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Sample records for a2 b1 b2

  1. Vavilosides A1/A2-B1/B2, new furostane glycosides from the bulbs of Allium vavilovii with cytotoxic activity.

    PubMed

    Zolfaghari, Behzad; Sadeghi, Masoud; Troiano, Raffaele; Lanzotti, Virginia

    2013-04-01

    A phytochemical analysis of the bulbs of Allium vavilovii M. Pop. & Vved. was attained for the first time extensively, affording to the isolation of four new furostanol saponins, named vavilosides A1/A2-B1/B2 (1a/b-2a/2b), as two couple of isomers in equilibrium, together with ascalonicoside A1/A2 (3a/3b) and 22-O-methyl ascalonicoside A1/A2 (4a/4b), previously isolated from shallot, Allium ascalonicum. High concentrations of kaempferol, kaempferide, and kaempferol 4(I)-glucoside were also isolated. The chemical structures of the new compounds, established through a combination of extensive nuclear magnetic resonance, mass spectrometry and chemical analyses, were identified as (25R)-furost-5(6)-en-1β,3β,22α,26-tetraol 1-O-α-L-rhamnopyranosyl-(1→2)-O-β-D-galactopyranosyl 26-O-α-L-rhamnopyranoside (vaviloside A1), (25R)-furost-5(6)-en-1β,3β,22β,26-tetraol 1-O-α-L-rhamnopyranosyl-(1→2)-O-β-D-galactopyranosyl 26-O-α-L-rhamnopyranoside (vaviloside A2), (25R)-furost-5(6)-en-1β,3β,22α,26-tetraol 1-O-α-L-rhamnopyranosyl-(1→2)-O-β-D-xylopyranosyl 26-O-α-L-rhamnopyranoside (vaviloside B1), (25R)-furost-5(6)-en-1β,3β,22β,26-tetraol 1-O-α-L-rhamnopyranosyl-(1→2)-O-β-d-xylopyranosyl 26-O-α-L-rhamnopyranoside (vaviloside B2). The isolated saponins showed cytotoxic activity on J-774, murine monocyte/macrophage, and WEHI-164, murine fibrosarcoma, cell lines with the following rank: vaviloside B1/B2>ascalonicoside A1/A2>vaviloside A1/A2. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. Identification and characterization of TLR7, TLR8a2, TLR8b1 and TLR8b2 genes in Atlantic salmon (Salmo salar).

    PubMed

    Lee, P T; Zou, J; Holland, J W; Martin, S A M; Kanellos, T; Secombes, C J

    2013-10-01

    Mammalian Toll-like receptor (TLR) 7 and 8 are responsible for recognizing viral single-stranded RNA (ssRNA) and are activated by anti-viral imidazoquinoline compounds, leading to a series of defensive mechanisms being launched to protect the host against viruses. In this study, we identified two TLR7 (with one probably a pseudogene) and three TLR8 genes, namely TLR8a2, TLR8b1 and TLR8b2 from Atlantic salmon (Salmo salar) whole-genome shotgun (WGS) contigs. Bioinformatics analysis showed that salmon TLR7 and TLR8a2 are closely related to the corresponding trout orthologs, however, salmon TLR8b1 and TLR8b2 share the highest amino acid sequence similarity to zebrafish TLR8b and formed a subfamily of the piscine TLR8 molecules in phylogenetic tree analysis. A conserved gene synteny was found with the salmon TLR7/8a members as seen in other vertebrate loci. Deduced domain organisation of salmon TLR7 and TLR8 molecules showed similar structural features, with equal numbers of leucine-rich repeats (LRRs) and insertion motifs. Individual TLR molecules were expressed in a similar pattern between parr and post-smolts, with a high expression level in immune tissues. Promoter analysis predicted several transcription factor binding sites in the TLR8a1/2 and TLR8b1 5' flanking regions, namely C/EBP, AP-1, STAT, NFκB, and IRF family, suggesting cytokine regulation of the genes. Hence, three recombinant cytokines, type I IFN, IFNγ and IL-1β were used to study the regulation of the salmon TLR gene expression levels in primary head kidney cells and the Salmon Head Kidney-1 (SHK-1) cell line. Salmon TLR7 and TLR8a1 gene expression was more sensitive to type I IFN and IFNγ treatment in primary head kidney cells and SHK-1 cells respectively, with no significant up-regulation of TLR8a2 and TLR8b2 by any of the treatments. On the other hand, salmon TLR8a1 and TLR8b1 were most sensitive to IL-1β treatment in SHK-1 cells and primary head kidney cells, respectively. TLR8b2 was

  3. Properties of L=1 B(1) and B(2)* mesons.

    PubMed

    Abazov, V M; Abbott, B; Abolins, M; Acharya, B S; Adams, M; Adams, T; Aguilo, E; Ahn, S H; Ahsan, M; Alexeev, G D; Alkhazov, G; Alton, A; Alverson, G; Alves, G A; Anastasoaie, M; Ancu, L S; Andeen, T; Anderson, S; Andrieu, B; Anzelc, M S; Arnoud, Y; Arov, M; Arthaud, M; Askew, A; Asman, B; Assis Jesus, A C S; Atramentov, O; Autermann, C; Avila, C; Ay, C; Badaud, F; Baden, A; Bagby, L; Baldin, B; Bandurin, D V; Banerjee, S; Banerjee, P; Barberis, E; Barfuss, A-F; Bargassa, P; Baringer, P; Barreto, J; Bartlett, J F; Bassler, U; Bauer, D; Beale, S; Bean, A; Begalli, M; Begel, M; Belanger-Champagne, C; Bellantoni, L; Bellavance, A; Benitez, J A; Beri, S B; Bernardi, G; Bernhard, R; Berntzon, L; Bertram, I; Besançon, M; Beuselinck, R; Bezzubov, V A; Bhat, P C; Bhatnagar, V; Biscarat, C; Blazey, G; Blekman, F; Blessing, S; Bloch, D; Bloom, K; Boehnlein, A; Boline, D; Bolton, T A; Borissov, G; Bos, K; Bose, T; Brandt, A; Brock, R; Brooijmans, G; Bross, A; Brown, D; Buchanan, N J; Buchholz, D; Buehler, M; Buescher, V; Burdin, S; Burke, S; Burnett, T H; Buszello, C P; Butler, J M; Calfayan, P; Calvet, S; Cammin, J; Caron, S; Carvalho, W; Casey, B C K; Cason, N M; Castilla-Valdez, H; Chakrabarti, S; Chakraborty, D; Chan, K M; Chan, K; Chandra, A; Charles, F; Cheu, E; Chevallier, F; Cho, D K; Choi, S; Choudhary, B; Christofek, L; Christoudias, T; Cihangir, S; Claes, D; Clément, C; Clément, B; Coadou, Y; Cooke, M; Cooper, W E; Corcoran, M; Couderc, F; Cousinou, M-C; Crépé-Renaudin, S; Cutts, D; Cwiok, M; da Motta, H; Das, A; Davies, G; De, K; de Jong, S J; de Jong, P; De La Cruz-Burelo, E; Martins, C De Oliveira; Degenhardt, J D; Déliot, F; Demarteau, M; Demina, R; Denisov, D; Denisov, S P; Desai, S; Diehl, H T; Diesburg, M; Dominguez, A; Dong, H; Dudko, L V; Duflot, L; Dugad, S R; Duggan, D; Duperrin, A; Dyer, J; Dyshkant, A; Eads, M; Edmunds, D; Ellison, J; Elvira, V D; Enari, Y; Eno, S; Ermolov, P; Evans, H; Evdokimov, A; Evdokimov, V N; Ferapontov, A V; Ferbel, T; Fiedler, F; Filthaut, F; Fisher, W; Fisk, H E; Ford, M; Fortner, M; Fox, H; Fu, S; Fuess, S; Gadfort, T; Galea, C F; Gallas, E; Galyaev, E; Garcia, C; Garcia-Bellido, A; Gavrilov, V; Gay, P; Geist, W; Gelé, D; Gerber, C E; Gershtein, Y; Gillberg, D; Ginther, G; Gollub, N; Gómez, B; Goussiou, A; Grannis, P D; Greenlee, H; Greenwood, Z D; Gregores, E M; Grenier, G; Gris, Ph; Grivaz, J-F; Grohsjean, A; Grünendahl, S; Grünewald, M W; Guo, J; Guo, F; Gutierrez, P; Gutierrez, G; Haas, A; Hadley, N J; Haefner, P; Hagopian, S; Haley, J; Hall, I; Hall, R E; Han, L; Hanagaki, K; Hansson, P; Harder, K; Harel, A; Harrington, R; Hauptman, J M; Hauser, R; Hays, J; Hebbeker, T; Hedin, D; Hegeman, J G; Heinmiller, J M; Heinson, A P; Heintz, U; Hensel, C; Herner, K; Hesketh, G; Hildreth, M D; Hirosky, R; Hobbs, J D; Hoeneisen, B; Hoeth, H; Hohlfeld, M; Hong, S J; Hooper, R; Hossain, S; Houben, P; Hu, Y; Hubacek, Z; Hynek, V; Iashvili, I; Illingworth, R; Ito, A S; Jabeen, S; Jaffré, M; Jain, S; Jakobs, K; Jarvis, C; Jesik, R; Johns, K; Johnson, C; Johnson, M; Jonckheere, A; Jonsson, P; Juste, A; Käfer, D; Kahn, S; Kajfasz, E; Kalinin, A M; Kalk, J R; Kalk, J M; Kappler, S; Karmanov, D; Kasper, J; Kasper, P; Katsanos, I; Kau, D; Kaur, R; Kaushik, V; Kehoe, R; Kermiche, S; Khalatyan, N; Khanov, A; Kharchilava, A; Kharzheev, Y M; Khatidze, D; Kim, H; Kim, T J; Kirby, M H; Kirsch, M; Klima, B; Kohli, J M; Konrath, J-P; Kopal, M; Korablev, V M; Kothari, B; Kozelov, A V; Krop, D; Kryemadhi, A; Kuhl, T; Kumar, A; Kunori, S; Kupco, A; Kurca, T; Kvita, J; Lacroix, F; Lam, D; Lammers, S; Landsberg, G; Lazoflores, J; Lebrun, P; Lee, W M; Leflat, A; Lehner, F; Lellouch, J; Lesne, V; Leveque, J; Lewis, P; Li, J; Li, Q Z; Li, L; Lietti, S M; Lima, J G R; Lincoln, D; Linnemann, J; Lipaev, V V; Lipton, R; Liu, Y; Liu, Z; Lobo, L; Lobodenko, A; Lokajicek, M; Lounis, A; Love, P; Lubatti, H J; Lyon, A L; Maciel, A K A; Mackin, D; Madaras, R J; Mättig, P; Magass, C; Magerkurth, A; Makovec, N; Mal, P K; Malbouisson, H B; Malik, S; Malyshev, V L; Mao, H S; Maravin, Y; Martin, B; McCarthy, R; Melnitchouk, A; Mendes, A; Mendoza, L; Mercadante, P G; Merkin, M; Merritt, K W; Meyer, J; Meyer, A; Michaut, M; Millet, T; Mitrevski, J; Molina, J; Mommsen, R K; Mondal, N K; Moore, R W; Moulik, T; Muanza, G S; Mulders, M; Mulhearn, M; Mundal, O; Mundim, L; Nagy, E; Naimuddin, M; Narain, M; Naumann, N A; Neal, H A; Negret, J P; Neustroev, P; Nilsen, H; Nomerotski, A; Novaes, S F; Nunnemann, T; O'Dell, V; O'Neil, D C; Obrant, G; Ochando, C; Onoprienko, D; Oshima, N; Osta, J; Otec, R; Y Garzón, G J Otero; Owen, M; Padley, P; Pangilinan, M; Parashar, N; Park, S-J; Park, S K; Parsons, J; Partridge, R; Parua, N; Patwa, A; Pawloski, G; Penning, B; Perea, P M; Peters, K; Peters, Y; Pétroff, P; Petteni, M; Piegaia, R; Piper, J; Pleier, M-A; Podesta-Lerma, P L M; Podstavkov, V M; Pogorelov, Y; Pol, M-E; Polozov, P; Pompos, A; Pope, B G; Popov, A V; Potter, C; da Silva, W L Prado; Prosper, H B; Protopopescu, S; Qian, J; Quadt, A; Quinn, B; Rakitine, A; Rangel, M S; Rani, K J; Ranjan, K; Ratoff, P N; Renkel, P; Reucroft, S; Rich, P; Rijssenbeek, M; Ripp-Baudot, I; Rizatdinova, F; Robinson, S; Rodrigues, R F; Royon, C; Rubinov, P; Ruchti, R; Safronov, G; Sajot, G; Sánchez-Hernández, A; Sanders, M P; Santoro, A; Savage, G; Sawyer, L; Scanlon, T; Schaile, D; Schamberger, R D; Scheglov, Y; Schellman, H; Schieferdecker, P; Schliephake, T; Schmitt, C; Schwanenberger, C; Schwartzman, A; Schwienhorst, R; Sekaric, J; Sengupta, S; Severini, H; Shabalina, E; Shamim, M; Shary, V; Shchukin, A A; Shivpuri, R K; Shpakov, D; Siccardi, V; Simak, V; Sirotenko, V; Skubic, P; Slattery, P; Smirnov, D; Smith, R P; Snow, J; Snow, G R; Snyder, S; Söldner-Rembold, S; Sonnenschein, L; Sopczak, A; Sosebee, M; Soustruznik, K; Souza, M; Spurlock, B; Stark, J; Steele, J; Stolin, V; Stone, A; Stoyanova, D A; Strandberg, J; Strandberg, S; Strang, M A; Strauss, M; Strauss, E; Ströhmer, R; Strom, D; Strovink, M; Stutte, L; Sumowidagdo, S; Svoisky, P; Sznajder, A; Talby, M; Tamburello, P; Tanasijczuk, A; Taylor, W; Telford, P; Temple, J; Tiller, B; Tissandier, F; Titov, M; Tokmenin, V V; Tomoto, M; Toole, T; Torchiani, I; Trefzger, T; Tsybychev, D; Tuchming, B; Tully, C; Tuts, P M; Unalan, R; Uvarov, S; Uvarov, L; Uzunyan, S; Vachon, B; van den Berg, P J; van Eijk, B; Van Kooten, R; van Leeuwen, W M; Varelas, N; Varnes, E W; Vartapetian, A; Vasilyev, I A; Vaupel, M; Verdier, P; Vertogradov, L S; Verzocchi, M; Villeneuve-Seguier, F; Vint, P; Vokac, P; Von Toerne, E; Voutilainen, M; Vreeswijk, M; Wagner, R; Wahl, H D; Wang, L; Wang, M H L S; Warchol, J; Watts, G; Wayne, M; Weber, M; Weber, G; Weerts, H; Wenger, A; Wermes, N; Wetstein, M; White, A; Wicke, D; Wilson, G W; Williams, M R J; Wimpenny, S J; Wobisch, M; Wood, D R; Wyatt, T R; Xie, Y; Yacoob, S; Yamada, R; Yan, M; Yasuda, T; Yatsunenko, Y A; Yip, K; Yoo, H D; Youn, S W; Yu, J; Yu, C; Yurkewicz, A; Zatserklyaniy, A; Zeitnitz, C; Zhang, D; Zhao, T; Zhou, B; Zhu, J; Zielinski, M; Zieminska, D; Zieminski, A; Zivkovic, L; Zutshi, V; Zverev, E G

    2007-10-26

    This Letter presents the first strong evidence for the resolution of the excited B mesons B(1) and B(2)* as two separate states in fully reconstructed decays to B(+)(*)pi(-). The mass of B(1) is measured to be 5720.6+/-2.4+/-1.4 MeV/c(2) and the mass difference DeltaM between B(2)* and B(1) is 26.2+/-3.1+/-0.9 MeV/c;{2}, giving the mass of the B(2)* as 5746.8+/-2.4+/-1.7 MeV/c(2). The production rate for B(1) and B(2)* mesons is determined to be a fraction (13.9+/-1.9+/-3.2)% of the production rate of the B+ meson.

  4. Characterization of dual agonists for kinin B1 and B2 receptors and their biased activation of B2 receptors

    PubMed Central

    Zhang, Xianming; Lowry, Jessica L.; Brovkovych, Viktor; Skidgel, Randal A.

    2012-01-01

    Kinin B1 and B2 receptors (kB1R and kB2R) play important roles in many physiological and pathological processes. In some cases, kB1R or kB2R activation can have overlapping or complementary beneficial effects, thus an activator of both receptors might be advantageous. We found that replacement of the C-terminal Arg in the natural kB2R activators bradykinin (BK) or kallidin (KD) with Lys (K9-BK or K10-KD) resulted in agonists that effectively stimulate the downstream signaling of both the kB1R and kB2R as measured by increased inositol turnover, intracellular calcium, ERK1/2 phosphorylation, arachidonic acid release and NO production. However, K9-BK and K10-KD displayed some characteristics of biased agonism for kB2Rs as indicated by the rapid kinetics of ERK1/2 phosphorylation induced by K9-BK or K10-KD compared with the prolonged response mediated by BK or KD. In contrast, kinetics of ERK phosphorylation stimulated by K10-KD activation of the kB1R was as same as that induced by known kB1R agonist des-Arg10-KD. Furthermore, the endocytosis of kB2Rs mediated by K9-BK and K10-KD was remarkably less than that induced by BK and KD respectively. K10-KD stimulated kB1R and kB2R-dependent calcium responses and ERK1/2 phosphorylation in bovine endothelial cells. In cytokine-treated human endothelial cells, K10-KD stimulated ERK1/2 phosphorylation and a transient peak of NO production that was primarily kB2R-dependent. K10-KD also stimulated prolonged NO production that was both kB1R and kB2R-dependent. These data provide the first examples of dual agonists of kB1R and kB2R, and a biased agonist of kB2R and may provide useful clues for developing dual modulators of kB1Rs and kB2Rs for potential therapeutic use. PMID:22522052

  5. Primary Role for Kinin B1and B2Receptors in Glioma Proliferation.

    PubMed

    Nicoletti, Natália Fontana; Sénécal, Jacques; da Silva, Vinicius Duval; Roxo, Marcelo R; Ferreira, Nelson Pires; de Morais, Rafael Leite T; Pesquero, João Bosco; Campos, Maria Martha; Couture, Réjean; Morrone, Fernanda Bueno

    2017-12-01

    This study investigated the role of kinins and their receptors in malignant brain tumors. As a first approach, GL-261 glioma cells were injected (2 × 10 5 cells in 2 μl/2 min) into the right striatum of adult C57/BL6 wild-type, kinin B 1 and B 2 receptor knockout (KOB 1 R and KOB 2 R) and B 1 and B 2 receptor double knockout mice (KOB 1 B 2 R). The animals received the selective B 1 R (SSR240612) and/or B 2 R (HOE-140) antagonists by intracerebroventricular (i.c.v.) route at 5, 10, and 15 days. The tumor size quantification, mitotic index, western blot analysis, quantitative autoradiography, immunofluorescence, and confocal microscopy were carried out in brain tumor samples, 20 days after tumor induction. Our results revealed an uncontrolled tumor growing in KOB 1 R or SSR240612-treated mice, which was blunted by B 2 R blockade with HOE-140, suggesting a crosstalk between B 1 R and B 2 R in tumor growing. Combined treatment with B 1 R and B 2 R antagonists normalized the upregulation of tumor B 1 R and decreased the tumor size and the mitotic index, as was seen in double KOB 1 B 2 R. The B 1 R was detected on astrocytes in the tumor, indicating a close relationship between this receptor and astroglial cells. Noteworthy, an immunohistochemistry analysis of tumor samples from 16 patients with glioma diagnosis revealed a marked B 1 R immunopositivity in low-grade gliomas or in older glioblastoma individuals. Furthermore, the clinical data revealed a significantly higher immunopositivity for B 1 R, when compared to a lower B 2 R immunolabeling. Taken together, our results show that blocking simultaneously both kinin receptors or alternatively stimulating B 1 R may be of therapeutic value in the treatment of brain glioblastoma growth and malignancy.

  6. Intrinsic fluorescence spectra characteristics of vitamin B1, B2, and B6

    NASA Astrophysics Data System (ADS)

    Yang, Hui; Xiao, Xue; Zhao, Xuesong; Hu, Lan; Lv, Caofang; Yin, Zhangkun

    2015-11-01

    This paper presents the intrinsic fluorescence characteristics of vitamin B1, B2 and B6 measured with 3D fluorescence Spectrophotometer. Three strong fluorescence areas of vitamin B2 locate at λex/λem=270/525nm, 370/525nm and 450/525nm, one fluorescence areas of vitamin B1 locates at λex/λem=370/460nm, two fluorescence areas of vitamin B6 locates at λex/λem=250/370nm and 325/370nm were found. The influence of pH of solution to the fluorescence profile was also discussed. Using the PARAFAC algorithm, 10 vitamin B1, B2 and B6 mixed solutions were successfully decomposed, and the emission profiles, excitation profiles, central wavelengths and the concentration of the three components were retrieved precisely through about 5 iteration times.

  7. B1 and B2 kinin receptor participation in hyperproliferative and inflammatory skin processes in mice.

    PubMed

    Pietrovski, Evelise Fernandes; Paludo, Kátia Sabrina; Mendes, Daniel Augusto Gasparin Bueno; Guimarães, Fernando de Souza Fonseca; Veiga, Silvio Sanchez; Buchi, Dorly de Freitas; Fonseca, Raphael Gomes; Zampronio, Aleksander Roberto; Bader, Michael; Pesquero, João Bosco; Ferreira, Juliano; Otuki, Michel Fleith; Cabrini, Daniela Almeida

    2011-10-01

    Kinins are released during dermal injury and inflammation and seem to contribute to the pathogenesis of cutaneous diseases. Participation of kinins in skin inflammatory process was evaluated using knockout mice and non-peptide kinin receptor antagonists. Chronic skin inflammation was induced by multiple applications of TPA in mice ear. The B(2) knockout mice (B(2)(-/-)) showed a significant increase of ear weight (23 ± 10%) and epidermal cellular hyperproliferation and acanthosis formation upon histological analysis when compared with wildtype mice. Also, evaluation of PCNA levels by Western blot and immunohistochemistry confirmed the increase in the epidermis hyperproliferation in the ear skin of B(2)(-/-) mice. In contrast, no modification in these parameters was detected in B(1) knockout mice (B(1)(-/-)). However, mice lacking both kinin receptors (B(1)B(2)(-/-)) presented a considerable reduction of epidermis thickness and in PCNA levels. Following the establishment of skin inflammation (5th day of TPA application) treatment with the non-peptide antagonists SSR 240612 (B(1) receptor antagonist), FR 173657 (B(2) receptor antagonist), or SSR 240612 plus FR 173657 topically applied, caused a significant inhibition of ear weight (20 ± 5%, 34 ± 4% and 32 ± 6%, respectively). In the histological analysis, the antagonists produced a reduction in epidermal hyperplasia and acanthosis formation; but the treatment with a combination of the two antagonists did not increase efficacy. Kinin receptors seem to be involved in the control of the keratinocyte hyperproliferative process, and non-peptide kinin receptor antagonists may be useful tools in the treatment of hyperproliferative skin disorders. Copyright © 2011 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

  8. First-principles study of B1 to B2 phase transition in PbS

    NASA Astrophysics Data System (ADS)

    Bhambhani, P.; Munjal, N.; Sharma, G.; Vyas, V.; Sharma, B. K.

    2012-07-01

    The high pressure structural phase transition in PbS has been studied by means of first-principles total energy calculations which are based on linear combination of atomic orbitals (LCAO) method within local density approximation (LDA). In the present study, the exchange scheme of Becke and correlation functional of von-Barth-Hedin (VBH) are employed. It is observed that more stable phase for PbS is NaCl type (B1) and PbS transforms to the CsCl type (B2) structure under high pressure (22.8 GPa). The calculated value of transition pressure (Pt) from B1 to B2 structure is found in good agreement with the earlier experimental and theoretical investigations.

  9. [In vitro study of vitamins B1, B2 and B6 adsorption on zeolite].

    PubMed

    Basić, Zorica; Kilibarda, Vesna; Dobrić, Silva; Resanović, Radmila

    2011-01-01

    Zeolites are the hydratised alumosilicates of alcali and earthalcali cations, which have a long three-dimensional crystal structure. Preparations on the basis of zeolites are used for adsorption of organic and nonorganic toxic substances and they, also, find more and more use in veterinary and human medicine and pharmacy. The aim of this study was to evaluate the possibilities of zeolite to adsorb vitamins B1, B2 and B6 in acid and neutral solutions, as well as the characteristics of the process (saturability, reversibility and competitiveness). The specific and sensitive HPLC method with fluorescent detector was used for determination of vitamins B1, B2 and B6. Analyte separation and detection were carried out by applying the reverse-phase method on column C18. An in vitro experiment was done by testing the influence of pH value (2 and 7), concentration of vitamin solution (1, 2 and 5 mg/L), the length of contact with zeolite (10-180 min) and cation competitiveness on the exchange capacity, which is achieved by media and zeolite contact, as well as a possible vitamins desorption through changing pH value of the solution at 37 degrees C. Jon competitiveness was examined by adding commercial feed mixture (grower) with a defined content of the examined vitamins in zeolite solutions the pH = 2 and pH = 7. Vitamins B1, B2 and B6 were stable in both pH=2 and pH = 7 solutions at 37 degrees C, in the defined time intervals. In acid solution concentrations of vitamins significantly declined in the first 10 min, with no significant decline in further 30 min for all the three concentrations tests. In neutral solution, after the addition of 1% zeolite, decrease in vitamins concentrations was slightly lower than in acid solution, but also significant in the first 10 min of the contact with zeolite. It was found that zeolite, which adsorbed vitamins in acid solution, transferred in the neutral one released a significant quantity of adsorbed vitamins after 30 min of extraction

  10. Cyclin B2-null mice develop normally and are fertile whereas cyclin B1-null mice die in utero

    PubMed Central

    Brandeis, Michael; Rosewell, Ian; Carrington, Mark; Crompton, Tessa; Jacobs, Mary Ann; Kirk, Jane; Gannon, Julian; Hunt, Tim

    1998-01-01

    Two B-type cyclins, B1 and B2, have been identified in mammals. Proliferating cells express both cyclins, which bind to and activate p34cdc2. To test whether the two B-type cyclins have distinct roles, we generated lines of transgenic mice, one lacking cyclin B1 and the other lacking cyclin B2. Cyclin B1 proved to be an essential gene; no homozygous B1-null pups were born. In contrast, nullizygous B2 mice developed normally and did not display any obvious abnormalities. Both male and female cyclin B2-null mice were fertile, which was unexpected in view of the high levels and distinct patterns of expression of cyclin B2 during spermatogenesis. We show that the expression of cyclin B1 overlaps the expression of cyclin B2 in the mature testis, but not vice versa. Cyclin B1 can be found both on intracellular membranes and free in the cytoplasm, in contrast to cyclin B2, which is membrane-associated. These observations suggest that cyclin B1 may compensate for the loss of cyclin B2 in the mutant mice, and implies that cyclin B1 is capable of targeting the p34cdc2 kinase to the essential substrates of cyclin B2. PMID:9539739

  11. Kinetics of the B1-B2 phase transition in KCl under rapid compression

    SciTech Connect

    Lin, Chuanlong; Smith, Jesse S.; Sinogeikin, Stanislav V.

    2016-01-28

    Kinetics of the B1-B2 phase transition in KCl has been investigated under various compression rates (0.03–13.5 GPa/s) in a dynamic diamond anvil cell using time-resolved x-ray diffraction and fast imaging. Our experimental data show that the volume fraction across the transition generally gives sigmoidal curves as a function of pressure during rapid compression. Based upon classical nucleation and growth theories (Johnson-Mehl-Avrami-Kolmogorov theories), we propose a model that is applicable for studying kinetics for the compression rates studied. The fit of the experimental volume fraction as a function of pressure provides information on effective activation energy and average activation volume at amore » given compression rate. The resulting parameters are successfully used for interpreting several experimental observables that are compression-rate dependent, such as the transition time, grain size, and over-pressurization. The effective activation energy (Q{sub eff}) is found to decrease linearly with the logarithm of compression rate. When Q{sub eff} is applied to the Arrhenius equation, this relationship can be used to interpret the experimentally observed linear relationship between the logarithm of the transition time and logarithm of the compression rates. The decrease of Q{sub eff} with increasing compression rate results in the decrease of the nucleation rate, which is qualitatively in agreement with the observed change of the grain size with compression rate. The observed over-pressurization is also well explained by the model when an exponential relationship between the average activation volume and the compression rate is assumed.« less

  12. Fumonisins B1 and B2 in agricultural products consumed in South Korea: an exposure assessment.

    PubMed

    Seo, Eunkyoung; Yoon, Yohan; Kim, Kyeongyeol; Shim, Won-Bo; Kuzmina, Nina; Oh, Keum-Soon; Lee, Jong-Ok; Kim, Dong-Sul; Suh, Junghyuck; Lee, Soo-Hyung; Chung, Kee-Hey; Chung, Duck-Hwa

    2009-02-01

    To survey fumonisins B1 (FB1) and B2 (FB2) in agricultural products consumed in South Korea and provide an exposure assessment, ground samples were extracted (80% MeOH), filtered (0.2 microm), and cleaned up. After evaporation, dry residues were reconstituted in 50% MeOH, and a 50-micro1 aliquot of this sample was mixed with 200 micro1 of o-phthaldialdehyde for derivatization. The derivatives were analyzed with a high-performance liquid chromatography system equipped with a fluorescence detector. For validation of the detection procedure, linearity, accuracy, precision, detection limit, and quantification limit were determined. The validated detection method was then used to survey fumonisins in white rice, brown rice, barley, barley tea, beer, wheat flour, millet, dried corn, corn flour, corn tea, canned corn, popcorn, and breakfast cereal. Retention times for FB1 and FB2 standards were 7 and 18 min, respectively. Linearity (R2 = 0.99995 to 0.99998), accuracy (81.47 to 108.83%), precision (2.35 to 5.77), detection limit (25 ng/g or ng/ml), and quantification limit (37 ng/g or ng/ml) indicated that this procedure is capable of quantifying fumonisins in agricultural products. Only FB1-positive samples (5.12%, three dried corn samples and five corn flour samples) were found at 90.89 to 439.67 ng/g. According the survey results, an estimated daily intake of FB1 and FB2 in Korea was 0.087 ng/kg of body weight per day. These results indicate that continuous monitoring of these mycotoxins is necessary to establish appropriate risk assessment, and the maximum tolerable daily intake of fumonisins in Korea is lower than the 2 microg/kg set by the Joint Food and Agriculture Organization-World Health Organization Expert Committee.

  13. Variability of vitamins B1, B2 and minerals content in baobab (Adansonia digitata) leaves in East and West Africa

    PubMed Central

    Hyacinthe, Traoré; Charles, Parkouda; Adama, Korbo; Diarra, Compaoré-Sérémé; Dicko, Mamoudou H; Svejgaard, Jan J; Diawara, Bréhima

    2015-01-01

    The regional variability and age–age correlation on vitamin B1, vitamin B2 and minerals (Ca, Mg, P, K, Cu, Fe, Mn, Na, and Zn) concentration in baobab leaves were investigated. Baobab was cultivated from seeds from 11 countries including Benin, Burkina Faso, Kenya, Malawi, Mali, Mozambique, Niger, Tanzania, Togo, Senegal, and Sudan. Vitamins B1 and B2 content were assessed using microbiological VitaFast kits methods and minerals by atomic absorption and flame spectrometry methods. Overall, the results showed a higher content of vitamin B2 compared to vitamin B1 with the highest vitamin B2 content (1.04 ± 0.05 mg/100 g DM) from Senegal. The highest iron (Fe) content of 26.39 mg/100 g was found in baobab leaves from Mali. For age–age correlation, adult baobab leaves of Nankoun in Burkina Faso provided the highest calcium (Ca) content of 3373 mg/100 g. However, for provenance trial, young plants from three communities of Burkina Faso showed the highest calcium (Ca) and potassium (K) content. The study demonstrated that vitamins B1 and B2 and mineral contents in baobab leaves vary with the country and the age of the tree. Vitamin B1 content was higher in baobab leaves from ascendants compared to those from descendants, while in contrast vitamin B2 content was higher in the leaves from the descendants compared to their ascendants (mother tree). PMID:25649547

  14. Survey of breakfast and infant cereals for aflatoxins B1, B2, G1 and G2.

    PubMed

    Tam, J; Mankotia, M; Mably, M; Pantazopoulos, P; Neil, R J; Calway, P; Scott, P M

    2006-07-01

    Three hundred and forty-nine breakfast and infant cereal samples were collected at retail level across Canada from 2002 to 2005. They included rice-, soy-, barley-based and mixed-grain infant cereals, corn-, wheat-, rice-based and mixed-grain breakfast cereals, and were analysed for aflatoxins B1, B2, G1 and G2 using a modified AOAC International official method. An immunoaffinity column was used for the cleanup and purification of extracts. Determination of aflatoxins was by LC using post-column derivatization with pyridinium hydrobromide perbromide and fluorescence detection. Results indicated that 50% of both breakfast and infant cereals had detectable levels (limit of detection = 0.002 ng g-1) of aflatoxin B1, which is the most toxic of the four toxins. The levels found varied from 0.002 to 1.00 ng g-1 for aflatoxin B1, from 0.002 to 0.14 ng g-1 for aflatoxin B2, from 0.008 to 0.27 ng g-1 for aflatoxin G1, and from 0.008 to 0.048 ng g-1 for aflatoxin G2. Only 4% of the breakfast cereals and 1% of the infant cereals had aflatoxin B1 levels exceeding 0.1 ng g-1, which is the European Union maximum limit for aflatoxin B1 in baby foods and processed cereal-based foods for infants and young children.

  15. Comparative oncology: ErbB-1 and ErbB-2 homologues in canine cancer are susceptible to cetuximab and trastuzumab targeting

    PubMed Central

    Singer, Josef; Weichselbaumer, Marlene; Stockner, Thomas; Mechtcheriakova, Diana; Sobanov, Yury; Bajna, Erika; Wrba, Friedrich; Horvat, Reinhard; Thalhammer, Johann G.; Willmann, Michael; Jensen-Jarolim, Erika

    2012-01-01

    To facilitate comparative oncology trials we compared the biological and molecular homologies of canine (dog; Canis lupus familiaris) and human tumor-associated antigens ErbB-1 and -2. Further, we investigated whether they could serve as targets for anti-ErbB-1 (cetuximab) and anti-ErbB-2 antibodies (trastuzumab), which are highly relevant in human clinical oncology. Immunohistochemistry of canine mammary cancer showed ErbB-1 overexpression in 3/10 patients and ErbB-2 in 4/10. We report 91% amino acid homology for ErbB-1 and 92% for ErbB-2 between canine and human molecules. Modeling of canine on human ErbB-1 revealed that the cetuximab epitope only differs by 4 amino acids: Lys443 is replaced by Arg, Ser468 by Asn, Gly471 by Asp, and Asn473 by Lys in canines. The trastuzumab binding site is identical in human and canine ErbB-2 apart from a single amino acid change (Pro557 to Ser). Binding of cetuximab and trastuzumab to canine mammary carcinoma cells CF33, CF41, Sh1b and P114 was confirmed by flow cytometry. Both antibodies significantly inhibited canine tumor cell proliferation partly due to growth arrest in G0/G1 phase. We explain the lower efficiency on the tested canine than on human SKBR3 and A431 cells, by a 2-log lower expression level of the canine ErbB-1 and -2 molecules. Our results indicate significant homology of human and canine Erb-1 and -2 tumor associated antigens. The fact that the canine homologues express the cetuximab and trastuzumab epitopes may facilitate antibody-based immunotherapy in dogs. Importantly, the striking similarities of ErbB-1 and -2 molecules open up avenues towards comparative strategies for targeted drug development. PMID:22424313

  16. Recurrent aphthous ulceration: vitamin B1, B2 and B6 status and response to replacement therapy.

    PubMed

    Nolan, A; McIntosh, W B; Allam, B F; Lamey, P J

    1991-09-01

    An evaluation of the thiamine, riboflavin and pyridoxine (vitamin B1, B2 and B6) status of 60 patients with recurrent mouth ulcers was performed. Seventeen patients (28.2%) were found to be deficient in one or more of these vitamins. Replacement therapy of these vitamins was given to a study group of deficient patients and a non-deficient group for one month. At the end of therapy and after a follow-up period of 3 months, only those patients who had a B complex deficiency had a significant sustained clinical improvement in their mouth ulcers. Vitamin B1, B2 and B6 deficiencies should, therefore, be considered as another possible precipitating factor in recurrent aphthous ulceration.

  17. Modelling of three-dimensional structures of cytochromes P450 11B1 and 11B2.

    PubMed

    Belkina, N V; Lisurek, M; Ivanov, A S; Bernhardt, R

    2001-12-15

    The final steps of the biosynthesis of glucocorticoids and mineralocorticoids in the adrenal cortex require the action of two different cytochromes P450--CYP11B1 and CYP11B2. Homology modelling of the three-dimensional structures of these cytochromes was performed based on crystallographic coordinates of two bacterial P450s, CYP102 (P450BM-3) and CYP108 (P450terp). Principal attention was given to the modelling of the active sites and a comparison of the active site structures of CYP11B1 and CYP11B2 was performed. It can be demonstrated that key residue contacts within the active site appear to depend on the orientation of the heme. The obtained 3D structures of CYP11B1 and CYP11B2 were used for investigation of structure-function relationships of these enzymes. Previously obtained results on naturally occurring mutants and on mutants obtained by site-directed mutagenesis are discussed.

  18. Occurrence of Ochratoxins, Fumonisin B2 , Aflatoxins (B1 and B2 ), and Other Secondary Fungal Metabolites in Dried Date Palm Fruits from Egypt: A Mini-Survey.

    PubMed

    Abdallah, Mohamed F; Krska, Rudolf; Sulyok, Michael

    2018-02-01

    This study was conducted to investigate the natural co-occurrence of 295 fungal and bacterial metabolites in 28 samples of dried date palm fruits collected from different shops distributed in Assiut Governorate, Upper Egypt in 2016. Extraction and quantification of the target analytes were done using the "dilute and shoot" approach followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. In total, 30 toxic fungal metabolites were detected. Among these metabolites, 4 types of ochratoxins including ochratoxin type A and B were quantified in 3 samples (11%) with a contamination range from 1.48 to 6070 μg/kg for ochratoxin A and from 0.28 to 692 μg/kg for ochratoxin B. In addition, fumonisin B 2 was observed in 2 (7%) samples with contamination levels ranging from 4.99 to 16.2 μg/kg. The simultaneous detection of fumonisin B 2 in the same contaminated samples with ochratoxins indicates the fungal attack by Aspergillus niger species during storage. Only 1 sample was contaminated with aflatoxin B 1 (14.4 μg/kg) and B 2 (2.44 μg/kg). The highest maximum concentration (90400 μg/kg) was for kojic acid that contaminated 43% of the samples. To the best of the authors' knowledge, this is the first report of the natural co-occurrence of fumonisin B 2 and ochratoxin A and B in addition to a wide range of other fungal metabolites in date palm fruits. Mycotoxins are secondary metabolites produced by different fungi. These metabolites pose a potential risk on human health since they contaminate many food commodities. Among these, date palm fruits which are an integral part of diet in several countries. Therefore, detection of mycotoxins is a prerequisite to insure the safety of food. Here, different types of mycotoxins have been detected in levels that may have health hazard. © 2018 Institute of Food Technologists®.

  19. Biocontrol of aflatoxins B1, B2, G1, G2, and fumonisin B1 with 6,7-dimethoxycoumarin, a phytoalexin from Citrus sinensis.

    PubMed

    Mohanlall, Viresh; Odhav, Bharti

    2006-09-01

    Phytoalexins (stress-induced compounds) from Citrus sinensis cultivar Valencia were screened for antifungal and antimycotoxic activity against a test organism (Cladosporium cladosporoides) and mycotoxin-producing fungi Fusarium verticillioides and Aspergillus parasiticus. The active compound, a member of the coumarin family of compounds, has antifungal and antimycotoxic activities and was chemically identified. High-performance liquid chromatography results indicated that Valencia oranges contain a trace amount (0.36 microg/g) of scoparone in untreated fruit, but concentrations increased in UV-irradiated fruit (15.2 microg/g). Infection with Penicillium digitatum, a natural spoilage mold of citrus fruit, caused a 35.51-microg/g increase in the phytoalexin. UV absorption, infrared absorption, and 1H nuclear magnetic resonance spectroscopy revealed that this phytoalexin is identical to 6,7-dimethoxycoumarin. This is the first report indicating that the stress-induced compound, 6,7-dimethoxycoumarin, isolated from P. digitatum-infected Valencia fruit confers resistance against the mycotoxigenic fungi A. parasiticus and F. verticillioides and causes a reduction in production of fumonisin B1 and aflatoxins G1, G2, B1, and B2.

  20. Influence of nanosized amorphous silica on assimilation of vitamins B1, B2 and B6 in rats.

    PubMed

    Gmoshinsky, I V; Vrzhesinskaya, O A; Shumakova, A A; Shipelin, V A; Kodentsova, V M; Khotimchenko, S A

    2016-01-01

    Amorphous silica (SiO2) in the form of nanoparticles (NPs) is widely used as a food additive E551 in many enriched foods and food supplements. The aim of this study was to evaluate the effect of oral administration of SiO2 NPs on assimilation and metabolism of vitamins B1, B2 and B6 in laboratory rats. Amorphous SiO2 «Orisil-300 ®» was used with the size of the primary NPs 20-60 nm according to the electronic, atomic force microscopy and dynamic light scattering. The experiment was conducted on 8 groups of growing male Wistar rats (with initial body weight 70-80g) number, respectively, 7, 7, 10, 10, 12, 12, 14 and 16 animals. Animals of the 1st, 3rd, 4th and 5th groups received through­out the experiment balanced semi-synthetic diet. Animals of the 2nd group received a diet depleted of vitamins B1, B2 and B6 until day 21; animals of the 6th, 7th and 8th groups -the same diet from the 1st to the 21th day, and then, before the closure of the experiment, the diet provided with the indicated B vitamins at 100% of normal level. From day 22 of experiment and until the end at day 29 the animals of the 3rd and 6th groups received deionized water (placebo) through intragastric gavage; rat of the 4th and 7th groups -aqueous suspension of SiO2 dose of 1 mg/kg body weight /day, and the 5th and 8th group -100 mg/kg/day. Urinary excretion of thiamine, riboflavin, 4-pyridoxilic acid and liver and brain content of vitamins B1 and B2 (after acid and enzyme hydrolysis) were deter­mined by fluorimetric methods. It was found that rats in group 2 lagged in weight gain at day 21 significantly compared to group 1, and developed a marked deficiency of vitamins B1, B2 and B6 according to studied safety parameters. In groups from 6 to 8 at day 29 par­tial recovery was achieved in vitamin status. Administration of SiO2 to animal of groups 4 and 5, with normal consumption of B vitamins, had no significant effect on any param­eters of vitamin status in comparison to group 3. However

  1. The 3A2, 1A2, 3B2, and 1B2 electronic states of CH2: Small bond angle states

    NASA Astrophysics Data System (ADS)

    Yamaguchi, Yukio; Schaefer, Henry F., III

    1997-02-01

    Molecular structures with very small bond angles are a curiosity in chemistry. The two triplet (3A2 and 3B2) and two singlet (1A2 and 1B2) excited states of CH2 have been investigated systematically using ab initio electronic structure theory. For these four states total energies and physical properties including geometries, dipole moments, harmonic vibrational frequencies, and associated infrared intensities were determined with the single and double excitation configuration interaction (CISD) method using four different basis sets. It is confirmed in this study that the four states of CH2 all have bent structures with longer CH bond lengths and smaller bond angles than the four lower-lying (X˜, ã, b˜, and c˜) states of CH2. At the CISD optimized geometries single point energies were determined with complete active space self-consistent-field (CASSCF) and CASSCF second-order configuration interaction (SOCI) levels of theory. For the triplet excited states single point energies were also determined employing coupled cluster with single and double excitations (CCSD) and CCSD with perturbative triple excitations methods. At the CISD level with the largest basis set, the triple zeta plus triple polarizations with two sets of higher angular momentum and two sets of diffuse functions basis set [TZ3P(2 f,2d)+2diff], the bond angles were predicted to be 40.6° (3A2), 46.1° (1A2), 76.3° (3B2), and 81.3° (1B2), while the dipole moments were determined to be 2.35 (3A2), 2.26 (1A2), 1.69 (3B2), and 1.60 debye (1B2), respectively. With the most accurate method in this study, the CASSCF-SOCI level with the TZ3P(2 f,2d)+2diff basis set, the energy separations (Te value) between the ground state (X˜ 3B1) and the four excited states were predicted to be 73.7 kcal/mol (3.20 eV, 25 800 cm-1) for the 3A2 state, 96.8 kcal/mol (4.20 eV, 33 800 cm-1) for the 1A2 state, 151.0 kcal/mol (6.55 eV, 52 800 cm-1) for the 3B2 state, and 182.5 kcal/mol (7.91 eV, 63 800 cm-1) for the 1B2

  2. Application of renewable silver amalgam annular band electrode to voltammetric determination of vitamins C, B1 and B2.

    PubMed

    Baś, Bogusław; Jakubowska, Małgorzata; Górski, Łukasz

    2011-05-30

    In this work, the design and results of applying silver liquid amalgam film-modified silver solid amalgam annular band electrode (AgLAF-AgSAE), refreshed before each measurement, to voltammetric determination of vitamins C (VC), B(1) (VB1) and B(2) (VB2) are presented. The method is based on adsorptive accumulation of analytes at the AgLAF-AgSAE in a phosphate buffer (VB1), phosphate buffer with Triton X-100 (VB2) and an alkaline borate buffer with Triton X-100 (VC). The analytical parameters and procedure of electrode activation were optimized. The calibration graphs obtained for vitamins C, B(1) and B(2) are linear, respectively, for concentration range 0.05-12, 0.01-0.1 and 0.05-3 mg L(-1). The detection limits were calculated and equaled 0.02, 0.003 and 0.009 mg L(-1), while repeatability of the peak current was 2%, 1% and 3%, respectively. These results are comparable with results obtained for polarographic determination of the same vitamins using mercury electrodes. Finally, the AgLAF-AgSAE was applied to the determination of vitamins in pharmaceutical samples and fruit juices with satisfactory results. Copyright © 2011 Elsevier B.V. All rights reserved.

  3. 20 CFR Appendix B to Part 718 - Standards for Administration and Interpretation of Pulmonary Function Tests. Tables B1, B2, B3...

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... Interpretation of Pulmonary Function Tests. Tables B1, B2, B3, B4, B5, B6. B Appendix B to Part 718 Employees... Pulmonary Function Tests. Tables B1, B2, B3, B4, B5, B6. The following standards are established in... interpreting ventilatory function tests and that the best available medical evidence will be submitted in...

  4. 20 CFR Appendix B to Part 718 - Standards for Administration and Interpretation of Pulmonary Function Tests. Tables B1, B2, B3...

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... Interpretation of Pulmonary Function Tests. Tables B1, B2, B3, B4, B5, B6. B Appendix B to Part 718 Employees... Pulmonary Function Tests. Tables B1, B2, B3, B4, B5, B6. The following standards are established in... interpreting ventilatory function tests and that the best available medical evidence will be submitted in...

  5. 20 CFR Appendix B to Part 718 - Standards for Administration and Interpretation of Pulmonary Function Tests. Tables B1, B2, B3...

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... Interpretation of Pulmonary Function Tests. Tables B1, B2, B3, B4, B5, B6. B Appendix B to Part 718 Employees... Pulmonary Function Tests. Tables B1, B2, B3, B4, B5, B6. The following standards are established in... interpreting ventilatory function tests and that the best available medical evidence will be submitted in...

  6. 20 CFR Appendix B to Part 718 - Standards for Administration and Interpretation of Pulmonary Function Tests. Tables B1, B2, B3...

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... Interpretation of Pulmonary Function Tests. Tables B1, B2, B3, B4, B5, B6. B Appendix B to Part 718 Employees... Pulmonary Function Tests. Tables B1, B2, B3, B4, B5, B6. The following standards are established in... interpreting ventilatory function tests and that the best available medical evidence will be submitted in...

  7. Uncommon occurrence ratios of aflatoxin B1, B 2, G 1, and G 2 in maize and groundnuts from Malawi.

    PubMed

    Matumba, Limbikani; Sulyok, Michael; Njoroge, Samuel M C; Njumbe Ediage, Emmanuel; Van Poucke, Christof; De Saeger, Sarah; Krska, Rudolf

    2015-02-01

    We report an unusual aflatoxin profile in maize and groundnuts from Malawi, with aflatoxin G1 found routinely at equal or even higher levels than aflatoxin B1. Aflatoxin B1 (AFB1) ratio in a contaminated sample is generally greater than 50% of total aflatoxin (sum of aflatoxin B1, B2, G1, and G2). In Malawi, the aflatoxin occurrence ratios were determined by examining LC-MS/MS and HPLC fluorescence detection (FLD) data of 156 naturally contaminated raw maize and 80 groundnut samples collected in 2011 and 2012. Results showed that natural aflatoxin occurrence ratio differed. In 47% of the samples, the concentration of AFG1 was higher than that of AFB1. The mean concentration percentages of AFB1/AFB2/AFG1/AFG2 in reference to total aflatoxins were found to be 47:5:43:5%, respectively. The AFG1 and AFB1 50/50 trend was observed in maize and groundnuts and was consistent for samples collected in both years. If the AFB1 measurement was used to check compliance of total aflatoxin regulatory limit set at 10, 20, 100, and 200 μg/kg with an assumption that AFB1≥50% of the total aflatoxin content, 8, 13, 24, and 26% false negative rates would have occurred respectively. It is therefore important for legislation to consider total aflatoxins rather than AFB1 alone.

  8. Monitoring of aflatoxin G1, B1, G2, and B2 occurrence in some samples of walnut.

    PubMed

    Habibipour, Reza; Tamandegani, Parisa Rahimi; Farmany, Abbas

    2016-12-01

    This research was conducted to monitor the aflatoxigenic fungi and aflatoxin contamination of walnut in the Hamedan province. For this purpose, 40 samples were analyzed. Aspergillus, Alternaria, Rhizopus, Cladosporium, Fusarium, yeast, and some different bacteria were isolated from walnuts. Aspergillus is the most frequent genus. Aspergillus flavus was predominantly isolated. HPLC was used for evaluation of aflatoxin contamination of walnut samples. Aflatoxins G1 (AFG1), B1 (AFB1), G2 (AFG2), and B2 (AFB2) were produced by 20 isolates. AFG1 and AFB1 were being predominant at concentration ranges of 1.7-18.2 and 0-8.2 ngg -1 , respectively. Highest levels were found in one sample that was highly contaminated with Aspergillus flavus/Aspergillus parasiticus. Methyl beta cyclodextrin also was performed for detection of aflatoxigenic Aspergillus isolates. The results showed that only 31.6% (p < 0.05) of A. flavus and A. parasiticus isolates were able to produce aflatoxin. A significant difference was shown between shielded and unshielded walnut in aflatoxin contamination. The content of aflatoxin in most of the walnut samples did not reach to maximum tolerable limit for aflatoxin B1 in EU standard (p > 0.05). Thus, systematic and continues monitoring of walnuts is recommended.

  9. Effects of kinin B1 and B2 receptor antagonists on overactive urinary bladder syndrome induced by spinal cord injury in rats

    PubMed Central

    Forner, Stefânia; Andrade, Edinéia L; Martini, Alessandra C; Bento, Allisson F; Medeiros, Rodrigo; Koepp, Janice; Calixto, João B

    2012-01-01

    Background and Purpose Kinin B1 and B2 receptors have been implicated in physiological and pathological conditions of the urinary bladder. However, their role in overactive urinary bladder (OAB) syndrome following spinal cord injury (SCI) remains elusive. Experimental Approach We investigated the role of kinin B1 and B2 receptors in OAB after SCI in rats. Key Results SCI was associated with a marked inflammatory response and functional changes in the urinary bladder. SCI resulted in an up-regulation of B1 receptor mRNA in the urinary bladder, dorsal root ganglion and spinal cord, as well as in B1 protein in the urinary bladder and B1 and B2 receptor protein in spinal cord. Interestingly, both B1 and B2 protein expression were similarly distributed in detrusor muscle and urothelium of animals with SCI. In vitro stimulation of urinary bladder with the selective B1 or B2 agonist elicited a higher concentration-response curve in the SCI urinary bladder than in naive or sham urinary bladders. Cystometry revealed that treatment of SCI animals with the B2 selective antagonist icatibant reduced the amplitude and number of non-voiding contractions (NVCs). The B1 antagonist des-Arg9-[Leu8]-bradykinin reduced the number of NVCs while the non-peptide B1 antagonist SSR240612 reduced the number of NVCs, the urinary bladder capacity and increased the voiding efficiency and voided volume. Conclusions and Implications Taken together, these data show the important roles of B1 and B2 receptors in OAB following SCI in rats and suggest that blockade of these receptors could be a potential therapeutic target for controlling OAB. PMID:22862305

  10. 75 FR 65222 - Airworthiness Directives; Eurocopter France Model AS 350 B, BA, B1, B2, B3, and D, and Model...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-22

    ... CONTACT: J. R. Holton, Aviation Safety Engineer, FAA, Rotorcraft Directorate, Regulations and Guidance... Eurocopter France Model AS 350 B, BA, BB, B1, B2, B3, and D, and Model AS355 E, F, F1, F2, and N helicopters... to Model AS 350 B, BA, BB, B1, B2, B3, and D helicopters, and EASB No. 01.00.53, applicable to Model...

  11. 75 FR 34062 - Airworthiness Directives; Eurocopter France Model AS 350 B, BA, B1, B2, B3, and D, and Model...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-16

    ... Internet at http://www.regulations.gov . FOR FURTHER INFORMATION CONTACT: J.R. Holton, Aviation Safety... an unsafe condition for certain Eurocopter France Model AS 350 B, BA, BB, B1, B2, B3, and D, and..., BB, B1, B2, B3, and D helicopters, and EASB No. 01.00.53, applicable to Model AS355 E, F, F1, F2, and...

  12. Removal of fumonisin B1 and B2 from model solutions and red wine using polymeric substances.

    PubMed

    Carrasco-Sánchez, Verónica; Kreitman, Gal Y; Folch-Cano, Christian; Elias, Ryan J; Laurie, V Felipe

    2017-06-01

    Fumonisins are a group of mycotoxins found in various foods whose consumption is known to be harmful for human health. In this study, we evaluated the ability of three polymers (Polyvinylpolypyrrolidone, PVPP; a resin of N-vinyl-2-pyrrolidinone with ethylene glycol dimethacrylate and triallyl isocyanurate, PVP-DEGMA-TAIC; and poly(acrylamide-co-ethylene glycol-dimethacrylate), PA-EGDMA) to remove fumonisin B 1 (FB1) and fumonisin B 2 (FB2) from model solutions and red wine. Various polymer concentrations (1, 5 and 10mgmL -1 ) and contact times (2, 8 and 24h) were tested, with all polymers exhibiting fumonisin removal capacities (monitored by LC-MS). The impact of all polymers on polyphenol removal was also assessed. PA-EGDMA showed to be the most promising polymer, removing 71% and 95% of FB 1 , and FB 2 , respectively, with only a 22.2% reduction in total phenolics. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Effect of dietary acids on the formation of aflatoxin B2a as a means to detoxify aflatoxin B1.

    PubMed

    Rushing, Blake R; Selim, Mustafa I

    2016-09-01

    Aflatoxin B1 (AFB1) is a class 1 carcinogen and a common food contaminant worldwide with widely uncontrolled human exposure. The ability of organic acids to transform AFB1 into a known detoxified form, aflatoxin B2a (AFB2a), was investigated using high performance liquid chromatography-electrospray ionisation-time of flight mass spectrometry (HPLC/ESI/TOF/MS). The identity of the transformation product was confirmed by accurate mass measurement, chromatographic separation from other aflatoxins, H(1)-nuclear magnetic resonance (NMR) and infrared (IR) spectroscopy. Of the weak acids tested, citric acid was found to be the most effective for AFB2a formation. At room temperature, 1 M citric acid was able to convert > 97% of AFB1 to AFB2a over 96 h of treatment. Up to 98% transformation was achieved by boiling AFB1 in the presence of citric acid for 20 min. AFB1 hydration after ingestion was explored by spiking AFB1 into simulated gastric fluid containing citric acid. Under these conditions, > 71% of AFB1 was hydrated to AFB2a and did not show any reversion to the parent compound after being transferred to a neutral solution. These results provide a basis for a practical and effective method for detoxification of AFB1 in contaminated foods.

  14. Analgesic effects of microRNA-129-5p against bone cancer pain through the EphB1/EphrinB2 signaling pathway in mice.

    PubMed

    Yu, Shao-Nan; Liu, Gui-Feng; Li, Long-Yun; Zhao, Guo-Qing; Liu, Lin; Li, Xue-Feng

    2017-12-13

    The study aims to investigate the analgesic effects of microRNA-129-5p (miR-129-5p) on bone cancer pain (BCP) by targeting Eph receptor B1 (EphB1) through the EphB1/EphrinB2 signaling pathway. BCP mice models were established, and C3H/HeJ female mice were classified into the normal, blank, negative control (NC), miR-129-5p mimics, miR-129-5p inhibitors, EphB1 knockout (KO), and miR-129-5p inhibitors + EphB1 KO groups. RT-qPCR and western blotting were used to evaluate miR-129-5p expression, and mRNA and protein expressions of EphB1, p-EphB1, EphrinB2 and p-EphrinB2. EphB1 and EphrinB2 were highly activated in the tibias of BCP mice 7 days after operation. EphB1 is a target gene of miR-129-5p. The mechanical withdrawal threshold increased in the miR-129-5p mimics, EphB1 KO and miR-129-5p inhibitors + EphB1 KO groups, but decreased in the miR-129-5p inhibitors group. Compared with the blank and the NC groups, the expression of miR-129-5p was significantly increased in the miR-129-5p mimics group, and the mRNA and protein expressions of EphrinB2, p-EphrinB2, EphB1 and p-EphB1 were significantly decreased, while in the miR-129-5p inhibitors group, the results were opposite (all P < 0.05); the mRNA and protein expressions of EphrinB2, p-EphrinB2, EphB1 and p-EphB1 were significantly decreased in the EphB1 KO group (all P < 0.05); the expression of miR-129-5p was significantly decreased in the miR-129-5p inhibitors + EphB1 KO group (P < 0.05), while the mRNA and protein expressions of EphrinB2 and p-EphrinB2 were not significantly different (P > 0.05). The results indicated that up-regulated miR-129-5p alleviates BCP via down-regulation of the EphB1/EphrinB2 signaling pathway. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  15. The use of regenerated immunoaffinity columns for aflatoxins B1, B2, G1and G2in peanut confection.

    PubMed

    Iha, Maria Helena; Mini, Camila Alessandra; Okada, Isaura Akemi; Briganti, Rita de Cássia; Trucksess, Mary W

    2017-02-03

    The aim of this study was to investigate the feasibility of using multitime-regenerated immunoaffinity column (IAC) for aflatoxins B 1 , B 2 , G 1 and G 2 in peanut confection. After each use, the IAC was washed immediately with phosphate-buffered saline and stored for >12h prior to reuse. The evaluation procedure consisted of using extracts of naturallycontaminated peanut confection (4 replicates), aflatoxin-free peanut confection (duplicates), and aflatoxin-free peanut confection sample spiked with the 4 aflatoxins (AFT) at 3 levels in 4 replicates. Each day, 18 test extracts were analyzed using 18 designated IACs. After each use, the IACs were regenerated and reused for corresponding test extracts on the following day. This procedure was repeated daily over the course of 9days. Analytical steps included passing the test extracts through the IACs, washing the columns with water, and eluting AFT with methanol. The eluates were diluted with water and were subjected to reversed phase LC separation, post-column photochemical derivatization and fluorescence detection. After eluting AFT, IACs were immediately regenerated by washing with phosphate buffer solution and storing overnight at 8°C for re-use the following day. Results were analyzed using ANOVA and Tukey tests. The numbers of reuse varied for each AF: For AFB 1 AFB 2 , AFG 1 and AFG 2 could be reused for 9, 6, 6 and 0 times, respectively. According to AOAC method performance criteria, recoveries ranging from 70% to 125% are considered acceptable at the spiking levels used in this study. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Pharmacophore modeling and in silico / in vitro screening for human cytochrome P450 11B1 & cytochrome P450 11B2 inhibitors

    NASA Astrophysics Data System (ADS)

    Akram, Muhammad; Waratchareeyakul, Watcharee; Haupenthal, Joerg; Hartmann, Rolf W.; Schuster, Daniela

    2017-12-01

    Cortisol synthase (CYP11B1) is the main enzyme for the endogenous synthesis of cortisol and its inhibition is a potential way for the treatment of diseases associated with increased cortisol levels, such as Cushing’s syndrome, metabolic diseases, and delayed wound healing. Aldosterone synthase (CYP11B2) is the key enzyme for aldosterone biosynthesis and its inhibition is a promising approach for the treatment of congestive heart failure, cardiac fibrosis, and certain forms of hypertension. Both CYP11B1 and CYP11B2 are structurally very similar and expressed in the adrenal cortex. To facilitate the identification of novel inhibitors of these enzymes, ligand-based pharmacophore models of CYP11B1 and CYP11B2 inhibition were developed. A virtual screening of the SPECS database was performed with our pharmacophore queries. Biological evaluation of the selected hits lead to the discovery of three potent novel inhibitors of both CYP11B1 and CYP11B2 in the submicromolar range (compounds 8-10), one selective CYP11B1 inhibitor (Compound 11, IC50 = 2.5 µM), and one selective CYP11B2 inhibitor (compound 12, IC50 = 1.1 µM), respectively. The overall success rate of this prospective virtual screening experiment is 20.8% indicating good predictive power of the pharmacophore models.

  17. 76 FR 28637 - Airworthiness Directives; Eurocopter France Model AS350B, B1, B2, B3, BA, and EC130 B4 Helicopters

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-18

    ..., dated February 6, 2009, for the Model AS350B, BA, BB, B1, B2, and B3 helicopters; and ASB No. 80A003, Revision 1, dated February 6, 2009, for the Model EC130 B4 helicopters. The Model AS350 BB helicopter is.... Material Incorporated by Reference (j) You must use the specified portions of Eurocopter Alert Service...

  18. Optimization of chromatographic conditions for determination of aflatoxin B1, B2, G1 and G2 by using liquid chromatography-mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Ramadhaningtyas, Dillani Putri; Aryana, Nurhani; Aristiawan, Yosi; Styarini, Dyah

    2017-11-01

    The optimization of instrument condition and chromatographic separation for analysis of aflatoxin B1, B2, G1 and G2 using liquid chromatography tandem with mass spectrometer detector was conducted in the aim to provide more accurate and reliable analysis results. The aflatoxin known to be serious threat for human health as it is classified as the carcinogenic compounds. The aflatoxin B1, B2, G1 and G2 were selected due to its extensive contamination in various agricultural commodities. The best chromatographic separation was obtained using C-18 column with gradient elution of solvent 5 mM ammonium acetate and 0.1% formic acid in methanol at 7 minutes runtime analysis. The linearity of the detector showed satisfied results as the coefficient determination found to be 0.9994, 0.9996, 0.9998 and 0.9987 for aflatoxin B1, G1, B2, and G2 respectively in the range concentration from 1 to 20 ng/g. The quantifier ion selected for the aflatoxin B1, B2, G1 and G2 was m/z 285.1, 259, 243 and 313 respectively. The instrument precision at these quantifier ions also showed satisfied result with %RSD was around 3.4 to 6.8%. The optimized method present in this study can be used for further sample analysis.

  19. Role of Polycomb RYBP in Maintaining the B-1-to-B-2 B-Cell Lineage Switch in Adult Hematopoiesis

    PubMed Central

    Pavón, Leticia; Starowicz, Katarzyna; Pérez, Claudia; Bravo, Mónica; Ikawa, Tomokatsu; Koseki, Haruhiko

    2015-01-01

    Polycomb chromatin modifiers regulate hematopoietic pluripotent stem and progenitor cell self-renewal and expansion. Polycomb complex redundancy and biochemical heterogeneity complicate the unraveling of the functional contributions of distinct components. We have studied the hematopoietic activity of RYBP, a direct interactor and proposed modulator of RING1A/RING1B-dependent histone H2A monoubiquitylation (H2AUb). Using a mouse model to conditionally inactivate Rybp in adult hematopoiesis, we have found that RYBP deletion results in a reversion of B-1-to-B-2 B-cell progenitor ratios, i.e., of the innate (predominantly fetal) to acquired (mostly adult) immunity precursors. Increased numbers of B-1 progenitors correlated with a loss of pre-proB cells, the B-2 progenitors. RYBP-deficient stem and progenitor cell populations (LKS) and isolated common lymphoid progenitors (CLP) gave rise to increased numbers of B-1 progenitors in vitro. Rybp inactivation, however, did not result in changes of global H2AUb and did not interact genetically with Ring1A or Ring1B deletions. These results show that a sustained regulation of the B-1-to-B-2 switch is needed throughout adult life and that RYBP plays an important role in keeping B-2 dominance, most likely independently of its Polycomb affiliation. PMID:26711264

  20. Biological Roles of Hydroxysteroid (11-Beta) Dehydrogenase 1 (HSD11B1), HSD11B2, and Glucocorticoid Receptor (NR3C1) in Sheep Conceptus Elongation.

    PubMed

    Brooks, Kelsey; Burns, Gregory; Spencer, Thomas E

    2015-08-01

    In sheep, the elongating conceptus synthesizes and secretes interferon tau (IFNT) as well as prostaglandins (PGs) and cortisol. The enzymes, hydroxysteroid (11-beta) dehydrogenase 1 (HSD11B1) and HSD11B2 interconvert cortisone and cortisol. In sheep, HSD11B1 is expressed and active in the conceptus trophectoderm as well as in the endometrial luminal epithelia; in contrast, HSD11B2 expression is most abundant in conceptus trophectoderm. Cortisol is a biologically active glucocorticoid and ligand for the glucocorticoid receptor (NR3C1 or GR) and mineralocorticoid receptor (NR3C2 or MR). Expression of MR is not detectable in either the ovine endometrium or conceptus during early pregnancy. In tissues that do not express MR, HSD11B2 protects cells from the growth-inhibiting and/or proapoptotic effects of cortisol, particularly during embryonic development. In study one, an in utero loss-of-function analysis of HSD11B1 and HSD11B2 was conducted in the conceptus trophectoderm using morpholino antisense oligonucleotides (MAOs) that inhibit mRNA translation. Elongating, filamentous conceptuses were recovered on Day 14 from ewes infused with control morpholino or HSD11B2 MAO. In contrast, HSD11B1 MAO resulted in severely growth-retarded conceptuses or conceptus fragments with apoptotic trophectoderm. In study two, clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 genome editing was used to determine the role of GR in conceptus elongation and development. Elongating, filamentous-type conceptuses (12-14 cm in length) were recovered from ewes gestating control embryos (n = 7/7) and gestating GR-edited embryos (n = 6/7). These results support the idea that the effects of HSD11B1-derived cortisol on conceptus elongation are indirectly mediated by the endometrium and are not directly mediated through GR in the trophectoderm. © 2015 by the Society for the Study of Reproduction, Inc.

  1. Development of CYP11B1 and CYP11B2 assays utilizing homogenates of adrenal glands: Utility of monkey as a surrogate for human.

    PubMed

    Cerny, Matthew A; Csengery, Alexander; Schmenk, Jennifer; Frederick, Kosea

    2015-11-01

    Elevated levels of aldosterone are associated with arterial hypertension, congestive heart failure, chronic kidney disease, and obesity. Aldosterone is produced predominantly in the zona glomerulosa of the cortex of the adrenal gland by the enzyme aldosterone synthase (CYP11B2). Treatment of the above indications by decreasing production of aldosterone is thought to be of therapeutic benefit by lessening the deleterious effects of aldosterone mediated through both the mineralocorticoid receptor and also through so called non-genomic pathways. However, inhibition of the highly similar enzyme, CYP11B1, which is responsible for the production of cortisol, must be avoided in the development of clinically useful aldosterone synthase inhibitors due to the resulting impairment of the cortisol-induced stress response. In efforts to assess the interactions of compounds with the CYP11B enzymes, a variety of cell-based inhibitor screening assays for both CYP11B1 and CYP11B2 have been reported. Herein we report details of assays employing both cynomolgus monkey adrenal homogenate (CAH) and human adrenal homogenate (HAH) as sources of CYP11B1 and CYP11B2 enzymes. Utilizing both CAH and HAH, we have characterized the kinetics of the CYP11B1-mediated conversion of 11-deoxycortisol to cortisol and the CYP11B2-mediated oxidation of corticosterone to aldosterone. Inhibition assays for both CYP11B1 and CYP11B2 were subsequently developed. Based on a comparison of human and monkey amino acid sequences, kinetics data, and inhibition values derived from the HAH and CAH assays, evidence is provided in support of using cynomolgus monkey tissue-derived cell homogenates as suitable surrogates for the human enzymes. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. A Common Origin for B-1a and B-2 Lymphocytes in Clonal Pre- Hematopoietic Stem Cells.

    PubMed

    Hadland, Brandon K; Varnum-Finney, Barbara; Mandal, Pankaj K; Rossi, Derrick J; Poulos, Michael G; Butler, Jason M; Rafii, Shahin; Yoder, Mervin C; Yoshimoto, Momoko; Bernstein, Irwin D

    2017-06-06

    Recent evidence points to the embryonic emergence of some tissue-resident innate immune cells, such as B-1a lymphocytes, prior to and independently of hematopoietic stem cells (HSCs). However, whether the full hematopoietic repertoire of embryonic HSCs initially includes these unique lineages of innate immune cells has been difficult to assess due to lack of clonal assays that identify and assess HSC precursor (pre-HSC) potential. Here, by combining index sorting of single embryonic hemogenic precursors with in vitro HSC maturation and transplantation assays, we analyze emerging pre-HSCs at the single-cell level, revealing their unique stage-specific properties and clonal lineage potential. Remarkably, clonal pre-HSCs detected between E9.5 and E11.5 contribute to the complete B cell repertoire, including B-1a lymphocytes, revealing a previously unappreciated common precursor for all B cell lineages at the pre-HSC stage and a second embryonic origin for B-1a lymphocytes. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  3. Betacellulin-Induced Beta Cell Proliferation and Regeneration Is Mediated by Activation of ErbB-1 and ErbB-2 Receptors

    PubMed Central

    Oh, Yoon Sin; Shin, Seungjin; Lee, Youn-Jung; Kim, Eung Hwi; Jun, Hee-Sook

    2011-01-01

    Background Betacellulin (BTC), a member of the epidermal growth factor family, is known to play an important role in regulating growth and differentiation of pancreatic beta cells. Growth-promoting actions of BTC are mediated by epidermal growth factor receptors (ErbBs), namely ErbB-1, ErbB-2, ErbB-3 and ErbB-4; however, the exact mechanism for beta cell proliferation has not been elucidated. Therefore, we investigated which ErbBs are involved and some molecular mechanisms by which BTC regulates beta cell proliferation. Methodology/Principal Findings The expression of ErbB-1, ErbB-2, ErbB-3, and ErbB-4 mRNA was detected by RT-PCR in both a beta cell line (MIN-6 cells) and C57BL/6 mouse islets. Immunoprecipitation and western blotting analysis showed that BTC treatment of MIN-6 cells induced phosphorylation of only ErbB-1 and ErbB-2 among the four EGF receptors. BTC treatment resulted in DNA synthetic activity, cell cycle progression, and bromodeoxyuridine (BrdU)-positive staining. The proliferative effect was blocked by treatment with AG1478 or AG825, specific tyrosine kinase inhibitors of ErbB-1 and ErbB-2, respectively. BTC treatment increased mRNA and protein levels of insulin receptor substrate-2 (IRS-2), and this was blocked by the ErbB-1 and ErbB-2 inhibitors. Inhibition of IRS-2 by siRNA blocked cell cycle progression induced by BTC treatment. Streptozotocin-induced diabetic mice injected with a recombinant adenovirus expressing BTC and treated with AG1478 or AG825 showed reduced islet size, reduced numbers of BrdU-positive cells in the islets, and did not attain BTC-mediated remission of diabetes. Conclusions/Significance These results suggest that BTC exerts proliferative activity on beta cells through the activation of ErbB-1 and ErbB-2 receptors, which may increase IRS-2 expression, contributing to the regeneration of beta cells. PMID:21897861

  4. ASSESSMENT OF INTAKE AND NUTRITIONAL STATUS OF VITAMIN B1, B2, AND B6 IN MEN AND WOMEN WITH DIFFERENT PHYSICAL ACTIVITY LEVELS

    PubMed Central

    Hübner-Wozniak, E.; Lewandowska, I.

