importantly, we demonstrate that miR-10b also inhibits Tiam1-mediated Rac activation. These data provide a mechanism for the regulation of Tiam1-mediated Rac activation in breast cancer cells and need to be considered in the context of other reported functions for miR-10b.

  6. Development of 10B-Based 3He Replacement Neutron Detectors

    NASA Astrophysics Data System (ADS)

    King, Michael J.; Gozani, Tsahi; Hilliard, Donald B.

    2011-12-01

    Radiation portal monitors (RPM) are currently deployed at United States border crossings to passively inspect vehicles and persons for any emission of neutrons and/or gamma rays, which may indicate the presence of unshielded nuclear materials. The RPM module contains an organic scintillator with 3He proportional counters to detect gamma rays and thermalized neutrons, respectively. The supply of 3He is rapidly dwindling, requiring alternative detectors to provide the same function and performance. Our alternative approach is one consisting of a thinly-coated 10B flat-panel ionization chamber neutron detector that can be deployed as a direct drop-in replacement for current RPM 3He detectors. The uniqueness of our approach in providing a large-area detector is in the simplicity of construction, scalability of the unit cell detector, ease of adaptability to a variety of applications and low cost. Currently, Rapiscan Laboratories and Helicon Thin Film Systems have designed and developed an operational 100 cm2 multi-layer prototype 10BB-based ionization chamber.

  7. a New Method to Measure 10B Uptake in Lung Adenocarcinoma in Hospital Bnct

    NASA Astrophysics Data System (ADS)

    Donegani, E. M.; Basilico, F.; Bolognini, D.; Borasio, P.; Capelli, E.; Cappelletti, P.; Chiari, P.; Frigerio, M.; Gelosa, S.; Giannini, G.; Hasan, S.; Mattera, A.; Mauri, P.; Monti, A. F.; Ostinelli, A.; Prest, M.; Vallazza, E.; Zanini, A.

    2010-04-01

    Boron Neutron Capture Therapy (BNCT) is a radiotherapic technique still under development that could become crucial in the fight against some types of cancer (extended ones, located near vital organs or radio resistant). This binary technique requires the administration to the patient of a boron delivery agent and the irradiation with a thermal neutron beam. The high LET particles produced in the 10B(n,α)7Li reaction are exploited to destroy the tumour cells. This work presents a new system based on neutron autoradiography with a non-depleted self-triggering microstrip silicon detector, using a neutron beam produced by a hospital Linac. The system is fast, real time and allows the detection of 10B contents down to 25 ng. The main results on the study of 10B uptake in biological samples will be described in terms of kinetic curves (10B uptake as a function of time).

  8. VIEW OF ROOMS 10B AND 9B, LOOKING TOWARDS SIDE 1 ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    VIEW OF ROOMS 10B AND 9B, LOOKING TOWARDS SIDE 1 OF THE MLP - Cape Canaveral Air Force Station, Launch Complex 39, Mobile Launcher Platforms, Launcher Road, East of Kennedy Parkway North, Cape Canaveral, Brevard County, FL

  9. Neutron capture autoradiographic study of the biodistribution of 10B in tumor-bearing mice.

    PubMed

    Ogura, K; Yanagie, H; Eriguchi, M; Lehmann, E H; Kühne, G; Bayon, G; Kobayashi, H

    2004-10-01

    For the study on boron neutron capture therapy, the whole-body sections of tumor-bearing mice infused with 10B attached to CR-39 plastic track detectors were exposed to thermal and cold neutron beams. Neutron capture autoradiographic images obtained by the cold neutron irradiation were extremely superior in quality to those of the thermal neutron beams. From the autoradiographic images, the 10B reaction dose of the neutron-induced particles was estimated using the differential LET distribution.

  10. 40 CFR Appendix A-4 to Part 60 - Test Methods 6 through 10B

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 8 2013-07-01 2013-07-01 false Test Methods 6 through 10B A Appendix A-4 to Part 60 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) STANDARDS OF PERFORMANCE FOR NEW STATIONARY SOURCES (CONTINUED) Pt. 60, App. A-4 Appendix A-4 to Part 60—Test Methods 6 through 10B Method 6...

  11. 40 CFR Appendix A-4 to Part 60 - Test Methods 6 through 10B

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 8 2014-07-01 2014-07-01 false Test Methods 6 through 10B A Appendix A-4 to Part 60 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) STANDARDS OF PERFORMANCE FOR NEW STATIONARY SOURCES (CONTINUED) Pt. 60, App. A-4 Appendix A-4 to Part 60—Test Methods 6 through 10B Method 6...

  12. 40 CFR Appendix A-4 to Part 60 - Test Methods 6 through 10B

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 8 2012-07-01 2012-07-01 false Test Methods 6 through 10B A Appendix A-4 to Part 60 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) STANDARDS OF PERFORMANCE FOR NEW STATIONARY SOURCES (CONTINUED) Pt. 60, App. A-4 Appendix A-4 to Part 60—Test Methods 6 through 10B Method 6...

  13. 40 CFR Appendix A-4 to Part 60 - Test Methods 6 through 10B

    Code of Federal Regulations, 2010 CFR

    2015-07-01

    ... 40 Protection of Environment 8 2015-07-01 2015-07-01 false Test Methods 6 through 10B A Appendix A-4 to Part 60 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) STANDARDS OF PERFORMANCE FOR NEW STATIONARY SOURCES (CONTINUED) Pt. 60, App. A-4 Appendix A-4 to Part 60—Test Methods 6 through 10B Method...

  14. 40 CFR Appendix A-4 to Part 60 - Test Methods 6 through 10B

    Code of Federal Regulations, 2010 CFR

    2005-07-01

    ... 40 Protection of Environment 7 2005-07-01 2005-07-01 false Test Methods 6 through 10B A Appendix A-4 to Part 60 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) STANDARDS OF PERFORMANCE FOR NEW STATIONARY SOURCES (CONTINUED) Pt. 60, App. A-4 Appendix A-4 to Part 60—Test Methods 6 through 10B Method...

  15. 40 CFR Appendix A-4 to Part 60 - Test Methods 6 through 10B

    Code of Federal Regulations, 2010 CFR

    2016-07-01

    ... 40 Protection of Environment 9 2016-07-01 2016-07-01 false Test Methods 6 through 10B A Appendix A-4 to Part 60 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) STANDARDS OF PERFORMANCE FOR NEW STATIONARY SOURCES (CONTINUED) Pt. 60, App. A-4 Appendix A-4 to Part 60—Test Methods 6 through 10B Method...

  16. 40 CFR Appendix A-4 to Part 60 - Test Methods 6 through 10B

    Code of Federal Regulations, 2010 CFR

    2007-07-01

    ... 40 Protection of Environment 7 2007-07-01 2007-07-01 false Test Methods 6 through 10B A Appendix A-4 to Part 60 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) STANDARDS OF PERFORMANCE FOR NEW STATIONARY SOURCES (CONTINUED) Pt. 60, App. A-4 Appendix A-4 to Part 60—Test Methods 6 through 10B Method...

  17. Canonical Wnts, specifically Wnt-10b, show ability to maintain dermal papilla cells

    SciTech Connect

    Ouji, Yukiteru Nakamura-Uchiyama, Fukumi; Yoshikawa, Masahide

    2013-08-30

    Highlights: •First report on effects of various Wnts on DP cells. •Wnt-10b promoted trichogenesis, while Wnt-3a showed to a limited extent. •Canonical Wnts, specifically Wnt-10b, is important for DP cells maintenance. -- Abstract: Although Wnts are expressed in hair follicles (HFs) and considered to be crucial for maintaining dermal papilla (DP) cells, the functional differences among them remain largely unknown. In the present study, we investigated the effects of Wnts (Wnt-3a, 5a, 10b, 11) on the proliferation of mouse-derived primary DP cells in vitro as well as their trichogenesis-promoting ability using an in vivo skin reconstitution protocol. Wnt-10b promoted cell proliferation and trichogenesis, while Wnt-3a showed those abilities to a limited extent, and Wnt-5a and 11 had no effects. Furthermore, we investigated the effects of these Wnts on cultured DP cells obtained from versican-GFP transgenic mice and found that Wnt-10b had a potent ability to sustain their GFP-positivity. These results suggest that canonical Wnts, specifically Wnt-10b, play important roles in the maintenance of DP cells and trichogenesis.

  18. Wnt-10b secreted from lymphocytes promotes differentiation of skin epithelial cells

    SciTech Connect

    Ouji, Yukiteru . E-mail: oujix@naramed-u.ac.jp; Yoshikawa, Masahide; Shiroi, Akira; Ishizaka, Shigeaki

    2006-04-21

    Wnt-10b was originally isolated from lymphoid tissue and is known to be involved in a wide range of biological actions, while recently it was found to be expressed early in the development of hair follicles. However, few studies have been conducted concerning the role of Wnt-10b with the differentiation of skin epithelial cells. To evaluate its role in epithelial differentiation, we purified Wnt-10b from the supernatant of a concanavalin A-stimulated lymphocyte culture using an affinity column and investigated its effects on the differentiation of adult mouse-derived primary skin epithelial cells (MPSEC). MPSEC cultured with Wnt-10b showed morphological changes from cuboidal to spindle-shaped with inhibited proliferation, and also obtained characteristics of the hair shaft and inner root sheath of the hair follicle, represented by red-colored Ayoub Shklar staining, and reactions to AE-13 and AE-15 as seen with immunocytology. Further, RT-PCR analysis demonstrated the expression of mRNA for keratin 1, keratin 2, loricrin, mHa5, and mHb5, in association with a decreased expression of the basal cell marker keratin 5, in Wnt-10b-treated MPSEC. In addition, involvement of the canonical Wnt signal pathway was demonstrated by a TCF reporter (pTOPFLASH) assay. These results suggest that Wnt-10b promotes the differentiation of MPSEC and may play an important role in hair follicle development by promoting differentiation of epithelial cells.

  19. Modulating hair follicle size with Wnt10b/DKK1 during hair regeneration.

    PubMed

    Lei, Mingxing; Guo, Haiying; Qiu, Weiming; Lai, Xiangdong; Yang, Tian; Widelitz, Randall B; Chuong, Cheng-Ming; Lian, Xiaohua; Yang, Li

    2014-06-01

    Hair follicles have characteristic sizes corresponding to their cycle-specific stage. However, how the anagen hair follicle specifies its size remains elusive. Here, we showed that in response to prolonged ectopic Wnt10b-mediated β-catenin activation, regenerating anagen hair follicles grew larger in size. In particular, the hair bulb, dermal papilla and hair shaft became enlarged, while the formation of different hair types (Guard, Awl, Auchene and Zigzag) was unaffected. Interestingly, we found that the effect of exogenous WNT10b was mainly on Zigzag and less on the other kinds of hairs. We observed dramatically enhanced proliferation within the matrix, DP and hair shaft of the enlarged AdWnt10b-treated hair follicles compared with those of normal hair follicles at P98. Furthermore, expression of CD34, a specific hair stem cell marker, was increased in its number to the bulge region after AdWnt10b treatment. Ectopic expression of CD34 throughout the ORS region was also observed. Many CD34-positive hair stem cells were actively proliferating in AdWnt10b-induced hair follicles. Importantly, subsequent co-treatment with the Wnt inhibitor, DKK1, reduced hair follicle enlargement and decreased proliferation and ectopic localization of hair stem cells. Moreover, injection of DKK1 during early anagen significantly reduced the width of prospective hairs. Together, these findings strongly suggest that Wnt10b/DKK1 can modulate hair follicle size during hair regeneration.

  20. Design and Testing of a 10B4C Capsule for Spectral-Tailoring in Mixed-Spectrum Reactors

    SciTech Connect

    Greenwood, Lawrence R.; Wittman, Richard S.; Metz, Lori A.; Finn, Erin C.; Friese, Judah I.

    2014-04-11

    A boron carbide capsule highly enriched in 10B has been designed and used for spectral-tailoring experiments at the TRIGA reactor at Washington State University. New experiments show that enriching the boron to 96% B-10 results in additional absorption of neutrons in the resonance region thereby producing a neutron spectrum that is much closer to a pure 235U fission spectrum. A cadmium outer cover was used to reduce thermal heating. The neutron spectrum calculated with MCNP was found to be in very good agreement with measured activation rates from neutron fluence monitors.

  1. Human Glioma Growth is Controlled by MicroRNA-10b

    PubMed Central

    Gabriely, Galina; Yi, Ming; Narayan, Ravi S.; Niers, Johanna M.; Wurdinger, Thomas; Imitola, Jaime; Ligon, Keith L.; Kesari, Santosh; Esau, Christine; Stephens, Robert M.; Tannous, Bakhos A.; Krichevsky, Anna M.

    2011-01-01

    MicroRNA (miRNA) expression profiling studies revealed a number of miRNAs dysregulated in the malignant brain tumor, glioblastoma. Molecular functions of these miRNAs in gliomagenesis are mainly unknown. We show that inhibition of miR-10b, a miRNA not expressed in human brain and strongly up-regulated in both low-grade and high-grade gliomas, reduces glioma cell growth by cell cycle arrest and apoptosis. These cellular responses are mediated by augmented expression of the direct targets of miR-10b, including BCL2L11/Bim, TFAP2C/AP-2γ, CDKN1A/p21, and CDKN2A/p16, which normally protect cells from uncontrolled growth. Analysis of The Cancer Genome Atlas (TCGA) expression dataset reveals a strong positive correlation between numerous genes sustaining cellular growth and miR-10b levels in human glioblastomas, while pro-apoptotic genes anti-correlate with the expression of miR-10b. Furthermore, survival of glioblastoma patients expressing high levels of miR-10 family members is significantly reduced in comparison to patients with low miR-10 levels, indicating that miR-10 may contribute to glioma growth in vivo. Finally, inhibition of miR-10b in a mouse model of human glioma results in significant reduction of tumor growth. Altogether, our experiments validate an important role of miR-10b in gliomagenesis, reveal a novel mechanism of miR-10b-mediated regulation, and suggest the possibility of its future use as a therapeutic target in gliomas. PMID:21471404

  2. Human glioma growth is controlled by microRNA-10b.

    PubMed

    Gabriely, Galina; Yi, Ming; Narayan, Ravi S; Niers, Johanna M; Wurdinger, Thomas; Imitola, Jaime; Ligon, Keith L; Kesari, Santosh; Esau, Christine; Stephens, Robert M; Tannous, Bakhos A; Krichevsky, Anna M

    2011-05-15

    MicroRNA (miRNA) expression profiling studies revealed a number of miRNAs dysregulated in the malignant brain tumor glioblastoma. Molecular functions of these miRNAs in gliomagenesis are mainly unknown. We show that inhibition of miR-10b, a miRNA not expressed in human brain and strongly upregulated in both low-grade and high-grade gliomas, reduces glioma cell growth by cell-cycle arrest and apoptosis. These cellular responses are mediated by augmented expression of the direct targets of miR-10b, including BCL2L11/Bim, TFAP2C/AP-2γ, CDKN1A/p21, and CDKN2A/p16, which normally protect cells from uncontrolled growth. Analysis of The Cancer Genome Atlas expression data set reveals a strong positive correlation between numerous genes sustaining cellular growth and miR-10b levels in human glioblastomas, while proapoptotic genes anticorrelate with the expression of miR-10b. Furthermore, survival of glioblastoma patients expressing high levels of miR-10 family members is significantly reduced in comparison to patients with low miR-10 levels, indicating that miR-10 may contribute to glioma growth in vivo. Finally, inhibition of miR-10b in a mouse model of human glioma results in significant reduction of tumor growth. Altogether, our experiments validate an important role of miR-10b in gliomagenesis, reveal a novel mechanism of miR-10b-mediated regulation, and suggest the possibility of its future use as a therapeutic target in gliomas. ©2011 AACR

  3. Proteomic analysis on N, N′-dinitrosopiperazine-mediated metastasis of nasopharyngeal carcinoma 6-10B cells

    PubMed Central

    2012-01-01

    Background Nasopharyngeal carcinoma (NPC) has a high metastatic feature. N,N′-Dinitrosopiperazine (DNP) is involved in NPC metastasis, but its mechanism is not clear. The aim of this study is to reveal the pathogenesis of DNP-involved metastasis. 6-10B cells with low metastasis are from NPC cell line SUNE-1, were used to investigate the mechanism of DNP-mediated NPC metastasis. Results 6-10B cells were grown in DMEM containing 2H4-L-lysine and 13C 6 15 N4-L-arginine or conventional L-lysine and L-arginine, and identified the incorporation of amino acid by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Labeled 6-10B cells were treated with DNP at 0 -18 μM to establish the non-cytotoxic concentration (NCC) range. NCC was 0 -10 μM. Following treatment with DNP at this range, the motility and invasion of cells were detected in vitro, and DNP-mediated metastasis was confirmed in the nude mice. DNP increased 6-10B cell metastasis in vitro and vivo. DNP-induced protein expression was investigated using a quantitative proteomic. The SILAC-based approach quantified 2698 proteins, 371 of which showed significant change after DNP treatment (172 up-regulated and 199 down-regulated proteins). DNP induced the change in abundance of mitochondrial proteins, mediated the status of oxidative stress and the imbalance of redox state, increased cytoskeletal protein, cathepsin, anterior gradient-2, and clusterin expression. DNP also increased the expression of secretory AKR1B10, cathepsin B and clusterin 6-10B cells. Gene Ontology and Ingenuity Pathway analysis showed that DNP may regulate protein synthesis, cellular movement, lipid metabolism, molecular transport, cellular growth and proliferation signaling pathways. Conclusion DNP may regulate cytoskeletal protein, cathepsin, anterior gradient-2, and clusterin expression, increase NPC cells motility and invasion, is involved NPC metastasis. PMID:23157228

  4. Heteroatom-Containing Porphyrin Analogues.

    PubMed

    Chatterjee, Tamal; Shetti, Vijayendra S; Sharma, Ritambhara; Ravikanth, Mangalampalli

    2017-02-22

    The heteroatom-containing porphyrin analogues or core-modified porphyrins that resulted from the replacement of one or two pyrrole rings with other five-membered heterocycles such as furan, thiophene, selenophene, tellurophene, indene, phosphole, and silole are highly promising macrocycles and exhibit quite different physicochemical properties compared to regular azaporphyrins. The properties of heteroporphyrins depend on the nature and number of different heterocycle(s) present in place of pyrrole ring(s). The heteroporphyrins provide unique and unprecedented coordination environments for metals. Unlike regular porphyrins, the monoheteroporphyrins are known to stabilize metals in unusual oxidation states such as Cu and Ni in +1 oxidation states. The diheteroporphyrins, which are neutral macrocycles without ionizable protons, also showed interesting coordination chemistry. Thus, significant progress has been made in last few decades on core-modified porphyrins in terms of their synthesis, their use in building multiporphyrin arrays for light-harvesting applications, their use as ligands to form interesting metal complexes, and also their use for several other studies. The synthetic methods available in the literature allow one to prepare mono- and diheteroporphyrins and their functionalized derivatives, which were used extensively to prepare several covalent and noncovalent heteroporphyrin-based multiporphyrin arrays. The methods are also developed to synthesize different hetero analogues of porphyrin derivatives such as heterocorroles, heterochlorins, heterocarbaporphyrinoids, heteroatom-substituted confused porphyrins, and so on. This Review summarizes the key developments that have occurred in heteroporphyrin chemistry over the last four decades.

  5. miRNA-10b sponge: An anti-breast cancer study in vitro

    PubMed Central

    LIANG, AI-LING; ZHANG, TING-TING; ZHOU, NING; WU, CUI YUN; LIN, MAN-HUA; LIU, YONG-JUN

    2016-01-01

    Breast cancer is a malignant tumor with the highest incidence among women. Breast cancer metastasis is the major cause of treatment failure and mortality among such patients. MicroRNAs (miRNAs) are a class of small molecular non-coding regulatory RNAs, which act as oncogenes or tumor suppressors in breast cancer. miRNA-10b has been found to exhibit a high expression level in advanced and metastatic breast cancer, and is closely related to breast cancer metastasis. An miRNA sponge is an mRNA with several repeated sequences of complete or incomplete complementarity to the natural miRNA in its 3′ non-translating region. It acts as a sponge adsorbing miRNAs and ensures their separation from their targets and inhibits their function. The present study designed a sponge plasmid against miRNA-10b and transiently transfected it into high and low metastatic human breast cancer cell lines MDA-MB-231 and MCF-7, and analyzed the effects of the miRNA-10b sponge on the growth and proliferation, migration and invasion in these cell lines. qRT-PCR results found that the sponge plasmid effectively inhibited the expression of miRNA-10b, and upregulated the expression of the miRNA-10b target protein HOXD-10. The results from the CCK-8 assay found that the miRNA-10b sponge inhibited the growth of breast cancer cell lines MDA-MB-231 and MCF-7. Results of the plate cloning experiments indicated that the miRNA-10b sponge suppressed the colony formation of the MDA-MB-231 and MCF-7 cells. The results of wound healing and Transwell assays showed that the miRNA-10b sponge inhibited the migration and invasion of the breast cancer cell lines MDA-MB-231 and MCF-7. Our results demonstrated that the miRNA-10b sponge effectively inhibited the growth and proliferation of breast cancer MDA-MB-231 and MCF-7 cells. In addition, it also restrained the migration and invasion of human highly metastatic breast cancer MDA-MB-231 cells. PMID:26820121

  6. MiRNA-10b sponge: An anti-breast cancer study in vitro.

    PubMed

    Liang, Ai-Ling; Zhang, Ting-Ting; Zhou, Ning; Wu, Cui Yun; Lin, Man-Hua; Liu, Yong-Jun

    2016-04-01

    Breast cancer is a malignant tumor with the highest incidence among women. Breast cancer metastasis is the major cause of treatment failure and mortality among such patients. MicroRNAs (miRNAs) are a class of small molecular non-coding regulatory RNAs, which act as oncogenes or tumor suppressors in breast cancer. miRNA-10b has been found to exhibit a high expression level in advanced and metastatic breast cancer, and is closely related to breast cancer metastasis. An miRNA sponge is an mRNA with several repeated sequences of complete or incomplete complementarity to the natural miRNA in its 3' non-translating region. It acts as a sponge adsorbing miRNAs and ensures their separation from their targets and inhibits their function. The present study designed a sponge plasmid against miRNA-10b and transiently transfected it into high and low metastatic human breast cancer cell lines MDA-MB-231 and MCF-7, and analyzed the effects of the miRNA-10b sponge on the growth and proliferation, migration and invasion in these cell lines. qRT-PCR results found that the sponge plasmid effectively inhibited the expression of miRNA-10b, and upregulated the expression of the miRNA‑10b target protein HOXD-10. The results from the CCK-8 assay found that the miRNA-10b sponge inhibited the growth of breast cancer cell lines MDA-MB-231 and MCF-7. Results of the plate cloning experiments indicated that the miRNA-10b sponge suppressed the colony formation of the MDA-MB-231 and MCF-7 cells. The results of wound healing and Transwell assays showed that the miRNA-10b sponge inhibited the migration and invasion of the breast cancer cell lines MDA-MB-231 and MCF-7. Our results demonstrated that the miRNA-10b sponge effectively inhibited the growth and proliferation of breast cancer MDA-MB-231 and MCF-7 cells. In addition, it also restrained the migration and invasion of human highly metastatic breast cancer MDA-MB-231 cells.

  7. Data for the neutron interactions with /sup 6/Li and /sup 10/B

    SciTech Connect

    Poenitz, W.P.

    1984-01-01

    The /sup 10/B(n,..cap alpha..), /sup 10/B(n,..cap alpha../sub 1/) and, increasingly in more recent measurement, the /sup 6/Li(n,..cap alpha..) cross sections are the major references used in low energy experiments. Many data from modern measurements are available for the neutron interaction with /sup 6/Li, including total, scattering, and absolute and relative (n,..cap alpha..) cross sections. A consensus has been reached with these new /sup 6/Li + n data. In contrast, the data base for the /sup 10/B neutron interaction cross sections is unfortunately poor. This is even the case for the total cross section which is supposed to be the easiest quantity to be measured. The most serious deficiency is the absence of data from absolute measurements of the /sup 10/B(n,..cap alpha..) and /sup 10/B(n,..cap alpha../sub 1/) cross sections in the last 10 to 15 years. The available cross section data which were used for the ENDF/B-VI evaluation will be discussed. 43 references.

  8. Natural Analogue Synthesis Report

    SciTech Connect

    A. M. Simmons

    2002-05-01

    The purpose of this report is to present analogue studies and literature reviews designed to provide qualitative and quantitative information to test and provide added confidence in process models abstracted for performance assessment (PA) and model predictions pertinent to PA. This report provides updates to studies presented in the ''Yucca Mountain Site Description'' (CRWMS M and O 2000 [151945], Section 13) and new examples gleaned from the literature, along with results of quantitative studies conducted specifically for the Yucca Mountain Site Characterization Project (YMP). The intent of the natural analogue studies was to collect corroborative evidence from analogues to demonstrate additional understanding of processes expected to occur during postclosure at a potential Yucca Mountain repository. The report focuses on key processes by providing observations and analyses of natural and anthropogenic (human-induced) systems to improve understanding and confidence in the operation of these processes under conditions similar to those that could occur in a nuclear waste repository. The process models include those that represent both engineered and natural barrier processes. A second purpose of this report is to document the various applications of natural analogues to geologic repository programs, focusing primarily on the way analogues have been used by the YMP. This report is limited to providing support for PA in a confirmatory manner and to providing corroborative inputs for process modeling activities. Section 1.7 discusses additional limitations of this report. Key topics for this report are analogues to emplacement drift degradation, waste form degradation, waste package degradation, degradation of other materials proposed for the engineered barrier, seepage into drifts, radionuclide flow and transport in the unsaturated zone (UZ), analogues to coupled thermal-hydrologic-mechanical-chemical processes, saturated zone (SZ) transport, impact of radionuclide

  9. AP1- and NF-kappaB-binding sites conserved among mammalian WNT10B orthologs elucidate the TNFalpha-WNT10B signaling loop implicated in carcinogenesis and adipogenesis.

    PubMed

    Katoh, Masuko; Katoh, Masaru

    2007-04-01

    WNT signals are context-dependently transduced to canonical and non-canonical signaling cascades. We cloned and characterized wild-type human WNT10B, while another group cloned aberrant human WNT10B with Gly60Asp amino-acid substitution. Proto-oncogene WNT10B is expressed in gastric cancer, pancreatic cancer, breast cancer, esophageal cancer, and cervical cancer. Because WNT10B blocks adipocyte differentiation, coding SNP of WNT10B gene is associated with familial obesity. In 2001, we reported WNT10B upregulation by TNFalpha. Here, comparative integromics analyses on WNT10B orthologs were performed to elucidate the transcriptional mechanism of WNT10B. Chimpanzee WNT10B and cow Wnt10b genes were identified within NW_001223159.1 and AC150975.2 genome sequences, respectively, by using bioinformatics (Techint) and human intelligence (Humint). Chimpanzee WNT10B and cow Wnt10b showed 98.7% and 95.1% total-amino-acid identity with human WNT10B, respectively. N-terminal signal peptide, 24 Cys residues, two Asn-linked glycosylation sites, and Gly60 of human WNT10B were conserved among mammalian WNT10B orthologs. Transcription start site of human WNT10B gene was 106-bp upstream of NM_003394.2 RefSeq 5'-end. Number of GC di-nucleotide repeats just down-stream of WNT10B transcription start site varied among primates and human population. Comparative genomics analyses revealed that double AP1-binding sites in the 5'-flanking promoter region and NF-kappaB-binding site in intron 3 were conserved among human, chimpanzee, cow, mouse, and rat WNT10B orthologs. Because TNFalpha signaling through TNFR1 and TRADD/RIP/TRAF2 complex activates JUN kinase (JNK) and IkappaB kinase (IKK) signaling cascades, conserved AP1- and NF-kappaB-binding sites explain the mechanism of TNFalpha-induced WNT10B upregulation. TNFalpha-WNT10B signaling loop is the negative feedback mechanism of adipogenesis to prevent obesity and metabolic syndrome. On the other hand, TNFalpha-WNT10B signaling loop is

  10. Wnt-10b, uniquely among Wnts, promotes epithelial differentiation and shaft growth

    SciTech Connect

    Ouji, Yukiteru Yoshikawa, Masahide; Moriya, Kei; Nishiofuku, Mariko; Matsuda, Ryosuke; Ishizaka, Shigeaki

    2008-03-07

    Although Wnts are expressed in hair follicles throughout life from embryo to adult, and considered to be critical for their development and maturation, their roles remain largely unknown. In the present study, we investigated the effects of Wnts (Wnt-3a, Wnt-5a, Wnt-10b, and Wnt-11) on epithelial cell differentiation using adult mouse-derived primary skin epithelial cell (MPSEC) cultures and hair growth using hair follicle organ cultures. Only Wnt-10b showed evident promotion of epithelial cell differentiation and hair shaft growth, in contrast to Wnt-3a, 5a, and 11. Our results suggest that Wnt-10b is unique and plays an important role in differentiation of epithelial cells in the hair follicle.

  11. Analysis of 10B by PIGE with factor analytical gamma-ray peak identification.

    PubMed

    Savolainen, S; Räisänen, J; Eteläniemi, V; Abo Ramadan, U A; Kallio, M

    1995-09-01

    Studying the biodistribution of boronated compounds for B neutron capture therapy (BNCT) requires the accurate detection of low levels of boron (10B) in biological samples. Proton induced gamma-ray emission analysis (PIGE) of 10B was found to be viable in a study of low density lipoprotein (LDL), in tissue and blood samples. However, the method is sensitive to Na present in the samples and can therefore not be used for accurate measurements of 10B concentrations below 5 ppm in samples containing Na. PIGE can be considered to be an appropriate reference method for chemical B analysis. The factor analytical method presented here is the most objective way to separate Na and B peaks from each other, and the factorizing method can be applied in different forms of spectral analysis.

  12. Modulating hair follicle size with Wnt10b-DKK1 pair during hair regeneration

    PubMed Central

    Lei, Mingxing; Guo, Haiying; Qiu, Weiming; Lai, Xiangdong; Yang, Tian; Widelitz, Randall B.; Chuong, Cheng-Ming; Lian, Xiaohua; Yang, Li

    2015-01-01

    Hair follicles have characteristic sizes corresponding to their cycle specific stage. However, how the anagen hair follicle specifies its size remains elusive. Here, we show that in response to prolonged ectopic Wnt10b-mediated β-catenin activation, regenerating anagen hair follicles grow larger in size. In particular, the hair bulb, dermal papilla and hair shaft become enlarged. While the formation of different hair types (Guard, Awl, Auchene, and Zigzag) is unaffected. Interestingly, we found the effect of exogenous WNT10b was mainly on Zigzag and less on the other kinds of hairs. We observed dramatically enhanced proliferation within the matrix, DP and hair shaft of the enlarged AdWnt10b-treated hair follicles compared with those of normal hair follicles at P98. Furthermore, expression of CD34, a specific hair stem cell marker, was increased in its number to the bulge region after AdWnt10b treatment. Ectopic expression of CD34 throughout the ORS region was also observed. Many CD34 positive hair stem cells were actively proliferating in AdWnt10b-induced hair follicles. Importantly, subsequent co-treatment with the Wnt inhibitor, DKK1, reduced hair follicle enlargement, decreased proliferation and maintained proper hair stem cell localization. Moreover, injection of DKK1 during early anagen significantly reduced the width of prospective hairs. Together, these findings strongly suggest that a balance of Wnt10b/DKK1 governs reciprocal signaling between cutaneous epithelium and mesenchyme to regulate proper hair follicle size. PMID:24750467

  13. Low energy measurements of the 10B(p ,α )7Be reaction

    NASA Astrophysics Data System (ADS)

    Wiescher, M.; deBoer, R. J.; Görres, J.; Azuma, R. E.

    2017-04-01

    Background: The 11B(p,2 α ) 4He reaction is being discussed as a prime candidate for advanced aneutronic fusion fuel systems. Particular interest in this reaction has recently emerged for laser driven plasma systems for energy generation and jet-propulsion systems. The lack of long-lived radioactive reaction products has been suggested as the main advantage of proton-boron fusion fuel. However, 19% of natural boron is 10B, with the 10B(p ,α )7Be fusion reaction producing long-lived 7Be as a side product. Purpose: A detailed measurement of the 10B(p ,α )7Be reaction over the critical energy range of hot fusion plasma environments will help to determine the amount of 7Be radioactivity being produced. This information can be used in turn to monitor the actual fusion temperature by offline measurement of the extracted 7Be activity. The goal of the here presented experiment is to expand on the results of earlier experiments, covering a wider energy range of interest for aneutronic plasma fusion applications, including also both 10B(p ,α0)7Be and the 10B(p ,α1)7Be reaction channels. Method: The reaction cross section was measured over a wide energy range from Ep=400 to 1000 keV using particle detection and from Ep=80 to 1440 keV using γ -ray spectroscopic techniques. Reaction α particles were measured at different angles to obtain angular distribution information. The results are discussed in terms of an R -matrix analysis. Results: The cross section data cover a wider energy range than previously investigated and bridge a gap in the previously available data sets. The cross sections show good agreement with previous results in the low energy region and show that the 10B(p ,α0)7Be channel is considerably larger than that of the 10B(p ,α1)7Be channel up to Ep≈1 MeV . Conclusions: The new reaction data provides important new information about the reaction cross section over the entire energy range of plasma fusion facilities. This data, when coupled with

  14. 17 CFR 240.10b-3 - Employment of manipulative and deceptive devices by brokers or dealers.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... deceptive devices by brokers or dealers. 240.10b-3 Section 240.10b-3 Commodity and Securities Exchanges... Rules and Regulations Under the Securities Exchange Act of 1934 Manipulative and Deceptive Devices and Contrivances § 240.10b-3 Employment of manipulative and deceptive devices by brokers or dealers. (a) It...

  15. 17 CFR 240.10b-3 - Employment of manipulative and deceptive devices by brokers or dealers.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... deceptive devices by brokers or dealers. 240.10b-3 Section 240.10b-3 Commodity and Securities Exchanges... Rules and Regulations Under the Securities Exchange Act of 1934 Manipulative and Deceptive Devices and Contrivances § 240.10b-3 Employment of manipulative and deceptive devices by brokers or dealers. (a) It...

  16. 17 CFR 240.10b-3 - Employment of manipulative and deceptive devices by brokers or dealers.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... deceptive devices by brokers or dealers. 240.10b-3 Section 240.10b-3 Commodity and Securities Exchanges... Rules and Regulations Under the Securities Exchange Act of 1934 Manipulative and Deceptive Devices and Contrivances § 240.10b-3 Employment of manipulative and deceptive devices by brokers or dealers. (a) It...

  17. 17 CFR 240.10b-3 - Employment of manipulative and deceptive devices by brokers or dealers.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... deceptive devices by brokers or dealers. 240.10b-3 Section 240.10b-3 Commodity and Securities Exchanges... Rules and Regulations Under the Securities Exchange Act of 1934 Manipulative and Deceptive Devices and Contrivances § 240.10b-3 Employment of manipulative and deceptive devices by brokers or dealers. (a) It...

  18. 17 CFR 240.10b-3 - Employment of manipulative and deceptive devices by brokers or dealers.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... deceptive devices by brokers or dealers. 240.10b-3 Section 240.10b-3 Commodity and Securities Exchanges... Rules and Regulations Under the Securities Exchange Act of 1934 Manipulative and Deceptive Devices and Contrivances § 240.10b-3 Employment of manipulative and deceptive devices by brokers or dealers. (a) It...

  19. 33 CFR 157.10b - Segregated ballast tanks, dedicated clean ballast tanks, and special ballast arrangements for...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Continental Shelf oil. (a) Each tank vessel that is engaged in the transfer of crude oil from an offshore oil... Continental Shelf oil. 157.10b Section 157.10b Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF... VESSELS CARRYING OIL IN BULK Design, Equipment, and Installation § 157.10b Segregated ballast...

  20. 33 CFR 157.10b - Segregated ballast tanks, dedicated clean ballast tanks, and special ballast arrangements for...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Continental Shelf oil. (a) Each tank vessel that is engaged in the transfer of crude oil from an offshore oil... Continental Shelf oil. 157.10b Section 157.10b Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF... VESSELS CARRYING OIL IN BULK Design, Equipment, and Installation § 157.10b Segregated ballast...

  1. 33 CFR 157.10b - Segregated ballast tanks, dedicated clean ballast tanks, and special ballast arrangements for...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ..., dedicated clean ballast tanks, and special ballast arrangements for tank vessels transporting Outer Continental Shelf oil. 157.10b Section 157.10b Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF... VESSELS CARRYING OIL IN BULK Design, Equipment, and Installation § 157.10b Segregated ballast tanks...

  2. 33 CFR 157.10b - Segregated ballast tanks, dedicated clean ballast tanks, and special ballast arrangements for...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ..., dedicated clean ballast tanks, and special ballast arrangements for tank vessels transporting Outer Continental Shelf oil. 157.10b Section 157.10b Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF... VESSELS CARRYING OIL IN BULK Design, Equipment, and Installation § 157.10b Segregated ballast tanks...

  3. The multidomain xylanase Xyn10B as a cellulose-binding protein in Clostridium stercorarium.

    PubMed

    Ali, M K; Kimura, T; Sakka, K; Ohmiya, K

    2001-04-20

    The cells of Clostridium stercorarium F-9 grown on cellobiose bound to insoluble cellulose allomorphs such as phosphoric acid-swollen cellulose (ASC). Treatment of the cells with 3 M guanidine hydrochloride extracted surface-layer proteins from the cells and abolished the affinity of the cells for ASC. SDS-polyacrylamide gel electrophoresis, zymogram, and immunological analyses indicated that one of the major surface layer proteins was Xyn10B, which is a modular xylanase comprising two family 22 carbohydrate-binding modules (CBMs), a family 10 catalytic domain of glycosyl hydrolases, a family 9 CBM, and two S-layer homologous (SLH) domains. The C. stercorarium F-9 cells treated with guanidine hydrochloride coprecipitated with ASC upon the addition of a derivative of Xyn10B containing both a CBM and SLH domain in addition to a catalytic domain, but not a derivative without Xyn10B-SLH domains, suggesting that Xyn10B functioned as a cellulose-binding protein in C. stercorarium F-9.

  4. 17 CFR 240.10b-17 - Untimely announcements of record dates.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... Under the Securities Exchange Act of 1934 Manipulative and Deceptive Devices and Contrivances § 240.10b-17 Untimely announcements of record dates. (a) It shall constitute a “manipulative or deceptive... manipulative or deceptive device or contrivance comprehended within the purpose of this section; or (3)...

  5. 17 CFR 240.10b-17 - Untimely announcements of record dates.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... Under the Securities Exchange Act of 1934 Manipulative and Deceptive Devices and Contrivances § 240.10b-17 Untimely announcements of record dates. (a) It shall constitute a “manipulative or deceptive... manipulative or deceptive device or contrivance comprehended within the purpose of this section; or (3)...

  6. 17 CFR 240.10b-17 - Untimely announcements of record dates.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... Under the Securities Exchange Act of 1934 Manipulative and Deceptive Devices and Contrivances § 240.10b-17 Untimely announcements of record dates. (a) It shall constitute a “manipulative or deceptive... manipulative or deceptive device or contrivance comprehended within the purpose of this section; or (3)...

  7. 17 CFR 240.10b-17 - Untimely announcements of record dates.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Under the Securities Exchange Act of 1934 Manipulative and Deceptive Devices and Contrivances § 240.10b-17 Untimely announcements of record dates. (a) It shall constitute a “manipulative or deceptive... manipulative or deceptive device or contrivance comprehended within the purpose of this section; or (3)...

  8. 17 CFR 240.10b-17 - Untimely announcements of record dates.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... Under the Securities Exchange Act of 1934 Manipulative and Deceptive Devices and Contrivances § 240.10b-17 Untimely announcements of record dates. (a) It shall constitute a “manipulative or deceptive... manipulative or deceptive device or contrivance comprehended within the purpose of this section; or (3)...

  9. Aspartame and Its Analogues

    NASA Astrophysics Data System (ADS)

    Pavlova, L. A.; Komarova, T. V.; Davidovich, Yurii A.; Rogozhin, S. V.

    1981-04-01

    The results of studies on the biochemistry of the sweet taste are briefly reviewed. The methods of synthesis of "aspartame" — a sweet dipeptide — are considered, its structural analogues are described, and quantitative estimates are made of the degree of sweetness relative to sucrose. Attention is concentrated mainly on problems of the relation between the structure of the substance and its taste in the series of aspartyl derivatives. The bibliography includes 118 references.

  10. Germananes: Germanium Graphane Analogues

    NASA Astrophysics Data System (ADS)

    Goldberger, Joshua

    2014-03-01

    Graphene's success has shown that it is not only possible to create stable, single-atom thick sheets from a crystalline solid, but that these materials have fundamentally different properties than the parent material. Our interest focuses on the synthesis and properties of Group IV graphane analogues. We have synthesized for the first time, mm-scale crystals of a hydrogen-terminated germanium multilayered graphane analogue (germanane, GeH) from the topochemical deintercalation of CaGe2. This layered van der Waals solid is analogous to multilayered graphane. The surface layer of GeH only slowly oxidizes in air over the span of five months, while the underlying layers are resilient to oxidation. We demonstrate that it is possible to covalently terminate the external surface with organic substituents to tune the electronic structure, and enhance the stability. These materials represent a new class of covalently terminated graphane analogues having great potential for a wide range of optoelectronic and sensing applications, especially since theory predicts a direct band gap of 1.53 eV and an electron mobility of 18,000 cm2/Vs which is five times higher than that of bulk Ge.

  11. Quantum analogue computing.

    PubMed

    Kendon, Vivien M; Nemoto, Kae; Munro, William J

    2010-08-13

    We briefly review what a quantum computer is, what it promises to do for us and why it is so hard to build one. Among the first applications anticipated to bear fruit is the quantum simulation of quantum systems. While most quantum computation is an extension of classical digital computation, quantum simulation differs fundamentally in how the data are encoded in the quantum computer. To perform a quantum simulation, the Hilbert space of the system to be simulated is mapped directly onto the Hilbert space of the (logical) qubits in the quantum computer. This type of direct correspondence is how data are encoded in a classical analogue computer. There is no binary encoding, and increasing precision becomes exponentially costly: an extra bit of precision doubles the size of the computer. This has important consequences for both the precision and error-correction requirements of quantum simulation, and significant open questions remain about its practicality. It also means that the quantum version of analogue computers, continuous-variable quantum computers, becomes an equally efficient architecture for quantum simulation. Lessons from past use of classical analogue computers can help us to build better quantum simulators in future.

  12. Preparation and characterization of (10)B boric acid with high purity for nuclear industry.

    PubMed

    Zhang, Weijiang; Liu, Tianyu; Xu, Jiao

    2016-01-01

    Boric acid is often added into coolant as neutron capture agent for pressurized water reactor, whose amount is influenced by its abundance and purity. Therefore, the preparation of enriched (10)B boric acid with high purity is beneficial to nuclear industry. (10)B is also used in developing tumor-specific boronated drugs in boron neutron capture therapy. The boronated drug can be administered to patient intravenously, intratumorally, or deposited at tumor site in surgical excision. Thus, enriched (10)B boric acid is of practical significance in the field of medicine. Self-made boron trifluoride-methanol-complex solution was selected as one of the experimental reagents, and the preparation of (10)B acid was realized by one-step reaction for the complexes with water and calcium chloride. The determination of electrical conductivity in reaction process proves that the optimum reaction time was 16-20 h. Furthermore, the effect of reaction time, ratio of calcium chloride to complex as well as the amount of water on the purity and yield of boric acid was investigated. Finally, the optimum reaction time was 20 h, the optimal solid-liquid ratio (molar ratio) was 3:1, and the amount of water was 1 L of deionized water for each mol of the complex. H2O2 was added in the reaction process to remove Fe(2+). After recrystallization, IR spectra of (10)B boric acid was measured and compared with standard to verify the product of boric acid. The feasibility of the preparation method was determined by the detection of XRD of boric acid. To observe the morphology by polarizing microscope, crystal structure was obtained. The purity of the final product is 99.95 %, and the yield is 96.47 %. The ion concentration of boric acid accords with the national standard of high purity, which was determined by ICP.

  13. Concentrations and profiles of bisphenol A and other bisphenol analogues in foodstuffs from the United States and their implications for human exposure.

    PubMed

    Liao, Chunyang; Kannan, Kurunthachalam

    2013-05-15

    As the concern over the safety of bisphenol A (BPA) continues to grow, this compound is gradually being replaced, in industrial applications, with compounds such as bisphenol F (BPF) and bisphenol S (BPS). Occurrence of bisphenols, including BPA and BPS, has been reported in paper products and in environmental matrices. Information on the occurrence of bisphenols, other than BPA, in foodstuffs, however, is scarce. In this study, several bisphenol analogues, including BPA, BPF, and BPS, were analyzed in foodstuffs (N = 267) collected from Albany, NY, USA, using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Foodstuffs were divided into nine categories of beverages, dairy products, fats and oils, fish and seafood, cereals, meat and meat products, fruits, vegetables, and "others". Bisphenols were found in the majority (75%) of the food samples, and the total concentrations of bisphenols (ΣBPs: sum of eight bisphenols) were in the range of below the limit of quantification (LOQ) to 1130 ng/g fresh weight, with an overall mean value of 4.38 ng/g. The highest overall mean concentration of ΣBPs was found in the "others" category, which included condiments (preserved, ready-to-serve foods). A sample of mustard (dressing) and ginger, placed in the category of vegetables, contained the highest concentrations of 1130 ng/g for bisphenol F (BPF) and 237 ng/g for bisphenol P (BPP). Concentrations of BPs in beverages (mean = 0.341 ng/g) and fruits (0.698 ng/g) were low. The predominant bisphenol analogues found in foodstuffs were BPA and BPF, which accounted for 42 and 17% of the total BP concentrations, respectively. Canned foods contained higher concentrations of individual and total bisphenols in comparison to foods sold in glass, paper, or plastic containers. On the basis of measured concentrations and daily ingestion rates of foods, the daily dietary intakes of bisphenols (calculated from the mean concentration) were estimated to be 243, 142

  14. Fission products measured from highly-enriched uranium irradiated under 10B4C in a research reactor

    SciTech Connect

    Metz, Lori A.; Friese, Judah I.; Finn, Erin C.; Greenwood, Lawrence R.; Hines, Corey C.; King, Matthew D.; Wall, Donald E.

    2016-03-01

    Critical assemblies provide one method of achieving a fast neutron spectrum that is close to a 235U fission-energy neutron spectrum for nuclear data measurements. Previous work has demonstrated the use of a natural boron carbide capsule for spectral-tailoring in a mixed spectrum reactor as an alternate and complementary method for performing fission-energy neutron experiments. Previous fission products measurements showed that the neutron spectrum achievable with natural boron carbide was not as hard as what can be achieved with critical assemblies. New measurements performed with the Washington State University TRIGA reactor using a boron carbide capsule 96% enriched in 10B for irradiations resulted in a neutron spectrum very similar to a critical assembly and a pure 235U fission spectrum. The current work describes an experiment involving a highly-enriched uranium target irradiated under the new 10B4C capsule. Fission product yields were measured following radiochemical separations and are presented here. Reactor dosimetry measurements for characterizing neutron spectra and fluence for the enriched boron carbide capsule and critical assemblies are also discussed.

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

    PubMed

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

    2011-11-18

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

  16. WNT10B functional dualism: beta-catenin/Tcf-dependent growth promotion or independent suppression with deregulated expression in cancer.

    PubMed

    Yoshikawa, Hirohide; Matsubara, Kenichi; Zhou, Xiaoling; Okamura, Shu; Kubo, Takahiko; Murase, Yaeko; Shikauchi, Yuko; Esteller, Manel; Herman, James G; Wei Wang, Xin; Harris, Curtis C

    2007-11-01

    We found aberrant DNA methylation of the WNT10B promoter region in 46% of primary hepatocellular carcinoma (HCC) and 15% of colon cancer samples. Three of 10 HCC and one of two colon cancer cell lines demonstrated low or no expression, and 5-aza-2'deoxycytidine reactivated WNT10B expression with the induction of demethylation, indicating that WNT10B is silenced by DNA methylation in some cancers, whereas WNT10B expression is up-regulated in seven of the 10 HCC cell lines and a colon cancer cell line. These results indicate that WNT10B can be deregulated by either overexpression or silencing in cancer. We found that WNT10B up-regulated beta-catenin/Tcf activity. However, WNT10B-overexpressing cells demonstrated a reduced growth rate and anchorage-independent growth that is independent of the beta-catenin/Tcf activation, because mutant beta-catenin-transduced cells did not suppress growth, and dominant-negative hTcf-4 failed to alleviate the growth suppression by WNT10B. Although WNT10B expression alone inhibits cell growth, it acts synergistically with the fibroblast growth factor (FGF) to stimulate cell growth. WNT10B is bifunctional, one function of which is involved in beta-catenin/Tcf activation, and the other function is related to the down-regulation of cell growth through a different mechanism. We suggest that FGF switches WNT10B from a negative to a positive cell growth regulator.

  17. Fully analogue photonic reservoir computer.

    PubMed

    Duport, François; Smerieri, Anteo; Akrout, Akram; Haelterman, Marc; Massar, Serge

    2016-03-03

    Introduced a decade ago, reservoir computing is an efficient approach for signal processing. State of the art capabilities have already been demonstrated with both computer simulations and physical implementations. If photonic reservoir computing appears to be promising a solution for ultrafast nontrivial computing, all the implementations presented up to now require digital pre or post processing, which prevents them from exploiting their full potential, in particular in terms of processing speed. We address here the possibility to get rid simultaneously of both digital pre and post processing. The standalone fully analogue reservoir computer resulting from our endeavour is compared to previous experiments and only exhibits rather limited degradation of performances. Our experiment constitutes a proof of concept for standalone physical reservoir computers.

  18. Fully analogue photonic reservoir computer

    PubMed Central

    Duport, François; Smerieri, Anteo; Akrout, Akram; Haelterman, Marc; Massar, Serge

    2016-01-01

    Introduced a decade ago, reservoir computing is an efficient approach for signal processing. State of the art capabilities have already been demonstrated with both computer simulations and physical implementations. If photonic reservoir computing appears to be promising a solution for ultrafast nontrivial computing, all the implementations presented up to now require digital pre or post processing, which prevents them from exploiting their full potential, in particular in terms of processing speed. We address here the possibility to get rid simultaneously of both digital pre and post processing. The standalone fully analogue reservoir computer resulting from our endeavour is compared to previous experiments and only exhibits rather limited degradation of performances. Our experiment constitutes a proof of concept for standalone physical reservoir computers. PMID:26935166

  19. Selective radiography of 10B distribution in organs using cold and thermal neutron beams.

    PubMed

    Skvarc, Jure; Giacomelli, Marko; Yanagië, Hironobu; Kühne, Guido

    2002-01-01

    The investigation of boron biodistribution by neutron induced autoradiography was performed using a CR-39 etched track detector. Calibration samples, made of boronated chicken liver, and freeze-dried mouse tissue samples were irradiated both with thermal and cold neutrons. Digital images were made on the basis of track densities, with the selection of tracks due to 10B(n, alpha)7Li reaction. A comparison of results obtained both with thermal and cold neutrons demonstrated that it is possible to obtain equivalent results with both neutron sources, although the background noise due to recoil protons from the fast neutrons of the thermal neutron source is 15 % higher than that of the cold neutron source. 10B concentrations in the range of 0.5 ppm to 150 ppm were determined, with a standard deviation of 13 % and 8 % for the mouse tissue samples and calibration samples, respectively.

  20. Fast isotopic separation of (10) B and (11) B boric acid by capillary zone electrophoresis.

    PubMed

    Kamencev, Mikhail; Yakimova, Nina; Moskvin, Leonid; Kuchumova, Irina; Tkach, Kirill; Malinina, Yulia

    2016-11-01

    Fast isotopic separation of (10) B and (11) B boric acid by CZE was demonstrated. The BGE contained 25 mM phenylalanine and 5 mM putrescine (рН 8.95). The running conditions were +25 kV at 20°C with indirect photometric detection at 210 nm. Baseline separation was achieved in less than 9 min. RSD of migration times and corrected peak areas were less than 0.5 and 3%, respectively (n = 5). Linearity was demonstrated in the range 0.2-2 mM for (11) B and 0.2-0.5 mM for (10) B. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Characterization of a 10B-doped liquid scintillator as a capture-gated neutron spectrometer

    NASA Astrophysics Data System (ADS)

    Hunt, S.; Iliadis, C.; Longland, R.

    2016-03-01

    We use a 250 MHz digitizer to characterize the pulse shape discrimination of a BC-523A 10B-doped liquid scintillator with capture-gating capabilities. Our results are compared to recent work claiming pulse shape discrimination between fast and thermal neutron signals. The capture event is identified, and we explain the origin of signals that are often misinterpreted. We use the time-of-flight method to measure the detector energy resolution for fast incident monoenergetic neutrons and the intrinsic neutron detection efficiency. Monte Carlo simulations are performed and we find agreement between measured and simulated results. These steps are important for understanding 10B-doped capture-gated spectroscopy in mixed radiation environments, as efficiencies using capture-gating are rarely reported in the literature.

  2. Study of the 10B ( p ,α)7Be reaction through the indirect Trojan Horse method

    NASA Astrophysics Data System (ADS)

    Puglia, S. M. R.; Spitaleri, C.; Lamia, L.; Romano, S.; Burjan, V.; Carlin, N.; Chengbo, L.; Del Santo, M. G.; Kroha, V.; Hons, Z.; Irgaziev, B.; La Cognata, M.; Mrazek, J.; Mukhamedzhanov, A.; Munhoz, M. G.; Pizzone, R. G.; Qungang, W.; Rapisarda, G. G.; Shu-Hua, Z.; Sergi, M. L.; Somoryai, E.; Souza, F.; Szanto de Toledo, A.; Tabacaru, G.; Tumino, A.; Wakabayashi, Y.; Yamaguchi, H.

    2015-02-01

    Boron abundances in stellar atmospheres, as well as berillium and lithium ones, can give useful hints for non-standard transport processes discrimination in stars. They can also be relevant for understanding several astrophysical processes (e.g. primordial nucleosynthesis and spallation reactions in ISM). A comprehensive study of Li Be B abundances can therefore confirm or not the presence of non-standard mixing processes in stellar envelopes. For this reason nuclear processes producing or depleting boron isotope abundance need to be studied at astrophysical energies. The 10B ( p ,α)7Be reaction has been studied by means of the Trojan Horse Method. The Trojan Horse Method was thus applied to the 10B ( d ,α7Be ) n reaction, studied at 24 MeV. The obtained results will be discussed.

