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Sample records for s6 kinases s6ks

S6Ks isoforms contribute to viability, migration, docetaxel resistance and tumor formation of prostate cancer cells

International Nuclear Information System (INIS)

Amaral, Camila L.; Freitas, Lidia B.; Tamura, Rodrigo E.; Tavares, Mariana R.; Pavan, Isadora C. B.; Bajgelman, Marcio C.; Simabuco, Fernando M.

2016-01-01

The S6 Kinase (S6K) proteins are some of the main downstream effectors of the mammalian Target Of Rapamycin (mTOR) and act as key regulators of protein synthesis and cell growth. S6K is overexpressed in a variety of human tumors and is correlated to poor prognosis in prostate cancer. Due to the current urgency to identify factors involved in prostate cancer progression, we aimed to reveal the cellular functions of three S6K isoforms–p70-S6K1, p85-S6K1 and p54-S6K2–in prostate cancer, as well as their potential as therapeutic targets. In this study we performed S6K knockdown and overexpression and investigated its role in prostate cancer cell proliferation, colony formation, viability, migration and resistance to docetaxel treatment. In addition, we measured tumor growth in Nude mice injected with PC3 cells overexpressing S6K isoforms and tested the efficacy of a new available S6K1 inhibitor in vitro. S6Ks overexpression enhanced PC3-luc cell line viability, migration, resistance to docetaxel and tumor formation in Nude mice. Only S6K2 knockdown rendered prostate cancer cells more sensitive to docetaxel. S6K1 inhibitor PF-4708671 was particularly effective for reducing migration and proliferation of PC3 cell line. These findings demonstrate that S6Ks play an important role in prostate cancer progression, enhancing cell viability, migration and chemotherapy resistance, and place both S6K1 and S6K2 as a potential targets in advanced prostate cancer. We also provide evidence that S6K1 inhibitor PF-4708671 may be considered as a potential drug for prostate cancer treatment. The online version of this article (doi:10.1186/s12885-016-2629-y) contains supplementary material, which is available to authorized users
Ribosomal S6 Kinase Cooperates with Casein Kinase 2 to Modulate the Drosophila Circadian Molecular Oscillator

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Akten, Bikem; Tangredi, Michelle M.; Jauch, Eike; Roberts, Mary A.; Ng, Fanny; Raabe, Thomas; Jackson, F. Rob

2009-01-01

There is a universal requirement for post-translational regulatory mechanisms in circadian clock systems. Previous work in Drosophila has identified several kinases, phosphatases and an E3 ligase that are critical for determining the nuclear translocation and/or stability of clock proteins. The present study evaluated the function of p90 ribosomal S6 kinase (RSK) in the Drosophila circadian system. In mammals, RSK1 is a light- and clock-regulated kinase known to be activated by the MAPK pathway, but there is no direct evidence that it functions as a component of the circadian system. Here, we show that Drosophila S6KII RNA displays rhythms in abundance, indicative of circadian control. Importantly, an S6KII null mutant exhibits a short-period circadian phenotype that can be rescued by expression of the wild-type gene in clock neurons, indicating a role for S6KII in the molecular oscillator. Peak PER clock protein expression is elevated in the mutant, indicative of enhanced stability, whereas per mRNA level is decreased, consistent with enhanced feedback repression. Gene reporter assays show that decreased S6KII is associated with increased PER repression. Surprisingly, we demonstrate a physical interaction between S6KII and the Casein Kinase 2 regulatory subunit (CK2β), suggesting a functional relationship between the two kinases. In support of such a relationship, there are genetic interactions between S6KII and CK2 mutations, in vivo, which indicate that CK2 activity is required for S6KII action. We propose that the two kinases cooperate within clock neurons to fine-tune circadian period, improving the precision of the clock mechanism. PMID:19144847
Inhibition of mammalian S6 kinase by resveratrol suppresses autophagy.

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Armour, Sean M; Baur, Joseph A; Hsieh, Sherry N; Land-Bracha, Abigail; Thomas, Sheila M; Sinclair, David A

2009-06-03

Resveratrol is a plant-derived polyphenol that promotes health and disease resistance in rodent models, and extends lifespan in lower organisms. A major challenge is to understand the biological processes and molecular pathways by which resveratrol induces these beneficial effects. Autophagy is a critical process by which cells turn over damaged components and maintain bioenergetic requirements. Disruption of the normal balance between pro- and anti-autophagic signals is linked to cancer, liver disease, and neurodegenerative disorders. Here we show that resveratrol attenuates autophagy in response to nutrient limitation or rapamycin in multiple cell lines through a pathway independent of a known target, SIRT1. In a large-scalein vitro kinase screen we identified p70 S6 kinase (S6K1) as a target of resveratrol. Blocking S6K1 activity by expression of a dominant-negative mutant or RNA interference is sufficient to disrupt autophagy to a similar extent as resveratrol. Furthermore, co-administration of resveratrol with S6K1 knockdown does not produce an additive effect. These data indicate that S6K1 is important for the full induction of autophagy in mammals and raise the possibility that some of the beneficial effects of resveratrol are due to modulation of S6K1 activity.
Skeletal myocyte hypertrophy requires mTOR kinase activity and S6K1

International Nuclear Information System (INIS)

Park, In-Hyun; Erbay, Ebru; Nuzzi, Paul; Chen Jie

2005-01-01

The protein kinase mammalian target of rapamycin (mTOR) is a central regulator of cell proliferation and growth, with the ribosomal subunit S6 kinase 1 (S6K1) as one of the key downstream signaling effectors. A critical role of mTOR signaling in skeletal muscle differentiation has been identified recently, and an unusual regulatory mechanism independent of mTOR kinase activity and S6K1 is revealed. An mTOR pathway has also been reported to regulate skeletal muscle hypertrophy, but the regulatory mechanism is not completely understood. Here, we report the investigation of mTOR's function in insulin growth factor I (IGF-I)-induced C2C12 myotube hypertrophy. Added at a later stage when rapamycin no longer had any effect on normal myocyte differentiation, rapamycin completely blocked myocyte hypertrophy as measured by myotube diameter. Importantly, a concerted increase of average myonuclei per myotube was observed in IGF-I-stimulated myotubes, which was also inhibited by rapamycin added at a time when it no longer affected normal differentiation. The mTOR protein level, its catalytic activity, its phosphorylation on Ser2448, and the activity of S6K1 were all found increased in IGF-I-stimulated myotubes compared to unstimulated myotubes. Using C2C12 cells stably expressing rapamycin-resistant forms of mTOR and S6K1, we provide genetic evidence for the requirement of mTOR and its downstream effector S6K1 in the regulation of myotube hypertrophy. Our results suggest distinct mTOR signaling mechanisms in different stages of skeletal muscle development: While mTOR regulates the initial myoblast differentiation in a kinase-independent and S6K1-independent manner, the hypertrophic function of mTOR requires its kinase activity and employs S6K1 as a downstream effector
Metabolic control by S6 kinases depends on dietary lipids.

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Tamara R Castañeda

Full Text Available Targeted deletion of S6 kinase (S6K 1 in mice leads to higher energy expenditure and improved glucose metabolism. However, the molecular mechanisms controlling these effects remain to be fully elucidated. Here, we analyze the potential role of dietary lipids in regulating the mTORC1/S6K system. Analysis of S6K phosphorylation in vivo and in vitro showed that dietary lipids activate S6K, and this effect is not dependent upon amino acids. Comparison of male mice lacking S6K1 and 2 (S6K-dko with wt controls showed that S6K-dko mice are protected against obesity and glucose intolerance induced by a high-fat diet. S6K-dko mice fed a high-fat diet had increased energy expenditure, improved glucose tolerance, lower fat mass gain, and changes in markers of lipid metabolism. Importantly, however, these metabolic phenotypes were dependent upon dietary lipids, with no such effects observed in S6K-dko mice fed a fat-free diet. These changes appear to be mediated via modulation of cellular metabolism in skeletal muscle, as shown by the expression of genes involved in energy metabolism. Taken together, our results suggest that the metabolic functions of S6K in vivo play a key role as a molecular interface connecting dietary lipids to the endogenous control of energy metabolism.
The Р60-S6K1 isoform of ribosomal protein S6 kinase 1 is a product of alternative mRNA translation

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I. V. Zaiets

2018-07-01

Full Text Available Ribosomal protein S6 kinase 1 (S6K1 is a well-known downstream effector of mTORC1 (mechanistic target of rapamycin complex 1 participating primarily in the regulation of cell growth and metabolism. Deregulation of mTOR/S6K1 signaling can promote numerous human pathologies, including cancer, neurodegeneration, cardiovascular disease, and metabolic disorders. As existing data suggest, the S6K1 gene encodes several protein isoforms, including p85-S6K1, p70-S6K1, and p60-S6K1. The two of these isoforms, p85-S6K1 and p70-S6K1, were extensively studied to date. The origin and functional significance of the p60-S6K1 isoform remains a mystery, however, it was suggested that the isoform could be a product of alternative S6K1 mRNA translation. Herein we report the generation of HEK-293 cells exclusively expressing p60-S6K1 as a result of CRISPR/Cas9-mediated inactivation of p85/p70-S6K1 translation. Moreover, the generated modified cells displayed the elevated level of p60-S6K1 expression compared to that in wild-type HEK-293 cells. Our data confirm an assumption that p60-S6K1 is alternatively translated, most probably, from the common for both p70- and p85-S6K1 mRNA transcript and reveal a link between p60-S6K1 expression and such cellular processes as cell proliferation and motility. In addition, our findings indicate that the p60-S6K1 isoform of S6K1 may undergo a mode of regulation distinct from p70- and p85-S6K1 due to the absence of mTOR-regulated p60-S6K1 phosphorylation at T389 that is important for S6K1 activation.
Growth Inhibition by Bupivacaine Is Associated with Inactivation of Ribosomal Protein S6 Kinase 1

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Beigh, Mushtaq Ahmad; Showkat, Mehvish; Bashir, Basharat; Bashir, Asma; Hussain, Mahboob ul; Andrabi, Khurshid Iqbal

2014-01-01

Bupivacaine is an amide type long acting local anesthetic used for epidural anesthesia and nerve blockade in patients. Use of bupivacaine is associated with severe cytotoxicity and apoptosis along with inhibition of cell growth and proliferation. Although inhibition of Erk, Akt, and AMPK seemingly appears to mediate some of the bupivacaine effects, potential downstream targets that mediate its effect remain unknown. S6 kinase 1 is a common downstream effector of several growth regulatory pathways involved in cell growth and proliferation known to be affected by bupivacaine. We have accordingly attempted to relate the growth inhibitory effects of bupivacaine with the status of S6K1 activity and we present evidence that decrease in cell growth and proliferation by bupivacaine is mediated through inactivation of S6 kinase 1 in a concentration and time dependent manner. We also show that ectopic expression of constitutively active S6 kinase 1 imparts substantial protection from bupivacaine induced cytotoxicity. Inactivation of S6K1 though associated with loss of putative mTOR mediated phosphorylation did not correspond with loss of similar phosphorylations in 4EBP1 indicating that S6K1 inhibition was not mediated through inactivation of mTORC1 signaling pathway or its down regulation. PMID:24605337
[Protein kinase A inhibitor H-89 blocks polyploidization of SP600125-induced CMK cells by regulating phosphorylation of ribosomal protein S6 kinase 1].

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Zhao, Song; Yang, Jingang; Li, Changling; Xing, Sining; Yu, Ying; Liu, Shuo; Pu, Feifei; Ma, Dongchu

2016-10-01

Objective To investigate the regulatory effect of post-translation modification of ribosomal protein S6 kinase 1 (S6K1) on the polyploidization of megakaryocytes. Methods SP600125, a c-Jun N-terminal kinase (JNK) inhibitor, and H-89, a cAMP-dependent protein kinase (PKA) inhibitor, were used to treat CMK cells separately or in combination. With propidium iodide (PI) to dye DNA in the treated cells, the relative DNA content was detected by flow cytometry, and then the DNA polyploidy was analyzed. The change of expression and phosphorylation of ribosomal protein S6 kinase 1 (S6K1), an important mammalian target of rapamycin (mTOR) downstream target molecule, was analyzed by Western blotting. Molecular docking study and kinase activity assay were performed to analyze the combination of H-89 with S6K1 and the effect of H-89 on the activity of S6K1 kinase. Results SP600125 induced CMK cell polyploidization in a time-dependent and dose-dependent manner. At the same time, it increased the phosphorylation of S6K1 at Thr421/Ser424 and decreased the phosphorylation of S6K1 at Thr389. H-89 not only blocked polyploidization, but also decreased the phosphorylation of S6K1 at Thr421/Ser424 and increased the phosphorylation of S6K1 at Thr389. Molecular docking and kinase activity assay showed that H-89 occupied the ATP binding sites of S6K1 and inhibited its activity. Noticeably, both H-89 and SP600125 inhibited the activity of PKA. Moreover, the two drugs further inhibited the activity of PKA when used together. Therefore, these data indicated that H-89 blocked the SP600125-induced polyploidization of CMK cells mainly by changing S6K1 phosphorylation state, rather than its inhibitory effect on PKA. Conclusion H-89 can block the polyploidization of SP600125-induced CMK cells by regulating S6K1 phosphorylation state.
Ribosomal protein mutations induce autophagy through S6 kinase inhibition of the insulin pathway.

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Harry F Heijnen

Full Text Available Mutations affecting the ribosome lead to several diseases known as ribosomopathies, with phenotypes that include growth defects, cytopenia, and bone marrow failure. Diamond-Blackfan anemia (DBA, for example, is a pure red cell aplasia linked to the mutation of ribosomal protein (RP genes. Here we show the knock-down of the DBA-linked RPS19 gene induces the cellular self-digestion process of autophagy, a pathway critical for proper hematopoiesis. We also observe an increase of autophagy in cells derived from DBA patients, in CD34+ erythrocyte progenitor cells with RPS19 knock down, in the red blood cells of zebrafish embryos with RP-deficiency, and in cells from patients with Shwachman-Diamond syndrome (SDS. The loss of RPs in all these models results in a marked increase in S6 kinase phosphorylation that we find is triggered by an increase in reactive oxygen species (ROS. We show that this increase in S6 kinase phosphorylation inhibits the insulin pathway and AKT phosphorylation activity through a mechanism reminiscent of insulin resistance. While stimulating RP-deficient cells with insulin reduces autophagy, antioxidant treatment reduces S6 kinase phosphorylation, autophagy, and stabilization of the p53 tumor suppressor. Our data suggest that RP loss promotes the aberrant activation of both S6 kinase and p53 by increasing intracellular ROS levels. The deregulation of these signaling pathways is likely playing a major role in the pathophysiology of ribosomopathies.
p70S6 kinase signals cell survival as well as growth, inactivating the pro-apoptotic molecule BAD

DEFF Research Database (Denmark)

Harada, H; Andersen, Jens S.; Mann, M

2001-01-01

Cytokines often deliver simultaneous, yet distinct, cell growth and cell survival signals. The 70-kDa ribosomal protein S6 kinase (p70S6K) is known to regulate cell growth by inducing protein synthesis components. We purified membrane-based p70S6K as a kinase responsible for site-specific phospho...
Generation and characterization of polyclonal antibodies specific to N-terminal extension of p85 isoform of ribosomal protein S6 kinase 1 (p85 S6K1

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Savinska L. O.

2015-08-01

Full Text Available Aim. Generation of polyclonal antibodies specific to the ribosomal protein S6 kinase isoform – p85S6K1 and directed to the N-terminal (1–23 aa extension of p85S6K1. Methods. Animal immunization with synthetic (1–23 aa peptide, ELISA, Western blot, Immunoprecipitation, immunofluorescent analysis. Results. Polyclonal antibodies have been generated, which specifically recognize only p85 but not p70 isoform of S6K1 in western blot, immunoprecipitation and immunofluorescence analysis. Conclusions. The obtained antibodies can be recommended for studies on the p85S6K1 and other S6K1 isoforms possessing the N-terminal extension – the identification of binding protein partners, analysis of subcellular localization under different physiological conditions, elucidation of the signal transduction pathways involving different S6K1 isoforms.
Observation of B_{s}^{0}→D[over ¯]^{0}K_{S}^{0} and Evidence for B_{s}^{0}→D[over ¯]^{*}^{0}K_{S}^{0} Decays.

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Aaij, R; Abellán Beteta, C; Adeva, B; Adinolfi, M; Affolder, A; Ajaltouni, Z; Akar, S; Albrecht, J; Alessio, F; Alexander, M; Ali, S; Alkhazov, G; Alvarez Cartelle, P; Alves, A A; Amato, S; Amerio, S; Amhis, Y; An, L; Anderlini, L; Andreassi, G; Andreotti, M; Andrews, J E; Appleby, R B; Aquines Gutierrez, O; Archilli, F; d'Argent, P; Artamonov, A; Artuso, M; Aslanides, E; Auriemma, G; Baalouch, M; Bachmann, S; Back, J J; Badalov, A; Baesso, C; Baldini, W; Barlow, R J; Barschel, C; Barsuk, S; Barter, W; Batozskaya, V; Battista, V; Bay, A; Beaucourt, L; Beddow, J; Bedeschi, F; Bediaga, I; Bel, L J; Bellee, V; Belloli, N; Belyaev, I; Ben-Haim, E; Bencivenni, G; Benson, S; Benton, J; Berezhnoy, A; Bernet, R; Bertolin, A; Bettler, M-O; van Beuzekom, M; Bifani, S; Billoir, P; Bird, T; Birnkraut, A; Bizzeti, A; Blake, T; Blanc, F; Blouw, J; Blusk, S; Bocci, V; Bondar, A; Bondar, N; Bonivento, W; Borghi, S; Borisyak, M; Borsato, M; Bowcock, T J V; Bowen, E; Bozzi, C; Braun, S; Britsch, M; Britton, T; Brodzicka, J; Brook, N H; Buchanan, E; Burr, C; Bursche, A; Buytaert, J; Cadeddu, S; Calabrese, R; Calvi, M; Calvo Gomez, M; Campana, P; Campora Perez, D; Capriotti, L; Carbone, A; Carboni, G; Cardinale, R; Cardini, A; Carniti, P; Carson, L; Carvalho Akiba, K; Casse, G; Cassina, L; Castillo Garcia, L; Cattaneo, M; Cauet, Ch; Cavallero, G; Cenci, R; Charles, M; Charpentier, Ph; Chatzikonstantinidis, G; Chefdeville, M; Chen, S; Cheung, S-F; Chiapolini, N; Chrzaszcz, M; Cid Vidal, X; Ciezarek, G; Clarke, P E L; Clemencic, M; Cliff, H V; Closier, J; Coco, V; Cogan, J; Cogneras, E; Cogoni, V; Cojocariu, L; Collazuol, G; Collins, P; Comerma-Montells, A; Contu, A; Cook, A; Coombes, M; Coquereau, S; Corti, G; Corvo, M; Couturier, B; Cowan, G A; Craik, D C; Crocombe, A; Cruz Torres, M; Cunliffe, S; Currie, R; D'Ambrosio, C; Dall'Occo, E; Dalseno, J; David, P N Y; Davis, A; De Aguiar Francisco, O; De Bruyn, K; De Capua, S; De Cian, M; De Miranda, J M; De Paula, L; De Simone, P; Dean, C-T; Decamp, D; Deckenhoff, M; Del Buono, L; Déléage, N; Demmer, M; Derkach, D; Deschamps, O; Dettori, F; Dey, B; Di Canto, A; Di Ruscio, F; Dijkstra, H; Donleavy, S; Dordei, F; Dorigo, M; Dosil Suárez, A; Dovbnya, A; Dreimanis, K; Dufour, L; Dujany, G; Dungs, K; Durante, P; Dzhelyadin, R; Dziurda, A; Dzyuba, A; Easo, S; Egede, U; Egorychev, V; Eidelman, S; Eisenhardt, S; Eitschberger, U; Ekelhof, R; Eklund, L; El Rifai, I; Elsasser, Ch; Ely, S; Esen, S; Evans, H M; Evans, T; Falabella, A; Färber, C; Farley, N; Farry, S; Fay, R; Ferguson, D; Fernandez Albor, V; Ferrari, F; Ferreira Rodrigues, F; Ferro-Luzzi, M; Filippov, S; Fiore, M; Fiorini, M; Firlej, M; Fitzpatrick, C; Fiutowski, T; Fleuret, F; Fohl, K; Fol, P; Fontana, M; Fontanelli, F; Forshaw, D C; Forty, R; Frank, M; Frei, C; Frosini, M; Fu, J; Furfaro, E; Gallas Torreira, A; Galli, D; Gallorini, S; Gambetta, S; Gandelman, M; Gandini, P; Gao, Y; García Pardiñas, J; Garra Tico, J; Garrido, L; Gascon, D; Gaspar, C; Gauld, R; Gavardi, L; Gazzoni, G; 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Kenyon, I R; Kenzie, M; Ketel, T; Khairullin, E; Khanji, B; Khurewathanakul, C; Kirn, T; Klaver, S; Klimaszewski, K; Kochebina, O; Kolpin, M; Komarov, I; Koopman, R F; Koppenburg, P; Kozeiha, M; Kravchuk, L; Kreplin, K; Kreps, M; Krokovny, P; Kruse, F; Krzemien, W; Kucewicz, W; Kucharczyk, M; Kudryavtsev, V; Kuonen, A K; Kurek, K; Kvaratskheliya, T; Lacarrere, D; Lafferty, G; Lai, A; Lambert, D; Lanfranchi, G; Langenbruch, C; Langhans, B; Latham, T; Lazzeroni, C; Le Gac, R; van Leerdam, J; Lees, J-P; Lefèvre, R; Leflat, A; Lefrançois, J; Lemos Cid, E; Leroy, O; Lesiak, T; Leverington, B; Li, Y; Likhomanenko, T; Liles, M; Lindner, R; Linn, C; Lionetto, F; Liu, B; Liu, X; Loh, D; Longstaff, I; Lopes, J H; Lucchesi, D; Lucio Martinez, M; Luo, H; Lupato, A; Luppi, E; Lupton, O; Lusardi, N; Lusiani, A; Machefert, F; Maciuc, F; Maev, O; Maguire, K; Malde, S; Malinin, A; Manca, G; Mancinelli, G; Manning, P; Mapelli, A; Maratas, J; Marchand, J F; Marconi, U; Marin Benito, C; Marino, P; Marks, J; Martellotti, G; Martin, M; Martinelli, M; Martinez Santos, D; Martinez Vidal, F; Martins Tostes, D; Massacrier, L M; Massafferri, A; Matev, R; Mathad, A; Mathe, Z; Matteuzzi, C; Mauri, A; Maurin, B; Mazurov, A; McCann, M; McCarthy, J; McNab, A; McNulty, R; Meadows, B; Meier, F; Meissner, M; Melnychuk, D; Merk, M; Michielin, E; Milanes, D A; Minard, M-N; Mitzel, D S; Molina Rodriguez, J; Monroy, I A; Monteil, S; Morandin, M; Morawski, P; Mordà, A; Morello, M J; Moron, J; Morris, A B; Mountain, R; Muheim, F; Müller, D; Müller, J; Müller, K; Müller, V; Mussini, M; Muster, B; Naik, P; Nakada, T; Nandakumar, R; Nandi, A; Nasteva, I; Needham, M; Neri, N; Neubert, S; Neufeld, N; Neuner, M; Nguyen, A D; Nguyen, T D; Nguyen-Mau, C; Niess, V; Niet, R; Nikitin, N; Nikodem, T; Novoselov, A; O'Hanlon, D P; Oblakowska-Mucha, A; Obraztsov, V; Ogilvy, S; Okhrimenko, O; Oldeman, R; Onderwater, C J G; Osorio Rodrigues, B; Otalora Goicochea, J M; Otto, A; Owen, P; Oyanguren, A; Palano, A; Palombo, F; Palutan, M; Panman, J; Papanestis, A; Pappagallo, M; Pappalardo, L L; Pappenheimer, C; Parker, W; Parkes, C; Passaleva, G; Patel, G D; Patel, M; Patrignani, C; Pearce, A; Pellegrino, A; Penso, G; Pepe Altarelli, M; Perazzini, S; Perret, P; Pescatore, L; Petridis, K; Petrolini, A; Petruzzo, M; Picatoste Olloqui, E; Pietrzyk, B; Pikies, M; Pinci, D; Pistone, A; Piucci, A; Playfer, S; Plo Casasus, M; Poikela, T; Polci, F; Poluektov, A; Polyakov, I; Polycarpo, E; Popov, A; Popov, D; Popovici, B; Potterat, C; Price, E; Price, J D; Prisciandaro, J; Pritchard, A; Prouve, C; Pugatch, V; Puig Navarro, A; Punzi, G; Qian, W; Quagliani, R; Rachwal, B; Rademacker, J H; Rama, M; Ramos Pernas, M; Rangel, M S; Raniuk, I; Rauschmayr, N; Raven, G; Redi, F; Reichert, S; Dos Reis, A C; Renaudin, V; Ricciardi, S; Richards, S; Rihl, M; Rinnert, K; Rives Molina, V; Robbe, P; Rodrigues, A B; Rodrigues, E; Rodriguez Lopez, J A; Rodriguez Perez, P; Roiser, S; Romanovsky, V; Romero Vidal, A; Ronayne, J W; Rotondo, M; Ruf, T; Ruiz Valls, P; Saborido Silva, J J; Sagidova, N; Saitta, B; Salustino Guimaraes, V; Sanchez Mayordomo, C; Sanmartin Sedes, B; Santacesaria, R; Santamarina Rios, C; Santimaria, M; Santovetti, E; Sarti, A; Satriano, C; Satta, A; Saunders, D M; Savrina, D; Schael, S; Schiller, M; Schindler, H; Schlupp, M; Schmelling, M; Schmelzer, T; Schmidt, B; Schneider, O; Schopper, A; Schubiger, M; Schune, M-H; Schwemmer, R; Sciascia, B; Sciubba, A; Semennikov, A; Serra, N; Serrano, J; Sestini, L; Seyfert, P; Shapkin, M; Shapoval, I; Shcheglov, Y; Shears, T; Shekhtman, L; Shevchenko, V; Shires, A; Siddi, B G; Silva Coutinho, R; Silva de Oliveira, L; Simi, G; Sirendi, M; Skidmore, N; Skwarnicki, T; Smith, E; Smith, E; Smith, I T; Smith, J; Smith, M; Snoek, H; Sokoloff, M D; Soler, F J P; Soomro, F; Souza, D; Souza De Paula, B; Spaan, B; Spradlin, P; Sridharan, S; Stagni, F; Stahl, M; Stahl, S; Stefkova, S; Steinkamp, O; Stenyakin, O; Stevenson, S; Stoica, S; Stone, S; Storaci, B; Stracka, S; Straticiuc, M; Straumann, U; Sun, L; Sutcliffe, W; Swientek, K; Swientek, S; Syropoulos, V; Szczekowski, M; Szumlak, T; T'Jampens, S; Tayduganov, A; Tekampe, T; Tellarini, G; Teubert, F; Thomas, C; Thomas, E; van Tilburg, J; Tisserand, V; Tobin, M; Todd, J; Tolk, S; Tomassetti, L; Tonelli, D; Topp-Joergensen, S; Torr, N; Tournefier, E; Tourneur, S; Trabelsi, K; Traill, M; Tran, M T; Tresch, M; Trisovic, A; Tsaregorodtsev, A; Tsopelas, P; Tuning, N; Ukleja, A; Ustyuzhanin, A; Uwer, U; Vacca, C; Vagnoni, V; Valenti, G; Vallier, A; Vazquez Gomez, R; Vazquez Regueiro, P; Vázquez Sierra, C; Vecchi, S; van Veghel, M; Velthuis, J J; Veltri, M; Veneziano, G; Vesterinen, M; Viaud, B; Vieira, D; Vieites Diaz, M; Vilasis-Cardona, X; Volkov, V; Vollhardt, A; Voong, D; Vorobyev, A; Vorobyev, V; Voß, C; de Vries, J A; Waldi, R; Wallace, C; Wallace, R; Walsh, J; Wang, J; Ward, D R; Watson, N K; Websdale, D; Weiden, A; Whitehead, M; Wicht, J; Wilkinson, G; Wilkinson, M; Williams, M; Williams, M P; Williams, M; Williams, T; Wilson, F F; Wimberley, J; Wishahi, J; Wislicki, W; Witek, M; Wormser, G; Wotton, S A; Wraight, K; Wright, S; Wyllie, K; Xie, Y; Xu, Z; Yang, Z; Yu, J; Yuan, X; Yushchenko, O; Zangoli, M; Zavertyaev, M; Zhang, L; Zhang, Y; Zhelezov, A; Zhokhov, A; Zhong, L; Zhukov, V; Zucchelli, S

2016-04-22

The first observation of the B_{s}^{0}→D[over ¯]^{0}K_{S}^{0} decay mode and evidence for the B_{s}^{0}→D[over ¯]^{*0}K_{S}^{0} decay mode are reported. The data sample corresponds to an integrated luminosity of 3.0 fb^{-1} collected in pp collisions by LHCb at center-of-mass energies of 7 and 8 TeV. The branching fractions are measured to be B(B_{s}^{0}→D[over ¯]^{0}K[over ¯]^{0})=[4.3±0.5(stat)±0.3(syst)±0.3(frag)±0.6(norm)]×10^{-4},B(B_{s}^{0}→D[over ¯]^{*0}K[over ¯]^{0})=[2.8±1.0(stat)±0.3(syst)±0.2(frag)±0.4(norm)]×10^{-4},where the uncertainties are due to contributions coming from statistical precision, systematic effects, and the precision of two external inputs, the ratio f_{s}/f_{d} and the branching fraction of B^{0}→D[over ¯]^{0}K_{S}^{0}, which is used as a calibration channel.
First observation of the decay $B_{s}^{0} \\to K_{S}^{0} K^{*}(892)^{0}$

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Aaij, Roel; Adinolfi, Marco; Affolder, Anthony; Ajaltouni, Ziad; Akar, Simon; Albrecht, Johannes; Alessio, Federico; Alexander, Michael; Ali, Suvayu; Alkhazov, Georgy; Alvarez Cartelle, Paula; Alves Jr, Antonio Augusto; Amato, Sandra; Amerio, Silvia; Amhis, Yasmine; An, Liupan; Anderlini, Lucio; Anderson, Jonathan; Andreotti, Mirco; Andrews, Jason; Appleby, Robert; Aquines Gutierrez, Osvaldo; Archilli, Flavio; d'Argent, Philippe; Artamonov, Alexander; Artuso, Marina; Aslanides, Elie; Auriemma, Giulio; Baalouch, Marouen; Bachmann, Sebastian; Back, John; Badalov, Alexey; Baesso, Clarissa; Baldini, Wander; Barlow, Roger; Barschel, Colin; Barsuk, Sergey; Barter, William; Batozskaya, Varvara; Battista, Vincenzo; Bay, Aurelio; Beaucourt, Leo; Beddow, John; Bedeschi, Franco; Bediaga, Ignacio; Bel, Lennaert; Belyaev, Ivan; Ben-Haim, Eli; Bencivenni, Giovanni; Benson, Sean; Benton, Jack; Berezhnoy, Alexander; Bernet, Roland; Bertolin, Alessandro; Bettler, Marc-Olivier; van Beuzekom, Martinus; Bien, Alexander; 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Stoica, Sabin; Stone, Sheldon; Storaci, Barbara; Stracka, Simone; Straticiuc, Mihai; Straumann, Ulrich; Sun, Liang; Sutcliffe, William; Swientek, Krzysztof; Swientek, Stefan; Syropoulos, Vasileios; Szczekowski, Marek; Szczypka, Paul; Szumlak, Tomasz; T'Jampens, Stephane; Tekampe, Tobias; Teklishyn, Maksym; Tellarini, Giulia; Teubert, Frederic; Thomas, Christopher; Thomas, Eric; van Tilburg, Jeroen; Tisserand, Vincent; Tobin, Mark; Todd, Jacob; Tolk, Siim; Tomassetti, Luca; Tonelli, Diego; Topp-Joergensen, Stig; Torr, Nicholas; Tournefier, Edwige; Tourneur, Stephane; Trabelsi, Karim; Tran, Minh Tâm; Tresch, Marco; Trisovic, Ana; Tsaregorodtsev, Andrei; Tsopelas, Panagiotis; Tuning, Niels; Ukleja, Artur; Ustyuzhanin, Andrey; Uwer, Ulrich; Vacca, Claudia; Vagnoni, Vincenzo; Valenti, Giovanni; Vallier, Alexis; Vazquez Gomez, Ricardo; Vazquez Regueiro, Pablo; Vázquez Sierra, Carlos; Vecchi, Stefania; Velthuis, Jaap; Veltri, Michele; Veneziano, Giovanni; Vesterinen, Mika; Viaud, Benoit; Vieira, Daniel; 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2016-01-04

A search for $B_{(s)}^{0} \\to K_{S}^{0} K^{*}(892)^{0}$ decays is performed using $pp$ collision data, corresponding to an integrated luminosity of $1.0~\\text{fb}^{-1}$, collected with the LHCb detector at a centre-of-mass energy of $7~\\text{TeV}$. The $B_{s}^{0} \\to K_{S}^{0} K^{*}(892)^{0}$ decay is observed for the first time, with a significance of 7.1 standard deviations. The branching fraction is measured to be \\begin{equation*} \\mathcal{B}(B_{s}^{0} \\to \\bar{K}^{0} K^{*}(892)^{0}) + \\mathcal{B}(B_{s}^{0} \\to K^{0} \\bar{K}^{*}(892)^{0}) = (16.4 \\pm 3.4 \\pm 2.3) \\times 10^{-6},\\\\ \\end{equation*} where the first uncertainty is statistical and the second is systematic. No evidence is found for the decay $B^{0} \\to K_{S}^{0} K^{*}(892)^{0}$ and an upper limit is set on the branching fraction, $\\mathcal{B}(B^{0} \\to \\bar{K}^{0} K^{*}(892)^{0}) + \\mathcal{B}(B^{0} \\to K^{0} \\bar{K}^{*}(892)^{0}) < 0.96 \\ \\times 10^{-6}, $ at $90\\,\\% $ confidence level. All results are consistent with Standard Model pr...
Insulin receptors mediate growth effects in cultured fetal neurons. II. Activation of a protein kinase that phosphorylates ribosomal protein S6

International Nuclear Information System (INIS)

Heidenreich, K.A.; Toledo, S.P.

1989-01-01

As an initial attempt to identify early steps in insulin action that may be involved in the growth responses of neurons to insulin, we investigated whether insulin receptor activation increases the phosphorylation of ribosomal protein S6 in cultured fetal neurons and whether activation of a protein kinase is involved in this process. When neurons were incubated for 2 h with 32Pi, the addition of insulin (100 ng/ml) for the final 30 min increased the incorporation of 32Pi into a 32K microsomal protein. The incorporation of 32Pi into the majority of other neuronal proteins was unaltered by the 30-min exposure to insulin. Cytosolic extracts from insulin-treated neurons incubated in the presence of exogenous rat liver 40S ribosomes and [gamma-32P]ATP displayed a 3- to 8-fold increase in the phosphorylation of ribosomal protein S6 compared to extracts from untreated cells. Inclusion of cycloheximide during exposure of the neurons to insulin did not inhibit the increased cytosolic kinase activity. Activation of S6 kinase activity by insulin was dose dependent (seen at insulin concentration as low as 0.1 ng/ml) and reached a maximum after 20 min of incubation. Addition of phosphatidylserine, diolein, and Ca2+ to the in vitro kinase reaction had no effect on the phosphorylation of ribosomal protein S6. Likewise, treatment of neurons with (Bu)2cAMP did not alter the phosphorylation of ribosomal protein S6 by neuronal cytosolic extracts. We conclude that insulin activates a cytosolic protein kinase that phosphorylates ribosomal S6 in neurons and is distinct from protein kinase-C and cAMP-dependent protein kinase. Stimulation of this kinase may play a role in insulin signal transduction in neurons
Identification of the Raptor-binding motif on Arabidopsis S6 kinase and its use as a TOR signaling suppressor

Energy Technology Data Exchange (ETDEWEB)

Son, Ora; Kim, Sunghan; Hur, Yoon-Sun; Cheon, Choong-Ill, E-mail: ccheon@sookmyung.ac.kr

2016-03-25

TOR (target of rapamycin) kinase signaling plays central role as a regulator of growth and proliferation in all eukaryotic cells and its key signaling components and effectors are also conserved in plants. Unlike the mammalian and yeast counterparts, however, we found through yeast two-hybrid analysis that multiple regions of the Arabidopsis Raptor (regulatory associated protein of TOR) are required for binding to its substrate. We also identified that a 44-amino acid region at the N-terminal end of Arabidopsis ribosomal S6 kinase 1 (AtS6K1) specifically interacted with AtRaptor1, indicating that this region may contain a functional equivalent of the TOS (TOR-Signaling) motif present in the mammalian TOR substrates. Transient over-expression of this 44-amino acid fragment in Arabidopsis protoplasts resulted in significant decrease in rDNA transcription, demonstrating a feasibility of developing a new plant-specific TOR signaling inhibitor based upon perturbation of the Raptor-substrate interaction. - Highlights: • Multiple regions on the Arabidopsis Raptor protein were found to be involved in substrate binding. • N-terminal end of the Arabidopsis ribosomal S6 kinase 1 (AtS6K1) was responsible for interacting with AtRaptor1. • The Raptor-interacting fragment of AtS6K1 could be utilized as an effective inhibitor of plant TOR signaling.
Identification of the Raptor-binding motif on Arabidopsis S6 kinase and its use as a TOR signaling suppressor

International Nuclear Information System (INIS)

Son, Ora; Kim, Sunghan; Hur, Yoon-Sun; Cheon, Choong-Ill

2016-01-01

TOR (target of rapamycin) kinase signaling plays central role as a regulator of growth and proliferation in all eukaryotic cells and its key signaling components and effectors are also conserved in plants. Unlike the mammalian and yeast counterparts, however, we found through yeast two-hybrid analysis that multiple regions of the Arabidopsis Raptor (regulatory associated protein of TOR) are required for binding to its substrate. We also identified that a 44-amino acid region at the N-terminal end of Arabidopsis ribosomal S6 kinase 1 (AtS6K1) specifically interacted with AtRaptor1, indicating that this region may contain a functional equivalent of the TOS (TOR-Signaling) motif present in the mammalian TOR substrates. Transient over-expression of this 44-amino acid fragment in Arabidopsis protoplasts resulted in significant decrease in rDNA transcription, demonstrating a feasibility of developing a new plant-specific TOR signaling inhibitor based upon perturbation of the Raptor-substrate interaction. - Highlights: • Multiple regions on the Arabidopsis Raptor protein were found to be involved in substrate binding. • N-terminal end of the Arabidopsis ribosomal S6 kinase 1 (AtS6K1) was responsible for interacting with AtRaptor1. • The Raptor-interacting fragment of AtS6K1 could be utilized as an effective inhibitor of plant TOR signaling.
Molecular Characterization and Expression Analysis of S6K1 in Cashmere Goats (

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Wu Manlin

2013-08-01

Full Text Available p70 ribosomal S6 kinase (p70S6K can integrate nutrient and growth factor signals to promote cell growth and survival. We report our molecular characterization of the complementary DNA (cDNA that encodes the goat p70S6K gene 40S ribosomal S6 kinase 1 (S6K1 (GenBank accession GU144017 and its 3′ noncoding sequence in Inner Mongolia Cashmere goats (Capra hircus. Goat S6K1 cDNA was 2,272 bp and include an open reading frame (ORF of 1,578 bp, corresponding to a polypeptide of 525 amino acids, and a 694-residue 3′ noncoding sequence with a polyadenylation signal at nucleotides 2,218 to 2,223. The relative abundance of S6K1 mRNA was measured by real-time PCR in 6 tissues, and p70S6K expression was examined by immunohistochemistry in heart and testis. The phosphorylation of p70S6K is regulated by mitogen-activated protein kinase (MAPK signaling in fetal fibroblasts.
In silico binding affinity studies of N-9 substituted 6-(4-(4-propoxyphenylpiperazin-1-yl-9H-purine derivatives-Target for P70-S6K1 & PI3K-δ kinases

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Manjunath G. Sunagar

2018-03-01

Full Text Available P70-S6K1 & PI3K-δ kinases are identified to be involved in many physiological processes associated with cancer, therefore many of the inhibitors being designed to target these kinases are in clinical trials. In the current study we have exploited the N-9 substituted 6-(4-(4-propoxyphenyl piperazin-1-yl-9H-purine derivatives for their inhibitory properties with the above kinases. We have used an in silico docking study with seventeen purine derivatives for their binding affinity calculations. The binding affinities of these small molecules with P70-S6K1 & PI3K-δ were performed using AutoDock Vina. Among all the compounds, PP16 showed highest binding affinity of −14.7 kcal/mol with P70-S6K1 kinase & −17.2 kcal/mol with PI3K-δ kinases as compared to the molecules under clinical trials (PF-4708671 & IC-87114. Docking studies revealed that N-9 coumarine substituted purine derivative could be one of the potential ligands for the inhibition of P70-S6K1 & PI3K-δ kinases. Hence, this compound can be further investigated by in vitro and in vivo experiments for further validation.
Minimum K-S estimator using PH-transform technique

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Somchit Boonthiem

2016-07-01

Full Text Available In this paper, we propose an improvement of the Minimum Kolmogorov-Smirnov (K-S estimator using proportional hazards transform (PH-transform technique. The data of experiment is 47 fire accidents data of an insurance company in Thailand. This experiment has two operations, the first operation, we minimize K-S statistic value using grid search technique for nine distributions; Rayleigh distribution, gamma distribution, Pareto distribution, log-logistic distribution, logistic distribution, normal distribution, Weibull distribution, lognormal distribution, and exponential distribution and the second operation, we improve K-S statistic using PHtransform. The result appears that PH-transform technique can improve the Minimum K-S estimator. The algorithms give better the Minimum K-S estimator for seven distributions; Rayleigh distribution, logistic distribution, gamma distribution, Pareto distribution, log-logistic distribution, normal distribution, Weibull distribution, log-normal distribution, and exponential distribution while the Minimum K-S estimators of normal distribution and logistic distribution are unchanged
The mTOR kinase inhibitor Everolimus decreases S6 kinase phosphorylation but fails to reduce mutant huntingtin levels in brain and is not neuroprotective in the R6/2 mouse model of Huntington's disease

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Frentzel Stefan

2010-06-01

Full Text Available Abstract Background Huntington's disease (HD is a progressive neurodegenerative disorder caused by a CAG repeat expansion within the huntingtin gene. Mutant huntingtin protein misfolds and accumulates within neurons where it mediates its toxic effects. Promoting mutant huntingtin clearance by activating macroautophagy is one approach for treating Huntington's disease (HD. In this study, we evaluated the mTOR kinase inhibitor and macroautophagy promoting drug everolimus in the R6/2 mouse model of HD. Results Everolimus decreased phosphorylation of the mTOR target protein S6 kinase indicating brain penetration. However, everolimus did not activate brain macroautophagy as measured by LC3B Western blot analysis. Everolimus protected against early declines in motor performance; however, we found no evidence for neuroprotection as determined by brain pathology. In muscle but not brain, everolimus significantly decreased soluble mutant huntingtin levels. Conclusions Our data suggests that beneficial behavioral effects of everolimus in R6/2 mice result primarily from effects on muscle. Even though everolimus significantly modulated its target brain S6 kinase, this did not decrease mutant huntingtin levels or provide neuroprotection.

Ribosomal protein S6 kinase1 coordinates with TOR-Raptor2 to regulate thylakoid membrane biosynthesis in rice.

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Sun, Linxiao; Yu, Yonghua; Hu, Weiqin; Min, Qiming; Kang, Huiling; Li, Yilu; Hong, Yue; Wang, Xuemin; Hong, Yueyun

2016-07-01

Ribosomal protein S6 kinase (S6K) functions as a key component in the target of rapamycin (TOR) pathway involved in multiple processes in eukaryotes. The role and regulation of TOR-S6K in lipid metabolism remained unknown in plants. Here we provide genetic and pharmacological evidence that TOR-Raptor2-S6K1 is important for thylakoid galactolipid biosynthesis and thylakoid grana modeling in rice (Oryza sativa L.). Genetic suppression of S6K1 caused pale yellow-green leaves, defective thylakoid grana architecture. S6K1 directly interacts with Raptor2, a core component in TOR signaling, and S6K1 activity is regulated by Raptor2 and TOR. Plants with suppressed Raptor2 expression or reduced TOR activity by inhibitors mimicked the S6K1-deficient phenotype. A significant reduction in galactolipid content was found in the s6k1, raptor2 mutant or TOR-inhibited plants, which was accompanied by decreased transcript levels of the set of genes such as lipid phosphate phosphatase α5 (LPPα5), MGDG synthase 1 (MGD1), and DGDG synthase 1 (DGD1) involved in galactolipid synthesis, compared to the control plants. Moreover, loss of LPPα5 exhibited a similar phenotype with pale yellow-green leaves. These results suggest that TOR-Raptor2-S6K1 is important for modulating thylakoid membrane lipid biosynthesis, homeostasis, thus enhancing thylakoid grana architecture and normal photosynthesis ability in rice. Copyright © 2016 Elsevier B.V. All rights reserved.
Post-transcriptional gene silencing of ribosomal protein S6 kinase 1 restores insulin action in leucine-treated skeletal muscle

DEFF Research Database (Denmark)

Deshmukh, A; Salehzadeh, F; Metayer-Coustard, S

2009-01-01

Excessive nutrients, especially amino acids, impair insulin action on glucose metabolism in skeletal muscle. We tested the hypothesis that the branched-chain amino acid leucine reduces acute insulin action in primary myotubes via a negative feedback mechanism involving ribosomal protein S6 kinase 1...... to excessive leucine. In conclusion, S6K1 plays an important role in the regulation of insulin action on glucose metabolism in skeletal muscle....
Extracting $\\gamma$ from $B_{s(d)} \\to J/\\psi K_{S}$ and $B_{d(s)} \\to D^{+}_{d(s)} D^{-}_{d(s)}$

CERN Document Server

Fleischer, Robert

1999-01-01

A completely general parametrization of the time-dependent decay rates of the modes $B_s\\to J/\\psi K_S$ and $B_d\\to J/\\psi K_S$ is given, which are related to each other through the $U$-spin flavour symmetry of strong interactions. Owing to the interference of current--current and penguin processes, the $B_s\\to J/\\psi K_S$ observables probe the angle $\\gamma$ of the unitarity triangle. Using the $U$-spin symmetry, the overall normalization of the $B_s\\to J/\\psi K_S$ rate can be fixed with the help of the CP-averaged $B_d\\to J/\\psi K_{\\rm S}$ rate, providing a new strategy to determine $\\gamma$. This extraction of $\\gamma$ is not affected by any final-state-interaction effects, and its theoretical accuracy is only limited by $U$-spin-breaking corrections. As a by-product, this strategy allows us to take into account also the penguin effects in the determination of $\\beta$ from $B_d\\to J/\\psi K_S$, which are presumably very small, and to predict the direct CP asymmetry arising in this mode. An analogous strateg...
Measurement of the time-integrated CP asymmetry in $D^0 \\to K_S^0 K_S^0$ decays with LHCb

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Tuci, Giulia

2018-01-01

CP violation in charm has not yet been observed, although measurements of time-integrated CP asymmetries in $D^0 \\to K^+K^-$ and $D^0 \\to \\pi^+\\pi^- decays$ have reached a remarkable precision, O(0.1%). The $D^0 \\to K_S^0 K_S^0$ decay is a promising discovery channel for CP violation in charm. A prediction based on Standard Model gives an upper limit for the CP asymmetry of 1.1% (C.L. 95%). Further enhancements could result from contributions from physics beyond the Standard Model. We present a measurement of the time-integrated CP asymmetry in prompt $D^0 \\to K_S^0 K_S^0$ decays, performed using data collected with LHCb experiment in 2015 and 2016 at a 13 TeV pp center-of-mass energy (Run-2). This result improves the sensitivity obtained by LHCb in Run-1.
Mutagenic and cytotoxic properties of 6-thioguanine, S6-methylthioguanine, and guanine-S6-sulfonic acid.

Science.gov (United States)

Yuan, Bifeng; Wang, Yinsheng

2008-08-29

Thiopurine drugs, including 6-thioguanine ((S)G), 6-mercaptopurine, and azathioprine, are widely employed anticancer agents and immunosuppressants. The formation of (S)G nucleotides from the thiopurine prodrugs and their subsequent incorporation into nucleic acids are important for the drugs to exert their cytotoxic effects. (S)G in DNA can be methylated by S-adenosyl-l-methionine to give S(6)-methylthioguanine (S(6)mG) and oxidized by UVA light to render guanine-S(6)-sulfonic acid ((SO3H)G). Here, we constructed single-stranded M13 shuttle vectors carrying a (S)G, S(6)mG, or (SO3H)G at a unique site and allowed the vectors to propagate in wild-type and bypass polymerase-deficient Escherichia coli cells. Analysis of the replication products by using the competitive replication and adduct bypass and a slightly modified restriction enzyme digestion and post-labeling assays revealed that, although none of the three thionucleosides considerably blocked DNA replication in all transfected E. coli cells, both S(6)mG and (SO3H)G were highly mutagenic, which resulted in G-->A mutation at frequencies of 94 and 77%, respectively, in wild-type E. coli cells. Deficiency in bypass polymerases does not result in alteration of mutation frequencies of these two lesions. In contrast to what was found from previous steady-state kinetic analysis, our data demonstrated that 6-thioguanine is mutagenic, with G-->A transition occurring at a frequency of approximately 10%. The mutagenic properties of 6-thioguanine and its derivatives revealed in the present study offered important knowledge about the biological implications of these thionucleosides.
Mutagenic and Cytotoxic Properties of 6-Thioguanine, S6-Methylthioguanine, and Guanine-S6-sulfonic Acid*S⃞

OpenAIRE

Yuan, Bifeng; Wang, Yinsheng

2008-01-01

Thiopurine drugs, including 6-thioguanine (SG), 6-mercaptopurine, and azathioprine, are widely employed anticancer agents and immunosuppressants. The formation of SG nucleotides from the thiopurine prodrugs and their subsequent incorporation into nucleic acids are important for the drugs to exert their cytotoxic effects. SG in DNA can be methylated by S-adenosyl-l-methionine to give S6-methylthioguanine (S6mG) and oxidized by UVA light to render guanine-S6-sulfonic acid ...
Measurement of the $B_s^0\\to J/\\psi K_S^0$ branching fraction

CERN Document Server

Aaij, R; Adeva, B; Adinolfi, M; Adrover, C; Affolder, A; Ajaltouni, Z; Albrecht, J; Alessio, F; Alexander, M; Ali, S; Alkhazov, G; Alvarez Cartelle, P; Alves Jr, A A; Amato, S; Amhis, Y; Anderson, J; Appleby, R B; Aquines Gutierrez, O; Archilli, F; Arrabito, L; Artamonov, A; Artuso, M; Aslanides, E; Auriemma, G; Bachmann, S; Back, J J; Balagura, V; Baldini, W; Barlow, R J; Barschel, C; Barsuk, S; Barter, W; Bates, A; Bauer, C; Bauer, Th; Bay, A; Bediaga, I; Belogurov, S; Belous, K; Belyaev, I; Ben-Haim, E; Benayoun, M; Bencivenni, G; Benson, S; Benton, J; Bernet, R; Bettler, M -O; van Beuzekom, M; Bien, A; Bifani, S; Bird, T; Bizzeti, A; Bjørnstad, P M; Blake, T; Blanc, F; Blanks, C; Blouw, J; Blusk, S; Bobrov, A; Bocci, V; Bondar, A; Bondar, N; Bonivento, W; Borghi, S; Borgia, A; Bowcock, T J V; Bozzi, C; Brambach, T; van den Brand, J; Bressieux, J; Brett, D; Britsch, M; Britton, T; Brook, N H; Brown, H; Büchler-Germann, A; Burducea, I; Bursche, A; Buytaert, J; Cadeddu, S; Callot, O; Calvi, M; Calvo Gomez, M; Camboni, A; Campana, P; Carbone, A; Carboni, G; Cardinale, R; Cardini, A; Carson, L; Carvalho Akiba, K; Casse, G; Cattaneo, M; Cauet, Ch; Charles, M; Charpentier, Ph; Chiapolini, N; Ciba, K; Cid Vidal, X; Ciezarek, G; Clarke, P E L; Clemencic, M; Cliff, H V; Closier, J; Coca, C; Coco, V; Cogan, J; Collins, P; Comerma-Montells, A; Contu, A; Cook, A; Coombes, M; Corti, G; Couturier, B; Cowan, G A; Currie, R; D'Ambrosio, C; David, P; David, P N Y; De Bonis, I; De Bruyn, K; De Capua, S; De Cian, M; De Lorenzi, F; De Miranda, J M; De Paula, L; De Simone, P; Decamp, D; Deckenhoff, M; Degaudenzi, H; Del Buono, L; Deplano, C; Derkach, D; Deschamps, O; Dettori, F; Dickens, J; Dijkstra, H; Diniz Batista, P; Domingo Bonal, F; Donleavy, S; Dordei, F; Dosil Suárez, A; Dossett, D; Dovbnya, A; Dupertuis, F; Dzhelyadin, R; Dziurda, A; Easo, S; Egede, U; Egorychev, V; Eidelman, S; van Eijk, D; Eisele, F; Eisenhardt, S; Ekelhof, R; Eklund, L; Elsasser, Ch; Elsby, D; Esperante Pereira, D; Falabella, A; Färber, C; Fardell, G; Farinelli, C; Farry, S; Fave, V; Fernandez Albor, V; Ferro-Luzzi, M; Filippov, S; Fitzpatrick, C; Fontana, M; Fontanelli, F; Forty, R; Francisco, O; Frank, M; Frei, C; Frosini, M; Furcas, S; Gallas Torreira, A; Galli, D; Gandelman, M; Gandini, P; Gao, Y; Garnier, J-C; Garofoli, J; Garra Tico, J; Garrido, L; Gascon, D; Gaspar, C; Gauld, R; Gauvin, N; Gersabeck, M; Gershon, T; Ghez, Ph; Gibson, V; Gligorov, V V; Göbel, C; Golubkov, D; Golutvin, A; Gomes, A; Gordon, H; Grabalosa Gándara, M; Graciani Diaz, R; Granado Cardoso, L A; Graugés, E; Graziani, G; Grecu, A; Greening, E; Gregson, S; Gui, B; Gushchin, E; Guz, Yu; Gys, T; Hadjivasiliou, C; Haefeli, G; Haen, C; Haines, S C; Hampson, T; Hansmann-Menzemer, S; Harji, R; Harnew, N; Harrison, J; Harrison, P F; Hartmann, T; He, J; Heijne, V; Hennessy, K; Henrard, P; Hernando Morata, J A; van Herwijnen, E; Hicks, E; Holubyev, K; Hopchev, P; Hulsbergen, W; Hunt, P; Huse, T; Huston, R S; Hutchcroft, D; Hynds, D; Iakovenko, V; Ilten, P; Imong, J; Jacobsson, R; Jaeger, A; Jahjah Hussein, M; Jans, E; Jansen, F; Jaton, P; Jean-Marie, B; Jing, F; John, M; Johnson, D; Jones, C R; Jost, B; Kaballo, M; Kandybei, S; Karacson, M; Karbach, T M; Keaveney, J; Kenyon, I R; Kerzel, U; Ketel, T; Keune, A; Khanji, B; Kim, Y M; Knecht, M; Koopman, R F; Koppenburg, P; Korolev, M; Kozlinskiy, A; Kravchuk, L; Kreplin, K; Kreps, M; Krocker, G; Krokovny, P; Kruse, F; Kruzelecki, K; Kucharczyk, M; Kudryavtsev, V; Kvaratskheliya, T; La Thi, V N; Lacarrere, D; Lafferty, G; Lai, A; Lambert, D; Lambert, R W; Lanciotti, E; Lanfranchi, G; Langenbruch, C; Latham, T; Lazzeroni, C; Le Gac, R; van Leerdam, J; Lees, J -P; Lefèvre, R; Leflat, A; Lefrançois, J; Leroy, O; Lesiak, T; Li, L; Li Gioi, L; Lieng, M; Liles, M; Lindner, R; Linn, C; Liu, B; Liu, G; von Loeben, J; Lopes, J H; Lopez Asamar, E; Lopez-March, N; Lu, H; Luisier, J; Mac Raighne, A; Machefert, F; Machikhiliyan, I V; Maciuc, F; Maev, O; Magnin, J; Malde, S; Mamunur, R M D; Manca, G; Mancinelli, G; Mangiafave, N; Marconi, U; Märki, R; Marks, J; Martellotti, G; Martens, A; Martin, L; Martín Sánchez, A; Martinelli, M; Martinez Santos, D; Massafferri, A; Mathe, Z; Matteuzzi, C; Matveev, M; Maurice, E; Maynard, B; Mazurov, A; McGregor, G; McNulty, R; Meissner, M; Merk, M; Merkel, J; Miglioranzi, S; Milanes, D A; Minard, M -N; Molina Rodriguez, J; Monteil, S; Moran, D; Morawski, P; Mountain, R; Mous, I; Muheim, F; Müller, K; Muresan, R; Muryn, B; Muster, B; Mylroie-Smith, J; Naik, P; Nakada, T; Nandakumar, R; Nasteva, I; Needham, M; Neufeld, N; Nguyen, A D; Nguyen-Mau, C; Nicol, M; Niess, V; Nikitin, N; Nikodem, T; Nomerotski, A; Novoselov, A; Oblakowska-Mucha, A; Obraztsov, V; Oggero, S; Ogilvy, S; Okhrimenko, O; Oldeman, R; Orlandea, M; Otalora Goicochea, J M; Owen, P; Pal, B K; Palacios, J; Palano, A; Palutan, M; Panman, J; Papanestis, A; Pappagallo, M; Parkes, C; Parkinson, C J; Passaleva, G; Patel, G D; Patel, M; Paterson, S K; Patrick, G N; Patrignani, C; Pavel-Nicorescu, C; Pazos Alvarez, A; Pellegrino, A; Penso, G; Pepe Altarelli, M; Perazzini, S; Perego, D L; Perez Trigo, E; Pérez-Calero Yzquierdo, A; Perret, P; Perrin-Terrin, M; Pessina, G; Petrolini, A; Phan, A; Picatoste Olloqui, E; Pie Valls, B; Pietrzyk, B; Pilař, T; Pinci, D; Plackett, R; Playfer, S; Plo Casasus, M; Polok, G; Poluektov, A; Polycarpo, E; Popov, D; Popovici, B; Potterat, C; Powell, A; Prisciandaro, J; Pugatch, V; Puig Navarro, A; Qian, W; Rademacker, J H; Rakotomiaramanana, B; Rangel, M S; Raniuk, I; Raven, G; Redford, S; Reid, M M; dos Reis, A C; Ricciardi, S; Richards, A; Rinnert, K; Roa Romero, D A; Robbe, P; Rodrigues, E; Rodrigues, F; Rodriguez Perez, P; Rogers, G J; Roiser, S; Romanovsky, V; Rosello, M; Rouvinet, J; Ruf, T; Ruiz, H; Sabatino, G; Saborido Silva, J J; Sagidova, N; Sail, P; Saitta, B; Salzmann, C; Sannino, M; Santacesaria, R; Santamarina Rios, C; Santinelli, R; Santovetti, E; Sapunov, M; Sarti, A; Satriano, C; Satta, A; Savrie, M; Savrina, D; Schaack, P; Schiller, M; Schleich, S; Schlupp, M; Schmelling, M; Schmidt, B; Schneider, O; Schopper, A; Schune, M -H; Schwemmer, R; Sciascia, B; Sciubba, A; Seco, M; Semennikov, A; Senderowska, K; Sepp, I; Serra, N; Serrano, J; Seyfert, P; Shapkin, M; Shapoval, I; Shatalov, P; Shcheglov, Y; Shears, T; Shekhtman, L; Shevchenko, O; Shevchenko, V; Shires, A; Silva Coutinho, R; Skwarnicki, T; Smith, N A; Smith, E; Sobczak, K; Soler, F J P; Solomin, A; Soomro, F; Souza De Paula, B; Spaan, B; Sparkes, A; Spradlin, P; Stagni, F; Stahl, S; Steinkamp, O; Stoica, S; Stone, S; Storaci, B; Straticiuc, M; Straumann, U; Subbiah, V K; Swientek, S; Szczekowski, M; Szczypka, P; Szumlak, T; T'Jampens, S; Teodorescu, E; Teubert, F; Thomas, C; Thomas, E; van Tilburg, J; Tisserand, V; Tobin, M; Tolk, S; Topp-Joergensen, S; Torr, N; Tournefier, E; Tourneur, S; Tran, M T; Tsaregorodtsev, A; Tuning, N; Ubeda Garcia, M; Ukleja, A; Urquijo, P; Uwer, U; Vagnoni, V; Valenti, G; Vazquez Gomez, R; Vazquez Regueiro, P; Vecchi, S; Velthuis, J J; Veltri, M; Viaud, B; Videau, I; Vieira, D; Vilasis-Cardona, X; Visniakov, J; Vollhardt, A; Volyanskyy, D; Voong, D; Vorobyev, A; Vorobyev, V; Voss, H; Waldi, R; Wandernoth, S; Wang, J; Ward, D R; Watson, N K; Webber, A D; Websdale, D; Whitehead, M; Wiedner, D; Wiggers, L; Wilkinson, G; Williams, M P; Williams, M; Wilson, F F; Wishahi, J; Witek, M; Witzeling, W; Wotton, S A; Wyllie, K; Xie, Y; Xing, F; Xing, Z; Yang, Z; Young, R; Yushchenko, O; Zangoli, M; Zavertyaev, M; Zhang, F; Zhang, L; Zhang, W C; Zhang, Y; Zhelezov, A; Zhong, L; Zvyagin, A

2012-01-01

The $B_s^0\\to J/\\psi K_S^0$ branching fraction is measured in a data sample corresponding to 0.41$fb^{-1}$ of integrated luminosity collected with the LHCb detector at the LHC. This channel is sensitive to the penguin contributions affecting the sin2$\\beta$ measurement from $B^0\\to J/\\psi K_S^0$ The time-integrated branching fraction is measured to be $BF(B_s^0\\to J/\\psi K_S^0)=(1.83\\pm0.28)\\times10^{-5}$. This is the most precise measurement to date.
Metastatic triple-negative breast cancer is dependent on SphKs/S1P signaling for growth and survival.