    2013-01-01

    The purpose of the present study was to examine the nutritional status of vitamin B1, B2, and B6 in respect to dietary intake of these vitamins and activity coefficients of the erythrocyte enzymes transketolase, glutathione reductase, and aspartic aminotransferase in young men and women with different physical activity levels. The participants of this study were 20 women and 20 men with high physical activity (groups HAW and HAM, respectively), and 20 women and 20 men with low physical activity (groups LAW and LAM, respectively). The intake of vitamins B1, B2, B6, proteins, and calorie content of the diet was based on the average of the 4-day dietary recalls. To assess nutritional status of vitamin B1, B2, and B6, the activity coefficients (α) of erythrocyte transketolase (ETK), erythrocyte glutathione reductase (EGR), and erythrocyte aspartic aminotransferase (EAST) were estimated in blood hemolysates. The intake of the studied vitamins in the diet was statistically significantly lower in the female groups compared with the respective male groups. Deficiency of vitamin B6 in the diet was present more often in women than in men (in terms of the recommended dietary allowances [RDA]). Values of the activity coefficient αETK indicated that none of the groups in this study suffered the risk of vitamin B1 deficiency. The value of the activity coefficient αEGR indicated that the groups of women and men with low physical activity were more prone to vitamin B2 deficiency compared with the high physical activity groups. The risk of vitamin B6 deficiency (αEAST) in both male groups was higher than in both female groups. The obtained results do not allow for unequivocal determination of the impact of sex and the level of physical activity on intake and nutritional status of vitamin B1, B2, and B6. Independently of sex and the level of physical activity, the women and men consumed insufficient quantities of vitamins B1 and B6, although this was not always related to

  5. Kinin-B2 receptor mediated neuroprotection after NMDA excitotoxicity is reversed in the presence of kinin-B1 receptor agonists.

    PubMed

    Martins, Antonio H; Alves, Janaina M; Perez, Dinely; Carrasco, Marimeé; Torres-Rivera, Wilmarie; Eterović, Vesna A; Ferchmin, Pedro A; Ulrich, Henning

    2012-01-01

    Kinins, with bradykinin and des-Arg(9)-bradykinin being the most important ones, are pro-inflammatory peptides released after tissue injury including stroke. Although the actions of bradykinin are in general well characterized; it remains controversial whether the effects of bradykinin are beneficial or not. Kinin-B2 receptor activation participates in various physiological processes including hypotension, neurotransmission and neuronal differentiation. The bradykinin metabolite des-Arg(9)-bradykinin as well as Lys-des-Arg(9)-bradykinin activates the kinin-B1 receptor known to be expressed under inflammatory conditions. We have investigated the effects of kinin-B1 and B2 receptor activation on N-methyl-D-aspartate (NMDA)-induced excitotoxicity measured as decreased capacity to produce synaptically evoked population spikes in the CA1 area of rat hippocampal slices. Bradykinin at 10 nM and 1 µM concentrations triggered a neuroprotective cascade via kinin-B2 receptor activation which conferred protection against NMDA-induced excitotoxicity. Recovery of population spikes induced by 10 nM bradykinin was completely abolished when the peptide was co-applied with the selective kinin-B2 receptor antagonist HOE-140. Kinin-B2 receptor activation promoted survival of hippocampal neurons via phosphatidylinositol 3-kinase, while MEK/MAPK signaling was not involved in protection against NMDA-evoked excitotoxic effects. However, 100 nM Lys-des-Arg(9)-bradykinin, a potent kinin-B1 receptor agonist, reversed bradykinin-induced population spike recovery. The inhibition of population spikes recovery was reversed by PD98059, showing that MEK/MAPK was involved in the induction of apoptosis mediated by the B1 receptor. Bradykinin exerted protection against NMDA-induced excitotoxicity which is reversed in the presence of a kinin-B1 receptor agonist. As bradykinin is converted to the kinin-B1 receptor metabolite des-Arg(9)-bradykinin by carboxypeptidases, present in different areas

  6. Assessment of intake and nutritional status of vitamin b1, b2, and b6 in men and women with different physical activity levels.

    PubMed

    Malara, M; Hübner-Wozniak, E; Lewandowska, I

    2013-06-01

    The purpose of the present study was to examine the nutritional status of vitamin B1, B2, and B6 in respect to dietary intake of these vitamins and activity coefficients of the erythrocyte enzymes transketolase, glutathione reductase, and aspartic aminotransferase in young men and women with different physical activity levels. The participants of this study were 20 women and 20 men with high physical activity (groups HAW and HAM, respectively), and 20 women and 20 men with low physical activity (groups LAW and LAM, respectively). The intake of vitamins B1, B2, B6, proteins, and calorie content of the diet was based on the average of the 4-day dietary recalls. To assess nutritional status of vitamin B1, B2, and B6, the activity coefficients (α) of erythrocyte transketolase (ETK), erythrocyte glutathione reductase (EGR), and erythrocyte aspartic aminotransferase (EAST) were estimated in blood hemolysates. The intake of the studied vitamins in the diet was statistically significantly lower in the female groups compared with the respective male groups. Deficiency of vitamin B6 in the diet was present more often in women than in men (in terms of the recommended dietary allowances [RDA]). Values of the activity coefficient αETK indicated that none of the groups in this study suffered the risk of vitamin B1 deficiency. The value of the activity coefficient αEGR indicated that the groups of women and men with low physical activity were more prone to vitamin B2 deficiency compared with the high physical activity groups. The risk of vitamin B6 deficiency (αEAST) in both male groups was higher than in both female groups. The obtained results do not allow for unequivocal determination of the impact of sex and the level of physical activity on intake and nutritional status of vitamin B1, B2, and B6. Independently of sex and the level of physical activity, the women and men consumed insufficient quantities of vitamins B1 and B6, although this was not always related to

  7. Genotype and environment effects on the contents of vitamins B1, B2, B3, and B6 in wheat grain.

    PubMed

    Shewry, Peter R; Van Schaik, Frank; Ravel, Catherine; Charmet, Gilles; Rakszegi, Mariann; Bedo, Zoltan; Ward, Jane L

    2011-10-12

    The total contents of thiamine (vitamin B1), riboflavin (B2), and pyridoxine (B6) and the bioavailable forms of niacin (B3) were determined on wholemeal flours of 24 winter wheat varieties grown on four sites (United Kingdom, Poland, France, and Hungary) in 2007 and of two spring varieties grown on the same sites with the exception of Poland. The contents of vitamins B1 (5.53-13.55 μg/g dw), B2 (0.77-1.40 μg/g dw), and B6 (1.27-2.97 μg/g dw) were within the ranges reported previously, while the content of bioavailable vitamin B3 (0.16-1.74 μg/g dw) was about 10-15% of the total contents of vitamin B3 reported in previous studies. Strong correlations were observed between the contents of vitamins B1, B3, and B6, and partitioning of the variance in the contents of these three B vitamins showed that between 48 and 70% was accounted for by the environment. By contrast, the content of vitamin B2 was not correlated with the contents of other B vitamins, and 73% of the variance was ascribed to the error term, which suggests that this trait may be influenced by genotype × environment interactions. Whereas the contents of vitamins B1, B3, and B6 were correlated positively with the mean temperature from heading to harvest (r > 0.8), the content of vitamin B2 was positively correlated with precipitation during the 3 months prior to heading. These results are discussed in relation to the development of new wheat varieties with enhanced health benefits.

  8. Depletion of B2 but Not B1a B Cells in BAFF Receptor-Deficient ApoE−/− Mice Attenuates Atherosclerosis by Potently Ameliorating Arterial Inflammation

    PubMed Central

    Kyaw, Tin; Tay, Christopher; Hosseini, Hamid; Kanellakis, Peter; Gadowski, Tahlia; MacKay, Fabeinne; Tipping, Peter

    2012-01-01

    We have recently identified conventional B2 cells as atherogenic and B1a cells as atheroprotective in hypercholesterolemic ApoE−/− mice. Here, we examined the development of atherosclerosis in BAFF-R deficient ApoE−/− mice because B2 cells but not B1a cells are selectively depleted in BAFF-R deficient mice. We fed BAFF-R−/− ApoE−/− (BaffR.ApoE DKO) and BAFF-R+/+ApoE−/− (ApoE KO) mice a high fat diet (HFD) for 8-weeks. B2 cells were significantly reduced by 82%, 81%, 94%, 72% in blood, peritoneal fluid, spleen and peripheral lymph nodes respectively; while B1a cells and non-B lymphocytes were unaffected. Aortic atherosclerotic lesions assessed by oil red-O stained-lipid accumulation and CD68+ macrophage accumulation were decreased by 44% and 50% respectively. B cells were absent in atherosclerotic lesions of BaffR.ApoE DKO mice as were IgG1 and IgG2a immunoglobulins produced by B2 cells, despite low but measurable numbers of B2 cells and IgG1 and IgG2a immunoglobulin concentrations in plasma. Plasma IgM and IgM deposits in atherosclerotic lesions were also reduced. BAFF-R deficiency in ApoE−/− mice was also associated with a reduced expression of VCAM-1 and fewer macrophages, dendritic cells, CD4+ and CD8+ T cell infiltrates and PCNA+ cells in lesions. The expression of proinflammatory cytokines, TNF-α, IL1-β and proinflammatory chemokine MCP-1 was also reduced. Body weight and plasma cholesterols were unaffected in BaffR.ApoE DKO mice. Our data indicate that B2 cells are important contributors to the development of atherosclerosis and that targeting the BAFF-R to specifically reduce atherogenic B2 cell numbers while preserving atheroprotective B1a cell numbers may be a potential therapeutic strategy to reduce atherosclerosis by potently reducing arterial inflammation. PMID:22238605

  9. Evaluation of synergistic antimicrobial effect of vitamins (A, B1, B2, B6, B12, C, D, E and K) with antibiotics against resistant bacterial strains.

    PubMed

    Shahzad, Shakeel; Ashraf, M Adnan; Sajid, M; Shahzad, Aqeel; Rafique, Azhar; Mahmood, M Shahid

    2018-02-02

    Multiple drug resistant super bugs of Acinetobacter baumannii and methicillin-resistant Staphylococcus aureus (MRSA) are becoming challenge for healthcare professionals. In this study, vitamins were evaluated for synergistic activity with the antibiotics. Synergistic effect between antibiotic and stock solutions of vitamins is evaluated by using Kirby-Bauer disc diffusion assay. Distilled water and propylene glycol were used as solvent for water soluble vitamins and fat-soluble vitamins respectively. The final concentration of 10mg/ml of each water-soluble vitamin B1 (Thiamine), B2 (Riboflavin), B6 (Pyridoxine) B12 (Methylcobalamin), C (Ascorbic acid) and 0.1mg/ml of each fat soluble vitamin A (retinol), D (cholecalciferol) E (αTocopherol) K (Menadione) were used with the antibiotics. The results depicted that vitamin K and E have better synergistic activity with piperacillin-tazobactam, imipenem and doripenem antibiotics against A. baumannii. While vitamin B1, B2 and B12 showed remarkable synergistic activity with linezolid against MRSA. Vitamin B1 was further tested to have better synergism with antibiotics oxacillin, tetracycline, rifampicin and linezolid against MRSA. The fat-soluble vitamins E and K were good in synergism against Gram negative A. baumannii while water soluble vitamins as B1, B2 and B12 were effective against MRSA but not against A. baumannii. This synergistic action of vitamins with the antibiotics can be used as a tool to treat multiple drug resistant super bugs with further evaluation at molecular level. Copyright © 2018 International Society for Chemotherapy of Infection and Cancer. Published by Elsevier Ltd. All rights reserved.

  10. Metabolic engineering of indole glucosinolates in Chinese cabbage plants by expression of Arabidopsis CYP79B2, CYP79B3, and CYP83B1.

    PubMed

    Zang, Yun-Xiang; Lim, Myung-Ho; Park, Beom-Seok; Hong, Seung-Beom; Kim, Doo Hwan

    2008-04-30

    Indole glucosinolates (IG) play important roles in plant defense, plant-insect interactions, and stress responses in plants. In an attempt to metabolically engineer the IG pathway flux in Chinese cabbage, three important Arabidopsis cDNAs, CYP79B2, CYP79B3, and CYP83B1, were introduced into Chinese cabbage by Agrobacterium-mediated transformation. Overexpression of CYP79B3 or CYP83B1 did not affect IG accumulation levels, and overexpression of CYP79B2 or CYP79B3 prevented the transformed callus from being regenerated, displaying the phenotype of indole-3-acetic acid (IAA) overproduction. However, when CYP83B1 was overexpressed together with CYP79B2 and/or CYP79B3, the transformed calli were regenerated into whole plants that accumulated higher levels of glucobrassicin, 4-hydroxy glucobrassicin, and 4-methoxy glu-cobrassicin than wild-type controls. This result suggests that the flux in Chinese cabbage is predominantly channeled into IAA biosynthesis so that coordinate expression of the two consecutive enzymes is needed to divert the flux into IG biosynthesis. With regard to IG accumulation, overexpression of all three cDNAs was no better than overexpression of the two cDNAs. The content of neoglucobrassicin remained unchanged in all transgenic plants. Although glucobrassicin was most directly affected by overexpression of the transgenes, elevated levels of the parent IG, glucobrassicin, were not always accompanied by increases in 4-hydroxy and 4-methoxy glucobrassicin. However, one transgenic line producing about 8-fold increased glucobrassicin also accumulated at least 2.5 fold more 4-hydroxy and 4-methoxy glucobrassicin. This implies that a large glucobrassicin pool exceeding some threshold level drives the flux into the side chain modification pathway. Aliphatic glucosinolate content was not affected in any of the transgenic plants.

  11. Evaluation of FlaB1, FlaB2, FlaB3, and Tp0463 of Treponema pallidum for serodiagnosis of syphilis.

    PubMed

    Jiang, Chuanhao; Xiao, Jinhong; Xie, Yafeng; Xiao, Yongjian; Wang, Chuan; Kuang, Xingxing; Xu, Man; Li, Ranhui; Zeng, Tiebing; Liu, Shuanquan; Yu, Jian; Zhao, Feijun; Wu, Yimou

    2016-02-01

    Syphilis is a multistage disease caused by the invasive spirochete Treponema pallidum subsp. pallidum, and accurate diagnosis is important for the prevention and treatment of syphilis. Here, to identify appropriate diagnostic antigens for serodiagnosis of syphilis, 6 recombinant proteins were expressed in Escherichia coli and purified, including flagellins (FlaB1 [Tp0868], FlaB2 [Tp0792], and FlaB3 [Tp0870]), Tp0463, Tp0751, and Tp1038. The sensitivities were determined by screening sera from individuals with primary (n=82), secondary (n=115), latent (n=105), and congenital (n=65) syphilis. The specificities were determined by screening sera from uninfected controls (n=30) and potentially cross-reactive infections including Lyme disease (n=30), leptospirosis (n=5), and hepatitis B (n=30). Our data showed that FlaB1, FlaB2, FlaB3, Tp0463, and Tp1038 exhibited higher overall sensitivities and specificities for detecting IgG antibody, with 95.4% and 98.9%, 92.6% and 95.8%, 95.1% and 95.8%, 92.6% and 97.9%, and 95.9% and 98.9%, respectively. In contrast, Tp0751 demonstrated only an overall sensitivity of 39.2%. For comparison, the sensitivity and specificity of Architect Syphilis TP were determined to be 98.1% and 93.7%, respectively. In addition, FlaB1, FlaB2, FlaB3, and Tp0463 demonstrated excellent performance for detecting IgM antibody in primary and congenital syphilis, with sensitivities of 76.8% and 83.1%, 72.0% and 87.7%, 74.4% and 89.2%, and 64.6% and 75.3%, respectively. These results indicate that FlaB1, FlaB2, FlaB3, and Tp0463 could be as novel diagnostic candidates for serodiagnosis of syphilis. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Production of beauvericin, moniliformin, fusaproliferin, and fumonisins b(1), b(2), and b(3) by fifteen ex-type strains of fusarium species.

    PubMed

    Fotso, Joseph; Leslie, John F; Smith, J Scott

    2002-10-01

    Fifteen Fusarium species were analyzed by high-performance liquid chromatography for the production of six mycotoxins in corn grits cultures. Production of mycotoxins ranged from 66 to 2,500 micro g/kg for fumonisin B(1), 0.6 to 1,500 micro g/g for moniliformin, 2.2 to 720 micro g/g for beauvericin, and 12 to 130 micro g/g for fusaproliferin. Fumonisin B(2) (360 micro g/kg) was produced by two species, fumonisin B(3) was not detected in any of the 15 species examined, and Fusarium bulbicola produced none of the six mycotoxins that we analyzed.

  13. Production of Beauvericin, Moniliformin, Fusaproliferin, and Fumonisins B1, B2, and B3 by Fifteen Ex-Type Strains of Fusarium Species†

    PubMed Central

    Fotso, Joseph; Leslie, John F.; Smith, J. Scott

    2002-01-01

    Fifteen Fusarium species were analyzed by high-performance liquid chromatography for the production of six mycotoxins in corn grits cultures. Production of mycotoxins ranged from 66 to 2,500 μg/kg for fumonisin B1, 0.6 to 1,500 μg/g for moniliformin, 2.2 to 720 μg/g for beauvericin, and 12 to 130 μg/g for fusaproliferin. Fumonisin B2 (360 μg/kg) was produced by two species, fumonisin B3 was not detected in any of the 15 species examined, and Fusarium bulbicola produced none of the six mycotoxins that we analyzed. PMID:12324376

  14. First Observation of the P-Wave Spin-Singlet Bottomonium States h b(1P) and h b(2P)

    SciTech Connect

    Adachi, I.; Aihara, H.; Arinstein, K.

    2012-01-18

    We report the observation of the h b(1P) and h b(2P) spin-singlet bottomonium states produced in the reaction e⁺e⁻ → h b(nP)π⁺π⁻ with significances of 5.5σ and 11.2σ, respectively. We find that M[h b(1P)] = (9898.25±1.06+1.03 –1.07 )MeV/c² and M[h b(2P)] = (10259.76±0.64+1.43 –1.03 )MeV/c 2, which correspond to measurements of the P-wave hyperfine splittings ΔM HF = (1.62 ± 1.52)MeV/c² and (0.48+1.57 –1.22)MeV/c², respectively. We also report measurements of the cross sections for e⁺e⁻ → h b(nP)π⁺π⁻ relative to the cross section for the e⁺e⁻ Υ(2S)π⁺π⁻ reaction. These results are obtained from a 121.4 fb⁻¹ data sample collected withmore » the Belle detector near the Υ(5S) resonance at the KEKB asymmetric-energy e⁺e⁻ collider.« less

  15. Wave-of-Advance Models of the Diffusion of the Y Chromosome Haplogroup R1b1b2 in Europe

    PubMed Central

    Sjödin, Per; François, Olivier

    2011-01-01

    Whether or not the spread of agriculture in Europe was accompanied by movements of people is a long-standing question in archeology and anthropology, which has been frequently addressed with the help of population genetic data. Estimates on dates of expansion and geographic origins obtained from genetic data are however sensitive to the calibration of mutation rates and to the mathematical models used to perform inference. For instance, recent data on the Y chromosome haplogroup R1b1b2 (M269) have either suggested a Neolithic origin for European paternal lineages or a more ancient Paleolithic origin depending on the calibration of Y-STR mutation rates. Here we examine the date of expansion and the geographic origin of hgR1b1b2 considering two current estimates of mutation rates in a total of fourteen realistic wave-of-advance models. We report that a range expansion dating to the Paleolithic is unlikely to explain the observed geographical distribution of microsatellite diversity, and that whether the data is informative with respect to the spread of agriculture in Europe depends on the mutation rate assumption in a critical way. PMID:21720564

  16. Rapid analysis of aflatoxins B1, B2, and ochratoxin A in rice samples using dispersive liquid-liquid microextraction combined with HPLC.

    PubMed

    Lai, Xian-Wen; Sun, Dai-Li; Ruan, Chun-Qiang; Zhang, He; Liu, Cheng-Lan

    2014-01-01

    A novel, simple, and rapid method is presented for the analysis of aflatoxin B1, aflatoxin B2, and ochratoxin A in rice samples by dispersive liquid-liquid microextraction combined with LC and fluorescence detection. After extraction of the rice samples with a mixture of acetonitrile/water/acetic acid, mycotoxins were rapidly partitioned into a small volume of organic solvent (chloroform) by dispersive liquid-liquid microextraction. The three mycotoxins were simultaneously determined by LC with fluorescence detection after precolumn derivatization for aflatoxin B1 and B2. Parameters affecting both extraction and dispersive liquid-liquid microextraction procedures, including the extraction solvent, the type and volume of extractant, the volume of dispersive solvent, the addition of salt, the pH and the extraction time, were optimized. The optimized protocol provided an enrichment factor of approximately 1.25 and with detection of limits (0.06-0.5 μg/kg) below the maximum levels imposed by current regulations for aflatoxins and ochratoxin A. The mean recovery of three mycotoxins ranged from 82.9-112%, with a RSD less than 7.9% in all cases. The method was successfully applied to measure mycotoxins in commercial rice samples collected from local supermarkets in China. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. [Evaluation of sufficiency with vitamins C, B1 and B2 of newborn infants feeding different types of nutrition, by means of urinary excretion determination].

    PubMed

    Vrzhesinskaya, O A; Kodentsova, V M; Pereverzeva, O G; Gmoshinskaya, M V; Pustograev, N N

    2015-01-01

    With the help of non-invasive methods the sufficiency with vitamins C, B1 and B2 in 58 newborns (38-40 weeks of gestation) on breastfeeding as well as on mixed or artificial feeding has been evaluated. Urinary excretion and breast content of ascorbic acid (measured by visual titration), thiamin (by thiochrome fluorimetric method) andriboflavin (fluorimetrically by titration with riboflavin-binding protein) was determined on the 3-10th day after birth. 35 infants were exclusively breastfed. 40% of their mothers regularly took multivitamin supplements during pregnancy and 42.9%--both during pregnancy and after childbirth, 17.1% did not use vitamin complexes either duringpregnancy or after childbearing. The content of vitamins C, B1 and B2 in the breast milk of women who did not additionally intake vitamins during pregnancy and lactation, was reduced compared with that of mothers who took multivitamin supplements, and provided only a half of the needs of their child in these vitamins. All these babies have urinary excretion of vitamins below the lower limit of norm. Among infants whose mothers took multivitamin supplements during pregnancy, but stop taking them immediately after their birth, only 28.6% of newborns were provided with vitamin C, while all the children identified a lack of vitamins By and B2. The insufficiency with vitamins C and B1 was detected in one third of children breastfed by mothers who took vitamins during pregnancy and continued intaking them after birth, adequate supplied with vitamin B2 was 35.7% of the surveyed. Determination of vitamin urinary excretion (perg creatinine) is useful for vitamin status evaluation. The content of vitamins in breast milk can be used for assessment of vitamin status both a nursing woman and her child. Taking into consideration that the diet of a breastfeeding woman is not always the best, there is no doubt about the need to continue multivitamin intake during breastfeeding. The question on the doses of vitamins

  18. Exacerbation of DSS-induced colitis in mice lacking kinin B1 receptors through compensatory up-regulation of kinin B2 receptors: the role of tight junctions and intestinal homeostasis

    PubMed Central

    Marcon, R; Claudino, RF; Dutra, RC; Bento, AF; Schmidt, EC; Bouzon, ZL; Sordi, R; Morais, RLT; Pesquero, JB; Calixto, JB

    2013-01-01

    Background and Purpose Kinins are pro-inflammatory peptides that are released during tissue injury, including that caused by inflammatory bowel disease. Herein, we assessed the role and underlying mechanisms through which the absence of kinin B1 receptors exacerbates the development of dextran sulfate sodium (DSS)-induced colitis in mice. Experimental Approach B1 and B2 receptor antagonists and B1 receptor knockout mice (B1−/−) were used to assess the involvement of B1 and B2 receptor signalling in a DSS-colitis. B1 receptor, B2 receptor, occludin and claudin-4 expression, cytokine levels and cell permeability were evaluated in colon from wild-type (WT) and B1−/− mice. Key Results DSS-induced colitis was significantly exacerbated in B1−/− compared with WT mice. IL-1β, IFN-γ, keratinocyte-derived chemokine and macrophage inflammatory protein-2 were markedly increased in the colon from DSS-treated B1−/− compared with DSS-treated WT mice. Treatment of WT mice with a selective B1 receptor antagonist, DALBK or SSR240612, had no effect on DSS-induced colitis. Of note, B2 receptor mRNA expression was significantly up-regulated in colonic tissue from the B1−/− mice after DSS administration. Moreover, treatment with a selective B2 receptor antagonist prevented the exacerbation of colitis in B1−/− mice following DSS administration. The water- or DSS-treated B1−/− mice showed a decrease in occludin gene expression, which was partially prevented by the B2 receptor antagonist. Conclusions and Implications A loss of B1 receptors markedly exacerbates the severity of DSS-induced colitis in mice. The increased susceptibility of B1−/− may be associated with compensatory overexpression of B2 receptors, which, in turn, modulates tight junction expression. PMID:22889120

  19. Assessment of azole fungicides as a tool to control growth of Aspergillus flavus and aflatoxin B1and B2production in maize.

    PubMed

    Mateo, Eva M; Gómez, José Vicente; Gimeno-Adelantado, José Vicente; Romera, David; Mateo-Castro, Rufino; Jiménez, Misericordia

    2017-06-01

    Aspergillus flavus is a highly aflatoxin (AF)-producing species infecting maize and other crops. It is dominant in tropical regions, but it is also considered an emerging problem associated with climate change in Europe. The aim of this study was to assess the efficacy of azole fungicides (prochloraz, tebuconazole and a 2:1 (w/w) mixture of prochloraz plus tebuconazole) to control the growth of A. flavus and AF production in yeast-extract-sucrose (YES) agar and in maize kernels under different water activities (a w ) and temperatures. Aflatoxins B 1 and B 2 were determined by LC with fluorescence detection and post-column derivatisation of AFB 1 . In YES medium and maize grains inoculated with conidia of A. flavus, the growth rate (GR) of the fungus and AFB 1 and AFB 2 production were significantly influenced by temperature and treatment. In YES medium and maize kernels, optimal temperatures for GR and AF production were 37 and 25°C, respectively. In maize kernels, spore germination was not detected at the combination 37ºC/0.95 a w ; however, under these conditions germination was found in YES medium. All fungicides were more effective at 0.99 than 0.95 a w , and at 37 than 25ºC. Fungicides effectiveness was prochloraz > prochloraz plus tebuconazole (2:1) > tebuconazole. AFs were not detected in cultures containing the highest fungicide doses, and only very low AF levels were found in cultures containing 0.1 mg l - 1 prochloraz or 5.0 mg l - 1 tebuconazole. Azoles proved to be highly efficient in reducing A. flavus growth and AF production, although stimulation of AF production was found under particular conditions and low-dosage treatments. Maize kernels were a more favourable substrate for AF biosynthesis than YES medium. This paper is the first comparative study on the effects of different azole formulations against A. flavus and AF production in a semi-synthetic medium and in maize grain under different environmental conditions.

  20. Gluten-Free Flours from Different Raw Materials as the Source of Vitamin B1, B2, B3 and B6.

    PubMed

    Rybicka, Iga; Gliszczynska-Swiglo, Anna

    2017-01-01

    Gluten-free (GF) products are those with a natural absence or acceptable level (<20 mg/kg) of gluten. They should be a part of a diet for people with gluten-related disorders, like celiac disease. Recently the popularity of a gluten-free diet (GFD) has risen extremely, because a lot of healthy individuals exclude gluten from their menus. According to the literature data on nutritional deficiencies in the GFD, this trend seems to be risky. This paper describes the nutritional value of 14 flours from different GF raw materials from the aspect of B-group vitamin content (B 1 , B 2 , B 3 , B 6 ). Vitamins were determined using high performance liquid chromatography after enzymatic and acid hydrolysis of the samples. The vitamin contents significantly differed in the analysed flours. The content (in 100 g of the product) of vitamin B 1 ranged from 0.01 mg (amaranth flour) to 0.60 mg (teff flour), vitamin B 2 from 0.03 mg (GF flour with oats) to 0.22 mg (buckwheat flour), vitamin B 3 from below 0.01 mg (amaranth flour) to 6.02 mg (millet flour), and vitamin B 6 from 0.03 mg (acorn flour) to 0.69 mg (amaranth flour). The content of vitamins in the analysed GF flours was also compared to gluten-containing flours. Obtained results indicate that flours from teff, millet, chestnut, buckwheat, and amaranth are better sources of certain B-group vitamins than flours from corn, rice, and some flours with gluten.

  1. "Send & Hold" Clinical Decision Support Rules improvement to reduce unnecessary testing of vitamins A, E, K, B1, B2, B3, B6 and C.

    PubMed

    Rodriguez-Borja, Enrique; Corchon-Peyrallo, Africa; Barba-Serrano, Esther; Villalba Martínez, Celia; Carratala Calvo, Arturo

    2018-02-03

    We assessed the impact of several "send & hold" clinical decision support rules (CDSRs) within the electronical request system for vitamins A, E, K, B1, B2, B3, B6 and C for all outpatients at a large health department. When ordered through electronical request, providers (except for all our primary care physicians who worked as a non-intervention control group) were always asked to answer several compulsory questions regarding main indication, symptomatology, suspected diagnosis, vitamin active treatments, etc., for each vitamin test using a drop-down list format. After samples arrival, tests were later put on hold internally by our laboratory information system (LIS) until review for their appropriateness was made by two staff pathologists according to the provided answers and LIS records (i.e. "send & hold"). The number of tests for each analyte was compared between the 10-month period before and after CDSRs implementation in both groups. After implementation, vitamins test volumes decreased by 40% for vitamin A, 29% for vitamin E, 42% for vitamin K, 37% for vitamin B1, 85% for vitamin B2, 68% for vitamin B3, 65% for vitamin B6 and 59% for vitamin C (all p values 0.03 or lower except for vitamin B3), whereas in control group, the majority increased or remained stable. In patients with rejected vitamins, no new requests and/or adverse clinical outcome comments due to this fact were identified. "Send & hold" CDSRs are a promising informatics tool that can support in utilization management and enhance the pathologist's leadership role as tests specialist.

  2. Erythrocyte concentrations of B1, B2, B6 but not plasma C and E are reliable indicators of nutrition status in the presence of systemic inflammation.

    PubMed

    Ghashut, Rawia A; McMillan, Donald C; Kinsella, John; Talwar, Dinesh

    2017-02-01

    There is increasing evidence that the plasma concentration of vitamin D, carotenoids, zinc and selenium are associated with the magnitude of the systemic inflammatory response. In order to examine whether other vitamins may be affected and whether red cell concentrations are less affected by systemic inflammation the aim of the present study was to examine the effect of the systemic inflammatory response on red cell measurements of vitamins B1, B2 and B6, and plasma concentration of vitamin C and E in a large cohort of patients referred for a nutritional screen. Patients referred for nutritional assessment of B1 (n = 551), B2 (n = 251), B6 (n = 313), ascorbic acid (n = 494) and α-tocopherol (n = 395) concentrations. These vitamins were measured using routine laboratory methods. The median concentrations of vitamin B1 grouped according to C-reactive protein concentrations ≤10, 11-80 and >80 mg/L were 543, 664 and 766 ng/g Hb respectively (p < 0.001, 41% higher). The median concentration of vitamin B1 grouped according to albumin concentrations ≥35, 25-34 and <25 g/l were 547, 664 and 701 ng/g Hb respectively (p < 0.001, 28% higher). The median concentrations of red cell vitamin B2 grouped according to CRP concentrations ≤10, 11-80 and >80 mg/L were 2.2, 2.3 and 2.4 nmol/g Hb respectively (p < 0.001, 9% higher). The median red cell concentrations of vitamin B2 grouped according to albumin concentrations ≥35, 25-34 and <25 g/l were 2.1, 2.4 and 2.3 nmol/g Hb respectively (p < 0.001, 14% higher). The median concentrations of red cell vitamin B6 grouped according to CRP concentrations ≤10, 11-80 and >80 mg/L were 534, 548 and 767 pmol/g Hb respectively (p < 0.001, 44% higher). The median red cell concentrations of vitamin B6 grouped according to albumin concentrations ≥35, 25-34 and <25 g/l were 462, 644 and 840 pmol/g Hb respectively (p < 0.001, 82% higher). In contrast, the median plasma concentrations of ascorbic acid

  3. Phosphorylation statuses at different residues of lamin B2, B1, and A/C dynamically and independently change throughout the cell cycle

    SciTech Connect

    Kuga, Takahisa, E-mail: t-kuga@nibio.go.jp; Department of Molecular Diagnosis; Nozaki, Naohito

    2010-08-15

    Lamins, major components of the nuclear lamina, undergo phosphorylation at multiple residues during cell cycle progression, but their detailed phosphorylation kinetics remain largely undetermined. Here, we examined changes in the phosphorylation of major phosphorylation residues (Thr14, Ser17, Ser385, Ser387, and Ser401) of lamin B2 and the homologous residues of lamin B1, A/C during the cell cycle using novel antibodies to the site-specific phosphorylation. The phosphorylation levels of these residues independently changed during the cell cycle. Thr14 and Ser17 were phosphorylated during G{sub 2}/M phase to anaphase/telophase. Ser385 was persistently phosphorylated during mitosis to G{sub 1} phase, whereas Ser387 was phosphorylatedmore » discontinuously in prophase and G{sub 1} phase. Ser401 phosphorylation was enhanced in the G{sub 1}/S boundary. Immunoprecipitation using the phospho-antibodies suggested that metaphase-phosphorylation at Thr14, Ser17, and Ser385 of lamins occurred simultaneously, whereas G{sub 1}-phase phosphorylation at Ser385 and Ser387 occurred in distinct pools or with different timings. Additionally, we showed that lamin B2 phosphorylated at Ser17, but not Ser385, Ser387 and Ser401, was exclusively non-ionic detergent soluble, depolymerized forms in growing cells, implicating specific involvement of Ser17 phosphorylation in lamin depolymerization and nuclear envelope breakdown. These results suggest that the phosphorylations at different residues of lamins might play specific roles throughout the cell cycle.« less

  4. Structural Analysis and Biological Toxicity of Aflatoxins B1 and B2 Degradation Products Following Detoxification by Ocimum basilicum and Cassia fistula Aqueous Extracts.

    PubMed

    Iram, Wajiha; Anjum, Tehmina; Iqbal, Mazhar; Ghaffar, Abdul; Abbas, Mateen; Khan, Abdul Muqeet

    2016-01-01

    This study showed the comparison between Ocimum basilicum and Cassia fistula (leaves and branch) aqueous extracts for their ability to detoxify of aflatoxins B1 and B2 (AFB1; 100 μg L(-1) and AFB2; 50 μg L(-1)) by In Vitro assays and decontamination studies. Results indicated that O. basilicum leaves extract was found to be highly significant (P < 0.05) in degrading AFB1 and AFB2, i.e., 90.4 and 88.6%, respectively. However, O. basilicum branch, C. fistula leaves and branch extracts proved to be less efficient in degrading these aflatoxins, under optimized conditions, i.e., pH 8, temperature 30°C and incubation period of 72 h. Moreover the antifungal activity of these plants extracts were also tested. The findings depicted that O. basilicum leaves extract showed maximum growth inhibition of aflatoxigenic isolates, i.e., 82-87% as compared to other tested plants extracts. The structural elucidation of degraded toxin products by LCMS/MS analysis showed that nine degraded products of AFB1 and AFB2 were formed. MS/MS spectra showed that most of the products were formed by the removal of double bond in the terminal furan ring and modification of lactone group indicating less toxicity as compared to parent compounds. Brine shrimps bioassay further confirmed the low toxicity of degraded products, showing that O. basilicum leaves extract can be used as an effective tool for the detoxification of aflatoxins.

  5. Simultaneous determination of fumonisins B1 and B2 in different types of maize by matrix solid phase dispersion and HPLC-MS/MS.

    PubMed

    de Oliveira, Gabriel Barros; de Castro Gomes Vieira, Carolyne Menezes; Orlando, Ricardo Mathias; Faria, Adriana Ferreira

    2017-10-15

    This work involved the optimization and validation of a method, according to Directive 2002/657/EC and the Analytical Quality Assurance Manual of Ministério da Agricultura, Pecuária e Abastecimento, Brazil, for simultaneous extraction and determination of fumonisins B1 and B2 in maize. The extraction procedure was based on a matrix solid phase dispersion approach, the optimization of which employed a sequence of different factorial designs. A liquid chromatography-tandem mass spectrometry method was developed for determining these analytes using the selected reaction monitoring mode. The optimized method employed only 1g of silica gel for dispersion and elution with 70% ammonium formate aqueous buffer (50mmolL -1 , pH 9), representing a simple, cheap and chemically friendly sample preparation method. Trueness (recoveries: 86-106%), precision (RSD ≤19%), decision limits, detection capabilities and measurement uncertainties were calculated for the validated method. The method scope was expanded to popcorn kernels, white maize kernels and yellow maize grits. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Structural Elucidation and Toxicity Assessment of Degraded Products of Aflatoxin B1 and B2 by Aqueous Extracts of Trachyspermum ammi

    PubMed Central

    Iram, Wajiha; Anjum, Tehmina; Iqbal, Mazhar; Ghaffar, Abdul; Abbas, Mateen

    2016-01-01

    In this study aqueous extract of seeds and leaves of Trachyspermum ammi were evaluated for their ability to detoxify aflatoxin B1 and B2 (AFB1; 100 μg L−1 and AFB2; 50 μg L−1) by in vitro and in vivo assays. Results indicated that T. ammi seeds extract was found to be significant (P < 0.05) in degrading AFB1 and AFB2 i.e., 92.8 and 91.9% respectively. However, T. ammi leaves extract proved to be less efficient in degrading these aflatoxins, under optimized conditions i.e., pH 8, temperature 30°C and incubation period of 72 h. The structural elucidation of degraded toxin products by LCMS/MS analysis showed that eight degraded products of AFB1 and AFB2 were formed. MS/MS spectra showed that most of the products were formed by the removal of double bond in the terminal furan ring and modification of lactone group indicating less toxicity as compared to parent compounds. Brine shrimps bioassay further confirmed the low toxicity of degraded products, showing that T. ammi seeds extract can be used as an effective tool for the detoxification of aflatoxins. PMID:27064492

  7. Mass spectrometric identification and toxicity assessment of degraded products of aflatoxin B1 and B2 by Corymbia citriodora aqueous extracts

    PubMed Central

    Iram, Wajiha; Anjum, Tehmina; Iqbal, Mazhar; Ghaffar, Abdul; Abbas, Mateen

    2015-01-01

    This study explores the detoxification potential of Corymbia citriodora plant extracts against aflatoxin B1 and B2 (AFB1; 100 μg L−1 and AFB2; 50 μg L−1) in In vitro and In vivo assays. Detoxification was qualitatively and quantitatively analyzed by TLC and HPLC, respectively. The study was carried out by using different parameters of optimal temperature, pH and incubation time period. Results indicated that C. citriodora leaf extract(s) more effectively degrade AFB1 and AFB2 i.e. 95.21% and 92.95% respectively than C. citriodora branch extract, under optimized conditions. The structural elucidation of degraded toxin products was done by LCMS/MS analysis. Ten degraded products of AFB1 and AFB2 and their fragmentation pathways were proposed based on molecular formulas and MS/MS spectra. Toxicity of these degraded products was significantly reduced as compared to that of parent compounds because of the removal of double bond in the terminal furan ring. The biological toxicity of degraded toxin was further analyzed by brine shrimps bioassay, which showed that only 17.5% mortality in larvae was recorded as compared to untreated toxin where 92.5% mortality was observed after 96hr of incubation. Therefore, our finding suggests that C. citriodora leaf extract can be used as an effective tool for the detoxification of aflatoxins. PMID:26423838

  8. Structural Elucidation and Toxicity Assessment of Degraded Products of Aflatoxin B1 and B2 by Aqueous Extracts of Trachyspermum ammi.

    PubMed

    Iram, Wajiha; Anjum, Tehmina; Iqbal, Mazhar; Ghaffar, Abdul; Abbas, Mateen

    2016-01-01

    In this study aqueous extract of seeds and leaves of Trachyspermum ammi were evaluated for their ability to detoxify aflatoxin B1 and B2 (AFB1; 100 μg L(-1) and AFB2; 50 μg L(-1)) by in vitro and in vivo assays. Results indicated that T. ammi seeds extract was found to be significant (P < 0.05) in degrading AFB1 and AFB2 i.e., 92.8 and 91.9% respectively. However, T. ammi leaves extract proved to be less efficient in degrading these aflatoxins, under optimized conditions i.e., pH 8, temperature 30°C and incubation period of 72 h. The structural elucidation of degraded toxin products by LCMS/MS analysis showed that eight degraded products of AFB1 and AFB2 were formed. MS/MS spectra showed that most of the products were formed by the removal of double bond in the terminal furan ring and modification of lactone group indicating less toxicity as compared to parent compounds. Brine shrimps bioassay further confirmed the low toxicity of degraded products, showing that T. ammi seeds extract can be used as an effective tool for the detoxification of aflatoxins.

  9. Structural Analysis and Biological Toxicity of Aflatoxins B1 and B2 Degradation Products Following Detoxification by Ocimum basilicum and Cassia fistula Aqueous Extracts

    PubMed Central

    Iram, Wajiha; Anjum, Tehmina; Iqbal, Mazhar; Ghaffar, Abdul; Abbas, Mateen; Khan, Abdul Muqeet

    2016-01-01

    This study showed the comparison between Ocimum basilicum and Cassia fistula (leaves and branch) aqueous extracts for their ability to detoxify of aflatoxins B1 and B2 (AFB1; 100 μg L-1 and AFB2; 50 μg L-1) by In Vitro assays and decontamination studies. Results indicated that O. basilicum leaves extract was found to be highly significant (P < 0.05) in degrading AFB1 and AFB2, i.e., 90.4 and 88.6%, respectively. However, O. basilicum branch, C. fistula leaves and branch extracts proved to be less efficient in degrading these aflatoxins, under optimized conditions, i.e., pH 8, temperature 30°C and incubation period of 72 h. Moreover the antifungal activity of these plants extracts were also tested. The findings depicted that O. basilicum leaves extract showed maximum growth inhibition of aflatoxigenic isolates, i.e., 82–87% as compared to other tested plants extracts. The structural elucidation of degraded toxin products by LCMS/MS analysis showed that nine degraded products of AFB1 and AFB2 were formed. MS/MS spectra showed that most of the products were formed by the removal of double bond in the terminal furan ring and modification of lactone group indicating less toxicity as compared to parent compounds. Brine shrimps bioassay further confirmed the low toxicity of degraded products, showing that O. basilicum leaves extract can be used as an effective tool for the detoxification of aflatoxins. PMID:27471501

  10. [Effect of vitamins B1, B2, B6, folic acid and vitamin C on the motor activity of chicken's intestines in chronic experiments and in vitro].

    PubMed

    Nagórna-Stasiak, B; Wawrzeńska, M

    1987-01-01

    The studies were carried out on 33 chickens of the broiler breed in chronic experiments and in vitro. In the chronic experiments the motility of the jejunum under the influence of vitamins of group B and vitamine C was recorded in 8 chickens. The vitamins were used at concentrations from 10 mg/l to 2.5 x 10(3) mg/l. In the experiments in vitro, the motility of the isolated segment of the jejunum was recorded by the method of Magnus. In this part of experiments the chickens were divided into 3 groups, of which group I (15 chickens) were fed with DKA finischer mixture, group II (5 hens) received, besides the mixture, per os 200 mg of vitamin C for 2 weeks, group III (5 hens) received the mixture and for 2 weeks intraperitoneally 200 mg of vitamin C. The effect of vitamins of group B in vitro was determined in chickens of group I, whereas that of vitamin C in chickens of group I, II and III. At the same time the level of vitamin C in the wall of the jejunum was determined by the method of Roe-Kuenther. It was shown that vitamin B2 and folic acid caused stimulation of intestine motility in the chickens, while vitamin B1, B6 and C decreased the motoric activity. Increased level of vitamin C in the intestinal wall resulted in increased intestine sensitivity. Chicken intestines sensitivity to vitamins was 10 times stronger to vitamins than that of the intestines of rabbits.

  11. LXXLL motifs and AF-2 domain mediate SHP (NR0B2) homodimerization and DAX1(NR0B1)-DAX1A heterodimerization

    PubMed Central

    Iyer, Anita K.; Zhang, Yao-Hua; McCabe, Edward R.B.

    2007-01-01

    Small heterodimer partner (SHP; NR0B2) is an unusual orphan member of the nuclear receptor superfamily that functions as a corepressor of other nuclear receptors through heterodimeric interactions. Mutations in SHP are associated with mild obesity and insulin resistance. The protein domain structure of SHP is similar to Dosage-sensitive sex reversal adrenal hypoplasia congenita (AHC) critical region on the X chromosome, gene 1 (DAX1; NR0B1). Mutations in DAX1 cause AHC with associated hypogonadotropic hypogonadism. DAX1A is an alternatively spliced isoform of DAX1 that lacks the last 80 amino acids of the DAX1 C-terminal repressor domain and is replaced by a novel 10-amino acid motif. We have previously shown homodimerization of SHP and DAX1 individually, heterodimerization of DAX1 with SHP, and heterodimerization of DAX1 with DAX1A. In these studies, we investigated the domains and residues of SHP involved in SHP homodimerization and DAX1-SHP heterodimerization and also further characterized DAX1-DAX1 homodimerization and DAX1-DAX1A heterodimerization. We showed involvement of the SHP LXXLL motifs and AF-2 domain in SHP homodimerization and DAX1-SHP heterodimerization. We demonstrated redundancy of the LXXLL motifs in DAX1 homodimerization. While DAX1A subcellular localization is mostly cytoplasmic, DAX1-DAX1A heterodimers existed in the nucleus, suggesting differential functions for DAX1A in each compartment. We showed that the AF-2 domain of DAX1 is involved in DAX1-DAX1A heterodimerization. These results indicate that NR0B family members use similar mechanisms for homodimerization as well as heterodimerization. These resemble coactivator-receptor interactions that may have potential functional consequences for molecular mechanisms of the NR0B family. PMID:17686645

  12. Peritoneal B-1b and B-2 B-cells confer long-term protection from pneumococcal serotype 3 infection after vaccination with Prevnar-13 and are defective in sickle cell disease mice.

    PubMed

    Cotte, Christina; Szczepanek, Steven M

    2017-06-16

    Long-term immunity after inoculation with the pneumococcal conjugate vaccine (Prevnar-13) is impaired in sickle cell disease (SCD) mice. We sought to determine which B-cell subsets are defective in SCD mice after vaccination with Prevnar-13, yet confer long-term immunity in wild-type (WT) mice. We vaccinated WT and SCD mice three times at three week intervals with Prevnar-13. Fourteen weeks later, 5∗10 4 cells of isolated peritoneal B-1a, B-1b, and B-2 cells were harvested and intraperitoneally transferred to Rag -/- recipients. A week later recipients were intraperitoneally challenged with 10 3 CFU of Streptococcus pneumoniae (serotype 3). Recipient mice that received either B-1b or B-2 B-cells from WT mice survived challenge, whereas mice that received B-1a cells died. Recipient mice that received B-1a, B-1b, or B-2 cells from SCD mice died after challenge. Both B-1b and B-2 cells appear to confer long-term immunity after Prevnar-13 vaccination, yet neither subset functions properly in SCD mice. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Theoretical study of the 2A2-2B2 separation of the alkali superoxides

    NASA Technical Reports Server (NTRS)

    Bauschlicher, Charles W., Jr.; Sodupe, Mariona; Partridge, Harry; Langhoff, Stephen R.

    1992-01-01

    The computed 2A2-2B2 separations of the alkali superoxides are in good agreement with those deduced from electron-spin resonance spectra. The calculations definitively show that the ground state of CsO2 is 2A2. The larger than expected separation for CsO2, based on the trend from LiO2 to RbO2, is attributed primarily to the differential effects of core relaxation. The CsO2 dissociation energy is computed to be 42.7 kcal/mol, with an uncertainty conservatively estimated as +/- 4 kcal/mol.

  14. Divergent evolution of cis-acting peroxisome proliferator-activated receptor elements that differentially control the tandemly duplicated fatty acid-binding protein genes, fabp1b.1 and fabp1b.2, in zebrafish.

    PubMed

    Laprairie, Robert B; Denovan-Wright, Eileen M; Wright, Jonathan M

    2016-06-01

    Gene duplication is thought to facilitate increasing complexity in the evolution of life. The fate of most duplicated genes is nonfunctionalization: functional decay resulting from the accumulation of mutations. According to the duplication-degeneration-complementation (DDC) model, duplicated genes are retained by subfunctionalization, where the functions of the ancestral gene are sub-divided between duplicate genes, or by neofunctionalization, where one of the duplicates acquires a new function. Here, we report the differential regulation of the zebrafish tandemly duplicated fatty acid-binding protein genes, fabp1b.1 and fabp1b.2, by peroxisome proliferator-activated receptors (PPAR). fabp1b.1 mRNA levels were induced in tissue explants of liver, but not intestine, by PPAR agonists. fabp1b.1 promoter activity was induced to a greater extent by rosiglitazone (PPARγ-selective agonist) compared to WY 14,643 (PPARα-selective agonist) in HEK293A cells. Mutation of a peroxisome proliferator response element (PPRE) at -1232 bp in the fabp1b.1 promoter reduced PPAR-dependent activation. fabp1b.2 promoter activity was not affected by PPAR agonists. Differential regulation of the duplicated fabp1b promoters may be the result of PPRE loss in fabp1b.2 during a meiotic crossing-over event. Retention of PPAR inducibility in fabp1b.1 and not fabp1b.2 suggests unique regulation and function of the fabp1b duplicates.

  15. 26 CFR 1.509(a)-2 - Exclusion for certain organizations described in section 170(b)(1)(A).

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 7 2010-04-01 2010-04-01 true Exclusion for certain organizations described in....509(a)-2 Exclusion for certain organizations described in section 170(b)(1)(A). (a) General rule. Organizations described in section 170(b)(1)(A) (other than in clauses (vii) and (viii)) are excluded from the...

  16. High-Resolution Laser Spectroscopy of the Ã2B2- X˜2A1 and B˜2B1- X˜2A1 Systems of SrNH 2

    NASA Astrophysics Data System (ADS)

    Brazier, C. R.; Bernath, P. F.

    2000-05-01

    The 000 bands of the Ã2B2-X˜2A1 and B˜2B1-X˜2A1 systems of SrNH2 were observed at Doppler-limited resolution using a Broida oven source and laser-induced fluorescence detection. A full rotational analysis of both transitions was performed including Ka levels up to 5 and J levels up to 55. The B˜2B1 state was found to be extensively perturbed and only some of the subbands could be analyzed. The Ã2B2 and B˜2B1 states undergo a strong Coriolis-type interaction which results in extremely large spin-rotation splittings in both states, effectively splitting all levels with Ka‧ ≠ 0 into two well-separated spin components.

  17. High-Resolution Laser Spectroscopy of the Ã(2)B(2)-&Xtilde;(2)A(1) and &Btilde;(2)B(1)-&Xtilde;(2)A(1) Systems of SrNH(2).

    PubMed

    Brazier; Bernath

    2000-05-01

    The 0(0)(0) bands of the Ã(2)B(2)-&Xtilde;(2)A(1) and &Btilde;(2)B(1)-&Xtilde;(2)A(1) systems of SrNH(2) were observed at Doppler-limited resolution using a Broida oven source and laser-induced fluorescence detection. A full rotational analysis of both transitions was performed including K(a) levels up to 5 and J levels up to 55. The &Btilde;(2)B(1) state was found to be extensively perturbed and only some of the subbands could be analyzed. The Ã(2)B(2) and &Btilde;(2)B(1) states undergo a strong Coriolis-type interaction which results in extremely large spin-rotation splittings in both states, effectively splitting all levels with K(a)(') not equal 0 into two well-separated spin components. Copyright 2000 Academic Press.

  18. Biotransformation of the mineralocorticoid receptor antagonists spironolactone and canrenone by human CYP11B1 and CYP11B2: Characterization of the products and their influence on mineralocorticoid receptor transactivation.

    PubMed

    Schiffer, Lina; Müller, Anne-Rose; Hobler, Anna; Brixius-Anderko, Simone; Zapp, Josef; Hannemann, Frank; Bernhardt, Rita

    2016-10-01

    Spironolactone and its major metabolite canrenone are potent mineralocorticoid receptor antagonists and are, therefore, applied as drugs for the treatment of primary aldosteronism and essential hypertension. We report that both compounds can be converted by the purified adrenocortical cytochromes P450 CYP11B1 and CYP11B2, while no conversion of the selective mineralocorticoid receptor antagonist eplerenone was observed. As their natural function, CYP11B1 and CYP11B2 carry out the final steps in the biosynthesis of gluco- and mineralocorticoids. Dissociation constants for the new exogenous substrates were determined by a spectroscopic binding assay and demonstrated to be comparable to those of the natural substrates, 11-deoxycortisol and 11-deoxycorticosterone. Metabolites were produced at preparative scale with a CYP11B2-dependent Escherichia coli whole-cell system and purified by HPLC. Using NMR spectroscopy, the metabolites of spironolactone were identified as 11β-OH-spironolactone, 18-OH-spironolactone and 19-OH-spironolactone. Canrenone was converted to 11β-OH-canrenone, 18-OH-canrenone as well as to the CYP11B2-specific product 11β,18-diOH-canrenone. Therefore, a contribution of CYP11B1 and CYP11B2 to the biotransformation of drugs should be taken into account and the metabolites should be tested for their potential toxic and pharmacological effects. A mineralocorticoid receptor transactivation assay in antagonist mode revealed 11β-OH-spironolactone as pharmaceutically active metabolite, whereas all other hydroxylation products negate the antagonist properties of spironolactone and canrenone. Thus, human CYP11B1 and CYP11B2 turned out to metabolize steroid-based drugs additionally to the liver-dependent biotransformation of drugs. Compared with the action of the parental drug, changed properties of the metabolites at the target site have been observed. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Deregulated Levels of the NF-κB1, NF-κB2, and Rel Genes in Ukrainian Patients with Leukemia and Lymphoma in the Post-Chernobyl Period

    PubMed Central

    Savlı, Hakan; Akkoyunlu, Ramis Ufuk; Çine, Naci; Gluzman, Daniil F.; Zavelevich, Michael P.; Sklyarenko, Lilia M.; Koval, Stella V.; Sünnetçi, Deniz

    2016-01-01

    Objective: Nuclear factor kappa B (NF-κB) is an important transcription factor in cancer and NF-κB activation has been seen in angiogenesis, tumor progression, and metastasis. Relationships between specific NF-κB gene networks, leukemogenesis, and radiation exposure are still unknown. Our aim was to study the expression levels of the NF-κB1, NF-κB2, and Rel genes in hematological malignancies in the post-Chernobyl period. Materials and Methods: We analyzed gene expression levels of NF-κB1, NF-κB2, and Rel in 49 B-cell chronic lymphocytic leukemia, 8 B-cell non-Hodgkin’s lymphoma, 3 acute myeloid leukemia, 3 chronic myeloid leukemia, 2 hairy cell leukemia, 2 myelodysplastic syndrome, and 2 T-cell large granular lymphocytic leukemia patients using real-time polymerase chain reaction. Results: Expression levels of NF-κB1, NF-κB2, and Rel genes were found to be deregulated. Conclusion: These results could be accepted as specific gene traces to radiation-induced leukemia or as potential candidates for new diagnostic biomarker studies. Larger experiments and non-exposed control malignant cell populations are needed to clarify these suggestions. PMID:25912249

  20. Effects of the recombinant crustacean hyperglycemic hormones rCHH-B1 and rCHH-B2 on the osmo-ionic regulation of the shrimp Litopenaeus vannamei exposed to acute salinity stress.

    PubMed

    Camacho-Jiménez, Laura; Díaz, Fernando; Sánchez-Castrejón, Edna; Ponce-Rivas, Elizabeth

    2018-03-26

    The Pacific white shrimp Litopenaeus vannamei is a euryhaline organism that copes with salinity fluctuations in the environment; therefore, its osmotic and ionic regulation abilities are vital. Osmoregulation may be controlled by the crustacean hyperglycemic hormone (CHH), a neuropeptide mainly expressed in the eyestalks. In L. vannamei, CHH-B1 and CHH-B2 are CHH isoforms isolated from the eyestalks whose expression is influenced by environmental salinity. It has been suggested that they are involved in the response to salinity stress. To clarify this, we investigated the effect of the recombinant peptides, rCHH-B1 and rCHH-B2, on the osmo-ionic regulation of shrimp acutely exposed to different salinity conditions (8, 26 and 45‰). Both rCHHs promoted differential effects on the osmoregulatory capacity (OC) and the ionoregulatory capacity (IC) for hemolymph Na + and Cl - during iso-osmotic (26‰) and hyper-osmotic (45‰) transfers. These changes were linked to the changes observed in Na + /K + ATPase and carbonic anhydrase gene expression in gills, especially under high salinity conditions, suggesting that the hormones may regulate the expression of these genes. Glucose and protein levels measured during acute salinity transfer suggest their roles as sources of metabolic energy for osmotic regulation or as organic osmolytes. These results taken together suggest that both the CHH-B1 and CHH-B2 peptides are important regulators of the physiological response of L. vannamei to acute salinity fluctuations.

  1. Simultaneous Determination of Total Vitamins B1, B2, B3, and B6 in Infant Formula and Related Nutritionals by Enzymatic Digestion and LC-MS/MS: Single-Laboratory Validation, First Action 2015.14.

    PubMed

    Salvati, Louis M; McClure, Sean C; Reddy, Todime M; Cellar, Nicholas A

    2016-05-01

    This method provides simultaneous determination of total vitamins B1, B2, B3, and B6 in infant formula and related nutritionals (adult and infant). The method was given First Action for vitamins B1, B2, and B6, but not B3, during the AOAC Annual Meeting in September 2015. The method uses acid phosphatase to dephosphorylate the phosphorylated vitamin forms. It then measures thiamine (vitamin B1); riboflavin (vitamin B2); nicotinamide and nicotinic acid (vitamin B3); and pyridoxine, pyridoxal, and pyridoxamine (vitamin B6) from digested sample extract by liquid chromatography-tandem mass spectrometry. A single-laboratory validation was performed on 14 matrixes provided by the AOAC Stakeholder Panel on Infant Formula and Adult Nutritionals (SPIFAN) to demonstrate method effectiveness. The method met requirements of the AOAC SPIFAN Standard Method Performance Requirement for each of the three vitamins, including average over-spike recovery of 99.6 ± 3.5%, average repeatability of 1.5 ± 0.8% relative standard deviation, and average intermediate precision of 3.9 ± 1.3% relative standard deviation.

  2. Investigation of Non-Covalent Interactions of Aflatoxins (B1, B2, G1, G2, and M1) with Serum Albumin

    PubMed Central

    Poór, Miklós; Bálint, Mónika; Hetényi, Csaba; Gődér, Beatrix; Kunsági-Máté, Sándor; Lemli, Beáta

    2017-01-01

    Aflatoxins are widely spread mycotoxins produced mainly by Aspergillus species. Consumption of aflatoxin-contaminated foods and drinks causes serious health risks for people worldwide. It is well-known that the reactive epoxide metabolite of aflatoxin B1 (AFB1) forms covalent adducts with serum albumin. However, non-covalent interactions of aflatoxins with human serum albumin (HSA) are poorly characterized. Thus, in this study the complex formation of aflatoxins was examined with HSA applying spectroscopic and molecular modelling studies. Our results demonstrate that aflatoxins form stable complexes with HSA as reflected by binding constants between 2.1 × 104 and 4.5 × 104 dm3/mol. A binding free energy value of −26.90 kJ mol−1 suggests a spontaneous binding process between AFB1 and HSA at room-temperature, while the positive entropy change of 55.1 JK−1 mol−1 indicates a partial decomposition of the solvation shells of the interacting molecules. Modeling studies and investigations with site markers suggest that Sudlow’s Site I of subdomain IIA is the high affinity binding site of aflatoxins on HSA. Interaction of AFB1 with bovine, porcine, and rat serum albumins was also investigated. Similar stabilities of the examined AFB1-albumin complexes were observed suggesting the low species differences of the albumin-binding of aflatoxins. PMID:29068381

  3. Measurement of the production cross section ratio σ(χ b2(1P)) / σ(χ b1(1P)) in pp collisions at √(s) = 8 TeV

    DOE PAGES

    Khachatryan, Vardan

    2015-02-24

    Our measurement of the production cross section ratio σ(χ b2(1P))/σ(χ b1(1P)) is presented. The χ b1(1P) and χ b2(1P) bottomonium states, promptly produced in pp collisions at √(s) = 8 TeV , are detected by the CMS experiment at the CERN LHC through their radiative decays χ b1,2(1P)→Υ(1S)+γ. The emitted photons are measured through their conversion to e +e - pairs, whose reconstruction allows the two states to be resolved. The Υ(1S) is measured through its decay to two muons. An event sample corresponding to an integrated luminosity of 20.7 fb -1 is used to measure the cross section ratiomore » in a phase-space region defined by the photon pseudorapidity, |η γ|<1.0; the Υ(1S) rapidity, |y Υ|<1.5; and the Υ(1S) transverse momentum, 7T Υ<40 GeV . Finally, the cross section ratio shows no significant dependence on the Υ(1S) transverse momentum, with a measured average value of 0.85± 0.07 (stat + syst) ± 0.08 (BF), where the first uncertainty is the combination of the experimental statistical and systematic uncertainties and the second is from the uncertainty in the ratio of the χ b branching fractions.« less

  4. Measurement of the production cross section ratio σ (χb2 (1 P)) / σ (χb1 (1 P)) in pp collisions at √{ s} = 8 TeV

    NASA Astrophysics Data System (ADS)