  3. Association Analysis of WNT10B With Bone Mass and Structure Among Individuals of African Ancestry

    PubMed Central

    Zmuda, Joseph M; Yerges, Laura M; Kammerer, Candace M; Cauley, Jane A; Wang, Xiaojing; Nestlerode, Cara S; Wheeler, Victor W; Patrick, Alan L; Bunker, ClareAnn H; Moffett, Susan P; Ferrell, Robert E

    2009-01-01

    Wnts comprise a family of secreted growth factors that regulate the development and maintenance of many organs. Recently, Wnt10b was shown to stimulate osteoblastogenesis and bone formation in mice. To evaluate further the role of Wnt10b in bone health in humans, we performed bidirectional sequencing of ∼8 kb of the WNT10B gene region in 192 individuals (96 African, 96 white) to identify single nucleotide polymorphisms (SNPs). We identified 19 SNPs with minor allele frequency (MAF) ≥0.01. Ten of these SNPs were not present in the NCBI dbSNP database (build 127), whereas 10 of the 20 SNPs (50%) reported in dbSNP were not verified. We initially genotyped seven tagging SNPs that captured common (MAF ≥ 0.05) variation in the region with r 2 > 0.80 and a potentially functional SNP in exon 5 in 1035 Afro-Caribbean men ≥40 yr of age. Association analysis showed three SNPs in a 3′ region of linkage disequilibrium that were associated with DXA measures of hip BMD. Associations between two of these three SNPs (rs1051886, rs3741627) with hip BMD were replicated in an additional 980 Afro-Caribbean men (p < 0.05), in the combined sample of 2015 men (p ≤ 0.006), and in 416 individuals ≥18 yr of age (mean, 44 yr) belonging to eight extended, multigenerational Afro-Caribbean families with mean family size >50 (3535 relative pairs; p < 0.05). Further analysis showed that rs1051886 and rs3741627 were associated with cortical cross-sectional area, periosteal circumference, and BMC in the radius, such that individuals with the minor alleles had lower biomechanical indices of long-bone bending strength. This analysis implicates the WNT10B locus as a genetic element in the regulation of bone mass and structural geometry. PMID:19016593

  4. Heterogeneity of miR-10b expression in circulating tumor cells

    PubMed Central

    Gasch, Christin; Plummer, Prue N.; Jovanovic, Lidija; McInnes, Linda M.; Wescott, David; Saunders, Christobel M.; Schneeweiss, Andreas; Wallwiener, Markus; Nelson, Colleen; Spring, Kevin J.; Riethdorf, Sabine; Thompson, Erik W.; Pantel, Klaus; Mellick, Albert S.

    2015-01-01

    Circulating tumor cells (CTCs) in the blood of cancer patients are recognized as important potential targets for future anticancer therapies. As mediators of metastatic spread, CTCs are also promising to be used as ‘liquid biopsy’ to aid clinical decision-making. Recent work has revealed potentially important genotypic and phenotypic heterogeneity within CTC populations, even within the same patient. MicroRNAs (miRNAs) are key regulators of gene expression and have emerged as potentially important diagnostic markers and targets for anti-cancer therapy. Here, we describe a robust in situ hybridization (ISH) protocol, incorporating the CellSearch® CTC detection system, enabling clinical investigation of important miRNAs, such as miR-10b on a cell by cell basis. We also use this method to demonstrate heterogeneity of such as miR-10b on a cell-by-cell basis. We also use this method to demonstrate heterogeneity of miR-10b in individual CTCs from breast, prostate and colorectal cancer patients. PMID:26522916

  5. Cluster correlation effects in 12C+12C and 14N+10B fusion-evaporation reactions

    NASA Astrophysics Data System (ADS)

    Morelli, L.; Baiocco, G.; D'Agostino, M.; Gulminelli, F.; Bruno, M.; Cinausero, M.; Degerlier, M.; Fabris, D.; Gramegna, F.; Marchi, T.; Barlini, S.; Bini, M.; Casini, G.; Gelli, N.; Olmi, A.; Pasquali, G.; Piantelli, S.; Valdré, S.

    2015-04-01

    The decay of highly excited states of 24Mg is studied in fusion evaporation events completely detected in charge in the reactions 12C+12C and 14N+10B at 95 and 80 MeV incident energy respectively. The comparison of light charged particles measured spectra with statistical model predictions suggests that the dominant reaction mechanism is compound nucleus (CN) formation and decay. However, in both reactions, a discrepancy with statistical expectations is found for α particles detected in coincidence with Carbon, Oxigen and Neon residues. The comparison between the two reactions shows that this discrepancy is only partly explained by an entrance channel effect. Evidence for cluster correlations in excited 24Mg CN is suggested by the comparison between the measured and calculated branching ratios for the channels involving α particles.

  6. Space analogue studies in Antarctica

    NASA Technical Reports Server (NTRS)

    Lugg, D.; Shepanek, M.

    1999-01-01

    Medical research has been carried out on the Australian National Antarctic Research Expeditions (ANARE) for 50 years. As an extension of this program collaborative Australian/United States research on immunology, microbiology, psychology and remote medicine has produced important data and insight on how humans adapt to the stress of extreme isolation, confinement and the harsh environment of Antarctica. An outstanding analogue for the isolation and confinement of space missions (especially planetary outposts), ANARE has been used as an international research platform by Australia and the United States since 1993. Collaborative research has demonstrated a lowered responsiveness of the immune system under the isolation and confinement of Antarctic winter-over; a reduction of almost 50% in T cell proliferation to mitogen phytohaemogglutinin, as well as changes in latent herpesvirus states and the expansion of the polyclonal latent Epstein-Barr virus infected B cell populations. Although no clinically significant disease has been found to result from these immune changes, research is currently assessing the effects of psychological factors on the immune system. This and associated research performed to date and its relevance to both organisations is discussed, and comment made on possible extensions to the program in both medical and other fields.

  7. Space analogue studies in Antarctica.

    PubMed

    Lugg, D; Shepanek, M

    1999-01-01

    Medical research has been carried out on the Australian National Antarctic Research Expeditions (ANARE) for 50 years. As an extension of this program collaborative Australian/United States research on immunology, microbiology, psychology and remote medicine has produced important data and insight on how humans adapt to the stress of extreme isolation, confinement and the harsh environment of Antarctica. An outstanding analogue for the isolation and confinement of space missions (especially planetary outposts), ANARE has been used as an international research platform by Australia and the United States since 1993. Collaborative research has demonstrated a lowered responsiveness of the immune system under the isolation and confinement of Antarctic winter-over; a reduction of almost 50% in T cell proliferation to mitogen phytohaemogglutinin, as well as changes in latent herpesvirus states and the expansion of the polyclonal latent Epstein-Barr virus infected B cell populations. Although no clinically significant disease has been found to result from these immune changes, research is currently assessing the effects of psychological factors on the immune system. This and associated research performed to date and its relevance to both organisations is discussed, and comment made on possible extensions to the program in both medical and other fields.

  8. Space analogue studies in Antarctica

    NASA Technical Reports Server (NTRS)

    Lugg, D.; Shepanek, M.

    1999-01-01

    Medical research has been carried out on the Australian National Antarctic Research Expeditions (ANARE) for 50 years. As an extension of this program collaborative Australian/United States research on immunology, microbiology, psychology and remote medicine has produced important data and insight on how humans adapt to the stress of extreme isolation, confinement and the harsh environment of Antarctica. An outstanding analogue for the isolation and confinement of space missions (especially planetary outposts), ANARE has been used as an international research platform by Australia and the United States since 1993. Collaborative research has demonstrated a lowered responsiveness of the immune system under the isolation and confinement of Antarctic winter-over; a reduction of almost 50% in T cell proliferation to mitogen phytohaemogglutinin, as well as changes in latent herpesvirus states and the expansion of the polyclonal latent Epstein-Barr virus infected B cell populations. Although no clinically significant disease has been found to result from these immune changes, research is currently assessing the effects of psychological factors on the immune system. This and associated research performed to date and its relevance to both organisations is discussed, and comment made on possible extensions to the program in both medical and other fields.

  9. Space analogue studies in Antarctica

    NASA Astrophysics Data System (ADS)

    Lugg, D.; Shepanek, M.

    1999-09-01

    Medical research has been carried out on the Australian National Antarctic Research Expeditions (ANARE) for 50 years. As an extension of this program collaborative Australian/United States research on immunology, microbiology, psychology and remote medicine has produced important data and insight on how humans adapt to the stress of extreme isolation, confinement and the harsh environment of Antarctica. An outstanding analogue for the isolation and confinement of space missions (especially planetary outposts), ANARE has been used as an international research platform by Australia and the United States since 1993. Collaborative research has demonstrated a lowered responsiveness of the immune system under the isolation and confinement of Antarctic winter-over; a reduction of almost 50% in T cell proliferation to mltogen phytohaemogglutinin, as well as changes in latent herpesvirus states and the expansion of the polyclonal latent Epstein-Barr virus infected B cell populations. Although no clinically significant disease has been found to result from these immune changes, research is currently assessing the effects of psychological factors on the immune system. This and associated research performed to date and its relevance to both organisations is discussed, and comment made on possible extensions to the program in both medical and other fields.

  10. Analogue-to-Digital and Digital-to-Analogue Conversion.

    ERIC Educational Resources Information Center

    Gregory, Martin

    1997-01-01

    Discusses circuits for three-bit and four-bit analogue digital converters and digital analogue converters. These circuits feature slow operating speeds that enable the circuitry to be used to demonstrate the mode of operation using oscilloscopes and signal generators. (DDR)

  11. New investigations of the 10B(p,{\\alpha }_{0})7Be reaction at bombarding energies between 0.6 and 1 MeV

    NASA Astrophysics Data System (ADS)

    Lombardo, I.; Dell'Aquila, D.; Conte, F.; Francalanza, L.; La Cognata, M.; Lamia, L.; La Torre, R.; Spadaccini, G.; Spitaleri, C.; Vigilante, M.

    2016-08-01

    We measured the 10B(p,{α }0)7Be reaction in the bombarding energy domain of 0.6-1.0 MeV, a region where very few data (with large uncertainties) have been reported in the literature. Despite the experimental difficulties, due to the unfavourable reaction kinematics and the presence of contaminants in the 10B target, we were able to measure excitation functions at both forward and backward angles thanks to the use of the inverse absorber technique. The obtained angular distributions show a continuous shape evolution, testifying to the contributions of several resonant states in the 11C compound nucleus. An R-matrix analysis of some reaction and scattering channels allows us to refine the spectroscopy of 11C excited states.

  12. Mammary Analogue Secretory Carcinoma.

    PubMed

    Stevens, Todd M; Parekh, Vishwas

    2016-09-01

    Mammary analogue secretory carcinoma (MASC) is a recently described salivary gland tumor that shares the same histologic appearance and ETV6 gene (12p13) rearrangement as secretory carcinoma of the breast. Prior to its recognition, MASC cases were commonly labeled acinic cell carcinoma and adenocarcinoma, not otherwise specified. Despite distinctive histologic features, MASC may be difficult to distinguish from other salivary gland tumors, in particular zymogen-poor acinic cell carcinoma and low-grade salivary duct carcinoma. Although characteristic morphologic and immunohistochemical features form the basis of a diagnosis of MASC, the presence of an ETV6-NTRK3 gene fusion is confirmatory. Given its recent recognition the true prognostic import of MASC is not yet clearly defined.

  13. A novel chalcone-analogue as an optical sensor based on ground and excited states intramolecular charge transfer: A combined experimental and theoretical study

    NASA Astrophysics Data System (ADS)

    Fayed, Tarek A.

    2006-05-01

    Steady-state absorption and emission spectroscopic techniques as well as semiempirical quantum calculations at the AM1 and ZINDO/S levels have been used to investigate the intramolecular charge transfer (ICT) behaviour of a novel chalcone namely; 1-(2-pyridyl)-5-(4-dimethylaminophenyl)-penta-2,4-diene-1-one, DMAC. The ground state DMAC has a significant ICT character and a great sensitivity to the hydrogen bond donating ability of the medium as reflected from the change of the absorption spectra in pure and mixed organic solvents. On the other hand, its excited singlet state exhibits high ICT characters as manifested by the drastic solvatochromic effects. These results are consistent with the data of charge density calculations in both the ground and excited state, which indicates enhancement of the charge transfer from the dimethyl-amino group to the carbonyl oxygen upon excitation. Also, the dipole moment calculations indicates a highly dipolar excited singlet state (Δ μeg = 15.5 D). The solvent dependence of the fluorescence quantum yield of DMAC was interpreted on the basis of positive and negative solvatokinetic as well as the hydrogen bonding effects. Incorporation of the 2-pyridyl group in the chemical structure of the present DMAC led to design of a potential optical sensor for probing acidity of the medium and metal cations such as Zn 2+, Cd 2+ and Hg 2+. This was concluded from the high acidochromic and metallochromic behaviour of DMAC on adding such cations to its acetonitrile solutions.

  14. Characterization of the new NSLS infrared microspectroscopy beamline U10B

    SciTech Connect

    Carr, G.L.

    1999-07-19

    The first of several new infrared beamlines, built on a modified bending magnet port of the NSLS VUV ring, is now operational for mid-infrared microspectroscopy. The port simultaneously delivers 40 mrad by 40 mrad to two separate beamlines and spectrometer endstations designated U10A and U10B. The latter is equipped with a scanning infrared microspectrometer. The combination of this instrument and high brightness synchrotron radiation makes diffraction-limited microspectroscopy practical. This paper describes the beamline's performance and presents quantitative information on the diffraction-limited resolution.

  15. CHARACTERIZATION OF THE NEW NSLS INFARED MICROSPECTROSCOPY BEAMLINE U10B.

    SciTech Connect

    CARR,G.L.

    1999-07-19

    The first of several new infrared beamlines, built on a modified bending magnet port of the NSLS VUV ring, is now operational for mid-infrared microspectroscopy. The port simultaneously delivers 40 mrad by 40 mrad to two separate beamlines and spectrometer endstations designated U10A and U10B. The latter is equipped with a scanning infrared microspectrometer. The combination of this instrument and high brightness synchrotron radiation makes diffraction-limited microspectroscopy practical. This paper describes the beamline's performance and presents quantitative information on the diffraction-limited resolution.

  16. Salt bridges in the hyperthermophilic protein Ssh10b are resilient to temperature increases.

    PubMed

    Ge, Meng; Xia, Xia-Yu; Pan, Xian-Ming

    2008-11-14

    A double mutant cycle (DMC) approach was employed to estimate the effect of temperature on the contribution of two highly conserved salt bridges to protein stability in the hyperthermophilic protein Ssh10b. The coupling free energy were 2.4 +/- 0.4 kJ/mol at 298 K and 2.2 +/- 0.4 kJ/mol at 353 K for Glu-54/Arg-57, and 6.0 +/- 0.2 kJ/mol at 298 K and 5.9 +/- 0.6 kJ/mol at 353 K for Glu-36/Lys-68. The stability free energy of Ssh10b decrease greatly with increasing temperature, while the direct contribution of these two salt bridges to protein stability remain almost constant, providing evidence supporting the theoretical prediction that salt bridges are extremely resilient to temperature increases and thus are specially suited to improving protein stability at high temperatures. The reason for the difference in coupling free energy between salt bridges Glu-54/Arg-57 and Glu-36/Lys-68 is discussed. Comparing our results with published DMC data for the contribution of salt bridges to stability in other proteins, we found that the energy contribution of a salt bridge formed by two charged residues far apart in the primary sequence is higher than that of those formed between two very close ones. Implications of this finding are useful for engineering proteins with enhanced thermostability.

  17. Ultracold neutron detectors based on 10B converters used in the qBounce experiments☆

    PubMed Central

    Jenke, Tobias; Cronenberg, Gunther; Filter, Hanno; Geltenbort, Peter; Klein, Martin; Lauer, Thorsten; Mitsch, Kevin; Saul, Heiko; Seiler, Dominik; Stadler, David; Thalhammer, Martin; Abele, Hartmut

    2013-01-01

    Gravity experiments with very slow, so-called ultracold neutrons connect quantum mechanics with tests of Newton's inverse square law at short distances. These experiments face a low count rate and hence need highly optimized detector concepts. In the frame of this paper, we present low-background ultracold neutron counters and track detectors with micron resolution based on a 10B converter. We discuss the optimization of 10B converter layers, detector design and concepts for read-out electronics focusing on high-efficiency and low-background. We describe modifications of the counters that allow one to detect ultracold neutrons selectively on their spin-orientation. This is required for searches of hypothetical forces with spin–mass couplings. The mentioned experiments utilize a beam-monitoring concept which accounts for variations in the neutron flux that are typical for nuclear research facilities. The converter can also be used for detectors, which feature high efficiencies paired with high spatial resolution of 1–2μm. They allow one to resolve the quantum mechanical wave function of an ultracold neutron bound in the gravity potential above a neutron mirror. PMID:25843998

  18. Ultracold neutron detectors based on (10)B converters used in the qBounce experiments.

    PubMed

    Jenke, Tobias; Cronenberg, Gunther; Filter, Hanno; Geltenbort, Peter; Klein, Martin; Lauer, Thorsten; Mitsch, Kevin; Saul, Heiko; Seiler, Dominik; Stadler, David; Thalhammer, Martin; Abele, Hartmut

    2013-12-21

    Gravity experiments with very slow, so-called ultracold neutrons connect quantum mechanics with tests of Newton's inverse square law at short distances. These experiments face a low count rate and hence need highly optimized detector concepts. In the frame of this paper, we present low-background ultracold neutron counters and track detectors with micron resolution based on a (10)B converter. We discuss the optimization of (10)B converter layers, detector design and concepts for read-out electronics focusing on high-efficiency and low-background. We describe modifications of the counters that allow one to detect ultracold neutrons selectively on their spin-orientation. This is required for searches of hypothetical forces with spin-mass couplings. The mentioned experiments utilize a beam-monitoring concept which accounts for variations in the neutron flux that are typical for nuclear research facilities. The converter can also be used for detectors, which feature high efficiencies paired with high spatial resolution of [Formula: see text]. They allow one to resolve the quantum mechanical wave function of an ultracold neutron bound in the gravity potential above a neutron mirror.

  19. 10B(α,n)13N cross section measurement1

    NASA Astrophysics Data System (ADS)

    Liu, Qian; Febbraro, Michael; Deboer, Richard; Wiescher, Michael

    2016-09-01

    The reactoin 10B(α,n)13N has been identified as a possible background source for underground experiments at low energy. Previously the differential cross section data has only been available at energies above Eα = 1.0 MeV. An improved measurement of this reaction has been performed extensively down to 0.57 MeV. It has been measured with two deuterated liquid scintillators, EJ315 and EJ301D, and with the help of unfolding technique, neutron energy information can be extracted. EJ301D is a newly-developed neutron detector, with better pulse shape discrimination, and has been used to do angular distribution measurements. In addition, the (α ,α1 γ) and (α ,p3 γ) channels have been monitored independently by observation of the 718 keV γ transition in 10B and 3853 keV γ transition in 13C. Preliminary data analysis indicates the discovery of a new resonance in low energy region. Future measurements will be carried out at CASPAR using the same detectors. Research supported by NSF PHY-1430152, and JINA PHY-1419765.

  20. MicroRNA-10b downregulation mediates acute rejection of renal allografts by derepressing BCL2L11

    SciTech Connect

    Liu, Xiaoyou; Dong, Changgui; Jiang, Zhengyao; Wu, William K.K.; Chan, Matthew T.V.; Zhang, Jie; Li, Haibin; Qin, Ke; Sun, Xuyong

    2015-04-10

    Kidney transplantation is the major therapeutic option for end-stage kidney diseases. However, acute rejection could cause allograft loss in some of these patients. Emerging evidence supports that microRNA (miRNA) dysregulation is implicated in acute allograft rejection. In this study, we used next-generation sequencing to profile miRNA expression in normal and acutely rejected kidney allografts. Among 75 identified dysregulated miRNAs, miR-10b was the most significantly downregulated miRNAs in rejected allografts. Transfecting miR-10b inhibitor into human renal glomerular endothelial cells recapitulated key features of acute allograft rejection, including endothelial cell apoptosis, release of pro-inflammatory cytokines (interleukin-6, tumor necrosis factor α, interferon-γ, and chemokine (C–C motif) ligand 2) and chemotaxis of macrophages whereas transfection of miR-10b mimics had opposite effects. Downregulation of miR-10b directly derepressed the expression of BCL2L11 (an apoptosis inducer) as revealed by luciferase reporter assay. Taken together, miR-10b downregulation mediates many aspects of disease pathogenicity of acute kidney allograft rejection. Restoring miR-10b expression in glomerular endothelial cells could be a novel therapeutic approach to reduce acute renal allograft loss. - Highlights: • miR-10b was the most downregulated microRNAs in acutely rejected renal allografts. • miR-10b downregulation triggered glomerular endothelial cell apoptosis. • miR-10b downregulation induced release of pro-inflammatory cytokines. • miR-10b downregulation derepressed its pro-apoptotic target BCL2L11.

  1. High precision 11B/10B analysis with a simplified MC-ICP-MS

    NASA Astrophysics Data System (ADS)

    Tanimizu, M.; Nagaishi, K.

    2012-04-01

    Boron isotope ratio is a powerful tracer in the fields of geochemistry, biochemistry, and environmental chemistry. One important application of 11B/10B isotope ratio in geochemistry is as an indicator for paleo pH of seawater recorded in marine carbonates in deep-sea sediments. Boron isotope ratios are determined by TIMS or MC-ICP-MS with precisions of better than 0.1 % RSD, but a large inter-lab discrepancy of 0.6 % is still observed for actual carbonate samples (Foster, 2008). Here, we tried to determine B isotope ratio by MC-ICP-MS with a simple and common analytical techniques using a quartz sample introduction system with a PFA nebulizer, and compared to recently developed precise B isotope ratio analysis techniques by TIMS in positive ion detection mode determined as Cs2BO2+ ions with sample amount of <100 ng (Ishikawa and Nagaishi, 2011) and by MC-ICP-MS (Foster, 2008, Louvat et al., 2011). 11B/10B isotope ratios of a 50 ppb B solution dissolved in a HNO3, mannitol, HF-mixed solution were determined against an isotopic reference NIST-SRM 951 with a standard sample bracketing technique in the wet plasma condition. Resultant analytical reproducibility (twice standard deviation) was +/-0.02 % with a consumption of 50 ng B, and the washout time was comparable to that of NH3 gas addition to the introduction system (Foster, 2008). 11B/10B isotope ratios of actual carbonate sample and seawater were determined after simple chemical purification with a common cation exchange resin instead of a boron selective resin. Their relative differences from the standard were consistent with those determined by the positive TIMS within analytical uncertainty. Current potential of MC-ICP-MS for precise B isotopic analysis will be discussed. Foster, G., 2008. Seawater pH, pCO2 and [CO32-] variations in the Caribbean Sea over the last 130kyr: A boron isotope and B/Ca study of planktic foraminifera, Earth Planet. Sci. Lett., 271, 254-266. Ishikawa, T. and Nagaishi, K., 2011. High

  2. First Observation of the nu(17)-nu(4) Difference Bands of Diborane (10)B(2)H(6) and (11)B(2)H(6).

    PubMed

    Flaud; Lafferty; Bürger; Pawelke; Domenech; Bermejo

    2000-10-01

    An analysis of the nu(17)-nu(4) difference bands near 800 cm(-1) of two isotopic species, (10)B(2)H(6) and (11)B(2)H(6), of diborane has been carried out using infrared spectra recorded with a resolution of ca. 0.003 cm(-1). In addition, the nu(17) band of (10)B(2)H(6) has been recorded and assigned. Since this band in (11)B(2)H(6) had already been studied (R. L. Sams, T. A. Blake, S. W. Sharpe, J.-M. Flaud, and W. J. Lafferty, J. Mol. Spectrosc. 191, 331-342 (1998)), it was possible to derive precise energy levels and Hamiltonian constants for the 4(1) vibrational states of both isotopic species. Copyright 2000 Academic Press.

  3. Aging mechanism of butyrylcholinesterase inhibited by an N-methyl analogue of tabun: implications of the trigonal-bipyramidal transition state rearrangement for the phosphylation or reactivation of cholinesterases.

    PubMed

    Nachon, Florian; Carletti, Eugenie; Worek, Franz; Masson, Patrick

    2010-09-06

    Cholinesterases are the main target of organophosphorus nerve agents (OPs). Their inhibition results in cholinergic syndrome and death. The enzymes are inhibited by phosphylation of the catalytic serine enzyme, but can be reactivated by oximes to some extent. However, phosphylated cholinesterases undergo a side reaction that progressively prevents their reactivatability. This unimolecular reaction, termed "aging", has been investigated for decades. It was shown that most OP-ChE conjugates aged by O-dealkylation of an alkoxy substituent of the phosphorus atom, a mechanism involving the stabilization of a transient carbocation. In this paper we present structural data supporting a substitution-based mechanism for aging of the huBChE conjugate of an N-mono-methyl analogue of tabun. This mechanism involves an adjacent nucleophilic attack followed by Berry pseudorotation. A similar adjacent attack and subsequent rearrangement of the transition state have been recently proposed for tabun phosphylation of AChE. We suggest that a similar mechanism is also possible for oxime reactivation of phosphylated cholinesterases. This opens new perspectives in terms of reactivator design.

  4. Structure-based design, synthesis, and biochemical and pharmacological characterization of novel salvinorin A analogues as active state probes of the kappa-opioid receptor.

    PubMed

    Yan, Feng; Bikbulatov, Ruslan V; Mocanu, Viorel; Dicheva, Nedyalka; Parker, Carol E; Wetsel, William C; Mosier, Philip D; Westkaemper, Richard B; Allen, John A; Zjawiony, Jordan K; Roth, Bryan L

    2009-07-28

    Salvinorin A, the most potent naturally occurring hallucinogen, has attracted an increasing amount of attention since the kappa-opioid receptor (KOR) was identified as its principal molecular target by us [Roth, B. L., et al. (2002) Proc. Natl. Acad. Sci. U.S.A. 99, 11934-11939]. Here we report the design, synthesis, and biochemical characterization of novel, irreversible, salvinorin A-derived ligands suitable as active state probes of the KOR. On the basis of prior substituted cysteine accessibility and molecular modeling studies, C315(7.38) was chosen as a potential anchoring point for covalent labeling of salvinorin A-derived ligands. Automated docking of a series of potential covalently bound ligands suggested that either a haloacetate moiety or other similar electrophilic groups could irreversibly bind with C315(7.38). 22-Thiocyanatosalvinorin A (RB-64) and 22-chlorosalvinorin A (RB-48) were both found to be extraordinarily potent and selective KOR agonists in vitro and in vivo. As predicted on the basis of molecular modeling studies, RB-64 induced wash-resistant inhibition of binding with a strict requirement for a free cysteine in or near the binding pocket. Mass spectrometry (MS) studies utilizing synthetic KOR peptides and RB-64 supported the hypothesis that the anchoring residue was C315(7.38) and suggested one biochemical mechanism for covalent binding. These studies provide direct evidence of the presence of a free cysteine in the agonist-bound state of the KOR and provide novel insights into the mechanism by which salvinorin A binds to and activates the KOR.

  5. 100 keV 10-B + implantation into poly-(di-n-hexyl silane), (PDHSi)

    NASA Astrophysics Data System (ADS)

    Fink, D.; Müller, M.; Behar, M.; Papaleo, R. M.

    2006-07-01

    100 keV10B+ ions were implanted into poly-(di-n-hexyl silane) in different directions at a fluence of 1×1014 cm-2, and their depth distribution was determined by means of the neutron depth profiling technique. In no case were the projectile ions found to come to rest according to their predicted range profiles. Instead, they are always found to undergo considerable long-range migration. During the irradiation process this motion appears to be radiation-enhanced, and during the subsequent annealing steps one appears to deal with regular thermal diffusion. The implant redistribution is always found to be governed strongly by the self-created damage, insofar as both electronic and nuclear defects in the polymer act as trapping centers. Their population ratio is modified by thermal annealing.

  6. A double-helix neutron detector using micron-size 10B powder

    NASA Astrophysics Data System (ADS)

    Wang, Zhehui; Morris, C. L.; Bacon, J. D.; Brockwell, M. I.; Ramsey, J. C.

    2014-11-01

    A double-helix electrode configuration is combined with a 10B powder coating technique to build large-area (9 in.×36 in., or about 23 cm by 91 cm) neutron detectors. The neutron detection efficiency for each of the four prototypes is comparable to 3.7×103 cm3 of 3He inside a cylindrical tube 91 cm long. One unit has been operational continuously for 18 months and the change of efficiency is less than 1%. An analytic model for pulse height spectra is described and the predicted mean film thicknesses agree with the experiment to within 30%. Further detector optimization is possible through film texture, powder size, moderator box and gas. The estimated production cost per unit is less than 3k US and the technology is thus suitable for deployment in large numbers.

  7. A 10-b 75-MSPS subranging A/D converter with integrated sample and hold

    NASA Astrophysics Data System (ADS)

    Petschacher, Reinhard; Zojer, Bernhard; Astegher, Berthold; Jessner, Hermann; Lechner, Alexander

    1990-12-01

    The design of a fully differential two-step analog-to-digital converter (ADC) is presented. A sample-and-hold (S/H) circuit based on a unity-gain feedback amplifier, flash ADCs driven by differential resistor ladders, and a differential digital-to-analog converter (DAC) combined with the subtractor are described. The chip has been fabricated in a standard high-speed bipolar process and, by extensively utilizing compensation techniques, achieves + or - 1 LSB integral nonlinearity and low harmonic distortion. A 75 Msample/s conversion rate, not yet exceeded even by full-flash 10-b ADCs, has been achieved with a power consumption of 2 W. Due to the S/H circuit, the input bandwidth is 250 MHz; the effective resolution of 9 b at 5 MHz exhibits a gradual decrease over input frequency but still remains above 8 b up to 50 MHz.

  8. Combined TL and 10B-alanine ESR dosimetry for BNCT.

    PubMed

    Bartolotta, A; D'Oca, M C; Lo Giudice, B; Brai, M; Borio, R; Forini, N; Salvadori, P; Manera, S

    2004-01-01

    The dosimetric technique described in this paper is based on electron spin resonance (ESR) detectors using an alanine-boric compound acid enriched with (10)B, and beryllium oxide thermoluminescent (TL) detectors; with this combined dosimetry, it is possible to discriminate the doses due to thermal neutrons and gamma radiation in a mixed field. Irradiations were carried out inside the thermal column of a TRIGA MARK II water-pool-type research nuclear reactor, also used for Boron Neutron Capture therapy (BNCT) applications, with thermal neutron fluence from 10(9) to 10(14) nth cm(-2). The ESR dosemeters using the alanine-boron compound indicated ESR signals about 30-fold stronger than those using only alanine. Moreover, a negligible correction for the gamma contribution, measured with TL detectors, almost insensitive to thermal neutrons, was necessary. Therefore, a simultaneous analysis of our TL and ESR detectors allows discrimination between thermal neutron and gamma doses, as required in BNCT.

  9. Polyethyleneimine modified bentonite for the adsorption of amino black 10B

    NASA Astrophysics Data System (ADS)

    Du, Sen; Wang, Luyan; Xue, Ni; Pei, Meishan; Sui, Weiping; Guo, Wenjuan

    2017-08-01

    The modified bentonite with a graft amount of 30% was prepared by polyethylenimine reacting with the epoxy bonds on the molecular of (3-Glycidyloxypropyl) trimethoxysilane and being grafted on the bentonite to remove amino black10B. The effects of pH, time, temperature and concentration on the adsorption capacity were studied. As the pH value increases from 3 to 10, the adsorption capacity decreased from 264.5 to 140.4 mg/g. The adsorption process reached equilibrium at 90 min when pH=3. The adsorption kinetics indicates that the adsorption process was very fast and in accordance with the secondary adsorption kinetics. The data about thermodynamic equilibrium was consistent with the Langmuir model. The adsorption process mainly depended on electrostatic attraction and hydrogen bonding and the adsorption data of Bent-PGLYMO-PEI showed that the maximum adsorption capacity reached 327.7 mg/g.

  10. Tidal Dissipation in a Homogeneous Spherical Body. II. Three Examples: Mercury, IO, and Kepler-10 b

    NASA Astrophysics Data System (ADS)

    Makarov, Valeri V.; Efroimsky, Michael

    2014-11-01

    In Efroimsky & Makarov (Paper I), we derived from the first principles a formula for the tidal heating rate in a homogeneous sphere, compared it with the previously used formulae, and noted the differences. Now we present case studies: Mercury, Kepler-10 b, and a triaxial Io. A sharp frequency dependence of k 2/Q near spin-orbit resonances yields a sharp dependence of k 2/Q (and, therefore, of tidal heating) upon the spin rate. Thereby physical libration plays a major role in tidal heating of synchronously rotating planets. The magnitude of libration in the spin rate being defined by the planet's triaxiality, the latter becomes a factor determining the dissipation rate. Other parameters equal, a strongly triaxial synchronized body generates more heat than a similar body of a more symmetrical shape. After an initially triaxial object melts and loses its triaxiality, dissipation becomes less intensive; the body can solidify, with the tidal bulge becoming a new figure with triaxiality lower than the original. We derive approximate expressions for the dissipation rate in a Maxwell planet with the Maxwell time longer than the inverse tidal frequency. The expressions derived pertain to the 1:1 and 3:2 resonances and a nonresonant case; so they are applicable to most close-in super-Earths detected. In these planets, the heating outside synchronism is weakly dependent on the eccentricity and obliquity, provided both these parameters's values are moderate. According to our calculation, Kepler-10 b could hardly survive the intensive tidal heating without being synchronized, circularized, and reshaped through a complete or partial melt-down.

  11. Tidal dissipation in a homogeneous spherical body. II. Three examples: Mercury, Io, and Kepler-10 b

    SciTech Connect

    Makarov, Valeri V.; Efroimsky, Michael E-mail: michael.efroimsky@usno.navy.mil

    2014-11-01

    In Efroimsky and Makarov (Paper I), we derived from the first principles a formula for the tidal heating rate in a homogeneous sphere, compared it with the previously used formulae, and noted the differences. Now we present case studies: Mercury, Kepler-10 b, and a triaxial Io. A sharp frequency dependence of k {sub 2}/Q near spin-orbit resonances yields a sharp dependence of k {sub 2}/Q (and, therefore, of tidal heating) upon the spin rate. Thereby physical libration plays a major role in tidal heating of synchronously rotating planets. The magnitude of libration in the spin rate being defined by the planet's triaxiality, the latter becomes a factor determining the dissipation rate. Other parameters equal, a strongly triaxial synchronized body generates more heat than a similar body of a more symmetrical shape. After an initially triaxial object melts and loses its triaxiality, dissipation becomes less intensive; the body can solidify, with the tidal bulge becoming a new figure with triaxiality lower than the original. We derive approximate expressions for the dissipation rate in a Maxwell planet with the Maxwell time longer than the inverse tidal frequency. The expressions derived pertain to the 1:1 and 3:2 resonances and a nonresonant case; so they are applicable to most close-in super-Earths detected. In these planets, the heating outside synchronism is weakly dependent on the eccentricity and obliquity, provided both these parameters's values are moderate. According to our calculation, Kepler-10 b could hardly survive the intensive tidal heating without being synchronized, circularized, and reshaped through a complete or partial melt-down.

  12. CTLA4-Ig Induced T-Cell Anergy Promotes Wnt10b Production and Bone Formation

    PubMed Central

    Roser-Page, Susanne; Vikulina, Tatyana; Zayzafoon, Majd; Weitzmann, M. Neale

    2014-01-01

    Objective Rheumatoid arthritis (RA) is an inflammatory autoimmune disease characterized by severe joint erosion and systemic osteoporosis. Chronic T-cell activation is a hallmark of RA and agents that target the CD28 receptor on T-cells, needed for T-cell activation, are being increasingly employed as therapeutic agents in RA and other inflammatory diseases. Lymphocytes play complex roles in the regulation of the skeleton and although activated T-cells and B-cells secrete cytokines that promote skeletal decline, under physiological conditions lymphocytes also play key protective roles in the stabilization of skeletal mass. Consequently, disruption of T-cell costimulation may have unforeseen consequences on physiological bone turnover. In this study we investigate the impact of pharmacological CD28 T-cell costimulation blockade on physiological bone turnover and structure. Methods C57BL6 mice were treated with Cytotoxic T-lymphocyte-associated protein 4 (CTLA4)-Ig, a pharmacological CD28 antagonist, or irrelevant control antibody (Ig) and serum biochemical markers of bone turnover quantified by ELISA. Bone mineral density (BMD) and indices of bone structure were further quantified by dual energy X-ray absorptiometry (DEXA) and micro-computed tomography (μCT) respectively and static and dynamic indices of bone formation quantified using bone histomorphometry. Results Pharmacological disruption of CD28 T-cell costimulation in mice, significantly increased bone mass and enhanced indices of bone structure, a consequence of enhanced bone formation, concurrent with enhanced secretion of the bone anabolic factor Wnt10b by T-cells. Conclusion Inhibition of CD28 co-stimulation by CTLA4-Ig promotes T-cell Wnt10b production and bone formation and may represent a novel anabolic strategy for increasing bone mass in osteoporotic conditions. PMID:24757150

  13. Detection of the secondary eclipse of WASP-10b in the Ks-band

    NASA Astrophysics Data System (ADS)

    Cruz, Patricia; Barrado, David; Lillo-Box, Jorge; Diaz, Marcos; Birkby, Jayne; López-Morales, Mercedes; Hodgkin, Simon; Fortney, Jonathan J.

    2015-02-01

    Context. WASP-10b, a non-inflated hot Jupiter, was discovered around a K-dwarf in a near circular orbit (~0.06). Since its discovery in 2009, different published parameters for this system have led to a discussion about the size, density, and eccentricity of this exoplanet. Aims: In order to test the hypothesis of a circular orbit for WASP-10b, we observed its secondary eclipse in the Ks-band, where the contribution of planetary light is high enough to be detected from the ground. Methods: Observations were performed with the OMEGA2000 instrument at the 3.5 m telescope at Calar Alto (Almería, Spain), in staring mode during 5.4 continuous hours, with the telescope defocused, monitoring the target during the expected secondary eclipse. A relative light curve was generated and corrected from systematic effects, using the principal component analysis (PCA) technique. The final light curve was fitted using a transit model to find the eclipse depth and a possible phase shift. Results: The best model obtained from the Markov chain Monte Carlo analysis resulted in an eclipse depth of ΔF of 0.137%+0.013%-0.019% and a phase offset of Δφ of -0.0028 +0.0005-0.0004. The eclipse phase offset derived from our modeling has systematic errors that were not taken into account and should not be considered as evidence of an eccentric orbit. The offset in phase obtained leads to a value for | ecosω | of 0.0044. The derived eccentricity is too small to be of any significance. Based on observations collected at the Calar Alto Observatory, Almería, Spain.

  14. Effect of oxygen pressure during incubation with a (10)B-carrier on (10)B uptake capacity of cultured p53 wild-type and mutated tumor cells: dependency on p53 status of tumor cells and types of (10)B-carriers.

    PubMed

    Masunaga, Shin-ichiro; Tatebe, Hitoshi; Nishimura, Yasumasa; Tano, Keizo; Sanada, Yu; Moriwaki, Takahiro; Sakurai, Yoshinori; Tanaka, Hiroki; Suzuki, Minoru; Kondo, Natsuko; Maruhashi, Akira; Ono, Koji

    2016-01-01

    Purpose To evaluate the effect of oxygen pressure during incubation with a (10)B-carrier on (10)B uptake capacity of cultured p53 wild-type and mutated tumor cells. Materials and methods Cultured human head and neck squamous cell carcinoma cell line transfected with mutant TP53 (SAS/mp53), or with a neo vector as a control (SAS/neo) was incubated with L-para-boronophenylalanine-(10)B (BPA) or sodium mercaptoundecahydrododecaborate-(10)B (BSH) as a (10)B-carrier at the (10)B concentration of 60 ppm for 24 h under aerobic (20.7% of oxygen) or hypoxic (0.28% of oxygen) conditions. Immediately after incubation, cultured tumor cells received reactor thermal neutron beams, and a cell survival assay was performed. (10)B concentration of cultured SAS/neo or SAS/mp53 cells incubated under aerobic or hypoxic conditions was determined with a thermal neutron guide tube. Results Hypoxic incubation significantly decreased (10)B concentration of cultured cells with a clearer tendency observed following BPA than BSH treatment in both SAS/neo and SAS/mp53 cells. Following neutron beam irradiation, SAS/mp53 cells showed significantly higher relative biological effectiveness values than SAS/neo cells because of the significantly lower radiosensitivity of SAS/mp53 to γ-rays than SAS/neo cells. Conclusion Oxygen pressure during incubation with a (10)B-carrier had a critical impact on (10)B uptake of cultured tumor cells.

  15. The Effects of Long Duration Bed Rest as a Spaceflight Analogue on Resting State Sensorimotor Network Functional Connectivity and Neurocognitive Performance

    NASA Technical Reports Server (NTRS)

    Cassady, K.; Koppelmans, V.; Yuan, P.; Cooke, K.; De Dios, Y.; Stepanyan, V.; Szecsy, D.; Gadd, N.; Wood, S.; Reuter-Lorenz, P.; hide

    2015-01-01

    Long duration spaceflight has been associated with detrimental alterations in human sensorimotor systems and neurocognitive performance. Prolonged exposure to a head-down tilt position during long duration bed rest can resemble several effects of the microgravity environment such as reduced sensory inputs, body unloading and increased cephalic fluid distribution. The question of whether microgravity affects other central nervous system functions such as brain functional connectivity and its relationship with neurocognitive performance is largely unknown, but of potential importance to the health and performance of astronauts both during and post-flight. The aims of the present study are 1) to identify changes in sensorimotor resting state functional connectivity that occur with extended bed rest exposure, and to characterize their recovery time course; 2) to evaluate how these neural changes correlate with neurocognitive performance. Resting-state functional magnetic resonance imaging (rsfMRI) data were collected from 17 male participants. The data were acquired through the NASA bed rest facility, located at the University of Texas Medical Branch (Galveston, TX). Participants remained in bed with their heads tilted down six degrees below their feet for 70 consecutive days. RsfMRI data were obtained at seven time points: 7 and 12 days before bed rest; 7, 50, and 65 days during bed rest; and 7 and 12 days after bed rest. Functional connectivity magnetic resonance imaging (fcMRI) analysis was performed to measure the connectivity of sensorimotor networks in the brain before, during, and post-bed rest. We found a decrease in left putamen connectivity with the pre- and post-central gyri from pre bed rest to the last day in bed rest. In addition, vestibular cortex connectivity with the posterior cingulate cortex decreased from pre to post bed rest. Furthermore, connectivity between cerebellar right superior posterior fissure and other cerebellar regions decreased from

  16. The edaravone and 3-n-butylphthalide ring-opening derivative 10b effectively attenuates cerebral ischemia injury in rats

    PubMed Central

    Hua, Kai; Sheng, Xiao; Li, Ting-ting; Wang, Lin-na; Zhang, Yi-hua; Huang, Zhang-jian; Ji, Hui

    2015-01-01

    Aim: Compound 10b is a hybrid molecule of edaravone and a ring-opening derivative of 3-n-butylphthalide (NBP). The aim of this study was to examine the effects of compound 10b on brain damage in rats after focal cerebral ischemia. Methods: SD rats were subjected to 2-h-middle cerebral artery occlusion (MCAO). At the onset of reperfusion, the rats were orally treated with NBP (60 mg/kg), edaravone (3 mg/kg), NBP (60 mg/kg)+edaravone (3 mg/kg), or compound 10b (70, 140 mg/kg). The infarct volume, motor behavior deficits, brain water content, histopathological alterations, and activity of GSH, SOD, and MDA were analyzed 24 h after reperfusion. The levels of relevant proteins in the ipsilateral striatum were examined using immunoblotting. Results: Administration of compound 10b (70 or 140 mg/kg) significantly reduced the infarct volume and neurological deficits in MCAO rats. The neuroprotective effects of compound 10b were more pronounced compared to NBP, edaravone or NBP+edaravone. Furthermore, compound 10b significantly upregulated the protein levels of the cytoprotective molecules Bcl-2, HO-1, Nrf2, Trx, P-NF-κB p65, and IκB-α, while decreasing the expression of Bax, caspase 3, caspase 9, Txnip, NF-κB p65, and P-IκB-α. Conclusion: Oral administration of compound 10b effectively attenuates rat cerebral ischemia injury. PMID:26073328

  17. Promotion of hair follicle development and trichogenesis by Wnt-10b in cultured embryonic skin and in reconstituted skin

    SciTech Connect

    Ouji, Yukiteru . E-mail: oujix@naramed-u.ac.jp; Yoshikawa, Masahide; Shiroi, Akira; Ishizaka, Shigeaki

    2006-06-30

    We previously showed that Wnt-10b promoted the differentiation of primary skin epithelial cells (MPSEC) toward hair shaft and inner root sheath of the hair follicle (IRS) cells in vitro. In the present study, we found that Wnt-10b promotes the development of hair follicles using a culture of mouse embryonic skin tissue and trichogenesis using a reconstitution experiment with nude mice. Hair follicle development was observed in skin taken from mouse embryos on embryonic day 10.5 following a 2-day culture with recombinant Wnt-10b (rWnt-10b), however, not without rWnt-10b. Brown hair growth was observed at the site of reconstituted skin in Balb/c nude mice where dermal fibroblasts and keratinocytes, derived from C3H/HeN new born mice, were transplanted with Wnt-10b-producing COS cells (Wnt-COS). Without the co-transplantation of Wnt-COS, no hair growth was observed. Our results suggest an important role of Wnt-10b in the initiation of hair follicle development and following trichogenesis.

  18. MicroRNA-10b pleiotropically regulates invasion, angiogenicity and apoptosis of tumor cells resembling mesenchymal subtype of glioblastoma multiforme.

    PubMed

    Lin, J; Teo, S; Lam, D H; Jeyaseelan, K; Wang, S

    2012-10-04

    Glioblastoma multiforme (GBM) is a heterogeneous disease despite its seemingly uniform pathology. Deconvolution of The Cancer Genome Atlas's GBM gene expression data has unveiled the existence of distinct gene expression signature underlying discrete GBM subtypes. Recent conflicting findings proposed that microRNA (miRNA)-10b exclusively regulates glioma growth or invasion but not both. We showed that silencing of miRNA-10b by baculoviral decoy vectors in a glioma cell line resembling the mesenchymal subtype of GBM reduces its growth, invasion and angiogenesis while promoting apoptosis in vitro. In an orthotopic human glioma mouse model, inhibition of miRNA-10b diminishes the invasiveness, angiogenicity and growth of the mesenchymal subtype-like glioma cells in the brain and significantly prolonged survival of glioma-bearing mice. We demonstrated that the pleiotropic nature of miRNA-10b was due to its suppression of multiple tumor suppressors, including TP53, FOXO3, CYLD, PAX6, PTCH1, HOXD10 and NOTCH1. In particular, siRNA-mediated knockdown experiments identified TP53, PAX6, NOTCH1 and HOXD10 as invasion regulatory genes in our mesenchymal subtype-like glioma cells. By interrogating the REMBRANDT, we noted that dysregulation of many direct targets of miRNA-10b was associated with significantly poorer patient survival. Thus, our study uncovers a novel role for miRNA-10b in regulating angiogenesis and suggests that miRNA-10b may be a pleiotropic regulator of gliomagenesis.

  19. Benchmarking analogue models of brittle thrust wedges

    NASA Astrophysics Data System (ADS)

    Schreurs, Guido; Buiter, Susanne J. H.; Boutelier, Jennifer; Burberry, Caroline; Callot, Jean-Paul; Cavozzi, Cristian; Cerca, Mariano; Chen, Jian-Hong; Cristallini, Ernesto; Cruden, Alexander R.; Cruz, Leonardo; Daniel, Jean-Marc; Da Poian, Gabriela; Garcia, Victor H.; Gomes, Caroline J. S.; Grall, Céline; Guillot, Yannick; Guzmán, Cecilia; Hidayah, Triyani Nur; Hilley, George; Klinkmüller, Matthias; Koyi, Hemin A.; Lu, Chia-Yu; Maillot, Bertrand; Meriaux, Catherine; Nilfouroushan, Faramarz; Pan, Chang-Chih; Pillot, Daniel; Portillo, Rodrigo; Rosenau, Matthias; Schellart, Wouter P.; Schlische, Roy W.; Take, Andy; Vendeville, Bruno; Vergnaud, Marine; Vettori, Matteo; Wang, Shih-Hsien; Withjack, Martha O.; Yagupsky, Daniel; Yamada, Yasuhiro

    2016-11-01

    We performed a quantitative comparison of brittle thrust wedge experiments to evaluate the variability among analogue models and to appraise the reproducibility and limits of model interpretation. Fifteen analogue modeling laboratories participated in this benchmark initiative. Each laboratory received a shipment of the same type of quartz and corundum sand and all laboratories adhered to a stringent model building protocol and used the same type of foil to cover base and sidewalls of the sandbox. Sieve structure, sifting height, filling rate, and details on off-scraping of excess sand followed prescribed procedures. Our analogue benchmark shows that even for simple plane-strain experiments with prescribed stringent model construction techniques, quantitative model results show variability, most notably for surface slope, thrust spacing and number of forward and backthrusts. One of the sources of the variability in model results is related to slight variations in how sand is deposited in the sandbox. Small changes in sifting height, sifting rate, and scraping will result in slightly heterogeneous material bulk densities, which will affect the mechanical properties of the sand, and will result in lateral and vertical differences in peak and boundary friction angles, as well as cohesion values once the model is constructed. Initial variations in basal friction are inferred to play the most important role in causing model variability. Our comparison shows that the human factor plays a decisive role, and even when one modeler repeats the same experiment, quantitative model results still show variability. Our observations highlight the limits of up-scaling quantitative analogue model results to nature or for making comparisons with numerical models. The frictional behavior of sand is highly sensitive to small variations in material state or experimental set-up, and hence, it will remain difficult to scale quantitative results such as number of thrusts, thrust spacing

  20. 10B(n,α)7Li and 10B(n,α1γ)7Li cross section data up to 3 MeV incident neutron energy

    NASA Astrophysics Data System (ADS)

    Bevilacqua, Riccardo; Hambsch, Franz-Josef; Vidali, Marzio; Ruskov, Ivan; Lamia, Livio

    2017-09-01

    The 10B(n,α) reaction cross-section is a well-established neutron cross-section standard for incident neutron energies up to 1 MeV. However, above this energy limit there are only scarce direct (n,α) measurements available and these few experimental data are showing large inconsistencies with each other. These discrepancies are reflected in the evaluated data libraries: ENDF/B-VII.1, JEFF-3.1.2 and JENDL-4.0 are in excellent agreement up to 100 keV incident neutrons, whereas the 10B(n,α) data in the different libraries show large differences in the MeV region. To address these inconsistencies, we have measured the cross section of the two branches of the 10B(n,α) reaction for incident neutron energies up to 3 MeV. We present here the 10B(n,α) and the 10B(n,α1γ) reactions cross section data, their branching ratio and the total 10B(n,α) reaction cross section. The measurements were conducted with a dedicated Frisch-grid ionization chamber installed at the GELINA pulsed neutron source of the EC-JRC. We compare our results with existing experimental data and evaluations.

  1. Changes in charge density vs changes in formal oxidation states: The case of Sn halide perovskites and their ordered vacancy analogues

    NASA Astrophysics Data System (ADS)

    Dalpian, Gustavo M.; Liu, Qihang; Stoumpos, Constantinos C.; Douvalis, Alexios P.; Balasubramanian, Mahalingam; Kanatzidis, Mercouri G.; Zunger, Alex

    2017-07-01

    Shifting the Fermi energy in solids by doping, defect formation, or gating generally results in changes in the charge density distribution, which reflect the ability of the bonding pattern in solids to adjust to such external perturbations. In the traditional chemistry textbook, such changes are often described by the formal oxidation states (FOS) whereby a single atom type is presumed to absorb the full burden of the perturbation (change in charge) of the whole compound. In the present paper, we analyze the changes in the position-dependence charge density due to shifts of the Fermi energy on a general physical basis, comparing with the view of the FOS picture. We use the halide perovskites CsSn X3 (X =F , Cl, Br, I) as examples for studying the general principle. When the solar absorber CsSn I3 (termed 113) loses 50 % of its Sn atoms, thereby forming the ordered vacancy compound C s2Sn I6 (termed 216), the Sn is said in the FOS picture to change from Sn(II) to Sn(IV). To understand the electronic properties of these two groups we studied the 113 and 216 compound pairs CsSnC l3 and C s2SnC l6 , CsSnB r3 and C s2SnB r6 , and CsSn I3 and C s2Sn I6 , complementing them by CsSn F3 and C s2Sn F6 in the hypothetical cubic structure for completing the chemical trends. These materials were also synthesized by chemical routes and characterized by x-ray diffraction, 119Sn-Mössbauer spectroscopy, and K -edge x-ray absorption spectroscopy. We find that indeed in going from 113 to 216 (equivalent to the introduction of two holes per unit) there is a decrease in the s charge on Sn, in agreement with the FOS picture. However, at the same time, we observe an increase of the p charge via downshift of the otherwise unoccupied p level, an effect that tends to replenish much of the lost s charge. At the end, the change in the charge on the Sn site as a result of adding two holes to the unit cell is rather small. This effect is theoretically explained as a "self-regulating response

  2. Capability of NIPAM polymer gel in recording dose from the interaction of (10)B and thermal neutron in BNCT.

    PubMed

    Khajeali, Azim; Reza Farajollahi, Ali; Kasesaz, Yaser; Khodadadi, Roghayeh; Khalili, Assef; Naseri, Alireza

    2015-11-01

    The capability of N-isopropylacrylamide (NIPAM) polymer gel to record the dose resulting from boron neutron capture reaction in BNCT was determined. In this regard, three compositions of the gel with different concentrations of (10)B were prepared and exposed to gamma radiation and thermal neutrons. Unlike irradiation with gamma rays, the boron-loaded gels irradiated by neutron exhibited sensitivity enhancement compared with the gels without (10)B. It was also found that the neutron sensitivity of the gel increased by the increase of concentration of (10)B. It can be concluded that NIPAM gel might be suitable for the measurement of the absorbed dose enhancement due to (10)B and thermal neutron reaction in BNCT. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. The locus of microRNA-10b: a critical target for breast cancer insurgence and dissemination.

    PubMed

    Biagioni, Francesca; Bossel Ben-Moshe, Noa; Fontemaggi, Giulia; Yarden, Yosef; Domany, Eytan; Blandino, Giovanni

    2013-08-01

    Contemporary microRNA research has led to significant advances in our understanding of the process of tumorigenesis. MicroRNAs participate in different events of a cancer cell's life, through their ability to target hundreds of putative transcripts involved in almost every cellular function, including cell cycle, apoptosis, and differentiation. The relevance of these small molecules is even more evident in light of the emerging linkage between their expression and both prognosis and clinical outcome of many types of human cancers. This identifies microRNAs as potential therapeutic modifiers of cancer phenotypes. From this perspective, we overview here the miR-10b locus and its involvement in cancer, focusing on its role in the establishment (miR-10b*) and spreading (miR-10b) of breast cancer. We conclude that targeting the locus of microRNA 10b holds great potential for cancer treatment.

  4. Measurements of /sup 10/B(n,He) reaction rates in a mockup control rod in ZPPR

    SciTech Connect

    Brumbach, S.B.; Collins, P.J.; Oliver, B.M.

    1986-01-01

    This paper reports the first direct measurement of /sup 10/B capture rate in a mockup control rod in a critical assembly. The experiment used the helium accumulation fluence monitor (HAFM) technique. 13 refs.