Science.gov (United States)

Maiti, Aparna; Takabe, Kazuaki; Hait, Nitai C

2017-04-01

About 40,000 American women die from metastatic breast cancer each year despite advancements in treatment. Approximately, 15% of breast cancers are triple-negative for estrogen receptor, progesterone receptor, and HER2. Triple-negative cancer is characterized by more aggressive, harder to treat with conventional approaches and having a greater possibility of recurrence. Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid signaling mediator has emerged as a key regulatory molecule in breast cancer progression. Therefore, we investigated whether cytosolic sphingosine kinase type 1 (SphK1) and nuclear sphingosine kinase type 2 (SphK2), the enzymes that make S1P are critical for growth and PI3K/AKT, ERK-MAP kinase mediated survival signaling of lung metastatic variant LM2-4 breast cancer cells, generated from the parental triple-negative MDA-MB-231 human breast cancer cell line. Similar with previous report, SphKs/S1P signaling is critical for the growth and survival of estrogen receptor positive MCF-7 human breast cancer cells, was used as our study control. MDA-MB-231 did not show a significant effect of SphKs/S1P signaling on AKT, ERK, and p38 pathways. In contrast, LM2-4 cells that gained lung metastatic phenotype from primary MDA-MB-231 cells show a significant effect of SphKs/S1P signaling requirement on cell growth, survival, and cell motility. PF-543, a selective potent inhibitor of SphK1, attenuated epidermal growth factor (EGF)-mediated cell growth and survival signaling through inhibition of AKT, ERK, and p38 MAP kinase pathways mainly in LM2-4 cells but not in parental MDA-MB-231 human breast cancer cells. Moreover, K-145, a selective inhibitor of SphK2, markedly attenuated EGF-mediated cell growth and survival of LM2-4 cells. We believe this study highlights the importance of SphKs/S1P signaling in metastatic triple-negative breast cancers and targeted therapies. Copyright © 2017 Elsevier Inc. All rights reserved.
Expression and subcellular localization of p70S6 kinase under heart failure

Directory of Open Access Journals (Sweden)

Usenko V. S.

2010-11-01

Full Text Available The PI3K/PDK/Akt/mTOR/p70S6K signaling pathway is primary associated with the activation of insulin receptors and is important for cardiomyocytes survival. p70S6K is a key regulator of the speed and efficiency of protein biosynthesis within the cell. Recently the pro-apoptotic protein BAD has been identified as a new target for р70S6K1. BAD is inactivated in normal cardiomyocytes by р70S6K1 phosphorylation which prevents the cardiomyocytes apoptosis. Aim. To study possible changes in р70S6K1 expression and/or cellular localization at heart failure progression – in DCM- affected human myocardia and murine hearts with experimental DCM-like pathology. Methods. Western-blot analysis and immunohystochemistry. Results. The substantial decrease in р70S6K1 level was observed at the final stage of pathology progression and in the dynamics of DCM pathogenesis as well. For the first time relocalization of the protein to the connective tissue was shown according to the Western-blot results. Conclusions. The data obtained allow us to understand a possible role of р70S6K1 in the regulation of stress-induced apoptotic signaling in cardiomyocytes.
Identification of the Raptor-binding motif on Arabidopsis S6 kinase and its use as a TOR signaling suppressor.

Science.gov (United States)

Son, Ora; Kim, Sunghan; Hur, Yoon-Sun; Cheon, Choong-Ill

2016-03-25

TOR (target of rapamycin) kinase signaling plays central role as a regulator of growth and proliferation in all eukaryotic cells and its key signaling components and effectors are also conserved in plants. Unlike the mammalian and yeast counterparts, however, we found through yeast two-hybrid analysis that multiple regions of the Arabidopsis Raptor (regulatory associated protein of TOR) are required for binding to its substrate. We also identified that a 44-amino acid region at the N-terminal end of Arabidopsis ribosomal S6 kinase 1 (AtS6K1) specifically interacted with AtRaptor1, indicating that this region may contain a functional equivalent of the TOS (TOR-Signaling) motif present in the mammalian TOR substrates. Transient over-expression of this 44-amino acid fragment in Arabidopsis protoplasts resulted in significant decrease in rDNA transcription, demonstrating a feasibility of developing a new plant-specific TOR signaling inhibitor based upon perturbation of the Raptor-substrate interaction. Copyright © 2016 Elsevier Inc. All rights reserved.
[SP600125-induced polyploidization of megakaryocytic leukemia cell lines by ribosomal protein S6 kinase 1 depends on the degree of cell differentiation].

Science.gov (United States)

Wang, Lili; Yang, Jingang; Li, Changling; Xing, Sining; Yu, Ying; Liu, Shuo; Zhao, Song; Ma, Dongchu

2016-10-01

Objective To investigate regulatory role of ribosomal protein S6 kinase 1 (S6K1) in the polyploidization of different megakaryocytic leukemia cell lines at the different differentiation stages. Methods Megakaryocytic leukemia cell lines (Dami, Meg-01 and HEL cells) were induced towards polyploidization by SP600125, a c-Jun N-terminal kinase (JNK) inhibitor. The SP600125-inducing process was blocked by H-89, a cAMP-dependent protein kinase (PKA) inhibitor. The phenotype (CD41a, CD42a and CD42b) and DNA ploidy were detected by flow cytometry. The expression and phosphorylation of S6K1 and related proteins were detected by Western blotting. Results SP600125 induced polyploidization and increased the phosphorylation of eukaryotic initiation factor 4E binding protein 1 (4E-BP1) in Dami, Meg-01 and HEL cells. However, the effect of SP600125 on polyploidization of the three cell lines was different, with the strongest effect on Dami cells and the weakest on Meg-01 cells. Moreover, SP600125 increased the phosphorylation of S6K1 Thr421/Ser424 and decreased the phosphorylation of Thr389 in Dami cells. However, it only increased the phosphorylation of Thr389 in HEL cells and had no effect on the phosphorylation of S6K1 in Meg-01 cells. Interestingly, H-89 only partially blocked the polyploidization of Dami cells, although it decreased the phosphorylation of 4E-BP1 in all SP600125-induced three cell lines. Noticeably, H-89 decreased the phosphorylation of S6K1 Thr421/Ser424 and increased the phosphorylation of Thr389 in Dami cells. However, H-89 had no effect on the phosphorylation of Thr421/Ser424, although it increased the phosphorylation of Thr389 in Meg-01 and HEL cells. Phenotypic analysis showed that the three cell lines were at different levels of differentiation in megakaryocytic lineage, with the highest differentiation in Dami and the lowest in Meg-01 cells. Conclusion SP600125-induced polyploidization of megakaryocytic leukemia cell lines is dependent on the effect
PF-4708671, a specific inhibitor of p70 ribosomal S6 kinase 1, activates Nrf2 by promoting p62-dependent autophagic degradation of Keap1

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Park, Jeong Su [Severance Biomedical Science Institute (Korea, Republic of); Yonsei Biomedical Research Institute, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752 (Korea, Republic of); Kang, Dong Hoon [Department of Life Science and Ewha Research Center for Systems Biology (Korea, Republic of); The Research Center for Cell Homeostasis, Ewha Womans University, Seoul 127-750 (Korea, Republic of); Lee, Da Hyun [Severance Biomedical Science Institute (Korea, Republic of); Yonsei Biomedical Research Institute, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752 (Korea, Republic of); Bae, Soo Han, E-mail: soohanbae@yuhs.ac [Severance Biomedical Science Institute (Korea, Republic of); Yonsei Biomedical Research Institute, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752 (Korea, Republic of)

2015-10-23

p70 ribosomal S6 kinase 1 (S6K1) is an important serine/threonine kinase and downstream target of the mechanistic target of rapamycin complex 1 (mTORC1) signaling pathway. PF-4708671 is a specific inhibitor of S6K1, and prevents S6K1-mediated phosphorylation of the S6 protein. PF-4708671 treatment often leads to apoptotic cell death. However, the protective mechanism against PF-4708671-induced cell death has not been elucidated. The nuclear factor erythroid 2-related factor 2 (Nrf2)-Kelch-like ECH-associated protein 1 (Keap1) pathway is essential for protecting cells against oxidative stress. p62, an adaptor protein in the autophagic process, enhances Nrf2 activation through the impairment of Keap1 activity. In this study, we showed that PF-4708671 induces autophagic Keap1 degradation-mediated Nrf2 activation in p62-dependent manner. Furthermore, p62-dependent Nrf2 activation plays a crucial role in protecting cells from PF-4708671-mediated apoptosis. - Highlights: • PF-4708671, a S6K1-specific inhibitor, prevents S6K1-mediated S6 phosphorylation. • However, PF-4708671 treatment often leads to apoptotic cell death. • Protective mechanism against PF-4708671-induced cell death remains to be elucidated. • PF-4708671 induced p62-dependent, autophagic Keap1 degradation-mediated Nrf2 activation. • p62-dependent Nrf2 activation protects cells from PF-4708671-mediated apoptosis.
A Cancer Gene Selection Algorithm Based on the K-S Test and CFS

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Qiang Su

2017-01-01

Full Text Available Background. To address the challenging problem of selecting distinguished genes from cancer gene expression datasets, this paper presents a gene subset selection algorithm based on the Kolmogorov-Smirnov (K-S test and correlation-based feature selection (CFS principles. The algorithm selects distinguished genes first using the K-S test, and then, it uses CFS to select genes from those selected by the K-S test. Results. We adopted support vector machines (SVM as the classification tool and used the criteria of accuracy to evaluate the performance of the classifiers on the selected gene subsets. This approach compared the proposed gene subset selection algorithm with the K-S test, CFS, minimum-redundancy maximum-relevancy (mRMR, and ReliefF algorithms. The average experimental results of the aforementioned gene selection algorithms for 5 gene expression datasets demonstrate that, based on accuracy, the performance of the new K-S and CFS-based algorithm is better than those of the K-S test, CFS, mRMR, and ReliefF algorithms. Conclusions. The experimental results show that the K-S test-CFS gene selection algorithm is a very effective and promising approach compared to the K-S test, CFS, mRMR, and ReliefF algorithms.
Association between PI3K/Akt/mTOR/p70S6K signaling pathway and hepatic fibrosis

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WU Changhui

2015-11-01

Full Text Available Phosphoinositide 3-kinase (PI3K/protein kinase-B (AkT/mammalian target of rapamycin (mTOR/70-kDa ribosomal protein S6 kinase (p70S6K, PI3K/Akt/mTOR/p70S6K, is an important signaling pathway in the life activities of cells, and it plays an important role in promoting the growth, proliferation, invasion, and anti-apoptosis of cells and promoting angiogenesis. It was clarified that the PI3K/Akt/mTOR/p70S6K signaling pathway is involved in regulating the activities of hepatic stellate cell(HSC, thus influencing the development and progression of hepatic fibrosis. Analysis demonstrated that blocking any target of the PI3K/Akt/mTOR/p70S6K signaling pathway can inhibit the activation and proliferation of HSC, promote the apoptosis of HSC, inhibit the extracellular matrix secretion from HSC, and delay the progression of hepatic fibrosis. Blocking the pathway is expected to be a treatment strategy for hepatic fibrosis.
Lysine 356 is a critical residue for binding the C-6 phospho group of fructose 2,6-bisphosphate to the fructose-2,6-bisphosphatase domain of rat liver 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase.

Science.gov (United States)

Li, L; Lin, K; Correia, J J; Pilkis, S J

1992-08-15

Lysine 356 has been implicated by protein modification studies as a fructose-2,6-bisphosphate binding site residue in the 6-phosphofructo-2-kinase domain of rat liver 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (Kitajima, S., Thomas, H., and Uyeda, K. (1985) J. Biol. Chem. 260, 13995-14002). However, Lys-356 is found in the fructose-2,6-bisphosphatase domain (Bazan, F., Fletterick, R., and Pilkis, S. J. (1989) Proc. Natl. Acad. Sci. U.S.A. 86, 9642-9646). In order to ascertain whether Lys-356 is involved in fructose-2,6-bisphosphatase catalysis and/or domain/domain interactions of the bifunctional enzyme, Lys-356 was mutated to Ala, expressed in Escherichia coli, and then purified to homogeneity. Circular dichroism experiments indicated that the secondary structure of the Lys-356-Ala mutant was not significantly different from that of the wild-type enzyme. The Km for fructose 2,6-bisphosphate and the Ki for the noncompetitive inhibitor, fructose 6-phosphate, for the fructose-2,6-bisphosphatase of the Lys-356-Ala mutant were 2700- and 2200-fold higher, respectively, than those of the wild-type enzyme. However, the maximal velocity and the Ki for the competitive product inhibitor, inorganic phosphate, were unchanged compared to the corresponding values of the wild-type enzyme. Furthermore, in contrast to the wild-type enzyme, which exhibits substrate inhibition, there was no inhibition by substrate of the Lys-356-Ala mutant. In the presence of saturating substrate, inorganic phosphate, which acts by relieving fructose-6-phosphate and substrate inhibition, is an activator of the bisphosphatase. The Ka for inorganic phosphate of the Lys-356-Ala mutant was 1300-fold higher than that of the wild-type enzyme. The kinetic properties of the 6-phosphofructo-2-kinase of the Lys-356-Ala mutant were essentially identical with that of the wild-type enzyme. The results demonstrate that: 1) Lys-356 is a critical residue in fructose-2,6-bisphosphatase for binding the 6
Hsp60 and p70S6K form a complex in human cardiomyocytes

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Kroupskaya I. V.

2011-02-01

Full Text Available Molecular chaperon Hsp60 and protein kinase p70S6K play an important functional role in the regulation of cardiomyocytes vital function or apoptosis. Aim. To study a possibility of in vivo complex formation between Hsp60 and p70S6K in cardiomyocytes. Methods. Co-immunoprecipitation, Western-blot analysis. Results. We have identified in vivo interaction between molecular chaperone Hsp60 and two isoforms of proteinkinase p70S6K in human myocardium, normal and affected by cardiomyopathy. Conclusions. The results obtained suggest a possible participation of molecular chaperon Hsp60 in regulation of p70S6K activity in stressinduced apoptotic signaling pathway in cardiomyocytes.
IL-3 Maintains Activation of the p90S6K/RPS6 Pathway and Increases Translation in Human Eosinophils.

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Esnault, Stephane; Kelly, Elizabeth A B; Shen, Zhong-Jian; Johansson, Mats W; Malter, James S; Jarjour, Nizar N

2015-09-15

IL-5 is a major therapeutic target to reduce eosinophilia. However, all of the eosinophil-activating cytokines, such as IL-5, IL-3, and GM-CSF, are typically present in atopic diseases, including allergic asthma. As a result of the functional redundancy of these three cytokines on eosinophils and the loss of IL-5R on airway eosinophils, it is important to take IL-3 and GM-CSF into account to efficiently reduce tissue eosinophil functions. Moreover, these three cytokines signal through a common β-chain receptor but yet differentially affect protein production in eosinophils. Notably, the increased ability of IL-3 to induce the production of proteins, such as semaphorin-7A, without affecting mRNA levels suggests a unique influence of IL-3 on translation. The purpose of this study was to identify the mechanisms by which IL-3 distinctively affects eosinophil function compared with IL-5 and GM-CSF, with a focus on protein translation. Peripheral blood eosinophils were used to study intracellular signaling and protein translation in cells activated with IL-3, GM-CSF, or IL-5. We establish that, unlike GM-CSF or IL-5, IL-3 triggers prolonged signaling through activation of ribosomal protein S6 (RPS6) and the upstream kinase 90-kDa ribosomal S6 kinase (p90S6K). Blockade of p90S6K activation inhibited phosphorylation of RPS6 and IL-3-enhanced semaphorin-7A translation. Furthermore, in an allergen-challenged environment, in vivo phosphorylation of RPS6 and p90S6K was enhanced in human airway compared with circulating eosinophils. Our findings provide new insights into the mechanisms underlying differential activation of eosinophils by IL-3, GM-CSF, and IL-5. These observations identify IL-3 and its downstream intracellular signals as novel targets that should be considered to modulate eosinophil functions. Copyright © 2015 by The American Association of Immunologists, Inc.
Haloperidol Regulates the State of Phosphorylation of Ribosomal Protein S6 via Activation of PKA and Phosphorylation of DARPP-32

Science.gov (United States)

Valjent, Emmanuel; Bertran-Gonzalez, Jesus; Bowling, Heather; Lopez, Sébastien; Santini, Emanuela; Matamales, Miriam; Bonito-Oliva, Alessandra; Hervé, Denis; Hoeffer, Charles; Klann, Eric; Girault, Jean-Antoine; Fisone, Gilberto

2011-01-01

Administration of typical antipsychotic drugs, such as haloperidol, promotes cAMP-dependent signaling in the medium spiny neurons (MSNs) of the striatum. In this study, we have examined the effect of haloperidol on the state of phosphorylation of the ribosomal protein S6 (rpS6), a component of the small 40S ribosomal subunit. We found that haloperidol increases the phosphorylation of rpS6 at the dual site Ser235/236, which is involved in the regulation of mRNA translation. This effect was exerted in the MSNs of the indirect pathway, which express specifically dopamine D2 receptors (D2Rs) and adenosine A2 receptors (A2ARs). The effect of haloperidol was decreased by blockade of A2ARs or by genetic attenuation of the Gαolf protein, which couples A2ARs to activation of adenylyl cyclase. Moreover, stimulation of cAMP-dependent protein kinase A (PKA) increased Ser235/236 phosphorylation in cultured striatal neurons. The ability of haloperidol to promote rpS6 phosphorylation was abolished in knock-in mice deficient for PKA activation of the protein phosphatase-1 inhibitor, dopamine- and cAMP-regulated phosphoprotein of 32 kDa. In contrast, pharmacological or genetic inactivation of p70 rpS6 kinase 1, or extracellular signal-regulated kinases did not affect haloperidol-induced rpS6 phosphorylation. These results identify PKA as a major rpS6 kinase in neuronal cells and suggest that regulation of protein synthesis through rpS6 may be a potential target of antipsychotic drugs. PMID:21814187
The 4p-5d, 6d and 4p-6s, 7s transitions of Mo IX

International Nuclear Information System (INIS)

Khatoon, S.; Chaghtai, M.S.Z.; Rahimullah, K.

1979-01-01

The transitions 4p-5d, 6d and 4p-6s, 7s have been studied for the first time in Mo IX. The authors have identified 42 4p-5d, 36 4p-6d, 22 4p-6s and 22 4p-7s transitions, establishing 16 4p 3 5d, 14 4p 3 6d and all the ten 4p 3 6s, 7s levels of the spectrum concerned. The ionization energy is estimated to be (1 323 700 +- 700)cm -1 or (164.11 +- 0.09)eV. The spectrum was recorded in sliding and open spark discharges with a 5 m grazing incidence spectrograph of Lund University (Sweden) from about 40 A to 440 A. (Auth.)
Hydrogen peroxide mediates Rac1 activation of S6K1

International Nuclear Information System (INIS)

Bae, Gyu-Un; Kim, Yong Kee; Kwon, Hyoung-Keun; Park, Jong Woo; Lee, Eun Kyung; Paek, Se Jin; Choi, Wahn Soo; Jung, In Duk; Lee, Hoi Young; Cho, Eun-Jung; Lee, Hyang Woo; Han, Jeung-Whan

2004-01-01

We previously reported that hydrogen peroxide (H 2 O 2 ) mediates mitogen activation of ribosomal protein S6 kinase 1 (S6K1) which plays an important role in cell proliferation and growth. In this study, we investigated a possible role of H 2 O 2 as a molecular linker in Rac1 activation of S6K1. Overexpression of recombinant catalase in NIH-3T3 cells led to the drastic inhibition of H 2 O 2 production by PDGF, which was accompanied by a decrease in S6K1 activity. Similarly, PDGF activation of S6K1 was significantly inhibited by transient transfection or stable transfection of the cells with a dominant-negative Rac1 (Rac1N17), while overexpression of constitutively active Rac1 (Rac1V12) in the cells led to an increase in basal activity of S6K1. In addition, stable transfection of Rat2 cells with Rac1N17 dramatically attenuated the H 2 O 2 production by PDGF as compared with that in the control cells. In contrast, Rat2 cells stably transfected with Rac1V12 produced high level of H 2 O 2 in the absence of PDGF, comparable to that in the control cells stimulated with PDGF. More importantly, elimination of H 2 O 2 produced in Rat2 cells overexpressing Rac1V12 inhibited the Rac1V12 activation of S6K1, indicating the possible role of H 2 O 2 as a mediator in the activation of S6K1 by Rac1. However, H 2 O 2 could be also produced via other pathway, which is independent of Rac1 or PI3K, because in Rat2 cells stably transfected with Rac1N17, H 2 O 2 could be produced by arsenite, which has been shown to be a stimulator of H 2 O 2 production. Taken together, these results suggest that H 2 O 2 plays a pivotal role as a mediator in Rac1 activation of S6K1

Chitin-induced T6SS in Vibrio cholerae is dependent on ChiS activation.

Science.gov (United States)

Chourashi, Rhishita; Das, Suman; Dhar, Debarpan; Okamoto, Keinosuke; Mukhopadhyay, Asish K; Chatterjee, Nabendu Sekhar

2018-05-01

Vibrio cholerae regularly colonizes the chitinous exoskeleton of crustacean shells in the aquatic region. The type 6 secretion system (T6SS) in V. cholerae is an interbacterial killing device. This system is thought to provide a competitive advantage to V. cholerae in a polymicrobial community of the aquatic region under nutrient-poor conditions. V. cholerae chitin sensing is known to be initiated by the activation of a two-component sensor histidine kinase ChiS in the presence of GlcNAc2 (N,N'-diacetylchitobiose) residues generated by the action of chitinases on chitin. It is known that T6SS in V. cholerae is generally induced by chitin. However, the effect of ChiS activation on T6SS is unknown. Here, we found that ChiS inactivation resulted in impaired bacterial killing and reduced expression of T6SS genes. Active ChiS positively affected T6SS-mediated natural transformation in V. cholerae. ChiS depletion or inactivation also resulted in reduced colonization on insoluble chitin surfaces. Therefore, we have shown that V. cholerae colonization on chitinous surfaces activates ChiS, which promotes T6SS-dependent bacterial killing and horizontal gene transfer. We also highlight the importance of chitinases in T6SS upregulation.
The Sensor Kinase GacS Negatively Regulates Flagellar Formation and Motility in a Biocontrol Bacterium, Pseudomonas chlororaphis O6

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Ji Soo Kim

2014-06-01

Full Text Available The GacS/GacA two component system regulates various traits related to the biocontrol potential of plant-associated pseudomonads. The role of the sensor kinase, GacS, differs between strains in regulation of motility. In this study, we determined how a gacS mutation changed cell morphology and motility in Pseudomonas chlororaphis O6. The gacS mutant cells were elongated in stationary-phase compared to the wild type and the complemented gacS mutant, but cells did not differ in length in logarithmic phase. The gacS mutant had a two-fold increase in the number of flagella compared with the wild type strain; flagella number was restored to that of the wild type in the complemented gacS mutant. The more highly flagellated gacS mutant cells had greater swimming motilities than that of the wild type strain. Enhanced flagella formation in the gacS mutant correlated with increased expression of three genes, fleQ, fliQ and flhF, involved in flagellar formation. Expression of these genes in the complemented gacS mutant was similar to that of the wild type. These findings show that this root-colonizing pseudomonad adjusts flagella formation and cell morphology in stationary-phase using GacS as a major regulator.
Spectral analysis of 5s25p2(6p+6d+7s) configurations of Ba VI

International Nuclear Information System (INIS)

Sharma, M.K.; Tauheed, A.; Rahimullah, K.

2014-01-01

The sixth spectrum of barium (Ba VI) has been investigated with the aid of experimental recordings made on a 3-m normal incidence vacuum spectrograph of Antigonish laboratory (Canada) in the wavelength region 300–2080 Å using triggered spark as an excitation source. The spectral analysis has been extended considerably to include new configuration the 5s 2 5p 2 6p in odd parity matrix and the 5s 2 5p 2 6d and 5s 2 5p 2 7s configurations in even parity matrix. Previously reported levels of the ground configuration (5s 2 5p 3 ) and three lowest excited configurations the 5s5p 4 , 5s 2 5p 2 5d and 5s 2 5p 2 6s have been confirmed and the two unknown levels of the 5s 2 5p 2 5d configuration with J=9/2, have now been established through the identification of transitions from the 5s 2 5p 2 6p levels. All twenty one levels of the 5s 2 5p 2 6p configuration and twenty nine levels out of thirty six of the 5s 2 5p 2 6d and 5s 2 5p 2 7s configurations have now been established. Hartree–Fock calculations involving configuration interactions support the analyses. The accuracy of our wavelength measurement is ±0.005 Å for sharp lines. - Highlights: • The spectrum of Ba was recorded on a 3-m spectrograph with triggered spark source. • Atomic transitions for Ba VI were identified to established new energy levels. • CI calculations with relativistic corrections were made for theoretical predictions. • Weighted oscillator strength (gf) and transition probabilities (gA) were calculated
LHCb: Measurement of the time-dependent CP asymmetry in $B^{0} \\rightarrow J/\\psi K_S^0$

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Szilard, D

2012-01-01

The LHCb is one of the LHC experiments, specially designed to study CP violation and rare decays of b-quark. In this scenario, the decay $B^{0} \\rightarrow J/\\psi K_S^0$ is a well-known mode to study CP violation. The final state is the same for both CP eigenstates $B^0$ and $\\overline{B^0}$, which enables the interference through the b-quark oscillations.The CKM angle $\\beta$ can be extracted from the above decay. The time dependent decay rate asymmetry can be written as: $$ \\mathcal{A}_{J/\\psi K_S^0} (t) = S_{J/\\psi K_S^0} \\sin(\\Delta m_d t) - C_{J/\\psi K_S^0} \\cos( \\Delta m_d t) $$ where, in the standard model, the parameters $S_{J/\\psi K_S^0}$ and $C_{J/\\psi K_S^0}$ are connected to the CKM angle $\\beta$ through: $$S_{J/\\psi K_S^0} = \\sin 2 \\beta \\, \\rm{ and } \\, C_{J/\\psi K_S^0} = 0 $$ Here we report the time-dependent analysis in the $B^{0} \\rightarrow J/\\psi (\\mu^{+} \\mu^{-}) K_S^0 (\\pi^{+} \\pi^{-})$ decays. Using the $1fb^{-1}$ of integrated luminosity data collected in 2011 at LHCb operat...
Samsung Galaxy S6 for dummies

CERN Document Server

Hughes, Bill

2015-01-01

Explore the capabilities of your Samsung Galaxy S 6 with this definitive guide! Learning to use a new phone can be both difficult and frustrating. With confusing documentation and baffling support, the references provided by phone manufacturers can be intimidating. Enter Samsung Galaxy S 6 For Dummies! This extensive yet practical guide walks you through the most useful features of your new Samsung Galaxy S 6-and it shows you all the best tricks to getting the most out of your device. With an accessible and fun, yet informative writing style, this is a text that you'll refer to again and agai
S100A6 - New facts and features

Energy Technology Data Exchange (ETDEWEB)

Lesniak, Wieslawa; Slomnicki, Lukasz P. [Department of Molecular and Cellular Neurobiology, Nencki Institute of Experimental Biology, 02-093 Warsaw (Poland); Filipek, Anna, E-mail: a.filipek@nencki.gov.pl [Department of Molecular and Cellular Neurobiology, Nencki Institute of Experimental Biology, 02-093 Warsaw (Poland)

2009-12-25

S100A6 (calcyclin) is a 10.5 kDa Ca{sup 2+}-binding protein that belongs to the S100 protein family. S100A6 contains two EF-hand motifs responsible for binding of Ca{sup 2+}. It also binds Zn{sup 2+} through not yet identified structures. Binding of Ca{sup 2+} induces a conformational change in the S100A6 molecule which in consequence increases its overall hydrophobicity and allows for interaction with target proteins. S100A6 was found in different mammalian and avian (chicken) tissues. A high level of S100A6 is observed in epithelial cells, fibroblasts and in different kinds of cancer cells. The function of S100A6 is not clear at present, but it has been suggested that it may be involved in cell proliferation, cytoskeletal dynamics and tumorigenesis. Additionally, S100A6 might have some extracellular activities. This review presents new facts and features concerning the S100A6 protein.
Phosphorylation of ribosomal protein S6 kinase 1 at Thr421/Ser424 and dephosphorylation at Thr389 regulates SP600125-induced polyploidization of megakaryocytic cell lines.

Science.gov (United States)

Li, Chang-Ling; Yang, Jin-Gang; Lin, Di; Zhao, Yong-Shan; Liu, Shuo; Xing, Si-Ning; Zhao, Song; Chen, Cong-Qin; Jiang, Zhi-Ming; Pu, Fei-Fei; Cao, Jian-Ping; Ma, Dong-Chu

2014-01-01

Megakaryocytes (MKs) are one of the few cell types that become polyploid; however, the mechanisms by which these cells are designated to become polyploid are not fully understood. In this investigation, we successfully established two relatively synchronous polyploid cell models by inducing Dami and CMK cells with SP600125. We found that SP600125 induced the polyploidization of Dami and CMK cells, concomitant with the phosphorylation of ribosomal protein S6 kinase 1 (S6K1) at Thr421/Ser424 and dephosphorylation at Thr389. The polyploidization was partially blocked by H-89, a cAMP-dependent protein kinase (PKA) inhibitor, through direct binding to S6K1, leading to dephosphorylation at Thr421/Ser424 and phosphorylation at Thr389, independent of PKA. Overexpression of a rapamycin-resistant mutant of S6K1 further enhanced the inhibitory effect of LY294002 on the SP600125-induced polyploidization of Dami and CMK cells. SP600125 also induced the polyploidization of Meg-01 cells, which are derived from a patient with chronic myelogenous leukemia, without causing a significant change in S6K1 phosphorylation. Additionally, SP600125 induced the polyploidization of HEL cells, which are derived from a patient with erythroleukemia, and phosphorylation at Thr389 of S6K1 was detected. However, the polyploidization of both Meg-01 cells and HEL cells as a result of SP600125 treatment was lower than that of SP600125-induced Dami and CMK cells, and it was not blocked by H-89 despite the increased phosphorylation of S6K1 at Thr389 in both cell lines in response to H-89. Given that the Dami and CMK cell lines were derived from patients with acute megakaryocytic leukemia (AMKL) and expressed high levels of platelet-specific antigens, our data suggested that SP600125-induced polyploidization is cell-type specific, that these cell lines were more differentiated, and that phosphorylation at Thr421/Ser424 and dephosphorylation at Thr389 of S6K1 may play an important role in the SP600125
Phosphorylation of ribosomal protein S6 kinase 1 at Thr421/Ser424 and dephosphorylation at Thr389 regulates SP600125-induced polyploidization of megakaryocytic cell lines.

Directory of Open Access Journals (Sweden)

Chang-Ling Li

Full Text Available Megakaryocytes (MKs are one of the few cell types that become polyploid; however, the mechanisms by which these cells are designated to become polyploid are not fully understood. In this investigation, we successfully established two relatively synchronous polyploid cell models by inducing Dami and CMK cells with SP600125. We found that SP600125 induced the polyploidization of Dami and CMK cells, concomitant with the phosphorylation of ribosomal protein S6 kinase 1 (S6K1 at Thr421/Ser424 and dephosphorylation at Thr389. The polyploidization was partially blocked by H-89, a cAMP-dependent protein kinase (PKA inhibitor, through direct binding to S6K1, leading to dephosphorylation at Thr421/Ser424 and phosphorylation at Thr389, independent of PKA. Overexpression of a rapamycin-resistant mutant of S6K1 further enhanced the inhibitory effect of LY294002 on the SP600125-induced polyploidization of Dami and CMK cells. SP600125 also induced the polyploidization of Meg-01 cells, which are derived from a patient with chronic myelogenous leukemia, without causing a significant change in S6K1 phosphorylation. Additionally, SP600125 induced the polyploidization of HEL cells, which are derived from a patient with erythroleukemia, and phosphorylation at Thr389 of S6K1 was detected. However, the polyploidization of both Meg-01 cells and HEL cells as a result of SP600125 treatment was lower than that of SP600125-induced Dami and CMK cells, and it was not blocked by H-89 despite the increased phosphorylation of S6K1 at Thr389 in both cell lines in response to H-89. Given that the Dami and CMK cell lines were derived from patients with acute megakaryocytic leukemia (AMKL and expressed high levels of platelet-specific antigens, our data suggested that SP600125-induced polyploidization is cell-type specific, that these cell lines were more differentiated, and that phosphorylation at Thr421/Ser424 and dephosphorylation at Thr389 of S6K1 may play an important role in
K.S. Micro-Implant Placement Guide

OpenAIRE

Sharma, K; Sangwan, A

2014-01-01

A one of the greatest concerns with orthodontic mini-implants is risk of injury to dental roots during placement is, especially when they are inserted between teeth. Many techniques have been used to facilitate safe placement of interradicular miniscrews. Brass Wires or metallic markers are easy to place in the interproximal spaces, but because their relative positions may be inconsistent in different radio -graphic views, they are not always accurate. K.S. micro implant placement guide sugge...
Observation of the strongest 5s2 5p6 5d-(5s2 5p5 5d6s+5s25p6 7p) transitions in Au XI to Bi XV ions

International Nuclear Information System (INIS)

Churilov, S.S.; Joshi, Y.N.

2001-01-01

The spectra of gold till bismuth were studied in the 90-135 A region. Nine most intense lines belonging to the 5s 2 5p 6 5d-5s 2 5p 5 5d6s array were identified in Au XI to Bi XV ions. The 5s 2 5p 6 7p 2 P 3/2,1/2 levels in Au XI and the 5s 2 5p 6 7p 2 P 3/2 level in Hg XII were also identified. The observed wavelengths and intensities agree quite well with the Hartree-Fock calculations. (orig.)
Initiation factor eIF2B not p70 S6 kinase is involved in the activation of the PI-3K signalling pathway induced by the v=src oncogene

Czech Academy of Sciences Publication Activity Database

Vojtěchová, Martina; Šloncová, Eva; Kučerová, Dana; Jiřička, Jaroslav; Sovová, Vlasta; Tuháčková, Zdena

2003-01-01

Roč. 543, 1-3 (2003), s. 81-86 ISSN 0014-5793 R&D Projects: GA ČR GV312/96/K205; GA ČR GA301/00/0269; GA MZd NC5428 Institutional research plan: CEZ:AV0Z5052915 Keywords : phosphoinositide 3-kinase signalling pathway * mRNA translation * 70 kDa ribosomal protein S6 kinase Subject RIV: CE - Biochemistry Impact factor: 3.609, year: 2003
S6K1 is involved in polyploidization through its phosphorylation at Thr421/Ser424.

Science.gov (United States)

Ma, Dongchu; Yu, Huiying; Lin, Di; Sun, Yinghui; Liu, Liping; Liu, Yage; Dai, Bing; Chen, Wei; Cao, Jianping

2009-04-01

Studies on polyploidization of megakaryocytes have been hampered by the lack of synchronized polyploid megakaryocytes. In this study, a relatively synchronized polyploid cell model was successfully established by employing Dami cells treated with nocodazole. In nocodazole-induced cells, cyclin B expression oscillated normally as in diploid cells and polyploid megakaryocytes. By using the nocodazole-induced Dami cell model, we found that 4E-BP1 and Thr421/Ser424 of ribosomal S6 kinase 1(S6K1) were phosphorylated mostly at M-phase in cytoplasm and oscillated in nocodazole-induced polyploid Dami cells, concomitant with increased expression of p27 and cyclin D3. However, phosphorylation of 4E-BP1 and S6K1 on Thr421/Ser424 was significantly decreased in differentiated Dami cells induced by phorbol 12-myristate 13-acetate (PMA), concomitant with increased expression of cyclin D1 and p21 and cyclin D3. Overexpression of the kinase dead form of S6K1 containing the mutation Lys 100 --> Gln in PMA-induced Dami cells increased ploidy whereas overexpression of rapamycin-resistant form of S6K1 containing the mutations Thr421 --> Glu and Ser424 --> Asp significantly dephosphorylated 4E-BP1 and reduced expression of cyclin D1, cyclin D3, p21 and p27, and slightly decreased the ploidy of PMA-induced Dami cells, compared with treatment with PMA alone. Moreover, overexpression of rapamycin-resistant form of S6K1 significantly reversed polyploidization of nocodazole-induced Dami cells. Furthermore, MAP (a novel compound synthesized recently) partly blocked the phosphorylation of S6K1 on Thr421/Ser424 and decreased the expression of p27 and polyploidization in nocodazole-induced Dami cells. Taken together, these data suggested that S6K1/4E-BP1 pathway may play an important role in polyploidization of megakaryocytes. (c) 2008 Wiley-Liss, Inc.
Inhibition of p70S6K2 down-regulates Hedgehog/GLI pathway in non-small cell lung cancer cell lines

Directory of Open Access Journals (Sweden)

Kotani Hidehito

2009-07-01

Full Text Available Abstract Background The Hedgehog (HH pathway promotes tumorigenesis in a diversity of cancers. Activation of the HH signaling pathway is caused by overexpression of HH ligands or mutations in the components of the HH/GLI1 cascade, which lead to increased transactivation of GLI transcription factors. Although negative kinase regulators that antagonize the activity of GLI transcription factors have been reported, including GSK3β, PKA and CK1s, little is known regarding positive kinase regulators that are suitable for use on cancer therapeutic targets. The present study attempted to identify kinases whose silencing inhibits HH/GLI signalling in non-small cell lung cancer (NSCLC. Results To find positive kinase regulators in the HH pathway, kinome-wide siRNA screening was performed in a NSCLC cell line, A549, harboring the GLI regulatory reporter gene. This showed that p70S6K2-silencing remarkably reduced GLI reporter gene activity. The decrease in the activity of the HH pathway caused by p70S6K2-inhibition was accompanied by significant reduction in cell viability. We next investigated the mechanism for p70S6K2-mediated inhibition of GLI1 transcription by hypothesizing that GSK3β, a negative regulator of the HH pathway, is activated upon p70S6K2-silencing. We found that phosphorylated-GSK3β (Ser9 was reduced by p70S6K2-silencing, causing a decreased level of GLI1 protein. Finally, to further confirm the involvement of p70S6K2 in GLI1 signaling, down-regulation in GLI-mediated transcription by PI3KCA-inhibition was confirmed, establishing the pivotal role of the PI3K/p70S6K2 pathway in GLI1 cascade regulation. Conclusion We report herein that inhibition of p70S6K2, known as a downstream effector of the PI3K pathway, remarkably decreases GLI-mediated transactivation in NSCLC by reducing phosphorylated-GSK3β followed by GLI1 degradation. These results infer that p70S6K2 is a potential therapeutic target for NSCLC with hyperactivated HH/GLI pathway.
(Ph4P)S6—A Compound Containing the Cyclic Radical Anion S6.−

NARCIS (Netherlands)

Neumuller, F.; Schmock, R.; Kirmse, A.; Voigt, A.; Diefenbach, A.; Bickelhaupt, F.M.; Dehnicke, K.

2000-01-01

Two long S−S bonds link the two S3 fragments in the cyclic radical anion S6.−. This forms as orange‐red crystals with PPh4+ as the counterion in the reaction of sulfane with (tetraphenylphosphonium) hydrogen diazide. The anion has a chair conformation with C2h symmetry (see picture).
Observation of the B-s(0) -> J/psi (KsK +/-)-K-0 pi(-/+) decay

NARCIS (Netherlands)

Aaij, R.; Collaboration, Lhcb; Adeva, B.; Adinolfi, M.; Affolder, A.; Ajaltouni, Z.; Albrecht, J.; Alessio, F.; Alexander, M.; Ali, S.; Alkhazov, G.; Alvarez Cartelle, P.; Alves, A. A.; Amato, S.; Amerio, S.; Amhis, Y.; An, L.; Anderlini, L.; Anderson, J.; Andreassen, R.; Andreotti, M.; Andrews, J. E.; Appleby, R. B.; Gutierrez, O. Aquines; Archilli, F.; Artamonov, A.; Artuso, M.; Aslanides, E.; Auriemma, G.; Baalouch, M.; Bachmann, S.; Back, J. J.; Badalov, A.; Balagura, V.; Baldini, W.; Barlow, R. J.; Barschel, C.; Barsuk, S.; Barter, W.; Batozskaya, V.; Bay, A.; Beaucourt, L.; Beddow, J.; Bedeschi, F.; Bediaga, I.; Belogurov, S.; Belous, K.; Belyaev, I.; Ben-Haim, E.; Bencivenni, G.; Benson, S.; Benton, J.; Berezhnoy, A.; Bernet, R.; Bettler, M. -O; van Beuzekom, M.; Bien, A.; Bifani, S.; Bird, T.; Bizzetii, A.; Bjornstad, P. M.; Blake, T.; Blanc, F.; Blouw, J.; Blusk, S.; Bocci, V.; Bondar, A.; Bondar, N.; Bonivento, W.; Borghi, S.; Borgia, A.; Borsato, M.; Bowcock, T. J. V.; Bowen, E.; Bozzi, C.; Brambach, T.; van den Brand, J.; Bressieux, J.; Brett, D.; Britsch, M.; Britton, T.; Brodzicka, J.; Brook, N. H.; Brown, H.; Bursche, A.; Busetto, G.; Buytaert, J.; Cadeddu, S.; Calabrese, R.; Calvi, M.; Gomez, M. Calvo; Camboni, A.; Campana, P.; Perez, D. Campora; Carbone, A.; Carboni, G.; Cardinale, R.; Cardini, A.; Carranza-Mejia, H.; Carson, L.; Akiba, K. Carvalho; Casse, G.; Cassina, L.; Garcia, L. Castillo; Cattaneo, M.; Cauet, Ch; Cenci, R.; Charles, M.; Charpentier, Ph.; Chen, S.; Cheung, S. -F.; Chiapolini, N.; Chrzaszcz, M.; Ciba, K.; Vidal, X. Cid; Ciezarek, G.; Clarke, P. E. L.; Clemencic, M.; Cliff, H. V.; Closier, J.; Coco, V.; Cogan, J.; Cogneras, E.; Collins, P.; Comerma-Montells, A.; Contu, A.; Cook, A.; Coombes, M.; Coquereau, S.; Corti, G.; Corvo, M.; Counts, I.; Couturier, B.; Cowan, G. A.; Craik, D. C.; Cruz Torres, M.; Cunliffe, S.; Currie, R.; D'Ambrosio, C.; Dalseno, J.; David, P.; David, P. N. Y.; Davis, A.; De Bruyn, K.; De Capua, S.; De Cian, M.; De Miranda, J. M.; De Paula, L.; De Silva, W.; De Simone, P.; Decamp, D.; Deckenhoff, M.; Del Buono, L.; Deleage, N.; Derkach, D.; Deschamps, O.; Dettori, F.; Di Canto, A.; Dijkstra, H.; Donleavy, S.; Dordei, F.; Dorigo, M.; Dosil Suarez, A.; Dossett, D.; Dovbnya, A.; Dujany, G.; Dupertuis, F.; Durante, P.; Dzhelyadin, R.; Dziurda, A.; Dzyuba, A.; Easo, S.; Egede, U.; Egorychev, V.; Eidelman, S.; Eisenhardt, S.; Eitschberger, U.; Ekelhof, R.; Eklund, L.; El Rifai, I.; Elsasser, Ch.; Ely, S.; Esen, S.; Evans, T.; Falabella, A.; Faerber, C.; Farinelli, C.; Farley, N.; Farry, S.; Ferguson, D.; Fernandez Albor, V.; Rodrigues, F. Ferreira; Ferro-Luzzi, M.; Filippov, S.; Fiore, M.; Fiorini, M.; Firlej, M.; Fitzpatrick, C.; Fiutowski, T.; Fontana, M.; Fontanelli, F.; Forty, R.; Francisco, O.; Frank, M.; Frei, C.; Frosini, M.; Fu, J.; Furfaro, E.; Torreira, A. Gallas; Galli, D.; Gallorini, S.; Gambetta, S.; Gandelman, M.; Gandini, P.; Gao, Y.; Garofoli, J.; Tico, J. Garra; Garrido, L.; Gaspar, C.; Gauld, R.; Gavardi, L.; Gersabeck, E.; Gersabeck, M.; Gershon, T.; Ghez, Ph; Gianelle, A.; Giani', S.; Gibson, V.; Giubega, L.; Gligorov, V. V.; Goebel, C.; Golubkov, D.; Golutvin, A.; Gomes, A.; Gordon, H.; Gotti, C.; Gandara, M. Grabalosa; Diaz, R. Graciani; Cardoso, L. A. Granado; Grauges, E.; Graziani, G.; Grecu, A.; Greening, E.; Gregson, S.; Griffith, P.; Grillo, L.; Gruenberg, O.; Gui, B.; Gushchin, E.; Guz, Yu; Gys, T.; Hadjivasiliou, C.; Haefeli, G.; Haen, C.; Haines, S. C.; Hall, S.; Hamilton, B.; Hampson, T.; Han, X.; Hansmann-Menzemer, S.; Harnew, N.; Harnew, S. T.; Harrison, J.; Hartmann, T.; He, J.; Head, T.; Heijne, V.; Hennessy, K.; Henrard, P.; Henry, L.; Hernando Morata, J. A.; van Herwijnen, E.; Hess, M.; Hicheur, A.; Hill, D.; Hoballah, M.; Hombach, C.; Hulsbergen, W.; Hunt, P.; Hussain, N.; Hutchcroft, D.; Hynds, D.; Idzik, M.; Ilten, P.; Jacobsson, R.; Jaeger, A.; Jalocha, J.; Jans, E.; Jaton, P.; Jawahery, A.; Jezabek, M.; Jing, F.; John, M.; Johnson, D.; Jones, C. R.; Joram, C.; Jost, B.; Jurik, N.; Kaballo, M.; Kandybei, S.; Kanso, W.; Karacson, M.; Karbach, T. M.; Kelsey, M.; Kenyon, I. R.; Kete, T.; Khanji, B.; Khurewathanaku, C.; Klaver, S.; Kochebina, O.; Lpinii, M. Ko; Komarov, I.; Koopman, R. F.; Koppenburg, P.; Korolev, M.; Kozinskiy, A.; Kravchuk, L.; Kreplin, K.; Kreps, M.; Krocker, G.; Krokovny, P.; Kruse, F.; Kucharczyk, M.; Kudryavtsev, V.; Kurek, K.; Kvaratskheliya, T.; La Thi, V. N.; Lacarrere, D.; Lafferty, G.; Lai, A.; Lambert, D.; Lambert, R. W.; Lanciotti, E.; Lanfranchi, G.; Langenbruch, C.; Langhans, B.; Latham, T.; Lazzeroni, C.; Le Gac, R.; van Leerdam, J.; Lees, J. -P.; Lefevre, R.; Leflat, A.; Lefrancois, J.; Leo, S.; Leroy, O.; Lesiak, T.; Leverington, B.; Li, Y.; Liles, M.; Lindner, R.; Linn, C.; Lionetto, F.; Liu, B.; Liu, G.; Lohn, S.; Longtaff, I.; Lopes, J. H.; Lopez-March, N.; Lowdon, P.; Lu, H.; Lucchesi, D.; Luo, H.; Lupato, A.; Luppi, E.; Lupton, O.; Machefert, F.; Machikhiliyan, I. V.; Maciuc, F.; Maev, O.; Malde, S.; Manca, G.; Mancinelli, G.; Manzali, M.; Maratas, J.; Marchand, J. F.; Marconi, U.; Benito, C. Marin; Marino, P.; Maerki, R.; Marks, J.; Martellotti, G.; Martens, A.; Martin Sanchez, A.; Martinelli, M.; Martinez Santos, D.; Martinez Vida, F.; Martins Tostes, D.; Massafferri, A.; Matev, R.; Mathe, Z.; Matteuzzi, C.; Mazurov, A.; McCann, M.; McCarthy, J.; McNab, A.; McNulty, R.; McSkelly, B.; Meadows, B.; Meier, F.; Meissner, M.; Merk, M.; Milanes, D. A.; Minard, M. -N.; Moggi, N.; Molina Rodriguez, J.; Monteil, S.; Moran, D.; Morandin, M.; Morawski, P.; Morda, A.; Morello, M. J.; Moron, J.; Morris, A. -B.; Mountain, R.; Muheim, F.; Mueller, K.; Muresan, R.; Mussini, M.; Muster, B.; Naik, P.; Nakada, T.; Nandakumar, R.; Nasteva, I.; Needham, M.; Neri, N.; Neubert, S.; Neufeld, N.; Neuner, M.; Nguyen, A. D.; Nguyen, T. D.; Nguyen-Mau, C.; Nicol, M.; Niess, V.; Niet, R.; Nikitin, N.; Nikodem, T.; Novoselov, A.; Oblakowska-Mucha, A.; Obraztsov, V.; Oggero, S.; Ogilvy, S.; Okhrimenko, O.; Oldeman, R.; Onderwater, G.; Orlandea, M.; Goicochea, J. M. Otalora; Owen, P.; Oyanguren, A.; Pal, B. K.; Palano, A.; Palombo, F.; Palutan, M.; Panman, J.; Papanestis, A.; Pappagallo, M.; Parkes, C.; Parkinson, C. J.; Passaleva, G.; Patel, G. D.; Patel, M.; Patrignani, C.; Pazos Alvarez, A.; Pearce, A.; Pellegrino, A.; Altarelli, M. Pepe; Perazzini, S.; Trigo, E. Perez; Perret, P.; Perrin-Terrin, M.; Pescatore, L.; Pesen, E.; Petridis, K.; Petrolini, A.; Picatoste Olloqui, E.; Pietrzyk, B.; Pilar, T.; Pinci, D.; Pistone, A.; Playfer, S.; Plo Casasus, M.; Polci, F.; Poluektov, A.; Polycarpo, E.; Popov, A.; Popov, D.; Popovici, B.; Potterat, C.; Powell, A.; Prisciandaro, J.; Pritchard, A.; Prouve, C.; Pugatch, V.; Navarro, A. Puig; Punzi, G.; Qian, W.; Rachwal, B.; Rademacker, J. H.; Rakotomiaramanana, B.; Rama, M.; Rangel, M. S.; Raniuk, I.; Rauschmayr, N.; Raven, G.; Reichert, S.; Reid, M. M.; dos Reis, A. C.; Ricciardi, S.; Richards, A.; Rihl, M.; Rinnert, K.; Rives Molina, V.; Roa Romero, D. A.; Robbe, P.; Rodrigues, A. B.; Rodrigues, E.; Perez, P. Rodriguez; Roiser, S.; Romanovsky, V.; Romero Vidal, A.; Rotondo, M.; Rouvinet, J.; Ruf, T.; Ruffini, F.; Ruiz, H.; Ruiz Valls, P.; Sabatino, G.; Saborido Silva, J. J.; Sagidova, N.; Sail, P.; Saitta, B.; Salustino Guimaraes, V.; Sanchez Mayordomo, C.; Sanmartin Sedes, B.; Santacesaria, R.; Santamarina Rios, C.; Santovetti, E.; Sapunov, M.; Sarti, A.; Satriano, C.; Satta, A.; Savrie, M.; Savrina, D.; Schiller, M.; Schindler, H.; Schlupp, M.; Schmelling, M.; Schmidt, B.; Schneider, O.; Schopper, A.; Schune, M. -H.; Schwemmer, R.; Sciascia, B.; Sciubba, A.; Seco, M.; Semennikov, A.; Senderowska, K.; Sepp, I.; Serra, N.; Serrano, J.; Sestini, L.; Seyfert, P.; Shapkin, M.; Shapoval, I.; Shcheglov, Y.; Shears, T.; Shekhtman, L.; Shevchenko, V.; Shires, A.; Coutinho, R. Silva; Simi, G.; Sirendi, M.; Skidmore, N.; Skwarnicki, T.; Smith, N. A.; Smith, E.; Smith, E.; Smith, J.; Smith, M.; Snoek, H.; Sokoloff, M. D.; Soler, F. J. P.; Soomro, F.; Souza, D.; De Paula, B. Souza; Spaan, B.; Sparkes, A.; Spinella, F.; Spradlin, P.; Stagni, F.; Stahl, S.; Steinkamp, O.; Stenyakin, O.; Stevenson, S.; Stoica, S.; Stone, S.; Storaci, B.; Stracka, S.; Straticiuc, M.; Straumann, U.; Stroili, R.; Subbiah, V. K.; Sun, L.; Sutcliffe, W.; Swientek, K.; Swientek, S.; Syropoulos, V.; Szczekowski, M.; Szczypka, P.; Szilard, D.; Szumlak, T.; T'Jampens, S.; Teklishyn, M.; Tellarini, G.; Teubert, F.; Thomas, C.; Thomas, E.; van Tilburg, J.; Tisserand, V.; Tobin, M.; Tolk, S.; Tomassetti, L.; Tonelli, D.; Topp-Joergensen, S.; Torr, N.; Tournefier, E.; Tourneur, S.; Tran, M. T.; Tresch, M.; Tsaregorodtsev, A.; Tsopelas, P.; Tuning, N.; Garcia, M. Ubeda; Ukleja, A.; Ustyuzhanin, A.; Uwer, U.; Vagnoni, V.; Valenti, G.; Vallier, A.; Gomez, R. Vazquez; Regueiro, P. Vazquez; Sierra, C. Vazquez; Vecchi, S.; Velthuis, J. J.; Veltri, M.; Veneziano, G.; Vesterinen, M.; Viaud, B.; Vieira, D.; Vieites Diaz, M.; Vilasis-Cardona, X.; Vollhardt, A.; Volyanskyy, D.; Voong, D.; Vorobyev, A.; Vorobyev, V.; Voss, C.; Voss, H.; de Vries, J. A.; Waldi, R.; Wallace, C.; Wallace, R.; Walsh, J.; Wandernoth, S.; Wang, J.; Ward, D. R.; Watson, N. K.; Websdale, D.; Whitehead, M.; Wicht, J.; Wiedner, D.; Wilkinson, G.; Williams, M. P.; Williams, M.; Wilson, F. F.; Wimberley, J.; Wishahi, J.; Wislicki, W.; Witek, M.; Wormser, G.; Wotton, S. A.; Wright, S.; Wu, S.; Wyllie, K.; Xie, Y.; Xing, Z.; Xu, Z.; Yang, Z.; Yuan, X.; Yushchenko, O.; Zangoli, M.; Zavertyaev, M.; Zhang, F.; Zhang, L.; Zhang, W. C.; Zhang, Y.; Zhelezov, A.; Zhokhov, A.; Zhong, L.; Zvyagin, A.

2014-01-01

Decays of the form B-s(0) -> J/psi K(s)(0)h(+)h((1)-) (h((1)) = K, pi) are searched for in proton-proton collision data corresponding to an integrated luminosity of 1.0 fb(-1) recorded with the LHCb detector. The first observation of the B-s(0) -> J/psi (KsK +/-)-K-0 pi(-/+) decay is reported, with
The Arabidopsis TOR Kinase Specifically Regulates the Expression of Nuclear Genes Coding for Plastidic Ribosomal Proteins and the Phosphorylation of the Cytosolic Ribosomal Protein S6.

Science.gov (United States)

Dobrenel, Thomas; Mancera-Martínez, Eder; Forzani, Céline; Azzopardi, Marianne; Davanture, Marlène; Moreau, Manon; Schepetilnikov, Mikhail; Chicher, Johana; Langella, Olivier; Zivy, Michel; Robaglia, Christophe; Ryabova, Lyubov A; Hanson, Johannes; Meyer, Christian

2016-01-01

Protein translation is an energy consuming process that has to be fine-tuned at both the cell and organism levels to match the availability of resources. The target of rapamycin kinase (TOR) is a key regulator of a large range of biological processes in response to environmental cues. In this study, we have investigated the effects of TOR inactivation on the expression and regulation of Arabidopsis ribosomal proteins at different levels of analysis, namely from transcriptomic to phosphoproteomic. TOR inactivation resulted in a coordinated down-regulation of the transcription and translation of nuclear-encoded mRNAs coding for plastidic ribosomal proteins, which could explain the chlorotic phenotype of the TOR silenced plants. We have identified in the 5' untranslated regions (UTRs) of this set of genes a conserved sequence related to the 5' terminal oligopyrimidine motif, which is known to confer translational regulation by the TOR kinase in other eukaryotes. Furthermore, the phosphoproteomic analysis of the ribosomal fraction following TOR inactivation revealed a lower phosphorylation of the conserved Ser240 residue in the C-terminal region of the 40S ribosomal protein S6 (RPS6). These results were confirmed by Western blot analysis using an antibody that specifically recognizes phosphorylated Ser240 in RPS6. Finally, this antibody was used to follow TOR activity in plants. Our results thus uncover a multi-level regulation of plant ribosomal genes and proteins by the TOR kinase.
IL2-dependent phosphorylation of 40S ribosomal protein S6 is controlled by PI-3K/mTOR signalling in CTLL2 cells

Czech Academy of Sciences Publication Activity Database

Tuháčková, Zdena; Šloncová, Eva; Vojtěchová, Martina; Sovová, Vlasta

2004-01-01

Roč. 13, č. 4 (2004), s. 601-605 ISSN 1107-3756 R&D Projects: GA ČR GA301/00/0269 Institutional research plan: CEZ:AV0Z5052915 Keywords : MTOR /PI3-K signalling, p70 S 6 kinase, interleukin Subject RIV: CE - Biochemistry Impact factor: 3.190, year: 2004
Exploring the Υ(6S) → χ{sub bJ}φ and Υ(6S) → χ{sub bJ}ω hidden-bottom hadronic transitions

Energy Technology Data Exchange (ETDEWEB)

Huang, Qi; Wang, Bo; Liu, Xiang [Lanzhou University, School of Physical Science and Technology, Lanzhou (China); Lanzhou University and Institute of Modern Physics of CAS, Research Center for Hadron and CSR Physics, Lanzhou (China); Chen, Dian-Yong [Southeast University, Department of Physics, Nanjing (China); Matsuki, Takayuki [Tokyo Kasei University, Itabashi, Tokyo (Japan); Nishina Center, RIKEN, Theoretical Research Division, Wako, Saitama (Japan)

2017-03-15

In this work, we investigate the hadronic loop contributions to the Υ(6S) → χ{sub bJ}φ (J = 0, 1, 2) along with Υ(6S) → χ{sub bJ}ω (J=0, 1, 2) transitions. We predict that the branching ratios of Υ(6S) → χ{sub b0}φ, Υ(6S) → χ{sub b1}φ and Υ(6S) → χ{sub b2}φ are (0.68-4.62) x 10{sup -6}, (0.50-3.43) x 10{sup -6} and (2.22-15.18) x 10{sup -6}, respectively, and those of Υ(6S) → χ{sub b0}ω, Υ(6S) → χ{sub b1}ω and Υ(6S) → χ{sub b2}ω are (0.15-2.81) x 10{sup -3}, (0.63-11.68) x 10{sup -3}, and (1.08-20.02) x 10{sup -3}, respectively. Especially, some typical ratios, which reflect the relative magnitudes of the predicted branching ratios, are given, i.e., for Υ(6S) → χ{sub bJ}φ transitions, R{sup φ}{sub 10} = B[Υ(6S) → χ{sub b1}φ]/B[Υ(6S) → χ{sub b0}φ] ∼ 0.74, R{sup φ}{sub 20} = B[Υ(6S) → χ{sub b2}φ]/B[Υ(6S) → χ{sub b0}φ] ∼ 3.28, and R{sup φ}{sub 21} = B[Υ(6S) → χ{sub b2}φ]/B[Υ(6S) → χ{sub b1}φ] ∼ 4.43, and for Υ(6S) → χ{sub bJ}ω transitions, R{sup ω}{sub 10} = B[Υ(6S) → χ{sub b1}ω]/B[Υ(6S) → χ{sub b0}ω] ∼ 4.11, R{sup ω}{sub 20} = B[Υ(6S) → χ{sub b2}ω]/B[Υ(6S) → χ{sub b0}ω] ∼ 7.06, and R{sup ω}{sub 21} = B[Υ(6S) → χ{sub b2}ω]/B[Υ(6S) → χ{sub b1}ω] ∼ 1.72. With the running of BelleII in the near future, experimental measurement of these two kinds of transitions will be a potential research issue. (orig.)
Targeting Aberrant p70S6K Activation for Estrogen Receptor-Negative Breast Cancer Prevention.

Science.gov (United States)

Wang, Xiao; Yao, Jun; Wang, Jinyang; Zhang, Qingling; Brady, Samuel W; Arun, Banu; Seewaldt, Victoria L; Yu, Dihua

2017-11-01

The prevention of estrogen receptor-negative (ER-) breast cancer remains a major challenge in the cancer prevention field, although antiestrogen and aromatase inhibitors have shown adequate efficacy in preventing estrogen receptor-positive (ER + ) breast cancer. Lack of commonly expressed, druggable targets is a major obstacle for meeting this challenge. Previously, we detected the activation of Akt signaling pathway in atypical hyperplasic early-stage lesions of patients. In the current study, we found that Akt and the downstream 70 kDa ribosomal protein S6 kinase (p70S6K) signaling pathway was highly activated in ER - premalignant breast lesions and ER - breast cancer. In addition, p70S6K activation induced transformation of ER - human mammary epithelial cells (hMEC). Therefore, we explored the potential of targeting Akt/p70S6K in the p70S6K activated, ER - hMEC models and mouse mammary tumor models for the prevention of ER - breast cancer. We found that a clinically applicable Akt/p70S6K dual inhibitor, LY2780301, drastically decreased proliferation of hMECs with ErbB2-induced p70S6K activation via Cyclin B1 inhibition and cell-cycle blockade at G 0 -G 1 phase, while it did not significantly reverse the abnormal acinar morphology of these hMECs. In addition, a brief treatment of LY2780301 in MMTV- neu mice that developed atypical hyperplasia (ADH) and mammary intraepithelial neoplasia (MIN) lesions with activated p70S6K was sufficient to suppress S6 phosphorylation and decrease cell proliferation in hyperplasic MECs. In summary, targeting the aberrant Akt/p70S6K activation in ER - hMEC models in vitro and in the MMTV- neu transgenic mouse model in vivo effectively inhibited Akt/S6K signaling and reduced proliferation of hMECs in vitro and ADH/MIN lesions in vivo , indicating its potential in prevention of p70S6K activated ER - breast cancer. Cancer Prev Res; 10(11); 641-50. ©2017 AACR . ©2017 American Association for Cancer Research.
Identification of nucleosome assembly protein 1 (NAP1) as an interacting partner of plant ribosomal protein S6 (RPS6) and a positive regulator of rDNA transcription

Energy Technology Data Exchange (ETDEWEB)

Son, Ora [Department of Biological Science, Sookmyung Women' s University, Seoul 140-742 (Korea, Republic of); Kim, Sunghan [Department of Biological Science, Sookmyung Women' s University, Seoul 140-742 (Korea, Republic of); Department of Plant Science, Plant Genomics and Breeding Institute, Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul 151-921 (Korea, Republic of); Shin, Yun-jeong [Department of Biological Science, Sookmyung Women' s University, Seoul 140-742 (Korea, Republic of); Kim, Woo-Young [College of Pharmacy, Sookmyung Women' s University, Seoul 140-742 (Korea, Republic of); Koh, Hee-Jong, E-mail: heejkoh@snu.ac.kr [Department of Plant Science, Plant Genomics and Breeding Institute, Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul 151-921 (Korea, Republic of); Cheon, Choong-Ill, E-mail: ccheon@sookmyung.ac.kr [Department of Biological Science, Sookmyung Women' s University, Seoul 140-742 (Korea, Republic of)

2015-09-18

The ribosomal protein S6 (RPS6) is a downstream component of the signaling mediated by the target of rapamycin (TOR) kinase that acts as a central regulator of the key metabolic processes, such as protein translation and ribosome biogenesis, in response to various environmental cues. In our previous study, we identified a novel role of plant RPS6, which negatively regulates rDNA transcription, forming a complex with a plant-specific histone deacetylase, AtHD2B. Here we report that the Arabidopsis RPS6 interacts additionally with a histone chaperone, nucleosome assembly protein 1(AtNAP1;1). The interaction does not appear to preclude the association of RPS6 with AtHD2B, as the AtNAP1 was also able to interact with AtHD2B as well as with an RPS6-AtHD2B fusion protein in the BiFC assay and pulldown experiment. Similar to a positive effect of the ribosomal S6 kinase 1 (AtS6K1) on rDNA transcription observed in this study, overexpression or down regulation of the AtNAP1;1 resulted in concomitant increase and decrease, respectively, in rDNA transcription suggesting a positive regulatory role played by AtNAP1 in plant rDNA transcription, possibly through derepression of the negative effect of the RPS6-AtHD2B complex. - Highlights: • Nucleosome assembly protein 1 (AtNAP1) interacts with RPS6 as well as with AtHD2B. • rDNA transcription is regulated S6K1. • Overexpression or down regulation of AtNAP1 results in concomitant increase or decrease in rDNA transcription.