    Khachatryan, V.; Sirunyan, A. M.; Tumasyan, A.; Adam, W.; Bergauer, T.; Dragicevic, M.; Erö, J.; Fabjan, C.; Friedl, M.; Frühwirth, R.; Ghete, V. M.; Hartl, C.; Hörmann, N.; Hrubec, J.; Jeitler, M.; Kiesenhofer, W.; Knünz, V.; Krammer, M.; Krätschmer, I.; Liko, D.; Mikulec, I.; Rabady, D.; Rahbaran, B.; Rohringer, H.; Schöfbeck, R.; Strauss, J.; Taurok, A.; Treberer-Treberspurg, W.; Waltenberger, W.; Wulz, C.-E.; Mossolov, V.; Shumeiko, N.; Suarez Gonzalez, J.; Alderweireldt, S.; Bansal, M.; Bansal, S.; Cornelis, T.; De Wolf, E. A.; Janssen, X.; Knutsson, A.; Luyckx, S.; Ochesanu, S.; Roland, B.; Rougny, R.; Van De Klundert, M.; Van Haevermaet, H.; Van Mechelen, P.; Van Remortel, N.; Van Spilbeeck, A.; Blekman, F.; Blyweert, S.; D'Hondt, J.; Daci, N.; Heracleous, N.; Keaveney, J.; Lowette, S.; Maes, M.; Olbrechts, A.; Python, Q.; Strom, D.; Tavernier, S.; Van Doninck, W.; Van Mulders, P.; Van Onsem, G. P.; Villella, I.; Caillol, C.; Clerbaux, B.; De Lentdecker, G.; Dobur, D.; Favart, L.; Gay, A. P. R.; Grebenyuk, A.; Léonard, A.; Mohammadi, A.; Perniè, L.; Reis, T.; Seva, T.; Thomas, L.; Vander Velde, C.; Vanlaer, P.; Wang, J.; Adler, V.; Beernaert, K.; Benucci, L.; Cimmino, A.; Costantini, S.; Crucy, S.; Dildick, S.; Fagot, A.; Garcia, G.; Mccartin, J.; Ocampo Rios, A. A.; Ryckbosch, D.; Salva Diblen, S.; Sigamani, M.; Strobbe, N.; Thyssen, F.; Tytgat, M.; Yazgan, E.; Zaganidis, N.; Basegmez, S.; Beluffi, C.; Bruno, G.; Castello, R.; Caudron, A.; Ceard, L.; Da Silveira, G. G.; Delaere, C.; du Pree, T.; Favart, D.; Forthomme, L.; Giammanco, A.; Hollar, J.; Jez, P.; Komm, M.; Lemaitre, V.; Nuttens, C.; Pagano, D.; Perrini, L.; Pin, A.; Piotrzkowski, K.; Popov, A.; Quertenmont, L.; Selvaggi, M.; Vidal Marono, M.; Vizan Garcia, J. M.; Beliy, N.; Caebergs, T.; Daubie, E.; Hammad, G. H.; Aldá Júnior, W. L.; Alves, G. A.; Brito, L.; Correa Martins Junior, M.; Dos Reis Martins, T.; Mora Herrera, C.; Pol, M. E.; Carvalho, W.; Chinellato, J.; Custódio, A.; Da Costa, E. M.; De Jesus Damiao, D.; De Oliveira Martins, C.; Fonseca De Souza, S.; Malbouisson, H.; Matos Figueiredo, D.; Mundim, L.; Nogima, H.; Prado Da Silva, W. L.; Santaolalla, J.; Santoro, A.; Sznajder, A.; Tonelli Manganote, E. J.; Vilela Pereira, A.; Bernardes, C. A.; Dogra, S.; Fernandez Perez Tomei, T. R.; Gregores, E. M.; Mercadante, P. G.; Novaes, S. F.; Padula, Sandra S.; Aleksandrov, A.; Genchev, V.; Iaydjiev, P.; Marinov, A.; Piperov, S.; Rodozov, M.; Stoykova, S.; Sultanov, G.; Tcholakov, V.; Vutova, M.; Dimitrov, A.; Glushkov, I.; Hadjiiska, R.; Kozhuharov, V.; Litov, L.; Pavlov, B.; Petkov, P.; Bian, J. G.; Chen, G. M.; Chen, H. S.; Chen, M.; Du, R.; Jiang, C. H.; Liang, S.; Plestina, R.; Tao, J.; Wang, X.; Wang, Z.; Asawatangtrakuldee, C.; Ban, Y.; Guo, Y.; Li, Q.; Li, W.; Liu, S.; Mao, Y.; Qian, S. J.; Wang, D.; Zhang, L.; Zou, W.; Avila, C.; Chaparro Sierra, L. F.; Florez, C.; Gomez, J. P.; Gomez Moreno, B.; Sanabria, J. C.; Godinovic, N.; Lelas, D.; Polic, D.; Puljak, I.; Antunovic, Z.; Kovac, M.; Brigljevic, V.; Kadija, K.; Luetic, J.; Mekterovic, D.; Sudic, L.; Attikis, A.; Mavromanolakis, G.; Mousa, J.; Nicolaou, C.; Ptochos, F.; Razis, P. A.; Bodlak, M.; Finger, M.; Finger, M.; Assran, Y.; Ellithi Kamel, A.; Mahmoud, M. A.; Radi, A.; Kadastik, M.; Murumaa, M.; Raidal, M.; Tiko, A.; Eerola, P.; Fedi, G.; Voutilainen, M.; Härkönen, J.; Karimäki, V.; Kinnunen, R.; Kortelainen, M. J.; Lampén, T.; Lassila-Perini, K.; Lehti, S.; Lindén, T.; Luukka, P.; Mäenpää, T.; Peltola, T.; Tuominen, E.; Tuominiemi, J.; Tuovinen, E.; Wendland, L.; Tuuva, T.; Besancon, M.; Couderc, F.; Dejardin, M.; Denegri, D.; Fabbro, B.; Faure, J. L.; Favaro, C.; Ferri, F.; Ganjour, S.; Givernaud, A.; Gras, P.; Hamel de Monchenault, G.; Jarry, P.; Locci, E.; Malcles, J.; Rander, J.; Rosowsky, A.; Titov, M.; Baffioni, S.; Beaudette, F.; Busson, P.; Charlot, C.; Dahms, T.; Dalchenko, M.; Dobrzynski, L.; Filipovic, N.; Florent, A.; Granier de Cassagnac, R.; Mastrolorenzo, L.; Miné, P.; Mironov, C.; Naranjo, I. N.; Nguyen, M.; Ochando, C.; Paganini, P.; Regnard, S.; Salerno, R.; Sauvan, J. B.; Sirois, Y.; Veelken, C.; Yilmaz, Y.; Zabi, A.; Agram, J.-L.; Andrea, J.; Aubin, A.; Bloch, D.; Brom, J.-M.; Chabert, E. C.; Collard, C.; Conte, E.; Fontaine, J.-C.; Gelé, D.; Goerlach, U.; Goetzmann, C.; Le Bihan, A.-C.; Van Hove, P.; Gadrat, S.; Beauceron, S.; Beaupere, N.; Boudoul, G.; Bouvier, E.; Brochet, S.; Carrillo Montoya, C. A.; Chasserat, J.; Chierici, R.; Contardo, D.; Depasse, P.; El Mamouni, H.; Fan, J.; Fay, J.; Gascon, S.; Gouzevitch, M.; Ille, B.; Kurca, T.; Lethuillier, M.; Mirabito, L.; Perries, S.; Ruiz Alvarez, J. D.; Sabes, D.; Sgandurra, L.; Sordini, V.; Vander Donckt, M.; Verdier, P.; Viret, S.; Xiao, H.; Tsamalaidze, Z.; Autermann, C.; Beranek, S.; Bontenackels, M.; Edelhoff, M.; Feld, L.; Hindrichs, O.; Klein, K.; Ostapchuk, A.; Perieanu, A.; Raupach, F.; Sammet, J.; Schael, S.; Weber, H.; Wittmer, B.; Zhukov, V.; Ata, M.; Dietz-Laursonn, E.; Duchardt, D.; Erdmann, M.; Fischer, R.; Güth, A.; Hebbeker, T.; Heidemann, C.; Hoepfner, K.; Klingebiel, D.; Knutzen, S.; Kreuzer, P.; Merschmeyer, M.; Meyer, A.; Millet, P.; Olschewski, M.; Padeken, K.; Papacz, P.; Reithler, H.; Schmitz, S. A.; Sonnenschein, L.; Teyssier, D.; Thüer, S.; Weber, M.; Cherepanov, V.; Erdogan, Y.; Flügge, G.; Geenen, H.; Geisler, M.; Haj Ahmad, W.; Heister, A.; Hoehle, F.; Kargoll, B.; Kress, T.; Kuessel, Y.; Lingemann, J.; Nowack, A.; Nugent, I. M.; Perchalla, L.; Pooth, O.; Stahl, A.; Asin, I.; Bartosik, N.; Behr, J.; Behrenhoff, W.; Behrens, U.; Bell, A. J.; Bergholz, M.; Bethani, A.; Borras, K.; Burgmeier, A.; Cakir, A.; Calligaris, L.; Campbell, A.; Choudhury, S.; Costanza, F.; Diez Pardos, C.; Dooling, S.; Dorland, T.; Eckerlin, G.; Eckstein, D.; Eichhorn, T.; Flucke, G.; Garay Garcia, J.; Geiser, A.; Gunnellini, P.; Hauk, J.; Hempel, M.; Horton, D.; Jung, H.; Kalogeropoulos, A.; Kasemann, M.; Katsas, P.; Kieseler, J.; Kleinwort, C.; Krücker, D.; Lange, W.; Leonard, J.; Lipka, K.; Lobanov, A.; Lohmann, W.; Lutz, B.; Mankel, R.; Marfin, I.; Melzer-Pellmann, I.-A.; Meyer, A. B.; Mittag, G.; Mnich, J.; Mussgiller, A.; Naumann-Emme, S.; Nayak, A.; Novgorodova, O.; Nowak, F.; Ntomari, E.; Perrey, H.; Pitzl, D.; Placakyte, R.; Raspereza, A.; Ribeiro Cipriano, P. M.; Ron, E.; Sahin, M. Ö.; Salfeld-Nebgen, J.; Saxena, P.; Schmidt, R.; Schoerner-Sadenius, T.; Schröder, M.; Seitz, C.; Spannagel, S.; Vargas Trevino, A. D. R.; Walsh, R.; Wissing, C.; Aldaya Martin, M.; Blobel, V.; Centis Vignali, M.; Draeger, A. R.; Erfle, J.; Garutti, E.; Goebel, K.; Görner, M.; Haller, J.; Hoffmann, M.; Höing, R. S.; Kirschenmann, H.; Klanner, R.; Kogler, R.; Lange, J.; Lapsien, T.; Lenz, T.; Marchesini, I.; Ott, J.; Peiffer, T.; Pietsch, N.; Poehlsen, J.; Poehlsen, T.; Rathjens, D.; Sander, C.; Schettler, H.; Schleper, P.; Schlieckau, E.; Schmidt, A.; Seidel, M.; Sola, V.; Stadie, H.; Steinbrück, G.; Troendle, D.; Usai, E.; Vanelderen, L.; Barth, C.; Baus, C.; Berger, J.; Böser, C.; Butz, E.; Chwalek, T.; De Boer, W.; Descroix, A.; Dierlamm, A.; Feindt, M.; Frensch, F.; Giffels, M.; Hartmann, F.; Hauth, T.; Husemann, U.; Katkov, I.; Kornmayer, A.; Kuznetsova, E.; Lobelle Pardo, P.; Mozer, M. U.; Müller, Th.; Nürnberg, A.; Quast, G.; Rabbertz, K.; Ratnikov, F.; Röcker, S.; Simonis, H. J.; Stober, F. M.; Ulrich, R.; Wagner-Kuhr, J.; Wayand, S.; Weiler, T.; Wolf, R.; Anagnostou, G.; Daskalakis, G.; Geralis, T.; Giakoumopoulou, V. 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K.; Pant, L. M.; Shukla, P.; Topkar, A.; Aziz, T.; Banerjee, S.; Bhowmik, S.; Chatterjee, R. M.; Dewanjee, R. K.; Dugad, S.; Ganguly, S.; Ghosh, S.; Guchait, M.; Gurtu, A.; Kole, G.; Kumar, S.; Maity, M.; Majumder, G.; Mazumdar, K.; Mohanty, G. B.; Parida, B.; Sudhakar, K.; Wickramage, N.; Bakhshiansohi, H.; Behnamian, H.; Etesami, S. M.; Fahim, A.; Goldouzian, R.; Jafari, A.; Khakzad, M.; Mohammadi Najafabadi, M.; Naseri, M.; Paktinat Mehdiabadi, S.; Rezaei Hosseinabadi, F.; Safarzadeh, B.; Zeinali, M.; Felcini, M.; Grunewald, M.; Abbrescia, M.; Barbone, L.; Calabria, C.; Chhibra, S. S.; Colaleo, A.; Creanza, D.; De Filippis, N.; De Palma, M.; Fiore, L.; Iaselli, G.; Maggi, G.; Maggi, M.; My, S.; Nuzzo, S.; Pompili, A.; Pugliese, G.; Radogna, R.; Selvaggi, G.; Silvestris, L.; Singh, G.; Venditti, R.; Verwilligen, P.; Zito, G.; Abbiendi, G.; Benvenuti, A. C.; Bonacorsi, D.; Braibant-Giacomelli, S.; Brigliadori, L.; Campanini, R.; Capiluppi, P.; Castro, A.; Cavallo, F. R.; Codispoti, G.; Cuffiani, M.; Dallavalle, G. M.; Fabbri, F.; Fanfani, A.; Fasanella, D.; Giacomelli, P.; Grandi, C.; Guiducci, L.; Marcellini, S.; Masetti, G.; Montanari, A.; Navarria, F. L.; Perrotta, A.; Primavera, F.; Rossi, A. M.; Rovelli, T.; Siroli, G. P.; Tosi, N.; Travaglini, R.; Albergo, S.; Cappello, G.; Chiorboli, M.; Costa, S.; Giordano, F.; Potenza, R.; Tricomi, A.; Tuve, C.; Barbagli, G.; Ciulli, V.; Civinini, C.; D'Alessandro, R.; Focardi, E.; Gallo, E.; Gonzi, S.; Gori, V.; Lenzi, P.; Meschini, M.; Paoletti, S.; Sguazzoni, G.; Tropiano, A.; Benussi, L.; Bianco, S.; Fabbri, F.; Piccolo, D.; Ferro, F.; Lo Vetere, M.; Robutti, E.; Tosi, S.; Dinardo, M. E.; Fiorendi, S.; Gennai, S.; Gerosa, R.; Ghezzi, A.; Govoni, P.; Lucchini, M. T.; Malvezzi, S.; Manzoni, R. A.; Martelli, A.; Marzocchi, B.; Menasce, D.; Moroni, L.; Paganoni, M.; Pedrini, D.; Ragazzi, S.; Redaelli, N.; Tabarelli de Fatis, T.; Buontempo, S.; Cavallo, N.; Di Guida, S.; Fabozzi, F.; Iorio, A. O. M.; Lista, L.; Meola, S.; Merola, M.; Paolucci, P.; Azzi, P.; Bacchetta, N.; Bisello, D.; Branca, A.; Carlin, R.; Checchia, P.; Dall'Osso, M.; Dorigo, T.; Dosselli, U.; Galanti, M.; Gasparini, F.; Gasparini, U.; Giubilato, P.; Gonella, F.; Gozzelino, A.; Kanishchev, K.; Lacaprara, S.; Margoni, M.; Montecassiano, F.; Pazzini, J.; Pozzobon, N.; Ronchese, P.; Simonetto, F.; Tosi, M.; Zotto, P.; Zucchetta, A.; Zumerle, G.; Gabusi, M.; Ratti, S. P.; Riccardi, C.; Salvini, P.; Vitulo, P.; Biasini, M.; Bilei, G. M.; Ciangottini, D.; Fanò, L.; Lariccia, P.; Mantovani, G.; Menichelli, M.; Romeo, F.; Saha, A.; Santocchia, A.; Spiezia, A.; Androsov, K.; Azzurri, P.; Bagliesi, G.; Bernardini, J.; Boccali, T.; Broccolo, G.; Castaldi, R.; Ciocci, M. A.; Dell'Orso, R.; Donato, S.; Fiori, F.; Foà, L.; Giassi, A.; Grippo, M. T.; Ligabue, F.; Lomtadze, T.; Martini, L.; Messineo, A.; Moon, C. S.; Palla, F.; Rizzi, A.; Savoy-Navarro, A.; Serban, A. T.; Spagnolo, P.; Squillacioti, P.; Tenchini, R.; Tonelli, G.; Venturi, A.; Verdini, P. G.; Vernieri, C.; Barone, L.; Cavallari, F.; D'imperio, G.; Del Re, D.; Diemoz, M.; Grassi, M.; Jorda, C.; Longo, E.; Margaroli, F.; Meridiani, P.; Micheli, F.; Nourbakhsh, S.; Organtini, G.; Paramatti, R.; Rahatlou, S.; Rovelli, C.; Santanastasio, F.; Soffi, L.; Traczyk, P.; Amapane, N.; Arcidiacono, R.; Argiro, S.; Arneodo, M.; Bellan, R.; Biino, C.; Cartiglia, N.; Casasso, S.; Costa, M.; Degano, A.; Demaria, N.; Dujany, G.; Finco, L.; Mariotti, C.; Maselli, S.; Migliore, E.; Monaco, V.; Musich, M.; Obertino, M. M.; Ortona, G.; Pacher, L.; Pastrone, N.; Pelliccioni, M.; Pinna Angioni, G. L.; Potenza, A.; Romero, A.; Ruspa, M.; Sacchi, R.; Solano, A.; Staiano, A.; Tamponi, U.; Belforte, S.; Candelise, V.; Casarsa, M.; Cossutti, F.; Della Ricca, G.; Gobbo, B.; La Licata, C.; Marone, M.; Montanino, D.; Schizzi, A.; Umer, T.; Zanetti, A.; Chang, S.; Kropivnitskaya, A.; Nam, S. K.; Kim, D. H.; Kim, G. N.; Kim, M. S.; Kong, D. J.; Lee, S.; Oh, Y. D.; Park, H.; Sakharov, A.; Son, D. C.; Kim, T. J.; Kim, J. Y.; Song, S.; Choi, S.; Gyun, D.; Hong, B.; Jo, M.; Kim, H.; Kim, Y.; Lee, B.; Lee, K. S.; Park, S. K.; Roh, Y.; Choi, M.; Kim, J. H.; Park, I. C.; Park, S.; Ryu, G.; Ryu, M. S.; Choi, Y.; Choi, Y. K.; Goh, J.; Kim, D.; Kwon, E.; Lee, J.; Seo, H.; Yu, I.; Juodagalvis, A.; Komaragiri, J. R.; Md Ali, M. A. B.; Castilla-Valdez, H.; De La Cruz-Burelo, E.; Heredia-de La Cruz, I.; Lopez-Fernandez, R.; Sanchez-Hernandez, A.; Carrillo Moreno, S.; Vazquez Valencia, F.; Pedraza, I.; Salazar Ibarguen, H. A.; Casimiro Linares, E.; Morelos Pineda, A.; Krofcheck, D.; Butler, P. H.; Reucroft, S.; Ahmad, A.; Ahmad, M.; Hassan, Q.; Hoorani, H. R.; Khalid, S.; Khan, W. A.; Khurshid, T.; Shah, M. A.; Shoaib, M.; Bialkowska, H.; Bluj, M.; Boimska, B.; Frueboes, T.; Górski, M.; Kazana, M.; Nawrocki, K.; Romanowska-Rybinska, K.; Szleper, M.; Zalewski, P.; Brona, G.; Bunkowski, K.; Cwiok, M.; Dominik, W.; Doroba, K.; Kalinowski, A.; Konecki, M.; Krolikowski, J.; Misiura, M.; Olszewski, M.; Wolszczak, W.; Bargassa, P.; Beirão Da Cruz E Silva, C.; Faccioli, P.; Ferreira Parracho, P. G.; Gallinaro, M.; Nguyen, F.; Rodrigues Antunes, J.; Seixas, J.; Varela, J.; Vischia, P.; Golutvin, I.; Gorbunov, I.; Karjavin, V.; Konoplyanikov, V.; Korenkov, V.; Lanev, A.; Malakhov, A.; Matveev, V.; Mitsyn, V. V.; Moisenz, P.; Palichik, V.; Perelygin, V.; Shmatov, S.; Skatchkov, N.; Smirnov, V.; Tikhonenko, E.; Yuldashev, B. S.; Zarubin, A.; Golovtsov, V.; Ivanov, Y.; Kim, V.; Levchenko, P.; Murzin, V.; Oreshkin, V.; Smirnov, I.; Sulimov, V.; Uvarov, L.; Vavilov, S.; Vorobyev, A.; Vorobyev, An.; Andreev, Yu.; Dermenev, A.; Gninenko, S.; Golubev, N.; Kirsanov, M.; Krasnikov, N.; Pashenkov, A.; Tlisov, D.; Toropin, A.; Epshteyn, V.; Gavrilov, V.; Lychkovskaya, N.; Popov, V.; Safronov, G.; Semenov, S.; Spiridonov, A.; Stolin, V.; Vlasov, E.; Zhokin, A.; Andreev, V.; Azarkin, M.; Dremin, I.; Kirakosyan, M.; Leonidov, A.; Mesyats, G.; Rusakov, S. V.; Vinogradov, A.; Belyaev, A.; Boos, E.; Dubinin, M.; Dudko, L.; Ershov, A.; Gribushin, A.; Klyukhin, V.; Kodolova, O.; Lokhtin, I.; Obraztsov, S.; Petrushanko, S.; Savrin, V.; Snigirev, A.; Azhgirey, I.; Bayshev, I.; Bitioukov, S.; Kachanov, V.; Kalinin, A.; Konstantinov, D.; Krychkine, V.; Petrov, V.; Ryutin, R.; Sobol, A.; Tourtchanovitch, L.; Troshin, S.; Tyurin, N.; Uzunian, A.; Volkov, A.; Adzic, P.; Ekmedzic, M.; Milosevic, J.; Rekovic, V.; Alcaraz Maestre, J.; Battilana, C.; Calvo, E.; Cerrada, M.; Chamizo Llatas, M.; Colino, N.; De La Cruz, B.; Delgado Peris, A.; Domínguez Vázquez, D.; Escalante Del Valle, A.; Fernandez Bedoya, C.; Fernández Ramos, J. P.; Flix, J.; Fouz, M. C.; Garcia-Abia, P.; Gonzalez Lopez, O.; Goy Lopez, S.; Hernandez, J. M.; Josa, M. I.; Merino, G.; Navarro De Martino, E.; Pérez-Calero Yzquierdo, A.; Puerta Pelayo, J.; Quintario Olmeda, A.; Redondo, I.; Romero, L.; Soares, M. S.; Albajar, C.; de Trocóniz, J. F.; Missiroli, M.; Moran, D.; Brun, H.; Cuevas, J.; Fernandez Menendez, J.; Folgueras, S.; Gonzalez Caballero, I.; Lloret Iglesias, L.; Brochero Cifuentes, J. A.; Cabrillo, I. J.; Calderon, A.; Duarte Campderros, J.; Fernandez, M.; Gomez, G.; Graziano, A.; Lopez Virto, A.; Marco, J.; Marco, R.; Martinez Rivero, C.; Matorras, F.; Munoz Sanchez, F. J.; Piedra Gomez, J.; Rodrigo, T.; Rodríguez-Marrero, A. Y.; Ruiz-Jimeno, A.; Scodellaro, L.; Vila, I.; Vilar Cortabitarte, R.; Abbaneo, D.; Auffray, E.; Auzinger, G.; Bachtis, M.; Baillon, P.; Ball, A. H.; Barney, D.; Benaglia, A.; Bendavid, J.; Benhabib, L.; Benitez, J. F.; Bernet, C.; Bianchi, G.; Bloch, P.; Bocci, A.; Bonato, A.; Bondu, O.; Botta, C.; Breuker, H.; Camporesi, T.; Cerminara, G.; Colafranceschi, S.; D'Alfonso, M.; d'Enterria, D.; Dabrowski, A.; David, A.; De Guio, F.; De Roeck, A.; De Visscher, S.; Dobson, M.; Dordevic, M.; Dupont-Sagorin, N.; Elliott-Peisert, A.; Eugster, J.; Franzoni, G.; Funk, W.; Gigi, D.; Gill, K.; Giordano, D.; Girone, M.; Glege, F.; Guida, R.; Gundacker, S.; Guthoff, M.; Hammer, J.; Hansen, M.; Harris, P.; Hegeman, J.; Innocente, V.; Janot, P.; Kousouris, K.; Krajczar, K.; Lecoq, P.; Lourenço, C.; Magini, N.; Malgeri, L.; Mannelli, M.; Marrouche, J.; Masetti, L.; Meijers, F.; Mersi, S.; Meschi, E.; Moortgat, F.; Morovic, S.; Mulders, M.; Musella, P.; Orsini, L.; Pape, L.; Perez, E.; Perrozzi, L.; Petrilli, A.; Petrucciani, G.; Pfeiffer, A.; Pierini, M.; Pimiä, M.; Piparo, D.; Plagge, M.; Racz, A.; Rolandi, G.; Rovere, M.; Sakulin, H.; Schäfer, C.; Schwick, C.; Sharma, A.; Siegrist, P.; Silva, P.; Simon, M.; Sphicas, P.; Spiga, D.; Steggemann, J.; Stieger, B.; Stoye, M.; Treille, D.; Tsirou, A.; Veres, G. I.; Vlimant, J. R.; Wardle, N.; Wöhri, H. K.; Wollny, H.; Zeuner, W. D.; Bertl, W.; Deiters, K.; Erdmann, W.; Horisberger, R.; Ingram, Q.; Kaestli, H. C.; Kotlinski, D.; Langenegger, U.; Renker, D.; Rohe, T.; Bachmair, F.; Bäni, L.; Bianchini, L.; Bortignon, P.; Buchmann, M. A.; Casal, B.; Chanon, N.; Deisher, A.; Dissertori, G.; Dittmar, M.; Donegà, M.; Dünser, M.; Eller, P.; Grab, C.; Hits, D.; Lustermann, W.; Mangano, B.; Marini, A. C.; Martinez Ruiz del Arbol, P.; Meister, D.; Mohr, N.; Nägeli, C.; Nessi-Tedaldi, F.; Pandolfi, F.; Pauss, F.; Peruzzi, M.; Quittnat, M.; Rebane, L.; Rossini, M.; Starodumov, A.; Takahashi, M.; Theofilatos, K.; Wallny, R.; Weber, H. A.; Amsler, C.; Canelli, M. F.; Chiochia, V.; De Cosa, A.; Hinzmann, A.; Hreus, T.; Kilminster, B.; Lange, C.; Millan Mejias, B.; Ngadiuba, J.; Robmann, P.; Ronga, F. J.; Taroni, S.; Verzetti, M.; Yang, Y.; Cardaci, M.; Chen, K. H.; Ferro, C.; Kuo, C. M.; Lin, W.; Lu, Y. J.; Volpe, R.; Yu, S. S.; Chang, P.; Chang, Y. H.; Chang, Y. W.; Chao, Y.; Chen, K. F.; Chen, P. H.; Dietz, C.; Grundler, U.; Hou, W.-S.; Kao, K. Y.; Lei, Y. J.; Liu, Y. F.; Lu, R.-S.; Majumder, D.; Petrakou, E.; Tzeng, Y. M.; Wilken, R.; Asavapibhop, B.; Srimanobhas, N.; Suwonjandee, N.; Adiguzel, A.; Bakirci, M. N.; Cerci, S.; Dozen, C.; Dumanoglu, I.; Eskut, E.; Girgis, S.; Gokbulut, G.; Gurpinar, E.; Hos, I.; Kangal, E. E.; Kayis Topaksu, A.; Onengut, G.; Ozdemir, K.; Ozturk, S.; Polatoz, A.; Sogut, K.; Sunar Cerci, D.; Tali, B.; Topakli, H.; Vergili, M.; Akin, I. V.; Bilin, B.; Bilmis, S.; Gamsizkan, H.; Karapinar, G.; Ocalan, K.; Sekmen, S.; Surat, U. E.; Yalvac, M.; Zeyrek, M.; Gülmez, E.; Isildak, B.; Kaya, M.; Kaya, O.; Bahtiyar, H.; Barlas, E.; Cankocak, K.; Vardarlı, F. I.; Yücel, M.; Levchuk, L.; Sorokin, P.; Brooke, J. J.; Clement, E.; Cussans, D.; Flacher, H.; Frazier, R.; Goldstein, J.; Grimes, M.; Heath, G. P.; Heath, H. F.; Jacob, J.; Kreczko, L.; Lucas, C.; Meng, Z.; Newbold, D. M.; Paramesvaran, S.; Poll, A.; Senkin, S.; Smith, V. J.; Williams, T.; Bell, K. W.; Belyaev, A.; Brew, C.; Brown, R. M.; Cockerill, D. J. A.; Coughlan, J. A.; Harder, K.; Harper, S.; Olaiya, E.; Petyt, D.; Shepherd-Themistocleous, C. H.; Thea, A.; Tomalin, I. R.; Womersley, W. J.; Worm, S. D.; Baber, M.; Bainbridge, R.; Buchmuller, O.; Burton, D.; Colling, D.; Cripps, N.; Cutajar, M.; Dauncey, P.; Davies, G.; Della Negra, M.; Dunne, P.; Ferguson, W.; Fulcher, J.; Futyan, D.; Gilbert, A.; Hall, G.; Iles, G.; Jarvis, M.; Karapostoli, G.; Kenzie, M.; Lane, R.; Lucas, R.; Lyons, L.; Magnan, A.-M.; Malik, S.; Mathias, B.; Nash, J.; Nikitenko, A.; Pela, J.; Pesaresi, M.; Petridis, K.; Raymond, D. M.; Rogerson, S.; Rose, A.; Seez, C.; Sharp, P.; Tapper, A.; Vazquez Acosta, M.; Virdee, T.; Cole, J. E.; Hobson, P. R.; Khan, A.; Kyberd, P.; Leggat, D.; Leslie, D.; Martin, W.; Reid, I. D.; Symonds, P.; Teodorescu, L.; Turner, M.; Dittmann, J.; Hatakeyama, K.; Kasmi, A.; Liu, H.; Scarborough, T.; Charaf, O.; Cooper, S. I.; Henderson, C.; Rumerio, P.; Avetisyan, A.; Bose, T.; Fantasia, C.; Lawson, P.; Richardson, C.; Rohlf, J.; Sperka, D.; St. John, J.; Sulak, L.; Alimena, J.; Berry, E.; Bhattacharya, S.; Christopher, G.; Cutts, D.; Demiragli, Z.; Ferapontov, A.; Garabedian, A.; Heintz, U.; Kukartsev, G.; Laird, E.; Landsberg, G.; Luk, M.; Narain, M.; Segala, M.; Sinthuprasith, T.; Speer, T.; Swanson, J.; Breedon, R.; Breto, G.; Calderon De La Barca Sanchez, M.; Chauhan, S.; Chertok, M.; Conway, J.; Conway, R.; Cox, P. T.; Erbacher, R.; Gardner, M.; Ko, W.; Lander, R.; Miceli, T.; Mulhearn, M.; Pellett, D.; Pilot, J.; Ricci-Tam, F.; Searle, M.; Shalhout, S.; Smith, J.; Squires, M.; Stolp, D.; Tripathi, M.; Wilbur, S.; Yohay, R.; Cousins, R.; Everaerts, P.; Farrell, C.; Hauser, J.; Ignatenko, M.; Rakness, G.; Takasugi, E.; Valuev, V.; Weber, M.; Babb, J.; Burt, K.; Clare, R.; Ellison, J.; Gary, J. W.; Hanson, G.; Heilman, J.; Ivova Rikova, M.; Jandir, P.; Kennedy, E.; Lacroix, F.; Liu, H.; Long, O. R.; Luthra, A.; Malberti, M.; Nguyen, H.; Olmedo Negrete, M.; Shrinivas, A.; Sumowidagdo, S.; Wimpenny, S.; Andrews, W.; Branson, J. G.; Cerati, G. B.; Cittolin, S.; D'Agnolo, R. T.; Evans, D.; Holzner, A.; Kelley, R.; Klein, D.; Lebourgeois, M.; Letts, J.; Macneill, I.; Olivito, D.; Padhi, S.; Palmer, C.; Pieri, M.; Sani, M.; Sharma, V.; Simon, S.; Sudano, E.; Tadel, M.; Tu, Y.; Vartak, A.; Welke, C.; Würthwein, F.; Yagil, A.; Yoo, J.; Barge, D.; Bradmiller-Feld, J.; Campagnari, C.; Danielson, T.; Dishaw, A.; Flowers, K.; Franco Sevilla, M.; Geffert, P.; George, C.; Golf, F.; Gouskos, L.; Incandela, J.; Justus, C.; Mccoll, N.; Richman, J.; Stuart, D.; To, W.; West, C.; Apresyan, A.; Bornheim, A.; Bunn, J.; Chen, Y.; Di Marco, E.; Duarte, J.; Mott, A.; Newman, H. B.; Pena, C.; Rogan, C.; Spiropulu, M.; Timciuc, V.; Wilkinson, R.; Xie, S.; Zhu, R. Y.; Azzolini, V.; Calamba, A.; Carlson, B.; Ferguson, T.; Iiyama, Y.; Paulini, M.; Russ, J.; Vogel, H.; Vorobiev, I.; Cumalat, J. P.; Ford, W. T.; Gaz, A.; Luiggi Lopez, E.; Nauenberg, U.; Smith, J. G.; Stenson, K.; Ulmer, K. A.; Wagner, S. R.; Alexander, J.; Chatterjee, A.; Chu, J.; Dittmer, S.; Eggert, N.; Mirman, N.; Nicolas Kaufman, G.; Patterson, J. R.; Ryd, A.; Salvati, E.; Skinnari, L.; Sun, W.; Teo, W. D.; Thom, J.; Thompson, J.; Tucker, J.; Weng, Y.; Winstrom, L.; Wittich, P.; Winn, D.; Abdullin, S.; Albrow, M.; Anderson, J.; Apollinari, G.; Bauerdick, L. A. T.; Beretvas, A.; Berryhill, J.; Bhat, P. C.; Burkett, K.; Butler, J. N.; Cheung, H. W. K.; Chlebana, F.; Cihangir, S.; Elvira, V. D.; Fisk, I.; Freeman, J.; Gao, Y.; Gottschalk, E.; Gray, L.; Green, D.; Grünendahl, S.; Gutsche, O.; Hanlon, J.; Hare, D.; Harris, R. M.; Hirschauer, J.; Hooberman, B.; Jindariani, S.; Johnson, M.; Joshi, U.; Kaadze, K.; Klima, B.; Kreis, B.; Kwan, S.; Linacre, J.; Lincoln, D.; Lipton, R.; Liu, T.; Lykken, J.; Maeshima, K.; Marraffino, J. M.; Martinez Outschoorn, V. I.; Maruyama, S.; Mason, D.; McBride, P.; Mishra, K.; Mrenna, S.; Musienko, Y.; Nahn, S.; Newman-Holmes, C.; O'Dell, V.; Prokofyev, O.; Sexton-Kennedy, E.; Sharma, S.; Soha, A.; Spalding, W. J.; Spiegel, L.; Taylor, L.; Tkaczyk, S.; Tran, N. V.; Uplegger, L.; Vaandering, E. W.; Vidal, R.; Whitbeck, A.; Whitmore, J.; Yang, F.; Acosta, D.; Avery, P.; Bourilkov, D.; Carver, M.; Cheng, T.; Curry, D.; Das, S.; De Gruttola, M.; Di Giovanni, G. P.; Field, R. D.; Fisher, M.; Furic, I. K.; Hugon, J.; Konigsberg, J.; Korytov, A.; Kypreos, T.; Low, J. F.; Matchev, K.; Milenovic, P.; Mitselmakher, G.; Muniz, L.; Rinkevicius, A.; Shchutska, L.; Snowball, M.; Yelton, J.; Zakaria, M.; Hewamanage, S.; Linn, S.; Markowitz, P.; Martinez, G.; Rodriguez, J. L.; Adams, T.; Askew, A.; Bochenek, J.; Diamond, B.; Haas, J.; Hagopian, S.; Hagopian, V.; Johnson, K. F.; Prosper, H.; Veeraraghavan, V.; Weinberg, M.; Baarmand, M. M.; Hohlmann, M.; Kalakhety, H.; Yumiceva, F.; Adams, M. R.; Apanasevich, L.; Bazterra, V. E.; Berry, D.; Betts, R. R.; Bucinskaite, I.; Cavanaugh, R.; Evdokimov, O.; Gauthier, L.; Gerber, C. E.; Hofman, D. J.; Khalatyan, S.; Kurt, P.; Moon, D. H.; O'Brien, C.; Silkworth, C.; Turner, P.; Varelas, N.; Albayrak, E. A.; Bilki, B.; Clarida, W.; Dilsiz, K.; Duru, F.; Haytmyradov, M.; Merlo, J.-P.; Mermerkaya, H.; Mestvirishvili, A.; Moeller, A.; Nachtman, J.; Ogul, H.; Onel, Y.; Ozok, F.; Penzo, A.; Rahmat, R.; Sen, S.; Tan, P.; Tiras, E.; Wetzel, J.; Yetkin, T.; Yi, K.; Barnett, B. A.; Blumenfeld, B.; Bolognesi, S.; Fehling, D.; Gritsan, A. V.; Maksimovic, P.; Martin, C.; Swartz, M.; Baringer, P.; Bean, A.; Benelli, G.; Bruner, C.; Gray, J.; Kenny, R. P., III; Malek, M.; Murray, M.; Noonan, D.; Sanders, S.; Sekaric, J.; Stringer, R.; Wang, Q.; Wood, J. S.; Barfuss, A. F.; Chakaberia, I.; Ivanov, A.; Khalil, S.; Makouski, M.; Maravin, Y.; Saini, L. K.; Shrestha, S.; Skhirtladze, N.; Svintradze, I.; Gronberg, J.; Lange, D.; Rebassoo, F.; Wright, D.; Baden, A.; Belloni, A.; Calvert, B.; Eno, S. C.; Gomez, J. A.; Hadley, N. J.; Kellogg, R. G.; Kolberg, T.; Lu, Y.; Marionneau, M.; Mignerey, A. C.; Pedro, K.; Skuja, A.; Tonjes, M. B.; Tonwar, S. C.; Apyan, A.; Barbieri, R.; Bauer, G.; Busza, W.; Cali, I. A.; Chan, M.; Di Matteo, L.; Dutta, V.; Gomez Ceballos, G.; Goncharov, M.; Gulhan, D.; Klute, M.; Lai, Y. S.; Lee, Y.-J.; Levin, A.; Luckey, P. D.; Ma, T.; Paus, C.; Ralph, D.; Roland, C.; Roland, G.; Stephans, G. S. F.; Stöckli, F.; Sumorok, K.; Velicanu, D.; Veverka, J.; Wyslouch, B.; Yang, M.; Zanetti, M.; Zhukova, V.; Dahmes, B.; Gude, A.; Kao, S. C.; Klapoetke, K.; Kubota, Y.; Mans, J.; Pastika, N.; Rusack, R.; Singovsky, A.; Tambe, N.; Turkewitz, J.; Acosta, J. G.; Oliveros, S.; Avdeeva, E.; Bloom, K.; Bose, S.; Claes, D. R.; Dominguez, A.; Gonzalez Suarez, R.; Keller, J.; Knowlton, D.; Kravchenko, I.; Lazo-Flores, J.; Malik, S.; Meier, F.; Snow, G. R.; Dolen, J.; Godshalk, A.; Iashvili, I.; Kharchilava, A.; Kumar, A.; Rappoccio, S.; Alverson, G.; Barberis, E.; Baumgartel, D.; Chasco, M.; Haley, J.; Massironi, A.; Morse, D. M.; Nash, D.; Orimoto, T.; Trocino, D.; Wang, R.-J.; Wood, D.; Zhang, J.; Hahn, K. A.; Kubik, A.; Mucia, N.; Odell, N.; Pollack, B.; Pozdnyakov, A.; Schmitt, M.; Stoynev, S.; Sung, K.; Velasco, M.; Won, S.; Brinkerhoff, A.; Chan, K. M.; Drozdetskiy, A.; Hildreth, M.; Jessop, C.; Karmgard, D. J.; Kellams, N.; Lannon, K.; Luo, W.; Lynch, S.; Marinelli, N.; Pearson, T.; Planer, M.; Ruchti, R.; Valls, N.; Wayne, M.; Wolf, M.; Woodard, A.; Antonelli, L.; Brinson, J.; Bylsma, B.; Durkin, L. S.; Flowers, S.; Hill, C.; Hughes, R.; Kotov, K.; Ling, T. Y.; Puigh, D.; Rodenburg, M.; Smith, G.; Winer, B. L.; Wolfe, H.; Wulsin, H. W.; Driga, O.; Elmer, P.; Hebda, P.; Hunt, A.; Koay, S. A.; Lujan, P.; Marlow, D.; Medvedeva, T.; Mooney, M.; Olsen, J.; Piroué, P.; Quan, X.; Saka, H.; Stickland, D.; Tully, C.; Werner, J. S.; Zenz, S. C.; Zuranski, A.; Brownson, E.; Mendez, H.; Ramirez Vargas, J. E.; Barnes, V. E.; Benedetti, D.; Bolla, G.; Bortoletto, D.; De Mattia, M.; Hu, Z.; Jha, M. K.; Jones, M.; Jung, K.; Kress, M.; Leonardo, N.; Lopes Pegna, D.; Maroussov, V.; Merkel, P.; Miller, D. H.; Neumeister, N.; Radburn-Smith, B. C.; Shi, X.; Shipsey, I.; Silvers, D.; Svyatkovskiy, A.; Wang, F.; Xie, W.; Xu, L.; Yoo, H. D.; Zablocki, J.; Zheng, Y.; Parashar, N.; Stupak, J.; Adair, A.; Akgun, B.; Ecklund, K. M.; Geurts, F. J. M.; Li, W.; Michlin, B.; Padley, B. P.; Redjimi, R.; Roberts, J.; Zabel, J.; Betchart, B.; Bodek, A.; Covarelli, R.; de Barbaro, P.; Demina, R.; Eshaq, Y.; Ferbel, T.; Garcia-Bellido, A.; Goldenzweig, P.; Han, J.; Harel, A.; Khukhunaishvili, A.; Petrillo, G.; Vishnevskiy, D.; Ciesielski, R.; Demortier, L.; Goulianos, K.; Lungu, G.; Mesropian, C.; Arora, S.; Barker, A.; Chou, J. P.; Contreras-Campana, C.; Contreras-Campana, E.; Duggan, D.; Ferencek, D.; Gershtein, Y.; Gray, R.; Halkiadakis, E.; Hidas, D.; Kaplan, S.; Lath, A.; Panwalkar, S.; Park, M.; Patel, R.; Salur, S.; Schnetzer, S.; Somalwar, S.; Stone, R.; Thomas, S.; Thomassen, P.; Walker, M.; Rose, K.; Spanier, S.; York, A.; Bouhali, O.; Castaneda Hernandez, A.; Eusebi, R.; Flanagan, W.; Gilmore, J.; Kamon, T.; Khotilovich, V.; Krutelyov, V.; Montalvo, R.; Osipenkov, I.; Pakhotin, Y.; Perloff, A.; Roe, J.; Rose, A.; Safonov, A.; Sakuma, T.; Suarez, I.; Tatarinov, A.; Akchurin, N.; Cowden, C.; Damgov, J.; Dragoiu, C.; Dudero, P. R.; Faulkner, J.; Kovitanggoon, K.; Kunori, S.; Lee, S. W.; Libeiro, T.; Volobouev, I.; Appelt, E.; Delannoy, A. G.; Greene, S.; Gurrola, A.; Johns, W.; Maguire, C.; Mao, Y.; Melo, A.; Sharma, M.; Sheldon, P.; Snook, B.; Tuo, S.; Velkovska, J.; Arenton, M. W.; Boutle, S.; Cox, B.; Francis, B.; Goodell, J.; Hirosky, R.; Ledovskoy, A.; Li, H.; Lin, C.; Neu, C.; Wood, J.; Clarke, C.; Harr, R.; Karchin, P. E.; Kottachchi Kankanamge Don, C.; Lamichhane, P.; Sturdy, J.; Belknap, D. A.; Carlsmith, D.; Cepeda, M.; Dasu, S.; Dodd, L.; Duric, S.; Friis, E.; Hall-Wilton, R.; Herndon, M.; Hervé, A.; Klabbers, P.; Lanaro, A.; Lazaridis, C.; Levine, A.; Loveless, R.; Mohapatra, A.; Ojalvo, I.; Perry, T.; Pierro, G. A.; Polese, G.; Ross, I.; Sarangi, T.; Savin, A.; Smith, W. H.; Vuosalo, C.; Woods, N.

    2015-04-01

    A measurement of the production cross section ratio σ (χb2 (1 P)) / σ (χb1 (1 P)) is presented. The χb1 (1 P) and χb2 (1 P) bottomonium states, promptly produced in pp collisions at √{ s} = 8 TeV, are detected by the CMS experiment at the CERN LHC through their radiative decays χ b 1 , 2 (1 P) → ϒ (1 S) + γ. The emitted photons are measured through their conversion to e+e- pairs, whose reconstruction allows the two states to be resolved. The ϒ (1 S) is measured through its decay to two muons. An event sample corresponding to an integrated luminosity of 20.7 fb-1 is used to measure the cross section ratio in a phase-space region defined by the photon pseudorapidity, |ηγ | < 1.0; the ϒ (1 S) rapidity, |yϒ | < 1.5; and the ϒ (1 S) transverse momentum, 7 < pTϒ < 40 GeV. The cross section ratio shows no significant dependence on the ϒ (1 S) transverse momentum, with a measured average value of 0.85 ± 0.07 (stat +syst) ± 0.08 (BF), where the first uncertainty is the combination of the experimental statistical and systematic uncertainties and the second is from the uncertainty in the ratio of the χb branching fractions.

  5. A 2-D Array of Superconducting Magnesium Diboride (MgB2) Far-IR Thermal Detectors for Planetary Exploration

    NASA Technical Reports Server (NTRS)

    Lakew, Brook

    2009-01-01

    A 2-D array of superconducting Magnesium Diboride(MgB2) far IR thermal detectors has been fabricated. Such an array is intended to be at the focal plane of future generation thermal imaging far-IR instruments that will investigate the outer planets and their icy moons. Fabrication and processing of the pixels of the array as well as noise characterization of architectured MgB2 thin films will be presented. Challenges and solutions for improving the performance of the array will be discussed.

  6. Ascorbic acid deficiency decreases hepatic cytochrome P-450, especially CYP2B1/2B2, and simultaneously induces heme oxygenase-1 gene expression in scurvy-prone ODS rats.

    PubMed

    Kobayashi, Misato; Hoshinaga, Yukiko; Miura, Natsuko; Tokuda, Yuki; Shigeoka, Shigeru; Murai, Atsushi; Horio, Fumihiko

    2014-01-01

    The mechanisms underlying the decrease in hepatic cytochrome P-450 (CYP) content in ascorbic acid deficiency was investigated in scurvy-prone ODS rats. First, male ODS rats were fed a diet containing sufficient ascorbic acid (control) or a diet without ascorbic acid (deficient) for 18 days, with or without the intraperitoneal injection of phenobarbital. Ascorbic acid deficiency decreased hepatic microsomal total CYP content, CYP2B1/2B2 protein, and mitochondrial cytochrome oxidase (COX) complex IV subunit I protein, and simultaneously increased heme oxygenase-1 protein in microsomes and mitochondria. Next, heme oxygenase-1 inducers, that is lipopolysaccharide and hemin, were administered to phenobaribital-treated ODS rats fed sufficient ascorbic acid. The administration of these inducers decreased hepatic microsomal total CYP content, CYP2B1/2B2 protein, and mitochondrial COX complex IV subunit I protein. These results suggested that the stimulation of hepatic heme oxygenase-1 expression by ascorbic acid deficiency caused the decrease in CYP content in liver.

  7. Inhibition of NF-{kappa}B1 and NF-{kappa}B2 activation in prostate cancer cells treated with antibody against the carboxyl terminal domain of GRP78: Effect of p53 upregulation

    SciTech Connect

    Misra, U.K.; Kaczowka, S.; Pizzo, S.V., E-mail: Pizzo001@mc.duke.edu

    2010-02-19

    Ligation of cancer cell surface GRP78 by activated {alpha}{sub 2}-macroglobulin ({alpha}{sub 2}M{sup *}) triggers pro-proliferative and anti-apoptotic signaling pathways. Cancer patients who develop autoantibodies to the {alpha}{sub 2}M{sup *} binding site in GRP78 have a poor prognosis since these antibodies are receptor agonists. The NF-{kappa}B family of transcription factors induces expression of genes affecting cell growth and differentiation. NF-{kappa}B1 plays a major regulatory role in controlling innate immunity and inflammation, whereas NF-{kappa}B2 plays a greater role in cancer cell proliferation. Here we report that treatment of prostate cancer cells with antibody directed against the carboxyl terminal domain of GRP78 inhibitsmore » {alpha}{sub 2}M{sup *}-induced activation of NF-{kappa}B2 by {approx}50% while exerting a lesser effect of {approx}20% on NF-{kappa}B1 activation. Treatment of these cells nearly abolished {alpha}{sub 2}M{sup *}-induced activation of IKK{alpha} involved in the activation of NF-{kappa}B2. This antibody also suppressed {alpha}{sub 2}M{sup *}-induced phosphorylation of IKK{alpha}, IKK{alpha}/{beta}, I{kappa}B{alpha}, and I{kappa}B{beta} as well as levels of NIK. Antibody treatment of cancer cells elevated pro-apoptotic p21WAF and p27kip while reducing cyclin D1 levels. These studies demonstrate that antibody directed against the carboxyl terminal domain of GRP78 inhibits the pro-proliferative NF-{kappa}B signaling cascade in cancer cells.« less

  8. Regulation of insulin and type 1 insulin-like growth factor signaling and action by the Grb10/14 and SH2B1/B2 adaptor proteins.

    PubMed

    Desbuquois, Bernard; Carré, Nadège; Burnol, Anne-Françoise

    2013-02-01

    The effects of insulin and type 1 insulin-like growth factor (IGF-1) on metabolism, growth and survival are mediated by their association with specific receptor tyrosine kinases, which results in both receptor and substrate phosphorylation. Phosphotyrosine residues on receptors and substrates provide docking sites for signaling proteins containing SH2 (Src homology 2) domains, including molecular adaptors. This review focuses on the regulation of insulin/IGF-1 signaling and action by two adaptor families with a similar domain organization: the growth factor receptor-bound proteins Grb7/10/14 and the SH2B proteins. Both Grb10/14 and SH2B1/B2 associate with the activation loop of insulin/IGF-1 receptors through their SH2 domains, but association of Grb10/14 also involves their unique BPS domain. Consistent with Grb14 binding as a pseudosubstrate to the kinase active site, insulin/IGF-induced activation of receptors and downstream signaling pathways in cultured cells is inhibited by Grb10/14 adaptors, but is potentiated by SH2B1/B2 adaptors. Accordingly, Grb10 and Grb14 knockout mice show improved insulin/IGF sensitivity in vivo, and, for Grb10, overgrowth and increased skeketal muscle and pancreatic β-cell mass. Conversely, SH2B1-depleted mice display insulin and IGF-1 resistance, with peripheral depletion leading to reduced adiposity and neuronal depletion leading to obesity through associated leptin resistance. Grb10/14 and SH2B1 adaptors also modulate insulin/IGF-1 action by interacting with signaling components downstream of receptors and exert several tissue-specific effects. The identification of Grb10/14 and SH2B1 as physiological regulators of insulin signaling and action, together with observations that variants at their gene loci are associated with obesity and/or insulin resistance, highlight them as potential therapeutic targets for these conditions. © 2012 The Authors Journal compilation © 2012 FEBS.

  9. Comparison of the amount of bioaccessible fumonisin B1 and B2 in maize and rice inoculated with Fusarium verticillioides (MRC 826) and determined by in vitro digestion-preliminary results.

    PubMed

    Szabó-Fodor, J; Bors, I; Szabó, A; Kovács, M

    2016-08-01

    In this study the occurrence of hidden fumonisin B1 (FB1) and fumonisin B2 (FB2) was analysed, on two cereal substrates (maize and rice), inoculated with Fusarium verticillioides (MRC 826), in order to determine the ratio of hidden FB1 and FB2. Two parallel methods were applied: an in vitro human digestion sample pre-treatment and the routine extraction procedure, in both cases with subsequent LC-MS analysis. It was found that all samples showed higher concentration of total fumonisin B1 after digestion, as compared to that of free fumonisin analysed only after extraction. The percentage of the hidden form by maize was 18.8 % (±2.4) for FB1 and 36.8 % (±3.8) for FB2, while for rice it was 32.3 % (±11.3) and 58.0 (±6.8), respectively, expressed as the proportion to total fumonisin B1, for the total dataset. Significant differences were found in the FB1 and FB2 concentration measured after the different digestion phases (saliva, gastric and duodenal) in case of both matrixes. The results are useful for human risk assessment, since both humans and animals may be exposed to markedly higher toxin load, as determined merely by conventional analytical methods.

  10. Vitamin (B1, B2, B3 and B6) content and oxidative stability of Gastrocnemius muscle from dry-cured hams elaborated with different nitrifying salt contents and by two ageing times.

    PubMed

    Gratacós-Cubarsí, M; Sárraga, C; Castellari, M; Guàrdia, M D; Regueiro, J A García; Arnau, J

    2013-11-01

    The effect of the amount of added nitrate and nitrate plus nitrite to dry-cured hams on the vitamin (B1, B2, B3, B6) content, the antioxidant enzyme superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSHPx) activities and the thiobarbituric acid reactive substances (TBARS) was assessed in Gastrocnemius muscle at the end of two ripening processes. Five different curing mixtures (Hi-N: 600 KNO3; Lo-N: 150 KNO3; Hi-Mix: 600 KNO3+600 NaNO2; Lo-Mix: 150 KNO3+150 NaNO2; Hi-Mix/Asc: 600 KNO3+600 NaNO2+500 sodium ascorbate, expressed as mg of salts added on surface per kg of fresh ham) were evaluated in dry-cured hams aged for 11.5months (standard process, SP) and 22months (long process, LP). Minor differences in target parameters between the hams due to the process were found. The amount of nitrate when it was added alone or as a mixture of nitrate and nitrite, as well as the ascorbate addition to dry-cured hams did not affect vitamin B1, B2 and B3 contents. The level of vitamin B6 was affected by both the amount and the mixture of salts; the addition of nitrite reduced around 40% the content of vitamin B6, but it was not affected by nitrate or ascorbate. The activity of SOD and CAT decreased with the amount of nitrate and nitrite, while GSHPx and TBARS resulted unaffected. Copyright © 2013 Elsevier Ltd. All rights reserved.

  11. Broad-spectrum immunoaffinity cleanup for the determination of aflatoxins B1, B2, G1, G2, M1, M2 in Ophiocordyceps sinensis and its pharmaceutical preparations by ultra performance liquid chromatography tandem mass spectrometry.

    PubMed

    Sun, Shujuan; Xie, Jie; Peng, Tao; Shao, Bing; Zhu, Kui; Sun, Yuanze; Yao, Kai; Gu, Qiang; Zhang, Jing; Fan, Chunlin; Chen, Ying; Jiang, Haiyang

    2017-11-15

    An ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for the simultaneous determination of aflatoxins B 1 , B 2 , G 1 , G 2 , M 1 and M 2 (AFB 1 , AFB 2 , AFG 1 , AFG 2 , AFM 1 and AFM 2 ) in Ophiocordyceps sinensis and its pharmaceutical preparations. A rapid and reliable immunoaffinity column containing a broad-spectrum monoclonal antibody for six aflatoxins was used for sample cleanup. Under the optimized conditions, the home-made immunoaffinity column capacity were about 315, 319, 292, 102, 444 and 369ng/mL gel for AFB 1 , AFB 2 , AFG 1 , AFG 2 , AFM 1 and AFM 2 , respectively. Recoveries for all tested aflatoxins ranged from 79.28% to 103.42% with relative standard deviation less than 8%. The limits of quantitation were in the range of 0.008-0.045μg/kg. Among 31 real samples analyzed, one sample was contaminated with AFB 1 , AFB 2 and AFM 1 at levels of 0.483, 0.068 and 0.104μg/kg, respectively. The established method is simple, accurate, and can be effectively used to determine the aflatoxins in Ophiocordyceps sinensis and its pharmaceutical preparations. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Dietary intake of the water-soluble vitamins B1, B2, B6, B12 and C in 10 countries in the European Prospective Investigation into Cancer and Nutrition.

    PubMed

    Olsen, A; Halkjaer, J; van Gils, C H; Buijsse, B; Verhagen, H; Jenab, M; Boutron-Ruault, M C; Ericson, U; Ocké, M C; Peeters, P H M; Touvier, M; Niravong, M; Waaseth, M; Skeie, G; Khaw, K T; Travis, R; Ferrari, P; Sanchez, M J; Agudo, A; Overvad, K; Linseisen, J; Weikert, C; Sacerdote, C; Evangelista, A; Zylis, D; Tsiotas, K; Manjer, J; van Guelpen, B; Riboli, E; Slimani, N; Bingham, S

    2009-11-01

    To describe the intake of vitamins thiamine (B1), riboflavin (B2), B6 (pyridoxine), B12 (cobalamine) and C (ascorbic acid) and their food sources among 27 centres in 10 countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Between 1995 and 2000, 36 034 persons aged between 35 and 74 years were administered a standardized 24-h dietary recall using a computerized interview software programme (EPIC-SOFT). Intakes of the four B vitamins and vitamin C were estimated using the standardized EPIC Nutrient Database (ENDB). Mean intakes were adjusted for age and weighted by season and day of recall. Intake of B vitamins did not vary considerably between centres, except in the UK health-conscious cohort, in which substantially higher intakes of thiamine and lower intakes of vitamin B12 were reported compared with other centres. Overall, meat was the most important contributor to the B vitamins in all centres except in the UK health-conscious group. Vitamin C showed a clear geographical gradient, with higher intakes in the southern centres as compared with the northern ones; this was more pronounced in men than in women. Vegetables and fruits were major contributors to vitamin C in all centres, but juices and potatoes were also important sources in the northern centres. This study showed no major differences across centres in the mean intakes of B vitamins (thiamine, riboflavin, B6, B12), whereas a tendency towards a north-south gradient was observed for vitamin C.

  13. FOUR WAVE MIXING SPECTROSCOPY OF THE NO_3 tilde{B} ^2E' - tilde{X} ^2A_2' transition

    NASA Astrophysics Data System (ADS)

    Fukushima, Masaru; Ishiwata, Takashi

    2014-06-01

    The tilde{B} ^2E' - tilde{X} ^2A_2' electronic transition of NO_3 generated in a supersonic free jet expansion was investigated by four wave mixing ( 4WM ) spectroscopy. The degenerated 4WM and laser induced fluorescence ( LIF ) spectra around the 0_0^0 band region were measured simultaneously. The D4WM spectrum shows broad band features for the 0_0^0 band similar to that of the LIF spectrum. The broad 0_0^0 band does not consist of one sub-band, but of several bands. The intensity distribution of the sub-bands of the D4WM spectrum is similar, but not identical to that of the LIF spectrum.

  14. Ochratoxin A transport by the human breast cancer resistance protein (BCRP), multidrug resistance protein 2 (MRP2), and organic anion-transporting polypeptides 1A2, 1B1 and 2B1.

    PubMed

    Qi, Xiaozhe; Wagenaar, Els; Xu, Wentao; Huang, Kunlun; Schinkel, Alfred H

    2017-08-15

    Ochratoxin A (OTA) is a fungal secondary metabolite that can contaminate various foods. OTA has several toxic effects like nephrotoxicity, hepatotoxicity, and neurotoxicity in different animal species, but its mechanisms of toxicity are still unclear. How OTA accumulates in kidney, liver, and brain is as yet unknown, but transmembrane transport proteins are likely involved. We studied transport of OTA in vitro, using polarized MDCKII cells transduced with cDNAs of the efflux transporters mouse (m)Bcrp, human (h)BCRP, mMrp2, or hMRP2, and HEK293 cells overexpressing cDNAs of the human uptake transporters OATP1A2, OATP1B1, OATP1B3, or OATP2B1 at pH7.4 and 6.4. MDCKII-mBcrp cells were more resistant to OTA toxicity than MDCKII parental and hBCRP-transduced cells. Transepithelial transport experiments showed some apically directed transport by MDCKII-mBcrp cells at pH7.4, whereas both mBcrp and hBCRP clearly transported OTA at pH6.4. There was modest transport of OTA by mMrp2 and hMRP2 only at pH6.4. OATP1A2 and OATP2B1 mediated uptake of OTA both at pH7.4 and 6.4, but OATP1B1 only at pH7.4. There was no detectable transport of OTA by OATP1B3. Our data indicate that human BCRP and MRP2 can mediate elimination of OTA from cells, thus reducing OTA toxicity. On the other hand, human OATP1A2, OATP1B1, and OATP2B1 can mediate cellular uptake of OTA, which could aggravate OTA toxicity. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Analysis of fumonisins B1 and B2 in spices and aromatic and medicinal herbs by HPLC-FLD with on-line post-column derivatization and positive confirmation by LC-MS/MS.

    PubMed

    Kong, Weijun; Xie, Tingting; Li, Junyuan; Wei, Jianhe; Qiu, Feng; Qi, Aidi; Zheng, Yuguo; Yang, Meihua

    2012-07-07

    Fumonisins are produced by the fungus Fusarium verticillioides, which are known to cause fatal diseases in some animals and humans. Here, we describe a sensitive, reproducible and reliable analytical method for the quantitative determination of fumonisins B(1) (FB(1)) and B(2) (FB(2)) in 112 spices and aromatic and medicinal herbs marketed in China. This method is based on high performance liquid chromatography and fluorescence detection (HPLC-FLD) coupled to a new on-line post-column derivatization using ortho-phthaldialdehyde with 2-mercaptoethanol and immunoaffinity column clean-up. Under the optimized experimental conditions, a complete separation of FB(1) and FB(2) was obtained using a Synergi C(18) column and a gradient elution at 0.8 mL min(-1) with methanol and 0.1 M phosphate buffer at pH 3.15. The limits of detection for FB(1) and FB(2) were both 40 μg kg(-1). Good recoveries were found for spiked samples with FB(1) and FB(2), ranging from 82.34% to 98.16% for FB(1) and from 72.58% to 97.10% for FB(2), with relative standard deviation (RSD) < 7.0%. 5 spices, 11 aromatic herbs and 96 medicinal herbs including 93 normal samples and 19 visibly moldy samples, which were spoiled artificially, were analyzed. The results showed that 8 (42.1%) visibly moldy samples and 8 (8.6%) normal samples were contaminated with FB(1) at mean contents of 129.0 and 165.9 μg kg(-1), and with FB(2) at 1745.0 and 256.8 μg kg(-1), respectively. Positive confirmation of detected samples was performed by liquid chromatography tandem electrospray ionization mass spectrometry (LC-ESI-MS/MS), using a triple quadrupole analyzer and operated in the multiple reaction monitoring mode.

  16. Signaling mediated by the NF-κB sub-units NF-κB1, NF-κB2 and c-Rel differentially regulate Helicobacter felis-induced gastric carcinogenesis in C57BL/6 mice

    PubMed Central

    Burkitt, M D; Williams, J M; Duckworth, C A; O'Hara, A; Hanedi, A; Varro, A; Caamaño, J H; Pritchard, D M

    2013-01-01

    The classical nuclear factor-kappaB (NF-κB) signaling pathway has been shown to be important in a number of models of inflammation-associated cancer. In a mouse model of Helicobacter-induced gastric cancer, impairment of classical NF-κB signaling in the gastric epithelium led to the development of increased preneoplastic pathology, however the role of specific NF-κB proteins in Helicobacter-associated gastric cancer development remains poorly understood. To investigate this C57BL/6, Nfkb1−/−, Nfkb2−/− and c-Rel−/− mice were infected with Helicobacter felis for 6 weeks or 12 months. Bacterial colonization, gastric atrophy and preneoplastic changes were assessed histologically and cytokine expression was assessed by qPCR. Nfkb1−/− mice developed spontaneous gastric atrophy when maintained for 12 months in conventional animal house conditions. They also developed more pronounced gastric atrophy after short-term H. felis colonization with a similar extent of preneoplasia to wild-type (WT) mice after 12 months. c-Rel−/− mice developed a similar degree of gastric atrophy to WT mice; 3 of 6 of these animals also developed lymphoproliferative lesions after 12 months of infection. Nfkb2−/− mice developed minimal gastric epithelial pathology even 12 months after H. felis infection. These findings demonstrate that NF-κB1- and NF-κB2-mediated signaling pathways differentially regulate the epithelial consequences of H. felis infection in the stomach, while c-Rel-mediated signaling also appears to modulate the risk of lymphomagenesis in gastric mucosa-associated lymphoid tissue. PMID:23975431

  17. Inhibition of Inflammation and Bone Erosion by RNA Interference-Mediated Silencing of Heterogeneous Nuclear RNP A2/B1 in Two Experimental Models of Rheumatoid Arthritis.

    PubMed

    Herman, Sonja; Fischer, Anita; Presumey, Jessy; Hoffmann, Markus; Koenders, Marije I; Escriou, Virginie; Apparailly, Florence; Steiner, Guenter

    2015-09-01

    The nuclear protein heterogeneous nuclear RNP A2/B1 (hnRNP A2/B1) is involved in posttranscriptional regulation of gene expression. It is constitutively expressed in lymphoid organs and highly up-regulated in the synovial tissue of patients with rheumatoid arthritis (RA), who may also generate autoantibodies to this protein. This study was undertaken to investigate the potential involvement of hnRNP A2/B1 in the pathogenesis of autoimmune arthritis, by silencing hnRNP A2/B1 expression in 2 animal models of RA. Collagen-induced arthritis (CIA) and the K/BxN serum-transfer model were used as animal models of RA. Efficient silencing of hnRNP A2/B1 was achieved using a liposome-based carrier system for delivery of small interfering RNAs. Expression of hnRNP A2/B1 was analyzed by flow cytometry, reverse transcription-quantitative polymerase chain reaction, Western blotting, and immunohistochemistry. The number of osteoclasts was determined by tartrate-resistant acid phosphatase staining. Cytokine levels and anticollagen antibody levels were measured by enzyme-linked immunosorbent assay. Efficient silencing of hnRNP A2/B1 was achieved in all lymphoid organs. In both experimental models, the incidence and severity of arthritis were largely reduced and bone erosion was not detectable as compared to the control groups. Down-modulation of hnRNP A2/B1 significantly interfered with the production of proinflammatory cytokines from monocyte/macrophages, but not from T cells. Consistent with these findings, production of T cell cytokines was not impaired when cells were restimulated in vitro with type II collagen. Furthermore, levels of anticollagen antibodies were not affected by hnRNP A2/B1 silencing. Our findings suggest that hnRNP A2/B1 has an important role in regulation of the innate immune system, especially at the level of monocyte/macrophage activation. Therefore, down-modulation of hnRNP A2/B1 seems to affect primarily the effector phase of autoimmune arthritis. © 2015

  18. 26 CFR 1.509(a)-2 - Exclusion for certain organizations described in section 170(b)(1)(A).

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... United States. (b) Medical research organizations. In order to qualify under section 509(a)(1) as a medical research organization described in section 170(b)(1)(A)(iii), an organization must meet the... contribution for medical research before January 1 of the fifth calendar year which begins after the date such...

  19. 26 CFR 1.509(a)-2 - Exclusion for certain organizations described in section 170(b)(1)(A).

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... United States. (b) Medical research organizations. In order to qualify under section 509(a)(1) as a medical research organization described in section 170(b)(1)(A)(iii), an organization must meet the... contribution for medical research before January 1 of the fifth calendar year which begins after the date such...

  20. 26 CFR 1.509(a)-2 - Exclusion for certain organizations described in section 170(b)(1)(A).

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... United States. (b) Medical research organizations. In order to qualify under section 509(a)(1) as a medical research organization described in section 170(b)(1)(A)(iii), an organization must meet the... contribution for medical research before January 1 of the fifth calendar year which begins after the date such...

  1. 26 CFR 1.509(a)-2 - Exclusion for certain organizations described in section 170(b)(1)(A).

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... United States. (b) Medical research organizations. In order to qualify under section 509(a)(1) as a medical research organization described in section 170(b)(1)(A)(iii), an organization must meet the... contribution for medical research before January 1 of the fifth calendar year which begins after the date such...

  2. High-pressure behavior of A2B2O7 pyrochlore (A=Eu, Dy; B=Ti, Zr)

    NASA Astrophysics Data System (ADS)

    Rittman, Dylan R.; Turner, Katlyn M.; Park, Sulgiye; Fuentes, Antonio F.; Yan, Jinyuan; Ewing, Rodney C.; Mao, Wendy L.

    2017-01-01

    In situ high-pressure X-ray diffraction and Raman spectroscopy were used to determine the influence of composition on the high-pressure behavior of A2B2O7 pyrochlore (A = Eu, Dy; B = Ti, Zr) up to ˜50 GPa. Based on X-ray diffraction results, all compositions transformed to the high-pressure cotunnite structure. The B-site cation species had a larger effect on the transition pressure than the A-site cation species, with the onset of the phase transformation occurring at ˜41 GPa for B = Ti and ˜16 GPa B = Zr. However, the A-site cation affected the kinetics of the phase transformation, with the transformation for compositions with the smaller ionic radii, i.e., A = Dy, proceeding faster than those with a larger ionic radii, i.e., A = Eu. These results were consistent with previous work in which the radius-ratio of the A- and B-site cations determined the energetics of disordering, and compositions with more similarly sized A- and B-site cations had a lower defect formation energy. Raman spectra revealed differences in the degree of short-range order of the different compositions. Due to the large phase fraction of cotunnite at high pressure for B = Zr compositions, Raman modes for cotunnite could be observed, with more modes recorded for A = Eu than A = Dy. These additional modes are attributed to increased short-to-medium range ordering in the initially pyrochlore structured Eu2Zr2O7 as compared with the initially defect-fluorite structured Dy2Zr2O7.

  3. High-pressure behavior of A 2 B 2 O 7 pyrochlore (A=Eu, Dy; B=Ti, Zr)

    SciTech Connect

    Rittman, Dylan R.; Turner, Katlyn M.; Park, Sulgiye

    2017-01-28

    In situ high-pressure X-ray diffraction and Raman spectroscopy were used to determine the influence of composition on the high-pressure behavior of A 2B 2O 7 pyrochlore (A=Eu, Dy; B=Ti, Zr) up to ~50GPa. Based on X-ray diffraction results, all compositions transformed to the high-pressure cotunnite structure. The B-site cation species had a larger effect on the transition pressure than the A-site cation species, with the onset of the phase transformation occurring at ~41 GPa for B=Ti and ~16 GPa B=Zr. However, the A-site cation affected the kinetics of the phase transformation, with the transformation for compositions with the smaller ionicmore » radii, i.e., A=Dy, proceeding faster than those with a larger ionic radii, i.e., A=Eu. These results were consistent with previous work in which the radius-ratio of the A- and B-site cations determined the energetics of disordering, and compositions with more similarly sized A- and B-site cations had a lower defect formation energy. Raman spectra revealed differences in the degree of short-range order of the different compositions. Due to the large phase fraction of cotunnite at high pressure for B=Zr compositions, Raman modes for cotunnite could be observed, with more modes recorded for A=Eu than A=Dy. These additional modes are attributed to increased short-to-medium range ordering in the initially pyrochlore structured Eu 2Zr 2O 7 as compared with the initially defect-fluorite structured Dy 2Zr 2O 7.« less

  4. High-pressure behavior of A 2 B 2 O 7 pyrochlore (A=Eu, Dy; B=Ti, Zr)

    DOE PAGES

    Rittman, Dylan R.; Turner, Katlyn M.; Park, Sulgiye; ...

    2017-01-24

    In situ high-pressure X-ray diffraction and Raman spectroscopy were used to determine the influence of composition on the high-pressure behavior of A 2B 2O 7 pyrochlore (A = Eu, Dy; B = Ti, Zr) up to ~50 GPa. Based on X-ray diffraction results, all compositions transformed to the high-pressure cotunnite structure. The B-site cation species had a larger effect on the transition pressure than the A-site cation species, with the onset of the phase transformation occurring at ~41 GPa for B = Ti and ~16 GPa B = Zr. But, the A-site cation affected the kinetics of the phase transformation,more » with the transformation for compositions with the smaller ionic radii, i.e., A = Dy, proceeding faster than those with a larger ionic radii, i.e., A = Eu. Our results were consistent with previous work in which the radius-ratio of the A- and B-site cations determined the energetics of disordering, and compositions with more similarly sized A- and B-site cations had a lower defect formation energy. Raman spectra revealed differences in the degree of short-range order of the different compositions. Due to the large phase fraction of cotunnite at high pressure for B = Zr compositions, Raman modes for cotunnite could be observed, with more modes recorded for A = Eu than A = Dy. These additional modes are attributed to increased short-to-medium range ordering in the initially pyrochlore structured Eu 2Zr 2O 7 as compared with the initially defect-fluorite structured Dy 2Zr 2O 7.« less

  5. Phylogeography of Y-chromosome haplogroup O3a2b2-N6 reveals patrilineal traces of Austronesian populations on the eastern coastal regions of Asia

    PubMed Central

    Teo, Yik-Ying; Huang, Yun-Zhi; Wang, Ling-Xiang; Yu, Ge; Saw, Woei-Yuh; Ong, Rick Twee-Hee; Lu, Yan; Zhang, Chao; Xu, Shu-Hua; Jin, Li; Li, Hui

    2017-01-01

    Austronesian diffusion is considered one of the greatest dispersals in human history; it led to the peopling of an extremely vast region, ranging from Madagascar in the Indian Ocean to Easter Island in Remote Oceania. The Y-chromosome haplogroup O3a2b*-P164(xM134), a predominant paternal lineage of Austronesian populations, is found at high frequencies in Polynesian populations. However, the internal phylogeny of this haplogroup remains poorly investigated. In this study, we analyzed -seventeen Y-chromosome sequences of haplogroup O3a2b*-P164(xM134) and generated a revised phylogenetic tree of this lineage based on 310 non-private Y-chromosome polymorphisms. We discovered that all available O3a2b*-P164(xM134) samples belong to the newly defined haplogroup O3a2b2-N6 and samples from Austronesian populations belong to the sublineage O3a2b2a2-F706. Additionally, we genotyped a series of Y-chromosome polymorphisms in a large collection of samples from China. We confirmed that the sublineage O3a2b2a2b-B451 is unique to Austronesian populations. We found that O3a2b2-N6 samples are widely distributed on the eastern coastal regions of Asia, from Korea to Vietnam. Furthermore, we propose- that the O3a2b2a2b-B451 lineage represents a genetic connection between ancestors of Austronesian populations and ancient populations in North China, where foxtail millet was domesticated about 11,000 years ago. The large number of newly defined Y-chromosome polymorphisms and the revised phylogenetic tree of O3a2b2-N6 will be helpful to explore the origin of proto-Austronesians and the early diffusion process of Austronesian populations. PMID:28380021

  6. Phylogeography of Y-chromosome haplogroup O3a2b2-N6 reveals patrilineal traces of Austronesian populations on the eastern coastal regions of Asia.

    PubMed

    Wei, Lan-Hai; Yan, Shi; Teo, Yik-Ying; Huang, Yun-Zhi; Wang, Ling-Xiang; Yu, Ge; Saw, Woei-Yuh; Ong, Rick Twee-Hee; Lu, Yan; Zhang, Chao; Xu, Shu-Hua; Jin, Li; Li, Hui

    2017-01-01

    Austronesian diffusion is considered one of the greatest dispersals in human history; it led to the peopling of an extremely vast region, ranging from Madagascar in the Indian Ocean to Easter Island in Remote Oceania. The Y-chromosome haplogroup O3a2b*-P164(xM134), a predominant paternal lineage of Austronesian populations, is found at high frequencies in Polynesian populations. However, the internal phylogeny of this haplogroup remains poorly investigated. In this study, we analyzed -seventeen Y-chromosome sequences of haplogroup O3a2b*-P164(xM134) and generated a revised phylogenetic tree of this lineage based on 310 non-private Y-chromosome polymorphisms. We discovered that all available O3a2b*-P164(xM134) samples belong to the newly defined haplogroup O3a2b2-N6 and samples from Austronesian populations belong to the sublineage O3a2b2a2-F706. Additionally, we genotyped a series of Y-chromosome polymorphisms in a large collection of samples from China. We confirmed that the sublineage O3a2b2a2b-B451 is unique to Austronesian populations. We found that O3a2b2-N6 samples are widely distributed on the eastern coastal regions of Asia, from Korea to Vietnam. Furthermore, we propose- that the O3a2b2a2b-B451 lineage represents a genetic connection between ancestors of Austronesian populations and ancient populations in North China, where foxtail millet was domesticated about 11,000 years ago. The large number of newly defined Y-chromosome polymorphisms and the revised phylogenetic tree of O3a2b2-N6 will be helpful to explore the origin of proto-Austronesians and the early diffusion process of Austronesian populations.

  7. 75 FR 28188 - Airworthiness Directives; General Electric Company CF34-1A, -3A, -3A1, -3A2, -3B, and -3B1...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-20

    ... DEPARTMENT OF TRANSPORTATION Federal Aviation Administration 14 CFR Part 39 [Docket No. FAA-2007-27687; Directorate Identifier 2000-NE-42-AD; Amendment 39-16144; AD 2009-26-09] RIN 2120-AA64 Airworthiness Directives; General Electric Company CF34-1A, -3A, -3A1, -3A2, -3B, and -3B1 Turbofan Engines...

  8. β-Asarone Inhibits Invasion and EMT in Human Glioma U251 Cells by Suppressing Splicing Factor HnRNP A2/B1.

    PubMed

    Li, Li; Wu, Mingxia; Wang, Chengqiang; Yu, Zanyang; Wang, Hongmei; Qi, Hongyi; Xu, Xiaoyu

    2018-03-16

    β-asarone, the main component in the volatile oil of Acori tatarinowii Rhizoma, has been found to possess antitumor activity. However, its effect and mechanisms against tumor invasion and epithelial-mesenchymal transition (EMT) are still unclear. In this study, no or less cytotoxicity was caused by β-asarone within 0-120 μM in human glioma U251 cells for 48 h. β-asarone (30 and 60 μM) inhibited the migration of U251 cells in the wound healing assay, suppressed the invasion of U251 cells in the Boyden chamber invasion assay, and inhibited the adhesion of U251 cells onto the Matrigel. Moreover, β-asarone suppressed EMT with the up-regulation of E-cadherin and the down-regulation of vimentin. HnRNP A2/B1, a well-characterized oncogenic protein, was shown at a high basal level in U251 cells and β-asarone reduced hnRNP A2/B1 expression in a concentration and time-dependent way. Importantly, hnRNP A2/B1 overexpression significantly counteracted the inhibition of β-asarone on the migration, invasion, and adhesion of U251 cells and reversed the modulation of EMT markers by β-asarone. Additionally, β-asarone decreased the MMP-9 and p-STAT3 in U251 cells, which was also reversed by hnRNP A2/B1 overexpression. Together, our results suggest that hnRNP A2/B1 may be a potential molecular target underlying the inhibitory effect of β-asarone on invasion and EMT in glioma cells.

  9. Polymorphisms in androgen metabolism genes AR, CYP1B1, CYP19, and SRD5A2and prostate cancer risk and aggressiveness in Bulgarian patients.

    PubMed

    Kachakova, Darina; Mitkova, Atanaska; Popov, Elenko; Beltcheva, Olga; Vlahova, Alexandrina; Dikov, Tihomir; Christova, Svetlana; Mitev, Vanio; Slavov, Chavdar; Kaneva, Radka

    2016-04-19

    The aim of our study was to elucidate the role of polymorphisms in AR, CYP1B1, CYP19, and SRD5A2 genes for prostate cancer (PC) development in Bulgarian patients. We genotyped 246 PC patients and 261 controls (155 with benign prostate hyperplasia and 107 healthy population controls) using direct sequencing, PCR-RFLP, SSCP, and fragment analysis. The allele and genotype frequencies of most of the studied variants did not differ significantly between cases and controls. Increased frequencies of the C/C genotype and C allele of rs1056837 in CYP1B1, and genotype 7/8 of the (TTTA)n repeat polymorphism in CYP19, were observed in patients in comparison with controls.The 8/9 and the 7/12 genotypes of (TTTA)n in CYP19 showed suggestive evidence for association with decreased prostate cancer risk and the risk for aggressive disease, respectively. The haplotype analysis revealed 2 CYP1B1 haplotypes associated with PC risk reduction. Some CYP1B1 haplotypes and genotypes of the CYP19 (TTTA)n repeat appeared to be associated with disease risk or aggressiveness in Bulgarian PC patients. In contrast, the SRD5A2 polymorphisms (V89L and (TA)n repeat), the CAG repeat in AR, and the Arg264Cys variant in CYP19A1 are most likely not implicated in prostate carcinogenesis.