  5. CD8+ T cells mediate the regenerative PTH effect in hPDL cells via Wnt10b signaling.

    PubMed

    Wolf, Michael; Lossdörfer, Stefan; Marciniak, Jana; Römer, Piero; Kirschneck, Christian; Craveiro, Rogerio; Deschner, James; Jäger, Andreas

    2016-11-01

    It was the aim of the present investigation to examine whether the stimulating effect of parathyroid hormone (PTH) on human periodontal ligament (hPDL) cell proliferation and differentiation would be enhanced by hPDL/T-cell interaction involving Wnt10b signaling as a mediating pathway. hPDL cells were cultured from healthy premolar tissues of three adolescent orthodontic patients and exposed to PTH(1-34) in monocultures or co-cultures with CD8(+) T cells. At harvest, proliferation, alkaline phosphatase-specific activity (ALP), and osteocalcin production were determined by immunofluorescence cytochemistry, real-time PCR, biochemical assay, and ELISA. Wnt10b signaling was analyzed by the use of a specific WNT10b neutralizing antibody. PTH(1-34) stimulation of T cells significantly increased Wnt10b expression and production. Wnt10b exposure of hPDL cells enhanced proliferation and differentiation. PDL cells co-cultured with T cells showed a Wnt10b-dependent regulation of proliferation and differentiation parameters. The addition of a Wnt10b-neutralizing Ab to the co-culture medium resulted in a significant inhibition of the PTH(1-34) effect on proliferation, ALP-specific activity, and osteocalcin protein expression. Our findings provide novel insight into the mechanism of action of PTH on hPDL cells and establish the interplay of T cells and hPDL cells via the Wnt10b pathway as a modulating factor for the anabolic properties of the hormone in periodontal regeneration.

  6. Intronless WNT10B-short variant underlies new recurrent allele-specific rearrangement in acute myeloid leukaemia

    PubMed Central

    Lazzaroni, Francesca; Del Giacco, Luca; Biasci, Daniele; Turrini, Mauro; Prosperi, Laura; Brusamolino, Roberto; Cairoli, Roberto; Beghini, Alessandro

    2016-01-01

    Defects in the control of Wnt signaling have emerged as a recurrent mechanism involved in cancer pathogenesis and acute myeloid leukaemia (AML), including the hematopoietic regeneration-associated WNT10B in AC133bright leukaemia cells, although the existence of a specific mechanism remains unproven. We have obtained evidences for a recurrent rearrangement, which involved the WNT10B locus (WNT10BR) within intron 1 (IVS1) and flanked at the 5′ by non-human sequences whose origin remains to be elucidated; it also expressed a transcript variant (WNT10BIVS1) which was mainly detected in a cohort of patients with intermediate/unfavorable risk AML. We also identified in two separate cases, affected by AML and breast cancer respectively, a genomic transposable short form of human WNT10B (ht-WNT10B). The intronless ht-WNT10B resembles a long non-coding RNA (lncRNA), which suggests its involvement in a non-random microhomology-mediated recombination generating the rearranged WNT10BR. Furthermore, our studies supports an autocrine activation primed by the formation of WNT10B-FZD4/5 complexes in the breast cancer MCF7 cells that express the WNT10BIVS1. Chemical interference of WNT-ligands production by the porcupine inhibitor IWP-2 achieved a dose-dependent suppression of the WNT10B-FZD4/5 interactions. These results present the first evidence for a recurrent rearrangement promoted by a mobile ht-WNT10B oncogene, as a relevant mechanism for Wnt involvement in human cancer. PMID:27853307

  7. 5,10b-Ethanophenanthridine amaryllidaceae alkaloids inspire the discovery of novel bicyclic ring systems with activity against drug resistant cancer cells☆

    PubMed Central

    Henry, Sean; Kidner, Ria; Reisenauer, Mary R.; Magedov, Igor V.; Kiss, Robert; Mathieu, Véronique; Lefranc, Florence; Dasari, Ramesh; Evidente, Antonio; Yu, Xiaojie; Ma, Xiuye; Pertsemlidis, Alexander; Cencic, Regina; Pelletier, Jerry; Cavazos, David A.; Brenner, Andrew J.; Aksenov, Alexander V.; Rogelj, Snezna; Kornienko, Alexander; Frolova, Liliya V.

    2016-01-01

    Plants of the Amaryllidaceae family produce a large variety of alkaloids and non-basic secondary metabolites, many of which are investigated for their promising anticancer activities. Of these, crinine-type alkaloids based on the 5,10b-ethanophenanthridine ring system were recently shown to be effective at inhibiting proliferation of cancer cells resistant to various pro-apoptotic stimuli and representing tumors with dismal prognoses refractory to current chemotherapy, such as glioma, melanoma, non-small-cell lung, esophageal, head and neck cancers, among others. Using this discovery as a starting point and taking advantage of a concise biomimetic route to the crinine skeleton, a collection of crinine analogues were synthetically prepared and evaluated against cancer cells. The compounds exhibited single-digit micromolar activities and retained this activity in a variety of drug-resistant cancer cell cultures. This investigation resulted in the discovery of new bicyclic ring systems with significant potential in the development of effective clinical cancer drugs capable of overcoming cancer chemotherapy resistance. PMID:27218860

  8. 5,10b-Ethanophenanthridine amaryllidaceae alkaloids inspire the discovery of novel bicyclic ring systems with activity against drug resistant cancer cells.

    PubMed

    Henry, Sean; Kidner, Ria; Reisenauer, Mary R; Magedov, Igor V; Kiss, Robert; Mathieu, Véronique; Lefranc, Florence; Dasari, Ramesh; Evidente, Antonio; Yu, Xiaojie; Ma, Xiuye; Pertsemlidis, Alexander; Cencic, Regina; Pelletier, Jerry; Cavazos, David A; Brenner, Andrew J; Aksenov, Alexander V; Rogelj, Snezna; Kornienko, Alexander; Frolova, Liliya V

    2016-09-14

    Plants of the Amaryllidaceae family produce a large variety of alkaloids and non-basic secondary metabolites, many of which are investigated for their promising anticancer activities. Of these, crinine-type alkaloids based on the 5,10b-ethanophenanthridine ring system were recently shown to be effective at inhibiting proliferation of cancer cells resistant to various pro-apoptotic stimuli and representing tumors with dismal prognoses refractory to current chemotherapy, such as glioma, melanoma, non-small-cell lung, esophageal, head and neck cancers, among others. Using this discovery as a starting point and taking advantage of a concise biomimetic route to the crinine skeleton, a collection of crinine analogues were synthetically prepared and evaluated against cancer cells. The compounds exhibited single-digit micromolar activities and retained this activity in a variety of drug-resistant cancer cell cultures. This investigation resulted in the discovery of new bicyclic ring systems with significant potential in the development of effective clinical cancer drugs capable of overcoming cancer chemotherapy resistance.

  9. Boron uptake in tumors, cerebrum and blood from [10B]NA4B24H22S2

    DOEpatents

    Slatkin, Daniel N.; Micca, Peggy L.; Fairchild, Ralph G.

    1988-08-02

    A stable boronated (.sup.10 B-labeled) compound, sodium mercaptoundecahydrododecaborate is infused in the form of the disulfide dimer, [.sup.10 B]Na.sub.4 B.sub.24 H.sub.22 S.sub.2, at a dose of about 200 .mu.g .sup.10 B per gm body weight. The infusion is performed into the blood or peritoneal cavity of the patient slowly over a period of many days, perhaps one week or more, at the rate of roughly 1 .mu.g .sup.10 B per gm body weight per hour. Use of this particular boronated dimer in the manner or similarly to the manner so described permits radiotherapeutically effective amounts of boron to accumulate in tumors to be treated by boron neutron capture radiation therapy and also permits sufficient retention of boron in tumor after the cessation of the slow infusion, so as to allow the blood concentration of .sup.10 B to drop or to be reduced artificially to a radiotherapeutically effective level, less than one-half of the concentration of .sup.10 B in the tumor.

  10. Boron uptake in tumors, cerebrum and blood from [10B]NA4B24H22S2

    DOEpatents

    Slatkin, Daniel N.; Micca, Peggy L.; Fairchild, Ralph G.

    1988-01-01

    A stable boronated (.sup.10 B-labeled) compound, sodium mercaptoundecahydrododecaborate is infused in the form of the disulfide dimer, [.sup.10 B]Na.sub.4 B.sub.24 H.sub.22 S.sub.2, at a dose of about 200 .mu.g .sup.10 B per gm body weight. The infusion is performed into the blood or peritoneal cavity of the patient slowly over a period of many days, perhaps one week or more, at the rate of roughly 1 .mu.g .sup.10 B per gm body weight per hour. Use of this particular boronated dimer in the manner or similarly to the manner so described permits radiotherapeutically effective amounts of boron to accumulate in tumors to be treated by boron neutron capture radiation therapy and also permits sufficient retention of boron in tumor after the cessation of the slow infusion, so as to allow the blood concentration of .sup.10 B to drop or to be reduced artificially to a radiotherapeutically effective level, less than one-half of the concentration of .sup.10 B in the tumor.

  11. Genetic Variants in the Promoter Region of miR-10b and the Risk of Breast Cancer

    PubMed Central

    Chen, Jiaping; Jiang, Yue; Zhou, Jing; Liu, Sijun; Gu, Yayun; Jin, Guangfu; Hu, Zhibin; Ma, Hongxia; Shen, Hongbing

    2017-01-01

    Variants in microRNA genes may affect their expression by interfering with the microRNA maturation process and may substantially contribute to the risk of breast cancer. Recent studies have identified miR-10b as an interesting candidate because of its close association with the metastatic behavior of breast cancer. However, the roles of miR-10b-related single nucleotide polymorphisms in breast cancer susceptibility remain unclear. This case-control study evaluated the associations between variants in the upstream transcription regulation region of miR-10b and the risk of breast cancer among Chinese women. Seven potentially functional SNPs were investigated using genotyping assays. The potential biological functions of the identified positive SNPs were further evaluated using in silico databases. We found that rs4078756, which was located at the promoter region of miR-10b, was significantly associated with breast cancer risk (rs4078756 AG/GG versus AA, adjusted odds ratio: 1.17, 95% confidence interval: 1.02–1.35). The other six single nucleotide polymorphisms exhibited negative associations. Based on the in silico prediction, rs4078756 potentially regulated miR-10b expression through promoter activation or repression. These findings indicate that a potentially functional SNP (rs4078756) in the promoter region of miR-10b may contribute to breast cancer susceptibility among Chinese women. PMID:28691018

  12. Extra tyrosine in the carbohydrate-binding module of Irpex lacteus Xyn10B enhances its cellulose-binding ability.

    PubMed

    Nishijima, Hiroto; Nozaki, Kouichi; Mizuno, Masahiro; Arai, Tsutomu; Amano, Yoshihiko

    2015-01-01

    The xylanase (Xyn10B) that strongly adsorbs on microcrystalline cellulose was isolated from Driselase. The Xyn10B contains a Carbohydrate-binding module family 1 (CBM1) (IrpCBMXyn10B) at N-terminus. The canonical essential aromatic residues required for cellulose binding were conserved in IrpCBMXyn10B; however, its adsorption ability was markedly higher than that typically observed for the CBM1 of an endoglucanase from Trametes hirsuta (ThCBMEG1). An analysis of the CBM-GFP fusion proteins revealed that the binding capacity to cellulose (7.8 μmol/g) and distribution coefficient (2.0 L/μmol) of IrpCBMXyn10B-GFP were twofold higher than those of ThCBMEG1-GFP (3.4 μmol/g and 1.2 L/μmol, respectively), used as a reference structure. Besides the canonical aromatic residues (W24-Y50-Y51) of typical CBM1-containing proteins, IrpCBMXyn10B had an additional aromatic residue (Y52). The mutation of Y52 to Ser (IrpCBMY52S-GFP) reduced these adsorption parameters to 4.4 μmol/g and 1.5 L/μmol, which were similar to those of ThCBMEG1-GFP. These results indicate that Y52 plays a crucial role in strong cellulose binding.

  13. Magnetically modified sheaths of Leptothrix sp. as an adsorbent for Amido black 10B removal

    NASA Astrophysics Data System (ADS)

    Angelova, Ralitsa; Baldikova, Eva; Pospiskova, Kristyna; Safarikova, Mirka; Safarik, Ivo

    2017-04-01

    The goal of this study was to assess the biosorption of Amido black 10B dye from aqueous solutions on magnetically modified sheaths of Leptothrix sp. in a batch system. The magnetic modification of the sheaths was performed using both microwave synthesized iron oxide nano- and microparticles and perchloric acid stabilized ferrofluid. The native and both magnetically modified sheaths were characterized by SEM. Various parameters significantly affecting the adsorption process, such as pH, contact time, temperature and initial concentration, were studied in detail using the adsorbent magnetized by both methods. The highest adsorption efficiency was achieved at pH 2. The maximum adsorption capacities of both types of magnetized material at room temperature were found to be 339.2 and 286.1 mg of dye per 1 g of ferrofluid modified and microwave synthesized particles modified adsorbent, respectively. Thermodynamic study of dye adsorption revealed a spontaneous and endothermic process in the temperature range between 279.15 and 313.15 K. The data were fitted to various equilibrium and kinetic models. Experimental data matched well with the pseudo-second-order kinetics and Freundlich isotherm model. The Leptothrix sheaths have excellent efficacy for dye adsorption. This material can be used as an effective, low-cost adsorbent.

  14. Sensitivity Analysis Applied to the Validation of the 10 B Capture Reaction in Nuclear Fuel Casks

    SciTech Connect

    Goluoglu, S

    2004-03-18

    Boron has commonly been used in nuclear fuel casks to ensure a sufficient margin of subcriticality. The amount of boron used in most casks far exceeds the amount of boron present in any of the available benchmark experiments. Such heavy loadings of boron in the casks may result in considerable spectral differences as compared to the benchmarks, resulting in boron sensitivities that are very different from those of the benchmarks. Before the calculations to determine the nuclear safety margin for various fuel loadings are deemed acceptable, as part of the safety basis, the computer code and cross sections must be validated against experimental benchmarks that cover the area of applicability of the proposed cask design. Therefore, this study was performed to determine if these available benchmarks can be used to validate a criticality code and neutron cross sections for the fuel casks. The sensitivity/uncertainty methodology has been applied to several application cask systems with different boron areal densities. Although, the sensitivities of the nuclear fuel cask applications are not completely covered by the set of benchmarks that were used in this study with regard to the 10B capture cross section, the effect of this lack of coverage on the keff is minimal. Thus, the experimental biases are determined to be appropriate for the cask systems, and no additional bias (penalty) due to high boron loading need be imposed.

  15. Novel concept for neutron detection: proportional counter filled with (10)B nanoparticle aerosol.

    PubMed

    Amaro, F D; Monteiro, C M B; Dos Santos, J M F; Antognini, A

    2017-02-09

    The high neutron detection efficiency, good gamma-ray discrimination and non-toxicity of (3)He made of proportional counters filled with this gas the obvious choice for neutron detection, particularly in radiation portal monitors (RPM), used to control the illicit transport of nuclear material, of which neutron detectors are key components. (3)He is very rare and during the last decade this gas has become increasingly difficult to acquire. With the exception of BF3, which is toxic, no other gas can be used for neutron detection in proportional counters. We present an alternative where the (3)He atoms are replaced by nanoparticles made of another neutron sensitive material, (10)B. The particles are dispersed in a gaseous volume, forming an aerosol with neutron sensitive properties. A proportional counter filled with such aerosol was exposed to a thermal neutron beam and the recorded response indicates that the neutrons have interacted with the particles in the aerosol. This original technique, which transforms a standard proportional gas mixture into a neutron sensitive aerosol, is a breakthrough in the field of radiation detection and has the potential to become an alternative to the use of (3)He in proportional counters.

  16. Novel concept for neutron detection: proportional counter filled with 10B nanoparticle aerosol

    NASA Astrophysics Data System (ADS)

    Amaro, F. D.; Monteiro, C. M. B.; Dos Santos, J. M. F.; Antognini, A.

    2017-02-01

    The high neutron detection efficiency, good gamma-ray discrimination and non-toxicity of 3He made of proportional counters filled with this gas the obvious choice for neutron detection, particularly in radiation portal monitors (RPM), used to control the illicit transport of nuclear material, of which neutron detectors are key components. 3He is very rare and during the last decade this gas has become increasingly difficult to acquire. With the exception of BF3, which is toxic, no other gas can be used for neutron detection in proportional counters. We present an alternative where the 3He atoms are replaced by nanoparticles made of another neutron sensitive material, 10B. The particles are dispersed in a gaseous volume, forming an aerosol with neutron sensitive properties. A proportional counter filled with such aerosol was exposed to a thermal neutron beam and the recorded response indicates that the neutrons have interacted with the particles in the aerosol. This original technique, which transforms a standard proportional gas mixture into a neutron sensitive aerosol, is a breakthrough in the field of radiation detection and has the potential to become an alternative to the use of 3He in proportional counters.

  17. Novel concept for neutron detection: proportional counter filled with 10B nanoparticle aerosol

    PubMed Central

    Amaro, F. D.; Monteiro, C. M. B.; dos Santos, J. M. F.; Antognini, A.

    2017-01-01

    The high neutron detection efficiency, good gamma-ray discrimination and non-toxicity of 3He made of proportional counters filled with this gas the obvious choice for neutron detection, particularly in radiation portal monitors (RPM), used to control the illicit transport of nuclear material, of which neutron detectors are key components. 3He is very rare and during the last decade this gas has become increasingly difficult to acquire. With the exception of BF3, which is toxic, no other gas can be used for neutron detection in proportional counters. We present an alternative where the 3He atoms are replaced by nanoparticles made of another neutron sensitive material, 10B. The particles are dispersed in a gaseous volume, forming an aerosol with neutron sensitive properties. A proportional counter filled with such aerosol was exposed to a thermal neutron beam and the recorded response indicates that the neutrons have interacted with the particles in the aerosol. This original technique, which transforms a standard proportional gas mixture into a neutron sensitive aerosol, is a breakthrough in the field of radiation detection and has the potential to become an alternative to the use of 3He in proportional counters. PMID:28181520

  18. A new study of 10B(p,α)7Be reaction at low energies

    NASA Astrophysics Data System (ADS)

    Caciolli, A.; Depalo, R.; Broggini, C.; La Cognata, M.; Lamia, L.; Menegazzo, R.; Mou, L.; Puglia, S. M. R.; Rigato, V.; Romano, S.; Rossi Alvarez, C.; Sergi, M. L.; Spitaleri, C.; Tumino, A.

    2016-05-01

    The 10B(p,α)7Be reaction is of great interest since it has many applications in different fields of research such as nuclear astrophysics, nuclear physics, and models of new reactors for clean energy generation. This reaction has been studied at the AN2000 accelerator of the INFN National Laboratories of Legnaro (LNL). The total cross section has been measured in a wide energy range (250-1182 keV) by using the activation method. The decays of the 7Be nuclei produced by the reaction were measured at the low counting facility of LNL by using two fully shielded high-purity germanium detectors. The present dataset shows a large discrepancy with respect to one of the previous data at the same energies and reduces the total uncertainty to the level of 6%. An R-matrix calculation has been performed on the present data using the parameters from previous Trojan Horse measurements for the 10 and 500keV resonances. The present data do not lay on the R-matrix fit in one point suggesting the existence of a 11C level not observed yet. Further nuclear investigations are needed to confirm this hypothesis.

  19. PTH analogues and osteoporotic fractures.

    PubMed

    Verhaar, Harald J J; Lems, Willem F

    2010-09-01

    At present there are two parathyroid hormone (PTH) analogues (PTH 1 - 34 and PTH 1 - 84) registered for the treatment of established osteoporosis in postmenopausal women (PTH 1 - 34 and PTH 1 - 84) and in men (PTH 1 - 34 only) who are at increased risk of having a fracture. The efficacy and safety of PTH 1 - 34 and PTH 1 - 84 in the management of osteoporosis is evaluated by reviewing published literature and presentations from scientific meetings through to 2010. This review focuses on data on fracture risk reduction and safety endpoints of PTH analogues. The adverse reactions reported most are nausea, pain in the extremities, headache and dizziness. Exogenous PTH analogues, given as daily subcutaneous injections, stimulate bone formation, increase bone mass and bone strength, and improve calcium balance. In postmenopausal women with osteoporosis, PTH analogues reduced the risk of vertebral (PTH 1 - 34 and PTH 1 - 84) and non-vertebral fractures (only PTH 1 - 34). In men and women with glucocorticosteroid-induced osteoporosis, PTH 1 - 34 reduced the risk of vertebral fractures. In general, PTH analogues are well tolerated with an acceptable safety profile: they can be used for the prevention and treatment of fractures in postmenopausal women with severe, established osteoporosis.

  20. Evaluation of microRNA-10b prognostic significance in a prospective cohort of breast cancer patients

    PubMed Central

    2014-01-01

    Background MicroRNA-10b (miR-10b) has a prominent role in regulating tumor invasion and metastasis by targeting the HOXD10 transcriptional repressor and has been found up-regulated in several tumor types. Methods We evaluated the expression of miR-10b in paired tumor and normal specimens obtained from a prospective cohort of breast cancer patients with at least 36 months follow-up enrolled according to the REMARK guidelines (n = 150). RNA quality was measured and only samples with RNA Integrity Number (RIN) ≥7.0 were analyzed. Results The relative expression of miR-10b in tumor as compared to its normal counterpart (RER) was determined by RT-qPCR. miR-10b RERs were higher in the subgroup of patients with synchronous metastases (n = 11, Median 0.25; IQR 0.11-1.02) as compared with patients without metastases (n = 90, Median 0.09; IQR 0.04-0.29) (p = 0.028). In the subgroup of patients without synchronous metastases (n = 90), higher miR-10b RERs were associated with increased risk of disease progression and death in both univariable (HR 1.16, p = 0.021 and HR 1.20, p = 0.015 respectively for 0.10 unitary increase of miR-10b RERs levels) and multivariable (HR1.30, p < 0.001, and HR 1.31, p = 0.003 respectively for 0.10 unitary increase of miR-10b RERs levels) Cox regression models. The addition of miR-10b RERs to the Nottingham Prognostic Index (NPI) provided an improvement in discrimination power and risk reclassification abilities for the clinical outcomes at 36 months. Survival C-indices significantly increased from 0.849 to 0.889 (p = 0.009) for OS and from 0.735 to 0.767 (p = 0.050) for DFS. Conclusions Our results provide evidences that the addition of miR-10b RERs to the prognostic factors used in clinical routine could improve the prediction abilities for both overall mortality and disease progression in breast cancer patients. PMID:24897960

  1. Analogue modelling of syntectonic leucosomes in migmatitic schists

    NASA Astrophysics Data System (ADS)

    Druguet, Elena; Carreras, Jordi

    2006-10-01

    Migmatites from the Cap de Creus tectonometamorphic belt display a wide variety of structures, from those formed when the leucosomes were melt-bearing, to those developed during solid-state deformation. The observed field structures have been modelled by means of analogue experiments. The materials used in the models are layered plasticine as a schist analogue, and chocolate as analogue of the crystallizing leucosome. A model for the development of syntectonic migmatites is proposed in which initial melt-bearing patches, preferentially formed within fertile pelitic layers, progressively evolve towards lens-shaped veins. Furthermore, heterogeneous deformation of anisotropic metasediments facilitates formation of extensional sites for further melt accumulation and transport. Melt crystallization implies a rapid increase in effective viscosity of leucosomes producing a reversal in competence contrast with respect to the enclosing schists. During the whole process, deformation localizes around crystallizing veins, giving rise to different and contrasting structures for melt-bearing and for solid-state stages.

  2. Thermal conductivity changes upon neutron transmutation of {sup 10}B doped diamond

    SciTech Connect

    Jagannadham, K.; Verghese, K.; Butler, J. E.

    2014-08-28

    {sup 10}B doped p-type diamond samples were subjected to neutron transmutation reaction using thermal neutron flux of 0.9 × 10{sup 13} cm{sup −2} s{sup −1} and fast neutron flux of 0.09 × 10{sup 13} cm{sup −2} s{sup −1}. Another sample of epilayer grown on type IIa (110) single crystal diamond substrate was subjected to equal thermal and fast neutron flux of 10{sup 14} cm{sup −2} s{sup −1}. The defects in the diamond samples were previously characterized by different methods. In the present work, thermal conductivity of these diamond samples was determined at room temperature by transient thermoreflectance method. The thermal conductivity change in the samples as a function of neutron fluence is explained by the phonon scattering from the point defects and disordered regions. The thermal conductivity of the diamond samples decreased more rapidly initially and less rapidly for larger neutron fluence. In addition, the thermal conductivity in type IIb diamond decreased less rapidly with thermal neutron fluence compared to the decrease in type IIa diamond subjected to fast neutron fluence. It is concluded that the rate of production of defects during transmutation reaction is slower when thermal neutrons are used. The thermal conductivity of epilayer of diamond subjected to high thermal and fast neutron fluence is associated with the covalent carbon network in the composite structure consisting of disordered carbon and sp{sup 2} bonded nanocrystalline regions.

  3. Pressor effects of tryptamine analogues.

    PubMed Central

    Bosin, T R; Hixson, E J; Maickel, R P

    1976-01-01

    1. Methylation of tryptamine in the 1-position had little effect on the potency of the drug as a pressor agent in the intact anaesthetized rat. 2. In contrast, substitution of a benzo[b]thiophene ring system for the indole ring decreased the pressor activity. 3. Pretreatment of the animals with reserpine reduced the pressor effect of tryptamine and its benzo[b]thiophene analogue while increasing the effect of the 1-methylindole analogue. 4. Pretreatment with phenoxybenzamine reduced the pressor effect of all three compounds. PMID:1252662

  4. Synthesis and antitumoral evaluation of indole alkaloid analogues containing an hexahydropyrrolo[1',2',3':1,9a,9]imidazo[1,2-a]indole skeleton.

    PubMed

    Ventosa-Andrés, Pilar; González-Vera, Juan A; Valdivielso, Angel M; Teresa García-López, M; Herranz, Rosario

    2008-10-15

    The scope of acid-mediated cyclative additions of electrophiles to tryptophan-derived alpha-amino nitriles for the synthesis of 10b-substituted-1,2,4,5,10b,10c-hexahydropyrrolo[1',2',3':1,9a,9]imidazo[1,2-a]indoles analogues of indole alkaloids has been studied. The results demonstrate the high potential of the methodology for the synthesis of 10b-bromo-derivatives, by bromination with NBS, 10b-allyl-derivatives, by bromo-allyl exchange, and 10b-prenyl-derivatives, by reaction with prenyl bromide in the presence of Mg(NO(3))(2).6H(2)0. Some of the new pyrroloimidazoindole derivatives displayed moderate microM cytotoxicities in human cancer cell lines and at 10 microg/mL inhibited more than 50% EGFR or HIF-1alpha.

  5. dTAF10- and dTAF10b-Containing Complexes Are Required for Ecdysone-Driven Larval-Pupal Morphogenesis in Drosophila melanogaster

    PubMed Central

    Pahi, Zoltan; Kiss, Zsuzsanna; Komonyi, Orbán; Borsos, Barbara N.; Tora, Laszlo; Boros, Imre M.; Pankotai, Tibor

    2015-01-01

    In eukaryotes the TFIID complex is required for preinitiation complex assembly which positions RNA polymerase II around transcription start sites. On the other hand, histone acetyltransferase complexes including SAGA and ATAC, modulate transcription at several steps through modification of specific core histone residues. In this study we investigated the function of Drosophila melanogaster proteins TAF10 and TAF10b, which are subunits of dTFIID and dSAGA, respectively. We generated a mutation which eliminated the production of both Drosophila TAF10 orthologues. The simultaneous deletion of both dTaf10 genes impaired the recruitment of the dTFIID subunit dTAF5 to polytene chromosomes, while binding of other TFIID subunits, dTAF1 and RNAPII was not affected. The lack of both dTAF10 proteins resulted in failures in the larval-pupal transition during metamorphosis and in transcriptional reprogramming at this developmental stage. Surprisingly, unlike dSAGA mutations, dATAC subunit mutations resulted in very similar changes in the steady state mRNA levels of approximately 5000 genes as did ablation of both dTaf10 genes, indicating that dTAF10- and/or dTAF10b-containing complexes and dATAC affect similar pathways. Importantly, the phenotype resulting from dTaf10+dTaf10b mutation could be rescued by ectopically added ecdysone, suggesting that dTAF10- and/or dTAF10b-containing complexes are involved in the expression of ecdysone biosynthetic genes. Indeed, in dTaf10+dTaf10b mutants, cytochrome genes, which regulate ecdysone synthesis in the ring gland, were underrepresented. Therefore our data support the idea that the presence of dTAF10 proteins in dTFIID and/or dSAGA is required only at specific developmental steps. We propose that distinct forms of dTFIID and/or dSAGA exist during Drosophila metamorphosis, wherein different TAF compositions serve to target RNAPII at different developmental stages and tissues. PMID:26556600

  6. Assessment of (10)B concentration in boron neutron capture therapy: potential of image-guided therapy using (18)FBPA PET.

    PubMed

    Shimosegawa, Eku; Isohashi, Kayako; Naka, Sadahiro; Horitsugi, Genki; Hatazawa, Jun

    2016-12-01

    In boron neutron capture therapy (BNCT) for cancer, the accurate estimation of (10)B tissue concentrations, especially in neighboring normal organs, is important to avoid adverse effects. The (10)B concentration in normal organs after loading with (10)B, however, has not been established in humans. In this study, we performed 4-borono-2-[(18)F]-fluoro-phenylalanine ((18)FBPA) PET in healthy volunteers and estimated the chronological changes in the (10)B concentrations of normal organs. In 6 healthy volunteers, whole-body (18)FBPA PET scans were repeated 7 times during 1 h, and the mean (18)FBPA distributions of 13 organs were measured. Based on the (18)FBPA PET data, we then estimated the changes in the (10)B concentrations of the organs when the injection of a therapeutic dose of (10)BPA-fructose complex ((10)BPA-fr; 30 g, 500 mg/kg body weight) was assumed. The maximum mean (18)FBPA concentrations were reached at 2-6 min after injection in all the organs except the brain and urinary bladder. The mean (18)FBPA concentration in normal brain plateaued at 24 min after injection. When the injection of a therapeutic dose of (10)BPA-fr was assumed, the estimated mean (10)B concentration in the kidney increased to 126.1 ± 24.2 ppm at 3 min after injection and then rapidly decreased to 30.9 ± 7.4 ppm at 53 min. The estimated mean (10)B concentration in the bladder gradually increased and reached 383.6 ± 214.7 ppm at 51 min. The mean (10)B concentration in the brain was estimated to be 7.6 ± 1.5 ppm at 57 min. (18)FBPA PET has a potential to estimate (10)B concentration of normal organs before neutron irradiation of BNCT when several assumptions are validated in the future studies.

  7. Effect of electroporation on cell killing by boron neutron capture therapy using borocaptate sodium (10B-BSH).

    PubMed

    Ono, K; Kinashi, Y; Masunaga, S; Suzuki, M; Takagaki, M

    1998-12-01

    The cell membrane permeability of 10B-enriched borocaptate sodium (BSH) and the extent to which BSH is accumulated in cells are controversial. To elucidate these points and to enhance the accumulation of BSH in cells, the effect of electroporation on boron neutron capture therapy (BNCT) using BSH was investigated. The first group of SCCVII tumor cells was incubated in culture medium with 10B-BSH or 10B-enriched boric acid, and exposed to neutrons from the heavy water facility of the Kyoto University Reactor. More than 99% of neutrons were thermal neutrons at flux base. The second group was pretreated with electroporation in combination with 10B-BSH, and thereafter the cells were irradiated with neutrons. The cell-killing effect of BNCT was measured by colony formation assay. The surviving cell fraction decreased exponentially with neutron fluence, and addition of BSH significantly enhanced the cell-killing effect of NCT depending on 10B concentration and the preincubation time of cells in the BSH-containing culture medium. The electroporation of cells with BSH markedly enhanced the BNCT effect in comparison with that obtained with preincubation alone. The effect of BSH-BNCT with electroporation was almost equal to that of BNCT using 10B-boric acid at the same 10B concentration. The effect of BNCT on cells pretreated with BSH and electroporation was not reduced by repeated washing of the cells before neutron irradiation. Decrease of the effect of BSH-BNCT plus electroporation with increase in the waiting time between the electroporation and the neutron irradiation could be explained in terms of the extent of cell growth during that time. These data suggest that BSH penetrates the cells slowly and remains after washing. Electroporation can introduce BSH into the cells very efficiently, and BSH thus introduced stays in the cells and is not lost in spite of the intensive washing of the cells. Therefore, if electroporation is applied to tumors after BSH injection, 10B

  8. The human nucleophosmin 1 mutation A inhibits myeloid differentiation of leukemia cells by modulating miR-10b

    PubMed Central

    Zou, Qin; Tan, Shi; Yang, Zailin; Wang, Juan; Xian, Jingrong; Zhang, Shuaishuai; Jin, Hongjun; Yang, Liyuan; Wang, Lu; Zhang, Ling

    2016-01-01

    Mutations in the nucleophosmin 1 (NPM1) gene are the most frequent genetic alteration in acute myeloid leukemia (AML). Here, we showed that enforced expression of NPM1 mutation type A (NPM1-mA) inhibits myeloid differentiation of leukemia cells, whereas knockdown of NPM1-mA has the opposite effect. Our analyses of normal karyotype AML samples from The Cancer Genome Atlas (TCGA) dataset revealed that miR-10b is commonly overexpressed in NPM1-mutated AMLs. We also found high expression of miR-10b in primary NPM1-mutated AML blasts and NPM1-mA positive OCI-AML3 cells. In addition, NPM1-mA knockdown enhanced myeloid differentiation, while induced expression of miR-10b reversed this effect. Finally, we showed that KLF4 is downregulated in NPM1-mutated AMLs. These results demonstrated that miR-10b exerts its effects by repressing the translation of KLF4 and that NPM1-mA inhibits myeloid differentiation through the miR-10b/KLF4 axis. This sheds new light on the effect of NPM1 mutations' on leukemogenesis. PMID:27669739

  9. Microstructure and magnetic viscosity of bulk amorphous Nd60Fe20Al5Co10B5 alloy

    NASA Astrophysics Data System (ADS)

    Tan, X. H.; Xu, H.; Man, H.; Tang, Y. J.; Yang, L. P.; Bai, Q.

    2011-04-01

    The microstructure and magnetic viscosity of bulk amorphous Nd60Fe20Al5Co10B5,prepared by suction casting the molten alloy into a copper mold under an argon atmosphere, have been investigated. The results show that clusters with size 3-5 nm are found to be embedded in the amorphous matrix of as-cast bulk amorphous Nd60Fe20Al5Co10B5 alloy. The Nd60Fe20Al5Co10B5 alloy shows hard magnetic behavior at room temperature, with an intrinsic coercivity of 360 kA/m and a remanence of 69.39 mT. The magnetic viscosity of bulk amorphous Nd60Fe20Al5Co10B5 has been investigated on the major hysteresis loop, and simple logarithmic time dependence is observed. A value for the fluctuation field of 8.24 kA/m is obtained. Analysis based on a Henkel plot is used to confirm the existence of magnetic interaction among clusters. The coercivity mechanism responsible for the hard magnetic behavior of bulk amorphous Nd60Fe20Al5Co10B5 alloy is also discussed.

  10. Probing the Statistical Decay and α-clustering effects in 12C + 12C and 14N + 10B reactions

    NASA Astrophysics Data System (ADS)

    Morelli, L.; Baiocco, G.; D'Agostino, M.; Bruno, M.; Gulminelli, F.; Cinausero, M.; Degerlier, M.; Fabris, D.; Gramegna, F.; Marchi, T.; Barlini, S.; Bini, M.; Casini, G.; Gelli, N.; Lopez, A.; Pasquali, G.; Piantelli, S.; Valdrè, S.

    2014-03-01

    An experimental campaign has been undertaken at Laboratori Nazionali di Legnaro (LNL INFN), Italy, in order to progress in our understanding of the statistical properties of light nuclei at excitation energies above particle emission threshold, by measuring exclusive data from fusion-evaporation reactions. On the experimental side, a first reaction: 12C+12C at 95 MeV beam energy has been measured, using the GARFIELD + Ring Counter (RCo) apparatuses. Fusion-evaporation events have been exclusively selected out of the entire data set. The comparison to a dedicated Hauser-Feshbach calculation allows us to give constraints on the nuclear level density at high excitation energy for light systems ranging from C up to Mg. Out-of-equilibrium aα emission has been evidenced and attributed both to an entrance channel effect (favoured by the cluster nature of reaction partners), and, in more dissipative events, to the persistence of cluster correlations well above the 24Mg threshold for 6 α's decay. In order to study the same 24Mg compound nucleus at similar excitation energy with respect to this first reaction a new measurement, 14N + 10B at 5.7 A.MeV, was performed at LNL laboratories with the same experimental setup. The comparison between the two systems would allow us to further constrain the level density of light nuclei in the mass-excitation energy range of interest. In this perspective, deviations from a statistical behaviour can be used as a tool to get information on nuclear clustering, both in the ground-state for projectile and target and in the hot source formed in the collision.

  11. Prompt gamma neutron activation analysis of 10B and Gd in biological samples at the MEPhI reactor.

    PubMed

    Khokhlov, V F; Zaitsev, K N; Beliayev, V N; Kulakov, V N; Lipengolts, A A; Portnov, A A

    2009-07-01

    The purpose of the work was to build a prompt gamma neutron activation analysis (PGNAA) facility at the MEPhI reactor for analyzing the content of various elements for NCT. The facility was implemented on a monochromatic neutron beam. Methods of quantitative (10)B and Gd measurement have been developed for pharmacokinetic studies. The facility is capable of measuring 1 microg of (10)B and 10 microg of Gd in biological samples with an error less than 10%. The detection limit of the facility is 0.3 microg of (10)B and 2 microg of Gd. Neutron flux attenuation within biological tissue samples was estimated and a new system for determining the elemental concentration was suggested.

  12. Fluorescence Studies Of A Cholesterol-Analogue Probe

    NASA Astrophysics Data System (ADS)

    Drew, Jacinta; Szabo, Arthur G.; Morand, Peter

    1988-06-01

    A novel cholesterol-analogue probe1,2 with a diene-(2-naphthyl) fluorophore in the sidechain (Figure 1), hereafter referred to as DN-Chol, has had its steady-state and time-resolved fluorescence properties characterized in solvents and in various viscosity mineral oils.

  13. Reduction of TIP30 in esophageal squamous cell carcinoma cells involves promoter methylation and microRNA-10b

    SciTech Connect

    Dong, Wenjie; Shen, Ruizhe; Cheng, Shidan

    2014-10-31

    Highlights: • TIP30 expression is frequently suppressed in ESCC. • TIP30 was hypermethylated in ESCC. • Reduction of TIP30 was significantly correlated with LN metastasis. • miR-10b is a direct regulator of TIP30. - Abstract: TIP30 is a putative tumor suppressor that can promote apoptosis and inhibit angiogenesis. However, the role of TIP30 in esophageal squamous cell carcinoma (ESCC) biology has not been investigated. Immunohistochemistry was used to investigate the expression of TIP30 in 70 ESCC. Hypermethylation of TIP30 was evaluated by the methylation specific PCR (MSP) method in ESCC (tumor and paired adjacent non-tumor tissues). Lost expression of TIP30 was observed in 50 of 70 (71.4%) ESCC. 61.4% (43 of 70) of primary tumors analyzed displayed TIP30 hypermethylation, indicating that this aberrant characteristic is common in ESCC. Moreover, a statistically significant inverse association was found between TIP30 methylation status and expression of the TIP30 protein in tumor tissues (p = 0.001). We also found that microRNA-10b (miR-10b) targets a homologous DNA region in the 3′untranslated region of the TIP30 gene and represses its expression at the transcriptional level. Reporter assay with 3′UTR of TIP30 cloned downstream of the luciferase gene showed reduced luciferase activity in the presence of miR-10b, providing strong evidence that miR-10b is a direct regulator of TIP30. These results suggest that TIP30 expression is regulated by promoter methylation and miR-10b in ESCC.

  14. Structural Insights into the Specificity of Xyn10B from Paenibacillus barcinonensis and Its Improved Stability by Forced Protein Evolution*

    PubMed Central

    Gallardo, Óscar; Pastor, F. I. Javier; Polaina, Julio; Diaz, Pilar; Łysek, Robert; Vogel, Pierre; Isorna, Pablo; González, Beatriz; Sanz-Aparicio, Julia

    2010-01-01

    Paenibacillus barcinonensis is a soil bacterium bearing a complex set of enzymes for xylan degradation, including several secreted enzymes and Xyn10B, one of the few intracellular xylanases reported to date. The crystal structure of Xyn10B has been determined by x-ray analysis. The enzyme folds into the typical (β/α)8 barrel of family 10 glycosyl hydrolases (GH10), with additional secondary structure elements within the β/α motifs. One of these loops -L7- located at the β7 C terminus, was essential for xylanase activity as its partial deletion yielded an inactive enzyme. The loop contains residues His249–Glu250, which shape a pocket opened to solvent in close proximity to the +2 subsite, which has not been described in other GH10 enzymes. This wide cavity at the +2 subsite, where methyl-2,4-pentanediol from the crystallization medium was found, is a noteworthy feature of Xyn10B, as compared with the narrow crevice described for other GH10 xylanases. Docking analysis showed that this open cavity can accommodate glucuronic acid decorations of xylo-oligosaccharides. Co-crystallization experiments with conduramine derivative inhibitors supported the importance of this open cavity at the +2 subsite for Xyn10B activity. Several mutant derivatives of Xyn10B with improved thermal stability were obtained by forced evolution. Among them, mutant xylanases S15L and M93V showed increased half-life, whereas the double mutant S15L/M93V exhibited a further increase in stability, showing a 20-fold higher heat resistance than the wild type xylanase. All the mutations obtained were located on the surface of Xyn10B. Replacement of a Ser by a Leu residue in mutant xylanase S15L can increase hydrophobic packing efficiency and fill a superficial indentation of the protein, giving rise to a more compact structure of the enzyme. PMID:19940147

  15. Acute CNS syndrome from /sup 10/B(n,. cap alpha. )/sup 7/Li irradiation of mouse brain

    SciTech Connect

    Slatkin, D.N.; Stoner, R.D.; Rosander, K.M.; Kalef-Ezra, J.K.; Laissue, J.A.

    1986-01-01

    The purpose of this study is to compare absorbed doses of /sup 10/B-neutron capture radiation and x radiation in the brains of head-exposed, body-shielded mice, at LD/sub 50/ for acute (<4 days post exposure) mortality from the central nervous system (CNS) radiation syndrome. This comparison leads to an estimate of the in vivo relative biological effectiveness (RBE) of heavy particle radiation (helium and lithium ions) from the /sup 10/B(n,..cap alpha..)/sup 7/Li nuclear reaction.

  16. Insulin resistance via modification of PGC1α function identifying a possible preventive role of vitamin D analogues in chronic inflammatory state of obesity. A double blind clinical trial study.

    PubMed

    Mirzaei, K; Hossein-Nezhad, A; Keshavarz, S A; Eshaghi, S M; Koohdani, F; Saboor-Yaraghi, A A; Hosseini, S; Tootee, A; Djalali, M

    2014-02-01

    Obesity-induced chronic inflammation is a key component of the pathogenesis of insulin resistance. Mounting evidence has demonstrated anti-inflammatory characteristics for vitamin D. Although analogues of vitamin D3 have extensively been used in the treatment of various chronic inflammatory diseases, to our knowledge, no such research is conducted in regards with obesity. The aim of this double blind clinical trial study is to investigate whether alphacalcidol treatment in obese subjects can affect the cytokine profile and insulin resistance. Moreover, we evaluated the pathways of vitamin D receptor (VDR), PPARγ and PGC1α gene expressions which may lead to insulin resistance following treatment with either alphacalcidol or placebo. A total of 94 obese participants (BMI≥30) were recruited for the current double blind clinical trial study. Patients were divided into two intervention (N.=40) and control groups (N.=54) based on the stratified randomized method. One-Alpha® Capsules 1 microgram: alfacalcidol (1-α hydroxyvitamin D3) and placebo were given to subjects once a day for 8 weeks. Analysis of body composition was performed with use of Body Composition Analyzer. The circulating levels of TNF-α, IL-1β, IL-4, IL-6, IL-10, IL-13, IL-17, PTH, and 25-Hydroxy Vi-tamin D were measured with the use of EIA method. The PBMCs were separated from whole blood by Ficoll-hypaque technique. Total cellular RNA was extracted and the cDNA was synthesized. The real-time PCR using specific primer pairs for VDR, PGC1α, PPARγ, and β-actin was performed. The FPG, fat percent and PTH levels were decreased and the levels of HDL-cholesterol and 25-hydroxy vitamin D were significantly increased after treatment with Alfacalcidol. Regarding to cytokines levels, the levels of IL6 were significantly decreased and IL10 were significantly increased in Alfacalcidol group in comparison with the control group. The relative expressions of VDR, PGC1α, and PPARγ genes significantly

  17. Farnesyl Diphosphate Analogues with Aryl Moieties are Efficient Alternate Substrates for Protein Farnesyltransferase

    PubMed Central

    Subramanian, Thangaiah; Pais, June E.; Liu, Suxia; Troutman, Jerry M.; Suzuki, Yuta; Subramanian, Karunai Leela; Fierke, Carol; Andres, Douglas A.; Spielmann, H. Peter

    2012-01-01

    Farnesylation is an important post-translational modification essential for proper localization and function of many proteins. Transfer of the farnesyl group from farnesyl diphosphate (FPP) to proteins is catalyzed by protein farnesyltransferase (FTase). We employed a library of FPP analogues with a range of aryl groups substituting for individual isoprene moieties to examine some of the structural and electronic properties of analogue transfer to peptide catalyzed by FTase. Analysis of steady-state kinetics for modification of peptide substrates revealed that the multiple turnover activity depends on the analogue structure. Analogues where the first isoprene is replaced by a benzyl group and an analogue where each isoprene is replaced by an aryl group are good substrates. In sharp contrast with the steady-state reaction, the single turnover rate constant for dansyl-GCVLS alkylation was found to be the same for all analogues, despite the increased chemical reactivity of the benzyl analogues and the increased steric bulk of other analogues. However, the single turnover rate constant for alkylation does depend on the Ca1a2X peptide sequence. These results suggest that the isoprenoid transition state conformation is preferred over the inactive E•FPP• Ca1a2X ternary complex conformation. Furthermore, these data suggest that the farnesyl binding site in the exit groove may be significantly more selective for the farnesyl diphosphate substrate than the active site binding pocket and therefore might be a useful site for design of novel inhibitors. PMID:22989235

  18. Review of Insulin and its Analogues in Diabetes Mellitus

    PubMed Central

    Mane, Krishnappa; Chaluvaraju, KC; Niranjan, MS; Zaranappa, TR; Manjuthej, TR

    2012-01-01

    Diabetes is a metabolic disorder where in human body does not produce or properly uses insulin, a hormone that is required to convert sugar, starches and other food into energy. Diabetes finally leads to more complications and to prevent these complications insulin and its analogues are used. After more than half a century of treating diabetics with animal insulin’s, recombinant DNA technologies and advanced protein chemistry made human insulin preparations available in the early 1980s. As the next step, over the last decade, insulin analogues were constructed by changing the structure of the native protein with the goal of improving the therapeutic properties of it, because the pharmacokinetic characteristics of rapid, intermediate and long-acting preparations of human insulin make it almost impossible to achieve sustained normoglycemia. The first clinically available insulin analogue, lispro, confirmed the hopes by showing that improved glycaemic control can be achieved without an increase in hypoglycaemic events. Two new insulin analogues, insulin glargine and insulin aspart, have recently been approved for clinical use in the United States and several other analogues are being intensively tested. PMID:24826038

  19. The Trp53-Trp53inp1-Tnfrsf10b Pathway Regulates the Radiation Response of Mouse Spermatogonial Stem Cells

    PubMed Central

    Ishii, Kei; Ishiai, Masamichi; Morimoto, Hiroko; Kanatsu-Shinohara, Mito; Niwa, Ohtsura; Takata, Minoru; Shinohara, Takashi

    2014-01-01

    Summary Germ cells are thought to exhibit a unique DNA damage response that differs from that of somatic stem cells, and previous studies suggested that Trp53 is not involved in the survival of spermatogonial stem cells (SSCs) after irradiation. Here, we report a critical role for the Trp53-Trp53inp1-Tnfrsf10b pathway during radiation-induced SSC apoptosis. Spermatogonial transplantation revealed that Trp53 deficiency increased the survival of SSCs after irradiation. Although Bbc3, a member of the intrinsic apoptotic pathway, was implicated in apoptosis of germ and somatic stem cells, Bbc3 depletion inhibited apoptosis in committed spermatogonia, but not in SSCs. In contrast, inhibition of Tnfrsf10b, an extrinsic apoptosis regulator, rescued SSCs. Tnfrsf10b, whose deficiency protected SSCs, was upregulated by Trp53inp1 upon irradiation. These results suggest that the Trp53-Trp53inp1-Tnfrsf10b pathway responds to genotoxic damage in SSCs and that stem and progenitor cells exhibit distinct DNA damage responses in self-renewing tissue. PMID:25358794

  20. miR-10b*, a master inhibitor of the cell cycle, is down-regulated in human breast tumours.

    PubMed

    Biagioni, Francesca; Bossel Ben-Moshe, Noa; Fontemaggi, Giulia; Canu, Valeria; Mori, Federica; Antoniani, Barbara; Di Benedetto, Anna; Santoro, Raffaela; Germoni, Sabrina; De Angelis, Fernanda; Cambria, Anna; Avraham, Roi; Grasso, Giuseppe; Strano, Sabrina; Muti, Paola; Mottolese, Marcella; Yarden, Yosef; Domany, Eytan; Blandino, Giovanni

    2012-11-01

    Deregulated proliferation is a hallmark of cancer cells. Here, we show that microRNA-10b* is a master regulator of breast cancer cell proliferation and is downregulated in tumoural samples versus matched peritumoural counterparts. Two canonical CpG islands (5 kb) upstream from the precursor sequence are hypermethylated in the analysed breast cancer tissues. Ectopic delivery of synthetic microRNA-10b* in breast cancer cell lines or into xenograft mouse breast tumours inhibits cell proliferation and impairs tumour growth in vivo, respectively. We identified and validated in vitro and in vivo three novel target mRNAs of miR-10b* (BUB1, PLK1 and CCNA2), which play a remarkable role in cell cycle regulation and whose high expression in breast cancer patients is associated with reduced disease-free survival, relapse-free survival and metastasis-free survival when compared to patients with low expression. This also suggests that restoration of microRNA-10b* expression might have therapeutic promise.

  1. miR-10b*, a master inhibitor of the cell cycle, is down-regulated in human breast tumours

    PubMed Central

    Biagioni, Francesca; Bossel Ben-Moshe, Noa; Fontemaggi, Giulia; Canu, Valeria; Mori, Federica; Antoniani, Barbara; Di Benedetto, Anna; Santoro, Raffaela; Germoni, Sabrina; De Angelis, Fernanda; Cambria, Anna; Avraham, Roi; Grasso, Giuseppe; Strano, Sabrina; Muti, Paola; Mottolese, Marcella; Yarden, Yosef; Domany, Eytan; Blandino, Giovanni

    2012-01-01

    Deregulated proliferation is a hallmark of cancer cells. Here, we show that microRNA-10b* is a master regulator of breast cancer cell proliferation and is downregulated in tumoural samples versus matched peritumoural counterparts. Two canonical CpG islands (5 kb) upstream from the precursor sequence are hypermethylated in the analysed breast cancer tissues. Ectopic delivery of synthetic microRNA-10b* in breast cancer cell lines or into xenograft mouse breast tumours inhibits cell proliferation and impairs tumour growth in vivo, respectively. We identified and validated in vitro and in vivo three novel target mRNAs of miR-10b* (BUB1, PLK1 and CCNA2), which play a remarkable role in cell cycle regulation and whose high expression in breast cancer patients is associated with reduced disease-free survival, relapse-free survival and metastasis-free survival when compared to patients with low expression. This also suggests that restoration of microRNA-10b* expression might have therapeutic promise. PMID:23125021

  2. Uptake of [sup 10]B in gliosarcomas following the injection of gluthathione monoethyl ester and sulfhydryl borane

    SciTech Connect

    Joel, D.D.; Slatkin, D.N.; Coderre, J.A.

    1992-01-01

    The sulfhydryl borane Na[sub 2][sup 10]B[sub 12]H[sub 11]SH (BSH) was developed as a capture agent for BNCT about 20 years ago and is the compound currently used clinically in Japan for BNCT of malignant brain tumors. Tumor [sup 10]B concentrations following the infusion of the oxidized BSH, a disulfide dimer (Na[sub 4][sup 10]B[sub 24]H[sub 22]S[sub 2]), are nearly twice those obtained following administration of equal amounts of boron as BSH. Also, the rate of decrease of tumor [sup 10]B concentration is slower after dimer infusion than after BSH infusion. When BNCT was administered to rats bearing intracerebral gliosarcomas, the animals infused with dimer had a significant longer median survival time. Dimer, on the other hand, induces a moderately severe, but reversible, hepatotoxicity which may complicate its use in humans. Intracellular glutathione plays an important role in defense against radical-mediated tissue injury. Glutathione monoesters have been reported to have a protective effective on cisplatin toxicity and on radical-induced acute pancreatitis. We investigated the possibility of reducing dimer-induced hepatotoxicity by pre-administration of GSH-ME. The results indicate that not only does the pre-administration of GSH-ME markedly reduce dimer-induced hepatotoxicity, but also results in nearly a doubling of tumor boron concentration. Furthermore, GSH-ME markedly increases tumor boron uptake and retention following administration of BSH.

  3. Uptake of {sup 10}B in gliosarcomas following the injection of gluthathione monoethyl ester and sulfhydryl borane

    SciTech Connect

    Joel, D.D.; Slatkin, D.N.; Coderre, J.A.

    1992-12-31

    The sulfhydryl borane Na{sub 2}{sup 10}B{sub 12}H{sub 11}SH (BSH) was developed as a capture agent for BNCT about 20 years ago and is the compound currently used clinically in Japan for BNCT of malignant brain tumors. Tumor {sup 10}B concentrations following the infusion of the oxidized BSH, a disulfide dimer (Na{sub 4}{sup 10}B{sub 24}H{sub 22}S{sub 2}), are nearly twice those obtained following administration of equal amounts of boron as BSH. Also, the rate of decrease of tumor {sup 10}B concentration is slower after dimer infusion than after BSH infusion. When BNCT was administered to rats bearing intracerebral gliosarcomas, the animals infused with dimer had a significant longer median survival time. Dimer, on the other hand, induces a moderately severe, but reversible, hepatotoxicity which may complicate its use in humans. Intracellular glutathione plays an important role in defense against radical-mediated tissue injury. Glutathione monoesters have been reported to have a protective effective on cisplatin toxicity and on radical-induced acute pancreatitis. We investigated the possibility of reducing dimer-induced hepatotoxicity by pre-administration of GSH-ME. The results indicate that not only does the pre-administration of GSH-ME markedly reduce dimer-induced hepatotoxicity, but also results in nearly a doubling of tumor boron concentration. Furthermore, GSH-ME markedly increases tumor boron uptake and retention following administration of BSH.

  4. 75 FR 52344 - Sinicway International Logistics Ltd. Possible Violations of Sections 10(A)(1) and 10(B)(2) of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-25

    ... [Federal Register Volume 75, Number 164 (Wednesday, August 25, 2010)] [Notices] [Pages 52344-52345] [FR Doc No: 2010-21172] FEDERAL MARITIME COMMISSION [Docket No. 10-09] Sinicway International Logistics Ltd. Possible Violations of Sections 10(A)(1) and 10(B)(2) of the Shipping Act of 1984; Order...

  5. 76 FR 18761 - Worldwide Logistics Co., Ltd.; Possible Violations of Sections 10(a)(1) and 10(b)(2) of the...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-05

    ... From the Federal Register Online via the Government Publishing Office FEDERAL MARITIME COMMISSION Worldwide Logistics Co., Ltd.; Possible Violations of Sections 10(a)(1) and 10(b)(2) of the Shipping Act of 1984; Order of Investigation and Hearing Worldwide Logistics Co., Ltd. (Worldwide) is a company...