RPS6KA2, a putative tumour suppressor gene at 6q27 in sporadic epithelial ovarian cancer

DEFF Research Database (Denmark)

Bignone, P A; Lee, K Y; Liu, Y

2007-01-01

We had previously defined by allele loss studies a minimal region at 6q27 (between D6S264 and D6S297) to contain a putative tumour suppressor gene. The p90 ribosomal S6 kinase-3 gene (p90 Rsk-3, RPS6KA2) maps in this interval. It is a serine-threonine kinase that signals downstream of the mitogen...
Tungsten phosphanylarylthiolato complexes [W{PhP(2-SC6H4)2-kappa3S,S',P} 2] and [W{P(2-SC6H4)3-kappa4S,S',S",P}2]: synthesis, structures and redox chemistry.

Science.gov (United States)

Hildebrand, Alexandra; Lönnecke, Peter; Silaghi-Dumitrescu, Luminita; Hey-Hawkins, Evamarie

2008-09-14

PhP(2-SHC6H4)2 (PS2H2) reacts with WCl6 with reduction of tungsten to give the air-sensitive tungsten(IV) complex [W{PhP(2-SC6H4)2-kappa(3)S,S',P}2] (1). 1 is oxidised in air to [WO{PhPO(2-SC6H4)2-kappa(3)S,S',O}{PhP(2-SC6H4)2-kappa(3)S,S',P}] (2). The attempted synthesis of 2 by reaction of 1 with iodosobenzene as oxidising agent was unsuccessful. [W{P(2-SC6H4)3-kappa(4)S,S',S",P}2] (3) was formed in the reaction of P(2-SHC6H4)3 (PS3H3) with WCl6. The W(VI) complex 3 contains two PS3(3-) ligands, each coordinated in a tetradentate fashion resulting in a tungsten coordination number of eight. The reaction of 3 with AgBF4 yields the dinuclear tungsten complex [W2{P(2-SC6H4)3-kappa(4)S,S',S",P}3]BF4 (4). Complexes 1-4 were characterised by spectral methods and X-ray structure determination.
TAM receptors, Gas6, and protein S: roles in inflammation and hemostasis.

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van der Meer, Jonathan H M; van der Poll, Tom; van 't Veer, Cornelis

2014-04-17

TAM receptors (Tyro3, Axl, and Mer) belong to a family of receptor tyrosine kinases that have important effects on hemostasis and inflammation. Also, they affect cell proliferation, survival, adhesion, and migration. TAM receptors can be activated by the vitamin K-dependent proteins Gas6 and protein S. Protein S is more commonly known as an important cofactor for protein C as well as a direct inhibitor of multiple coagulation factors. To our knowledge, the functions of Gas6 are limited to TAM receptor activation. When activated, the TAM receptors have effects on primary hemostasis and coagulation and display an anti-inflammatory or a proinflammatory effect, depending on cell type. To comprehend the effects that the TAM receptors and their ligands have on hemostasis and inflammation, we compare studies that report the different phenotypes displayed by mice with deficiencies in the genes of this receptor family and its ligands (protein S(+/-), Gas6(-/-), TAM(-/-), and variations of these). In this manner, we aim to display which features are attributable to the different ligands. Because of the effects TAM receptors have on hemostasis, inflammation, and cancer growth, their modulation could make interesting therapeutic targets in thromboembolic disease, atherosclerosis, sepsis, autoimmune disease, and cancer.
A genome-wide siRNA screen in mammalian cells for regulators of S6 phosphorylation.

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Angela Papageorgiou

Full Text Available mTOR complex1, the major regulator of mRNA translation in all eukaryotic cells, is strongly activated in most cancers. We performed a genome-wide RNAi screen in a human cancer cell line, seeking genes that regulate S6 phosphorylation, readout of mTORC1 activity. Applying a stringent selection, we retrieved nearly 600 genes wherein at least two RNAis gave significant reduction in S6-P. This cohort contains known regulators of mTOR complex 1 and is significantly enriched in genes whose depletion affects the proliferation/viability of the large set of cancer cell lines in the Achilles database in a manner paralleling that caused by mTOR depletion. We next examined the effect of RNAi pools directed at 534 of these gene products on S6-P in TSC1 null mouse embryo fibroblasts. 76 RNAis reduced S6 phosphorylation significantly in 2 or 3 replicates. Surprisingly, among this cohort of genes the only elements previously associated with the maintenance of mTORC1 activity are two subunits of the vacuolar ATPase and the CUL4 subunit DDB1. RNAi against a second set of 84 targets reduced S6-P in only one of three replicates. However, an indication that this group also bears attention is the presence of rpS6KB1 itself, Rac1 and MAP4K3, a protein kinase that supports amino acid signaling to rpS6KB1. The finding that S6 phosphorylation requires a previously unidentified, functionally diverse cohort of genes that participate in fundamental cellular processes such as mRNA translation, RNA processing, DNA repair and metabolism suggests the operation of feedback pathways in the regulation of mTORC1 operating through novel mechanisms.
The Structure of the MAP2K MEK6 Reveals an Autoinhibitory Dimer

Energy Technology Data Exchange (ETDEWEB)

Min, Xiaoshan; Akella, Radha; He, Haixia; Humphreys, John M.; Tsutakawa, Susan E.; Lee, Seung-Jae; Tainer, John A.; Cobb, Melanie H.; Goldsmith, Elizabeth J.

2009-07-13

MAP2Ks are dual-specificity protein kinases functioning at the center of three-tiered MAP kinase modules. The structure of the kinase domain of the MAP2K MEK6 with phosphorylation site mimetic aspartic acid mutations (MEK6/{Delta}N/DD) has been solved at 2.3 {angstrom} resolution. The structure reveals an autoinhibited elongated ellipsoidal dimer. The enzyme adopts an inactive conformation, based upon structural queues, despite the phosphomimetic mutations. Gel filtration and small-angle X-ray scattering analysis confirm that the crystallographically observed ellipsoidal dimer is a feature of MEK6/{Delta}N/DD and full-length unphosphorylated wild-type MEK6 in solution. The interface includes the phosphate binding ribbon of each subunit, part of the activation loop, and a rare 'arginine stack' between symmetry-related arginine residues in the N-terminal lobe. The autoinhibited structure likely confers specificity on active MAP2Ks. The dimer may also serve the function in unphosphorylated MEK6 of preventing activation loop phosphorylation by inappropriate kinases.
LHCb: Search for CP violation in $B_0 \\to J/\\psi K_s^0$ decays with first LHCb data

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Santana Rangel, Murilo

2011-01-01

We report a measurement of the well-established CP violation in $B_0 \\to J/\\psi K_s^0$ decays. We perform a time-dependent analysis of the decays reconstructed in 35 pb $^{-1}$ of LHCb data that was taken in 2010. We measure the CP asymmetry parameter $S_{ J/\\psi K_s^0}$ , which is connected to the CKM angle $\\beta$ through $S_{ J/\\psi K_s^0}$ = sin2$\\beta$, neglecting CP violation in $B^0$-$ \\overline{B^0}$ mixing and decay. We find $S_{ J/\\psi K_s^0} $ = 0.53$^{+0.28}_{-0.29}$(stat) $\\pm$ 0.05(syst).
Physical and transcript map of the region between D6S264 and D6S149 on chromosome 6q27, the minimal region of allele loss in sporadic epithelial ovarian cancer

DEFF Research Database (Denmark)

Liu, Ying; Emilion, Gracy; Mungall, Andrew J

2002-01-01

We have previously shown a high frequency of allele loss at D6S193 (62%) on chromosomal arm 6q27 in ovarian tumours and mapped the minimal region of allele loss between D6S297 and D6S264 (3 cM). We isolated and mapped a single non-chimaeric YAC (17IA12, 260-280 kb) containing D6S193 and D6S297...
IL-3 maintains activation of the P90S6K/RPS6 pathway and increases translation in human eosinophils1

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Esnault, Stephane; Kelly, Elizabeth A.B.; Shen, Zhong-Jian; Johansson, Mats W.; Malter, James S.; Jarjour, Nizar N.

2015-01-01

IL-5 is a major therapeutic target to reduce eosinophilia. However, all of the eosinophil-activating cytokines IL-5, IL-3, and GM-CSF are typically present in atopic diseases including allergic asthma. Due to the functional redundancy of these 3 cytokines on eosinophils and the loss of IL-5 receptor on airway eosinophils, it is important to take IL-3 and GM-CSF into account to efficiently reduce tissue eosinophil functions. Moreover, these 3 cytokines signal through a common β-chain receptor, and yet differentially affect protein production in eosinophils. Notably, the increased ability of IL-3 to induce production of proteins such as semaphorin-7A without affecting mRNA level suggests a unique influence by IL-3 on translation. The purpose of this study is to identify the mechanisms by which IL-3 distinctively affects eosinophil function compared to IL-5 and GM-CSF, with a focus on protein translation. Peripheral blood eosinophils were used to study intracellular signaling and protein translation in cells activated with IL-3, GM-CSF or IL-5. We establish that, unlike GM-CSF or IL-5, IL-3 triggers prolonged signaling through activation of ribosomal protein (RP) S6 and the upstream kinase, p90S6K. Blockade of p90S6K activation inhibited phosphorylation of RPS6 and IL-3-enhanced semaphorin-7A translation. Furthermore, in an allergen-challenged environment, in vivo phosphorylation of RPS6 and p90S6K was enhanced in human airway compared to circulating eosinophils. Our findings provide new insights into the mechanisms underlying differential activation of eosinophils by IL-3, GM-CSF, and IL-5. These observations place IL-3 and its downstream intracellular signals as novel targets that should be considered to modulate eosinophil functions. PMID:26276876
A hexane fraction of guava Leaves (Psidium guajava L.) induces anticancer activity by suppressing AKT/mammalian target of rapamycin/ribosomal p70 S6 kinase in human prostate cancer cells.

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Ryu, Nae Hyung; Park, Kyung-Ran; Kim, Sung-Moo; Yun, Hyung-Mun; Nam, Dongwoo; Lee, Seok-Geun; Jang, Hyeung-Jin; Ahn, Kyoo Seok; Kim, Sung-Hoon; Shim, Bum Sang; Choi, Seung-Hoon; Mosaddik, Ashik; Cho, Somi K; Ahn, Kwang Seok

2012-03-01

This study was carried out to evaluate the anticancer effects of guava leaf extracts and its fractions. The chemical compositions of the active extracts were also determined. In the present study, we set out to determine whether the anticancer effects of guava leaves are linked with their ability to suppress constitutive AKT/mammalian target of rapamycin (mTOR)/ribosomal p70 S6 kinase (S6K1) and mitogen-activated protein kinase (MAPK) activation pathways in human prostate cancer cells. We found that guava leaf hexane fraction (GHF) was the most potent inducer of cytotoxic and apoptotic effects in PC-3 cells. The molecular mechanism or mechanisms of GHF apoptotic potential were correlated with the suppression of AKT/mTOR/S6K1 and MAPK signaling pathways. This effect of GHF correlated with down-regulation of various proteins that mediate cell proliferation, cell survival, metastasis, and angiogenesis. Analysis of GHF by gas chromatography and gas chromatography-mass spectrometry tentatively identified 60 compounds, including β-eudesmol (11.98%), α-copaene (7.97%), phytol (7.95%), α-patchoulene (3.76%), β-caryophyllene oxide (CPO) (3.63%), caryophylla-3(15),7(14)-dien-6-ol (2.68%), (E)-methyl isoeugenol (1.90%), α-terpineol (1.76%), and octadecane (1.23%). Besides GHF, CPO, but not phytol, also inhibited the AKT/mTOR/S6K1 signaling pathway and induced apoptosis in prostate cancer cells. Overall, these findings suggest that guava leaves can interfere with multiple signaling cascades linked with tumorigenesis and provide a source of potential therapeutic compounds for both the prevention and treatment of cancer.
Chronic Alcohol Consumption Alters Mammalian Target of Rapamycin (mTOR), Reduces Ribosomal p70S6 Kinase and p4E-BP1 Levels in Mouse Cerebral Cortex

OpenAIRE

Li, Qun; Ren, Jun

2007-01-01

Reduced insulin sensitivity following chronic alcohol consumption may contribute to alcohol-induced brain damage although the underlying mechanism(s) has not been elucidated. This study was designed to examine the effect of chronic alcohol intake on insulin signaling in mouse cerebral cortex. FVB mice were fed with a 4% alcohol diet for 16 weeks. Insulin receptor substrates (IRS-1, IRS-2) and post-receptor signaling molecules Akt, mammalian target of rapamycin (mTOR), ribosomal p70s6 kinase (...
K.s. Micro-implant placement guide.

Science.gov (United States)

Sharma, K; Sangwan, A

2014-09-01

A one of the greatest concerns with orthodontic mini-implants is risk of injury to dental roots during placement is, especially when they are inserted between teeth. Many techniques have been used to facilitate safe placement of interradicular miniscrews. Brass Wires or metallic markers are easy to place in the interproximal spaces, but because their relative positions may be inconsistent in different radio -graphic views, they are not always accurate. K.S. micro implant placement guide suggested in this article is simple design and easy in fabrication, required minimal equipment for fabrication and does not disturb the existing appliance system, clearly located in the radiograph and the mini-screw can be easily inserted through the guide reducing the chance of implant misplacement.
Proteomic Analysis of a Global Regulator GacS Sensor Kinase in the Rhizobacterium, Pseudomonas chlororaphis O6

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Chul Hong Kim

2014-06-01

Full Text Available The GacS/GacA system in the root colonizer Pseudomonas chlororaphis O6 is a key regulator of many traits relevant to the biocontrol function of this bacterium. Proteomic analysis revealed 12 proteins were down-regulated in a gacS mutant of P. chlororaphis O6. These GacS-regulated proteins functioned in combating oxidative stress, cell signaling, biosynthesis of secondary metabolism, and secretion. The extent of regulation was shown by real-time RT-PCR to vary between the genes. Mutants of P. chlororaphis O6 were generated in two GacS-regulated genes, trpE, encoding a protein involved in tryptophan synthesis, and prnA, required for conversion of tryptophan to the antimicrobial compound, pyrrolitrin. Failure of the trpE mutant to induce systemic resistance in tobacco against a foliar pathogen causing soft rot, Pectobacterium carotovorum SCCI, correlated with reduced colonization of root surfaces implying an inadequate supply of tryptophan to support growth. Although colonization was not affected by mutation in the prnA gene, induction of systemic resistance was reduced, suggesting that pyrrolnitrin was an activator of plant resistance as well as an antifungal agent. Study of mutants in the other GacS-regulated proteins will indicate further the features required for biocontrol-activity in this rhizobacterium.
A hepatic amino acid/mTOR/S6K-dependent signalling pathway modulates systemic lipid metabolism via neuronal signals.

Science.gov (United States)

Uno, Kenji; Yamada, Tetsuya; Ishigaki, Yasushi; Imai, Junta; Hasegawa, Yutaka; Sawada, Shojiro; Kaneko, Keizo; Ono, Hiraku; Asano, Tomoichiro; Oka, Yoshitomo; Katagiri, Hideki

2015-08-13

Metabolism is coordinated among tissues and organs via neuronal signals. Levels of circulating amino acids (AAs), which are elevated in obesity, activate the intracellular target of rapamycin complex-1 (mTORC1)/S6kinase (S6K) pathway in the liver. Here we demonstrate that hepatic AA/mTORC1/S6K signalling modulates systemic lipid metabolism via a mechanism involving neuronal inter-tissue communication. Hepatic expression of an AA transporter, SNAT2, activates the mTORC1/S6K pathway, and markedly elevates serum triglycerides (TGs), while downregulating adipose lipoprotein lipase (LPL). Hepatic Rheb or active-S6K expression have similar metabolic effects, whereas hepatic expression of dominant-negative-S6K inhibits TG elevation in SNAT2 mice. Denervation, pharmacological deafferentation and β-blocker administration suppress obesity-related hypertriglyceridemia with adipose LPL upregulation, suggesting that signals are transduced between liver and adipose tissue via a neuronal pathway consisting of afferent vagal and efferent sympathetic nerves. Thus, the neuronal mechanism uncovered here serves to coordinate amino acid and lipid levels and contributes to the development of obesity-related hypertriglyceridemia.
Crystal structure of the Hg4SiS6 and Hg4SiSe6 compounds

International Nuclear Information System (INIS)

Gulay, L.D.; Olekseyuk, I.D.; Parasyuk, O.V.

2002-01-01

The crystal structures of Hg 4 SiS 6 and Hg 4 SiSe 6 compounds were investigated using X-ray powder diffraction. These compounds crystallize in the monoclinic Cc space group with the lattice parameters a=1.23020(5), b=0.71031(4), c=1.22791(4) nm, β=109.721(3) deg. for Hg 4 SiS 6 and a=1.28110(4), b=0.74034(4), c=1.27471(1) nm, β=109.605(3) deg. for Hg 4 SiSe 6 . Atomic parameters were refined in the isotropic approximation (R I =0.0571 and R I =0.0555 for the Hg 4 SiS 6 and Hg 4 SiSe 6 , respectively)
Influence of supplementation with branched-chain amino acids in combination with resistance exercise on p70S6 kinase phosphorylation in resting and exercising human skeletal muscle.

Science.gov (United States)

Apró, W; Blomstrand, E

2010-11-01

Skeletal muscle growth is thought to be regulated by the mammalian target of rapamycin (mTOR) pathway, which can be activated by resistance exercise and branched-chain amino acids (BCAA). The major aim of the present study was to distinguish between the influence of resistance exercise and BCAA on key enzymes considered to be involved in the regulation of protein synthesis, including p70(S6) kinase (p70(S6k)). Nine healthy subjects (four men and five women) performed unilateral resistance exercise on two occasions separated by 1 month. Subjects were randomly supplied either a mixture of BCAA or flavoured water. Muscle biopsies were taken from both resting and exercising muscle before, after and 1 h after exercise. Phosphorylation of Akt was unaltered by either resistance exercise and/or BCAA supplementation whereas mTOR phosphorylation was enhanced (Pexercising and resting muscle following exercise in the absence (70-90%) and presence of BCAA supplementation (80-130%). Phosphorylation of p70(S6k) was unaffected by resistance exercise alone; however, BCAA intake increased (Pexercise. In resting muscle, a 5- and 16-fold increase in p70(S6k) was observed immediately after and 1 h after exercise, respectively, as compared to 11- and 30-fold increases in the exercising muscle. Phosphorylation of eukaryotic elongation factor 2 was attenuated 1 h after exercise (Pexercising muscle (30-50%) under both conditions. The present findings indicate that resistance exercise and BCAA exert both separate and combined effects on the p70(S6k) phosphorylation in an Akt-independent manner. © 2010 The Authors. Journal compilation © 2010 Scandinavian Physiological Society.
Assessment of the MARS-KS Code Using Atlas 6-inch cold leg Break Test

Energy Technology Data Exchange (ETDEWEB)

Kang, D. G.; Kim, J. S.; Ahn, S. H.; Seul, K. W. [Korea Institute of Nuclear Safety, Daejeon (Korea, Republic of)

2012-03-15

An integral effect test on the SBLOCA (Small-Break Loss of Coolant Accident) aiming at 6-inch cold leg bottom break, SB-CL-09, was conducted with the Atlas on November, 13, 2009, by KAERI. In this study, the calculations using MARS-KS Vt1.2 code were conducted for 6-inch cold leg break test of Atlas (SB-CL-09) which is the second domestic standard problem (Dsp-02) to assess MARS-KS code capability to simulate the transient thermal-hydraulic behavior for SBLOCA. The steady state was determined by conducting a null transient calculation and the errors between the calculated and measured values are acceptable for almost primary/secondary system parameters. The predicted pressurizer pressure agrees relatively well with the experimental data and the predicted break flow and mass are in good agreement with experiment. In MARS-KS calculation, the decrease of core collapsed water level is predicted well in blowdown phase, but just before LSC, water level is higher than experiment. However, the sudden decrease and increase of water level is higher than experiment. However, the sudden decrease and increase of water level at the LSC are predicted qualitatively. After LSC, there is another water level dip at Sit injection time which is not in experiment. It is considered that this phenomenon is caused by rapid depressurization of downcomer due to significant condensation rate of vapor in downcomer when Sit water flows in it. For the downcomer water level is predicted well, however, it is significantly over-predicted at SIT injection time, water level is predicted well, however, it is significantly over-predicted at SIT injection time after SIT water flows in downcomer. Predicted cladding temperature generally agrees well with the experiment, while there is peak at SIT injection time in calculation which is not in experiment. The loop seals of 1A, 2B intermediate leg are cleared around 400 seconds in experiment, while only that of 1A is cleared in MARS-KS calculation at the
Prolonged activation of S6K1 does not suppress IRS or PI-3 kinase signaling during muscle cell differentiation

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MacKenzie Matthew G

2010-05-01

Full Text Available Abstract Background Myogenesis in C2C12 cells requires the activation of the PI3K/mTOR signaling pathways. Since mTOR signaling can feedback through S6K1 to inhibit the activation of PI3K, the aim of this work was to assess whether feedback from S6K1 played a role in myogenesis and determine whether siRNA mediated knockdown of S6K1 would lead to an increased rate of myotube formation. Results S6K1 activity increased in a linear fashion following plating and was more than 3-fold higher after Day 3 of differentiation (subconfluent = 11.09 ± 3.05, Day 3 = 29.34 ± 3.58. IRS-1 levels tended to increase upon serum withdrawal but decreased approximately 2-fold (subconfluent = 0.88 ± 0.10, Day 3 = 0.42 ± 0.06 3 days following differentiation whereas IRS-2 protein remained stable. IRS-1 associated p85 was significantly reduced upon serum withdrawal (subconfluent = 0.86 ± 0.07, Day 0 = 0.31 ± 0.05, remaining low through day 1. IRS-2 associated p85 decreased following serum withdrawal (subconfluent = 0.96 ± 0.05, Day 1 = 0.56 ± 0.08 and remained suppressed up to Day 3 following differentiation (0.56 ± 0.05. Phospho-tyrosine associated p85 increased significantly from subconfluent to Day 0 and remained elevated throughout differentiation. siRNA directed against S6K1 and S6K2 did not result in changes in IRS-1 levels after either 48 or 96 hrs. Furthermore, neither 48 nor 96 hrs of S6K1 knockdown caused a change in myotube formation. Conclusions Even though S6K1 activity increases throughout muscle cell differentiation and IRS-1 levels decrease over this period, siRNA suggests that S6K1 is not mediating the decrease in IRS-1. The decrease in IRS-1/2 associated p85 together with the increase in phospho-tyrosine associated p85 suggests that PI3K associates primarily with scaffolds other than IRS-1/2 during muscle cell differentiation.
Fe-solubility of Ni7S6 and Ni9S8: Thermodynamic analysis

International Nuclear Information System (INIS)

Waldner, P.

2011-01-01

Experimental data on phase equilibria have been used for thermodynamic analysis of the iron solubility of the nickel sulfides Ni 7 S 6 and Ni 9 S 8 . For both compounds, a two-sublattice approach within the framework of the compound energy formalism has been applied to perform Gibbs free energy modelling at 0.1 MPa total pressure consistently embedded in recent thermodynamic assessment studies of other iron-nickel-sulfides. The predicted maxima of iron solubility around 3 at% of Ni 7 S 6 and 5.5 at% of Ni 9 S 8 are confirmed by experimental data. The calculations of complex ternary phase relations with Fe-bearing Ni 7 S 6 and Ni 9 S 8 gain further improvement. The first internally consistent description of all thermodynamically stable phases known in the literature for the iron-nickel-sulfur system is completed.
Pretest analysis document for Test S-FS-6

International Nuclear Information System (INIS)

Shaw, R.A.; Hall, D.G.

1985-05-01

This report documents the pretest analyses completed for Semiscale Test S-FS-6. This test will simulate a transient initiated by a 100% break in a steam generator bottom feedwater line downstream of the check valve. The initial conditions represent normal operating conditions for a C-E System 80 nuclear power plant. Predictions of transients resulting from feedwater line breaks in these plants have indicated that significant primary system overpressurization may occur. The enclosed analyses include a RELAP5/MOD2/CY21 code calculation and preliminary results from a facility hot, integrated test which was conducted to near S-FS-6 specifications. The results of these analyses indicate that the test objectives for Test S-FS-6 can be achieved. The primary system overpressurization will pose no threat to personnel or plant integrity
Hypoxia-induced invadopodia formation involves activation of NHE-1 by the p90 ribosomal S6 kinase (p90RSK.

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Fabrice Lucien

Full Text Available The hypoxic and acidic microenvironments in tumors are strongly associated with malignant progression and metastasis, and have thus become a central issue in tumor physiology and cancer treatment. Despite this, the molecular links between acidic pH- and hypoxia-mediated cell invasion/metastasis remain mostly unresolved. One of the mechanisms that tumor cells use for tissue invasion is the generation of invadopodia, which are actin-rich invasive plasma membrane protrusions that degrade the extracellular matrix. Here, we show that hypoxia stimulates the formation of invadopodia as well as the invasive ability of cancer cells. Inhibition or shRNA-based depletion of the Na(+/H(+ exchanger NHE-1, along with intracellular pH monitoring by live-cell imaging, revealed that invadopodia formation is associated with alterations in cellular pH homeostasis, an event that involves activation of the Na(+/H(+ exchange rate by NHE-1. Further characterization indicates that hypoxia triggered the activation of the p90 ribosomal S6 kinase (p90 RSK, which resulted in invadopodia formation and site-specific phosphorylation and activation of NHE-1. This study reveals an unsuspected role of p90RSK in tumor cell invasion and establishes p90RS kinase as a link between hypoxia and the acidic microenvironment of tumors.

Pharmacologic inhibition of S1P attenuates ATF6 expression, causes ER stress and contributes to apoptotic cell death.

Science.gov (United States)

Lebeau, Paul; Byun, Jae Hyun; Yousof, Tamana; Austin, Richard C

2018-04-22

Mammalian cells express unique transcription factors embedded in the endoplasmic reticulum (ER) membrane, such as the sterol regulatory element-binding proteins (SREBPs), that promote de novo lipogenesis. Upon their release from the ER, the SREBPs require proteolytic activation in the Golgi by site-1-protease (S1P). As such, inhibition of S1P, using compounds such as PF-429242 (PF), reduces cholesterol synthesis and may represent a new strategy for the management of dyslipidemia. In addition to the SREBPs, the unfolded protein response (UPR) transducer, known as the activating transcription factor 6 (ATF6), is another ER membrane-bound transcription factor that requires S1P-mediated activation. ATF6 regulates ER protein folding capacity by promoting the expression of ER chaperones such as the 78-kDa glucose-regulated protein (GRP78). ER-resident chaperones like GRP78 prevent and/or resolve ER polypeptide accumulation and subsequent ER stress-induced UPR activation by folding nascent polypeptides. Here we report that pharmacological inhibition of S1P reduced the expression of ATF6 and GRP78 and induced the activation of UPR transducers inositol-requiring enzyme-1α (IRE1α) and protein kinase RNA-like ER kinase (PERK). As a consequence, S1P inhibition also increased the susceptibility of cells to ER stress-induced cell death. Our findings suggest that S1P plays a crucial role in the regulation of ER folding capacity and also identifies a compensatory cross-talk between UPR transducers in order to maintain adequate ER chaperone expression and activity. Copyright © 2018. Published by Elsevier Inc.
(2aR*,5S*,6aS*,8aS*,E-Ethyl 5-hydroxy-7,7,8a-trimethyl-8-oxo-2,2a,6,6a,7,8,8a,8b-octahydro-1H-pentaleno[1,6-bc]oxepine-4-carboxylate

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Goverdhan Mehta

2012-12-01

Full Text Available The title compound, C17H24O5, featuring a 2-carbethoxy-3-oxepanone unit in its intramolecularly O—H...O hydrogen-bonded enol form, was obtained via [(CF3CO22Rh]2-catalysed intramolecular O—H bond insertion in the α-diazo-ω-hydroxy-β-ketoester, ethyl 4-[(1S,3aS,6R,6aS-6-hydroxy-2,2,3a-trimethyl-3-oxo-octahydropentalen-1-yl]-2-diazo-3-oxobutanoate. The seven-membered oxacyclic ring, thus constructed on a cis-fused diquinane platform, was found to adopt a distorted boat–sofa conformation.
mTORC1 Targets the Translational Repressor 4E-BP2, but Not S6 Kinase 1/2, to Regulate Neural Stem Cell Self-Renewal In Vivo

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Nathaniel W. Hartman

2013-10-01

Full Text Available The mammalian target of rapamycin complex 1 (mTORC1 integrates signals important for cell growth, and its dysregulation in neural stem cells (NSCs is implicated in several neurological disorders associated with abnormal neurogenesis and brain size. However, the function of mTORC1 on NSC self-renewal and the downstream regulatory mechanisms are ill defined. Here, we found that genetically decreasing mTORC1 activity in neonatal NSCs prevented their differentiation, resulting in reduced lineage expansion and aborted neuron production. Constitutive activation of the translational repressor 4E-BP1, which blocked cap-dependent translation, had similar effects and prevented hyperactive mTORC1 induction of NSC differentiation and promoted self-renewal. Although 4E-BP2 knockdown promoted NSC differentiation, p70 S6 kinase 1 and 2 (S6K1/S6K2 knockdown did not affect NSC differentiation but reduced NSC soma size and prevented hyperactive mTORC1-induced increase in soma size. These data demonstrate a crucial role of mTORC1 and 4E-BP for switching on and off cap-dependent translation in NSC differentiation.
Polarization and pressure effects in caesium 6S-8S two-photon spectroscopy

International Nuclear Information System (INIS)

Lee, Yi-Chi; Tsai, Chin-Chun; Chui, Hsiang-Chen; Chang, Yi-Hsiu; Chen, Ying-Yu

2010-01-01

This work analyses the effects of polarization and pressure in caesium 6S-8S two-photon spectroscopy. The linewidth was broadened and the frequency was shifted by a change of polarization states. The frequency shift and the linewidth broadening of the caesium 6S-8S two-photon transition were measured as a function of laser power using one single-frequency Ti:sapphire ring cavity laser, two caesium cells and two quarter-wave plates to ensure polarization states of light, and we showed that the linewidth cannot be evaluated just by fitting data to a Lorentzian shape. As determined by fitting the data to a Voigt profile, the natural linewidth is independent of the polarization states of the pump beams, the laser power and the pressure. Caesium 6S-8S two-photon transitions pumped by a circularly polarized beam have narrower linewidths and smaller shifts than those pumped by a linearly polarized beam. The light shift obtained by pumping with the circularly polarized beam is -6.75(57) Hz (mW mm -2 ) -1 , and that obtained by pumping with a linearly polarized beam is -7.25(45) Hz (mW mm -2 ) -1 . These results agree closely with theoretical calculations. The pressure shift is -588(387) Hz mPa -1 . This work shows how to evaluate two-photon transitions with a Voigt profile, and then helps us to understand two-photon transitions with different polarization states, and improve the signal quality obtained when they are used as frequency markers.
Electronic structure of Ag8GeS6

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D.I. Bletskan

2017-04-01

Full Text Available For the first time, the energy band structure, total and partial densities of states of Ag8GeS6 crystal were calculated using the ab initio density functional method in LDA and LDA+U approximations. Argyrodite is direct-gap semiconductor with the calculated band gap width Egd = 1.46 eV in the LDA+U approximation. The valence band of argyrodite contains four energy separated groups of occupied subzones. The unique feature of electron-energy structure of Ag8GeS6 crystal is the energy overlapping between the occupied d-states of Ag atoms and the delocalized valence p-states of S atoms in relatively close proximity to the valence band top.
Electron-impact-ionization dynamics of S F6

Science.gov (United States)

Bull, James N.; Lee, Jason W. L.; Vallance, Claire

2017-10-01

A detailed understanding of the dissociative electron ionization dynamics of S F6 is important in the modeling and tuning of dry-etching plasmas used in the semiconductor manufacture industry. This paper reports a crossed-beam electron ionization velocity-map imaging study on the dissociative ionization of cold S F6 molecules, providing complete, unbiased kinetic energy distributions for all significant product ions. Analysis of these distributions suggests that fragmentation following single ionization proceeds via formation of S F5 + or S F3 + ions that then dissociate in a statistical manner through loss of F atoms or F2, until most internal energy has been liberated. Similarly, formation of stable dications is consistent with initial formation of S F4 2 + ions, which then dissociate on a longer time scale. These data allow a comparison between electron ionization and photoionization dynamics, revealing similar dynamical behavior. In parallel with the ion kinetic energy distributions, the velocity-map imaging approach provides a set of partial ionization cross sections for all detected ionic fragments over an electron energy range of 50-100 eV, providing partial cross sections for S2 +, and enables the cross sections for S F4 2 + from S F+ to be resolved.
40 CFR 180.1281 - S-Abscisic Acid, (S)-5-(1-hydroxy-2,6,6-trimethyl-4-oxo-1-cyclohex-2-enyl)-3-methyl-penta-(2Z,4E...

Science.gov (United States)

2010-07-01

... 40 Protection of Environment 23 2010-07-01 2010-07-01 false S-Abscisic Acid, (S)-5-(1-hydroxy-2,6... Exemptions From Tolerances § 180.1281 S-Abscisic Acid, (S)-5-(1-hydroxy-2,6,6-trimethyl-4-oxo-1-cyclohex-2... from the requirement of a tolerance is established for residues of S-Abscisic Acid in or on all food...
Urenco`s experience of UF{sub 6} handling

Energy Technology Data Exchange (ETDEWEB)

Saelmans, F. [Urenco Almelo (Netherlands); Scane, C. [Urenco Capenhurst (United Kingdom); Christofzik, J. [Urenco Gronau (Germany)

1991-12-31

Urenco operates enrichment plants at three sites, Almelo (Netherlands), Capenhurst (United Kingdom) and Gronau (Germany). Current installed separative work capacity is 2,500 tSWpa. Since 1971, when the first pilot plants were built, enrichment production has totalled 18,000 tSW. During this last 20 years over 3,500 48 containers of UF{sub 6} have been fed to the plants, over 3,700 30 containers have been filled with product and delivered successfully to Urenco`s customers worldwide and over 3,000 48 containers of depleted tails have been filled and have either been returned to customers or retained for long term storage on site. The paper gives a brief outline of Urenco`s experience in handling UF{sub 6}: the equipment and methods used in receiving, feeding, filling, blending, liquid sampling, storing, moving on site and despatching of UF{sub 6} containers. Some of the difficulties experienced with UF{sub 6} containers are appended.
The Antiproliferative Effect of Cyclodipeptides from Pseudomonas aeruginosa PAO1 on HeLa Cells Involves Inhibition of Phosphorylation of Akt and S6k Kinases.

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Hernández-Padilla, Laura; Vázquez-Rivera, Dolores; Sánchez-Briones, Luis A; Díaz-Pérez, Alma L; Moreno-Rodríguez, José; Moreno-Eutimio, Mario A; Meza-Carmen, Victor; Cruz, Homero Reyes-De la; Campos-García, Jesús

2017-06-20

Pseudomonas aeruginosa PAO1, a potential pathogen of plants and animals, produces the cyclodipeptides cyclo(l-Pro-l-Tyr), cyclo(l-Pro-l-Phe), and cyclo(l-Pro-l-Val) (PAO1-CDPs), whose effects have been implicated in inhibition of human tumor cell line proliferation. Our purpose was to investigate in depth in the mechanisms of HeLa cell proliferation inhibition by the PAO1-CDPs. The results indicate that PAO1-CDPs, both purified individually and in mixtures, inhibited HeLa cell proliferation by arresting the cell cycle at the G0-G1 transition. The crude PAO1-CDPs mixture promoted cell death in HeLa cells in a dose-dependent manner, showing efficacy similar to that of isolated PAO1-CDPs (LD 50 of 60-250 µM) and inducing apoptosis with EC 50 between 0.6 and 3.0 µM. Moreover, PAO1-CDPs showed a higher proapoptotic activity (~10³-10⁵ fold) than their synthetic analogs did. Subsequently, the PAO1-CDPs affected mitochondrial membrane potential and induced apoptosis by caspase-9-dependent pathway. The mechanism of inhibition of cells proliferation in HeLa cells involves inhibition of phosphorylation of both Akt-S473 and S6k-T389 protein kinases, showing a cyclic behavior of their expression and phosphorylation in a time and concentration-dependent fashion. Taken together our findings indicate that PI3K-Akt-mTOR-S6k signaling pathway blockage is involved in the antiproliferative effect of the PAO1-CDPs.
Immunohistochemical Characterization of S100A6 in the Murine Ovary

International Nuclear Information System (INIS)

Hanaue, Mayu; Miwa, Naofumi; Takamatsu, Ken

2012-01-01

S100 proteins comprise a large family of Ca 2+ -binding proteins and exhibit a variety of intra- and extracellular functions. Despite our growing knowledge about the biology of S100 proteins in some tissues such as brain and smooth muscle, little is known about S100 proteins in the normal mammalian reproductive tissue. In the present study, we investigated the distribution pattern of S100A6 (alternatively named calcyclin) in the murine ovary by immunohistochemical study using specific antibody. S100A6 was localized substantially in the cytoplasm of luteal cells, with concomitant expression of S100A11, another S100 protein, but not in the other type of cells such as oocytes, follicle epithelial cells (granulosa cells), and cells of stroma including theca interna cells in the murine ovary. S100A6-immunoreactive corpora lutea (CLs) were divided into two types: homogeneously and heterogeneously stained CLs, and possibly they may represent differentiating and mature CL, respectively. Our regression analysis revealed that expression level of S100A6 positively correlated with that of cytochrome P450 11A, a steroidogenic enzyme in the heterogeously stained CL. These results suggested that S100A6 may contribute to differentiation of steroidogenic activity of luteal cells in a synergistic manner with S100A11 by facilitating some shared functions
Role of Bruton's tyrosine kinase (BTK) in growth and metastasis of INA6 myeloma cells

International Nuclear Information System (INIS)

Bam, R; Venkateshaiah, S U; Khan, S; Ling, W; Randal, S S; Li, X; Zhang, Q; Rhee, F van; Barlogie, B; Epstein, J; Yaccoby, S

2014-01-01

Bruton's tyrosine kinase (BTK) and the chemokine receptor CXCR4 are linked in various hematologic malignancies. The aim of the study was to understand the role of BTK in myeloma cell growth and metastasis using the stably BTK knockdown luciferase-expressing INA6 myeloma line. BTK knockdown had reduced adhesion to stroma and migration of myeloma cells toward stromal cell-derived factor-1. BTK knockdown had no effect on short-term in vitro growth of myeloma cells, although clonogenicity was inhibited and myeloma cell growth was promoted in coculture with osteoclasts. In severe combined immunodeficient-rab mice with contralaterally implanted pieces of bones, BTK knockdown in myeloma cells promoted their proliferation and growth in the primary bone but suppressed metastasis to the contralateral bone. BTK knockdown myeloma cells had altered the expression of genes associated with adhesion and proliferation and increased mammalian target of rapamycin signaling. In 176 paired clinical samples, BTK and CXCR4 expression was lower in myeloma cells purified from a focal lesion than from a random site. BTK expression in random-site samples was correlated with proportions of myeloma cells expressing cell surface CXCR4. Our findings highlight intratumoral heterogeneity of myeloma cells in the bone marrow microenvironment and suggest that BTK is involved in determining proliferative, quiescent or metastatic phenotypes of myeloma cells
Exploring the ϒ (4 S ,5 S ,6 S )→hb(1 P )η hidden-bottom hadronic transitions

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Zhang, Yawei; Li, Gang

2018-01-01

Recently, the Belle Collaboration has reported the measurement of the spin-flipping transition ϒ (4 S )→hb(1 P )η with an unexpectedly large branching ratio: B (ϒ (4 S )→hb(1 P )η )=(2.18 ±0.11 ±0.18 )×10-3 . Such a large branching fraction contradicts with the anticipated suppression for the spin flip. In this work, we examine the effects induced by intermediate bottomed meson loops and point out that these effects are significantly important. Using the effective Lagrangian approach (ELA), we find the experimental data on ϒ (4 S )→hb(1 P )η can be accommodated with the reasonable inputs. We then explore the decays ϒ (5 S ,6 S )→hb(1 P )η and find that these two channels also have sizable branching fractions. We also calculate these processes in the framework of nonrelativistic effective field theory (NREFT). For the decays ϒ (4 S )→hb(1 P )η , the NREFT results are at the same order of magnitude but smaller than the ELA results by a factor of 2 to 5. For the decays ϒ (5 S ,6 S )→hb(1 P )η , the NREFT results are smaller than the ELA results by approximately 1 order of magnitude. We suggest a future experiment Belle-II to search for the ϒ (5 S ,6 S )→hb(1 P )η decays, which will be helpful for understanding the transition mechanism.
Population data on D6S2879 and D6S2806 markers located at HLA-DRB1 region in the Iranians: Identifying the signatures of balancing and directional selection

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Mansoureh Tajadod

2011-12-01

Full Text Available In this study, the genetic diversity and neutrality test for the MHC microsatellite loci, D6S2879 and D6S2806, located within the HLA-DRB1 gene region, were investigated. The genotyping data from 73 unrelated individuals were analyzed for Shannon index, the effective allele number of the markers and neutrality test by use of PyPop and Popgene32 programs. The Shannon index for D6S2879 and D6S2806 markers in the studied population was 1.0372 and 0.8601, respectively. The Fnd value computed for D6S2879 and D6S2806 markers were also estimated -0.8449 and 0.9904, respectively. The results obtained from Ewens-Watterson test indicated that D6S2879 and D6S2806 markers were under balancing and directional selection in the Iranian populations, respectively. The data suggested the presence of a selection force on HLA-DRB1 gene region in the Iranian populations.
S6K1 and 4E-BP1 are independent regulated and control cellular growth in bladder cancer.

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Roman Nawroth

Full Text Available Aberrant activation and mutation status of proteins in the phosphatidylinositol-3-kinase (PI3K/Akt/mammalian target of rapamycin (mTOR and the mitogen activated protein kinase (MAPK signaling pathways have been linked to tumorigenesis in various tumors including urothelial carcinoma (UC. However, anti-tumor therapy with small molecule inhibitors against mTOR turned out to be less successful than expected. We characterized the molecular mechanism of this pathway in urothelial carcinoma by interfering with different molecular components using small chemical inhibitors and siRNA technology and analyzed effects on the molecular activation status, cell growth, proliferation and apoptosis. In a majority of tested cell lines constitutive activation of the PI3K was observed. Manipulation of mTOR or Akt expression or activity only regulated phosphorylation of S6K1 but not 4E-BP1. Instead, we provide evidence for an alternative mTOR independent but PI3K dependent regulation of 4E-BP1. Only the simultaneous inhibition of both S6K1 and 4E-BP1 suppressed cell growth efficiently. Crosstalk between PI3K and the MAPK signaling pathway is mediated via PI3K and indirect by S6K1 activity. Inhibition of MEK1/2 results in activation of Akt but not mTOR/S6K1 or 4E-BP1. Our data suggest that 4E-BP1 is a potential new target molecule and stratification marker for anti cancer therapy in UC and support the consideration of a multi-targeting approach against PI3K, mTORC1/2 and MAPK.
Polo-like kinase 1 (PLK1) and protein phosphatase 6 (PP6) regulate DNA-dependent protein kinase catalytic subunit (DNA-PKcs) phosphorylation in mitosis.

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Douglas, Pauline; Ye, Ruiqiong; Trinkle-Mulcahy, Laura; Neal, Jessica A; De Wever, Veerle; Morrice, Nick A; Meek, Katheryn; Lees-Miller, Susan P

2014-06-25

The protein kinase activity of the DNA-PKcs (DNA-dependent protein kinase catalytic subunit) and its autophosphorylation are critical for DBS (DNA double-strand break) repair via NHEJ (non-homologous end-joining). Recent studies have shown that depletion or inactivation of DNA-PKcs kinase activity also results in mitotic defects. DNA-PKcs is autophosphorylated on Ser2056, Thr2647 and Thr2609 in mitosis and phosphorylated DNA-PKcs localize to centrosomes, mitotic spindles and the midbody. DNA-PKcs also interacts with PP6 (protein phosphatase 6), and PP6 has been shown to dephosphorylate Aurora A kinase in mitosis. Here we report that DNA-PKcs is phosphorylated on Ser3205 and Thr3950 in mitosis. Phosphorylation of Thr3950 is DNA-PK-dependent, whereas phosphorylation of Ser3205 requires PLK1 (polo-like kinase 1). Moreover, PLK1 phosphorylates DNA-PKcs on Ser3205 in vitro and interacts with DNA-PKcs in mitosis. In addition, PP6 dephosphorylates DNA-PKcs at Ser3205 in mitosis and after IR (ionizing radiation). DNA-PKcs also phosphorylates Chk2 on Thr68 in mitosis and both phosphorylation of Chk2 and autophosphorylation of DNA-PKcs in mitosis occur in the apparent absence of Ku and DNA damage. Our findings provide mechanistic insight into the roles of DNA-PKcs and PP6 in mitosis and suggest that DNA-PKcs' role in mitosis may be mechanistically distinct from its well-established role in NHEJ.
Structure of the S6 spirel arm in the Andromeda galaxy

International Nuclear Information System (INIS)

Efremov, Yu.N.

1982-01-01

The distribution of stars across the spiral arm S6 in M 31 within Baade's Field 4 is investigated. It is found that the brightest stars are concentrated to the middle line of the arm where the maximal star density is also observed. The symmetry of the arm S6 may be explained by its position near the corotation radius that followed from the spiral pattern velocity Ωsub(P) approximately 10 km/s kpc determined by the age gradient in the arm S4. The similarity between the structure of the arm S6 and that of the spiral arms near the Sun is pointed out [ru
Comparitive study of fluorescence lifetime quenching of rhodamine 6G by MoS2 and Au-MoS2

Science.gov (United States)

Shakya, Jyoti; Kasana, Parath; Mohanty, T.

2018-04-01

Time resolved fluorescence study of Rhodamine 6G (R6G) in the presence of Molybdenum disulfide (MoS2) nanosheets and gold doped MoS2 (Au-MoS2) have been carried out and discussed. We have analyzed the fluorescence decay curves of R6G and it is observed that Au-MoS2 is a better fluorescence lifetime quencher as compare to MoS2 nanosheets. Also, the energy transfer efficiency and energy transfer rate from R6G to MoS2 and Au-MoS2 has been calculated and found higher for Au-MoS2.
The TRPM6 Kinase Domain Determines the Mg·ATP Sensitivity of TRPM7/M6 Heteromeric Ion Channels*

Science.gov (United States)

Zhang, Zheng; Yu, Haijie; Huang, Junhao; Faouzi, Malika; Schmitz, Carsten; Penner, Reinhold; Fleig, Andrea

2014-01-01

The transient receptor potential melastatin member 7 (TRPM7) and member 6 (TRPM6) are divalent cation channel kinases essential for magnesium (Mg2+) homeostasis in vertebrates. It remains unclear how TRPM6 affects divalent cation transport and whether this involves functional homomeric TRPM6 plasma membrane channels or heteromeric channel assemblies with TRPM7. We show that homomeric TRPM6 is highly sensitive to intracellular free Mg2+ and therefore unlikely to be active at physiological levels of [Mg2+]i. Co-expression of TRPM7 and TRPM6 produces heteromeric TRPM7/M6 channels with altered pharmacology and sensitivity to intracellular Mg·ATP compared with homomeric TRPM7. Strikingly, the activity of heteromeric TRPM7/M6 channels is independent of intracellular Mg·ATP concentrations, essentially uncoupling channel activity from cellular energy status. Disruption of TRPM6 kinase phosphorylation activity re-introduces Mg·ATP sensitivity to the heteromeric channel similar to that of TRPM7. Thus, TRPM6 modulates the functionality of TRPM7, and the TRPM6 kinase plays a critical role in tuning the phenotype of the TRPM7·M6 channel complex. PMID:24385424
The TRPM6 kinase domain determines the Mg·ATP sensitivity of TRPM7/M6 heteromeric ion channels.

Science.gov (United States)

Zhang, Zheng; Yu, Haijie; Huang, Junhao; Faouzi, Malika; Schmitz, Carsten; Penner, Reinhold; Fleig, Andrea

2014-02-21

The transient receptor potential melastatin member 7 (TRPM7) and member 6 (TRPM6) are divalent cation channel kinases essential for magnesium (Mg(2+)) homeostasis in vertebrates. It remains unclear how TRPM6 affects divalent cation transport and whether this involves functional homomeric TRPM6 plasma membrane channels or heteromeric channel assemblies with TRPM7. We show that homomeric TRPM6 is highly sensitive to intracellular free Mg(2+) and therefore unlikely to be active at physiological levels of [Mg(2+)]i. Co-expression of TRPM7 and TRPM6 produces heteromeric TRPM7/M6 channels with altered pharmacology and sensitivity to intracellular Mg·ATP compared with homomeric TRPM7. Strikingly, the activity of heteromeric TRPM7/M6 channels is independent of intracellular Mg·ATP concentrations, essentially uncoupling channel activity from cellular energy status. Disruption of TRPM6 kinase phosphorylation activity re-introduces Mg·ATP sensitivity to the heteromeric channel similar to that of TRPM7. Thus, TRPM6 modulates the functionality of TRPM7, and the TRPM6 kinase plays a critical role in tuning the phenotype of the TRPM7·M6 channel complex.
TOR and S6K1 promote translation reinitiation of uORF-containing mRNAs via phosphorylation of eIF3h.

Science.gov (United States)

Schepetilnikov, Mikhail; Dimitrova, Maria; Mancera-Martínez, Eder; Geldreich, Angèle; Keller, Mario; Ryabova, Lyubov A

2013-04-17

Mammalian target-of-rapamycin (mTOR) triggers S6 kinase (S6K) activation to phosphorylate targets linked to translation in response to energy, nutrients, and hormones. Pathways of TOR activation in plants remain unknown. Here, we uncover the role of the phytohormone auxin in TOR signalling activation and reinitiation after upstream open reading frame (uORF) translation, which in plants is dependent on translation initiation factor eIF3h. We show that auxin triggers TOR activation followed by S6K1 phosphorylation at T449 and efficient loading of uORF-mRNAs onto polysomes in a manner sensitive to the TOR inhibitor Torin-1. Torin-1 mediates recruitment of inactive S6K1 to polysomes, while auxin triggers S6K1 dissociation and recruitment of activated TOR instead. A putative target of TOR/S6K1-eIF3h-is phosphorylated and detected in polysomes in response to auxin. In TOR-deficient plants, polysomes were prebound by inactive S6K1, and loading of uORF-mRNAs and eIF3h was impaired. Transient expression of eIF3h-S178D in plant protoplasts specifically upregulates uORF-mRNA translation. We propose that TOR functions in polysomes to maintain the active S6K1 (and thus eIF3h) phosphorylation status that is critical for translation reinitiation.

Thio-, selenido-, and telluridogermanates(III): K/sub 6/Ge/sub 2/S/sub 6/, K/sub 6/Ge/sub 2/Se/sub 6/, and Na/sub 6/Ge/sub 2/Te/sub 6/

Energy Technology Data Exchange (ETDEWEB)

Eisenmann, B; Kieselbach, E; Schaefer, H; Schrod, H [Technische Hochschule Darmstadt (Germany, F.R.). Fachbereich Anorganische Chemie und Kernchemie

1984-09-01

The new compounds K/sub 6/Ge/sub 2/S/sub 6/ and K/sub 6/Ge/sub 2/Se/sub 6/ crystallize in the monoclinic system, space group C2/m (No 12). The compounds are isotypic and form the K/sub 6/Si/sub 2/Te/sub 6/ structure. Na/sub 6/Ge/sub 2/Te/sub 6/ crystallizes in the K/sub 6/Sn/sub 2/Te/sub 6/ structure, monoclinic, space group P2/sub 1//c (No 14). The lattice constants are given.
Viral factor TAV recruits TOR/S6K1 signalling to activate reinitiation after long ORF translation

Science.gov (United States)

Schepetilnikov, Mikhail; Kobayashi, Kappei; Geldreich, Angèle; Caranta, Carole; Robaglia, Christophe; Keller, Mario; Ryabova, Lyubov A

2011-01-01

The protein kinase TOR (target-of-rapamycin) upregulates translation initiation in eukaryotes, but initiation restart after long ORF translation is restricted by largely unknown pathways. The plant viral reinitiation factor transactivator–viroplasmin (TAV) exceptionally promotes reinitiation through a mechanism involving retention on 80S and reuse of eIF3 and the host factor reinitiation-supporting protein (RISP) to regenerate reinitiation-competent ribosomal complexes. Here, we show that TAV function in reinitiation depends on physical association with TOR, with TAV–TOR binding being critical for both translation reinitiation and viral fitness. Consistently, TOR-deficient plants are resistant to viral infection. TAV triggers TOR hyperactivation and S6K1 phosphorylation in planta. When activated, TOR binds polyribosomes concomitantly with polysomal accumulation of eIF3 and RISP—a novel and specific target of TOR/S6K1—in a TAV-dependent manner, with RISP being phosphorylated. TAV mutants defective in TOR binding fail to recruit TOR, thereby abolishing RISP phosphorylation in polysomes and reinitiation. Thus, activation of reinitiation after long ORF translation is more complex than previously appreciated, with TOR/S6K1 upregulation being the key event in the formation of reinitiation-competent ribosomal complexes. PMID:21343906
Aging-associated dysfunction of Akt/protein kinase B: S-nitrosylation and acetaminophen intervention.

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Miaozong Wu

Full Text Available BACKGROUND: Aged skeletal muscle is characterized by an increased incidence of metabolic and functional disorders, which if allowed to proceed unchecked can lead to increased morbidity and mortality. The mechanism(s underlying the development of these disorders in aging skeletal muscle are not well understood. Protein kinase B (Akt/PKB is an important regulator of cellular metabolism and survival, but it is unclear if aged muscle exhibits alterations in Akt function. Here we report a novel dysfunction of Akt in aging muscle, which may relate to S-nitrosylation and can be prevented by acetaminophen intervention. PRINCIPAL FINDINGS: Compared to 6- and 27-month rats, the phosphorylation of Akt (Ser473 and Thr308 was higher in soleus muscles of very aged rats (33-months. Paradoxically, these increases in Akt phosphorylation were associated with diminished mammalian target of rapamycin (mTOR phosphorylation, along with decreased levels of insulin receptor beta (IR-beta, phosphoinositide 3-kinase (PI3K, phosphatase and tensin homolog deleted on chromosome 10 (PTEN and phosphorylation of phosphoinositide-dependent kinase-1 (PDK1 (Ser241. In vitro Akt kinase measurements and ex vivo muscle incubation experiments demonstrated age-related impairments of Akt kinase activity, which were associated with increases in Akt S-nitrosylation and inducible nitric oxide synthase (iNOS. Impairments in Akt function occurred parallel to increases in myocyte apoptosis and decreases in myocyte size and the expression of myosin and actin. These age-related disorders were attenuated by treating aged (27-month animals with acetaminophen (30 mg/kg body weight/day for 6-months. CONCLUSIONS: These data demonstrate that Akt dysfunction and increased S-nitrosylation of Akt may contribute to age-associated disorders in skeletal muscle and that acetaminophen may be efficacious for the treatment of age-related muscle dysfunction.
A study of 6S workplace improvement in Ergonomic Laboratory

Science.gov (United States)

Sari, AD; Suryoputro, MR; Rahmillah, FI

2017-12-01

This article discusses 6S implementation in Ergonomic Laboratory, Department of Industrial Engineering, Islamic University of Indonesia. This research is improvement project of 5S implementation in Ergonomic laboratory. Referring to the 5S implementation of the previous year, there have been improvements from environmental conditions or a more organized workplace however there is still a lack of safety aspects. There are several safeties problems such as equipment arrangement, potential hazards of room dividers that cause injury several times, placement of fire extinguisher, no evacuation path and assembly point in case of fire, as well as expired hydrant condition and lack of awareness of stakeholders related to safety. Therefore, this study aims to apply the 6S kaizen method to the Ergonomic laboratory to facilitate the work process, reduce waste, improve work safety and improve staff performance. Based on the score 6S assessment increased audit results by 32 points, before implementation is 75 point while after implementation is 107 point. This has implications for better use for mitigate people in laboratory area, save time when looking for tools and materials, safe workplace, as well as improving the culture and spirit of ‘6S’ on staff due to better and safetier working environment.
Search for the CP-Violating Decays Υ(4S)→B0B¯0→J/ψKS0+J/ψ(ηc)KS0

Science.gov (United States)

Tajima, O.; Hazumi, M.; Adachi, I.; Aihara, H.; Aulchenko, V.; Aushev, T.; Bakich, A. M.; Barberio, E.; Bay, A.; Bedny, I.; Bhardwaj, V.; Bitenc, U.; Bozek, A.; Bračko, M.; Browder, T. E.; Chang, M.-C.; Chang, P.; Chen, A.; Chen, K.-F.; Chen, W. T.; Cheon, B. G.; Chiang, C.-C.; Chistov, R.; Cho, I.-S.; Choi, Y.; Choi, Y. K.; Dalseno, J.; Danilov, M.; Dash, M.; Drutskoy, A.; Eidelman, S.; Epifanov, D.; Go, A.; Gokhroo, G.; Golob, B.; Haba, J.; Hayasaka, K.; Hayashii, H.; Heffernan, D.; Hokuue, T.; Hoshi, Y.; Hou, W.-S.; Hsiung, Y. B.; Hyun, H. J.; Iijima, T.; Ikado, K.; Inami, K.; Ishikawa, A.; Ishino, H.; Itoh, R.; Iwasaki, M.; Iwasaki, Y.; Joshi, N. J.; Kah, D. H.; Kaji, H.; Kang, J. H.; Kataoka, S. U.; Kawai, H.; Kawasaki, T.; Kichimi, H.; Kim, H. J.; Kim, H. O.; Kim, S. K.; Kim, Y. J.; Kinoshita, K.; Korpar, S.; Križan, P.; Krokovny, P.; Kumar, R.; Kuo, C. C.; Kwon, Y.-J.; Lange, J. S.; Lee, J. S.; Lee, M. J.; Lee, S. E.; Lesiak, T.; Li, J.; Lin, S.-W.; Liventsev, D.; Mandl, F.; Marlow, D.; McOnie, S.; Medvedeva, T.; Mitaroff, W.; Miyabayashi, K.; Miyake, H.; Miyata, H.; Mizuk, R.; Mohapatra, D.; Nagasaka, Y.; Nakano, E.; Nakao, M.; Nishida, S.; Nitoh, O.; Noguchi, S.; Nozaki, T.; Ogawa, S.; Ohshima, T.; Okuno, S.; Ozaki, H.; Pakhlov, P.; Pakhlova, G.; Park, C. W.; Park, H.; Pestotnik, R.; Piilonen, L. E.; Sahoo, H.; Sakai, Y.; Schneider, O.; Sekiya, A.; Senyo, K.; Sevior, M. E.; Shapkin, M.; Shen, C. P.; Shibuya, H.; Shiu, J.-G.; Shwartz, B.; Singh, J. B.; Sokolov, A.; Somov, A.; Stanič, S.; Starič, M.; Sumisawa, K.; Sumiyoshi, T.; Takasaki, F.; Tanaka, M.; Taylor, G. N.; Teramoto, Y.; Trabelsi, K.; Uehara, S.; Ueno, K.; Uglov, T.; Unno, Y.; Uno, S.; Urquijo, P.; Usov, Y.; Varner, G.; Varvell, K. E.; Vervink, K.; Villa, S.; Vinokurova, A.; Wang, C. C.; Wang, C. H.; Wang, M.-Z.; Wang, P.; Watanabe, Y.; Wedd, R.; Won, E.; Yabsley, B. D.; Yamaguchi, A.; Yamashita, Y.; Yamauchi, M.; Yuan, C. Z.; Yusa, Y.; Zhang, C. C.; Zhang, Z. P.; Zhilich, V.; Zhulanov, V.; Zupanc, A.