  10. Genetic modification of potato against microbial diseases: in vitro and in planta activity of a dermaseptin B1 derivative, MsrA2.

    PubMed

    Osusky, Milan; Osuska, Lubica; Kay, William; Misra, Santosh

    2005-08-01

    Dermaseptin B1 is a potent cationic antimicrobial peptide found in skin secretions of the arboreal frog Phyllomedusa bicolor. A synthetic derivative of dermaseptin B1, MsrA2 (N-Met-dermaseptin B1), elicited strong antimicrobial activities against various phytopathogenic fungi and bacteria in vitro. To assess its potential for plant protection, MsrA2 was expressed at low levels (1-5 microg/g of fresh tissue) in the transgenic potato (Solanum tuberosum L.) cv. Desiree. Stringent challenges of these transgenic potato plants with a variety of highly virulent fungal phytopathogens--Alternaria, Cercospora, Fusarium, Phytophthora, Pythium, Rhizoctonia and Verticillium species--and with the bacterial pathogen Erwinia carotovora demonstrated that the plants had an unusually broad-spectrum and powerful resistance to infection. MsrA2 profoundly protected both plants and tubers from diseases such as late blight, dry rot and pink rot and markedly extended the storage life of tubers. Due to these properties in planta, MsrA2 is proposed as an ideal antimicrobial peptide candidate to significantly increase resistance to phytopathogens and improve quality in a variety of crops worldwide with the potential to obviate fungicides and facilitate storage under difficult conditions.

  11. Hypervelocity Impact (HVI). Volume 2; WLE Small-Scale Fiberglass Panel Flat Multi-Layer Targets A-1, A-2, and B-1

    NASA Technical Reports Server (NTRS)

    Gorman, Michael R.; Ziola, Steven M.

    2007-01-01

    During 2003 and 2004, the Johnson Space Center's White Sands Testing Facility in Las Cruces, New Mexico conducted hypervelocity impact tests on the space shuttle wing leading edge. Hypervelocity impact tests were conducted to determine if Micro-Meteoroid/Orbital Debris impacts could be reliably detected and located using simple passive ultrasonic methods. The objective of Targets A-1, A-2, and B-2 was to study hypervelocity impacts through multi-layered panels simulating Whipple shields on spacecraft. Impact damage was detected using lightweight, low power instrumentation capable of being used in flight.

  12. Magnetic damping in sputter-deposited C o2MnGe Heusler compounds with A 2 ,B 2 , and L 21 orders: Experiment and theory

    NASA Astrophysics Data System (ADS)

    Shaw, Justin M.; Delczeg-Czirjak, Erna K.; Edwards, Eric R. J.; Kvashnin, Yaroslav; Thonig, Danny; Schoen, Martin A. W.; Pufall, Matt; Schneider, Michael L.; Silva, Thomas J.; Karis, Olof; Rice, Katherine P.; Eriksson, Olle; Nembach, Hans T.

    2018-03-01

    We show that very low values of the magnetic damping parameter can be achieved in sputter deposited polycrystalline films of C o2MnGe annealed at relatively low temperatures ranging from 240 °C to 400 °C. Damping values as low as 0.0014 are obtained with an intrinsic value of 0.0010 after spin-pumping contributions are considered. Of importance to most applications is the low value of inhomogeneous linewidth that yields measured linewidths of 1.8 and 5.1 mT at 10 and 40 GHz, respectively. The damping parameter monotonically decreases as the B 2 order of the films increases. This trend is reproduced and explained by ab initio calculations of the electronic structure and damping parameter. Here, the damping parameter is calculated as the structure evolves from A 2 to B 2 to L 21 orders. The largest decrease in the damping parameter occurs during the A 2 to B 2 transition as the half-metallic phase becomes established.

  13. hnRNP A2/B1 interacts with influenza A viral protein NS1 and inhibits virus replication potentially through suppressing NS1 RNA/protein levels and NS1 mRNA nuclear export

    SciTech Connect

    Wang, Yimeng; Zhou, Jianhong; Du, Yuchun, E-mail: ydu@uark.edu

    2014-01-20

    The NS1 protein of influenza viruses is a major virulence factor and exerts its function through interacting with viral/cellular RNAs and proteins. In this study, we identified heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNP A2/B1) as an interacting partner of NS1 proteins by a proteomic method. Knockdown of hnRNP A2/B1 by small interfering RNA (siRNA) resulted in higher levels of NS vRNA, NS1 mRNA, and NS1 protein in the virus-infected cells. In addition, we demonstrated that hnRNP A2/B1 proteins are associated with NS1 and NS2 mRNAs and that knockdown of hnRNP A2/B1 promotes transport of NS1 mRNA from the nucleus to themore » cytoplasm in the infected cells. Lastly, we showed that knockdown of hnRNP A2/B1 leads to enhanced virus replication. Our results suggest that hnRNP A2/B1 plays an inhibitory role in the replication of influenza A virus in host cells potentially through suppressing NS1 RNA/protein levels and NS1 mRNA nucleocytoplasmic translocation. - Highlights: • Cellular protein hnRNP A2/B1 interacts with influenza viral protein NS1. • hnRNP A2/B1 suppresses the levels of NS1 protein, vRNA and mRNA in infected cells. • hnRNP A2/B1 protein is associated with NS1 and NS2 mRNAs. • hnRNP A2/B1 inhibits the nuclear export of NS1 mRNAs. • hnRNP A2/B1 inhibits influenza virus replication.« less

  14. VHL genetic alteration in CCRCC does not determine de-regulation of HIF, CAIX, hnRNP A2/B1 and osteopontin.

    PubMed

    Nyhan, Michelle J; El Mashad, Shereen M; O'Donovan, Tracey R; Ahmad, Sarfraz; Collins, Chris; Sweeney, Paul; Rogers, Eamonn; O'Sullivan, Gerald C; McKenna, Sharon L

    2011-06-01

    Von Hippel-Lindau (VHL) tumour suppressor gene inactivation is associated with clear cell renal cell carcinoma (CCRCC) development. The VHL protein (pVHL) has been proposed to regulate the expression of several proteins including Hypoxia Inducible Factor-α (HIF-α), carbonic anhydrase (CA)IX, heterogeneous nuclear ribonucleoprotein (hnRNP)A2/B1 and osteopontin. pVHL has been characterized in vitro, however, clinical studies are limited. We evaluated the impact of VHL genetic alterations on the expression of several pVHL protein targets in paired normal and tumor tissue. The VHL gene was sequenced in 23 CCRCC patients and VHL transcript levels were evaluated by Real-Time RT-PCR. Expression of pVHL's protein targets were determined by Western blotting in 17 paired patient samples. VHL genetic alterations were identified in 43.5% (10/23) of CCRCCs. HIF-1α, HIF-2α and CAIX were up-regulated in 88.2% (15/17), 100% (17/17) and 88.2% (15/17) of tumors respectively and their expression is independent of VHL status. hnRNP A2/B1 and osteopontin expression was variable in CCRCCs and had no association with VHL genetic status. As expression of these proposed pVHL targets can be achieved independently of VHL mutation (and possibly by hypoxia alone), this data suggests that other pVHL targets may be more crucial in renal carcinogenesis.

  15. Development of Multiple Heart-Cutting Two-Dimensional Liquid Chromatography Coupled to Quadrupole-Orbitrap High Resolution Mass Spectrometry for Simultaneous Determination of Aflatoxin B1, B2, G1, G2, and Ochratoxin A in Snus, a Smokeless Tobacco Product.

    PubMed

    Qi, Dawei; Fei, Ting; Liu, Hong; Yao, Heming; Wu, Da; Liu, Baizhan

    2017-11-15

    The combination of multiple heart-cutting two-dimensional liquid chromatography (MHC-LC/LC) and quadrupole-orbitrap high-resolution mass spectrometry (HRMS) for simultaneous determination of the aflatoxins and ochratoxin A in snus is presented in this work. A C18 capillary column was used as the first dimension (1D) to isolate the aflatoxins and ochratoxin A from the complex matrices; then, a 2-position/10-port high-pressure valve equipped with two 60 μL loops was employed to transfer the heart-cuts of 1D-LC into a pentafluorophenyl (PFP) column for the second dimension (2D) separation. With the better separation of the MHC-LC/LC system, the sensitivity of the method was improved, which is essential for the trace mycotoxins analysis. Furthermore, HRMS performed in parallel reaction monitoring mode was employed to eliminate the interferences, and the sample pretreatment procedure was simplified. A new approach utilizing ethyl acetate with 1% formic acid/water solution was adopted to extract aflatoxins and ochratoxin A in snus, which provided parallel recoveries for aflatoxins and ochratoxin A with higher responses in comparison with the QuEChERS method. A dynamic range between 0.2 and 20 μg/kg was achieved with LOQs of 0.05 μg/kg for aflatoxin B 1 , 0.1 μg/kg for aflatoxin B 2 , G 1 , G 2 , and 1.0 μg/kg for ochratoxin A in dry mass of product. The results revealed that the established method exhibited good repeatability and recovery and could be used as a rapid and reliable approach for routine analysis of aflatoxins and ochratoxin A in snus.

  16. Genetic link with cholelithiasis among pediatric SCA Tunisian patients: Examples of UGT1A1, SLCO1A2 and SLCO1B1.

    PubMed

    Chaouch, Leila; Kalai1, Miniar; Darragi, Imen; Boudrigua, Imen; Chaouachi, Dorra; Ammar, Slim Ben; Mellouli, F; Bjaoui, M; Abbes, Salem

    2016-03-01

    Hyperbilirubinemia is often observed in chronic hemolysis and results in the formation of pigment cholelithiasis that could be increased by the presence of defected enzymes involved in the bilirubin metabolism. Indeed, this is the first report that interested in the study of polymorphisms in genes encoded for enzymes involved in the bilirubin metabolism: rs 4149056 of SLCO1B1 and rs4149000 of SLCO1A2 in combination with rs8175347 and rs887829 of UGT1A1 in order to find a correlation between the polymorphisms studied and the presence of gallstones in a population of sickle cell anemia (SCA) pediatric Tunisians. Our study involved 102 unrelated Tunisian subjects. All SCA patients are children (less than 16 years old) and were characterized by hyperbilirubinemia and 52 of them have cholelithiasis. The polymorphisms of the candidate genes were analyzed for all subjects by PCR/sequencing. Genotype and allele frequencies between cases and controls were compared using Pearson's chi-square test with a significance threshold of P < 0.05 (compare 2, version 1.02). The novelty of this report is that children carrying the combined genotype of the rs studied: (TA7TA7)/TT/TC/GA have a higher risk to develop gallstones (P = 0.0027, RR = 18.27 (20.0061-915.28)). Altogether our data provide the implication of UGT1A1 and SLCO1A2 in sickle cell anemia-related cholelithiasis.

  17. Synthesis and characterization of monoisomeric 1,8,15,22-substituted (A3B and A2B2) phthalocyanines and phthalocyanine-fullerene dyads.

    PubMed

    Ranta, Jenni; Kumpulainen, Tatu; Lemmetyinen, Helge; Efimov, Alexander

    2010-08-06

    Synthesis and characterization of three phthalocyanine-fullerene (Pc-C(60)) dyads, corresponding monoisomeric phthalocyanines (Pc), and building blocks, phthalonitriles, are described. Six novel bisaryl phthalonitriles were prepared by the Suzuki-Miyaura coupling reaction from trifluoromethanesulfonic acid 2,3-dicyanophenyl ester and various oxaborolanes. Two phthalonitriles were selected for the synthesis of A(3)B- and A(2)B(2)-type phthalocyanines. Phthalonitrile 4 has a bulky 3,5-di-tert-butylphenyl substituent at the alpha-phthalo position, which forces only one regioisomer to form and greatly increases the solubility of phthalocyanine. Phthalonitrile 8 has a 3-phenylpropanol side chain at the alpha-position making further modifications of the side group possible. Synthesized monoisomeric A(3)B- and A(2)B(2)-type phthalocyanines are modified by attachment of malonic residues. Finally, fullerene is covalently linked to phthalocyanine with one or two malonic bridges to produce Pc-C(60) dyads. Due to the monoisomeric structure and increased solubility of phthalocyanines, the quality of NMR spectra of the compounds is enhanced significantly, making detailed NMR analysis of the structures possible. The synthesized dyads have different orientations of phthalocyanine and fullerene, which strongly influence the electron transfer (ET) from phthalocyanine to fullerene moiety. Fluorescence quenchings of the dyads were measured in both polar and nonpolar solvents, and in all cases, the quenching was more efficient in the polar environment. As expected, most efficient fluorescence quenching was observed for dyad 20b, with two linkers and phthalocyanine and fullerene in face-to-face orientation.

  18. Transition moments, radiative transition probabilities, and radiative lifetimes for the band systems A 2Π-X 2Σ+, B 2Σ+-X 2Σ+, and A 2Π-A´ 2Δ of scandium monosulfide, ScS

    NASA Astrophysics Data System (ADS)

    Romeu, João Gabriel Farias; Belinassi, Antonio Ricardo; Ornellas, Fernando R.

    2018-05-01

    A manifold of electronic states of ScS was investigated with special emphasis on the low-lying states X 2Σ+, A´ 2Δ, A 2Π, and B 2Σ+. For all states, potential energy curves were constructed covering internuclear distances from the equilibrium region through the dissociation limit. For the above states, besides providing the most accurate set of theoretical spectroscopic parameters to date, we have also computed dipole moment functions, transitions dipole moment functions, the associated radiative transition probabilities, and radiative lifetimes. For the states known experimentally, X 2Σ+, A 2Π, and B 2Σ+, our results significantly expand our present knowledge of the energetic profile of these states thus providing a new perspective for understanding the limited spectral data for this species known so far. For the new state, A´ 2Δ, yet unobserved experimentally, our results are sufficiently reliable and accurate to guide spectroscopists on further studies of this species.

  19. Accurate potential energy function and spectroscopic study of the X2Σ+, A2Π and B2Σ+ states of the CP radical

    NASA Astrophysics Data System (ADS)

    Liu, Yu-Fang; Jia, Yi

    2011-03-01

    This paper calculates the equilibrium internuclear separations, the harmonic frequencies and the potential energy curves of the X2Σ+, A2Π and B2Σ+ states of the CP radical by the highly accurate valence internally contracted multireference configuration interaction method with correlation-consistent basis sets (aug-cc-pV6Z for C atom and aug-cc-pVQZ for P atom). The potential energy curves are all fitted with the analytic potential energy function by the least-square fitting. Employing the analytic potential energy function, we determine the spectroscopic constants (Be, αe and ωeχe) of these states. For the X2Σ+ state, the obtained values of De, Be, αe, ωeχe, Re and ωe are 5.4831 eV, 0.792119 cm-1, 0.005521 cm-1, 6.89653 cm-1, 0.15683 nm, 12535.11 cm-1, respectively. For the A2Π state, the present values of De, Be, αe, ωeχe, Re and ωe are 4.586 eV, 0.703333 cm-1, 0.005458 cm-1, 6.03398 cm-1, 0.16613 nm, 1057.89 cm-1, respectively. For the B2Σ+ state, the present values of De, Be, αe, ωeχe, Re and ωe are 3.506 eV, 0.677561 cm-1, 0.00603298 cm-1, 5.68809 cm-1, 0.1696 nm, 822.554 cm-1, respectively. For these states, the vibrational states with the rotational quantum number J equals zero (J = 0) are studied by solving the radial nuclear Schrödinger equation using the Numerov method. For each vibrational state, the vibrational level, the classical turning points, the rotational inertial and the centrifugal distortion constants are calculated. Comparison is made with recent theoretical and experimental results. Project supported by the National Natural Science Foundation of China (Grant No. 10874064) and the Program for Science & Technology Innovation Talents in Universities of Henan Province in China (Grant No. 2008HASTIT008).

  20. Nuclear waste disposal—pyrochlore (A2B2O7): Nuclear waste form for the immobilization of plutonium and "minor" actinides

    NASA Astrophysics Data System (ADS)

    Ewing, Rodney C.; Weber, William J.; Lian, Jie

    2004-06-01

    During the past half-century, the nuclear fuel cycle has generated approximately 1400 metric tons of plutonium and substantial quantities of the "minor" actinides, such as Np, Am, and Cm. The successful disposition of these actinides has an important impact on the strategy for developing advanced nuclear fuel cycles, weapons proliferation, and the geologic disposal of high-level radioactive waste. During the last decade, there has been substantial interest in the use of the isometric pyrochlore structure-type, A2B2O7, for the immobilization of actinides. Most of the interest has focused on titanate-pyrochlore because of its chemical durability; however, these compositions experience a radiation-induced transition from the crystalline-to-aperiodic state due to radiation damage from the alpha-decay of actinides. Depending on the actinide concentration, the titanate pyrochlore will become amorphous in less than 1000 years of storage. Recently, systematic ion beam irradiations of a variety of pyrochlore compositions has revealed that many zirconate pyrochlores do not become amorphous, but remain crystalline as a defect fluorite structure-type due to disordering of the A- and B-site cations. The zirconate pyrochlores will remain crystalline even to very high doses, greater than 100 displacements per atom. Systematic experimental studies of actinide-doped and ion beam-irradiated pyrochlore, analyses of natural U- and Th-bearing pyrochlore, and simulations of the energetics of the disordering process now provide a rather detailed understanding of the structural and chemical controls on the response of pyrochlore to radiation. These results provide a solid basis for predicting the behavior and durability of pyrochlore used to immobilize plutonium.

  1. Design synthesis and evaluation of the inhibitory selectivity of novel trans-resveratrol analogues on human recombinant CYP1A1 CYP1A2 and CYP1B1

    USDA-ARS?s Scientific Manuscript database

    A series of trans-stilbene derivatives containing 4’-thiomethyl substituent were synthesized and evaluated for inhibitory activities on human recombinant cytochrome P450(s): CYP1A1, CYP1A2, and CYP1B1. CYP1A2-related metabolism of stilbene derivatives was estimated by using NADPH oxidation assay. A...

  2. Inhibition of Intestinal OATP2B1 by the Calcium Receptor Antagonist Ronacaleret Results in a Significant Drug-Drug Interaction by Causing a 2-Fold Decrease in Exposure of Rosuvastatin.

    PubMed

    Johnson, Marta; Patel, Dipal; Matheny, Christopher; Ho, May; Chen, Liangfu; Ellens, Harma

    2017-01-01

    Rosuvastatin is a widely prescribed antihyperlipidemic which undergoes limited metabolism, but is an in vitro substrate of multiple transporters [organic anion transporting polypeptide 1B1 (OATP1B1), OATP1B3, OATP1A2, OATP2B1, sodium-taurocholate cotransporting polypeptide, breast cancer resistance protein (BCRP), multidrug resistance protein 2 (MRP2), MRP4, organic anion transporter 3]. It is therefore frequently used as a probe substrate in clinical drug-drug interaction (DDI) studies to investigate transporter inhibition. Although each of these transporters is believed to play a role in rosuvastatin disposition, multiple pharmacogenetic studies confirm that OATP1B1 and BCRP play an important role in vivo. Ronacaleret, a drug-development candidate for treatment of osteoporosis (now terminated), was shown to inhibit OATP1B1 in vitro (IC 50 = 11 µM), whereas it did not inhibit BCRP. Since a DDI risk through inhibition of OATP1B1 could not be discharged, a clinical DDI study was performed with rosuvastatin before initiation of phase II trials. Unexpectedly, coadministration with ronacaleret decreased rosuvastatin exposure by approximately 50%, whereas time of maximal plasma concentration and terminal half-life remained unchanged, suggesting decreased absorption and/or enhanced first-pass elimination of rosuvastatin. Of the potential in vivo rosuvastatin transporter pathways, two might explain the observed results: intestinal OATP2B1 and hepatic MRP4. Further investigations revealed that ronacaleret inhibited OATP2B1 (in vitro IC 50 = 12 µM), indicating a DDI risk through inhibition of absorption. Ronacaleret did not inhibit MRP4, discharging the possibility of enhanced first-pass elimination of rosuvastatin (reduced basolateral secretion from hepatocytes into blood). Therefore, a likely mechanism of the observed DDI is inhibition of intestinal OATP2B1, demonstrating the in vivo importance of this transporter in rosuvastatin absorption in humans. Copyright © 2016

  3. No evidence for priming response in Galleria mellonella larvae exposed to toxin protein PirA2B2 from Photorhabdus luminescens TT01: An association with the inhibition of the host cellular immunity.

    PubMed

    Wu, Gongqing; Yi, Yunhong; Sun, Jianyu; Li, Mei; Qiu, Lihong

    2015-11-17

    There is accumulating evidence that many invertebrates including insects can acquire enhanced immune protection against subsequently pathogens infection through immune priming. However, whether the toxin protein from pathogenic bacteria can induce such priming response remains unclear. Here we cloned, expressed and purified the toxin Photorhabdus insect-related proteins A2B2 (PirA2B2) from Photorhabdus luminescens TT01. We primed Galleria mellonella with sublethal dose of PirA2B2 and then challenged the larvae with viable P. luminescens TT01 at 48 h after priming. We found no evidence for immune priming in G. mellonella larvae exposed to PirA2B2. Priming the larvae with PirA2B2 did not improve their resistance in a subsequent challenge with P. luminescens TT01. Whereas a robust priming response was observed when the larvae exposed to lipopolysaccharide (LPS) extracted from P. luminescens TT01. Because the larvae primed with LPS showed significant higher resistance against P. luminescens TT01 infection than those of the PBS and BSA controls. Furthermore, we investigated the changes of the cellular immune parameters, such as hemocyte counts, phagocytic activity and encapsulation ability of the hemocytes, after priming. We found that the toxin PirA2B2 significantly decreased the cellular immunity of the larvae, whereas the LPS significantly increased them. These results indicated that the degree of priming response in G. mellonella correlated positively to the levels of cellular immune parameters, and the underlying mechanism in regulating the immune priming of invertebrates was not homologous to that of the immunological memory of vertebrates. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Development and in-house validation of a robust and sensitive solid-phase extraction liquid chromatography/tandem mass spectrometry method for the quantitative determination of aflatoxins B1, B2, G1, G2, ochratoxin A, deoxynivalenol, zearalenone, T-2 and HT-2 toxins in cereal-based foods.

    PubMed

    Lattanzio, Veronica M T; Gatta, Stefania Della; Suman, Michele; Visconti, Angelo

    2011-07-15

    A sensitive and robust liquid chromatography/tandem mass spectrometry (LC/MS/MS) method was developed for the simultaneous determination of aflatoxins (B(1), B(2), G(1), G(2)), ochratoxin A, deoxynivalenol, zearalenone, T-2 and HT-2 toxins in cereal-based foods. Samples were extracted with a mixture of acetonitrile/water (84:16, v/v) and cleaned up through a polymeric solid-phase extraction column. Detection and quantification of the nine mycotoxins were performed by reversed-phase liquid chromatography coupled with electrospray ionization triple quadrupole mass spectrometry (LC/ESI-MS/MS), using fully (13)C-isotope-labelled mycotoxins as internal standards. The method was validated in-house for five different cereal processed products, namely barley, oat and durum wheat flours, rye- and wheat-based crisp bread. Recoveries and repeatability of the whole analytical procedure were evaluated at contamination levels encompassing the EU maximum permitted levels for each tested mycotoxin. Recoveries ranged from 89 to 108% for deoxynivalenol, from 73 to 114% for aflatoxins, from 85 to 114% for T-2 and HT-2 toxins, from 64 to 97% for zearalenone, from 74 to 102% for ochratoxin A. Relative standard deviations were less than 16% for all tested mycotoxins and matrices. Limits of detection (signal-to-noise ratio 3:1) ranged from 0.1 to 59.2 µg/kg. The trueness of the results obtained by the proposed method was demonstrated by analysis of reference materials for aflatoxins, deoxynivalenol, zearalenone. The use of inexpensive clean-up cartridges and the increasing availability of less expensive LC/MS/MS instrumentation strengthen the potential of the proposed method for its effective application for reliable routine analysis to assess compliance of tested cereal products with current regulation. Copyright © 2011 John Wiley & Sons, Ltd.

  5. Ionic-liquid-based dispersive liquid-liquid microextraction combined with magnetic solid-phase extraction for the determination of aflatoxins B1 , B2 , G1 , and G2 in animal feeds by high-performance liquid chromatography with fluorescence detection.

    PubMed

    Zhao, Jiao; Zhu, Yan; Jiao, Yang; Ning, Jinyan; Yang, Yaling

    2016-10-01

    A novel two-step extraction technique combining ionic-liquid-based dispersive liquid-liquid microextraction with magnetic solid-phase extraction was developed for the preconcentration and separation of aflatoxins in animal feedstuffs before high-performance liquid chromatography coupled with fluorescence detection. In this work, ionic liquid 1-octyl-3-methylimidazolium hexafluorophosphate was used as the extractant in dispersive liquid-liquid microextraction, and hydrophobic pelargonic acid modified Fe 3 O 4 magnetic nanoparticles as an efficient adsorbent were applied to retrieve the aflatoxins-containing ionic liquid. Notably, the target of magnetic nanoparticles was the ionic liquid rather than the aflatoxins. Because of the rapid mass transfer associated with the dispersive liquid-liquid microextraction and magnetic solid phase steps, fast extraction could be achieved. The main parameters affecting the extraction recoveries of aflatoxins were investigated and optimized. Under the optimum conditions, vortexing at 2500 rpm for 1 min in the dispersive liquid-liquid microextraction and magnetic solid-phase extraction and then desorption by sonication for 2 min with acetonitrile as eluent. The recoveries were 90.3-103.7% with relative standard deviations of 3.2-6.4%. Good linearity was observed with correlation coefficients ranged from 0.9986 to 0.9995. The detection limits were 0.632, 0.087, 0.422 and 0.146 ng/mL for aflatoxins B 1 , B2, G1, and G2, respectively. The results were also compared with the pretreatment method carried out by conventional immunoaffinity columns. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Digoxin is not a substrate for organic anion-transporting polypeptide transporters OATP1A2, OATP1B1, OATP1B3, and OATP2B1 but is a substrate for a sodium-dependent transporter expressed in HEK293 cells.

    PubMed

    Taub, Mitchell E; Mease, Kirsten; Sane, Rucha S; Watson, Cory A; Chen, Liangfu; Ellens, Harma; Hirakawa, Brad; Reyner, Eric L; Jani, Marton; Lee, Caroline A

    2011-11-01

    Digoxin, an orally administered cardiac glycoside cardiovascular drug, has a narrow therapeutic window. Circulating digoxin levels (maximal concentration of ∼1.5 ng/ml) require careful monitoring, and the potential for drug-drug interactions (DDI) is a concern. Increases in digoxin plasma exposure caused by inhibition of P-glycoprotein (P-gp) have been reported. Digoxin has also been described as a substrate of various organic anion-transporting polypeptide (OATP) transporters, posing a risk that inhibition of OATPs may result in a clinically relevant DDI similar to what has been observed for P-gp. Although studies in rats have shown that Oatps contribute to the disposition of digoxin, the role of OATPs in the disposition of digoxin in humans has not been clearly defined. Using two methods, Boehringer Ingelheim, GlaxoSmithKline, Pfizer, and Solvo observed that digoxin is not a substrate of OATP1A2, OATP1B1, OATP1B3, and OATP2B1. However, digoxin inhibited the uptake of probe substrates of OATP1B1 (IC(50) of 47 μM), OATP1B3 (IC(50) > 8.1 μM), and OATP2B1 (IC(50) > 300 μM), but not OATP1A2 in transfected cell lines. It is interesting to note that digoxin is a substrate of a sodium-dependent transporter endogenously expressed in HEK293 cells because uptake of digoxin was significantly greater in cells incubated with sodium-fortified media compared with incubations conducted in media in which sodium was absent. Thus, although digoxin is not a substrate for the human OATP transporters evaluated in this study, in addition to P-gp-mediated efflux, its uptake and pharmacokinetic disposition may be partially facilitated by a sodium-dependent transporter.

  7. Suppression of HPV-16 late L1 5′-splice site SD3632 by binding of hnRNP D proteins and hnRNP A2/B1 to upstream AUAGUA RNA motifs

    PubMed Central

    Li, Xiaoze; Johansson, Cecilia; Glahder, Jacob; Mossberg, Ann-Kristin; Schwartz, Stefan

    2013-01-01

    Human papillomavirus type 16 (HPV-16) 5′-splice site SD3632 is used exclusively to produce late L1 mRNAs. We identified a 34-nt splicing inhibitory element located immediately upstream of HPV-16 late 5′-splice site SD3632. Two AUAGUA motifs located in these 34 nt inhibited SD3632. Two nucleotide substitutions in each of the HPV-16 specific AUAGUA motifs alleviated splicing inhibition and induced late L1 mRNA production from episomal forms of the HPV-16 genome in primary human keratinocytes. The AUAGUA motifs bind specifically not only to the heterogeneous nuclear RNP (hnRNP) D family of RNA-binding proteins including hnRNP D/AUF, hnRNP DL and hnRNP AB but also to hnRNP A2/B1. Knock-down of these proteins induced HPV-16 late L1 mRNA expression, and overexpression of hnRNP A2/B1, hnRNP AB, hnRNP DL and the two hnRNP D isoforms hnRNP D37 and hnRNP D40 further suppressed L1 mRNA expression. This inhibition may allow HPV-16 to hide from the immune system and establish long-term persistent infections with enhanced risk at progressing to cancer. There is an inverse correlation between expression of hnRNP D proteins and hnRNP A2/B1 and HPV-16 L1 production in the cervical epithelium, as well as in cervical cancer, supporting the conclusion that hnRNP D proteins and A2/B1 inhibit HPV-16 L1 mRNA production. PMID:24013563

  8. Human B-1 cells take the stage

    PubMed Central

    Rothstein, Thomas L.; Griffin, Daniel O.; Holodick, Nichol E.; Quach, Tam D.; Kaku, Hiroaki

    2013-01-01

    B-1cells play critical roles in defending against microbial invasion and in housekeeping removal of cellular debris. B-1cells secrete natural antibody and manifest functions that influence T cell expansion and differentiation and in these and other ways differ from conventional B-2 cells. B-1-cells were originally studied in mice where they are easily distinguished from B-2cells, but their identity in the human system remained poorly defined for many years. Recently, functional criteria for human B-1cells were established on the basis of murine findings, and reverse engineering resulted in identification of the phenotypic profile, CD20+CD27+CD43+CD70−, for B-1cells found in both umbilical cord blood and adult peripheral blood. Human B-1cells may contribute to multiple disease states through production of autoantibody and stimulation/modulation of T cell activity. Human B-1cells could be a rich source of antibodies useful in treating diseases present in elderly populations where natural antibody protection may have eroded. Manipulation of human B-1cell numbers and/or activity may be a new avenue for altering T cell function and treating immune dyscrasias. PMID:23692567

  9. Steric effect in the energy transfer reaction of oriented CO (a 3Π, v'=0, Ω=1 and 2) + NO (X 2Π) → NO (A 2Σ+, B 2Π) + CO (X 1Σ+).

    PubMed

    Ohoyama, H; Matsuura, Y

    2011-07-21

    The oriented CO (a (3)Π, v' = 0, Ω = 1 and 2) beam has been prepared by using an electric hexapole and applied to the energy transfer reaction of CO (a (3)Π, v' = 0, Ω = 1 and 2) + NO (X (2)Π) → NO (A (2)Σ(+), B (2)Π) + CO (X (1)Σ(+)). The emission spectra of NO (A (2)Σ(+), B(2)Π) have been measured at three orientation configurations (C-end, O-end, random). The shape of the emission spectra (and/or the internal excitation of products) turns out to be insensitive to the molecular orientation. The vibrational distributions of NO (A (2)Σ(+), v' = 0-2) and NO (B (2)Π, v' = 0-2) are determined to be N(v'=0):N(v'=1):N(v'=2) = 1:0.40 ± 0.05:0.10 ± 0.05 and N(v'=0):N(v'=1):N(v'= 2) = 1:0.6 ± 0.1:0.7 ± 0.1, respectively, and the branching ratio γ/β [=NO (A (2)Σ(+))/NO (B (2)Π)] is estimated to be γ/β ∼ 0.3 ± 0.1 by means of spectral simulation. These vibrational distributions of NO (A, B) can be essentially attributed to the product-pair correlations between CO (X, v″) and NO (A (2)Σ(+), v' = 0-2), NO (B (2)Π, v' = 0-2) due to energetic restriction under the vibrational distribution of CO (X, v″) produced from the vertical transition of CO (a (3)Π, v' = 0) → CO (X, v″) in the course of energy transfer. The steric opacity function has been determined at two wavelength regions: 220 < λ < 290 nm [NO (A → X) is dominant]; 320 < λ < 400 nm [NO (B → X) is dominant]. For both channels NO (A (2)Σ(+), B(2)Π), a significant CO (a (3)Π) alignment effect is recognized; the largest reactivity at the sideways direction with the small reactivity at the molecular axis direction is observed. These CO (a (3)Π) alignment effects can be essentially attributed to the steric asymmetry on two sets of molecular orbital overlap, [CO (2π) + NO (6σ (2π))] and [CO (5σ) + NO (1π (2π))]. All experimental observations support the electron exchange mechanism that is operative through the formation of a weakly bound complex OCNO. © 2011 American

  10. Comparison of isolated cranberry (Vaccinium macrocarpon Ait.) proanthocyanidins to catechin and procyanidins A2 and B2 for use as standards in the 4-(dimethylamino)cinnamaldehyde assay.

    PubMed

    Feliciano, Rodrigo P; Shea, Michael P; Shanmuganayagam, Dhanansayan; Krueger, Christian G; Howell, Amy B; Reed, Jess D

    2012-05-09

    The 4-(dimethylamino)cinnamaldehyde (DMAC) assay is currently used to quantify proanthocyanidin (PAC) content in cranberry products. However, this method suffers from issues of accuracy and precision in the analysis and comparison of PAC levels across a broad range of cranberry products. Current use of procyanidin A2 as a standard leads to an underestimation of PACs content in certain cranberry products, especially those containing higher molecular weight PACs. To begin to address the issue of accuracy, a method for the production of a cranberry PAC standard, derived from an extraction of cranberry (c-PAC) press cake, was developed and evaluated. Use of the c-PAC standard to quantify PAC content in cranberry samples resulted in values that were 2.2 times higher than those determined by procyanidin A2. Increased accuracy is critical for estimating PAC content in relationship to research on authenticity, efficacy, and bioactivity, especially in designing clinical trials for determination of putative health benefits.

  11. Einstein A coefficients for rovibronic lines of the A2Π → X2Σ+ and B2Σ+ → X2Σ+ transitions of CaH and CaD

    NASA Astrophysics Data System (ADS)

    Alavi, S. Fatemeh; Shayesteh, Alireza

    2018-02-01

    Calcium monohydride is an important diatomic molecule appearing in the spectra of sunspots and M dwarfs. We report complete line lists with Einstein A coefficients for the A2Π-X2Σ+ and B2Σ+-X2Σ+ electronic transitions of CaH and CaD radicals. The most recent ab initio transition dipole moments and potential energy curves were used for the calculation of vibronic band intensities, taking the Herman-Wallis effect into account, and the rotational line strengths were calculated using the PGOPHER program of Western. For the A2Π and B2Σ+ excited states of CaH and CaD, new off-diagonal electronic matrix elements were included in the Hamiltonian matrix, and new sets of spectroscopic constants were determined in order to accurately reproduce the line positions and relative intensities of the observed branches in laboratory spectra. For both CaH and CaD isotopologues, Einstein A coefficients were calculated for all possible rovibronic transitions from the v΄ = 0-3 vibrational levels of the A2Π state and the v΄ = 0-2 vibrational levels of the B2Σ+ state to the v″ = 0-4 vibrational levels of the X2Σ+ ground state. The line lists and intensities reported here can be used to accurately determine the amounts of CaH and CaD in stellar environments.

  12. Laser Spectroscopy of the A2Pi-X2Sigma+ and B2Sigma+-X2Sigma+ Transition of Calcium-CCD and StrontiumCCD

    NASA Astrophysics Data System (ADS)

    Faridian, Ahmad

    The family of molecules consisting of an alkaline earth metal atom bonded to an organic ligand has been under intensive investigation recently, since these molecules playa significant role in synthesis of organic compounds, and since some members like MgNC and MgCN have been detected in stellar atmospheres. Our group has previously studied CaCCH, MgCCH, and in this work we consider the A2pi--X˜2Sigma + transition of CaCCD, SrCCH and SrCCD and the B˜ 2Sigma+ --X˜2 Sigma+ transition of CaCCH and CaCCD. Two different molecular sources have been used to produce the molecules. The CaCCD, SrCCD and SrCCH molecules were created in a pulsed-jet laser ablation source through reaction of metal atoms ablated from a solid rod with methane gas entrained in helium. High-resolution spectra were collected through laser-induced fluorescence following excitation of the molecules formed in the jet with a CW ring dye laser. Results of the analysis are compared to those of a previous high-resolution study of CaCCH and SrCCH. The data providing information on the lambda-doubling parameter p and allow for an estimate of the position of the B˜2Sigma+ state for both isotopes. The B˜2Sigma + --X˜2Sigma+ transition for CaCCD has been observed using the cavity ring down spectroscopy technique in the jet source. The B˜ 2Sigma+ --X˜2 Sigma+ transition of CaCCH has been studied using a Broida oven in which the vaporized calcium atoms react with acetylene.

  13. Avermectin B1

    Integrated Risk Information System (IRIS)

    Avermectin B1 ; CASRN 65195 - 55 - 3 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogenic E

  14. Effect of beta-naphthoflavone on AhR-regulated genes (CYP1A1, 1A2, 1B1, 2S1, Nrf2, and GST) and antioxidant enzymes in various brain regions of pig.

    PubMed

    Nannelli, Annalisa; Rossignolo, Francesco; Tolando, Roberto; Rossato, Paolo; Longo, Vincenzo; Gervasi, P Giovanni

    2009-11-30

    The constitutive and inducible expression of aryl hydrocarbon receptor (AhR) and of the AhR-regulated genes coding for CYP1A1, CYP1A2, CYP1B1, CYP2S1, and Nrf2 was investigated by real-time or traditional PCR in cerebral areas (cortex, cerebellum, midbrain, and hippocampus), blood-brain interfaces (meninges and brain microvessels) and liver obtained from control pigs and from pigs treated with beta-naphthoflavone (betaNF), a potent AhR agonist. The enzymatic activities of ethoxyresorufin-O-deethylase (EROD), and methoxyresorufin-O-deethylase (MEROD), marker for CYP1A1 and CYP1A2, the GST and various antioxidant enzymes (catalase, superoxide dismutase, GSSG-reductase, and GSH-peroxidase) were also determined in the same CNS regions. The AhR, CYP1A1, CYP1A2, CYP1B1, Nrf2 mRNAs were detected, although at different extent, in all the CNS regions, while CYP2S1 mRNA was detected only in midbrain. In the blood-brain interfaces, the constitutive basal expression of AhR and CYP1A1 was comparable to the hepatic one and even higher for CYP1B1 and Nrf2. The treatment with betaNF determined the induction of CYP1A1 and 1B1 (but not of AhR, CYP1A2, and Nrf2) mRNA levels in various CNS areas; notably, CYP1A1 mRNA was increased to about 300-fold in the microvessels. The analysis of enzymatic activities revealed that EROD, but not MEROD, was induced in microsomes but not in mitochondria of all the CNS areas. However, the mitochondrial EROD activities were comparable (in midbrain, meninges) or higher (in cortex, cerebellum, hippocampus) than the microsomal ones, suggesting an important metabolic function of CYP1A1 in this subcellular localization. The activities of GST and antioxidant enzymes were detected in all CNS tissues, with levels lower than the hepatic ones, but found quite evenly distributed and marginally affected by betaNF treatment. The high expression of metabolic enzymes found in blood-brain interfaces could represent a very important defence toward toxins of CNS.

  15. Characterization of the X~ 2A1, A~ 2B1, and X~ 2Π electronic states of the Ga2H molecule and the X~ 2A' and A~ 2A'' isomerization transition states connecting the three minima

    NASA Astrophysics Data System (ADS)

    Wang, Hongyan; Wang, Suyun; Yan, Ge; Yamaguchi, Yukio; Schaefer, Henry F.

    2006-01-01

    A wide range of highly correlated ab initio methods has been used to predict the geometrical parameters of the linear (X˜Π2) and H-bridged (X˜A12 and ÃB12) Ga2H isomers and two isomerization transition states (X˜A'2 and ÃA″2) connecting the three minima. Dipole moments and vibrational frequencies are also obtained. The global minimum X˜A12 ground state of the H-bridged GaHGa isomer is predicted to lie only 1.6 [1.9 with the zero-point vibrational energy (ZPVE) corrections] kcalmol-1 below the ÃB12 state. The X˜A12 state lies 5.4kcalmol-1 below the X˜Π2 ground state of the linear GaGaH isomer at the coupled-cluster with single, double, and perturbative triple excitations [CCSD(T)] level of theory with the augmented correlation-consistent polarized valence quadruple-zeta (aug-cc-pVQZ) basis set. The full triples coupled-cluster method is found to alter these CCSD(T) predictions by as much as 0.3kcalmol-1. The forward isomerization barriers from the linear ground state to the X˜A'2 and ÃA″2 transition states are determined to be 3.3 and 5.3kcalmol-1, respectively. The reverse isomerization barrier between the X˜A12 GaHGa structure and the X˜Π2 GaGaH structure is predicted to be 8.6 (8.2 with the ZPVE corrections) kcalmol-1 at the aug-cc-pVQZ CCSD(T) level of theory.

  16. Mass spectroscopy identifies the splicing-associated proteins, PSF, hnRNP H3, hnRNP A2/B1, and TLS/FUS as interacting partners of the ZNF198 protein associated with rearrangement in myeloproliferative disease

    SciTech Connect

    Kasyapa, Chitta S.; Kunapuli, Padmaja; Cowell, John K.

    2005-09-10

    ZNF198 is fused with FGFR1 in an atypical myeloproliferative disease that results in constitutive activation of the kinase domain and mislocalization to the cytoplasm. We have used immunoprecipitation of a GFP-tagged ZNF198 combined with MALDI-TOF mass spectroscopy to identify interacting proteins. P splicing factor (PSF) was identified as one of the proteins and this interaction was confirmed by Western blotting. Other proteins identified were the spliceosomal components hnRNP A2/B1, hnRNP H3, and TLS/FUS. PSF is also known to interact with PTB, another member of the hnRNP family of proteins, and we further demonstrated that PTB interacts with ZNF198. The interactionmore » between TLS/FUS and ZNF198 was confirmed using Western blot analysis. In 293 cells expressing the ZNF198/FGFR1 fusion protein, neither PSF nor PTB binds to the fusion protein, possibly because of their differential localization in the cell.« less

  17. Atomic structure and electronic properties of A2B2XY (A = Si-Pb, B = Cl-I, and XY = PN and SiS) inorganic double helices: first principles calculations.

    PubMed

    Bijoy, T K; Murugan, P; Kumar, Vijay

    2018-03-05

    We study the structural stability and electronic properties of new classes of DNA-like inorganic double helices of the type A 2 B 2 XY (A = Si-Pb, B = Cl-I, and XY = PN and SiS) by employing first principles density functional theory (DFT) calculations including van der Waals interactions. In these quaternary double helices PN or SiS forms the inner helix while the AB helix wraps around the inner helix and the two are interconnected. We find that the bromides and iodides of Ge, Sn, and Pb as well as Pb 2 Cl 2 PN form structurally stable double helices while Ge 2 I 2 SiS as well as bromides and iodides of Sn and Pb have stable double helices. The atomic structures of different double helices have been analyzed in detail to understand the stability of these systems as there is up to about 80% difference in the interatomic distances in the two helices which is remarkable. Also in these new classes of double helices there is polar covalent bonding in the inner helix due to heteroatoms. We have calculated the DDEC6 partial atomic charges and bond orders which suggest strong covalent bonding in the inner helix. The electronic structure reveals that these double helices are semiconducting and in many cases the band gap is direct. Furthermore, we have studied the effects of doping and found that hole doping is the most appropriate way to tuning their electronic properties.

  18. Characterization of differences in substrate specificity among CYP1A1, CYP1A2 and CYP1B1: an integrated approach employing molecular docking and molecular dynamics simulations.

    PubMed

    Kesharwani, Siddharth S; Nandekar, Prajwal P; Pragyan, Preeti; Rathod, Vijay; Sangamwar, Abhay T

    2016-08-01

    Recent trends in new drug discovery of anticancer drugs have made oncologists more aware of the fact that the new drug discovery must target the developing mechanism of tumorigenesis to improve the therapeutic efficacy of antineoplastic drugs. The drugs designed are expected to have high affinity towards the novel targets selectively. Current research highlights overexpression of CYP450s, particularly cytochrome P450 1A1 (CYP1A1), in tumour cells, representing a novel target for anticancer therapy. However, the CYP1 family is identified as posing significant problems in selectivity of anticancer molecules towards CYP1A1. Three members have been identified in the human CYP1 family: CYP1A1, CYP1A2 and CYP1B1. Although sequences of the three isoform have high sequence identity, they have distinct substrate specificities. The understanding of macromolecular features that govern substrate specificity is required to understand the interplay between the protein function and dynamics, design novel antitumour compounds that could be specifically metabolized by only CYP1A1 to mediate their antitumour activity and elucidate the reasons for differences in substrate specificity profile among the three proteins. In the present study, we employed a combination of computational methodologies: molecular docking and molecular dynamics simulations. We utilized eight substrates for elucidating the difference in substrate specificity of the three isoforms. Lastly, we conclude that the substrate specificity of a particular substrate depends upon the type of the active site residues, the dynamic motions in the protein structure upon ligand binding and the physico-chemical characteristics of a particular ligand. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  19. B1-B2 phase transition mechanism and pathway of PbS under pressure

    NASA Astrophysics Data System (ADS)

    Adeleke, Adebayo A.; Yao, Yansun

    2018-03-01

    Experimental studies at finite Pressure-Temperature (P-T) conditions and a theoretical study at 0 K of the phase transition in lead sulphide (PbS) have been inconclusive. Many studies that have been done to understand structural transformation in PbS can broadly be classified into two main ideological streams—one with Pnma and another with Cmcm orthorhombic intermediate phase. To foster better understanding of this phenomenon, we present the result of the first-principles study of phase transition in PbS at finite temperature. We employed the particle swarm-intelligence optimization algorithm for the 0 K structure search and first-principles metadynamics simulations to study the phase transition pathway of PbS from the ambient pressure, 0 K Fm-3m structure to the high-pressure Pm-3m phase under experimentally achievable P-T conditions. Significantly, our calculation shows that both streams are achievable under specific P-T conditions. We further uncover new tetragonal and monoclinic structures of PbS with space group P21/c and I41/amd, respectively. We propose the P21/c and I41/amd as a precursor phase to the Pnma and Cmcm phases, respectively. We investigated the stability of the new structures and found them to be dynamically stable at their stability pressure range. Electronic structure calculations reveal that both P21/c and I41/amd phases are semiconducting with direct and indirect bandgap energies of 0.69(5) eV and 0.97(3) eV, respectively. In general, both P21/c and I41/amd phases were found to be energetically competitive with their respective orthorhombic successors.

  20. NMR solution structures and MD-simulation of procyanidin B1, B2, and C1

    USDA-ARS?s Scientific Manuscript database

    Procyanidins are polyphenols associated with a variety of benefits to the health of both plants and animals. Procyanidins provide increased defense against microbes, act as strong antioxidants, and may decrease the incidence of cancer. Key to understanding how procyanidins function requires understa...

  1. The mechanism of Lactobacillus strains for their ability to remove fumonisins B1 and B2.

    PubMed

    Zhao, Hongfei; Wang, Xiao; Zhang, Junwen; Zhang, Jun; Zhang, Bolin

    2016-11-01

    Two Lactobacillus strains, L. plantarum B7 and L. pentosus X8, exhibited high efficiency in removing fumonisins (FB1 and FB2) from aqueous medium. 52.9% FB1 and 85.2% FB2 were bound by L. plantarum B7, and 58.0% FB1 and 86.5% FB2 by L. pentosus X8, respectively. Temperature, incubation time, and pH affected the binding ability of two strains. Cell viability was not necessary for the binding ability. The various components of cell wall were determined for their ability to absorb FBS. The results revealed that the intact peptidoglycans exhibited the greatest capacity in binding FBs. Especially the better structural integrity of the peptidoglycans the more FBs was bound. Thus, the absorption of two bacterial cells to FBs is proposed to be a physical process, and peptidoglycans should be the main binding site. Additionally, Caco-2 cell lines were used to evaluate the ability of the two strains to reduce the damage of FBs in vitro. Caco-2 cell's death was reduced after the cell lines were subjected to both viable and non-viable L. pentosus X8, respectively. The two Lactobacillus strains might be used as a biological detoxification for the removal of FBs from diet and feed in the future. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. MISR Level 1A CCD, 1B1, 1B2, and Browse Products

    Atmospheric Science Data Center

    2013-04-01

    ... Fixed a bug associated with the orbit to orbit propagation method. Stage 3 Validated: GRP_ELLIPSOID, ... Rev K  (PDF). Initiated orbit-to-orbit propagation of navigation corrections for the D-aft camera. Two bugs were fixed ...

  3. Modulating the Strength and Threshold of NOTCH Oncogenic Signals by mir-181a-1/b-1

    PubMed Central

    Wang, Song; Schaffert, Steven; Gong, Xue; Yue, Sibiao; Luong, Richard; Min, Hyeyoung; Yashiro-Ohtani, Yumi; Davis, Mark; Pear, Warren; Chen, Chang-Zheng

    2012-01-01

    Oncogenes, which are essential for tumor initiation, development, and maintenance, are valuable targets for cancer therapy. However, it remains a challenge to effectively inhibit oncogene activity by targeting their downstream pathways without causing significant toxicity to normal tissues. Here we show that deletion of mir-181a-1/b-1 expression inhibits the development of Notch1 oncogene-induced T cell acute lymphoblastic leukemia (T-ALL). mir-181a-1/b-1 controls the strength and threshold of Notch activity in tumorigenesis in part by dampening multiple negative feedback regulators downstream of NOTCH and pre-T cell receptor (TCR) signaling pathways. Importantly, although Notch oncogenes utilize normal thymic progenitor cell genetic programs for tumor transformation, comparative analyses of mir-181a-1/b-1 function in normal thymocyte and tumor development demonstrate that mir-181a-1/b-1 can be specifically targeted to inhibit tumor development with little toxicity to normal development. Finally, we demonstrate that mir-181a-1/b-1, but not mir-181a-2b-2 and mir-181-c/d, controls the development of normal thymic T cells and leukemia cells. Together, these results illustrate that NOTCH oncogene activity in tumor development can be selectively inhibited by targeting the molecular networks controlled by mir-181a-1/b-1. PMID:22916024

  4. Genetic and Methylation-Induced Loss of miR-181a2/181b2 within chr9q33.3 Facilitates Tumor Growth of Cervical Cancer through the PIK3R3/Akt/FoxO Signaling Pathway.

    PubMed

    Mei, Qian; Li, Xiang; Zhang, Kang; Wu, Zhiqiang; Li, Xiaolei; Meng, Yuanguang; Guo, Mingzhou; Luo, Guangbin; Fu, Xiaobing; Han, Weidong

    2017-01-15

    Loss of Chr9q31-33 is one of the most common chromosome imbalances of cervical cancer, but the underlying mechanism has not been well documented. The loss of heterozygosity (LOH) status of Chr9q31-33 was investigated utilizing 26 microsatellite markers. We detected the expression of miR-181a2/181b2 by qRT-PCR analysis of cervical cancer cell lines and 100 paired tumor samples and corresponding adjacent non-tumor tissues. Kaplan-Meier and Cox proportional hazard regression analyses were performed to identify the prognostic value of miR-181a2/181b2. Regulation of expression was analyzed by methylation-specific PCR. The tumor-suppressing effects of miR-181a2/181b2 were determined in vitro and in vivo The target gene and signaling pathway that mediated the function of miR-181a2/181b2 were also identified. Chr9q33.3 was identified as one of the most deleted regions in cervical cancer. Underexpression of miR-181a2/181b2 was detected in 46% of cervical cancer and was induced by the LOH of chr9q33.3 and promoter hypermethylation. Attenuated miR-181a2/181b2 expression predicted a poor prognostic phenotype and advanced clinical stage of cervical cancer. miR-181a2/181b2 prominently dampened cell-cycle progression, suppressed cell growth, and promoted apoptosis of tumor cells in vitro They also effectively impeded tumor formation and growth in vivo miR-181a2/181b2 exert the tumor suppressor ability by depressing the direct target PIK3R3 (p55γ) and consequently modulating the PIK3R3/Akt/FoxO signaling pathway. We demonstrated a cause-and-effect event beginning from loss of chr9q33.3, a frequent event in cervical cancer, to the underexpression of miR-181a2/181b2, leading to the elevated activation of the PI3K pathway. Clin Cancer Res; 23(2); 575-86. ©2016 AACR. ©2016 American Association for Cancer Research.

  5. Cytochrome P450 2A13 enhances the sensitivity of human bronchial epithelial cells to aflatoxin B1-induced DNA damage

    SciTech Connect

    Yang, Xuejiao; Jiaojiang District Center for Disease Control and Prevention, 518 Jingdong Rd., Taizhou 318000; Zhang, Zhan

    2013-07-15

    Cytochrome P450 2A13 (CYP2A13) mainly expresses in human respiratory system and mediates the metabolic activation of aflatoxin B1 (AFB1). Our previous study suggested that CYP2A13 could increase the cytotoxic and apoptotic effects of AFB1 in immortalized human bronchial epithelial cells (BEAS-2B). However, the role of CYP2A13 in AFB1-induced DNA damage is unclear. Using BEAS-2B cells that stably express CYP2A13 (B-2A13), CYP1A2 (B-1A2), and CYP2A6 (B-2A6), we compared their effects in AFB1-induced DNA adducts, DNA damage, and cell cycle changes. BEAS-2B cells that were transfected with vector (B-vector) were used as a control. The results showed that AFB1 (5–80 nM) dose-more » and time-dependently induced DNA damage in B-2A13 cells. AFB1 at 10 and 80 nM significantly augmented this effect in B-2A13 and B-1A2 cells, respectively. B-2A6 cells showed no obvious DNA damage, similar to B-vector cells and the vehicle control. Similarly, compared with B-vector, B-1A2 or B-2A6 cells, B-2A13 cells showed more sensitivity in AFB1-induced γH2AX expression, DNA adduct 8-hydroxy-deoxyguanosine formation, and S-phase cell-cycle arrest. Furthermore, AFB1 activated the proteins related to DNA damage responses, such as ATM, ATR, Chk2, p53, BRCA1, and H2AX, rather than the proteins related to DNA repair. These effects could be almost completely inhibited by 100 μM nicotine (a substrate of CYP2A13) or 1 μM 8-methoxypsoralen (8-MOP; an inhibitor of CYP enzyme). Collectively, these findings suggest that CYP2A13 plays an important role in low-concentration AFB1-induced DNA damage, possibly linking environmental airborne AFB1 to genetic injury in human respiratory system. - Highlights: • CYP2A13 plays a critical role in low concentration of AFB1-induced DNA damage. • B-2A13 cells were more sensitive to AFB1 than B-1A2 cells and B-2A6 cells. • AFB1 dose- and time-dependently induced DNA damage in B-2A13 cells • AFB1-induced DNA adducts and damage can be inhibited by

  6. Determination of Aflatoxin B1 in Smokeless Tobacco Products by Use of UHPLC-MS/MS.

    PubMed

    Zitomer, Nicholas; Rybak, Michael E; Li, Zhong; Walters, Matthew J; Holman, Matthew R

    2015-10-21

    This work developed a UHPLC-MS/MS method for the detection and quantitation of aflatoxins in smokeless tobacco products, which was then used to determine aflatoxin B1 concentrations in 32 smokeless tobacco products commercially available in the United States. Smokeless tobacco products were dried, milled, and amended with (13)C17-labeled internal standards, extracted in water/methanol solution in the presence of a surfactant, isolated through use of immunoaffinity column chromatography, and reconstituted in mobile phase prior to UHPLC-MS/MS analysis. The method was capable of baseline separation of aflatoxins B1, B2, G1, and G2 in a 2.5 min run by use of a fused core C18 column and a water/methanol gradient. MS/MS transition (m/z) 313.3 → 241.2 was used for aflatoxin B1 quantitation, with 313.3 → 285.1 used for confirmation. The limit of detection (LOD) for aflatoxin B1 was 0.007 parts per billion (ppb). Method imprecision for aflatoxin B1 (expressed as coefficient of variation) ranged from 5.5 to 9.4%. Spike recoveries were 105-111%. Aflatoxin B1 concentrations in the smokeless tobacco products analyzed ranged from B1 was most frequently detected in dry snuffs and chews, whereas all moist snuff products tested were below LOD. The amounts of aflatoxin B1 detected were low relative to the 20 ppb regulatory limit established by the U.S. Food and Drug Administration for foods and feeds.

  7. Determination of Aflatoxin B1 in Smokeless Tobacco Products by use of UHPLC-MS/MS

    PubMed Central

    Zitomer, Nicholas; Rybak, Michael E.; Li, Zhong; Walters, Matthew J.; Holman, Matthew R.

    2017-01-01

    We have developed a UHPLC-MS/MS method for the detection and quantitation of aflatoxins in smokeless tobacco products and used it to determine aflatoxin B1 concentrations in 32 smokeless tobacco products commercially available in the US. Smokeless tobacco products were dried, milled and amended with 13C17-labelled internal standards, extracted in water/methanol solution in the presence of a surfactant, isolated through use of immunoaffinity column chromatography and reconstituted in mobile phase prior to UHPLC-MS/MS analysis. Our method was capable of baseline separation of aflatoxins B1, B2, G1 and G2 in a 2.5 min run by use of a fused core C18 column and a water/methanol gradient. MS/MS transition (m/z) 313.3>241.2 was used for aflatoxin B1 quantitation, with 313.3>285.1 used for confirmation. The limit of detection (LOD) for aflatoxin B1 was 0.007 parts per billion (ppb). Method imprecision for aflatoxin B1 (expressed as coefficient of variation) ranged from 5.5% to 9.4%. Spike recoveries were 105–111%. Aflatoxin B1 concentrations in the smokeless tobacco products analysed ranged from B1 was most frequently detected in dry snuffs and chews, whereas all moist snuff products tested were below LOD. The amounts of aflatoxin B1 we detected were low relative to the 20 ppb regulatory limit established by the Food and Drug Administration for foods and feeds. PMID:26452144

  8. Role of B-1a cells in autoimmunity.

    PubMed

    Duan, Byian; Morel, Laurence

    2006-07-01

    B-1a cells are distinguished from conventional B cells (B2) by their developmental origin, their surface marker expression and their functions. They were originally identified as a B cell subset of fetal origin that expresses the pan-T cell surface glycoprotein, CD5. B-1a cells also differ from B2 by the expression levels of several surface markers, including IgM, IgD, CD43 and B220 [R. Berland, H.H. Wortis, Origins and functions of B-1 cells with notes on the role of CD5. Ann Rev Immunol, 20 (2002) 253-300.]. The majority of B-1a cells are located in peritoneal and pleural cavities. Compared to B2 cells, B-1a are long-lived, non-circulating, with reduced BCR diversity and affinity [A.B. Kantor, C.E. Merrill, L.A. Herzenberg, J.L. Hillson, An unbiased analysis of V-H-D-J(H) sequences from B-1a, B-1b, and conventional B cells. J Immunol, 158 (1997) 1175-1186.]. B-1a cells are largely responsible for the production of circulating IgM referred to as natural antibodies. These low affinity antibodies are polyreactive and constitute as such a first line of defense against bacterial pathogens [M.C. Carroll, A.P. Prodeus, Linkages of innate and adaptive immunity. Curr Opin Immunol, 10 (1998) 36-40.]. This polyreactivity also results into the recognition of autoantigens, which serves in the clearance of apoptosis products. The weak autoreactivity of the B-1a cells has been postulated to play a role in autoimmune pathogenesis. In addition, other characteristics, such as the production of high level of IL-10 [A. O'Garra, R. Chang, N. Go, R. Hastings, G. Haughton, M. Howard, et al. Ly-1 B (B-1) cells are the main source of B cell-derived interleukin 10. Eur J Immunol, 22 (1992) 711-717.] and enhanced antigen presentation capacities [C. Mohan, L. Morel, P. Yang, E.K. Wakeland, Accumulation of splenic B1a cells with potent antigen-presenting capability in NZM2410 lupus-prone mice. Arthritis and Rheumatism, 41 (1998) 1652-1662.], have implicated B-1a cells in autoimmunity. This

  9. A Novel Biochemical Pathway of ErbB2 Down-Regulation

    DTIC Science & Technology

    2004-07-01

    regulation of ErbB2 as a therapeutic strategy. Recent finding that geldanamycin, an ansamycin antibiotic with anti-tumor activity, induces ErbB2 down...degradation is selective for ErbB2 as compared to ErbB 1 (EGF receptor). Finally, we have used Cbl- resistant ErbB2 mutant to show that CHIP-mediated...regulation analyses of ErbB2. - Establish the Cbl- resistant ErbB2 mutants - Generated and characterized anti-CHIP antibodies. - Generated GFP-tagged

  10. B1-Metallo-beta-Lactamases: Where do we stand?

    PubMed Central

    Mojica, Maria F.; Bonomo, Robert A.; Fast, Walter

    2015-01-01

    Metallo-beta-Lactamases (MBLs) are class B β-lactamases that hydrolyze almost all clinically-available β-lactam antibiotics. MBLs feature the distinctive αβ/βα sandwich fold of the metallo-hydrolase / oxidoreductase superfamily and possess a shallow active-site groove containing one or two divalent zinc ions, flanked by flexible loops. According to sequence identity and zinc ion dependence, MBLs are classified into three subclasses (B1, B2 and B3), of which the B1 subclass enzymes have emerged as the most clinically significant. Differences among the active site architectures, the nature of zinc ligands, and the catalytic mechanisms have limited the development of a common inhibitor. In this review, we will describe the molecular epidemiology and structural studies of the most prominent representatives of class B1 MBLs (NDM-1, IMP-1 and VIM-2) and describe the implications for inhibitor design to counter this growing clinical threat. PMID:26424398

  11. B-1 AFT Nacelle Flow Visualization Study

    NASA Technical Reports Server (NTRS)

    Celniker, Robert

    1975-01-01

    A 2-month program was conducted to perform engineering evaluation and design tasks to prepare for visualization and photography of the airflow along the aft portion of the B-1 nacelles and nozzles during flight test. Several methods of visualizing the flow were investigated and compared with respect to cost, impact of the device on the flow patterns, suitability for use in the flight environment, and operability throughout the flight. Data were based on a literature search and discussions with the test personnel. Tufts were selected as the flow visualization device in preference to several other devices studied. A tuft installation pattern has been prepared for the right-hand aft nacelle area of B-1 air vehicle No.2. Flight research programs to develop flow visualization devices other than tufts for use in future testing are recommended. A design study was conducted to select a suitable motion picture camera, to select the camera location, and to prepare engineering drawings sufficient to permit installation of the camera. Ten locations on the air vehicle were evaluated before the selection of the location in the horizontal stabilizer actuator fairing. The considerations included cost, camera angle, available volume, environmental control, flutter impact, and interference with antennas or other instrumentation.

  12. The Vaporization of B2O3(l) to B2O3(g) and B2O2(g)

    NASA Technical Reports Server (NTRS)

    Jacobson, Nathan S.; Myers, Dwight L.

    2011-01-01

    The vaporization of B2O3 in a reducing environment leads to formation of both B2O3(g) and B2O2(g). While formation of B2O3(g) is well understood, many questions about the formation of B2O2(g) remain. Previous studies using B(s) + B2O3(l) have led to inconsistent thermodynamic data. In this study, it was found that after heating, B(s) and B2O3(l) appear to separate and variations in contact area likely led to the inconsistent vapor pressures of B2O2(g). To circumvent this problem, an activity of boron is fixed with a two-phase mixture of FeB and Fe2B. Both second and third law enthalpies of formation were measured for B2O2(g) and B2O3(g). From these the enthalpies of formation at 298.15 K are calculated to be -479.9 +/- 41.5 kJ/mol for B2O2(g) and -833.4 +/- 13.1 kJ/mol for B2O3(g). Ab initio calculations to determine the enthalpies of formation of B2O2(g) and B2O3(g) were conducted using the W1BD composite method and show good agreement with the experimental values.

  13. 15 CFR 8b.1 - Purpose.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... of handicap in any program or activity receiving Federal financial assistance. The purpose of this... 15 Commerce and Foreign Trade 1 2010-01-01 2010-01-01 false Purpose. 8b.1 Section 8b.1 Commerce... HANDICAPPED IN FEDERALLY ASSISTED PROGRAMS OPERATED BY THE DEPARTMENT OF COMMERCE General Provisions § 8b.1...

  14. 7 CFR 15b.1 - Purpose.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... FEDERAL FINANCIAL ASSISTANCE General Provisions § 15b.1 Purpose. The purpose of this part is to implement... 7 Agriculture 1 2010-01-01 2010-01-01 false Purpose. 15b.1 Section 15b.1 Agriculture Office of the... receiving Federal financial assistance. ...

  15. 32 CFR 242b.1 - Regents.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 2 2010-07-01 2010-07-01 false Regents. 242b.1 Section 242b.1 National Defense Department of Defense (Continued) OFFICE OF THE SECRETARY OF DEFENSE (CONTINUED) MISCELLANEOUS GENERAL... SCIENCES § 242b.1 Regents. (a) History and name. The Congress of the United States in the Uniformed...

  16. 32 CFR 242b.1 - Regents.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 32 National Defense 2 2013-07-01 2013-07-01 false Regents. 242b.1 Section 242b.1 National Defense Department of Defense (Continued) OFFICE OF THE SECRETARY OF DEFENSE (CONTINUED) MISCELLANEOUS GENERAL... SCIENCES § 242b.1 Regents. (a) History and name. The Congress of the United States in the Uniformed...

  17. 32 CFR 242b.1 - Regents.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 32 National Defense 2 2011-07-01 2011-07-01 false Regents. 242b.1 Section 242b.1 National Defense Department of Defense (Continued) OFFICE OF THE SECRETARY OF DEFENSE (CONTINUED) MISCELLANEOUS GENERAL... SCIENCES § 242b.1 Regents. (a) History and name. The Congress of the United States in the Uniformed...

  18. 32 CFR 242b.1 - Regents.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 32 National Defense 2 2012-07-01 2012-07-01 false Regents. 242b.1 Section 242b.1 National Defense Department of Defense (Continued) OFFICE OF THE SECRETARY OF DEFENSE (CONTINUED) MISCELLANEOUS GENERAL... SCIENCES § 242b.1 Regents. (a) History and name. The Congress of the United States in the Uniformed...

  19. 32 CFR 242b.1 - Regents.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 32 National Defense 2 2014-07-01 2014-07-01 false Regents. 242b.1 Section 242b.1 National Defense Department of Defense (Continued) OFFICE OF THE SECRETARY OF DEFENSE (CONTINUED) MISCELLANEOUS GENERAL... SCIENCES § 242b.1 Regents. (a) History and name. The Congress of the United States in the Uniformed...

  20. 42 CFR 52b.2 - Definitions.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 1 2012-10-01 2012-10-01 false Definitions. 52b.2 Section 52b.2 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GRANTS NATIONAL INSTITUTES OF HEALTH CONSTRUCTION GRANTS § 52b.2 Definitions. As used in this part: Act means the Public Health Service Act, as...

  1. 42 CFR 52b.2 - Definitions.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 1 2013-10-01 2013-10-01 false Definitions. 52b.2 Section 52b.2 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GRANTS NATIONAL INSTITUTES OF HEALTH CONSTRUCTION GRANTS § 52b.2 Definitions. As used in this part: Act means the Public Health Service Act, as...

  2. 42 CFR 52b.2 - Definitions.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 1 2011-10-01 2011-10-01 false Definitions. 52b.2 Section 52b.2 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GRANTS NATIONAL INSTITUTES OF HEALTH CONSTRUCTION GRANTS § 52b.2 Definitions. As used in this part: Act means the Public Health Service Act, as...

  3. 42 CFR 52b.2 - Definitions.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 1 2014-10-01 2014-10-01 false Definitions. 52b.2 Section 52b.2 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GRANTS NATIONAL INSTITUTES OF HEALTH CONSTRUCTION GRANTS § 52b.2 Definitions. As used in this part: Act means the Public Health Service Act, as...

  4. 42 CFR 52b.2 - Definitions.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Definitions. 52b.2 Section 52b.2 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GRANTS NATIONAL INSTITUTES OF HEALTH CONSTRUCTION GRANTS § 52b.2 Definitions. As used in this part: Act means the Public Health Service Act, as...

  5. 32 CFR 806b.2 - Basic guidelines.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 32 National Defense 6 2011-07-01 2011-07-01 false Basic guidelines. 806b.2 Section 806b.2 National Defense Department of Defense (Continued) DEPARTMENT OF THE AIR FORCE ADMINISTRATION PRIVACY ACT PROGRAM Overview of the Privacy Act Program § 806b.2 Basic guidelines. This part implements the Privacy Act of 1974...

  6. 32 CFR 806b.2 - Basic guidelines.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 6 2010-07-01 2010-07-01 false Basic guidelines. 806b.2 Section 806b.2 National Defense Department of Defense (Continued) DEPARTMENT OF THE AIR FORCE ADMINISTRATION PRIVACY ACT PROGRAM Overview of the Privacy Act Program § 806b.2 Basic guidelines. This part implements the Privacy Act of 1974 1 and applies to records on living ...

  7. 18 CFR 1b.2 - Scope.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Scope. 1b.2 Section 1b.2 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES RULES RELATING TO INVESTIGATIONS § 1b.2 Scope. This part applies to investigations...

  8. Farnesylation of lamin B1 is important for retention of nuclear chromatin during neuronal migration

    PubMed Central

    Jung, Hea-Jin; Nobumori, Chika; Goulbourne, Chris N.; Tu, Yiping; Lee, John M.; Tatar, Angelica; Wu, Daniel; Yoshinaga, Yuko; de Jong, Pieter J.; Coffinier, Catherine; Fong, Loren G.; Young, Stephen G.