  6. 17 CFR 240.10b-18 - Purchases of certain equity securities by the issuer and others.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... harbor” from liability for manipulation under sections 9(a)(2) of the Act and § 240.10b-5 under the Act...). (a) Definitions. Unless otherwise provided, all terms used in this section shall have the same meaning as in the Act. In addition, the following definitions shall apply: (1) ADTV means the...

  7. 17 CFR 240.10b-18 - Purchases of certain equity securities by the issuer and others.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... harbor” from liability for manipulation under sections 9(a)(2) of the Act and § 240.10b-5 under the Act...). (a) Definitions. Unless otherwise provided, all terms used in this section shall have the same meaning as in the Act. In addition, the following definitions shall apply: (1) ADTV means the...

  8. 17 CFR 240.10b-18 - Purchases of certain equity securities by the issuer and others.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... harbor” from liability for manipulation under sections 9(a)(2) of the Act and § 240.10b-5 under the Act...). (a) Definitions. Unless otherwise provided, all terms used in this section shall have the same meaning as in the Act. In addition, the following definitions shall apply: (1) ADTV means the...

  9. 17 CFR 240.10b-18 - Purchases of certain equity securities by the issuer and others.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... harbor” from liability for manipulation under sections 9(a)(2) of the Act and § 240.10b-5 under the Act...). (a) Definitions. Unless otherwise provided, all terms used in this section shall have the same meaning as in the Act. In addition, the following definitions shall apply: (1) ADTV means the...

  10. Two-dimensional combinatorial screening enables the bottom-up design of a microRNA-10b inhibitor.

    PubMed

    Velagapudi, Sai Pradeep; Disney, Matthew D

    2014-03-21

    The RNA motifs that bind guanidinylated kanamycin A (G Kan A) and guanidinylated neomycin B (G Neo B) were identified via two-dimensional combinatorial screening (2DCS). The results of these studies enabled the "bottom-up" design of a small molecule inhibitor of oncogenic microRNA-10b.

  11. Resonances in (11)C observed in the (4)He((7)Be, alpha)(7)Be and (4)He((7)Be, p)(10)B reactions

    SciTech Connect

    Freer, M.; Ashwood, N. I.; Curtis, N.; Malcolm, J.; Munoz-Britton, T.; Price, D.; Wheldon, C.; Achouri, N. L.; Demaret, P.; Bardayan, Daniel W; Pain, Steven D; Brown, S.; Catford, W.; Harlin, Christopher W; Thomas, J. S.; Wilson, G.; Chipps, K.; Milin, M.; Raabe, R.; Soic, N.

    2012-01-01

    Measurements of the {sup 4}He({sup 7}Be,{alpha}){sup 7}Be and {sup 4}He({sup 7}Be,p){sup 10}B reactions were performed using {sup 7}Be beam energies of 7.1 and 23 MeV and a helium-4 target, employing the thick target technique. Resonances were observed between E{sub x}({sup 11}C) = 8.6 to 13.8 MeV. An R-matrix analysis was performed to characterize the spins and partial widths. This analysis showed that the observed sequence of states was consistent with that found for {sup 7}Li + {alpha} resonant scattering populating resonances in {sup 11}B. A comparison of the proposed partial widths for decay with the Wigner limit indicates that several of the states are associated with cluster-like structures.

  12. 10B+ZnS(Ag) as an alternative to 3He-based detectors for Radiation Portal Monitors

    NASA Astrophysics Data System (ADS)

    Guzman-Garcia, Karen Arlet; Vega-Carrillo, Hector Rene; Gallego, Eduardo; Gonzalez-Gonzalez, Juan Antonio; Lorente, Alfredo; Ibañez-Fernandez, Sviatoslav

    2017-09-01

    Typical radiation portal monitor systems, RPM, deployed to detect illicit trafficking of radioactive materials include a set of gamma-ray detectors and neutron detectors. Usually the employed neutron detectors are pressurized 3He-based neutron detectors tubes. Due the shortage of 3He reported since 2009, the amount of 3He available for use in gas proportional counter neutron detectors has become limited, while the demand has significantly increased, especially for homeland security applications. For this reason, many different alternatives are being investigated for its use in RPM systems. The aim of this work is to study a scintillation detector ZnS(Ag) mixed with highly enriched 10B, 10B+ZnS(Ag). Using Monte Carlo methods, MCNPX code, the response of two neutron detectors based on 10B+ZnS(Ag), manufactured by BridgePort Instruments LLC with different geometries, were estimated by calculating the number of 10B(n,α)7 Li reactions for 29 monoenergetic neutron sources. Measurements and models were made, and both detectors were compared. The importance of the distance with respect to the ground was studied. The response with a 252Cf moderated neutron source (0.5 cm lead and 2.5 cm polyethylene) was calculated in order to compare with other studied alternatives in the USA by Pacific National Northwest Laboratory, PNNL. With these results we conclude that neutron detectors using 10B+ZnS(Ag) are an interesting alternative for replacing 3He detectors. From the analysis with MCNPX we propose an improvement in the detector design.

  13. LaBr3γ-ray spectrometer for detecting 10B in debris of melted nuclear fuel

    NASA Astrophysics Data System (ADS)

    Koizumi, Mitsuo; Tsuchiya, Harufumi; Kitatani, Fumito; Harada, Hideo; Heyse, Jan; Kopecky, Stefan; Mondelaers, Willy; Paradela, Carlos; Schillebeeckx, Peter

    2016-11-01

    Neutron resonance densitometry has been proposed as a nondestructive analytical method for quantifying special nuclear material (SNM) in the rock- and particle-like debris that is to be removed from the Fukushima Daiichi nuclear power plant. The method is based on neutron resonance transmission analysis (NRTA) and neutron resonance capture analysis combined with prompt-γ-ray analysis (NRCA/PGA). Although quantification of SNM will predominantly rely on NRTA, this will be hampered by the presence of strong neutron-absorbing matrix materials, in particular 10B. Results obtained with NRCA/PGA are used to improve the interpretation of NRTA data. Prompt γ rays originating from the 10B(n, αγ) reaction are used to assess the amount of 10B. The 478 keV γ rays from 10B, however, need to be measured under a high-radiation environment, especially because of 137Cs. To meet this requirement, we developed a well-shaped γ-ray spectrometer consisting of one cylindrical and four rectangular-cuboid LaBr3 scintillators combined with a fast data-acquisition system. Furthermore, to improve the gain stability of the main detector, a special high-voltage divider was developed. Because of the reduction in gain shift, a 3.8% resolution at 662 keV was obtained for long-term measurements. By using the data-acquisition system, which consists of eight 250 MHz digitizers, input signals of over 500 kHz per channel were recorded. The work reported herein demonstrates that, with such a spectrometer, the impact of the Compton edge of 662 keV γ rays from 137Cs is significantly reduced, which allows the 10B amount to be determined with greater sensitivity.

  14. Search for the isovector monopole resonance via the 28Si(10Be,10B+ γ)28Al reaction

    NASA Astrophysics Data System (ADS)

    Scott, Michael; e11021 Collaboration Team

    2013-10-01

    The isovector giant monopole resonance (IVGMR) is a fundamental mode of collective oscillation in which the neutron and proton fluids in a nucleus radially expand and contract in an out-of-phase manner. Observation of the IVGMR has been difficult due to the lack of a probe that will excite only its non-spin-flip (ΔS = 0) transitions. The IVGMR's spin-transfer (ΔS = 1) counterpart, the isovector spin giant monopole resonance, is much more strongly excited at bombarding energies higher than 60 MeV/ u. By way of the (10Be,10B+ γ) charge-exchange reaction, the selectivity for the excitation of the IVGMR can be gained. In this probe, the superallowed Fermi transition 10Be(0+,g.s.) -->10B(01+,1.74 MeV, T = 1) allows a nearly pure isolation of the ΔS = 0 component by detecting the 1022 keV gamma rays from the deexcitation of the 10B. We measured the double differential cross sections for the 28Si(10Be,10B+ γ) reaction at 100 MeV/ u using the large acceptance S800 Spectrometer at the National Superconducting Cyclotron Laboratory with the GRETINA array detecting the gamma rays emitted from the 10B ejectile. In this presentation, we will report preliminary reults of the IVGMR in 28Al. GRETINA was funded by the US DOE - Office of Science. Operation of the array at NSCL is supported by NSF under Cooperative Agreement PHY-1102511(NSCL) and DOE under grant DE-AC02-05CH11231(LBNL).

  15. Neuronal Analogues of Conditioning Paradigms

    DTIC Science & Technology

    1984-04-24

    Although the mechanisms of interneuronal communication have been well established, the changes underlying most forms of learning have thus far eluded...stimulating electrodes on one of the connectives was adjusted so as to produce a small excitatory postsynaptic potential ( EPSP ) in the impaled cell...two stimuli would constitute a neuronal analogue of conditioning by producing an increased EPSP in response to the test stimulus alone. If so, then

  16. Desferrithiocin Analogue Uranium Decorporation Agents

    PubMed Central

    Bergeron, Raymond J.; Wiegand, Jan; Singh, Shailendra

    2010-01-01

    Purpose Previous systematic structure-activity studies of the desferrithiocin (DFT) platform have allowed the design and synthesis of analogues and derivatives of DFT that retain the exceptional iron-clearing activity of the parent, while eliminating its adverse effects. We hypothesized that a similar approach could be adopted to identify DFT-related analogues that could effectively decorporate uranium. Materials and Methods The decorporation properties of nine DFT-related analogues were determined in a bile duct-cannulated rat model. Diethylenetriaminepentaacetic acid (DTPA) served as a positive control. Selected ligands also underwent multiple and delayed dosing regimens. Uranium excretion in urine and bile or stool was determined by inductively coupled plasma mass spectroscopy (ICP-MS); tissue levels of uranium were also assessed. Results The two best clinical candidates are (S)-4,5-dihydro-2-[2-hydroxy-4-(3,6,9-trioxadecyloxy)phenyl]-4-methyl-4-thiazolecarboxylic acid [(S)-4'-(HO)-DADFT-PE (9)], with a 57% reduction in kidney uranium levels on oral (p.o.) administration and (S)-4,5-dihydro-2-[2-hydroxy-3-(3,6,9-trioxadecyloxy)phenyl]-4-methyl-4-thiazolecarboxylic acid [(S)-3'-(HO)-DADFT-PE (10)], with a 62% renal reduction on p.o. administration. The majority of the metal excretion promoted by these analogues is in the bile, thus further reducing kidney actinide exposure. Conclusions While 9 administered p.o. or subcutaneously (s.c.) immediately post-metal is an effective decorporation agent, withholding the dose (s.c.) until 4 h reduced the activity of the compound. Conversion of 9 to its isopropyl ester may circumvent this issue. PMID:19399680

  17. Slip dynamics in an analogue faultzone

    NASA Astrophysics Data System (ADS)

    Rudolf, Michael; Rosenau, Matthias; Oncken, Onno

    2017-04-01

    Elastic stress in the lithosphere releases through slip along pre-existing planes of weakness (fault zones). Slip events may occur on many spatial and temporal scales. They range from short-term localised seismic slip (earthquakes) to aseismic slip transients and long-term distributed slip in cataclastic or ductile shear zones. The interplay of seismic and aseismic fault slip is poorly understood, potentially complex and very costly to model numerically. Therefore, we designed an analogue experiment using a rate-and-state frictional material (fused glass beads), that shows unstable (seismic) and stable (aseismic) slip. This is embedded in an elastic material (ballistic gelatin) that models upper crustal elastic rebound. In the analogue model presented here, we examine the influence of multiple parameters on the slip dynamics and overall statistics of ruptures within a glass bead shear zone. We use a customised rotary shear apparatus (Schulze ring-shear tester) to monitor shear stress during shear. The apparatus allows a direct control of shear rate and normal stress. Its transparent lid enables concurrent monitoring of the frictional contact surface. Digital image correlation is used to measure on-fault deformation. Because of the rate-and-state frictional properties of glass beads (a-b = -0.0138), the used setup produces regular stick-slip events under certain normal loading and strain rate conditions. Preliminary analysis shows the following: The events feature statistics similar to natural slip systems, i.e. a magnitude distribution similar to single faults. Estimated moment magnitudes of the laboratory earthquakes range from MW = -7 to -6. A Gutenberg-Richter like decay up to a certain corner magnitude followed by a characteristic peak is observable. With decreasing loading rate the recurrence time and size of events increase exponentially with exponents similar to natural events. Rupture dynamics are characterised by a transition from two-dimensional crack

  18. Substrate analogues for isoprenoid enzymes

    SciTech Connect

    Stremler, K.E.

    1987-01-01

    Diphosphonate analogues of geranyl diphosphate, resistant to degradation by phosphatases, were found to be alternate substrates for the reaction with farnesyl diphosphate synthetase isolated from avian liver. The difluoromethane analogue was shown to be the better alternate substrate, in agreement with solvolysis results which indicate that the electronegativity of the difluoromethylene unit more closely approximates that of the normal bridging oxygen. The usefulness of the C/sub 10/ difluoro analogue, for detecting low levels of isoprenoid enzymes in the presence of high levels of phosphatase activity, was demonstrated with a cell-free preparation from lemon peel. A series of C/sub 5/ through C/sub 15/ homoallylic and allylic diphosphonates, as well as two 5'-nucleotide diphosphonates, was prepared in high overall yield using the activation-displacement sequence. Radiolabeled samples of several of the allylic diphosphonates were prepared with tritium located at C1. A series of geraniols, stereospecifically deuterated at C1, was prepared. The enantiomeric purities and absolute configurations were determined by derivatization as the mandelate esters for analysis by /sup 1/H NMR. The stereochemistry of the activation-displacement sequence was examined using C1-deuterated substrates.

  19. Study of the nucleon radiative captures 8Li(n,γ)9Li, 9Be(p,γ)10B, 10Be(n,γ)11Be, 10B(p,γ)11C, and 16O(p,γ)17F at thermal and astrophysical energies

    NASA Astrophysics Data System (ADS)

    Dubovichenko, Sergey; Dzhazairov-Kakhramanov, Albert

    We have studied the neutron-capture reactions 8Li(n,γ)9Li and its role in the primordial nucleosynthesis. The n +8Li →9Li + γ reaction has a significant astrophysical interest because it includes one of the variants of chain of primordial nucleosynthesis processes of the Universe and thermonuclear reactions in type II supernovae. Furthermore, we consider the 9Be(p,γ)10B reaction in the astrophysical energy range in the modified potential cluster model (MPCM) with splitting of orbital states according to Young tableaux and, in some cases, with forbidden states (FS). The reaction 9Be(p,γ)10B plays an important role in primordial and stellar nucleosynthesis of light elements in the p shell. Hydrogen burning in second-generation stars occurs via the proton-proton (pp) chain and CNO cycle, with the 9Be(p,γ)10B reaction serving as an intermediate link between these cycles. Furthermore, the possibility of describing available experimental data for the total reaction cross-sections of neutron radiative capture on 10Be at thermal and astrophysical energies has been shown. This reaction is a part of one of the variants of the chain of primordial nucleosynthesis of the Universe due to which the elements with a mass of A > 11-12 may be formed. The results in the field of study of thermonuclear proton-capture reaction on 10B at ultralow, i.e., astrophysical energies will be presented further. The possibility of description of the experimental data for the astrophysical S-factor of the proton radiative capture on 16O to the ground state (GS) of 17F was considered in the frame of the MPCM with FS and classification of the states according to Young tableaux. It was shown that on the basis of the E1 transitions from the states of p16O scattering to the GS of 17F in the p16O channel generally succeed to explain the value of measured cross-sections at astrophysical energies.

  20. The silicate and carbon-rich models of CoRoT-7b, Kepler-9d and Kepler-10b

    NASA Astrophysics Data System (ADS)

    Gong, Yan-Xiang; Zhou, Ji-Lin

    2012-06-01

    Possible bulk compositions of the super-Earth exoplanets CoRoT-7b, Kepler-9d, and Kepler-10b are investigated by applying a commonly used silicate model and a non-standard carbon model. Their internal structures are deduced using a suitable equation of state for the materials. The degeneracy problems of their compositions can be partly overcome, based on the fact that all three planets are extremely close to their host stars. By analyzing the numerical results, we conclude: 1) the iron core of CoRoT-7b is not more than 27% of its total mass within 1σ mass-radius error bars, so an Earth-like composition is less likely, but its carbon rich model can be compatible with an Earth-like core/mantle mass fraction; 2) Kepler-10b is more likely to have a Mercury-like composition, with its old age implying that its high iron content may be a result of strong solar wind or giant impact; 3) the transiting-only super-Earth Kepler-9d is also discussed. Combining its possible composition with the formation theory, we can place some constraints on its mass and bulk composition.

  1. New measurement of the 10B(n,α)7 Li through the Trojan Horse Method

    NASA Astrophysics Data System (ADS)

    Spartá, Roberta

    2016-04-01

    B(n,α) Li reaction cross section has been measured using the Trojan Horse method, with the specific aim to separate the α1 contribution (coming from the first Li excited level) by the αo (related to the Li ground state), using a very thin target. Preliminary results are shown of the three-body B(d,α7 Li)H cross section.

  2. Characteristics of BDE dependent on 10B concentration for accelerator-based BNCT using near-threshold 7Li(p,n)7Be direct neutrons.

    PubMed

    Tanaka, K; Kobayashi, T; Bengua, G; Nakagawa, Y; Endo, S; Hoshi, M

    2004-11-01

    The characteristics boron-dose enhancer (BDE) was evaluated as to the dependence on the (10)B concentration for BNCT using near-threshold (7)Li(p,n)(7)Be direct neutrons. The treatable protocol depth (TPD) was utilized as an evaluation index. MCNP-4B calculations were performed for near-threshold (7)Li(p,n)(7)Be at a proton energy of 1.900MeV and for a polyethylene BDE. Consequently, the TPD was increased by increasing T/N ratio, i.e., the ratio of the (10)B concentration in the tumor ((10)B(Tumor)) to that in the normal tissue ((10)B(Normal)), and by increasing (10)B(Tumor) and (10)B(Normal) for constant T/N ratio. It has been found that the BDE becomes unnecessary from the viewpoint of increasing the TPD, when (10)B(Tumor) is over a certain level.

  3. Extreme projection of a proton into the pi-cloud of an aromatic ring: record shielding of an aromatic proton in trans-10b-methyl-10c-(1-naphthyl)-10b,10c-dihydropyrene.

    PubMed

    Ting, Yuhua; Lai, Yee-Hing

    2004-01-28

    A synthetic sequence involving dithiametacyclophane --> metacyclophanediene --> dihydropyrene was employed to prepare trans-10b-methyl-10c-(2-naphthyl)- and trans-10b-methyl-10c-(1-naphthyl)-10b,10c-dihydropyrene 5 and 6, respectively. Both exhibit a strong diamagnetic ring current despite the introduction of an internal bulky substituent within the pi-electron cloud. Their electronic spectra suggest interaction between the two near-perpendicular naphthyl and dihydropyrenyl pi systems, resulting in red shift and band broadening. All naphthyl protons are well resolved in their 1H NMR spectra due to a strong shielding effect of the dihydropyrene ring. The most shielded protons in 5 and 6 are H1' and H2' at delta 2.47 and 1.42, respectively, being 5.25 and 5.95 ppm shifted from those of reference protons. There is evidence for free rotation on the NMR time scale of the 2-naphthyl ring in 5 with a preference for a particular conformer, whereas the 1-naphthyl ring in 6 is conformationally rigid with its H2' projecting deeply into the pi-cloud, thus accounting for the most shielded aromatic proton (H2' in 6) reported to date.

  4. Isoxazole analogues bind the System xc− Transporter: Structure-activity Relationship and Pharmacophore Model

    PubMed Central

    Patel, Sarjubhai A.; Rajale, Trideep; O’Brien, Erin; Burkhart, David J.; Nelson, Jared K.; Twamley, Brendan; Blumenfeld, Alex; Szabon-Watola, Monika I.; Gerdes, John M.; Bridges, Richard J.; Natale, Nicholas R.

    2009-01-01

    Analogues of amino methylisoxazole propionic acid (AMPA), were prepared from a common intermediate 12, including lipophilic analogues using lateral metalation and electrophilic quenching, and were evaluated at System xc−. Both the 5-naphthylethyl-(16) and 5-naphthylmethoxymethyl-(17) analogues adopt an E-conformation in the solid state, yet while the former has robust binding at System xc−, the latter is virtually devoid of activity. The most potent analogues were amino acid naphthyl-ACPA 7g, and hydrazone carboxylic acid, 11e Y=Y′=3,5-(CF3)2, which both inhibited glutamate up-take by the System xc− transporter with comparable potency to the endogenous substrate cystine, whereas in contrast the closed isoxazolo[3,4-d] pyridazinones 13 have significantly lower activity. A preliminary pharmacophore model has been constructed to provide insight into the analogue structure-activity relationships. PMID:19932968

  5. Effect of heating rates on the crystallization process of Fe64Co16Zr10B10 amorphous alloy

    NASA Astrophysics Data System (ADS)

    Yu, Wanqiu; Zeng, Haoqun; Sun, Yaming; Sun, Yajuan; Hua, Zhong

    2017-05-01

    Fe64Co16Zr10B10 amorphous alloy prepared by a single roller melt spinning was annealed at 550, 600, 650 and 750 °C for 1 h under different heating rates. The thermal property, microstructure and magnetic property of alloys are investigated by simultaneous thermal analyzer (STA), X-ray diffraction (XRD), transmission electron microscopy (TEM) and vibrating sample magnetometer (VSM). At the same heating temperature, the crystallization of amorphous alloy is different along with the change of heating rate. The relationship between the heating rate and the microstructure is studied. The heating rates affect the distribution of elements and result in the difference in the crystallization products. Coercivity (Hc) of Fe64Co16Zr10B10 alloy at the initial crystallization stage can be improved by the decrease of heating rate.

  6. Unusual Multiple Production of N-Acylhomoserine Lactones a by Burkholderia sp. Strain C10B Isolated from Dentine Caries

    PubMed Central

    Goh, Share Yuan; Tan, Wen-Si; Khan, Saad Ahmed; Chew, Hooi Pin; Kasim, Noor Hayaty Abu; Yin, Wai-Fong; Chan, Kok-Gan

    2014-01-01

    Bacteria realize the ability to communicate by production of quorum sensing (QS) molecules called autoinducers, which regulate the physiological activities in their ecological niches. The oral cavity could be a potential area for the presence of QS bacteria. In this study, we report the isolation of a QS bacterial isolate C10B from dentine caries. Preliminary screening using Chromobacterium violaceum CV026 biosensor showed that isolate C10B was able to produce N-acylhomoserine lactones (AHLs). This bacterium was further identified as a member of Burkholderia, an opportunistic pathogen. The isolated Burkholderia sp. was confirmed to produce N-hexanoyl-L-homoserine lactone (C6-HSL), N-octanoyl-L-homoserine lactone (C8-HSL), N-decanoyl-L-homoserine lactone (C10-HSL) and N-dodecanoyl-L-homoserine lactone (C12-HSL). PMID:24854358

  7. Study of the {sup 10}B(p,α){sup 7}Be reaction through the indirect Trojan Horse method

    SciTech Connect

    Puglia, S. M. R.; Spitaleri, C.; Lamia, L.; Romano, S.; La Cognata, M.; Pizzone, R. G.; Rapisarda, G. G.; Sergi, M. L.; Burjan, V.; Kroha, V.; Hons, Z.; Mrazek, J.; Carlin, N.; Del Santo, M. G.; Munhoz, M. G.; Souza, F.; Szanto de Toledo, A.; Chengbo, L.; Qungang, W.; Shu-Hua, Z.; and others

    2015-02-24

    Boron abundances in stellar atmospheres, as well as berillium and lithium ones, can give useful hints for non-standard transport processes discrimination in stars. They can also be relevant for understanding several astrophysical processes (e.g. primordial nucleosynthesis and spallation reactions in ISM). A comprehensive study of Li Be B abundances can therefore confirm or not the presence of non-standard mixing processes in stellar envelopes. For this reason nuclear processes producing or depleting boron isotope abundance need to be studied at astrophysical energies. The {sup 10}B(p,α){sup 7}Be reaction has been studied by means of the Trojan Horse Method. The Trojan Horse Method was thus applied to the {sup 10}B(d,α{sup 7}Be)n reaction, studied at 24 MeV. The obtained results will be discussed.

  8. Genetic variation in APOJ, LPL, and TNFRSF10B affects plasma fatty acid distribution in Alaskan Eskimos.

    PubMed

    Voruganti, V Saroja; Cole, Shelley A; Ebbesson, Sven O E; Göring, Harald H H; Haack, Karin; Laston, Sandra; Wenger, Charlotte R; Tejero, M Elizabeth; Devereux, Richard B; Fabsitz, Richard R; MacCluer, Jean W; Umans, Jason G; Howard, Barbara V; Comuzzie, Anthony G

    2010-06-01

    Alterations in plasma fatty acid distribution are linked to metabolic abnormalities related to type 2 diabetes and cardiovascular disease. The aim of this study was to investigate genetic factors influencing plasma fatty acid distribution in Alaskan Eskimos from the Genetics of Coronary Artery Disease in Alaska Natives (GOCADAN) study. Fatty acids in plasma were measured by gas chromatography in 761 related individuals (>35 y of age). Quantitative genetic analyses showed that fatty acid distribution is significantly heritable (P < 0.001), with heritabilities ranging from 0.33 to 0.55. A genome-wide scan for plasma fatty acids identified a 20-cM region on chromosome 8 (p12-p21) with a quantitative trait locus for monounsaturated fatty acids (logarithm of odds score = 3.8). The same region had a quantitative trait locus for polyunsaturated fatty acids (logarithm of odds score = 2.6). We genotyped single nucleotide polymorphisms (SNPs) in candidate genes in 8p12-p21 and found a significant association between fatty acids and SNPs in apolipoprotein J (APOJ), lipoprotein lipase (LPL), macrophage scavenger receptor 1 (MSR1), and tumor necrosis factor receptor superfamily member 10b (TNFRSF10B). A Bayesian quantitative trait nucleotide analysis based on a measured genotype model showed that SNPs in LPL, TNFRSF10B, and APOJ had strong statistical evidence of a functional effect (posterior probability > or =75%) on plasma fatty acid distribution. The results indicate that there is strong genetic influence on plasma fatty acid distribution and that genetic variation in APOJ, LPL, and TNFRSF10B may play a role. The GOCADAN study was registered at www.clinicaltrials.gov as NCT00006192.

  9. Beam-Port Design of a Radiobiological Dosimetry Experiment for {sup 10}B-Enhanced {sup 252}Cf Brachytherapy

    SciTech Connect

    Carla White; C.-K. Chris Wang; David Halpern; Casey Moore

    2000-11-12

    It has been previously suggested that the incorporation of {sup 10}B-labeled drugs into tumor cells might significantly increase the dose to the peripheral tumor cells in {sup 252}Cf brachytherapy. The dose enhancement comes from the thermal neutron capture reactions of {sup 10}B(n, {alpha}){sup 7}Li. As a new cancer treatment modality, this so-called {sup 10}{und B}-{und E}nhanced {sup 252}{und C}f {und B}rachy{und t}herapy (BECBT) is currently being commercialized by Isotron. One of the challenges for implementing BECBT has been to determine the maximum tolerable dose (MTD) to the normal tissue surrounding a tumor. Because the relative biological effectiveness for the {sup 10}B(n, {alpha}){sup 7}Li reaction products is greater than that for fission neutrons, the MTD should decrease as {sup 10}B concentration increases for BECBT. To more precisely determine the MTD for BECBT, we intend to conduct both in vitro (cell culture) and in vivo (rat) experiments with a 50-mg {sup 252}Cf source. We will use cell survival fraction and normal brain necrosis as the biological end points for the cell-culture experiments and rat experiments, respectively. To carry out these experiments, the neutron field to which the samples are exposed must contain a significant portion of thermal neutrons. The rat experiments further require the use of a very small and well-collimated neutron beam to effectively irradiate the rat brain while minimizing the dose to its whole body. This paper discusses the design criteria for the experimental neutron beam port and the computational work leading to its optimal configuration.

  10. Utilization of monocrotophos as phosphorus source by Pseudomonas aeruginosa F10B and Clavibacter michiganense subsp. insidiosum SBL 11.

    PubMed

    Singh, Subhas; Singh, Dileep Kumar

    2003-02-01

    Monocrotophos (dimethyl (E)-1-methyl-2-(methylcarbamoyl) vinyl phosphate, or MCP), an organophosphorus insecticide, was used as a sole phosphorus source by the microorganisms isolated from the soil. None of the isolates could utilize MCP as a sole source of carbon. Two of the potential microbial isolates, Pseudomonas aeruginosa F10B and Clavibacter michiganense subsp. insidiosum SBL 11, could utilize MCP as a sole source of phosphorus. Pseudomonas aeruginosa F10B showed a lag phase of 4 h, while in the case of C. michiganense subsp. insidiosum SBL 11, it was 8 h when cultured in the presence of MCP. The generation time for both strains was increased in the medium containing MCP. It was 2.15 h for P. aeruginosa F10B in MCP medium as compared with 1.29 h in basal medium, while in case of C. michiganense subsp. insidiosum SBL 11 it was increased to 3.4 h in MCP medium as compared with 1.28 h in basal medium. These two strains were able to degrade technical MCP in shake-flask culture up to 98.9 and 86.9%, respectively, and pure MCP up to 79 and 80%, respectively, within 24 h at 37 degrees C. The optimal concentration of MCP required for the normal growth was 500 ppm. In the substrate preference study, Tris-p-nitrophenyl phosphate was the most preferred substrate followed by paraoxon. The enzyme responsible for the break down of MCP was phosphotriesterase, which was localized on the membrane-bound fraction of the disrupted cells. The gene responsible for the production of phosphotriesterase (opd) in P. aeruginosa F10B was plasmid-borne.

  11. Spectroscopy of AT 2017gay, another outburst of PT And/M31N 1957-10b

    NASA Astrophysics Data System (ADS)

    Williams, S. C.; Darnley, M. J.

    2017-08-01

    AT 2017gay was discovered by E. Conseil on 2017 Aug 15.00 (see TNS). Comparing the position to previous M31 nova candidates, we find that it is very close to the position of M31N 2010-12a (as noted by E. Conseil), which was another outburst of PT And/M31N 1957-10b, and thus AT 2017gay is very likely to be another outburst of that system.

  12. Microstructural evolution of HFIR-irradiated low activation F82H and F82H-{sup 10}B steels

    SciTech Connect

    Wakai, E.; Shiba, K.; Sawai, T.; Hashimoto, N.; Robertson, J.P.; Klueh, R.L.

    1998-03-01

    Microstructures of reduced-activation F82H (8Cr-2W-0.2V-0.04Ta) and the F82H steels doped with {sup 10}B, irradiated at 250 and 300 C to 3 and 57 dpa in the High Flux Isotope Reactor (HFIR), were examined by TEM. In the F82H irradiated at 250 C to 3 dpa, dislocation loops, small unidentified defect clusters with a high number density, and a few MC precipitates were observed in the matrix. The defect microstructure after 300 C irradiation to 57 dpa is dominated by the loops, and the number density of loops was lower than that of the F82H-{sup 10}B steel. Cavities were observed in the F82H-{sup 10}B steels, but the swelling value is insignificant. Small particles of M{sub 6}C formed on the M{sub 23}C{sub 6} carbides that were present in both steels before the irradiation at 300 C to 57 dpa. A low number density of MC precipitate particles formed in the matrix during irradiation at 300 C to 57 dpa.

  13. Choline Analogues in Malaria Chemotherapy

    PubMed Central

    Peyrottes, Suzanne; Caldarelli, Sergio; Wein, Sharon; Périgaud, Christian; Pellet, Alain; Vial, Henri

    2012-01-01

    Emerging resistance against well-established anti-malaria drugs warrants the introduction of new therapeutic agents with original mechanisms of action. Inhibition of membrane-based phospholipid biosynthesis, which is crucial for the parasite, has thus been proposed as a novel and promising therapeutic strategy. This review compiles literature concerning the design and study of choline analogues and related cation derivatives as potential anti-malarials. It covers advances achieved over the last two decades and describes: the concept validation, the design and selection of a clinical candidate (Albitiazolium), back-up derivatives while also providing insight into the development of prodrug approaches. PMID:22607139

  14. Ecstasy analogues found in cacti.

    PubMed

    Bruhn, Jan G; El-Seedi, Hesham R; Stephanson, Nikolai; Beck, Olof; Shulgin, Alexander T

    2008-06-01

    Human interest in psychoactive phenethylamines is known from the use of mescaline-containing cacti and designer drugs such as Ecstasy. From the alkaloid composition of cacti we hypothesized that substances resembling Ecstasy might occur naturally. In this article we show that lophophine, homopiperonylamine and lobivine are new minor constituents of two cactus species, Lophophora williamsii (peyote) and Trichocereus pachanoi (San Pedro). This is the first report of putatively psychoactive phenethylamines besides mescaline in these cacti. A search for further biosynthetic analogues may provide new insights into the structure-activity relationships of mescaline. An intriguing question is whether the new natural compounds can be called "designer drugs."

  15. FUNCTION GENERATOR FOR ANALOGUE COMPUTERS

    DOEpatents

    Skramstad, H.K.; Wright, J.H.; Taback, L.

    1961-12-12

    An improved analogue computer is designed which can be used to determine the final ground position of radioactive fallout particles in an atomic cloud. The computer determines the fallout pattern on the basis of known wind velocity and direction at various altitudes, and intensity of radioactivity in the mushroom cloud as a function of particle size and initial height in the cloud. The output is then displayed on a cathode-ray tube so that the average or total luminance of the tube screen at any point represents the intensity of radioactive fallout at the geographical location represented by that point. (AEC)

  16. Template polymerization of nucleotide analogues

    NASA Technical Reports Server (NTRS)

    Orgel, L. E.

    1991-01-01

    Recent work on the template-directed reactions of the natural D-nucleotides has made it clear that l-nucleotides and nucleotide-like derivatives of other sugars would strongly inhibit the formation of long oligonucleotides. Consequently, attention is focusing on molecules simpler than nucleotides that might have acted as monomers of an information transfer system. We have begun a general exploration of the template directed reactions of diverse peptide analogues. I will present work by Dr. Taifeng Wu on oxidative oligomerization of phosphorothioates and of Dr. Mary Tohidi on the cyclic polymerization of nucleoside and related cyclic pyrophosphates.

  17. Photoinduced ferrimagnetic systems in Prussian blue analogues C(I)xCo4[Fe(CN)6]y (C(I) = alkali cation). 4. Characterization of the ferrimagnetism of the photoinduced metastable state in Rb1.8Co4[Fe(CN)6]3.3-13H2O by K edges X-ray magnetic circular dichroism.

    PubMed

    Champion, G; Escax, V; Cartier Dit Moulin, C; Bleuzen, A; Villain, F; Baudelet, F; Dartyge, E; Verdaguer, M

    2001-12-19

    In Part 2 of this work, the electronic and local structure of the photoinduced metastable magnetic state of the Prussian blue analogue Rb1.8Co4[Fe(CN)6]3.3-13H2O were characterized. To determine directly the relative orientation of the magnetic moments of Co(II) and Fe(III) ions in the metastable state, and the nature of the exchange interaction between them, we performed X-ray magnetic circular dichroism (XMCD) experiments at the cobalt and iron K edges. We present the first direct experimental evidence of the antiferromagnetic interaction between the cobalt and the iron ions, leading to the ferrimagnetism of the photoinduced metastable state.

  18. Wnt10b Activates the Wnt, Notch and NFκB Pathways in U2OS Osteosarcoma Cells

    PubMed Central

    Mödder, Ulrike I.; Oursler, Merry Jo; Khosla, Sundeep; Monroe, David G.

    2011-01-01

    Although osteosarcoma represents the most common bone malignancy, the molecular and cellular mechanisms influencing its pathogenesis have remained elusive. Recent evidence has suggested that the Wnt signaling pathway may play a crucial role in osteosarcoma. This study employed a microarray approach to discover novel genes and pathways involved in Wnt signaling in osteosarcoma. We developed a Wnt10b-expressing cell line using the human U2OS osteosarcoma model (U2OS-Wnt10b) and performed microarray and pathway analyses using parental U2OS cells as control. Differential expression of 1003 genes encompassing 28 pathways was noted. The Wnt, NFκB and Notch pathways were chosen for further study based on their known importance in bone biology. Known Wnt-responsive genes Axin-2 (4.9-fold), CD44 (2.1-fold), endothelin-1 (4.2-fold) and sclerostin domain containing-1 (43-fold) were regulated by Wnt10b. The proinflammatory cytokines interleukin-1α and tumor necrosis factor-α, known inducers of NFκB, were upregulated both at the transcript and protein level, and NFκB reporter activity was stimulated 3.8-fold, confirming NFκB activation. Interestingly, genes involved in Notch signaling [Notch-1 (2.4-fold) and Jagged-1 (3.1-fold)] were upregulated, whereas the Notch inhibitor, lunatic fringe, was downregulated (8.2-fold). This resulted in the activation of the classic Notch-responsive genes, hairy and enhancer of split-1 (Hes-1; 2.2-fold) and hairy/enhancer-of-split related with YRPW motif-1 (Hey-1; 2.5-fold). A Hey-1 reporter construct was regulated 9.1-fold in U2OS-Wnt10b cells, confirming Notch activation. Interestingly, Wnt3a failed to induce the Notch and NFκB pathways, demonstrating Wnt-specificity. In conclusion, our data demonstrate that Wnt10b, but not Wnt3a, stimulates the NFκB and Notch pathways in U2OS osteosarcoma cells. PMID:21321991

  19. The Valles natural analogue project

    SciTech Connect

    Stockman, H.; Krumhansl, J.; Ho, C.; McConnell, V.

    1994-12-01

    The contact between an obsidian flow and a steep-walled tuff canyon was examined as an analogue for a highlevel waste repository. The analogue site is located in the Valles Caldera in New Mexico, where a massive obsidian flow filled a paleocanyon in the Battleship Rock tuff. The obsidian flow provided a heat source, analogous to waste panels or an igneous intrusion in a repository, and caused evaporation and migration of water. The tuff and obsidian samples were analyzed for major and trace elements and mineralogy by INAA, XRF, X-ray diffraction; and scanning electron microscopy and electron microprobe. Samples were also analyzed for D/H and {sup 39}Ar/{sup 4O} isotopic composition. Overall,the effects of the heating event seem to have been slight and limited to the tuff nearest the contact. There is some evidence of devitrification and migration of volatiles in the tuff within 10 meters of the contact, but variations in major and trace element chemistry are small and difficult to distinguish from the natural (pre-heating) variability of the rocks.

  20. q-bosons and the q-analogue quantized field

    NASA Technical Reports Server (NTRS)

    Nelson, Charles A.

    1995-01-01

    The q-analogue coherent states are used to identify physical signatures for the presence of a 1-analogue quantized radiation field in the q-CS classical limits where the absolute value of z is large. In this quantum-optics-like limit, the fractional uncertainties of most physical quantities (momentum, position, amplitude, phase) which characterize the quantum field are O(1). They only vanish as O(1/absolute value of z) when q = 1. However, for the number operator, N, and the N-Hamiltonian for a free q-boson gas, H(sub N) = h(omega)(N + 1/2), the fractional uncertainties do still approach zero. A signature for q-boson counting statistics is that (Delta N)(exp 2)/ (N) approaches 0 as the absolute value of z approaches infinity. Except for its O(1) fractional uncertainty, the q-generalization of the Hermitian phase operator of Pegg and Barnett, phi(sub q), still exhibits normal classical behavior. The standard number-phase uncertainty-relation, Delta(N) Delta phi(sub q) = 1/2, and the approximate commutation relation, (N, phi(sub q)) = i, still hold for the single-mode q-analogue quantized field. So, N and phi(sub q) are almost canonically conjugate operators in the q-CS classical limit. The q-analogue CS's minimize this uncertainty relation for moderate (absolute value of z)(exp 2).

  1. Norcantharimide analogues possessing terminal phosphate esters and their anti-cancer activity.

    PubMed

    Robertson, Mark J; Gordon, Christopher P; Gilbert, Jayne; McCluskey, Adam; Sakoff, Jennette A

    2011-09-15

    A family of norcantharidin analogues possessing a terminal alcohol (ethanol, propanol, butanol, pentanol, hexanol and cyclohexanol) moiety were treated with either chlorodiethyl, chlorodiphenyl or chloro-bis-trichloroethyl-phosphate to afford highly focused libraries of the corresponding phosphate esters. Subsequent biological screening against a panel of nine human cancer cell lines identified a trend between the ease of phosphate unmasking (phosphate ester hydrolysis) and cell death. The most potent analogues possessed either a diphenyl or a bis-trichloroethyl moiety. The effect of alkyl spacer was also examined with the hexyl analogues typically more potent. 4-Aza-4-(3-{bis(2,2,2-trichloroethyl)phosphate}propyl)-10-oxatricyclo[5.2.1.0]decane-3,5-dione (10b) was the most potent analogue synthesised with an average GI(50) of 11 μM across a panel of nine human carcinoma cell lines: colon carcinoma (HT29 and SW480); breast carcinoma (MCF-7); ovarian carcinoma (A2780); lung carcinoma (H460); skin carcinoma (A431); prostate carcinoma (DU145); neuronal carcinoma (BE2-C) and brain carcinoma (SJ-G2). This represents a fivefold improvement in anti-proliferative activity relative to the lead, norcantharidin. Crown Copyright © 2011. Published by Elsevier Ltd. All rights reserved.

  2. Current european regulatory perspectives on insulin analogues

    PubMed Central

    2011-01-01

    Insulin analogues are increasingly considered as an alternative to human insulin in the therapy of diabetes mellitus. Insulin analogues (IAs) are chemically different from human insulin and may have different pharmacokinetic or pharmacodynamic properties. The significance of the modifications of the insulin molecule for the safety profile of IAs must be considered. This review describes the regulatory procedure and the expectations for the scientific content of European marketing authorization applications for innovative IAs submitted to the European Medicines Agency. Particular consideration is given to a potential cancer hazard. Specific regulatory guidance on how to address a possible carcinogenic or tumor promoting effect of innovative IAs in non-clinical studies is available. After marketing authorization, the factual access of patients to the new product will be determined to great extent by health technology assessment bodies, reimbursement decisions and the price. Whereas the marketing authorization is a European decision, pricing and reimbursement are national or regional responsibilities. The assessment of benefit and risk by the European Medicines Agency is expected to influence future decisions on price and reimbursement on a national or regional level. Collaborations between regulatory agencies and health technology assessment bodies have been initiated on European and national level to facilitate the use of the European Medicines Agency's benefit risk assessment as basis on which to build the subsequent health technology assessment. The option for combined or joint scientific advice procedures with regulators and health technology assessment bodies on European level or on a national level in several European Member States may help applicants to optimize their development program and dossier preparation in regard of both European marketing authorization application and reimbursement decisions. PMID:21736748

  3. 17 CFR 240.10b5-1 - Trading “on the basis of” material nonpublic information in insider trading cases.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Trading âon the basis ofâ material nonpublic information in insider trading cases. 240.10b5-1 Section 240.10b5-1 Commodity and... Deceptive Devices and Contrivances § 240.10b5-1 Trading “on the basis of” material nonpublic information...

  4. The role of the "Casimir force analogue" at the microscopic processes of crystallization and melting

    NASA Astrophysics Data System (ADS)

    Chuvildeev, V. N.; Semenycheva, A. V.

    2016-10-01

    Melting (crystallization), a phase transition from a crystalline solid to a liquid state, is a common phenomenon in nature. We suggest a new factor, "the Casimir force analogue", to describe mechanisms of melting and crystallization. The Casimir force analogue is a force occurring between the surfaces of solid and liquid phases of metals caused by different energy density of phonons of these phases. It explains abrupt changes in geometry and thermodynamic parameters at a melting point. "The Casimir force analogue" helps to estimate latent melting heat and to gain an insight into a solid-liquid transition problem.

  5. Measurements of D{sub {sigma}} and D{sub {gamma}} for {sup 10}B(p,p{prime}){sup 10}B inelastic scattering at E{sub p}=200 MeV

    SciTech Connect

    Chang, S.; Stephenson, E.J.; Bacher, A.D.

    1993-10-01

    We report measurements of the two linear combinations of the in-plane polarization transfer coefficients, D{sub {sigma}} = D{sub SS`} cos {alpha} + D{sub SL`} sin {alpha} and D{lambda} = D{sub LS`} cos {alpha} + D{sub LL`} sin {alpha}, where {alpha} = 235{degrees} is the spin procession angle in the IUCF K600 spectrometer, for the inelastic scattering of 200 MeV protons from {sup 10}B at {theta}{sub lab} = 20{degrees}, 31{degrees}, 40{degrees}, 48{degrees} and 60{degrees}. The isovector 0h{omega} 3{sup +} {r_arrow} 0{sup +} transition at 1.74 MeV is of particular interest as a test of the medium modification of the effective NN interaction. Theoretical calculations employing DWBA86 use distortions constrained by proton elastic scattering on {sup 10}B and a (p{sub 3/2}){sup 2} formfactor consistent with electron scattering results. The evidence, for modifications of the short-range tensor force will be discussed.

  6. Could CoRoT-7b and Kepler-10b be remnants of evaporated gas or ice giants?

    PubMed Central

    Leitzinger, M.; Odert, P.; Kulikov, Yu.N.; Lammer, H.; Wuchterl, G.; Penz, T.; Guarcello, M.G.; Micela, G.; Khodachenko, M.L.; Weingrill, J.; Hanslmeier, A.; Biernat, H.K.; Schneider, J.

    2011-01-01

    We present thermal mass loss calculations over evolutionary time scales for the investigation if the smallest transiting rocky exoplanets CoRoT-7b (∼1.68REarth) and Kepler-10b (∼1.416REarth) could be remnants of an initially more massive hydrogen-rich gas giant or a hot Neptune-class exoplanet. We apply a thermal mass loss formula which yields results that are comparable to hydrodynamic loss models. Our approach considers the effect of the Roche lobe, realistic heating efficiencies and a radius scaling law derived from observations of hot Jupiters. We study the influence of the mean planetary density on the thermal mass loss by placing hypothetical exoplanets with the characteristics of Jupiter, Saturn, Neptune, and Uranus to the orbital location of CoRoT-7b at 0.017 AU and Kepler-10b at 0.01684 AU and assuming that these planets orbit a K- or G-type host star. Our findings indicate that hydrogen-rich gas giants within the mass domain of Saturn or Jupiter cannot thermally lose such an amount of mass that CoRoT-7b and Kepler-10b would result in a rocky residue. Moreover, our calculations show that the present time mass of both rocky exoplanets can be neither a result of evaporation of a hydrogen envelope of a “Hot Neptune” nor a “Hot Uranus”-class object. Depending on the initial density and mass, these planets most likely were always rocky planets which could lose a thin hydrogen envelope, but not cores of thermally evaporated initially much more massive and larger objects. PMID:21969736

  7. Could CoRoT-7b and Kepler-10b be remnants of evaporated gas or ice giants?

    PubMed

    Leitzinger, M; Odert, P; Kulikov, Yu N; Lammer, H; Wuchterl, G; Penz, T; Guarcello, M G; Micela, G; Khodachenko, M L; Weingrill, J; Hanslmeier, A; Biernat, H K; Schneider, J

    2011-10-01

    We present thermal mass loss calculations over evolutionary time scales for the investigation if the smallest transiting rocky exoplanets CoRoT-7b (∼1.68REarth) and Kepler-10b (∼1.416REarth) could be remnants of an initially more massive hydrogen-rich gas giant or a hot Neptune-class exoplanet. We apply a thermal mass loss formula which yields results that are comparable to hydrodynamic loss models. Our approach considers the effect of the Roche lobe, realistic heating efficiencies and a radius scaling law derived from observations of hot Jupiters. We study the influence of the mean planetary density on the thermal mass loss by placing hypothetical exoplanets with the characteristics of Jupiter, Saturn, Neptune, and Uranus to the orbital location of CoRoT-7b at 0.017 AU and Kepler-10b at 0.01684 AU and assuming that these planets orbit a K- or G-type host star. Our findings indicate that hydrogen-rich gas giants within the mass domain of Saturn or Jupiter cannot thermally lose such an amount of mass that CoRoT-7b and Kepler-10b would result in a rocky residue. Moreover, our calculations show that the present time mass of both rocky exoplanets can be neither a result of evaporation of a hydrogen envelope of a "Hot Neptune" nor a "Hot Uranus"-class object. Depending on the initial density and mass, these planets most likely were always rocky planets which could lose a thin hydrogen envelope, but not cores of thermally evaporated initially much more massive and larger objects.

  8. Could CoRoT-7b and Kepler-10b be remnants of evaporated gas or ice giants?

    NASA Astrophysics Data System (ADS)

    Leitzinger, M.; Odert, P.; Kulikov, Yu. N.; Lammer, H.; Wuchterl, G.; Penz, T.; Guarcello, M. G.; Micela, G.; Khodachenko, M. L.; Weingrill, J.; Hanslmeier, A.; Biernat, H. K.; Schneider, J.

    2011-10-01

    We present thermal mass loss calculations over evolutionary time scales for the investigation if the smallest transiting rocky exoplanets CoRoT-7b (∼1.68REarth) and Kepler-10b (∼1.416REarth) could be remnants of an initially more massive hydrogen-rich gas giant or a hot Neptune-class exoplanet. We apply a thermal mass loss formula which yields results that are comparable to hydrodynamic loss models. Our approach considers the effect of the Roche lobe, realistic heating efficiencies and a radius scaling law derived from observations of hot Jupiters. We study the influence of the mean planetary density on the thermal mass loss by placing hypothetical exoplanets with the characteristics of Jupiter, Saturn, Neptune, and Uranus to the orbital location of CoRoT-7b at 0.017 AU and Kepler-10b at 0.01684 AU and assuming that these planets orbit a K- or G-type host star. Our findings indicate that hydrogen-rich gas giants within the mass domain of Saturn or Jupiter cannot thermally lose such an amount of mass that CoRoT-7b and Kepler-10b would result in a rocky residue. Moreover, our calculations show that the present time mass of both rocky exoplanets can be neither a result of evaporation of a hydrogen envelope of a “Hot Neptune” nor a “Hot Uranus”-class object. Depending on the initial density and mass, these planets most likely were always rocky planets which could lose a thin hydrogen envelope, but not cores of thermally evaporated initially much more massive and larger objects.

  9. Stimulated emission in black holes and in analogue gravity

    NASA Astrophysics Data System (ADS)

    Belgiorno, F.; Cacciatori, S. L.

    2016-11-01

    Stimulated emission by black holes is discussed in light of the analogue gravity program. We first consider initial quantum states containing a definite number of particles, and then we take into account the case where the initial state is a coherent state. The latter case is particularly significant in the case where Hawking radiation is studied in dielectric black holes, and the emission is stimulated by a laser probe. We are particularly interested in the case of the electromagnetic field, for which examples of stimulated radiation are considered.

  10. Development of a prompt gamma neutron activation analysis facility for 10B concentration measurements at RA-3: design stage.

    PubMed

    Gonçalves-Carralves, Manuel L Sztejnberg; Gadan, Mario A; Bortolussi, Silva; Pinto, Julián; Ojeda, Juan; Langan, Sebastián; Quintana, Jorge; Miller, Marcelo E

    2011-12-01

    A PGNAA facility is being developed for (10)B concentration measurements at RA-3 reactor. Its design targets detection limits better than tenths of a microgram and irradiation times on the order of minutes. Computational models were developed, which estimated thermal neutron fluxes in irradiation position to be larger than 10(9) n cm(-2) s(-1). Calculated amounts of photons and fast neutrons make necessary for filter/moderator arrangements. An irradiation device was designed and numerically tested, which is being built and is to be used for performing characterizing measurements. Copyright © 2011 Elsevier Ltd. All rights reserved.

  11. The 10B based Jalousie neutron detector - An alternative for 3He filled position sensitive counter tubes

    NASA Astrophysics Data System (ADS)

    Henske, M.; Klein, M.; Köhli, M.; Lennert, P.; Modzel, G.; Schmidt, C. J.; Schmidt, U.

    2012-09-01

    Over the last decades 3He filled proportional counter tubes were the working horse employed to serve as neutron counters especially in cases where large area coverage was required. Today the lack of 3He demands the development of an alternative technology. Here we present a prototype neutron detector that is based on a concept with solid 10B as neutron converter and aims for large area neutron detection applications. We report on first experimental results obtained with this prototype to demonstrate the feasibility and operational readiness of our concept.

  12. CO2 Capture with Enzyme Synthetic Analogue

    SciTech Connect

    Cordatos, Harry

    2010-11-08

    Overview of an ongoing, 2 year research project partially funded by APRA-E to create a novel, synthetic analogue of carbonic anhydrase and incorporate it into a membrane for removal of CO2 from flue gas in coal power plants. Mechanism background, preliminary feasibility study results, molecular modeling of analogue-CO2 interaction, and program timeline are provided.

  13. Macrolactam analogues of macrolide natural products.

    PubMed

    Hügel, Helmut M; Smith, Andrew T; Rizzacasa, Mark A

    2016-12-07

    The chemical modification of macrolide natural products into aza- or lactam analogues is a strategy employed to improve their metabolic stability and biological activity. The methods for the synthesis of several lactam analogues of macrolide natural products are highlighted and aspects of their biological properties presented.

  14. Observation of the Isovector Giant Monopole Resonance via the 28Si (10Be, 10B* [1.74 MeV ]) Reaction at 100 A MeV

    NASA Astrophysics Data System (ADS)

    Scott, M.; Zegers, R. G. T.; Almus, R.; Austin, Sam M.; Bazin, D.; Brown, B. A.; Campbell, C.; Gade, A.; Bowry, M.; Galès, S.; Garg, U.; Harakeh, M. N.; Kwan, E.; Langer, C.; Loelius, C.; Lipschutz, S.; Litvinova, E.; Lunderberg, E.; Morse, C.; Noji, S.; Perdikakis, G.; Redpath, T.; Robin, C.; Sakai, H.; Sasamoto, Y.; Sasano, M.; Sullivan, C.; Tostevin, J. A.; Uesaka, T.; Weisshaar, D.

    2017-04-01

    The (10Be, 10B* [1.74 MeV ] ) charge-exchange reaction at 100 A MeV is presented as a new probe for isolating the isovector (Δ T =1 ) nonspin-transfer (Δ S =0 ) response of nuclei, with 28Si being the first nucleus studied. By using a secondary 10Be beam produced by fast fragmentation of 18O nuclei at the NSCL Coupled Cyclotron Facility, applying the dispersion-matching technique with the S800 magnetic spectrometer to determine the excitation energy in 28Al, and performing high-resolution γ -ray tracking with the Gamma-Ray Energy Tracking In-beam Nuclear Array (GRETINA) to identify the 1022-keV γ ray associated with the decay from the 1.74-MeV T =1 isobaric analog state in 10B, a Δ S =0 excitation-energy spectrum in 28Al was extracted. Monopole and dipole contributions were determined through a multipole-decomposition analysis, and the isovector giant dipole resonance and isovector giant monopole resonance (IVGMR) were identified. The results show that this probe is a powerful tool for studying the elusive IVGMR, which is of interest for performing stringent tests of modern density functional theories at high excitation energies and for constraining the bulk properties of nuclei and nuclear matter. The extracted distributions were compared with theoretical calculations based on the normal-modes formalism and the proton-neutron relativistic time-blocking approximation. Calculated cross sections based on these strengths underestimate the data by about a factor of 2, which likely indicates deficiencies in the reaction calculations based on the distorted wave Born approximation.