2007-11-01

We report the first search for CP-violating decays of the Υ(4S) using a data sample that contains 535×106 Υ(4S) mesons with the Belle detector at the KEKB asymmetric-energy e+e- collider. A partial reconstruction technique is employed to enhance the signal sensitivity. No significant signals were observed. We obtain an upper limit of 4×10-7 at the 90% confidence level for the branching fractions of the CP violating modes, Υ(4S)→B0B¯0→J/ψKS0+J/ψ(ηc)KS0. Extrapolating the result, we find that an observation with 5σ significance is expected with a 30ab-1 data sample, which is within the reach of a future super B factory.
Altered Regulation of Contraction-Induced Akt/mTOR/p70S6k Pathway Signaling in Skeletal Muscle of the Obese Zucker Rat

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Anjaiah Katta

2009-01-01

Full Text Available Increased muscle loading results in the phosphorylation of the 70 kDa ribosomal S6 kinase (p70S6k, and this event is strongly correlated with the degree of muscle adaptation following resistance exercise. Whether insulin resistance or the comorbidities associated with this disorder may affect the ability of skeletal muscle to activate p70S6k signaling following an exercise stimulus remains unclear. Here, we compare the contraction-induced activation of p70S6k signaling in the plantaris muscles of lean and insulin resistant obese Zucker rats following a single bout of increased contractile loading. Compared to lean animals, the basal phosphorylation of p70S6k (Thr389; 37.2% and Thr421/Ser424; 101.4%, Akt (Thr308; 25.1%, and mTOR (Ser2448; 63.0% was higher in obese animals. Contraction increased the phosphorylation of p70S6k (Thr389, Akt (Ser473, and mTOR (Ser2448 in both models however the magnitude and kinetics of activation differed between models. These results suggest that contraction-induced activation of p70S6k signaling is altered in the muscle of the insulin resistant obese Zucker rat.
AF-6 Protects Against Dopaminergic Dysfunction and Mitochondrial Abnormalities in Drosophila Models of Parkinson’s Disease

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Adeline H. Basil

2017-08-01

Full Text Available Afadin 6 (AF-6 is an F-actin binding multidomain-containing scaffolding protein that is known for its function in cell-cell adhesion. Interestingly, besides this well documented role, we recently found that AF-6 is a Parkin-interacting protein that augments Parkin/PINK1-mediated mitophagy. Notably, mutations in Parkin and PINK1 are causative of recessively inherited forms of Parkinson’s disease (PD and aberrant mitochondrial homeostasis is thought to underlie PD pathogenesis. Given the novel role of AF-6 in mitochondrial quality control (QC, we hypothesized that AF-6 overexpression may be beneficial to PD. Using the Drosophila melanogaster as a model system, we demonstrate in this study that transgenic overexpression of human AF-6 in parkin and also pink1 null flies rescues their mitochondrial pathology and associated locomotion deficit, which results in their improved survival over time. Similarly, AF-6 overexpression also ameliorates the pathological phenotypes in flies expressing the Leucine Rich Repeat Kinase 2 (LRRK2 G2019S mutant, a mutation that is associated with dominantly-inherited PD cases in humans. Conversely, when endogenous AF-6 expression is silenced, it aggravates the disease phenotypes of LRRK2 mutant flies. Aside from these genetic models, we also found that AF-6 overexpression is protective against the loss of dopaminergic neurons in flies treated with rotenone, a mitochondrial complex I inhibitor commonly used to generate animal models of PD. Taken together, our results demonstrate that AF-6 protects against dopaminergic dysfunction and mitochondrial abnormalities in multiple Drosophila models of PD, and suggest the therapeutic value of AF-6-related pathways in mitigating PD pathogenesis.
Absence of the kinase S6k1 mimics the effect of chronic endurance exercise on glucose tolerance and muscle oxidative stress

Directory of Open Access Journals (Sweden)

C. Binsch

2017-11-01

Conclusions: In high-fat fed mice, loss of S6K1 mimics endurance exercise training by reducing mitochondrial ROS production and upregulating oxidative utilization of ketone bodies. Pharmacological targeting of S6K1 may improve the outcome of exercise-based interventions in obesity and diabetes.
Analysis of standard problem six (Semiscale test S-02-6) data

International Nuclear Information System (INIS)

Cartmill, C.E.

1977-08-01

Test S-02-6 of the Semiscale Mod-1 blowdown heat transfer test series was conducted to supply data for the U.S. Nuclear Regulatory Commission Standard Problem Six. To determine the credibility of the data and thus establish the validity of Standard Problem Six, an analysis of the results of Test S-02-6 was performed and is presented. This analysis consisted of investigations of system hydraulic and core thermal data. The credibility of the system hydraulic data was investigated through comparisons of the data with data and calculations from related sources (Test S-02-4) and, when necessary, through assessment of physical events. The credibility of the core thermal data was based on a thorough analysis of physical events. The results of these investigations substantiate the validity of Test S-02-6 data
Vitamin K-dependent proteins GAS6 and Protein S and TAM receptors in patients of systemic lupus erythematosus: correlation with common genetic variants and disease activity.

Science.gov (United States)

Recarte-Pelz, Pedro; Tàssies, Dolors; Espinosa, Gerard; Hurtado, Begoña; Sala, Núria; Cervera, Ricard; Reverter, Joan Carles; de Frutos, Pablo García

2013-03-12

Growth arrest-specific gene 6 protein (GAS6) and protein S (ProS) are vitamin K-dependent proteins present in plasma with important regulatory functions in systems of response and repair to damage. They interact with receptor tyrosine kinases of the Tyro3, Axl and MerTK receptor tyrosine kinase (TAM) family, involved in apoptotic cell clearance (efferocytosis) and regulation of the innate immunity. TAM-deficient mice show spontaneous lupus-like symptoms. Here we tested the genetic profile and plasma levels of components of the system in patients with systemic lupus erythematosus (SLE), and compare them with a control healthy population. Fifty SLE patients and 50 healthy controls with matched age, gender and from the same geographic area were compared. Genetic analysis was performed in GAS6 and the TAM receptor genes on SNPs previously identified. The concentrations of GAS6, total and free ProS, and the soluble forms of the three TAM receptors (sAxl, sMerTK and sTyro3) were measured in plasma from these samples. Plasma concentrations of GAS6 were higher and, total and free ProS were lower in the SLE patients compared to controls, even when patients on oral anticoagulant treatment were discarded. Those parameters correlated with SLE disease activity index (SLEDAI) score, GAS6 being higher in the most severe cases, while free and total ProS were lower. All 3 soluble receptors increased its concentration in plasma of lupus patients. The present study highlights that the GAS6/ProS-TAM system correlates in several ways with disease activity in SLE. We show here that this correlation is affected by common polymorphisms in the genes of the system. These findings underscore the importance of mechanism of regulatory control of innate immunity in the pathology of SLE.
Proseek single-plex protein assay kit system to detect sAxl and Gas6 in serological material of brain tumor patients

Directory of Open Access Journals (Sweden)

Heidi Jaksch-Bogensperger

2018-06-01

Full Text Available • The receptor tyrosine kinase (RTK Axl and its ligand Gas6 are critically involved in the pathogenesis of high-grade glioma (HGG. Both proteins were found to be overexpressed e.g. in tumor cells, mediating cell proliferation and migration as well as tumor angiogenesis and neuroinflammation. The extracellular domain of Axl (sAxl and Gas6 were found in the peri-tumoral edema and blood of animals as well as in human glioma tissue. Therefore, we monitored the level of sAxl and Gas6 in human blood samples. To increase the sensitivity of protein detection beyond commonly used standard methods we preliminary tested the innovative Proseek Single-Plex Protein Assay Kit System from Olink Bioscience together with new antibodies against the soluble RTK sAxl and its ligand Gas6. We conclude that the Proseek method is a highly sensitive and fast procedure that can be used as a possible powerful tool compared to routinely used ELISA-methods.
Inclusive production of charged hadrons and $K_{s}^{0}$ mesons in photon-photon collisions

CERN Document Server

Ackerstaff, K.; Allison, John; Altekamp, N.; Anderson, K.J.; Anderson, S.; Arcelli, S.; Asai, S.; Ashby, S.F.; Axen, D.; Azuelos, G.; Ball, A.H.; Barberio, E.; Barlow, Roger J.; Bartoldus, R.; Batley, J.R.; Baumann, S.; Bechtluft, J.; Behnke, T.; Bell, Kenneth Watson; Bella, G.; Bentvelsen, S.; Bethke, S.; Betts, S.; Biebel, O.; Biguzzi, A.; Bird, S.D.; Blobel, V.; Bloodworth, I.J.; Bobinski, M.; Bock, P.; Bohme, J.; Boutemeur, M.; Braibant, S.; Bright-Thomas, P.; Brown, Robert M.; Burckhart, H.J.; Burgard, C.; Burgin, R.; Capiluppi, P.; Carnegie, R.K.; Carter, A.A.; Carter, J.R.; Chang, C.Y.; Charlton, David G.; Chrisman, D.; Ciocca, C.; Clarke, P.E.L.; Clay, E.; Cohen, I.; Conboy, J.E.; Cooke, O.C.; Couyoumtzelis, C.; Coxe, R.L.; Cuffiani, M.; Dado, S.; Dallavalle, G.Marco; Davis, R.; De Jong, S.; del Pozo, L.A.; De Roeck, A.; Desch, K.; Dienes, B.; Dixit, M.S.; Doucet, M.; Dubbert, J.; Duchovni, E.; Duckeck, G.; Duerdoth, I.P.; Eatough, D.; Estabrooks, P.G.; Etzion, E.; Evans, H.G.; Fabbri, F.; Fanfani, A.; Fanti, M.; Faust, A.A.; Fiedler, F.; Fierro, M.; Fischer, H.M.; Fleck, I.; Folman, R.; Furtjes, A.; Futyan, D.I.; Gagnon, P.; Gary, J.W.; Gascon, J.; Gascon-Shotkin, S.M.; Geich-Gimbel, C.; Geralis, T.; Giacomelli, G.; Giacomelli, P.; Gibson, V.; Gibson, W.R.; Gingrich, D.M.; Glenzinski, D.; Goldberg, J.; Gorn, W.; Grandi, C.; Gross, E.; Grunhaus, J.; Gruwe, M.; Hanson, G.G.; Hansroul, M.; Hapke, M.; Hargrove, C.K.; Hartmann, C.; Hauschild, M.; Hawkes, C.M.; Hawkings, R.; Hemingway, R.J.; Herndon, M.; Herten, G.; Heuer, R.D.; Hildreth, M.D.; Hill, J.C.; Hillier, S.J.; Hobson, P.R.; Hocker, James Andrew; Homer, R.J.; Honma, A.K.; Horvath, D.; Hossain, K.R.; Howard, R.; Huntemeyer, P.; Igo-Kemenes, P.; Imrie, D.C.; Ishii, K.; Jacob, F.R.; Jawahery, A.; Jeremie, H.; Jimack, M.; Joly, A.; Jones, C.R.; Jovanovic, P.; Junk, T.R.; Karlen, D.; Kartvelishvili, V.; Kawagoe, K.; Kawamoto, T.; Kayal, P.I.; Keeler, R.K.; Kellogg, R.G.; Kennedy, B.W.; Klier, A.; Kluth, S.; Kobayashi, T.; Kobel, M.; Koetke, D.S.; Kokott, T.P.; Kolrep, M.; Komamiya, S.; Kowalewski, Robert V.; Kress, T.; Krieger, P.; von Krogh, J.; Kyberd, P.; Lafferty, G.D.; Lanske, D.; Lauber, J.; Lautenschlager, S.R.; Lawson, I.; Layter, J.G.; Lazic, D.; Lee, A.M.; Lefebvre, E.; Lellouch, D.; Letts, J.; Levinson, L.; Liebisch, R.; List, B.; Littlewood, C.; Lloyd, A.W.; Lloyd, S.L.; Loebinger, F.K.; Long, G.D.; Losty, M.J.; Ludwig, J.; Lui, D.; Macchiolo, A.; Macpherson, A.; Mannelli, M.; Marcellini, S.; Markopoulos, C.; Martin, A.J.; Martin, J.P.; Martinez, G.; Mashimo, T.; Mattig, Peter; McDonald, W.John; McKenna, J.; Mckigney, E.A.; McMahon, T.J.; McPherson, R.A.; Meijers, F.; Menke, S.; Merritt, F.S.; Mes, H.; Meyer, J.; Michelini, A.; Mihara, S.; Mikenberg, G.; Miller, D.J.; Mir, R.; Mohr, W.; Montanari, A.; Mori, T.; Nagai, K.; Nakamura, I.; Neal, H.A.; Nellen, B.; Nisius, R.; O'Neale, S.W.; Oakham, F.G.; Odorici, F.; Ogren, H.O.; Oreglia, M.J.; Orito, S.; Palinkas, J.; Pasztor, G.; Pater, J.R.; Patrick, G.N.; Patt, J.; Perez-Ochoa, R.; Petzold, S.; Pfeifenschneider, P.; Pilcher, J.E.; Pinfold, J.; Plane, David E.; Poffenberger, P.; Poli, B.; Polok, J.; Przybycien, M.; Rembser, C.; Rick, H.; Robertson, S.; Robins, S.A.; Rodning, N.; Roney, J.M.; Roscoe, K.; Rossi, A.M.; Rozen, Y.; Runge, K.; Runolfsson, O.; Rust, D.R.; Sachs, K.; Saeki, T.; Sahr, O.; Sang, W.M.; Sarkisian, E.K.G.; Sbarra, C.; Schaile, A.D.; Schaile, O.; Scharf, F.; Scharff-Hansen, P.; Schieck, J.; Schmitt, B.; Schmitt, S.; Schoning, A.; Schorner, T.; Schroder, Matthias; Schumacher, M.; Schwick, C.; Scott, W.G.; Seuster, R.; Shears, T.G.; Shen, B.C.; Shepherd-Themistocleous, C.H.; Sherwood, P.; Siroli, G.P.; Sittler, A.; Skuja, A.; Smith, A.M.; Snow, G.A.; Sobie, R.; Soldner-Rembold, S.; Sproston, M.; Stahl, A.; Stephens, K.; Steuerer, J.; Stoll, K.; Strom, David M.; Strohmer, R.; Tafirout, R.; Talbot, S.D.; Tanaka, S.; Taras, P.; Tarem, S.; Teuscher, R.; Thiergen, M.; Thomson, M.A.; von Torne, E.; Torrence, E.; Towers, S.; Trigger, I.; Trocsanyi, Z.; Tsur, E.; Turcot, A.S.; Turner-Watson, M.F.; Van Kooten, Rick J.; Vannerem, P.; Verzocchi, M.; Vikas, P.; Voss, H.; Wackerle, F.; Wagner, A.; Ward, C.P.; Ward, D.R.; Watkins, P.M.; Watson, A.T.; Watson, N.K.; Wells, P.S.; Wermes, N.; White, J.S.; Wiesler, T.; Wilson, G.W.; Wilson, J.A.; Wyatt, T.R.; Yamashita, S.; Yekutieli, G.; Zacek, V.; Zer-Zion, D.

1999-01-01

The production of charged hadrons and K_s mesons in the collisions of quasi-real photons has been measured using the OPAL detector at LEP. The data were taken at e+e- centre-of-mass energies of 161 and 172 GeV. The differential cross-sections as a function of the transverse momentum and the pseudorapidity of the charged hadrons and K_s mesons have been compared to the leading order Monte Carlo simulations of PHOJET and PYTHIA and to perturbative next-to-leading order (NLO) QCD calculations. The distributions have been measured in the range 10-125 GeV of the hadronic invariant mass W. By comparing the transverse momentum distribution of charged hadrons measured in gamma-gamma interactions with gamma-proton and meson-proton data we find evidence for hard photon interactions in addition to the purely hadronic photon interactions.
Higher proliferation of peritumoral endothelial cells to IL-6/sIL-6R than tumoral endothelial cells in hepatocellular carcinoma

International Nuclear Information System (INIS)

Zhuang, Peng-Yuan; Wang, Jian-Dong; Tang, Zhao-Hui; Zhou, Xue-Ping; Quan, Zhi-Wei; Liu, Ying-Bin; Shen, Jun

2015-01-01

This study aimed to explore the responses to the interleukin-6 (IL-6)/soluble interleukin-6 receptor (sIL-6R) complex in peritumoral endothelial cells (PECs) and tumor endothelial cells (TECs), as well as determine the signaling pathways in the angiogenesis of hepatocellular carcinoma (HCC). The expression of IL-6, IL-6R, gp130, CD68, HIF-1α, and microvessel density (MVD) were assessed with an orthotopic xenograft model in nude mice. ECs were incubated under hypoxic conditions to detect IL-6 and gp130. The proliferation of PECs and TECs in the presence of IL-6 and sIL-6R, as well as the expression of gp130, JAK2/STAT3, PI3K/AKT in endothelial cells were measured. Peritumoral IL-6, IL-6R, gp130, CD68, and HIF-1α expression, as well as MVD, gradually increased during tumor growth. Hypoxia could directly induce IL-6 expression, but not gp130 in PECs. The co-culture of IL-6/sIL-6R induced much higher PEC proliferation and gp130 expression, as well as the elevated phosphorylation of JAK2 and STAT3, however not the phosphorylation of PI3K and AKT. PECs exhibited higher proliferation in response to IL-6/sIL-6R co-treatment compared with TECs in HCC via the up-regulation of gp130 /JAK2/STAT3. PEC and its associated peritumoral angiogenesis microenvironment may be a potential novel target for anti-angiogenic treatment. The online version of this article (doi:10.1186/s12885-015-1763-2) contains supplementary material, which is available to authorized users
Pressure induced phase transition in Pb6Bi2S9

DEFF Research Database (Denmark)

Olsen, Lars Arnskov; Friese, Karen; Makovicky, Emil

2011-01-01

consists of two types of moduli with SnS/TlI archetype structure in which the Pb and Bi lone pairs are strongly expressed. The mechanism of the phase transition is described in detail and the results are compared to the closely related phase transition in Pb3Bi2S6 (lillianite).......The crystal structure of Pb6Bi2S9 is investigated at pressures between 0 and 5.6 GPa with X-ray diffraction on single-crystals. The pressure is applied using diamond anvil cells. Heyrovskyite (Bbmm, a = 13.719(4) Å, b = 31.393(9) Å, c = 4.1319(10) Å, Z = 4) is the stable phase of Pb6Bi2S9...... at ambient conditions and is built from distorted moduli of PbS-archetype structure with a low stereochemical activity of the Pb2+ and Bi3+ lone electron pairs. Heyrovskyite is stable until at least 3.9 GPa and a first-order phase transition occurs between 3.9 and 4.8 GPa. A single-crystal is retained after...
Serotonin 6 receptor controls alzheimer?s disease and depression

OpenAIRE

Yun, Hyung-Mun; Park, Kyung-Ran; Kim, Eun-Cheol; Kim, Sanghyeon; Hong, Jin Tae

2015-01-01

Alzheimer?s disease (AD) and depression in late life are one of the most severe health problems in the world disorders. Serotonin 6 receptor (5-HT6R) has caused much interest for potential roles in AD and depression. However, a causative role of perturbed 5-HT6R function between two diseases was poorly defined. In the present study, we found that a 5-HT6R antagonist, SB271036 rescued memory impairment by attenuating the generation of A? via the inhibition of ?-secretase activity and the inact...
Isotope Shifts and Hyperfine Structure in the[Xe]4f(7)5d 6s(2) D-2(J)->[Xe]4f(7)5d 6s 6p F-9(J+1) Transitions of Gadolinium

International Nuclear Information System (INIS)

Blaum, K.; Bushaw, Bruce A.; Diel, S; Geppert, Ch; Kuschnick, A; Muller, P.; Nortershauser, W.; Schmitt, A.; Wendt, K.

1999-01-01

High-resolution resonance ionization mass spectrometry has been used to measure isotope shifts and hyperfine structure in all[Xe] 4f 7 5d 6s2 9DJ ---[Xe] 4f 7 5d 6s 6p 9FJ+1 (J= 2-6) and the[Xe] 4f 7 5d 6s2 9D6---[Xe] 4f 7 5d 6s 6p 9D5 transitions of gadolinium (Gd I). Gadolinium atoms in an atomic beam were excited with a tunable single-frequency laser in the wavelength range of 422 - 429 nm. Resonant excitation was followed by photoionization with the 363.8 nm line of an argon ion laser and resulting ions were mass separated and detected with a quadrupole mass spectrometer. Isotope shifts for all stable gadolinium isotopes in these transitions have been measured for the first time. Additionally, the hyperfine structure constants of the upper states have been derived for the isotopes 155, 157Gd and are compared with previous work. Using prior experimental values for the mean nuclear charge radii, derived from the combination of muonic atoms and electron scattering data, field shift a nd specific mass shift coefficients for the investigated transitions have been determined and nuclear charge parameters l for the minor isotopes 152, 154Gd have been calculated
Inositol Hexakisphosphate Kinase-3 Regulates the Morphology and Synapse Formation of Cerebellar Purkinje Cells via Spectrin/Adducin

Science.gov (United States)

Fu, Chenglai; Xu, Jing; Li, Ruo-Jing; Crawford, Joshua A.; Khan, A. Basit; Ma, Ting Martin; Cha, Jiyoung Y.; Snowman, Adele M.; Pletnikov, Mikhail V.

2015-01-01

The inositol hexakisphosphate kinases (IP6Ks) are the principal enzymes that generate inositol pyrophosphates. There are three IP6Ks (IP6K1, 2, and 3). Functions of IP6K1 and IP6K2 have been substantially delineated, but little is known of IP6K3's role in normal physiology, especially in the brain. To elucidate functions of IP6K3, we generated mice with targeted deletion of IP6K3. We demonstrate that IP6K3 is highly concentrated in the brain in cerebellar Purkinje cells. IP6K3 physiologically binds to the cytoskeletal proteins adducin and spectrin, whose mutual interactions are perturbed in IP6K3-null mutants. Consequently, IP6K3 knock-out cerebella manifest abnormalities in Purkinje cell structure and synapse number, and the mutant mice display deficits in motor learning and coordination. Thus, IP6K3 is a major determinant of cytoskeletal disposition and function of cerebellar Purkinje cells. SIGNIFICANCE STATEMENT We identified and cloned a family of three inositol hexakisphosphate kinases (IP6Ks) that generate the inositol pyrophosphates, most notably 5-diphosphoinositol pentakisphosphate (IP7). Of these, IP6K3 has been least characterized. In the present study we generated IP6K3 knock-out mice and show that IP6K3 is highly expressed in cerebellar Purkinje cells. IP6K3-deleted mice display defects of motor learning and coordination. IP6K3-null mice manifest aberrations of Purkinje cells with a diminished number of synapses. IP6K3 interacts with the cytoskeletal proteins spectrin and adducin whose altered disposition in IP6K3 knock-out mice may mediate phenotypic features of the mutant mice. These findings afford molecular/cytoskeletal mechanisms by which the inositol polyphosphate system impacts brain function. PMID:26245967
Amplitude analysis of the D+ -> K-S(0)pi + (0)(pi) Dalitz plot

NARCIS (Netherlands)

Ablikim, M.; Achasov, M. N.; Ai, X. C.; Albayrak, O.; Albrecht, M.; Ambrose, D. J.; An, F. F.; An, Q.; Bai, J. Z.; Ferroli, R. Baldini; Ban, Y.; Bennett, J. V.; Bertani, M.; Bian, J. M.; Boger, E.; Bondarenko, O.; Boyko, I.; Braun, S.; Briere, R. A.; Cai, H.; Cai, X.; Cakir, O.; Calcaterra, A.; Cao, G. F.; Cetin, S. A.; Chang, J. F.; Chelkov, G.; Chen, G.; Chen, H. S.; Chen, J. C.; Chen, M. L.; Chen, S. J.; Chen, X.; Chen, X. R.; Chen, Y. B.; Cheng, H. P.; Chu, X. K.; Chu, Y. P.; Cronin-Hennessy, D.; Dai, H. L.; Dai, J. P.; Dedovich, D.; Deng, Z. Y.; Denig, A.; Denysenko, I.; Kalantar-Nayestanaki, N.; Kavatsyuk, M.; Loehner, H.; Messchendorp, J. G.; Moeini, H.

2014-01-01

We perform an analysis of the D+ -> K-S(0)pi + (0)(pi) Dalitz plot using a data set of 2.92 fb(-1) of e(+) e(-) collisions at the (3770) mass accumulated by the BESIII experiment, in which 166694 candidate events are selected with a background of 15.1%. The Dalitz plot is found to be well
Shake-up transitions in S 2p, S 2s and F 1s photoionization of the SF6 molecule

International Nuclear Information System (INIS)

Decleva, P; Fronzoni, G; Kivimaeki, A; Alvarez Ruiz, J; Svensson, S

2009-01-01

Shake-up transitions occurring upon core photoionization in the SF 6 molecule have been studied experimentally and theoretically. The S 2p, S 2s and F 1s shake-up satellite photoelectron spectra were measured using Al Ka radiation at 1487 eV photon energy. They have been interpreted with the aid of ab initio configuration interaction calculations in the sudden-limit approximation. For the S 2p spectrum, conjugate shake-up transitions were also calculated. Clear evidence of conjugate processes is observed in the S 2p shake-up spectrum measured at 230 eV photon energy. The experimental and theoretical S 2p and S 2s shake-up spectra show very similar structures mainly due to orbital relaxation involving S 3s and 3p participation. For the calculation of the F 1s shake-up spectrum, the symmetry lowering of the molecule in the final states was considered, resulting in a good agreement with the experiment.
S6K1 in the central nervous system regulates energy expenditure via MC4R/CRH pathways in response to deprivation of an essential amino acid.

Science.gov (United States)

Xia, Tingting; Cheng, Ying; Zhang, Qian; Xiao, Fei; Liu, Bin; Chen, Shanghai; Guo, Feifan

2012-10-01

It is well established that the central nervous system (CNS), especially the hypothalamus, plays an important role in regulating energy homeostasis and lipid metabolism. We have previously shown that hypothalamic corticotropin-releasing hormone (CRH) is critical for stimulating fat loss in response to dietary leucine deprivation. The molecular mechanisms underlying the CNS regulation of leucine deprivation-stimulated fat loss are, however, still largely unknown. Here, we used intracerebroventricular injection of adenoviral vectors to identify a novel role for hypothalamic p70 S6 kinase 1 (S6K1), a major downstream effector of the kinase mammalian target of rapamycin, in leucine deprivation stimulation of energy expenditure. Furthermore, we show that the effect of hypothalamic S6K1 is mediated by modulation of Crh expression in a melanocortin-4 receptor-dependent manner. Taken together, our studies provide a new perspective for understanding the regulation of energy expenditure by the CNS and the importance of cross-talk between nutritional control and regulation of endocrine signals.

Observation of the CP-conserving $K_{S} \\rightarrow \\pi^{+}\\pi^{- }\\pi^{0}$ decay amplitude

CERN Document Server

Adler, R; Angelopoulos, Angelos; Aspostolakis, A; Aslanides, Elie; Backenstoss, Gerhard; Bee, C P; Behnke, O; Benelli, A; Bennet, J; Bertin, V; Bienlein, J K; Blanc, F; Bloch, P; Bula, C; Carlson, P J; Carroll, M; Carvalho, J; Cawley, E; Charalambous, S; Chardin, G; Chertok, M B; Cody, A; Danielsson, M; Dejardin, M; Derré, J; Dodgson, M; Duclos, J; Ealet, A; Eckart, B; Eleftheriadis, C; Evangelou, I; Faravel, L; Fassnacht, P; Faure, J L; Felder, C; Ferreira-Marques, R; Fetscher, W; Fidecaro, Maria; Filipcic, A; Francis, D; Fry, J; Fuglesang, C; Gabathuler, Erwin; Gamet, R; Garreta, D; Geralis, T; Gerber, H J; Go, A; Gumplinger, P; Guyot, C; Harrison, P F; Haselden, A; Hayman, P J; Henry-Coüannier, F; Heyes, W G; Hollander, R W; Hubert, E; Jansson, K; Johner, H U; Jon-And, K; Kettle, P R; Kochowski, Claude; Kokkas, P; Kreuger, R; Lawry, T; Le Gac, R; Leimgruber, F; Liolios, A; Machado, E; Maley, P; Mandic, I; Manthos, N; Marel, Gérard; Mikuz, M; Miller, J; Montanet, François; Nakada, Tatsuya; Onofre, A; Pagels, B; Papadopoulos, I M; Pavlopoulos, P; Pelucchi, F; Pinto da Cunha, J; Policarpo, Armando; Polivka, G; Postma, H; Rickenbach, R; Roberts, B L; Rozaki, E; Ruf, T; Sacks, L; Sakelliou, L; Sanders, P; Santoni, C; Sarigiannis, K; Schäfer, M; Schaller, L A; Schietinger, T; Schopper, A; Schune, P; Soares, A; Tauscher, Ludwig; Thibault, C; Touchard, F; Touramanis, C; Triantis, F A; Tröster, D A; Van Beveren, E; van Eijk, C W E; Varner, G S; Vlachos, S; Weber, P; Wigger, O; Witzig, C; Wolter, M; Yéche, C; Zavrtanik, D; Zimmerman, D

1996-01-01

The interference between CP-conserving $\\ks$ and $\\kl \\rightarrow \\threepi$ decay amplitudes was observed by studying the decay rate asymmetries between initial $\\ko$ and $\\kob$ separately for the phase space regions $E_{\\mbox{\\rm \\scriptsize CM}}(\\pi^+)> E_{\\mbox{\\rm \\scriptsize CM}}(\\pi^-)$ and $E_{\\mbox{\\rm \\scriptsize CM}}(\\pi^+)< E_{\\mbox{\\rm \\scriptsize CM}}(\\pi^-)$. For the parameter $\\lambda$ we found $\\mbox{\\rm Re}(\\lambda )=0.036\\pm0.010(\\mbox{\\rm stat.}) ^{+0.002}_{-0.003} (\\mbox{\\rm syst.)}$ and $\\mbox{Im}(\\lambda)$ consistent with zero, leading for the CP-conserving $\\ks \\rightarrow \\threepi$ decay, to a branching ratio $\\mbox{\\rm B} = \\left[4.1 ^{+2.5}_{-1.9 } (\\mbox{\\rm stat.}) ^{+0.5} _{-0.6} (\\mbox{\\rm syst.)}\\right] \\times 10^{-7}$.
Novel derivatives of 6-mercaptopurine: synthesis, characterization and antiproliferative activities of S-allylthio-mercaptopurines.

Science.gov (United States)

Miron, T; Arditti, F; Konstantinovski, L; Rabinkov, A; Mirelman, D; Berrebi, A; Wilchek, M

2009-02-01

Biologically active S-allylthio derivatives of 6-mercaptopurine (6-MP) and 6-mercaptopurine riboside (6-MPR) were synthesized. The products, S-allylthio-6-mercaptopurine (SA-6MP) and S-allylthio-6-mercaptopurine riboside (SA-6MPR) were characterized. The antiproliferative activity of the new prodrugs was tested on human leukemia and monolayer cell lines, and compared to that of their parent reactants. The new prodrugs acted by a concentration-dependent mechanism. They inhibited cell proliferation and induced-apoptosis more efficiently than the parent molecules. Leukemia cell lines were more sensitive to the new prodrugs than monolayer cell lines. Higher hydrophobicity of the derivatives improves their penetration into cells, where upon reaction with glutathione, S-allylthioglutathione (GSSA) is formed, and 6-MP or 6-MPR is released for further processing.
Fisetin inhibits human melanoma cell growth through direct binding to p70S6K and mTOR: findings from 3-D melanoma skin equivalents and computational modeling.

Science.gov (United States)

Syed, Deeba N; Chamcheu, Jean-Christopher; Khan, Mohammad Imran; Sechi, Mario; Lall, Rahul K; Adhami, Vaqar M; Mukhtar, Hasan

2014-06-01

The incidence of melanoma continues to rise. Inspite of treatment advances, the prognosis remains grim once the disease has metastasized, emphasizing the need to explore additional therapeutic strategies. One such approach is through the use of mechanism-based dietary intervention. We previously showed that the flavonoid fisetin inhibits melanoma cell proliferation, in vitro and in vivo. Here, we studied fisetin-mediated regulation of kinases involved in melanoma growth and progression. Time-course analysis in 3-D melanoma constructs that transitioned from radial to vertical growth showed that fisetin treatment resulted in significant decrease in melanocytic lesions in contrast to untreated controls that showed large tumor nests and invading disseminated cells. Further studies in melanoma cultures and mouse xenografts showed that fisetin-mediated growth inhibition was associated with dephosphorylation of AKT, mTOR and p70S6K proteins. In silico modeling indicated direct interaction of fisetin with mTOR and p70S6K with favorable free energy values. These findings were validated by cell-free competition assays that established binding of fisetin to p70S6K and mTOR while little affinity was detected with AKT. Kinase activity studies reflected similar trend with % inhibition observed for p70S6K and mTOR at lower doses than AKT. Our studies characterized, for the first time, the differential interactions of any botanical agent with kinases involved in melanoma growth and demonstrate that fisetin inhibits mTOR and p70S6K through direct binding while the observed inhibitory effect of fisetin on AKT is mediated indirectly, through targeting interrelated pathways. Published by Elsevier Inc.
Akt-dependent Activation of the Heart 6-Phosphofructo-2-kinase/Fructose-2,6-bisphosphatase (PFKFB2) Isoenzyme by Amino Acids*

Science.gov (United States)

Novellasdemunt, Laura; Tato, Irantzu; Navarro-Sabate, Aurea; Ruiz-Meana, Marisol; Méndez-Lucas, Andrés; Perales, Jose Carlos; Garcia-Dorado, David; Ventura, Francesc; Bartrons, Ramon; Rosa, Jose Luis

2013-01-01

Reciprocal regulation of metabolism and signaling allows cells to modulate their activity in accordance with their metabolic resources. Thus, amino acids could activate signal transduction pathways that control cell metabolism. To test this hypothesis, we analyzed the effect of amino acids on fructose-2,6-bisphosphate (Fru-2,6-P2) metabolism. We demonstrate that amino acids increase Fru-2,6-P2 concentration in HeLa and in MCF7 human cells. In conjunction with this, 6-phosphofructo-2-kinase activity, glucose uptake, and lactate concentration were increased. These data correlate with the specific phosphorylation of heart 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase (PFKFB2) isoenzyme at Ser-483. This activation was mediated by the PI3K and p38 signaling pathways. Furthermore, Akt inactivation blocked PFKFB2 phosphorylation and Fru-2,6-P2 production, thereby suggesting that the above signaling pathways converge at Akt kinase. In accordance with these results, kinase assays showed that amino acid-activated Akt phosphorylated PFKFB2 at Ser-483 and that knockdown experiments confirmed that the increase in Fru-2,6-P2 concentration induced by amino acids was due to PFKFB2. In addition, similar effects on Fru-2,6-P2 metabolism were observed in freshly isolated rat cardiomyocytes treated with amino acids, which indicates that these effects are not restricted to human cancer cells. In these cardiomyocytes, the glucose consumption and the production of lactate and ATP suggest an increase of glycolytic flux. Taken together, these results demonstrate that amino acids stimulate Fru-2,6-P2 synthesis by Akt-dependent PFKFB2 phosphorylation and activation and show how signaling and metabolism are inextricably linked. PMID:23457334
Photocatalytic activity of Bi_2WO_6/Bi_2S_3 heterojunctions: the facilitation of exposed facets of Bi_2WO_6 substrate

International Nuclear Information System (INIS)

Yan, Long; Wang, Yufei; Shen, Huidong; Zhang, Yu; Li, Jian; Wang, Danjun

2017-01-01

Highlights: • Bi_2S_3/Bi_2WO_6 hybrids with exposed (020) Bi_2WO_6 facets have been synthesized. • X-ray photoelectron spectroscopy reveals that a small amount of Bi_2S_3 was formed. • The enhanced photoactivity of hybrids is due to heterojunction and (020) facets. • A possible photocatalytic degradation mechanism is proposed. - Abstract: Bi_2S_3/Bi_2WO_6 hybrid architectures with exposed (020) Bi_2WO_6 facets have been synthesized via a controlled anion exchange approach. X-ray photoelectron spectroscopy (XPS) reveals that a small amount of Bi_2S_3 was formed on the surface of Bi_2WO_6 during the anion exchange process, thus leading to the transformation from the Bi_2WO_6 to Bi_2S_3/Bi_2WO_6. A rhodamine B (RhB) aqueous solution was chosen as model organic pollutants to evaluate the photocatalytic activities of the Bi_2S_3/Bi_2WO_6 catalysts. Under visible light irradiation, the Bi_2S_3/Bi_2WO_6-TAA displayed the excellent visible light photoactivities compared with pure Bi_2S_3, Bi_2WO_6 and other composite photocatalysts. The efficient photocatalytic activity of the Bi_2S_3/Bi_2WO_6-TAA composite microspheres was ascribed to the constructed heterojunctions and the inner electric field caused by the exposed (020) Bi_2WO_6 facets. Active species trapping experiments revealed that h"+ and O_2·"− are the main active species in the photocatalytic process. Furthermore, the as-obtained photocatalysts showed good photocatalytic activity after four recycles. The results presented in this study provide a new concept for the rational design and development of highly efficient photocatalysts.
Rewriting Revolutionary Myths: Photography in Castro’s Cuba and Tania Bruguera’s Tatlin’s Whisper#6

Directory of Open Access Journals (Sweden)

Louisa Söllner

2014-11-01

Full Text Available Photography was a key medium for creating, spreading, and cementing myths about the Cuban Revolution and its leaders. In the first part of this essay, I’ll explore several iconic images as well as responses to these pictures, all parts of a Cuban “cross-national memory discourse” (cf. Quiroga, 2005. Walter Benjamin’s media philosophy can help in developing insights about the functioning of these photographs. In the second part of the paper, I turn to Tania Bruguera’s piece Tatlin’s Whisper#6 (staged at the 10th Havana Biennial in 2009, which radically rewrites the poetics of the images and aspires to create a sense of participation and direct involvement.
6S-1 RNA function leads to a delay in sporulation in Bacillus subtilis.

Science.gov (United States)

Cavanagh, Amy T; Wassarman, Karen M

2013-05-01

We have discovered that 6S-1 RNA (encoded by bsrA) is important for appropriate timing of sporulation in Bacillus subtilis in that cells lacking 6S-1 RNA sporulate earlier than wild-type cells. The time to generate a mature spore once the decision to sporulate has been made is unaffected by 6S-1 RNA, and, therefore, we propose that it is the timing of onset of sporulation that is altered. Interestingly, the presence of cells lacking 6S-1 RNA in coculture leads to all cell types exhibiting an early-sporulation phenotype. We propose that cells lacking 6S-1 RNA modify their environment in a manner that promotes early sporulation. In support of this model, resuspension of wild-type cells in conditioned medium from ΔbsrA cultures also resulted in early sporulation. Use of Escherichia coli growth as a reporter of the nutritional status of conditioned media suggested that B. subtilis cells lacking 6S-1 RNA reduce the nutrient content of their environment earlier than wild-type cells. Several pathways known to impact the timing of sporulation, such as the skf- and sdp-dependent cannibalism pathways, were eliminated as potential targets of 6S-1 RNA-mediated changes, suggesting that 6S-1 RNA activity defines a novel mechanism for altering the timing of onset of sporulation. In addition, 6S-2 RNA does not influence the timing of sporulation, providing further evidence of the independent influences of these two related RNAs on cell physiology.
Measurement of the branching ratios of D(+) and D(+)(s) hadronic decays to four-body final states containing a K(S).

Science.gov (United States)

Link, J M; Reyes, M; Yager, P M; Anjos, J C; Bediaga, I; Göbel, C; Magnin, J; Massafferi, A; de Miranda, J M; Pepe, I M; dos Reis, A C; Simão, F R; Carrillo, S; Casimiro, E; Sánchez-Hernández, A; Uribe, C; Vázquez, F; Cinquini, L; Cumalat, J P; O'Reilly, B; Ramirez, J E; Vaandering, E W; Butler, J N; Cheung, H W; Gaines, I; Garbincius, P H; Garren, L A; Gottschalk, E; Kasper, P H; Kreymer, A E; Kutschke, R; Bianco, S; Fabbri, F L; Sarwar, S; Zallo, A; Cawlfield, C; Kim, D Y; Rahimi, A; Wiss, J; Gardner, R; Chung, Y S; Kang, J S; Ko, B R; Kwak, J W; Lee, K B; Park, H; Alimonti, G; Boschini, M; Caccianiga, B; D'Angelo, P; DiCorato, M; Dini, P; Giammarchi, M; Inzani, P; Leveraro, F; Malvezzi, S; Menasce, D; Mezzadri, M; Milazzo, L; Moroni, L; Pedrini, D; Pontoglio, C; Prelz, F; Rovere, M; Sala, A; Sala, S; Davenport, T F; Agostino, L; Arena, V; Boca, G; Bonomi, G; Gianini, G; Liguori, G; Merlo, M; Pantea, D; Ratti, S P; Riccardi, C; Segoni, I; Viola, L; Vitulo, P; Hernandez, H; Lopez, A M; Mendez, H; Mendez, L; Mirles, A; Montiel, E; Olaya, D; Paris, A; Quinones, J; Rivera, C; Xiong, W; Zhang, Y; Wilson, J R; Cho, K; Handler, T; Engh, D; Hosack, M; Johns, W E; Nehring, M; Sheldon, P D; Stenson, K; Webster, M; Sheaff, M

2001-10-15

We have studied hadronic four-body decays of D(+) and D(+)(s) mesons with a K(S) in the final state using data recorded during the 1996-1997 fixed-target run of the Fermilab high energy photoproduction experiment FOCUS. We report a new branching ratio measurement of gamma(D(+)-->K(S)K-pi(+)pi(+))/gamma(D(+)-->K(S)pi(+)pi(+)pi(-)) = 0.0768+/-0.0041+/-0.0032. We make the first observation of three new decay modes with branching ratios gamma(D(+)-->K(S)K+pi(+)pi(-))/gamma(D(+)-->K(S)pi(+)pi(+)pi(-)) = 0.0562+/-0.0039+/-0.0040, gamma(D(+)-->K(S)K+K-pi(+))/gamma(D(+)-->K(S)pi(+)pi(+)pi(-)) = 0.0077+/-0.0015+/-0.0009, and gamma(D(+)(s)-->K(S)K+pi(+)pi(-))/gamma(D(+)(s)-->K(S)K-pi(+)pi(+)) = 0.586+/-0.052+/-0.043, where in each case the first error is statistical and the second error is systematic.
Model-independent measurement of the CKM angle $\\gamma$ using $B^0 \\to D K^{\\ast 0}$ decays with $D \\to K_{S}^{0} \\pi^{+} \\pi^{-}$ and $K_{S}^{0} K^{+} K^{-}$

CERN Document Server

Aaij, Roel; Adeva, Bernardo; Adinolfi, Marco; Ajaltouni, Ziad; Akar, Simon; Albrecht, Johannes; Alessio, Federico; Alexander, Michael; Ali, Suvayu; Alkhazov, Georgy; Alvarez Cartelle, Paula; Alves Jr, Antonio Augusto; Amato, Sandra; Amerio, Silvia; Amhis, Yasmine; An, Liupan; Anderlini, Lucio; Andreassi, Guido; Andreotti, Mirco; Andrews, Jason; Appleby, Robert; Aquines Gutierrez, Osvaldo; Archilli, Flavio; d'Argent, Philippe; Artamonov, Alexander; Artuso, Marina; Aslanides, Elie; Auriemma, Giulio; Baalouch, Marouen; Bachmann, Sebastian; Back, John; Badalov, Alexey; Baesso, Clarissa; Baker, Sophie; Baldini, Wander; Barlow, Roger; Barschel, Colin; Barsuk, Sergey; Barter, William; Batozskaya, Varvara; Battista, Vincenzo; Bay, Aurelio; Beaucourt, Leo; Beddow, John; Bedeschi, Franco; Bediaga, Ignacio; Bel, Lennaert; Bellee, Violaine; Belloli, Nicoletta; Belyaev, Ivan; Ben-Haim, Eli; Bencivenni, Giovanni; Benson, Sean; Benton, Jack; Berezhnoy, Alexander; Bernet, Roland; Bertolin, Alessandro; Betti, Federico; Bettler, Marc-Olivier; van Beuzekom, Martinus; Bifani, Simone; Billoir, Pierre; Bird, Thomas; Birnkraut, Alex; Bizzeti, Andrea; Blake, Thomas; Blanc, Frédéric; Blouw, Johan; Blusk, Steven; Bocci, Valerio; Bondar, Alexander; Bondar, Nikolay; Bonivento, Walter; Borgheresi, Alessio; Borghi, Silvia; Borisyak, Maxim; Borsato, Martino; Boubdir, Meriem; Bowcock, Themistocles; Bowen, Espen Eie; Bozzi, Concezio; Braun, Svende; Britsch, Markward; Britton, Thomas; Brodzicka, Jolanta; Buchanan, Emma; Burr, Christopher; Bursche, Albert; Buytaert, Jan; Cadeddu, Sandro; Calabrese, Roberto; Calvi, Marta; Calvo Gomez, Miriam; Campana, Pierluigi; Campora Perez, Daniel; Capriotti, Lorenzo; Carbone, Angelo; Carboni, Giovanni; Cardinale, Roberta; Cardini, Alessandro; Carniti, Paolo; Carson, Laurence; Carvalho Akiba, Kazuyoshi; Casse, Gianluigi; Cassina, Lorenzo; Castillo Garcia, Lucia; Cattaneo, Marco; Cauet, Christophe; Cavallero, Giovanni; Cenci, Riccardo; Charles, Matthew; Charpentier, Philippe; Chatzikonstantinidis, Georgios; Chefdeville, Maximilien; Chen, Shanzhen; Cheung, Shu-Faye; Chobanova, Veronika; Chrzaszcz, Marcin; Cid Vidal, Xabier; Ciezarek, Gregory; Clarke, Peter; Clemencic, Marco; Cliff, Harry; Closier, Joel; Coco, Victor; Cogan, Julien; Cogneras, Eric; Cogoni, Violetta; Cojocariu, Lucian; Collazuol, Gianmaria; Collins, Paula; Comerma-Montells, Albert; Contu, Andrea; Cook, Andrew; Coquereau, Samuel; Corti, Gloria; Corvo, Marco; Couturier, Benjamin; Cowan, Greig; Craik, Daniel Charles; Crocombe, Andrew; Cruz Torres, Melissa Maria; Cunliffe, Samuel; Currie, Robert; D'Ambrosio, Carmelo; Dall'Occo, Elena; Dalseno, Jeremy; David, Pieter; Davis, Adam; De Aguiar Francisco, Oscar; De Bruyn, Kristof; De Capua, Stefano; De Cian, Michel; De Miranda, Jussara; De Paula, Leandro; De Simone, Patrizia; Dean, Cameron Thomas; Decamp, Daniel; Deckenhoff, Mirko; Del Buono, Luigi; Déléage, Nicolas; Demmer, Moritz; Derkach, Denis; Deschamps, Olivier; Dettori, Francesco; Dey, Biplab; Di Canto, Angelo; Dijkstra, Hans; Dordei, Francesca; Dorigo, Mirco; Dosil Suárez, Alvaro; Dovbnya, Anatoliy; Dreimanis, Karlis; Dufour, Laurent; Dujany, Giulio; Dungs, Kevin; Durante, Paolo; Dzhelyadin, Rustem; Dziurda, Agnieszka; Dzyuba, Alexey; Easo, Sajan; Egede, Ulrik; Egorychev, Victor; Eidelman, Semen; Eisenhardt, Stephan; Eitschberger, Ulrich; Ekelhof, Robert; Eklund, Lars; El Rifai, Ibrahim; Elsasser, Christian; Ely, Scott; Esen, Sevda; Evans, Hannah Mary; Evans, Timothy; Falabella, Antonio; Färber, Christian; Farley, Nathanael; Farry, Stephen; Fay, Robert; Fazzini, Davide; Ferguson, Dianne; Fernandez Albor, Victor; Ferrari, Fabio; Ferreira Rodrigues, Fernando; Ferro-Luzzi, Massimiliano; Filippov, Sergey; Fiore, Marco; Fiorini, Massimiliano; Firlej, Miroslaw; Fitzpatrick, Conor; Fiutowski, Tomasz; Fleuret, Frederic; Fohl, Klaus; Fontana, Marianna; Fontanelli, Flavio; Forshaw, Dean Charles; Forty, Roger; Frank, Markus; Frei, Christoph; Frosini, Maddalena; Fu, Jinlin; Furfaro, Emiliano; Gallas Torreira, Abraham; Galli, Domenico; Gallorini, Stefano; Gambetta, Silvia; Gandelman, Miriam; Gandini, Paolo; Gao, Yuanning; García Pardiñas, Julián; Garra Tico, Jordi; Garrido, Lluis; Garsed, Philip John; Gascon, David; Gaspar, Clara; Gavardi, Laura; Gazzoni, Giulio; Gerick, David; Gersabeck, Evelina; Gersabeck, Marco; Gershon, Timothy; Ghez, Philippe; Gianì, Sebastiana; Gibson, Valerie; Girard, Olivier Göran; Giubega, Lavinia-Helena; Gligorov, V.V.; Göbel, Carla; Golubkov, Dmitry; Golutvin, Andrey; Gomes, Alvaro; Gotti, Claudio; Grabalosa Gándara, Marc; Graciani Diaz, Ricardo; Granado Cardoso, Luis Alberto; Graugés, Eugeni; Graverini, Elena; Graziani, Giacomo; Grecu, Alexandru; Griffith, Peter; Grillo, Lucia; Grünberg, Oliver; Gushchin, Evgeny; Guz, Yury; Gys, Thierry; Hadavizadeh, Thomas; Hadjivasiliou, Christos; Haefeli, Guido; Haen, Christophe; Haines, Susan; Hall, Samuel; Hamilton, Brian; Han, Xiaoxue; Hansmann-Menzemer, Stephanie; Harnew, Neville; Harnew, Samuel; Harrison, Jonathan; He, Jibo; Head, Timothy; Heister, Arno; Hennessy, Karol; Henrard, Pierre; Henry, Louis; Hernando Morata, Jose Angel; van Herwijnen, Eric; Heß, Miriam; Hicheur, Adlène; Hill, Donal; Hoballah, Mostafa; Hombach, Christoph; Hongming, Li; Hulsbergen, Wouter; Humair, Thibaud; Hushchyn, Mikhail; Hussain, Nazim; Hutchcroft, David; Idzik, Marek; Ilten, Philip; Jacobsson, Richard; Jaeger, Andreas; Jalocha, Pawel; Jans, Eddy; Jawahery, Abolhassan; John, Malcolm; Johnson, Daniel; Jones, Christopher; Joram, Christian; Jost, Beat; Jurik, Nathan; Kandybei, Sergii; Kanso, Walaa; Karacson, Matthias; Karbach, Moritz; Karodia, Sarah; Kecke, Matthieu; Kelsey, Matthew; Kenyon, Ian; Kenzie, Matthew; Ketel, Tjeerd; Khairullin, Egor; Khanji, Basem; Khurewathanakul, Chitsanu; Kirn, Thomas; Klaver, Suzanne; Klimaszewski, Konrad; Kolpin, Michael; Komarov, Ilya; Koopman, Rose; Koppenburg, Patrick; Kozeiha, Mohamad; Kravchuk, Leonid; Kreplin, Katharina; Kreps, Michal; Krokovny, Pavel; Kruse, Florian; Krzemien, Wojciech; Kucewicz, Wojciech; Kucharczyk, Marcin; Kudryavtsev, Vasily; Kuonen, Axel Kevin; Kurek, Krzysztof; Kvaratskheliya, Tengiz; Lacarrere, Daniel; Lafferty, George; Lai, Adriano; Lambert, Dean; Lanfranchi, Gaia; Langenbruch, Christoph; Langhans, Benedikt; Latham, Thomas; Lazzeroni, Cristina; Le Gac, Renaud; van Leerdam, Jeroen; Lees, Jean-Pierre; Lefèvre, Regis; Leflat, Alexander; Lefrançois, Jacques; Lemos Cid, Edgar; Leroy, Olivier; Lesiak, Tadeusz; Leverington, Blake; Li, Yiming; Likhomanenko, Tatiana; Lindner, Rolf; Linn, Christian; Lionetto, Federica; Liu, Bo; Liu, Xuesong; Loh, David; Longstaff, Iain; Lopes, Jose; Lucchesi, Donatella; Lucio Martinez, Miriam; Luo, Haofei; Lupato, Anna; Luppi, Eleonora; Lupton, Oliver; Lusardi, Nicola; Lusiani, Alberto; Lyu, Xiao-Rui; Machefert, Frederic; Maciuc, Florin; Maev, Oleg; Maguire, Kevin; Malde, Sneha; Malinin, Alexander; Manca, Giulia; Mancinelli, Giampiero; Manning, Peter Michael; Mapelli, Alessandro; Maratas, Jan; Marchand, Jean François; Marconi, Umberto; Marin Benito, Carla; Marino, Pietro; Marks, Jörg; Martellotti, Giuseppe; Martin, Morgan; Martinelli, Maurizio; Martinez Santos, Diego; Martinez Vidal, Fernando; Martins Tostes, Danielle; Massacrier, Laure Marie; Massafferri, André; Matev, Rosen; Mathad, Abhijit; Mathe, Zoltan; Matteuzzi, Clara; Mauri, Andrea; Maurin, Brice; Mazurov, Alexander; McCann, Michael; McCarthy, James; McNab, Andrew; McNulty, Ronan; Meadows, Brian; Meier, Frank; Meissner, Marco; Melnychuk, Dmytro; Merk, Marcel; Merli, Andrea; Michielin, Emanuele; Milanes, Diego Alejandro; Minard, Marie-Noelle; Mitzel, Dominik Stefan; Molina Rodriguez, Josue; Monroy, Ignacio Alberto; Monteil, Stephane; Morandin, Mauro; Morawski, Piotr; Mordà, Alessandro; Morello, Michael Joseph; Moron, Jakub; Morris, Adam Benjamin; Mountain, Raymond; Muheim, Franz; Müller, Dominik; Müller, Janine; Müller, Katharina; Müller, Vanessa; Mussini, Manuel; Muster, Bastien; Naik, Paras; Nakada, Tatsuya; Nandakumar, Raja; Nandi, Anita; Nasteva, Irina; Needham, Matthew; Neri, Nicola; Neubert, Sebastian; Neufeld, Niko; Neuner, Max; Nguyen, Anh Duc; Nguyen-Mau, Chung; Niess, Valentin; Nieswand, Simon; Niet, Ramon; Nikitin, Nikolay; Nikodem, Thomas; Novoselov, Alexey; O'Hanlon, Daniel Patrick; Oblakowska-Mucha, Agnieszka; Obraztsov, Vladimir; Ogilvy, Stephen; Okhrimenko, Oleksandr; Oldeman, Rudolf; Onderwater, Gerco; Osorio Rodrigues, Bruno; Otalora Goicochea, Juan Martin; Otto, Adam; Owen, Patrick; Oyanguren, Maria Aranzazu; Palano, Antimo; Palombo, Fernando; Palutan, Matteo; Panman, Jacob; Papanestis, Antonios; Pappagallo, Marco; Pappalardo, Luciano; Pappenheimer, Cheryl; Parker, William; Parkes, Christopher; Passaleva, Giovanni; Patel, Girish; Patel, Mitesh; Patrignani, Claudia; Pearce, Alex; Pellegrino, Antonio; Penso, Gianni; Pepe Altarelli, Monica; Perazzini, Stefano; Perret, Pascal; Pescatore, Luca; Petridis, Konstantinos; Petrolini, Alessandro; Petruzzo, Marco; Picatoste Olloqui, Eduardo; Pietrzyk, Boleslaw; Pikies, Malgorzata; Pinci, Davide; Pistone, Alessandro; Piucci, Alessio; Playfer, Stephen; Plo Casasus, Maximo; Poikela, Tuomas; Polci, Francesco; Poluektov, Anton; Polyakov, Ivan; Polycarpo, Erica; Popov, Alexander; Popov, Dmitry; Popovici, Bogdan; Potterat, Cédric; Price, Eugenia; Price, Joseph David; Prisciandaro, Jessica; Pritchard, Adrian; Prouve, Claire; Pugatch, Valery; Puig Navarro, Albert; Punzi, Giovanni; Qian, Wenbin; Quagliani, Renato; Rachwal, Bartolomiej; Rademacker, Jonas; Rama, Matteo; Ramos Pernas, Miguel; Rangel, Murilo; Raniuk, Iurii; Raven, Gerhard; Redi, Federico; Reichert, Stefanie; dos Reis, Alberto; Renaudin, Victor; Ricciardi, Stefania; Richards, Sophie; Rihl, Mariana; Rinnert, Kurt; Rives Molina, Vincente; Robbe, Patrick; Rodrigues, Ana Barbara; Rodrigues, Eduardo; Rodriguez Lopez, Jairo Alexis; Rodriguez Perez, Pablo; Rogozhnikov, Alexey; Roiser, Stefan; Romanovsky, Vladimir; Romero Vidal, Antonio; Ronayne, John William; Rotondo, Marcello; Ruf, Thomas; Ruiz Valls, Pablo; Saborido Silva, Juan Jose; Sagidova, Naylya; Saitta, Biagio; Salustino Guimaraes, Valdir; Sanchez Mayordomo, Carlos; Sanmartin Sedes, Brais; Santacesaria, Roberta; Santamarina Rios, Cibran; Santimaria, Marco; Santovetti, Emanuele; Sarti, Alessio; Satriano, Celestina; Satta, Alessia; Saunders, Daniel Martin; Savrina, Darya; Schael, Stefan; Schiller, Manuel; Schindler, Heinrich; Schlupp, Maximilian; Schmelling, Michael; Schmelzer, Timon; Schmidt, Burkhard; Schneider, Olivier; Schopper, Andreas; Schubiger, Maxime; Schune, Marie Helene; Schwemmer, Rainer; Sciascia, Barbara; Sciubba, Adalberto; Semennikov, Alexander; Sergi, Antonino; Serra, Nicola; Serrano, Justine; Sestini, Lorenzo; Seyfert, Paul; Shapkin, Mikhail; Shapoval, Illya; Shcheglov, Yury; Shears, Tara; Shekhtman, Lev; Shevchenko, Vladimir; Shires, Alexander; Siddi, Benedetto Gianluca; Silva Coutinho, Rafael; Silva de Oliveira, Luiz Gustavo; Simi, Gabriele; Sirendi, Marek; Skidmore, Nicola; Skwarnicki, Tomasz; Smith, Eluned; Smith, Iwan Thomas; Smith, Jackson; Smith, Mark; Snoek, Hella; Sokoloff, Michael; Soler, Paul; Soomro, Fatima; Souza, Daniel; Souza De Paula, Bruno; Spaan, Bernhard; Spradlin, Patrick; Sridharan, Srikanth; Stagni, Federico; Stahl, Marian; Stahl, Sascha; Stefkova, Slavomira; Steinkamp, Olaf; Stenyakin, Oleg; Stevenson, Scott; Stoica, Sabin; Stone, Sheldon; Storaci, Barbara; Stracka, Simone; Straticiuc, Mihai; Straumann, Ulrich; Sun, Liang; Sutcliffe, William; Swientek, Krzysztof; Swientek, Stefan; Syropoulos, Vasileios; Szczekowski, Marek; Szumlak, Tomasz; T'Jampens, Stephane; Tayduganov, Andrey; Tekampe, Tobias; Tellarini, Giulia; Teubert, Frederic; Thomas, Christopher; Thomas, Eric; van Tilburg, Jeroen; Tisserand, Vincent; Tobin, Mark; Tolk, Siim; Tomassetti, Luca; Tonelli, Diego; Topp-Joergensen, Stig; Tournefier, Edwige; Tourneur, Stephane; Trabelsi, Karim; Traill, Murdo; Tran, Minh Tâm; Tresch, Marco; Trisovic, Ana; Tsaregorodtsev, Andrei; Tsopelas, Panagiotis; Tuning, Niels; Ukleja, Artur; Ustyuzhanin, Andrey; Uwer, Ulrich; Vacca, Claudia; Vagnoni, Vincenzo; Valat, Sebastien; Valenti, Giovanni; Vallier, Alexis; Vazquez Gomez, Ricardo; Vazquez Regueiro, Pablo; Vázquez Sierra, Carlos; Vecchi, Stefania; van Veghel, Maarten; Velthuis, Jaap; Veltri, Michele; Veneziano, Giovanni; Vesterinen, Mika; Viaud, Benoit; Vieira, Daniel; Vieites Diaz, Maria; Vilasis-Cardona, Xavier; Volkov, Vladimir; Vollhardt, Achim; Voong, David; Vorobyev, Alexey; Vorobyev, Vitaly; Voß, Christian; de Vries, Jacco; Waldi, Roland; Wallace, Charlotte; Wallace, Ronan; Walsh, John; Wang, Jianchun; Ward, David; Watson, Nigel; Websdale, David; Weiden, Andreas; Whitehead, Mark; Wicht, Jean; Wilkinson, Guy; Wilkinson, Michael; Williams, Mark Richard James; Williams, Matthew; Williams, Mike; Williams, Timothy; Wilson, Fergus; Wimberley, Jack; Wishahi, Julian; Wislicki, Wojciech; Witek, Mariusz; Wormser, Guy; Wotton, Stephen; Wraight, Kenneth; Wright, Simon; Wyllie, Kenneth; Xie, Yuehong; Xu, Zhirui; Yang, Zhenwei; Yin, Hang; Yu, Jiesheng; Yuan, Xuhao; Yushchenko, Oleg; Zangoli, Maria; Zavertyaev, Mikhail; Zhang, Liming; Zhang, Yanxi; Zhelezov, Alexey; Zheng, Yangheng; Zhokhov, Anatoly; Zhong, Liang; Zhukov, Valery; Zucchelli, Stefano

2016-06-21

A binned Dalitz plot analysis of the decays $B^0 \\to D K^{\\ast 0}$, with $D \\to K_{S}^{0} \\pi^{+} \\pi^{-}$ and $D \\to K_{S}^{0} K^{+} K^{-}$, is performed to measure the observables $x_\\pm$ and $y_\\pm$, which are related to the CKM angle $\\gamma$ and the hadronic parameters of the decays. The $D$ decay strong phase variation over the Dalitz plot is taken from measurements performed at the CLEO-c experiment, making the analysis independent of the $D$ decay model. With a sample of proton-proton collision data, corresponding to an integrated luminosity of $3.0\\,\\rm{fb}^{-1}$, collected by the LHCb experiment, the values of the $CP$ violation parameters are found to be $x_+ = 0.05 \\pm 0.35 \\pm 0.02$, $x_-=-0.31\\pm 0.20 \\pm 0.04$, $y_+=-0.81\\pm 0.28\\pm 0.06$ and $y_-=0.31\\pm 0.21 \\pm 0.05$, where the first uncertainties are statistical and the second systematic. These observables correspond to values $\\gamma$ = $(71 \\pm 20)^\\circ$, $r_{B^0} = 0.56\\pm 0.17$ and $\\delta_{B^0} = (204\\,^{+21}_{-20})^\\circ$. The parame...
Handling of UF6 in U.S. gaseous diffusion plants

International Nuclear Information System (INIS)

Legeay, A.J.

1978-01-01

A comprehensive systems analysis of UF 6 handling has been made in the three U.S. gaseous diffusion plants and has resulted in a significant impact on the equipment design and the operating procedures of these facilities. The equipment, facilities, and industrial practices in UF 6 handling operations as they existed in the early 1970's are reviewed with particular emphasis placed on the changes which have been implemented. The changes were applied to the systems and operating methods which evolved from the design, startup, and operation of the Oak Ridge Gaseous Diffusion Plant in 1945
Tris(dibenzoylmethanido-κ2O,O′[(6S,8S-(+-7,7-dimethyl-3-(2-pyridyl-5,6,7,8-tetrahydro-6,8-methanoisoquinoline-κ2N,N′]gadolinium(III

Directory of Open Access Journals (Sweden)

Xi-Li Li

2009-09-01

Full Text Available In the title compound, [Gd(C15H11O23(C17H18N2], the GdIII atom is coordinated by six O atoms from three β-diketonate ligands and two N atoms from a chiral ligand LS,S-(+-7,7-dimethyl-3-(2-pyridyl-5,6,7,8-tetrahydro-6,8-methanoisoquinoline, in a coordination geometry best described as distorted square-antiprismatic.
Soluble interleukin 6 receptor (sIL-6R) mediates colonic tumor cell adherence to the vascular endothelium: a mechanism for metastatic initiation?