    2013-01-01

    The role of protein farnesylation in lamin A biogenesis and the pathogenesis of progeria has been studied in considerable detail, but the importance of farnesylation for the B-type lamins, lamin B1 and lamin B2, has received little attention. Lamins B1 and B2 are expressed in nearly every cell type from the earliest stages of development, and they have been implicated in a variety of functions within the cell nucleus. To assess the importance of protein farnesylation for B-type lamins, we created knock-in mice expressing nonfarnesylated versions of lamin B1 and lamin B2. Mice expressing nonfarnesylated lamin B2 developed normally and were free of disease. In contrast, mice expressing nonfarnesylated lamin B1 died soon after birth, with severe neurodevelopmental defects and striking nuclear abnormalities in neurons. The nuclear lamina in migrating neurons was pulled away from the chromatin so that the chromatin was left “naked” (free from the nuclear lamina). Thus, farnesylation of lamin B1—but not lamin B2—is crucial for brain development and for retaining chromatin within the bounds of the nuclear lamina during neuronal migration. PMID:23650370

  9. SOFIA FIFI-LS Observations of Sgr B1

    NASA Astrophysics Data System (ADS)

    Simpson, Janet P.; Colgan, Sean; Cotera, Angela; Kaufman, Michael; Stolovy, Susan

    2018-01-01

    Although Sgr B1 is the third most luminous H II region in the Galactic Center, after the region ionized by the central star cluster Sgr A and the very young star-forming region Sgr B2, it has surprisingly not been well studied. Because Sgr B1 is found with Sgr B2 in a common envelope of molecular gas and far-infrared (FIR) emission, it has been assumed that the two sources are physically related, even though the ionized gas of Sgr B1 is much more extended and there are evolved-star indicators of a significantly greater age than Sgr B2. This presents a problem because the current paradigm of Galactic Center gas motions and star formation requires that the entire Sgr B complex must have reasonably similar ages. To clarify the situation, we have mapped Sgr B1 with the FIFI-LS spectrometer on SOFIA in the FIR lines of [O III] 52 and 88 micron, [O I] 146 micron, and [C II] 158 micron. For the most part, we find little correlation of the density-sensitive ratio of the [O III] lines with the radio VLA images or the FIR Herschel PACS images, from which we infer that the structures seen in those images are not due to density enhancements but are due to bubbles of gas and dust seen edge-on. The [C II] 158 micron line correlates much better with the structure seen in the Herschal PACS Blue 60-85 micron image than it does with the Red 130-210 micron image, which is dominated by the massive molecular cloud seen at higher Galactic latitude. Sgr B1 is largely covered by spectra from the Spitzer Infrared Spectrograph Archive, from which we measure mid-infrared lines of [Ne II], [Ne III], [Si II], [S III], and [Ar II]. From the ratios of these lines with the observed FIR lines we find that there are at least six small regions with significantly higher excitation than their surroundings; we infer that these regions contain the stars that excite the gas. Our presentation will describe these results in further detail.

  10. Ab initio calculations on the X (2)B1 and A (2)A1 states of AsH2, and Franck-Condon simulation, including anharmonicity, of the A(0,0,0)-X single vibronic level emission spectrum of AsH2.

    PubMed

    Lee, Edmond P F; Mok, Daniel K W; Chau, Foo-Tim; Dyke, John M

    2010-06-21

    Restricted-spin coupled-cluster single-double plus perturbative triple excitation {RCCSD(T)} calculations were carried out on the X (2)B(1) and A (2)A(1) states of AsH(2) employing the fully relativistic small-core effective core potential (ECP10MDF) for As and basis sets of up to the augmented correlation-consistent polarized valence quintuple-zeta (aug-cc-pV5Z) quality. Minimum-energy geometrical parameters and relative electronic energies were evaluated, including contributions from extrapolation to the complete basis set limit and from outer core correlation of the As 3d(10) electrons employing additional tight 4d3f2g2h functions designed for As. In addition, simplified, explicitly correlated CCSD(T)-F12 calculations were also performed employing different atomic orbital basis sets of up to aug-cc-pVQZ quality, and associated complementary auxiliary and density-fitting basis sets. The best theoretical estimate of the relative electronic energy of the A (2)A(1) state of AsH(2) relative to the X (2)B(1) state including zero-point energy correction (T(0)) is 19,954(32) cm(-1), which agrees very well with available experimental T(0) values of 19,909.4531(18) and 19,909.4910(17) cm(-1) obtained from recent laser induced fluorescence and cavity ringdown absorption spectroscopic studies. In addition, potential energy functions (PEFs) of the X (2)B(1) and A (2)A(1) states of AsH(2) were computed at different RCCSD(T) and CCSD(T)-F12 levels. These PEFs were used in variational calculations of anharmonic vibrational wave functions, which were then utilized to calculate Franck-Condon factors (FCFs) between these two states, using a method which includes allowance for anharmonicity and Duschinsky rotation. The A(0,0,0)-X single vibronic level (SVL) emission spectrum of AsH(2) was simulated using these computed FCFs. Comparison between simulated and available experimental vibrationally resolved spectra of the A(0,0,0)-X SVL emission of AsH(2), which consist essentially of

  11. Laboratory detection of a new interstellar free radical CH2CN(2B1)

    NASA Technical Reports Server (NTRS)

    Saito, Shuji; Yamamoto, Satoshi; Irvine, W. M.; Ziurys, L. M.; Suzuki, Hiroko

    1988-01-01

    An asymmetric-top free radical CH2CN with a 2B1 ground state was detected by laboratory microwave spectroscopy. The radical was produced in a free-space absorption cell by a DC glow discharge in pure CH3CN gas. About 60 fine-structure components were observed for the N = 11-10 to 14-13 a-type rotational transitions in the frequency region of 220-260 GHz. Hyperfine resolved components for the N = 4-3 and 5-4 transitions were resolved in the 80 and 100 GHz regions, respectively. Molecular constants were determined and U100602 and U80484 from Sgr B2, and U40240 and U20120 from TMC-1 were assigned to the N = 5-4, 4-3, 2-1, and 1-0 transitions with K(-1) = 0 of the CH2CN radical.

  12. 18 CFR 1b.1 - Definitions.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 18 Conservation of Power and Water Resources 1 2012-04-01 2012-04-01 false Definitions. 1b.1 Section 1b.1 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF... pipelines, electric utilities and hydroelectric projects. ...

  13. 18 CFR 1b.1 - Definitions.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 18 Conservation of Power and Water Resources 1 2014-04-01 2014-04-01 false Definitions. 1b.1 Section 1b.1 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF... pipelines, electric utilities and hydroelectric projects. ...

  14. 18 CFR 1b.1 - Definitions.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 18 Conservation of Power and Water Resources 1 2013-04-01 2013-04-01 false Definitions. 1b.1 Section 1b.1 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF... pipelines, electric utilities and hydroelectric projects. ...

  15. 18 CFR 1b.1 - Definitions.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Definitions. 1b.1 Section 1b.1 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF... pipelines, electric utilities and hydroelectric projects. [43 FR 27174, June 23, 1978, as amended by Order...

  16. 18 CFR 1b.1 - Definitions.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 18 Conservation of Power and Water Resources 1 2011-04-01 2011-04-01 false Definitions. 1b.1 Section 1b.1 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF... and informally any matter within the Commission's jurisdiction concerning natural gas pipelines, oil...

  17. 18 CFR 3b.1 - Purpose.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Purpose. 3b.1 Section 3b.1 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES COLLECTION, MAINTENANCE, USE, AND DISSEMINATION OF RECORDS OF IDENTIFIABLE PERSONAL...

  18. Degradation kinetics of aflatoxin B1 and B2 in filter paper and rough rice by using pulsed light irradiation

    USDA-ARS?s Scientific Manuscript database

    Rough rice is susceptible to contamination by aflatoxins, which are highly toxic, mutagenic and carcinogenic compounds. To develop aflatoxin degradation technology for rice with the use of pulsed light (PL) treatment, the objective of this study was to investigate the degradation characters of aflat...

  19. Attenuation of Persistent Experimental Pancreatitis Pain by a Bradykinin B2 Receptor Antagonist

    PubMed Central

    Chen, Qingmin; Vera-Portocarrero, Louis P.; Ossipov, Michael H.; Vardanyan, Marina; Lai, Josephine; Porreca, Frank

    2017-01-01

    Objective The role of bradykinin (BK) receptors in activating and sensitizing peripheral nociceptors is well known. Recently, we showed that spinal dynorphin was pronociceptive through direct or indirect BK receptor activation. Here, we explored the potential role of BK receptors in pain associated with persistent pancreatitis in rats. Methods Experimental pancreatitis and abdominal hypersensitivity were induced by intravenous administrations of dibutyltin dichloride (DBTC). [des-Arg9-Leu8]BK (B1 antagonist) and HOE 140 (B2 antagonist) were given by intraperitoneal or intrathecal injection. Dynorphin antiserum was given intrathecally. Reverse transcription–polymerase chain reaction was used to detect spinal mRNA for BK receptors. Results Dibutyltin dichloride–induced pancreatitis upregulated B1 and B2 mRNA in the thoracic dorsal root ganglion and B2, but not B1, in the pancreas. No changes in spinal B1 or B2 mRNA were observed. Intraperitoneal or intrathecal administration of HOE 140 dose dependently abolished DBTC-induced abdominal hypersensitivity, whereas [des-Arg9-Leu8]BK was without effect by either route of administration. Antiserum to dynorphin (intrathecal) abolished DBTC-induced hypersensitivity. Conclusions These results suggest that blockade of peripheral or spinal BK B2 receptors may be an effective approach for diminishing pain associated with pancreatitis. Moreover, it is suggested that spinal dynorphin may maintain pancreatitis pain through direct or indirect activation of BK B2 receptors in the spinal cord. PMID:20531238

  20. MR fingerprinting with simultaneous B1 estimation.

    PubMed

    Buonincontri, Guido; Sawiak, Stephen J

    2016-10-01

    MR fingerprinting (MRF) can be used for quantitative estimation of physical parameters in MRI. Here, we extend the method to incorporate B1 estimation. The acquisition is based on steady state free precession MR fingerprinting with a Cartesian trajectory. To increase the sensitivity to the B1 profile, abrupt changes in flip angle were introduced in the sequence. Slice profile and B1 effects were included in the dictionary and the results from two- and three-dimensional (3D) acquisitions were compared. Acceleration was demonstrated using retrospective undersampling in the phase encode directions of 3D data exploiting redundancy between MRF frames at the edges of k-space. Without B1 estimation, T2 and B1 were inaccurate by more than 20%. Abrupt changes in flip angle improved B1 maps. T1 and T2 values obtained with the new MRF methods agree with classical spin echo measurements and are independent of the B1 field profile. When using view sharing reconstruction, results remained accurate (error <10%) when sampling under 10% of k-space from the 3D data. The methods demonstrated here can successfully measure T1, T2, and B1. Errors due to slice profile can be substantially reduced by including its effect in the dictionary or acquiring data in 3D. Magn Reson Med 76:1127-1135, 2016. © 2015 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. © 2015 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.

  1. 12 CFR 264b.2 - Definitions.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Federal Reserve System (“Board”), officers, and other employees of the Board, including experts or... 12 Banks and Banking 3 2010-01-01 2010-01-01 false Definitions. 264b.2 Section 264b.2 Banks and Banking FEDERAL RESERVE SYSTEM (CONTINUED) BOARD OF GOVERNORS OF THE FEDERAL RESERVE SYSTEM RULES...

  2. 18 CFR 3b.2 - Definitions.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 18 Conservation of Power and Water Resources 1 2011-04-01 2011-04-01 false Definitions. 3b.2 Section 3b.2 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF... another agency, * * *”, includes any executive department, military department, Government corporation...

  3. 18 CFR 3b.2 - Definitions.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Definitions. 3b.2 Section 3b.2 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF... another agency, * * *”, includes any executive department, military department, Government corporation...

  4. Flavonoids exhibit diverse effects on CYP11B1 expression and cortisol synthesis

    SciTech Connect

    Cheng, Li-Chuan; Li, Lih-Ann, E-mail: lihann@nhri.org.tw

    2012-02-01

    CYP11B1 catalyzes the final step of cortisol biosynthesis. The effects of flavonoids on transcriptional expression and enzyme activity of CYP11B1 were investigated using the human adrenocortical H295R cell model. All tested nonhydroxylated flavones including 3′,4′-dimethoxyflavone, α-naphthoflavone, and β-naphthoflavone upregulated CYP11B1 expression and cortisol production, whereas apigenin and quercetin exhibited potent cytotoxicity and CYP11B1 repression at high concentrations. Nonhydroxylated flavones stimulated CYP11B1-catalyzed cortisol formation at transcriptional level. Resveratrol increased endogenous and substrate-supported cortisol production like nonhydroxylated flavones tested, but it had no effect on CYP11B1 gene expression and enzyme activity. Resveratrol appeared to alter cortisol biosynthesis at an earlier step. Themore » Ad5 element situated in the − 121/− 106 region was required for basal and flavone-induced CYP11B1 expression. Overexpression of COUP-TFI did not improve the responsiveness of Ad5 to nonhydroxylated flavones. Although COUP-TFI overexpression increased CYP11B1 and CYP11B2 promoter activation, its effect was not mediated through the common Ad5 element. Treating cells with PD98059 (a flavone-type MEK1 inhibitor) increased CYP11B1 promoter activity, but not involving ERK signaling because phosphorylation of ERK1/2 remained unvarying throughout the course of treatment. Likewise, AhR was not responsible for the CYP11B1-modulating effects of flavonoids because inconsistency with their effects on AhR activation. 3′,4′-dimethoxyflavone and 8-Br-cAMP additively activated CYP11B1 promoter activity. H-89 reduced 3′,4′-dimethoxyflavone-induced CYP11B1 promoter activation but to a lesser extent as compared to its inhibition on cAMP-induced transactivation. Our data suggest that constant exposure to nonhydroxylated flavones raises a potential risk of high basal and cAMP-induced cortisol synthesis in consequence of increased

  5. The purification step is not crucial in EIA measurements of thromboxane B2 and 11-dehydrothromboxane B2 in human plasma.

    PubMed

    Sadilkova, Lenka; Paluch, Zoltan; Mottlova, Jirina; Bednar, Frantisek; Alusik, Stefan

    2012-01-01

    Thromboxane B2 (TxB2) and particularly 11-dehydrothromboxane B2 (11-dTxB2) are widely used as prognostic risk markers of platelet activation in cardiovascular diseases. The main errors in TxB2 and 11-dTxB2 determination include either low concentrations of circulating TxB2 (1 - 2 pg/mL) and 11-dTxB2 (0.9 - 4.3 pg/mL) or rather high transiency (mean TxB2 half-life is approximately 5 minutes) as well as an incorrect pre-analytical phase set up. The aim of this study was to investigate the impact of a widely used purification step on the results of enzyme immunosorbent assay (EIA)--based measurement of the two selected thromboxanes. For the purpose of this study, 20 plasma samples (10 healthy donors, 10 patients under treatment with acetylsalicylic acid) were screened for TxB2 and 11-dTxB2 concentrations using commercial competitive EIA kits (Cayman Chemicals, Tallinn, Estonia; Neogen, Lexington, KY, USA) with or without the introduction of the purification procedure. The purification step does not significantly affect the results of EIA measurements of the two of TxA2 metabolites (TxB2, 11-dTxB2) in human plasma. The levels of TxB2 and 11-dTxB2 determined in the plasma samples were not significantly changed (p < 0.05) when the purification step was omitted compared to the purified samples. This study establishes a protocol allowing for reliable and reproducible plasma TxB2 and 11-dTxB2 EIA measurement for routine basic screening of platelet function.

  6. 26 CFR 1.179B-1T - Deduction for capital costs incurred in complying with Environmental Protection Agency sulfur...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... complying with Environmental Protection Agency sulfur regulations (temporary). 1.179B-1T Section 1.179B-1T... capital costs incurred in complying with Environmental Protection Agency sulfur regulations (temporary... Protection Agency (EPA). This section also provides rules for making elections under section 179B. (2...

  7. A Novel CYP11B2-Specific Imaging Agent for Detection of Unilateral Subtypes of Primary Aldosteronism.

    PubMed

    Abe, Tsutomu; Naruse, Mitsuhide; Young, William F; Kobashi, Nobuya; Doi, Yoshihiro; Izawa, Akihiro; Akama, Kei; Okumura, Yuki; Ikenaga, Miho; Kimura, Hiroyuki; Saji, Hideo; Mukai, Kuniaki; Matsumoto, Hiroki

    2016-03-01

    Although adrenal vein sampling is the standard method to distinguish unilateral from bilateral forms of primary aldosteronism, it is an invasive and technically difficult procedure. (11)C-metomidate (MTO)-positron emission tomography was reported as a potential replacement for adrenal vein sampling. However, MTO has low selectivity for CYP11B2 over CYP11B1. This study aimed to determine the selectivity of (18)F-CDP2230, a new imaging agent, for CYP11B2 over CYP11B1 and determine whether the biodistribution profile of (18)F-CDP2230 is favorable for imaging CYP11B2. The IC50 of CDP2230 for the enzymatic activities of CYP11B2 and CYP11B1 was determined using cells with stable expression of either enzyme. In vitro autoradiography of human adrenal sections with aldosterone-producing adenomas was performed to confirm the specific binding ability of (18)F-CDP2230 to CYP11B2-expressing regions. Furthermore, positron emission tomography and magnetic resonance imaging were performed to evaluate the biodistribution of (18)F-CDP2230 in rats. Although CDP2230 showed a significantly lower affinity for CYP11B2 and CYP11B1 than did MTO analogues, its selectivity for CYP11B2 over CYP11B1 was higher than that of MTO analogues. In vitro autoradiography revealed that the binding of (18)F-CDP2230 to CYP11B2-expressing regions in the adrenal gland was more specific than that of (123)I-IMTO. Moreover, the biodistribution study showed that (18)F-CDP2230 accumulated in adrenal glands with low background uptake. Our study showed a high selectivity of (18)F-CDP2230 for CYP11B2 over CYP11B1 with a favorable biodistribution for imaging CYP11B2. (18)F-CDP2230 is a promising imaging agent for detecting unilateral subtypes of primary aldosteronism.

  8. 26 CFR 301.7701(b)-2 - Closer connection exception.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...) PROCEDURE AND ADMINISTRATION PROCEDURE AND ADMINISTRATION Definitions § 301.7701(b)-2 Closer connection...) Tax home—(1) Definition. For purposes of section 7701 (b) and the regulations under that section, the term “tax home” has the same meaning that it has for purposes of section 162(a)(2) (relating to travel...

  9. Depletion of the xynB2 gene upregulates β-xylosidase expression in C. crescentus.

    PubMed

    Corrêa, Juliana Moço; Mingori, Moara Rodrigues; Gandra, Rinaldo Ferreira; Loth, Eduardo Alexandre; Seixas, Flávio Augusto Vicente; Simão, Rita de Cássia Garcia

    2014-01-01

    Caulobacter crescentus is able to express several enzymes involved in the utilization of lignocellulosic biomasses. Five genes, xynB1-5, that encode β-xylosidases are present in the genome of this bacterium. In this study, the xynB2 gene, which encodes β-xylosidase II (CCNA_02442), was cloned under the control of the PxylX promoter to generate the O-xynB2 strain, which overexpresses the enzyme in the presence of xylose. In addition, a null mutant strain, Δ-xynB2, was created by two homologous recombination events where the chromosomal xynB2 gene was replaced by a copy that was disrupted by the spectinomycin-resistant cassette. We demonstrated that C. crescentus cells lacking β-xylosidase II upregulates the xynB genes inducing β-xylosidase activity. Transcriptional analysis revealed that xynB1 (RT-PCR analysis) and xynB2 (lacZ transcription fusion) gene expression was induced in the Δ-xynB2 cells, and high β-xylosidase activity was observed in the presence of different agro-industrial residues in the null mutant strain, a characteristic that can be explored and applied in biotechnological processes. In contrast, overexpression of the xynB2 gene caused downregulation of the expression and activity of the β-xylosidase. For example, the β-xylosidase activity that was obtained in the presence of sugarcane bagasse was 7-fold and 16-fold higher than the activity measured in the C. crescentus parental and O-xynB2 cells, respectively. Our results suggest that β-xylosidase II may have a role in controlling the expression of the xynB1 and xynB2 genes in C. crescentus.

  10. VirB1* promotes T-pilus formation in the vir-Type IV secretion system of Agrobacterium tumefaciens.

    PubMed

    Zupan, John; Hackworth, Cheryl A; Aguilar, Julieta; Ward, Doyle; Zambryski, Patricia

    2007-09-01

    The vir-type IV secretion system of Agrobacterium is assembled from 12 proteins encoded by the virB operon and virD4. VirB1 is one of the least-studied proteins encoded by the virB operon. Its N terminus is a lytic transglycosylase. The C-terminal third of the protein, VirB1*, is cleaved from VirB1 and secreted to the outside of the bacterial cell, suggesting an additional function. We show that both nopaline and octopine strains produce abundant amounts of VirB1* and perform detailed studies on nopaline VirB1*. Both domains are required for wild-type virulence. We show here that the nopaline type VirB1* is essential for the formation of the T pilus, a subassembly of the vir-T4SS composed of processed and cyclized VirB2 (major subunit) and VirB5 (minor subunit). A nopaline virB1 deletion strain does not produce T pili. Complementation with full-length VirB1 or C-terminal VirB1*, but not the N-terminal lytic transglycosylase domain, restores T pili containing VirB2 and VirB5. T-pilus preparations also contain extracellular VirB1*. Protein-protein interactions between VirB1* and VirB2 and VirB5 were detected in the yeast two-hybrid assay. We propose that VirB1 is a bifunctional protein required for virT4SS assembly. The N-terminal lytic transglycosylase domain provides localized lysis of the peptidoglycan cell wall to allow insertion of the T4SS. The C-terminal VirB1* promotes T-pilus assembly through protein-protein interactions with T-pilus subunits.

  11. Cytochrome P450 2A13 mediates the neoplastic transformation of human bronchial epithelial cells at a low concentration of aflatoxin B1.

    PubMed

    Zhang, Zhan; Lu, Huiyuan; Huan, Fei; Meghan, Cromie; Yang, Xuejiao; Wang, Yun; Wang, Xichen; Wang, Xinru; Wang, Shou-Lin

    2014-04-01

    Cytochrome P450 2A13 (CYP2A13), mainly expressed in human respiratory tract, is highly efficient in the metabolic activation of aflatoxin (AF) B1 (AFB1) and is assumed to play a role in human lung tumorigenesis in airborne AFB1 exposure. To validate the assumption, we exposed human bronchial epithelial (BEAS-2B) cells stably expressing CYP2A13 (B-2A13), CYP1A2 (B-1A2) and CYP2A6 (B-2A6) to 0.1-10 nM AFB1 for 30-50 passages. B-2A13 cells showed increased sensitivity to 0.1 nM AFB1-induced neoplastic transformation and the formation of tumors in nude mice were observed at passage 30 (P30) while it occurred at P50 B-1A2 cells. B-2A6, similar to vector control, showed no neoplastic transformation in this condition. Additionally, AFB1-DNA adducts and 8-OHdG significantly increased in transformed P40 B-2A13, in parallel with the upregulation of p-ATR, p-BRCA1, Mre11, Rad50 and Rad51. However, the apoptosis of P40 cells was near normal, while the expression of Bax, C-Caspase 3 and C-PARP increased passage-dependently. Inhibition of ATR (ATR siRNA or NU6027) reversely increased the apoptosis of P40 B-2A13 cells in parallel with the upregulation of Bax, C-Caspase 3 and C-PARP, suggesting that ATR plays an important role in maintaining cell survival via antiapoptosis. Additionally, activation of ATR was necessary to neoplastic transformation since blockage of ATR in P40 cells inhibited DNA damage repair response and anchorage-independent growth. Our data demonstrated that CYP2A13 played a critical role in AFB1-induced neoplastic transformation. ATR-mediated the dysfunction of apoptosis and DNA damage repair might be involved. These results help establish a linkage between airborne AFB1 and human respiratory carcinoma. © 2013 UICC.

  12. New silicate-germanate Cs2Pb2[(Si0.6Ge0.4)2O7] from the series A2Pb2[B2O7], A = K, Cs, B = Si, Ge with the umbrella-like [PbO3]4- group

    NASA Astrophysics Data System (ADS)

    Belokoneva, Elena L.; Morozov, Ivan A.; Volkov, Anatoly S.; Dimitrova, Olga V.; Stefanovich, Sergey Yu.

    2018-04-01

    New silicate-germanate Cs2Pb2[(Si0.6Ge0.4)2O7] was synthesized in multi-components hydrothermal solution with 20 w.% concentration of Cs2CO3 mineralizer, pH = 10. Novel mixed compound belongs to the structure type A2Pb2[B2O7] previously indicated for powders with A = K, B=Si or Ge. Singe crystal structure determination of Cs2Pb2[(Si0.6Ge0.4)2O7] revealed the need for the correction of the space group of the earlier suggested structural model from P-3 to P-3m1, as well as for the splitting of the Pb-atom position. Umbrella-like groups [PbO3]4- are located between [(Si,Ge)O4]4- tetrahedra in mica-like honeycomb layers and play the role of tetrahedra with the Pb-lone-pair as the forth apex. Crystal chemical comparison revealed similarities and differences with the classical structure type of α-celsian Ba[Al2Si2O8] with the tetrahedral double layer. Recently investigated nonlinear optical acentric borates Pb2(BO3)(NO3) and Pb2(BO3)Cl are both related to this structural type, possessing umbrella-like groups [PbO3]4- and honeycomb layers [Pb2(BO3)]+ with the BO3-triangles on the tetrahedral positions.

  13. A search for cyanopolyynes in L1157-B1

    NASA Astrophysics Data System (ADS)

    Mendoza, Edgar; Lefloch, B.; Ceccarelli, C.; Kahane, C.; Jaber, A. A.; Podio, L.; Benedettini, M.; Codella, C.; Viti, S.; Jimenez-Serra, I.; Lepine, J. R. D.; Boechat-Roberty, H. M.; Bachiller, R.

    2018-04-01

    We present here a systematic search for cyanopolyynes in the shock region L1157-B1 and its associated protostar L1157-mm in the framework of the Large Program`Astrochemical Surveys At IRAM' (ASAI), dedicated to chemical surveys of solar-type star-forming regions with the IRAM 30-m telescope. Observations of the millimeter windows between 72 and 272 GHz permitted the detection of HC3N and its 13C isotopologues, and HC5N (for the first time in a protostellar shock region). In the shock, the analysis of the line profiles shows that the emission arises from the outflow cavities associated with L1157-B1 and L1157-B2. Molecular abundances and excitation conditions were obtained from the analysis of the Spectral Line Energy Distributions under the assumption of Local Thermodynamical Equilibrium or using a radiative transfer code in the Large Velocity Gradient approximation. Towards L1157 mm, the HC3N emission arises from the cold envelope (T_rot=10K) and a higher-excitation region (Trot = 31K) of smaller extent around the protostar. We did not find any evidence of 13C or D fractionation enrichment towards L1157-B1. We obtain a relative abundance ratio HC3N/HC5N of 3.3 in the shocked gas. We find an increase by a factor of 30 of the HC3N abundance between the envelope of L1157-mm and the shock region itself. Altogether, these results are consistent with a scenario in which the bulk of HC3N was produced by means of gas phase reactions in the passage of the shock. This scenario is supported by the predictions of a parametric shock code coupled with the chemical model UCL_CHEM.

  14. Evolutionary implication of B-1 lineage cells from innate to adaptive immunity.

    PubMed

    Zhu, Lv-yun; Shao, Tong; Nie, Li; Zhu, Ling-yun; Xiang, Li-xin; Shao, Jian-zhong

    2016-01-01

    The paradigm that B cells mainly play a central role in adaptive immunity may have to be reevaluated because B-1 lineage cells have been found to exhibit innate-like functions, such as phagocytic and bactericidal activities. Therefore, the evolutionary connection of B-1 lineage cells between innate and adaptive immunities have received much attention. In this review, we summarized various innate-like characteristics of B-1 lineage cells, such as natural antibody production, antigen-presenting function in primary adaptive immunity, and T cell-independent immune responses. These characteristics seem highly conserved between fish B cells and mammalian B-1 cells during vertebrate evolution. We proposed an evolutionary outline of B cells by comparing biological features, including morphology, phenotype, ontogeny, and functional activity between B-1 lineage cells and macrophages or B-2 cells. The B-1 lineage may be a transitional cell type between phagocytic cells (e.g., macrophages) and B-2 cells that functionally connects innate and adaptive immunities. Our discussion would contribute to the understanding on the origination of B cells specialized in adaptive immunity from innate immunity. The results might provide further insight into the evolution of the immune system as a whole. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Microcin determinants are associated with B2 phylogroup of human fecal Escherichia coli isolates.

    PubMed

    Micenková, Lenka; Bosák, Juraj; Štaudová, Barbora; Kohoutová, Darina; Čejková, Darina; Woznicová, Vladana; Vrba, Martin; Ševčíková, Alena; Bureš, Jan; Šmajs, David

    2016-06-01

    Escherichia coli strains are classified into four main phylogenetic groups (A, B1, B2, and D) and strains of these phylogroups differ in a number of characteristics. This study tested whether human fecal E. coli isolates belonging to different phylogroups differ in prevalence of bacteriocinogenic isolates and prevalence of individual bacteriocinogenic determinants. A set of 1283 fecal E. coli isolates from patients with different diseases was tested for the presence of DNA regions allowing classification into E. coli phylogroups and for the ability to produce bacteriocins (23 colicins and 7 microcins). Of the isolates tested, the most common was phylogroup B2 (38.3%) followed by phylogroups A (28.3%), D (26.3%) and B1 (7.2%). Altogether, 695 bacteriocin producers were identified representing 54.2% of all tested isolates. The highest prevalence of bacteriocin producers was found in group B2 (60.3%) and the lowest in group B1 (44.6%). Determinants encoding colicins E1, Ia, and microcin mV were most common in phylogroup A, determinants encoding microcins mM and mH47 were most common in phylogroup B2, and determinant encoding mB17 was most common in phylogroup D. The highest prevalence of bacteriocinogeny was found in phylogroup B2, suggesting that bacteriocinogeny and especially the synthesis of microcins was associated with virulent and resident E. coli strains. © 2016 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.

  16. 18 CFR 3b.2 - Definitions.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... Section 3b.2 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES COLLECTION, MAINTENANCE, USE, AND DISSEMINATION OF RECORDS OF IDENTIFIABLE PERSONAL... or the granting of access to a record, by oral, written, electronic or mechanical communication. ...

  17. 18 CFR 3b.2 - Definitions.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... Section 3b.2 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES COLLECTION, MAINTENANCE, USE, AND DISSEMINATION OF RECORDS OF IDENTIFIABLE PERSONAL... or the granting of access to a record, by oral, written, electronic or mechanical communication. ...

  18. 18 CFR 3b.2 - Definitions.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... Section 3b.2 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES COLLECTION, MAINTENANCE, USE, AND DISSEMINATION OF RECORDS OF IDENTIFIABLE PERSONAL... or the granting of access to a record, by oral, written, electronic or mechanical communication. ...

  19. OATP1B1 Polymorphism as a Determinant of Erythromycin Disposition

    PubMed Central

    Lancaster, CS; Bruun, GH; Peer, CJ; Mikkelsen, TS; Corydon, TJ; Gibson, AA; Hu, S; Orwick, SJ; Mathijssen, RHJ; Figg, WD; Baker, SD; Sparreboom, A

    2012-01-01

    Previous studies have demonstrated that the pharmacokinetic profile of erythromycin, a probe for CYP3A4 activity, is affected by inhibitors or inducers of hepatic solute carriers. We hypothesized that these interactions are mediated by OATP1B1 (gene symbol, SLCO1B1), a polypeptide expressed on the basolateral surface of hepatocytes. Using stably transfected Flp-In T-REx 293 cells, erythromycin was found to be a substrate for OATP1B1*1A (wildtype) with a Km of ~13 µM, and its transport was reduced by ~50% in cells expressing OATP1B1*5 (V174A). Deficiency of the ortholog transporter Oatp1b2 in mice was associated with a 52% decrease in the metabolic rate of erythromycin (P = 0.000043). In line with these observations, in humans, the c.521T>C variant in SLCO1B1 (rs4149056), encoding OATP1B1*5, was associated with a genotype-dosage dependent decline in erythromycin metabolism (P = 0.0072). These results suggest that impaired OATP1B1 function can alter erythromycin metabolism independently of changes in CYP3A4 activity. PMID:22990751

  20. Tensor-polarized structure function b1 in the standard convolution description of the deuteron

    NASA Astrophysics Data System (ADS)

    Cosyn, W.; Dong, Yu-Bing; Kumano, S.; Sargsian, M.

    2017-04-01

    Tensor-polarized structure functions of a spin-1 hadron are additional observables, which do not exist for the spin-1 /2 nucleon. They could probe novel aspects of the internal hadron structure. Twist-2 tensor-polarized structure functions are b1 and b2, and they are related by the Callan-Gross-like relation in the Bjorken scaling limit. In this work, we theoretically calculate b1 in the standard convolution description for the deuteron. Two different theoretical models, a basic convolution description and a virtual nucleon approximation, are used for calculating b1, and their results are compared with the HERMES measurement. We found large differences between our theoretical results and the data. Although there is still room to improve by considering higher-twist effects and in the experimental extraction of b1 from the spin asymmetry Az z, there is a possibility that the large differences require physics beyond the standard deuteron model for their interpretation. Future b1 studies could shed light on a new field of hadron physics. In particular, detailed experimental studies of b1 will start soon at the Thomas Jefferson National Accelerator Facility. In addition, there are possibilities to investigate tensor-polarized parton distribution functions and b1 at Fermi National Accelerator Laboratory and a future electron-ion collider. Therefore, further theoretical studies are needed for understanding the tensor structure of the spin-1 deuteron, including a new mechanism to explain the large differences between the current data and our theoretical results.

  1. HCl absorption toward Sagittarius B2

    NASA Technical Reports Server (NTRS)

    Zmuidzinas, J.; Blake, G. A.; Carlstrom, J.; Keene, J.; Miller, D.

    1995-01-01

    We have detected the 626 GHz J = 1 approaches 0 transition of hydrogen chloride (H(sup 35)Cl) in absorption against the blending of the three hyperfine components of this transition by the velocity profile of Sgr B2 observed in other species. The apparent optical depth of the line is tau approximately equal to 1, and the minimum HCl column density is 1.6 x 10(exp 14)/sq cm. A detailed radiative transfer model was constructed which includes collisional and radiative excitation, absorption and emission by dust, and the radial variation of temperature and density. Good agreement between the model and the data is obtained for HCl/H2 approximately 1.1 x 10(exp -9). Comparison of this result to chemical models indicates that the depletion factor of gas-phase chlorine is between 50-180 in the molecular envelope surrounding the SgrB2(N) and (M) dust cores.

  2. Beneficial effects of kinin B1 receptor antagonism on plasma fatty acid alterations and obesity in Zucker diabetic fatty rats.

    PubMed

    Talbot, Sébastien; Dias, Jenny Pena; El Midaoui, Adil; Couture, Réjean

    2016-07-01

    Kinins are the endogenous ligands of the constitutive B2 receptor (B2R) and the inducible B1 receptor (B1R). Whereas B2R prevents insulin resistance, B1R is involved in insulin resistance and metabolic syndrome. However, the contribution of B1R in type 2 diabetes associated with obesity remains uncertain. The aim of the present study was to examine the impact of 1-week treatment with a selective B1R antagonist (SSR240612, 10 mg/kg per day, by gavage) on hyperglycemia, hyperinsulinemia, leptinemia, body mass gain, and abnormal plasma fatty acids in obese Zucker diabetic fatty (ZDF) rats. Treatment with SSR240612 abolished the body mass gain and reduced polyphagia, polydipsia, and plasma fatty acid alterations in ZDF rats without affecting hyperglycemia, hyperinsulinemia, and hyperleptinemia. The present study suggests that the upregulated B1R plays a role in body mass gain and circulating fatty acid alterations in ZDF rats. However, mechanisms other than B1R induction would be implicated in glucose metabolism disorder in ZDF rats, based on the finding that SSR240612 did not reverse hyperglycemia and hyperinsulinemia.

  3. Overview of Facility Nos. B1 and N2, Facility 5 (right) ...

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

    Overview of Facility Nos. B-1 and N-2, Facility 5 (right) and Facility 9 (left) in center of photo, with water tank in background. Facility No. B-1 seen in elevation view, and Facility No. N-2 to right of photo, view facing east - U.S. Naval Base, Pearl Harbor, South Quay Wall & Repair Wharf, L-shaped portion of quay walls starting at east side of mouth of Dry Dock No. 1, continuing along ocean side of Sixth Street, adjacent to Pier B-2, Pearl City, Honolulu County, HI

  4. Blocking of bradykinin receptor B1 protects from focal closed head injury in mice by reducing axonal damage and astroglia activation

    PubMed Central

    Albert-Weissenberger, Christiane; Stetter, Christian; Meuth, Sven G; Göbel, Kerstin; Bader, Michael; Sirén, Anna-Leena; Kleinschnitz, Christoph

    2012-01-01

    The two bradykinin receptors B1R and B2R are central components of the kallikrein–kinin system with different expression kinetics and binding characteristics. Activation of these receptors by kinins triggers inflammatory responses in the target organ and in most situations enhances tissue damage. We could recently show that blocking of B1R, but not B2R, protects from cortical cryolesion by reducing inflammation and edema formation. In the present study, we investigated the role of B1R and B2R in a closed head model of focal traumatic brain injury (TBI; weight drop). Increased expression of B1R in the injured hemispheres of wild-type mice was restricted to the later stages after brain trauma, i.e. day 7 (P<0.05), whereas no significant induction could be observed for the B2R (P>0.05). Mice lacking the B1R, but not the B2R, showed less functional deficits on day 3 (P<0.001) and day 7 (P<0.001) compared with controls. Pharmacological blocking of B1R in wild-type mice had similar effects. Reduced axonal injury and astroglia activation could be identified as underlying mechanisms, while inhibition of B1R had only little influence on the local inflammatory response in this model. Inhibition of B1R may become a novel strategy to counteract trauma-induced neurodegeneration. PMID:22569191

  5. Blocking of bradykinin receptor B1 protects from focal closed head injury in mice by reducing axonal damage and astroglia activation.

    PubMed

    Albert-Weissenberger, Christiane; Stetter, Christian; Meuth, Sven G; Göbel, Kerstin; Bader, Michael; Sirén, Anna-Leena; Kleinschnitz, Christoph

    2012-09-01

    The two bradykinin receptors B1R and B2R are central components of the kallikrein-kinin system with different expression kinetics and binding characteristics. Activation of these receptors by kinins triggers inflammatory responses in the target organ and in most situations enhances tissue damage. We could recently show that blocking of B1R, but not B2R, protects from cortical cryolesion by reducing inflammation and edema formation. In the present study, we investigated the role of B1R and B2R in a closed head model of focal traumatic brain injury (TBI; weight drop). Increased expression of B1R in the injured hemispheres of wild-type mice was restricted to the later stages after brain trauma, i.e. day 7 (P<0.05), whereas no significant induction could be observed for the B2R (P>0.05). Mice lacking the B1R, but not the B2R, showed less functional deficits on day 3 (P<0.001) and day 7 (P<0.001) compared with controls. Pharmacological blocking of B1R in wild-type mice had similar effects. Reduced axonal injury and astroglia activation could be identified as underlying mechanisms, while inhibition of B1R had only little influence on the local inflammatory response in this model. Inhibition of B1R may become a novel strategy to counteract trauma-induced neurodegeneration.

  6. B-2 Extremely High Frequency SATCOM and Computer Increment 1 (B-2 EHF Inc 1)

    DTIC Science & Technology

    2015-12-01

    Selected Acquisition Report ( SAR ) RCS: DD-A&T(Q&A)823-224 B-2 Extremely High Frequency SATCOM and Computer Increment 1 (B-2 EHF Inc 1) As of FY... SAR March 23, 2016 16:05:26 UNCLASSIFIED 2 Table of Contents Common Acronyms and Abbreviations for MDAP Programs 3 Program Information...Unit Cost B-2 EHF Inc 1 December 2015 SAR March 23, 2016 16:05:26 UNCLASSIFIED 3 PB - President’s Budget PE - Program Element PEO - Program Executive

  7. Interplay between the kinin B1 receptor and inducible nitric oxide synthase in insulin resistance

    PubMed Central

    Haddad, Youssef

    2016-01-01

    Background and Purpose Kinins are vasoactive and pro‐inflammatory peptides whose biological effects are mediated by two GPCRs, named B1 and B2 receptors. While the B2 receptor plays a protective role in the cardiovascular system via the activation of endothelial NOS, the B1 receptor is associated with vascular inflammation, insulin resistance and diabetic complications. Because the B1 receptor is a potent activator of the inducible form of NOS (iNOS), this study has addressed the role of iNOS in the deleterious effects of B1 receptors in insulin resistance. Experimental Approach Male Sprague–Dawley rats (50–75 g) had free access to a drinking solution containing 10% d‐glucose or tap water (control) for 9 weeks. During the last week, a selective iNOS inhibitor (1400W, 1 mg·kg−1 twice daily) or its vehicle was administered s.c. Key Results Prolonged glucose treatment caused insulin resistance and several hallmarks of type 2 diabetes. Whereas the treatment with 1400W had no impact on the elevated systolic blood pressure and leptin levels in glucose‐fed rats, it significantly reversed or attenuated hyperglycaemia, hyperinsulinaemia, insulin resistance (HOMA index), body weight gain, peroxynitrite formation (nitrotyrosine expression) and the up‐regulation of biomarkers of inflammation (B1 receptor, carboxypeptidase M, iNOS and IL‐1β) in renal cortex and aorta and to some extent in the liver. Conclusions and Implications Pharmacological blockade of iNOS prevents the formation of peroxynitrite, which amplifies the pro‐inflammatory effects of B1 receptors through a positive feedback mechanism. Hence, targeting iNOS can prevent the deleterious effects of B1 receptors in insulin resistance and peripheral inflammation. PMID:27059924

  8. Interplay between the kinin B1 receptor and inducible nitric oxide synthase in insulin resistance.

    PubMed

    Haddad, Youssef; Couture, Réjean

    2016-06-01

    Kinins are vasoactive and pro-inflammatory peptides whose biological effects are mediated by two GPCRs, named B1 and B2 receptors. While the B2 receptor plays a protective role in the cardiovascular system via the activation of endothelial NOS, the B1 receptor is associated with vascular inflammation, insulin resistance and diabetic complications. Because the B1 receptor is a potent activator of the inducible form of NOS (iNOS), this study has addressed the role of iNOS in the deleterious effects of B1 receptors in insulin resistance. Male Sprague-Dawley rats (50-75 g) had free access to a drinking solution containing 10% d-glucose or tap water (control) for 9 weeks. During the last week, a selective iNOS inhibitor (1400W, 1 mg·kg(-1) twice daily) or its vehicle was administered s.c. Prolonged glucose treatment caused insulin resistance and several hallmarks of type 2 diabetes. Whereas the treatment with 1400W had no impact on the elevated systolic blood pressure and leptin levels in glucose-fed rats, it significantly reversed or attenuated hyperglycaemia, hyperinsulinaemia, insulin resistance (HOMA index), body weight gain, peroxynitrite formation (nitrotyrosine expression) and the up-regulation of biomarkers of inflammation (B1 receptor, carboxypeptidase M, iNOS and IL-1β) in renal cortex and aorta and to some extent in the liver. Pharmacological blockade of iNOS prevents the formation of peroxynitrite, which amplifies the pro-inflammatory effects of B1 receptors through a positive feedback mechanism. Hence, targeting iNOS can prevent the deleterious effects of B1 receptors in insulin resistance and peripheral inflammation. © 2016 The British Pharmacological Society.

  9. EphrinB1 expression is dysregulated and promotes oncogenic signaling in medulloblastoma.

    PubMed

    McKinney, Nicole; Yuan, Liangping; Zhang, Hongying; Liu, Jingbo; Cho, Yoon-Jae; Rushing, Elisabeth; Schniederjan, Matthew; MacDonald, Tobey J

    2015-01-01

    Eph receptors and ephrin ligands are master regulators of oncogenic signaling required for proliferation, migration, and metastasis. Yet, Eph/ephrin expression and activity in medulloblastoma (MB), the most common malignant brain tumor of childhood, remains poorly defined. We hypothesized that Eph/ephrins are differentially expressed by sonic hedgehog (SHH) and non-SHH MB and that specific members contribute to the aggressive phenotype. Affymetrix gene expression profiling of 29 childhood MB, separated into SHH (N = 11) and non-SHH (N = 18), was performed followed by protein validation of selected Eph/ephrins in another 60 MB and two MB cell lines (DAOY, D556). Functional assays were performed using MB cells overexpressing or deleted for selected ephrins. We found EPHB4 and EFNA4 almost exclusively expressed by SHH MB, whereas EPHA2, EPHA8, EFNA1 and EFNA3 are predominantly expressed by non-SHH MB. The remaining family members, except EFNB1, are ubiquitously expressed by over 70-90 % MB, irrespective of subgroup. EFNB1 is the only member differentially expressed by 28 % of SHH and non-SHH MB. Corresponding protein expression for EphB/ephrinB1 and B2 was validated in MB. Only ephrinB2 was also detected in fetal cerebellum, indicating that EphB/ephrinB1 expression is MB-specific. EphrinB1 immunopositivity localizes to tumor cells within MB with the highest proliferative index. EphrinB1 overexpression promotes EphB activation, alters F-actin distribution and morphology, decreases adhesion, and significantly promotes proliferation. Either silencing or overexpression of ephrinB1 impairs migration. These results indicate that EphrinB1 is uniquely dysregulated in MB and promotes oncogenic responses in MB cells, implicating ephrinB1 as a potential target.

  10. Cyclic Di-GMP Binding by an Assembly ATPase (PilB2) and Control of Type IV Pilin Polymerization in the Gram-Positive Pathogen Clostridium perfringens

    PubMed Central

    Hendrick, William A.; Orr, Mona W.; Murray, Samantha R.; Lee, Vincent T.

    2017-01-01

    ABSTRACT The Gram-positive pathogen Clostridium perfringens possesses type IV pili (TFP), which are extracellular fibers that are polymerized from a pool of pilin monomers in the cytoplasmic membrane. Two proteins that are essential for pilus functions are an assembly ATPase (PilB) and an inner membrane core protein (PilC). Two homologues each of PilB and PilC are present in C. perfringens, called PilB1/PilB2 and PilC1/PilC2, respectively, along with four pilin proteins, PilA1 to PilA4. The gene encoding PilA2, which is considered the major pilin based on previous studies, is immediately downstream of the pilB2 and pilC2 genes. Purified PilB2 had ATPase activity, bound zinc, formed hexamers even in the absence of ATP, and bound the second messenger molecule cyclic di-GMP (c-di-GMP). Circular dichroism spectroscopy of purified PilC2 indicated that it retained its predicted degree of alpha-helical secondary structure. Even though no direct interactions between PilB2 and PilC2 could be detected in vivo or in vitro even in the presence of c-di-GMP, high levels of expression of a diguanylate cyclase from C. perfringens (CPE1788) stimulated polymerization of PilA2 in a PilB2- and PilC2-dependent manner. These results suggest that PilB2 activity is controlled by c-di-GMP levels in vivo but that PilB2-PilC2 interactions are either transitory or of low affinity, in contrast to results reported previously from in vivo studies of the PilB1/PilC1 pair in which PilC1 was needed for polar localization of PilB1. This is the first biochemical characterization of a c-di-GMP-dependent assembly ATPase from a Gram-positive bacterium. IMPORTANCE Type IV pili (TFP) are protein fibers involved in important bacterial functions, including motility, adherence to surfaces and host cells, and natural transformation. All clostridia whose genomes have been sequenced show evidence of the presence of TFP. The genetically tractable species Clostridium perfringens was used to study proteins

  11. Cyclic Di-GMP Binding by an Assembly ATPase (PilB2) and Control of Type IV Pilin Polymerization in the Gram-Positive Pathogen Clostridium perfringens.

    PubMed

    Hendrick, William A; Orr, Mona W; Murray, Samantha R; Lee, Vincent T; Melville, Stephen B

    2017-05-15

    The Gram-positive pathogen Clostridium perfringens possesses type IV pili (TFP), which are extracellular fibers that are polymerized from a pool of pilin monomers in the cytoplasmic membrane. Two proteins that are essential for pilus functions are an assembly ATPase (PilB) and an inner membrane core protein (PilC). Two homologues each of PilB and PilC are present in C. perfringens , called PilB1/PilB2 and PilC1/PilC2, respectively, along with four pilin proteins, PilA1 to PilA4. The gene encoding PilA2, which is considered the major pilin based on previous studies, is immediately downstream of the pilB2 and pilC2 genes. Purified PilB2 had ATPase activity, bound zinc, formed hexamers even in the absence of ATP, and bound the second messenger molecule cyclic di-GMP (c-di-GMP). Circular dichroism spectroscopy of purified PilC2 indicated that it retained its predicted degree of alpha-helical secondary structure. Even though no direct interactions between PilB2 and PilC2 could be detected in vivo or in vitro even in the presence of c-di-GMP, high levels of expression of a diguanylate cyclase from C. perfringens (CPE1788) stimulated polymerization of PilA2 in a PilB2- and PilC2-dependent manner. These results suggest that PilB2 activity is controlled by c-di-GMP levels in vivo but that PilB2-PilC2 interactions are either transitory or of low affinity, in contrast to results reported previously from in vivo studies of the PilB1/PilC1 pair in which PilC1 was needed for polar localization of PilB1. This is the first biochemical characterization of a c-di-GMP-dependent assembly ATPase from a Gram-positive bacterium. IMPORTANCE Type IV pili (TFP) are protein fibers involved in important bacterial functions, including motility, adherence to surfaces and host cells, and natural transformation. All clostridia whose genomes have been sequenced show evidence of the presence of TFP. The genetically tractable species Clostridium perfringens was used to study proteins involved in

  12. B11 NMR in the layered diborides OsB2 and RuB2

    NASA Astrophysics Data System (ADS)

    Suh, B. J.; Zong, X.; Singh, Y.; Niazi, A.; Johnston, D. C.

    2007-10-01

    B11 nuclear magnetic resonance (NMR) measurements have been performed on B11 enriched OsB2 and RuB2 polycrystalline powder samples in an external field of 4.7T and in the temperature range, 4.2KB2 and RuB2 , respectively. The experimental results indicate that a p character dominates the conduction electron wave function at the B site with a negligibly small s character in both compounds.

  13. Mold occurrence and aflatoxin B(1) and fumonisin B(1) determination in corn samples in Venezuela.

    PubMed

    Medina-Martínez, M S; Martínez, A J

    2000-07-01

    Fumonisins are mycotoxins produced mainly by Fusarium moniliforme and Fusarium proliferatum, which have been associated with several animal and human diseases. Aflatoxins are hepatotoxic, mutagenic, and teratogenic metabolites produced by Aspergillus flavus and Aspergillus parasiticus. Both have been reported at high levels in corn. This study was pursued to determine mold, aflatoxin B(1) (AFTB(1)), and fumonisin B(1) (FB(1)) levels in white and yellow corn. Mold levels were determined using potato dextrose agar and identification of the main genus of molds present in corn, AFTB(1) levels by immunoaffinity chromatography, and FB(1) levels by a Bond-Elut SAX cartridge and HPLC. AFTB(1) an

  14. A subset of AID-dependent B-1a cells initiates hypersensitivity and pneumococcal pneumonia resistance.

    PubMed

    Askenase, Phillip W; Bryniarski, Krzysztof; Paliwal, Vipin; Redegeld, Frank; Groot Kormelink, Thomas; Kerfoot, Steven; Hutchinson, Andrew T; van Loveren, Henk; Campos, Regis; Itakura, Atsuko; Majewska-Szczepanik, Monika; Yamamoto, Natsuo; Nazimek, Katarzyn; Szczepanik, Marian; Ptak, Wold

    2015-12-01

    We propose that there is a special B-1a B cell subset ("sB-1a" cells) that mediates linked processes very early after immunization to initiate cutaneous contact sensitivity (CS), delayed-type hypersensitivity (DTH), and immune resistance to pneumococcal pneumonia. Our published data indicate that in CS and DTH, these initiating processes are required for elicitation of the delayed onset and late-occurring classical T cell-mediated responses. sB-1a cells resemble memory B2 cells, as they are stimulated within 1 h of immunization and depend on T helper cytokines-uniquely IL-4 from hepatic iNKT cells--for activation and rapid migration from the peritoneal cavity to the spleen to secrete IgM antibody (Ab) and Ab-derived free light chains (FLCs) by only 1 day after immunization. Unlike conventional B-1a (cB-1a) cell-produced IgM natural Ab, IgM Ab produced by sB-1a cells has high Ag affinity owing to immunoglobulin V-region mutations induced by activation-induced cytidine deaminase (AID). The dominant cB-1a cells are increased in immunized AID-deficient mice but do not mediate initiation, CS, or pneumonia resistance because natural Ab has relatively low Ag affinity because of unmutated germ-line V regions. In CS and DTH, sB-1a IgM Ag affinity is sufficiently high to mediate complement activation for generation of C5a that, together with vasoactive mediators such as TNF-α released by FLC-sensitized mast cells, activate local endothelium for extravascular recruitment of effector T cells. We conclude by discussing the possibility of functional sB-1 cells in humans. © 2015 New York Academy of Sciences.

  15. Lattice Thermal Conductivity from Atomistic Simulations: ZrB2 and HfB2

    NASA Technical Reports Server (NTRS)

    Lawson, John W.; Daw, Murray S.; Bauschlicher, Charles W.

    2012-01-01

    Ultra high temperature ceramics (UHTC) including ZrB2 and HfB2 have a number of properties that make them attractive for applications in extreme environments. One such property is their high thermal conductivity. Computational modeling of these materials will facilitate understanding of fundamental mechanisms, elucidate structure-property relationships, and ultimately accelerate the materials design cycle. Progress in computational modeling of UHTCs however has been limited in part due to the absence of suitable interatomic potentials. Recently, we developed Tersoff style parameterizations of such potentials for both ZrB2 and HfB2 appropriate for atomistic simulations. As an application, Green-Kubo molecular dynamics simulations were performed to evaluate the lattice thermal conductivity for single crystals of ZrB2 and HfB2. The atomic mass difference in these binary compounds leads to oscillations in the time correlation function of the heat current, in contrast to the more typical monotonic decay seen in monoatomic materials such as Silicon, for example. Results at room temperature and at elevated temperatures will be reported.

  16. Effect of the allelic variant of alcohol dehydrogenase ADH1B*2 on ethanol metabolism.

    PubMed

    Kang, Gaeun; Bae, Kyung-Yeol; Kim, Sung-Wan; Kim, Jin; Shin, Hee-Young; Kim, Jae-Min; Shin, Il-Seon; Yoon, Jin-Sang; Kim, Jong-Keun

    2014-06-01

    It has been known that ADH1B*2 allele has a protective effect against the development of alcohol dependence. However, the protection mechanism is still unknown. We investigated whether ADH1B gene polymorphism affects ethanol (EtOH) metabolism. In a parent study, we conducted a randomized crossover trials on 24 healthy male subjects who were selected by genotyping: 12 with ALDH2*1/*1 (active form) and 12 with ALDH2*1/*2 (inactive form). In the present study, the 24 subjects were reclassified into 2 groups of 11 with ADH1B*1/*2 and 13 with ADH1B*2/*2 according to the ADH1B genotypes. Each subject was administered 1 of 3 doses of EtOH (0.25, 0.5, 0.75 g/kg) or a placebo in 4 trials. After the administration of alcohol, blood EtOH and acetaldehyde concentrations were measured 9 times over 4 hours. In the case of EtOH, the area under the concentration-time curve from 0 to 4 hours (AUC0-4 ) and the peak blood concentration of EtOH (Cmax ) in subjects with ADH1B*2/*2 were significantly higher than those in subjects with ADH1B*1/*2 at all 3 dosages before stratifying by ALDH2 genotype. However, after stratifying by ALDH2 genotype, a statistically significant difference between ADH1B*2/*2 and ADH1B*1/*2 was found only at the 0.5 g/kg dosage regardless of ALDH2 genotype. In the case of acetaldehyde, the AUC0-4 and Cmax of acetaldehyde of ADH1B*2/*2 after administration of 0.25 g/kg alcohol and the AUC0-4 of acetaldehyde of ADH1B*2/*2 at 0.5 g/kg were significantly higher than corresponding values of ADH1B*1/*2 only in the group of ALDH2*1/*2. Our findings indicate that the blood EtOH concentrations of ADH1B*2/*2 group are higher than those of ADH1B*1/*2 group regardless of ALDH2 genotype, and the blood acetaldehyde concentrations of ADH1B*2/*2 are also higher than those of ADH1B*1/*2 only in the ALDH2*1/*2 group. To our knowledge, this is the first report to demonstrate the association of ADH1B*2 allele with blood EtOH and acetaldehyde levels in humans, and these results

  17. Vitamin B1 (thiamine) and dementia

    PubMed Central

    Gibson, Gary E.; Hirsch, Joseph A.; Fonzetti, Pasquale; Jordon, Barry D.; Cirio, Rosanna T.; Elder, Jessica

    2016-01-01

    The earliest and perhaps best example of an interaction between nutrition and dementia is related to thiamine (vitamin B1). Throughout the last century, research showed that thiamine deficiency is associated with neurological problems, including cognitive deficits and encephalopathy. Multiple similarities exist between classical thiamine deficiency and Alzheimer’s disease (AD) in that both are associated with cognitive deficits and reductions in brain glucose metabolism. Thiamine-dependent enzymes are critical components of glucose metabolism that are reduced in the brains of AD patients and by thiamine deficiency, and their decline could account for the reduction in glucose metabolism. In preclinical models, reduced thiamine can drive AD-like abnormalities, including memory deficits, plaques, and hyperphosphorylation of tau. Furthermore, excess thiamine diminishes AD-like pathologies. In addition to dietary deficits, drugs, or other manipulations that interfere with thiamine absorption can cause thiamine deficiency. Elucidating the reasons why the brains of AD patients are functionally thiamine deficient and determining the effects of thiamine restoration may provide critical information to help treat patients with AD. PMID:26971083

  18. Adsorption of aflatoxin B1 on montmorillonite.

    PubMed

    Desheng, Q; Fan, L; Yanhu, Y; Niya, Z

    2005-06-01

    The isothermal adsorption and the adsorptive mechanism of aflatoxin B1 (AFB1) on calcium montmorillonite (Mont) were studied in vitro trials. The maximum amounts of AFB1 on Mont in aqueous solution at 2 and pH 8 were 613.5 and 628.9 microg of AFB1 /g of Mont, respectively. The structure of AFB1-Mont was measured by x-ray diffraction and infrared absorption spectrum. The results suggested that the mechanism of AFB1 on Mont was AFB1 sorbed onto the edge of Mont by a double hydrogen bond, and AFB1 molecules did not penetrate into the interlayer area of Mont. The Mont, when added to the diet of broiler chicken at 0.5%, significantly diminished the adverse effects of feeding 200 microg of AFB1 /kg of feed. And the concentrations of Ca, P, Cu, Fe, Zn in the broiler bones were not affected by AFB1 and Mont, but the concentrations of Mn, Pb, and F were decreased by Mont.

  19. Effects of prolonged oral administration of fumonisin B1 and aflatoxin B1 in rats.

    PubMed

    Pozzi, C R; Corrêa, B; Xavier, J G; Direito, G M; Orsi, R B; Matarazzo, S V

    2001-01-01

    The effects of prolonged oral administration (21 days) of fumonisin B1 (FB1) and aflatoxin B1 (AFB1) were evaluated on male Wistar rats. The animals were housed in individual metabolic cages and submitted to the following treatments: 1-0 microg AFB1 + 0 mg FB1/100g bw.; 2-72 microg AFB1+ 0 mg FB1/100 g bw; 3-0 microg AFB1 + 0.5 mg FB1 g bw; 4-0 microg AFB1 + 1.5 mg FB1/100 g bw; 5-72 microg AFB1 + 0.5 mg FB1/100g bw; 6-72 microgAFB1 + 1.5 mg FB1/100g bw. On day 21, the rats were sacrificed for evaluation. The results showed that treated animals presented differences in body weight and absolute/relative weights of liver and kidney as well as altered hepatic function and cholesterol blood levels. Rats fed with the greatest doses of AFB1 and FB1 gained less weight (2.79 g/day) at the end of the experimental period; their blood concentrations of liver enzymes aspartate aminotransferase (AST) and alkaline phosphatase (AP) were above control levels (130.35 micro/l and 471.00 micro/l, respectively). Blood cholesterol increased in the groups treated with the highest dose of FB1 or FB1 associated with AFB1. Histopathology revealed the occurrence of apoptosis in the liver of rats exposed to FB1. The association of aflatoxin B1 with fumonisin B1 at higher dose probably potentiated the effects of the higher dose of fumonisin B1 acting singly.

  20. B-1a transitional cells are phenotypically distinct and are lacking in mice deficient in IκBNS

    PubMed Central

    Pedersen, Gabriel K.; Àdori, Monika; Khoenkhoen, Sharesta; Dosenovic, Pia; Beutler, Bruce; Karlsson Hedestam, Gunilla B.

    2014-01-01

    B-1 cells mediate early protection against infection by responding to T cell-independent (TI) antigens found on the surface of various pathogens. Mice with impaired expression of the atypical IκB protein IκBNS have markedly reduced frequencies of B-1 cells. We used a mouse strain with dysfunctional IκBNS derived from an N-ethyl-N-nitrosourea (ENU) screen, named bumble, to investigate the point in the development of B-1 cells where IκBNS is required. The presence of wild-type (wt) peritoneal cells in mixed wt/bumble chimeras did not rescue the development of bumble B-1 cells, but wt peritoneal cells transferred to bumble mice restored natural IgM levels and response to TI antigens. The bumble and wt mice displayed similar levels of fetal liver B-1 progenitors and splenic neonatal transitional B (TrB) cells, both of which were previously shown to give rise to B-1 cells. Interestingly, we found that a subset of wt neonatal TrB cells expressed common B-1a markers (TrB-1a) and that this cell population was absent in the bumble neonatal spleen. Sorted TrB-1a (CD93+IgM+CD5+) cells exclusively generated B-1a cells when adoptively transferred, whereas sorted CD93+IgM+CD5− cells gave rise to B-2 cells and, to a lesser extent, B-1b and B-1a cells. This study identifies a phenotypically distinct splenic population of TrB-1a cells and establishes that the development of B-1a cells is blocked before this stage in the absence of IκBNS. PMID:25228759

  1. Portal hypertensive response to bradykinin in inflamed or cirrhotic rat livers is mediated by B2-type receptors.

    PubMed

    Loureiro-Silva, M R; Molina, H M; Borges, D R

    2001-01-01

    We have shown that the portal hypertensive response to bradykinin in normal rats is mediated by B2 receptors. By using isolated and exsanguinated rat liver perfusion, we studied the portal hypertensive response to bradykinin or des-Arg9-bradykinin (B1 agonist) in inflamed or cirrhotic rat livers. Livers were perfused with bovine serum albumin Krebs-Henseleit buffer (pH 7.4; 37 degrees C) at a constant flow rate, in the absence or presence of des-Arg9[Leu8]-bradykinin or HOE 140 (B1 and B2 receptor antagonists, respectively). Bradykinin (140 nmol) or des-Arg9-bradykinin was injected as a bolus via the afferent route to the liver. Basal perfusion pressure in liver-cirrhotic rats was higher than in normal rats. In normal, inflamed, or liver-cirrhotic rats, the presence of the B1 antagonist did not change the portal hypertensive response to bradykinin, while the B2 antagonist abolished this response. A 140-nmol dose of des-Arg9-bradykinin did not change the perfusion pressure; 700 nmol of this B1 agonist produced an insignificant perfusion pressure increase. The perfusion pressure increase induced by bradykinin in cirrhotic livers was lower than in normal livers. The portal hypertensive response to bradykinin in inflamed or cirrhotic rat livers is mediated by B2 receptors, but not B1 receptors, and there is a contracting hyporeactivity to bradykinin in cirrhotic rat livers.

  2. The Effects of Bisphenol A (BPA) on ErbB2 Positive Breast Cancer

    DTIC Science & Technology

    2010-11-01

    observed in the protein expression of erbB2 between any of the treatment groups (Figure 1). This indicates that the accelerated carcinogenesis...mice, it was still capable of significantly increasing erbB3 activation as compared to control (pɘ.05). The protein expression of erbB1/EGFR was...found a dose-dependent increase in protein expression. Accordingly, BPA 2500 exhibited a significant increase in the expression of amphiregulin as

  3. ALDH1B1 as a Modulator of Pancreatic Adenocarcinoma

    PubMed Central

    Singh, Surendra; Arcaroli, John J.; Orlicky, David J.; Chen, Ying; Messersmith, Wells A.; Bagby, Stacey; Purkey, Alicia; Quackenbush, Kevin S.; Thompson, David C.; Vasiliou, Vasilis

    2016-01-01

    Objectives The aim of the current study was to examine expression and the role, if any, of ALDH1B1 in pancreatic adenocarcinoma. Methods A tissue microarray of 61 pancreatic cancer patients were evaluated for protein expression of ALDH1B1 by immunohistochemistry. ALDH1B1 siRNA was used to assess the contribution of ALDH1B1 on proliferation of pancreatic cancer cells. Results In normal human pancreas, ALDH1B1 is abundantly expressed in glandular cells, but sparsely in the ducts (ALDH1B1 immunopositivity = 16.7 ± 1.7). In pancreatic ductal carcinoma, we found high ALDH1B1 expression in ductal cancerous tissues (ALDH1B1 immunopositivity = 197.2 ± 29.4). Analysis of ALDH1B1 expression in a human pancreatic adenocarcinoma tissue microarray showed the greatest expression in tumors that were more invasive. A variation in ALDH1B1 expression was also observed in 16 human pancreatic cancer cell lines. Knockdown of ALDH1B1 caused a 35% reduction in cell growth in the high ALDH1B1-expressing cell lines. Conclusion Our data show for the first time that ALDH1B1 is expressed at very high levels in human pancreatic cancer and it contributes to proliferation in these tumor cells. These data suggest a potential modulatory role for ALDH1B1 in pancreatic cancer. PMID:26566217

  4. A monoclonal antibody targeting ErbB2 domain III inhibits ErbB2 signaling and suppresses the growth of ErbB2-overexpressing breast tumors.

    PubMed

    Meng, Y; Zheng, L; Yang, Y; Wang, H; Dong, J; Wang, C; Zhang, Y; Yu, X; Wang, L; Xia, T; Zhang, D; Guo, Y; Li, B

    2016-03-21

    The anti-ErbB2 antibodies trastuzumab and pertuzumab in combination have recently been approved for the treatment of patients with ErbB2-positive metastatic breast cancer. Pertuzumab, which binds to ErbB2 near the center of domain II, and trastuzumab, which binds to the juxtamembrane region of ErbB2 domain IV, directly interfere with domain II- and domain IV-mediated heterodimerization contacts, respectively. In this study, we report a novel anti-ErbB2 antibody, 3E10, which binds to an epitope in domain III that appears to be located opposite to the dimerization interfaces in domain II and domain IV of ErbB2. Our data show that the 3E10 antibody inhibits ErbB2 heterodimerization via a mechanism that strikingly differs from trastuzumab and pertuzumab. It could be speculated that the 3E10 antibody may affect ErbB2 heterodimerization by causing major conformational changes of ErbB2. Furthermore, 3E10 provides synergistic inhibition of ErbB2 heterodimerization and signaling in combination with either trastuzumab or pertuzumab. The combination of these three anti-ErbB2 antibodies that have complementary mechanisms of action appears to be an extremely potent ErbB2 heterodimerization blocker. Compared with trastuzumab plus pertuzumab, the combination of trastuzumab, pertuzumab and 3E10 provides a more potent blockade of ErbB2 signaling. Consistent with this, trastuzumab plus pertuzumab plus 3E10 results in greater in vitro and in vivo antitumor activity in ErbB2-overexpressing breast tumor models, suggesting its potential use for treating ErbB2-overexpressing breast cancer.

  5. A monoclonal antibody targeting ErbB2 domain III inhibits ErbB2 signaling and suppresses the growth of ErbB2-overexpressing breast tumors

    PubMed Central

    Meng, Y; Zheng, L; Yang, Y; Wang, H; Dong, J; Wang, C; Zhang, Y; Yu, X; Wang, L; Xia, T; Zhang, D; Guo, Y; Li, B

    2016-01-01

    The anti-ErbB2 antibodies trastuzumab and pertuzumab in combination have recently been approved for the treatment of patients with ErbB2-positive metastatic breast cancer. Pertuzumab, which binds to ErbB2 near the center of domain II, and trastuzumab, which binds to the juxtamembrane region of ErbB2 domain IV, directly interfere with domain II- and domain IV-mediated heterodimerization contacts, respectively. In this study, we report a novel anti-ErbB2 antibody, 3E10, which binds to an epitope in domain III that appears to be located opposite to the dimerization interfaces in domain II and domain IV of ErbB2. Our data show that the 3E10 antibody inhibits ErbB2 heterodimerization via a mechanism that strikingly differs from trastuzumab and pertuzumab. It could be speculated that the 3E10 antibody may affect ErbB2 heterodimerization by causing major conformational changes of ErbB2. Furthermore, 3E10 provides synergistic inhibition of ErbB2 heterodimerization and signaling in combination with either trastuzumab or pertuzumab. The combination of these three anti-ErbB2 antibodies that have complementary mechanisms of action appears to be an extremely potent ErbB2 heterodimerization blocker. Compared with trastuzumab plus pertuzumab, the combination of trastuzumab, pertuzumab and 3E10 provides a more potent blockade of ErbB2 signaling. Consistent with this, trastuzumab plus pertuzumab plus 3E10 results in greater in vitro and in vivo antitumor activity in ErbB2-overexpressing breast tumor models, suggesting its potential use for treating ErbB2-overexpressing breast cancer. PMID:26999718

  6. Controlled indole-3-acetaldoxime production through ethanol-induced expression of CYP79B2.

    PubMed

    Mikkelsen, Michael Dalgaard; Fuller, Victoria L; Hansen, Bjarne Gram; Nafisi, Majse; Olsen, Carl Erik; Nielsen, Henrik Bjørn; Halkier, Barbara Ann

    2009-05-01

    Indole-3-acetaldoxime (IAOx) is a key branching point between primary and secondary metabolism. IAOx serves as an intermediate in the biosynthesis of indole glucosinolates (I-GLSs), camalexin and the plant hormone indole-3-acetic acid (IAA). The cytochrome P450s CYP79B2 and CYP79B3 catalyze the conversion of tryptophan to IAOx. CYP83B1 channels IAOx into I-GLS biosynthesis, CYP71A13 channels IAOx into camalexin biosynthesis, whereas the IAOx-metabolizing enzyme in IAA biosynthesis is not known. In this report, we demonstrate controlled production of I-GLSs by introducing an ethanol (EtOH)-inducible CYP79B2 construct into double (cyp79b2 cyp79b3) or triple (cyp79b2 cyp79b3 cyp83b1) mutant lines. We show EtOH-dependent induction of camalexin and identify a number of candidate IAA homeostasis- or defense-related genes by clustered microarray analysis. The transgenic mutant lines are thus promising tools for elucidating the interplay between primary and secondary metabolism.