  15. Continuous analogues of matrix factorizations

    PubMed Central

    Townsend, Alex; Trefethen, Lloyd N.

    2015-01-01

    Analogues of singular value decomposition (SVD), QR, LU and Cholesky factorizations are presented for problems in which the usual discrete matrix is replaced by a ‘quasimatrix’, continuous in one dimension, or a ‘cmatrix’, continuous in both dimensions. Two challenges arise: the generalization of the notions of triangular structure and row and column pivoting to continuous variables (required in all cases except the SVD, and far from obvious), and the convergence of the infinite series that define the cmatrix factorizations. Our generalizations of triangularity and pivoting are based on a new notion of a ‘triangular quasimatrix’. Concerning convergence of the series, we prove theorems asserting convergence provided the functions involved are sufficiently smooth. PMID:25568618

  16. The future of somatostatin analogue therapy.

    PubMed

    Stewart, P M; James, R A

    1999-10-01

    Since its discovery almost 30 years ago, the mode of action and therapeutic applications of somatostatin have been defined. In particular the cloning and characterization of somatostatin receptor subtypes has facilitated the development of high affinity analogues. In the context of pituitary disease, long-acting somatostatin analogues (octreotide, lanreotide) have been used to treat a variety of pituitary tumours but are most efficacious for the treatment of GH and TSH-secreting adenomas. In patients with acromegaly, depot preparations of these analogues are administered intramuscularly every 10-28 days and provide consistent suppression of GH levels to < 5 mU/l in approximately 50-65% of all cases. Even more specific somatostatin receptor analogues are under development. Finally, radiolabelled somatostatin analogue scintigraphy and, in larger doses, therapy, are now established tools in the evaluation and treatment of neuroendocrine tumours.

  17. Antinociceptive activity of glycosidic enkephalin analogues.

    PubMed

    Rodríguez, R E; Rodríguez, F D; Sacristán, M P; Torres, J L; Reig, F; García Antón, J M; Valencia, G

    1990-01-01

    The antinociceptive activity of two new enkephalin analogues: N1.5-(beta-D-glucopyranosyl)[D-Met2, Pro5]enkephalinamide and N1.5-(beta-D-galactopyranosyl)[D-Met2, Pro5]enkephalinamide was assessed using the tail immersion and paw pressure behavioural tests. Both enkephalin analogues appear to be more active than morphine when injected either into the fourth ventricle or intrathecally; the galactose analogue is more than 5000 times more active than morphine when injected into the fourth ventricle. The analgesic effects produced by the analogues are partially reversed by SC naloxone (0.1 mg/kg) and totally reversed when the dose of naloxone used was 1 mg/kg, suggesting that the analogues act upon more than one type of opiate receptor (mu/delta).

  18. Fluorescent polyene ceramide analogues as membrane probes.

    PubMed

    Nieves, Ingrid; Artetxe, Ibai; Abad, José Luis; Alonso, Alicia; Busto, Jon V; Fajarí, Lluís; Montes, L Ruth; Sot, Jesús; Delgado, Antonio; Goñi, Félix M

    2015-03-03

    Three ceramide analogues have been synthesized, with sphingosine-like chains containing five conjugated double bonds. Pentaene I has an N-palmitoyl acyl chain, while the other two pentaenes contain also a doxyl radical, respectively, at C5 (Penta5dox) and at C16 (Penta16dox) positions of the N-acyl chain. Pentaene I maximum excitation and emission wavelengths in a phospholipid bilayer are 353 and 478 nm, respectively. Pentaene I does not segregate from the other lipids in the way natural ceramide does, but rather mixes with them in a selective way according to the lipid phases involved. Fluorescence confocal microscopy studies show that when lipid domains in different physical states coexist, Pentaene I emission is higher in gel than in fluid domains, and in liquid-ordered than in liquid-disordered areas. Electron paramagnetic resonance of the pentaene doxyl probes confirms that these molecules are sensitive to the physical state of the bilayer. Calorimetric and fluorescence quenching experiments suggest that the lipids under study orient themselves in lipid bilayers with their polar moieties located at the lipid-water interface. The doxyl radical in the N-acyl chain quenches the fluorescence of the pentaene group when in close proximity. Because of this property, Penta16dox can detect gel-fluid transitions in phospholipids. The availability of probes for lipids in the gel phase is important in view of novel evidence for the existence of gel microdomains in cell membranes.

  19. Purification and characterization of phosphotriesterases from Pseudomonas aeruginosa F10B and Clavibacter michiganense subsp. insidiosum SBL11.

    PubMed

    Das, Subhas; Singh, Dileep Kumar

    2006-02-01

    A microbial biodegradation of monocrotophos was studied in the present investigation. The monocrotophos-degrading enzyme was purified and characterized from two soil bacterial strains. The cells were disrupted and the membrane-bound fractions were studied for purification and characterization. Solubilization of the membrane-bound fractions released nearly 80% of the bound protein. Phase separation further enriched the enzyme fraction 34-41 times. The enzyme phosphotriesterase (PTE) from both the strains was purified to more than 1000-fold with 13%-16% yield. Purified PTE from Clavibacter michiganense subsp. insidiosum SBL11 is a monomeric enzyme with a molecular mass of 43.5 kDa (pI of 7.5), while PTE from Pseudomonas aeruginosa F10B is a heterodimeric enzyme with a molecular mass of 43 and 41 kDa (pI of 7.9 and 7.35). Both purified enzymes are stable enzymes with peak activity at pH 9.0. The enzyme from strain F10B was more thermostable (half-life=7.3 h) than that from SBL11 (half-life=6.4 h at 50 degrees C), while both showed the same temperature optimum of 37 degrees C. Inhibitors like dithiothreitol and EDTA inhibited the purified enzyme, while p-chloromercuribenzoic acid and indoleacetic acid had a very little effect.

  20. Neutron reflectometry on highly absorbing films and its application to 10B4C-based neutron detectors

    PubMed Central

    Piscitelli, F.; Khaplanov, A.; Devishvili, A.; Schmidt, S.; Höglund, C.; Birch, J.; Dennison, A. J. C.; Gutfreund, P.; Hall-Wilton, R.; Van Esch, P.

    2016-01-01

    Neutron reflectometry is a powerful tool used for studies of surfaces and interfaces. The absorption in the typical studied materials is neglected and this technique is limited only to the reflectivity measurement. For strongly absorbing nuclei, the absorption can be directly measured by using the neutron-induced fluorescence technique which exploits the prompt particle emission of absorbing isotopes. This technique is emerging from soft matter and biology where highly absorbing nuclei, in very small quantities, are used as a label for buried layers. Nowadays, the importance of absorbing layers is rapidly increasing, partially because of their application in neutron detection; a field that has become more active also due to the 3He-shortage. We extend the neutron-induced fluorescence technique to the study of layers of highly absorbing materials, in particular 10B4C. The theory of neutron reflectometry is a commonly studied topic; however, when a strong absorption is present the subtle relationship between the reflection and the absorption of neutrons is not widely known. The theory for a general stack of absorbing layers has been developed and compared to measurements. We also report on the requirements that a 10B4C layer must fulfil in order to be employed as a converter in neutron detection. PMID:26997902

  1. Central nervous system radiation syndrome in mice from preferential 10B(n, alpha)7Li irradiation of brain vasculature

    SciTech Connect

    Slatkin, D.N.; Stoner, R.D.; Rosander, K.M.; Kalef-Ezra, J.A.; Laissue, J.A.

    1988-06-01

    Ionizing radiations were directed at the heads of anesthetized mice in doses that evoked the acute central nervous system (CNS) radiation syndrome. Irradiations were done using either a predominantly thermal neutron field at a nuclear reactor after intraperitoneal injection of 10B-enriched boric acid or 250-kilovolt-peak x-rays with and without previous intraperitoneal injection of equivalent unenriched boric acid. Since 10B concentrations were approximately equal to 3-fold higher in blood than in cerebral parenchyma during the reactor irradiations, more radiation from alpha and 7Li particles was absorbed by brain endothelial cells than by brain parenchymal cells. Comparison of the LD50 dose for CNS radiation lethality from the reactor experiments with the LD50 dose from the x-ray experiments gives results compatible with morphologic evidence that endothelial cell damage is a major determinant of acute lethality from the CNS radiation syndrome. It was also observed that boric acid is a low linear energy transfer radiation-enhancement agent in vivo.

  2. Experimental evaluation of the isotopic exchange equilibrium 10B(OH) 3+ 11B(OH) 4-= 11B(OH) 3+ 10B(OH) 4- in aqueous solution

    NASA Astrophysics Data System (ADS)

    Byrne, Robert H.; Yao, Wensheng; Klochko, Kateryna; Tossell, John A.; Kaufman, Alan J.

    2006-04-01

    The precision of spectrophotometric measurements of indicator absorbance ratios is sufficient to allow evaluation of small isotopically induced differences in the dissociation constant of boric acid ( KB). The quotient of 11KB and 10KB, obtained using isotopically ⩾99% pure borate/boric acid buffers, provides an equilibrium constant for the reaction 10B(OH) 3+ 11B(OH) 4-⇔ 11B(OH) 3+ 10B(OH) 4- which heretofore had not been experimentally determined. Previous theoretical and semi-empirical evaluations of this equilibrium, which is important for assessments of the paleo-pH of seawater and the paleo- pCO 2 of the atmosphere, have yielded constants, 11-10KB= 10KB/ 11KB, that have ranged between 1.0194 and approximately 1.033. The experimentally determined value 11-10KB=1.028 5±0.001 6 (mean±95% confidence interval) obtained at 25 °C and 0.63 molal (mol kg -1 H 2O) ionic strength is in much better agreement with recent theoretical assessments of 11-10KB that have ranged between 1.026 and 1.033, than the much-cited original estimate (1.0194) of Kakihana et al. (1977) [Fundamental studies on the ion-exchange separation of boron isotopes. Bulletin of Chemical Society of Japan 50, 158-163]. Since the activity quotient for the fractionation reaction is almost equal to unity, it is expected that the 11-10KB value obtained in this study will be applicable over a wide range of solution compositions and ionic strengths.

  3. Numerical simulation of an experimental analogue of a planetary magnetosphere

    NASA Astrophysics Data System (ADS)

    Liao, Andy Sha; Li, Shule; Hartigan, Patrick; Graham, Peter; Fiksel, Gennady; Frank, Adam; Foster, John; Kuranz, Carolyn

    2015-12-01

    Recent improvements to the Omega Laser Facility's magneto-inertial fusion electrical discharge system (MIFEDS) have made it possible to generate strong enough magnetic fields in the laboratory to begin to address the physics of magnetized astrophysical flows. Here, we adapt the MHD code AstroBEAR to create 2D numerical models of an experimental analogue of a planetary magnetosphere. We track the secular evolution of the magnetosphere analogue and we show that the magnetospheric components such as the magnetopause, magnetosheath, and bow shock, should all be observable in experimental optical band thermal bremsstrahlung emissivity maps, assuming equilibrium charge state distributions of the plasma. When the magnetosphere analogue nears the steady state, the mid-plane altitude of the magnetopause from the wire surface scales as the one-half power of the ratio of the magnetic pressure at the surface of the free wire to the ram pressure of an unobstructed wind; the mid-plane thickness of the magnetosheath is directly related to the radius of the magnetopause. This behavior conforms to Chapman and Ferraro's theory of planetary magnetospheres. Although the radial dependence of the magnetic field strength differs between the case of a current-carrying wire and a typical planetary object, the major morphological features that develop when a supersonic flow passes either system are identical. Hence, this experimental concept is an attractive one for studying the dynamics of planetary magnetospheres in a controlled environment.

  4. Potential role of microRNA-10b down-regulation in cardiomyocyte apoptosis in aortic stenosis patients.

    PubMed

    Gallego, Idoia; Beaumont, Javier; López, Begoña; Ravassa, Susana; Gómez-Doblas, Juan José; Moreno, María Ujué; Valencia, Félix; de Teresa, Eduardo; Díez, Javier; González, Arantxa

    2016-12-01

    MicroRNAs have been associated with cardiomyocyte apoptosis, a process involved in myocardial remodelling in aortic valve (Av) stenosis (AS). Our aim was to analyse whether the dysregulation of myocardial microRNAs was related to cardiomyocyte apoptosis in AS patients. Endomyocardial biopsies were obtained from 28 patients with severe AS (based on pressure gradients and Av area) referred for Av replacement and from necropsies of 10 cardiovascular disease-free control subjects. AS patients showed an increased (P<0.001) cardiomyocyte apoptotic index (CMAI) compared with controls. Two clusters of patients were identified according to the CMAI: group 1 (CMAI ≤ 0.08%; n=16) and group 2 (CMAI > 0.08%; n=12). Group 2 patients presented lower cardiomyocyte density (P<0.001) and ejection fraction (P<0.05), and higher troponin T levels (P<0.05), prevalence of heart failure (HF; P<0.05) and NT-proBNP levels (P<0.05) than those from group 1. miRNA expression profile analysed in 5 patients randomly selected from each group showed 64 microRNAs down-regulated and 6 up-regulated (P<0.05) in group 2 compared with group 1. Those microRNAs with the highest fold-change were validated in the full two groups corroborating that miR-10b, miR-125b-2* and miR-338-3p were down-regulated (P<0.05) in group 2 compared with group 1 and control subjects. These three microRNAs were inversely correlated (P<0.05) with the CMAI. Inhibition of miR-10b induced an increase (P<0.05) of apoptosis and increased expression (P<0.05) of apoptosis protease-activating factor-1 (Apaf-1) in HL-1 cardiomyocytes. In conclusion, myocardial down-regulation of miR-10b may be involved in increased cardiomyocyte apoptosis in AS patients, probably through Apaf-1 up-regulation, contributing to cardiomyocyte damage and to the development of HF. © 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

  5. Plant Volatile Analogues Strengthen Attractiveness to Insect

    PubMed Central

    Sun, Yufeng; Yu, Hao; Zhou, Jing-Jiang; Pickett, John A.; Wu, Kongming

    2014-01-01

    Green leaf bug Apolygus lucorum (Meyer-Dür) is one of the major pests in agriculture. Management of A. lucorum was largely achieved by using pesticides. However, the increasing population of A. lucorum since growing Bt cotton widely and the increased awareness of ecoenvironment and agricultural product safety makes their population-control very challenging. Therefore this study was conducted to explore a novel ecological approach, synthetic plant volatile analogues, to manage the pest. Here, plant volatile analogues were first designed and synthesized by combining the bioactive components of β-ionone and benzaldehyde. The stabilities of β-ionone, benzaldehyde and analogue 3 g were tested. The electroantennogram (EAG) responses of A. lucorum adult antennae to the analogues were recorded. And the behavior assay and filed experiment were also conducted. In this study, thirteen analogues were acquired. The analogue 3 g was demonstrated to be more stable than β-ionone and benzaldehyde in the environment. Many of the analogues elicited EAG responses, and the EAG response values to 3 g remained unchanged during seven-day period. 3 g was also demonstrated to be attractive to A. lucorum adults in the laboratory behavior experiment and in the field. Its attractiveness persisted longer than β-ionone and benzaldehyde. This indicated that 3 g can strengthen attractiveness to insect and has potential as an attractant. Our results suggest that synthetic plant volatile analogues can strengthen attractiveness to insect. This is the first published study about synthetic plant volatile analogues that have the potential to be used in pest control. Our results will support a new ecological approach to pest control and it will be helpful to ecoenvironment and agricultural product safety. PMID:24911460

  6. Nuclear structure with accurate chiral perturbation theory nucleon-nucleon potential: Application to 6Li and 10B

    SciTech Connect

    Navratil, P; Caurier, E

    2003-10-14

    The authors calculate properties of A = 6 system using the accurate charge-dependent nucleon-nucleon (NN) potential at fourth order of chiral perturbation theory. By application of the ab initio no-core shell model (NCSM) and a variational calculation in the harmonic oscillator basis with basis size up to 16 {h_bar}{Omega} they obtain the {sup 6}Li binding energy of 28.5(5) MeV and a converged excitation spectrum. Also, they calculate properties of {sup 10}B using the same NN potential in a basis space of up to 8 {h_bar}{Omega}. The results are consistent with results obtained by standard accurate NN potentials and demonstrate a deficiency of Hamiltonians consisting of only two-body terms. At this order of chiral perturbation theory three-body terms appear. It is expected that inclusion of such terms in the Hamiltonian will improve agreement with experiment.

  7. Evaluating 10B-enriched Boric Acid, Bromide, and Heat as Tracers of Recycled Groundwater Flow near MAR Operations

    NASA Astrophysics Data System (ADS)

    Becker, T.; Clark, J. F.

    2012-12-01

    County, CA, USA) has been in progress since September 6, 2011, following injection of boric acid enriched in boron-10 (10B) and bromide (Br-) tracers. Tracer concentrations are collected at 9 monitoring wells that have pre-experiment estimated travel times between 0.5 to 180 days. Results indicate that 10B-enriched boric acid is an effective deliberate tracer at MAR sites; however, the ion's movement is slightly retarded relative to bromide by the substrate. 10B/Br- travel time ratios range from 1 to 1.4. In addition to the two deliberate geochemical tracers, heat is being evaluated as a possible intrinsic tracer at MAR sites. At the time of the experiment (late summer), reclaimed water was significantly warmer (~20°F) than the native groundwater as it entered the system. Time series are developed from loggers outfitted at each monitoring well, with measurements recorded hourly accurate to one thousandth of a degree. Results are similar to 10B & Br- travel times and validate the potential of heat as an intrinsic tracer.

  8. {sup 4}H-SiC neutron sensors based on ion implanted {sup 10}B neutron converter layer

    SciTech Connect

    Issa, F.; Ottaviani, L.; Vervisch, V.; Ferone, R.; Palais, O.; Szalkai, D.; Klix, A.; Vermeeren, L.; Lyoussi, A.; Kuznetsov, A.; Lazar, M.; Hallen, A.

    2015-07-01

    In the framework of the I{sub S}MART project the main aim is to develop an innovative complete radiation detection system based on silicon carbide technology in view to detect neutrons (thermal and fast) and photons for harsh environments. In the present work two geometries have been realized based on ion implantation of boron. In the first geometry, {sup 10}B ions have been implanted into the Al metallic contact to create the neutron converter layer. In the second geometry one single process has been used to realize both the p+-layer and the neutron converter layer. The technological processes followed to fabricate these detectors, with a study of their electrical behavior and their responses under thermal neutron irradiations are addressed in this paper. (authors)

  9. Morphology and magnetic behavior of cobalt rich amorphous/nanocrystalline (Co-Ni)70Ti10B20 alloyed powders

    NASA Astrophysics Data System (ADS)

    Raanaei, Hossein; Mohammad-Hosseini, Vahid

    2016-09-01

    The effect of milling time on microstructural and magnetic behavior of mechanically alloyed Co49Ni21Ti10B20 is investigated by using X-ray diffraction, scanning electron microscopy, transmission electron microscopy, energy dispersive X-ray spectroscopy, differential scanning calorimetry and vibrating sample magnetometer. It is shown, with increasing milling time, the crystallite size decreases and finally reaches to a low value after 190 h of milling time. The increase in microstrain is also observed during the milling process. The results indicate the coexistence between amorphous and nanocrystalline phases after 190 h of milling time. Moreover, the lowest magnetic coercivity of about 39 Oe at the final milling stage is observed. The results of annealed sample reveal structural ordering of constituent elements.

  10. Nuclear Astrophysics at LNL: The 10B(p, α )7Be Reaction Studied at the AN2000 Accelerator

    NASA Astrophysics Data System (ADS)

    Caciolli, Antonio

    The National Laboratory of Legnaro (LNL) has a wealth of experience in Nuclear Physics measurements. Recently a new effort to perform Nuclear Astrophysics studies has been initiated. This effort started with the collaboration of LNL with the LUNA (Laboratory for Underground Nuclear Astrophysics) collaboration for the study of targets. In 2014 the study of 10B(p, α )7Be was performed in order to give a precise normalisation to the indirect measurements. As a matter of fact, a normalization problem was raised in previous works due to discrepancies in the results of different experimental datasets. At LNL the cross section was determined by measuring the activated samples at the low counting facility of the LNL laboratory. The analysis of that experiment is now complete and a detailed report of the obtained results will be presented in this contribution.

  11. A 10-b 50-MS/s 820- μW SAR ADC With On-Chip Digital Calibration.

    PubMed

    Yoshioka, Masato; Ishikawa, Kiyoshi; Takayama, Takeshi; Tsukamoto, Sanroku

    2010-12-01

    This 10-b 50-MSamples/s SAR analog-to-digital converter (ADC) features on-chip digital calibration techniques, comparator offset cancellation, a capacitor digital-to-analog converter (CDAC) linearity calibration, and internal clock control to compensate for PVT variations. A split-CDAC reduces the exponential increase in the number of unit capacitors needed and enables the input load capacitance to be as small as the kT/C noise restriction. The prototype fabricated in 65 nm 1P7M complementary metal-oxide semiconductor with MIM capacitor achieves 56.6 dB SNDR at 50-MSamples/s, 25-MHz input frequency and consumes 820 μW from a 1.0-V supply, including the digital calibration circuits. The figure of merit was 29.7 fJ/conversion-step under the Nyquist condition. The ADC occupied an active area of 0.039 mm(2) .

  12. Condensed matter analogues of cosmology

    NASA Astrophysics Data System (ADS)

    Kibble, Tom; Srivastava, Ajit

    2013-10-01

    It is always exciting when developments in one branch of physics turn out to have relevance in a quite different branch. It would be hard to find two branches farther apart in terms of energy scales than early-universe cosmology and low-temperature condensed matter physics. Nevertheless ideas about the formation of topological defects during rapid phase transitions that originated in the context of the very early universe have proved remarkably fruitful when applied to a variety of condensed matter systems. The mathematical frameworks for describing these systems can be very similar. This interconnection has led to a deeper understanding of the phenomena in condensed matter systems utilizing ideas from cosmology. At the same time, one can view these condensed matter analogues as providing, at least in a limited sense, experimental access to the phenomena of the early universe for which no direct probe is possible. As this special issue well illustrates, this remains a dynamic and exciting field. The basic idea is that when a system goes through a rapid symmetry-breaking phase transition from a symmetric phase into one with spontaneously broken symmetry, the order parameter may make different choices in different regions, creating domains that when they meet can trap defects. The scale of those domains, and hence the density of defects, is constrained by the rate at which the system goes through the transition and the speed with which order parameter information propagates. This is what has come to be known as the Kibble-Zurek mechanism. The resultant scaling laws have now been tested in a considerable variety of different systems. The earliest experiments illustrating the analogy between cosmology and condensed matter were in liquid crystals, in particular on the isotropic-to-nematic transition, primarily because it is very easy to induce the phase transition (typically at room temperature) and to image precisely what is going on. This field remains one of the

  13. Set-up and calibration of a method to measure 10B concentration in biological samples by neutron autoradiography

    NASA Astrophysics Data System (ADS)

    Gadan, M. A.; Bortolussi, S.; Postuma, I.; Ballarini, F.; Bruschi, P.; Protti, N.; Santoro, D.; Stella, S.; Cansolino, L.; Clerici, A.; Ferrari, C.; Zonta, A.; Zonta, C.; Altieri, S.

    2012-03-01

    A selective uptake of boron in the tumor is the base of Boron Neutron Capture Therapy, which can destroy the tumor substantially sparing the normal tissue. In order to deliver a lethal dose to the tumor, keeping the dose absorbed by normal tissues below the tolerance level, it is mandatory to know the 10B concentration present in each kind of tissue at the moment of irradiation. This work presents the calibration procedure adopted for a boron concentration measurement method based on neutron autoradiography, where biological samples are deposited on sensitive films and irradiated in the thermal column of the TRIGA reactor (University of Pavia). The latent tracks produced in the film by the charged particles coming from the neutron capture in 10B are made visible by a proper etching, allowing the measurement of the track density. A calibration procedure with standard samples provides curves of track density as a function of boron concentration, to be used in the measurement of biological samples. In this paper, the bulk etch rate parameter and the calibration curves obtained for both liquid samples and biological tissues with known boron concentration are presented. A bulk etch rate value of (1.64 ± 0.02) μm/h and a linear dependence with etching time were found. The plots representing the track density versus the boron concentration in a range between 5 and 50 μg/g (ppm) are linear, with an angular coefficient of (1.614 ± 0.169)·10-3 tracks/(μm2 ppm) for liquids and (1.598 ± 0.097)·10-2 tracks/(μm2 ppm) for tissues.

  14. Actions of Thyroid Hormone Analogues on Chemokines

    PubMed Central

    Glinsky, Gennadi V.

    2016-01-01

    The extracellular domain of plasma membrane integrin αvβ3 contains a receptor for thyroid hormone (L-thyroxine, T4; 3,5,3′-triiodo-L-thyronine, T3); this receptor also binds tetraiodothyroacetic acid (tetrac), a derivative of T4. Tetrac inhibits the binding of T4 and T3 to the integrin. Fractalkine (CX3CL1) is a chemokine relevant to inflammatory processes in the CNS that are microglia-dependent but also important to normal brain development. Expression of the CX3CL1 gene is downregulated by tetrac, suggesting that T4 and T3 may stimulate fractalkine expression. Independently of its specific receptor (CX3CR1), fractalkine binds to αvβ3 at a site proximal to the thyroid hormone-tetrac receptor and changes the physical state of the integrin. Tetrac also affects expression of the genes for other CNS-relevant chemokines, including CCL20, CCL26, CXCL2, CXCL3, and CXCL10. The chemokine products of these genes are important to vascularity of the brain, particularly of the choroid plexus, to inflammatory processes in the CNS and, in certain cases, to neuroprotection. Thyroid hormones are known to contribute to regulation of each of these CNS functions. We propose that actions of thyroid hormone and hormone analogues on chemokine gene expression contribute to regulation of inflammatory processes in brain and of brain blood vessel formation and maintenance. PMID:27493972

  15. Sensitivity of groundwater recharge using climatic analogues and HYDRUS-1D

    NASA Astrophysics Data System (ADS)

    Leterme, B.; Mallants, D.; Jacques, D.

    2012-08-01

    The sensitivity of groundwater recharge to different climate conditions was simulated using the approach of climatic analogue stations, i.e. stations presently experiencing climatic conditions corresponding to a possible future climate state. The study was conducted in the context of a safety assessment of a future near-surface disposal facility for low and intermediate level short-lived radioactive waste in Belgium; this includes estimation of groundwater recharge for the next millennia. Groundwater recharge was simulated using the Richards based soil water balance model HYDRUS-1D and meteorological time series from analogue stations. This study used four analogue stations for a warmer subtropical climate with changes of average annual precipitation and potential evapotranspiration from -42% to +5% and from +8% to +82%, respectively, compared to the present-day climate. Resulting water balance calculations yielded a change in groundwater recharge ranging from a decrease of 72% to an increase of 3% for the four different analogue stations. The Gijon analogue station (Northern Spain), considered as the most representative for the near future climate state in the study area, shows an increase of 3% of groundwater recharge for a 5% increase of annual precipitation. Calculations for a colder (tundra) climate showed a change in groundwater recharge ranging from a decrease of 97% to an increase of 32% for four different analogue stations, with an annual precipitation change from -69% to -14% compared to the present-day climate.

  16. An analogue conceptual rainfall-runoff model for educational purposes

    NASA Astrophysics Data System (ADS)

    Herrnegger, Mathew; Riedl, Michael; Schulz, Karsten

    2016-04-01

    Conceptual rainfall-runoff models, in which runoff processes are modelled with a series of connected linear and non-linear reservoirs, remain widely applied tools in science and practice. Additionally, the concept is appreciated in teaching due to its somewhat simplicity in explaining and exploring hydrological processes of catchments. However, when a series of reservoirs are used, the model system becomes highly parametrized and complex and the traceability of the model results becomes more difficult to explain to an audience not accustomed to numerical modelling. Since normally the simulations are performed with a not visible digital code, the results are also not easily comprehensible. This contribution therefore presents a liquid analogue model, in which a conceptual rainfall-runoff model is reproduced by a physical model. This consists of different acrylic glass containers representing different storage components within a catchment, e.g. soil water or groundwater storage. The containers are equipped and connected with pipes, in which water movement represents different flow processes, e.g. surface runoff, percolation or base flow. Water from a storage container is pumped to the upper part of the model and represents effective rainfall input. The water then flows by gravity through the different pipes and storages. Valves are used for controlling the flows within the analogue model, comparable to the parameterization procedure in numerical models. Additionally, an inexpensive microcontroller-based board and sensors are used to measure storage water levels, with online visualization of the states as time series data, building a bridge between the analogue and digital world. The ability to physically witness the different flows and water levels in the storages makes the analogue model attractive to the audience. Hands-on experiments can be performed with students, in which different scenarios or catchment types can be simulated, not only with the analogue but

  17. MicroRNA 10b promotes abnormal expression of the proto-oncogene c-Jun in metastatic breast cancer cells

    PubMed Central

    Knirsh, Revital; Ben-Dror, Iris; Modai, Shira; Shomron, Noam; Vardimon, Lily

    2016-01-01

    MicroRNAs have been shown to act as oncogenes or tumor suppressers via various cellular pathways. Specifically, in breast cancer, upregulation of miR-10b is positively associated with aggressiveness of tumors. However, the mechanism by which miR-10b contributes to cell malignancy is largely unknown. Here we show that at the receiving end of the miR-10b pathway is the proto-oncogene c-Jun, a transcription factor that plays a critical role in stimulation of cell proliferation and tumor progression. c-Jun is known to be translationally activated by loss of cell contacts or restructuring of the cytoskeleton. A comprehensive analysis of miRNA expression exhibited a significant increase in miR-10b expression. This was supported by analysis of breast cancer cells, which showed that loss of E-cadherin in metastatic cells is accompanied by elevation of miR-10b and interestingly, by a marked increase in accumulation of c-Jun. Silencing miR-10b in metastatic breast cancer cells leads to a decline in c-Jun expression, whereas overexpression of miR-10b in HaCaT cells is sufficient to elevate the accumulation of c-Jun. The increase in c-Jun protein accumulation in metastatic cells is not accompanied by an increase in c-Jun mRNA and is not dependent on MAPK activity. Knockdown and overexpression experiments revealed that the increase is mediated by NF1 and RhoC, downstream targets of miR-10b that affect cytoskeletal dynamics through the ROCK pathway. Overall, we show the ability of miR-10b to activate the expression of c-Jun through RhoC and NF1, which represents a novel pathway for promoting migration and invasion of human cancer cells. PMID:27494896

  18. MicroRNA-10b inhibition reduces E2F1-mediated transcription and miR-15/16 activity in glioblastoma

    PubMed Central

    Teplyuk, Nadiya M.; Uhlmann, Erik J.; Wong, Andus Hon-Kit; Karmali, Priya; Basu, Meenakshi; Gabriely, Galina; Jain, Anant; Wang, Yang; Chiocca, E. Antonio; Stephens, Robert; Marcusson, Eric; Yi, Ming; Krichevsky, Anna M.

    2015-01-01

    MicroRNA-10b (miR-10b) is commonly elevated in glioblastoma (GBM), while not expressed in normal brain tissues. Targeted inhibition of miR-10b has pleiotropic effects on GBM derived cell lines, it reduces GBM growth in animal models, but does not affect normal neurons and astrocytes. This data raises the possibility of developing miR-10b-targeting GBM therapy. However, the mechanisms contributing to miR-10b-mediated glioma cell survival and proliferation are unexplored. We found that inhibition of miR-10b has distinct effects on specific glioma cell lines. In cells expressing high levels of tumor suppressor p21WAF1/Cip1, it represses E2F1-mediated transcription, leading to down-regulation of multiple E2F1 target genes encoding for S-phase specific proteins, epigenetic modulators, and miRNAs (e.g. miR-15/16), and thereby stalling progression through the S-phase of cell cycle. Subsequently, miR-15/16 activities are reduced and many of their direct targets are de-repressed, including ubiquitin ligase FBXW7 that destabilizes Cyclin E. Conversely, GBM cells expressing low p21 level, or after p21 knock-down, exhibit weaker or no E2F1 response to miR-10b inhibition. Comparative analysis of The Cancer Genome Atlas revealed a strong correlation between miR-10b and multiple E2F target genes in GBM and low-grade glioma. Taken together, these findings indicate that miR-10b regulates E2F1-mediated transcription in GBM, in a p21-dependent fashion. PMID:25738367

  19. Analogue gravity models from conformal rescaling

    NASA Astrophysics Data System (ADS)

    Hossenfelder, Sabine; Zingg, Tobias

    2017-08-01

    Analogue gravity is based on a mathematical identity between quantum field theory in curved space-time and the propagation of perturbations in certain condensed matter systems. But not every curved space-time can be simulated in such a way. For analogue gravity to work, one needs not only a condensed matter system that generates the desired metric tensor, but this system then also has to obey its own equations of motion. However, the relation to the metric tensor usually overdetermines the equations of the underlying condensed matter system, such that they in general cannot be fulfilled. In this case the desired metric does not have an analogue. Here, we show that the class of metrics that have an analogue is larger than previously thought. The reason is that the analogue metric is only defined up to a choice of parametrization of the perturbation in the underlying condensed matter system. In this way, the class of analogue gravity models can be vastly expanded.

  20. The analogue method for precipitation prediction: finding better analogue situations at a sub-daily time step

    NASA Astrophysics Data System (ADS)

    Horton, Pascal; Obled, Charles; Jaboyedoff, Michel

    2017-07-01

    Analogue methods (AMs) predict local weather variables (predictands) such as precipitation by means of a statistical relationship with predictors at a synoptic scale. The analogy is generally assessed on gradients of geopotential heights first to sample days with a similar atmospheric circulation. Other predictors such as moisture variables can also be added in a successive level of analogy. The search for candidate situations similar to a given target day is usually undertaken by comparing the state of the atmosphere at fixed hours of the day for both the target day and the candidate analogues. This is a consequence of using standard daily precipitation time series, which are available over longer periods than sub-daily data. However, it is unlikely for the best analogy to occur at the exact same hour for the target and candidate situations. A better analogue situation may be found with a time shift of several hours since a better fit can occur at different times of the day. In order to assess the potential for finding better analogues at a different hour, a moving time window (MTW) has been introduced. The MTW resulted in a better analogy in terms of the atmospheric circulation and showed improved values of the analogy criterion on the entire distribution of the extracted analogue dates. The improvement was found to increase with the analogue rank due to an accumulation of better analogues in the selection. A seasonal effect has also been identified, with larger improvements shown in winter than in summer. This may be attributed to stronger diurnal cycles in summer that favour predictors taken at the same hour for the target and analogue days. The impact of the MTW on the precipitation prediction skill has been assessed by means of a sub-daily precipitation series transformed into moving 24 h totals at 12, 6, and 3 h time steps. The prediction skill was improved by the MTW, as was the reliability of the prediction. Moreover, the improvements were greater for days

  1. Projected Future Climate Analogues and Climate "Velocities" in North America

    NASA Astrophysics Data System (ADS)

    Shafer, S. L.; Bartlein, P. J.

    2014-12-01

    Future climate changes may have significant effects on many North American ecosystems. One way of assessing the potential impacts of future climate change is to use future climate analogues of present climate to evaluate the spatial extent and rates of future climate change. We used a set of Coupled Model Intercomparison Project phase 5 (CMIP5) coupled atmosphere-ocean general circulation model (AOGCM) future climate simulations (2006-2100) produced under representative concentration pathway scenario RCP8.5. We regridded these data to a 10-km equal-area grid of North America. Modern climate data (1961-1990 30-year mean) were interpolated to the same 10-km grid. The projected future climate data were analyzed using 10-year mean values of monthly and seasonal temperature and precipitation and a set of derived annual bioclimatic variables (e.g., growing degree days) considered to be ecologically significant. Potential future climate analogues were calculated for each grid cell using Euclidean distances to identify similar climates occurring elsewhere in North America. We identify regions that are projected to retain climates similar to present in the future (e.g., parts of the southeastern United States) and regions where present climates are projected to become less common or to disappear in the future (e.g., high elevation sites in western North America). We also calculate the rates of change in locations of similar climates (i.e., climate analogue velocities) and compare our results with simulated paleoclimate velocities over the past 22 kyr (from TraCE-21ka transient climate simulations for 22 ka-present). We discuss the implications of these results for conservation and natural resource management in North America. We also describe a web application being developed to allow researchers, decision makers, and members of the public, to visualize, explore, and use the climate analogue data.

  2. The neutral analogue of Roussin's red salt anion: a density functional study.

    PubMed

    Sárosi, Menyhárt B; Silaghi-Dumitrescu, Luminiţa; King, R Bruce

    2012-05-07

    Density functional calculations on the experimentally unknown neutral analogue of Roussin's red salt anion, namely Fe(2)(NO)(4)S(2), predict ground state structures with diradical character. The presence of a reactive diradical ground state with unpaired electrons for the neutral Fe(2)(NO)(4)S(2) system could explain why it has not yet been synthesized.

  3. Nanometer-scale investigation of compositional and structural evolution during crystallization of melt-spun Co84Nb10B6 metallic glass

    NASA Astrophysics Data System (ADS)

    Lusby, Thomas Alan

    2000-08-01

    Nanocrystalline materials are increasingly showing progress in the quest to control the properties of a solid. As the building blocks of matter approach sizes on the order of 100 nanometers or less, nearly every physical property of the material is altered. One class of nanocrystalline material that has received considerable attention in recent decades and especially in the last several years is that of the metallic glass. This research project was performed in order to obtain a better understanding of the formation of nanocrystalline structure in a Co-based metallic glass. Ribbons of a Co84Nb10B6 metallic glass were rapidly quenched by the melt spinning technique. Field Ion Microscopy (FIM), Atom Probe Field Ion Microscopy (APFIM) and Transmission Electron Microscopy (TEM) were applied to study the micro-structural and nanocompositional changes of Co84Nb10B6 due to annealing. The as-quenched metallic glass was determined to be amorphous by FIM and APFIM. Subsequent annealing at various temperatures and times produced specimens in different stages of phase separation and nanocrystallinity. Crystal nuclei in specimens annealed for one hour at 500, 550, and 600 C were constant in size (4 nm) but increased in number density with increasing temperature. Annealing at 700 C for one hour produced a fully crystalline, three-phase material. The phases consist of a nanocrystalline boride phase, a nanocrystalline Co3Nb phase, both with average grain sizes of 20--50 nm, and a relatively pure cobalt matrix. The various phases exhibited significantly different field evaporation and imaging behavior in the FIM. Prior to this work, it was hypothesized that boron atoms segregating to grain boundaries played a role in limiting the grain growth of this nanocrystalline material. The composition fluctuations across several grain boundaries were analyzed and there was no evidence of boron accumulation. The results of this work suggest another mechanism must be keeping the grains of this

  4. Planetary habitability: lessons learned from terrestrial analogues

    NASA Astrophysics Data System (ADS)

    Preston, Louisa J.; Dartnell, Lewis R.

    2014-01-01

    Terrestrial analogue studies underpin almost all planetary missions and their use is essential in the exploration of our Solar system and in assessing the habitability of other worlds. Their value relies on the similarity of the analogue to its target, either in terms of their mineralogical or geochemical context, or current physical or chemical environmental conditions. Such analogue sites offer critical ground-truthing for astrobiological studies on the habitability of different environmental parameter sets, the biological mechanisms for survival in extreme environments and the preservation potential and detectability of biosignatures. The 33 analogue sites discussed in this review have been selected on the basis of their congruence to particular extraterrestrial locations. Terrestrial field sites that have been used most often in the literature, as well as some lesser known ones which require greater study, are incorporated to inform on the astrobiological potential of Venus, Mars, Europa, Enceladus and Titan. For example, the possibility of an aerial habitable zone on Venus has been hypothesized based on studies of life at high-altitudes in the terrestrial atmosphere. We also demonstrate why many different terrestrial analogue sites are required to satisfactorily assess the habitability of the changing environmental conditions throughout Martian history, and recommend particular sites for different epochs or potential niches. Finally, habitable zones within the aqueous environments of the icy moons of Europa and Enceladus and potentially in the hydrocarbon lakes of Titan are discussed and suitable analogue sites proposed. It is clear from this review that a number of terrestrial analogue sites can be applied to multiple planetary bodies, thereby increasing their value for astrobiological exploration. For each analogue site considered here, we summarize the pertinent physiochemical environmental features they offer and critically assess the fidelity with which

  5. 17 CFR 240.10b-21 - Deception in connection with a seller's ability or intent to deliver securities on the date...

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... Act of 1934 Manipulative and Deceptive Devices and Contrivances § 240.10b-21 Deception in connection... thereunder. (a) It shall also constitute a “manipulative or deceptive device or contrivance” as used...

  6. 17 CFR 240.10b-21 - Deception in connection with a seller's ability or intent to deliver securities on the date...

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... Act of 1934 Manipulative and Deceptive Devices and Contrivances § 240.10b-21 Deception in connection... thereunder. (a) It shall also constitute a “manipulative or deceptive device or contrivance” as used...

  7. 17 CFR 240.10b-21 - Deception in connection with a seller's ability or intent to deliver securities on the date...

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... Act of 1934 Manipulative and Deceptive Devices and Contrivances § 240.10b-21 Deception in connection... thereunder. (a) It shall also constitute a “manipulative or deceptive device or contrivance” as used...

  8. 17 CFR 240.10b5-1 - Trading “on the basis of” material nonpublic information in insider trading cases.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... Deceptive Devices and Contrivances § 240.10b5-1 Trading “on the basis of” material nonpublic information in... in any other respect. (a) General. The “manipulative and deceptive devices” prohibited by Section...

  9. 17 CFR 240.10b5-1 - Trading “on the basis of” material nonpublic information in insider trading cases.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... Deceptive Devices and Contrivances § 240.10b5-1 Trading “on the basis of” material nonpublic information in... in any other respect. (a) General. The “manipulative and deceptive devices” prohibited by Section...

  10. 17 CFR 240.10b-21 - Deception in connection with a seller's ability or intent to deliver securities on the date...

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... Act of 1934 Manipulative and Deceptive Devices and Contrivances § 240.10b-21 Deception in connection... thereunder. (a) It shall also constitute a “manipulative or deceptive device or contrivance” as used...

  11. 17 CFR 240.10b-21 - Deception in connection with a seller's ability or intent to deliver securities on the date...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Act of 1934 Manipulative and Deceptive Devices and Contrivances § 240.10b-21 Deception in connection... thereunder. (a) It shall also constitute a “manipulative or deceptive device or contrivance” as used...

  12. 17 CFR 240.10b5-1 - Trading “on the basis of” material nonpublic information in insider trading cases.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... Deceptive Devices and Contrivances § 240.10b5-1 Trading “on the basis of” material nonpublic information in... in any other respect. (a) General. The “manipulative and deceptive devices” prohibited by Section...

  13. 17 CFR 240.10b5-1 - Trading “on the basis of” material nonpublic information in insider trading cases.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... Deceptive Devices and Contrivances § 240.10b5-1 Trading “on the basis of” material nonpublic information in... in any other respect. (a) General. The “manipulative and deceptive devices” prohibited by Section...

  14. (10)B/(11)B isotopic ratio and atomic composition of boron carbide: Determination by proton induced γ-ray emission and proton elastic backscattering spectrometry.

    PubMed

    Sunitha, Y; Kumar, Sanjiv

    2017-10-01

    The (10)B/(11)B isotopic ratio and the atomic composition of boron carbide, an important non-metallic ceramic, have been determined non-destructively by the particle induced γ-ray emission (PIGE) and elastic backscattering spectrometry (EBS) techniques with proton beams. The analysis has been performed on powder as well as sintered ceramics containing boron in natural or (10)B enriched composition. The PIGE technique, performed at a 4.0-4.2MeV proton energy, utilizes the (10)B(p,αγ)(7)Be, (10)B(p,p'γ)(10)B and (11)B(p, p'γ)(11)B nuclear reactions for (a) the isotopic analysis of boron and (b) the determination of total boron, and the (13)C(p,p'γ)(13)C nuclear reaction for the determination of carbon. The irradiation conditions were optimized by determining the thick targets yields of prompt γ-rays, characteristic of these reactions, in the 3.0-4.2MeV proton energy range. The quantitative analysis was performed by comparison with standards taking into account the attenuation of γ-rays in the specimens. The uncertainty in the determination of the (10)B/(11)B isotopic ratio and the B/C atomic ratio is about 2% and about 5% respectively. The analysis by EBS, on the other hand, involves the (10)B(p,p)(10)B, (11)B(p,p)(11)B and (12)C(p,p)(12)C elastic scatterings at the 2.0MeV proton energy. This method too yields satisfactory results. Between the two, PIGE is the method of choice for bulk analysis while EBS is useful in discerning compositional variations in surface regions. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Glucagonlike Peptide 2 Analogue Teduglutide

    PubMed Central

    Chaturvedi, Lakshmi S.; Basson, Marc D.

    2015-01-01

    IMPORTANCE Short bowel syndrome occurs when a shortened intestine cannot absorb sufficient nutrients or fluids. Teduglutide is a recombinant analogue of human glucagonlike peptide 2 that reduces dependence on parenteral nutrition in patients with short bowel syndrome by promoting enterocytic proliferation, increasing the absorptive surface area. However, enterocyte function depends not only on the number of cells that are present but also on differentiated features that facilitate nutrient absorption and digestion. OBJECTIVE To test the hypothesis that teduglutide impairs human intestinal epithelial differentiation. DESIGN AND SETTING We investigated the effects of teduglutide in the modulation of proliferation and differentiation in human Caco-2 intestinal epithelial cells at a basic science laboratory. This was an in vitro study using Caco-2 cells, a human-derived intestinal epithelial cell line commonly used to model enterocytic biology. EXPOSURE Cells were exposed to teduglutide or vehicle control. MAINOUTCOMESAND MEASURES We analyzed the cell cycle by bromodeoxyuridine incorporation or propidium iodide staining and flow cytometry and measured cell proliferation by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay. We used quantitative reverse transcription–polymerase chain reaction to assay the expression of the enterocytic differentiation markers villin, sucrase-isomaltase, glucose transporter 2 (GLUT2), and dipeptidyl peptidase 4 (DPP-4), as well as that of the putative differentiation signals schlafen 12 (SLFN12) and caudal-related homeobox intestine-specific transcription factor (Cdx2). Villin promoter activity was measured by a luciferase-based assay. RESULTS The MTS assay demonstrated that teduglutide increased cell numbers by a mean (SD) of 10% (2%) over untreated controls at a maximal 500nM (n = 6, P < .05). Teduglutide increased bromodeoxyuridine-positive cells vs untreated controls by a mean (SD

  16. Distribution of 10B after infusion of Na210B12H11SH into a patient with malignant astrocytoma: implications for boron neutron capture therapy.

    PubMed

    Finkel, G C; Poletti, C E; Fairchild, R G; Slatkin, D N; Sweet, W H

    1989-01-01

    If a sufficient concentration of the stable isotope 10B is introduced into a neoplasm, radiation therapy can be effected by short-range heavy charged particles from the disintegration of 10B by slow neutrons. Brain tumors were irradiated postoperatively by Hatanaka and co-workers in Japan using a 1 to 2 hour intraarterial infusion of 10B-enriched Na2B12H11SH (Na210B12H11SH) before exposure of the tumor-bearing area of the brain to slow neutrons from a 100 kilowatt nuclear reactor. The clinical outcome of such boron neutron capture therapy has been favorably impressive in some patients, but its efficacy in brain tumors needs improvement. In our study, a terminally ill patient with malignant astrocytoma was infused intravenously with Na210B12H11SH for 25 hours. The postmortem distribution of 10B in unfixed, frozen, tumor-bearing brain and spinal cord tissues was studied by comparing representative cryostat sections of these specimens with neutron-induced heavy charged particle radiographs of the same sections. Preferential accumulation of 10B was observed in the tumor, with relatively little accumulation of 10B in the parenchyma of the central nervous system.

  17. Boron uptake in tumors, cerebrum and blood from (/sup 10/B)Na/sub 4/B/sub 24/H/sub 22/S/sub 2/

    DOEpatents

    Slatkin, D.N.; Micca, P.L.; Fairchild, R.G.

    1986-03-11

    A stable boronated (/sup 10/B-labeled) compound, sodium mercaptoundecahydrododecaborate is infused in the form of the disulfide dimer, (/sup 10/B)Na/sub 4/B/sub 24/H/sub 22/S/sub 2/, at a dose of about 200 ..mu..g /sup 10/B per gm body weight. The infusion is preformed into the blood or peritoneal cavity of the patient slowly over a period of many days, perhaps one week or more, at the rate of roughly 1 ..mu..g /sup 10/B per gm body weight per hour. Use of this particular boronated dimer in the manner or similarly to the manner so described permits radiotherapeutically effective amounts of boron to accumulate in tumors to be treated by boron neutron capture radiation therapy and also permits sufficient retention of boron in tumor after the cessation of the slow infusion, so as to allow the blood concentration of /sup 10/B to drop or to be reduced artificially to a radiotherapeutically effective level, less than one-half of the concentration of /sup 10/B in the tumor. 1 tab.

  18. Revisiting the birth locations of pulsars B1929+10, B2020+28, and B2021+51

    NASA Astrophysics Data System (ADS)

    Kirsten, Franz; Vlemmings, Wouter; Campbell, Robert M.; Kramer, Michael; Chatterjee, Shami

    2015-05-01

    We present new proper motion and parallax measurements obtained with the European VLBI Network (EVN) at 5GHz for the three isolated pulsars B1929+10, B2020+28, and B2021+51. For B1929+10 we combined our data with earlier VLBI measurements and confirm the robustness of the astrometric parameters of this pulsar. For pulsars B2020+28 and B2021+51 our observations indicate that both stars are almost a factor of two closer to the solar system than previously thought, placing them at a distance of 1.39-0.06+0.05 and 1.25-0.17+ 0.14kpc. Using our new astrometry, we simulated the orbits of all three pulsars in the Galactic potential with the aim to confirm or reject previously proposed birth locations. Our observations ultimately rule out a claimed binary origin of B1929+10 and the runaway star ζ Ophiuchi in Upper Scorpius. A putative common binary origin of B2020+28 and B2021+51 in the Cygnus Superbubble is also very unlikely.

  19. A Bayesian Atmospheric Retrieval Performed on HAT-P-16b and WASP-11b/HAT-P-10b

    NASA Astrophysics Data System (ADS)

    McIntyre, Kathleen J.; Harrington, Joseph; Challener, Ryan C.; Hardin, Matthew Ryan; Bowman, Oliver Oliver; Foster, Andrew S. D.; Lenius, Maria; Hartman, Joel D.; Bakos, Gaspar; Blecic, Jasmina; Cubillos, Patricio; Ariston Hardy, Ryan; Cameron, Andrew

    2016-10-01

    HAT-P-16b is a hot (equilibrium temperature 1626 ± 40 K, assuming zero Bond albedo and efficient energy redistribution), 4.19 ± 0.09 Jupiter-mass exoplanet orbiting an F8 star every 2.775960 ± 0.000003 days (Buchhave et al 2010). WASP-11b/HAT-P-10b is a cooler (1020 ± 17 K), 0.487 ± 0.018 Jupiter-mass exoplanet orbiting a K3 star every 3.7224747 ± 0.0000065 days (Bakos et al. 2009, co-discovered by West et al. 2008). We observed secondary eclipses of both planets using the 3.6 μm and 4.5 μm channels of the Spitzer Space Telescope's Infrared Array Camera (program ID 60003). We applied our Bayesian Atmospheric Radiative Transfer (BART) code to constrain the temperature-pressure profiles and atmospheric molecular abundances of the two planets. Spitzer is operated by the Jet Propulsion Laboratory, California Institute of Technology, under a contract with NASA. This work was supported by NASA Planetary Atmospheres grant NNX12AI69G and NASA Astrophysics Data Analysis Program grant NNX13AF38G.

  20. 10B areal density: A novel approach for design and fabrication of B4C/6061Al neutron absorbing materials

    NASA Astrophysics Data System (ADS)

    Li, Yuli; Wang, Wenxian; Zhou, Jun; Chen, Hongsheng; Zhang, Peng

    2017-04-01

    In this paper, a novel approach to evaluate the neutron shielding performance of a boron-containing neutron absorbing material was proposed for the first time through the establishment of a direct relationship between 10B areal density (10BAD) of the material and its neutron absorption ratio. It is found when the 10BAD of a material is greater than 0.034 g/cm2, the material will achieve a good neutron shielding performance. Based on this proposed approach, B4C/6061Al composite plates with different B4C content (10 wt%, 20 wt%, 30 wt%) were successfully fabricated using vacuum hot pressing followed by hot-extrusion. The characteristics of the B4C/Al interface were studied in details using transmission electron microscopy (TEM), and the effects of B4C particle content on microstructure and mechanical properties of the Al matrix were investigated. Through current studies, B4C/6061Al composite plates possessing good neutron shielding performance and tensile strength are found to be able to be fabricated using either 20 wt% of B4C content with a plate thickness of 4.5 mm or 30 wt% B4C content with a plate thickness of 3 mm.

  1. Bisphenol Analogues Other Than BPA: Environmental Occurrence, Human Exposure, and Toxicity-A Review.

    PubMed

    Chen, Da; Kannan, Kurunthachalam; Tan, Hongli; Zheng, Zhengui; Feng, Yong-Lai; Wu, Yan; Widelka, Margaret

    2016-06-07

    Numerous studies have investigated the environmental occurrence, human exposure, and toxicity of bisphenol A (BPA). Following stringent regulations on the production and usage of BPA, several bisphenol analogues have been produced as a replacement for BPA in various applications. The present review outlines the current state of knowledge on the occurrence of bisphenol analogues (other than BPA) in the environment, consumer products and foodstuffs, human exposure and biomonitoring, and toxicity. Whereas BPA was still the major bisphenol analogue found in most environmental monitoring studies, BPF and BPS were also frequently detected. Elevated concentrations of BPAF, BPF, and BPS (i.e., similar to or greater than that of BPA) have been reported in the abiotic environment and human urine from some regions. Many analogues exhibit endocrine disrupting effects, cytotoxicity, genotoxicity, reproductive toxicity, dioxin-like effects, and neurotoxicity in laboratory studies. BPAF, BPB, BPF, and BPS have been shown to exhibit estrogenic and/or antiandrogenic activities similar to or even greater than that of BPA. Knowledge gaps and research needs have been identified, which include the elucidation of environmental occurrences, persistence, and fate of bisphenol analogues (other than BPA), sources and pathways for human exposure, effects on reproductive systems and the mammary gland, mechanisms of toxicity from coexposure to multiple analogues, metabolic pathways and products, and the impact of metabolic modification on toxicity.

  2. The role of nonmagnetic d0 vs. d10B-type cations on the magnetic exchange interactions in osmium double perovskites

    NASA Astrophysics Data System (ADS)

    Feng, Hai L.; Yamaura, Kazunari; Tjeng, Liu Hao; Jansen, Martin

    2016-11-01

    Polycrystalline samples of double perovskites Ba2BOsO6 (B=Sc, Y, In) were synthesized by solid state reactions. They adopt the cubic double perovskite structures (space group, Fm-3m) with ordered B and Os arrangements. Ba2BOsO6 (B=Sc, Y, In) show antiferromagnetic transitions at 93 K, 69 K, and 28 K, respectively. The Weiss-temperatures are -590 K for Ba2ScOsO6, -571 K for Ba2YOsO6, and -155 K for Ba2InOsO6. Sc3+ and Y3+ have the open-shell d0 electronic configuration, while In3+ has the closed-shell d10. This indicates that a d0 B-type cation induces stronger overall magnetic exchange interactions in comparison to a d10. Comparison of Ba2BOsO6 (B=Sc, Y, In) to their Sr and Ca analogues shows that the structural distortions weaken the overall magnetic exchange interactions.