LENUS (Irish Health Repository)

Dowdall, J F

2012-02-03

The mechanisms by which surgery increases metastatic proliferation remain poorly characterized, although endotoxin and immunocytes play a role. Recent evidence suggests that endothelial adherence of tumor cells may be important in the formation of metastases. Soluble receptors of interleukin-6 (sIL-6R) shed by activated neutrophils exert IL-6 effects on endothelial cells, which are unresponsive under normal circumstances. This study examined the hypothesis that sIL-6R released by surgical stress increases tumor cell adherence to the endothelium. Neutrophils (PMN) were stimulated with lipopolysaccharide, C-reactive protein (CRP), and tumor necrosis factor-alpha. Soluble IL-6R release was measured by enzyme-linked immunosorbent assay. Colonic tumor cells transfected with green fluorescent protein and endothelial cells were exposed to sIL-6R, and tumor cell adherence and transmigration were measured by fluorescence microscopy. Basal release of sIL-6R from PMN was 44.7 +\\/- 8.2 pg\\/ml at 60 min. This was significantly increased by endotoxin and CRP (131 +\\/- 16.8 and 84.1 +\\/- 5.3, respectively; both P < 0.05). However, tumor necrosis factor-alpha did not significantly alter sIL-6R release. Endothelial and tumor cell exposure to sIL-6R increased tumor cell adherence by 71.3% within 2 h but did not significantly increase transmigration, even at 6 h. Mediators of surgical stress induce neutrophil release of a soluble receptor for IL-6 that enhances colon cancer cell endothelial adherence. Since adherence to the endothelium is now considered to be a key event in metastatic genesis, these findings have important implications for colon cancer treatment strategies.
Neutron scattering studies of the coexistence of long-range magnetic order and superconductivity in Dy12Mo6S8 and Tb12Mo6S8

International Nuclear Information System (INIS)

Thomlinson, W.; Shirane, G.; Moncton, D.E.; Ishikawa, M.; Fischer, O.

1978-10-01

Both Dy 1 2 Mo 6 S 8 and Tb 1 2 Mo 6 S 8 are superconducting below T/sub c/ = 2.05 K. Neutron scattering studies show that these compounds in zero applied magnetic field develop long-range antiferromagnetic order (greater than 300 A) at T/sub M/ = 0.4 K and T/sub M/ = 1.0 K, respectively, which does not destroy the superconducting state. Magnetization measurements at temperatures below T/sub M/ suggest the development of ferromagnetic order as the applied magnetic field increases. In the case of Tb 1 2 Mo 6 S 8 the neutron data show long-range ferromagnetic order developing for H greater than or equal to H/sub c2/ = 1.9 kOe where H/sub c2/ is the upper critical field for superconductivity. However, for Dy 1 2 Mo 6 S 8 long-range ferromagnetic order begins to develop at H = 200 Oe, a field much less than H/sub c2/ = 1.2 kOe. As the ferromagnetic intensity increases, the antiferromagnetic intensity decreases. Between H = 200 Oe and H = 1.2 kOe both ferromagnetic and antiferromagnetic order occur with the sample in the superconducting state
Symmetric group: Algebraic formulas for some S/sub f/ 6j symbols and S/sub f/containsS/sub f/1 x S/sub f/2 3jm symbols

International Nuclear Information System (INIS)

Haase, R.W.; Dirl, R.

1986-01-01

Explicit rank-dependent expressions have been obtained for some symmetric group (S/sub f/) 6j symbols and some S/sub f/containsS/sub f/ 1 x S/sub f/ 2 3jm symbols using Butler's recursion method. A key point in deriving these results is the use of the reduced notation introduced by Murnaghan to label irreps. Various symmetries of the 6j and 3jm symbols have been imposed. These include the complex conjugation, permutation, and transpose conjugation. We incorporate a new symmetry that arises from the occurrence of the two isomorphic direct product groups S/sub f/ 1 x S/sub f/ 2 and S/sub f/ 2 x S/sub f/ 1 as subgroups of S/sub f/. In relation to the tables of 6j and 3jm symbols presented, a discussion is given of the symmetric group-unitary group duality
Beam-Energy Dependence of Directed Flow of Λ, Λ[over ¯], K^{±}, K_{s}^{0}, and ϕ in Au+Au Collisions.

Science.gov (United States)

Adamczyk, L; Adams, J R; Adkins, J K; Agakishiev, G; Aggarwal, M M; Ahammed, Z; Ajitanand, N N; Alekseev, I; Anderson, D M; Aoyama, R; Aparin, A; Arkhipkin, D; Aschenauer, E C; Ashraf, M U; Attri, A; Averichev, G S; Bai, X; Bairathi, V; Barish, K; Behera, A; Bellwied, R; Bhasin, A; Bhati, A K; Bhattarai, P; Bielcik, J; Bielcikova, J; Bland, L C; Bordyuzhin, I G; Bouchet, J; Brandenburg, J D; Brandin, A V; Brown, D; Bunzarov, I; Butterworth, J; Caines, H; Calderón de la Barca Sánchez, M; Campbell, J M; Cebra, D; Chakaberia, I; Chaloupka, P; Chang, Z; Chankova-Bunzarova, N; Chatterjee, A; Chattopadhyay, S; Chen, X; Chen, J H; Chen, X; Cheng, J; Cherney, M; Christie, W; Contin, G; Crawford, H J; Das, S; De Silva, L C; Dedovich, T G; Deng, J; Derevschikov, A A; Didenko, L; Dilks, C; Dong, X; Drachenberg, J L; Draper, J E; Dunkelberger, L E; Dunlop, J C; Efimov, L G; Elsey, N; Engelage, J; Eppley, G; Esha, R; Esumi, S; Evdokimov, O; Ewigleben, J; Eyser, O; Fatemi, R; Fazio, S; Federic, P; Federicova, P; Fedorisin, J; Feng, Z; Filip, P; Finch, E; Fisyak, Y; Flores, C E; Fujita, J; Fulek, L; Gagliardi, C A; Garand, D; Geurts, F; Gibson, A; Girard, M; Grosnick, D; Gunarathne, D S; Guo, Y; Gupta, A; Gupta, S; Guryn, W; Hamad, A I; Hamed, A; Harlenderova, A; Harris, J W; He, L; Heppelmann, S; Heppelmann, S; Hirsch, A; Horvat, S; Huang, X; Huang, B; Huang, T; Huang, H Z; Humanic, T J; Huo, P; Igo, G; Jacobs, W W; Jentsch, A; Jia, J; Jiang, K; Jowzaee, S; Judd, E G; Kabana, S; Kalinkin, D; Kang, K; Kapukchyan, D; Kauder, K; Ke, H W; Keane, D; Kechechyan, A; Khan, Z; Kikoła, D P; Kim, C; Kisel, I; Kisiel, A; Kochenda, L; Kocmanek, M; Kollegger, T; Kosarzewski, L K; Kraishan, A F; Krauth, L; Kravtsov, P; Krueger, K; Kulathunga, N; Kumar, L; Kvapil, J; Kwasizur, J H; Lacey, R; Landgraf, J M; Landry, K D; Lauret, J; Lebedev, A; Lednicky, R; Lee, J H; Li, C; Li, X; Li, Y; Li, W; Lidrych, J; Lin, T; Lisa, M A; Liu, P; Liu, H; Liu, Y; Liu, F; Ljubicic, T; Llope, W J; Lomnitz, M; Longacre, R S; Luo, S; Luo, X; Ma, Y G; Ma, L; Ma, R; Ma, G L; Magdy, N; Majka, R; Mallick, D; Margetis, S; Markert, C; Matis, H S; Meehan, K; Mei, J C; Miller, Z W; Minaev, N G; Mioduszewski, S; Mishra, D; Mizuno, S; Mohanty, B; Mondal, M M; Morozov, D A; Mustafa, M K; Nasim, Md; Nayak, T K; Nelson, J M; Nie, M; Nigmatkulov, G; Niida, T; Nogach, L V; Nonaka, T; Nurushev, S B; Odyniec, G; Ogawa, A; Oh, K; Okorokov, V A; Olvitt, D; Page, B S; Pak, R; Pandit, Y; Panebratsev, Y; Pawlik, B; Pei, H; Perkins, C; Pile, P; Pluta, J; Poniatowska, K; Porter, J; Posik, M; Pruthi, N K; Przybycien, M; Putschke, J; Qiu, H; Quintero, A; Ramachandran, S; Ray, R L; Reed, R; Rehbein, M J; Ritter, H G; Roberts, J B; Rogachevskiy, O V; Romero, J L; Roth, J D; Ruan, L; Rusnak, J; Rusnakova, O; Sahoo, N R; Sahu, P K; Salur, S; Sandweiss, J; Saur, M; Schambach, J; Schmah, A M; Schmidke, W B; Schmitz, N; Schweid, B R; Seger, J; Sergeeva, M; Seto, R; Seyboth, P; Shah, N; Shahaliev, E; Shanmuganathan, P V; Shao, M; Sharma, A; Sharma, M K; Shen, W Q; Shi, S S; Shi, Z; Shou, Q Y; Sichtermann, E P; Sikora, R; Simko, M; Singha, S; Skoby, M J; Smirnov, N; Smirnov, D; Solyst, W; Song, L; Sorensen, P; Spinka, H M; Srivastava, B; Stanislaus, T D S; Strikhanov, M; Stringfellow, B; Suaide, A A P; Sugiura, T; Sumbera, M; Summa, B; Sun, Y; Sun, X M; Sun, X; Surrow, B; Svirida, D N; Tang, Z; Tang, A H; Taranenko, A; Tarnowsky, T; Tawfik, A; Thäder, J; Thomas, J H; Timmins, A R; Tlusty, D; Todoroki, T; Tokarev, M; Trentalange, S; Tribble, R E; Tribedy, P; Tripathy, S K; Trzeciak, B A; Tsai, O D; Ullrich, T; Underwood, D G; Upsal, I; Van Buren, G; van Nieuwenhuizen, G; Vasiliev, A N; Videbæk, F; Vokal, S; Voloshin, S A; Vossen, A; Wang, G; Wang, Y; Wang, F; Wang, Y; Webb, J C; Webb, G; Wen, L; Westfall, G D; Wieman, H; Wissink, S W; Witt, R; Wu, Y; Xiao, Z G; Xie, G; Xie, W; Xu, J; Xu, Z; Xu, Q H; Xu, Y F; Xu, N; Yang, S; Yang, Y; Yang, C; Yang, Q; Ye, Z; Ye, Z; Yi, L; Yip, K; Yoo, I-K; Yu, N; Zbroszczyk, H; Zha, W; Zhang, Z; Zhang, J B; Zhang, J; Zhang, S; Zhang, Y; Zhang, X P; Zhang, J; Zhang, S; Zhao, J; Zhong, C; Zhou, C; Zhou, L; Zhu, X; Zhu, Z; Zyzak, M

2018-02-09

Rapidity-odd directed-flow measurements at midrapidity are presented for Λ, Λ[over ¯], K^{±}, K_{s}^{0}, and ϕ at sqrt[s_{NN}]=7.7, 11.5, 14.5, 19.6, 27, 39, 62.4, and 200 GeV in Au+Au collisions recorded by the Solenoidal Tracker detector at the Relativistic Heavy Ion Collider. These measurements greatly expand the scope of data available to constrain models with differing prescriptions for the equation of state of quantum chromodynamics. Results show good sensitivity for testing a picture where flow is assumed to be imposed before hadron formation and the observed particles are assumed to form via coalescence of constituent quarks. The pattern of departure from a coalescence-inspired sum rule can be a valuable new tool for probing the collision dynamics.
Voltage profile, structural prediction, and electronic calculations for MgxMo6S8

CSIR Research Space (South Africa)

Kganyago, KR

2003-03-01

Full Text Available the binary Mo6S8 and MgAMo6S8 ~see Table III!, the Mo-Mo distances decrease by (0.521)%. This decrease corresponds to an an- isotropic contraction of the Mo6 octahedron. The Mo cluster of the rhombohedral compounds forms an elongated octahe- dron of symmetry...
AIDS Kaposi sarcoma-derived cells produce and respond to interleukin 6

International Nuclear Information System (INIS)

Miles, S.A.; Rezai, A.R.; Salazar-Gonzalez, J.F.; Meyden, M.V.; Stevens, R.H.; Mitsuyasu, R.T.; Martinez-Maza, O.; Logan, D.M.; Taga, Tetsuya; Hirano, Toshio; Kishimoto, Tadamitsu

1990-01-01

Cell lines derived from Kaposi sarcoma lesions of patients with AIDS (AIDS-KS cells) produce several cytokines, including an endothelial cell growth factor, interleukin 1β, and basic fibroblast growth factor. Since exposure to human immunodeficiency virus increases interleukin 6 (IL-6) production in monocytes and endothelial cells produce IL-6, the authors examined IL-6 expression and response in AIDS-KS cell lines and IL-6 expression in AIDS Kaposi sarcoma tissue. The AIDS-KS cell lines (N521J and EKS3) secreted large amounts of immunoreactive and biologically active IL-6. The authors found both IL-6 and IL-6 receptor (IL-6-R) RNA by slot blot hybridization analysis of AIDS-KS cells. The IL-6-R was functional, as [ 3 H]thymidine incorporation by AIDS-KS cells increased significantly after exposure to human recombinant IL-6 (hrIL-6) at >10 units/ml. When AIDS-KS cells (EKS3) were exposed to IL-6 antisense oligonucleotide, cellular proliferation decreased by nearly two-thirds, with a corresponding decrease in the production of IL-6. These results show that both IL-6 and IL-6-R are produced by AIDS-KS cells and that IL-6 is required for optimal AIDS-KS cell proliferation, and they suggest that IL-6 is an autocrine growth factor for AIDS-KS cells
S6K1 Is Required for Increasing Skeletal Muscle Force during Hypertrophy.

Science.gov (United States)

Marabita, Manuela; Baraldo, Martina; Solagna, Francesca; Ceelen, Judith Johanna Maria; Sartori, Roberta; Nolte, Hendrik; Nemazanyy, Ivan; Pyronnet, Stéphane; Kruger, Marcus; Pende, Mario; Blaauw, Bert

2016-10-04

Loss of skeletal muscle mass and force aggravates age-related sarcopenia and numerous pathologies, such as cancer and diabetes. The AKT-mTORC1 pathway plays a major role in stimulating adult muscle growth; however, the functional role of its downstream mediators in vivo is unknown. Here, we show that simultaneous inhibition of mTOR signaling to both S6K1 and 4E-BP1 is sufficient to reduce AKT-induced muscle growth and render it insensitive to the mTORC1-inhibitor rapamycin. Surprisingly, lack of mTOR signaling to 4E-BP1 only, or deletion of S6K1 alone, is not sufficient to reduce muscle hypertrophy or alter its sensitivity to rapamycin. However, we report that, while not required for muscle growth, S6K1 is essential for maintaining muscle structure and force production. Hypertrophy in the absence of S6K1 is characterized by compromised ribosome biogenesis and the formation of p62-positive protein aggregates. These findings identify S6K1 as a crucial player for maintaining muscle function during hypertrophy. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.
The effects of sulfur intercalation on the optical properties of artificial 'hackmanite', Na8[Al6Si6O24]Cl1.8S0.1; 'sulfosodalite', Na8[Al6Si6O24]S; and natural tugtupite, Na8

DEFF Research Database (Denmark)

Warner, Terence Edwin; Hutzen Andersen, Jan

2012-01-01

.8S0.1 destroys the tenebrescence and induces a permanently pale blue and, at higher temperature, a pale green coloration. The effect on Na8[Al6Si6O24]S induced similar colorations but of a deeper hue. Annealing tugtupite, Na8[Be2Al2Si8O24](Cl,S)2-x under a sulfur atmosphere over the range 600-700 °C......, destroyed the tenebrescence and resulted in a colourless tugtupite; but did not effect the photoluminescence. This suggests that the chemical species responsible for the tenebrescence in tugtupite is unlikely to be the same as that for the luminescence....
Involvement of S6K1 in mitochondria function and structure in HeLa cells.

Science.gov (United States)

Park, Jisoo; Tran, Quangdon; Mun, Kisun; Masuda, Kouhei; Kwon, So Hee; Kim, Seon-Hwan; Kim, Dong-Hoon; Thomas, George; Park, Jongsun

2016-12-01

The major biological function of mitochondria is to generate cellular energy through oxidative phosphorylation. Apart from cellular respiration, mitochondria also play a key role in signaling processes, including aging and cancer metabolism. It has been shown that S6K1-knockout mice are resistant to obesity due to enhanced beta-oxidation, with an increased number of large mitochondria. Therefore, in this report, the possible involvement of S6K1 in regulating mitochondria dynamics and function has been investigated in stable lenti-shS6K1-HeLa cells. Interestingly, S6K1-stably depleted HeLa cells showed phenotypical changes in mitochondria morphology. This observation was further confirmed by detailed image analysis of mitochondria shape. Corresponding molecular changes were also observed in these cells, such as the induction of mitochondrial fission proteins (Drp1 and Fis1). Oxygen consumption is elevated in S6K1-depeleted HeLa cells and FL5.12 cells. In addition, S6K1 depletion leads to enhancement of ATP production in cytoplasm and mitochondria. However, the relative ratio of mitochondrial ATP to cytoplasmic ATP is actually decreased in lenti-shS6K1-HeLa cells compared to control cells. Lastly, induction of mitophagy was found in lenti-shS6K1-HeLa cells with corresponding changes of mitochondria shape on electron microscope analysis. Taken together, our results indicate that S6K1 is involved in the regulation of mitochondria morphology and function in HeLa cells. This study will provide novel insights into S6K1 function in mitochondria-mediated cellular signaling. Copyright © 2016 Elsevier Inc. All rights reserved.

Optical frequency measurements of 6s 2S1/2-6p 2P3/2 transition in a 133Cs atomic beam using a femtosecond laser frequency comb

International Nuclear Information System (INIS)

Gerginov, V.; Tanner, C.E.; Diddams, S.; Bartels, A.; Hollberg, L.

2004-01-01

Optical frequencies of the hyperfine components of the D 2 line in 133 Cs are determined using high-resolution spectroscopy and a femtosecond laser frequency comb. A narrow-linewidth probe laser excites the 6s 2 S 1/2 (F=3,4)→6p 2 P 3/2 (F=2,3,4,5) transition in a highly collimated atomic beam. Fluorescence spectra are taken by scanning the laser frequency over the excited-state hyperfine structure. The laser optical frequency is referenced to a Cs fountain clock via a reference laser and a femtosecond laser frequency comb. A retroreflected laser beam is used to estimate and minimize the Doppler shift due to misalignment between the probe laser and the atomic beam. We achieve an angular resolution on the order of 5x10 -6 rad. The final uncertainties (∼±5 kHz) in the frequencies of the optical transitions are a factor of 20 better than previous results [T. Udem et al., Phys. Rev. A 62, 031801 (2000).]. We find the centroid of the 6s 2 S 1/2 →6p 2 P 3/2 transition to be f D2 =351 725 718.4744(51) MHz
Evolutionary conservation of nuclear and nucleolar targeting sequences in yeast ribosomal protein S6A

International Nuclear Information System (INIS)

Lipsius, Edgar; Walter, Korden; Leicher, Torsten; Phlippen, Wolfgang; Bisotti, Marc-Angelo; Kruppa, Joachim

2005-01-01

Over 1 billion years ago, the animal kingdom diverged from the fungi. Nevertheless, a high sequence homology of 62% exists between human ribosomal protein S6 and S6A of Saccharomyces cerevisiae. To investigate whether this similarity in primary structure is mirrored in corresponding functional protein domains, the nuclear and nucleolar targeting signals were delineated in yeast S6A and compared to the known human S6 signals. The complete sequence of S6A and cDNA fragments was fused to the 5'-end of the LacZ gene, the constructs were transiently expressed in COS cells, and the subcellular localization of the fusion proteins was detected by indirect immunofluorescence. One bipartite and two monopartite nuclear localization signals as well as two nucleolar binding domains were identified in yeast S6A, which are located at homologous regions in human S6 protein. Remarkably, the number, nature, and position of these targeting signals have been conserved, albeit their amino acid sequences have presumably undergone a process of co-evolution with their corresponding rRNAs
Downstream of tyrosine kinase/docking protein 6, as a novel substrate of tropomyosin-related kinase C receptor, is involved in neurotrophin 3-mediated neurite outgrowth in mouse cortex neurons

Directory of Open Access Journals (Sweden)

Yuan Jian

2010-06-01

Full Text Available Abstract Background The downstream of tyrosine kinase/docking protein (Dok adaptor protein family has seven members, Dok1 to Dok7, that act as substrates of multiple receptor tyrosine kinase and non-receptor tyrosine kinase. The tropomyosin-related kinase (Trk receptor family, which has three members (TrkA, TrkB and TrkC, are receptor tyrosine kinases that play pivotal roles in many stages of nervous system development, such as differentiation, migration, axon and dendrite projection and neuron patterning. Upon related neurotrophin growth factor stimulation, dimerisation and autophosphorylation of Trk receptors can occur, recruiting adaptor proteins to mediate signal transduction. Results In this report, by using yeast two-hybrid assays, glutathione S-transferase (GST precipitation assays and coimmunoprecipitation (Co-IP experiments, we demonstrate that Dok6 selectively binds to the NPQY motif of TrkC through its phosphotyrosine-binding (PTB domain in a kinase activity-dependent manner. We further confirmed their interaction by coimmunoprecipitation and colocalisation in E18.5 mouse cortex neurons, which provided more in vivo evidence. Next, we demonstrated that Dok6 is involved in neurite outgrowth in mouse cortex neurons via the RNAi method. Knockdown of Dok6 decreased neurite outgrowth in cortical neurons upon neurotrophin 3 (NT-3 stimulation. Conclusions We conclude that Dok6 interacts with the NPQY motif of the TrkC receptor through its PTB domain in a kinase activity-dependent manner, and works as a novel substrate of the TrkC receptor involved in NT-3-mediated neurite outgrowth in mouse cortex neurons.
Measuring KS0K± interactions using Pb–Pb collisions at sNN=2.76 TeV

Directory of Open Access Journals (Sweden)

S. Acharya

2017-11-01

Full Text Available We present the first ever measurements of femtoscopic correlations between the KS0 and K± particles. The analysis was performed on the data from Pb–Pb collisions at sNN=2.76 TeV measured by the ALICE experiment. The observed femtoscopic correlations are consistent with final-state interactions proceeding via the a0(980 resonance. The extracted kaon source radius and correlation strength parameters for KS0K− are found to be equal within the experimental uncertainties to those for KS0K+. Comparing the results of the present study with those from published identical-kaon femtoscopic studies by ALICE, mass and coupling parameters for the a0 resonance are tested. Our results are also compatible with the interpretation of the a0 having a tetraquark structure instead of that of a diquark.
Supersymmetric AdS6 solutions of type IIB supergravity

International Nuclear Information System (INIS)

Kim, Hyojoong; Kim, Nakwoo; Suh, Minwoo

2015-01-01

We study the general requirement for supersymmetric AdS 6 solutions in type IIB supergravity. We employ the Killing spinor technique and study the differential and algebraic relations among various Killing spinor bilinears to find the canonical form of the solutions. Our result agrees precisely with the work of Apruzzi et al. (JHEP 1411:099, 2014), which used the pure spinor technique. Hoping to identify the geometry of the problem, we also computed four-dimensional theory through the dimensional reduction of type IIB supergravity on AdS 6 . This effective action is essentially a non-linear sigma model with five scalar fields parametrizing SL(3,ℝ)/SO(2,1), modified by a scalar potential and coupled to Einstein gravity in Euclidean signature. We argue that the scalar potential can be explained by a subgroup CSO(1,1,1) ⊂SL(3,ℝ) in a way analogous to gauged supergravity
Mice deficient in ribosomal protein S6 phosphorylation suffer from muscle weakness that reflects a growth defect and energy deficit.

Directory of Open Access Journals (Sweden)

Igor Ruvinsky

role has been assigned for ribosomal protein S6 kinase 1, even though it regulates myoblast growth in an rpS6 phosphorylation-independent fashion.
Phosphorylation of mTOR and S6RP predicts the efficacy of everolimus in patients with metastatic renal cell carcinoma

International Nuclear Information System (INIS)

Li, Siming; Kong, Yan; Si, Lu; Chi, Zhihong; Cui, Chuanliang; Sheng, Xinan; Guo, Jun

2014-01-01

The incidence of renal cell cancer (RCC) has been increasing for the past decade, and the 5-year survival for patients with metastatic RCC (mRCC) is rather low. Everolimus (RAD001), a new inhibitor for mammalian target of rapamycin (mTOR), is generally well tolerated, and demonstrates clinical benefit to patients with anti-VEGF-refractory mRCC. However, factors for selection of patients who may benefit from everolimus remain largely unknown. Here we aimed to explore potential molecular indicators for mRCC patients who may benefit from everolimus treatment. Paraffin-embedded tumor tissue specimens derived from 18 mRCC patients before everolimus treatment, who participated the phase 1b trial of everolimus in VEGF receptor (VEGFR)-tyrosine kinase inhibitor (TKI)-refractory Chinese patients with mRCC (clinicaltrials.gov, NCT01152801), were examined for the expression levels of phosphorylated AKT, mTOR, eukaryotic initiation factor 4E (eIF4E) binding protein-1 (4EBP1) and 40S ribosomal protein S6 (S6RP) by immunohistochemistry. Clinical benefit rate (complete response [CR], partial response [PR], plus stable disease [SD] ≥ 6 months) and progression-free survival time (PFS) were correlated with expression levels of these mTOR-associated molecules. In these 18 patients, there were 1 PR, 15 SDs (including 9 SDs ≥ 6 months), and 2 progressive diseases (PD). The clinical benefit rate (CBR) was 55.6% (10/18), and the median PFS time was 8.4 months. Patients with positive expression of phospho-mTOR showed a better CBR (71.4% versus 0%, P = 0.023) and PFS time (11.3 versus 3.7 months, P = 0.001) than those patients with negative expression. The median PFS of patients with positive phospho-S6RP expression was longer (11.3 versus 3.7 months, P = 0.002) than that of patients negative for phospho-S6RP expression. However, expression levels of phospho-4EBP1 and phospho-AKT were unassociated to efficacy of everolimus treatment with respect to CBR and PFS. Co-expression of
Rational design and enantioselective synthesis of (1R,4S,5R,6S)-3-azabicyclo[3.3.0]octane-4,6-dicarboxylic acid - a novel inhibitor at human glutamate transporter subtypes 1, 2, and 3

DEFF Research Database (Denmark)

Bunch, Lennart; Nielsen, Birgitte; Jensen, Anders A.

2006-01-01

The natural product kainic acid is used as template for the rational design of a novel conformationally restricted (S)-glutamic acid (Glu) analogue, (1R,4S,5R,6S)-3-azabicyclo[3.3.0]octane-4,6-dicarboxylic acid (1a). The target structure 1a was synthesized from commercially available (S)-pyroglut......The natural product kainic acid is used as template for the rational design of a novel conformationally restricted (S)-glutamic acid (Glu) analogue, (1R,4S,5R,6S)-3-azabicyclo[3.3.0]octane-4,6-dicarboxylic acid (1a). The target structure 1a was synthesized from commercially available (S...
Measurement of the time-integrated C P asymmetry in D"0→K_S"0K_S"0 decays

International Nuclear Information System (INIS)

Aaij, R.; Adeva, B.; Adinolfi, M.; Affolder, A.

2015-01-01

The time-integrated C P asymmetry in the decay D"0→K_S"0K_S"0 is measured using 3 fb"−"1 of proton-proton collision data collected by the LHCb experiment at centre-of-mass energies of 7 and 8 TeV. The flavour of the D"0 meson is determined by use of the decay D"∗"+→D"0π"+ and its charge conjugate mode. The result is A_C _P=−0.029±0.052±0.022, where the first uncertainty is statistical and the second systematic. The result is consistent with Standard Model expectations and improves the uncertainty with respect to the only previous measurement of this quantity by more than a factor of three.
Quasimolecular emission near the Xe(5p 56s 1,3 P 1 - 5p 6 1 S 0) and Kr (4p 55s 1,3 P 1 - 4p 6 1 S 0) resonance lines induced by collisions with He atoms

Science.gov (United States)

Alekseeva, O. S.; Devdariani, A. Z.; Grigorian, G. M.; Lednev, M. G.; Zagrebin, A. L.

2017-02-01

This study is devoted to the theoretical investigation of the quasimolecular emission of Xe*-He and Kr*-He collision pairs near the Xe (5p 56s 1,3 P 1 - 5p 6 1 S 0) and Kr (4p 55s 1,3 P 1 - 4p 6 1 S 0) resonance atomic lines. The potential curves of the quasimolecules Xe(5p 56s) + He and Kr(4p 55s) + He have been obtained with the use of the effective Hamiltonian and pseudopotential methods. Based on these potential curves the processes of quasimolecular emission of Xe*+He and Kr*+He mixtures have been considered and the spectral distributions I(ħΔω) of photons emitted have been obtained in the framework of quasistatic approximation.
LncMAPK6 drives MAPK6 expression and liver TIC self-renewal.

Science.gov (United States)

Huang, Guanqun; Jiang, Hui; He, Yueming; Lin, Ye; Xia, Wuzheng; Luo, Yuanwei; Liang, Min; Shi, Boyun; Zhou, Xinke; Jian, Zhixiang

2018-05-15

Liver tumor initiating cells (TICs) have self-renewal and differentiate capacities, and largely contribute to tumor initiation, metastasis and drug resistance. MAPK signaling is a critical pathway in many biological processes, while its role in liver TICs hasn't been explored. Online-available dataset was used for unbiased screening. Liver TICs were examined CD133 FACS or oncosphere formation. TIC self-renewal was detected by oncosphere formation and tumor initiation assay. LncRNA function was detected by loss of function or gain of function assays. The molecular mechanism of lncRNA was explored by RNA pulldown, RNA immunoprecipitation, ChIP, western blot and double FISH. Here, we examined the expression profiles of MAPK components (MAPKs, MAP2Ks, MAP3Ks, MAP4Ks), and found MAPK6 is most highly expressed in liver cancer samples. Moreover, a divergent lncRNA (long noncoding RNA) of MAPK6, termed lncMAPK6 here, is also overexpressed along with liver tumorigenesis. LncMAPK6 promotes liver tumor propagation and TIC self-renewal through MAPK6. LncMAPK6 interacts with and recruits RNA polymerase II to MAPK6 promoter, and finally activates the transcription of MAPK6. Through MAPK6 transcriptional regulation, lncMAPK6 drives MARK signaling activation. LncMAPK6-MAPK6 pathway can be used for liver TIC targeting. Altogether, lncMAPK6 promotes MARK signaling and the self-renewal of liver TICs through MAPK6 expression. MAPK6 was the most highly expressed MAPK component in liver cancer and liver TICs and lncMAPK6 participated in the transcriptional regulation of MAPK6in cis. This work revealed the importance role of MAPK signaling in liver TIC self-renewal and added a new layer for liver TIC and MAPK6 expression regulation.
Magnetism and superconductivity in Eu(Ho)Mo6S8

International Nuclear Information System (INIS)

Capone, D.W. II; Lai Fook, M.S.; Guertin, R.P.; Hinks, D.G.; Dunlap, B.D.; Foner, S.; Abou-Aly, A.I.; Brooks, J.S.

1984-10-01

A variety of ambient and high pressure experimental results reveal the interplay between magnetism and superconductivity in Ho doped samples of the pressure induced superconductor, EuMo 6 S 8 . Ho concentrations up to 50 atomic percent of the rare earth ions were used. High resolution magnetic measurements are consistent with the crystalline electric field ground state for the Ho 3+ ions being a magnetic doublet consisting largely of J/sub z/ = 18. The results of high pressure magnetization experiments reveal negligible effects of reduced lattice constant on the rare earth-rare earth interactions. Resistivity in a 10 atomic percent sample for P = 10 kbar shows the suppression of a P = 0 structural transition, metallic conductivity down to low temperatures, and finally superconductivity at 8 K. The upper critical field, H/sub c2/(T), for this sample was measured for P = 7, 10 and 12 kbar and showed strong reentrant behavior (dH/sub c2/(T)/dT > 0 as T → 0 K). A minimum with field in the resistivity above H/sub c2/ was also observed at lowest temperatures. The H/sub c2/(T) data are compared with those of EuMo 6 S 8 at high pressure, which shows positive curvature, and HoMo 6 S 8 , in which superconductivity is quenched by ferromagnetism at low temperatures. 14 references, 4 figures
On supersymmetric AdS6 solutions in 10 and 11 dimensions

Science.gov (United States)

Gutowski, J.; Papadopoulos, G.

2017-12-01

We prove a non-existence theorem for smooth, supersymmetric, warped AdS 6 solutions with connected, compact without boundary internal space in D = 11 and (massive) IIA supergravities. In IIB supergravity we show that if such AdS 6 solutions exist, then the NSNS and RR 3-form fluxes must be linearly independent and certain spinor bilinears must be appropriately restricted. Moreover we demonstrate that the internal space admits an so(3) action which leaves all the fields invariant and for smooth solutions the principal orbits must have co-dimension two. We also describe the topology and geometry of internal spaces that admit such a so(3) action and show that there are no solutions for which the internal space has topology F × S 2, where F is an oriented surface.
Role and regulation of 90 kDa ribosomal S6 kinase (RSK) in signal transduction

DEFF Research Database (Denmark)

Frödin, M; Gammeltoft, S

1999-01-01

), which were among the first substrates of ERK to be discovered and which has proven to be a ubiquitous and versatile mediator of ERK signal transduction. RSK is composed of two functional kinase domains that are activated in a sequential manner by a series of phosphorylations. Recently, a family of RSK......-related kinases that are activated by ERK as well as p38 MAPK were discovered and named mitogen- and stress-activated protein kinases (MSK). A number of cellular functions of RSK have been proposed. (1) Regulation of gene expression via association and phosphorylation of transcriptional regulators including c...
Advanced `KS-6` dry type lubricant for aluminum sheet forming; Arumi ban seikeiyo koseino kokei junkatsuzai `KS-5`

Energy Technology Data Exchange (ETDEWEB)

Matsui, K.; Sugita, T.; Imamura, Y. [Kobe Steel, Ltd., Kobe (Japan)

1997-09-01

The advanced `KS-5` dry film type lubricant was developed for press forming of aluminum sheets. KS-5 uses water- soluble resin poly-alkylene-oxide superior in formability, weldability and adhesivity, and contains higher fatty-acid soap as oil solvent to improve a formability. The verification test result of KS-5 is as follows. Both stretchability and drawability were confirmed through a ball head stretching test and a cylinder drawing test as formability test, respectively, and a forming height more than that of mild steel sheets was obtained by using the solid lubricant showing a high stretchability. The drawability of nearly 80% of that of mild steel sheets was also obtained showing a high formability. Since the amount of the solid lubricant has reciprocal effect on the formability and degreasing property, it is important to select the suitable amount of the solid lubricant according to use conditions. Lubricants generally deteriorate a spot weldability, however, this lubricant has no practical problems by coating rust preventive oil. 3 refs., 8 figs., 3 tabs.
TAM receptors, Gas6, and protein S: roles in inflammation and hemostasis

NARCIS (Netherlands)

van der Meer, Jonathan H. M.; van der Poll, Tom; van 't Veer, Cornelis

2014-01-01

TAM receptors (Tyro3, Axl, andMer) belong to a family of receptor tyrosine kinases that have important effects on hemostasis and inflammation. Also, they affect cell proliferation, survival, adhesion, and migration. TAM receptors can be activated by the vitamin K-dependent proteins Gas6 and protein
First principles prediction of the magnetic properties of Fe-X6 (X = S, C, N, O, F) doped monolayer MoS2

KAUST Repository

Feng, Nan; Mi, Wenbo; Cheng, Yingchun; Guo, Zaibing; Schwingenschlö gl, Udo; Bai, Haili

2014-01-01

Using first-principles calculations, we have investigated the electronic structure and magnetic properties of Fe-X 6 clusters (X = S, C, N, O, and F) incorporated in 4 4 monolayer MoS 2, where a Mo atom is substituted by Fe and its nearest S atoms are substituted by C, N, O, and F. Single Fe and Fe-F 6 substituions make the system display half-metallic properties, Fe-C 6 and Fe-N 6 substitutions lead to a spin gapless semiconducting behavior, and Fe-O 6 doped monolayer MoS 2 is semiconducting. Magnetic moments of 1.93, 1.45, 3.18, 2.08, and 2.21...? B are obtained for X = S, C, N, O, and F, respectively. The different electronic and magnetic characters originate from hybridization between the X and Fe/Mo atoms. Our results suggest that cluster doping can be an efficient strategy for exploring two-dimensional diluted magnetic semiconductors.
First principles prediction of the magnetic properties of Fe-X6 (X = S, C, N, O, F) doped monolayer MoS2

KAUST Repository

Feng, Nan

2014-02-05

Using first-principles calculations, we have investigated the electronic structure and magnetic properties of Fe-X 6 clusters (X = S, C, N, O, and F) incorporated in 4 4 monolayer MoS 2, where a Mo atom is substituted by Fe and its nearest S atoms are substituted by C, N, O, and F. Single Fe and Fe-F 6 substituions make the system display half-metallic properties, Fe-C 6 and Fe-N 6 substitutions lead to a spin gapless semiconducting behavior, and Fe-O 6 doped monolayer MoS 2 is semiconducting. Magnetic moments of 1.93, 1.45, 3.18, 2.08, and 2.21...? B are obtained for X = S, C, N, O, and F, respectively. The different electronic and magnetic characters originate from hybridization between the X and Fe/Mo atoms. Our results suggest that cluster doping can be an efficient strategy for exploring two-dimensional diluted magnetic semiconductors.
Unitary Supermultiplets of $OSp(8^{*}|4)$ and the $AdS_{7}/CFT_{6}$ Duality

CERN Document Server

Günaydin, M; Gunaydin, Murat; Takemae, Seiji

2000-01-01

We study the unitary supermultiplets of the N=4 d=7 anti-de Sitter (AdS_7) superalgebra OSp(8^*|4), with the even subalgebra SO(6,2) X USp(4), which is the symmetry superalgebra of M-theory on AdS_7 X S^4. We give a complete classification of the positive energy doubleton and massless supermultiplets of OSp(8^*|4) . The ultra-short doubleton supermultiplets do not have a Poincaré limit in AdS_7 and correspond to superconformal field theories on the boundary of AdS_7 which can be identified with d=6 Minkowski space. We show that the six dimensional Poincare mass operator vanishes identically for the doubleton representations. By going from the compact U(4) basis of SO^*(8)=SO(6,2) to the noncompact basis SU^*(4)XD (d=6 Lorentz group times dilatations) one can associate the positive (conformal) energy representations of SO^*(8) with conformal fields transforming covariantly under the Lorentz group in d=6. The oscillator method used for the construction of the unitary supermultiplets of OSp(8^*|4) can be given ...
Auxin efflux by PIN-FORMED proteins is activated by two different protein kinases, D6 PROTEIN KINASE and PINOID

KAUST Repository

Zourelidou, Melina; Absmanner, Birgit; Weller, Benjamin; Barbosa, Inê s CR; Willige, Bjö rn C; Fastner, Astrid; Streit, Verena; Port, Sarah A; Colcombet, Jean; de la Fuente van Bentem, Sergio; Hirt, Heribert; Kuster, Bernhard; Schulze, Waltraud X; Hammes, Ulrich Z; Schwechheimer, Claus

2014-01-01

The development and morphology of vascular plants is critically determined by synthesis and proper distribution of the phytohormone auxin. The directed cell-to-cell distribution of auxin is achieved through a system of auxin influx and efflux transporters. PIN-FORMED (PIN) proteins are proposed auxin efflux transporters, and auxin fluxes can seemingly be predicted based on the-in many cells-asymmetric plasma membrane distribution of PINs. Here, we show in a heterologous Xenopus oocyte system as well as in Arabidopsis thaliana inflorescence stems that PIN-mediated auxin transport is directly activated by D6 PROTEIN KINASE (D6PK) and PINOID (PID)/WAG kinases of the Arabidopsis AGCVIII kinase family. At the same time, we reveal that D6PKs and PID have differential phosphosite preferences. Our study suggests that PIN activation by protein kinases is a crucial component of auxin transport control that must be taken into account to understand auxin distribution within the plant.

Auxin efflux by PIN-FORMED proteins is activated by two different protein kinases, D6 PROTEIN KINASE and PINOID

KAUST Repository

Zourelidou, Melina

2014-06-19

The development and morphology of vascular plants is critically determined by synthesis and proper distribution of the phytohormone auxin. The directed cell-to-cell distribution of auxin is achieved through a system of auxin influx and efflux transporters. PIN-FORMED (PIN) proteins are proposed auxin efflux transporters, and auxin fluxes can seemingly be predicted based on the-in many cells-asymmetric plasma membrane distribution of PINs. Here, we show in a heterologous Xenopus oocyte system as well as in Arabidopsis thaliana inflorescence stems that PIN-mediated auxin transport is directly activated by D6 PROTEIN KINASE (D6PK) and PINOID (PID)/WAG kinases of the Arabidopsis AGCVIII kinase family. At the same time, we reveal that D6PKs and PID have differential phosphosite preferences. Our study suggests that PIN activation by protein kinases is a crucial component of auxin transport control that must be taken into account to understand auxin distribution within the plant.
Regulation of androgen receptor transactivity and mTOR-S6 kinase pathway by Rheb in prostate cancer cell proliferation.

Science.gov (United States)

Kobayashi, Takashi; Shimizu, Yosuke; Terada, Naoki; Yamasaki, Toshinari; Nakamura, Eijiro; Toda, Yoshinobu; Nishiyama, Hiroyuki; Kamoto, Toshiyuki; Ogawa, Osamu; Inoue, Takahiro

2010-06-01

Ras homolog-enriched in brain (Rheb), a small GTP-binding protein, is associated with prostate carcinogenesis through activating mammalian target of rapamycin (mTOR) signaling pathway. This study aimed to elucidate whether Rheb promotes proliferation of prostate cancer cells and can act as a potent therapeutic target in prostate cancer. Prostate cancer cell lines and human prostatic tissues were examined for the expression of Rheb. The effects of forced expression or knockdown of Rheb on cell proliferation were also examined. Semi-quantitative and quantitative RT-PCR were performed to evaluate mRNA expression. Western blotting was used to examine protein expression. Cell count and WST-1 assay were used to measure cell proliferation. Fluorescence-activated cell sorting was used to assess the cell cycle. Rheb mRNA and protein expression was higher in more aggressive, androgen-independent prostate cancer cell lines PC3, DU145, and C4-2, compared with the less aggressive LNCaP. Rheb expression was higher in cancer tissues than in benign prostatic epithelia. Forced expression of Rheb in LNCaP cells accelerated proliferation without enhancing androgen receptor transactivity. Attenuation of Rheb expression or treatment with the mTOR inhibitor rapamycin decreased proliferation of PC3 and DU145 cells, with a decrease in the activated form of p70S6 kinase, one of the main targets of mTOR. Rheb potentiates proliferation of prostate cancer cells and inhibition of Rheb or mTOR can lead to suppressed proliferation of aggressive prostate cancer cell lines in vitro. Rheb and the mTOR pathway are therefore probable targets for suppressing prostate cancer.
Final report of APMP.QM-S6: clenbuterol in porcine meat

Science.gov (United States)

Sin, D. W.-M.; Ho, C.; Yip, Y.-C.

2016-01-01

At the CCQM Organic Analysis Working Group (OAWG) Meeting held in April 2012 and the APMP TCQM Meeting held in November 2012, an APMP supplementary comparison (APMP.QM-S6) on the determination of clenbuterol in porcine meat was supported by the OAWG and APMP TCQM. This comparison was organized by the Government Laboratory, Hong Kong. In order to accommodate a wider participation, a pilot study (APMP.QM-P22) was run in parallel to APMP.QM-S6. This study provided the means for assessing the measurement capabilities for determination of low-polarity measurands in a procedure that requires extraction, clean-up, analytical separation, and selective detection in a food matrix. A total of 7 institutes registered for the supplementary comparison and 6 of them submitted their results. 4 results were included for SCRV calculation. All participating laboratories applied Isotope Dilution Liquid Chromatography-Tandem Mass Spectrometry (ID-LCMS/MS) technique with clenbuterol-d9 as internal standard spiked for quantitation in this programme. KEY WORDS FOR SEARCH APMP.QM-S6 and Clenbuterol Main text To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCQM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).
Comparative Immunohistochemical Analysis of Ochratoxin A Tumourigenesis in Rats and Urinary Tract Carcinoma in Humans; Mechanistic Significance of p-S6 Ribosomal Protein Expression

Directory of Open Access Journals (Sweden)

Sarah Pinder

2012-09-01

Full Text Available Ochratoxin A (OTA is considered to be a possible human urinary tract carcinogen, based largely on a rat model, but no molecular genetic changes in the rat carcinomas have yet been defined. The phosphorylated-S6 ribosomal protein is a marker indicating activity of the mammalian target of rapamycin, which is a serine/threonine kinase with a key role in protein biosynthesis, cell proliferation, transcription, cellular metabolism and apoptosis, while being functionally deregulated in cancer. To assess p-S6 expression we performed immunohistochemistry on formalin-fixed and paraffin-embedded tumours and normal tissues. Marked intensity of p-S6 expression was observed in highly proliferative regions of rat renal carcinomas and a rare angiosarcoma, all of which were attributed to prolonged exposure to dietary OTA. Only very small OTA-generated renal adenomas were negative for p-S6. Examples of rat subcutaneous fibrosarcoma and testicular seminoma, as well as of normal renal tissue, showed no or very weak positive staining. In contrast to the animal model, human renal cell carcinoma, upper urinary tract transitional cell carcinoma from cases of Balkan endemic nephropathy, and a human angiosarcoma were negative for p-S6. The combined findings are reminiscent of constitutive changes in the rat tuberous sclerosis gene complex in the Eker strain correlated with renal neoplasms, Therefore rat renal carcinogenesis caused by OTA does not obviously mimic human urinary tract tumourigenesis.
78 FR 14097 - Pulse Oximeters-Premarket Notification Submissions [510(k)s]; Guidance for Industry and Food and...

Science.gov (United States)

2013-03-04

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2007-D-0205 (Formerly 2007D-0252)] Pulse Oximeters--Premarket Notification Submissions [510(k)s]; Guidance for Industry and Food and Drug Administration Staff; Availability AGENCY: Food and Drug Administration, HHS. ACTION...
Room-Temperature Synthesis of Thiostannates from {[Ni(tren)]2[Sn2S6]}n.

Science.gov (United States)

Hilbert, Jessica; Näther, Christian; Weihrich, Richard; Bensch, Wolfgang

2016-08-15

The compound {[Ni(tren)]2[Sn2S6]}n (1) (tren = tris(2-aminoethyl)amine, C6H18N4) was successfully applied as source for the room-temperature synthesis of the new thiostannates [Ni(tren)(ma)(H2O)]2[Sn2S6]·4H2O (2) (ma = methylamine, CH5N) and [Ni(tren)(1,2-dap)]2[Sn2S6]·2H2O (3) (1,2-dap = 1,2-diaminopropane, C3H10N2). The Ni-S bonds in the Ni2S2N8 bioctahedron in the structure of 1 are analyzed with density functional theory calculations demonstrating significantly differing Ni-S bond strengths. Because of this asymmetry they are easily broken in the presence of an excess of ma or 1,2-dap immediately followed by Ni-N bond formation to N donor atoms of the amine ligands thus generating [Ni(tren)(amine)](2+) complexes. The chemical reactions are fast, and compounds 2 and 3 are formed within 1 h. The synthesis concept presented here opens hitherto unknown possibilities for preparation of new thiostannates.
Identification of p90 Ribosomal S6 Kinase 2 as a Novel Host Protein in HBx Augmenting HBV Replication by iTRAQ-Based Quantitative Comparative Proteomics.

Science.gov (United States)

Yan, Li-Bo; Yu, You-Jia; Zhang, Qing-Bo; Tang, Xiao-Qiong; Bai, Lang; Huang, FeiJun; Tang, Hong

2018-05-01

The aim of this study was to screen for novel host proteins that play a role in HBx augmenting Hepatitis B virus (HBV) replication. Three HepG2 cell lines stably harboring different functional domains of HBx (HBx, HBx-Cm6, and HBx-Cm16) were cultured. ITRAQ technology integrated with LC-MS/MS analysis was applied to identify the proteome differences among these three cell lines. In brief, a total of 70 different proteins were identified among HepG2-HBx, HepG2-HBx-Cm6, and HepG2-HBx-Cm16 by double repetition. Several differentially expressed proteins, including p90 ribosomal S6 kinase 2 (RSK2), were further validated. RSK2 was expressed at higher levels in HepG2-HBx and HepG2-HBx-Cm6 compared with HepG2-HBx-Cm16. Furthermore, levels of HBV replication intermediates were decreased after silencing RSK2 in HepG2.2.15. An HBx-minus HBV mutant genome led to decreased levels of HBV replication intermediates and these decreases were restored to levels similar to wild-type HBV by transient ectopic expression of HBx. After silencing RSK2 expression, the levels of HBV replication intermediates synthesized from the HBx-minus HBV mutant genome were not restored to levels that were observed with wild-type HBV by transient HBx expression. Based on iTRAQ quantitative comparative proteomics, RSK2 was identified as a novel host protein that plays a role in HBx augmenting HBV replication. © 2018 The Authors. Proteomics - Clinical Application Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
U.S. Fish and Wildlife Service regional alternative transportation evaluation : region 6

Science.gov (United States)

2014-04-01

The U.S. Fish and Wildlife Service (FWS) and the U.S. Department of Transportation (DOT) Volpe Center (Volpe Center) conducted a regional alternative transportation evaluation (RATE) in Region 6, which is comprised of Colorado, Kansas, Montana, Nebra...
Peculiarities in electronic properties of molybdenum ternary sulphides PbMo6S8

International Nuclear Information System (INIS)

Shevchenko, A.D.; Aleksandrov, O.V.; Drozdova, S.V.; Kalyuzhnaya, G.A.; Kiseleva, K.V.; Primachenko, V.F.; Shevchuk, N.V.; Yachmenev, V.E.

1982-01-01

Effect of technological parameters of PbMo 6 S 8 on its superconducting and structural properties has been studied. For the first time lattice instability was discovered from X-ray diffraction investigations of PbMo 6 S 8 in the temperature range from 4.2 to 300 K near 80 K. pleasured were temperature dependences of specific resistance rho(Tsub(c)+-300 K), magnetic susceptibility chi(sub(c)+-300 K) and specific heat Csub(p)(2+-300 K) of the PbMo 6 S 8 system. Combined analysis of experimental results obtained and literature data on inelastic neutron scattering at 4.2 and 300 K permitted for the first time, to calculate quantitatively photon thermal capacity and its anharmonic component, temperature dependence #betta#subH(T) of electron heat capacity coefficient, zonal density of electron states Nsub(BS)(Esub(F)) at the Fermi level and electron-phonon interaction constant lambda(T). It is discovered that rho(T), #betta#sub(H)(T) and lambda(T) dependences behave themselves anomalously near temperatures approximately 80 K where lattice instability takes place and high-field superconductivity in PbMo 6 S 8 results from a large value of Nsub(BS)(Esub(F))
Table_S6.xls

Indian Academy of Sciences (India)

Vit4

369, 6, 406, -0.01, 0.0057, 0.0108. 370, 7, 334, -0.048, 0.0081, 0.0264. 371. 372, 48, 1vzwA, 1, 224, 0.005, 0.005, 0. 373, 2, 224, 0.005, 0.005, 0. 374, 3, 224, 0.005, 0.005, 0. 375, 4, 222, 0.004, 0.0053, 0.0061. 376, 5, 221, -0.001, 0.0043, 0.0079. 377, 6, 213, 0.01, 0.0049, 0.0153. 378. 379, 49, 1xagA, 1, 353, 0.001, 0.0008 ...
Determination of standard molar Gibbs energy of formation of Sm6UO12(s)

International Nuclear Information System (INIS)

Sahu, Manjulata; Dash, Smruti

2015-01-01

The standard molar Gibbs energies of formation of Sm 6 UO 12 (s) have been measured using an oxygen concentration cell with yttria stabilized zirconia as solid electrolyte. Δ f G o m (T) for Sm 6 UO 12 (s) has been calculated using the measured and required thermodynamic data from the literature. The calculated Gibbs energy expression in the temperature range 899 to 1127 K can be given as: Δ f G o m (Nd 6 UO 12 , s,T)/(±2.3) kJ∙ mol -1 = -6681 +1.099 (T/K) (899-1127 K)(T/K). (author)
A 2-GS/s 6-bit self-calibrated flash ADC

Energy Technology Data Exchange (ETDEWEB)

Zhang Youtao; Chen Chen [National Key Laboratory of Monolithic Integrated Circuits and Modules, Nanjing Electronic Devices Institute, Nanjing 210016 (China); Li Xiaopeng; Zhang Min; Liu Ao, E-mail: zhangyt@nedc-ic.co [Nanjing Electronic Devices Institute, Nanjing 210016 (China)

2010-09-15

A single channel 2-GS/s 6-bit ADC with cascade resistive averaging and self foreground calibration is demonstrated in 0.18-{mu}m CMOS. The calibration method based on DAC trimming improves the linearity and dynamic performance further. The peak DNL and INL are measured as 0.34 and 0.22 LSB, respectively. The SNDR and SFDR have achieved 36.5 and 45.9 dB, respectively, with 1.22 MHz input signal and 2 GS/s. The proposed ADC, including on-chip track-and-hold amplifiers and clock buffers, consumes 570 mW from a single 1.8 V supply while operating at 2 GS/s. (semiconductor integrated circuits)
CBL-interacting protein kinase 6 negatively regulates immune response to Pseudomonas syringae in Arabidopsis.

Science.gov (United States)

Sardar, Atish; Nandi, Ashis Kumar; Chattopadhyay, Debasis

2017-06-15

Cytosolic calcium ion (Ca2+) is an essential mediator of the plant innate immune response. Here, we report that a calcium-regulated protein kinase Calcineurin B-like protein (CBL)-interacting protein kinase 6 (CIPK6) functions as a negative regulator of immunity against the bacterial pathogen Pseudomonas syringae in Arabidopsis thaliana. Arabidopsis lines with compromised expression of CIPK6 exhibited enhanced disease resistance to the bacterial pathogen and to P. syringae harboring certain but not all avirulent effectors, while restoration of CIPK6 expression resulted in abolition of resistance. Plants overexpressing CIPK6 were more susceptible to P. syringae. Enhanced resistance in the absence of CIPK6 was accompanied by increased accumulation of salicylic acid and elevated expression of defense marker genes. Salicylic acid accumulation was essential for improved immunity in the absence of CIPK6. CIPK6 negatively regulated the oxidative burst associated with perception of pathogen-associated microbial patterns (PAMPs) and bacterial effectors. Accelerated and enhanced activation of the mitogen-activated protein kinase cascade in response to bacterial and fungal elicitors was observed in the absence of CIPK6. The results of this study suggested that CIPK6 negatively regulates effector-triggered and PAMP-triggered immunity in Arabidopsis. © The Author 2017. Published by Oxford University Press on behalf of the Society for Experimental Biology.
Electrocatalysis of hemoglobin in ionic liquid BMIMPF6 and CuS nanosphere composite films

Directory of Open Access Journals (Sweden)

Wei Sun

2011-12-01

Full Text Available Ionic liquid 1-butyl-3-methylimidazolium hexafluorophosphate (BMIMPF6 was mixed homogeneously with nanometer-sized semiconductor CuS sphere to form a new nanocomposite material, which was further used for the immobilization of hemoglobin (Hb on the surface of carbon paste electrode (CPE. Direct electrochemistry of Hb in BMIMPF6-CuS composite film was carefully investigated with a pair of quasi-reversible redox peaks appeared and the formal potential (E0' was got as -135 mV (vs. SCE in pH 7.0 phosphate buffer solution, which was due to the enhanced direct electron transfer rate of Hb in the biocompatible matrix. The BMIMPF6-CuS-Hb/CPE showed excellent electrocatalytic activity to the reduction of hydrogen peroxide with the kinetic parameters for the electrocatalytic reaction evaluated. The results indicated that the BMIMPF6-CuS nanocomposite could be used for the preparation of electrochemical biosensor.
Synthesis of new dithiacobaltaborane clusters derived from arachno-6,8-S2B7H9

International Nuclear Information System (INIS)

Kang, S.O.; Sneddon, L.G.