  7. Cognitive and cerebrovascular improvements following kinin B1 receptor blockade in Alzheimer’s disease mice

    PubMed Central

    2013-01-01

    Background Recent evidence suggests that the inducible kinin B1 receptor (B1R) contributes to pathogenic neuroinflammation induced by amyloid-beta (Aβ) peptide. The present study aims at identifying the cellular distribution and potentially detrimental role of B1R on cognitive and cerebrovascular functions in a mouse model of Alzheimer’s disease (AD). Methods Transgenic mice overexpressing a mutated form of the human amyloid precursor protein (APPSwe,Ind, line J20) were treated with a selective and brain penetrant B1R antagonist (SSR240612, 10 mg/kg/day for 5 or 10 weeks) or vehicle. The impact of B1R blockade was measured on i) spatial learning and memory performance in the Morris water maze, ii) cerebral blood flow (CBF) responses to sensory stimulation using laser Doppler flowmetry, and iii) reactivity of isolated cerebral arteries using online videomicroscopy. Aβ burden was quantified by ELISA and immunostaining, while other AD landmarks were measured by western blot and immunohistochemistry. Results B1R protein levels were increased in APP mouse hippocampus and, prominently, in reactive astrocytes surrounding Aβ plaques. In APP mice, B1R antagonism with SSR240612 improved spatial learning, memory and normalized protein levels of the memory-related early gene Egr-1 in the dentate gyrus of the hippocampus. B1R antagonism restored sensory-evoked CBF responses, endothelium-dependent dilations, and normalized cerebrovascular protein levels of endothelial nitric oxide synthase and B2R. In addition, SSR240612 reduced (approximately 50%) microglial, but not astroglial, activation, brain levels of soluble Aβ1-42, diffuse and dense-core Aβ plaques, and it increased protein levels of the Aβ brain efflux transporter lipoprotein receptor-related protein-1 in cerebral microvessels. Conclusion These findings show a selective upregulation of astroglial B1R in the APP mouse brain, and the capacity of the B1R antagonist to abrogate amyloidosis, cerebrovascular and

  8. A Hard(y) Look at B-1 Cell Development and Function.

    PubMed

    Baumgarth, Nicole

    2017-11-15

    A small population of B cells exists in lymphoid tissues and body cavities of mice that is distinct in development, phenotype, and function from the majority (B-2) B cell population. This population, originally termed "Ly-1" and now "B-1," has received renewed interest as an innate-like B cell population of fetal-derived hematopoiesis, responsible for natural Ab production and rapid immune responses. Molecular analyses have begun to define fetal and adult hematopoiesis, while cell-fate mapping studies have revealed complex developmental origins of B-1 cells. Together the studies provide a more detailed understanding of B-1 cell regulation and function. This review outlines studies that defined B-1 cells as natural Ab- and cytokine-producing B cells of fetal origin, with a focus on work conducted by R.R. Hardy, an early pioneer and codiscoverer of B-1 cells, whose seminal contributions enhanced our understanding of this enigmatic B cell population. Copyright © 2017 by The American Association of Immunologists, Inc.

  9. Aging Converts Innate B1a Cells into Potent CD8+ T Cell Inducers

    PubMed Central

    Lee-Chang, Catalina; Bodogai, Monica; Moritoh, Kanako; Chen, Xin; Wersto, Robert; Sen, Ranjan; Young, Howard A.; Croft, Michael; Ferrucci, Luigi; Biragyn, Arya

    2016-01-01

    B-cell dysregulation in aging is thought to mostly occur in conventional B2 cells without affecting innate B1 cells. Elderly humans and mice also accumulate 4-1BBL+ MHC class-IHi CD86Hi B cells of unknown origin. Here we report that these cells, termed 4BL cells, are activated murine and possibly human B1a cells. The activation is mediated by aging human monocytes and murine peritoneal macrophages. The 4BL cells induce expression of 4-1BBL and IFNγR1 on B1a cells resulting in subsequent up regulation of membrane TNFα (mTNFα) and CD86. As a result, B1a cells induce expression of granzyme B in CD8+T cells by targeting TNFR2 via mTNFα while providing co-stimulation with CD86. Thus, for the first time, these results indicate that aging affects the function of B1a cells. Upon aging, these cells lose their tumor-supporting activity and become inducers of potentially antitumor and autoimmune CD8+T cells. PMID:26983789

  10. Aging Converts Innate B1a Cells into Potent CD8+ T Cell Inducers.

    PubMed

    Lee-Chang, Catalina; Bodogai, Monica; Moritoh, Kanako; Chen, Xin; Wersto, Robert; Sen, Ranjan; Young, Howard A; Croft, Michael; Ferrucci, Luigi; Biragyn, Arya

    2016-04-15

    B cell dysregulation in aging is thought to mostly occur in conventional B2 cells without affecting innate B1 cells. Elderly humans and mice also accumulate 4-1BBL(+)MHC class-I(Hi)CD86(Hi)B cells of unknown origin. In this article, we report that these cells, termed 4BL cells, are activated murine and possibly human B1a cells. The activation is mediated by aging human monocytes and murine peritoneal macrophages. They induce expression and activation of 4-1BBL and IFN-γR1 on B1a cells to subsequently upregulate membrane TNF-α and CD86. As a result, activated B1a/4BL cells induce expression of granzyme B in CD8(+)T cells by targeting TNFR2 via membrane TNF-α and providing costimulation with CD86. Thus, for the first time, to our knowledge, these results indicate that aging affects the function of B1a cells. Upon aging, these cells lose their tumor-supporting activity and become inducers of potentially antitumor and autoimmune CD8(+)T cells. Copyright © 2016 by The American Association of Immunologists, Inc.

  11. 77 FR 14767 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-13

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  13. 40 CFR Figure B-1 to Subpart B of... - Example

    Code of Federal Regulations, 2013 CFR

    2013-07-01

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    Code of Federal Regulations, 2014 CFR

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    Code of Federal Regulations, 2012 CFR

    2012-07-01

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    Federal Register 2010, 2011, 2012, 2013, 2014

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    Federal Register 2010, 2011, 2012, 2013, 2014

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    Federal Register 2010, 2011, 2012, 2013, 2014

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    Federal Register 2010, 2011, 2012, 2013, 2014

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    Federal Register 2010, 2011, 2012, 2013, 2014

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    Code of Federal Regulations, 2010 CFR

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    Federal Register 2010, 2011, 2012, 2013, 2014

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  6. 26 CFR 1.267(b)-1 - Relationships.

    Code of Federal Regulations, 2013 CFR

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  7. 26 CFR 1.267(b)-1 - Relationships.

    Code of Federal Regulations, 2011 CFR

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  8. 26 CFR 1.267(b)-1 - Relationships.

    Code of Federal Regulations, 2014 CFR

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  9. 26 CFR 1.267(b)-1 - Relationships.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 3 2012-04-01 2012-04-01 false Relationships. 1.267(b)-1 Section 1.267(b)-1...) INCOME TAXES (CONTINUED) Items Not Deductible § 1.267(b)-1 Relationships. (a) In general. (1) The persons... partnership separately. Therefore, if the other person and a partner are within any one of the relationships...

  10. 26 CFR 1.672(b)-1 - Nonadverse party.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 8 2011-04-01 2011-04-01 false Nonadverse party. 1.672(b)-1 Section 1.672(b)-1...) INCOME TAXES (CONTINUED) Grantors and Others Treated As Substantial Owners § 1.672(b)-1 Nonadverse party. A nonadverse party is any person who is not an adverse party. ...

  11. 26 CFR 1.672(b)-1 - Nonadverse party.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 8 2010-04-01 2010-04-01 false Nonadverse party. 1.672(b)-1 Section 1.672(b)-1...) INCOME TAXES Grantors and Others Treated As Substantial Owners § 1.672(b)-1 Nonadverse party. A nonadverse party is any person who is not an adverse party. ...

  12. 49 CFR 178.33b-1 - Compliance.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 3 2011-10-01 2011-10-01 false Compliance. 178.33b-1 Section 178.33b-1 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY... Containers, and Linings § 178.33b-1 Compliance. (a) Required in all details. (b) ...

  13. The immunoglobulin heavy chain 3' regulatory region superenhancer controls mouse B1 B-cell fate and late VDJ repertoire diversity.

    PubMed

    Ghazzaui, Nour; Issaoui, Hussein; Saintamand, Alexis; Oblet, Christelle; Carrion, Claire; Denizot, Yves

    2018-02-13

    The immunoglobulin heavy chain (IgH) 3' regulatory region (3'RR) superenhancer controls B2 B-cell IgH transcription and cell fate at the mature stage but not early repertoire diversity. B1 B cells represent a small percentage of total B cells differing from B2 B cells by several points such as precursors, development, functions, and regulation. B1 B cells act at the steady state to maintain homeostasis in the organism and during the earliest phases of an immune response, setting them at the interface between innate and acquired immunity. We investigated the role of the 3'RR superenhancer on B1 B-cell fate. Similar to B2 B cells, the 3'RR controls μ transcription and cell fate in B1 B cells. In contrast to B2 B cells, 3'RR deletion affects B1 B-cell late repertoire diversity. Thus, differences exist for B1 and B2 B-cell 3'RR control during B-cell maturation. For the first time, these results highlight the contribution of the 3'RR superenhancer at this interface between innate and acquired immunity. © 2018 by The American Society of Hematology.

  14. The immunoglobulin heavy chain 3′ regulatory region superenhancer controls mouse B1 B-cell fate and late VDJ repertoire diversity

    PubMed Central

    Ghazzaui, Nour; Issaoui, Hussein; Saintamand, Alexis; Oblet, Christelle; Carrion, Claire

    2018-01-01

    The immunoglobulin heavy chain (IgH) 3′ regulatory region (3′RR) superenhancer controls B2 B-cell IgH transcription and cell fate at the mature stage but not early repertoire diversity. B1 B cells represent a small percentage of total B cells differing from B2 B cells by several points such as precursors, development, functions, and regulation. B1 B cells act at the steady state to maintain homeostasis in the organism and during the earliest phases of an immune response, setting them at the interface between innate and acquired immunity. We investigated the role of the 3′RR superenhancer on B1 B-cell fate. Similar to B2 B cells, the 3′RR controls μ transcription and cell fate in B1 B cells. In contrast to B2 B cells, 3′RR deletion affects B1 B-cell late repertoire diversity. Thus, differences exist for B1 and B2 B-cell 3′RR control during B-cell maturation. For the first time, these results highlight the contribution of the 3′RR superenhancer at this interface between innate and acquired immunity. PMID:29437640

  15. EphrinB2 signaling in osteoblasts promotes bone mineralization by preventing apoptosis.

    PubMed

    Tonna, Stephen; Takyar, Farzin M; Vrahnas, Christina; Crimeen-Irwin, Blessing; Ho, Patricia W M; Poulton, Ingrid J; Brennan, Holly J; McGregor, Narelle E; Allan, Elizabeth H; Nguyen, Huynh; Forwood, Mark R; Tatarczuch, Liliana; Mackie, Eleanor J; Martin, T John; Sims, Natalie A

    2014-10-01

    Cells that form bone (osteoblasts) express both ephrinB2 and EphB4, and previous work has shown that pharmacological inhibition of the ephrinB2/EphB4 interaction impairs osteoblast differentiation in vitro and in vivo. The purpose of this study was to determine the role of ephrinB2 signaling in the osteoblast lineage in the process of bone formation. Cultured osteoblasts from mice with osteoblast-specific ablation of ephrinB2 showed delayed expression of osteoblast differentiation markers, a finding that was reproduced by ephrinB2, but not EphB4, RNA interference. Microcomputed tomography, histomorphometry, and mechanical testing of the mice lacking ephrinB2 in osteoblasts revealed a 2-fold delay in bone mineralization, a significant reduction in bone stiffness, and a 50% reduction in osteoblast differentiation induced by anabolic parathyroid hormone (PTH) treatment, compared to littermate sex- and age-matched controls. These defects were associated with significantly lower mRNA levels of late osteoblast differentiation markers and greater levels of osteoblast and osteocyte apoptosis, indicated by TUNEL staining and transmission electron microscopy of bone samples, and a 2-fold increase in annexin V staining and 7-fold increase in caspase 8 activation in cultured ephrinB2 deficient osteoblasts. We conclude that osteoblast differentiation and bone strength are maintained by antiapoptotic actions of ephrinB2 signaling within the osteoblast lineage. © FASEB.

  16. VirB1* Promotes T-Pilus Formation in the vir-Type IV Secretion System of Agrobacterium tumefaciens▿ †

    PubMed Central

    Zupan, John; Hackworth, Cheryl A.; Aguilar, Julieta; Ward, Doyle; Zambryski, Patricia

    2007-01-01

    The vir-type IV secretion system of Agrobacterium is assembled from 12 proteins encoded by the virB operon and virD4. VirB1 is one of the least-studied proteins encoded by the virB operon. Its N terminus is a lytic transglycosylase. The C-terminal third of the protein, VirB1*, is cleaved from VirB1 and secreted to the outside of the bacterial cell, suggesting an additional function. We show that both nopaline and octopine strains produce abundant amounts of VirB1* and perform detailed studies on nopaline VirB1*. Both domains are required for wild-type virulence. We show here that the nopaline type VirB1* is essential for the formation of the T pilus, a subassembly of the vir-T4SS composed of processed and cyclized VirB2 (major subunit) and VirB5 (minor subunit). A nopaline virB1 deletion strain does not produce T pili. Complementation with full-length VirB1 or C-terminal VirB1*, but not the N-terminal lytic transglycosylase domain, restores T pili containing VirB2 and VirB5. T-pilus preparations also contain extracellular VirB1*. Protein-protein interactions between VirB1* and VirB2 and VirB5 were detected in the yeast two-hybrid assay. We propose that VirB1 is a bifunctional protein required for virT4SS assembly. The N-terminal lytic transglycosylase domain provides localized lysis of the peptidoglycan cell wall to allow insertion of the T4SS. The C-terminal VirB1* promotes T-pilus assembly through protein-protein interactions with T-pilus subunits. PMID:17631630

  17. Caenorhabditis elegans Semi-Automated Liquid Screen Reveals a Specialized Role for the Chemotaxis Gene cheB2 in Pseudomonas aeruginosa Virulence

    PubMed Central

    Garvis, Steven; Munder, Antje; Ball, Geneviève; de Bentzmann, Sophie; Wiehlmann, Lutz; Ewbank, Jonathan J.; Tümmler, Burkhard; Filloux, Alain

    2009-01-01

    Pseudomonas aeruginosa is an opportunistic human pathogen that causes infections in a variety of animal and plant hosts. Caenorhabditis elegans is a simple model with which one can identify bacterial virulence genes. Previous studies with C. elegans have shown that depending on the growth medium, P. aeruginosa provokes different pathologies: slow or fast killing, lethal paralysis and red death. In this study, we developed a high-throughput semi-automated liquid-based assay such that an entire genome can readily be scanned for virulence genes in a short time period. We screened a 2,200-member STM mutant library generated in a cystic fibrosis airway P. aeruginosa isolate, TBCF10839. Twelve mutants were isolated each showing at least 70% attenuation in C. elegans killing. The selected mutants had insertions in regulatory genes, such as a histidine kinase sensor of two-component systems and a member of the AraC family, or in genes involved in adherence or chemotaxis. One mutant had an insertion in a cheB gene homologue, encoding a methylesterase involved in chemotaxis (CheB2). The cheB2 mutant was tested in a murine lung infection model and found to have a highly attenuated virulence. The cheB2 gene is part of the chemotactic gene cluster II, which was shown to be required for an optimal mobility in vitro. In P. aeruginosa, the main player in chemotaxis and mobility is the chemotactic gene cluster I, including cheB1. We show that, in contrast to the cheB2 mutant, a cheB1 mutant is not attenuated for virulence in C. elegans whereas in vitro motility and chemotaxis are severely impaired. We conclude that the virulence defect of the cheB2 mutant is not linked with a global motility defect but that instead the cheB2 gene is involved in a specific chemotactic response, which takes place during infection and is required for P. aeruginosa pathogenicity. PMID:19662168

  18. Caenorhabditis elegans semi-automated liquid screen reveals a specialized role for the chemotaxis gene cheB2 in Pseudomonas aeruginosa virulence.

    PubMed

    Garvis, Steven; Munder, Antje; Ball, Geneviève; de Bentzmann, Sophie; Wiehlmann, Lutz; Ewbank, Jonathan J; Tümmler, Burkhard; Filloux, Alain

    2009-08-01

    Pseudomonas aeruginosa is an opportunistic human pathogen that causes infections in a variety of animal and plant hosts. Caenorhabditis elegans is a simple model with which one can identify bacterial virulence genes. Previous studies with C. elegans have shown that depending on the growth medium, P. aeruginosa provokes different pathologies: slow or fast killing, lethal paralysis and red death. In this study, we developed a high-throughput semi-automated liquid-based assay such that an entire genome can readily be scanned for virulence genes in a short time period. We screened a 2,200-member STM mutant library generated in a cystic fibrosis airway P. aeruginosa isolate, TBCF10839. Twelve mutants were isolated each showing at least 70% attenuation in C. elegans killing. The selected mutants had insertions in regulatory genes, such as a histidine kinase sensor of two-component systems and a member of the AraC family, or in genes involved in adherence or chemotaxis. One mutant had an insertion in a cheB gene homologue, encoding a methylesterase involved in chemotaxis (CheB2). The cheB2 mutant was tested in a murine lung infection model and found to have a highly attenuated virulence. The cheB2 gene is part of the chemotactic gene cluster II, which was shown to be required for an optimal mobility in vitro. In P. aeruginosa, the main player in chemotaxis and mobility is the chemotactic gene cluster I, including cheB1. We show that, in contrast to the cheB2 mutant, a cheB1 mutant is not attenuated for virulence in C. elegans whereas in vitro motility and chemotaxis are severely impaired. We conclude that the virulence defect of the cheB2 mutant is not linked with a global motility defect but that instead the cheB2 gene is involved in a specific chemotactic response, which takes place during infection and is required for P. aeruginosa pathogenicity.

  19. Effects of oral administration of aflatoxin B1 and fumonisin B1 in rabbits (Oryctolagus cuniculus).

    PubMed

    Orsi, R B; Oliveira, C A F; Dilkin, P; Xavier, J G; Direito, G M; Corrêa, B

    2007-12-15

    The effects of prolonged oral administration (21 days) of fumonisin B(1) (FB(1)) and aflatoxin B(1) (AFB(1)) were studied in male New Zealand rabbits by clinical, pathological, biochemical and sphingolipid analyses. Twenty-four animals were randomly divided into the following four experimental groups: (A) 0 mg FB(1)+0 microg AFB(1)/(kg body weight(bw)day) (control); (B) 0 mg FB(1)+30 microg AFB(1)/(kg bw day); (C) 1.5 mg FB(1)/(kg bw day)+30 microg AFB(1)/(kg bw day); (D) 1.5 mg FB(1)/(kg bw day)+0 microg AFB(1). Animals from group B and principally from group C presented clinical signs of intoxication. Rabbits from group C presented a lower body weight gain than controls. Differences were observed between intoxicated rabbits and controls with respect to absolute and relative liver and kidney weight, hepatic function, serum urea and creatinine levels and Sa/So ratio. The most frequent hepatic and renal injuries were vacuolar degeneration of the liver and kidney as shown by the histopathological and serum biochemical results. Combined administration of AFB(1) and FB(1) resulted in synergistic toxic effects both in the liver and in the kidney, but hepatic injuries were more marked.

  20. Electronic Commerce in Tourism in China: B2B or B2C?

    NASA Astrophysics Data System (ADS)

    Li, Hongxiu; Suomi, Reima

    E-commerce has significantly changed the distribution channels of travel products in the world including China. Online channels are growing important in travel service distribution. In China tourism industry has been developed rapidly with the economic development, more and more international travel service providers are trying to expand their Chinese market through the Internet. This paper sheds lights on the e-commerce development models in China for international travel service providers. It explores the current e-tourism in China from the three different participants in the value chain in tourism industry - consumer, travel agent and travel service provider. The paper also identifies the barriers in B2C arena in international outbound travel market, and discusses the possible approaches for international travel service providers to develop their e-commerce in the huge Chinese market. The results in this study reveal that international travel service providers should focus on B2B model to expand their electronic market in China. B2C development in tourism largely depends on the change of Chinese customers' behavior and the change of international tourism regulations. The findings of the study are expected to assist international travel service providers to understand current e-tourism in China and to support their planning for future e-commerce development in China.

  1. Progenitor B-1 B-cell acute lymphoblastic leukemia is associated with collaborative mutations in 3 critical pathways

    PubMed Central

    Gough, Sheryl M.; Goldberg, Liat; Pineda, Marbin; Walker, Robert L.; Zhu, Yuelin J.; Bilke, Sven; Chung, Yang Jo; Dufraine, Joseph; Kundu, Subhadip; Jacoby, Elad; Fry, Terry J.; Fischer, Susanna; Panzer-Grümayer, Renate; Meltzer, Paul S.

    2017-01-01

    B-1 and B-2 lymphocytes are derived from distinct developmental pathways and represent layered arms of the innate and adaptive immune systems, respectively. In contrast to a majority of murine B-cell malignancies, which stain positive with the B220 antibody, we discovered a novel form of B-cell leukemia in NUP98-PHF23 (NP23) transgenic mice. The immunophenotype (Lin− B220− CD19+ AA4.1+) was identical to that of progenitor (pro) B-1 cells, and VH gene usage was skewed toward 3′ V regions, similar to murine fetal liver B cells. Moreover, the gene expression profile of these leukemias was most similar to that of fetal liver pro-B fraction BC, a known source of B-1 B cells, further supporting a pro–B-1 origin of these leukemias. The NP23 pro–B-1 acute lymphoblastic leukemias (ALLs) acquired spontaneous mutations in both Bcor and Janus kinase (Jak) pathway (Jak1/2/3 and Stat5a) genes, supporting a hypothesis that mutations in 3 critical pathways (stem-cell self-renewal, B-cell differentiation, and cytokine signaling) collaborate to induce B-cell precursor (BCP) ALL. Finally, the thymic stromal lymphopoietin (Tslp) cytokine is required for murine B-1 development, and chromosomal rearrangements resulting in overexpression of the TSLP receptor (CRLF2) are present in some patients with high-risk BCP-ALL (referred to as CRLF2r ALL). Gene expression profiles of NP23 pro–B-1 ALL were more similar to that of CRLF2r ALL than non-CRLF2r ALL, and analysis of VH gene usage from patients with CRLF2r ALL demonstrated preferential usage of VH regions used by human B-1 B cells, leading to the suggestion that this subset of patients with BCP-ALL has a malignancy of B-1, rather than B-2, B-cell origin. PMID:29296821

  2. Tunneling in a linear B2H6-HCl dimer

    NASA Astrophysics Data System (ADS)

    Chuang, Carl; Klots, T. D.; Ruoff, R. S.; Emilsson, Tryggvi; Gutowsky, H. S.

    1991-08-01

    Rotational spectra have been observed for eight isotopic species of the diborane-HCl complex with a Balle-Flygare, pulsed nozzle, Fourier transform microwave spectrometer. The dimer has a linear, or at most slightly bent B-BṡṡṡH/DCl equilibrium structure with the H/D end of the HCl attracted symmetrically to a terminal BH2 group of the diborane. Three B2H6-HCl species homonuclear in the boron were observed to tunnel while those with 10B11BH6 or DCl did not. The tunneling splits each rotational transition into two components of comparable intensity, separated by several MHz depending on J and K. The a-dipole transitions are characteristic of a prolate, very near symmetric top; only K=0 and ±1 transitions were found. Rotational constants are reported for all species. The B¯, DJ, H, (B-C), and DJK constants determined for 11B2H6-H35Cl are for the A1 tunneling state 1273.364(1) MHz, 5.56(5) kHz, 1.0(8) Hz, 5.3(2) MHz, and -2.1(3) MHz; for the A2 tunneling state 1273.856(1) MHz, 11.64(7) kHz, 33.1(9) Hz, 5.70(4) MHz, and -3.21(5) MHz. The chlorine hyperfine structure gives the average torsional displacement of the H/DCl from the a axis to be 26.3° for the HCl complexes and 22.5° for the DCl. The torsional displacement of the B2H6 was found by an inertial analysis of the complexes with HCl. It is very anisotropic, being close to 0° in the ethylene plane and about 9° in the BH2B bridging plane. It is suggested that in the tunneling the B2H6 reorients by 180° in the bridging plane, coupled with a gear-like counter rotation of the HCl by 360°. The BṡṡṡH distance is 2.693 Å in the dimers with HCl and the BṡṡṡD distance is slightly longer, 2.702 Å.

  3. Structure and Oxidation of Pyrrole Adducts Formed between Aflatoxin B2aand Biological Amines.

    PubMed

    Rushing, Blake R; Selim, Mustafa I

    2017-06-19

    Aflatoxin B 2a has been shown to bind to proteins through a dialdehyde intermediate under physiological conditions. The proposed structure of this adduct has been published showing a Schiff base interaction, but adequate verification using structural elucidation instrumental techniques has not been performed. In this work, we synthesized the aflatoxin B 2a amino acid adduct under alkaline conditions, and the formation of a new product was determined using high performance liquid chromatography-time-of-flight mass spectrometry. The resulting accurate mass was used to generate a novel proposed chemical structure of the adduct in which the dialdehyde forms a pyrrole ring with primary amines rather than the previously proposed Schiff base interaction. The pyrrole structure was confirmed using 1 H, 13 C, correlation spectroscopy, heteronuclear single quantum correlation, and heteronuclear multiple bond correlation NMR and tandem mass spectrometry. Reaction kinetics show that the reaction is overall second order and that the rate increases as pH increases. Additionally, this study shows for the first time that aflatoxin B 2a dialdehyde forms adducts with phosphatidylethanolamines and does so through pyrrole ring formation, which makes it the first aflatoxin-lipid adduct to be structurally identified. Furthermore, oxidation of the pyrrole adduct produced a product that was 16 m/z heavier. When the aflatoxin B 2a -lysine (ε) adduct was oxidized, it gave a product with an accurate mass, mass fragmentation pattern, and 1 H NMR spectrum that match aflatoxin B 1 -lysine, which suggest the transformation of the pyrrole ring to a pyrrolin-2-one ring. These data give new insight into the fate and chemical properties of biological adducts formed from aflatoxin B 2a as well as possible interferences with known aflatoxin B 1 exposure biomarkers.

  4. Determinants of Human Cyclin B1 Association with Mitotic Chromosomes

    PubMed Central

    Pfaff, Kathleen L.; King, Randall W.

    2013-01-01

    Cyclin B1–CDK1 activity is essential for mitotic entry, but questions remain regarding how the activity of this kinase is spatially regulated. Previous studies showed that the cyclin B1 subunit localizes to several compartments of a mitotic cell, including the centrosomes, mitotic spindle, kinetochores and chromosomes via distinct sequence elements. Mitotic chromosome association occurs through the unstructured N-terminal domain of cyclin B1 and is independent of CDK1 binding. Here, we use live cell imaging of human cyclin B1 fused to GFP to precisely define the sequence elements within cyclin B1 that mediate its association with condensed mitotic chromosomes. We find that a short, evolutionarily conserved N-terminal motif is required for cyclin B1 to localize to mitotic chromosomes. We further reveal a role for arginine residues within and near the destruction box sequence in the chromosome association of cyclin B1. Additionally, our data suggest that sequences further downstream in cyclin B1, such as the cytoplasmic retention sequence and the cyclin box, may negatively modulate chromosome association. Because multiple basic residues are required for cyclin B1 association with mitotic chromosomes, electrostatic interactions with DNA may facilitate cyclin B1 localization to chromosomes. PMID:23505570

  5. B1 -sensitivity analysis of quantitative magnetization transfer imaging.

    PubMed

    Boudreau, Mathieu; Stikov, Nikola; Pike, G Bruce

    2018-01-01

    To evaluate the sensitivity of quantitative magnetization transfer (qMT) fitted parameters to B 1 inaccuracies, focusing on the difference between two categories of T 1 mapping techniques: B 1 -independent and B 1 -dependent. The B 1 -sensitivity of qMT was investigated and compared using two T 1 measurement methods: inversion recovery (IR) (B 1 -independent) and variable flip angle (VFA), B 1 -dependent). The study was separated into four stages: 1) numerical simulations, 2) sensitivity analysis of the Z-spectra, 3) healthy subjects at 3T, and 4) comparison using three different B 1 imaging techniques. For typical B 1 variations in the brain at 3T (±30%), the simulations resulted in errors of the pool-size ratio (F) ranging from -3% to 7% for VFA, and -40% to > 100% for IR, agreeing with the Z-spectra sensitivity analysis. In healthy subjects, pooled whole-brain Pearson correlation coefficients for F (comparing measured double angle and nominal flip angle B 1 maps) were ρ = 0.97/0.81 for VFA/IR. This work describes the B 1 -sensitivity characteristics of qMT, demonstrating that it varies substantially on the B 1 -dependency of the T 1 mapping method. Particularly, the pool-size ratio is more robust against B 1 inaccuracies if VFA T 1 mapping is used, so much so that B 1 mapping could be omitted without substantially biasing F. Magn Reson Med 79:276-285, 2018. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

  6. Assembly studies of six intestinal intermediate filament (IF) proteins B2, C1, C2, D1, D2, and E1 in the nematode C. elegans.

    PubMed

    Karabinos, Anton; Schünemann, Jürgen; Parry, David A D

    2017-03-01

    The dimerisation properties of six intestine-expressed intermediate filament (IF) proteins (B2, C1, C2, D1, D2, E1) were analysed in blot overlay assay on membranes containing all of the eleven recombinant C. elegans IF proteins (A1, A2, A3, A4, B1, B2, C1, C2, D1, D2, and E1). The interactions detected in the blot assays exclusively comprise intestine-expressed IF proteins and the protein A4, which is found in the dauer larva intestine. About 86% of these interactions are heterotypic, while the remaining interactions relate to C1, C2, and D2 homodimers. These multiple modes of interaction were also supported by calculations of the numbers of possible interchain ionic interactions derived from the individual rod sequences. The results predict that the six B2, C1, C2, D1, D2, and E1 IF proteins are able to form as many as eleven different heteropolymeric and three homopolymeric IFs in the C. elegans intestine. This simple model of the intestinal IF meshwork enables us to speculate that our previously reported triple RNAi worms arrested or decreased their growth because of feeding reduction due to morphological defects of the mechanically compromised intestine. © 2017 Wiley Periodicals, Inc.

  7. 32 CFR 242b.2 - Meetings of the Board.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 32 National Defense 2 2013-07-01 2013-07-01 false Meetings of the Board. 242b.2 Section 242b.2 National Defense Department of Defense (Continued) OFFICE OF THE SECRETARY OF DEFENSE (CONTINUED... THE HEALTH SCIENCES § 242b.2 Meetings of the Board. (a) Regular meetings. (1) The Board shall hold at...

  8. 32 CFR 242b.2 - Meetings of the Board.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 32 National Defense 2 2011-07-01 2011-07-01 false Meetings of the Board. 242b.2 Section 242b.2 National Defense Department of Defense (Continued) OFFICE OF THE SECRETARY OF DEFENSE (CONTINUED... THE HEALTH SCIENCES § 242b.2 Meetings of the Board. (a) Regular meetings. (1) The Board shall hold at...

  9. 32 CFR 242b.2 - Meetings of the Board.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 32 National Defense 2 2014-07-01 2014-07-01 false Meetings of the Board. 242b.2 Section 242b.2 National Defense Department of Defense (Continued) OFFICE OF THE SECRETARY OF DEFENSE (CONTINUED... THE HEALTH SCIENCES § 242b.2 Meetings of the Board. (a) Regular meetings. (1) The Board shall hold at...

  10. 32 CFR 242b.2 - Meetings of the Board.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 32 National Defense 2 2012-07-01 2012-07-01 false Meetings of the Board. 242b.2 Section 242b.2 National Defense Department of Defense (Continued) OFFICE OF THE SECRETARY OF DEFENSE (CONTINUED... THE HEALTH SCIENCES § 242b.2 Meetings of the Board. (a) Regular meetings. (1) The Board shall hold at...

  11. 32 CFR 242b.2 - Meetings of the Board.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 2 2010-07-01 2010-07-01 false Meetings of the Board. 242b.2 Section 242b.2 National Defense Department of Defense (Continued) OFFICE OF THE SECRETARY OF DEFENSE (CONTINUED... THE HEALTH SCIENCES § 242b.2 Meetings of the Board. (a) Regular meetings. (1) The Board shall hold at...

  12. 45 CFR 5b.2 - Purpose and scope.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 45 Public Welfare 1 2010-10-01 2010-10-01 false Purpose and scope. 5b.2 Section 5b.2 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION PRIVACY ACT REGULATIONS § 5b.2... Public Health Service Commissioned Corps; experts and consultants whose temporary (not in excess of 1...

  13. 45 CFR 5b.2 - Purpose and scope.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 45 Public Welfare 1 2011-10-01 2011-10-01 false Purpose and scope. 5b.2 Section 5b.2 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION PRIVACY ACT REGULATIONS § 5b.2... Public Health Service Commissioned Corps; experts and consultants whose temporary (not in excess of 1...

  14. 26 CFR 1.663(b)-2 - Election.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 8 2010-04-01 2010-04-01 false Election. 1.663(b)-2 Section 1.663(b)-2 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Estates and Trusts Which May Accumulate Income Or Which Distribute Corpus § 1.663(b)-2 Election...

  15. Protein-RNA Networks Regulated by Normal and ALS-Associated Mutant HNRNPA2B1 in the Nervous System.

    PubMed

    Martinez, Fernando J; Pratt, Gabriel A; Van Nostrand, Eric L; Batra, Ranjan; Huelga, Stephanie C; Kapeli, Katannya; Freese, Peter; Chun, Seung J; Ling, Karen; Gelboin-Burkhart, Chelsea; Fijany, Layla; Wang, Harrison C; Nussbacher, Julia K; Broski, Sara M; Kim, Hong Joo; Lardelli, Rea; Sundararaman, Balaji; Donohue, John P; Javaherian, Ashkan; Lykke-Andersen, Jens; Finkbeiner, Steven; Bennett, C Frank; Ares, Manuel; Burge, Christopher B; Taylor, J Paul; Rigo, Frank; Yeo, Gene W

    2016-11-23

    HnRNPA2B1 encodes an RNA binding protein associated with neurodegeneration. However, its function in the nervous system is unclear. Transcriptome-wide crosslinking and immunoprecipitation in mouse spinal cord discover UAGG motifs enriched within ∼2,500 hnRNP A2/B1 binding sites and an unexpected role for hnRNP A2/B1 in alternative polyadenylation. HnRNP A2/B1 loss results in alternative splicing (AS), including skipping of an exon in amyotrophic lateral sclerosis (ALS)-associated D-amino acid oxidase (DAO) that reduces D-serine metabolism. ALS-associated hnRNP A2/B1 D290V mutant patient fibroblasts and motor neurons differentiated from induced pluripotent stem cells (iPSC-MNs) demonstrate abnormal splicing changes, likely due to increased nuclear-insoluble hnRNP A2/B1. Mutant iPSC-MNs display decreased survival in long-term culture and exhibit hnRNP A2/B1 localization to cytoplasmic granules as well as exacerbated changes in gene expression and splicing upon cellular stress. Our findings provide a cellular resource and reveal RNA networks relevant to neurodegeneration, regulated by normal and mutant hnRNP A2/B1. VIDEO ABSTRACT. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. 29 CFR 2530.200b-1 - Computation periods.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 9 2010-07-01 2010-07-01 false Computation periods. 2530.200b-1 Section 2530.200b-1 Labor... Provisions § 2530.200b-1 Computation periods. (a) General. Under sections 202, 203 and 204 of the Act and... specified period—in general, a twelve-consecutive-month period—referred to herein as a “computation period...

  17. Construction of HEK293 cells stably expressing wild-type organic anion transporting polypeptide 1B1 (OATP1B1*1a) and variant OATP1B1*1b and OATP1B1*15.

    PubMed

    Chen, M; Qu, B X; Chen, X L; Hu, H H; Jiang, H D; Yu, L S; Zhou, Q; Zeng, S

    2016-06-01

    A transgenic cell line stably expressing the human organic anion transporting polypeptide (OATP1B1) was established. Human Embryonic Kidney 293 (HEK293) cell line stably expressing OATP1B1*1a sequence was amplified through PCR with the extracted total RNA as templates from human liver, then subcloned into the plasmid pMD19-T and verified by sequencing. OATP1B1*1b/OATP1B1*15 mutant sequences were obtained by site-directed mutation PCR with pMD19-T/ OATP1B1*1a as templates. The plasmids pcDNA3.1(+)/OATP1B1*1a, *1b and *15 were constructed and transfected into HEK293 cell line using Lipofectamine 2000 transfection reagent. Several stable transfected clones were obtained after selection with G418. Using rosuvastatin as a probe substrate of OATP1B1, the intracellular rosuvastatin accumulation in HEK293 and HEK-OATP1B1*1a, *1b and *15 monoclone cells were validated by a ultra-performance liquid chromatography-tandem mass spectrometry. OATP1B1 mRNA and protein expression were detected by RT-PCR and Western blot, respectively. The results from RT-PCR, rosuvastatin uptake and Western blot assay indicated that human OATP1B1 was highly expressed in transfected cells compared with controls. The HEK-293 cell lines stably expressing human OATP1B1-wild and variant (HEK-OATP1B1, *1b and *15) are potential models to study drug transport in vitro.

  18. Role of Porphyromonas gingivalis FeoB2 in metal uptake and oxidative stress protection.

    PubMed

    He, Jia; Miyazaki, Hiroshi; Anaya, Cecilia; Yu, Fan; Yeudall, W Andrew; Lewis, Janina P

    2006-07-01

    Porphyromonas gingivalis, a gram-negative anaerobic bacterium, is a recognized periodontopathogen. It exhibits a high degree of aerotolerance and is able to survive in host cells, indicating that efficient oxidative stress protection mechanisms must be present in this organism. Manganese homeostasis plays a major role in oxidative stress protection in a variety of organisms; however, the transport and role of this metal in P. gingivalis is not well understood. Analysis of the genome of P. gingivalis W83 revealed the presence of two genes encoding homologs of a ferrous iron transport protein, FeoB1 and FeoB2. FeoB2 has been implicated in manganese accumulation in P. gingivalis. We sought to determine the role of the FeoB2 protein in metal transport as well as its contribution to resistance to oxygen radicals. Quantitative reverse transcriptase PCR analyses demonstrated that expression of feoB2 is induced in the presence of oxygen. The role of FeoB2 was investigated using an isogenic mutant strain deficient in the putative transporter. We characterized the FeoB2-mediated metal transport using (55)Fe(2+) and (54)Mn(2+). The FeoB2-deficient mutant had dramatically reduced rates of manganese uptake (0.028 pmol/min/10(7) bacteria) compared with the parental strain (0.33 pmol/min/10(7) bacteria) (after 20 min of uptake using 50 nM of (54)Mn(2+)). The iron uptake rates, however, were higher in the mutant strain (0.75 pmol/min/10(7) bacteria) than in the wild type (0.39 pmol/min/10(7) bacteria). Interestingly, reduced survival rates were also noted for the mutant strain after exposure to H(2)O(2) and to atmospheric oxygen compared to the parental strain cultured under the same conditions. In addition, in vitro infection of host cells with the wild type, the FeoB2-deficient mutant, and the same-site revertant revealed that the mutant had a significantly decreased capability for intracellular survival in the host cells compared to the wild-type strain. Our results demonstrate

  19. Expression and Initial Characterization of Human ALDH3B1

    PubMed Central

    Marchitti, Satori A.; Orlicky, David J.; Vasiliou, Vasilis

    2007-01-01

    Aldehyde dehydrogenases (ALDHs) are critical enzymes in the metabolism of endogenous and exogenous aldehydes. The human genome contains nineteen putatively functional ALDH genes; ALDH3B1 belongs to the ALDH3 family. While recent studies have linked the ALDH3B1 locus to schizophrenia, nothing was known, until now, about the properties and significance of the ALDH3B1 protein. The aim of this study was to characterize the ALDH3B1 protein. Human ALDH3B1 was baculovirus-expressed and found to be catalytically active towards medium- and long-chain aliphatic aldehydes and the aromatic aldehyde benzaldehyde. Western blot analyses indicate that ALDH3B1 is highly expressed in kidney and liver and moderately expressed in various brain regions. ALDH3B1-transfected HEK293 cells were significantly protected against cytotoxicity induced by the lipid-peroxidation product octanal when compared to vector-transfected cells. This study shows for the first time the functionality, expression and protective role of ALDH3B1 and indicates a potential physiological role of ALDH3B1 against oxidative stress. PMID:17382292

  20. Expression and initial characterization of human ALDH3B1.

    PubMed

    Marchitti, Satori A; Orlicky, David J; Vasiliou, Vasilis

    2007-05-11

    Aldehyde dehydrogenases (ALDHs) are critical enzymes in the metabolism of endogenous and exogenous aldehydes. The human genome contains 19 putatively functional ALDH genes; ALDH3B1 belongs to the ALDH3 family. While recent studies have linked the ALDH3B1 locus to schizophrenia, nothing was known, until now, about the properties and significance of the ALDH3B1 protein. The aim of this study was to characterize the ALDH3B1 protein. Human ALDH3B1 was baculovirus-expressed and found to be catalytically active towards medium- and long-chain aliphatic aldehydes and the aromatic aldehyde benzaldehyde. Western blot analyses indicate that ALDH3B1 is highly expressed in kidney and liver and moderately expressed in various brain regions. ALDH3B1-transfected HEK293 cells were significantly protected against cytotoxicity induced by the lipid peroxidation product octanal when compared to vector-transfected cells. This study shows for the first time the functionality, expression and protective role of ALDH3B1 and indicates a potential physiological role of ALDH3B1 against oxidative stress.

  1. Prediction of B1 to B10 phase transition in LuN under pressure: An ab-initio investigation

    SciTech Connect

    Sahoo, B. D., E-mail: bdsahoo@barc.gov.in; Mukherjee, D.; Joshi, K. D.

    2016-05-23

    Ab-initio total energy calculations have been performed in lutetium nitride (LuN) as a function of hydrostatic compression to understand the high pressure behavior of this compound. Our calculations predict a phase transition from ambient rocksalt type structure (B1 phase) to a tetragonal structure (B10 phase) at ~ 240 GPa. The phase transition has been identified as first order in nature with volume discontinuity of ~ 6%. The predicted high pressure phase has been found to be stable up to at least 400 GPa, the maximum pressure up to which calculations have been performed.Further, to substantiate the results of static lattice calculations analysismore » of lattice dynamic stability of B1 and B10 phase has been carried out at different pressures. Apart from this, we have analyzed the lattice dynamic stability CsCl type (B2) phase around the 240 GPa, the pressure reported for B1 to B2 transition in previous all-electron calculations by Gupta et al. 2013. We find that the B2 structure is lattice dynamically unstable at this pressure and remains unstable up to ~ 400 GPa, ruling out the possibility of B1 to B2 phase transition at least up to ~ 400 GPa. Further, the theoretically determined equation of state has been utilized to derive various physical quantities such as zero pressure equilibrium volume, bulk modulus, and pressure derivative of bulk modulus of B1 phase at ambient conditions.« less

  2. Antipsychotic potential of quinazoline ErbB1 inhibitors in a schizophrenia model established with neonatal hippocampal lesioning.

    PubMed

    Mizuno, Makoto; Iwakura, Yuriko; Shibuya, Masako; Zheng, Yingjun; Eda, Takeyoshi; Kato, Taisuke; Takasu, Yohei; Nawa, Hiroyuki

    2010-01-01

    Hyper-signaling of the epidermal growth factor receptor family (ErbB) is implicated in the pathophysiology of schizophrenia. Various quinazoline inhibitors targeting ErbB1 or ErbB2 - 4 have been developed as anti-cancer agents and might be useful for antipsychotic treatment. In the present study, we used an animal model of schizophrenia established by neonatal hippocampal lesioning and evaluated the neurobehavioral consequences of ErbB1-inhibitor treatment. Subchronic administration of the ErbB1 inhibitor ZD1839 to the cerebroventricle of rats receiving neonatal hippocampal lesioning ameliorated deficits in prepulse inhibition as well as those in the latent inhibition of tone-dependent fear learning. There were no apparent adverse effects on basal learning scores or locomotor activity, however. The administration of other ErbB1 inhibitors, PD153035 and OSI-774, similarly attenuated the prepulse inhibition impairment of this animal model. In parallel, there were decreases in ErbB1 phosphorylation in animals treated with ErbB1 inhibitors. These results indicate an antipsychotic potential of quinazoline ErbB1 inhibitors. ErbB receptor tyrosine kinases may be novel therapeutic targets for schizophrenia or its related psychotic symptoms.

  3. 75 FR 69938 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-16

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 10-44] 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, Department of Defense. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

  4. 75 FR 69947 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-16

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 10-45] 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, Department of Defense. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

  5. 75 FR 69957 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-16

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 10-38] 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security Cooperation Agency. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

  6. 75 FR 69971 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-16

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 10-58] 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security Cooperation Agency. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

  7. 75 FR 69926 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-16

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 10-52] 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, Department of Defense. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

  8. 75 FR 69960 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-16

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 10-43] 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security Cooperation Agency. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

  9. 75 FR 69931 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-16

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 10-46] 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, Department of Defense. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

  10. 75 FR 69953 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-16

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 10-57] 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security Cooperation Agency. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

  11. 75 FR 69922 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-16

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 10-50] 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, Department of Defense. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

  12. 26 CFR 1.503(b)-1 - Prohibited transactions.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 7 2010-04-01 2010-04-01 true Prohibited transactions. 1.503(b)-1 Section 1.503... (CONTINUED) INCOME TAXES (CONTINUED) Exempt Organizations § 1.503(b)-1 Prohibited transactions. (a) In general. The term prohibited transaction means any transaction set forth in section 503(b) engaged in by...

  13. 26 CFR 1.503(b)-1 - Prohibited transactions.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 7 2011-04-01 2009-04-01 true Prohibited transactions. 1.503(b)-1 Section 1.503... (CONTINUED) INCOME TAXES (CONTINUED) Exempt Organizations § 1.503(b)-1 Prohibited transactions. (a) In general. The term prohibited transaction means any transaction set forth in section 503(b) engaged in by...

  14. 26 CFR 1.503(b)-1 - Prohibited transactions.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 7 2012-04-01 2012-04-01 false Prohibited transactions. 1.503(b)-1 Section 1... (CONTINUED) INCOME TAXES (CONTINUED) Exempt Organizations § 1.503(b)-1 Prohibited transactions. (a) In general. The term prohibited transaction means any transaction set forth in section 503(b) engaged in by...

  15. 26 CFR 1.503(b)-1 - Prohibited transactions.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 7 2014-04-01 2013-04-01 true Prohibited transactions. 1.503(b)-1 Section 1.503... (CONTINUED) INCOME TAXES (CONTINUED) Exempt Organizations § 1.503(b)-1 Prohibited transactions. (a) In general. The term prohibited transaction means any transaction set forth in section 503(b) engaged in by...

  16. 26 CFR 1.503(b)-1 - Prohibited transactions.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 7 2013-04-01 2013-04-01 false Prohibited transactions. 1.503(b)-1 Section 1... (CONTINUED) INCOME TAXES (CONTINUED) Exempt Organizations § 1.503(b)-1 Prohibited transactions. (a) In general. The term prohibited transaction means any transaction set forth in section 503(b) engaged in by...

  17. 75 FR 11865 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-12

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal No. 10-12] 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, DoD. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification to fulfill the...

  18. 75 FR 81993 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-29

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal No. 10-62] 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security Cooperation Agency. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

  19. 75 FR 60424 - 36(b)(1) Arms Sales Notifications

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-30

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 10-28 and 10-30] 36(b)(1) Arms Sales Notifications AGENCY: Defense Security Cooperation Agency, DoD. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of two section 36(b)(1) arms sales notifications to...

  20. 76 FR 38371 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-30

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 11-16] 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security Cooperation Agency. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

  1. 76 FR 18731 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-05

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 10-78] 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, DoD. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This is...

  2. 75 FR 9182 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-01

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal No. 09-28] 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, DoD. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification to fulfill the...

  3. 75 FR 74011 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-30

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 10-24] 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security Cooperation Agency. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

  4. 76 FR 37078 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-24

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 10-68] 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security Cooperation Agency. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

  5. 75 FR 62792 - 36(b)(1) Arms Sales Notifications

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-13

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 10-20, 10-23, and 10-42] 36(b)(1) Arms Sales Notifications AGENCY: Defense Security Cooperation Agency, DoD. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of three section 36(b)(1) arms sales notifications...

  6. 77 FR 46417 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-03

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 12-39] 36(b)(1) Arms Sales... Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...)(1) Of the Arms Export Control Act, as amended (i) Prospective Purchaser: Thailand (ii) Total...

  7. 76 FR 37071 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-24

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 10-03] 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security Cooperation Agency. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

  8. 75 FR 74014 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-30

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 10-49] 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security Cooperation Agency. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

  9. 76 FR 26707 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-09

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 11-10] 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, Department of Defense. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

  10. 75 FR 62767 - 36(b)(1) Arms Sales Notifications

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-13

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 10-53, 10-54, 10-55, 10-59, 10-60, 10-61, and 10-63] 36(b)(1) Arms Sales Notifications AGENCY: Defense Security Cooperation Agency, DoD... 36(b)(1) arms sales notifications to fulfill the requirements of section 155 of Public Law 104-164...

  11. 75 FR 48646 - 36(b)(1) Arms Sales Notifications

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-11

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 10-27, 10-31 and 10-41] 36(b)(1) Arms Sales Notifications AGENCY: Defense Security Cooperation Agency, DoD. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of three section 36(b)(1) arms sales notifications...

  12. 76 FR 37075 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-24

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 10-77] 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security Cooperation Agency. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

  13. 78 FR 703 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-04

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 12-12] 36(b)(1) Arms Sales... Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...) of the Arms Export Control Act, as amended (i) Prospective Purchaser: Turkey (ii) Total Estimated...

  14. 76 FR 8716 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-15

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 11-05] 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, DoD. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This is...

  15. 75 FR 20571 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-20

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 10-04 and 10-14] 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, DoD. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of two section 36(b)(1) arms sales notifications to...

  16. 76 FR 18726 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-05

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 11-08] 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, DoD ACTION: Notice SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This is published...

  17. 76 FR 29212 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-20

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 10-75] 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, Department of Defense. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

  18. 76 FR 28956 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-19

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal No. 11-11] 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security Cooperation Agency. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

  19. 78 FR 50043 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-16

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 12-67] 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, Department of Defense. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

  20. 78 FR 36536 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-18

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 13-25] 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, Department of Defense. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

  1. 76 FR 72184 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-22

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 11-41] 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security Cooperation Agency. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

  2. SerpinB1 Promotes Pancreatic β Cell Proliferation

    SciTech Connect

    El Ouaamari, Abdelfattah; Dirice, Ercument; Gedeon, Nicholas

    2016-01-01

    Compensatory β-cell growth in response to insulin resistance is a common feature in diabetes. We recently reported that liver-derived factors participate in this compensatory response in the liver insulin receptor knockout (LIRKO) mouse, a model of significant islet hyperplasia. Here we show that serpinB1 is a liver-derived secretory protein that controls β-cell proliferation. SerpinB1 is abundant in the hepatocyte secretome and sera derived from LIRKO mice. SerpinB1 and small molecule compounds that partially mimic serpinB1 activity enhanced proliferation of zebrafish, mouse and human β-cells. We report that serpinB1-induced β-cell replication requires protease inhibition activity and mice lacking serpinB1 exhibit attenuatedmore » β-cell replication in response to insulin resistance. Finally, SerpinB1-treatment of islets modulated signaling proteins in growth and survival pathways such as MAPK, PKA and GSK3. Together, these data implicate SerpinB1 as a protein that can potentially be harnessed to enhance functional β-cell mass in patients with diabetes.« less

  3. 78 FR 62590 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-22

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 13-43] 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security Cooperation Agency. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

  4. 78 FR 15001 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-08

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 13-05] 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency. Department of Defense. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

  5. 78 FR 62592 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-22

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 13-51] 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, Department of Defense. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

  6. 77 FR 42704 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-20

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 12-10] 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, Department of Defense. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

  7. 78 FR 62588 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-22

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 13-53] 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, Department of Defense. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

  8. 77 FR 75617 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-21

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 12-68] 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, Department of Defense. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

  9. 78 FR 62600 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-22

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 13-47] 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, Department of Defense. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

  10. 77 FR 51780 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-27

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 12-42] 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security Cooperation Agency. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

  11. 26 CFR 1.280B-1 - Demolition of structures.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 3 2013-04-01 2013-04-01 false Demolition of structures. 1.280B-1 Section 1... (CONTINUED) INCOME TAXES (CONTINUED) Items Not Deductible § 1.280B-1 Demolition of structures. (a) In general. Section 280B provides that, in the case of the demolition of any structure, no deduction otherwise...

  12. 26 CFR 1.280B-1 - Demolition of structures.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 3 2010-04-01 2010-04-01 false Demolition of structures. 1.280B-1 Section 1... (CONTINUED) INCOME TAXES Items Not Deductible § 1.280B-1 Demolition of structures. (a) In general. Section 280B provides that, in the case of the demolition of any structure, no deduction otherwise allowable...

  13. 26 CFR 1.280B-1 - Demolition of structures.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 3 2011-04-01 2011-04-01 false Demolition of structures. 1.280B-1 Section 1... (CONTINUED) INCOME TAXES (CONTINUED) Items Not Deductible § 1.280B-1 Demolition of structures. (a) In general. Section 280B provides that, in the case of the demolition of any structure, no deduction otherwise...

  14. 26 CFR 1.280B-1 - Demolition of structures.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 3 2012-04-01 2012-04-01 false Demolition of structures. 1.280B-1 Section 1... (CONTINUED) INCOME TAXES (CONTINUED) Items Not Deductible § 1.280B-1 Demolition of structures. (a) In general. Section 280B provides that, in the case of the demolition of any structure, no deduction otherwise...

  15. 26 CFR 1.665(b)-1A - Accumulation distributions.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 8 2011-04-01 2011-04-01 false Accumulation distributions. 1.665(b)-1A Section... TAX (CONTINUED) INCOME TAXES (CONTINUED) Treatment of Excess Distributions of Trusts Applicable to Taxable Years Beginning on Or After January 1, 1969 § 1.665(b)-1A Accumulation distributions. (a) In...

  16. 26 CFR 1.665(b)-1A - Accumulation distributions.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 8 2010-04-01 2010-04-01 false Accumulation distributions. 1.665(b)-1A Section... TAX (CONTINUED) INCOME TAXES Treatment of Excess Distributions of Trusts Applicable to Taxable Years Beginning on Or After January 1, 1969 § 1.665(b)-1A Accumulation distributions. (a) In general. (1) For any...

  17. 76 FR 68432 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-04

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 11-37] 36(b)(1) Arms Sales... Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This.... FOR FURTHER INFORMATION CONTACT: Ms. B. English, DSCA/DBO/CFM, (703) 601-3740. The following is a copy...

  18. 76 FR 35188 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-16

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 11-22] 36(b)(1) Arms Sales... Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This.... FOR FURTHER INFORMATION CONTACT: Ms. B. English, DSCA/DBO/CFM, (703) 601-3740. The following is a copy...

  19. 77 FR 49430 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-16

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 12-38] 36(b)(1) Arms Sales... Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This.... FOR FURTHER INFORMATION CONTACT: Ms. B. English, DSCA/DBO/CFM, (703) 601-3740. The following is a copy...

  20. 75 FR 107 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-04

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 09-67 and 09-72] 36(b)(1) Arms... Department of Defense is publishing the unclassified text of two section 36(b)(1) arms sales notifications to... CONTACT: Ms. B. English, DSCA/DBO/CFM, (703) 601-3740. SUPPLEMENTARY INFORMATION: The following are copies...

  1. 76 FR 68429 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-04

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 11-31] 36(b)(1) Arms Sales... Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This.... FOR FURTHER INFORMATION CONTACT: Ms. B. English, DSCA/DBO/CFM, (703) 601-3740. The following is a copy...

  2. 76 FR 40703 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-11

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 11-07] 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security Cooperation Agency. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This...

  3. 75 FR 114 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-04

    ... and 09-78] 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, DoD. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of six section 36(b)(1... 1996. FOR FURTHER INFORMATION CONTACT: Ms. B. English, DSCA/DBO/CFM, (703) 601-3740. SUPPLEMENTARY...

  4. 75 FR 51445 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-20

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal No. 10-34] 36(b)(1) Arms Sales... Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification to fulfill the requirements of section 155 of Public Law 104-164 dated 21 July 1996. FOR FURTHER INFORMATION CONTACT: Ms. B...

  5. 75 FR 42708 - 36(b)(1) Arms Sales Notifications

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-22

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 10-09, 10-33, and 10-37] 36(b)(1... Department of Defense is publishing the unclassified text of three section 36(b)(1) arms sales notifications... INFORMATION CONTACT: Ms. B. English, DSCA/DBO/CFM, (703) 601-3740. SUPPLEMENTARY INFORMATION: The following...

  6. 75 FR 5971 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-05

    ... and 10-07] 36(b)(1) Arms Sales Notification AGENCY: Defense Security Cooperation Agency, DoD. ACTION: Notice. SUMMARY: The Department of Defense is publishing the unclassified text of six section 36(b)(1... 1996. FOR FURTHER INFORMATION CONTACT: Ms. B. English, DSCA/DBO/CFM, (703) 601-3740. SUPPLEMENTARY...

  7. 75 FR 47275 - 36(b)(1) Arms Sales Notifications

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-05

    ... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 10-32 and 10-35] 36(b)(1) Arms... Department of Defense is publishing the unclassified text of two section 36(b)(1) arms sales notifications to... CONTACT: Ms. B. English, DSCA/DBO/CFM, (703) 601-3740. SUPPLEMENTARY INFORMATION: The following are copies...

  8. 75 FR 80293 - Airworthiness Directives; Eurocopter France Model AS 350 B, BA, B1, B2, B3, and D, and Model...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-22

    ..., Amendment 39-16487 (75 FR 65222, October 22, 2010), requires replacing all servo-controls that are... corrected to read as follows: Table 1 Component Part No. (P/N) Serial No. (S/N) Main rotor servo-control..., inclusive. Tail rotor servo-control...... P/N SC5072....... S/N 222M, 306M, or 309. [[Page 80294

  9. Ethnomathematics: The use of multiple linier regression Y = b 1 X 1 + b 2 X 2 + e in traditional house construction Saka Roras in Songan Village

    NASA Astrophysics Data System (ADS)

    Darmayasa, J. B.; Wahyudin; Mulyana, T.

    2018-01-01

    Ethnomathematics may be the connecting bridge between culture and technology and arts. Therefore, the exploration of mathematics values that intersects with cultural anthropology should be significantly conducted. One case containing such issue is the construction of Traditional House of Saka Roras in Bali. Thus, this research aimed to explore the mathematic concept adopted in the construction of such traditional Bale (house) located in Songan Village, Kintamani, Bali. Specifically, this research also aimed to investigate the selection of linear regression coefficient for the saka (pillar) in the Bale. This research applied Embedded Mix-Method Design. Meanwhile, the data collection was conducted by interview, observation and measurement of pillars of 32 Bale Saka Roras. The result of this research revealed that the connection between the width and height of pillars was stated in the formula Y = 26,3 + 18,2X, where X acted as stimulus variable. The coefficient value amounted to 18.2 showed that most preceding architects in Songan Village were more likely to use 19 as the coefficient towards the pillar width than the other coefficients such as 17, 20 and 21 as mentioned in book/palm-leaf manuscript entitled Kosala-Kosali. The last but not least, the researchers also figured out that the pillar width depended on the length of the house-owner candidate’s index finger.

  10. 76 FR 70046 - Airworthiness Directives; Eurocopter France Model AS350B, B1, B2, B3, BA, C, D, and D1; and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-10

    ... are intended to prevent separation of the bearing ball from its outer race, rubbing of the body of the... movement. This action may be performed by an owner/operator (pilot) holding at least a private pilot... 4. Will not have a significant economic impact, positive or negative, on a substantial number of...

  11. 75 FR 22508 - Airworthiness Directives; Eurocopter France Model AS350B, BA, B1, B2, B3, C, D, and D1; AS 355E...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-29

    ... that it: Does not include the Model BB helicopters but does include Model AS350C, D1 and AS 355 NP...) Does not include the Model BB helicopters but does include the Model AS350C and D1 and Model AS355NP..., contains related information. Joint Aircraft System/Component (JASC) Code (j) The JASC Code is 25...

  12. 75 FR 63050 - Airworthiness Directives; Eurocopter France (Eurocopter) Model AS350B, BA, B1, B2, B3, D, AS355E...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-10-14

    ..., and 555 helicopters. EASB No. 53.00.37 relates to 2 Model 350 (350 BB and 350 L1) helicopters that are... different Eurocopter model helicopters. EASB 53.00.37 relates to 2 Model 350 (350 BB and 350 L1) helicopters... (j) EASA Emergency AD No. 2007-0139-E, dated May 15, 2007 (corrected May 23, 2007), contains related...

  13. 75 FR 79988 - Airworthiness Directives; Eurocopter France Model AS350B, B1, B2, B3, BA, and EC130 B4 Helicopters

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-12-21

    ... gearbox. Each affected helicopter had a starter-generator manufactured by one company. Investigation... that failure of the 41-tooth pinion in the engine accessory gearbox resulted in engine flameouts. Each... due to failure of the 41-tooth pinion in the engine accessory gearbox. The failure of this pinion...

  14. 75 FR 50874 - Airworthiness Directives; Eurocopter France (Eurocopter) Model AS350B, BA, B1, B2, C, D, and D1...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-18

    ... requires visually inspecting the tail gearbox (TGB) control lever for a crack. If a crack is found, this AD... gearbox (TGB) control lever, part number (P/N) 350A33-1058-00, P/N 350A33-1058-01, P/N 350A33-1058-02, or...

  15. Effectiveness of pulsed light treatment for degradation and detoxification of aflatoxin B1 and B2 in rough rice and rice bran

    USDA-ARS?s Scientific Manuscript database

    Aflatoxins primarily accumulate in the hull and bran layers of rough rice making these by-products of rice milling unsuitable for animal feed or human consumption. Contaminated rough rice is also a potential source of aflatoxin exposure to workers handling the grain during post-harvest storage and p...

  16. Investigating Criterial Discourse Features across Second Language Development: Lexical Bundles in Rated Learner Essays, CEFR B1, B2 and C1

    ERIC Educational Resources Information Center

    Chen, Yu-Hua; Baker, Paul

    2016-01-01

    In this study, we investigated criterial discourse features in L2 writing through the use of recurrent word combinations, a.k.a. lexical bundles, taking a corpus-driven and expert-judged approach by examining L2 English data across various proficiency levels from L1 Chinese learners. Proficiency was determined by a robust rating procedure which is…

  17. 20 CFR Appendix B to Part 718 - Standards for Administration and Interpretation of Pulmonary Function Tests. Tables B1, B2, B3...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Standards for Administration and...' Benefits EMPLOYMENT STANDARDS ADMINISTRATION, DEPARTMENT OF LABOR FEDERAL COAL MINE HEALTH AND SAFETY ACT... support of a claim for black lung benefits. If it is established that one or more standards have not been...

  18. Cloning and expression of the recombinant crustacean hyperglycemic hormone isoform B2 (rCHH-B2) and its effects on the metabolism and osmoregulation of the Pacific white shrimp Litopenaeus vannamei.

    PubMed

    Camacho-Jiménez, Laura; Sánchez-Castrejón, Edna; Díaz, Fernando; Aguilar, Manuel B; Muñoz-Márquez, Ma Enriqueta; Ponce-Rivas, Elizabeth

    2017-11-01

    Crustacean hyperglycemic hormones (CHHs) are multifunctional neuropeptides ubiquitous in crustaceans. In Litopenaeus vannamei, CHH-B2 is a CHH eyestalk isoform whose expression has been shown to vary with enviromental conditions, suggesting its relevance for ecophysiological performance of shrimp, controlling processes related to metabolism and osmo-ionic regulation. To study the involvement of CHH-B2 in these processes, we cloned and expressed a recombinant version with a free C-terminal glycine (rCHH-B2-Gly) in the methylotrophic yeast Pichia pastoris. The rCHH-B2-Gly peptide secreted to the culture medium was purified by RP-HPLC and used for in vivo glucose, triglyceride, and osmoregulation dose-response analyses with juvenile shrimp. The peptide was also amidated at the C-terminus using an α-amidating enzyme to produce rCHH-B2-amide. The shrimp showed a dose-dependent effect of rCHH-B2-Gly to hemolymph glucose and triglyceride levels, inducing maximal increases by injecting 500 and 1000pmol of hormone, respectively. Additionally, 10pmol of hormone was sufficient to reduce the hypo-osmoregulatory capacity of shrimp at 35‰. These findings suggest that CHH-B2 has regulatory roles in carbohydrate and lipid metabolism, and a potential involvement in osmoregulation of L. vannamei. Injection of 100pmol of rCHH-B2-amide increased glucose and triglyceride levels by 15 and 28%, respectively in comparison with rCHH-B2-Gly, suggesting an important role for the C-terminal amidation. Additionally, an in silico structural analysis done with the CHH-B1 and rCHH-B2-Gly peptides suggests that the C-terminal region may be relevant for the activity of the L. vannamei isoforms and explain the functional divergence from other crustacean CHH/CHH-like peptides. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. B2B Models for DoD Acquisition

    DTIC Science & Technology

    2008-01-15

    implementation of computer-based information systems. Specifically, he is interested in B2B and B2C e- commerce , enterprise resource planning, e-procurement...business (B2B) e- commerce refers to transactions between businesses conducted electronically over the Internet, intranets, extranets, or private...types of electronic marketplace participation: 1) Sell-side, 2) Buy- side, 3) Exchanges, and 4) Collaborative commerce . In sell-side commerce , there

  20. Nucleolin-binding by ErbB2 enhances tumorigenicity of ErbB2-positive breast cancer.

    PubMed

    Wolfson, Eya; Goldenberg, Maria; Solomon, Shira; Frishberg, Amit; Pinkas-Kramarski, Ronit

    2016-10-04

    ErbB2 is an important member of the ErbB family, which activates growth and proliferation signaling pathways. ErbB2 is often overexpressed in various malignancies, especially in breast cancer, and is a common target for anti-cancer drugs. Breast cancer is currently one of the leading mortality causes in women, and acquired resistance to ErbB2-targeted therapies is a major obstacle in its treatment. Thus, understanding ErbB2-mediated signaling is crucial for further development of anti-cancer therapeutics and disease treatment. Previously, we have reported that the ErbB receptors interact with the major nucleolar protein nucleolin. In addition to its function in the nucleoli of cells, nucleolin participates in various cellular processes at the cytoplasm and cell-surface. Deregulated nucleolin is frequently overexpressed on the membrane of cancer cells. Here, we show that nucleolin increases colony formation and anchorage-independent growth of ErbB2-overexpressing cells. Importantly, this enhanced tumorigenicity also occurs in human ErbB2-positive breast cancer patients; namely, nucleolin overexpression in these patients is associated with reduced patient survival rates and increased disease-risk. ErbB2-nucleolin complexes are formed endogenously in both normal and cancer cells, and their effect on tumorigenicity is mediated through activation of ErbB2 signaling. Accordingly, nucleolin inhibition reduces cell viability and ErbB2 activation in ErbB2-positive cancer cells.

  1. B2B Models for DoD Acquisition

    DTIC Science & Technology

    2007-07-30

    ar^qb=p`elli=lc=_rpfkbpp=C=mr_if`=mlif`v - i - k^s^i=mlpqdo^ar^qb=p`elli= Abstract A central vision of B2B e- commerce is that of an electronic ...interest is in the analysis, design and implementation of computer-based information systems. Specifically, he is interested in B2B and B2C e- commerce ...i=mlpqdo^ar^qb=p`elli= = Introduction Business-to-business (B2B) e- commerce refers to transactions between businesses conducted electronically over

  2. B2A peptide on ceramic granules enhance posterolateral spinal fusion in rabbits compared with autograft.

    PubMed

    Smucker, Joseph D; Bobst, John A; Petersen, Emily B; Nepola, James V; Fredericks, Douglas C

    2008-05-20

    Six groups of 10 animals underwent single level, uninstrumented posterolateral lumbar fusions. Graft sites were implanted with autologous bone, autologous bone plus B2A coated granules with concentrations of 0-, 50-, 100-, or 300 microg/mL, or no graft material. Explanted motion segments were analyzed by Faxitron radiographs, computerized tomography (CT), manual palpation, and histology. The synthetic peptide B2A2-K-NS (B2A) was evaluated as a novel agent for augmenting spinal fusion in a posterolateral, noninstrumented rabbit lumbar spine fusion model. There have been many efforts to increase the rate of posterolateral spinal fusion while, at the same time minimizing, use of autologous bone with its inherent harvest morbidity. B2A coated ceramic granules (0-, 50-, 100-, and 300 microg/mL) were mixed 1:1 with autogenous iliac crest bone and implanted. Autogenous bone alone was used as a positive control. Fusion was assessed at 6 weeks via radiographs and manual palpation. These results were confirmed with histology and CT. Fusion results from palpation and radiographic evaluations were similar. CT and histology confirmed bridging bone across the transverse processes for fused spines. The highest fusion rates were observed in the 100 mug B2A/mL group-89% in comparison to 33% for uncoated granules (0 microg B2A/mL) and 63% for autograft alone. These differences were statistically significant. All investigated B2A concentrations demonstrated increased fusion rates. Fusion masses resulting from the implantation of 100 mug B2A/mL granules demonstrated new woven bone: fused to the transverse processes, within granule pores, bridging bone across the transverse processes, and bridging residual bone graft and granules. It was concluded that each investigated concentration of B2A coated granules in a 1:1 mixture with autograft increased fusion rates in comparison to controls in this rabbit model.

  3. The physical and chemical structure of Sagittarius B2. II. Continuum millimeter emission of Sgr B2(M) and Sgr B2(N) with ALMA

    NASA Astrophysics Data System (ADS)

    Sánchez-Monge, Á.; Schilke, P.; Schmiedeke, A.; Ginsburg, A.; Cesaroni, R.; Lis, D. C.; Qin, S.-L.; Müller, H. S. P.; Bergin, E.; Comito, C.; Möller, Th.

    2017-07-01

    Context. The two hot molecular cores Sgr B2(M) and Sgr B2(N), which are located at the center of the giant molecular cloud complex Sagittarius B2, have been the targets of numerous spectral line surveys, revealing a rich and complex chemistry. Aims: We seek to characterize the physical and chemical structure of the two high-mass star-forming sites Sgr B2(M) and Sgr B2(N) using high-angular resolution observations at millimeter wavelengths, reaching spatial scales of about 4000 au. Methods: We used the Atacama Large Millimeter/submillimeter Array (ALMA) to perform an unbiased spectral line survey of both regions in the ALMA band 6 with a frequency coverage from 211 GHz to 275 GHz. The achieved angular resolution is 0.̋4, which probes spatial scales of about 4000 au, I.e., able to resolve different cores and fragments. In order to determine the continuum emission in these line-rich sources, we used a new statistical method, STATCONT, which has been applied successfully to this and other ALMA datasets and to synthetic observations. Results: We detect 27 continuum sources in Sgr B2(M) and 20 sources in Sgr B2(N). We study the continuum emission variation across the ALMA band 6 (I.e., spectral index) and compare the ALMA 1.3 mm continuum emission with previous SMA 345 GHz and VLA 40 GHz observations to study the nature of the sources detected. The brightest sources are dominated by (partially optically thick) dust emission, while there is an important degree of contamination from ionized gas free-free emission in weaker sources. While the total mass in Sgr B2(M) is distributed in many fragments, most of the mass in Sgr B2(N) arises from a single object, with filamentary-like structures converging toward the center. There seems to be a lack of low-mass dense cores in both regions. We determine H2 volume densities for the cores of about 107-109 cm-3 (or 105-107 M⊙ pc-3), I.e., one to two orders of magnitude higher than the stellar densities of super star clusters. We

  4. Cell type-specific localization of Ephs pairing with ephrin-B2 in the rat postnatal pituitary gland.

    PubMed

    Yoshida, Saishu; Kato, Takako; Kanno, Naoko; Nishimura, Naoto; Nishihara, Hiroto; Horiguchi, Kotaro; Kato, Yukio

    2017-10-01

    Sox2-expressing stem/progenitor cells in the anterior lobe of the pituitary gland form two types of micro-environments (niches): the marginal cell layer and dense cell clusters in the parenchyma. In relation to the mechanism of regulation of niches, juxtacrine signaling via ephrin and its receptor Eph is known to play important roles in various niches. The ephrin and Eph families are divided into two subclasses to create ephrin/Eph signaling in co-operation with confined partners. Recently, we reported that ephrin-B2 localizes specifically to both pituitary niches. However, the Ephs interacting with ephrin-B2 in these pituitary niches have not yet been identified. Therefore, the present study aims to identify the Ephs interacting with ephrin-B2 and the cells that produce them in the rat pituitary gland. In situ hybridization and immunohistochemistry demonstrated cell type-specific localization of candidate interacting partners for ephrin-B2, including EphA4 in cells located in the posterior lobe, EphB1 in gonadotropes, EphB2 in corticotropes, EphB3 in stem/progenitor cells and EphB4 in endothelial cells in the adult pituitary gland. In particular, double-immunohistochemistry showed cis-interactions between EphB3 and ephrin-B2 in the apical cell membranes of stem/progenitor cell niches throughout life and trans-interactions between EphB2 produced by corticotropes and ephrin-B2 located in the basolateral cell membranes of stem/progenitor cells in the early postnatal pituitary gland. These data indicate that ephrin-B2 plays a role in pituitary stem/progenitor cell niches by selective interaction with EphB3 in cis and EphB2 in trans.