  3. Synthesis and biological evaluation of aromatic analogues of conduritol F, L-chiro-inositol, and dihydroconduritol F structurally related to the amaryllidaceae anticancer constituents.

    PubMed

    Kireev, Artem S; Nadein, Oleg N; Agustin, Vincent J; Bush, Nancy E; Evidente, Antonio; Manpadi, Madhuri; Ogasawara, Marcia A; Rastogi, Shiva K; Rogelj, Snezna; Shors, Scott T; Kornienko, Alexander

    2006-07-21

    Pancratistatin is a potent anticancer natural product, whose clinical evaluation is hampered by the limited natural abundance and the stereochemically complex structure undermining practical chemical preparation. Fifteen aromatic analogues of conduritol F, l-chiro-inositol, and dihydroconduritol F that possess four of the six pancratistatin stereocenters have been synthesized and evaluated for anticancer activity. These compounds serve as truncated pancratistatin analogues lacking the lactam ring B, but retaining the crucial C10a-C10b bond with the correct stereochemistry. The lack of activity of these compounds provides further insight into pancratistatin's minimum structural requirements for cytotoxicity, particularly the criticality of the intact phenanthridone skeleton. Significantly, these series provide rare examples of simple aromatic conduritol and inositol analogues and, therefore, this study expands the chemistry and biology of these important classes of compounds.

  4. Investigation of HVDC inverter with series compensation on analogue simulator

    SciTech Connect

    Nyati, S.; Gueth, G. ); Mathur, R.M. ); Koschik, V. )

    1990-04-01

    HVdc converters connected into weak ac systems require effective application of voltage control devices to ensure satisfactory voltage control and recovery following disturbances. Both an MOV arrangement and a series capacitor were found to be potentially very cost effective solutions in investigations using digital simulation. However, although the series capacitor performed well in controlling temporary overvoltage following HVdc load rejection, satisfactory recovery from faults was difficult to obtain. This paper presents a follow-up study which uses a state-of-the-art analogue simulator to further investigate the performance of the MOV and series capacitor arrangements, especially the fault recovery performance of the latter.

  5. Analogue Aharonov-Bohm effect in neo-Newtonian theory

    NASA Astrophysics Data System (ADS)

    Anacleto, M. A.; Salako, I. G.; Brito, F. A.; Passos, E.

    2015-12-01

    We address the issues of the scattering of massless planar scalar waves by an acoustic black hole in neo-Newtonian hydrodynamics. We then compute the differential cross section through the use of the partial wave approach in the neo-Newtonian theory which is a modification of the usual Newtonian theory that correctly incorporates the effects of pressure. We mainly show that the scattering of planar waves leads to a modified analogue Aharonov-Bohm effect due to a nontrivial response of the parameters defining the equation of state.

  6. Organofluorine Isoselenocyanate Analogues of Sulforaphane: Synthesis and Anticancer Activity.

    PubMed

    Cierpiał, Tomasz; Łuczak, Jerzy; Kwiatkowska, Małgorzata; Kiełbasiński, Piotr; Mielczarek, Lidia; Wiktorska, Katarzyna; Chilmonczyk, Zdzisław; Milczarek, Małgorzata; Karwowska, Katarzyna

    2016-10-07

    A series of previously unknown sulforaphane analogues with organofluorine substituents bonded to the sulfinyl sulfur atom, an isoselenocyanate moiety in place of the isothiocyanate group, the central sulfur atom in various oxidation states, and different numbers of methylene groups in the central alkyl chain were synthesized and fully characterized. All new compounds were tested for their biological properties in vitro and demonstrated much higher anticancer activity against two breast cancer cell lines than that shown by native sulforaphane; at the same time, the compounds were less toxic for normal cells. The influence of the particular structural changes in the molecules on the cytotoxicity is discussed.

  7. Reduced peptide bond pseudopeptide analogues of neurotensin.

    PubMed

    Doulut, S; Rodriguez, M; Lugrin, D; Vecchini, F; Kitabgi, P; Aumelas, A; Martinez, J

    1992-01-01

    Pseudopeptide analogues of the C-terminal hexapeptide of neurotensin (H-Arg-Arg-Pro-Tyr-Ile-Leu-OH) were obtained by replacing each peptide bond by the reduced peptide bond CH2NH. The resulting analogues were then examined for their ability to inhibit binding of labeled neurotensin to new-born mouse brain membranes and for stimulation of guinea pig ileum contraction. Replacement of the Ile12-Leu13, Tyr11-Ile12, Pro10-Tyr11 and Lys9-Pro10 peptide bonds resulted in about 2000-, 3400-, 200- and 3400-fold losses, respectively, in binding affinity and 400-, 750-, 250- and 300-fold losses, respectively, in biological activity. Replacement of both Arg8 and Arg9 by lysine led to an analogue exhibiting the same pharmacological profile as the C-terminal hexapeptide of neurotensin. Interestingly, replacement of the Lys8-Lys9 peptide bond by the CH2NH bond produced an analogue exhibiting the same affinity for neurotensin receptors, but 10 times more potent in stimulating guinea pig ileum contraction. N-terminal protected analogues (by the Boc group) showed decreased potency as compared with their amino-free corresponding compounds.

  8. Analogue Downscaling of Seasonal Rainfall Forecasts

    NASA Astrophysics Data System (ADS)

    Charles, A. N.; Timbal, B.; Hendon, H.

    2010-12-01

    We have taken an existing statistical downscaling model (SDM), based on meteorological analogues that was developed for downscaling climate change projections (Timbal et al 2009), and applied it in the seasonal forecasting context to produce downscaled rainfall hindcasts from a coupled model seasonal forecast system (POAMA). Downscaling of POAMA forecasts is required to provide seasonal climate information at local scales of interest. Analogue downscaling is a simple technique to generate rainfall forecasts appropriate to the local scale by conditioning on the large scale predicted GCM circulation and the local topography and climate. Analogue methods are flexible and have been shown to produce good results when downscaling 20th century South Eastern Australian rainfall output from climate models. A set of re-forecasts for three month rainfall at 170 observing stations in the South Murray Darling region of Australia were generated using predictors from the POAMA re-forecasts as input for the analogue SDM. The predictors were optimised over a number of different GCMS in previous climate change downscaling studies. Downscaling with the analogue SDM results in predicted rainfall with realistic variance while maintaining the modest predictive skill of the dynamical model. Evaluation of the consistency between the large scale mean of downscaled and direct GCM output precipitation is encouraging.

  9. On the mechanical analogue of DNA.

    PubMed

    Yakushevich, Ludmila

    2017-03-01

    The creation of mechanical analogues of biological systems is known as a useful instrument that helps to understand better the dynamical mechanisms of the functioning of living organisms. Mechanical analogues of biomolecules are usually constructed for imitation of their internal mobility, which is one of the most important properties of the molecules. Among the different types of internal motions, angular oscillations of nitrous bases are of special interest because they make a substantial contribution to the base pairs opening that in turn is an important element of the process of the DNA-protein recognition. In this paper, we investigate the possibility to construct a mechanical analogue for imitation of angular oscillations of nitrous bases in inhomogeneous DNA. It is shown that the analogue has the form of a mechanical chain of non-identical pendulums that oscillate in the gravitational field of the Earth and coupled by identical springs. The masses and lengths of pendulums, as well as the distances between neighboring pendulums and the rigidity of springs are calculated. To illustrate the approach, we present the result of construction of the mechanical analogue of the fragment of the sequence of bacteriophage T7D.

  10. Past and present of analogue modelling, and its future trend

    NASA Astrophysics Data System (ADS)

    Koyi, Hemin

    2015-04-01

    Since Hull (1815) published his article on modelling, analogue modelling has expanded to simulate both a wider range of tectonic regimes and target more challenging set-ups, and has become an integrated part of the fields of tectonics and structural geology. Establishment of new laboratories testifies for the increased attention the technique receives. The ties between modellers and field geoscientists have become stronger with the focus being on understanding the parameters that govern the evolution of a tectonic regime and the processes that dominate it. Since the first sand castle was built with damp sand on a beach, sand has proven to be an appropriate material analogue. Even though granular materials is the most widely used analogue material, new materials are also (re)introduced as rock analogues. Emphasis has been on more precise measurements of the mechanical properties of the materials and on minimizing the preparation effects, which have a great impact on scaling, interpretations and benchmarking. The analytical technique used to quantify model results has also seen a great deal of improvement. In addition to X-ray tomography used to visualise internal structures of models, new techniques (e.g. PIV, high-resolution laser scanning, and interferometry) have enabled monitoring kinematics with a higher precision. Benchmarking exercises have given modelling an additional checking tool by outlining, in addition to the rheology of the modelling materials, the impact of different preparation approaches, the effect of boundary conditions, and the human factor on model results. However, despite the different approaches and deformation rigs, results of models of different tectonic laboratories have shown a great deal of similarities. Even with the introduction of more sophisticated numerical codes and usage of more powerful computers which enable the simulation of more challenging material properties and combinations of those, and 3D model set-up, analogue modelling

  11. High affinity ATP/ADP analogues as new tools for studying CFTR gating

    PubMed Central

    Zhou, Zhen; Wang, Xiaohui; Li, Min; Sohma, Yoshiro; Zou, Xiaoqin; Hwang, Tzyh-Chang

    2005-01-01

    Previous studies using non-hydrolysable ATP analogues and hydrolysis-deficient cystic fibrosis transmembrane conductance regulator (CFTR) mutants have indicated that ATP hydrolysis precedes channel closing. Our recent data suggest that ATP binding is also important in modulating the closing rate. This latter hypothesis predicts that ATP analogues with higher binding affinities should stabilize the open state more than ATP. Here we explore the possibility of using N6-modified ATP/ADP analogues as high-affinity ligands for CFTR gating, since these analogues have been shown to be more potent than native ATP/ADP in other ATP-binding proteins. Among the three N6-modified ATP analogues tested, N6-(2-phenylethyl)-ATP (P-ATP) was the most potent, with a K½ of 1.6 ± 0.4 μm (>50-fold more potent than ATP). The maximal open probability (Po) in the presence of P-ATP was ∼30% higher than that of ATP, indicating that P-ATP also has a higher efficacy than ATP. Single-channel kinetic analysis showed that as [P-ATP] was increased, the opening rate increased, whereas the closing rate decreased. The fact that these two kinetic parameters have different sensitivities to changes of [P-ATP] suggests an involvement of two different ATP-binding sites, a high-affinity site modulating channel closing and a low affinity site controlling channel opening. The effect of P-ATP on the stability of open states was more evident when ATP hydrolysis was abolished, either by mutating the nucleotide-binding domain 2 (NBD2) Walker B glutamate (i.e. E1371) or by using the non-hydrolysable ATP analogue AMP-PNP. Similar strategies to develop nucleotide analogues with a modified adenine ring could be valuable for future studies of CFTR gating. PMID:16223764

  12. Genetic engineering to produce polyketide analogues.

    PubMed

    Reeves, Christopher D; Rodriguez, Eduardo

    2009-01-01

    Polyketides are pharmaceutically important and structurally diverse natural products. Creating analogues for drug development can be done with chemistry, but this is generally restricted to a few accessible functional groups. Analogues can also be made by genetic engineering, which is particularly effective for polyketides synthesized by a modular polyketide synthase (PKS). Such a PKS displays colinearity, which means that the structural features along the polyketide chain are determined by the catalytic specificities in corresponding modules along a molecular assembly line. The assembly line can be genetically engineered through addition, deletion, or mutation of catalytic domains or the reorganization of whole modules. Chemically synthesized precursors also can be fed to engineered assembly lines to further expand the repertoire of analogues. These various methods are discussed with an aim of providing a guide to the strategies most likely to succeed in a given circumstance. Recent information that could be relevant to future polyketide engineering projects is also discussed.

  13. Synthesis and anticancer evaluation of spermatinamine analogues.

    PubMed

    Moosa, Basem A; Sagar, Sunil; Li, Song; Esau, Luke; Kaur, Mandeep; Khashab, Niveen M

    2016-03-15

    Spermatinamine was isolated from an Australian marine sponge, Pseudoceratina sp. as an inhibitor of isoprenylcysteine carboxyl methyltransferase (Icmt), an attractive and novel anticancer target. Herein, we report the synthesis of spermatinamine analogues and their cytotoxic evaluation against three human cancer cell lines, that is, cervix adenocarcinoma (HeLa), breast adenocarcinoma (MCF-7), and prostate carcinoma (DU145). Analogues 12, 14 and 15 were found to be the most potent against one or more cell lines with the IC50 values in the range of 5-10 μM. The obtained results suggested that longer polyamine linker along with aromatic oxime substitution provided the most potent analogue compounds against cancer cell lines. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Antimalarial Properties of Simplified Kalihinol Analogues.

    PubMed

    Daub, Mary Elisabeth; Prudhomme, Jacques; Ben Mamoun, Choukri; Le Roch, Karine G; Vanderwal, Christopher D

    2017-03-09

    Several kalihinol natural products, members of the broader isocyanoterpene family of antimalarial agents, are potent inhibitors of Plasmodium falciparum, the agent of the most severe form of human malaria. Our previous total synthesis of kalihinol B provided a blueprint to generate many analogues within this family, some as complex as the natural product and some much simplified and easier to access. Each analogue was tested for blood-stage antimalarial activity using both drug-sensitive and -resistant P. falciparum strains. Many considerably simpler analogues of the kalihinols retained potent activity, as did a compound with a different decalin scaffold made in only three steps from sclareolide. Finally, one representative compound showed reasonable stability toward microsomal metabolism, suggesting that the isonitrile functional group that is critical for activity is not an inherent liability in these compounds.

  15. Accurate Ab Initio Calculation of the Isotopic Exchange Equilibrium 10B(OH)3 + 11B(OH)4- = 11B(OH)3 + 10B(OH)4- In Aqueous Solution

    NASA Astrophysics Data System (ADS)

    Tossell, J. A.

    2005-12-01

    For more than a decade the B isotopic compositions of marine carbonates have been used as paleo-pH proxies for seawater and to reconstruct paleo-[CO2] concentrations in the atmosphere. A necessary step is this process is the accurate determination of the equilibrium constant, K, for the reaction shown in the title above. This equilibrium constant has been recently calculated using ab initio quantum chemical methods applied to nanoclusters containing the solutes B(OH)3 and B(OH)4- coordinated by large numbers of explicit solvent molecules, a computationally difficult procedure. To obtain the most accurate possible value for K the calculated vibrational frequencies were scaled to best fit the limited experimental data available. The value of K obtained (@ 25°C) was 1.027 (significantly larger than the long used value of 1.0194). Even more recently a purely experimental value of K= 1.0265 ± 0.0015 has been obtained through an accurate spectrophotometric determination of the difference of pKa's of commercially available bulk samples of >99% enriched 10B(OH)3(s) and 11B(OH)3 (s). Since we now know the correct experimental value and have a calculation, admittedly a difficult and slightly parameterized one, which matches the experimental result (which was obtained after the calculation), it is worthwhile to analyze the steps in the theoretical calculation of K in more detail. We need to establish a general procedure which can yield accurate K values for other similar aqueous species even if we have no accurate experimental value for K and no vibrational spectral data. To this end we will examine the dependence of the calculated values of vibrational frequencies, isotopomer frequency differences and K values on a number of factors, including (a) the quantum mechanical level (basis set and treatment of electron correlation) used for the free solutes, (b) the incorporation of aqueous medium effects, (c) the effects of vibrational anharmonicity, (d) incorporation of the

  16. GABAA Receptor Modulation by Etomidate Analogues

    PubMed Central

    Pejo, Ervin; Santer, Peter; Wang, Lei; Dershwitz, Philip; Husain, S. Shaukat; Raines, Douglas E.

    2015-01-01

    Background Etomidate is a highly potent anesthetic agent that is believed to produce hypnosis by enhancing γ-aminobutyric acid type A (GABAA) receptor function. We characterized the GABAA receptor and hypnotic potencies of etomidate analogues. We then used computational techniques to build statistical and graphical models that relate the potencies of these etomidate analogues to their structures in order to identify the specific molecular determinants of potency. Methods GABAA receptor potencies were defined with voltage-clamp electrophysiology using α1β3γ2 receptors harboring a channel mutation (α1(L264T)) that enhances anesthetic sensitivity (n = 36 – 60 measurements per concentration-response curve). The hypnotic potencies of etomidate analogues were defined using a loss of righting reflexes assay in Sprague Dawley rats (n = 9 – 21 measurements per dose-response curve). Three-dimensional quantitative structure-activity relationships were determined in silico using comparative molecular field analysis. Results The GABAA receptor and hypnotic potencies of etomidate and the etomidate analogues ranged by 91-fold and 53-fold, respectively. These potency measurements were significantly correlated (r2 = 0.72), but neither measurement correlated with drug hydrophobicity (r2 = 0.019 and 0.005, respectively). Statistically significant and predictive comparative molecular field analysis models were generated and a pharmacophore model was built that revealed both the structural elements in etomidate analogues associated with high potency and the interactions that these elements make with the etomidate binding site. Conclusion There are multiple specific structural elements in etomidate and etomidate analogues that mediate GABAA receptor modulation. Modifying any one element can alter receptor potency by an order of magnitude or more. PMID:26691905

  17. Insulin analogues: action profiles beyond glycaemic control.

    PubMed

    Eckardt, Kristin; Eckel, Jürgen

    2008-02-01

    A variety of studies have documented significant improvements in the treatment of type 1 and 2 diabetes after the introduction of artificial insulins. This review gives an overview of insulin analogues which are currently approved for therapeutical use. Clinical data regarding the efficiency to control blood glucose level as well as improving HbA1c level in comparison to conventional insulin preparations in type 1 and 2 diabetic patients are summarized. Furthermore, special features of insulin analogues regarding their signalling properties are discussed with focus on the proliferative effects of insulin glargine as well as some recent data of insulin detemir.

  18. Classical Simulated Annealing Using Quantum Analogues

    NASA Astrophysics Data System (ADS)

    La Cour, Brian R.; Troupe, James E.; Mark, Hans M.

    2016-08-01

    In this paper we consider the use of certain classical analogues to quantum tunneling behavior to improve the performance of simulated annealing on a discrete spin system of the general Ising form. Specifically, we consider the use of multiple simultaneous spin flips at each annealing step as an analogue to quantum spin coherence as well as modifications of the Boltzmann acceptance probability to mimic quantum tunneling. We find that the use of multiple spin flips can indeed be advantageous under certain annealing schedules, but only for long anneal times.

  19. Selection of Actinide Chemical Analogues for WIPP Tests: Potential Nonradioactive Sorbing and Nonsorbing Tracers for Study of Ion Transport in the Environment

    SciTech Connect

    Dale Spall; Robert Villarreal

    1998-08-01

    Chemical characteristics of the actinides (Th, U, Np, Pu, Am) have been studied relative to nonradioactive chemical elements that have similar characteristics in an attempt to identify a group of actinide chemical analogues that are nonradioactive. In general, the chemistries of the actinides, especially U, Np, Pu, and Am, are very complex and attempts to identify a single chemical analogue for each oxidation state were not successful. However, the rationale for selecting a group of chemical analogues that would mimic the actinides as a group is provided. The categorization of possible chemical analogues (tracers) with similar chemical properties was based on the following criteria. Categorization was studied according.

  20. Adsorption of Amido Black 10B from aqueous solutions onto Zr (IV) surface-immobilized cross-linked chitosan/bentonite composite

    NASA Astrophysics Data System (ADS)

    Zhang, Lujie; Hu, Pan; Wang, Jing; Huang, Ruihua

    2016-04-01

    Zr(IV) surface-immobilized cross-linked chitosan/bentonite composite was synthesized by immersing cross-linked chitosan/bentonite composite in zirconium oxychloride solution, and characterized by X-ray diffraction, Fourier transform infrared spectroscopy, Scanning electron microscopy techniques. The adsorption of an anionic dye, Amido Black 10B, from aqueous solution by Zr(IV) loaded cross-linked chitosan/bentonite composite was investigated as a function of loading amount of Zr(IV), adsorbent dosage, pH value of initial dye solution, and ionic strength. The removal of Amido Black 10B increased with an increase in loading amount of Zr(IV) and adsorbent dosage, but decreased with an increase in pH or ionic strength. The adsorption of AB10B onto Zr(IV) loaded cross-linked chitosan/bentonite composite was favored at lower pH values and higher temperatures. The Langmuir isotherm model fitted well with the equilibrium adsorption isotherm data and the maximum monolayer adsorption capacity was 418.4 mg/g at natural pH value and 298 K. The pseudo-second-order kinetic model well described the adsorption process of Amido Black 10B onto Zr(IV) loaded cross-linked chitosan/bentonite composite. The possible mechanisms controlling Amido Black 10B adsorption included hydrogen bonding and electrostatic interactions.

  1. Novel homozygous mutations in the WNT10B gene underlying autosomal recessive split hand/foot malformation in three consanguineous families.

    PubMed

    Aziz, Abdul; Irfanullah; Khan, Saadullah; Zimri, Faridullah Khan; Muhammad, Noor; Rashid, Sajid; Ahmad, Wasim

    2014-01-25

    Split-hand/split-foot malformation (SHFM), representing variable degree of median clefts of hands and feet, is a genetically heterogeneous group of limb malformations with seven loci mapped on different human chromosomes. However, only 3 genes (TP63, WNT10B, DLX5) for the seven loci have been identified. The study, presented here, described three consanguineous Pakistani families segregating SHFM in autosomal recessive manner. Linkage in the families was searched by genotyping microsatellite markers and mutation screening of candidate gene was performed by Sanger DNA sequencing. Clinical features of affected members of these families exhibited SHFM phenotype with involvement of hands and feet. Genotyping using microsatellite markers mapped the families to WNT10B gene at SHFM6 on chromosome 12q13.11-q13. Subsequently, sequence analysis of WNT10B gene revealed a novel 4-bp deletion mutation (c.1165_1168delAAGT) in one family and 7-bp duplication (c.300_306dupAGGGCGG) in two other families. Structure-based analysis showed a significant conformational shift in the active binding site of mutated WNT10B (p.Lys388Glufs*36), influencing binding with Fzd8. The mutations identified in the WNT10B gene extend the body of evidence implicating it in the pathogenesis of SHFM.

  2. Loss of Bone and Wnt10b Expression in Male Type 1 Diabetic Mice Is Blocked by the Probiotic Lactobacillus reuteri

    PubMed Central

    Zhang, Jing; Motyl, Katherine J.; Irwin, Regina; MacDougald, Ormond A.; Britton, Robert A.

    2015-01-01

    Type 1 diabetes (T1D)–induced osteoporosis is characterized by a predominant suppression of osteoblast number and activity, as well as increased bone marrow adiposity but no change in osteoclast activity. The fundamental mechanisms and alternative anabolic treatments (with few side effects) for T1D bone loss remain undetermined. Recent studies by our laboratory and others indicate that probiotics can benefit bone health. Here, we demonstrate that Lactobacillus reuteri, a probiotic with anti-inflammatory and bone health properties, prevents T1D-induced bone loss and marrow adiposity in mice. We further found that L. reuteri treatment prevented the suppression of Wnt10b in T1D bone. Consistent with a role for attenuated bone Wnt10b expression in T1D osteoporosis, we observed that bone-specific Wnt10b transgenic mice are protected from T1D bone loss. To examine the mechanisms of this protection, we focused on TNF-α, a cytokine up-regulated in T1D that causes suppression of osteoblast Wnt10b expression in vitro. Addition of L. reuteri prevented TNF-α–mediated suppression of Wnt10b and osteoblast maturation markers. Taken together, our findings reveal a mechanism by which T1D causes bone loss and open new avenues for use of probiotics to benefit the bone. PMID:26135835

  3. Expression levels of microRNA-145 and microRNA-10b are associated with metastasis in non-small cell lung cancer.

    PubMed

    Li, Yongwen; Li, Ying; Liu, Jinghao; Fan, Yaguang; Li, Xin; Dong, Ming; Liu, Hongyu; Chen, Jun

    2016-01-01

    Although metastasis remains the overwhelming cause of death for patients with non-small cell lung cancer (NSCLC), the underlying mechanisms of metastasis remain unknown. Accumulating evidence suggests that microRNAs (miRNAs) are key players in the regulation of tumor cell invasion and metastasis. Expression of miR-9, miR-10b, miR-145, and miR-155, 4 miRNAs previously shown to play roles in metastasis in other tumor types, was compared in lymph node (LN)-positive NSCLC versus LN-negative NSCLC. Expression of miR-145 was significantly lower in LN-positive NSCLC (P < 0.05), while expression of miR-10b was significantly higher (P < 0.05). Expression of both miR-145 and miR-10b was correlated with lymph node metastasis in NSCLC (both Ps < 0.001). In addition, miR-10b facilitated the migration and invasion of lung cancer cell line A549, while miR-145 suppressed the migration and invasion capacity of A549 in vitro. These results suggest that miR-10b and miR-145 may act as an oncogene or tumor suppressor gene, respectively, in NSCLC metastasis.

  4. Expression levels of microRNA-145 and microRNA-10b are associated with metastasis in non-small cell lung cancer

    PubMed Central

    Li, Yongwen; Li, Ying; Liu, Jinghao; Fan, Yaguang; Li, Xin; Dong, Ming; Liu, Hongyu; Chen, Jun

    2016-01-01

    ABSTRACT Although metastasis remains the overwhelming cause of death for patients with non-small cell lung cancer (NSCLC), the underlying mechanisms of metastasis remain unknown. Accumulating evidence suggests that microRNAs (miRNAs) are key players in the regulation of tumor cell invasion and metastasis. Expression of miR-9, miR-10b, miR-145, and miR-155, 4 miRNAs previously shown to play roles in metastasis in other tumor types, was compared in lymph node (LN)-positive NSCLC versus LN-negative NSCLC. Expression of miR-145 was significantly lower in LN-positive NSCLC (P < 0.05), while expression of miR-10b was significantly higher (P < 0.05). Expression of both miR-145 and miR-10b was correlated with lymph node metastasis in NSCLC (both Ps < 0.001). In addition, miR-10b facilitated the migration and invasion of lung cancer cell line A549, while miR-145 suppressed the migration and invasion capacity of A549 in vitro. These results suggest that miR-10b and miR-145 may act as an oncogene or tumor suppressor gene, respectively, in NSCLC metastasis. PMID:26909466

  5. HATS9-b and HATS10-b: Two Compact Hot Jupiters in Field 7 of the K2 Mission

    NASA Astrophysics Data System (ADS)

    Brahm, R.; Jordán, A.; Hartman, J. D.; Bakos, G. Á.; Bayliss, D.; Penev, K.; Zhou, G.; Ciceri, S.; Rabus, M.; Espinoza, N.; Mancini, L.; de Val-Borro, M.; Bhatti, W.; Sato, B.; Tan, T. G.; Csubry, Z.; Buchhave, L.; Henning, T.; Schmidt, B.; Suc, V.; Noyes, R. W.; Papp, I.; Lázár, J.; Sári, P.

    2015-07-01

    We report the discovery of two transiting extrasolar planets by the HATSouth survey. HATS-9b orbits an old (10.8 ± 1.5 Gyr) V = 13.3 G dwarf star with a period P≈ 1.9153 days. The host star has a mass of 1.03 {M}⊙ , radius of 1.503 {R}⊙ , and effective temperature 5366 ± 70 K. The planetary companion has a mass of 0.837 {M}{{J}} and radius of 1.065 {R}{{J}}, yielding a mean density of 0.85 {{g}} {{cm}}-3. HATS-10b orbits a V = 13.1 G dwarf star with a period P≈ 3.3128 days. The host star has a mass of 1.1 {M}⊙ , radius of 1.11 {R}⊙ , and effective temperature 5880 ± 120 K. The planetary companion has a mass of 0.53 {M}{{J}} and radius of 0.97 {R}{{J}}, yielding a mean density of 0.7 {{g}} {{cm}}-3. Both planets are compact in comparison with planets receiving similar irradiation from their host stars and lie in the nominal coordinates of Field 7 of K2, but only HATS-9b falls on working silicon. Future characterization of HATS-9b with the exquisite photometric precision of the Kepler telescope may provide measurements of its reflected light signature. The HATSouth network is operated by a collaboration consisting of Princeton University (PU), the Max Planck Institute for Astronomy (MPIA), the Australian National University (ANU), and the Pontificia Universidad Católica de Chile (PUC). The station at Las Campanas Observatory (LCO) of the Carnegie Institute is operated by PU in conjunction with PUC, the station at the High Energy Spectroscopic Survey (H.E.S.S.) site is operated in conjunction with MPIA, and the station at Siding Spring Observatory (SSO) is operated jointly with ANU. Based in part on data collected at Subaru Telescope, which is operated by the National Astronomical Observatory of Japan. Based in part on observations made with the MPG 2.2 m Telescope at the ESO Observatory in La Silla. This paper uses observations obtained with facilities of the Las Cumbres Observatory Global Telescope. Based on observations obtained with the Apache

  6. Cellular effect of thermal neutron capture treatment using 10B1-para-boronophenylalanine: lethal effect on melanoma cells with different degrees of X-ray sensitivity.

    PubMed

    Utsumi, H; Tano, K; Mizuma, N; Kobayashi, T; Ichihashi, M

    1996-09-01

    We studied the effect of neutron capture treatment using 10B-compound on X-ray sensitive P-39 and X-ray resistant G-361 human melanoma cell lines, and found a high lethal effect of boron neutron capture therapy in comparison with conventional ionizing radiation. The P-39 line was sensitive to thermal neutron radiation, and extremely sensitive to bleomycin treatment, whereas the G-361 line was resistant to both forms of treatment; however, the two cell lines had similar sensitivity to thermal neutron radiation after pretreatment with 10B1-para-boronophenylalanine (10B1-BPA, 200 micrograms/ml medium). These results show that the thermal neutron capture products (a 7Li nucleus and alpha particle) are highly damaging and short range in tumor cells and thus more efficiently inactivate melanoma cells irrespective of x-ray sensitivity, than conventional X-ray-irradiation.

  7. R-matrix Analysis of the 10B(p,{alpha})7Be and 11B(p,{alpha})8Be Reactions at Stellar Energies

    SciTech Connect

    Trabelsi, A.; Belhout, A.; Fouka, M.; Messahel, L.; Ouichaoui, S.

    2006-04-26

    The available experimental astrophysical S(E) factor data for the 10B(p,{alpha}0.1)7Be and 11B(p,{alpha}0.1)8Be reactions have been analyzed over the C.M. proton energy ranges up to E = 1.00 MeV and 1.45 MeV, respectively, using the R-matrix theory. The extrapolated SBN(E) factor values for bare nuclei led to a stellar rate consistent with the most recent calculations in the case of the 11B(p,{alpha})8Be reaction, and to a 10B(p,{alpha})7Be rate significantly different from previously reported ones at the lowest stellar temperatures. The electron screening enhancement factors have also been extracted. Mainly results concerning the 10B(p,{alpha})7Be reaction are presented here.

  8. Dumb holes: analogues for black holes.

    PubMed

    Unruh, W G

    2008-08-28

    The use of sonic analogues to black and white holes, called dumb or deaf holes, to understand the particle production by black holes is reviewed. The results suggest that the black hole particle production is a low-frequency and low-wavenumber process.

  9. Differential Client Attractiveness in a Counseling Analogue

    ERIC Educational Resources Information Center

    Davis, Carl S.; And Others

    1977-01-01

    Investigated variations in conceptual complexity level of counselor and client on counselor attraction to the client. Counselor trainees rated attractiveness of clients following two counseling analogue tasks in which the client was depicted as exhibiting high or low conceptual level. More complex clients are more attractive across both levels.…

  10. CO2 Capture with Enzyme Synthetic Analogue

    SciTech Connect

    Cordatos, Harry

    2010-03-01

    Project overview provides background on carbonic anhydrase transport mechanism for CO2 in the human body and proposed approach for ARPA-E project to create a synthetic enzyme analogue and utilize it in a membrane for CO2 capture from flue gas.

  11. Solanapyrone analogues from a Hawaiian fungicolous fungus

    USDA-ARS?s Scientific Manuscript database

    Four new solanayrone analogues (solanapyrones J-M; 1-4) have been isolated from an unidentified fungicolous fungus collected in Hawaii. The structures and relative configurations of these compounds were determined by analysis of ID NMR, 2D NMR, and MS data. Solanapyrone J(1) showed antifungal acti...

  12. Analoguing Creativity & Culture: A Method for Metaphors.

    ERIC Educational Resources Information Center

    Thompson, Timothy N.

    Adding to the benefits of using metaphors as tools, "analoguing" (a method of analysis that focuses on metaphors for meanings in use and meanings of metaphors in use) helps avoid excessive categorization and separation by looking for unities and patterns in phenomena rather than for divisions. Six months of observation of patterns of…

  13. Inactivation of ca10a and ca10b Genes Leads to Abnormal Embryonic Development and Alters Movement Pattern in Zebrafish

    PubMed Central

    Aspatwar, Ashok; Barker, Harlan R.; Saralahti, Anni K.; Bäuerlein, Carina A.; Ortutay, Csaba; Pan, Peiwen; Kuuslahti, Marianne; Parikka, Mataleena; Rämet, Mika; Parkkila, Seppo

    2015-01-01

    Carbonic anhydrase related proteins (CARPs) X and XI are highly conserved across species and are predominantly expressed in neural tissues. The biological role of these proteins is still an enigma. Ray-finned fish have lost the CA11 gene, but instead possess two co-orthologs of CA10. We analyzed the expression pattern of zebrafish ca10a and ca10b genes during embryonic development and in different adult tissues, and studied 61 CARP X/XI-like sequences to evaluate their phylogenetic relationship. Sequence analysis of zebrafish ca10a and ca10b reveals strongly predicted signal peptides, N-glycosylation sites, and a potential disulfide, all of which are conserved, suggesting that all of CARP X and XI are secretory proteins and potentially dimeric. RT-qPCR showed that zebrafish ca10a and ca10b genes are expressed in the brain and several other tissues throughout the development of zebrafish. Antisense morpholino mediated knockdown of ca10a and ca10b showed developmental delay with a high rate of mortality in larvae. Zebrafish morphants showed curved body, pericardial edema, and abnormalities in the head and eye, and there was increased apoptotic cell death in the brain region. Swim pattern showed abnormal movement in morphant zebrafish larvae compared to the wild type larvae. The developmental phenotypes of the ca10a and ca10b morphants were confirmed by inactivating these genes with the CRISPR/Cas9 system. In conclusion, we introduce a novel zebrafish model to investigate the mechanisms of CARP Xa and CARP Xb functions. Our data indicate that CARP Xa and CARP Xb have important roles in zebrafish development and suppression of ca10a and ca10b expression in zebrafish larvae leads to a movement disorder. PMID:26218428

  14. Asymmetry of charged-particle emission in the capture of polarized thermal neutrons by /sup 3/He and /sup 10/B nuclei

    SciTech Connect

    Vesna, V.A.; Egorov, A.I.; Kolomenskii, E.A.; Lobashev, V.M.; Pirozhkov, A.N.; Smotritskii, L.M.; Titov, N.A.

    1981-04-20

    Measurements by an integrating method yield an upper limit on the magnitude of the P-odd asymmetry in the reactions /sup 3/He(n,p)/sup 3/H and /sup 10/B(n,..cap alpha..)/sup 7/Li. There is a left--right asymmetry in the reaction /sup 10/B(n,..cap alpha../sub 0/)/sup 7/Li with a coefficient a/sub R/L = (0.77 +- 0.06) x 10/sup -4/.

  15. 1H and 10B NMR and MRI investigation of boron- and gadolinium-boron compounds in boron neutron capture therapy.

    PubMed

    Bonora, M; Corti, M; Borsa, F; Bortolussi, S; Protti, N; Santoro, D; Stella, S; Altieri, S; Zonta, C; Clerici, A M; Cansolino, L; Ferrari, C; Dionigi, P; Porta, A; Zanoni, G; Vidari, G

    2011-12-01

    (10)B molecular compounds suitable for Boron Neutron Capture Therapy (BNCT) are tagged with a Gd(III) paramagnetic ion. The newly synthesized molecule, Gd-BPA, is investigated as contrast agent in Magnetic Resonance Imaging (MRI) with the final aim of mapping the boron distribution in tissues. Preliminary Nuclear Magnetic Resonance (NMR) measurements, which include (1)H and (10)B relaxometry in animal tissues, proton relaxivity of the paramagnetic Gd-BPA molecule in water and its absorption in tumoral living cells, are reported. Copyright © 2011 Elsevier Ltd. All rights reserved.

  16. [Dmt(1)]DALDA analogues modified with tyrosine analogues at position 1.

    PubMed

    Cai, Yunxin; Lu, Dandan; Chen, Zhen; Ding, Yi; Chung, Nga N; Li, Tingyou; Schiller, Peter W

    2016-08-01

    Analogues of [Dmt(1)]DALDA (H-Dmt-d-Arg-Phe-Lys-NH2; Dmt=2',6'-dimethyltyrosine), a potent μ opioid agonist peptide with mitochondria-targeted antioxidant activity were prepared by replacing Dmt with various 2',6'-dialkylated Tyr analogues, including 2',4',6'-trimethyltyrosine (Tmt), 2'-ethyl-6'-methyltyrosine (Emt), 2'-isopropyl-6'-methyltyrosine (Imt) and 2',6'-diethyltyrosine (Det). All compounds were selective μ opioid agonists and the Tmt(1)-, Emt(1) and Det(1)-analogues showed subnanomolar μ opioid receptor binding affinities. The Tmt(1)- and Emt(1)-analogues showed improved antioxidant activity compared to the Dmt(1)-parent peptide in the DPPH radical-scavenging capacity assay, and thus are of interest as drug candidates for neuropathic pain treatment. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. Ultrafast excited-state dynamics and photolysis in base-off B12 coenzymes and analogues: absence of the trans-nitrogenous ligand opens a channel for rapid nonradiative decay.

    PubMed

    Peng, Jian; Tang, Kuo-Chun; McLoughlin, Kaitlin; Yang, Yang; Forgach, Danika; Sension, Roseanne J

    2010-09-30

    Ultrafast transient absorption spectroscopy was used to investigate the photochemistry of adenosylcobalamin (AdoCbl), methylcobalamin (MeCbl), and n-propylcobalamin (PrCbl) at pH 2 where the axial nitrogenous ligand is replaced by a water molecule. The evolution of the difference spectrum reveals the internal conversion process and spectral characteristics of the S(1) excited state. The photolysis yield in the base-off cobalamins is controlled by competition between internal conversion and bond homolysis. This is in direct contrast to the process in most base-on alkylcobalamins where primary photolysis occurs with near unit quantum yield and the photolysis yield is controlled by competition between diffusive separation of the radical pair and geminate recombination. The absence of the axial nitrogenous ligand in the base-off cobalamins modifies the electronic structure and opens a channel for fast nonradiative decay. This channel competes effectively with the channel for bond dissociation, dropping the quantum yield for primary radical pair formation from unity in base-on PrCbl and AdoCbl to 0.2 ± 0.1 and 0.12 ± 0.06 in base-off PrCbl and AdoCbl, respectively. The photolysis of base-off MeCbl is similar to that of base-off AdoCbl and PrCbl with competition between rapid nonradiative decay leading to ground state recovery and formation of a radical pair following bond homolysis.

  18. A novel lunar bed rest analogue.

    PubMed

    Cavanagh, Peter R; Rice, Andrea J; Licata, Angelo A; Kuklis, Matthew M; Novotny, Sara C; Genc, Kerim O; Englehaupt, Ricki K; Hanson, Andrea M

    2013-11-01

    Humans will eventually return to the Moon and thus there is a need for a ground-based analogue to enable the study of physiological adaptations to lunar gravity. An important unanswered question is whether or not living on the lunar surface will provide adequate loading of the musculoskeletal system to prevent or attenuate the bone loss that is seen in microgravity. Previous simulations have involved tilting subjects to an approximately 9.5 degrees angle to achieve a lunar gravity component parallel to the long-axis of the body. However, subjects in these earlier simulations were not weight-bearing, and thus these protocols did not provide an analogue for load on the musculoskeletal system. We present a novel analogue which includes the capability to simulate standing and sitting in a lunar loading environment. A bed oriented at a 9.5 degrees angle was mounted on six linear bearings and was free to travel with one degree of freedom along rails. This allowed approximately 1/6 body weight loading of the feet during standing. "Lunar" sitting was also successfully simulated. A feasibility study demonstrated that the analogue was tolerated by subjects for 6 d of continuous bed rest and that the reaction forces at the feet during periods of standing were a reasonable simulation of lunar standing. During the 6 d, mean change in the volume of the quadriceps muscles was -1.6% +/- 1.7%. The proposed analogue would appear to be an acceptable simulation of lunar gravity and deserves further exploration in studies of longer duration.

  19. q-bosons and the q-analogue quantized field

    SciTech Connect

    Nelson, C.A.

    1994-12-31

    The q-analogue coherent states {vert_bar}z >{sub q} are used to identify physical signatures for the presence of a q-analogue quantized radiation field in the {vert_bar} >{sub q} classical limit where {vert_bar}z{vert_bar} is large. In this quantum-optics-like limit, the fractional uncertainties of most physical quantities (momentum, position, amplitude, phase) which characterize the quantum field are O(1). They only vanish as O(1/{vert_bar}z{vert_bar}) when q = 1. However, for the number operator, N, and the N-Hamiltonian for a free q-boson gas, H{sub N} = {Dirac_h}{omega}(N + 1/2), the fractional uncertainties do still approach zero. A signature for q-boson counting statistics is that ({Delta}N){sup 2}/ {yields} 0 as {vert_bar}z{vert_bar} {yields} {infinity}. Except for its O(1) fractional uncertainty, the q-generalization of the Hermitian phase operator of Pegg and Barnett, {phi}{sub q}, still exhibits normal classical behavior. The standard number-phase uncertainty-relation, {Delta}N {Delta}{phi}{sub q} = 1/2, and the approximate commutation relation, [N,{phi}{sub q}] = i, still hold for the single-mode q-analogue quantized field. So, N and {phi}{sub q} are almost canonically conjugate operators in the {vert_bar}z >{sub q} classical limit. The {vert_bar}z >{sub q} CS`s minimize this uncertainty relation for moderate {vert_bar}z{vert_bar}{sup 2}.

  20. Photophysical properties of a synthetic, carbonyl-containing (N = 6+Cdbnd O) carotenoid analogue

    NASA Astrophysics Data System (ADS)

    Niedzwiedzki, Dariusz M.

    2014-05-01

    Retinyl-1 is a synthetic carotenoid analogue belonging to the retinal analogues family. It has six conjugated carbon-carbon double bonds with a carbonyl group conjugated to the π-electron system. Presence of the carbonyl group in vicinity of the conjugated carbon-carbon backbone leads to unique excited state properties that are extremely sensitive to solvent polarity and temperature. The simplicity of the synthesis of Retinyl-1 and ease of attachment to synthetic tetrapyrrole chromophores make Retinyl-1 attractive for use in artificial photosynthetic systems.

  1. Photophysical properties of a synthetic, carbonyl-containing (N=6+CO) carotenoid analogue

    SciTech Connect

    Niedzwiedzki, Dariusz M.

    2014-05-01

    Retinyl-1 is a synthetic carotenoid analogue belonging to the retinal analogues family. It has six conjugated carbon–carbon double bonds with a carbonyl group conjugated to the π-electron system. Presence of the carbonyl group in vicinity of the conjugated carbon–carbon backbone leads to unique excited state properties that are extremely sensitive to solvent polarity and temperature. The simplicity of the synthesis of Retinyl-1 and ease of attachment to synthetic tetrapyrrole chromophores make Retinyl-1 attractive for use in artificial photosynthetic systems.

  2. Why do people appeal to the courts for access to medication? The case of insulin analogues in Bahia (Brazil).

    PubMed

    Lisboa, Erick Soares; Souza, Luis Eugenio Portela Fernandes de

    2017-06-01

    Insulin analogues have been the object of controversy concerning their therapeutic superiority to human insulin. Perhaps, in part, because of this, insulin analogues are frequently the subject of lawsuits. The judicialization of health has been well studied, but little is known about the reasons that lead people to go to the courts to obtain access to medicines on SUS (the Brazilian National Health System). Therefore, this study aims to analyze the reasons that led people to appeal to the courts to obtain access to insulins analogues in the state of Bahia. This is a case study based on documentary sources. Between 2010 and 2013, 149 lawsuits requiring insulin analogues from the state health authority were filed in the courts. The main reasons for the appeal to the courts, cited in the cases, can be grouped into four categories: the users' lack of finances, an essential need for insulin analogue, the duty and obligation of the state to provide them and bureaucratic difficulties. People turned to the courts, mostly, because doctors who accompany their patients have shifted from the official policy, believing that insulin analogues are better than human insulins. They also recognize that the public health system does not distribute them nor does it give doctors the wherewithal to purchase them with their own resources.

  3. Analogue VLSI for probabilistic networks and spike-time computation.

    PubMed

    Murray, A

    2001-02-01

    The history and some of the methods of analogue neural VLSI are described. The strengths of analogue techniques are described, along with residual problems to be solved. The nature of hardware-friendly and hardware-appropriate algorithms is reviewed and suggestions are offered as to where analogue neural VLSI's future lies.

  4. Tryptophan analogues. 1. Synthesis and antihypertensive activity of positional isomers.

    PubMed

    Safdy, M E; Kurchacova, E; Schut, R N; Vidrio, H; Hong, E

    1982-06-01

    A series of tryptophan analogues having the carboxyl function at the beta-position was synthesized and tested for antihypertensive activity. The 5-methoxy analogue 46 exhibited antihypertensive activity in the rat via the oral route and was much more potent than the normal tryptophan analogue. The methyl ester was found to be a critical structural feature for activity.

  5. Fluorescence Turn-On Sensing of DNA Duplex Formation by a Tricyclic Cytidine Analogue

    PubMed Central

    Burns, Dillon D.; Teppang, Kristine L.; Lee, Raymond W.; Lokensgard, Melissa E.; Purse, Byron W.

    2017-01-01

    Most fluorescent nucleoside analogues are quenched when base stacked and some maintain their brightness, but there has been little progress toward developing nucleoside analogues that markedly increase their fluorescence upon duplex formation. Here, we report on the design and synthesis of a new tricyclic cytidine analogue, 8-diethylamino-tC (8-DEA-tC), that responds to DNA duplex formation with up to a 20-fold increase in fluorescent quantum yield as compared with the free nucleoside, depending on neighboring bases. This turn-on response to duplex formation is the greatest of any reported nucleoside analogue that can participate in Watson–Crick base pairing. Measurements of the quantum yield of 8-DEA-tC mispaired with adenosine and, separately, opposite an abasic site show that there is almost no fluorescence increase without the formation of correct Watson–Crick hydrogen bonds. Kinetic isotope effects from the use of deuterated buffer show that the duplex protects 8-DEA-tC against quenching by excited state proton transfer. These results, supported by DFT calculations, suggest a rationale for the observed photophysical properties that is dependent on duplex integrity and the electronic structure of the analogue. PMID:28080035

  6. Fluorescence Turn-On Sensing of DNA Duplex Formation by a Tricyclic Cytidine Analogue.

    PubMed

    Burns, Dillon D; Teppang, Kristine L; Lee, Raymond W; Lokensgard, Melissa E; Purse, Byron W

    2017-02-01

    Most fluorescent nucleoside analogues are quenched when base stacked and some maintain their brightness, but there has been little progress toward developing nucleoside analogues that markedly increase their fluorescence upon duplex formation. Here, we report on the design and synthesis of a new tricyclic cytidine analogue, 8-diethylamino-tC (8-DEA-tC), that responds to DNA duplex formation with up to a 20-fold increase in fluorescent quantum yield as compared with the free nucleoside, depending on neighboring bases. This turn-on response to duplex formation is the greatest of any reported nucleoside analogue that can participate in Watson-Crick base pairing. Measurements of the quantum yield of 8-DEA-tC mispaired with adenosine and, separately, opposite an abasic site show that there is almost no fluorescence increase without the formation of correct Watson-Crick hydrogen bonds. Kinetic isotope effects from the use of deuterated buffer show that the duplex protects 8-DEA-tC against quenching by excited state proton transfer. These results, supported by DFT calculations, suggest a rationale for the observed photophysical properties that is dependent on duplex integrity and the electronic structure of the analogue.

  7. Combining miR10b-targeted nanotherapy with low-dose doxorubicin elicits durable regressions of metastatic breast cancer

    PubMed Central

    Yoo, Byunghee; Kavishwar, Amol; Ross, Alana; Wang, Ping; Tabassum, Doris P.; Polyak, Kornelia; Barteneva, Natalia; Petkova, Victoria; Pantazopoulos, Pamela; Tena, Aseda; Moore, Anna; Medarova, Zdravka

    2015-01-01

    The therapeutic promise of microRNA in cancer has yet to be realized. In this study, we identified and therapeutically exploited a new role for miR-10b at the metastatic site, which links its overexpression to tumor cell viability and proliferation. In the protocol developed, we combined a miR-10b-inhibitory nanodrug with low-dose anthracycline to achieve complete durable regressions of metastatic disease in a murine model of metastatic breast cancer. Mechanistic investigations suggested a potent anti-proliferative, pro-apoptotic effect of the nanodrug in the metastatic cells, potentiated by a cell-cycle arrest produced by administration of the low-dose anthracycline. miR-10b was overexpressed specifically in cells with high metastatic potential, suggesting a role for this miRNA as a metastasis-specific therapeutic target. Taken together, our results implied the existence of pathways that regulate the viability and proliferation of tumor cells only after they have acquired the ability to grow at distant metastatic sites. As illustrated by miR-10b targeting, such metastasis-dependent apoptotic pathways would offer attractive targets for further therapeutic exploration. PMID:26359455

  8. Development of a simple and rapid method of precisely identifying the position of 10B atoms in tissue: an improvement in standard alpha autoradiography.

    PubMed

    Tanaka, Hiroki; Sakurai, Yoshinori; Suzuki, Minoru; Masunaga, Shin-ichiro; Takamiya, Koichi; Maruhashi, Akira; Ono, Koji

    2014-03-01

    Boron neutron capture therapy (BNCT) can be utilized to selectively kill cancer cells using a boron compound that accumulates only in cancer cells and not in normal cells. Tumor-bearing animals treated by BNCT are routinely used to evaluate long-term antitumor effects of new boron compounds. Alpha-autoradiography is one of the methods employed in the evaluation of antitumor effects. However, a standard alpha-autoradiography cannot detect the microdistribution of (10)B because of the difficulty associated with the superposition of a tissue sample image and etched pits on a track detector with the etching process. In order to observe the microdistribution of (10)B, some special methods of alpha-autoradiography have been developed that make use of a special track detector, or the atomic force microscope combined with X-ray and UV light irradiation. In contrast, we propose, herein, a simple and rapid method of precisely identifying the position of (10)B using the imaging process and the shape of etched pits, such as their circularity, without the need to use special track detectors or a microscope. A brief description of this method and its verification test are presented in this article. We have established a method of detecting the microdistribution of (10)B with submicron deviation between the position of etched pits and the position of reaction in a tissue sample, for a given circularity of etched pits.

  9. 17 CFR 240.10b-1 - Prohibition of use of manipulative or deceptive devices or contrivances with respect to certain...

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... manipulative or deceptive devices or contrivances with respect to certain securities exempted from registration... Securities Exchange Act of 1934 Manipulative and Deceptive Devices and Contrivances § 240.10b-1 Prohibition of use of manipulative or deceptive devices or contrivances with respect to certain...

  10. 17 CFR 240.10b-1 - Prohibition of use of manipulative or deceptive devices or contrivances with respect to certain...

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... manipulative or deceptive devices or contrivances with respect to certain securities exempted from registration... Securities Exchange Act of 1934 Manipulative and Deceptive Devices and Contrivances § 240.10b-1 Prohibition of use of manipulative or deceptive devices or contrivances with respect to certain...

  11. 17 CFR 240.10b-1 - Prohibition of use of manipulative or deceptive devices or contrivances with respect to certain...

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... manipulative or deceptive devices or contrivances with respect to certain securities exempted from registration... Securities Exchange Act of 1934 Manipulative and Deceptive Devices and Contrivances § 240.10b-1 Prohibition of use of manipulative or deceptive devices or contrivances with respect to certain...

  12. 17 CFR 240.10b-1 - Prohibition of use of manipulative or deceptive devices or contrivances with respect to certain...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... manipulative or deceptive devices or contrivances with respect to certain securities exempted from registration... Securities Exchange Act of 1934 Manipulative and Deceptive Devices and Contrivances § 240.10b-1 Prohibition of use of manipulative or deceptive devices or contrivances with respect to certain...

  13. 17 CFR 240.10b-1 - Prohibition of use of manipulative or deceptive devices or contrivances with respect to certain...

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... manipulative or deceptive devices or contrivances with respect to certain securities exempted from registration... Securities Exchange Act of 1934 Manipulative and Deceptive Devices and Contrivances § 240.10b-1 Prohibition of use of manipulative or deceptive devices or contrivances with respect to certain...

  14. Development of a simple and rapid method of precisely identifying the position of 10B atoms in tissue: an improvement in standard alpha autoradiography

    PubMed Central

    Tanaka, Hiroki; Sakurai, Yoshinori; Suzuki, Minoru; Masunaga, Shin-ichiro; Takamiya, Koichi; Maruhashi, Akira; Ono, Koji

    2014-01-01

    Boron neutron capture therapy (BNCT) can be utilized to selectively kill cancer cells using a boron compound that accumulates only in cancer cells and not in normal cells. Tumor-bearing animals treated by BNCT are routinely used to evaluate long-term antitumor effects of new boron compounds. Alpha-autoradiography is one of the methods employed in the evaluation of antitumor effects. However, a standard alpha-autoradiography cannot detect the microdistribution of 10B because of the difficulty associated with the superposition of a tissue sample image and etched pits on a track detector with the etching process. In order to observe the microdistribution of 10B, some special methods of alpha-autoradiography have been developed that make use of a special track detector, or the atomic force microscope combined with X-ray and UV light irradiation. In contrast, we propose, herein, a simple and rapid method of precisely identifying the position of 10B using the imaging process and the shape of etched pits, such as their circularity, without the need to use special track detectors or a microscope. A brief description of this method and its verification test are presented in this article. We have established a method of detecting the microdistribution of 10B with submicron deviation between the position of etched pits and the position of reaction in a tissue sample, for a given circularity of etched pits. PMID:24142968

  15. Low-level laser treatment stimulates hair growth via upregulating Wnt10b and β-catenin expression in C3H/HeJ mice.

    PubMed

    Zhang, Tiran; Liu, Liqiang; Fan, Jincai; Tian, Jia; Gan, Cheng; Yang, Zengjie; Jiao, Hu; Han, Bing; Liu, Zheng

    2017-07-01

    This study was conducted in order to evaluate the role of low-level laser treatment (LLLT) in hair growth in C3H/HeJ mice. Healthy C57BL/6 mice were randomly divided into two groups: with and without low-level laser treatment. The skin color of each mouse was observed each day. Skin samples were collected for H&E, immunofluorescence, PCR, and western blot analysis, to observe the morphology of hair follicles and detect the expression levels of Wnt10b and β-catenin. Observation of skin color demonstrated that black pigmentation started significantly earlier in the laser group than in the control group. Hair follicle number in both groups showed no difference; however, the hair follicle length presented a significant difference. Wnt10b protein was detected on the second day in hair matrix cells in the LLLT group but not in the control group. PCR and western blot results both illustrated that expression of Wnt10b and β-catenin was significantly higher in the LLLT group than in the control group. Our study illustrated that low-level laser treatment can promote hair regrowth by inducing anagen phase of hair follicles via initiating the Wnt10b/β-catenin pathway.