1988-01-01

A series of air-stable dithiacobaltaborane clusters has been isolated from either the reaction of the arachno-S 2 B 7 H 8 - anion with cobalt chloride and pentamethylcyclopentadienide or the reaction of neutral arachno-6,8-S 2 B 7 H 9 with cobalt atoms and pentamethylcyclopentadiene. Thus, the reaction of arachno-S 2 B 7 H 8 - with CoCl 2 and C 5 (CH 3 ) 5 - in THF gave, as the major products, the triple-decker compound nido-4,6-η-C 5 (CH 3 ) 52 Co 2 -3,5-S 2 B 2 H 2 (I) and the 11-vertex cluster nido-8,10(η-C 5 (CH 3 ) 5 ) 2 Co 2 -7,9-S 2 B 7 H 7 (III). Also isolated in smaller amounts were a chloride derivative of I, nido-1-Cl-4,6-(η-C 5 (CH 3 ) 5 ) 2 Co 2 -3,5-S 2 B 2 H (II), two isomers of III, nido-3,10-(η-C 5 (CH 3 ) 5 ) 2 Co 2 -7,9-S 2 B 7 H 7 (IV) and nido-3,5-(η-C 5 (CH 3 ) 5 ) 2 Co 2 -7,9-S 2 B 7 H 7 (V), and the eight-boron cluster nido-8-(η-C 5 (CH 3 ) 5 )Co-7,9-S 2 B 8 H 8 (VI). Other trace products of the reaction included the six-boron clusters nido-5,8-(η-C 5 (CH 3 ) 5 ) 2 Co 2 -6,9-S 2 B 6 H 6 (VII) and arachno-7-(η-C 5 (CH 3 ) 5 )Co-6,8-S 2 B 6 H 8 (VIII). Compound III was found to isomerize at 250 degree C to IV, which could then be converted to V at 300 degree C. The reaction of cobalt atoms with arachno-6,8-S 2 B 7 H 9 in the presence of pentamethylcyclopentadiene gave VIII as the major product; however, a number of other clusters including I, V, VI, and [(η-C 5 (CH 3 ) 5 ) 2 Co] + [(SB 10 H 10 ) 2 Co] - were isolated in trace amounts. 16 references, 6 figures, 3 tables
The crystal structure of Cu_1.6Pb_1.6Bi_6.4S₁₂, a new 44.8 Å derivative of the bismuthinite-aikinite solid-solution series

DEFF Research Database (Denmark)

Topa, Dan; Balic-Zunic, Tonci; Makovicky, Emil

2000-01-01

Cu1.6Pb1.6Bi6.4S12, aikinite-bismuthinite derivative, crystal structure, Felbertal, scheelite deposit, Austria......Cu1.6Pb1.6Bi6.4S12, aikinite-bismuthinite derivative, crystal structure, Felbertal, scheelite deposit, Austria...
Improved limit on the branching fraction of the rare decay K-S(0) -> mu(+)mu(-)

NARCIS (Netherlands)

Aaij, R.; Adeva, B.; Ajaltouni, Z.; Akar, S.; Alessio, F.; Alexander, M.; Ali, S.; Alkhazov, G.; Cartelle, P. Alvarez; Alves, A. A., Jr.; Amato, S.; Amerio, S.; Amhis, Y.; An, L.; Anderlini, L.; Andreassi, G.; Andreotti, M.; Andrews, J. E.; Appleby, R. B.; Archilli, F.; d'Argent, P.; Romeu, J. Arnau; Artamonov, A.; Artuso, M.; Aslanides, E.; Auriemma, G.; Baalouch, M.; Babuschkin, I.; Bachmann, S.; Back, J. J.; Badalov, A.; Baesso, C.; Baker, S.; Balagura, V.; Baldini, W.; Baranov, A.; Barlow, R. J.; Barschel, C.; Barsuk, S.; Barter, W.; Baryshnikov, F.; Baszczyk, M.; Batozskaya, V.; Battista, V.; Bay, A.; Beaucourt, L.; Beddow, J.; Bedeschi, F.; Bediaga, I.; Beiter, A.; Bel, L. J.; Bellee, V.; Belloli, N.; Belous, K.; Belyaev, I.; Ben-Haim, E.; Bencivenni, G.; Benson, S.; Beranek, S.; Berezhnoy, A.; Bernet, R.; Bertolin, A.; Betancourt, C.; Betti, F.; Bettler, M. -O.; van Beuzekom, M.; Bezshyiko, Ia.; Bifani, S.; Billoir, P.; Birnkraut, A.; Bitadze, A.; Bizzeti, A.; Blake, T.; Blanc, F.; Blouw, J.; Blusk, S.; Bocci, V.; Boettcher, T.; Bondar, A.; Bondar, N.; Bonivento, W.; Bordyuzhin, I.; Borgheresi, A.; Borghi, S.; Borisyak, M.; Borsato, M.; Bossu, F.; Boubdir, M.; Bowcock, T. J. V.; Bowen, E.; Bozzi, C.; Britton, T.; Brodzicka, J.; Buchanan, E.; Burr, C.; Bursche, A.; Buytaert, J.; Cadeddu, S.; Calabrese, R.; Calvi, M.; Calvo Gomez, M.; Camboni, A.; Campana, P.; Perez, D. H. Campora; Capriotti, L.; Carbone, A.; Carboni, G.; Cardinale, R.; Cardini, A.; Carniti, P.; Carvalho Akiba, K.; Casse, G.; Cassina, L.; Garcia, L. Castillo; Cattaneo, M.; Cavallero, G.; Cenci, R.; Chamont, D.; Charles, M.; Charpentier, Ph.; Chatzikonstantinidis, G.; Chefdeville, M.; Cheung, S. F.; Chobanova, V.; Chrzaszcz, M.; Chubykin, A.; Cid Vidal, X.; Ciezarek, G.; Clarke, P. E. L.; Clemencic, M.; Cliff, H. V.; Closier, J.; Coco, V.; Cogan, J.; Cogneras, E.; Cogoni, V.; Cojocariu, L.; Collins, P.; Comerma-Montells, A.; Contu, A.; Cook, A.; Coombs, G.; Coquereau, S.; Corti, G.; Corvo, M.; Sobral, C. M. Costa; Couturier, B.; Cowan, G. A.; Craik, D. C.; Crocombe, A.; Cruz Torres, M.; Currie, R.; D'Ambrosio, C.; Da Cunha Marinho, F.; Dall'Occo, E.; Dalseno, J.; Davis, A.; De Bruyn, K.; De Capua, S.; De Cian, M.; De Miranda, J. M.; De Paula, L.; De Serio, M.; De Simone, P.; Dean, C. T.; Decamp, D.; Deckenhoff, M.; Del Buono, L.; Dembinski, H. -P.; Demmer, M.; Dendek, A.; Derkach, D.; Deschamps, O.; Dettori, F.; Dey, B.; Di Canto, A.; Di Nezza, P.; Dordei, F.; Dorigo, M.; Dosil Suarez, A.; Dovbnya, A.; Dreimanis, K.; Dujany, G.; Dungs, K.; Durante, P.; Dzhelyadin, R.; Dziewiecki, M.; Dziurda, A.; Dzyuba, A.; Deleage, N.; Easo, S.; Ebert, M.; Egede, U.; Egorychev, V.; Eidelman, S.; Eisenhardt, S.; Eitschberger, U.; Ekelhof, R.; Eklund, L.; Ely, S.; Esen, S.; Evans, H. M.; Evans, T.; Falabella, A.; Farley, N.; Farry, S.; Fay, R.; Fazzini, D.; Ferguson, D.; Fernandez, G.; Fernandez Prieto, A.; Ferrari, F.; Ferreira Rodrigues, F.; Ferro-Luzzi, M.; Filippov, S.; Fini, R. A.; Fiore, M.; Fiorini, M.; Firlej, M.; Fitzpatrick, C.; Fiutowski, T.; Fleuret, F.; Fohl, K.; Fontana, M.; Fontanelli, F.; Forshaw, D. C.; Forty, R.; Lima, V. Franco; Frank, M.; Frei, C.; Fu, J.; Funk, W.; Furfaro, E.; Farber, C.; Gallas Torreira, A.; Galli, D.; Gallorini, S.; Gambetta, S.; Gandelman, M.; Gandini, P.; Gao, Y.; Garcia Martin, L. M.; Garcia Pardinas, J.; Tico, J. Garra; Garrido, L.; Garsed, P. J.; Gascon, D.; Gaspar, C.; Gavardi, L.; Gazzoni, G.; Gerick, D.; Gersabeck, E.; Gersabeck, M.; Gershon, T.; Ghez, Ph.; Giani, S.; Gibson, V.; Girard, O. G.; Giubega, L.; Gizdov, K.; Gligorov, V. V.; Golubkov, D.; Golutvin, A.; Gomes, A.; Gorelov, I. V.; Gotti, C.; Govorkova, E.; Graciani Diaz, R.; Cardoso, L. A. Granado; Grauges, E.; Graverini, E.; Graziani, G.; Grecu, A.; Greim, R.; Grillo, L.; Cazon, B. R. Gruberg; Gruenberg, O.; Gushchin, E.; Guz, Yu.; Gys, T.; Gobel, C.; Hadavizadeh, T.; Hadjivasiliou, C.; Haefeli, G.; Haen, C.; Haines, S. C.; Hamilton, B.; Han, X.; Hansmann-Menzemer, S.; Harnew, N.; Harnew, S. T.; Harrison, J.; Hatch, M.; Head, T.; Heister, A.; Hennessy, K.; Henrard, P.; van Herwijnen, E.; Hess, M.; Hicheur, A.; Hill, D.; Hombach, C.; Hopchev, P. H.; Huard, Z. -C.; Hulsbergen, W.; Humair, T.; Hushchyn, M.; Hutchcroft, D.; Idzik, M.; Ilten, P.; Jacobsson, R.; Jalocha, J.; Jans, E.; Jawahery, A.; John, M.; Jones, C. R.; Joram, C.; Jost, B.; Jurik, N.; Kandybei, S.; Karacson, M.; Kariuki, J. M.; Karodia, S.; Kecke, M.; Kelsey, M.; Kenzie, M.; Ketel, T.; Khairullin, E.; Khanji, B.; Khurewathanakul, C.; Kirn, T.; Klaver, S.; Klimaszewski, K.; Klimkovich, T.; Koliiev, S.; Kolpin, M.; Komarov, I.; Kopecna, R.; Koppenburg, P.; Kosmyntseva, A.; Kotriakhova, S.; Kozeiha, M.; Kravchuk, L.; Kreps, M.; Krokovny, P.; Kruse, F.; Krzemien, W.; Kucewicz, W.; Kucharczyk, M.; Kudryavtsev, V.; Kuonen, A. K.; Kurek, K.; Kvaratskheliya, T.; Lacarrere, D.; Lafferty, G.; Lai, A.; Lanfranchi, G.; Langenbruch, C.; Latham, T.; Lazzeroni, C.; Le Gac, R.; van Leerdam, J.; Leflat, A.; Lefrancois, J.; Lefevre, R.; Lemaitre, F.; Lemos Cid, E.; Leroy, O.; Lesiak, T.; Leverington, B.; Likhomanenko, T.; Lindner, R.; Lionetto, F.; Loh, D.; Longstaff, I.; Lopes, J. H.; Lucchesi, D.; Lucio Martinez, M.; Luo, H.; Lupato, A.; Luppi, E.; Lupton, O.; Lusiani, A.; Lyu, X.; Machefert, F.; Maciuc, F.; Maev, O.; Maguire, K.; Malde, S.; Malinin, A.; Maltsev, T.; Manca, G.; Mancinelli, G.; Manning, P.; Maratas, J.; Marchand, J. F.; Marconi, U.; Marin Benito, C.; Marinangeli, M.; Marino, P.; Marks, J.; Martellotti, G.; Martin, M.; Martinelli, M.; Martinez Santos, D.; Martinez Vidal, F.; Martins Tostes, D.; Massacrier, L. M.; Massafferri, A.; Matev, R.; Mathad, A.; Mathe, Z.; Matteuzzi, C.; Mauri, A.; Maurice, E.; Maurin, B.; Mazurov, A.; McCann, M.; McNab, A.; McNulty, R.; Meadows, B.; Meier, F.; Melnychuk, D.; Merk, M.; Merli, A.; Michielin, E.; Milanes, D. A.; Minard, M. -N.; Mitzel, D. S.; Mogini, A.; Molina Rodriguez, J.; Monroy, I. A.; Monteil, S.; Morandin, M.; Morello, M. J.; Morgunova, O.; Moron, J.; Morris, A. B.; Mountain, R.; Muheim, F.; Mussini, M.; Mueller, D.; Mueller, J.; Mueller, K.; Mueller, V.; Naik, P.; Nakada, T.; Nandakumar, R.; Nandi, A.; Nasteva, I.; Needham, M.; Neri, N.; Neubert, S.; Neufeld, N.; Neuner, M.; Nguyen-Mau, C.; Nieswand, S.; Niet, R.; Nikitin, N.; Nikodem, T.; Nogay, A.; Novoselov, A.; O'Hanlon, D. P.; Oblakowska-Mucha, A.; Obraztsov, V.; Ogilvy, S.; Oldeman, R.; Onderwater, C. J. G.; Ossowska, A.; Otalora Goicochea, J. M.; Owen, P.; Oyanguren, A.; Pais, P. R.; Palano, A.; Palutan, M.; Papanestis, A.; Pappagallo, M.; Pappalardo, L. L.; Pappenheimer, C.; Parker, W.; Parkes, C.; Passaleva, G.; Pastore, A.; Patel, M.; Patrignani, C.; Pearce, A.; Pellegrino, A.; Penso, G.; Altarelli, M. Pepe; Perazzini, S.; Perret, P.; Pescatore, L.; Petridis, K.; Petrolini, A.; Petrov, A.; Petruzzo, M.; Picatoste Olloqui, E.; Pietrzyk, B.; Pikies, M.; Pinci, D.; Pistone, A.; Piucci, A.; Placinta, V.; Playfer, S.; Plo Casasus, M.; Poikela, T.; Polci, F.; Lener, M. Poli; Poluektov, A.; Polyakov, I.; Polycarpo, E.; Pomery, G. J.; Ponce, S.; Popov, A.; Popov, D.; Popovici, B.; Poslavskii, S.; Potterat, C.; Price, E.; Prisciandaro, J.; Prouve, C.; Pugatch, V.; Navarro, A. Puig; Punzi, G.; Qian, W.; Quagliani, R.; Rachwal, B.; Rademacker, J. H.; Rama, M.; Ramos Pernas, M.; Rangel, M. S.; Raniuk, I.; Ratnikov, F.; Raven, G.; Redi, F.; Reichert, S.; dos Reis, A. C.; Remon Alepuz, C.; Renaudin, V.; Ricciardi, S.; Richards, S.; Rihl, M.; Rinnert, K.; Rives Molina, V.; Robbe, P.; Rodrigues, A. B.; Rodrigues, E.; Rodriguez Lopez, J. A.; Perez, P. Rodriguez; Rogozhnikov, A.; Roiser, S.; Rollings, A.; Romanovskiy, V.; Romero Vidal, A.; Ronayne, J. W.; Rotondo, M.; Rudolph, M. S.; Ruf, T.; Ruiz Valls, P.; Saborido Silva, J. J.; Sadykhov, E.; Sagidova, N.; Saitta, B.; Salustino Guimaraes, V.; Sanchez Gonzalo, D.; Sanchez Mayordomo, C.; Sanmartin Sedes, B.; Santacesaria, R.; Santamarina Rios, C.; Santimaria, M.; Santovetti, E.; Satriano, C.; Satta, A.; Saunders, D. M.; Savrina, D.; Schael, S.; Schellenberg, M.; Schiller, M.; Schindler, H.; Schlupp, M.; Schmelling, M.; Schmelzer, T.; Schmidt, B.; Schneider, O.; Schopper, A.; Schreiner, H. F.; Schubert, K.; Schubiger, M.; Schune, M. -H.; Schwemmer, R.; Sciascia, B.; Sciubba, A.; Semennikov, A.; Sergi, A.; Serra, N.; Serrano, J.; Sestini, L.; Seyfert, P.; Shapkin, M.; Shapoval, I.; Shcheglov, Y.; Shears, T.; Shekhtman, L.; Shevchenko, V.; Siddi, B. G.; Coutinho, R. Silva; Silva de Oliveira, L.; Simi, G.; Simone, S.; Sirendi, M.; Skidmore, N.; Skwarnicki, T.; Smith, J.; Smith, M.; Soares Lavra, L.; Sokoloff, M. D.; Soler, F. J. P.; Souza De Paula, B.; Spaan, B.; Spradlin, P.; Sridharan, S.; Stagni, F.; Stahl, M.; Stahl, S.; Stefko, P.; Stefkova, S.; Steinkamp, O.; Stemmle, S.; Stenyakin, O.; Stevens, H.; Stoica, S.; Stone, S.; Storaci, B.; Stracka, S.; Stramaglia, M. E.; Straticiuc, M.; Straumann, U.; Sun, L.; Sutcliffe, W.; Swientek, K.; Syropoulos, V.; Szczekowski, M.; Szumlak, T.; T'Jampens, S.; Tayduganov, A.; Tekampe, T.; Tellarini, G.; Teubert, F.; van Tilburg, J.; Tilley, M. J.; Tisserand, V.; Tobin, M.; Tolk, S.; Tomassetti, L.; Tonelli, D.; Topp-Joergensen, S.; Toriello, F.; Tourinho Jadallah Aoude, R.; Tournefier, E.; Tourneur, S.; Trabelsi, K.; Traill, M.; Tran, M. T.; Tresch, M.; Trisovic, A.; Tsaregorodtsev, A.; Tsopelas, P.; Tully, A.; Tuning, N.; Ukleja, A.; Ustyuzhanin, A.; Uwer, U.; Vacca, C.; Vagnoni, V.; Valassi, A.; Valat, S.; Valenti, G.; Gomez, R. Vazquez; Vazquez Regueiro, P.; Vecchi, S.; van Veghel, M.; Velthuis, J. J.; Veltri, M.; Veneziano, G.; Venkateswaran, A.; Verlage, T. A.; Vernet, M.; Vesterinen, M.; Barbosa, J. V. Viana; Viaud, B.; Vieites Diaz, M.; Viemann, H.; Vilasis-Cardona, X.; Vitti, M.; Volkov, V.; Vollhardt, A.; Voneki, B.; Vorobyev, A.; Vorobyev, V.; Voss, C.; Vazquez Sierra, C.; Waldi, R.; Wallace, C.; Wallace, R.; Walsh, J.; Ward, D. R.; Wark, H. M.; Watson, N. K.; Websdale, D.; Weiden, A.; Whitehead, M.; Wicht, J.; Wilkinson, G.; Wilkinson, M.; Williams, M.; Williams, M. P.; Williams, M.; Wilson, F. F.; Wimberley, J.; Winn, M. A.; Wishahi, J.; Wislicki, W.; Witek, M.; Wormser, G.; Wotton, S. A.; Wraight, K.; Wyllie, K.; Xie, Y.; Yang, Z.; Yao, Y.; Yin, H.; Yuan, X.; Yushchenko, O.; Zarebski, K. A.; Zavertyaev, M.; Zhelezov, A.; Zhukov, V.; Zucchelli, S.

2017-01-01

A search for the decay K 0 S →μ + μ − KS0→μ+μ− is performed, based on a data sample of proton-proton collisions corresponding to an integrated luminosity of 3 fb −1 3 fb −1 , collected by the LHCb experiment at centre-of-mass energies of 7 and 8TeV TeV . The observed yield is consistent with the
Single Source 5-dimensional (Space-, Wavelength-, Time-, Polarization-, Quadrature-) 43 Tbit/s Data Transmission of 6 SDM × 6 WDM × 1.2 Tbit/s Nyquist-OTDM-PDM-QPSK

DEFF Research Database (Denmark)

Hu, Hao; Ye, Feihong; Medhin, Ashenafi Kiros

2014-01-01

We demonstrate 43-Tbit/s transmission over 67.4-km seven-core fiber using a single source. Each of the 6 outer cores carries 6 Nyquist-WDM channels using 320-Gbaud Nyquist- OTDM-PDM-QPSK 330-GHz spaced, and the center core carries 10-GHz clock pulses....
Nitrogen Adsorption and Hydrogenation on a MoFe6S9 Complex

DEFF Research Database (Denmark)

Rod, Thomas Holm; Hammer, Bjørk; Nørskov, Jens Kehlet

1999-01-01

The enzyme nitrogenase catalyzes the biological nitrogen fixation where N-2 is reduced to NH3. Density functional calculations are presented of the bonding and hydrogenation of N-2 on a MoFe6S9 complex constructed to model aspects of the active site of nitrogenase. N-2 is found to bind end on to ...... on to one of the Fe atoms. A complete energy diagram for the addition of hydrogen to the MoFe6S9 complex with and without N-2 is given, and a mechanism for ammonia synthesis is proposed on this basis....
Partial purification and characterization of a wortmannin-sensitive and insulin-stimulated protein kinase that activates heart 6-phosphofructo-2-kinase.

OpenAIRE

Deprez, J; Bertrand, L; Alessi, D R; Krause, U; Hue, L; Rider, M H

2000-01-01

A wortmannin-sensitive and insulin-stimulated protein kinase (WISK), which phosphorylates and activates cardiac 6-phosphofructo-2-kinase (PFK-2), was partially purified from perfused rat hearts. Immunoblotting showed that WISK was devoid of protein kinase B (PKB), serum- and glucocorticoid-regulated protein kinase and protein kinase Czeta (PKCzeta). Comparison of the inhibition of WISK, PKCalpha and PKCzeta by different protein kinase inhibitors suggested that WISK was not a member of the PKC...

Desempeño de la calidad del servicio (QoS sobre IPv6

Directory of Open Access Journals (Sweden)

Octavio José Salcedo Parra

2011-06-01

Full Text Available New applications such as VoIP, e-commerce and video conferencing are sensitive to network performance, making the network capacity to provide quality of service is increasingly important. IPv6 was developed to solve some of the problems of IPv4, such as QoS, security and IP address exhaustion. Current IP networks provide better trafficdelivery effort, therefore, offer no guarantee of quality service. However, there are services, including voice, with stringent requirements for delay and delay variation (jitter, which makes it necessary to add functionality to IP networks based on this protocol are capable of supporting such services. For its part, IPv6 uses 2 fields that can be used to implement QoS, which are: Flow Label and Traffic Class. This article describes the mechanisms and architectures that are used to provide QoS on a network. Later, you specify the features that use both IPv4 and IPv6 to implement QoS. In the last sections present the results of the comparison of 2 scenarios, which are evaluated.
Involvement of ribosomal protein L6 in assembly of functional 50S ribosomal subunit in Escherichia coli cells

International Nuclear Information System (INIS)

Shigeno, Yuta; Uchiumi, Toshio; Nomura, Takaomi

2016-01-01

Ribosomal protein L6, an essential component of the large (50S) subunit, primarily binds to helix 97 of 23S rRNA and locates near the sarcin/ricin loop of helix 95 that directly interacts with GTPase translation factors. Although L6 is believed to play important roles in factor-dependent ribosomal function, crucial biochemical evidence for this hypothesis has not been obtained. We constructed and characterized an Escherichia coli mutant bearing a chromosomal L6 gene (rplF) disruption and carrying a plasmid with an arabinose-inducible L6 gene. Although this ΔL6 mutant grew more slowly than its wild-type parent, it proliferated in the presence of arabinose. Interestingly, cell growth in the absence of arabinose was biphasic. Early growth lasted only a few generations (LI-phase) and was followed by a suspension of growth for several hours (S-phase). This suspension was followed by a second growth phase (LII-phase). Cells harvested at both LI- and S-phases contained ribosomes with reduced factor-dependent GTPase activity and accumulated 50S subunit precursors (45S particles). The 45S particles completely lacked L6. Complete 50S subunits containing L6 were observed in all growth phases regardless of the L6-depleted condition, implying that the ΔL6 mutant escaped death because of a leaky expression of L6 from the complementing plasmid. We conclude that L6 is essential for the assembly of functional 50S subunits at the late stage. We thus established conditions for the isolation of L6-depleted 50S subunits, which are essential to study the role of L6 in translation. - Highlights: • We constructed an in vivo functional assay system for Escherichia coli ribosomal protein L6. • Growth of an E. coli ΔL6 mutant was biphasic when L6 levels were depleted. • The ΔL6 mutant accumulated 50S ribosomal subunit precursors that sedimented at 45S. • L6 is a key player in the late stage of E. coli 50S subunit assembly.
Involvement of ribosomal protein L6 in assembly of functional 50S ribosomal subunit in Escherichia coli cells

Energy Technology Data Exchange (ETDEWEB)

Shigeno, Yuta [Division of Applied Biology, Faculty of Textile Science and Technology, Shinshu University, Ueda 386-8567 (Japan); Uchiumi, Toshio [Department of Biology, Faculty of Science, Niigata University, Niigata 950-2181 (Japan); Nomura, Takaomi, E-mail: nomurat@shinshu-u.ac.jp [Division of Applied Biology, Faculty of Textile Science and Technology, Shinshu University, Ueda 386-8567 (Japan)

2016-04-22

Ribosomal protein L6, an essential component of the large (50S) subunit, primarily binds to helix 97 of 23S rRNA and locates near the sarcin/ricin loop of helix 95 that directly interacts with GTPase translation factors. Although L6 is believed to play important roles in factor-dependent ribosomal function, crucial biochemical evidence for this hypothesis has not been obtained. We constructed and characterized an Escherichia coli mutant bearing a chromosomal L6 gene (rplF) disruption and carrying a plasmid with an arabinose-inducible L6 gene. Although this ΔL6 mutant grew more slowly than its wild-type parent, it proliferated in the presence of arabinose. Interestingly, cell growth in the absence of arabinose was biphasic. Early growth lasted only a few generations (LI-phase) and was followed by a suspension of growth for several hours (S-phase). This suspension was followed by a second growth phase (LII-phase). Cells harvested at both LI- and S-phases contained ribosomes with reduced factor-dependent GTPase activity and accumulated 50S subunit precursors (45S particles). The 45S particles completely lacked L6. Complete 50S subunits containing L6 were observed in all growth phases regardless of the L6-depleted condition, implying that the ΔL6 mutant escaped death because of a leaky expression of L6 from the complementing plasmid. We conclude that L6 is essential for the assembly of functional 50S subunits at the late stage. We thus established conditions for the isolation of L6-depleted 50S subunits, which are essential to study the role of L6 in translation. - Highlights: • We constructed an in vivo functional assay system for Escherichia coli ribosomal protein L6. • Growth of an E. coli ΔL6 mutant was biphasic when L6 levels were depleted. • The ΔL6 mutant accumulated 50S ribosomal subunit precursors that sedimented at 45S. • L6 is a key player in the late stage of E. coli 50S subunit assembly.
Dysregulation of X-Linked Gene Expression in Klinefelter’s Syndrome and Association With Verbal Cognition

Science.gov (United States)

Vawter, Marquis P.; Harvey, Philip D.; DeLisi, Lynn E.

2007-01-01

Klinefelter’s Syndrome (KS) is a chromosomal karyotype with one or more extra X chromosomes. KS individuals often show language impairment and the phenotype might be due to overexpression of genes on the extra X chromosome(s). We profiled mRNA derived from lymphoblastoid cell lines from males with documented KS and control males using the Affymetrix U133P microarray platform. There were 129 differentially expressed genes (DEGs) in KS group compared with controls after Benjamini–Hochberg false discovery adjustment. The DEGs included 14 X chromosome genes which were significantly over-represented. The Y chromosome had zero DEGs. In exploratory analysis of gene expression–cognition relationships, 12 DEGs showed significant correlation of expression with measures of verbal cognition in KS. Overexpression of one pseudoautosomal gene, GTPBP6 (GTP binding protein 6, putative) was inversely correlated with verbal IQ (r = −0.86, P < 0.001) and four other measures of verbal ability. Overexpression of XIST was found in KS compared to XY controls suggesting that silencing of many genes on the X chromosome might occur in KS similar to XX females. The microarray findings for eight DEGs were validated by quantitative PCR. The 14 X chromosome DEGs were not differentially expressed in prior studies comparing female and male brains suggesting a dysregulation profile unique to KS. Examination of X-linked DEGs, such as GTPBP6, TAF9L, and CXORF21, that show verbal cognition–gene expression correlations may establish a causal link between these genes, neurodevelopment, and language function. A screen of candidate genes may serve as biomarkers of KS for early diagnosis. PMID:17347996
Ribosomal protein S6 phosphorylation is controlled by TOR and modulated by PKA in Candida albicans.

Science.gov (United States)

Chowdhury, Tahmeena; Köhler, Julia R

2015-10-01

TOR and PKA signaling pathways control eukaryotic cell growth and proliferation. TOR activity in model fungi, such as Saccharomyces cerevisiae, responds principally to nutrients, e.g., nitrogen and phosphate sources, which are incorporated into the growing cell mass; PKA signaling responds to the availability of the cells' major energy source, glucose. In the fungal commensal and pathogen, Candida albicans, little is known of how these pathways interact. Here, the signal from phosphorylated ribosomal protein S6 (P-S6) was defined as a surrogate marker for TOR-dependent anabolic activity in C. albicans. Nutritional, pharmacologic and genetic modulation of TOR activity elicited corresponding changes in P-S6 levels. The P-S6 signal corresponded to translational activity of a GFP reporter protein. Contributions of four PKA pathway components to anabolic activation were then examined. In high glucose concentrations, only Tpk2 was required to upregulate P-S6 to physiologic levels, whereas all four tested components were required to downregulate P-S6 in low glucose. TOR was epistatic to PKA components with respect to P-S6. In many host niches inhabited by C. albicans, glucose is scarce, with protein being available as a nitrogen source. We speculate that PKA may modulate TOR-dependent cell growth to a rate sustainable by available energy sources, when monomers of anabolic processes, such as amino acids, are abundant. © 2015 John Wiley & Sons Ltd.
PAIN IN A PARKINSON`S DISEASE RODENT ANIMAL MODEL INDUCED WITH 6-HYDROXYDOPAMINE

Directory of Open Access Journals (Sweden)

Antioch, I

2017-06-01

Full Text Available Pain phenomenon, the unpleasant sensory and emotional event, appears to evidently intrude in Parkinson disease (PD, a disease formally considered to be restricted only to motor deficits. Although over a half of persons with PD suffer from pain manifestations, there are very few reports targeting this issue. Considering the cases when motor symptoms of PD are eclipsed by severe pain disclosure, there is an obvious need of clarifying the intricate implications of pain in PD context. Because there are few studies researching the link between pain and PD in clinical context, but as well in animal models we chose to explore the effects of pain stimuli on a rodent model of PD. Materials and methods: We experimentally induced a PD model in Wistar rats (n=12 by injecting in the substantia nigra, a brain area known to be involved in PD occurrence, one dose of a 6-hydroxidopamine (6-OHDA solution (8µm 6-OHDA base and 4µm physiological saline, utilizing neurosurgery, while their control peers received same dose of saline solution. Two weeks after the intervention the animals were subjected to the hot-plate test, a behavioral task for acquiring pain sensitivity. Results: There was noticed a statistical significant (F(1,10 = 5.67, p=0.038 sensibility of the 6-OHDA rats to thermal pain stimuli (8.2 s ± 0.8 s in 6-OHDA group as compared to their peers (13.8 s ± 1.6 s in controls. Conclusions: The involvement of pain in PD animal models is demonstrated raising questions of how it influences PD evolution. Moreover, this result increases awareness of deficient diagnostic methods of pain in PD and as a consequence, poor treatment of pain manifestations.
S -Nitrosylation inhibits the kinase activity of tomato phosphoinositide-dependent kinase 1 (PDK1)

Energy Technology Data Exchange (ETDEWEB)

Liu, Jian-Zhong; Duan, Jicheng; Ni, Min; Liu, Zhen; Qiu, Wen-Li; Whitham, Steven A.; Qian, Wei-Jun

2017-09-29

It is well known that the reactive oxygen species, nitric oxide (NO), can trigger cell death in plants, but the underlying molecular mechanisms are not well understood. Here, we provide evidence that NO may trigger cell death in tomato (Solanum lycopersicon) through inhibiting the phosphoinositide-dependent kinase 1 (PDK1) kinase activity via S-nitrosylation. Biotin-switch assays and LC-MS/MS analyses demonstrated that SlPDK1 was a target of S-nitrosylation modification, which primarily occurred on the cysteine residue at position 128 (Cys128). Accordingly, the kinase activity of SlPDK1 was inhibited by S-nitrosoglutathione (GSNO) both in vitro and in vivo in a concentration-dependent manner, indicating that SlPDK1 activity is regulated by S-nitrosylation. The inhibition of SlPDK1 kinase activity by GSNO was reversible in the presence of a reducing agent but synergistically enhanced by hydrogen peroxide (H2O2). Mutation of Cys128 to serine completely abolished SlPDK1 kinase activity, suggesting that S-nitrosylation of Cys128 is responsible for the inhibition of the kinase activity of SlPDK1. In sum, our results established a potential link between NO-triggered cell death and inhibition of the kinase activity of tomato PDK1, a conserved negative regulator of cell death in yeasts, mammals and plants. Nitric oxide (NO) potentiates the induction of hypersensitive cell death in soybean cells by reactive oxygen species (ROS) (1). However, the molecular mechanism of the NO-induced cell death remains an enigma. One potential mechanism is that the activity of proteins that control cell death may be altered by a post-translational modification, S-nitrosylation. S-nitrosylation is the addition of the NO moiety to thiol groups, including cysteine (Cys) residues in proteins, to form S-nitrosothiols (SNOs). S-nitrosylation is an enzyme-independent post-translational and labile modification that can function as an on/off switch of protein activity (2- 4). Thousands of diverse
Üks kaame naine väikses kambris ... : [luuletused] / Gyula Illyés ; tlk. Sander Liivak, Ene Asu-Õunas

Index Scriptorium Estoniae

Illyés, Gyula

2004-01-01

Sisu: Üks kaame naine väikses kambris ... ; Sa ei saa pageda ; Purukslöödud vägi ; Mäe otsas puhkan ... ; Kodumaa kõrgel ; Magav naine ; Doleo, ergo surm ; Bart̤k ; Üks lause vägivallast ; Jalutuskäik varjuga ; Tuuline öö ; Liginev külm ; Viltune puri ; Näod ; Aovalgus ; Korraloomine ; Värdjate sünd ; Charoni vene ; Tõusul ; Leegihingaja ; Lähenev vaikus ; Teekond videvikul ; Pärg. Andmeid autori kohta lk. 87-88
Intracellular S1P Generation Is Essential for S1P-Induced Motility of Human Lung Endothelial Cells: Role of Sphingosine Kinase 1 and S1P Lyase

Science.gov (United States)

Berdyshev, Evgeny V.; Gorshkova, Irina; Usatyuk, Peter; Kalari, Satish; Zhao, Yutong; Pyne, Nigel J.; Pyne, Susan; Sabbadini, Roger A.; Garcia, Joe G. N.; Natarajan, Viswanathan

2011-01-01

Background Earlier we have shown that extracellular sphingosine-1-phosphate (S1P) induces migration of human pulmonary artery endothelial cells (HPAECs) through the activation of S1P1 receptor, PKCε, and PLD2-PKCζ-Rac1 signaling cascade. As endothelial cells generate intracellular S1P, here we have investigated the role of sphingosine kinases (SphKs) and S1P lyase (S1PL), that regulate intracellular S1P accumulation, in HPAEC motility. Methodology/Principal Findings Inhibition of SphK activity with a SphK inhibitor 2-(p-Hydroxyanilino)-4-(p-Chlorophenyl) Thiazole or down-regulation of Sphk1, but not SphK2, with siRNA decreased S1Pint, and attenuated S1Pext or serum-induced motility of HPAECs. On the contrary, inhibition of S1PL with 4-deoxypyridoxine or knockdown of S1PL with siRNA increased S1Pint and potentiated motility of HPAECs to S1Pext or serum. S1Pext mediates cell motility through activation of Rac1 and IQGAP1 signal transduction in HPAECs. Silencing of SphK1 by siRNA attenuated Rac1 and IQGAP1 translocation to the cell periphery; however, knockdown of S1PL with siRNA or 4-deoxypyridoxine augmented activated Rac1 and stimulated Rac1 and IQGAP1 translocation to cell periphery. The increased cell motility mediated by down-regulation was S1PL was pertussis toxin sensitive suggesting “inside-out” signaling of intracellularly generated S1P. Although S1P did not accumulate significantly in media under basal or S1PL knockdown conditions, addition of sodium vanadate increased S1P levels in the medium and inside the cells most likely by blocking phosphatases including lipid phosphate phosphatases (LPPs). Furthermore, addition of anti-S1P mAb to the incubation medium blocked S1Pext or 4-deoxypyridoxine-dependent endothelial cell motility. Conclusions/Significance These results suggest S1Pext mediated endothelial cell motility is dependent on intracellular S1P production, which is regulated, in part, by SphK1 and S1PL. PMID:21304987
Intracellular S1P generation is essential for S1P-induced motility of human lung endothelial cells: role of sphingosine kinase 1 and S1P lyase.

Directory of Open Access Journals (Sweden)

Evgeny V Berdyshev

Full Text Available BACKGROUND: Earlier we have shown that extracellular sphingosine-1-phosphate (S1P induces migration of human pulmonary artery endothelial cells (HPAECs through the activation of S1P(1 receptor, PKCε, and PLD2-PKCζ-Rac1 signaling cascade. As endothelial cells generate intracellular S1P, here we have investigated the role of sphingosine kinases (SphKs and S1P lyase (S1PL, that regulate intracellular S1P accumulation, in HPAEC motility. METHODOLOGY/PRINCIPAL FINDINGS: Inhibition of SphK activity with a SphK inhibitor 2-(p-Hydroxyanilino-4-(p-Chlorophenyl Thiazole or down-regulation of Sphk1, but not SphK2, with siRNA decreased S1P(int, and attenuated S1P(ext or serum-induced motility of HPAECs. On the contrary, inhibition of S1PL with 4-deoxypyridoxine or knockdown of S1PL with siRNA increased S1P(int and potentiated motility of HPAECs to S1P(ext or serum. S1P(ext mediates cell motility through activation of Rac1 and IQGAP1 signal transduction in HPAECs. Silencing of SphK1 by siRNA attenuated Rac1 and IQGAP1 translocation to the cell periphery; however, knockdown of S1PL with siRNA or 4-deoxypyridoxine augmented activated Rac1 and stimulated Rac1 and IQGAP1 translocation to cell periphery. The increased cell motility mediated by down-regulation was S1PL was pertussis toxin sensitive suggesting "inside-out" signaling of intracellularly generated S1P. Although S1P did not accumulate significantly in media under basal or S1PL knockdown conditions, addition of sodium vanadate increased S1P levels in the medium and inside the cells most likely by blocking phosphatases including lipid phosphate phosphatases (LPPs. Furthermore, addition of anti-S1P mAb to the incubation medium blocked S1P(ext or 4-deoxypyridoxine-dependent endothelial cell motility. CONCLUSIONS/SIGNIFICANCE: These results suggest S1P(ext mediated endothelial cell motility is dependent on intracellular S1P production, which is regulated, in part, by SphK1 and S1PL.
Investigation on thermophysical properties of RE{sub 6}UO{sub 12}(s) (RE = La, Pr, Nd, Sm)

Energy Technology Data Exchange (ETDEWEB)

Sahu, Manjulata, E-mail: manju@barc.gov.in [Radioanalytical Chemistry Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400085 (India); Krishnan, K. [Fuel Chemistry Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400085 (India); Jain, Dheeraj [Chemistry Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400085 (India); Saxena, M.K. [Radioanalytical Chemistry Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400085 (India); Dash, Smruti [Product development Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400085 (India)

2016-08-10

Highlights: • Synthesis of RE{sub 6}UO{sub 12}(s)(RE = La, Pr, Nd, Sm) was performed by combustion method and characterization by XRD. • Thermal expansion measurements were carried out on RE{sub 6}UO{sub 12}(s)(RE = Pr, and Sm) using HT-XRD. • Heat capacity of RE{sub 6}UO{sub 12}(s)(RE = La, Pr, Nd, Sm) was measured in the temperature range 300–870 K. • The nonstoichiometry in RE{sub 6}UO{sub 12}(s) was checked using TG, XPS, chemical analysis and electrical conductivity measurement. - Abstract: RE{sub 6}UO{sub 12}(s) (RE = La, Pr, Nd, Sm) was synthesized by citrate-nitrate combustion method. The synthesis condition for Pr{sub 6}UO{sub 12}(s) was optimized. Nonstoichiometry in these rare earth uranates in argon atmosphere was analysed using various techniques like thermogravimetry (TG), X-ray photo electron spectroscopy (XPS), chemical analysis and electrical conductivity measurements. Thermal expansions of RE{sub 6}UO{sub 12}(s) (RE = Pr and Sm) was studied in the temperature range 298–1273 K by high temperature X-ray powder diffractometry and compared with that of similar rare earth compounds reported in the literature. Heat capacity of RE{sub 6}UO{sub 12}(s) (RE = La, Pr, Nd, Sm) was measured by differential scanning calorimetry in the temperature range 300–870 K. Enthalpy, entropy and Gibbs energy functions of these compounds were computed from the measured heat capacity data.
D-Glucosamine inhibits proliferation of human cancer cells through inhibition of p70S6K

International Nuclear Information System (INIS)

Oh, Hyun-Ji; Lee, Jason S.; Song, Dae-Kyu; Shin, Dong-Hoon; Jang, Byeong-Churl; Suh, Seong-Il; Park, Jong-Wook; Suh, Min-Ho; Baek, Won-Ki

2007-01-01

Although D-glucosamine has been reported as an inhibitor of tumor growth both in vivo and in vitro, the mechanism for the anticancer effect of D-glucosamine is still unclear. Since there are several reports suggesting D-glucosamine inhibits protein synthesis, we examined whether D-glucosamine affects p70S6 K activity, an important signaling molecule involved in protein translation. In the present study, we found D-glucosamine inhibited the activity of p70S6K and the proliferation of DU145 prostate cancer cells and MDA-MB-231 breast cancer cells. D-Glucosamine decreased phosphorylation of p70S6K, and its downstream substrates RPS6, and eIF-4B, but not mTOR and 4EBP1 in DU145 cells, suggesting that D-glucosamine induced inhibition of p70S6K is not through the inhibition of mTOR. In addition, D-glucosamine enhanced the growth inhibitory effects of rapamycin, a specific inhibitor of mTOR. These findings suggest that D-glucosamine can inhibit growth of cancer cells through dephosphorylation of p70S6K
Trapping {BW12}2 tungstoborate: synthesis and crystal structure of hybrid [{(H2BW12O42)2O}{Mo6O6S6(OH)4(H2O)2}]14- anion.

Science.gov (United States)

Korenev, V S; Abramov, P A; Vicent, C; Mainichev, D A; Floquet, S; Cadot, E; Sokolov, M N; Fedin, V P

2012-12-28

Reaction between monolacunary {BW(11)} tungstoborate and oxothiocationic building block, {Mo(2)O(2)S(2)}, results in the formation of a new polyoxothiometalate with a unique architecture in which two [H(2)BW(12)O(43)](9-) tungstoborate subunits are linked together with a hexamolybdate [Mo(V)(6)O(6)S(6)(OH)(4)(H(2)O)(2)](2+) bridge.
Knockdown of MAGEA6 Activates AMP-Activated Protein Kinase (AMPK) Signaling to Inhibit Human Renal Cell Carcinoma Cells.

Science.gov (United States)

Ye, Xueting; Xie, Jing; Huang, Hang; Deng, Zhexian

2018-01-01

Melanoma antigen A6 (MAGEA6) is a cancer-specific ubiquitin ligase of AMP-activated protein kinase (AMPK). The current study tested MAGEA6 expression and potential function in renal cell carcinoma (RCC). MAGEA6 and AMPK expression in human RCC tissues and RCC cells were tested by Western blotting assay and qRT-PCR assay. shRNA method was applied to knockdown MAGEA6 in human RCC cells. Cell survival and proliferation were tested by MTT assay and BrdU ELISA assay, respectively. Cell apoptosis was tested by the TUNEL assay and single strand DNA ELISA assay. The 786-O xenograft in nude mouse model was established to test RCC cell growth in vivo. MAGEA6 is specifically expressed in RCC tissues as well as in the established (786-O and A498) and primary human RCC cells. MAGEA6 expression is correlated with AMPKα1 downregulation in RCC tissues and cells. It is not detected in normal renal tissues nor in the HK-2 renal epithelial cells. MAGEA6 knockdown by targeted-shRNA induced AMPK stabilization and activation, which led to mTOR complex 1 (mTORC1) in-activation and RCC cell death/apoptosis. AMPK inhibition, by AMPKα1 shRNA or the dominant negative AMPKα1 (T172A), almost reversed MAGEA6 knockdown-induced RCC cell apoptosis. Conversely, expression of the constitutive-active AMPKα1 (T172D) mimicked the actions by MAGEA6 shRNA. In vivo, MAGEA6 shRNA-bearing 786-O tumors grew significantly slower in nude mice than the control tumors. AMPKα1 stabilization and activation as well as mTORC1 in-activation were detected in MAGEA6 shRNA tumor tissues. MAGEA6 knockdown inhibits human RCC cells via activating AMPK signaling. © 2018 The Author(s). Published by S. Karger AG, Basel.
No-carrier-added (NCA) synthesis of 6-[18F]fluoro-L-DOPA using 3,5,6,7,8,8a-hexahydro-7,7,8a-trimethyl-[6S-(6α, 8α, 8αβ)]-6,8-methano-2H-1,4-benzoxazin-2-one

International Nuclear Information System (INIS)

Horti, A.; Yale Univ., West Haven, CT; Redmond, D.E. Jr.; Soufer, R.

1995-01-01

3,5,6,7,8,8a-Hexahydro-7,7,8a-trimethyl-[6S-(6α,8α , 8αβ)]-6,8-methano-2H-1,4-benzoxazino-2-one (2) was investigated as chiral auxiliary for asymmetric NCA nucleophilic synthesis of 6-[ 18 F]Fluoro-L-DOPA. Direct condensation of 3,4-dimethoxy-2-[ 18 F]fluorobenzaldehyde (1a) or 6-[ 18 F]fluoro-piperonal (1b) in the presence of NaH with 2 gave the corresponding [ 18 F]-3-[(2-fluorophenyl)methylene]-3,5,6,7,8,8a-hexahydro-7,7,8 a-trimethyl-[6S-(3Z,3α,6α,8α,8αβ)]-6, 8-methano-2H-1,4-benzoxazin-2-one derivative 3a or 3b as a single stereoisomer. L-Selectride promoted hydrogenation of the olefinic double bond of these derivatives, in presence of tertbutyl alcohol, afforded the corresponding [ 18 F]-3-[(2-fluorophenyl) methyl]-3,5,6,7,8,8a-hexahydro-7,7,8a-trimethyl-[3S-(3α, 6α, 8α8αβ)]-6,8-methano-2H-1,4-benzoxazin-2-one derivatives (4a,b) without affecting the orientation of diasterofacial discrimination. Deprotection of the derivatives 4a,b yielded 6-[ 18 F]fluoro-L-DOPA (e.e. >90%, 3% radiochemical yield (EOB), total synthesis time 125 min, specific activity >2000 mCi/μmol). Direct deprotection/reduction of the compounds 3a,b provides the enantiomeric mixture of 6-[ 18 F]fluoro-D,L-DOPA (10-12% radiochemical yield) and, after chiral separation, 6-[ 18 F]fluoro-L-DOPA (e.e. 98%, 4-5% radiochemical yield). (author)
SF6 gas insulated power substations. Effects of fast transients (VFT) on the equipment and adjacent equipment of the Itaipu Binacional SF6 insulated power substations; Subestaciones aisladas a gas SF6. Efectos de los transitorios rapidos (VFT's) sobre equipos y equipos adyacentes de las SE's SF6 de Itaipu Binacional

Energy Technology Data Exchange (ETDEWEB)

Santacruz Martinez, Miguel [Usina Hidroelectrica de Itaipu, Assuncao (Paraguay)]. E-mail: santcruz@itaipu.gov.py

2001-07-01

With the operation starting of the S F6 gas substations in high voltage systems occurs a new form of overvoltage presently known as Very Fast Transients. This paper aims the phenomenon characterization, defining the origins and the behaviour of the electric systems, and briefly presents the damages caused by the phenomenon on the equipment and adjacent equipment of S F6 gas insulated substations of the Itaipu Binacional, mainly on the power transformers and oil/S F6 isolators of the step-up transformers. These equipment was modified or are been modified as a consequence of the this overvoltage effects.
Discrepancy between low levels of mTOR activity and high levels of p-S6 in primary central nervous system lymphoma may be explained by PAS domain-containing serine/threonine-protein kinase-mediated phosphorylation

DEFF Research Database (Denmark)

Marosvari, Dora; Nagy, Noemi; Kriston, Csilla

2018-01-01

The primary aim of this study was to determine mTOR-pathway activity in primary central nervous system lymphoma (PCNSL), which could be a potential target for therapy. After demonstrating that p-S6 positivity largely exceeded mTOR activity, we aimed to identify other pathways that may lead to S6...... phosphorylation. We measured mTOR activity with immunohistochemistry for p-mTOR and its downstream effectors p(T389)-p70S6K1, p-S6, and p-4EBP1 in 31 cases of PCNSL and 51 cases of systemic diffuse large B-cell lymphoma (DLBCL) and evaluated alternative S6 phosphorylation pathways with p-RSK, p(T229)-p70S6K1...... responsible for S6 phosphorylation, PASK proved to be positive in all cases of PCNSL and DLBCL. Inhibition of PASK resulted in reduced expression of p-S6 in BHD1-cells. This is the first study demonstrating an mTOR independent p-S6 activity in PCNSL and that PASK may contribute to the phosphorylation of S6...
Simion 3D Version 6.0 User`s Manual

Energy Technology Data Exchange (ETDEWEB)

Dahl, D.A.

1995-11-01

The original SIMION was an electrostatic lens analysis and design program developed by D.C. McGilvery at Latrobe University, Bundoora Victoria, Australia, 1977. SIMION for the PC, developed at the Idaho National Engineering Laboratory, shares little more than its name with the original McGilvery version. INEL`s fifth major SIMION release, version 6.0, represents a quantum improvement over previous versions. This C based program can model complex problems using an ion optics workbench that can hold up to 200 2D and/or 3D electrostatic/magnetic potential arrays. Arrays can have up to 10,000,000 points. SIMION 3D`s 32 bit virtual Graphics User Interface provides a highly interactive advanced user environment. All potential arrays are visualized as 3D objects that the user can cut away to inspect ion trajectories and potential energy surfaces. User programs have been greatly extended in versatility and power. A new geometry file option supports the definition of highly complex array geometry. Extensive algorithm modifications have dramatically improved this version`s computational speed and accuracy.
Sequence of the amino-terminal region of rat liver ribosomal proteins S4, S6, S8, L6, L7a, L18, L27, L30, L37, L37a, and L39.

Science.gov (United States)

Wittmann-Liebold, B; Geissler, A W; Lin, A; Wool, I G

1979-01-01

The sequence of the amino-terminal region of eleven rat liver ribosomal proteins--S4, S6, S8, L6, L7a, L18, L27, L30, L37a, and L39--was determined. The analysis confirmed the homogeneity of the proteins and suggests that they are unique, since no extensive common sequences were found. The N-terminal regions of the rat liver proteins were compared with amino acid sequences in Saccharomyces cerevisiae and in Escherichia coli ribosomal proteins. It seems likely that the proteins L37 from rat liver and Y55 from yeast ribosomes are homologous. It is possible that rat liver L7a or L37a or both are related to S cerevisiae Y44, although the similar sequences are at the amino-terminus of the rat liver proteins and in an internal region of Y44. A number of similarities in the sequences of rat liver and E coli ribosomal proteins have been found; however, it is not yet possible to say whether they connote a common ancestry.
Electrocatalysis of hemoglobin in ionic liquid BMIMPF 6 and CuS ...

African Journals Online (AJOL)

The results indicated that the BMIMPF6-CuS nanocomposite could be used for the preparation of electrochemical biosensor. KEY WORDS: Hemoglobin, Direct electrochemistry, Copper sulfide nanosphere, 1-Butyl-3-methylimidazolium hexafluorophosphate, Hydrogen peroxide. Bull. Chem. Soc. Ethiop. 2011, 25(3) ...

Measurements of the branching fractions for D+→KS0KS0K+, KS0KS0π+ and D0→KS0KS0, KS0KS0KS0

Directory of Open Access Journals (Sweden)

M. Ablikim

2017-02-01

Full Text Available By analyzing 2.93fb−1 of data taken at the ψ(3770 resonance peak with the BESIII detector, we measure the branching fractions for the hadronic decays D+→KS0KS0K+, D+→KS0KS0π+, D0→KS0KS0 and D0→KS0KS0KS0. They are determined to be B(D+→KS0KS0K+=(2.54±0.05stat.±0.12sys.×10−3, B(D+→KS0KS0π+=(2.70±0.05stat.±0.12sys.×10−3, B(D0→KS0KS0=(1.67±0.11stat.±0.11sys.×10−4 and B(D0→KS0KS0KS0=(7.21±0.33stat.±0.44sys.×10−4, where the second one is measured for the first time and the others are measured with significantly improved precision over the previous measurements.
HSP90 inhibitors potentiate PGF2α-induced IL-6 synthesis via p38 MAP kinase in osteoblasts.

Directory of Open Access Journals (Sweden)

Kazuhiko Fujita

Full Text Available Heat shock protein 90 (HSP90 that is ubiquitously expressed in various tissues, is recognized to be a major molecular chaperone. We have previously reported that prostaglandin F2α (PGF2α, a potent bone remodeling mediator, stimulates the synthesis of interleukin-6 (IL-6 through p44/p42 mitogen-activated protein (MAP kinase and p38 MAP kinase in osteoblast-like MC3T3-E1 cells, and that Rho-kinase acts at a point upstream of p38 MAP kinase. In the present study, we investigated the involvement of HSP90 in the PGF2α-stimulated IL-6 synthesis and the underlying mechanism in MC3T3-E1 cells. Geldanamycin, an inhibitor of HSP90, significantly amplified both the PGF2α-stimulated IL-6 release and the mRNA expression levels. In addition, other HSP90 inhibitors, 17-allylamino-17demethoxy-geldanamycin (17-AAG and 17-dimethylamino-ethylamino-17-demethoxy-geldanamycin (17-DMAG and onalespib, enhanced the PGF2α-stimulated IL-6 release. Geldanamycin, 17-AAG and onalespib markedly strengthened the PGF2α-induced phosphorylation of p38 MAP kinase. Geldanamycin and 17-AAG did not affect the PGF2α-induced phosphorylation of p44/p42 MAP kinase and myosin phosphatase targeting subunit (MYPT-1, a substrate of Rho-kinase, and the protein levels of RhoA and Rho-kinase. In addition, HSP90-siRNA enhanced the PGF2α-induced phosphorylation of p38 MAP kinase. Furthermore, SB203580, an inhibitor of p38 MAP kinase, significantly suppressed the amplification by geldanamycin, 17-AAG or 17-DMAG of the PGF2α-stimulated IL-6 release. Our results strongly suggest that HSP90 negatively regulates the PGF2α-stimulated IL-6 synthesis in osteoblasts, and that the effect of HSP90 is exerted through regulating p38 MAP kinase activation.
Observation of $S=+1$ Narrow Resonances in the System $pK^0_s$ from $p+\\rm {C_3H_8}$ Collision at 10 GeV/$c$

CERN Document Server

Aslanyan, P Zh; Rikhvitskaya, G G

2004-01-01

Experimental data from a 2 m propane bubble chamber have been analyzed to search for an exotic baryon state, the $\\Theta^+$ baryon, in the $pK^0_s$ decay mode for the reaction $p+{\\rm C_3H_8}$ at 10 GeV/$c$. The $pK^0_s$ invariant mass spectrum shows resonant structures with $M_{p K_s^0}=1540\\pm 8$, $1613\\pm10$, $1821\\pm11$ MeV/$c^2$ and $\\Gamma_{p K_s^0}= 9.2\\pm1.8$, $16.1\\pm4.1$, $28.0\\pm9.4$ MeV/$c^2$. The statistical significance of these peaks has been estimated as $5.5$, $4.8$ and $5.0$ s.d., respectively. There are also small peaks in mass regions of 1487 (3.0 s.d.), 1690 (3.6 s.d.) and 1980 (3.0 s.d.) MeV/$c^2$.
Insights into the Inhibition of the p90 Ribosomal S6 Kinase (RSK) by the Flavonol Glycoside SL0101 from the 1.5 Å Crystal Structure of the N-Terminal Domain of RSK2 with Bound Inhibitor

Energy Technology Data Exchange (ETDEWEB)

Utepbergenov, Darkhan; Derewenda, Urszula; Olekhnovich, Natalya; Szukalska, Gabriela; Banerjee, Budhaditya; Hilinski, Michael K.; Lannigan, Deborah A.; Stukenberg, P. Todd; Derewenda, Zygmunt S. (Lodz - Poland); (UV)

2012-09-11

The p90 ribosomal S6 family of kinases (RSK) are potential drug targets, due to their involvement in cancer and other pathologies. There are currently only two known selective inhibitors of RSK, but the basis for selectivity is not known. One of these inhibitors is a naturally occurring kaempferol-a-l-diacetylrhamnoside, SL0101. Here, we report the crystal structure of the complex of the N-terminal kinase domain of the RSK2 isoform with SL0101 at 1.5 {angstrom} resolution. The refined atomic model reveals unprecedented structural reorganization of the protein moiety, as compared to the nucleotide-bound form. The entire N-lobe, the hinge region, and the aD-helix undergo dramatic conformational changes resulting in a rearrangement of the nucleotide binding site with concomitant formation of a highly hydrophobic pocket spatially suited to accommodate SL0101. These unexpected results will be invaluable in further optimization of the SL0101 scaffold as a promising lead for a novel class of kinase inhibitors.
Observation of the rare decays $K_{s} \\to \\pi^{0} \\mu^{+} \\mu^{-}$

CERN Document Server

Batley, J Richard; Lazzeroni, C; Munday, D J; Patel, M; Slater, M W; AWotton, S; Arcidiacono, R; Bocquet, G; Ceccucci, A; Cundy, Donald C; Doble, Niels T; Falaleev, V; Gatignon, L; Gonidec, A; Grafström, P; Kubischta, Werner; Marchetto, F; Mikulec, I; Norton, A; Panzer-Steindel, B; Rubin, P; Wahl, H; Monnier, E; Swallow, E; Winston, R; Goudzovski, E; Gurev, D; Khristov, P Z; Kekelidze, Vladimir D; Kozhuharov, V; Litov, L; Madigozhin, D T; Molokanova, N A; Potrebenikov, Yu K; Stoynev, S; Zinchenko, A I; Sacco, R; Walker, A; Baldini, W; Dalpiaz, Pietro; Duclos, J; Frabetti, P L; Gianoli, A; Martini, M; Petrucci, F; Scarpa, M; Savrié, M; Bizzeti, A; Calvetti, M; Graziani, G; Iacopini, E; Lenti, M; Martelli, F; Ruggiero, G; Veltri, M; Behler, M; Eppard, K; Eppard, M; Hirstius, A; Kleinknecht, K; Koch, U; Masetti, L; Marouelli, P; Moosbrugger, U; Morales-Morales, C; Peters, A; Wanke, R; Winhart, A; Dabrowski, A; Fonseca-Martin, T; Szleper, M; Velasco, M; Anzivino, Giuseppina; Cenci, P; Imbergamo, E; Lamanna, G; Lubrano, P; Michetti, A; Nappi, A; Pepé, M; Petrucci, M C; Piccini, M; Valdata, M; Cerri, C; Collazuol, G; Costantini, F; Fantechi, R; Fiorini, Luca; Giudici, Sergio; Mannelli, I; Pierazzini, G M; Sozzi, M; Cheshkov, C; Chèze, J B; De Beer, M; Debu, P; Gouge, G; Marel, Gérard; Mazzucato, E; Peyaud, B; Vallage, B; Holder, M; Maier, A; Ziolkowski, M; Biino, C; Cartiglia, N; Clemencic, M; Goy-Lopez, S; Menichetti, E; Pastrone, N; Wislicki, W; Dibon, Heinz; Jeitler, Manfred; Markytan, Manfred; Neuhofer, G; Widhalm, L

2004-01-01

A search for the decay Ks -> pi0 mu+ mu- has been made by the NA48/1 Colaboration at the CERN SPS accelerator. The data were collected during 2002 with a high intensity Ks beam. Six events were found with a background expectation of 0.22^+0.18_0.11 events. Using a vector matrix element and unit form factor, the measured branching ratio is B(Ks -> pi0 mu+ mu-) = [2.9^+1.5_1.2(stat) +- 0.2 (syst)] x 10^9.
Deficiencia de glucosa-6-fosfato deshidrogenasa en un paciente con síndrome de Down

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Francisco R. Cammarata Scalisi

2012-07-01

Full Text Available El síndrome de Down, es una alteración genética que ocurre cuando un individuo exhibe todo o una parte específica adicional del cromosoma 21 y es la entidad más frecuentemente asociada a retardo mental. La deficiencia de glucosa-6-fosfato deshidrogenasa, es el defecto enzimático más común en humanos y presenta patrón de herencia ligado al cromosoma X recesivo. Se debe a la mutación del gen G6PD, el cual causa diversos fenotipos bioquímicos y clínicos. Reportamos un caso de lactante menor masculino, evaluado en la Unidad de Genética Médica de la Universidad de Los Andes, con el diagnóstico de deficiencia de glucosa-6-fosfato deshidrogenasa con doble mutación A376G y G202A y síndrome de Down con estudio citogenético 47, XY, +21. Palabras clave:Síndrome de Down; deficiencia de glucosa-6-fosfato deshidrogenasa; G6PD; A37G6; G202A. Glucose-6-phosphate dehydrogenase deficiency in a patient with Down syndrome Abstract Down syndrome, is a genetic disorder that occurring when an individual exhibits all or part of an extra copy of chromosome 21 and the most common entity associated mental retardation. Glucose-6-phosphate dehydrogenase deficiency, is the most common human enzyme defect and has a X-linked recessive inheritance. Due to mutations in the G6PD gene, which cause many biochemical and clinical phenotypes. We reported a case of child male, evaluated in the Unit of Medical Genetics of the University of The Andes, with diagnosis of glucose-6-phosphate dehydrogenase deficiency with double mutation A376G and G202A and Down syndrome with cytogenetic study 47, XY, + 21.
6S RNA modulates growth and antibiotic production in Streptomyces coelicolor

Czech Academy of Sciences Publication Activity Database

Mikulík, Karel; Bobek, Jan; Zídková, J.; Felsberg, Jürgen

2014-01-01

Roč. 98, č. 16 (2014), s. 7185-7197 ISSN 0175-7598 R&D Projects: GA ČR GAP302/10/0468 Institutional support: RVO:61388971 Keywords : 6SRNA * Secondary structure * pRNAs Subject RIV: EE - Microbiology, Virology Impact factor: 3.337, year: 2014
Ghrelin promotes human non-small cell lung cancer A549 cell proliferation through PI3K/Akt/mTOR/P70S6K and ERK signaling pathways.

Science.gov (United States)

Zhu, Jianhua; Yao, Jianfeng; Huang, Rongfu; Wang, Yueqin; Jia, Min; Huang, Yan

2018-04-06

Ghrelin is a gastric acyl-peptide that plays an important role in cell proliferation. In the present study, we explored the role of ghrelin in A549 cell proliferation and the possible molecular mechanisms. We found that ghrelin promotes A549 cell proliferation, knockdown of the growth hormone secretagogue receptor (GHSR) attenuated A549 cell proliferation caused by ghrelin. Ghrelin induced the rapid phosphorylation of phosphatidylinositol 3-kinase (PI3K), Akt, ERK, mammalian target of rapamycin (mTOR) and P70S6K. PI3K inhibitor (LY 294002), ERK inhibitor (PD98059) and mTOR inhibitor (Rapamycin) inhibited ghrelin-induced A549 cell proliferation. Moreover, GHSR siRNA inhibited phosphorylation of PI3K, Akt, ERK, mTOR and P70S6K induced by ghrelin. Akt and mTOR/P70S6K phosphorylation was inhibited by LY 294002 but not by PD98059. These results indicate that ghrelin promotes A549 cell proliferation via GHSR-dependent PI3K/Akt/mTOR/P70S6K and ERK signaling pathways. Copyright © 2018 Elsevier Inc. All rights reserved.
Anisotropic thermal properties and ferroelectric phase transitions in layered CuInP2S6 and CuInP2Se6 crystals

Science.gov (United States)

Liubachko, V.; Shvalya, V.; Oleaga, A.; Salazar, A.; Kohutych, A.; Pogodin, A.; Vysochanskii, Yu. M.

2017-12-01

Thermal diffusivity and thermal conductivity have been studied for the layered crystals CuInP2S6, CuInP2Se6 from 30 K to 350 K, showing a relevant thermal anisotropy. Heat is much more efficiently transferred within the layers than perpendicular to them. The ferrielectric transition in CuInP2S6 is proven to be clearly first order while the ferroelectric one in CuInP2Se6 has a weak first order character. The behavior of the thermal conductivity as a function of temperature in the ferroelectric phases shows that heat conduction is phonon driven. Disorder in the paraelectric phases due to hopping motions of Cu ions significantly reduces the thermal conductivity to extremely low values.
Expression of the cytochrome P450s, CYP6P3 and CYP6M2 are significantly elevated in multiple pyrethroid resistant populations of Anopheles gambiae s.s. from Southern Benin and Nigeria

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Ranson Hilary

2008-11-01

Full Text Available Abstract Background Insecticide resistance in Anopheles mosquitoes is threatening the success of malaria control programmes. This is particularly true in Benin where pyrethroid resistance has been linked to the failure of insecticide treated bed nets. The role of mutations in the insecticide target sites in conferring resistance has been clearly established. In this study, the contribution of other potential resistance mechanisms was investigated in Anopheles gambiae s.s. from a number of localities in Southern Benin and Nigeria. The mosquitoes were sampled from a variety of breeding sites in a preliminary attempt to investigate the role of contamination of mosquito breeding sites in selecting for resistance in adult mosquitoes. Results All mosquitoes sampled belonged to the M form of An. gambiae s.s. There were high levels of permethrin resistance in an agricultural area (Akron and an urban area (Gbedjromede, low levels of resistance in mosquito samples from an oil contaminated site (Ojoo and complete susceptibility in the rural Orogun location. The target site mutation kdrW was detected at high levels in two of the populations (Akron f = 0.86 and Gbedjromede f = 0.84 but was not detected in Ojoo or Orogun. Microarray analysis using the Anopheles gambiae detox chip identified two P450s, CYP6P3 and CYP6M2 up regulated in all three populations, the former was expressed at particularly high levels in the Akron (12.4-fold and Ojoo (7.4-fold populations compared to the susceptible population. Additional detoxification and redox genes were also over expressed in one or more populations including two cuticular pre-cursor genes which were elevated in two of the three resistant populations. Conclusion Multiple resistance mechanisms incurred in the different breeding sites contribute to resistance to permethrin in Benin. The cytochrome P450 genes, CYP6P3 and CYP6M2 are upregulated in all three resistant populations analysed. Several additional potential
Synthesis and physico-chemical properties of (R,S)-6-ditrideuteriomethylamino-4,4-diphenylheptan-3-one hydrochloride (methadone-d6)

International Nuclear Information System (INIS)

Gerardy, B.M.; Poupaert, J.H.; Vandervorst, D.; Dumont, P.; Declerq, J.-P.; Meerssche, M. van; Portoghese, P.S.

1985-01-01

A reaction sequence is described to synthesize (R,S)-6-ditrideuteriomethylamino-4,4-diphenylheptan-3-one hydrochloride (methado-ne-d 6 .HC1) in 10.5% overall yield starting from dimethylamine-d 6 hydrochloride. While methadone-d 6 .HC1 had rather similar physicochemical properties compared to methadone.HC1 in the solid phase, a divergent behaviour was observed in solution (pKa, chromatographic and 13 C-NMR data). A higher basicity along with a more important hydrophilicity were observed for the d 6 -derivative. A 13 C-NMR study showed significant differences in the 13 C chemical shifts, which were attributed in part to the intrinsic nature of D itself and in part to a conformational perturbation. The longer duration of antinociceptive action, along with higher tsub(1/2) and clearance, and the depression of the metabolic N-demethylation process were the only biological properties modified by the deuteration. (author)
Photo-induced effects of the virgin Ge_2_4_._9Sb_1_1_._6S_6_3_._5 film

International Nuclear Information System (INIS)

Knotek, P.; Tichy, L.; Kutalek, P.