  5. Study of the Multiplexing Schemes for COMPASS B1 Signals

    NASA Astrophysics Data System (ADS)

    Liu, Wei; Hu, Yuan; Zhan, Xingqun

    With the development of COMPASS system, finding suitable and efficient multiplexing solutions have become important for the system signal design. In this paper, based on the alternative BOC (AltBOC) modulation technique, the multiplexing scheme for COMPASS Phase II B1 signals is proposed. Then, to combine all COMPASS Phase III (CP III) B1 components into a composite signal with constant envelope, the generalized majority voting (GMV) technique is employed based on the characteristics of CP III B1 signals. The proposed multiplexing schemes also provide potential opportunities for GNSS modernization and construction, such as GPS, Galileo, etc.

  6. Transfer of aflatoxin B1 and fumonisin B1 from naturally contaminated raw materials to beer during an industrial brewing process.

    PubMed

    Pietri, A; Bertuzzi, T; Agosti, B; Donadini, G

    2010-10-01

    The aim of this research was to determine the fate of aflatoxins (AFs) and fumonisins (FBs) naturally occurring in raw materials (maize grit and malted barley) during four industrial brewing processes. The aflatoxin B(1) (AFB(1)) level in raw materials varied from 0.31 to 14.85 microg kg(-1), while the fumonisin B(1) (FB(1)) level (only in maize grit) varied from 1146 to 3194 microg kg(-1). The concentration in finished beer ranged from 0.0015 to 0.022 microg l(-1) for AFB(1) and from 37 to 89 microg l(-1) for FB(1); the other aflatoxins and fumonisin B(2) were not found in beer samples. The average percentage of toxins recovered in finished beer, referring to the amounts contained in raw materials, were 1.5% +/- 0.8% for AFB(1) and 50.7% +/- 4.7% for FB(1). These results were mainly due to the different solubility of the two mycotoxins during the mashing process. If raw materials comply with the limits fixed by European Commission Regulations, the contribution of a moderate daily consumption of beer to AFB(1) and FB(1) intake does not contribute significantly to the exposure of the consumer.

  7. Bispecific antibody to ErbB2 overcomes trastuzumab resistance through comprehensive blockade of ErbB2 heterodimerization.

    PubMed

    Li, Bohua; Meng, Yanchun; Zheng, Lei; Zhang, Xunmin; Tong, Qing; Tan, Wenlong; Hu, Shi; Li, Hui; Chen, Yang; Song, Jinjing; Zhang, Ge; Zhao, Lei; Zhang, Dapeng; Hou, Sheng; Qian, Weizhu; Guo, Yajun

    2013-11-01

    The anti-ErbB2 antibody trastuzumab has shown significant clinical benefits in metastatic breast cancer. However, resistance to trastuzumab is common. Heterodimerization between ErbB2 and other ErbBs may redundantly trigger cell proliferation signals and confer trastuzumab resistance. Here, we developed a bispecific anti-ErbB2 antibody using trastuzumab and pertuzumab, another ErbB2-specific humanized antibody that binds to a distinct epitope from trastuzumab. This bispecific antibody, denoted as TPL, retained the full binding activities of both parental antibodies and exhibited pharmacokinetic properties similar to those of a conventional immunoglobulin G molecule. Unexpectedly, TPL showed superior ErbB2 heterodimerization-blocking activity over the combination of both parental monoclonal antibodies, possibly through steric hindrance and/or inducing ErbB2 conformational change. Further data indicated that TPL potently abrogated ErbB2 signaling in trastuzumab-resistant breast cancer cell lines. In addition, we showed that TPL was far more effective than trastuzumab plus pertuzumab in inhibiting the growth of trastuzumab-resistant breast cancer cell lines, both in vitro and in vivo. Importantly, TPL treatment eradicated established trastuzumab-resistant tumors in tumor-bearing nude mice. Our results suggest that trastuzumab-resistant breast tumors remain dependent on ErbB2 signaling and that comprehensive blockade of ErbB2 heterodimerization may be an effective therapeutic avenue. The unique potential of TPL to overcome trastuzumab resistance warrants its consideration as a promising treatment in the clinic.

  8. The bradykinin B1 receptor and the central regulation of blood pressure in spontaneously hypertensive rats

    PubMed Central

    Emanueli, Costanza; Chao, Julie; Regoli, Domenico; Chao, Lee; Ni, Aiguo; Madeddu, Paolo

    1999-01-01

    We evaluated if the brain bradykinin (BK) B1 receptor is involved in the regulation of blood pressure (BP) in conscious rats.Basal mean BP and HR were 115±2 and 165±3 mmHg and 345±10 and 410±14 beats min−1 in Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHR), respectively. Intracerebroventricular (i.c.v.) injection of 1 nmol B1 receptor agonist Lys-desArg9-BK significantly increased the BP of WKY and SHR by 7±1 and 19±2 mmHg, respectively. One nmol Sar[D-Phe8]-desArg9-BK, a kininase-resistant B1 agonist, increased the BP of WKY and SHR by 19±2 and 17±2 mmHg, respectively and reduced HR in both strains.I.c.v. injection of 0.01 nmol B1 antagonists, LysLeu8-desArg9-BK or AcLys[D-βNal7,Ile8]-desArg9-BK (R715), significantly decreased mean BP in SHR (by 9±2 mmHg the former and 14±3 mmHg the latter compound), but not in WKY. In SHR, the BP response to R715 was associated to tachycardia.I.c.v. Captopril, a kininase inhibitor, increased the BP of SHR, this response being partially prevented by i.c.v. R715 and reversed into a vasodepressor effect by R715 in combination with the B2 antagonist Icatibant.I.c.v. antisense oligodeoxynucleotides (ODNs) targeted to the B1 receptor mRNA decreased BP in SHR, but not in WKY. HR was not altered in either strain. Distribution of fluorescein-conjugated ODNs was detected in brain areas surrounding cerebral ventricles.Our results indicate that the brain B1 receptor participates in the regulation of BP. Activation of the B1 receptor by kinin metabolites could participate in the pathogenesis of hypertension in SHR. PMID:10372819

  9. 78 FR 30896 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-23

    ...The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This is published to fulfill the requirements of section 155 of Public Law 104-164 dated July 21, 1996.

  10. 78 FR 31523 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-24

    ...The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This is published to fulfill the requirements of section 155 of Public Law 104-164 dated July 21, 1996.

  11. 76 FR 68434 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-04

    ...The Department of Defense is publishing the unclassified text of a section 36(b)(1) arms sales notification. This is published to fulfill the requirements of section 155 of Public Law 104-164 dated July 21, 1996.

  12. Supercritical Fluid Extraction of Aflatoxin B 1 from Soil

    EPA Science Inventory

    This research describes the development of a Supercritical Fluid Extraction (SFE) method to recover aflatoxin B1 from fortified soil. The effects of temperature, pressure, modifier (identity and percentage), and extraction type were assessed. Using the optimized SFE conditions, ...

  13. 26 CFR 31.3306(b)-1 - Wages.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Unemployment Tax Act (Chapter 23, Internal Revenue Code of 1954) § 31.3306(b)-1 Wages. (a) Applicable law and... restaurant or hotel employees, or to seamen or other employees aboard vessels, since generally these items...

  14. Blimp-1-dependent and -independent natural antibody production by B-1 and B-1-derived plasma cells.

    PubMed

    Savage, Hannah P; Yenson, Vanessa M; Sawhney, Sanjam S; Mousseau, Betty J; Lund, Frances E; Baumgarth, Nicole

    2017-09-04

    Natural antibodies contribute to tissue homeostasis and protect against infections. They are secreted constitutively without external antigenic stimulation. The differentiation state and regulatory pathways that enable continuous natural antibody production by B-1 cells, the main cellular source in mice, remain incompletely understood. Here we demonstrate that natural IgM-secreting B-1 cells in the spleen and bone marrow are heterogeneous, consisting of (a) terminally differentiated B-1-derived plasma cells expressing the transcriptional regulator of differentiation, Blimp-1, (b) Blimp-1 + , and (c) Blimp-1 neg phenotypic B-1 cells. Blimp-1 neg IgM-secreting B-1 cells are not simply intermediates of cellular differentiation. Instead, they secrete similar amounts of IgM in wild-type and Blimp-1-deficient (PRDM-1 ΔEx1A ) mice. Blimp-1 neg B-1 cells are also a major source of IgG3. Consequently, deletion of Blimp-1 changes neither serum IgG3 levels nor the amount of IgG3 secreted per cell. Thus, the pool of natural antibody-secreting B-1 cells is heterogeneous and contains a distinct subset of cells that do not use Blimp-1 for initiation or maximal antibody secretion. © 2017 Savage et al.

  15. 17 CFR 240.10b-2 - [Reserved

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false [Reserved] 240.10b-2 Section 240.10b-2 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION (CONTINUED) GENERAL RULES AND REGULATIONS, SECURITIES EXCHANGE ACT OF 1934 Rules and Regulations Under the Securities...

  16. 17 CFR 240.12b-2 - Definitions.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... Securities Act of 1933: Provided, That information contained in any such document shall be deemed to have... 17 Commodity and Securities Exchanges 3 2011-04-01 2011-04-01 false Definitions. 240.12b-2 Section 240.12b-2 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION (CONTINUED) GENERAL...

  17. 26 CFR 53.4942(b)-2 - Alternative tests.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 17 2012-04-01 2012-04-01 false Alternative tests. 53.4942(b)-2 Section 53.4942....4942(b)-2 Alternative tests. (a) Assets test—(1) In general. A private foundation will satisfy the assets test under the provisions of this paragraph if substantially more than half of the foundation's...

  18. 26 CFR 53.4942(b)-2 - Alternative tests.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 17 2011-04-01 2011-04-01 false Alternative tests. 53.4942(b)-2 Section 53.4942....4942(b)-2 Alternative tests. (a) Assets test—(1) In general. A private foundation will satisfy the assets test under the provisions of this paragraph if substantially more than half of the foundation's...

  19. 26 CFR 53.4942(b)-2 - Alternative tests.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 17 2013-04-01 2013-04-01 false Alternative tests. 53.4942(b)-2 Section 53.4942....4942(b)-2 Alternative tests. (a) Assets test—(1) In general. A private foundation will satisfy the assets test under the provisions of this paragraph if substantially more than half of the foundation's...

  20. 26 CFR 53.4942(b)-2 - Alternative tests.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 17 2014-04-01 2014-04-01 false Alternative tests. 53.4942(b)-2 Section 53.4942....4942(b)-2 Alternative tests. (a) Assets test—(1) In general. A private foundation will satisfy the assets test under the provisions of this paragraph if substantially more than half of the foundation's...

  1. 26 CFR 53.4942(b)-2 - Alternative tests.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 17 2010-04-01 2010-04-01 false Alternative tests. 53.4942(b)-2 Section 53.4942....4942(b)-2 Alternative tests. (a) Assets test—(1) In general. A private foundation will satisfy the assets test under the provisions of this paragraph if substantially more than half of the foundation's...

  2. Interconversion of aflatoxin B1 and aflatoxicol by several fungi.

    PubMed

    Nakazato, M; Morozumi, S; Saito, K; Fujinuma, K; Nishima, T; Kasai, N

    1990-05-01

    Four fungal strains, namely, Aspergillus niger, Eurotium herbariorum, a Rhizopus sp., and non-aflatoxin (AF)-producing Aspergillus flavus, which could convert AF-B1 to aflatoxicol (AFL), could also reconvert AFL to AF-B1. The interconversion of AF-B1 to AFL and of AFL to AF-B1 was ascertained to occur during proliferation of the fungi. These reactions were distinctly observed in cell-free systems obtained from disrupted mycelia of A. flavus and the Rhizopus sp., but they were not observed in culture filtrates from intact (nondisrupted) mycelia of the same strains. The interconversion activities of AF-B1 and AFL were not observed when the cell-free systems were preheated at 100 degrees C. These findings strongly suggest that the interconversion of AF-B1 and AFL is mediated by intracellular enzymes of A. flavus and the Rhizopus sp. In addition, the isomerization of AFL-A to AFL-B observed in culture medium was also found to occur by the lowering of the culture pH.

  3. UNC93B1 mediates differential trafficking of endosomal TLRs

    PubMed Central

    Lee, Bettina L; Moon, Joanne E; Shu, Jeffrey H; Yuan, Lin; Newman, Zachary R; Schekman, Randy; Barton, Gregory M

    2013-01-01

    UNC93B1, a multipass transmembrane protein required for TLR3, TLR7, TLR9, TLR11, TLR12, and TLR13 function, controls trafficking of TLRs from the endoplasmic reticulum (ER) to endolysosomes. The mechanisms by which UNC93B1 mediates these regulatory effects remain unclear. Here, we demonstrate that UNC93B1 enters the secretory pathway and directly controls the packaging of TLRs into COPII vesicles that bud from the ER. Unlike other COPII loading factors, UNC93B1 remains associated with the TLRs through post-Golgi sorting steps. Unexpectedly, these steps are different among endosomal TLRs. TLR9 requires UNC93B1-mediated recruitment of adaptor protein complex 2 (AP-2) for delivery to endolysosomes while TLR7, TLR11, TLR12, and TLR13 utilize alternative trafficking pathways. Thus, our study describes a mechanism for differential sorting of endosomal TLRs by UNC93B1, which may explain the distinct roles played by these receptors in certain autoimmune diseases. DOI: http://dx.doi.org/10.7554/eLife.00291.001 PMID:23426999

  4. The 1990 vertical distribution of two important halons (F-12B1 and F-13B1) in the tropics

    NASA Technical Reports Server (NTRS)

    Singh, O. N.; Borchers, R.; Lal, Shyam; Subbarya, B. H.; Krueger, Bernd C.; Fabian, Peter

    1994-01-01

    The first vertical profiles of F-12B1 and F-13B1 had been obtained in the tropical troposphere and stratosphere by us in 1987. The measurement of these substances responsible for almost the entire anthropogenic contribution to the stratospheric BrO(x) budget is important in the tropics, as tropical upwelling provides their injection along with that of other pollutants, into the stratosphere. To ascertain the trends of these distributions and foster the data, the 1987 experiment was repeated in April 1990. Like 1987, the MPAE cryogenic whole air sampler was launched on a balloon from Hyderabad, India (17.5 deg N), and 14 samples were collected between 10 and 35 km altitude. The results obtained by means of GC and GC-MS analyses showed that the atmospheric abundance of both F-12B1 and F-13B1 is increasing at a fast rate, respectively by about 15 percent and 10 percent per year. From 1987 to 1990, F-12B1 and F-13B1 tropospheric mixing ratios have been growing from 1.2 and 1.3 ppt to 1.8 and 1.7 ppt, respectively. The vertical profiles will be discussed.

  5. Continuum radiative transfer Modeling of Sagittarius B2

    NASA Astrophysics Data System (ADS)

    Schmiedeke, A.; Schilke, P.; Möller, Th.; Sánchez-Monge, Á.; Bergin, E.; Comito, C.; Csengeri, T.; Lis, D. C.; Molinari, S.; Qin, S. L.; Rolffs, R.

    2015-05-01

    We present results from radiative transfer modeling of the continuum emission towards Sagittarius B2 (hereafter Sgr B2). We have developed a radiative transfer framework - Pandora - that employs RADMC-3D (Dullemond 2012) for a self-consistent determination of the dust temperature. With this pipeline, we have set-up a single model that consistently reproduces the thermal dust and free-free continuum emission of Sgr B2 spanning four orders of magnitude in spatial scales (0.02-45 pc) and two orders of magnitude in frequency (20-4000 GHz).

  6. Identifying transient protein-protein interactions in EphB2 signaling by Blue Native PAGE and Mass Spectrometry

    PubMed Central

    Darie, Costel C.; Deinhardt, Katrin; Zhang, Guoan; Cardasis, Helene S.; Chao, Moses V.; Neubert, Thomas A.

    2012-01-01

    Receptor tyrosine kinases (RTKs) are proteins that upon ligand stimulation undergo dimerization and autophosphorylation. Eph receptors (EphRs) are RTKs that are found in different cell types, from both tissues that are developing and from mature tissues and play important roles in the development of the central nervous system and peripheral nervous system. EphRs also play roles in synapse formation, neural crest formation, angiogenesis and in remodeling the vascular system. Interaction of EphRs with their ephrin ligands leads to activation of signal transduction pathways and to formation of many transient protein-protein interactions that ultimately leads to cytoskeletal remodeling. However, the sequence of events at the molecular level is not well-understood. We used Blue Native PAGE (BN-PAGE) and mass spectrometry (MS) to analyze the transient protein-protein interactions that resulted from stimulation of EphB2 receptors by their ephrinB1-Fc ligands. We analyzed the phosphotyrosine-containing protein complexes immunoprecipitated (pY-IPs) from the cell lysates of both unstimulated (−) and ephrinB1-Fc-stimulated (+) NG108 cells. Our experiments allowed us to identify many signaling proteins, either known to be part of EphB2 signaling or new for this pathway, which are involved in transient protein-protein interactions upon ephrinB1-Fc stimulation. These data led us to investigate the roles in EphB2 signaling of proteins such as FAK, WAVEs, and Nischarin. PMID:21932443

  7. Occurrence of aflatoxin B1 in natural products

    PubMed Central

    Prado, Guilherme; Altoé, Aline F.; Gomes, Tatiana C. B.; Leal, Alexandre S.; Morais, Vanessa A. D.; Oliveira, Marize S.; Ferreira, Marli B.; Gomes, Mateus B.; Paschoal, Fabiano N.; von S. Souza, Rafael; Silva, Daniela A.; Cruz Madeira, Jovita E. G.

    2012-01-01

    The media claims for the consumption of natural resource-based food have gradually increased in both developing and developed countries. The interest in the safety of these products is partially due to the possible presence of toxigenic fungi acting as mycotoxin producers, such as aflatoxins produced during the secondary metabolism of Aspergillus flavus, A. parasiticus and A. nomius. Aflatoxins, mainly aflatoxin B1, are directly associated with liver cancer in human beings. This paper is aimed at evaluating the presence of aflatoxin B1 in a few vegetable drugs, dried plant extracts and industrialized products traded in 2010 in the city of Belo Horizonte, State of Minas Gerais, Brazil. The method used for the quantification of aflatoxin B1 was based on extraction through acetone:water (85:15), immunoaffinity column purification followed by separation and detection in high efficiency liquid chromatography. Under the conditions of analysis, the Limits of Detection and Quantification were 0.6 µg kg-1 and 1.0 µg kg-1 respectively. The complete sets of analyses were carried out in duplicate. Aflatoxin B1 was noticed in a single sample (< 1.0 µg kg-1). The results revealed low aflatoxin B1 contamination in the products under analysis. However, it is required to establish a broad monitoring program in order to obtain additional data and check up on the actual extension of contamination. PMID:24031973

  8. Vitamin B1 Deficiency Does not Affect the Liver Concentrations of the Other Seven Kinds of B-Group Vitamins in Rats

    PubMed Central

    Shibata, Katsumi; Shimizu, Atsushi; Fukuwatari, Tsutomu

    2013-01-01

    We aimed to determine the effects of vitamin B1 deficiency on vitamin contents of urine, liver, and blood. In the current study, rats were divided into 3 groups (n = 5, each group): the first was freely fed a complete diet (ad lib-fed control group); the second freely fed a vitamin B1-free diet (vitamin B1 deficient group); and the third pair-fed a complete diet with the same amounts of the vitamin B1 deficient group (pair-fed control group). The experimental period was for 15 days. The blood concentrations of vitamin B2, PLP, vitamin B12, folic acid, and biotin were lower in the pair-fed control than in the ad lib-fed control and those of nicotinamide and pantothenic acid were the same. We conclude that Vitamin B1 deficiency did not affect concentrations of the other B-group vitamins. PMID:23935367

  9. Bending strain tolerance of MgB2 superconducting wires

    NASA Astrophysics Data System (ADS)

    Kováč, P.; Hušek, I.; Melišek, T.; Kulich, M.; Kopera, L.

    2016-04-01

    This work describes the strain tolerance of MgB2 superconductors subjected to variable bending stresses. Bending of MgB2 wire was done at room temperature in different modes: (i) direct bending of straight annealed samples to variable diameters and by (ii) indirect bending by straightening of bent and annealed samples. I c-bending strain characteristics of samples made by in situ PIT and by the internal magnesium diffusion (IMD) process were measured at 4.2 K. The results show a good agreement between the direct and indirect bending mode, which allows easier estimation of limits important for the winding process of MgB2 superconductors with brittle filaments. A comparison of MgB2 wires made by in situ PIT and IMD processes showed improved strain tolerance for IMD due to better grain connectivity the low annealing temperature, which does not appear to reduce the mechanical strength of sheath material.

  10. B-B bond activation and NHC ring-expansion reactions of diboron(4) compounds, and accurate molecular structures of B2(NMe2)4, B2eg2, B2neop2 and B2pin2.

    PubMed

    Eck, Martin; Würtemberger-Pietsch, Sabrina; Eichhorn, Antonius; Berthel, Johannes H J; Bertermann, Rüdiger; Paul, Ursula S D; Schneider, Heidi; Friedrich, Alexandra; Kleeberg, Christian; Radius, Udo; Marder, Todd B

    2017-03-14

    In this detailed study we report on the structures of the widely employed diboron(4) compounds bis(pinacolato)diboron (B 2 pin 2 ) and bis(neopentyl glycolato)diboron (B 2 neop 2 ), as well as bis(ethylene glycolato)diboron (B 2 eg 2 ) and tetrakis(dimethylamino)diboron (B 2 (NMe 2 ) 4 ), and their reactivity, along with that of bis(catecholato)diboron (B 2 cat 2 ) with backbone saturated and backbone unsaturared N-heterocyclic carbenes (NHCs) of different steric demand. Depending on the nature of the diboron(4) compound and the NHC used, Lewis-acid/Lewis-base adducts or NHC ring-expansion products stemming from B-B and C-N bond activation have been observed. The corresponding NHC adducts and NHC ring-expanded products were isolated and characterised via solid-state and solution NMR spectroscopy and X-ray diffraction. In general, we observed B-B bond and C-N bond activation at low temperature for B 2 eg 2 , at room temperature for B 2 neop 2 and at higher temperature for B 2 cat 2 . The reactivity strongly depends on steric effects of the NHCs and the diboron(4) compounds, as well as on the corresponding Lewis-basicity and Lewis-acidity. Our results provide profound insight into the chemistry of these diboron(4) reagents with the nowadays ubiquitous NHCs, the stability of the corresponding NHC adducts and on B-B bond activation using Lewis-bases in general. We demonstrate that B-B bond activation may be triggered even at temperatures as low as -40 °C to -30 °C without any metal species involved. For example, the reactions of B 2 eg 2 with sterically less demanding NHCs such as Me 2 Im Me and iPr 2 Im in solution led to the corresponding ring-expanded products at low temperatures. Furthermore, boronium [L 2 B(OR) 2 ] + and borenium [LB(OR) 2 ] + cations have been observed from the reaction of the bis-borate B 2 eg 3 with the NHCs iPr 2 Im and Me 2 Im Me , which led to the conclusion that the activation of bis-borates with NHCs (or Lewis-bases in general) might be

  11. Rapid on-site sensing aflatoxin B1 in food and feed via a chromatographic time-resolved fluoroimmunoassay.

    PubMed

    Zhang, Zhaowei; Tang, Xiaoqian; Wang, Du; Zhang, Qi; Li, Peiwu; Ding, Xiaoxia

    2015-01-01

    Aflatoxin B1 poses grave threats to food and feed safety due to its strong carcinogenesis and toxicity, thus requiring ultrasensitive rapid on-site determination. Herein, a portable immunosensor based on chromatographic time-resolved fluoroimmunoassay was developed for sensitive and on-site determination of aflatoxin B1 in food and feed samples. Chromatographic time-resolved fluoroimmunoassay offered a magnified positive signal and low signal-to-noise ratio in time-resolved mode due to the absence of noise interference caused by excitation light sources. Compared with the immunosensing performance in previous studies, this platform demonstrated a wider dynamic range of 0.2-60 μg/kg, lower limit of detection from 0.06 to 0.12 µg/kg, and considerable recovery from 80.5% to 116.7% for different food and feed sample matrices. It was found to be little cross-reactivity with other aflatoxins (B2, G1, G2, and M1). In the case of determination of aflatoxin B1 in peanuts, corn, soy sauce, vegetable oil, and mouse feed, excellent agreement was found when compared with aflatoxin B1 determination via the conversational high-performance liquid chromatography method. The chromatographic time-resolved fluoroimmunoassay affords a powerful alternative for rapid on-site determination of aflatoxin B1 and holds a promise for food safety in consideration of practical food safety and environmental monitoring.

  12. Rapid On-Site Sensing Aflatoxin B1 in Food and Feed via a Chromatographic Time-Resolved Fluoroimmunoassay

    PubMed Central

    Wang, Du; Zhang, Qi; Li, Peiwu; Ding, Xiaoxia

    2015-01-01

    Aflatoxin B1 poses grave threats to food and feed safety due to its strong carcinogenesis and toxicity, thus requiring ultrasensitive rapid on-site determination. Herein, a portable immunosensor based on chromatographic time-resolved fluoroimmunoassay was developed for sensitive and on-site determination of aflatoxin B1 in food and feed samples. Chromatographic time-resolved fluoroimmunoassay offered a magnified positive signal and low signal-to-noise ratio in time-resolved mode due to the absence of noise interference caused by excitation light sources. Compared with the immunosensing performance in previous studies, this platform demonstrated a wider dynamic range of 0.2-60 μg/kg, lower limit of detection from 0.06 to 0.12 µg/kg, and considerable recovery from 80.5% to 116.7% for different food and feed sample matrices. It was found to be little cross-reactivity with other aflatoxins (B2, G1, G2, and M1). In the case of determination of aflatoxin B1 in peanuts, corn, soy sauce, vegetable oil, and mouse feed, excellent agreement was found when compared with aflatoxin B1 determination via the conversational high-performance liquid chromatography method. The chromatographic time-resolved fluoroimmunoassay affords a powerful alternative for rapid on-site determination of aflatoxin B1 and holds a promise for food safety in consideration of practical food safety and environmental monitoring. PMID:25874803

  13. Formation of polycrystalline MgB2 synthesized by powder in sealed tube method with different initial boron phase

    NASA Astrophysics Data System (ADS)

    Yudanto, Sigit Dwi; Imaduddin, Agung; Kurniawan, Budhy; Manaf, Azwar

    2018-04-01

    Magnesium diboride, MgB2 is a new high critical temperature superconductor that discovered in the beginning of the 21st century. The MgB2 has a simple crystal structure and a high critical temperature, which can be manufactured in several forms like thin films, tapes, wires including bulk in the large scale. For that reason, the MgB2 has good prospects for various applications in the field of electronic devices. In the current work, we have explored the synthesis of MgB2 polycrystalline using powder in a sealed tube method. Different initial boron phase for the synthesized of MgB2 polycrystalline were used. These were, in addition to magnesium powders, crystalline boron, amorphous boron and combination both of them were respectively fitted in the synthesis. The raw materials were mixed in a stoichiometric ratio of Mg: B=1:2, ground using agate mortar, packed into stainless steel SS304. The pack was then sintered at temperature of 800°C for 2 hours in air atmosphere. Phase formation of MgB2 polycrystalline in difference of initial boron phase was characterized using XRD and SEM. Referring to the diffraction pattern and microstructure observation, MgB2 polycrystalline was formed, and the formation was effective when using the crystalline Mg and fully amorphous B as the raw materials. The critical temperature of the specimen was evaluated by the cryogenic magnet. The transition temperature of the MgB2 specimen synthesized using crystalline magnesium and full amorphous boron is 42.678 K (ΔTc = 0.877 K).

  14. 17 CFR 240.9b-1 - Options disclosure document.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 17 Commodity and Securities Exchanges 3 2011-04-01 2011-04-01 false Options disclosure document... Securities Exchange Act of 1934 Hypothecation of Customers' Securities § 240.9b-1 Options disclosure document. (a) Definitions. The following definitions shall apply for the purpose of this rule. (1) Options...

  15. 17 CFR 240.9b-1 - Options disclosure document.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Options disclosure document... Securities Exchange Act of 1934 Hypothecation of Customers' Securities § 240.9b-1 Options disclosure document. (a) Definitions. The following definitions shall apply for the purpose of this rule. (1) Options...

  16. 76 FR 60469 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-29

    ... Proposed Issuance of Letter of Offer Pursuant to Section 36(b)(1) of the Arms Export Control Act, as... Other 400 million Total 750 million * As defined in Section 47(6) of the Arms Export Control Act. (iii... Export Control Act Annex Item No. vii (vii) Sensitivity of Technology: 1. The MH-60R SEAHAWK Multi...

  17. 77 FR 38777 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-06-29

    ... Issuance of Letter of Offer Pursuant to Section 36(b)(1) of the Arms Export Control Act, as amended (i... billion. Total 1.015 billion. * As defined in Section 47(6) of the Arms Export Control Act. (iii... Systems (SINCGARS), 200 M2 Chrysler Mount Machine Guns, 400 7.62MM M240 Machine Guns, 12,049,842...

  18. 77 FR 49434 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-16

    ... Pursuant to Section 36(b)(1) of the Arms Export Control Act, as Amended (i) Prospective Purchaser: Brazil... Standard (RAM/RS), with ancillary equipment, and machine guns. Also included are the upgrade of Brazil's... Maintainability/Rebuild to Standard (RAM/RS), with ancillary equipment, and machine guns. Also included are the...

  19. 26 CFR 31.3306(b)-1 - Wages.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) EMPLOYMENT TAXES AND COLLECTION OF INCOME TAX AT SOURCE EMPLOYMENT TAXES AND COLLECTION OF INCOME TAX AT SOURCE Federal Unemployment Tax Act (Chapter 23, Internal Revenue Code of 1954) § 31.3306(b)-1 Wages. (a) Applicable law and...

  20. 26 CFR 31.3306(b)-1 - Wages.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) EMPLOYMENT TAXES AND COLLECTION OF INCOME TAX AT SOURCE EMPLOYMENT TAXES AND COLLECTION OF INCOME TAX AT SOURCE Federal Unemployment Tax Act (Chapter 23, Internal Revenue Code of 1954) § 31.3306(b)-1 Wages. (a) Applicable law and...

  1. 26 CFR 31.3306(b)-1 - Wages.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) EMPLOYMENT TAXES AND COLLECTION OF INCOME TAX AT SOURCE EMPLOYMENT TAXES AND COLLECTION OF INCOME TAX AT SOURCE Federal Unemployment Tax Act (Chapter 23, Internal Revenue Code of 1954) § 31.3306(b)-1 Wages. (a) Applicable law and...

  2. 26 CFR 31.3306(b)-1 - Wages.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) EMPLOYMENT TAXES AND COLLECTION OF INCOME TAX AT SOURCE EMPLOYMENT TAXES AND COLLECTION OF INCOME TAX AT SOURCE Federal Unemployment Tax Act (Chapter 23, Internal Revenue Code of 1954) § 31.3306(b)-1 Wages. (a) Applicable law and...

  3. 77 FR 13564 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-07

    ... to better support its own air defense needs. The proposed sale of AIM-9X-2 missiles will enhance... DEPARTMENT OF DEFENSE Office of the Secretary [Transmittal Nos. 11-53] 36(b)(1) Arms Sales Notification AGENCY: Department of Defense, Defense Security Cooperation Agency. ACTION: Notice. SUMMARY: The...

  4. 26 CFR 31.3231(b)-1 - Who are employees.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... TAXES AND COLLECTION OF INCOME TAX AT SOURCE EMPLOYMENT TAXES AND COLLECTION OF INCOME TAX AT SOURCE Railroad Retirement Tax Act (Chapter 22, Internal Revenue Code of 1954) General Provisions § 31.3231(b)-1... operations consisting of the mining of coal, the preparation of coal, the handling (other than movement by...

  5. 26 CFR 1.167(b)-1 - Straight line method.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 2 2010-04-01 2010-04-01 false Straight line method. 1.167(b)-1 Section 1.167(b... Straight line method. (a) In general. Under the straight line method the cost or other basis of the... may be reduced to a percentage or fraction. The straight line method may be used in determining a...

  6. Lattice Thermal Conductivity of Ultra High Temperature Ceramics ZrB2 and HfB2 from Atomistic Simulations

    NASA Technical Reports Server (NTRS)

    Lawson, John W.; Murray, Daw S.; Bauschlicher, Charles W., Jr.

    2011-01-01

    Atomistic Green-Kubo simulations are performed to evaluate the lattice thermal conductivity for single crystals of the ultra high temperature ceramics ZrB2 and HfB2 for a range of temperatures. Recently developed interatomic potentials are used for these simulations. Heat current correlation functions show rapid oscillations which can be identified with mixed metal-Boron optical phonon modes. Agreement with available experimental data is good.

  7. On the active site of mononuclear B1 metallo β-lactamases: a computational study

    NASA Astrophysics Data System (ADS)

    Sgrignani, Jacopo; Magistrato, Alessandra; Dal Peraro, Matteo; Vila, Alejandro J.; Carloni, Paolo; Pierattelli, Roberta

    2012-04-01

    Metallo-β-lactamases (MβLs) are Zn(II)-based bacterial enzymes that hydrolyze β-lactam antibiotics, hampering their beneficial effects. In the most relevant subclass (B1), X-ray crystallography studies on the enzyme from Bacillus Cereus point to either two zinc ions in two metal sites (the so-called `3H' and `DCH' sites) or a single Zn(II) ion in the 3H site, where the ion is coordinated by Asp120, Cys221 and His263 residues. However, spectroscopic studies on the B1 enzyme from B. Cereus in the mono-zinc form suggested the presence of the Zn(II) ion also in the DCH site, where it is bound to an aspartate, a cysteine, a histidine and a water molecule. A structural model of this enzyme in its DCH mononuclear form, so far lacking, is therefore required for inhibitor design and mechanistic studies. By using force field based and mixed quantum-classical (QM/MM) molecular dynamics (MD) simulations of the protein in aqueous solution we constructed such structural model. The geometry and the H-bond network at the catalytic site of this model, in the free form and in complex with two common β-lactam drugs, is compared with experimental and theoretical findings of CphA and the recently solved crystal structure of new B2 MβL from Serratia fonticola (Sfh-I). These are MβLs from the B2 subclass, which features an experimentally well established mono-zinc form, in which the Zn(II) is located in the DCH site. From our simulations the ɛɛδ and δɛδ protomers emerge as possible DCH mono-zinc reactive species, giving a novel contribution to the discussion on the MβL reactivity and to the drug design process.

  8. Magnetic resonance imaging is comparable to computed tomography for determination of glenoid version but does not accurately distinguish between Walch B2 and C classifications.

    PubMed

    Lowe, Jeremiah T; Testa, Edward J; Li, Xinning; Miller, Suzanne; DeAngelis, Joseph P; Jawa, Andrew

    2017-04-01

    Computed tomography (CT) scan is the standard for the preoperative assessment of glenoid version and morphology before total shoulder arthroplasty. However, the capacity of magnetic resonance imaging (MRI) to visualize bone morphology has improved with advancing technology. The purpose of this study was to compare the accuracy of MRI to CT for assessment of glenoid version and Walch classification. Three fellowship-trained shoulder surgeons assessed glenoid version and Walch classification of 30 patients with primary shoulder osteoarthritis who received both CT and MRI scans before total shoulder arthroplasty. Version measurements, Walch classification, and observer agreement were compared. Mean glenoid version was -15.5° and -18.6° by CT and MRI, respectively (P = .17). Interobserver reliability coefficients were good for both imaging modalities (CT, 0.73; MRI, 0.62). Intraobserver coefficients were good to excellent for CT (range, 0.76-0.87) and good for MRI (range, 0.75-0.79). For Walch classification, interobserver reliability for both modalities was merely fair, whereas intraobserver reliability was moderate to good. Although identification of type A1, A2, and B1 was nearly identical between CT and MRI, there was observer disagreement on type B2 (P = .001) and C glenoids (P = .03). Specifically, MRI underidentified type B2 and overidentified type C compared with CT. MRI is largely comparable to CT scan for evaluation of the glenoid, with similar measurements of version and identification of less extreme Walch glenoids. However, MRI is less accurate at distinguishing between type B2 and C glenoids. Copyright © 2017 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

  9. A systematic expression analysis implicates Plexin-B2 and its ligand Sema4C in the regulation of the vascular and endocrine system.

    PubMed

    Zielonka, Matthias; Xia, Jingjing; Friedel, Roland H; Offermanns, Stefan; Worzfeld, Thomas

    2010-09-10

    Plexins serve as receptors for semaphorins and play important roles in the developing nervous system. Plexin-B2 controls decisive developmental programs in the neural tube and cerebellum. However, whether Plexin-B2 also regulates biological functions in adult nonneuronal tissues is unknown. Here we show by two methodologically independent approaches that Plexin-B2 is expressed in discrete cell types of several nonneuronal tissues in the adult mouse. In the vasculature, Plexin-B2 is selectively expressed in functionally specialized endothelial cells. In endocrine organs, Plexin-B2 localizes to the pancreatic islets of Langerhans and to both cortex and medulla of the adrenal gland. Plexin-B2 expression is also detected in certain types of immune and epithelial cells. In addition, we report on a systematic comparison of the expression patterns of Plexin-B2 and its ligand Sema4C, which show complementarity or overlap in some but not all tissues. Furthermore, we demonstrate that Plexin-B2 and its family member Plexin-B1 display largely nonredundant expression patterns. This work establishes Plexin-B2 and Sema4C as potential regulators of the vascular and endocrine system and provides an anatomical basis to understand the biological functions of this ligand-receptor pair. Copyright 2010 Elsevier Inc. All rights reserved.

  10. SEMA3C drives cancer growth by transactivating multiple receptor tyrosine kinases via Plexin B1.

    PubMed

    Peacock, James W; Takeuchi, Ario; Hayashi, Norihiro; Liu, Liangliang; Tam, Kevin J; Al Nakouzi, Nader; Khazamipour, Nastaran; Tombe, Tabitha; Dejima, Takashi; Lee, Kevin Ck; Shiota, Masaki; Thaper, Daksh; Lee, Wilson Cw; Hui, Daniel Hf; Kuruma, Hidetoshi; Ivanova, Larissa; Yenki, Parvin; Jiao, Ivy Zf; Khosravi, Shahram; Mui, Alice L-F; Fazli, Ladan; Zoubeidi, Amina; Daugaard, Mads; Gleave, Martin E; Ong, Christopher J

    2018-02-01

    Growth factor receptor tyrosine kinase (RTK) pathway activation is a key mechanism for mediating cancer growth, survival, and treatment resistance. Cognate ligands play crucial roles in autocrine or paracrine stimulation of these RTK pathways. Here, we show SEMA3C drives activation of multiple RTKs including EGFR, ErbB2, and MET in a cognate ligand-independent manner via Plexin B1. SEMA3C expression levels increase in castration-resistant prostate cancer (CRPC), where it functions to promote cancer cell growth and resistance to androgen receptor pathway inhibition. SEMA3C inhibition delays CRPC and enzalutamide-resistant progression. Plexin B1 sema domain-containing:Fc fusion proteins suppress RTK signaling and cell growth and inhibit CRPC progression of LNCaP xenografts post-castration in vivo SEMA3C inhibition represents a novel therapeutic strategy for treatment of advanced prostate cancer. © 2018 The Authors. Published under the terms of the CC BY 4.0 license.

  11. ORM-Based Semantics of B2B Transactions

    NASA Astrophysics Data System (ADS)

    Balsters, H.; van Blommestein, F.

    After widespread implementation of Enterprise Resource Planning and Personal Information Management, the next wave in the application of ICT is headed towards business to business (B2B) communication. B2B has a number of specific aspects, one of them being negotiation. This aspect has been largely neglected by present implementations of standard EDI- or XML-messaging and by B2B webservice implementations. In this paper a precise model is given of the negotiation process. The requirements of a potential Buyer and the offer of a potential Seller are matched and, if the negotiation is successful, a contract is concluded. The negotiation process model is represented in ORM, extended with dynamic constraints. Our model may be implemented in the databases of the trading partners and in message- or service definitions.

  12. Josephson Effect in MgB2 Break Junctions

    NASA Astrophysics Data System (ADS)

    Gonnelli, R. S.; Calzolari, A.; Daghero, D.; Ummarino, G. A.; Stepanov, V. A.; Giunchi, G.; Ceresara, S.; Ripamonti, G.

    2001-08-01

    We present the first observation of the dc and ac Josephson effect in MgB2 break junctions. The junctions, obtained at 4.2 K in high-quality, high-density polycrystalline metallic MgB2 samples, show a nonhysteretic dc Josephson effect. By irradiating the junctions with microwaves we observe clear Shapiro steps spaced by the ideal ΔV value. The temperature dependence of the dc Josephson current and the dependence of the height of the steps on the microwave power are obtained. These results directly prove the existence of pairs with charge 2e in MgB2 and give evidence of the superconductor-normal metal-superconductor weak link character of these junctions.

  13. Tissue Kallikrein Alleviates Cerebral Ischemia-Reperfusion Injury by Activating the B2R-ERK1/2-CREB-Bcl-2 Signaling Pathway in Diabetic Rats

    PubMed Central

    Yuan, Kunxiong; Hu, Bin; Sang, Hongfei; Xie, Yi; Xu, Lili; Cao, Qinqin; Chen, Xin; Zhao, Lingling; Liu, Xinfeng; Liu, Ling; Zhang, Renliang

    2016-01-01

    Diabetes mellitus (DM) substantially increases the risk of ischemic stroke and reduces the tolerance to ischemic insults. Tissue kallikrein (TK) has been demonstrated to protect neurons from ischemia/reperfusion (I/R) injury in orthoglycemic model by activating the bradykinin B2 receptor (B2R). Considering the differential effects of B2R or bradykinin B1 receptor (B1R) on cardioprotection and neuroprotection in I/R with or without diabetes, this study was designed to investigate the role of TK during cerebral I/R injury in streptozotocin-induced diabetic rats. Intravenous injection of TK inhibited apoptosis in neurons, alleviated edema and inflammatory reactions after focal cerebral I/R, significantly reduced the infarct volume, and improved functional recovery. These beneficial effects were accompanied by activation of the extracellular signal-regulated kinase 1/2 (ERK1/2), cAMP response element-binding (CREB), and Bcl-2 signal proteins. Inhibition of the B2R or ERK1/2 pathway abated the effects of TK, whereas an antagonist of B1R enhanced the effects. These findings reveal that the neuroprotective effect of TK against cerebral I/R injury in streptozotocin-induced diabetic rats mainly involves the enhancement of B2R and ERK1/2-CREB-Bcl-2 signaling pathway activity. PMID:27446506

  14. Selective inhibitor of platelet-activating factor acetylhydrolases 1b2 and 1b3 that impairs cancer cell survival.

    PubMed

    Chang, Jae Won; Zuhl, Andrea M; Speers, Anna E; Niessen, Sherry; Brown, Steven J; Mulvihill, Melinda M; Fan, Yi Chiao; Spicer, Timothy P; Southern, Mark; Scampavia, Louis; Fernandez-Vega, Virneliz; Dix, Melissa M; Cameron, Michael D; Hodder, Peter S; Rosen, Hugh; Nomura, Daniel K; Kwon, Ohyun; Hsu, Ku-Lung; Cravatt, Benjamin F

    2015-04-17

    Platelet-activating factor acetylhydrolases (PAFAHs) 1b2 and 1b3 are poorly characterized serine hydrolases that form a complex with a noncatalytic protein (1b1) to regulate brain development, spermatogenesis, and cancer pathogenesis. Determining physiological substrates and biochemical functions for the PAFAH1b complex would benefit from selective chemical probes that can perturb its activity in living systems. Here, we report a class of tetrahydropyridine reversible inhibitors of PAFAH1b2/3 discovered using a fluorescence polarization-activity-based protein profiling (fluopol-ABPP) screen of the NIH 300,000+ compound library. The most potent of these agents, P11, exhibited IC50 values of ∼40 and 900 nM for PAFAH1b2 and 1b3, respectively. We confirm selective inhibition of PAFAH1b2/3 in cancer cells by P11 using an ABPP protocol adapted for in situ analysis of reversible inhibitors and show that this compound impairs tumor cell survival, supporting a role for PAFAH1b2/3 in cancer.

  15. Novel Drugs that Target ErbB2

    DTIC Science & Technology

    2011-05-01

    fatty acid amide hydrolase ( FAAH ) would increase production of endocannabinoids, we investigated the effects of FAAH knockdown by RNA interference on...expression of Sp proteins and ErbB2 (Supplemental Figure 1). The results show that FAAH knockdown does not affect expression of Sp1 or ErbB2...suggesting that the effects of BA are not due to inhibition of FAAH . Previous studies showed that drug-induced repression of Sp1, Sp3 and Sp4 mRNA

  16. Josephson tunneling in MgB 2 break junctions

    NASA Astrophysics Data System (ADS)

    Li, Zhuang-Zhi; Xuan, Yi; Tao, Hong-Jie; Luo, Peng-Shun; Ren, Zhi-An; Che, Guang-Can; Zhao, Bai-Ru; Zhao, Zhong-Xian

    2002-04-01

    Josephson effects in break junctions of MgB 2 sintered at ambient pressure, have been investigated. The measured I- V characteristics of the junctions and the current step heights of the Shapiro steps can well be fitted with the resistively shunted junction model. Relatively large IcRn was obtained, which ranges from 1.4 to 4.2 mV. The temperature dependence of the Josephson critical current indicated that our break junctions were of the SNS weak link. The apparent deviation in the Fraunhofer pattern implied inhomogeneous current flow in the MgB 2 break junctions.

  17. Lamin B1 mediated demyelination: Linking Lamins, Lipids and Leukodystrophies

    PubMed Central

    Padiath, Quasar S.

    2016-01-01

    ABSTRACT Autosomal Dominant Leukodystrophy (ADLD), a fatal adult onset demyelinating disorder, is the only human disease that has been linked to mutations of the nuclear lamina protein, lamin B1, and is primarily caused by duplications of the LMNB1 gene. Why CNS myelin is specifically targeted and the mechanisms underlying ADLD are unclear. Recent work from our group has demonstrated that over expression of lamin B1 in oligodendrocytes, the myelin producing cells in the CNS, resulted in age dependent epigenetic modifications, transcriptional down-regulation of lipogenic gene expression and significant reductions of myelin-enriched lipids. Given the high lipid content of meylin, we hypothesize that lipid loss is one of the primary drivers of the demyelination phenotype. These results can, at least partially, explain the age dependence and cell type specificity in ADLD and are discussed in the context of the existing literature, in an attempt to delineate potential pathways underlying the disease phenotype. PMID:27854160

  18. High temperature Ir segregation in Ir-B ceramics: Effect of oxygen presence on stability of IrB 2 and other Ir-B phases

    DOE PAGES

    Xie, Zhilin; Terracciano, Anthony C.; Cullen, David A.; ...

    2015-05-13

    The formation of IrB 2, IrB 1.35, IrB 1.1 and IrB monoboride phases in the Ir–B ceramic nanopowder was confirmed during mechanochemical reaction between metallic Ir and elemental B powders. The Ir–B phases were analysed after 90 h of high energy ball milling and after annealing of the powder for 72 h at 1050°C in vacuo. The iridium monoboride (IrB) orthorhombic phase was synthesised experimentally for the first time and identified by powder X-ray diffraction. Additionally, the ReB 2 type IrB 2 hexagonal phase was also produced for the first time and identified by high resolution transmission electron microscope. Irmore » segregation along disordered domains of the boron lattice was found to occur during high temperature annealing. Furthermore, these nanodomains may have useful catalytic properties.« less

  19. The minimal-ABC trees with B1-branches.

    PubMed

    Dimitrov, Darko; Du, Zhibin; Fonseca, Carlos M da

    2018-01-01

    The atom-bond connectivity index (or, for short, ABC index) is a molecular structure descriptor bridging chemistry to graph theory. It is probably the most studied topological index among all numerical parameters of a graph that characterize its topology. For a given graph G = (V, E), the ABC index of G is defined as [Formula: see text], where di denotes the degree of the vertex i, and ij is the edge incident to the vertices i and j. A combination of physicochemical and the ABC index properties are commonly used to foresee the bioactivity of different chemical composites. Additionally, the applicability of the ABC index in chemical thermodynamics and other areas of chemistry, such as in dendrimer nanostars, benzenoid systems, fluoranthene congeners, and phenylenes is well studied in the literature. While finding of the graphs with the greatest ABC-value is a straightforward assignment, the characterization of the tree(s) with minimal ABC index is a problem largely open and has recently given rise to numerous studies and conjectures. A B1-branch of a graph is a pendent path of order 2. In this paper, we provide an important step forward to the full characterization of these minimal trees. Namely, we show that a minimal-ABC tree contains neither 4 nor 3 B1-branches. The case when the number of B1-branches is 2 is also considered.

  20. Manipulation of EphB2 regulatory motifs and SH2 binding sites switches MAPK signaling and biological activity.

    PubMed

    Tong, Jiefei; Elowe, Sabine; Nash, Piers; Pawson, Tony

    2003-02-21

    Signaling by the Eph family of receptor tyrosine kinases (RTKs) is complex, because they can interact with a variety of intracellular targets, and can potentially induce distinct responses in different cell types. In NG108 neuronal cells, activated EphB2 recruits p120RasGAP, in a fashion that is associated with down-regulation of the Ras-Erk mitogen-activated kinase (MAPK) pathway and neurite retraction. To pursue the role of the Ras-MAPK pathway in EphB2-mediated growth cone collapse, and to explore the biochemical and biological functions of Eph receptors, we sought to re-engineer the signaling properties of EphB2 by manipulating its regulatory motifs and SH2 binding sites. An EphB2 mutant that retained juxtamembrane (JM) RasGAP binding sites but incorporated a Grb2 binding motif at an alternate RasGAP binding site within the kinase domain had little effect on basal Erk MAPK activation. In contrast, elimination of all RasGAP binding sites, accompanied by the addition of a Grb2 binding site within the kinase domain, led to an increase in phospho-Erk levels in NG108 cells following ephrin-B1 stimulation. Functional assays indicated a correlation between neurite retraction and the ability of the EphB2 mutants to down-regulate Ras-Erk MAPK signaling. These data suggest that EphB2 can be designed to repress, stabilize, or activate the Ras-Erk MAPK pathway by the manipulation of RasGAP and Grb2 SH2 domain binding sites and support the notion that Erk MAPK regulation plays a significant role in axon guidance. The behavior of EphB2 variants with mutations in the JM region and kinase domains suggests an intricate pattern of regulation and target recognition by Eph receptors.

  1. Differential Conductance Measurements of MgB2/I/Pb Heterojunctions and all-MgB2 Junctions

    NASA Astrophysics Data System (ADS)

    Cusick, David; Eckhardt, Matthew; Dai, Wenqing; Li, Qi; Chen, Ke; Cunnane, Daniel; Zhuang, C. G.; Xi, X. X.; Naito, Michio; Ramos, Roberto

    2015-03-01

    We present our work characterizing several types of Magnesium Diboride Josephson junctions, including MgB2/I/Pb heterojunctions and all-MgB2 junctions. We will report on the I-V and dI/dV-V data collected at various temperatures using both a cryocooler-based experimental platform between 2 and 20 Kelvin and using a 3He probe platform between 0.3 and 1.0 Kelvin. These were both developed by undergraduates in a liberal arts university. Using high-sampling rates with a 24-bit data acquisition card and access to a broad of range of temperatures, we track and report energy gap distributions and temperature-dependent features of dI/dV peaks of MgB2, comparing these with theoretical predictions. R.C.R. acknowledges support from National Science Foundation Grant # DMR-1206561.

  2. Hexagonal OsB 2: Sintering, microstructure and mechanical properties

    DOE PAGES

    Xie, Zhilin; Lugovy, Mykola; Orlovskaya, Nina; ...

    2015-02-07

    In this study, the metastable high pressure ReB 2-type hexagonal OsB 2 bulk ceramics was produced by spark plasma sintering. The phase composition, microstructure, and mechanical behavior of the sintered OsB 2 were studied by X-ray diffraction, optical microscopy, TEM, SEM, EDS, and nanoindentation. The produced ceramics was rather porous and contained a mixture of hexagonal (~80 wt.%) and orthorhombic (~20 wt.%) phases as identified by X-ray diffraction and EBSD analysis. Two boron-rich phases, which do not contain Os, were also identified by TEM and SEM/EDS analysis. Nanoindentation measurements yielded a hardness of 31 ± 9 GPa and Young’s modulusmore » of 574 ± 112 GPa, indicating that the material is rather hard and very stiff; but, it is very prone to crack formation and propagation, which is indicative of a very brittle nature of this material. Improvements in the sintering regime are required in order to produce dense, homogeneous and single phase hexagonal OsB 2 bulk ceramics.« less

  3. 17 CFR 270.8b-2 - Definitions.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... REGULATIONS, INVESTMENT COMPANY ACT OF 1940 § 270.8b-2 Definitions. Unless the context otherwise requires, the..., if no closing date has been adopted, the calendar year ending on December 31. (f) Investment income. The term “investment income” means the aggregate of net operating income or loss from real estate and...

  4. 26 CFR 1.167(b)-2 - Declining balance method.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 2 2010-04-01 2010-04-01 false Declining balance method. 1.167(b)-2 Section 1... Declining balance method. (a) Application of method. Under the declining balance method a uniform rate is... declining balance rate may be determined without resort to formula. Such rate determined under section 167(b...

  5. Superconducting state in (W, Ta)5SiB2

    NASA Astrophysics Data System (ADS)

    Fukuma, M.; Kawashima, K.; Akimitsu, J.

    We characterize the superconducting state in a boro-silicide (W, Ta)5SiB2, with Tc of 6.5 K by means of magnetization, electrical resistivity, and specific heat measurements. As x increased, the transition temperature Tc abruptly enhances from 5.8 to 6.5 K. The magnetization versus magnetic field (M-H) curve indicated that (W, Ta)5SiB2 was a conventional type-II superconductor. The estimated lower critical field Hc1(0) and upper critical field Hc2(T) are about 121 Oe and 14.7 kOe, respectively. The penetration depth λ(0) and coherence length ξ(0) are calculated to be approximately 369 and 14.9 nm, respectively, using Ginzburg-Landau (GL) equations. Specific heat data shows the superconductivity in W4.5Ta0.5SiB2 belongs to a week-coupling BCS superconductor. Finally, we discuss the increasing of Tc in of (W, Ta)5SiB2 system.

  6. Compare the Difference of B-cell Epitopes of EgAgB1 and EgAgB3 Proteins Selected through Bioinformatic Analysis

    NASA Astrophysics Data System (ADS)

    An, Mengting; Zhang, Fengbo; Zhu, Yuejie; Zhao, Xiao; Ding, Jianbing

    2018-01-01

    Cystic echinococcosis, as a zoonosis, seriously endangers humans and animals, so early diagnosis of this disease is particularly important. Therefore, this study is to predict B-cell epitopes of EgAgB1 and EgAgB3 proteins by bioinformatics software. B-cell epitopes of EgAgB1 and EgAgB3 proteins are predicted using DNAStar and IEDB software. The results suggest that there are two potential B-cell epitopes in EgAgB1, which located in the 8-15 and 31-37 amino acid residue segments. And two potential B-cell epitopes in EgAgB2, located in the 20∼27 and 47∼53 amino acid residue segments. This study predicted the B-cell epitopes of EgAgB1 and EgAgB3 proteins, which laid the foundation for the early diagnosis of Cystic echinococcosis.

  7. High Dietary Vitamin D Prevents Hypocalcemia and Osteomalacia in CYP27B1 Knockout Mice12

    PubMed Central

    Rowling, Matthew J.; Gliniak, Christy; Welsh, JoEllen; Fleet, James C.

    2008-01-01

    Mice lacking 25-hydroxycholecalciferol [25(OH)D]-1α-hydroxylase (CYP27B1) are growth retarded, hypocalcemic, and have poor bone mineralization. We tested whether high dietary cholecalciferol (VD3) could exert effects in the absence of CYP27B1 in vivo. Weanling male wild-type (WT) and CYP27B1 knockout (KO) mice were fed either a 2% calcium (Ca), 20% lactose rescue diet or an AIN93G diet (0.5% Ca, 0.4% phosphorus) containing 1000 (1K, the rodent requirement, 25 μg), 10,000 (10K, 250 μg), or 20,000 (20K, 500 μg) IU VD3/kg diet until 12 wk when blood and tissues were taken. Serum 25(OH)D was >90 nmol/L in the 1K diet group and increased >4-fold in mice fed 10K and 20K diets. The 1K diet impaired growth and caused hypocalcemia in KO mice; the 10K and 20K diets were as effective as the high Ca rescue diet in preventing these outcomes. High VD3 restored expression of vitamin D-regulated genes in intestine (calbindin D9K) and kidney (CYP27B1, 24-hydroxylase, calbindin D9K) of KO mice. Micro-computed tomography of femora revealed complete recovery of cortical bone in KO mice fed either the rescue or 10K diets but only partial recovery of trabecular bone measures (e.g. 40% lower bone volume, 20% lower trabecular thickness, and 23% increase in trabecular separation). These data show that very high serum 25(OH)D can influence Ca and bone metabolism independent of its conversion to 1,25 dihydroxycholecalciferol. However, neither high dietary Ca nor high dietary VD3 is sufficient to fully recover the phenotype of CYP27B1 KO mice. PMID:18029472

  8. Preparation and characterisation of Os doped MgB2

    NASA Astrophysics Data System (ADS)

    Grivel, J.-C.; Namazkar, S.; Alexiou, A.; Holte, O. J.

    2014-12-01

    Polycrystalline samples with Mg1-xOsxB2.04 nominal stoichiometry were made by reacting elemental powders at 800 °C under argon atmosphere. Based on XRD diffraction patterns, EDS analysis and magnetisation measurements, it is found that Os can replace up to about 1 at.% Mg in the MgB2 lattice. Beyond this doping level, unreacted Os and Mg-rich Mg-Os impurity phases are formed. The a-axis parameter contracts upon doping while the superconducting transition temperature decreases at a rate of 2.1 K/at.% Os substitution. At 10 K, Os doping induces an improvement of the normalised critical current density under applied magnetic fields in excess of 0.5 T, indicating a modest enhancement of flux pinning in this range.

  9. Mass Customized Technical Textiles in the B2B Sector

    NASA Astrophysics Data System (ADS)

    Gebhardt, R.; Barteld, M.; Grafmüller, L.; Mosig, T.; Weiß, M.

    2017-10-01

    Mass Customization is a great opportunity for textile companies for both staying competitive in high-wage countries and offering inexpensive, customized products. Within the area of Technical Textiles, this study focuses on the B2B sector and shows the status quo, potentials and strengths. Both management and technological issues are addressed. For the former, business models and the value co-creation process are dealt with, for the latter, the focus is on modelling.

  10. Superconducting and Normal State Properties of OsB2*

    NASA Astrophysics Data System (ADS)

    Singh, Yogesh; Niazi, A.; Zong, X.; Suh, B. J.; Vannette, M. W.; Prozorov, R.; Johnston, D. C.

    2007-03-01

    OsB2 is a layered superhard metallic material that was found to superconduct below Tc= 2.1 K.^1 We report the first detailed measurements of the static and dynamic magnetic susceptibilities χ, electrical resistivity, heat capacity Cp, penetration depth, and ^11B NMR on OsB2 to characterize its superconducting and normal state properties. The results confirm that OsB2 is a bulk superconductor below Tc= 2.1 K@. Its properties can be described by a close to weak-coupling s-wave BCS model with an electron-phonon coupling constant λ= 0.4--0.5, δ(0)/(kBTc) 1.9, a small Ginzburg-Landau parameter κ of order 5 or less, and a small zero-temperature critical magnetic field of roughly 500 Oe. The ^11B NMR measurements in the normal state show a nuclear spin-lattice relaxation time T1= 2.1 s at room temperature and a Korringa law with T1T = 610 s.K at lower T, and a correspondingly small T-independent Knight shift. These results indicate a small s character of the conduction electron wave function at the B site at the Fermi level. Our results will be compared to corresponding data for MgB2.1. J. K. Vandenberg et al., Mater. Res. Bull. 10, 889 (1975).^*Supported by the USDOE under Contract No. W-7405-Eng-82. Permanent address: Dept. Phys., The Catholic Univ. Korea.

  11. TD-AltBOC: A new COMPASS B2 modulation

    NASA Astrophysics Data System (ADS)

    Tang, Zuping; Zhou, Hongwei; Wei, Jiaolong; Yan, Tao; Liu, Yuqi; Ran, Yihang; Zhou, Yanling

    2011-06-01

    AltBOC(15,10) is the baseline of COMPASS B2 signal modulation. It is a BOC-like signal having different PN codes in the lower and the upper main split lobes, which allow one signal service per lobe. The two lobes can be received and processed separately like two BPSK(10) signals, or coherently processed to achieve better performance. Interoperability among COMPASS B2, Galileo E5 and GPS L5 is also achievable using AltBOC modulation. However, Galileo's 4-code AltBOC has drawbacks such as low efficiency and great receiver complexity. This paper presents a new modulation type named TD-AltBOC (Time Division AltBOC). The signal generation scheme and receiving method are presented, and are compared with AltBOC in the areas of power spectrum, ranging accuracy, anti-multipath performance, anti-interference performance, processing flexibility and complexity. Analysis results show TD-AltBOC has similar spectrum characteristics, interoperability, flexibility and anti-interference performance with AltBOC. When the frontend bandwidth is more than 50 MHz, TD-AltBOC can achieve better ranging accuracy and anti-multipath performance. It also has such advantages as high efficiency and low receiver complexity. TD-AltBOC could be a good solution to COMPASS B2 navigation signal.

  12. Agent-based services for B2B electronic commerce

    NASA Astrophysics Data System (ADS)

    Fong, Elizabeth; Ivezic, Nenad; Rhodes, Tom; Peng, Yun

    2000-12-01

    The potential of agent-based systems has not been realized yet, in part, because of the lack of understanding of how the agent technology supports industrial needs and emerging standards. The area of business-to-business electronic commerce (b2b e-commerce) is one of the most rapidly developing sectors of industry with huge impact on manufacturing practices. In this paper, we investigate the current state of agent technology and the feasibility of applying agent-based computing to b2b e-commerce in the circuit board manufacturing sector. We identify critical tasks and opportunities in the b2b e-commerce area where agent-based services can best be deployed. We describe an implemented agent-based prototype system to facilitate the bidding process for printed circuit board manufacturing and assembly. These activities are taking place within the Internet Commerce for Manufacturing (ICM) project, the NIST- sponsored project working with industry to create an environment where small manufacturers of mechanical and electronic components may participate competitively in virtual enterprises that manufacture printed circuit assemblies.

  13. Modernization of B-2 Data, Video, and Control Systems Infrastructure

    NASA Technical Reports Server (NTRS)

    Cmar, Mark D.; Maloney, Christian T.; Butala, Vishal D.

    2012-01-01

    The National Aeronautics and Space Administration (NASA) Glenn Research Center (GRC) Plum Brook Station (PBS) Spacecraft Propulsion Research Facility, commonly referred to as B-2, is NASA s third largest thermal-vacuum facility with propellant systems capability. B-2 has completed a modernization effort of its facility legacy data, video and control systems infrastructure to accommodate modern integrated testing and Information Technology (IT) Security requirements. Integrated systems tests have been conducted to demonstrate the new data, video and control systems functionality and capability. Discrete analog signal conditioners have been replaced by new programmable, signal processing hardware that is integrated with the data system. This integration supports automated calibration and verification of the analog subsystem. Modern measurement systems analysis (MSA) tools are being developed to help verify system health and measurement integrity. Legacy hard wired digital data systems have been replaced by distributed Fibre Channel (FC) network connected digitizers where high speed sampling rates have increased to 256,000 samples per second. Several analog video cameras have been replaced by digital image and storage systems. Hard-wired analog control systems have been replaced by Programmable Logic Controllers (PLC), fiber optic networks (FON) infrastructure and human machine interface (HMI) operator screens. New modern IT Security procedures and schemes have been employed to control data access and process control flows. Due to the nature of testing possible at B-2, flexibility and configurability of systems has been central to the architecture during modernization.

  14. Modernization of B-2 Data, Video, and Control Systems Infrastructure

    NASA Technical Reports Server (NTRS)

    Cmar, Mark D.; Maloney, Christian T.; Butala, Vishal D.

    2012-01-01

    The National Aeronautics and Space Administration (NASA) Glenn Research Center (GRC) Plum Brook Station (PBS) Spacecraft Propulsion Research Facility, commonly referred to as B-2, is NASA's third largest thermal-vacuum facility with propellant systems capability. B-2 has completed a modernization effort of its facility legacy data, video and control systems infrastructure to accommodate modern integrated testing and Information Technology (IT) Security requirements. Integrated systems tests have been conducted to demonstrate the new data, video and control systems functionality and capability. Discrete analog signal conditioners have been replaced by new programmable, signal processing hardware that is integrated with the data system. This integration supports automated calibration and verification of the analog subsystem. Modern measurement systems analysis (MSA) tools are being developed to help verify system health and measurement integrity. Legacy hard wired digital data systems have been replaced by distributed Fibre Channel (FC) network connected digitizers where high speed sampling rates have increased to 256,000 samples per second. Several analog video cameras have been replaced by digital image and storage systems. Hard-wired analog control systems have been replaced by Programmable Logic Controllers (PLC), fiber optic networks (FON) infrastructure and human machine interface (HMI) operator screens. New modern IT Security procedures and schemes have been employed to control data access and process control flows. Due to the nature of testing possible at B-2, flexibility and configurability of systems has been central to the architecture during modernization.

  15. Discovery of ^{13}CCC in SgrB2(M)

    NASA Astrophysics Data System (ADS)

    Giesen, Thomas; Mookerjea, Bhaswati; Stutzki, Jürgen; Breier, Alexander A.; Buechling, Thomas; Fuchs, Guido W.

    2017-06-01

    Small carbon chain molecules like linear C_3 are thought to play a crucial role in the formation of larger, complex molecules, including pre-biotic species. The formation pathways of organic molecules with carbon chains as backbones is by far not well understood. Studies of isotope fractionation have proven to be a useful tool of tracing chemical reaction pathways and to elucidate formation and destruction processes of interstellar molecules. Recent velocity-resolved observations in the far-infrared have resulted in the detection of C_3 ro-vibrational transitions in the warm envelopes of star-forming hot cores W31C, W49N and DR21(OH). Multiple far-infrared transitions of C_3 have also been detected towards the Galactic center molecular clouds SgrB2(M) and Sgr B2(N). Since C^+ is involved in an important step of the formation route of the C_3 molecule, it is likely that effects of isotopic fractionation of C^+ will manifest itself in the ^{12}C_3/^{13}CCC and ^{12}C_3/C^{13}CC ratios as well. Based on high resolution THz- laboratory measurements of C_3 and its ^{13}C-isotopologues conducted at the Kassel laboratories, we used the GREAT-receiver onboard SOFIA for a first ever detection of ^{13}CCC towards SgrB2(M). In this talk we present results and possible implications of the observation.

  16. Selenidation of epitaxial silicene on ZrB2

    NASA Astrophysics Data System (ADS)

    Wiggers, F. B.; Yamada-Takamura, Y.; Kovalgin, A. Y.; de Jong, M. P.

    2018-01-01

    The deposition of elemental Se on epitaxial silicene on ZrB2 thin films was investigated with synchrotron-based core-level photoelectron spectroscopy and low-energy electron diffraction. The deposition of Se at room temperature caused the appearance of Si 2p peaks with chemical shifts of n × 0.51 ± 0.04 eV (n = 1-4), suggesting the formation of SiSe2. This shows that capping the silicene monolayer, without affecting its structural and electronic properties, is not possible with Se. The annealing treatments that followed caused the desorption of Se and Si, resulting in the etching of the Si atoms formerly part of the silicene layer, and the formation of bare ZrB2(0001) surface area. In addition, a ZrB2(0001)-(√7 × 3)R40.9° surface reconstruction was observed, attributed to a Se-termination of the surface of the transition metal diboride thin film.

  17. Fine-Filament MgB2 Superconductor Wire

    NASA Technical Reports Server (NTRS)

    Cantu, Sherrie

    2015-01-01

    Hyper Tech Research, Inc., has developed fine-filament magnesium diboride (MgB2) superconductor wire for motors and generators used in turboelectric aircraft propulsion systems. In Phase I of the project, Hyper Tech demonstrated that MgB2 multifilament wires (<10 micrometers) could reduce alternating current (AC) losses that occur due to hysteresis, eddy currents, and coupling losses. The company refined a manufacturing method that incorporates a magnesium-infiltration process and provides a tenfold enhancement in critical current density over wire made by a conventional method involving magnesium-boron powder mixtures. Hyper Tech also improved its wire-drawing capability to fabricate fine multifilament strands. In Phase II, the company developed, manufactured, and tested the wire for superconductor and engineering current density and AC losses. Hyper Tech also fabricated MgB2 rotor coil packs for a superconducting generator. The ultimate goal is to enable low-cost, round, lightweight, low-AC-loss superconductors for motor and generator stator coils operating at 25 K in next-generation turboelectric aircraft propulsion systems.

  18. The relevance of kalikrein-kinin system via activation of B2receptor in LPS-induced fever in rats.

    PubMed

    Soares, Denis de Melo; Santos, Danielle R; Rummel, Christoph; Ott, Daniela; Melo, Míriam C C; Roth, Joachim; Calixto, João B; Souza, Glória E P

    2017-11-01

    This study evaluated the involvement of endogenous kallikrein-kinin system and the bradykinin (BK) B 1 and B 2 receptors on LPS- induced fever and the POA cells involved in this response. Male Wistar rats received either i.v. (1 mg/kg), i.c.v. (20 nmol) or i.h. (2 nmol) injections of icatibant (B 2 receptor antagonist) 30 or 60 min, respectively, before the stimuli. DALBK (B 1 receptor antagonist) was given either 15min before BK (i.c.v.) or 30 min before LPS (i.v.). Captopril (5 mg/kg, sc.,) was given 1 h prior LPS or BK. Concentrations of BK and total kininogenon CSF, plasma and tissue kallikrein were evaluated. Rectal temperatures (rT) were assessed by telethermometry. Ca ++ signaling in POA cells was performed in rat pup brain tissue microcultures. Icatibant reduced LPS fever while, captopril exacerbated that response, an effect abolished by icatibant. Icatibant (i.h.) reduced fever to BK (i.h.) but not that induced by LPS (i.v.). BK increased intracellular calcium concentration in neurons and astrocytes. LPS increased levels of bradykinin, tissue kallikrein and total kininogen. BK (i.c.v.) increased rT and decreased tail skin temperature. Captopril potentiated BK-induced fever an effect abolished by icatibant. DALBK reduced the fever induced by BK. BK (i.c.v.) increased the CSF PGE 2 concentration. Effect abolished by indomethacin (i.p.). LPS activates endogenous kalikrein-kinin system leading to production of BK, which by acting on B 2 -receptors of POA cells causes prostaglandin synthesis that in turn produces fever. Thus, a kinin B 2 -receptor antagonist that enters into the brain could constitute a new and interesting strategy to treat fever. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Rupatadine effectively prevents the histamine-induced up regulation of histamine H1R and bradykinin B2R receptor gene expression in the rat paw.