  16. MDCK Cystogenesis Driven by Cell Stabilization within Computational Analogues

    PubMed Central

    Engelberg, Jesse A.; Datta, Anirban; Mostov, Keith E.; Hunt, C. Anthony

    2011-01-01

    The study of epithelial morphogenesis is fundamental to increasing our understanding of organ function and disease. Great progress has been made through study of culture systems such as Madin-Darby canine kidney (MDCK) cells, but many aspects of even simple morphogenesis remain unclear. For example, are specific cell actions tightly coupled to the characteristics of the cell's environment or are they more often cell state dependent? How does the single lumen, single cell layer cyst consistently emerge from a variety of cell actions? To improve insight, we instantiated in silico analogues that used hypothesized cell behavior mechanisms to mimic MDCK cystogenesis. We tested them through in vitro experimentation and quantitative validation. We observed novel growth patterns, including a cell behavior shift that began around day five of growth. We created agent-oriented analogues that used the cellular Potts model along with an Iterative Refinement protocol. Following several refinements, we achieved a degree of validation for two separate mechanisms. Both survived falsification and achieved prespecified measures of similarity to cell culture properties. In silico components and mechanisms mapped to in vitro counterparts. In silico, the axis of cell division significantly affects lumen number without changing cell number or cyst size. Reducing the amount of in silico luminal cell death had limited effect on cystogenesis. Simulations provide an observable theory for cystogenesis based on hypothesized, cell-level operating principles. PMID:21490722

  17. Carbon storage at defect sites in mantle mineral analogues

    NASA Astrophysics Data System (ADS)

    Wu, Jun; Buseck, Peter R.

    2013-10-01

    A significant fraction of Earth's carbon resides in the mantle, but the mode of carbon storage presents a long-standing problem. The mantle contains fluids rich in carbon dioxide and methane, carbonate-bearing melts, carbonate minerals, graphite, diamond and carbides, as well as dissolved carbon atoms in metals. However, it is uncertain whether these can sufficiently account for the total amount of carbon thought to be stored in the mantle and the volume of carbon degassed from the mantle at volcanoes. Moreover, such carbon hosts should significantly affect the physical and chemical behaviour of the mantle, including its melting temperature, electrical conductivity and oxidation state. Here we use in situ transmission electron microscopy to measure the storage of carbon within common mantle mineral analogues--nickel-doped lanthanum chromate perovskite and titanium dioxide--in laboratory experiments at high pressure and temperature. We detect elevated carbon concentrations at defect sites in the nanocrystals, maintained at high pressures within annealed carbon nanocages. Specifically, our experiments show that small stacking faults within the mantle analogue materials are effective carbon sinks at mantle conditions, potentially providing an efficient mechanism for carbon storage in the mantle. Furthermore, this carbon can be readily released under lower pressure conditions, and may therefore help to explain carbon release in volcanic eruptions.

  18. Receptor-mediated uptake of boron-rich neuropeptide y analogues for boron neutron capture therapy.

    PubMed

    Ahrens, Verena M; Frank, René; Boehnke, Solveig; Schütz, Christian L; Hampel, Gabriele; Iffland, Dorothée S; Bings, Nicolas H; Hey-Hawkins, Evamarie; Beck-Sickinger, Annette G

    2015-01-01

    Peptidic ligands selectively targeting distinct G protein-coupled receptors that are highly expressed in tumor tissue represent a promising approach in drug delivery. Receptor-preferring analogues of neuropeptide Y (NPY) bind and activate the human Y1 receptor subtype (hY1 receptor), which is found in 90% of breast cancer tissue and in all breast-cancer-derived metastases. Herein, novel highly boron-loaded Y1 -receptor-preferring peptide analogues are described as smart shuttle systems for carbaboranes as (10) B-containing moieties. Various positions in the peptide were screened for their susceptibility to carbaborane modification, and the most promising positions were chosen to create a multi-carbaborane peptide containing 30 boron atoms per peptide with excellent activation and internalization patterns at the hY1 receptor. Boron uptake studies by inductively coupled plasma mass spectrometry revealed successful uptake of the multi-carbaborane peptide into hY1 -receptor-expressing cells, exceeding the required amount of 10(9) boron atoms per cell. This result demonstrates that the NPY/hY receptor system can act as an effective transport system for boron-containing moieties.

  19. MicroRNAs 10a and 10b Regulate the Expression of Human Platelet Glycoprotein Ibα for Normal Megakaryopoiesis

    PubMed Central

    Zhang, Zuping; Ran, Yali; Shaw, Tanner S.; Peng, Yuandong

    2016-01-01

    MicroRNAs are a class of small non-coding RNAs that bind to the three prime untranslated region (3′-UTR) of target mRNAs. They cause a cleavage or an inhibition of the translation of target mRNAs, thus regulating gene expression. Here, we employed three prediction tools to search for potential miRNA target sites in the 3′-UTR of the human platelet glycoprotein (GP) 1BA gene. A luciferase reporter assay shows that miR-10a and -10b sites are functional. When miR-10a or -10b mimics were transfected into the GP Ibβ/GP IX-expressing cells, along with a DNA construct harboring both the coding and 3′-UTR sequences of the human GP1BA gene, we found that they inhibit the transient expression of GP Ibα on the cell surface. When the miR-10a or -10b mimics were introduced into murine progenitor cells, upon megakaryocyte differentiation, we found that GP Ibα mRNA expression was markedly reduced, suggesting that a miRNA-induced mRNA degradation is at work. Thus, our study identifies GP Ibα as a novel target of miR-10a and -10b, suggesting that a drastic reduction in the levels of miR-10a and -10b in the late stage of megakaryopoiesis is required to allow the expression of human GP Ibα and the formation of the GP Ib-IX-V complex. PMID:27834869

  20. Detection of secondary eclipses of WASP-10b and Qatar-1b in the Ks band and the correlation between Ks-band temperature and stellar activity.

    NASA Astrophysics Data System (ADS)

    Cruz, Patricia; Barrado, David; Lillo-Box, Jorge; Diaz, Marcos; López-Morales, Mercedes; Birkby, Jayne; Fortney, Jonathan J.; Hodgkin, Simon

    2017-10-01

    The Calar Alto Secondary Eclipse study was a program dedicated to observe secondary eclipses in the near-IR of two known close-orbiting exoplanets around K-dwarfs: WASP-10b and Qatar-1b. Such observations reveal hints on the orbital configuration of the system and on the thermal emission of the exoplanet, which allows the study of the brightness temperature of its atmosphere. The observations were performed at the Calar Alto Observatory (Spain). We used the OMEGA2000 instrument (Ks band) at the 3.5m telescope. The data was acquired with the telescope strongly defocused. The differential light curve was corrected from systematic effects using the Principal Component Analysis (PCA) technique. The final light curve was fitted using an occultation model to find the eclipse depth and a possible phase shift by performing a MCMC analysis. The observations have revealed a secondary eclipse of WASP-10b with depth of 0.137%, and a depth of 0.196% for Qatar-1b. The observed phase offset from expected mid-eclipse was of -0.0028 for WASP-10b, and of -0.0079 for Qatar-1b. These measured offsets led to a value for |ecosω| of 0.0044 for the WASP-10b system, leading to a derived eccentricity which was too small to be of any significance. For Qatar-1b, we have derived a |ecosω| of 0.0123, however, this last result needs to be confirmed with more data. The estimated Ks-band brightness temperatures are of 1647 K and 1885 K for WASP-10b and Qatar-1b, respectively. We also found an empirical correlation between the (R'HK) activity index of planet hosts and the Ks-band brightness temperature of exoplanets, considering a small number of systems.

  1. Study of a (10)B+ZnS(Ag) neutron detector as an alternative to (3)He-based detectors in Homeland Security.

    PubMed

    Guzmán-García, Karen A; Vega-Carrillo, Héctor René; Gallego, Eduardo; Lorente-Fillol, Alfredo; Méndez-Villafañe, Roberto; Gonzalez, Juan A; Ibañez-Fernandez, Sviatoslav

    2016-11-01

    The response of a scintillation neutron detector of ZnS(Ag) with (10)B was calculated, using the MCNPX Monte Carlo Code. The detector consists of four panels of polymethyl methacrylate (PMMA) and five thin layers of ~0.017cm thick (10)B+ZnS(Ag) in contact with the PMMA. The response was calculated for the bare detector and with different thicknesses of High Density Polyethylene, HDPE, moderator for 29 monoenergetic sources as well as (241)AmBe and (252)Cf neutrons sources. In these calculations the reaction rate (10)B(n, α)(7)Li and the neutron fluence in the sensitive area of the detector (10)B+ZnS(Ag) was estimated. Measurements were made at the Neutron Measurements Laboratory, Universidad Politécnica de Madrid, LMN-UPM, to quantify the detections in counts per second in response to a (252)Cf neutron source separated 200cm. The MCNPX computations were compared with measurements to estimate the efficiency of ZnS(Ag) for detecting the α that is created in the (10)B(n, α)(7)Li reaction. After validating new models with different geometries it will be possible to improve the detector response trying to achieve a sensitivity of 2.5cps-ng(252)Cf comparable with the response requirements for (3)He detectors installed in the Radiation Portal Monitors, RPMs. This type of detector can be considered an alternative to the (3)He detectors for detection of Special Nuclear Material, SNM.

  2. Structure of Mandelate Racemase with Bound Intermediate Analogues Benzohydroxamate and Cupferron

    SciTech Connect

    Lietzan, Adam D.; Nagar, Mitesh; Pellmann, Elise A.; Bourque, Jennifer R.; Bearne, Stephen L.; Maurice, Martin St.

    2012-05-09

    Mandelate racemase (MR, EC 5.1.2.2) from Pseudomonas putida catalyzes the Mg{sup 2+}-dependent interconversion of the enantiomers of mandelate, stabilizing the altered substrate in the transition state by 26 kcal/mol relative to the substrate in the ground state. To understand the origins of this binding discrimination, we determined the X-ray crystal structures of wild-type MR complexed with two analogues of the putative aci-carboxylate intermediate, benzohydroxamate and Cupferron, to 2.2-{angstrom} resolution. Benzohydroxamate is shown to be a reasonable mimic of the transition state and/or intermediate because its binding affinity for 21 MR variants correlates well with changes in the free energy of transition state stabilization afforded by these variants. Both benzohydroxamate and Cupferron chelate the active site divalent metal ion and are bound in a conformation with the phenyl ring coplanar with the hydroxamate and diazeniumdiolate moieties, respectively. Structural overlays of MR complexed with benzohydroxamate, Cupferron, and the ground state analogue (S)-atrolactate reveal that the para carbon of the substrate phenyl ring moves by 0.8-1.2 {angstrom} between the ground state and intermediate state, consistent with the proposal that the phenyl ring moves during MR catalysis while the polar groups remain relatively fixed. Although the overall protein structure of MR with bound intermediate analogues is very similar to that of MR with bound (S)-atrolactate, the intermediate-Mg{sup 2+} distance becomes shorter, suggesting a tighter complex with the catalytic Mg{sup 2+}. In addition, Tyr 54 moves closer to the phenyl ring of the bound intermediate analogues, contributing to an overall constriction of the active site cavity. However, site-directed mutagenesis experiments revealed that the role of Tyr 54 in MR catalysis is relatively minor, suggesting that alterations in enzyme structure that contribute to discrimination between the altered substrate in the

  3. Synthesis and cytotoxicity properties of amiodarone analogues.

    PubMed

    Bigler, Laurent; Spirli, Carlo; Fiorotto, Romina; Pettenazzo, Andrea; Duner, Elena; Baritussio, Aldo; Follath, Ferenc; Ha, Huy Riem

    2007-06-01

    Amiodarone (AMI) is a potent antiarrhythmic agent; however, its clinical use is limited due to numerous side effects. In order to investigate the structure--cytotoxicity relationship, AMI analogues were synthesized, and then, using rabbit alveolar macrophages, were tested for viability and for the ability to interfere with the degradation of surfactant protein A (SP-A) and with the accumulation of an acidotropic dye. Our data revealed that modification of the diethylamino-beta-ethoxy group of the AMI molecule may affect viability, the ability to degrade SP-A and vacuolation differently. In particular, PIPAM (2d), an analogue with a piperidyl moiety, acts toward the cells in a similar manner to AMI, but is less toxic. Thus, it would be possible to reduce the cytotoxicity of AMI by modifying its chemical structure.

  4. Optimization of propafenone analogues as antimalarial leads.

    PubMed

    Lowes, David J; Guiguemde, W Armand; Connelly, Michele C; Zhu, Fangyi; Sigal, Martina S; Clark, Julie A; Lemoff, Andrew S; Derisi, Joseph L; Wilson, Emily B; Guy, R Kiplin

    2011-11-10

    Propafenone, a class Ic antiarrythmic drug, inhibits growth of cultured Plasmodium falciparum. While the drug's potency is significant, further development of propafenone as an antimalarial would require divorcing the antimalarial and cardiac activities as well as improving the pharmacokinetic profile of the drug. A small array of propafenone analogues was designed and synthesized to address the cardiac ion channel and PK liabilities. Testing of this array revealed potent inhibitors of the 3D7 (drug sensitive) and K1 (drug resistant) strains of P. falciparum that possessed significantly reduced ion channel effects and improved metabolic stability. Propafenone analogues are unusual among antimalarial leads in that they are more potent against the multidrug resistant K1 strain of P. falciparum compared to the 3D7 strain.

  5. Antitumoral cyclic peptide analogues of chlamydocin.

    PubMed

    Bernardi, E; Fauchere, J L; Atassi, G; Viallefont, P; Lazaro, R

    1993-01-01

    A series of cyclic tetrapeptides bearing the bioactive alkylating group on an epsilon-amino-lysyl function have been examined for their antitumoral activity on L1210 and P388 murine leukemia cell lines. One analogue belonging to the chlamydocin family and bearing a beta-chloroethylnitrosourea group was found to be potent at inhibiting L1210 cell proliferation and had a higher therapeutic index than the reference compound bis-beta-chloroethylnitrosourea (BCNU) on the in vivo P388-induced leukemia model.

  6. The Brookhaven electron analogue, 1953--1957

    SciTech Connect

    Plotkin, M.

    1991-12-18

    The following topics are discussed on the Brookhaven electron analogue: L.J. Haworth and E.L. VanHorn letters; Original G.K. Green outline for report; General description; Parameter list; Mechanical Assembly; Alignment; Degaussing; Vacuum System; Injection System; The pulsed inflector; RF System; Ferrite Cavity; Pick-up electrodes and preamplifiers; Radio Frequency power amplifier; Lens supply; Controls and Power; and RF acceleration summary.

  7. The Brookhaven electron analogue, 1953--1957

    SciTech Connect

    Plotkin, M.

    1991-12-18

    The following topics are discussed on the Brookhaven electron analogue: L.J. Haworth and E.L. VanHorn letters; Original G.K. Green outline for report; General description; Parameter list; Mechanical Assembly; Alignment; Degaussing; Vacuum System; Injection System; The pulsed inflector; RF System; Ferrite Cavity; Pick-up electrodes and preamplifiers; Radio Frequency power amplifier; Lens supply; Controls and Power; and RF acceleration summary.

  8. Synthesis of constrained analogues of tryptophan

    PubMed Central

    Negrato, Marco; Abbiati, Giorgio; Dell’Acqua, Monica

    2015-01-01

    Summary A Lewis acid-catalysed diastereoselective [4 + 2] cycloaddition of vinylindoles and methyl 2-acetamidoacrylate, leading to methyl 3-acetamido-1,2,3,4-tetrahydrocarbazole-3-carboxylate derivatives, is described. Treatment of the obtained cycloadducts under hydrolytic conditions results in the preparation of a small library of compounds bearing the free amino acid function at C-3 and pertaining to the class of constrained tryptophan analogues. PMID:26664620

  9. Polyamine analogues targeting epigenetic gene regulation.

    PubMed

    Huang, Yi; Marton, Laurence J; Woster, Patrick M; Casero, Robert A

    2009-11-04

    Over the past three decades the metabolism and functions of the polyamines have been actively pursued as targets for antineoplastic therapy. Interactions between cationic polyamines and negatively charged nucleic acids play a pivotal role in DNA stabilization and RNA processing that may affect gene expression, translation and protein activity. Our growing understanding of the unique roles that the polyamines play in chromatin regulation, and the discovery of novel proteins homologous with specific regulatory enzymes in polyamine metabolism, have led to our interest in exploring chromatin remodelling enzymes as potential therapeutic targets for specific polyamine analogues. One of our initial efforts focused on utilizing the strong affinity that the polyamines have for chromatin to create a backbone structure, which could be combined with active-site-directed inhibitor moieties of HDACs (histone deacetylases). Specific PAHAs (polyaminohydroxamic acids) and PABAs (polyaminobenzamides) polyamine analogues have demonstrated potent inhibition of the HDACs, re-expression of p21 and significant inhibition of tumour growth. A second means of targeting the chromatin-remodelling enzymes with polyamine analogues was facilitated by the recent identification of flavin-dependent LSD1 (lysine-specific demethylase 1). The existence of this enzyme demonstrated that histone lysine methylation is a dynamic process similar to other histone post-translational modifications. LSD1 specifically catalyses demethylation of mono- and di-methyl Lys4 of histone 3, key positive chromatin marks associated with transcriptional activation. Structural and catalytic similarities between LSD1 and polyamine oxidases facilitated the identification of biguanide, bisguanidine and oligoamine polyamine analogues that are potent inhibitors of LSD1. Cellular inhibition of LSD1 by these unique compounds led to the re-activation of multiple epigenetically silenced genes important in tumorigenesis. The use of

  10. Blood Loss Estimation Using Gauze Visual Analogue

    PubMed Central

    Ali Algadiem, Emran; Aleisa, Abdulmohsen Ali; Alsubaie, Huda Ibrahim; Buhlaiqah, Noora Radhi; Algadeeb, Jihad Bagir; Alsneini, Hussain Ali

    2016-01-01

    Background Estimating intraoperative blood loss can be a difficult task, especially when blood is mostly absorbed by gauze. In this study, we have provided an improved method for estimating blood absorbed by gauze. Objectives To develop a guide to estimate blood absorbed by surgical gauze. Materials and Methods A clinical experiment was conducted using aspirated blood and common surgical gauze to create a realistic amount of absorbed blood in the gauze. Different percentages of staining were photographed to create an analogue for the amount of blood absorbed by the gauze. Results A visual analogue scale was created to aid the estimation of blood absorbed by the gauze. The absorptive capacity of different gauze sizes was determined when the gauze was dripping with blood. The amount of reduction in absorption was also determined when the gauze was wetted with normal saline before use. Conclusions The use of a visual analogue may increase the accuracy of blood loss estimation and decrease the consequences related to over or underestimation of blood loss. PMID:27626017

  11. Thymidine analogues for tracking DNA synthesis.

    PubMed

    Cavanagh, Brenton L; Walker, Tom; Norazit, Anwar; Meedeniya, Adrian C B

    2011-09-15

    Replicating cells undergo DNA synthesis in the highly regulated, S-phase of the cell cycle. Analogues of the pyrimidine deoxynucleoside thymidine may be inserted into replicating DNA, effectively tagging dividing cells allowing their characterisation. Tritiated thymidine, targeted using autoradiography was technically demanding and superseded by 5-bromo-2-deoxyuridine (BrdU) and related halogenated analogues, detected using antibodies. Their detection required the denaturation of DNA, often constraining the outcome of investigations. Despite these limitations BrdU alone has been used to target newly synthesised DNA in over 20,000 reviewed biomedical studies. A recent breakthrough in "tagging DNA synthesis" is the thymidine analogue 5-ethynyl-2'-deoxyuridine (EdU). The alkyne group in EdU is readily detected using a fluorescent azide probe and copper catalysis using 'Huisgen's reaction' (1,3-dipolar cycloaddition or 'click chemistry'). This rapid, two-step biolabelling approach allows the tagging and imaging of DNA within cells whilst preserving the structural and molecular integrity of the cells. The bio-orthogonal detection of EdU allows its application in more experimental assays than previously possible with other "unnatural bases". These include physiological, anatomical and molecular biological experimentation in multiple fields including, stem cell research, cancer biology, and parasitology. The full potential of EdU and related molecules in biomedical research remains to be explored.

  12. Activation of Wnt/beta-catenin signaling increases insulin sensitivity through a reciprocal regulation of Wnt10b and SREBP-1c in skeletal muscle cells.

    PubMed

    Abiola, Mounira; Favier, Maryline; Christodoulou-Vafeiadou, Eleni; Pichard, Anne-Lise; Martelly, Isabelle; Guillet-Deniau, Isabelle

    2009-12-30

    Intramyocellular lipid accumulation is strongly related to insulin resistance in humans, and we have shown that high glucose concentration induced de novo lipogenesis and insulin resistance in murin muscle cells. Alterations in Wnt signaling impact the balance between myogenic and adipogenic programs in myoblasts, partly due to the decrease of Wnt10b protein. As recent studies point towards a role for Wnt signaling in the pathogenesis of type 2 diabetes, we hypothesized that activation of Wnt signaling could play a crucial role in muscle insulin sensitivity. Here we demonstrate that SREBP-1c and Wnt10b display inverse expression patterns during muscle ontogenesis and regeneration, as well as during satellite cells differentiation. The Wnt/beta-catenin pathway was reactivated in contracting myotubes using siRNA mediated SREBP-1 knockdown, Wnt10b over-expression or inhibition of GSK-3beta, whereas Wnt signaling was inhibited in myoblasts through silencing of Wnt10b. SREBP-1 knockdown was sufficient to induce Wnt10b protein expression in contracting myotubes and to activate the Wnt/beta-catenin pathway. Conversely, silencing Wnt10b in myoblasts induced SREBP-1c protein expression, suggesting a reciprocal regulation. Stimulation of the Wnt/beta-catenin pathway i) drastically decreased SREBP-1c protein and intramyocellular lipid deposition in myotubes; ii) increased basal glucose transport in both insulin-sensitive and insulin-resistant myotubes through a differential activation of Akt and AMPK pathways; iii) restored insulin sensitivity in insulin-resistant myotubes. We conclude that activation of Wnt/beta-catenin signaling in skeletal muscle cells improved insulin sensitivity by i) decreasing intramyocellular lipid deposition through downregulation of SREBP-1c; ii) increasing insulin effects through a differential activation of the Akt/PKB and AMPK pathways; iii) inhibiting the MAPK pathway. A crosstalk between these pathways and Wnt/beta-catenin signaling in skeletal

  13. Synthesis and biological assay of erlotinib analogues and BSA-conjugated erlotinib analogue.

    PubMed

    Boobalan, Ramalingam; Liu, Kuang-Kai; Chao, Jui-I; Chen, Chinpiao

    2017-04-15

    A series of erlotinib analogues that have structural modification at 6,7-alkoxyl positions is efficiently synthesized. The in vitro anti-tumor activity of synthesized compounds is studied in two non-small cell lung cancer (NSCLC) cell lines (A549 and H1975). Among the synthesized compounds, the iodo compound 6 (ETN-6) exhibits higher anti-cancer activity compared to erlotinib. An efficient method is developed for the conjugation of erlotinib analogue-4, alcohol compound, with protein, bovine serum albumin (BSA), via succinic acid linker. The in vitro anti-tumor activity of the protein attached erlotinib analogue, 8 (ETN-4-Suc-BSA), showed stronger inhibitory activity in both A549 and H1975 NSCLC cell lines. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Mechanism of cis-prenyltransferase reaction probed by substrate analogues.

    PubMed

    Lu, Yen-Pin; Liu, Hon-Ge; Teng, Kuo-Hsun; Liang, Po-Huang

    2010-10-01

    Undecaprenyl pyrophosphate synthase (UPPS) is a cis-type prenyltransferases which catalyzes condensation reactions of farnesyl diphosphate (FPP) with eight isopentenyl pyrophosphate (IPP) units to generate C(55) product. In this study, we used two analogues of FPP, 2-fluoro-FPP and [1,1-(2)H(2)]FPP, to probe the reaction mechanism of Escherichia coli UPPS. The reaction rate of 2-fluoro-FPP with IPP under single-turnover condition is similar to that of FPP, consistent with the mechanism without forming a farnesyl carbocation intermediate. Moreover, the deuterium secondary KIE of 0.985±0.022 measured for UPPS reaction using [1,1-(2)H(2)]FPP supports the associative transition state. Unlike the sequential mechanism used by trans-prenyltransferases, our data demonstrate E. coli UPPS utilizes the concerted mechanism. Copyright © 2010 Elsevier Inc. All rights reserved.

  15. Phosphorus-based SAHA analogues as histone deacetylase inhibitors.

    PubMed

    Kapustin, Galina V; Fejér, György; Gronlund, Jennifer L; McCafferty, Dewey G; Seto, Edward; Etzkorn, Felicia A

    2003-08-21

    [structure: see text] Three analogues of suberoyl anilide hydroxamic acid (SAHA) with phosphorus metal-chelating functionalities were synthesized as inhibitors of histone deacetylases (HDACs). The compounds showed weak activity for HeLa nuclear extracts (IC(50) = 0.57-6.1 mM), HDAC8 (IC(50) = 0.28-0.41 mM), and histone-deacetylase-like protein (HDLP, IC(50) = 0.33-1.9 mM), suggesting that the transition state of HDAC is not analogous to zinc proteases. Antiproliferative activity against A2780 cancer cells (IC(50) = 0.11-0.12 mM), comparable to SAHA (0.15 mM), was observed.

  16. Search for P-odd asymmetry in the. cap alpha. emission in the capture of polarized thermal neutrons by /sup 6/Li and /sup 10/B nuclei

    SciTech Connect

    Vesna, V.A.; Egorov, A.I.; Kolomenskii, A.; Kornyushkin, A.F.; Lobashev, V.M.; Okunev, I.S.; Peskov, B.G.; Pirozhkov, A.N.; Smotritskii, L.M.; Titov, N.A.

    1983-09-10

    Measurements by an integral method in a geometry ruling out an effect of a P-even left-right asymmetry have yielded limitations on the magnitude of the P-odd asymmetry in several reactions: Vertical Bara/sub p/Vertical Bar<1.4 x 10/sup -6/ for the reaction /sup 6/Li(n,..cap alpha..)/sup 3/H, Vertical Bara/sub p/Vertical Bar<8 x 10/sup -6/ for the reaction /sup 10/B(n,..cap alpha../sub 0/)/sup 7/Li, and Vertical Bara/sub p/Vertical Bar<1.5 x 10/sup -6/ for the reaction /sup 10/B(n,..cap alpha../sub 1/)/sup 7/Li* (90% confidence level).

  17. Spectrum integrated (n,He) cross section comparisons and least squares analyses for /sup 6/Li and /sup 10/B in benchmark fields

    SciTech Connect

    Schenter, R.E.; Oliver, B.M.; Farrar, H. IV

    1986-06-01

    Spectrum integrated cross sections for /sup 6/Li and /sup 10/B from five benchmark fast reactor neutron fields are compared with calculated values obtained using the ENDF/B-V Cross Section Files. The benchmark fields include the Coupled Fast Reactivity Measurements Facility (CFRMF) at the Idaho National Engineering Laboratory, the 10% Enriched U-235 Critical Assembly (BIG-10) at Los Alamos National Laboratory, the Sigma-Sigma and Fission Cavity fields of the BR-1 reactor at CEN/SCK, and the Intermediate Energy Standard Neutron Field (ISNF) at the National Bureau of Standards. Results from least square analyses using the FERRET computer code to obtain adjusted cross section values and their uncertainties are presented. Input to these calculations include the above five benchmark data sets. These analyses indicate a need for revision in the ENDF/B-V files for the /sup 10/B and /sup 6/Li cross sections for energies above 50 keV.

  18. Inhibition of ATP Synthase by Chlorinated Adenosine Analogue

    PubMed Central

    Chen, Lisa S.; Nowak, Billie J.; Ayres, Mary L.; Krett, Nancy L.; Rosen, Steven T.; Zhang, Shuxing; Gandhi, Varsha

    2009-01-01

    8-Chloroadenosine (8-Cl-Ado) is a ribonucleoside analogue that is currently in clinical trial for chronic lymphocytic leukemia. Based on the decline in cellular ATP pool following 8-Cl-Ado treatment, we hypothesized that 8-Cl-ADP and 8-Cl-ATP may interfere with ATP synthase, a key enzyme in ATP production. Mitochondrial ATP synthase is composed of two major parts; FO intermembrane base and F1 domain, containing α and β subunits. Crystal structures of both α and β subunits that bind to the substrate, ADP, are known in tight binding (αdpβdp) and loose binding (αtpβtp) states. Molecular docking demonstrated that 8-Cl-ADP/8-Cl-ATP occupied similar binding modes as ADP/ATP in the tight and loose binding sites of ATP synthase, respectively, suggesting that the chlorinated nucleotide metabolites may be functional substrates and inhibitors of the enzyme. The computational predictions were consistent with our whole cell biochemical results. Oligomycin, an established pharmacological inhibitor of ATP synthase, decreased both ATP and 8-Cl-ATP formation from exogenous substrates, however, did not affect pyrimidine nucleoside analogue triphosphate accumulation. Synthesis of ATP from ADP was inhibited in cells loaded with 8-Cl-ATP. These biochemical studies are in consent with the computational modeling; in the αtpβtp state 8-Cl-ATP occupies similar binding as ANP, a non-hydrolyzable ATP mimic that is a known inhibitor. Similarly, in the substrate binding site (αdpβdp) 8-Cl-ATP occupies a similar position as ATP mimic ADP-BeF3 −. Collectively, our current work suggests that 8-Cl-ADP may serve as a substrate and the 8-Cl-ATP may be an inhibitor of ATP synthase. PMID:19477165

  19. First observation of P-odd asymmetry of α-particle emission in the 10B (n , α)7Li nuclear reaction

    NASA Astrophysics Data System (ADS)

    Gledenov, Yu. M.; Nesvizhevsky, V. V.; Sedyshev, P. V.; Shul'gina, E. V.; Szalanski, P.; Vesna, V. A.

    2017-06-01

    We present measurements of P-odd asymmetry of emission of α-particles in the 10B (n , α)7Li nuclear reaction, which are carried out using beams of polarized cold neutrons at Petersburg Nuclear Physics Institute (PNPI, Gatchina, Russia) and Institut Max von Laue - Paul Langevin (ILL, Grenoble, France) nuclear reactors. The α-particle detector is an ionization chamber with insensitive gaseous layer.

  20. Effects of employing a 10B-carrier and manipulating intratumour hypoxia on local tumour response and lung metastatic potential in boron neutron capture therapy

    PubMed Central

    Masunaga, S; Sakurai, Y; Tanaka, H; Suzuki, M; Liu, Y; Kondo, N; Maruhashi, A; Kinashi, Y; Ono, K

    2012-01-01

    Objectives To evaluate the effects of employing a 10B-carrier and manipulating intratumour hypoxia on local tumour response and lung metastatic potential in boron neutron capture therapy (BNCT) by measuring the response of intratumour quiescent (Q) cells. Methods B16-BL6 melanoma tumour-bearing C57BL/6 mice were continuously given 5-bromo-2′-deoxyuridine (BrdU) to label all proliferating (P) cells. The tumours received reactor thermal neutron beam irradiation following the administration of a 10B-carrier [L-para-boronophenylalanine-10B (BPA) or sodium mercaptoundecahydrododecaborate-10B (BSH)] in combination with an acute hypoxia-releasing agent (nicotinamide) or mild temperature hyperthermia (MTH). Immediately after the irradiation, cells from some tumours were isolated and incubated with a cytokinesis blocker. The responses of the Q and total (P+Q) cell populations were assessed based on the frequency of micronuclei using immunofluorescence staining for BrdU. In other tumour-bearing mice, macroscopic lung metastases were enumerated 17 days after irradiation. Results BPA-BNCT increased the sensitivity of the total tumour cell population more than BSH-BNCT. However, the sensitivity of Q cells treated with BPA was lower than that of BSH-treated Q cells. With or without a 10B–carrier, MTH enhanced the sensitivity of the Q cell population. Without irradiation, nicotinamide treatment decreased the number of lung metastases. With irradiation, BPA-BNCT, especially in combination with nicotinamide treatment, showed the potential to reduce the number of metastases more than BSH-BNCT. Conclusion BSH-BNCT in combination with MTH improves local tumour control, while BPA-BNCT in combination with nicotinamide may reduce the number of lung metastases. PMID:22391496

  1. Complex energy approaches for calculating isobaric analogue states

    SciTech Connect

    Betan, R. Id; Kruppa, A. T.; Vertse, T.

    2008-10-15

    Parameters of isobaric analog resonance (IAR) are calculated in the framework of the Lane model using different methods. In the standard method, the direct numerical solution of the coupled channel (CC) Lane equations served as a reference for checking two complex energy methods, namely the complex energy shell model (CXSM) and the complex scaling (CS) approaches. The IAR parameters calculated by the CXSM and the CS methods agree with that of the CC results within 1 keV for all partial waves considered. Although the CXSM and the CS methods have similarities, an important difference is that only the CXSM method offers a direct way for studying the configurations of the IAR wave function.

  2. Purification, crystallization and crystallographic analysis of Clostridium thermocellum endo-1,4-β-d-xylanase 10B in complex with xylohexaose

    SciTech Connect

    Najmudin, Shabir; Pinheiro, Benedita A.; Romão, Maria J.; Prates, José A. M.; Fontes, Carlos M. G. A.

    2008-08-01

    The N-terminal moiety of C. thermocellum endo-1,4-β-d-xylanase 10B, comprising a carbohydrate-binding module (CBM22-1) and a GH10 E337A mutant domain, has been crystallized in complex with xylohexaose. The crystals belong to the trigonal space group P3{sub 2}21, contain a dimer in the asymmetric unit and diffract to beyond 2.0 Å resolution. The cellulosome of Clostridium thermocellum is a highly organized multi-enzyme complex of cellulases and hemicellulases involved in the hydrolysis of plant cell-wall polysaccharides. The bifunctional multi-modular xylanase Xyn10B is one of the hemicellulase components of the C. thermocellum cellulosome. The enzyme contains an internal glycoside hydrolase family 10 catalytic domain (GH10) and a C-terminal family 1 carbohydrate esterase domain (CE1). The N-terminal moiety of Xyn10B (residues 32–551), comprising a carbohydrate-binding module (CBM22-1) and the GH10 E337A mutant, was crystallized in complex with xylohexaose. The crystals belong to the trigonal space group P3{sub 2}21 and contain a dimer in the asymmetric unit. The crystals diffracted to beyond 2.0 Å resolution.

  3. A microenvironment-sensitive fluorescent pyrimidine ribonucleoside analogue: synthesis, enzymatic incorporation, and fluorescence detection of a DNA abasic site.

    PubMed

    Tanpure, Arun A; Srivatsan, Seergazhi G

    2011-11-04

    Base-modified fluorescent ribonucleoside-analogue probes are valuable tools in monitoring RNA structure and function because they closely resemble the structure of natural nucleobases. Especially, 2-aminopurine, a highly environment-sensitive adenosine analogue, is the most extensively utilized fluorescent nucleoside analogue. However, only a few isosteric pyrimidine ribonucleoside analogues that are suitable for probing the structure and recognition properties of RNA molecules are available. Herein, we describe the synthesis and photophysical characterization of a small series of base-modified pyrimidine ribonucleoside analogues derived from tagging indole, N-methylindole, and benzofuran onto the 5-position of uracil. One of the analogues, based on a 5-(benzofuran-2-yl)pyrimidine core, shows emission in the visible region with a reasonable quantum yield and, importantly, displays excellent solvatochromism. The corresponding triphosphate substrate is effectively incorporated into oligoribonucleotides by T7 RNA polymerase to produce fluorescent oligoribonucleotide constructs. Steady-state and time-resolved spectroscopic studies with fluorescent oligoribonucleotide constructs demonstrate that the fluorescent ribonucleoside photophysically responds to subtle changes in its environment brought about by the interaction of the chromophore with neighboring bases. In particular, the emissive ribonucleoside, if incorporated into an oligoribonucleotide, positively reports the presence of a DNA abasic site with an appreciable enhancement in fluorescence intensity. The straightforward synthesis, amicability to enzymatic incorporation, and sensitivity to changes in the microenvironment highlight the potential of the benzofuran-conjugated pyrimidine ribonucleoside as an efficient fluorescent probe to investigate nucleic acid structure, dynamics, and recognition events.

  4. A Visual Analogue Scale in the Assessment of Dental Anxiety

    PubMed Central

    Luyk, Neil H.; Beck, Frank M.; Weaver, Joel M.

    1988-01-01

    The purpose of this study is to determine the validity of the visual analogue scale (VAS) in the assessment of changing levels of dental anxiety, through correlation with the dental anxiety scale (DAS) and the state portion (A-state) of the statetrait anxiety inventory (STAI). Forty-five adult patients attending an oral surgery clinic for a routine dental extraction participated. Before any treatment, each patient completed the DAS, the STAI, and a 100mm VAS. The order of administration was randomly determined. Following completion of the dental extraction under local anesthesia and just before discharge, the patients were once more asked to complete the DAS, the A-State, and a VAS which were again randomly ordered. All three measures demonstrate a significant reduction in mean anxiety scores from presurgery to postsurgery. There are significant correlations among the three measures both pre- and postsurgery. The VAS appears to correlate well with both the DAS and the A-State under changing levels of anxiety. PMID:3166350

  5. Cardiac specific effects of thyroid hormone analogues.

    PubMed

    Danzi, S; Klein, I

    2011-10-01

    There is significant interest in development of thyroid hormone analogues to harness specific properties as therapeutic agents for a variety of clinical indications including obesity, hypercholesterolemia, heart failure, and thyrotoxicosis. To date, most analogues have been designed to target liver specific effects, which can promote weight loss and lipid lowering through either tissue specific uptake or thyroid hormone receptor (TR) β isoform selectivity at the same time minimizing the unwanted cardiac and bone effects. We have developed a molecular biomarker assay to study the induction of the transcription of the cardiac specific α-myosin heavy chain (MHC) gene as a more sensitive and specific measure of thyroid hormone action on cardiac myocytes. We tested 5 TRβ and 1 TRα selective agonists as well as 2 putative TR antagonists in our α-MHC hnRNA assay. Using reverse transcription and polymerase chain reaction, we measured the induction of the α-MHC primary transcript in response to administration of drug. The TRα and only 2 of the TRβ agonists were highly active, when compared to the effect of T3, at the level of the cardiac myocyte. In addition, our data suggests that the reason that the antagonist NH-3 is not able to block the T3-mediated induction of α-MHC is that it does not get transported into the cardiac myocyte. Our data suggest that this assay will be useful in preclinical studies of the potential cardiac specific effects of thyroid hormone analogues and that predictions of function based on structure are not necessarily accurate or complete. © Georg Thieme Verlag KG Stuttgart · New York.

  6. Polyamine analogues bind human serum albumin.

    PubMed

    Beauchemin, R; N'soukpoé-Kossi, C N; Thomas, T J; Thomas, T; Carpentier, R; Tajmir-Riahi, H A

    2007-10-01

    Polyamine analogues show antitumor activity in experimental models, and their ability to alter activity of cytotoxic chemotherapeutic agents in breast cancer is well documented. Association of polyamines with nucleic acids and protein is included in their mechanism of action. The aim of this study was to examine the interaction of human serum albumin (HSA) with several polyamine analogues, such as 1,11-diamino-4,8-diazaundecane (333), 3,7,11,15-tetrazaheptadecane.4HCl (BE-333), and 3,7,11,15,19-pentazahenicosane.5HCl (BE-3333), in aqueous solution at physiological conditions using a constant protein concentration and various polyamine contents (microM to mM). FTIR, UV-visible, and CD spectroscopic methods were used to determine the polyamine binding mode and the effects of polyamine complexation on protein stability and secondary structure. Structural analysis showed that polyamines bind nonspecifically (H-bonding) via polypeptide polar groups with binding constants of K333 = 9.30 x 10(3) M(-1), KBE-333 = 5.63 x 10(2) M(-1), and KBE-3333 = 3.66 x 10(2) M(-1). The protein secondary structure showed major alterations with a reduction of alpha-helix from 55% (free protein) to 43-50% and an increase of beta-sheet from 17% (free protein) to 29-36% in the 333, BE-333, and BE-3333 complexes, indicating partial protein unfolding upon polyamine interaction. HSA structure was less perturbed by polyamine analogues compared to those of the biogenic polyamines.

  7. The Lehmer Matrix and Its Recursive Analogue

    DTIC Science & Technology

    2010-01-01

    for failing to comply with a collection of information if it does not display a currently valid OMB control number . 1. REPORT DATE 2010 2. REPORT...TYPE 3. DATES COVERED 00-00-2010 to 00-00-2010 4. TITLE AND SUBTITLE The Lehmer matrix and its recursive analogue 5a. CONTRACT NUMBER 5b...GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER 5e. TASK NUMBER 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND

  8. New synthetic approaches towards analogues of bedaquiline.

    PubMed

    Priebbenow, Daniel L; Barbaro, Lisa; Baell, Jonathan B

    2016-10-12

    Multi-drug resistant tuberculosis (MDR-TB) is of growing global concern and threatens to undermine increasing efforts to control the worldwide spread of tuberculosis (TB). Bedaquiline has recently emerged as a new drug developed to specifically treat MDR-TB. Despite being highly effective as a result of its unique mode of action, bedaquiline has been associated with significant toxicities and as such, safety concerns are limiting its clinical use. In order to access pharmaceutical agents that exhibit an improved safety profile for the treatment of MDR-TB, new synthetic pathways to facilitate the preparation of bedaquiline and analogues thereof have been discovered.

  9. Conformationally constrained analogues of L-prolyl-l-leucylglycinamide

    SciTech Connect

    Yu, K.L.

    1986-01-01

    The tripeptide, L-prolyl-L-leucylglycinamide (PLG), has been shown to modulate the pharmacological response of the neurotransmitter, dopamine, in the central nervous system. Many physical studies have suggested that PLG can exist in a type II ..beta..-bend conformation. In this study several types of conformationally constrained analogues capable of mimicking different types of conformations of PLG have been designed to answer two questions: (1) Is the type II ..beta..-bend the bioactive conformation of PLG. (2) Does the Leu-Gly amide bond of PLG need to be in a cis or trans configuration in order for it to bind to its receptor. The analogues of PLG that have been synthesized include the following: (1) Lactam analogues, (2) Cyclic peptides, (3) Olefinic analogue, and (4) Tetazole analogues. The analogues synthesized were tested in a (/sup 3/H)-ADTN binding assay to determine their ability to enhance the binding of this dopamine agonist to dopamine receptors.

  10. miR-10b-5p expression in Huntington's disease brain relates to age of onset and the extent of striatal involvement.

    PubMed

    Hoss, Andrew G; Labadorf, Adam; Latourelle, Jeanne C; Kartha, Vinay K; Hadzi, Tiffany C; Gusella, James F; MacDonald, Marcy E; Chen, Jiang-Fan; Akbarian, Schahram; Weng, Zhiping; Vonsattel, Jean Paul; Myers, Richard H

    2015-03-01

    MicroRNAs (miRNAs) are small non-coding RNAs that recognize sites of complementarity of target messenger RNAs, resulting in transcriptional regulation and translational repression of target genes. In Huntington's disease (HD), a neurodegenerative disease caused by a trinucleotide repeat expansion, miRNA dyregulation has been reported, which may impact gene expression and modify the progression and severity of HD. We performed next-generation miRNA sequence analysis in prefrontal cortex (Brodmann Area 9) from 26 HD, 2 HD gene positive, and 36 control brains. Neuropathological information was available for all HD brains, including age at disease onset, CAG-repeat size, Vonsattel grade, and Hadzi-Vonsattel striatal and cortical scores, a continuous measure of the extent of neurodegeneration. Linear models were performed to examine the relationship of miRNA expression to these clinical features, and messenger RNA targets of associated miRNAs were tested for gene ontology term enrichment. We identified 75 miRNAs differentially expressed in HD brain (FDR q-value <0.05). Among the HD brains, nine miRNAs were significantly associated with Vonsattel grade of neuropathological involvement and three of these, miR-10b-5p, miR-10b-3p, and miR-302a-3p, significantly related to the Hadzi-Vonsattel striatal score (a continuous measure of striatal involvement) after adjustment for CAG length. Five miRNAs (miR-10b-5p, miR-196a-5p, miR-196b-5p, miR-10b-3p, and miR-106a-5p) were identified as having a significant relationship to CAG length-adjusted age of onset including miR-10b-5p, the mostly strongly over-expressed miRNA in HD cases. Although prefrontal cortex was the source of tissue profiled in these studies, the relationship of miR-10b-5p expression to striatal involvement in the disease was independent of cortical involvement. Correlation of miRNAs to the clinical features clustered by direction of effect and the gene targets of the observed miRNAs showed association to

  11. U.S. Nuclear Regulatory Commission natural analogue research program

    SciTech Connect

    Kovach, L.A.; Ott, W.R.

    1995-09-01

    This article describes the natural analogue research program of the U.S. Nuclear Regulatory Commission (US NRC). It contains information on the regulatory context and organizational structure of the high-level radioactive waste research program plan. It also includes information on the conditions and processes constraining selection of natural analogues, describes initiatives of the US NRC, and describes the role of analogues in the licensing process.

  12. CO2 Removal using a Synthetic Analogue of Carbonic Anhydrase

    SciTech Connect

    Cordatos, Harry

    2010-09-14

    Project attempts to develop a synthetic analogue for carbonic anhydrase and incorporate it in a membrane for separation of CO2 from coal power plant flue gas. Conference poster presents result of first 9 months of project progress including concept, basic system architecture and membrane properties target, results of molecular modeling for analogue - CO2 interaction, and next steps of testing analogue resistance to flue gas contaminants.

  13. Isoelectronic analogues of PN: Remarkably stable multiply charged cations

    SciTech Connect

    Wong, Ming Wah; Radom, L. )

    1990-01-25

    The structures and stabilities of PN and its 27 isoelectronic analogues, CS, SiO, BCl, AlF, BeAr, MgNe, Sn{sup +}, PO{sup +}, CCl{sup +}, SiF{sup +}, BAr{sup +}, AlNe{sup +}, SO{sup 2+}, NCl{sup 2+}, PF{sup 2+}, CAr{sup 2+}, SiNe{sup 2+}, OCl{sup 3+}, SF{sup 3+}, NAr{sup 3+}, PNe{sup 3+}, FCl{sup 4+}, OAr{sup 4+}, SNe{sup 4+}, FAr{sup 5+}, ClNe{sup 5+}, and ArNe{sup 6+}, have been examined by ab initio molecular orbital theory. The CASSCF/6-311G(MC)(d) level was used to determine the ground-state potential energy curves and spectroscopic constants for the 28 diatomic systems. Equilibrium structures were also obtained with the 6-311G(MC)(d) basis set at the MP3 and ST4CCD levels, and dissociation energies were determined at the MP4/6-311 + G(MC)(2df) and MP4/6-311 + G(MC)(3d2f) levels. For the neutral and monocation analogues of PN, the calculated equilibrium geometries (at MP3/6-311G(MC)(d)) and dissociation energies (at MP4/6-311 + G(MC)(3d2f)) are in very good agreement with available experimental values. All the dication analogues of PN, namely, SO{sup 2+}, NCl{sup 2+}, PF{sup 2+}, CAr{sup 2+}, and SiNe{sup 2+}, are predicted to be experimentally observable species. Of these, the SO{sup 2+}, NCl{sup 2+}, and CAr{sup 2+} dications are calculated to be kinetically stable species, with large barriers associated with the exothermic charge-separation reactions, while the PF{sup 2+} and SiNe{sup 2+} dications are predicted not only to be kinetically stable but also to be thermodynamically stable species.

  14. Synthesis of a cyanopeptide-analogue with trypsin activating properties.

    PubMed

    Radau, G; Rauh, D

    2000-04-17

    An efficient synthesis of a peptidic analogue of cyanobacterial metabolites with proposed serine protease inhibitory activity has been developed. Surprisingly, one trypsin activating compound was obtained.

  15. Self-Powered Analogue Smart Skin.

    PubMed

    Shi, Mayue; Zhang, Jinxin; Chen, Haotian; Han, Mengdi; Shankaregowda, Smitha A; Su, Zongming; Meng, Bo; Cheng, Xiaoliang; Zhang, Haixia

    2016-04-26

    The progress of smart skin technology presents unprecedented opportunities for artificial intelligence. Resolution enhancement and energy conservation are critical to improve the perception and standby time of robots. Here, we present a self-powered analogue smart skin for detecting contact location and velocity of the object, based on a single-electrode contact electrification effect and planar electrostatic induction. Using an analogue localizing method, the resolution of this two-dimensional smart skin can be achieved at 1.9 mm with only four terminals, which notably decreases the terminal number of smart skins. The sensitivity of this smart skin is remarkable, which can even perceive the perturbation of a honey bee. Meanwhile, benefiting from the triboelectric mechanism, extra power supply is unnecessary for this smart skin. Therefore, it solves the problems of batteries and connecting wires for smart skins. With microstructured poly(dimethylsiloxane) films and silver nanowire electrodes, it can be covered on the skin with transparency, flexibility, and high sensitivity.

  16. Enzymatic synthesis of lipid II and analogues.

    PubMed

    Huang, Lin-Ya; Huang, Shih-Hsien; Chang, Ya-Chih; Cheng, Wei-Chieh; Cheng, Ting-Jen R; Wong, Chi-Huey

    2014-07-28

    The emergence of antibiotic resistance has prompted active research in the development of antibiotics with new modes of action. Among all essential bacterial proteins, transglycosylase polymerizes lipid II into peptidoglycan and is one of the most favorable targets because of its vital role in peptidoglycan synthesis. Described in this study is a practical enzymatic method for the synthesis of lipid II, coupled with cofactor regeneration, to give the product in a 50-70% yield. This development depends on two key steps: the overexpression of MraY for the synthesis of lipid I and the use of undecaprenol kinase for the preparation of polyprenol phosphates. This method was further applied to the synthesis of lipid II analogues. It was found that MraY and undecaprenol kinase can accept a wide range of lipids containing various lengths and configurations. The activity of lipid II analogues for bacterial transglycolase was also evaluated. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Long-term predictions using natural analogues

    SciTech Connect

    Ewing, R.C.

    1995-09-01

    One of the unique and scientifically most challenging aspects of nuclear waste isolation is the extrapolation of short-term laboratory data (hours to years) to the long time periods (10{sup 3}-10{sup 5} years) required by regulatory agencies for performance assessment. The direct validation of these extrapolations is not possible, but methods must be developed to demonstrate compliance with government regulations and to satisfy the lay public that there is a demonstrable and reasonable basis for accepting the long-term extrapolations. Natural systems (e.g., {open_quotes}natural analogues{close_quotes}) provide perhaps the only means of partial {open_quotes}validation,{close_quotes} as well as data that may be used directly in the models that are used in the extrapolation. Natural systems provide data on very large spatial (nm to km) and temporal (10{sup 3}-10{sup 8} years) scales and in highly complex terranes in which unknown synergisms may affect radionuclide migration. This paper reviews the application (and most importantly, the limitations) of data from natural analogue systems to the {open_quotes}validation{close_quotes} of performance assessments.

  18. Analogue modulation of back-propagating action potentials enables dendritic hybrid signalling

    PubMed Central

    Brunner, János; Szabadics, János

    2016-01-01

    We report that back-propagating action potentials (bAPs) are not simply digital feedback signals in dendrites but also carry analogue information about the overall state of neurons. Analogue information about the somatic membrane potential within a physiological range (from −78 to −64 mV) is retained by bAPs of dentate gyrus granule cells as different repolarization speeds in proximal dendrites and as different peak amplitudes in distal regions. These location-dependent waveform changes are reflected by local calcium influx, leading to proximal enhancement and distal attenuation during somatic hyperpolarization. The functional link between these retention and readout mechanisms of the analogue content of bAPs critically depends on high-voltage-activated, inactivating calcium channels. The hybrid bAP and calcium mechanisms report the phase of physiological somatic voltage fluctuations and modulate long-term synaptic plasticity in distal dendrites. Thus, bAPs are hybrid signals that relay somatic analogue information, which is detected by the dendrites in a location-dependent manner. PMID:27703164

  19. Analogue modulation of back-propagating action potentials enables dendritic hybrid signalling.

    PubMed

    Brunner, János; Szabadics, János

    2016-10-05

    We report that back-propagating action potentials (bAPs) are not simply digital feedback signals in dendrites but also carry analogue information about the overall state of neurons. Analogue information about the somatic membrane potential within a physiological range (from -78 to -64 mV) is retained by bAPs of dentate gyrus granule cells as different repolarization speeds in proximal dendrites and as different peak amplitudes in distal regions. These location-dependent waveform changes are reflected by local calcium influx, leading to proximal enhancement and distal attenuation during somatic hyperpolarization. The functional link between these retention and readout mechanisms of the analogue content of bAPs critically depends on high-voltage-activated, inactivating calcium channels. The hybrid bAP and calcium mechanisms report the phase of physiological somatic voltage fluctuations and modulate long-term synaptic plasticity in distal dendrites. Thus, bAPs are hybrid signals that relay somatic analogue information, which is detected by the dendrites in a location-dependent manner.

  20. Erbium: YAG laser (2,940 nm) treatment stimulates hair growth through upregulating Wnt 10b and β-catenin expression in C57BL/6 mice.

    PubMed

    Ke, Jin; Guan, Huiwen; Li, Shan; Xu, Li; Zhang, Li; Yan, Yuehua

    2015-01-01

    To evaluate the role of 2,940 nm erbium: YAG laser in hair growth in C57BL/6 mice. Anagen was experimentally induced by depilation. Healthy C57BL/6 mice (n=22) were randomly divided into four groups, with treatment of laser or minoxidil, or with combined laser and minoxidil treatments. The skin color of each mouse was observed each day. The time from telogen (pink skin color) to anagen (black coloration) phase and from anagen (black coloration) to catagen (all hairs grew out of the depilated skin) have been recorded. Hematoxylin and eosin (H&E) assay was done at fifteen days after the first treatment for each group to observe hair follicles and hair cycle score. Western blot analysis was utilized to detect the expression levels of Wnt 10-b and β-catenin. Black pigmentation started significantly earlier both in the laser and combination group than in the control group. Moreover, the time from anagen to catagen in the laser, minoxidil and combination groups were all significantly shorter from the control group. Histopathology with H&E staining showed an obvious increase in the number of hair follicles in the anagen phase caused by the treatment of 2,940 nm erbium: YAG laser and minoxidil. Similarly, the percentage of hair follicles in anagen VI accounted for 19.5%, 37.5%, 41.5% and 44% in control, laser, minoxidil, and combination group, respectively. Western blot analysis showed that both the levels of Wnt 10b and β-catenin were significantly increased by the treatment of 2,940 nm erbium: YAG laser. Our findings showed that 2,940-nm Er: YAG laser could promote hair growth by inducing hair cycle transition from telogen to anagen phases in C57BL/6 mice through up regulating Wnt 10b and β-catenin. These results suggest that 2,940-nm Er: YAG laser may be a potential therapy for hair loss.