2015-01-01

Amorphous Ge_2_4_._9Sb_1_1_._6S_6_3_._5 film was prepared through thermal evaporation. A blue shift of the optical band gap by approximately 100 meV was observed as a result of self-bleaching process of protected film aged for two years. The magnitude of the light induced blue shift of the optical band of the virgin film is primarily dependent on the light penetration depth and on the light intensity. The kinetics of photo-bleaching follows the stretch exponential function with a formal rate of bleaching depending on the light intensity while the saturated state is independent from the light intensity. The far infrared spectra indicate that ageing, illumination by over-band gap-photons and annealing of the virgin film are mainly accompanied by the film network ordering. Illumination by UV light photons led to a blue shift accompanied by the significant oxidation as evidenced by the results of the far infrared spectra and the energy dispersive analysis. - Highlights: • “Giant” photo-induced effects in virgin Ge_2_4_._9Sb_1_1_._6S_6_3_._5 film • The role of the film thickness, the wavelengths and intensity of excitation photons • The changes of the photo-sensitivity due to the self-ageing process • The high-intensity illumination (> 10 W/cm"2) led to the different processes
Measurements of time-dependent CP violation in B0→ωKS0, f0(980)KS0, KS0π0 and K+K-KS0 decays

Science.gov (United States)

Chao, Y.; Chen, K.-F.; Miyake, H.; Tajima, O.; Trabelsi, K.; Abe, K.; Abe, K.; Adachi, I.; Aihara, H.; Anipko, D.; Bakich, A. M.; Barberio, E.; Bitenc, U.; Bizjak, I.; Blyth, S.; Bondar, A.; Bračko, M.; Browder, T. E.; Chang, M.-C.; Chang, P.; Chen, A.; Chen, W. T.; Cheon, B. G.; Chistov, R.; Choi, Y.; Choi, Y. K.; Cole, S.; Dalseno, J.; Danilov, M.; Dash, M.; Dragic, J.; Drutskoy, A.; Eidelman, S.; Fratina, S.; Gabyshev, N.; Golob, B.; Ha, H.; Haba, J.; Hara, K.; Hara, T.; Hastings, N. C.; Hayashii, H.; Hazumi, M.; Heffernan, D.; Higuchi, T.; Hokuue, T.; Hoshi, Y.; Hou, W.-S.; Hsiung, Y. B.; Iijima, T.; Ikado, K.; Inami, K.; Ishikawa, A.; Ishino, H.; Itoh, R.; Iwasaki, M.; Iwasaki, Y.; Kaji, H.; Kang, J. H.; Kapusta, P.; Kawai, H.; Kawasaki, T.; Kim, H. J.; Kim, H. O.; Kim, Y. J.; Kinoshita, K.; Korpar, S.; Križan, P.; Krokovny, P.; Kulasiri, R.; Kumar, R.; Kuo, C. C.; Kuzmin, A.; Kwon, Y.-J.; Lee, M. J.; Lesiak, T.; Limosani, A.; Lin, S.-W.; Liventsev, D.; Matsumoto, T.; McOnie, S.; Miyabayashi, K.; Miyata, H.; Miyazaki, Y.; Mizuk, R.; Mohapatra, D.; Moloney, G. R.; Nakahama, Y.; Nakano, E.; Nakao, M.; Natkaniec, Z.; Nishida, S.; Nitoh, O.; Ogawa, S.; Okuno, S.; Olsen, S. L.; Onuki, Y.; Ozaki, H.; Pakhlov, P.; Pakhlova, G.; Park, C. W.; Pestotnik, R.; Piilonen, L. E.; Sakai, Y.; Satoyama, N.; Schietinger, T.; Schneider, O.; Schwartz, A. J.; Seidl, R.; Senyo, K.; Sevior, M. E.; Shapkin, M.; Shibuya, H.; Singh, J. B.; Somov, A.; Soni, N.; Stanič, S.; Starič, M.; Stoeck, H.; Sumisawa, K.; Sumiyoshi, T.; Suzuki, S.; Takasaki, F.; Tamai, K.; Tanaka, M.; Taylor, G. N.; Teramoto, Y.; Tian, X. C.; Tikhomirov, I.; Tsukamoto, T.; Uehara, S.; Ueno, K.; Unno, Y.; Uno, S.; Ushiroda, Y.; Usov, Y.; Varner, G.; Varvell, K. E.; Villa, S.; Vinokurova, A.; Wang, C. H.; Watanabe, Y.; Won, E.; Yabsley, B. D.; Yamaguchi, A.; Yamashita, Y.; Yamauchi, M.; Yusa, Y.; Zhilich, V.; Zhulanov, V.; Zupanc, A.

2007-11-01

We present measurements of time-dependent CP asymmetries in B0→ωKS0, f0(980)KS0, KS0π0 and K+K-KS0 decays based on a sample of 535×106 BB¯ pairs collected at the Υ(4S) resonance with the Belle detector at the KEKB energy-asymmetric e+e- collider. One neutral B meson is fully reconstructed in one of the specified decay channels, and the flavor of the accompanying B meson is identified from its decay products. CP-violation parameters for each of the decay modes are obtained from the asymmetries in the distributions of the proper-time intervals between the two B decays.
Na7 [Fe2S6 ] , Na2 [FeS2 ] and Na2 [FeSe2 ] : New 'reduced' sodium chalcogenido ferrates

Science.gov (United States)

Stüble, Pirmin; Peschke, Simon; Johrendt, Dirk; Röhr, Caroline

2018-02-01

Three new 'reduced' FeII containing sodium chalcogenido ferrates were obtained applying a reductive synthetic route. The mixed-valent sulfido ferrate Na7 [Fe2S6 ] , which forms bar-shaped crystals with metallic greenish luster, was synthesized in pure phase from natural pyrite and elemental sodium at a maximum temperature of 800 °C. Its centrosymmetric triclinic structure (SG P 1 bar , a = 764.15(2), b = 1153.70(2), c = 1272.58(3) pm, α = 62.3325 (7) , β = 72.8345 (8) , γ = 84.6394 (8) ° , Z = 3, R1 = 0.0185) exhibits two crystallographically different [Fe2S6 ] 7 - dimers of edge-sharing [FeS4 ] tetrahedra, with somewhat larger Fe-S distances than in the fully oxidized FeIII dimers of e.g. Na6 [Fe2III S6 ] . In contrast to the localized AFM ordered pure di-ferrates(III), the Curie-Weiss behavior of the magnetic susceptibility proves the rarely observed valence-delocalized S = 9/2 state of the mixed-valent FeIII /FeII dimer. The nearly spin-only value of the magnetic moment combined with the chemical bonding not generally differing from that in pure ferrates(II) and (III), provides a striking argument, that the reduction of the local Fe spin moments observed in all condensed sulfido ferrate moieties is connected with the AFM spin ordering. The two isotypic ferrates(II) Na2 [FeS2 ] and Na2 [FeSe2 ] with chain-like structural units (SG Ibam, a = 643.54(8)/ 660.81(1), b = 1140.2(2)/1190.30(2) c = 562.90(6)/585.59(1) pm, Z = 4, R1 = 0.0372/0.0466) crystallize in the K2 [ZnO2 ] -type structure. Although representing merely further members of the common series of chalcogenido metallates(II) Na2 [MIIQ2 ] , these two new phases, together with Na6 [FeS4 ] and Li2 [FeS2 ] , are the only examples of pure FeII alkali chalcogenido ferrates. The new compounds allow for a general comparison of di- and chain ferrates(II) and (III) and mixed-valent analogs concerning the electronic and magnetic properties (including Heisenberg super-exchange and double-exchange interactions
Adaptive Controller for 6-DOF Parallel Robot Using T-S Fuzzy Inference

Directory of Open Access Journals (Sweden)

Xue Jian

2013-02-01

Full Text Available 6-DOF parallel robot always appears in the form of Stewart platform. It has been widely used in industry for the benefits such as strong structural stiffness, high movement accuracy and so on. Space docking technology makes higher requirements of motion accuracy and dynamic performance to the control method on 6-DOF parallel robot. In this paper, a hydraulic 6-DOF parallel robot was used to simulate the docking process. Based on this point, this paper gave a thorough study on the design of an adaptive controller to eliminate the asymmetric of controlled plant and uncertain load force interference. Takagi-Sugeno (T-S fuzzy inference model was used to build the fuzzy adaptive controller. With T-S model, the controller directly imposes adaptive control signal on the plant to make sure that the output of plant could track the reference model output. The controller has simple structure and is easy to implement. Experiment results show that the controller can eliminate asymmetric and achieve good dynamic performance, and has good robustness to load interference.
Tyrosine phosphorylation of LRP6 by Src and Fer inhibits Wnt/β-catenin signalling

Science.gov (United States)

Chen, Qing; Su, Yi; Wesslowski, Janine; Hagemann, Anja I; Ramialison, Mirana; Wittbrodt, Joachim; Scholpp, Steffen; Davidson, Gary

2014-01-01

Low-density lipoprotein receptor-related proteins 5 and 6 (LRP5/6) function as transmembrane receptors to transduce Wnt signals. A key mechanism for signalling is Wnt-induced serine/threonine phosphorylation at conserved PPPSPxS motifs in the LRP6 cytoplasmic domain, which promotes pathway activation. Conserved tyrosine residues are positioned close to all PPPSPxS motifs, which suggests they have a functional significance. Using a cell culture-based cDNA expression screen, we identified the non-receptor tyrosine kinases Src and Fer as novel LRP6 modifiers. Both Src and Fer associate with LRP6 and phosphorylate LRP6 directly. In contrast to the known PPPSPxS Ser/Thr kinases, tyrosine phosphorylation by Src and Fer negatively regulates LRP6-Wnt signalling. Epistatically, they function upstream of β-catenin to inhibit signalling and in agreement with a negative role in regulating LRP6, MEF cells lacking these kinases show enhanced Wnt signalling. Wnt3a treatment of cells enhances tyrosine phosphorylation of endogenous LRP6 and, mechanistically, Src reduces cell surface LRP6 levels and disrupts LRP6 signalosome formation. Interestingly, CK1γ inhibits Fer-induced LRP6 phosphorylation, suggesting a mechanism whereby CK1γ acts to de-represses inhibitory LRP6 tyrosine phosphorylation. We propose that LRP6 tyrosine phosphorylation by Src and Fer serves a negative regulatory function to prevent over-activation of Wnt signalling at the level of the Wnt receptor, LRP6. Subject Categories Membrane & Intracellular Transport; Post-translational Modifications, Proteolysis & Proteomics PMID:25391905
Photocatalytic activity of Bi{sub 2}WO{sub 6}/Bi{sub 2}S{sub 3} heterojunctions: the facilitation of exposed facets of Bi{sub 2}WO{sub 6} substrate

Energy Technology Data Exchange (ETDEWEB)

Yan, Long [School of Chemistry and Chemical Engineering, Yulin University, Shaanxi Key Laboratory of Low Metamorphic Coal Clean Utilization, Yulin 71900 (China); School of Chemistry and Chemical Engineering, Yan’an University, Shaanxi Key Laboratory of Chemical Reaction Engineering, Yan’an 716000 (China); Wang, Yufei [School of Chemistry and Chemical Engineering, Yulin University, Shaanxi Key Laboratory of Low Metamorphic Coal Clean Utilization, Yulin 71900 (China); Shen, Huidong; Zhang, Yu [School of Chemistry and Chemical Engineering, Yan’an University, Shaanxi Key Laboratory of Chemical Reaction Engineering, Yan’an 716000 (China); Li, Jian [School of Chemistry and Chemical Engineering, Yulin University, Shaanxi Key Laboratory of Low Metamorphic Coal Clean Utilization, Yulin 71900 (China); Wang, Danjun, E-mail: yulyanlong@aliyun.com [School of Chemistry and Chemical Engineering, Yan’an University, Shaanxi Key Laboratory of Chemical Reaction Engineering, Yan’an 716000 (China)

2017-01-30

Highlights: • Bi{sub 2}S{sub 3}/Bi{sub 2}WO{sub 6} hybrids with exposed (020) Bi{sub 2}WO{sub 6} facets have been synthesized. • X-ray photoelectron spectroscopy reveals that a small amount of Bi{sub 2}S{sub 3} was formed. • The enhanced photoactivity of hybrids is due to heterojunction and (020) facets. • A possible photocatalytic degradation mechanism is proposed. - Abstract: Bi{sub 2}S{sub 3}/Bi{sub 2}WO{sub 6} hybrid architectures with exposed (020) Bi{sub 2}WO{sub 6} facets have been synthesized via a controlled anion exchange approach. X-ray photoelectron spectroscopy (XPS) reveals that a small amount of Bi{sub 2}S{sub 3} was formed on the surface of Bi{sub 2}WO{sub 6} during the anion exchange process, thus leading to the transformation from the Bi{sub 2}WO{sub 6} to Bi{sub 2}S{sub 3}/Bi{sub 2}WO{sub 6}. A rhodamine B (RhB) aqueous solution was chosen as model organic pollutants to evaluate the photocatalytic activities of the Bi{sub 2}S{sub 3}/Bi{sub 2}WO{sub 6} catalysts. Under visible light irradiation, the Bi{sub 2}S{sub 3}/Bi{sub 2}WO{sub 6}-TAA displayed the excellent visible light photoactivities compared with pure Bi{sub 2}S{sub 3}, Bi{sub 2}WO{sub 6} and other composite photocatalysts. The efficient photocatalytic activity of the Bi{sub 2}S{sub 3}/Bi{sub 2}WO{sub 6}-TAA composite microspheres was ascribed to the constructed heterojunctions and the inner electric field caused by the exposed (020) Bi{sub 2}WO{sub 6} facets. Active species trapping experiments revealed that h{sup +} and O{sub 2}·{sup −} are the main active species in the photocatalytic process. Furthermore, the as-obtained photocatalysts showed good photocatalytic activity after four recycles. The results presented in this study provide a new concept for the rational design and development of highly efficient photocatalysts.
Evaluation of a C57BL/6J × 129S1/SvImJ Hybrid Nestin-Thymidine Kinase Transgenic Mouse Model for Studying the Functional Significance of Exercise-Induced Adult Hippocampal Neurogenesis.

Science.gov (United States)

Hamilton, G F; Majdak, P; Miller, D S; Bucko, P J; Merritt, J R; Krebs, C P; Rhodes, J S

2015-01-01

New neurons are continuously generated in the adult hippocampus but their function remains a mystery. The nestin thymidine kinase (nestin-TK) transgenic method has been used for selective and conditional reduction of neurogenesis for the purpose of testing the functional significance of new neurons in learning, memory and motor performance. Here we explored the nestin-TK model on a hybrid genetic background (to increase heterozygosity, and "hybrid vigor"). Transgenic C57BL/6J (B6) were crossed with 129S1/SvImJ (129) producing hybrid offspring (F1) with the B6 half of the genome carrying a herpes simplex virus thymidine kinase (TK) transgene regulated by a modified nestin promoter. In the presence of exogenously administered valganciclovir, new neurons expressing TK undergo apoptosis. Female B6 nestin-TK mice ( n = 80) were evaluated for neurogenesis reduction as a positive control. Male and female F1 nestin-TK mice ( n = 223) were used to determine the impact of neurogenesis reduction on the Morris water maze (MWM) and rotarod. All mice received BrdU injections to label dividing cells and either valganciclovir or control chow, with or without a running wheel for 30 days. Both the F1 and B6 background displayed approximately 50% reduction in neurogenesis, a difference that did not impair learning and memory on the MWM or rotarod performance. Running enhanced neurogenesis and performance on the rotarod but not MWM suggesting the F1 background may not be suitable for studying pro-cognitive effects of exercise on MWM. Greater reduction of neurogenesis may be required to observe behavioral impacts. Alternatively, new neurons may not play a critical role in learning, or compensatory mechanisms in pre-existing neurons could have masked the deficits. Further work using these and other models for selectively reducing neurogenesis are needed to establish the functional significance of adult hippocampal neurogenesis in behavior.
No-carrier-added (NCA) synthesis of 6-[{sup 18}F]fluoro-L-DOPA using 3,5,6,7,8,8a-hexahydro-7,7,8a-trimethyl-[6S-(6{alpha}, 8{alpha}, 8{alpha}{beta})]-6,8-methano-2H-1,4-benzoxazin-2-one

Energy Technology Data Exchange (ETDEWEB)

Horti, A. [Yale Univ., New Haven, CT (United States). School of Medicine]|[Yale Univ., West Haven, CT (United States). PET Center; Redmond, D.E. Jr. [Yale Univ., New Haven, CT (United States). School of Medicine; Soufer, R. [Yale Univ., West Haven, CT (United States). PET Center

1995-12-31

3,5,6,7,8,8a-Hexahydro-7,7,8a-trimethyl-[6S-(6{alpha},8{alpha} , 8{alpha}{beta})]-6,8-methano-2H-1,4-benzoxazino-2-one (2) was investigated as chiral auxiliary for asymmetric NCA nucleophilic synthesis of 6-[{sup 18}F]Fluoro-L-DOPA. Direct condensation of 3,4-dimethoxy-2-[{sup 18}F]fluorobenzaldehyde (1a) or 6-[{sup 18}F]fluoro-piperonal (1b) in the presence of NaH with 2 gave the corresponding [{sup 18}F]-3-[(2-fluorophenyl)methylene]-3,5,6,7,8,8a-hexahydro-7,7,8 a-trimethyl-[6S-(3Z,3{alpha},6{alpha},8{alpha},8{alpha}{beta})]-6, 8-methano-2H-1,4-benzoxazin-2-one derivative 3a or 3b as a single stereoisomer. L-Selectride promoted hydrogenation of the olefinic double bond of these derivatives, in presence of tertbutyl alcohol, afforded the corresponding [{sup 18}F]-3-[(2-fluorophenyl) methyl]-3,5,6,7,8,8a-hexahydro-7,7,8a-trimethyl-[3S-(3{alpha}, 6{alpha}, 8{alpha}8{alpha}{beta})]-6,8-methano-2H-1,4-benzoxazin-2-one derivatives (4a,b) without affecting the orientation of diasterofacial discrimination. Deprotection of the derivatives 4a,b yielded 6-[{sup 18}F]fluoro-L-DOPA (e.e. >90%, 3% radiochemical yield (EOB), total synthesis time 125 min, specific activity >2000 mCi/{mu}mol). Direct deprotection/reduction of the compounds 3a,b provides the enantiomeric mixture of 6-[{sup 18}F]fluoro-D,L-DOPA (10-12% radiochemical yield) and, after chiral separation, 6-[{sup 18}F]fluoro-L-DOPA (e.e. 98%, 4-5% radiochemical yield). (author).
FXR blocks the growth of liver cancer cells through inhibiting mTOR-s6K pathway

Energy Technology Data Exchange (ETDEWEB)

Huang, Xiongfei, E-mail: xiongfeihuang@hotmail.com [Department of Pathology and Institute of Oncology, Preclinical School, Fujian Medical University, Fuzhou 350108, Fujian (China); Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Medical University, Fuzhou 350108, Fujian (China); Zeng, Yeting [Department of Pathology and Institute of Oncology, Preclinical School, Fujian Medical University, Fuzhou 350108, Fujian (China); Wang, Xinrui [Department of Biochemistry and Molecular Biology, Fujian Medical University, Fuzhou 350108, Fujian (China); Ma, Xiaoxiao [Department of Diabetes Complications and Metabolism, Diabetes & Metabolism Research Institute, Beckman Research Institute, City of Hope, CA 91010 (United States); Li, Qianqian; Li, Ningbo; Su, Hongying [Department of Pathology and Institute of Oncology, Preclinical School, Fujian Medical University, Fuzhou 350108, Fujian (China); Huang, Wendong [Department of Diabetes Complications and Metabolism, Diabetes & Metabolism Research Institute, Beckman Research Institute, City of Hope, CA 91010 (United States)

2016-05-27

The nuclear receptor Farnesoid X Receptor (FXR) is likely a tumor suppressor in liver tissue but its molecular mechanism of suppression is not well understood. In this study, the gene expression profile of human liver cancer cells was investigated by microarray. Bioinformatics analysis of these data revealed that FXR might regulate the mTOR/S6K signaling pathway. This was confirmed by altering the expression level of FXR in liver cancer cells. Overexpression of FXR prevented the growth of cells and induced cell cycle arrest, which was enhanced by the mTOR/S6K inhibitor rapamycin. FXR upregulation also intensified the inhibition of cell growth by rapamycin. Downregulation of FXR produced the opposite effect. Finally, we found that ectopic expression of FXR in SK-Hep-1 xenografts inhibits tumor growth and reduces expression of the phosphorylated protein S6K. Taken together, our data provide the first evidence that FXR suppresses proliferation of human liver cancer cells via the inhibition of the mTOR/S6K signaling pathway. FXR expression can be used as a biomarker of personalized mTOR inhibitor treatment assessment for liver cancer patients. -- Highlights: •FXR inhibits the proliferation of liver cancer cells by prolonging G0/G1 phase. •Microarray results indicate that mTOR-S6k signaling is involved in cellular processes in which FXR plays an important role. •FXR blocks the growth of liver cancer cells via the inhibition of the mTOR/S6K signaling pathway in vitro and in vivo.

FXR blocks the growth of liver cancer cells through inhibiting mTOR-s6K pathway

International Nuclear Information System (INIS)

Huang, Xiongfei; Zeng, Yeting; Wang, Xinrui; Ma, Xiaoxiao; Li, Qianqian; Li, Ningbo; Su, Hongying; Huang, Wendong

2016-01-01

The nuclear receptor Farnesoid X Receptor (FXR) is likely a tumor suppressor in liver tissue but its molecular mechanism of suppression is not well understood. In this study, the gene expression profile of human liver cancer cells was investigated by microarray. Bioinformatics analysis of these data revealed that FXR might regulate the mTOR/S6K signaling pathway. This was confirmed by altering the expression level of FXR in liver cancer cells. Overexpression of FXR prevented the growth of cells and induced cell cycle arrest, which was enhanced by the mTOR/S6K inhibitor rapamycin. FXR upregulation also intensified the inhibition of cell growth by rapamycin. Downregulation of FXR produced the opposite effect. Finally, we found that ectopic expression of FXR in SK-Hep-1 xenografts inhibits tumor growth and reduces expression of the phosphorylated protein S6K. Taken together, our data provide the first evidence that FXR suppresses proliferation of human liver cancer cells via the inhibition of the mTOR/S6K signaling pathway. FXR expression can be used as a biomarker of personalized mTOR inhibitor treatment assessment for liver cancer patients. -- Highlights: •FXR inhibits the proliferation of liver cancer cells by prolonging G0/G1 phase. •Microarray results indicate that mTOR-S6k signaling is involved in cellular processes in which FXR plays an important role. •FXR blocks the growth of liver cancer cells via the inhibition of the mTOR/S6K signaling pathway in vitro and in vivo.
Teoretisk och praktisk genomgång av IPv6 och dess säkerhetsaspekter

OpenAIRE

Andersson, David

2012-01-01

Den här uppsatsen går teoretiskt och praktiskt igenom IPv6 för att skapa en förståelse för det nya protokollet. Uppsatsen beskriver utöver den teoretiska genomgången av protokollet även det praktiska arbete som ligger bakom implementationen som är tänkt att kunna ge såväl privatpersoner som mindre organisationer tillgång till en säker IPv6 lösning även om Internetleverantören endast kan erbjuda IPv4. Arbetet är gjort på eget initiativ då behovet av kunskap kring IPv6 växer lavinartat och då...
Array analyses of SmKS waves and the stratification of Earth's outermost core

Science.gov (United States)

Kaneshima, Satoshi

2018-03-01

We perform array analyses of SmKS waves in order to investigate the Vp structure of the Earth's outermost core. For earthquakes recorded by broadband seismometer networks in the world, we measure differential travel times between S3KS and S2KS, between S4KS and S3KS, and between S5KS and S3KS by array techniques. The differential times are well fit by a Vp model of the Earth's outermost core, KHOMC (Kaneshima and Helffrich, 2013). Differential slownesses of S4KS and S2KS relative to S2KS are also measured for the highest quality data. The measured slownesses, with unique sensitivity to the outer core 200-400 km below the CMB, are matched by KHOMC. These observations consolidate the evidence for the presence at the top of the outer core of a layer that has a distinctively steeper Vp gradient than the bulk of the outer core. We invert new SmKS differential time data set by a tau-p method and attempt to refine the Vp profile of KHOMC. The essential features of KHOMC are preserved after the model refinement. However, the newly estimated layer thickness is nearly 450 km, which is thicker than that of KHOMC. The Vp anomalies relative to PREM for the depths 400-800 km below the CMB are less than 0.03 km/s, consistent with the degree of agreement between different Vp models for the depth range.
(1S-1,2-O-Benzylidene-α-d-glucurono-6,3-lactone

Directory of Open Access Journals (Sweden)

David J. Watkin

2009-02-01

Full Text Available X-ray crystallographic analysis has established that the major product from the protection of d-glucoronolactone with benzaldehyde is (1S-1,2-O-benzylidene-α-d-glucurono-6,3-lactone, C13H12O6, rather than the R epimer. The crystal structure exists as O—H...O hydrogen-bonded chains of molecules lying parallel to the a axis. The absolute configuration was determined by the use of d-glucuronolactone as the starting material.
Magnetism and superconductivity in Eu(Ho)Mo/sub 6/S/sub 8/

Energy Technology Data Exchange (ETDEWEB)

Capone, D.W. II; Lai Fook, M.S.; Guertin, R.P.; Hinks, D.G.; Dunlap, B.D.; Foner, S.; Abou-Aly, A.I.; Brooks, J.S.

1984-10-01

A variety of ambient and high pressure experimental results reveal the interplay between magnetism and superconductivity in Ho doped samples of the pressure induced superconductor, EuMo/sub 6/S/sub 8/. Ho concentrations up to 50 atomic percent of the rare earth ions were used. High resolution magnetic measurements are consistent with the crystalline electric field ground state for the Ho/sup 3 +/ ions being a magnetic doublet consisting largely of J/sub z/ = 18. The results of high pressure magnetization experiments reveal negligible effects of reduced lattice constant on the rare earth-rare earth interactions. Resistivity in a 10 atomic percent sample for P = 10 kbar shows the suppression of a P = 0 structural transition, metallic conductivity down to low temperatures, and finally superconductivity at 8 K. The upper critical field, H/sub c2/(T), for this sample was measured for P = 7, 10 and 12 kbar and showed strong reentrant behavior (dH/sub c2/(T)/dT > 0 as T ..-->.. 0 K). A minimum with field in the resistivity above H/sub c2/ was also observed at lowest temperatures. The H/sub c2/(T) data are compared with those of EuMo/sub 6/S/sub 8/ at high pressure, which shows positive curvature, and HoMo/sub 6/S/sub 8/, in which superconductivity is quenched by ferromagnetism at low temperatures. 14 references, 4 figures.
Optimization of Thixoforging Parameters for C70S6 Steel Connecting Rods

Science.gov (United States)

Özkara, İsa Metin; Baydoğan, Murat

2016-11-01

A microalloyed steel, C70S6, with a solidification interval of 1390-1479 °C, was thixoforged in the semisolid state in a closed die at temperatures in the range 1400-1475 °C to form a 1/7 scaled-down model of a passenger vehicle connecting rod. Die design and an optimized thixoforging temperature eliminated the excessive flash and other problems during forging. Tension test samples from connecting rods thixoforged at the optimum temperature of 1440 °C exhibited nearly the same hardness, yield strength, and ultimate tensile strength as conventional hot forged samples but ductility decreased by about 45% due to grain boundary ferrite network formed during cooling from the thixoforging temperature. Thus, C70S6-grade steel can be thixoforged at 1440 °C to form flash-free connecting rods. This conclusion was also validated using FEA analysis.
High resolution emission Fourier transform infrared spectra of the 4p-5s and 5p-6s bands of ArH.

Science.gov (United States)

Baskakov, O I; Civis, S; Kawaguchi, K

2005-03-15

In the 2500-8500 cm(-1) region several strong emission bands of (40)ArH were observed by Fourier transform spectroscopy through a dc glow discharge in a mixture of argon and hydrogen. Rotational-electronic transitions of the two previously unstudied 4p-5s and 5p-6s,v = 0-0, bands of (40)ArH were measured and assigned in the 6060 and 3770 cm(-1) regions, respectively. A simultaneous fit of the emission transitions of the 4p-5s and 5p-6s bands and an extended set of transitions of the 6s-4p band observed by Dabrowski, Tokaryk, and Watson [J. Mol. Spectrosc. 189, 95 (1998)] and remeasured in the present work yielded consistent values of the spectroscopic parameters of the electronic states under investigation. In the branch of the 4p-5s band with transitions of type (Q)Q(f(3)e) we observed a narrowing in the linewidths with increasing rotational quantum number N. The rotational dependence of the linewidth is caused by predissociation of the 5s state by the repulsive ground 4s state through homogeneous coupling and changes in overlap integrals of the vibrational wave functions with the rotational level. Analysis was based on the Fermi's golden rule approximation model. In the 4p-5s band region a vibrational sequence ofv(')-v(")=1-1, 2-2, and 3-3 were recorded and a number of transitions belonging to the strongest (Q)Q(f(3)e) form branch of the 1-1 band were analyzed.
The monoclonal S9.6 antibody exhibits highly variable binding affinities towards different R-loop sequences.

Directory of Open Access Journals (Sweden)

Fabian König

Full Text Available The monoclonal antibody S9.6 is a widely-used tool to purify, analyse and quantify R-loop structures in cells. A previous study using the surface plasmon resonance technology and a single-chain variable fragment (scFv of S9.6 showed high affinity (0.6 nM for DNA-RNA and also a high affinity (2.7 nM for RNA-RNA hybrids. We used the microscale thermophoresis method allowing surface independent interaction studies and electromobility shift assays to evaluate additional RNA-DNA hybrid sequences and to quantify the binding affinities of the S9.6 antibody with respect to distinct sequences and their GC-content. Our results confirm high affinity binding to previously analysed sequences, but reveals that binding affinities are highly sequence specific. Our study presents R-loop sequences that independent of GC-content and in different sequence variations exhibit either no binding, binding affinities in the micromolar range and as well high affinity binding in the nanomolar range. Our study questions the usefulness of the S9.6 antibody in the quantitative analysis of R-loop sequences in vivo.
Daniel 6: There and back again – A deity’s tale

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Joseph J. de Bruyn

2015-04-01

Full Text Available This article states that, with his narrative, the author of Daniel 6 creates the presence of Elohim outside Jerusalem and Israel, within non-Israelite environments. Applying a body-space frameset to the texts of Daniel 6 helps to read the text as a construction of concepts. With his narrative the author creates the presence of Elohim outside Jerusalem and Israel, within non-Israelite environments. Furthermore, a spatial frameset shows that the story of Daniel 6 can be read as a conclusion to a larger narrative that stretches from Daniel 1–6. In this narrative the author utilises spatial concepts such as the character of Daniel; the lion’s den; Jerusalem and King Darius, to establish the omnipresence of the God of Israel. In constructing this presence of-God reality the author conveys a message of hope and trust in the authority of the God of Israel. In this regard Daniel 6 is not just a story about the character Daniel being persecuted for his faith; rather it is a story about the God of Israel establishing his presence and his ability to act through and within space and time.
The high-risk HPV E6 target scribble (hScrib is required for HPV E6 expression in cervical tumour-derived cell lines

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Christian Kranjec

2016-12-01

Full Text Available The ability of high-risk HPV E6 oncoproteins to target cellular proteins which harbor PDZ domains is believed to play an important role in the virus life cycle and to influence the ability of these viruses to bring about malignant transformation. Whilst many of these PDZ proteins are potential tumour suppressors, involved in the control of cell polarity and cell-contact, recent studies suggest that mislocalisation or overexpression might result in the emergence of oncogenic functions. This has been shown most clearly for two E6 targets, hDlg and hScrib. In this study we show that hScrib plays such a role in HeLa cells, where its expression is required for maintaining high levels of HPV-18 E6 protein. Loss of hScrib has no effect on E6 stability but results in lower levels of E6 transcription and a reduced rate of E6 translation. We further show that, in the context of cervical tumour-derived cell lines, both hScrib and E6 cooperate in the activation of the S6 kinase signaling pathway, and thereby contribute towards maintaining high rates of protein translation. These results indicate that the residual hScrib that is present within HPV transformed cells is pro-oncogenic, and highlights the dual functions of E6 cell polarity targets. Keywords: HPV E6, hScrib, S6 kinase, Protein translation
[4,6-Dimethylpyrimidine-2(1H-thione-κS]iodidobis(triphenylphosphane-κPcopper(I

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Chaveng Pakawatchai

2012-06-01

Full Text Available In the mononuclear title complex, [CuI(C6H8N2S(C18H15P2], the CuI ion is in a slightly distorted tetrahedral coordination geometry formed by two P atoms from two triphenylphosphane ligands, one S atom from a 4,6-dimethylpyrimidine-2(1H-thione ligand and one iodide ion. There is an intramolecular N—H...I hydrogen bond. In the crystal, π–π stacking interactions [centroid–centroid distance = 3.594 (1 Å] are observed.
Nonlinkage of D6S260, a putative schizophrenia locus, to bipolar affective disorder

Energy Technology Data Exchange (ETDEWEB)

Adams, L.J.; Mitchell, P.B. [Univ. of South Wales (Australia); Salmon, J. [Garvan Institute of Medical Research, Sydney, New South Wales (Australia)] [and others

1996-09-20

To examine whether genes that predispose to schizophrenia also confer a predisposition to other psychiatric disorders such as bipolar affective disorder (BAD), we tested for linkage between the recently identified schizophrenia susceptibility locus D6S260 and the inheritance of BAD in 12 large Australian pedigrees. We found no evidence for linkage over a region of 12-27 cM from the D6S260 locus, depending on the model used. Our results therefore do not provide support for the continuum theory of psychosis. 13 refs., 2 tabs.
Phylogenetic relationships of the Gomphales based on nuc-25S-rDNA, mit-12S-rDNA, and mit-atp6-DNA combined sequences

Science.gov (United States)

Admir J. Giachini; Kentaro Hosaka; Eduardo Nouhra; Joseph Spatafora; James M. Trappe

2010-01-01

Phylogenetic relationships among Geastrales, Gomphales, Hysterangiales, and Phallales were estimated via combined sequences: nuclear large subunit ribosomal DNA (nuc-25S-rDNA), mitochondrial small subunit ribosomal DNA (mit-12S-rDNA), and mitochondrial atp6 DNA (mit-atp6-DNA). Eighty-one taxa comprising 19 genera and 58 species...
The Human Papillomavirus Type 16 E6 Oncoprotein Activates mTORC1 Signaling and Increases Protein Synthesis ▿ †

OpenAIRE

Spangle, Jennifer M.; Münger, Karl

2010-01-01

The mammalian target of rapamycin (mTOR) kinase acts as a cellular rheostat that integrates signals from a variety of cellular signal transduction pathways that sense growth factor and nutrient availability as well as intracellular energy status. It was previously reported that the human papillomavirus type 16 (HPV16) E6 oncoprotein may activate the S6 protein kinase (S6K) through binding and E6AP-mediated degradation of the mTOR inhibitor tuberous sclerosis complex 2 (TSC2) (Z. Lu, X. Hu, Y....
RNAi Mediated Silencing of LRRK2G2019S in Parkinson’s Disease

Science.gov (United States)

2013-08-01

WT, but not LRRK2 mutant, protected 446 dopaminergic neurons against rotenone or paraquat toxicity, 447Q12 agents which compromise [52]. The...and animal models of G2019S-mediated neurotoxicity to establish a novel therapy for PD. To achieve this objective we proposed the following Specific...kinase domain (kinase dead mutants) diminishes neurotoxicity and basal kinase levels appear to be required for the toxicity of all LRRK2 mutants [6
Solid Oxide Galvanic Cell to determine thermochemical data of Dy6UO12(s)

International Nuclear Information System (INIS)

Sahu, Manjulata; Dash, Smruti; Sen, B.K.; Venugopal, V.

2010-01-01

The rare earth elements such as Sm, Eu, Gd, and Dy have very high thermal neutron absorption cross sections and their oxides are utilized as burnable poisons in nuclear reactor to maintain constant reactivity of the core. These oxides form solid solution with urania as their ionic radii are within 20% of that of urania. Rare earth oxides-urania solid solutions are also beneficial in preventing oxidation of UO 2 (s). RE 6 UO I2 (s) (RE = rare earth) type of compounds are known to exist in RE-U-O system and their formation cannot be ruled out under transient conditions. The data on Gibbs energy of formation of compounds in RE-U-O system is therefore essential to predict the feasibility. Theoretically, the measurement of the e.m.f. of a suitable galvanic cell is one of the most accurate methods to obtain Gibbs energy of formation of compounds if e.m.f cell operates reversibly. In this study, the standard molar Gibbs energy of formation of Dy 6 UO I2 (s) was determined using solid oxide galvanic cell technique. The Gibbs energy of formation of Dy 6 UO 12 (s) is reported for the first time
The Daidzein Metabolite, 6,7,4'-Trihydroxyisoflavone, Is a Novel Inhibitor of PKCα in Suppressing Solar UV-Induced Matrix Metalloproteinase 1

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Tae-Gyu Lim

2014-11-01

Full Text Available Soy isoflavone is an attractive source of functional cosmetic materials with anti-wrinkle, whitening and skin hydration effects. After consumption, the majority of soy isoflavones are converted to their metabolites in the human gastrointestinal tract. To understand the physiological impact of soy isoflavone on the human body, it is necessary to evaluate and address the biological function of its metabolites. In this study, we investigated the effect of 6,7,4'-trihydroxyisoflavone (6,7,4'-THIF, a major metabolite of daidzein, against solar UV (sUV-induced matrix metalloproteinases (MMPs in normal human dermal fibroblasts. MMPs play a critical role in the degradation of collagen in skin, thereby accelerating the aging process of skin. The mitogen-activated protein/extracellular signal-regulated kinase (MEK/extracellular signal-regulated kinase (ERK, mitogen-activated protein kinase (MKK3/6/p38 and MKK4/c-Jun N-terminal kinases (JNK signaling pathways are known to modulate MMP-1 function, and their activation by sUV was significantly reduced by 6,7,4'-THIF pretreatment. Our results also indicated that the enzyme activity of protein kinase C (PKCα, an upstream regulator of MKKs signaling, is suppressed by 6,7,4'-THIF using the in vitro kinase assay. Furthermore, the direct interaction between 6,7,4'-THIF and endogenous PKCα was confirmed using the pull-down assay. Not only sUV-induced MMP-1 expression, but also sUV-induced signaling pathway activation were decreased in PKCα knockdown cells. Overall, we elucidated the inhibitory effect of 6,7,4'-THIF on sUV-induced MMPs and suggest PKCα as its direct molecular target.
Solid oxide galvanic cell for determination of Gibbs energy of formation of Tb6UO12(s)

International Nuclear Information System (INIS)

Sahu, Manjulata; Dash, Smruti

2013-01-01

Citrate-nitrate combustion method was used to synthesise Tb 6 UO 12 (s). Gibbs energy of formation of Tb 6 UO 12 (s) was measured using solid oxide galvanic cell in the temperature range 957-1175 K. (author)
78 FR 100 - Guidance for Industry and Food and Drug Administration Staff; Refuse To Accept Policy for 510(k)s...

Science.gov (United States)

2013-01-02

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-D-0523] Guidance for Industry and Food and Drug Administration Staff; Refuse To Accept Policy for 510(k)s; Availability AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug...
Role of p70S6K1-mediated phosphorylation of eIF4B and PDCD4 proteins in the regulation of protein synthesis.

Science.gov (United States)

Dennis, Michael D; Jefferson, Leonard S; Kimball, Scot R

2012-12-14

Modulation of mRNA binding to the 40 S ribosomal subunit during translation initiation controls not only global rates of protein synthesis but also regulates the pattern of protein expression by allowing for selective inclusion, or exclusion, of mRNAs encoding particular proteins from polysomes. The mRNA binding step is modulated by signaling through a protein kinase known as the mechanistic target of rapamycin complex 1 (mTORC1). mTORC1 directly phosphorylates the translational repressors eIF4E binding proteins (4E-BP) 1 and 2, releasing them from the mRNA cap binding protein eIF4E, thereby promoting assembly of the eIF4E·eIF4G complex. mTORC1 also phosphorylates the 70-kDa ribosomal protein S6 kinase 1 (p70S6K1), which subsequently phosphorylates eIF4B, and programmed cell death 4 (PDCD4), which sequesters eIF4A from the eIF4E·eIF4G complex, resulting in repressed translation of mRNAs with highly structured 5'-untranslated regions. In the present study, we compared the role of the 4E-BPs in the regulation of global rates of protein synthesis to that of eIF4B and PDCD4. We found that maintenance of eIF4E interaction with eIF4G was not by itself sufficient to sustain global rates of protein synthesis in the absence of mTORC1 signaling to p70S6K1; phosphorylation of both eIF4B and PDCD4 was additionally required. We also found that the interaction of eIF4E with eIF4G was maintained in the liver of fasted rats as well as in serum-deprived mouse embryo fibroblasts lacking both 4E-BP1 and 4E-BP2, suggesting that the interaction of eIF4G with eIF4E is controlled primarily through the 4E-BPs.

A model-independent approach to mixing in prompt $D^{0} \\rightarrow K_S^0 \\pi^+ \\pi^-$ decays at LHCb

CERN Document Server

Torr, Nicholas; Charles, Matthew

This thesis presents a measurement of the charm mixing parameters $x_D$ and $y_D$ in prompt $D^{0} \\rightarrow K_S^0 \\pi^+ \\pi^-$ decays using 1 fb$^{-1}$ of data collected by the LHCb experiment during 2011. \\par Mixing in charm is predicted to be small within the Standard Model, but there are significant uncertainties associated with calculating the long range contributions to the decay. Recent measurements made by LHCb and others have confirmed that mixing in charm exists at a rate of less than 1 %. With LHCb due to collect more data and Belle II being commissioned, the reduction of systematic uncertainties will become increasingly important. The $D^{0} \\rightarrow K_S^0 \\pi^+ \\pi^-$ decay provides sensitivity to both the magnitude and relative sign between the mixing parameters. It is also one of the few channels that can measure $x_D$ directly. It is therefore crucial to study this mode in detail as more data becomes available. The work presented in this thesis utilises a model-independent description of...
Sinnerite, Cu6As4S9, from the Lengenbach Quarry, Binn Valley, Switzerland

DEFF Research Database (Denmark)

Bindi, Luca; Makovicky, Emil; Nestola, Fabrizio

2013-01-01

We have characterized the crystal structure of sinnerite, Cu6As4S9, a rare sulfosalt mineral from the ores of the Lengenbach quarry, Binn Valley, Canton Valais, Switzerland, by single-crystal X-ray diffraction and chemical analysis. We found sinnerite to be structurally identical to synthetic Cu6As...
Inhibition of Early Stages of HIV-1 Assembly by INI1/hSNF5 Transdominant Negative Mutant S6 ▿

Science.gov (United States)

Cano, Jennifer; Kalpana, Ganjam V.

2011-01-01

INI1/hSNF5 is an HIV-1 integrase (IN) binding protein specifically incorporated into virions. A truncated mutant of INI1 (S6, amino acids 183 to 294) harboring the minimal IN binding Rpt1 domain potently inhibits HIV-1 particle production in a transdominant manner. The inhibition requires interaction of S6 with IN within Gag-Pol. While INI1 is a nuclear protein and harbors a masked nuclear export signal (NES), the transdominant negative mutant S6 is cytoplasmic, due to the unmasking of NES. Here, we examined the effects of subcellular localization of S6 on HIV-1 inhibition and further investigated the stages of assembly that are affected. We found that targeting a nuclear localization signal-containing S6 variant [NLS-S6(Rpt1)] to the nucleoplasm (but not to the nucleolus) resulted in complete reversal of inhibition of particle production. Electron microscopy indicated that although no electron-dense particles at any stage of assembly were seen in cells expressing S6, virions were produced in cells expressing the rescue mutant NLS-S6(Rpt1) to wild-type levels. Immunofluorescence analysis revealed that p24 exhibited a diffuse pattern of localization within the cytoplasm in cells expressing S6 in contrast to accumulation along the membrane in controls. Pulse-chase analysis indicated that in S6-expressing cells, although Gag(Pr55gag) protein translation was unaffected, processing and release of p24 were defective. Together, these results indicate that expression of S6 in the cytoplasm interferes with trafficking of Gag-Pol/Gag to the membrane and causes a defective processing leading to inhibition of assembly at an early stage prior to particle formation and budding. PMID:21159874
Deficiencia de glucosa-6-fosfato deshidrogenasa en un paciente con síndrome de Down

OpenAIRE

Francisco R. Cammarata Scalisi; Harry Sánchez; Graciela Cammarata Scalisi; Nayra Cabral Alfonso; Osmoire Moreno; Miguel Alonzo Bastardo Ramos; Gustavo Gil

2012-01-01

El síndrome de Down, es una alteración genética que ocurre cuando un individuo exhibe todo o una parte específica adicional del cromosoma 21 y es la entidad más frecuentemente asociada a retardo mental. La deficiencia de glucosa-6-fosfato deshidrogenasa, es el defecto enzimático más común en humanos y presenta patrón de herencia ligado al cromosoma X recesivo. Se debe a la mutación del gen G6PD, el cual causa diversos fenotipos bioquímicos y clínicos. Reportamos un caso de lactante menor masc...
Lean and Obese Zucker Rat Extensor Digitorum Longus Muscle high-frequency electrical stimulation (HFES Data: Regulation of p70S6kinase Associated Proteins

Directory of Open Access Journals (Sweden)

Kevin M. Rice

2018-02-01

Full Text Available Anaerobic exercise has been advocated as a prescribed treatment for the management of diabetes: however, alterations in exercise-induced signaling remain largely unexplored in the diabetic muscle. Here, we compare the basal and the in situ contraction-induced phosphorylation of the AKT, GSK3beta, mTor, p70s6K, Pten, and Shp2 in the lean and obese (fa/fa Zucker rat Extensor Digitorum Longus (EDL muscle following a single bout of contractile stimuli. This article represents data associated with prior publications from our lab (Katta et al., 2009a, 2009b; Tullgren et al., 1991 [1–3] and concurrent Data in Brief articles (Ginjupalli et al., 2017a, 2017b; Rice et al., 2017a, 2017b [4–7]. Keywords: Diabetes, Skeletal muscle, High-frequency electrical stimulation (HFES, Zucker rat, Extensor Digitorum Longus, p70s6k
Designing of molecular architecture, synthesis and properties of the next generation of state-of-the-art high-performance thermoplastic fluoro-poly(ether amide)s, (6F-PEA), fluoro-poly(ether amide-imide)s (6F-PEAI), and their co-polymers

International Nuclear Information System (INIS)

Vora, Rohitkumar H.

2010-01-01

Graphical abstract: Molecular architectures of next generation of high-performance advanced heat stable thermoplastic polymer compositions of fluoro-poly(ether amide) (6F-PA) and fluoro-poly(ether amide-imide) (6F-PEAI) having di-ether diamines moieties were designed based on fluoro-polyimide (6F-PI) chemistry, and polymers were synthesized using two novel state-of-the-art 2-(3,4'-carboxy anhydrophenyl-2(4-carboxyphenyl) hexafluoropropane (6FTMA) and 2,2'-bis(4-carboxyphenyl) hexafluropropane (6F-DAc) monomers. Their copolymers: fluoro-copoly(ether amide-(ether imide))s (6F-co(PEA-PEI)), fluoro-copoly(ether amide-(ether amide-imide))s (6F-co(PEA-PEAI)) and fluoro-copoly(ether amide-imide-(ether imide))s (6F-co(PEAI-PEI)) were also designed and synthesized using 2,2'-bis(3,4-dicarboxyphenyl) hexafluoropropane dianhydrides (6FDA) for the advanced aerospace, defense and industrial engineering applications. -- Abstract: A new generation of high-performance polymers for the advanced industrial, aerospace and defense engineering applications are being investigated in the academic and industrial research institutions throughout the world. Fluoro-polyimides (6F-PI) are one such sub-class of high-performance polyimide polymers. In the last 25 years a number of fluoro-polyimides have been reported but only a handful of them have been commercialized. This paper describes the 6F-polyimide chemistry-based designed molecular architectures and synthesis of two series of next generation of heat stable thermoplastic polymer compositions having di-ether diamines moieties, such as fluoro-poly(ether amide) (6F-PA) and fluoro-poly(ether amide-imide) (6F-PEAI) using the novel state-of-the-art 2-(3,4'-carboxy anhydrophenyl-2(4-carboxyphenyl) hexafluoropropane (6F-TMA) and 2,2'-bis(4-carboxyphenyl) hexafluoropropane (6F-DAc) monomers. Their co-polymers: fluoro-copoly(ether amide-(ether imide))s (6F-co(PEA-PEI)), fluoro-copoly(ether amide-(ether amide-imide))s (6F-co(PEA-PEAI)) and fluoro
Study of counter current flow limitation model of MARS-KS and SPACE codes under Dukler's air/water flooding test conditions

International Nuclear Information System (INIS)

Lee, Won Woong; Kim, Min Gil; Lee, Jeong Ik; Bang, Young Seok

2015-01-01

In particular, CCFL(the counter current flow limitation) occurs in components such as hot leg, downcomer annulus and steam generator inlet plenum during LOCA which is possible to have flows in two opposite directions. Therefore, CCFL is one of the thermal-hydraulic models which has significant effect on the reactor safety analysis code performance. In this study, the CCFL model will be evaluated with MARS-KS based on two-phase two-field governing equations and SPACE code based on two-phase three-field governing equations. This study will be conducted by comparing MARS-KS code which is being used for evaluating the safety of a Korean Nuclear Power Plant and SPACE code which is currently under assessment for evaluating the safety of the designed nuclear power plant. In this study, comparison of the results of liquid upflow and liquid downflow rate for different gas flow rate from two code to the famous Dukler's CCFL experimental data are presented. This study will be helpful to understand the difference between system analysis codes with different governing equations, models and correlations, and further improving the accuracy of system analysis codes. In the nuclear reactor system, CCFL is an important phenomenon for evaluating the safety of nuclear reactors. This is because CCFL phenomenon can limit injection of ECCS water when CCFL occurs in components such as hot leg, downcomer annulus or steam generator inlet plenum during LOCA which is possible to flow in two opposite directions. Therefore, CCFL is one of the thermal-hydraulic models which has significant effect on the reactor safety analysis code performance. In this study, the CCFL model was evaluated with MARS-KS and SPACE codes for studying the difference between system analysis codes with different governing equations, models and correlations. This study was conducted by comparing MARS-KS and SPACE code results of liquid upflow and liquid downflow rate for different gas flow rate to the famous Dukler's
NMR Spectroscopic Characterization of Methylcobalt(III) Compounds with Classical Ligands. Crystal Structures of [Co(NH(3))(5)(CH(3))]S(2)O(6), trans-[Co(en)(2)(NH(3))(CH(3))]S(2)O(6) (en = 1,2-Ethanediamine), and [Co(NH(3))(6)]-mer,trans-[Co(NO(2))(3)(NH(

DEFF Research Database (Denmark)

Kofod, Pauli; Harris, Pernille; Larsen, Sine

1997-01-01

magnetic resonance spectroscopy and by absorption spectroscopy. Single-crystal X-ray structure determinations at 122.0(5) K were performed on [Co(NH(3))(5)(CH(3))]S(2)O(6) (1), trans-[Co(en)(2)(NH(3))(CH(3))]S(2)O(6) (2), and [Co(NH(3))(6)]-mer,trans-[Co(NO(2))(3)(NH(3))(2)(CH(3))](2)-trans-[Co(NO(2...
Ribosomal Protein S6 Kinase (RSK-2 as a central effector molecule in RON receptor tyrosine kinase mediated epithelial to mesenchymal transition induced by macrophage-stimulating protein

Directory of Open Access Journals (Sweden)

Zhang Rui-Wen

2011-05-01

Full Text Available Abstract Background Epithelial to mesenchymal transition (EMT occurs during cancer cell invasion and malignant metastasis. Features of EMT include spindle-like cell morphology, loss of epithelial cellular markers and gain of mesenchymal phenotype. Activation of the RON receptor tyrosine kinase by macrophage-stimulating protein (MSP has been implicated in cellular EMT program; however, the major signaling determinant(s responsible for MSP-induced EMT is unknown. Results The study presented here demonstrates that RSK2, a downstream signaling protein of the Ras-Erk1/2 pathway, is the principal molecule that links MSP-activated RON signaling to complete EMT. Using MDCK cells expressing RON as a model, a spindle-shape based screen was conducted, which identifies RSK2 among various intracellular proteins as a potential signaling molecule responsible for MSP-induced EMT. MSP stimulation dissociated RSK2 with Erk1/2 and promoted RSK2 nuclear translocation. MSP strongly induced RSK2 phosphorylation in a dose-dependent manner. These effects relied on RON and Erk1/2 phosphorylation, which is significantly potentiated by transforming growth factor (TGF-β1, an EMT-inducing cytokine. Specific RSK inhibitor SL0101 completely prevented MSP-induced RSK phosphorylation, which results in inhibition of MSP-induced spindle-like morphology and suppression of cell migration associated with EMT. In HT-29 cancer cells that barely express RSK2, forced RSK2 expression results in EMT-like phenotype upon MSP stimulation. Moreover, specific siRNA-mediated silencing of RSK2 but not RSK1 in L3.6pl pancreatic cancer cells significantly inhibited MSP-induced EMT-like phenotype and cell migration. Conclusions MSP-induced RSK2 activation is a critical determinant linking RON signaling to cellular EMT program. Inhibition of RSK2 activity may provide a therapeutic opportunity for blocking RON-mediated cancer cell migration and subsequent invasion.
The Pattern of CP Asymmetries in $b\\to s$ Transitions

CERN Document Server

Buchalla, Gerhard; Nir, Y; Raz, G; Buchalla, Gerhard; Hiller, Gudrun; Nir, Yosef; Raz, Guy

2005-01-01

New CP violating physics in $b\\to s$ transitions will modify the CP asymmetries in B decays into final CP eigenstates ($\\phi K_S$, $\\eta^\\prime K_S$, $\\pi^0 K_S$, $\\omega K_S$, $\\rho^0 K_S$ and $\\eta K_S$) from their Standard Model values. In a model independent analysis, the pattern of deviations can be used to probe which Wilson coefficients get a significant contribution from the new physics. We demonstrate this idea using several well-motivated models of new physics, and apply it to current data.
Isolation and structures of sulfonium salts derived from thioethers: [{o-C(6)H(4)(CH(2)SMe)(2)}H][NbF(6)] and [{[9]aneS(3)}H][NbF(6)].

Science.gov (United States)

Jura, Marek; Levason, William; Reid, Gillian; Webster, Michael

2009-10-07

Two very unusual sulfonium salts, [{o-C(6)H(4)(CH(2)SMe)(2)}H][NbF(6)] and [{[9]aneS(3)}H][NbF(6)], obtained from reaction of the thioethers with NbF(5) in CH(2)Cl(2) solution, are reported and their structures described; the eight-coordinate tetrafluoro Nb(v) cation of the dithioether is obtained from the same reaction.
GPU acceleration of Dock6's Amber scoring computation.

Science.gov (United States)

Yang, Hailong; Zhou, Qiongqiong; Li, Bo; Wang, Yongjian; Luan, Zhongzhi; Qian, Depei; Li, Hanlu

2010-01-01

Dressing the problem of virtual screening is a long-term goal in the drug discovery field, which if properly solved, can significantly shorten new drugs' R&D cycle. The scoring functionality that evaluates the fitness of the docking result is one of the major challenges in virtual screening. In general, scoring functionality in docking requires a large amount of floating-point calculations, which usually takes several weeks or even months to be finished. This time-consuming procedure is unacceptable, especially when highly fatal and infectious virus arises such as SARS and H1N1, which forces the scoring task to be done in a limited time. This paper presents how to leverage the computational power of GPU to accelerate Dock6's (http://dock.compbio.ucsf.edu/DOCK_6/) Amber (J. Comput. Chem. 25: 1157-1174, 2004) scoring with NVIDIA CUDA (NVIDIA Corporation Technical Staff, Compute Unified Device Architecture - Programming Guide, NVIDIA Corporation, 2008) (Compute Unified Device Architecture) platform. We also discuss many factors that will greatly influence the performance after porting the Amber scoring to GPU, including thread management, data transfer, and divergence hidden. Our experiments show that the GPU-accelerated Amber scoring achieves a 6.5× speedup with respect to the original version running on AMD dual-core CPU for the same problem size. This acceleration makes the Amber scoring more competitive and efficient for large-scale virtual screening problems.
U.S. Environmental Protection Agency, Region 6 National Priorities List (NPL) Sites - 05/12/2014

Data.gov (United States)

U.S. Environmental Protection Agency — Point locations for sites in U.S. Environmental Protection Agency, Region 6 which are documented as being part of the National Priorities List as of May 12, 2014....
Interleukin-6 induces S100A9 expression in colonic epithelial cells through STAT3 activation in experimental ulcerative colitis.

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Min Jeoung Lee

Full Text Available BACKGROUND: Intestinal epithelium is essential for maintaining normal intestinal homeostasis; its breakdown leads to chronic inflammatory pathologies, such as inflammatory bowel diseases (IBDs. Although high concentrations of S100A9 protein and interleukin-6 (IL-6 are found in patients with IBD, the expression mechanism of S100A9 in colonic epithelial cells (CECs remains elusive. We investigated the role of IL-6 in S100A9 expression in CECs using a colitis model. METHODS: IL-6 and S100A9 expression, signal transducer and activator of transcription 3 (STAT3 phosphorylation, and infiltration of immune cells were analyzed in mice with dextran sulfate sodium (DSS-induced colitis. The effects of soluble gp130-Fc protein (sgp130Fc and S100A9 small interfering (si RNA (si-S100A9 on DSS-induced colitis were evaluated. The molecular mechanism of S100A9 expression was investigated in an IL-6-treated Caco-2 cell line using chromatin immunoprecipitation assays. RESULTS: IL-6 concentrations increased significantly in the colon tissues of DSS-treated mice. sgp130Fc or si-S100A9 administration to DSS-treated mice reduced granulocyte infiltration in CECs and induced the down-regulation of S100A9 and colitis disease activity. Treatment with STAT3 inhibitors upon IL-6 stimulation in the Caco-2 cell line demonstrated that IL-6 mediated S100A9 expression through STAT3 activation. Moreover, we found that phospho-STAT3 binds directly to the S100A9 promoter. S100A9 may recruit immune cells into inflamed colon tissues. CONCLUSIONS: Elevated S100A9 expression in CECs mediated by an IL-6/STAT3 signaling cascade may play an important role in the development of colitis.
41.6 Gb/s RZ-DPSK to NRZ-DPSK Format Conversion in a Microring Resonator

DEFF Research Database (Denmark)

Xiong, Meng; Ozolins, Oskars; Ding, Yunhong

2012-01-01

RZ-DPSK to NRZ-DPSK format conversion in a silicon microring resonator is demonstrated experimentally for the first time at 41.6 Gb/s. The converted signal eye diagrams and bit-error-rate measurements show the good performance of the scheme........RZ-DPSK to NRZ-DPSK format conversion in a silicon microring resonator is demonstrated experimentally for the first time at 41.6 Gb/s. The converted signal eye diagrams and bit-error-rate measurements show the good performance of the scheme.....
The 5s25p2 - (5s25p5d + 5s5p3 + 5s25p6s + 5s25p7s) transitions in Sb II and 5s25p - (5s5p2 + 5s2nl) transitions in Sb III

International Nuclear Information System (INIS)

Arcimowicz, B.; Joshi, Y.N.; Kaufman, V.

1989-01-01

The spectrum of antimony was photographed in the 575-2300 A region (1A 10 -10 m) using a hollow cathode and a triggered spark source. The analysis of the 5s 2 5p 2 - (5s 2 5p5d + 5s5p 3 + 5s 2 5p6s + 5s 2 5p7s) transitions in Sb II spectrum was revised and interpreted on the basis of multiconfiguration interaction calculations. Accurate wavelength measurements of Sb III lines lead to a revised ground-state 5s 2 5p 2 P interval value of 6574.5 cm -1 . (author). 15 refs., 9 tabs., 1 fig
Ribosomal S6K1 in POMC and AgRP Neurons Regulates Glucose Homeostasis but Not Feeding Behavior in Mice

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Mark A. Smith

2015-04-01

Full Text Available Hypothalamic ribosomal S6K1 has been suggested as a point of convergence for hormonal and nutrient signals in the regulation of feeding behavior, bodyweight, and glucose metabolism. However, the long-term effects of manipulating hypothalamic S6K1 signaling on energy homeostasis and the cellular mechanisms underlying these roles are unclear. We therefore inactivated S6K1 in pro-opiomelanocortin (POMC and agouti-related protein (AgRP neurons, key regulators of energy homeostasis, but in contrast to the current view, we found no evidence that S6K1 regulates food intake and bodyweight. In contrast, S6K1 signaling in POMC neurons regulated hepatic glucose production and peripheral lipid metabolism and modulated neuronal excitability. S6K1 signaling in AgRP neurons regulated skeletal muscle insulin sensitivity and was required for glucose sensing by these neurons. Our findings suggest that S6K1 signaling is not a general integrator of energy homeostasis in the mediobasal hypothalamus but has distinct roles in the regulation of glucose homeostasis by POMC and AgRP neurons.
Gene S characterization of Hantavirus species Seoul virus isolated from Rattus norvegicuson an Indonesian island

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Dian Perwitasari

2014-08-01

Full Text Available AbstrakLatar belakang: Hantavirus hidup dan berkembang biak di tubuh hewan pengerat, salah satunya Rattus norvegicus yang banyak ditemukan di daerah kepulauan di Indonesia. Hantavirus spesies Seoul virus (SEOV adalah virus RNA negatif rantai tunggal yang termasuk dalam keluarga Bunyaviridae, mempunyai beberapa gen spesifik terutama gen S yang dapat dikembangkan untuk uji diagnostik. Tujuan penelitian ini ialah untuk mengetahui karakter dari gen S dari Hantavirus spesies Seoulvirus.Metode:Pada penelitian ini dilakukan sekuensing gen S yang berasal dari jaringan paru-paru rodensia. Fragmen DNA yang disekuensing menggunakan primer DNA SEOS-28F danSEOS -360R,VNS-1501F dan VNS-CSR. Hasil sekuensing dianalisis menggunakan program seqscapedan dianalisis menggunakan program Bioedit dan Mega5. Analisis filogenetik untuk homologi nukleotida dan asam amino dari ketiga strain Kepulauan Seribu tersebut dibandingkan dengan spesies hantavirus lainnya yang diambil dari genebank. Hasil:Analisis Homologi nukleotida dan asam amino antara strain Kepulauan Seribu dengan SEOV menunjukkan homologi nukleotida tertinggi pada strain KS74 (88,4% dan terendah pada KS90 (87,2%, sedangkan homologi asam amino tertinggi adalah strain KS74 (91.3% dan terendah pada strain KS90 (89,5%. Kesimpulan:Karakter gen S virus yang ditemukan di Kepulauan Seribu sebanding dengan virus SEOV yang ditemukan di Singapura dan Korea. (Health Science Indones 2014;1:1-6Kata kunci:Seoul virus, gen S, Kepulauan Seribu, IndonesiaAbstractBackground: Hantavirus lives and reproduces in the body of rodents. Rattus norvegicuswas one found in the Kepulauan Seribu islands of Indonesia. Hantavirus species Seoul virus (SEOV is a negative single chain RNA viruses included in the family Bunyaviridae. It has a few specific genes, especially genes S that can be developed for a diagnostic test. The aim of this study was to ascertain the character of gene S of hantavirus species Seoul virus. Methods: Gene
Phospholipid composition and a polybasic motif determine D6 PROTEIN KINASE polar association with the plasma membrane and tropic responses.