    PubMed

    Molyva, Dimitra; Kalokasidis, Konstantinos; Poulios, Christos; Dedi, Hara; Karkavelas, George; Mirtsou, Vassiliki; Goulas, Antonis

    2014-12-01

    Activation of histamine H1 receptor (H1R) is a well-known hallmark of allergic and inflammatory pathology. Both types of bradykinin receptors (B1R and B2R) are also known to contribute significantly to the latter and some sort of functional interaction between them and H1R has been alluded to in the past. Here we use an experimental model of rat paw oedema formation to examine the effect of exogenously added histamine on the gene expression of H1R and bradykinin receptors B1R and B2R, alone or in combination to rupatadine, a second generation antihistamine agent. Histamine-induced oedema formation was monitored with a plethysmometer. The gene expression of H1R, B1R and B2R was analyzed with both conventional and real-time PCR. Rupatadine fumarate was used in pure form and administered intraperitoneally, prior to histamine injection into the paw. Microscopy of haematoxylin and eosin-stained sections of paw tissue was used to examine effects on tissue architecture. Histamine injection into the paw resulted in significant up regulation of H1R and B2R without inducing significant cellular infiltration, but appears to affect less the expression of B1R. Rupatadine was, under the conditions used in this study, very effective in preventing this effect and in suppressing oedema formation through its antihistamine action. Rupatadine has a suppressing effect on H1R and B2R gene expression which could add to its efficacy towards allergy and allergy-like conditions. Copyright © 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  20. Fractographic Analysis of HfB2-SiC and ZrB2-SiC Composites

    NASA Technical Reports Server (NTRS)

    Mecholsky, J.J., Jr.; Ellerby, D. T.; Johnson, S. M.; Stackpoole, M. M.; Loehman, R. E.; Arnold, Jim (Technical Monitor)

    2001-01-01

    Hafnium diboride-silicon carbide and zirconium diboride-silicon carbide composites are potential materials for high temperature leading edge applications on reusable launch vehicles. In order to establish material constants necessary for evaluation of in-situ fracture, bars fractured in four point flexure were examined using fractographic principles. The fracture toughness was determined from measurements of the critical crack sizes and the strength values, and the crack branching constants were established to use in forensic fractography of materials for future flight applications. The fracture toughnesses range from about 13 MPam (sup 1/2) at room temperature to about 6 MPam (sup 1/2) at 1400 C for ZrB2-SiC composites and from about 11 MPam (sup 1/2) at room temperature to about 4 MPam (sup 1/2) at 1400 C for HfB2-SiC composites.

  1. New insights into the stereochemical requirements of the bradykinin B2 receptor antagonists binding

    NASA Astrophysics Data System (ADS)

    Lupala, Cecylia S.; Gomez-Gutierrez, Patricia; Perez, Juan J.

    2016-01-01

    Bradykinin (BK) is a member of the kinin family, released in response to inflammation, trauma, burns, shock, allergy and some cardiovascular diseases, provoking vasodilatation and increased vascular permeability among other effects. Their actions are mediated through at least two G-protein coupled receptors, B1 a receptor up-regulated during inflammation episodes or tissue trauma and B2 that is constitutively expressed in a variety of cell types. The goal of the present work is to carry out a structure-activity study of BK B2 antagonism, taking into account the stereochemical features of diverse non-peptide antagonists and the way these features translate into ligand anchoring points to complementary regions of the receptor, through the analysis of the respective ligand-receptor complex. For this purpose an atomistic model of the BK B2 receptor was built by homology modeling and subsequently refined embedded in a lipid bilayer by means of a 600 ns molecular dynamics trajectory. The average structure from the last hundred nanoseconds of the molecular dynamics trajectory was energy minimized and used as model of the receptor for docking studies. For this purpose, a set of compounds with antagonistic profile, covering maximal diversity were selected from the literature. Specifically, the set of compounds include Fasitibant, FR173657, Anatibant, WIN64338, Bradyzide, CHEMBL442294, and JSM10292. Molecules were docked into the BK B2 receptor model and the corresponding complexes analyzed to understand ligand-receptor interactions. The outcome of this study is summarized in a 3D pharmacophore that explains the observed structure-activity results and provides insight into the design of novel molecules with antagonistic profile. To prove the validity of the pharmacophore hypothesized a virtual screening process was also carried out. The pharmacophore was used as query to identify new hits using diverse databases of molecules. The results of this study revealed a set of new

  2. Asymmetric Dual-Band Tracking Technique for Optimal Joint Processing of BDS B1I and B1C Signals.

    PubMed

    Wang, Chuhan; Cui, Xiaowei; Ma, Tianyi; Zhao, Sihao; Lu, Mingquan

    2017-10-16

    Along with the rapid development of the Global Navigation Satellite System (GNSS), satellite navigation signals have become more diversified, complex, and agile in adapting to increasing market demands. Various techniques have been developed for processing multiple navigation signals to achieve better performance in terms of accuracy, sensitivity, and robustness. This paper focuses on a technique for processing two signals with separate but adjacent center frequencies, such as B1I and B1C signals in the BeiDou global system. The two signals may differ in modulation scheme, power, and initial phase relation and can be processed independently by user receivers; however, the propagation delays of the two signals from a satellite are nearly identical as they are modulated on adjacent frequencies, share the same reference clock, and undergo nearly identical propagation paths to the receiver, resulting in strong coherence between the two signals. Joint processing of these signals can achieve optimal measurement performance due to the increased Gabor bandwidth and power. In this paper, we propose a universal scheme of asymmetric dual-band tracking (ASYM-DBT) to take advantage of the strong coherence, the increased Gabor bandwidth, and power of the two signals in achieving much-reduced thermal noise and more accurate ranging results when compared with the traditional single-band algorithm.

  3. Asymmetric Dual-Band Tracking Technique for Optimal Joint Processing of BDS B1I and B1C Signals

    PubMed Central

    Wang, Chuhan; Cui, Xiaowei; Ma, Tianyi; Lu, Mingquan

    2017-01-01

    Along with the rapid development of the Global Navigation Satellite System (GNSS), satellite navigation signals have become more diversified, complex, and agile in adapting to increasing market demands. Various techniques have been developed for processing multiple navigation signals to achieve better performance in terms of accuracy, sensitivity, and robustness. This paper focuses on a technique for processing two signals with separate but adjacent center frequencies, such as B1I and B1C signals in the BeiDou global system. The two signals may differ in modulation scheme, power, and initial phase relation and can be processed independently by user receivers; however, the propagation delays of the two signals from a satellite are nearly identical as they are modulated on adjacent frequencies, share the same reference clock, and undergo nearly identical propagation paths to the receiver, resulting in strong coherence between the two signals. Joint processing of these signals can achieve optimal measurement performance due to the increased Gabor bandwidth and power. In this paper, we propose a universal scheme of asymmetric dual-band tracking (ASYM-DBT) to take advantage of the strong coherence, the increased Gabor bandwidth, and power of the two signals in achieving much-reduced thermal noise and more accurate ranging results when compared with the traditional single-band algorithm. PMID:29035350

  4. Stability of Aflatoxin B1 and Ochratoxin A in Brewing

    PubMed Central

    Chu, F. S.; Chang, C. C.; Ashoor, Samy H.; Prentice, N.

    1975-01-01

    The stability of aflatoxin B1 and ochratoxin A in brewing was investigated by adding the purified toxins to the raw materials at 1 and 10 μg/g levels during mashing in a conventional micro-brewing process. The results indicate that both toxins are stable to heat and are insensitive to cooker mash treatment. Both mycotoxins were partially removed in the mashing and brewing processes. About 14 to 18% and 27 to 28% of the added toxins were found in the final beers brewed from starting materials containing 1 and 10 μg, respectively, of either toxin per g. The possible route of transmission of mycotoxins into beer is discussed. PMID:1115503

  5. Competition for vitamin B1 (thiamin) structures numerous ecological interactions.

    PubMed

    Kraft, Clifford E; Angert, Esther R

    2017-06-01

    Thiamin (vitamin B1) is a cofactor required for essential biochemical reactions in all living organisms, yet free thiamin is scarce in the environment. The diversity of biochemical pathways involved in the acquisition, degradation, and synthesis of thiamin indicates that organisms have evolved numerous ecological strategies for meeting this nutritional requirement. In this review we synthesize information from multiple disciplines to show how the complex biochemistry of thiamin influences ecological outcomes of interactions between organisms in environments ranging from the open ocean and the Australian outback to the gastrointestinal tract of animals. We highlight population and ecosystem responses to the availability or absence of thiamin. These include widespread mortality of fishes, birds, and mammals, as well as the thiamin-dependent regulation of ocean productivity. Overall, we portray thiamin biochemistry as the foundation for molecularly mediated ecological interactions that influence survival and abundance of a vast array of organisms.

  6. 76 FR 60457 - 36(b)(1) Arms Sales Notification

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-29

    ...: 36 M777A2 Howitzers, 54 M119A2 Howitzers, 6 AN/TPQ-36(V) Fire Finder Radar Systems, 24 Advanced Field... for 36 M777A2 Howitzers, 54 M119A2 Howitzers, 6 AN/TPQ- 36(V) Fire Finder Radar Systems, 24 Advanced... armed forces. The proposed sale of this equipment will not alter the basic military balance in the...

  7. SLC9B1 methylation predicts fetal intolerance of labor.

    PubMed

    Knight, Anna K; Conneely, Karen N; Kilaru, Varun; Cobb, Dawayland; Payne, Jennifer L; Meilman, Samantha; Corwin, Elizabeth J; Kaminsky, Zachary A; Dunlop, Anne L; Smith, Alicia K

    2018-01-01

    Fetal intolerance of labor is a common indication for delivery by Caesarean section. Diagnosis is based on the presence of category III fetal heart rate tracing, which is an abnormal heart tracing associated with increased likelihood of fetal hypoxia and metabolic acidemia. This study analyzed data from 177 unique women who, during their prenatal visits (7-15 weeks and/or 24-32 weeks) to Atlanta area prenatal care clinics, consented to provide blood samples for DNA methylation (HumanMethylation450 BeadChip) and gene expression (Human HT-12 v4 Expression BeadChip) analyses. We focused on 57 women aged 18-36 (mean 25.4), who had DNA methylation data available from their second prenatal visit. DNA methylation patterns at CpG sites across the genome were interrogated for associations with fetal intolerance of labor. Four CpG sites (P value <8.9 × 10 -9 , FDR <0.05) in gene SLC9B1, a Na + /H + exchanger, were associated with fetal intolerance of labor. DNA methylation and gene expression were negatively associated when examined longitudinally during pregnancy using a linear mixed-effects model. Positive predictive values of methylation of these four sites ranged from 0.80 to 0.89, while negative predictive values ranged from 0.91 to 0.92. The four CpG sites were also associated with fetal intolerance of labor in an independent cohort (the Johns Hopkins Prospective PPD cohort). Therefore, fetal intolerance of labor could be accurately predicted from maternal blood samples obtained between 24-32 weeks gestation. Fetal intolerance of labor may be accurately predicted from maternal blood samples obtained between 24-32 weeks gestation by assessing DNA methylation patterns of SLC9B1. The identification of pregnant women at elevated risk for fetal intolerance of labor may allow for the development of targeted treatments or management plans.

  8. Expression and functional characterization of the Agrobacterium VirB2 amino acid substitution variants in T-pilus biogenesis, virulence, and transient transformation efficiency.

    PubMed

    Wu, Hung-Yi; Chen, Chao-Ying; Lai, Erh-Min

    2014-01-01

    Agrobacterium tumefaciens is a phytopathogenic bacterium that causes crown gall disease by transferring transferred DNA (T-DNA) into the plant genome. The translocation process is mediated by the type IV secretion system (T4SS) consisting of the VirD4 coupling protein and 11 VirB proteins (VirB1 to VirB11). All VirB proteins are required for the production of T-pilus, which consists of processed VirB2 (T-pilin) and VirB5 as major and minor subunits, respectively. VirB2 is an essential component of T4SS, but the roles of VirB2 and the assembled T-pilus in Agrobacterium virulence and the T-DNA transfer process remain unknown. Here, we generated 34 VirB2 amino acid substitution variants to study the functions of VirB2 involved in VirB2 stability, extracellular VirB2/T-pilus production and virulence of A. tumefaciens. From the capacity for extracellular VirB2 production (ExB2+ or ExB2-) and tumorigenesis on tomato stems (Vir+ or Vir-), the mutants could be classified into three groups: ExB2-/Vir-, ExB2-/Vir+, and ExB2+/Vir+. We also confirmed by electron microscopy that five ExB2-/Vir+ mutants exhibited a wild-type level of virulence with their deficiency in T-pilus formation. Interestingly, although the five T-pilus-/Vir+ uncoupling mutants retained a wild-type level of tumorigenesis efficiency on tomato stems and/or potato tuber discs, their transient transformation efficiency in Arabidopsis seedlings was highly attenuated. In conclusion, we have provided evidence for a role of T-pilus in Agrobacterium transformation process and have identified the domains and amino acid residues critical for VirB2 stability, T-pilus biogenesis, tumorigenesis, and transient transformation efficiency.

  9. Expression and Functional Characterization of the Agrobacterium VirB2 Amino Acid Substitution Variants in T-pilus Biogenesis, Virulence, and Transient Transformation Efficiency

    PubMed Central

    Wu, Hung-Yi; Chen, Chao-Ying; Lai, Erh-Min

    2014-01-01

    Agrobacterium tumefaciens is a phytopathogenic bacterium that causes crown gall disease by transferring transferred DNA (T-DNA) into the plant genome. The translocation process is mediated by the type IV secretion system (T4SS) consisting of the VirD4 coupling protein and 11 VirB proteins (VirB1 to VirB11). All VirB proteins are required for the production of T-pilus, which consists of processed VirB2 (T-pilin) and VirB5 as major and minor subunits, respectively. VirB2 is an essential component of T4SS, but the roles of VirB2 and the assembled T-pilus in Agrobacterium virulence and the T-DNA transfer process remain unknown. Here, we generated 34 VirB2 amino acid substitution variants to study the functions of VirB2 involved in VirB2 stability, extracellular VirB2/T-pilus production and virulence of A. tumefaciens. From the capacity for extracellular VirB2 production (ExB2+ or ExB2−) and tumorigenesis on tomato stems (Vir+ or Vir−), the mutants could be classified into three groups: ExB2−/Vir−, ExB2−/Vir+, and ExB2+/Vir+. We also confirmed by electron microscopy that five ExB2−/Vir+ mutants exhibited a wild-type level of virulence with their deficiency in T-pilus formation. Interestingly, although the five T-pilus−/Vir+ uncoupling mutants retained a wild-type level of tumorigenesis efficiency on tomato stems and/or potato tuber discs, their transient transformation efficiency in Arabidopsis seedlings was highly attenuated. In conclusion, we have provided evidence for a role of T-pilus in Agrobacterium transformation process and have identified the domains and amino acid residues critical for VirB2 stability, T-pilus biogenesis, tumorigenesis, and transient transformation efficiency. PMID:24971727

  10. First observation of the hadronic transition Υ(4S)→ηh b(1P) and new measurement of the h b(1P) and η b(1S) parameters

    SciTech Connect

    Tamponi, Umberto; Mussa, Roberto; Abdesselam, A.

    2015-09-29

    Using a sample of 771.6 × 10 6 Υ(4S) decays collected by the Belle experiment at the KEKB e +e - collider, we observe for the first time the transition Υ(4S) → ηh b(1P) with the branching fraction B[Υ(4S) → ηh b(1P)] = (2.18 ± 0.11 ± 0.18) × 10 -3 and we measure the h b(1P) mass M hb(1P ) = (9899.3 ± 0.4 ± 1.0) MeV/c 2 , corresponding to the hyperfine splitting ΔM HF (1P) = (0.6 ± 0.4 ± 1.0) MeV/c 2 . Using the transition h b(1P) → γηb(1S), we measure the ηb(1S)more » mass Mηb(1S) = (9400.7 ± 1.7 ± 1.6) MeV/c 2 , corresponding to ΔMHF (1S) = (59.6 ± 1.7 ± 1.6) MeV/c 2 , the ηb(1S) width Γηb(1S) = (8+6 -5 ± 5) MeV/c 2 and the branching fraction B[hb(1P) → γηb(1S)] = (56 ± 8 ± 4)%.« less

  11. Negative ion chemical ionization mass spectrometric method for confirmation of identity of aflatoxin B1: collaborative study.

    PubMed

    Park, D L; Diprossimo, V; Abdel-Malek, E; Trucksess, M W; Nesheim, S; Brumley, W C; Sphon, J A; Barry, T L; Petzinger, G

    1985-01-01

    An interlaboratory study of a negative ion chemical ionization mass spectrometric (MS) confirmation procedure for aflatoxin B1 was conducted in laboratories in the United States, England, and West Germany. Twelve partially purified, dry film extracts from naturally and artificially contaminated roasted peanuts, cottonseed, and ginger root containing varying quantities of aflatoxin B1 were distributed to the participating laboratories. The extracts required additional cleanup before MS analysis, using either an acidic alumina column and preparative thin layer chromatography (TLC) or a 2-dimensional TLC procedure. Recovery of purified aflatoxin B1 was influenced by the degree of recovery of sample from acid alumina and/or the TLC plate and incomplete elution of aflatoxin B1 from silica gel. Factors affecting MS confirmation included the purity and recovery of aflatoxin and MS instrument sensitivity. Aflatoxin B1 identity was confirmed in 19.5, 90.9, and 100% of samples containing less than 5, 5-10, and greater than 10 ng aflatoxin B1/g product, respectively, by solid probe introduction using full mass scans. The MS method has been adopted official first action.

  12. Effects of vitamin B2 on neutrophil functions in cattle.

    PubMed

    Osame, S; Araki, S; Kimura, M

    1995-06-01

    Vitamin B2 was intramuscularly administered to Holstein cattle and the ensuing changes in peripheral blood neutrophil function were investigated. The neutrophil count displayed a significant increase at 1-2 days after administration, while nitroblue tetrazolium reducing activity and phagocytic bactericidal activity were enhanced at 1-4 days after administration in calves and at 1-6 days after administration in adult cows. The increases in the neutrophil count and the activation of neutrophil functions were observed, being manifested at dosages of 10 mg/kg or greater for calves and 5 mg/kg or greater for adult cows.

  13. Interpretive geologic bedrock map of the Tanana B-1 Quadrangle, Central Alaska

    USGS Publications Warehouse

    Reifenstuh, Rocky R.; Dover, James H.; Newberry, Rainer J.; Calutice, Karen H.; Liss, Shirley A.; Blodgett, Robert B.; Budtzen, Thomas K.; Weber, Florence R.

    1997-01-01

    This report provides detailed (1:63,360-scale) mapping of the Tanana B-1 Quadrangle (250 square miles; equivalent to four 7.5 minute quadrangles). The area is part of the Manley Hot Springs-Tofty mining districts and adjacent to the Rampart mining district to the north of the Tanana A-1 and A-2 Quadrangles. This report includes detailed bedrock, structural, stratigraphic, and geochronologic data. Based on the resulting geologic maps, field investigations, and laboratory materials analyses, the project has also generated derivative maps of geologic construction materials and geologic hazards.

  14. UDP-glycosyltransferase 72B1 catalyzes the glucose conjugation of monolignols and is essential for the normal cell wall lignification in Arabidopsis thaliana.

    PubMed

    Lin, Ji-Shan; Huang, Xu-Xu; Li, Qin; Cao, Yingping; Bao, Yan; Meng, Xia-Fei; Li, Yan-Jie; Fu, Chunxiang; Hou, Bing-Kai

    2016-10-01

    Glycosylation of monolignols has been found to be widespread in land plants since the 1970s. However, whether monolignol glycosylation is crucial for cell wall lignification and how it exerts effects are still unknown. Here, we report the identification of a mutant ugt72b1 showing aggravated and ectopic lignification in floral stems along with arrested growth and anthocyanin accumulation. Histochemical assays and thioacidolysis analysis confirmed the enhanced lignification and increased lignin biosynthesis in the ugt72b1 mutant. The loss of UDP-glycosyltransferase UGT72B1 function was responsible for the lignification phenotype, as demonstrated by complementation experiments. Enzyme activity analysis indicated that UGT72B1 could catalyze the glucose conjugation of monolignols, especially coniferyl alcohol and coniferyl aldehyde, which was confirmed by analyzing monolignol glucosides of UGT72B1 transgenic plants. Furthermore, the UGT72B1 gene was strongly expressed in young stem tissues, especially xylem tissues. However, UGT72B1 paralogs, such as UGT72B2 and UGT72B3, had weak enzyme activity toward monolignols and weak expression in stem tissues. Transcriptomic profiling showed that UGT72B1 knockout resulted in extensively increased transcript levels of genes involved in monolignol biosynthesis, lignin polymerization and cell wall-related transcription factors, which was confirmed by quantitative real-time PCR assays. These results provided evidence that monolignol glucosylation catalyzed by UGT72B1 was essential for normal cell wall lignification, thus offering insight into the molecular mechanism of cell wall development and cell wall lignification. © 2016 The Authors The Plant Journal © 2016 John Wiley & Sons Ltd.

  15. Ocular Application of the Kinin B1 Receptor Antagonist LF22-0542 Inhibits Retinal Inflammation and Oxidative Stress in Streptozotocin-Diabetic Rats

    PubMed Central

    Pouliot, Mylène; Talbot, Sébastien; Sénécal, Jacques; Dotigny, Florence; Vaucher, Elvire; Couture, Réjean

    2012-01-01

    Purpose Kinin B1 receptor (B1R) is upregulated in retina of Streptozotocin (STZ)-diabetic rats and contributes to vasodilation of retinal microvessels and breakdown of the blood-retinal barrier. Systemic treatment with B1R antagonists reversed the increased retinal plasma extravasation in STZ rats. The present study aims at determining whether ocular application of a water soluble B1R antagonist could reverse diabetes-induced retinal inflammation and oxidative stress. Methods Wistar rats were made diabetic with STZ (65 mg/kg, i.p.) and 7 days later, they received one eye drop application of LF22-0542 (1% in saline) twice a day for a 7 day-period. The impact was determined on retinal vascular permeability (Evans blue exudation), leukostasis (leukocyte infiltration using Fluorescein-isothiocyanate (FITC)-coupled Concanavalin A lectin), retinal mRNA levels (by qRT-PCR) of inflammatory (B1R, iNOS, COX-2, ICAM-1, VEGF-A, VEGF receptor type 2, IL-1β and HIF-1α) and anti-inflammatory (B2R, eNOS) markers and retinal level of superoxide anion (dihydroethidium staining). Results Retinal plasma extravasation, leukostasis and mRNA levels of B1R, iNOS, COX-2, VEGF receptor type 2, IL-1β and HIF-1α were significantly increased in diabetic retinae compared to control rats. All these abnormalities were reversed to control values in diabetic rats treated with LF22-0542. B1R antagonist also significantly inhibited the increased production of superoxide anion in diabetic retinae. Conclusion B1R displays a pathological role in the early stage of diabetes by increasing oxidative stress and pro-inflammatory mediators involved in retinal vascular alterations. Hence, topical application of kinin B1R antagonist appears a highly promising novel approach for the treatment of diabetic retinopathy. PMID:22470485

  16. Analysis of the Defect Structure of B2 Feal Alloys

    NASA Technical Reports Server (NTRS)

    Bozzolo, Guillermo; Ferrante, John; Noebe, Ronald D.; Amador, Carlos

    1995-01-01

    The Bozzolo, Ferrante and Smith (BFS) method for alloys is applied to the study of the defect structure of B2 FeAI alloys. First-principles Linear Muffin Tin Orbital calculations are used to determine the input parameters to the BFS method used in this work. The calculations successfully determine the phase field of the B2 structure, as well as the dependence with composition of the lattice parameter. Finally, the method is used to perform 'static' simulations where instead of determining the ground state configuration of the alloy with a certain concentration of vacancies, a large number of candidate ordered structures are studied and compared, in order to determine not only the lowest energy configurations but other possible metastable states as well. The results provide a description of the defect structure consistent with available experimental data. The simplicity of the BFS method also allows for a simple explanation of some of the essential features found in the concentration dependence of the heat of formation, lattice parameter and the defect structure.

  17. Characterization of MgB2 Superconducting Hot Electron Bolometers

    NASA Technical Reports Server (NTRS)

    Cunnane, D.; Kawamura, J. H.; Wolak, M. A.; Acharya, N.; Tan, T.; Xi, X. X.; Karasik, B. S.

    2014-01-01

    Hot-Electron Bolometer (HEB) mixers have proven to be the best tool for high-resolution spectroscopy at the Terahertz frequencies. However, the current state of the art NbN mixers suffer from a small intermediate frequency (IF) bandwidth as well as a low operating temperature. MgB2 is a promising material for HEB mixer technology in view of its high critical temperature and fast thermal relaxation allowing for a large IF bandwidth. In this work, we have fabricated and characterized thin-film (approximately 15 nanometers) MgB2-based spiral antenna-coupled HEB mixers on SiC substrate. We achieved the IF bandwidth greater than 8 gigahertz at 25 degrees Kelvin and the device noise temperature less than 4000 degrees Kelvin at 9 degrees Kelvin using a 600 gigahertz source. Using temperature dependencies of the radiation power dissipated in the device we have identified the optical loss in the integrated microantenna responsible as a cause of the limited sensitivity of the current mixer devices. From the analysis of the current-voltage (IV) characteristics, we have derived the effective thermal conductance of the mixer device and estimated the required local oscillator power in an optimized device to be approximately 1 microwatts.

  18. Compressibility behaviour of conducting ceramic TiB2

    NASA Astrophysics Data System (ADS)

    Arpita Aparajita, A. N.; Kumar, N. R. Sanjay; Shekar, N. V. Chandra; Kalavathi, S.

    2017-09-01

    To address the large spread in the bulk modulus value of TiB2 reported in literature, high pressure compressibility study of a phase pure polycrystalline sample has been carried out using in situ high pressure x-ray diffraction technique (HPXRD) in angle dispersive mode. The study has been done up to 23 GPa at ambient temperature with methanol-ethanol-water (MEW) as pressure transmitting medium. The hexagonal lattice has been found to be stable in the pressure range studied. The isothermal bulk modulus is estimated to be 333(6) GPa by employing 3rd order Birch-Murnaghan equation of state. The obtained high value of bulk modulus is understood in terms of band filling effect, and the nature of bonding between B-B and Ti-B in TiB2. Compressibility along ‘a’ and ‘c’ axis is found to be anisotropic with compressibility values of 0.93(2) TPa-1 and 1.14(2) TPa-1 respectively. From the estimated bond lengths for Ti-B and B-B it is found that B-B bonds are less compressible compared to Ti-B bonds which is in accordance with the respective nature of Ti-B and B-B bonds. A change in the rate of bond contraction was seen around 12 GPa which is due to the bond hardening for both Ti-B and B-B bonds with pressure.

  19. Quench dynamics in MgB2 Rutherford cables

    NASA Astrophysics Data System (ADS)

    Cubero, A.; Navarro, R.; Kováč, P.; Kopera, L.; Rindfleisch, M.; Martínez, E.

    2018-04-01

    The generation and propagation of quench induced by a local heat disturbance or by overcurrents in MgB2 Rutherford cables have been studied experimentally. The analysed cable is composed of 12 strands of monocore MgB2/Nb/Cu10Ni wire and has a transposition length of about 27 mm. Measurements of intra- and inter-strand voltages have been performed to analyse the superconducting-to-normal transition behaviour of these cables during quench. In case of external hot-spots, two different time-dynamic regimes have been observed, a slow stage for the formation of the minimum propagation zone (MPZ), and a fast dynamics once the quench is triggered and propagates to the rest of the cable. Significant local variations of the quench propagation velocity across the strands around the MPZ have been observed, but with average quench propagation velocities closely correlated with the predictions given by one-dimensional-geometry models. For quench induced by overcurrents (i.e. with applied currents higher than the critical current) the nucleation of many normal zones distributed within the cable, which overlap during quench propagation, gives a distinctive and faster quench dynamics.

  20. B1-control receive array coil (B-RAC) for reducing B1+ inhomogeneity in abdominal imaging at 3T-MRI

    NASA Astrophysics Data System (ADS)

    Kaneko, Yukio; Soutome, Yoshihisa; Habara, Hideta; Bito, Yoshitaka; Ochi, Hisaaki

    2018-02-01

    B1+ inhomogeneity in the human body increases as the nuclear magnetic resonance (NMR) frequency increases. Various methods have thus been developed to reduce B1+ inhomogeneity, such as a dielectric pad, a coupling coil, parallel transmit, and radio-frequency (RF) shimming. However, B1+ inhomogeneity still remains in some cases of abdominal imaging. In this study, we developed a B1-control receive array coil (B-RAC). Unlike the conventional receive array coil, B-RAC reduces B1+ inhomogeneity by using additional PIN diodes to generate the inductive loop during the RF transmit period. The inductive loop can generate dense and sparse regions of the magnetic flux, which can be used to compensate for B1+ inhomogeneity. First, B-RAC is modeled in the numerical simulation, and the spatial distributions of B1+ in a phantom and a human model were analyzed. Next, we fabricated a 12-channel B-RAC and measured receive sensitivity and B1+ maps in a 3T-MRI experiment. It was demonstrated that B-RAC can reduce B1+ inhomogeneity in the phantom and human model without increasing the maximum local specific absorption rate (SAR) in the body. B-RAC was also found to have almost the same the receive sensitivity as the conventional receive coil. Using RF shimming combined with B-RAC was revealed to more effectively reduce B1+ inhomogeneity than using only RF shimming. Therefore, B-RAC can reduce B1+ inhomogeneity while maintaining the receive sensitivity.

  1. Generation and characterization of a Cyp4b1 null mouse and the role of CYP4B1 in the activation and toxicity of Ipomeanol.

    PubMed

    Parkinson, Oliver T; Liggitt, H Denny; Rettie, Allan E; Kelly, Edward J

    2013-08-01

    4-Ipomeanol (IPO) is a prototypical pulmonary toxin that requires P450-mediated metabolic activation to reactive intermediates in order to elicit its toxic effects. CYP4B1 is a pulmonary enzyme that has been shown, in vitro, to have a high capacity for bioactivating IPO. In order to determine, unambiguously, the role of CYP4B1 in IPO bioactivation in vivo, we generated Cyp4b1 null mice following targeted disruption of the gene downstream of exon 1. Cyp4b1 (-/-) mice are viable and healthy, with no overt phenotype, and no evidence of compensatory upregulation of other P450 isoforms in any of the tissues examined. Pulmonary and renal microsomes prepared from male Cyp4b1 (-/-) mice exhibited no detectable expression of the protein and catalyzed the in vitro bioactivation of IPO at < 10% of the rates observed in tissue microsomes from Cyp4b1 (+/+) animals. Administration of IPO (20mg/kg) to Cyp4b1 (+/+) mice resulted in characteristic lesions in the lung, and to a lesser extent in the kidney, which were completely absent in Cyp4b1 (-/-) mice. We conclude that CYP4B1 is a critical enzyme for the bioactivation of IPO in vivo and that the Cyp4b1 (-/-) mouse is a useful model for studying CYP4B1-dependent metabolism and toxicity.

  2. Generation and Characterization of a Cyp4b1 Null Mouse and the Role of CYP4B1 in the Activation and Toxicity of Ipomeanol

    PubMed Central

    Kelly, Edward J.

    2013-01-01

    4-Ipomeanol (IPO) is a prototypical pulmonary toxin that requires P450-mediated metabolic activation to reactive intermediates in order to elicit its toxic effects. CYP4B1 is a pulmonary enzyme that has been shown, in vitro, to have a high capacity for bioactivating IPO. In order to determine, unambiguously, the role of CYP4B1 in IPO bioactivation in vivo, we generated Cyp4b1 null mice following targeted disruption of the gene downstream of exon 1. Cyp4b1 −/− mice are viable and healthy, with no overt phenotype, and no evidence of compensatory upregulation of other P450 isoforms in any of the tissues examined. Pulmonary and renal microsomes prepared from male Cyp4b1 −/− mice exhibited no detectable expression of the protein and catalyzed the in vitro bioactivation of IPO at < 10% of the rates observed in tissue microsomes from Cyp4b1 +/+ animals. Administration of IPO (20mg/kg) to Cyp4b1 +/+ mice resulted in characteristic lesions in the lung, and to a lesser extent in the kidney, which were completely absent in Cyp4b1 −/− mice. We conclude that CYP4B1 is a critical enzyme for the bioactivation of IPO in vivo and that the Cyp4b1 −/− mouse is a useful model for studying CYP4B1-dependent metabolism and toxicity. PMID:23748241

  3. ACE inhibition enhances bradykinin relaxations through nitric oxide and B1 receptor activation in bovine coronary arteries

    PubMed Central

    Gauthier, Kathryn M.; Cepura, Cody J.; Campbell, William B.

    2014-01-01

    Bradykinin causes vascular relaxations through release of endothelial relaxing factors including prostacyclin, nitric oxide (NO) and epoxyeicosatrienoic acids (EETs). Bradykinin is metabolized by angiotensin converting enzyme (ACE) and ACE inhibition enhances bradykinin relaxations. Our goal was to characterize the role of bradykinin receptors and endothelial factors in ACE inhibitor-enhanced relaxations in bovine coronary arteries. In U46619 preconstricted arteries, bradykinin (10−11−10−8M) caused concentration-dependent relaxations (maximal relaxation ≥100%, log EC50=−9.8±0.1). In the presence of the NO synthase inhibitor, N-nitro-L-arginine (L-NA, 30 µM) and the cyclooxygenase inhibitor, indomethacin (10 µM), relaxations were reduced by an inhibitor of EET synthesis, miconazole (10 µM) (maximal relaxation =55±10%). Bradykinin relaxations were inhibited by the bradykinin 2 (B2) receptor antagonist, D-Arg0-Hyp3-Thi5,8-D-Phe7-bradykinin (1 µM) (log EC50=−8.5±0.1) but not altered by the B1 receptor antagonist, des-Arg9[Leu8]bradykinin (1 µM). Mass spectrometric analysis of bovine coronary artery bradykinin metabolites revealed a time-dependent increase in bradykinin (1–5) and (1–7) suggesting metabolism by ACE. ACE inhibition with captopril (50 µM) enhanced bradykinin relaxations (log EC50=−10.3±0.1). The enhanced relaxations were eliminated by L-NA, the B1 receptor antagonist but not the B2 receptor antagonist. Our results demonstrate that ACE inhibitor-enhanced bradykinin relaxations of bovine coronary arteries occur through endothelial cell B1 receptor activation and NO. PMID:23729620

  4. B-1 Cell Immunoglobulin Directed Against Oxidation-Specific Epitopes

    PubMed Central

    Tsiantoulas, Dimitrios; Gruber, Sabrina; Binder, Christoph J.

    2013-01-01

    Natural antibodies (NAbs) are pre-existing antibodies with germline origin that arise in the absence of previous exposure to foreign antigens. NAbs are produced by B-1 lymphocytes and are primarily of the IgM isotype. There is accumulating evidence that – in addition to their role in antimicrobial host defense – NAbs exhibit important housekeeping functions by facilitating the non-immunogenic clearance of apoptotic cells as well as the removal of (neo-)self antigens. These properties are largely mediated by the ability of NAbs to recognize highly conserved and endogenously generated structures, which are exemplified by so-called oxidation-specific epitopes (OSEs) that are products of lipid peroxidation. The generation of OSEs as well as their interaction with the immune system have been studied extensively in the context of atherosclerosis, a chronic inflammatory disease of the vascular wall that is characterized by the accumulation of cellular debris and oxidized low-density lipoproteins (OxLDL). Both apoptotic cells as well as OxLDL carry OSEs that are targeted by NAbs. Therefore, OSEs represent stress-induced neo self-structures that mediate recognition of metabolic waste (e.g., cellular debris) by NAbs, allowing its safe disposal, which has fundamental implications in health and disease. PMID:23316200

  5. Metabolic intervention of aflatoxin B1 toxicity by curcumin.

    PubMed

    Nayak, Sujatha; Sashidhar, R B

    2010-02-17

    Curcumin, bioactive principle of turmeric (Curcuma longa Linn) is an important constituent of Indian traditional medicine. Turmeric has been known to possess several therapeutic properties. The modulatory effect of dietary curcumin (0.05%, w/w) on drug metabolizing and general marker enzymes of liver and formation of AFB(1)-adducts (DNA and protein) due to dietary AFB(1) exposure for a period of 6 weeks in a rodent model, have been evaluated. Drug metabolizing enzymes CYP1A1, GSHT, UGT1A and general marker enzymes (LDH, ALT, AST, ALP and gamma-GT) of liver were estimated by standardized methods. Aflatoxin adducts (DNA and protein) were quantitated by indirect competitive ELISA. Dietary curcumin enhanced GSHT (p<0.001) and UGT1A1 (p<0.05) activity and significantly reduced the activity of CYP1A1 (p<0.001), in rats exposed to aflatoxin B(1). Supplementation of curcumin in the diet normalized the altered activities of LDH and ALT. At molecular level, curcumin significantly reduced AFB(1)-N(7)-guanine adduct (p<0.001) excretion in the urine, DNA adduct (p<0.05) in the liver and albumin adduct (p<0.001) in the serum. The experimental results substantiates that curcumin intervention ameliorates the AFB(1) induced toxicity. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

  6. Decomposition and detoxification of aflatoxin B1 by lactic acid.

    PubMed

    Aiko, Visenuo; Edamana, Prasad; Mehta, Alka

    2016-04-01

    A degradation study of aflatoxin B1 (AFB1) was carried out using a combination of physical and chemical methods. AFB1 was heated at 80 °C in the presence of acetic, citric and lactic acids for various time periods. The cytotoxicity of the degraded AFB1 and its products were determined by MTT assay. The results showed that among the three organic acids lactic acid was most efficient in degrading AFB1. Although complete degradation was not observed, up to 85% degradation of AFB1 was obtained when heated for 120 min. Degradation of AFB1 was confirmed by the reduced toxicity on HeLa cells using MTT assay. Treatment with lactic acid resulted in the conversion of AFB1 into two degradation products. These products were observed at lower retention factors of 0.63 and 0.38, which were identified as AFB2 and AFB2a, respectively. The cytotoxicity of AFB2a exhibited much reduced toxicity on HeLa cells compared to that of AFB1. The results have shown the efficiency of lactic acid in degrading AFB1. This study suggest that lactic acid may be considered for use in the food and feed industry since it is present naturally in food and is considered safe. © 2015 Society of Chemical Industry.

  7. Chronic effects of fumonisin B1 on ducks.

    PubMed

    Tran, S T; Auvergne, A; Benard, G; Bailly, J D; Tardieu, D; Babilé, R; Guerre, P

    2005-01-01

    Partially purified fumonisin B1 (FB1) was orally administrated for 77 d to 5 groups of 8 mule ducks starting at 7 d of age; the concentrations corresponded to 5 diets containing 0, 2, 8, 32, and 128 mg of FB1/kg of feed. No mortality was observed, and no effects on feed consumption and body weight gain were observed at the end of the treatment period. But, surprisingly, FB1 ingested at 32 and 128 mg/kg led to decreased body weight from d 28 to 63 and from d 7 to 63, respectively. FB1 had no effect on the relative weight of heart and breast muscle, whereas a significant increases in the relative weights of gizzard, spleen, and liver were measured in ducks receiving 32 and 128 mg of FB1/kg of feed without evidence of detectable microscopic modification of these organs. FB1 had no significant effect of the serum aspartate aminotransferase and gamma-glutamyltransferase levels but increased serum total protein, cholesterol, alanine aminotransferase, lactate dehydrogenase, alkaline phosphatase levels when 128 mg of FB1/kg of feed was given. Serum, liver, and kidney sphinganine to sphingosine ratio was significantly increased in ducks fed 8 to 128 mg of FB1/kg of feed. The biggest increase was observed in kidneys, suggesting that this organ is the most sensitive to detect FB1-induced disruption of sphingolipid metabolism.

  8. Co-current Doping Effect of Nanoscale Carbon and Aluminum Nitride on Critical Current Density and Flux Pinning Properties of Bulk MgB2 Superconductors

    NASA Astrophysics Data System (ADS)

    Tripathi, D.; Dey, T. K.

    2018-05-01

    The effect of nanoscale aluminum nitride (n-AlN) and carbon (n-C) co-doping on superconducting properties of polycrystalline bulk MgB2 superconductor has been investigated. Polycrystalline pellets of MgB2, MgB2 + 0.5 wt% AlN (nano), MgB_{1.99}C_{0.01} and MgB_{1.99}C_{0.01} + 0.5 wt% AlN (nano) have been synthesized by a solid reaction process under inert atmosphere. The transition temperature (TC) estimated from resistivity measurement indicates only a small decrease for C (nano) and co-doped MgB2 samples. The magnetic field response of investigated samples has been measured at 4, 10, and 20 K in the field range ± 6 T. MgB2 pellets co-doped with 0.5 wt% n-AlN and 1 wt% n-C display appreciable enhancement in critical current density (J_C) of MgB2 in both low (≥ 3 times), as well as, high-field region (≥ 15 times). J_C versus H behavior of both pristine and doped MgB2 pellets is well explained in the light of the collective pinning model. Further, the normalized pinning force density f_p(= F_p/F_{pmax}) displays a fair correspondence with the scaling procedure proposed by Eisterer et al. Moreover, the scaled data of the pinning force density (i.e., f_p{-}h data) of the investigated pellets at different temperature are well interpreted by a modified Dew-Hughes expression reported by Sandu and Chee.

  9. Co-current Doping Effect of Nanoscale Carbon and Aluminum Nitride on Critical Current Density and Flux Pinning Properties of Bulk MgB2 Superconductors

    NASA Astrophysics Data System (ADS)

    Tripathi, D.; Dey, T. K.

    2018-01-01

    The effect of nanoscale aluminum nitride (n-AlN) and carbon (n-C) co-doping on superconducting properties of polycrystalline bulk MgB2 superconductor has been investigated. Polycrystalline pellets of MgB2 , MgB2 + 0.5 wt% AlN (nano), MgB_{1.99}C_{0.01} and MgB_{1.99}C_{0.01} + 0.5 wt% AlN (nano) have been synthesized by a solid reaction process under inert atmosphere. The transition temperature (TC) estimated from resistivity measurement indicates only a small decrease for C (nano) and co-doped MgB2 samples. The magnetic field response of investigated samples has been measured at 4, 10, and 20 K in the field range ± 6 T. MgB2 pellets co-doped with 0.5 wt% n-AlN and 1 wt% n-C display appreciable enhancement in critical current density (J_C ) of MgB2 in both low (≥ 3 times), as well as, high-field region (≥ 15 times). J_C versus H behavior of both pristine and doped MgB2 pellets is well explained in the light of the collective pinning model. Further, the normalized pinning force density f_p(= F_p/F_{pmax}) displays a fair correspondence with the scaling procedure proposed by Eisterer et al. Moreover, the scaled data of the pinning force density (i.e., f_p{-}h data) of the investigated pellets at different temperature are well interpreted by a modified Dew-Hughes expression reported by Sandu and Chee.

  10. Structural and thermodynamic properties of AlB2 compound

    NASA Astrophysics Data System (ADS)

    Zhou, Xiao-Lin; Liu, Ke; Chen, Xiang-Rong; Zhu, Jun

    2006-12-01

    We employ a first-principles plane wave method with the relativistic analytic pseudopotential of Hartwigsen, Goedecker and Hutter (HGH) scheme in the frame of DFT to calculate the equilibrium lattice parameters and the thermodynamic properties of AlB2 compound with hcp structure. The obtained lattice parameters are in good agreement with the available experimental data and those calculated by others. Through the quasi-harmonic Debye model, obtained successfully are the dependences of the normalized lattice parameters a/a0 and c/c0 on pressure P, the normalized primitive cell volume V/V0 on pressure P, the variation of the thermal expansion α with pressure P and temperature T, as well as the Debye temperature ΘD and the heat capacity CV on pressure P and temperature T.

  11. Harmonic and anharmonic phonons in MgB2

    NASA Astrophysics Data System (ADS)

    Calandra, Matteo

    2005-03-01

    The discovery ootnotetext J. Nagamatsu, N. Nakagawa, T. Muranaka, Y. Zenitani, and J. Akimitsu, Nature (London) 410, 63 (2001). of a 39 K critical superconducting temperature in MgB2 has challenged our understanding of electron-phonon mediated superconductivity. Several mechanisms have been proposed to explain the large critical temperature, including a double gap structure and anharmonic effects. Much attention has been devoted to the study of the E2g phonon mode, an anti-phase vibration of the two boron atoms parallel to the hexagonal plane. In Raman spectra ootnotetextJ. W. Quilty, S. Lee, A. Yamamoto, and S. Tajima, Phys. Rev. Lett. 88, 087001 (2002) an E2g symmetry feature, commonly attributed to the E2g phonon mode, is strongly damped, an effect which has been ascribed to large electron-phonon coupling and large anharmonic effects of the E2g mode. The interpretation of the magnitude of each effect is, however, very controversial, mostly because accurate phonon dispersion measurements by neutron spectroscopy are not yet available due to the small size of MgB2 single crystals.In this talk we show how the magnitude of anharmonic effects can be determined using a joined experimental and theoretical approach. We measure, for the first time, the phonon dispersion and lifetime in MgB2 single crystals with inelastic X-ray scattering ootnotetextA. Shukla, M. Calandra, M. d'Astuto, M. Lazzeri, F. Mauri, C. Bellin, M. Krisch, J. Karpinski, S. M. Kazakov, J. Jun, D. Daghero, and K. Parlinski, Phys. Rev. Lett. 90, 095506 (2003). This experimental technique allows accurate determination of phonon spectra even in the case of small single crystals. By using first principles calculations we obtain the harmonic phonon dispersion in MgB2 (in agreement with previous calculations ootnotetextY. Kong, O. V. Dolgov, O. Jepsen, and O. K. Andersen, Phys. Rev. B 64, 020501(R) (2001)). We evaluate the magnitude of anharmonic effects by calculating the anharmonic contributions to the

  12. Centaur Rocket in Space Propulsion Research Facility (B-2)

    NASA Image and Video Library

    1969-07-21

    A Centaur second-stage rocket in the Space Propulsion Research Facility, better known as B‒2, operating at NASA’s Plum Brook Station in Sandusky, Ohio. Centaur was designed to be used with an Atlas booster to send the Surveyor spacecraft to the moon in the mid-1960s. After those missions, the rocket was modified to launch a series of astronomical observation satellites into orbit and send space probes to other planets. Researchers conducted a series of systems tests at the Plum Brook test stands to improve the Centaur fuel pumping system. Follow up full-scale tests in the B-2 facility led to the eventual removal of the boost pumps from the design. This reduced the system’s complexity and significantly reduced the cost of a Centaur rocket. The Centaur tests were the first use of the new B-2 facility. B‒2 was the world's only high altitude test facility capable of full-scale rocket engine and launch vehicle system level tests. It was created to test rocket propulsion systems with up to 100,000 pounds of thrust in a simulated space environment. The facility has the unique ability to maintain a vacuum at the rocket’s nozzle while the engine is firing. The rocket fires into a 120-foot deep spray chamber which cools the exhaust before it is ejected outside the facility. B‒2 simulated space using giant diffusion pumps to reduce chamber pressure 10-6 torr, nitrogen-filled cold walls create cryogenic temperatures, and quartz lamps replicate the radiation of the sun.

  13. Spermatotoxic effect of aflatoxin B(1) in the albino mouse.

    PubMed

    Agnes, V F; Akbarsha, M A

    2003-01-01

    With the background that the foodborne mycotoxin aflatoxin B(1) (AFB(1)) could be toxic to the male reproductive mechanism in man as well as wild and domestic animals, the present study was aimed at finding the effect of AFB(1) on sperm. The Swiss albino mouse was the test animal. AFB(1,) suspended in corn oil and ethanol (95:5, v/v), was administered intraperitoneally to 90-day-old mice at a daily dose of 50 microg/kg body weight for 7, 15, 35 and 45 days. The analysis consisted of fertility testing and counts, motility and abnormalities of the cauda epididymidal sperm, adopting light- as well as electron-microscopy. The fertility of the treated mice was reduced drastically. Sperm concentration in the epididymis and sperm motility decreased whereas sperm abnormalities increased. In particular, sperm abnormalities like two axonemes in a common cytoplasm, sticking together of heads/tails, etc., were noted. A higher percentage of cauda epididymidal spermatozoa than in the control mice retained the cytoplasmic droplet (CD) and such retention was dependent on the duration of the treatment. Spermatozoa retaining the CD were inhibited in motility. Sperm CD of AFB(1)-treated mice contained electron-dense spherical inclusions, which are hypothesized as lipid inclusions produced from the lamellae through the spherical vesicles of the CD. The results indicate disruption of the spermatogenic as well as androgenic compartments of the testis by AFB(1). The results also reflect an alteration of epididymal function towards the post-testicular sperm maturation process by AFB(1).

  14. Genetic screening of non-classic CAH females with hyperandrogenemia identifies a novel CYP11B1 gene mutation.

    PubMed

    Shammas, Christos; Byrou, Stefania; Phelan, Marie M; Toumba, Meropi; Stylianou, Charilaos; Skordis, Nicos; Neocleous, Vassos; Phylactou, Leonidas A

    2016-04-01

    Congenital adrenal hyperplasia (CAH) is an endocrine autosomal recessive disorder with various symptoms of diverse severity. Mild hyperandrogenemia is the most commonclinical feature in non-classic CAH patients and 95% of the cases are identified by mutations in the CYP21A2 gene. In the present study, the second most common cause for non-classic CAH (NC-CAH), 11β-hydroxylase deficiency due to mutations in the CYP11B1 gene, is investigated. Screening of the CYP21A2 and CYP11B1 genes by direct sequencing was carried out for the detection of possible genetic defects in patients with suspected CAH. It wasobserved that CYP11B1 variants co-exist only in rare cases along with mutations in CYP21A2 in patients clinically diagnosed with CAH. A total of 23 NC-CAH female patients out of 75 were identified with only one mutation in the CYP21A2 gene. The novel CYP11B1 gene mutation, p.Val484Asp, was identified in a patient with CAH in the heterozygous state. The structural characterization of the novel p.Val484Asp was found to likely cause distortion of the surrounding beta sheet and indirect destabilization of the cavity that occurs on the opposite face of the structural elements, leading to partial impairment of the enzymatic activity. CYP21A2 gene mutations are the most frequent genetic defects in cases of NC-CAH even when these patients are in the heterozygous state. These mutations have a diverse phenotype giving rise to a variable extent of cortisol synthesis impairment; it is also clear that CYP11B1 mutants are a rare type of defects causing CAH.

  15. Pulmonary oedema producing toxin from Mesobuthus tamulus venom augments cardio-respiratory reflexes through B2 kinin receptors.

    PubMed

    Alex, Anitha B; Akella, Aparna; Tiwari, Anil K; Deshpande, Shripad B

    2014-01-01

    The current study was undertaken to compare the effects of pulmonary oedema producing toxin (PO-Tx) isolated from Mesobuthus tamulus venom on cardio-respiratory reflexes with exogenously administered bradykinin (BK) and to delineate the type of BK receptors mediating these responses. Jugular venous injection of phenyldiguanide (PDG) in anaesthetized rats produced reflex bradycardia, hypotension and apnoea. The PDG-induced reflex was augmented (two folds) by PO-Tx. The pulmonary water content in PO-Tx treated group was also increased. The PO-Tx-induced reflex changes as well as pulmonary oedema were blocked by-Hoe-140 implicating the involvement of B2 kinin receptors. Exogenous BK also produced augmentation (two folds) of the PDG-induced reflexes and increased the pulmonary water content. The BK-induced augmentation was blocked by pre-treatment with des-Arg10 Hoe 140 (a B1 receptor antagonist) and Hoe 140 (B2 receptor antagonist). However, these antagonists did not prevent the development of BK-induced pulmonary oedema. Present results indicate that PO-Tx augmented the PDG-induced reflex responses similar to BK and the PO-Tx induced augmentation of reflexes is mediated through B2 receptors.

  16. Effects of HfB2 and HfN Additions on the Microstructures and Mechanical Properties of TiB2-Based Ceramic Tool Materials

    PubMed Central

    An, Jing; Song, Jinpeng; Liang, Guoxing; Gao, Jiaojiao; Xie, Juncai; Cao, Lei; Wang, Shiying; Lv, Ming

    2017-01-01

    The effects of HfB2 and HfN additions on the microstructures and mechanical properties of TiB2-based ceramic tool materials were investigated. The results showed that the HfB2 additive not only can inhibit the TiB2 grain growth but can also change the morphology of some TiB2 grains from bigger polygons to smaller polygons or longer ovals that are advantageous for forming a relatively fine microstructure, and that the HfN additive had a tendency toward agglomeration. The improvement of flexural strength and Vickers hardness of the TiB2-HfB2 ceramics was due to the relatively fine microstructure; the decrease of fracture toughness was ascribed to the formation of a weaker grain boundary strength due to the brittle rim phase and the poor wettability between HfB2 and Ni. The decrease of the flexural strength and Vickers hardness of the TiB2-HfN ceramics was due to the increase of defects such as TiB2 coarse grains and HfN agglomeration; the enhancement of fracture toughness was mainly attributed to the decrease of the pore number and the increase of the rim phase and TiB2 coarse grains. The toughening mechanisms of TiB2-HfB2 ceramics mainly included crack bridging and transgranular fracture, while the toughening mechanisms of TiB2-HfN ceramics mainly included crack deflection, crack bridging, transgranular fracture, and the core-rim structure. PMID:28772821

  17. Determination of fumonisin B1 levels in body fluids and hair from piglets fed fumonisin B1-contaminated diets.

    PubMed

    Souto, Pollyana C M C; Jager, Alessandra V; Tonin, Fernando G; Petta, Tânia; Di Gregório, Mayra C; Cossalter, Anne-Marie; Pinton, Philippe; Oswald, Isabelle P; Rottinghaus, George E; Oliveira, Carlos A F

    2017-10-01

    The levels of fumonisin B 1 (FB 1 ) residues in plasma, urine, feces and hair from 24 piglets fed FB 1 -contaminated diets containing 3.1, 6.1 or 9.0 μg FB 1 .g -1 for 28 days were determined using liquid chromatography coupled to mass spectrometry (LC-MS/MS). The levels of FB 1 in plasma, urine, feces and pooled hair (n = 3) samples varied from 0.15 to 1.08 μg.L -1 , 16.09-75.01 μg.L -1 , 1.87-13.89 μg.g -1 and 2.08-8.09 ng.g -1 , respectively. Significant correlations (r = 0.808-0.885; P < 0.001; N = 18) were found between FB 1 intake and plasma FB 1 on days 7, 14, 21 and 28. However, urinary FB 1 correlated with FB 1 intake only on days 7 and 14 (r = 0.561-572; P = 0.02; N = 18). A significant correlation (r = 0.509; P = 0.02; N = 24) was also found for the first time between FB 1 in hair samples and FB 1 intake. Plasma and urinary FB 1 are good biomarkers of early exposure of pigs to low dietary FB 1 levels, although plasma is recommended to assess prolonged exposure (>14 days). The possibility to evaluate hair as a biomarker of fumonisin exposure was established, although further studies are needed to provide physiologically based toxicokinetics of residual FB 1 in the pig hair. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Lightweight MgB2 superconducting 10 MW wind generator

    NASA Astrophysics Data System (ADS)

    Marino, I.; Pujana, A.; Sarmiento, G.; Sanz, S.; Merino, J. M.; Tropeano, M.; Sun, J.; Canosa, T.

    2016-02-01

    The offshore wind market demands a higher power rate and more reliable turbines in order to optimize capital and operational costs. The state-of-the-art shows that both geared and direct-drive conventional generators are difficult to scale up to 10 MW and beyond due to their huge size and weight. Superconducting direct-drive wind generators are considered a promising solution to achieve lighter weight machines. This work presents an innovative 10 MW 8.1 rpm direct-drive partial superconducting generator using MgB2 wire for the field coils. It has a warm iron rotor configuration with the superconducting coils working at 20 K while the rotor core and the armature are at ambient temperature. A cooling system based on cryocoolers installed in the rotor extracts the heat from the superconducting coils by conduction. The generator's main parameters are compared against a permanent magnet reference machine, showing a significant weight and size reduction. The 10 MW superconducting generator concept will be experimentally validated with a small-scale magnetic machine, which has innovative components such as superconducting coils, modular cryostats and cooling systems, and will have similar size and characteristics as the 10 MW generator.

  19. The Conserved nhaAR Operon Is Drastically Divergent between B2 and Non-B2 Escherichia coli and Is Involved in Extra-Intestinal Virulence

    PubMed Central

    Lescat, Mathilde; Reibel, Florence; Pintard, Coralie; Dion, Sara; Glodt, Jérémy; Gateau, Cecile; Launay, Adrien; Ledda, Alice; Cruvellier, Stephane; Tourret, Jérôme; Tenaillon, Olivier

    2014-01-01

    The Escherichia coli species is divided in phylogenetic groups that differ in their virulence and commensal distribution. Strains belonging to the B2 group are involved in extra-intestinal pathologies but also appear to be more prevalent as commensals among human occidental populations. To investigate the genetic specificities of B2 sub-group, we used 128 sequenced genomes and identified genes of the core genome that showed marked difference between B2 and non-B2 genomes. We focused on the gene and its surrounding region with the strongest divergence between B2 and non-B2, the antiporter gene nhaA. This gene is part of the nhaAR operon, which is in the core genome but flanked by mobile regions, and is involved in growth at high pH and high sodium concentrations. Consistently, we found that a panel of non-B2 strains grew faster than B2 at high pH and high sodium concentrations. However, we could not identify differences in expression of the nhaAR operon using fluorescence reporter plasmids. Furthermore, the operon deletion had no differential impact between B2 and non-B2 strains, and did not result in a fitness modification in a murine model of gut colonization. Nevertheless, sequence analysis and experiments in a murine model of septicemia revealed that recombination in nhaA among B2 strains was observed in strains with low virulence. Finally, nhaA and nhaAR operon deletions drastically decreased virulence in one B2 strain. This effect of nhaAR deletion appeared to be stronger than deletion of all pathogenicity islands. Thus, a population genetic approach allowed us to identify an operon in the core genome without strong effect in commensalism but with an important role in extra-intestinal virulence, a landmark of the B2 strains. PMID:25268639

  20. The conserved nhaAR operon is drastically divergent between B2 and non-B2 Escherichia coli and is involved in extra-intestinal virulence.

    PubMed

    Lescat, Mathilde; Reibel, Florence; Pintard, Coralie; Dion, Sara; Glodt, Jérémy; Gateau, Cecile; Launay, Adrien; Ledda, Alice; Cruveiller, Stephane; Cruvellier, Stephane; Tourret, Jérôme; Tenaillon, Olivier

    2014-01-01

    The Escherichia coli species is divided in phylogenetic groups that differ in their virulence and commensal distribution. Strains belonging to the B2 group are involved in extra-intestinal pathologies but also appear to be more prevalent as commensals among human occidental populations. To investigate the genetic specificities of B2 sub-group, we used 128 sequenced genomes and identified genes of the core genome that showed marked difference between B2 and non-B2 genomes. We focused on the gene and its surrounding region with the strongest divergence between B2 and non-B2, the antiporter gene nhaA. This gene is part of the nhaAR operon, which is in the core genome but flanked by mobile regions, and is involved in growth at high pH and high sodium concentrations. Consistently, we found that a panel of non-B2 strains grew faster than B2 at high pH and high sodium concentrations. However, we could not identify differences in expression of the nhaAR operon using fluorescence reporter plasmids. Furthermore, the operon deletion had no differential impact between B2 and non-B2 strains, and did not result in a fitness modification in a murine model of gut colonization. Nevertheless, sequence analysis and experiments in a murine model of septicemia revealed that recombination in nhaA among B2 strains was observed in strains with low virulence. Finally, nhaA and nhaAR operon deletions drastically decreased virulence in one B2 strain. This effect of nhaAR deletion appeared to be stronger than deletion of all pathogenicity islands. Thus, a population genetic approach allowed us to identify an operon in the core genome without strong effect in commensalism but with an important role in extra-intestinal virulence, a landmark of the B2 strains.

  1. Ceramic granules enhanced with B2A peptide for lumbar interbody spine fusion: an experimental study using an instrumented model in sheep.

    PubMed

    Cunningham, Bryan W; Atkinson, Brent L; Hu, Nianbin; Kikkawa, Jun; Jenis, Louis; Bryant, Joseph; Zamora, Paul O; McAfee, Paul C

    2009-04-01

    New generations of devices for spinal interbody fusion are expected to arise from the combined use of bioactive peptides and porous implants. The purpose of this dose-ranging study was to evaluate the fusion characteristics of porous ceramic granules (CGs) coated with the bioactive peptide B2A2-K-NS (B2A) by using a model of instrumented lumbar interbody spinal fusion in sheep. Instrumented spinal arthrodesis was performed in 40 operative sites in 20 adult sheep. In each animal, posterior instrumentation (pedicle screw and rod) and a polyetheretherketone cage were placed in 2 single-level procedures (L2-3 and L4-5). All cages were packed with graft material prior to implantation. The graft materials were prepared by mixing (1:1 vol/vol) CGs with or without a B2A coating and morselized autograft. Ceramic granules were coated with B2A at 50, 100, 300, and 600 microg/ml granules (50-B2A/CG, 100-B2A/CG, 300-B2A/CG, and 600-B2A/CG, respectively), resulting in 4 B2A-coated groups plus a control group (uncoated CGs). Graft material from each of these groups was implanted in 8 operative sites. Four months after arthrodesis, interbody fusion status was assessed with CT, and the interbody site was further evaluated with quantitative histomorphometry. All B2A/CG groups had higher CT-confirmed interbody fusion rates compared with those in controls (CGs only). Seven of 8 sites were fused in the 50-B2A/CG, 100-B2A/CG, and 300-B2A/CG groups, whereas 5 of 8 sites were fused in the group that had received uncoated CGs. New woven and lamellar bone spanned the fusion sites with excellent osseointegration. There was no heterotopic ossification or other untoward events attributed to the use of B2A/CG in any group. Each B2A/CG treatment produced more new bone than that in the CG group. Bioactive treatment with B2A effectively enhanced the fusion capacity of porous CGs. These findings suggest that B2A/CG may well represent a new generation of biomaterials for lumbar interbody fusion and

  2. A plant cyclin B2 is degraded early in mitosis and its ectopic expression shortens G2-phase and alleviates the DNA-damage checkpoint.

    PubMed

    Weingartner, Magdalena; Pelayo, Helvia R; Binarova, Pavla; Zwerger, Karin; Melikant, Balázs; de la Torre, Consuelo; Heberle-Bors, Erwin; Bögre, László

    2003-02-01

    Mitotic progression is timely regulated by the accumulation and degradation of A- and B-type cyclins. In plants, there are three classes of A-, and two classes of B-type cyclins, but their specific roles are not known. We have generated transgenic tobacco plants in which the ectopic expression of a plant cyclin B2 gene is under the control of a tetracycline-inducible promoter. We show that the induction of cyclin B2 expression in cultured cells during G2 phase accelerates the entry into mitosis and allows cells to override the replication checkpoint induced by hydroxyurea in the simultaneous presence of caffeine or okadaic acid, drugs that are known to alleviate checkpoint control. These results indicate that in plants, a B2-type cyclin is a rate-limiting regulator for the entry into mitosis and a cyclin B2-CDK complex might be a target for checkpoint control pathways. The cyclin B2 localization and the timing of its degradation during mitosis corroborate these conclusions: cyclin B2 protein is confined to the nucleus and during mitosis it is only present during a short time window until mid prophase, but it is effectively degraded from this timepoint onwards. Although cyclin B2 is not present in cells arrested by the spindle checkpoint in metaphase, cyclin B1 is accumulating in these cells. Ectopic expression of cyclin B2 in developing plants interferes with differentiation events and specifically blocks root regeneration, indicating the importance of control mechanisms at the G2- to M-phase transition during plant developmental processes.

  3. Fasitibant chloride, a kinin B2 receptor antagonist, and dexamethasone interact to inhibit carrageenan-induced inflammatory arthritis in rats

    PubMed Central

    Valenti, Claudio; Giuliani, Sandro; Cialdai, Cecilia; Tramontana, Manuela; Maggi, Carlo Alberto

    2012-01-01

    BACKGROUND AND PURPOSE Bradykinin, through the kinin B2 receptor, is involved in inflammatory processes related to arthropathies. B2 receptor antagonists inhibited carrageenan-induced arthritis in rats in synergy with anti-inflammatory steroids. The mechanism(s) underlying this drug interaction was investigated. EXPERIMENTAL APPROACH Drugs inhibiting inflammatory mediators released by carrageenan were injected, alone or in combination, into the knee joint of pentobarbital anaesthetized rats 30 min before intra-articular administration of carrageenan. Their effects on the carrageenan-induced inflammatory responses (joint pain, oedema and neutrophil recruitment) and release of inflammatory mediators (prostaglandins, IL-1β, IL-6 and the chemokine GRO/CINC-1), were assessed after 6 h. KEY RESULTS The combination of fasitibant chloride (MEN16132) and dexamethasone was more effective than each drug administered alone in inhibiting knee joint inflammation and release of inflammatory mediators. Fasitibant chloride, MK571, atenolol, des-Arg9-[Leu8]-bradykinin (B2 receptor, leukotriene, catecholamine and B1 receptor antagonists, respectively) and dexketoprofen (COX inhibitor), reduced joint pain and, except for the latter, also diminished joint oedema. A combination of drugs inhibiting joint pain (fasitibant chloride, des-Arg9-[Leu8]-bradykinin, dexketoprofen, MK571 and atenolol) and oedema (fasitibant chloride, des-Arg9-[Leu8]-bradykinin, MK571 and atenolol) abolished the respective inflammatory response, producing inhibition comparable with that achieved with the combination of fasitibant chloride and dexamethasone. MK571 alone was able to block neutrophil recruitment. CONCLUSIONS AND IMPLICATIONS Bradykinin-mediated inflammatory responses to intra-articular carrageenan were not controlled by steroids, which were not capable of preventing bradykinin effects either by direct activation of the B2 receptor, or through the indirect effects mediated by release of eicosanoids

  4. Lattice Thermal Conductivity of Ultra High Temperature Ceramics (UHTC) ZrB2 and HfB2 from Atomistic Simulations

    NASA Technical Reports Server (NTRS)

    Lawson, JOhn W.; Daw, Murray S.; Bauschlicher, Charles W.

    2011-01-01

    Ultra high temperature ceramics (UHTC) including ZrB2 and HfB2 are candidate materials for applications in extreme environments because of their high melting point, good mechanical properties and reasonable oxidation resistance. Unlike many ceramics, these materials have high thermal conductivity which can be advantageous, for example, to reduce thermal shock. Recently, we developed Tersoff style interatomic potentials for both ZrB2 and HfB2 appropriate for atomistic simulations. As an application, Green-Kubo molecular dynamics simulations were performed to evaluate the lattice thermal conductivity for single crystals of ZrB2 and HfB2. The atomic mass difference in these binary compounds leads to oscillations in the time correlation function of the heat current. Results at room temperature and at elevated temperatures will be reported.

  5. Beyond the exchange--the future of B2B.

    PubMed

    Wise, R; Morrison, D

    2000-01-01

    Using the Internet to facilitate business-to-business commerce promises many benefits, such as dramatic cost reductions and greater access to buyers and sellers. Yet little is known about how B2B e-commerce will evolve. The authors argue that changes in the financial services industry over the past two decades provide important clues. Exchanges, they say, are not the primary source of value in information-intensive markets; value tends to accumulate among a diverse group of specialists that focus on such tasks as packaging, standard setting, arbitrage, and information management. Because scale and liquidity are vitally important to efficient trading, today's exchanges will consolidate into a relatively small set of mega-exchanges. Originators will handle the origination and aggregation of complex transactions before sending them on to mega-exchanges for execution. E-speculators, seeking to capitalize on an abundance of market information, will tend to concentrate where relatively standardized products can be transferred easily among a large group of buyers. In many markets, a handful of independent solution providers with well-known brand names and solid reputations will thrive alongside mega-exchanges. Sell-side asset exchanges will create the networks and provide the tools to allow suppliers to trade orders among themselves, sometimes after initial transactions with customers are made on the mega-exchanges. For many companies, traditional skills in such areas as product development, manufacturing, and marketing may become relatively less important, while the ability to understand and capitalize on market dynamics may become considerably more important.

  6. The Photometric Behavior of Comet Hyakutake (1996 B2)

    NASA Astrophysics Data System (ADS)

    Schleicher, D. G.; Osip, D. J.

    2000-10-01

    We present results from narrowband photometry of Comet Hyakutake (1996 B2) obtained at Lowell Observatory from 1996 February 9 to April 14. Previous analysis of these data and corresponding CCD images of the dust coma were used to determine Hyakutake's rotation period as being 6.23+/-0.03 hr (Schleicher, Millis, Osip, and Lederer, 1998, Icarus 131, 233). New analyses have investigated the trends of dust and gas production as a function of heliocentric distance, the characteristics of the major outburst which occured a few days prior to perigee, and the nature of the trends in derived production rates as a function of aperture size and rotational phase. We have also determined a refined rotation period of 6.266+/-0.008 hr, after accounting for these effects and combining our data with the CCD lightcurve measurements of Lisse et al. (1999, Icarus 140, 189). The combined lightcurves permits us to constrain the onset time of the outburst to Mar 20.0+/-0.3. We unexpectedly measured a change in dust color as a function of heliocentric distance, with the UV continuum (3650 Å) having an r-dependence 0.31 steeper that the continuum at 4845 Å. The r-dependences of the carbon--bearing species, CN, C2, and C3, were all similar to the dust, while OH and NH were much more shallow -- significantly less than expected with a standard water vaporization model, possibly due to a strong seasonal effect. Our derived water production implies a peak active area on the nucleus of about 30 km2, and a minimum effective radius of 1.5 km. The ratio of the trace species to water classifies this comet as ``typical'' in our current compositional taxonomy [cf. A'Hearn et al., 1995, Icarus 118, 223]. This research was supported by NASA.

  7. Hot corrosion of the B2 nickel aluminides

    NASA Technical Reports Server (NTRS)

    Ellis, David L.

    1993-01-01

    The hot corrosion behavior of the B2 nickel aluminides was studied to determine the inherent hot corrosion resistance of the beta nickel aluminides and to develop a mechanism for the hot corrosion of the beta nickel aluminides. The effects of the prior processing of the material, small additions of zirconium, stoichiometry of the materials, and preoxidation of the samples were also examined. Additions of 2, 5, and 15 w/o chromium were used to determine the effect of chromium on the hot corrosion of the beta nickel aluminides and the minimum amount of chromium necessary for good hot corrosion resistance. The results indicate that the beta nickel aluminides have inferior inherent hot corrosion resistance despite their excellent oxidation resistance. Prior processing and zirconium additions had no discernible effect on the hot corrosion resistance of the alloys. Preoxidation extended the incubation period of the alloys only a few hours and was not considered to be an effective means of stopping hot corrosion. Stoichiometry was a major factor in determining the hot corrosion resistance of the alloys with the higher aluminum alloys having a definitely superior hot corrosion resistance. The addition of chromium to the alloys stopped the hot corrosion attack in the alloys tested. From a variety of experimental results, a complex hot corrosion mechanism was proposed. During the early stages of the hot corrosion of these alloys the corrosion is dominated by a local sulphidation/oxidation form of attack. During the intermediate stages of the hot corrosion, the aluminum depletion at the surface leads to a change in the oxidation mechanism from a protective external alumina layer to a mixed nickel-aluminum spinel and nickel oxide that can occur both externally and internally. The material undergoes extensive cracking during the later portions of the hot corrosion.