  1. Altered Expression of Raet1e, a Major Histocompatibility Complex Class 1–Like Molecule, Underlies the Atherosclerosis Modifier Locus Ath11 10b

    PubMed Central

    Rodríguez, José M.; Wolfrum, Susanne; Robblee, Megan; Chen, Kwan Y.; Gilbert, Zachary N.; Choi, Jae-Hoon; Teupser, Daniel; Breslow, Jan L.

    2014-01-01

    Rationale Quantitative trait locus mapping of an intercross between C57.Apoe−/− and FVB.Apoe−/− mice revealed an atherosclerosis locus controlling aortic root lesion area on proximal chromosome 10, Ath11. In a previous work, subcongenic analysis showed Ath11 to be complex with proximal (10a) and distal (10b) regions. Objective To identify the causative genetic variation underlying the atherosclerosis modifier locus Ath11 10b. Methods and Results We now report subcongenic J, which narrows the 10b region to 5 genes, Myb, Hbs1L, Aldh8a1, Sgk1, and Raet1e. Sequence analysis of these genes revealed no amino acid coding differences between the parental strains. However, comparing aortic expression of these genes between F1.Apoe−/− Chr10SubJ(B/F) and F1.Apoe−/− Chr10SubJ(F/F) uncovered a consistent difference only for Raet1e, with decreased, virtually background, expression associated with increased atherosclerosis in the latter. The key role of Raet1e was confirmed by showing that transgene-induced aortic overexpression of Raet1e in F1.Apoe−/− Chr10SubJ(F/F) mice decreased atherosclerosis. Promoter reporter constructs comparing C57 and FVB sequences identified an FVB mutation in the core of the major aortic transcription start site abrogating activity. Conclusions This nonbiased approach has revealed Raet1e, a major histocompatibility complex class 1–like molecule expressed in lesional aortic endothelial cells and macrophage-rich regions, as a novel atherosclerosis gene and represents one of the few successes of the quantitative trait locus strategy in complex diseases. PMID:23948654

  2. An analogue of Weyl’s law for quantized irreducible generalized flag manifolds

    SciTech Connect

    Matassa, Marco E-mail: mmatassa@math.uio.no

    2015-09-15

    We prove an analogue of Weyl’s law for quantized irreducible generalized flag manifolds. This is formulated in terms of a zeta function which, similarly to the classical setting, satisfies the following two properties: as a functional on the quantized algebra it is proportional to the Haar state and its first singularity coincides with the classical dimension. The relevant formulas are given for the more general case of compact quantum groups.

  3. KELT-10b: the first transiting exoplanet from the KELT-South survey - a hot sub-Jupiter transiting a V = 10.7 early G-star

    NASA Astrophysics Data System (ADS)

    Kuhn, Rudolf B.; Rodriguez, Joseph E.; Collins, Karen A.; Lund, Michael B.; Siverd, Robert J.; Colón, Knicole D.; Pepper, Joshua; Stassun, Keivan G.; Cargile, Phillip A.; James, David J.; Penev, Kaloyan; Zhou, George; Bayliss, Daniel; Tan, T. G.; Curtis, Ivan A.; Udry, Stephane; Segransan, Damien; Mawet, Dimitri; Dhital, Saurav; Soutter, Jack; Hart, Rhodes; Carter, Brad; Gaudi, B. Scott; Myers, Gordon; Beatty, Thomas G.; Eastman, Jason D.; Reichart, Daniel E.; Haislip, Joshua B.; Kielkopf, John; Bieryla, Allyson; Latham, David W.; Jensen, Eric L. N.; Oberst, Thomas E.; Stevens, Daniel J.

    2016-07-01

    We report the discovery of KELT-10b, the first transiting exoplanet discovered using the KELT-South telescope. KELT-10b is a highly inflated sub-Jupiter mass planet transiting a relatively bright V = 10.7 star (TYC 8378-64-1), with Teff = 5948 ± 74 K, log g = 4.319_{-0.030}^{+0.020} and [Fe/H] = 0.09_{-0.10}^{+0.11}, an inferred mass M* = 1.112_{-0.061}^{+0.055} M⊙ and radius R* = 1.209_{-0.035}^{+0.047} R⊙. The planet has a radius Rp = 1.399_{-0.049}^{+0.069} RJ and mass Mp = 0.679_{-0.038}^{+0.039} MJ. The planet has an eccentricity consistent with zero and a semimajor axis a = 0.052 50_{-0.000 97}^{+0.000 86} au. The best-fitting linear ephemeris is T0 = 2457 066.720 45 ± 0.000 27 BJDTDB and P = 4.166 2739 ± 0.000 0063 d. This planet joins a group of highly inflated transiting exoplanets with a larger radius and smaller mass than that of Jupiter. The planet, which boasts deep transits of 1.4 per cent, has a relatively high equilibrium temperature of Teq = 1377_{-23}^{+28} K, assuming zero albedo and perfect heat redistribution. KELT-10b receives an estimated insolation of 0.817_{-0.054}^{+0.068} × 109 erg s-1 cm-2, which places it far above the insolation threshold above which hot Jupiters exhibit increasing amounts of radius inflation. Evolutionary analysis of the host star suggests that KELT-10b may not survive beyond the current subgiant phase, depending on the rate of in-spiral of the planet over the next few Gyr. The planet transits a relatively bright star and exhibits the third largest transit depth of all transiting exoplanets with V < 11 in the Southern hemisphere, making it a promising candidate for future atmospheric characterization studies.

  4. Analysis of new high-precision transit light curves of WASP-10 b: starspot occultations, small planetary radius, and high metallicity

    NASA Astrophysics Data System (ADS)

    Maciejewski, G.; Raetz, St.; Nettelmann, N.; Seeliger, M.; Adam, C.; Nowak, G.; Neuhäuser, R.

    2011-11-01

    Context. The WASP-10 planetary system is intriguing because different values of radius have been reported for its transiting exoplanet. The host star exhibits activity in terms of photometric variability, which is caused by the rotational modulation of the spots. Moreover, a periodic modulation has been discovered in transit timing of WASP-10 b, which could be a sign of an additional body perturbing the orbital motion of the transiting planet. Aims: We attempt to refine the physical parameters of the system, in particular the planetary radius, which is crucial for studying the internal structure of the transiting planet. We also determine new mid-transit times to confirm or refute observed anomalies in transit timing. Methods: We acquired high-precision light curves for four transits of WASP-10 b in 2010. Assuming various limb-darkening laws, we generated best-fit models and redetermined parameters of the system. The prayer-bead method and Monte Carlo simulations were used to derive error estimates. Results: Three transit light curves exhibit signatures of the occultations of dark spots by the planet during its passage across the stellar disk. The influence of stellar activity on transit depth is taken into account while determining system parameters. The radius of WASP-10 b is found to be no greater than 1.03+0.07-0.03 Jupiter radii, a value significantly smaller than most previous studies indicate. We calculate interior structure models of the planet, assuming a two-layer structure with one homogeneous envelope atop a rock core. The high value of the WASP-10 b's mean density allows one to consider the planet's internal structure including 270 to 450 Earth masses of heavy elements. Our new mid-transit times confirm that transit timing cannot be explained by a constant period if all literature data points are considered. They are consistent with the ephemeris assuming a periodic variation of transit timing. We show that possible starspot features affecting the

  5. Expression and hormone regulation of Wnt2, 3, 4, 5a, 7a, 7b and 10b in normal human endometrium and endometrial carcinoma.

    PubMed Central

    Bui, T. D.; Zhang, L.; Rees, M. C.; Bicknell, R.; Harris, A. L.

    1997-01-01

    Wnt genes are transforming to mouse breast epithelium and are hormonally regulated in vivo. To assess their role in another endocrine-responsive human cancer, the expression of seven Wnt genes (Wnt 2, 3, 4, 5a, 7a, 7b and 10b) in normal human endometrium and endometrial cells, and endometrial carcinoma tissues and cell lines was investigated by ribonuclease protection analysis. Wnt2, 3, 4 and 5a mRNAs but not Wnt7a, 7b or 10b mRNAs were expressed in primary culture of normal endometrial epithelial (NEE) and stromal (NES) cells. In contrast, in four endometrial carcinoma cell lines (RL95-2, HEC-1-A, AN3 CA and Ishikawa), Wnt2 and Wnt3 mRNAs were absent. Wnt4 was expressed in only one out of four cell lines (RL95-2), and Wnt5a was much lower. Wnt7a and Wnt7b mRNAs were expressed in three out of four cell lines (RL95-2, HEC-1-A and Ishikawa). Wnt10b mRNA was expressed in RL95-2 and AN3 CA. In fresh tissues, all Wnt genes apart from Wnt10b were expressed in normal endometrium and endometrial carcinoma. Similar to the cell lines, the level of Wnt4 mRNA expression was significantly higher in the normal endometrium than endometrial carcinoma. Wnt2, 3 and 5a mRNAs were also lower in endometrial carcinoma compared with normal endometrium. There was no difference in the level of Wnt2, 3, 4 and 5a mRNA expression between proliferative phase and secretory phase of the menstrual cycle, or between either menstrual phase and the first trimester of pregnancy. In vitro, progesterone and/or 17beta-oestradiol had no effect on Wnt2, 3, 4, 5a and 7b mRNA expression in NES and all endometrial carcinoma cell lines. The data indicate that all Wnt genes were expressed in vitro, six out of seven Wnt genes (Wnt 2, 3, 4, 5a, 7a and 7b) were expressed endogenously in the human endometrium, their mRNA expression was hormonally independent and Wnt4 gene down-regulation as well as down-regulation of Wnt 2, 3 and 5a may be associated with endometrial carcinoma. Images Figure 1 Figure 3 Figure 4

  6. FBPA PET in boron neutron capture therapy for cancer: prediction of (10)B concentration in the tumor and normal tissue in a rat xenograft model.

    PubMed

    Hanaoka, Kohei; Watabe, Tadashi; Naka, Sadahiro; Kanai, Yasukazu; Ikeda, Hayato; Horitsugi, Genki; Kato, Hiroki; Isohashi, Kayako; Shimosegawa, Eku; Hatazawa, Jun

    2014-12-01

    Boron neutron capture therapy (BNCT) is a molecular radiation treatment based on the (10)B (n, α) (7)Li nuclear reaction in cancer cells, in which delivery of (10)B by 4-borono-phenylalanine conjugated with fructose (BPA-fr) to the cancer cells is of critical importance. The PET tracer 4-borono-2-(18) F-fluoro-phenylalanine (FBPA) has been used to predict the accumulation of BPA-fr before BNCT. However, because of the difference in chemical structure between BPA-fr and FBPA and the difference in the dose administered between BPA-fr (therapeutic dose) and FBPA (tracer dose), the predictive value of FBPA PET for BPA-fr accumulation in the tumor and normal tissues is not yet clearly proven. We conducted this study to validate FBPA PET as a useful test to predict the accumulation of BPA-fr in the tumor and normal tissues before BNCT. RGC-6 rat glioma cells (1.9 × 10(7)) were implanted subcutaneously in seven male F344 rats. On day 20 after the tumor implantation, dynamic PET scan was performed on four rats after injection of FBPA for 1 h. Whole-body PET/CT was performed 1 h after intravenous injection of the FBPA solution (30.5 ± 0.7 MBq, 1.69 ± 1.21 mg/kg). PET accumulation of FBPA in the tumor tissue and various normal tissues was estimated as a percentage of the injected dose per gram (%ID/g). One hour after the PET/CT scan, BPA-fructose (167.32 ± 18.65 mg/kg) was injected intravenously, and the rats were dissected 1 h after the BPA-fr injection. The absolute concentration of (10)B in the autopsied tissues and blood was measured by inductively coupled plasma optical emission spectrometry (ICP-OES). The highest absolute concentration of (10)B determined by ICP-OES was found in the kidney (4.34 ± 0.84 %ID/g), followed by the pancreas (2.73 ± 0.63 %ID/g), and the tumor (1.44 ± 0.44 %ID/g). A significant positive correlation was found between the accumulation levels of BPA-fr and FBPA (r = 0.91, p < 0.05). FBPA PET can

  7. Space Analogue Environments: Are the Populations Comparable?

    NASA Astrophysics Data System (ADS)

    Sandal, G. M.

    Background: Much of our present understanding about psychology in space is based on studies of groups operating in so-called analogue environments where personnel are exposed to many of the same stressors as those experienced by astronauts in space. One possible problem with extrapolating results is that personnel operating in various hazardous and confined environments might differ in characteristics influencing coping, interaction, and performance. The object of this study was to compare the psychological similarity of these populations in order to get a better understanding of whether this extrapolation is justifiable. The samples investigated include polar crossings (N= 22), personnel on Antarctic research stations (N= 183), several military occupations (N= 187), and participants in space simulation studies (N=20). Methods: Personnel in each of these environments were assessed using the Personality Characteristic Inventory (PCI) and Utrecht Coping List (UCL). The PCI is a multidimensional trait assessment battery that measures various aspects of achievement orientation and social competence. The UCL is a questionnaire designed to assess habitual coping strategies when encountering stressful or demanding situations. Results: Only minor differences in use of habitual coping strategies were evident across the different samples. In relation to personality scores, the military subjects and participants in space simulation studies indicated higher competitiveness and negative instrumentality compared to both the personnel on Antarctic research stations and participants in polar expedition. Among the personnel on Antarctic research stations, significant gender differences were found with women scoring lower on competitiveness, negative instrumentality and impatience/irritability. Compared to the other samples, the participants in polar expeditions were found to be more homogeneous in personality and no significant gender differences were evident on the traits that

  8. A nonlinear dynamic analogue model of substorms

    NASA Astrophysics Data System (ADS)

    Klimas, A. J.; Baker, D. N.; Roberts, D. A.; Fairfield, D. H.; Büchner, J.

    Linear prediction filter studies have shown that the magnetospheric response to energy transfer from the solar wind contains both directly driven and unloading components. These studies have also shown that the magnetospheric response is significantly nonlinear and, thus, the linear prediction filtering technique and other correlative techniques which assume a linear magnetospheric response cannot give a complete deacription of that response. Here, the solar wind-magnetosphere interaction is discussed within the framework of deterministic nonlinear dynamics. An earlier dripping faucet mechanical analogue to the magnetosphere is first reviewed and then the plasma physical counterpart to the mechanical model is constructed. A Faraday loop in the magnetotail is considered and the relationship of electric potentials on the loop to changes in the magnetic flux threading the loop is developed. This approach leads to a model of geomagnetic activity which is similar to the earlier mechanical model but described in terms of the geometry and plasma contents of the magnetotail. This Faraday loop response model contains analogues to both the directly driven and the storage-release magnetospheric responses and it includes, in a fundamental way, the inherent nonlinearity of the solar wind-magnetosphere system. It can be chancterized as a nonlinear, damped harmonic oscillator that is driven by the loading-unloading substorm cycle. The model is able to explain many of the features of the linear prediction filter results. In particular, at low geomagnetic activity levels the model exbibits the "regular dripping" response which provides an explanation for the unloading component at 1 hour lag in the linear prediction filters. Further, the model suggests that the disappearance of the unloading component in the linear prediction filters at high geomagnetic activity levels is due to a chaotic transition beyond which the loading-unloading mechanism becomes aperiodic. The model predicts

  9. Heavy Precipitation in Regional Climate Models: Does it Pay to Play Analogue?

    NASA Astrophysics Data System (ADS)

    Gao, X.; Schlosser, C. A.

    2016-12-01

    Regional models in general simulate the extreme precipitation statistics better than general circulation models (GCMs) as a result of more realistic representation of topography and better ability to resolve mesoscale processes, land surface-atmosphere interaction, and dynamics and vertical motion. Through an analogue method that employs the resolved large-scale atmospheric conditions to detect the occurrence of heavy precipitation event, multi-GCM median of late 20th century heavy precipitation frequency is more consistent with observation and inter-model variance is smaller as compared to the corresponding results using model-simulated precipitation. In this study, we explore whether the analogue method, when used with the higher-resolution regional climate model simulations (yet driven by coarser weather/climate information at the larger scale) from the North American Regional Climate Change Assessment Program (NARCCAP), can result in further improvement in detecting heavy precipitation events. Combinations of different atmospheric variables for circulation features (geopotential height and wind shear), moisture plumes (surface specific humidity and column precipitable water), and convective instability (convective available potential energy, CAPE) are examined to construct the analogue schemes for the summer (JJA) of the Midwestern United States (MWST), which is among the weaker regions in model performance for simulated summer U.S. precipitation. We employ gridded precipitation-gauge observations and global atmospheric reanalysis to calibrate and validate the analogue method to be implemented at the spatial resolution comparable to that of NARCCAP models (approximately 50 km). We also explore the effect of lateral boundary conditions on the performance of analogue schemes by comparing the integrations driven by reanalysis to those driven by global climate models. Projected mid-century future changes in summer heavy precipitation frequency are further assessed

  10. Analogue Divider by Averaging a Triangular Wave

    NASA Astrophysics Data System (ADS)

    Selvam, Krishnagiri Chinnathambi

    2017-03-01

    A new analogue divider circuit by averaging a triangular wave using operational amplifiers is explained in this paper. The triangle wave averaging analog divider using operational amplifiers is explained here. The reference triangular waveform is shifted from zero voltage level up towards positive power supply voltage level. Its positive portion is obtained by a positive rectifier and its average value is obtained by a low pass filter. The same triangular waveform is shifted from zero voltage level to down towards negative power supply voltage level. Its negative portion is obtained by a negative rectifier and its average value is obtained by another low pass filter. Both the averaged voltages are combined in a summing amplifier and the summed voltage is given to an op-amp as negative input. This op-amp is configured to work in a negative closed environment. The op-amp output is the divider output.

  11. Derivatisable Cyanobactin Analogues: A Semisynthetic Approach

    PubMed Central

    Oueis, Emilia; Adamson, Catherine; Mann, Greg; Ludewig, Hannes; Redpath, Philip; Migaud, Marie

    2015-01-01

    Abstract Many natural cyclic peptides have potent and potentially useful biological activities. Their use as therapeutic starting points is often limited by the quantities available, the lack of known biological targets and the practical limits on diversification to fine‐tune their properties. We report the use of enzymes from the cyanobactin family to heterocyclise and macrocyclise chemically synthesised substrates so as to allow larger‐scale syntheses and better control over derivatisation. We have made cyclic peptides containing orthogonal reactive groups, azide or dehydroalanine, that allow chemical diversification, including the use of fluorescent labels that can help in target identification. We show that the enzymes are compatible and efficient with such unnatural substrates. The combination of chemical synthesis and enzymatic transformation could help renew interest in investigating natural cyclic peptides with biological activity, as well as their unnatural analogues, as therapeutics. PMID:26507241

  12. A simple analogue of lung mechanics.

    PubMed

    Sherman, T F

    1993-12-01

    A model of the chest and lungs can be easily constructed from a bottle of water, a balloon, a syringe, a rubber stopper, glass and rubber tubing, and clamps. The model is a more exact analogue of the body than the classic apparatus of Hering in two respects: 1) the pleurae and intrapleural fluid are represented by water rather than air, and 2) the subatmospheric "intrapleural" pressure is created by the elasticity of the "lung" (balloon) rather than by a vacuum pump. With this model, students can readily see how the lung is inflated and deflated by movements of the "diaphragm and chest" (syringe plunger) and how intrapleural pressures change as this is accomplished.

  13. Naturalness in an emergent analogue spacetime.

    PubMed

    Liberati, Stefano; Visser, Matt; Weinfurtner, Silke

    2006-04-21

    Effective field theories (EFTs) have been widely used as a framework in order to place constraints on the Planck suppressed Lorentz violations predicted by various models of quantum gravity. There are, however, technical problems in the EFT framework when it comes to ensuring that small Lorentz violations remain small--this is the essence of the "naturalness" problem. Herein we present an "emergent" spacetime model, based on the "analogue gravity" program, by investigating a specific condensed-matter system. Specifically, we consider the class of two-component BECs subject to laser-induced transitions between the components, and we show that this model is an example for Lorentz invariance violation due to ultraviolet physics. Furthermore, our model explicitly avoids the naturalness problem, and makes specific suggestions regarding how to construct a physically reasonable quantum gravity phenomenology.

  14. Analogue Divider by Averaging a Triangular Wave

    NASA Astrophysics Data System (ADS)

    Selvam, Krishnagiri Chinnathambi

    2017-08-01

    A new analogue divider circuit by averaging a triangular wave using operational amplifiers is explained in this paper. The triangle wave averaging analog divider using operational amplifiers is explained here. The reference triangular waveform is shifted from zero voltage level up towards positive power supply voltage level. Its positive portion is obtained by a positive rectifier and its average value is obtained by a low pass filter. The same triangular waveform is shifted from zero voltage level to down towards negative power supply voltage level. Its negative portion is obtained by a negative rectifier and its average value is obtained by another low pass filter. Both the averaged voltages are combined in a summing amplifier and the summed voltage is given to an op-amp as negative input. This op-amp is configured to work in a negative closed environment. The op-amp output is the divider output.

  15. A hypnotic analogue of clinical confabulation.

    PubMed

    Cox, Rochelle E; Barnier, Amanda J

    2015-01-01

    Confabulation-fabricated or distorted memories about oneself-occurs in many disorders, but there is no reliable technique for investigating it in the laboratory. The authors used hypnosis to model clinical confabulation by giving subjects a suggestion for either (a) amnesia for everything that had happened since they started university, (b) amnesia for university plus an instruction to fill in memory gaps, or (c) confusion about the temporal order of university events. They then indexed different types of memory on a confabulation battery. The amnesia suggestion produced the most confabulation, especially for personal semantic information. Notably, subjects confabulated by making temporal confusions. The authors discuss the theoretical implications of this first attempt to model clinical confabulation and the potential utility of such analogues.

  16. Jupiter analogues and planets of active stars

    NASA Astrophysics Data System (ADS)

    Kürster, M.; Zechmeister, M.; Endl, M.; Lo Curto, G.; Hartman, H.; Nilsson, H.; Henning, T.; Hatzes, A. P.; Cochran, W. D.

    2013-04-01

    Combined results are now available from a 15 year long search for Jupiter analogues around solar-type stars using the ESO CAT + CES, ESO 3.6 m + CES, and ESO 3.6 m + HARPS instruments. They comprise planet (co-)discoveries (ι Hor and HR 506) and confirmations (three planets in HR 3259) as well as non-confirmations of planets (HR 4523 and ɛ Eri) announced elsewhere. A long-term trend in ɛ Ind found by our survey is probably attributable to a Jovian planet with a period >30 yr, but we cannot fully exclude stellar activity effects as the cause. A 3.8 year periodic variation in HR 8323 can be attributed to stellar activity.

  17. Terrestrial Analogues for Lunar Impact Melt Flows

    NASA Technical Reports Server (NTRS)

    Neish, C. D.; Hamilton, C. W.; Hughes, S. S.; Nawotniak, S. Kobs; Garry, W. B.; Skok, J. R.; Elphic, R. C.; Schaefer, E.; Carter, L. M.; Bandfield, J. L.; hide

    2016-01-01

    Lunar impact melt deposits have unique physical properties. They have among the highest observed radar returns at S-Band (12.6 cm wavelength), implying that they are rough at the decimeter scale. However, they are also observed in high-resolution optical imagery to be quite smooth at the meter scale. These characteristics distinguish them from well-studied terrestrial analogues, such as Hawaiian pahoehoe and ?a ?a lava flows. The morphology of impact melt deposits can be related to their emplacement conditions, so understanding the origin of these unique surface properties will help to inform us as to the circumstances under which they were formed. In this work, we seek to find a terrestrial analogue for well-preserved lunar impact melt flows by examining fresh lava flows on Earth. We compare the radar return and high-resolution topographic variations of impact melt flows to terrestrial lava flows with a range of surface textures. The lava flows examined in this work range from smooth Hawaiian pahoehoe to transitional basaltic flows at Craters of the Moon (COTM) National Monument and Preserve in Idaho to rubbly and spiny pahoehoe-like flows at the recent eruption at Holuhraun in Iceland. The physical properties of lunar impact melt flows appear to differ from those of all the terrestrial lava flows studied in this work. This may be due to (a) differences in post-emplacement modification processes or (b) fundamental differences in the surface texture of the melt flows due to the melts' unique emplacement and/or cooling environment. Information about the surface properties of lunar impact melt deposits will be critical for future landed missions that wish to sample these materials.

  18. Terrestrial analogues for lunar impact melt flows

    NASA Astrophysics Data System (ADS)

    Neish, C. D.; Hamilton, C. W.; Hughes, S. S.; Nawotniak, S. Kobs; Garry, W. B.; Skok, J. R.; Elphic, R. C.; Schaefer, E.; Carter, L. M.; Bandfield, J. L.; Osinski, G. R.; Lim, D.; Heldmann, J. L.

    2017-01-01

    Lunar impact melt deposits have unique physical properties. They have among the highest observed radar returns at S-Band (12.6 cm wavelength), implying that they are rough at the decimeter scale. However, they are also observed in high-resolution optical imagery to be quite smooth at the meter scale. These characteristics distinguish them from well-studied terrestrial analogues, such as Hawaiian pāhoehoe and ´a´ā lava flows. The morphology of impact melt deposits can be related to their emplacement conditions, so understanding the origin of these unique surface properties will help to inform us as to the circumstances under which they were formed. In this work, we seek to find a terrestrial analogue for well-preserved lunar impact melt flows by examining fresh lava flows on Earth. We compare the radar return and high-resolution topographic variations of impact melt flows to terrestrial lava flows with a range of surface textures. The lava flows examined in this work range from smooth Hawaiian pāhoehoe to transitional basaltic flows at Craters of the Moon (COTM) National Monument and Preserve in Idaho to rubbly and spiny pāhoehoe-like flows at the recent eruption at Holuhraun in Iceland. The physical properties of lunar impact melt flows appear to differ from those of all the terrestrial lava flows studied in this work. This may be due to (a) differences in post-emplacement modification processes or (b) fundamental differences in the surface texture of the melt flows due to the melts' unique emplacement and/or cooling environment. Information about the surface properties of lunar impact melt deposits will be critical for future landed missions that wish to sample these materials.

  19. Natural analogues of nuclear waste glass corrosion.

    SciTech Connect

    Abrajano, T.A. Jr.; Ebert, W.L.; Luo, J.S.

    1999-01-06

    This report reviews and summarizes studies performed to characterize the products and processes involved in the corrosion of natural glasses. Studies are also reviewed and evaluated on how well the corrosion of natural glasses in natural environments serves as an analogue for the corrosion of high-level radioactive waste glasses in an engineered geologic disposal system. A wide range of natural and experimental corrosion studies has been performed on three major groups of natural glasses: tektite, obsidian, and basalt. Studies of the corrosion of natural glass attempt to characterize both the nature of alteration products and the reaction kinetics. Information available on natural glass was then compared to corresponding information on the corrosion of nuclear waste glasses, specifically to resolve two key questions: (1) whether one or more natural glasses behave similarly to nuclear waste glasses in laboratory tests, and (2) how these similarities can be used to support projections of the long-term corrosion of nuclear waste glasses. The corrosion behavior of basaltic glasses was most similar to that of nuclear waste glasses, but the corrosion of tektite and obsidian glasses involves certain processes that also occur during the corrosion of nuclear waste glasses. The reactions and processes that control basalt glass dissolution are similar to those that are important in nuclear waste glass dissolution. The key reaction of the overall corrosion mechanism is network hydrolysis, which eventually breaks down the glass network structure that remains after the initial ion-exchange and diffusion processes. This review also highlights some unresolved issues related to the application of an analogue approach to predicting long-term behavior of nuclear waste glass corrosion, such as discrepancies between experimental and field-based estimates of kinetic parameters for basaltic glasses.

  20. Terrestrial Analogues for Lunar Impact Melt Flows

    NASA Technical Reports Server (NTRS)

    Neish, C. D.; Hamilton, C. W.; Hughes, S. S.; Nawotniak, S. Kobs; Garry, W. B.; Skok, J. R.; Elphic, R. C.; Schaefer, E.; Carter, L. M.; Bandfield, J. L.; Osinski, G. R.; Lim, D.; Heldmann, J. L.

    2016-01-01

    Lunar impact melt deposits have unique physical properties. They have among the highest observed radar returns at S-Band (12.6 cm wavelength), implying that they are rough at the decimeter scale. However, they are also observed in high-resolution optical imagery to be quite smooth at the meter scale. These characteristics distinguish them from well-studied terrestrial analogues, such as Hawaiian pahoehoe and ?a ?a lava flows. The morphology of impact melt deposits can be related to their emplacement conditions, so understanding the origin of these unique surface properties will help to inform us as to the circumstances under which they were formed. In this work, we seek to find a terrestrial analogue for well-preserved lunar impact melt flows by examining fresh lava flows on Earth. We compare the radar return and high-resolution topographic variations of impact melt flows to terrestrial lava flows with a range of surface textures. The lava flows examined in this work range from smooth Hawaiian pahoehoe to transitional basaltic flows at Craters of the Moon (COTM) National Monument and Preserve in Idaho to rubbly and spiny pahoehoe-like flows at the recent eruption at Holuhraun in Iceland. The physical properties of lunar impact melt flows appear to differ from those of all the terrestrial lava flows studied in this work. This may be due to (a) differences in post-emplacement modification processes or (b) fundamental differences in the surface texture of the melt flows due to the melts' unique emplacement and/or cooling environment. Information about the surface properties of lunar impact melt deposits will be critical for future landed missions that wish to sample these materials.

  1. Induction of abortion by different prostaglandin analogues.

    PubMed

    Bygdeman, M; Wiqvist, N

    1974-01-01

    The clinical advantages and disadvantages of intra amniotic administration of PGF2alpha in comparison with hypertonic saline has recently been summarized by the Prostaglandin Task Force within the World Health Organization Expanded program. The investigation comprised approximately 1,500 patients treated randomly with the two methods. The main advantage of the PG method was a significantly shorter induction-abortion interval and a lesser risk for serious complications and the significant disadvantage a slight increase in the mean frequency of minor complaints in terms of diarrhoea and vomiting. With PGF2alpha it seems difficult to obtain a "one shot" method to terminate second trimester pregnancy even with the intra-amniotic route of administration. The 15-methyl analogues seem more promising in this respect. The uterine response following administration of this compound is characterized by a more gradual initiation of uterine stimulation and a sustained effect, One intraamniotic injection of 2.5 mg 15-methyl-PGF2alpha induced abortion in nearly 100% of the cases and the incidence of side effects was low. Promising results with this compound have also been obtained following a single extra-amniotic instillation or by repeated intramuscular injections. Vaginal administration of 15-methyl PGF2alpha or its methyl ester can also be used for termination of pregnancy. Recently orally active PG analogues have become available for clinical testing. One of these compounds, 16,16-dimethyl-PGE2 may in some cases stimulate uterine contractility sufficiently to induce a second trimester abortion following repeated oral administration.

  2. Tren-based analogues of bacillibactin: structure and stability.

    PubMed

    Dertz, Emily A; Xu, Jide; Raymond, Kenneth N

    2006-07-10

    Synthetic analogues were designed to highlight the effect of the glycine moiety of bacillibactin on the overall stability of the ferric complex as compared to synthetic analogues of enterobactin. Insertion of a variety of amino acids to catecholamide analogues based on a Tren (tris(2-aminoethyl)amine) backbone increased the overall acidity of the ligands, causing an enhancement of the stability of the resulting ferric complex as compared to TRENCAM. Solution thermodynamic behavior of these siderophores and their synthetic analogues was investigated through potentiometric and spectrophotometric titrations. X-ray crystallography, circular dichroism, and molecular modeling were used to determine the chirality and geometry of the ferric complexes of bacillibactin and its analogues. In contrast to the Tren scaffold, addition of a glycine to the catechol chelating arms causes an inversion of the trilactone backbone, resulting in opposite chiralities of the two siderophores and a destabilization of the ferric complex of bacillibactin compared to ferric enterobactin.

  3. New results on P -odd asymmetry of γ -quanta emission in 10B(n, α)7Li* rightarrow γ + 7Li(g.s.) nuclear reaction

    NASA Astrophysics Data System (ADS)

    Vesna, V. A.; Gledenov, Yu. M.; Nesvizhevsky, V. V.; Sedyshev, P. V.; Shulgina, E. V.

    2011-03-01

    A series of ultra-sensitive experiments has been carried out in 2001-2009 at the ILL measuring P -odd asymmetry in γ -quanta emission in the nuclear reaction 10B ( n, α) 7Li* rightarrow γ + 7Li(g.s.) with polarized cold neutrons. The resulting value of the asymmetry coefficient is ensuremath α_{P-odd}= +(0.0 ± 2.6_{stat} ± 1.1_{syst}) × 10^{-8} . These experiments profited from high-intensity PF1B neutron facility and a new version of the integral measuring method: for decreasing experimental uncertainties, the frequency of neutron spin-flip was higher than a typical reactor power noise frequency. Using the new value, we constrain the weak neutral current constant in the cluster model framework to ensuremath f_{π}^{^{10}B} ≤ 0.6 × 10^{-7} (at 90% c.l.). This constraint agrees with that following from the nuclear reaction 6Li ( n, α) 3H : ensuremath f_{π}^{6Li} ≤ 1.1 × 10^{-7} (at 90% c.l.). However, they both contradict the "best" value in the quark model by Desplanques, Donoughe, and Holstein ensuremath f_{π}^{DDH}=4.6\\cdot 10^{-7} . We invite experts in the field to contribute to the theoretical analysis of the problem.

  4. THE ORBITAL PHASES AND SECONDARY TRANSITS OF KEPLER-10b. A PHYSICAL INTERPRETATION BASED ON THE LAVA-OCEAN PLANET MODEL

    SciTech Connect

    Rouan, D.; Deeg, H. J.; Demangeon, O.; Samuel, B.; Cavarroc, C.; Leger, A.; Fegley, B.

    2011-11-10

    The Kepler mission has made an important observation: the first detection of photons from a terrestrial planet by observing its phase curve (Kepler-10b). This opens a new field in exoplanet science: the possibility of obtaining information about the atmosphere and surface of rocky planets, objects of prime interest. In this Letter, we apply the Lava-ocean model to interpret the observed phase curve. The model, a planet without atmosphere and a surface partially made of molten rocks, has been proposed for planets of the class of CoRoT-7b, i.e., rocky planets very close to their star (at a few stellar radii). Kepler-10b is a typical member of this family. It predicts that the light from the planet has an important emission component in addition to the reflected one, even in the Kepler spectral band. Assuming an isotropical reflection of light by the planetary surface (Lambertian-like approximation), we find that a Bond albedo of {approx}50% can account for the observed amplitude of the phase curve, as opposed to a first attempt where an unusually high value was found. We propose a physical process to explain this still large value of the albedo. The overall interpretation can be tested in the future with instruments such as the James Webb Space Telescope or the Exoplanet Characterization Observatory. Our model predicts a spectral dependence that is clearly distinguishable from that of purely reflected light and from that of a planet at a uniform temperature.

  5. Astrophysical Impact of the Updated 9Be(p,α)6Li and 10B(p,α)7Be Reaction Rates As Deduced By THM

    NASA Astrophysics Data System (ADS)

    Lamia, L.; Spitaleri, C.; Tognelli, E.; Degl'Innocenti, S.; Pizzone, R. G.; Prada Moroni, P. G.

    2015-10-01

    The complete understanding of the stellar abundances of lithium, beryllium, and boron represents one of the most interesting open problems in astrophysics. These elements are largely used to probe stellar structure and mixing phenomena in different astrophysical scenarios, such as pre-main-sequence or main-sequence stars. Their different fragility against (p,α) burning reactions allows one to investigate different depths of the stellar interior. Such fusion mechanisms are triggered at temperatures between T ≈ (2-5) × {10}6 K, thus defining a corresponding Gamow energy between ≈ 3-10 keV, where S(E)-factor measurements need to be performed to get reliable reaction rate evaluations. The Trojan Horse Method is a well defined procedure to measure cross sections at Gamow energies overcoming the uncertainties due to low-energy S(E)-factor extrapolation as well as electron screening effects. Taking advantage of the {\\mathtt{THM}} measure of the 9Be(p,α)6Li and 10B(p,α)7Be cross sections, the corresponding reaction rates have been calculated and compared with the evaluations by the NACRE collaboration, widely used in the literature. The impact on surface abundances of the updated 9Be and 10B (p,α) burning rates is discussed for pre-MS stars.

  6. Generalized uncertainty principle and analogue of quantum gravity in optics

    NASA Astrophysics Data System (ADS)

    Braidotti, Maria Chiara; Musslimani, Ziad H.; Conti, Claudio

    2017-01-01

    The design of optical systems capable of processing and manipulating ultra-short pulses and ultra-focused beams is highly challenging with far reaching fundamental technological applications. One key obstacle routinely encountered while implementing sub-wavelength optical schemes is how to overcome the limitations set by standard Fourier optics. A strategy to overcome these difficulties is to utilize the concept of a generalized uncertainty principle (G-UP) which has been originally developed to study quantum gravity. In this paper we propose to use the concept of G-UP within the framework of optics to show that the generalized Schrödinger equation describing short pulses and ultra-focused beams predicts the existence of a minimal spatial or temporal scale which in turn implies the existence of maximally localized states. Using a Gaussian wavepacket with complex phase, we derive the corresponding generalized uncertainty relation and its maximally localized states. Furthermore, we numerically show that the presence of nonlinearity helps the system to reach its maximal localization. Our results may trigger further theoretical and experimental tests for practical applications and analogues of fundamental physical theories.

  7. Mechanism of cis-prenyltransferase reaction probed by substrate analogues

    SciTech Connect

    Lu, Yen-Pin; Liu, Hon-Ge; Teng, Kuo-Hsun; Liang, Po-Huang

    2010-10-01

    Research highlights: {yields} The extremely slow trans-OPPS reaction using 2-Fluoro-FPP supports the sequential mechanism with the carbocation intermediate. {yields} The similar UPPS reaction rate under single turnover supports the concerted mechanism, without the carbocation intermediate. {yields} The secondary kinetic isotope effect also supports associate transition state for UPPS reaction, without the carbocation intermediate. -- Abstract: Undecaprenyl pyrophosphate synthase (UPPS) is a cis-type prenyltransferases which catalyzes condensation reactions of farnesyl diphosphate (FPP) with eight isopentenyl pyrophosphate (IPP) units to generate C{sub 55} product. In this study, we used two analogues of FPP, 2-fluoro-FPP and [1,1-{sup 2}H{sub 2}]FPP, to probe the reaction mechanism of Escherichia coli UPPS. The reaction rate of 2-fluoro-FPP with IPP under single-turnover condition is similar to that of FPP, consistent with the mechanism without forming a farnesyl carbocation intermediate. Moreover, the deuterium secondary KIE of 0.985 {+-} 0.022 measured for UPPS reaction using [1,1-{sup 2}H{sub 2}]FPP supports the associative transition state. Unlike the sequential mechanism used by trans-prenyltransferases, our data demonstrate E. coli UPPS utilizes the concerted mechanism.

  8. Analogues of uracil nucleosides with intrinsic fluorescence (NIF-analogues): synthesis and photophysical properties.

    PubMed

    Segal, Meirav; Fischer, Bilha

    2012-02-28

    Uridine cannot be utilized as fluorescent probe due to its extremely low quantum yield. For improving the uracil fluorescence characteristics we extended the natural chromophore at the C5 position by coupling substituted aromatic rings directly or via an alkenyl or alkynyl linker to create fluorophores. Extension of the uracil base was achieved by treating 5-I-uridine with the appropriate boronic acid under the Suzuki coupling conditions. Analogues containing an alkynyl linker were obtained from 5-I-uridine and the suitable boronic acid in a Sonogashira coupling reaction. The uracil fluorescent analogues proposed here were designed to satisfy the following requirements: a minimal chemical modification at a position not involved in base-pairing, resulting in relatively long absorption and emission wavelengths and high quantum yield. 5-((4-Methoxy-phenyl)-trans-vinyl)-2'-deoxy-uridine, 6b, was found to be a promising fluorescent probe. Probe 6b exhibits a quantum yield that is 3000-fold larger than that of the natural chromophore (Φ 0.12), maximum emission (478 nm) which is 170 nm red shifted as compared to uridine, and a Stokes shift of 143 nm. In addition, since probe 6b adopts the anti conformation and S sugar puckering favored by B-DNA, it makes a promising nucleoside analogue to be incorporated in an oligonucleotide probe for detection of genetic material.

  9. Synthesis and Characterization of Mixed III-V and II-VI Semiconductor Monomers Included in the Borate Sodalite Analogue

    DTIC Science & Technology

    1993-04-30

    Characterization of Mixed III-V and .I-VI N00014-k0-J-er59Semiconductor Monomrers Included in the Borate Sodalite Analogue ..... C LL AU N.𔃾 K.L. Moran...dependent static and magic angle spinning and solid state NMR experiments. Inclusion of GaP within the borate sodalite analogue results in the formation of an...properties of compounds can be dramatically altered by inclusion into the sodalite framework, which is one of several reasons why this zeolite structure

  10. Redox Viscosity of Iron Rich Silicate Melts - Martian Mantle Analogues.

    NASA Astrophysics Data System (ADS)

    Dingwell, D. B.

    2004-12-01

    The dependence of shear viscosity on the oxidation state of ferrosilicate melts has been measured using the concentric cylinder method and a gas mixing furnace. Two different simple Fe-bearing systems have been studied to date: (i) anorthite-diopside eutectic composition (AnDi) with variable amount of Fe (up to 20 wt%) as a basalt analogue and (ii) sodium disilicate (NS2 up to 30 wt % Fe). In addition, the compositional range has been extended to include the more complex SNC meteorite composition, a composition more relevant to Mars. The measurements were performed under air, CO2 and CO2-CO mixture at 1 atm and in a temperature range of 1300 to 1350 \\ºC. The experimental procedure involve a continuous measurement of viscosity during stepwise reduction state. The melt was reduced by flowing CO2 and then successively reducing mixtures of CO2-CO through the alumina muffle tube. Gas flow rates were electronically controlled using Tylan mass flow controllers and oxygen fugacity was directly measured using a sensor and calculated with Nernst equation. The composition and oxidation state of the melt was monitored by obtaining a melt sample after each redox equilibrium step. The melts were sampled by dipping an alumina rod into the sample and drawing out a drop of liquid, which was then plunged into water for quenching. The resulting glasses were analyzed by electron microprobe, and the volumetric potassium dichromate titration were employed to determine FeO. In addition, the redox dependence of viscosity of our samples have been compared with data from literature (Mysen et al. 1985, Dingwell and Virgo, 1988; Dingwell 1989, Dingwell 1991). The viscosity of all melts investigated herein decreases with melt reduction. The viscosity decrease is, in general, a nonlinear function of oxidation state expressed as Fe2+/Fetot and can be fitted using logarithmic equation.

  11. In silico analysis of regulatory networks underlines the role of miR-10b-5p and its target BDNF in huntington's disease.

    PubMed

    Müller, Sören

    2014-01-01

    Non-coding RNAs (ncRNAs) play various roles during central nervous system development. MicroRNAs (miRNAs) are a class of ncRNAs that exert their function together with argonaute proteins by post-transcriptional gene silencing of messenger RNAs (mRNAs). Several studies provide evidence for alterations in miRNA expression in patients with neurodegenerative diseases. Among these is huntington's disease (HD), a dominantly inherited fatal disorder characterized by deregulation of neuronal-specific mRNAs as well as miRNAs. Recently, next-generation sequencing (NGS) miRNA profiles from human HD and neurologically normal control brain tissues were reported. Five consistently upregulated miRNAs affect the expression of genes involved in neuronal differentiation, neurite outgrowth, cell death and survival. We re-analyzed the NGS data publicly available in array express and detected nineteen additional differentially expressed miRNAs. Subsequently, we connected these miRNAs to genes implicated in HD development and network analysis pointed to miRNA-mediated downregulation of twenty-two genes with roles in the pathogenesis as well as treatment of the disease. In silico prediction and reporter systems prove that levels of BDNF, a central node in the miRNA-mRNA regulatory network, can be post-transcriptionally controlled by upregulated miR-10b-5p and miR-30a-5p. Reduced BDNF expression is associated with neuronal dysfunction and death in HD. Moreover, the 3'UTR of CREB1 harbors a predicted binding site for these two miRNAs. CREB1 is similarly downregulated in HD and overexpression decreased susceptibility to 3-nitropropionic-induced toxicity in a cell model. In contradiction to these observations, it is presumed that miR-10b-5p upregulation in HD exerts a neuroprotective role in response to the mutation in the huntingtin gene. Therefore, the function of miR-10b-5p and especially its effect on BDNF expression in HD requires further academic research.

  12. Erbium: YAG laser (2,940 nm) treatment stimulates hair growth through upregulating Wnt 10b and β-catenin expression in C57BL/6 mice

    PubMed Central

    Ke, Jin; Guan, Huiwen; Li, Shan; Xu, Li; Zhang, Li; Yan, Yuehua

    2015-01-01

    Aim: To evaluate the role of 2,940 nm erbium: YAG laser in hair growth in C57BL/6 mice. Methods: Anagen was experimentally induced by depilation. Healthy C57BL/6 mice (n=22) were randomly divided into four groups, with treatment of laser or minoxidil, or with combined laser and minoxidil treatments. The skin color of each mouse was observed each day. The time from telogen (pink skin color) to anagen (black coloration) phase and from anagen (black coloration) to catagen (all hairs grew out of the depilated skin) have been recorded. Hematoxylin and eosin (H&E) assay was done at fifteen days after the first treatment for each group to observe hair follicles and hair cycle score. Western blot analysis was utilized to detect the expression levels of Wnt 10-b and β-catenin. Results: Black pigmentation started significantly earlier both in the laser and combination group than in the control group. Moreover, the time from anagen to catagen in the laser, minoxidil and combination groups were all significantly shorter from the control group. Histopathology with H&E staining showed an obvious increase in the number of hair follicles in the anagen phase caused by the treatment of 2,940 nm erbium: YAG laser and minoxidil. Similarly, the percentage of hair follicles in anagen VI accounted for 19.5%, 37.5%, 41.5% and 44% in control, laser, minoxidil, and combination group, respectively. Western blot analysis showed that both the levels of Wnt 10b and β-catenin were significantly increased by the treatment of 2,940 nm erbium: YAG laser. Conclusion: Our findings showed that 2,940-nm Er: YAG laser could promote hair growth by inducing hair cycle transition from telogen to anagen phases in C57BL/6 mice through up regulating Wnt 10b and β-catenin. These results suggest that 2,940-nm Er: YAG laser may be a potential therapy for hair loss. PMID:26885014

  13. Analogue of the quantum Hanle effect and polarization conversion in non-Hermitian plasmonic metamaterials.

    PubMed

    Ginzburg, Pavel; Rodríguez-Fortuño, Francisco J; Martínez, Alejandro; Zayats, Anatoly V

    2012-12-12

    The Hanle effect, one of the first manifestations of quantum theory introducing the concept of coherent superposition between pure states, plays a key role in numerous aspects of science varying from applicative spectroscopy to fundamental astrophysical investigations. Optical analogues of quantum effects help to achieve deeper understanding of quantum phenomena and, in turn, to develop cross-disciplinary approaches to realizations of new applications in photonics. Here we show that metallic nanostructures can be designed to exhibit a plasmonic analogue of the quantum Hanle effect and the associated polarization rotation. In the original Hanle effect, time-reversal symmetry is broken by a static magnetic field. We achieve this by introducing dissipative level crossing of localized surface plasmons due to nonuniform losses, designed using a non-Hermitian formulation of quantum mechanics. Such artificial plasmonic "atoms" have been shown to exhibit strong circular birefringence and circular dichroism which depends on the value of loss or gain in the metal-dielectric nanostructure.

  14. Natural geochemical analogues of the near field of high-level nuclear waste repositories

    SciTech Connect

    Apps, J.A.

    1995-09-01

    United States practice has been to design high-level nuclear waste (HLW) geological repositories with waste densities sufficiently high that repository temperatures surrounding the waste will exceed 100{degrees}C and could reach 250{degrees}C. Basalt and devitrified vitroclastic tuff are among the host rocks considered for waste emplacement. Near-field repository thermal behavior and chemical alteration in such rocks is expected to be similar to that observed in many geothermal systems. Therefore, the predictive modeling required for performance assessment studies of the near field could be validated and calibrated using geothermal systems as natural analogues. Examples are given which demonstrate the need for refinement of the thermodynamic databases used in geochemical modeling of near-field natural analogues and the extent to which present models can predict conditions in geothermal fields.

  15. Functionalized Congener Approach to Muscarinic Antagonists: Analogues of Pirenzepine

    PubMed Central

    Karton, Yishai; Bradbury, Barton J.; Baumgold, Jesse; Paek, Robert; Jacobson, Kenneth A.

    2012-01-01

    The M1-selective muscarinic receptor antagonist pirenzepine (5,11-dihydro-11-[(4-methyl-1-piperazinyl)acetyl]-6H-pyrido[2,3-b] [1,4]benzodiazepin-6-one) was derivatized to explore points of attachment of functionalized side chains for the synthesis of receptor probes and ligands for affinity chromatography. The analogues prepared were evaluated in competitive binding assays versus [3H]-N-methylscopolamine at four muscarinic receptor subtypes (m1AChR-m4AChR) in membranes from rat heart tissue and transfected A9L cells. 9-(Hydroxymethyl)pirenzepine, 8-(methylthio)pirenzepine, and a series of 8-aminosulfonyl derivatives were synthesized. Several 5-substituted analogues of pirenzepine also were prepared. An alternate series of analogues substituted on the 4-position of the piperazine ring was prepared by reaction of 4-desmethylpirenzepine with various electrophiles. An N-chloroethyl analogue of pirenzepine was shown to form a reactive aziridine species in aqueous buffer yet failed to affinity label muscarinic receptors. Within a series of aminoalkyl analogues, the affinity increased as the length of the alkyl chain increased. Shorter chain analogues were generally much less potent than pirenzepine, and longer analogues (7–10 carbons) were roughly as potent as pirenzepine at m1 receptors, but were nonselective. Depending on the methylene chain length, acylation or alkyl substitution of the terminal amine also influenced the affinity at muscarinic receptors. PMID:2066986

  16. Design of multi-epitope, analogue-based cancer vaccines.

    PubMed

    Fikes, John D; Sette, Alessandro

    2003-09-01

    The current objective of our cancer programme is to develop an effective vaccine based on rationally designed T cell epitope analogues, for use in the adjuvant setting for non-small cell lung cancer (NSCLC) and colon cancer. Analogue epitopes, enhanced for either human leukocyte antigen (HLA) binding or T cell receptor (TCR) signalling, have been shown to be more effective at breaking immunological tolerance than cognate wild-type epitopes. Although encouraging early-phase clinical data has been obtained by others using a limited number of HLA-A2-restricted epitope analogues, the clinical benefits and immune correlates for vaccines comprised of multiple epitope analogues restricted by multiple HLA supertypes remains to be investigated. Clinical studies are currently being conducted on EP-2101, a prototype vaccine that delivers multiple HLA-A2-restricted analogue epitopes. In parallel, fixed anchor and heteroclitic analogues restricted by three other commonly expressed HLA supertypes are being identified. These analogues will be incorporated into future vaccines including optimised minigenes (epigenes) and tested in preclinical and clinical studies addressing various different cancer indications.

  17. Analogues of erectile dysfunction drugs: an under-recognised threat.

    PubMed

    Poon, W T; Lam, Y H; Lai, C K; Chan, Albert Y W; Mak, Tony W L

    2007-10-01

    To investigate the problem of drug analogue adulteration in male erectile dysfunction health products. Survey of over-the-counter male erectile dysfunction health products available in convenience stores and pharmacies in Hong Kong. Tertiary referral centre for clinical toxicology analysis in Hong Kong. The pattern and extent of adulteration of male erectile dysfunction health products with sildenafil, tadalafil, and vardenafil as well as their structurally modified analogues. Of 26 products studied, one (4%) was found to contain undeclared sildenafil, while 14 (54%) contained drug analogues of different kinds. The latter included acetildenafil, hydroxyacetildenafil, hydroxyhomosildenafil, and piperidenafil. The first three were analogues of sildenafil and the last was an analogue of vardenafil. One young patient presented with ataxia after taking an acetildenafil-containing product. The positive rate of concealed drug analogues in male erectile dysfunction health products is alarmingly high. Such analogues are difficult to detect by ordinary laboratory methods, and might be used in an attempt to evade regulatory inspection. Without going through the stringent drug testing process, the adverse effects of these chemicals remain largely unknown and unpredictable. Effective surveillance system and control measures are needed urgently. The medical profession and the public should be alerted to this under-recognised threat.

  18. Hot Fire Ignition Test with Densified Liquid Hydrogen using a RL10B-2 Cryogenic H2/O2 Rocket Engine

    NASA Technical Reports Server (NTRS)

    McNelis, Nancy B.; Haberbusch, Mark S.

    1997-01-01

    Enhancements to propellants provide an opportunity to either increase performance of an existing vehicle, or reduce the size of a new vehicle. In the late 1980's the National AeroSpace Plane (NASP) reopened the technology chapter on densified propellants, in particular hydrogen. Since that point in time the NASA Lewis Research Center (LERC) in Cleveland, Ohio has been leading the way to provide critical research on the production and transfer of densified propellants. On October 4, 1996 NASA LeRC provided another key demonstration towards the advancement of densified propellants as a viable fuel. Successful ignition of an RL10B-2 engine was achieved with near triple point liquid hydrogen.

  19. Effects of Mo addition on thermal stability and magnetic properties of a ferromagnetic Fe75P10C10B5 metallic glass

    NASA Astrophysics Data System (ADS)

    Zhang, Wei; Jia, Xingjie; Li, Yanhui; Fang, Canfeng

    2014-05-01

    The effects of Mo content on the thermal stability, glass-forming ability (GFA), magnetic and mechanical properties of Fe75-xMoxP10C10B5 (x = 0-10) metallic glasses were investigated. The stabilization of supercooled liquid and GFA were significantly enhanced by addition of Mo. Although the saturation magnetization (Is) of the alloys reduced with increasing Mo content, the coercive force (Hc) decreased. The metallic glasses with x = 2.5-7.5 exhibit low glass transition temperature of 733-749 K, large supercooled liquid region of 61-96 K, and high GFA with critical fully glassy sample diameters of 1.5-3.0 mm. They also possess rather high Is of 0.81-1.11 T, low Hc of 2.07-4.87 A/m, high Vicker's hardness of 860-992, high compressive yield strength of over 3000 MPa with a distinct plastic strain.

  20. Nuclear structure of {sup 10}B studied with (e,e{prime}), ({pi},{pi}{prime}) and ({gamma},{pi}) reactions

    SciTech Connect

    Sato, T.; Odagawa, N.; Ohtsubo, H.; Lee, T.S.H.

    1994-05-01

    The authors studied nuclear structure of {sup 10}B using (e,e{prime}),({pi},{pi}{prime}) and ({gamma},{pi}) reactions under the distorted wave impulse approximation (DWIA). For this purpose the off-shell dependence of the amplitude was taken into account in the momentum space DWIA. They used the off-shell elementary amplitude of ({pi},{pi}) and ({gamma},{pi}) by the model of Nozawa, Blankleider and Lee. The first order core polarization effects were incorporated with the p-shell wave functions of Cohen and Kurath and Hauge and Maripuu. It was shown that the core-polarization effects greatly improve the agreement with the experimental data and that the simultaneous study of these reactions is useful to probe the spin structure of p-shell nuclei.