Science.gov (United States)

Barbosa, Inês C R; Shikata, Hiromasa; Zourelidou, Melina; Heilmann, Mareike; Heilmann, Ingo; Schwechheimer, Claus

2016-12-15

Polar transport of the phytohormone auxin through PIN-FORMED (PIN) auxin efflux carriers is essential for the spatiotemporal control of plant development. The Arabidopsis thaliana serine/threonine kinase D6 PROTEIN KINASE (D6PK) is polarly localized at the plasma membrane of many cells where it colocalizes with PINs and activates PIN-mediated auxin efflux. Here, we show that the association of D6PK with the basal plasma membrane and PINs is dependent on the phospholipid composition of the plasma membrane as well as on the phosphatidylinositol phosphate 5-kinases PIP5K1 and PIP5K2 in epidermis cells of the primary root. We further show that D6PK directly binds polyacidic phospholipids through a polybasic lysine-rich motif in the middle domain of the kinase. The lysine-rich motif is required for proper PIN3 phosphorylation and for auxin transport-dependent tropic growth. Polybasic motifs are also present at a conserved position in other D6PK-related kinases and required for membrane and phospholipid binding. Thus, phospholipid-dependent recruitment to membranes through polybasic motifs might not only be required for D6PK-mediated auxin transport but also other processes regulated by these, as yet, functionally uncharacterized kinases. © 2016. Published by The Company of Biologists Ltd.
Bioaugmentation with endophytic bacterium E6S homologous to Achromobacter piechaudii enhances metal rhizoaccumulation in host Sedum plumbizincicola

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Ying eMa

2016-02-01

Full Text Available Application of hyperaccumulator–endophyte symbiotic systems is a potential approach to improve phytoremediation efficiency, since some beneficial endophytic bacteria are able to detoxify heavy metals, alter metal solubility in soil and facilitate plant growth. The objective of this study was to isolate multi-metal resistant and plant beneficial endophytic bacteria and to evaluate their role in enhancing plant growth and metal accumulation/translocation. The metal resistant endophytic bacterial strain E6S was isolated from stems of the Zn/Cd hyperaccumulator plant Sedum plumbizincicola growing in metalliferous mine soils using Dworkin and Foster salts minimal agar medium with 1-aminocyclopropane-1-carboxylate (ACC as the sole nitrogen source, and identified as homologous to Achromobacter piechaudii based on morphological and biochemical characteristics, partial 16S rDNA sequence and phylogenetic analysis. Strain E6S showed high level of resistance to various metals (Cd, Zn and Pb. Besides utilizing ACC, strain E6S exhibited plant beneficial traits, such as solubilization of phosphate and production of indole-3-acetic acid. Inoculation with E6S significantly increased the bioavailability of Cd, Zn and Pb in soil. In addition, bacterial cells bound considerable amounts of metal ions in the following order: Zn ˃ Cd ˃ Pb. Inoculation of E6S significantly stimulated plant biomass, uptake and bioaccumulation of Cd, Zn and Pb. However, E6S greatly reduced the root to shoot translocation of Cd and Zn, indicating that bacterial inoculation assisted the host plant to uptake and store heavy metals in its root system. Inoculation with the endophytic bacterium E6S homologous to A. piechaudii can improve phytostabilization of metalliferous soils due to its effective ability to enhance in situ metal rhizoaccumulation in plants.

39 CFR 6.6 - Quorum and voting.

Science.gov (United States)

2010-07-01

... 39 Postal Service 1 2010-07-01 2010-07-01 false Quorum and voting. 6.6 Section 6.6 Postal Service....6 Quorum and voting. As provided by 39 U.S.C. 205(c), the Board acts by resolution upon a majority... the compensation and benefits of the Postmaster General and Deputy Postmaster General, 39 U.S.C. 205(c...
Ascofuranone suppresses EGF-induced HIF-1α protein synthesis by inhibition of the Akt/mTOR/p70S6K pathway in MDA-MB-231 breast cancer cells

Energy Technology Data Exchange (ETDEWEB)

Jeong, Yun-Jeong; Cho, Hyun-Ji [Research Institute of Biomedical Engineering and Department of Medicine, Catholic University of Daegu School of Medicine, Daegu 705-718 (Korea, Republic of); Magae, Junji [Magae Bioscience Institute, 49-4 Fujimidai, Tsukuba 300-1263 (Japan); Lee, In-Kyu [Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu 700-721 (Korea, Republic of); Park, Keun-Gyu, E-mail: kpark@knu.ac.kr [Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu 700-721 (Korea, Republic of); Chang, Young-Chae, E-mail: ycchang@cu.ac.kr [Research Institute of Biomedical Engineering and Department of Medicine, Catholic University of Daegu School of Medicine, Daegu 705-718 (Korea, Republic of)

2013-12-15

Hypoxia-inducible factor (HIF)-1 plays an important role in tumor progression, angiogenesis and metastasis. In this study, we investigated the potential molecular mechanisms underlying the anti-angiogenic effect of ascofuranone, an isoprenoid antibiotic from Ascochyta viciae, in epidermal growth factor (EGF)-1 responsive human breast cancer cells. Ascofuranone significantly and selectively suppressed EGF-induced HIF-1α protein accumulation, whereas it did not affect the expression of HIF-1β. Furthermore, ascofuranone inhibited the transcriptional activation of vascular endothelial growth factor (VEGF) by reducing protein HIF-1α. Mechanistically, we found that the inhibitory effects of ascofuranone on HIF-1α protein expression are associated with the inhibition of synthesis HIF-1α through an EGF-dependent mechanism. In addition, ascofuranone suppressed EGF-induced phosphorylation of Akt/mTOR/p70S6 kinase, but the phosphorylation of ERK/JNK/p38 kinase was not affected by ascofuranone. These results suggest that ascofuranone suppresses EGF-induced HIF-1α protein translation through the inhibition of Akt/mTOR/p70S6 kinase signaling pathways and plays a novel role in the anti-angiogenic action. - Highlights: • Inhibitory effect of ascofuranone on HIF-1α expression is EGF-specific regulation. • Ascofuranone decreases HIF-1α protein synthesis through Akt/mTOR pathways. • Ascofuranone suppresses EGF-induced VEGF production and tumor angiogenesis.
Investigations of the trend followed in heat capacity of Re_6UO_1_2 (s) along lanthanide series

International Nuclear Information System (INIS)

Sahu, Manjulata; Saxena, M.K.; Rawat, Deepak; Dash, Smruti

2017-01-01

The compound RE_6UO_1_2 (s) (RE = Ho, Er, Tm, Yb and Lu) was synthesized by complex polymerisation method and characterised using X-ray diffraction (XRD). Heat capacity measurements of RE_6UO_1_2 (s) were performed with heat flux-type differential scanning calorimeter in the temperature range of 300-870 K. The trend in heat capacity along the rare earth series was proposed for RE_6UO_1_2 (s) and thermodynamic functions were generated. (author)
Dopaminergic neurotoxicant 6-OHDA induces oxidative damage through proteolytic activation of PKC{delta} in cell culture and animal models of Parkinson's disease

Energy Technology Data Exchange (ETDEWEB)

Latchoumycandane, Calivarathan; Anantharam, Vellareddy; Jin, Huajun; Kanthasamy, Anumantha; Kanthasamy, Arthi, E-mail: arthik@iastate.edu

2011-11-15

The neurotoxicant 6-hydroxydopamine (6-OHDA) is used to investigate the cellular and molecular mechanisms underlying selective degeneration of dopaminergic neurons in Parkinson's disease (PD). Oxidative stress and caspase activation contribute to the 6-OHDA-induced apoptotic cell death of dopaminergic neurons. In the present study, we sought to systematically characterize the key downstream signaling molecule involved in 6-OHDA-induced dopaminergic degeneration in cell culture and animal models of PD. Treatment of mesencephalic dopaminergic neuronal N27 cells with 6-OHDA (100 {mu}M) for 24 h significantly reduced mitochondrial activity and increased cytosolic cytochrome c, followed by sequential activation of caspase-9 and caspase-3. Co-treatment with the free radical scavenger MnTBAP (10 {mu}M) significantly attenuated 6-OHDA-induced caspase activities. Interestingly, 6-OHDA induced proteolytic cleavage and activation of protein kinase C delta (PKC{delta}) was completely suppressed by treatment with a caspase-3-specific inhibitor, Z-DEVD-FMK (50 {mu}M). Furthermore, expression of caspase-3 cleavage site-resistant mutant PKC{delta}{sup D327A} and kinase dead PKC{delta}{sup K376R} or siRNA-mediated knockdown of PKC{delta} protected against 6-OHDA-induced neuronal cell death, suggesting that caspase-3-dependent PKC{delta} promotes oxidative stress-induced dopaminergic degeneration. Suppression of PKC{delta} expression by siRNA also effectively protected N27 cells from 6-OHDA-induced apoptotic cell death. PKC{delta} cleavage was also observed in the substantia nigra of 6-OHDA-injected C57 black mice but not in control animals. Viral-mediated delivery of PKC{delta}{sup D327A} protein protected against 6-OHDA-induced PKC{delta} activation in mouse substantia nigra. Collectively, these results strongly suggest that proteolytic activation of PKC{delta} is a key downstream event in dopaminergic degeneration, and these results may have important translational value for
(1S,3S,8R,9S,10R-9,10-Epoxy-3,7,7,10-tetramethyltricyclo[6.4.0.01,3]dodecane

Directory of Open Access Journals (Sweden)

Abdoullah Bimoussa

2014-04-01

Full Text Available The title compound, C16H26O, was synthesized by treating (1S,3S,8R-3,7,7,10-tetramethyltricyclo[6.4.0.01,3]dodec-9-ene with metachloroperbenzoic acid. The molecule is built up from two fused six- and seven-membered rings. The six-membered ring has a half-chair conformation, whereas the seven-membered ring displays a boat conformation. In the crystal, there are no significant intermolecular interactions present.
Ribosomal S6K1 in POMC and AgRP Neurons Regulates Glucose Homeostasis but Not Feeding Behavior in Mice.

Science.gov (United States)

Smith, Mark A; Katsouri, Loukia; Irvine, Elaine E; Hankir, Mohammed K; Pedroni, Silvia M A; Voshol, Peter J; Gordon, Matthew W; Choudhury, Agharul I; Woods, Angela; Vidal-Puig, Antonio; Carling, David; Withers, Dominic J

2015-04-21

Hypothalamic ribosomal S6K1 has been suggested as a point of convergence for hormonal and nutrient signals in the regulation of feeding behavior, bodyweight, and glucose metabolism. However, the long-term effects of manipulating hypothalamic S6K1 signaling on energy homeostasis and the cellular mechanisms underlying these roles are unclear. We therefore inactivated S6K1 in pro-opiomelanocortin (POMC) and agouti-related protein (AgRP) neurons, key regulators of energy homeostasis, but in contrast to the current view, we found no evidence that S6K1 regulates food intake and bodyweight. In contrast, S6K1 signaling in POMC neurons regulated hepatic glucose production and peripheral lipid metabolism and modulated neuronal excitability. S6K1 signaling in AgRP neurons regulated skeletal muscle insulin sensitivity and was required for glucose sensing by these neurons. Our findings suggest that S6K1 signaling is not a general integrator of energy homeostasis in the mediobasal hypothalamus but has distinct roles in the regulation of glucose homeostasis by POMC and AgRP neurons. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.
(3R,6S,7aS-3-Phenyl-6-(phenylsulfanylperhydropyrrolo[1,2-c]oxazol-5-one

Directory of Open Access Journals (Sweden)

Anthony D. Woolhouse

2009-05-01

Full Text Available Molecules of the title compound [systematic name: (2R,5S,7S-2-phenyl-7-phenylsulfanyl-1-aza-3-oxabicyclo[3.3.0]octan-8-one], C18H17NO2S, form high quality crystals even though they are only packed using C—H...O(carbonyl and weak C—H...S interactions. The dihedral angle between the aromatic rings is 85.53 (5°. The fused rings adopt envelope and twist conformations.
Development and operation of a 6LiF:ZnS(Ag)-scintillating plastic capture-gated detector

Science.gov (United States)

Wilhelm, K.; Nattress, J.; Jovanovic, I.

2017-01-01

We report on the design, construction, and operation of a capture-gated neutron detector based on a heterogeneous scintillating structure comprising two scintillator types. A flat, 500 μm thick sheet composed of a mixture of lithium-6-fluoride capture agent, 6LiF, and zinc sulfide phosphor, ZnS(Ag), is wrapped around scintillating polyvinyl toluene (PVT) in a form of cylinder. The 6LiF: ZnS(Ag) sheet uses an aluminum foil backing as a support for the scintillating material and as an optical reflector, and its optical properties have been characterized independently. The composite scintillator was tested using 252Cf, DD fusion, 137Cs, and 60Co sources. The intrinsic detection efficiency for neutrons from an unmoderated 252Cf source and rejection of gammas from 137Cs were measured to be 3.6 % and 10-6, respectively. A figure of merit for pulse shape discrimination of 4.6 was achieved, and capture-gated spectroscopic analysis is demonstrated.
IR, FT-ICR-MS studies on (1'S, 6'S)-1-cyclopropyl-7-(2,8-diazabicyclo[4.3.0] non-8-yl)-6-fluoro-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid hydrochloride salt.

Science.gov (United States)

Lin, Zhiwei

2014-01-01

The infrared spectra of (1'S, 6'S)-1-cyclopropyl-7-(2,8-diazabicyclo[4.3.0] non-8-yl)-6-fluoro-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid hydrochloride salt (CLF-HCl) were studied and compared with free base. Their fragmentation pathways were investigated using tandem mass spectrometric (MS/MS) techniques on Fourier-transform ion cyclotron resonance spectrum, and many characteristic fragment ions were found. Copyright © 2013 Elsevier B.V. All rights reserved.
Branching fraction and CP asymmetry of the decays B+→KS0π+ and B+→KS0K+

NARCIS (Netherlands)

Aaij, R.; Adeva, B.; Adrover, C.; Affolder, A.; Ajaltouni, Z.; Alessio, F.; Alexander, M.; Ali, S.; Alkhazov, G.; Alvarez Cartelle, P.; Alves, A. A.; Amato, S.; Amerio, S.; Amhis, Y.; Anderlini, L.; Anderson, J.; Andreassen, R.; Andrews, J. E.; Appleby, R. B.; Aquines Gutierrez, O.; Archilli, F.; Artamonov, A.; Artuso, M.; Aslanides, E.; Auriemma, G.; Baalouch, M.; Bachmann, S.; Back, J. J.; Baesso, C.; Balagura, V.; Baldini, W.; Barlow, R. J.; Barschel, C.; Barsuk, S.; Barter, W.; Bauer, Th; Bay, A.; Beddow, J.; Bedeschi, F.; Bediaga, I.; Belogurov, S.; Belous, K.; Belyaev, I.; Ben-Haim, E.; Bencivenni, G.; Benson, S.; Benton, J.; Berezhnoy, A.; Bernet, R.; Bettler, M. O.; van Beuzekom, M.; Bien, A.; Bifani, S.; Bird, T.; Bizzeti, A.; Bjørnstad, P. M.; Blake, T.; Blanc, F.; Blouw, J.; Blusk, S.; Bocci, V.; Bondar, A.; Bondar, N.; Bonivento, W.; Borghi, S.; Borgia, A.; Bowcock, T. J.V.; Bowen, E.; Bozzi, C.; Brambach, T.; van den Brand, J.; Bressieux, J.; Brett, D.; Britsch, M.; Britton, T.; Brook, N. H.; Brown, H.; Burducea, I.; Bursche, A.; Busetto, G.; Buytaert, J.; Cadeddu, S.; Callot, O.; Calvi, M.; Calvo Gomez, M.; Camboni, A.; Campana, P.; Campora Perez, D.; Carbone, A.; Carboni, G.; Cardinale, R.; Cardini, A.; Carranza-Mejia, H.; Carvalho Akiba, K.; Casse, G.; Castillo Garcia, L.; Cattaneo, M.; Cauet, Ch; Cenci, R.; Charles, M.; Charpentier, Ph; Chen, P.; Chiapolini, N.; Chrzaszcz, M.; Ciba, K.; Cid Vidal, X.; Ciezarek, G.; Clarke, P. E.L.; Clemencic, M.; Cliff, H. V.; Closier, J.; Coca, C.; Coco, V.; Cogan, J.; Cogneras, E.; Collins, P.; Comerma-Montells, A.; Contu, A.; Cook, A.; Coombes, M.; Coquereau, S.; Corti, G.; Couturier, B.; Cowan, G. A.; Craik, D. C.; Cunliffe, S.; Currie, R.; D'Ambrosio, C.; David, P.; Davis, A.; De Bonis, I.; De Bruyn, K.; De Capua, S.; De Cian, M.; De Miranda, J. M.; De Paula, L.; De Silva, W.; De Simone, P.; Decamp, D.; Deckenhoff, M.; Del Buono, L.; Déléage, N.; Derkach, D.; Deschamps, O.; Dettori, F.; Di Canto, A.; Dogaru, M.; Donleavy, S.; Dordei, F.; Dosil Suárez, A.; Dossett, D.; Dovbnya, A.; Dupertuis, F.; Durante, P.; Dzhelyadin, R.; Dziurda, A.; Dzyuba, A.; Easo, S.; Egede, U.; Egorychev, V.; Eidelman, S.; van Eijk, D.; Eisenhardt, S.; Eitschberger, U.; Ekelhof, R.; Eklund, L.; El Rifai, I.; Elsasser, Ch; Falabella, A.; Färber, C.; Fardell, G.; Farinelli, C.; Farry, S.; Ferguson, D.; Fernandez Albor, V.; Ferreira Rodrigues, F.; Ferro-Luzzi, M.; Filippov, S.; Fiore, M.; Fitzpatrick, C.; Fontana, M.; Fontanelli, F.; Forty, R.; Francisco, O.; Frank, M.; Frei, C.; Frosini, M.; Furcas, S.; Furfaro, E.; Gallas Torreira, A.; Galli, D.; Gandelman, M.; Gandini, P.; Gao, Y.; Garofoli, J.; Garosi, P.; Garra Tico, J.; Garrido, L.; Gaspar, C.; Gauld, R.; Gersabeck, E.; Gersabeck, M.; Gershon, T.; Ghez, Ph; Gibson, V.; Giubega, L.; Gligorov, V. V.; Göbel, C.; Golubkov, D.; Golutvin, A.; Gomes, A.; Gorbounov, P.; Gordon, H.; Gotti, C.; Grabalosa Gándara, M.; Graciani Diaz, R.; Granado Cardoso, L. A.; Graugés, E.; Graziani, G.; Grecu, A.; Greening, E.; Gregson, S.; Grünberg, O.; Gui, B.; Gushchin, E.; Guz, Yu; Gys, T.; Hadjivasiliou, C.; Haefeli, G.; Haen, C.; Haines, S. C.; Hall, S.; Hamilton, B.; Hampson, T.; Hansmann-Menzemer, S.; Harnew, N.; Harnew, S. T.; Harrison, J.; Head, T.; Heijne, V.; Hennessy, K.; Henrard, P.; Hernando Morata, J. A.; van Herwijnen, E.; Hess, M.; Hicheur, A.; Hicks, E.; Hill, D.; Hoballah, M.; Hombach, C.; Hopchev, P.; Hulsbergen, W.; Hunt, P.; Huse, T.; Hussain, N.; Hutchcroft, D.; Hynds, D.; Iakovenko, V.; Idzik, M.; Ilten, P.; Jacobsson, R.; Jaeger, A.; Jans, E.; Jaton, P.; Jawahery, A.; Jing, F.; John, M.; Jones, C. R.; Joram, C.; Jost, B.; Kaballo, M.; Kandybei, S.; Kanso, W.; Karacson, M.; Karbach, T. M.; Kenyon, I. R.; Ketel, T.; Keune, A.; Khanji, B.; Kochebina, O.; Komarov, I.; Koopman, R. F.; Koppenburg, P.; Korolev, M.; Kozlinskiy, A.; Kravchuk, L.; Kreplin, K.; Kreps, M.; Krocker, G.; Krokovny, P.; Kruse, F.; Kucharczyk, M.; Kudryavtsev, V.; Kvaratskheliya, T.; La Thi, V. N.; Lacarrere, D.; Lafferty, G.; Lai, A.; Lambert, D.; Lambert, R. W.; Lanciotti, E.; Lanfranchi, G.; Langenbruch, C.; Latham, T.; Lazzeroni, C.; Le Gac, R.; van Leerdam, J.; Lees, J. P.; Lefèvre, R.; Leflat, A.; Lefrançois, J.; Leo, S.; Leroy, O.; Lesiak, T.; Leverington, B.; Li Gioi, L.; Liles, M.; Lindner, R.; Linn, C.; Lohn, S.; Longstaff, I.; Lopes, J. H.; Lopez-March, N.; Lu, H.; Lucchesi, D.; Luisier, J.; Luo, H.; Machefert, F.; Machikhiliyan, I. V.; Maciuc, F.; Maev, O.; Malde, S.; Manca, G.; Mancinelli, G.; Maratas, J.; Marconi, U.; Marino, P.; Märki, R.; Marks, J.; Martellotti, G.; Martín Sánchez, A.; Martinelli, M.; Martinez Santos, D.; Martins Tostes, D.; Martynov, A.; Massafferri, A.; Matev, R.; Mathe, Z.; Matteuzzi, C.; Maurice, E.; Mazurov, A.; McCarthy, J.; McNab, A.; McNulty, R.; McSkelly, B.; Meadows, B.; Meier, F.; Meissner, M.; Merk, M.; Milanes, D. A.; Minard, M. N.; Molina Rodriguez, J.; Monteil, S.; Moran, D.; Morawski, P.; Mordà, A.; Morello, M. J.; Mountain, R.; Mous, I.; Muheim, F.; Müller, K.; Muresan, R.; Muryn, B.; Muster, B.; Naik, P.; Nakada, T.; Nandakumar, R.; Nasteva, I.; Needham, M.; Neubert, S.; Neufeld, N.; Nguyen, A. D.; Nguyen-Mau, C.; Nicol, M.; Niess, V.; Niet, R.; Nikitin, N.; Nikodem, T.; Nomerotski, A.; Novoselov, A.; Oblakowska-Mucha, A.; Obraztsov, V.; Oggero, S.; Ogilvy, S.; Okhrimenko, O.; Oldeman, R.; Orlandea, M.; Otalora Goicochea, J. M.; Owen, P.; Oyanguren, A.; Pal, B. K.; Palano, A.; Palczewski, T.; Palutan, M.; Panman, J.; Papanestis, A.; Pappagallo, M.; Parkes, C.; Parkinson, C. J.; Passaleva, G.; Patel, G. D.; Patel, M.; Patrick, G. N.; Patrignani, C.; Pavel-Nicorescu, C.; Pazos Alvarez, A.; Pellegrino, A.; Penso, G.; Pepe Altarelli, M.; Perazzini, S.; Perez Trigo, E.; Pérez-Calero Yzquierdo, A.; Perret, P.; Perrin-Terrin, M.; Pescatore, L.; Pesen, E.; Petridis, K.; Petrolini, A.; Phan, A.; Picatoste Olloqui, E.; Pietrzyk, B.; Pilař, T.; Pinci, D.; Playfer, S.; Plo Casasus, M.; Polci, F.; Polok, G.; Poluektov, A.; Polycarpo, E.; Popov, A.; Popov, D.; Popovici, B.; Potterat, C.; Powell, A.; Prisciandaro, J.; Pritchard, A.; Prouve, C.; Pugatch, V.; Puig Navarro, A.; Punzi, G.; Qian, W.; Rademacker, J. H.; Rakotomiaramanana, B.; Rangel, M. S.; Raniuk, I.; Rauschmayr, N.; Raven, G.; Redford, S.; Reid, M. M.; dos Reis, A. C.; Ricciardi, S.; Richards, A.; Rinnert, K.; Rives Molina, V.; Roa Romero, D. A.; Robbe, P.; Roberts, D. A.; Rodrigues, E.; Rodriguez Perez, P.; Roiser, S.; Romanovsky, V.; Romero Vidal, A.; Rouvinet, J.; Ruf, T.; Ruffini, F.; Ruiz, H.; Ruiz Valls, P.; Sabatino, G.; Saborido Silva, J. J.; Sagidova, N.; Sail, P.; Saitta, B.; Salustino Guimaraes, V.; Sanmartin Sedes, B.; Sannino, M.; Santacesaria, R.; Santamarina Rios, C.; Santovetti, E.; Sapunov, M.; Satriano, C.; Satta, A.; Savrie, M.; Savrina, D.; Schaack, P.; Schiller, M.; Schindler, H.; Schlupp, M.; Schmelling, M.; Schmidt, B.; Schneider, O.; Schopper, A.; Schune, M. H.; Schwemmer, R.; Sciascia, B.; Sciubba, A.; Seco, M.; Semennikov, A.; Senderowska, K.; Sepp, I.; Serra, N.; Serrano, J.; Seyfert, P.; Shapkin, M.; Shapoval, I.; Shatalov, P.; Shcheglov, Y.; Shears, T.; Shekhtman, L.; Shevchenko, O.; Shevchenko, V.; Shires, A.; Silva Coutinho, R.; Sirendi, M.; Skidmore, N.; Skwarnicki, T.; Smith, N. A.; Smith, J.; Smith, M.; Sokoloff, M. D.; Soler, F. J.P.; Soomro, F.; Souza, D.; Souza De Paula, B.; Spaan, B.; Sparkes, A.; Spradlin, P.; Stagni, F.; Stahl, S.; Steinkamp, O.; Stevenson, S.; Stoica, S.; Stone, S.; Storaci, B.; Straticiuc, M.; Straumann, U.; Subbiah, V. K.; Sun, L.; Swientek, S.; Syropoulos, V.; Szczekowski, M.; Szczypka, P.; Szumlak, T.; T'Jampens, S.; Teklishyn, M.; Teodorescu, E.; Teubert, F.; Thomas, C.; van Tilburg, J.; Tisserand, V.; Tobin, M.; Tolk, S.; Tonelli, D.; Topp-Joergensen, S.; Torr, N.; Tournefier, E.; Tourneur, S.; Tran, M. T.; Tresch, M.; Tsaregorodtsev, A.; Tsopelas, P.; Tuning, N.; Ubeda Garcia, M.; Ukleja, A.; Urner, D.; Ustyuzhanin, A.; Uwer, U.; Vagnoni, V.; Valenti, G.; Vallier, A.; Vazquez Gomez, R.; Vazquez Regueiro, P.; Vázquez Sierra, C.; Vecchi, S.; Velthuis, J. J.; Veltri, M.; Veneziano, G.; Vesterinen, M.; Viaud, B.; Vieira, D.; Vilasis-Cardona, X.; Vollhardt, A.; Volyanskyy, D.; Voong, D.; Vorobyev, A.; Vorobyev, V.; Voß, C.; Waldi, R.; Wallace, C.; Wallace, R.; Wandernoth, S.; Ward, D. R.; Watson, N. K.; Webber, A. D.; Websdale, D.; Whitehead, M.; Wicht, J.; Wiechczynski, J.; Wiedner, D.; Wilkinson, G.; Williams, M. P.; Williams, M.; Wilson, F. F.; Wimberley, J.; Wishahi, J.; Wislicki, W.; Witek, M.; Wotton, S. A.; Wright, S.; Wyllie, K.; Xie, Y.; Xing, Z.; Yang, Z.; Young, R.; Yuan, X.; Yushchenko, O.; Zangoli, M.; Zavertyaev, M.; Zhang, F.; Zhang, W. C.; Zhelezov, A.; Zhokhov, A.; Zhong, L.; Zvyagin, A.

2013-01-01

An analysis of B+→KS0π+ and B+→KS0K+ decays is performed with the LHCb experiment. The pp collision data used correspond to integrated luminosities of 1fb-1 and 2fb-1 collected at centre-of-mass energies of √s=7TeV and √s=8TeV, respectively. The ratio of branching fractions and the direct CP
Synthesis, structural, electronic and linear electro-optical features of new quaternary Ag2Ga2SiS6 compound

Science.gov (United States)

Piasecki, M.; Myronchuk, G. L.; Parasyuk, O. V.; Khyzhun, O. Y.; Fedorchuk, A. O.; Pavlyuk, V. V.; Kozer, V. R.; Sachanyuk, V. P.; El-Naggar, A. M.; Albassam, A. A.; Jedryka, J.; Kityk, I. V.

2017-02-01

For the first time phase equilibria and phase diagram of the AgGaS2-SiS2 system were successfully explored by differential thermal and X-ray phase analysis methods. Crystal structure of low-temperature (LT) modification of Ag2Ga2SiS6 (LT- Ag2Ga2SiS6) was studied by X-ray powder method and it belongs to tetragonal space group I-42d, with unit cell parameters a=5.7164(4) Å, c=9.8023(7) Å, V=320.32(7) Å3. Additional details regarding the crystal structure exploration are available at the web page Fachinformationszentrum Karlsruhe. X-ray photoelectron core-level and valence-band spectra were measured for pristine LT- Ag2Ga2SiS6 crystal surface. In addition, the X-ray photoelectron valence-band spectrum of LT-Ag2Ga2SiS6 was matched on a common energy scale with the X-ray emission S Kβ1,3 and Ga Kβ2 bands, which give information on the energy distribution of the S 3p and Ga 4p states, respectively. The presented X-ray spectroscopy results indicate that the valence S p and Ga p atomic states contribute mainly to the upper and central parts of the valence band of LT-Ag2Ga2SiS6, respectively, with a less significant contribution also to other valence-band regions. Band gap energy was estimated by measuring the quantum energy in the spectral range of the fundamental absorption. We have found that energy gap Eg is equal to 2.35 eV at 300 K. LT-Ag2Ga2SiS6 is a photosensitive material and reveals two spectral maxima on the curve of spectral photoconductivity spectra at λmax1 =590 nm and λmax2 =860 nm. Additionally, linear electro-optical effect of LT-Ag2Ga2SiS6 for the wavelengths of a cw He-Ne laser at 1150 nm was explored.
The valence state of uranium in K{sub 6}Cu{sub 12}U{sub 2}S{sub 15}

Energy Technology Data Exchange (ETDEWEB)

Schilder, H; Speldrich, M; Lueken, H; Sutorik, A C; Kanatzidis, M G

2004-07-14

The paramagnetic behaviour of K{sub 6}Cu{sub 12}U{sub 2}S{sub 15} has been analysed, regarding copper as diamagnetic (Cu{sup +}), sulfur as mixed-valent S{sup 2-}/S{sup -} with magnetically silent delocalized S{sup -} holes in the valence band, and the actinide as either U{sup 5+}[5f{sup 1}] or U{sup 4+}[5f{sup 2}] in trigonally distorted octahedral surrounding (pseudosymmetry 3-bar) of sulfur. Fitting procedures have been carried out, accounting for spin-orbit coupling, ligand-field potential (parameters B{sup k}{sub q}), interelectronic repulsion (for U{sup 4+}[5f{sup 2}]), cooperative magnetic effects (molecular field parameter {lambda}), and applied magnetic field. Keeping the ratios B{sup 4}{sub 3}/B{sup 4}{sub 0}, B{sup 6}{sub 3}/B{sup 6}{sub 0}, B{sup 6}{sub 6}/B{sup 6}{sub 0} on their point charge electrostatic values with respect to the sulfur ligands, the three axial parameters B{sup k}{sub 0} (k=2,4,6) and {lambda} were refined. Agreement between measured and calculated susceptibility data was obtained for U{sup 5+} with B{sup k}{sub 0} values expected for octahedral surrounding and {lambda}<0 speaking for antiferromagnetic interactions. The U{sup 4+} model does yield a fit of comparable quality, but gives B{sup k}{sub 0} values that are unreasonable with respect to sign and magnitude. To conclude, on the basis of the magnetic properties the title compound is a 5f{sup 1} system corresponding to the elements formal charges (K{sup +}){sub 6}(Cu{sup +}){sub 12}(U{sup 5+}){sub 2}(S{sup 2-}){sub 13}(S{sup -}){sub 2}.
The Effects of IGF-1 on TNF-α-Treated DRG Neurons by Modulating ATF3 and GAP-43 Expression via PI3K/Akt/S6K Signaling Pathway.

Science.gov (United States)

Zhang, Lei; Yue, Yaping; Ouyang, Meishuo; Liu, Huaxiang; Li, Zhenzhong

2017-05-01

Upregulation of the pro-inflammatory cytokine tumor necrosis factor α (TNF-α) is involved in the development and progression of numerous neurological disorders. Recent reports have challenged the concept that TNF-α exhibits only deleterious effects of pro-inflammatory destruction, and have raised the awareness that it may play a beneficial role in neuronal growth and function in particular conditions, which prompts us to further investigate the role of this cytokine. Insulin-like growth factor-1 (IGF-1) is a cytokine possessing powerful neuroprotective effects in promoting neuronal survival, neuronal differentiation, neurite elongation, and neurite regeneration. The association of IGF-1 with TNF-α and the biological effects, produced by interaction of IGF-1 and TNF-α, on neuronal outgrowth status of primary sensory neurons are still to be clarified. In the present study, using an in vitro model of primary cultured rat dorsal root ganglion (DRG) neurons, we demonstrated that TNF-α challenge at different concentrations elicited diverse biological effects. Higher concentration of TNF-α (10 ng/mL) dampened neurite outgrowth, induced activating transcription factor 3 (ATF3) expression, reduced growth-associated protein 43 (GAP-43) expression, and promoted GAP-43 and ATF3 coexpression, which could be reversed by IGF-1 treatment; while lower concentration of TNF-α (1 ng/mL) promoted neurite sprouting, decreased ATF3 expression, increased GAP-43 expression, and inhibited GAP-43 and ATF3 coexpression, which could be potentiated by IGF-1 supplement. Moreover, IGF-1 administration restored the activation of Akt and p70 S6 kinase (S6K) suppressed by higher concentration of TNF-α (10 ng/mL) challenge. In contrast, lower concentration of TNF-α (1 ng/mL) had no significant effect on Akt or S6K activation, and IGF-1 administration activated these two kinases. The effects of IGF-1 were abrogated by phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002. These data
Methylation of 6-mercaptopurine and 6-thioguanine by thiopurine S-methyltransferase. A comparison of activity in red blood cell samples of 199 blood donors.

Science.gov (United States)

Kröplin, T; Iven, H

2000-07-01

To compare 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG) as substrates for the methylation reaction catalysed by the enzyme thiopurine S-methyltransferase (TPMT). TPMT activity in haemolysed red blood cells of healthy blood donors was determined twice, using the same experimental setting and equal molar concentrations of 6-TG and 6-MP as substrates. After extraction, the reaction products 6-methyl-TG and 6-methyl-MP were quantified using specific high-performance liquid chromatography procedures. The medians of the TPMT activities from 199 blood donors were 54.4 nmol 6-MTG g(-1)Hb h(-1) when measured with 6-TG as the substrate and 35.8 nmol 6-MMP g(-1) Hb h(-1) when measured with 6-MP. The correlation coefficient for the 199 pairs of values was 0.8695. On average, TPMT activity was 34% lower with 6-MP as substrate than with 6-TG as substrate.
Optimization of {sup 6}LiF:ZnS(Ag) Scintillator Light Yield Using Geant4

Energy Technology Data Exchange (ETDEWEB)

Yehuda-Zada, Y. [Nuclear Research Center Negev, Beer-Sheva (Israel); Ben-Gurion University (Israel); Pritchard, K.; Ziegler, J.B.; Cooksey, C.; Siebein, K. [National Institute of Standards and Technology, Gaithersburg, Maryland (United States); Jackson, M.; Hurlbut, C. [Eljen Technology, Sweetwater Texas (United States); Kadmon, Y.; Cohen, Y.; Maliszewskyj, N.C. [Nuclear Research Center Negev, Beer-Sheva (Israel); Ibberson, R.M.; Majkrzak, C.F. [National Institute of Standards and Technology, Gaithersburg, Maryland (United States); Orion, Y. [Ben-Gurion University (Israel); Osovizky, A. [National Institute of Standards and Technology, Gaithersburg, Maryland (United States); Rotem Industries Ltd, Rotem Industrial Park (Israel); University of Maryland (United States)

2015-07-01

Neutrons provide an effective tool to probe materials structure. Neutron diffraction is a method to determine the atomic and magnetic structure of a material based on neutron scattering. By this method a collimated incident beam of thermal neutrons heat the examined sample and based on the obtained diffraction pattern information on the structure of the material is provided. Research for developing a novel cold neutron detector for Chromatic Analysis Neutron Diffractometer Or Reflectometer (CANDOR) is underway at the NIST center for neutron research. The system unique design is aimed to provide over ten times fold faster analysis of materials than conventional system. In order to achieve the fast analysis a large number of neutron detectors is required. A key design constraint for this detector is the thickness of the neutron sensitive element. This is met using {sup 6}LiF:ZnS(Ag) scintillation material with embedded wavelength shifting (WLS) fibers conducting scintillation light to silicon photomultiplier photo-sensors. The detector sensitivity is determined by both the neutron capture probability ({sup 6}Li density) and the detectable light output produced by the ZnS(Ag) ionization, the latter of which is hindered by the fluorescence absorption of the scintillation light by the ZnS. Tradeoffs between the neutron capture probability, stimulated light production and light attenuation for determining the optimal stoichiometry of the {sup 6}LiF and ZnS(Ag) as well as the volume ratio of scintillator and fiber. Simulations performed using the GEANT4 Monte Carlo package were made in order to optimize the detector design. GEANT4 enables the investigation of the neutron interaction with the detector, the ionization process and the light transfer process following the nuclear process. The series of conversions required for this detector were modelled: - A cold neutron enters the sensor and is captured by {sup 6}Li in the scintillator mixture ({sup 6}Li (n,α) {sup 3}H
Rational Arithmetic Mathematica Functions to Evaluate the Two-Sided One Sample K-S Cumulative Sampling Distribution

Directory of Open Access Journals (Sweden)

J. Randall Brown

2007-06-01

Full Text Available One of the most widely used goodness-of-fit tests is the two-sided one sample Kolmogorov-Smirnov (K-S test which has been implemented by many computer statistical software packages. To calculate a two-sided p value (evaluate the cumulative sampling distribution, these packages use various methods including recursion formulae, limiting distributions, and approximations of unknown accuracy developed over thirty years ago. Based on an extensive literature search for the two-sided one sample K-S test, this paper identifies an exact formula for sample sizes up to 31, six recursion formulae, and one matrix formula that can be used to calculate a p value. To ensure accurate calculation by avoiding catastrophic cancelation and eliminating rounding error, each of these formulae is implemented in rational arithmetic. For the six recursion formulae and the matrix formula, computational experience for sample sizes up to 500 shows that computational times are increasing functions of both the sample size and the number of digits in the numerator and denominator integers of the rational number test statistic. The computational times of the seven formulae vary immensely but the Durbin recursion formula is almost always the fastest. Linear search is used to calculate the inverse of the cumulative sampling distribution (find the confidence interval half-width and tables of calculated half-widths are presented for sample sizes up to 500. Using calculated half-widths as input, computational times for the fastest formula, the Durbin recursion formula, are given for sample sizes up to two thousand.
Lattice instability in the non-superconducting compound EuMo6S8

International Nuclear Information System (INIS)

Baillif, R.; Junod, A.; Lachal, B.; Muller, J.; Yvon, K.

1981-01-01

Electrical resistivity and specific heat measurements were performed on bulk Eusub(1.1)Mo 6 S 8 together with low-temperature X-ray powder diffractometry. These investigations revealed a structural phase transition (occuring at 109 K) from the room-temperature rhombohedral structure to a low-temperature triclinic distorted structure in which the compound exhibits a non-metallic behavior. (author)
Ibrutinib: a first in class covalent inhibitor of Bruton’s tyrosine kinase

Science.gov (United States)

Davids, Matthew S; Brown, Jennifer R

2015-01-01

Ibrutinib (formerly PCI-32765) is a potent, covalent inhibitor of Bruton’s tyrosine kinase, a kinase downstream of the B-cell receptor that is critical for B-cell survival and proliferation. In preclinical studies, ibrutinib bound to Bruton’s tyrosine kinase with high affinity, leading to inhibition of B-cell receptor signaling, decreased B-cell activation and induction of apoptosis. In clinical studies, ibrutinib has been well-tolerated and has demonstrated profound anti-tumor activity in a variety of hematologic malignancies, most notably chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL), leading to US FDA approval for relapsed CLL and MCL. Ongoing studies are evaluating ibrutinib in other types of non-Hodgkin’s lymphoma, such as diffuse large B-cell lymphoma and Waldenström’s macrogobulinemia, in larger Phase III studies in CLL and MCL, and in combination studies with monoclonal antibodies and chemotherapy. Future studies will combine ibrutinib with other promising novel agents currently in development in hematologic malignancies. PMID:24941982
6d N=(1,0) theories on S{sup 1}/T{sup 2} and class S theories: part II

Energy Technology Data Exchange (ETDEWEB)

Ohmori, Kantaro; Shimizu, Hiroyuki [Department of Physics, Faculty of Science, University of Tokyo,Bunkyo-ku, Tokyo 133-0022 (Japan); Tachikawa, Yuji [Department of Physics, Faculty of Science, University of Tokyo,Bunkyo-ku, Tokyo 133-0022 (Japan); Institute for the Physics and Mathematics of the Universe, University of Tokyo,Kashiwa, Chiba 277-8583 (Japan); Yonekura, Kazuya [Institute for the Physics and Mathematics of the Universe, University of Tokyo,Kashiwa, Chiba 277-8583 (Japan); School of Natural Sciences, Institute for Advanced Study,Princeton, NJ 08540 (United States)

2015-12-21

We study the T{sup 2} compactification of a class of 6d N=(1,0) theories that is Higgsable to N=(2,0) theories. We show that the resulting 4d N=2 theory at the origin of the Coulomb branch and the parameter space is generically given by two superconformal matter sectors coupled by an infrared-free gauge multiplet and another conformal gauge multiplet. Our analysis utilizes the 5d theories obtained by putting the same class of 6d theories on S{sup 1}. Our class includes, among others, the 6d theories describing multiple M5 branes on an ALE singularity, and we analyze them in detail. The resulting 4d theory has manifestly both the SL(2,ℤ) and the full flavor symmetry. We also discuss in detail the special cases of 6d theories where the infrared-free gauge multiplet is absent. In an appendix, we give a field-theoretical argument for an F-theoretic constraint that forbids a particular 6d anomaly-free matter content, as an application of our analysis.
The PDZ Ligand Domain of the Human Papillomavirus Type 16 E6 Protein Is Required for E6's Induction of Epithelial Hyperplasia In Vivo

Science.gov (United States)

Nguyen, Marie L.; Nguyen, Minh M.; Lee, Denis; Griep, Anne E.; Lambert, Paul F.

2003-01-01

Human papillomaviruses (HPVs) are the causative agent of warts. Infections with high-risk HPVs are associated with anogenital and head and neck cancers. One of the viral genes responsible for HPV's oncogenic activity is E6. Mice expressing the HPV-16 E6 protein in their epidermis (K14E6WT) develop epithelial hyperplasia and squamous carcinomas. Numerous cellular proteins interact with E6, some of which can be grouped based on common amino acid motifs in their E6-binding domains. One such group, the PDZ partners, including hDLG, hSCRIBBLE, MUPP1, and MAGI, bind to the carboxy-terminal four amino acids of E6 through their PDZ domains. E6's interaction with the PDZ partners leads to their degradation. Additionally, E6's binding to PDZ proteins has been correlated with its ability to transform baby rat kidney cells in tissue culture and to confer tumorigenicity onto cells in xenograft experiments. To address whether the ability of E6 to bind PDZ domain partners is necessary for E6 to confer epithelial hyperproliferation in vivo, we generated transgenic mice that express in stratified squamous epithelia a mutant of E6 lacking the last six amino acids at its carboxyl terminus, E6Δ146-151, from the human keratin 14 (K14) promoter. The K14E6Δ146-151 mice exhibit a radiation response similar to that of the K14E6WT mice, demonstrating that this protein, as predicted, retains an ability to inactivate p53. However, the K14E6Δ146-151 mice fail to display epithelial hyperplasia. These results indicate that an interaction of E6 with PDZ partners is necessary for its induction of epithelial hyperplasia. PMID:12768014

Pressure-induced magnetic collapse and metallization of TlF e1.6S e2

Science.gov (United States)

Naumov, P. G.; Filsinger, K.; Shylin, S. I.; Barkalov, O. I.; Ksenofontov, V.; Qi, Y.; Palasyuk, T.; Schnelle, W.; Medvedev, S. A.; Greenblatt, M.; Felser, C.

2017-08-01

The crystal structure, magnetic ordering, and electrical resistivity of TlF e1.6S e2 were studied at high pressures. Below ˜7 GPa , TlF e1.6S e2 is an antiferromagnetically ordered semiconductor with a ThC r2S i2 -type structure. The insulator-to-metal transformation observed at a pressure of ˜7 GPa is accompanied by a loss of magnetic ordering and an isostructural phase transition. In the pressure range ˜7.5 -11 GPa a remarkable downturn in resistivity, which resembles a superconducting transition, is observed below 15 K. We discuss this feature as the possible onset of superconductivity originating from a phase separation in a small fraction of the sample in the vicinity of the magnetic transition.
Risk of classical Kaposi sarcoma by plasma levels of Epstein-Barr virus antibodies, sCD26, sCD23 and sCD30

Directory of Open Access Journals (Sweden)

Viviano Enza

2010-10-01

Full Text Available Abstract Background To clarify the immunological alterations leading to classical Kaposi sarcoma (cKS among people infected with KS-associated herpesvirus (KSHV. Methods In a population-based study of 119 cKS cases, 105 KSHV-seropositive controls, and 155 KSHV-seronegative controls, we quantified plasma soluble cluster of differentiation (sCD levels and antibodies against Epstein-Barr virus nuclear antigen-1 (anti-EBNA-1 and viral capsid antigen (anti-VCA. Differences between groups in prevalence of low-tertile anti-EBNA-1 and high-tertile anti-VCA were compared by logistic regression. Continuous levels between groups and by presence of cKS co-factors among controls were compared by linear regression and Mann-Whitney-Wilcoxon methods. Results Comparisons of cKS cases to seropositive controls and of seropositive to seronegative controls revealed no significant differences. However, controls with known cKS cofactors (male sex, nonsmoking, diabetes and cortisone use had significantly lower levels of anti-EBNA (P = 0.0001 - 0.07 and anti-VCA (P = 0.0001 - 0.03. Levels of sCD26 were significantly lower for male and non-smoking controls (Padj ≤ 0.03, and they were marginally lower with older age and cortisone use (Padj ≤ 0.09. Conclusions Anti-EBV and sCD26 levels were associated with cofactors for cKS, but they did not differ between cKS cases and matched controls. Novel approaches and broader panels of assays are needed to investigate immunological contributions to cKS.
Overexpression of Notch3 and pS6 Is Associated with Poor Prognosis in Human Ovarian Epithelial Cancer

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Zhaoxia Liu

2016-01-01

Full Text Available Notch3 and pS6 play important roles in tumor angiogenesis. To assess the expression of Notch3 and pS6 in Chinese ovarian epithelial cancer patients, a ten-year follow-up study was performed in ovarian epithelial cancer tissues from 120 specimens of human ovarian epithelial cancer, 30 specimens from benign ovarian tumors, and 30 samples from healthy ovaries by immunohistochemistry. The results indicate that the expression of Notch3 and pS6 was higher in ovarian epithelial cancer than in normal ovary tissues and in benign ovarian tumor tissues (p0.05 but positively associated with clinical stage, pathological grading, histologic type, lymph node metastasis, and ascites (p<0.05 or p<0.01. A follow-up survey of 64 patients with ovarian epithelial cancer showed that patients with high Notch3 and pS6 expression had a shorter survival time (p<0.01, in which the clinical stage (p<0.05 and Notch3 expression (p<0.01 played important roles. In conclusion, Notch3 and pS6 are significantly related to ovarian epithelial cancer development and prognosis, and their combination represents a potential biomarker and therapeutic target in ovarian tumor angiogenesis.
An empirical assessment of near-source strong ground motion for a 6.6 m{sub b} (7.5 M{sub S}) earthquake in the Eastern United States

Energy Technology Data Exchange (ETDEWEB)

Campbell, Kenneth W

1984-06-01

To help assess the impact of the current U.S. Geological Survey position on the seismic safety of nuclear power plants in the Eastern United States (EUS), several techniques for estimating near-source strong ground motion for a Charleston size earthquake were evaluated. The techniques for estimating the near-source strong ground motion for a 6.6 m{sub b} (7.5 M{sub S}) in the Eastern United States which were assessed are methods based on site specific analyses, semi-theoretical scaling techniques, and intensity-based estimates. The first involves the statistical analysis of ground motion records from earthquakes and recording stations having the same general characteristics (earthquakes with magnitudes of 7.5 M{sub S} or larger, epicentral distances of 25 km or less, and sites of either soil or rock). Some recommendations for source and characterization scaling of the bias resulting primarily from an inadequate sample of near-source recordings from earthquakes of large magnitude are discussed. The second technique evaluated requires that semi-theoretical estimates of peak ground motion parameters for a 6.6 m{sub b} (7.5 M{sub S}) earthquake be obtained from scaling relations. Each relation uses a theoretical expression between peak acceleration magnitude and distance together with available strong motion data (majority coming from California) to develop a scaling relation appropriate for the Eastern United States. None of the existing ground motion models for the EUS include the potential effects of source or site characteristics. Adjustments to account for fault mechanisms, site topography, site geology, and the size and embedment of buildings are discussed. The final approach used relations between strong ground motion parameters and Modified Mercalli Intensity in conjunction with two methods to estimate peak parameters for a 6.6 m{sub s} (7.5 M{sub S}) earthquake. As with other techniques, adjustment of peak acceleration estimates are discussed. Each method
Phosphorylation of Ribosomal Protein S6 Mediates Mammalian Target of Rapamycin Complex 1-Induced Parathyroid Cell Proliferation in Secondary Hyperparathyroidism.

Science.gov (United States)

Volovelsky, Oded; Cohen, Gili; Kenig, Ariel; Wasserman, Gilad; Dreazen, Avigail; Meyuhas, Oded; Silver, Justin; Naveh-Many, Tally

2016-04-01

Secondary hyperparathyroidism is characterized by increased serum parathyroid hormone (PTH) level and parathyroid cell proliferation. However, the molecular pathways mediating the increased parathyroid cell proliferation remain undefined. Here, we found that the mTOR pathway was activated in the parathyroid of rats with secondary hyperparathyroidism induced by either chronic hypocalcemia or uremia, which was measured by increased phosphorylation of ribosomal protein S6 (rpS6), a downstream target of the mTOR pathway. This activation correlated with increased parathyroid cell proliferation. Inhibition of mTOR complex 1 by rapamycin decreased or prevented parathyroid cell proliferation in secondary hyperparathyroidism rats and in vitro in uremic rat parathyroid glands in organ culture. Knockin rpS6(p-/-) mice, in which rpS6 cannot be phosphorylated because of substitution of all five phosphorylatable serines with alanines, had impaired PTH secretion after experimental uremia- or folic acid-induced AKI. Uremic rpS6(p-/-) mice had no increase in parathyroid cell proliferation compared with a marked increase in uremic wild-type mice. These results underscore the importance of mTOR activation and rpS6 phosphorylation for the pathogenesis of secondary hyperparathyroidism and indicate that mTORC1 is a significant regulator of parathyroid cell proliferation through rpS6. Copyright © 2016 by the American Society of Nephrology.
Cocrystals of 6-propyl-2-thiouracil: N-H···O versus N-H···S hydrogen bonds.

Science.gov (United States)

Tutughamiarso, Maya; Egert, Ernst

2011-11-01

In order to investigate the relative stability of N-H···O and N-H···S hydrogen bonds, we cocrystallized the antithyroid drug 6-propyl-2-thiouracil with two complementary heterocycles. In the cocrystal pyrimidin-2-amine-6-propyl-2-thiouracil (1/2), C(4)H(5)N(3)·2C(7)H(10)N(2)OS, (I), the `base pair' is connected by one N-H···S and one N-H···N hydrogen bond. Homodimers of 6-propyl-2-thiouracil linked by two N-H···S hydrogen bonds are observed in the cocrystal N-(6-acetamidopyridin-2-yl)acetamide-6-propyl-2-thiouracil (1/2), C(9)H(11)N(3)O(2)·2C(7)H(10)N(2)OS, (II). The crystal structure of 6-propyl-2-thiouracil itself, C(7)H(10)N(2)OS, (III), is stabilized by pairwise N-H···O and N-H···S hydrogen bonds. In all three structures, N-H···S hydrogen bonds occur only within R(2)(2)(8) patterns, whereas N-H···O hydrogen bonds tend to connect the homo- and heterodimers into extended networks. In agreement with related structures, the hydrogen-bonding capability of C=O and C=S groups seems to be comparable.
Quantitation of intracellular metabolites of [35S]-6-mercaptopurine in L5178Y cells grown in time-course incubates.

Science.gov (United States)

Breter, H J; Zahn, R K

1979-09-01

6-Mercaptopurine (6MP) metabolism was quantitatively determined in L5178Y murine lymphoma. Cells grown in time-course incubates with [35S]-6MP were extracted with cold perchloric acid, and the buffered extracts were subjected to high-performance liquid cation-exchange chromatography prior to and after hydrolysis with alkaline phosphatase. Free sulfate, 6-thiouric acid, 6-thioxanthosine, 6-thioguanosine, 6-thioinosine, free 6MP, and 6-methylthioinosine were separated from each other; identified in the radiochromatograms by elution volume, UV spectroscopic data, and enzymatic peak-shifting analyses with purine nucleoside phosphorylase; and quantitatively determined by means of 35S radioactivity. Gross intracellular 35S concentrations remained constant at 5 x 10(-5) M after 1 hr of incubation. 6MP metabolism in L5178Y cells was distinguished into an early phase (to 1 hr of incubation) in which 6MP was predominantly catabolized to 6-thiouric acid and free sulfate, into an intermediate phase (to 8 hr) in which substantial amounts of free 6MP and of ribonucleotides of 6-thioxanthosine and 6-thioguanosine were present while the concentrations of nonnucleotide oxidation products sharply decreased, and into a late phase (to 24 hr) in which the ribonucleotides of 6MP, of 6-thioguanosine and, in particular, of 6-methylthioinosine were the most abundant metabolites.
Expression of S100A6 in Rat Hippocampus after Traumatic Brain Injury Due to Lateral Head Acceleration

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Bo Fang

2014-04-01

Full Text Available In a rat model of traumatic brain injury (TBI, we investigated changes in cognitive function and S100A6 expression in the hippocampus. TBI-associated changes in this protein have not previously been reported. Rat S100A6 was studied via immunohistochemical staining, Western blot, and reverse transcription-polymerase chain reaction (RT-PCR after either lateral head acceleration or sham. Reduced levels of S100A6 protein and mRNA were observed 1 h after TBI, followed by gradual increases over 6, 12, 24, and 72 h, and then a return to sham level at 14 day. Morris water maze (MWM test was used to evaluate animal spatial cognition. TBI- and sham-rats showed an apparent learning curve, expressed as escape latency. Although TBI-rats displayed a relatively poorer cognitive ability than sham-rats, the disparity was not significant early post-injury. Marked cognitive deficits in TBI-rats were observed at 72 h post-injury compared with sham animals. TBI-rats showed decreased times in platform crossing in the daily MWM test; the performance at 72 h post-injury was the worst. In conclusion, a reduction in S100A6 may be one of the early events that lead to secondary cognitive decline after TBI, and its subsequent elevation is tightly linked with cognitive improvement. S100A6 may play important roles in neuronal degeneration and regeneration in TBI.
Molybdenum Cluster Chalcogenides: In Situ X-Ray Studies on the Formation of Cu xMo 6S 8 via Electron/Ion Transfer

Science.gov (United States)

Fischer, C.; Gocke, E.; Stege, U.; Schöllhorn, R.

1993-01-01

Systematic structural investigation have been performed on the formation of the ternary Chevrel phase system CuxMo6S8 by topotactic intercalation of copper into Mo6S8 via electron/ion transfer reactions. In high-temperature synthesis the homogeneity range of CuxMo6S8 formation corresponds to 1.8 ≤ x ≤ 3.66, while by galvanostatic or potentiostatic reduction of binary Mo6S8 at ambiet temperature in aqueous CuSO4 or aprotic CuCl/Ch3CN electrolyte the terminal rhombohedral phase Cu4Mo6S8 with the maximum number of electrons per Mo6 cluster can be obtained. The phase range 1 ≤ x ≤ 4 of CuxMo6S8 as obtained by galvanostatic reduction of Mo6S8 in aqueous CuSO4 electrolyte has been determined by in situ X-ray experiments. Warburg oxygen manometry has proved to be a new and powerful analytical tool for examination of the Cu content of ternary phase CuxMo6S8. Thermodiffractometry and 63 Cu NMR studies of Cu2Mo6S8 (high-temperature phase) reveal a phase-transition rhombohedral/triclinic in a broad temperature range between 285 and 200 K. Superconducting properties (temperature-dependent ac susceptibility) of high temperature and electrochemically prepared Cu phases are reported.
Investigation of the fabrication process of hot-worked stainless-steel and Mo sheathed PbMo6 S8 wires

International Nuclear Information System (INIS)

Yamasaki, H.; Kimura, Y.

1988-01-01

Stainless-steel and Mo sheathed PbMo 6 S 8 wires have been fabricated by hot working from modified PbS, Mo, and MoS 2 mixed powders which were prepared by reacting Pb, Mo, and S at 530 0 C. Critical current densities were investigated for different preparation conditions, and it is revealed that obtaining continuous current path between PbMo 6 S 8 grains is the most important factor to achieve high critical current density. The J/sub c/ value of 2.8 x 10 4 Acm 2 (8 T), 7.8 x 10 3 Acm 2 (15 T), and 1.3 x 10 3 Acm 2 (23 T) was observed for the PbMo 6 S/sub 7.0/ wire heat treated at 700 0 C.copic
Overexpression of ubiquitous 6-phosphofructo-2-kinase in the liver of transgenic mice results in weight gain

International Nuclear Information System (INIS)

Duran, Joan; Navarro-Sabate, Aurea; Pujol, Anna; Perales, Jose C.; Manzano, Anna; Obach, Merce; Gomez, Marta; Bartrons, Ramon

2008-01-01

Fructose 2,6-bisphosphate (Fru-2,6-P 2 ) is an important metabolite that controls glycolytic and gluconeogenic pathways in several cell types. Its synthesis and degradation are catalyzed by the bifunctional enzyme 6-phosphofructo-2-kinase/fructose 2,6-bisphosphatase (PFK-2). Four genes, designated Pfkfb1-4, codify the different PFK-2 isozymes. The Pfkfb3 gene product, ubiquitous PFK-2 (uPFK-2), has the highest kinase/bisphosphatase activity ratio and is associated with proliferation and tumor metabolism. A transgenic mouse model that overexpresses uPFK-2 under the control of the phosphoenolpyruvate carboxykinase promoter was designed to promote sustained and elevated Fru-2,6-P 2 levels in the liver. Our results demonstrate that in diet-induced obesity, high Fru-2,6-P 2 levels in transgenic livers caused changes in hepatic gene expression profiles for key gluconeogenic and lipogenic enzymes, as well as an accumulation of lipids in periportal cells, and weight gain
IL-6, Antioxidant Capacity and Muscle Damage Markers Following High-Intensity Interval Training Protocols

OpenAIRE

Cipryan, Lukas

2017-01-01

Abstract The aim of this study was to investigate changes of interleukin-6 (IL-6), total antioxidant capacity (TAC) and muscle damage markers (creatine kinase (CK), myoglobin and lactate dehydrogenase (LDH)) in response to three different high-intensity interval training (HIIT) protocols of identical external work. Twelve moderately-trained males participated in the three HIIT trials which consisted of a warm-up, followed by 12 min of 15 s, 30 s or 60 s HIIT sequences with the work/rest ratio...
The application of a "6S Lean" initiative to improve workflow for emergency eye examination rooms.

Science.gov (United States)

Nazarali, Samir; Rayat, Jaspreet; Salmonson, Hilary; Moss, Theodora; Mathura, Pamela; Damji, Karim F

2017-10-01

Ophthalmology residents on call at the Royal Alexandra Hospital identified workplace disorganization and lack of standardization in emergency eye examination rooms as an impediment to efficient patient treatment. The aim of the study was to use the "6S Lean" model to improve workflow in eye examination rooms at the Royal Alexandra Hospital. With the assistance of quality improvement consultants, the "6S Lean" model was applied to the current operation of the emergency eye clinic examination rooms. This model, considering 8 waste categories, was then used to recommend and implement changes to the examination rooms and to workplace protocols to enhance efficiency and safety. Eye examination rooms were improved with regards to setup, organization of supplies, inventory control, and maintenance. All targets were achieved, and the 5S audit checklist score increased by 33 points from 44 to 77. Implementation of the 6S methodology is a simple approach that removes inefficiencies from the workplace. The ophthalmology clinic removed waste from all 8 waste categories, increased audit results, mitigated patient and resident safety risks, and ultimately redirected resident time back to patient care delivery. Copyright © 2017 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.
Lack of influence of CYP2D6 genotype on the clearance of (R)-, (S)- and racemic-methadone

DEFF Research Database (Denmark)

Coller, J K; Joergensen, C; Foster, D J R

2007-01-01

OBJECTIVE: To investigate the influence of CYP2D6 genotype on the oral clearance of (R)-, (S)- and rac-methadone. METHODS: In this retrospective study, CYP2D6 genotypes were identified in 56 methadone maintained subjects. Plasma concentrations of (R)-, (S)- and rac-methadone were determined by st...
Training processes in under 6s football competition: The transition from ingenuity to institutionalization

OpenAIRE

Abel Merino Orozco; Ana Arraiz Pérez; Fernando Sabirón Sierra

2016-01-01

Under 6s football competition is a school sport that has inherent educational implications. Moreover, it is a booming non-formal socio-educational framework where families and children lay training expectations and dreams. The aim is to comprehend the emerging learning processes promoted in this environment for 6 years-old children, when the child starts the institutionalization process in the ruled sport. The research uses a case study design, the ethnographic mode, through participant obser...
Study of structural and morphological properties of thermally evaporated Sn{sub 2}Sb{sub 6}S{sub 11} thin films

Energy Technology Data Exchange (ETDEWEB)

Ben Mehrez, N., E-mail: najia.benmehrez@gmail.com [Université Tunis El Manar, Laboratoire de Photovoltaïque et Matériaux Semi-conducteurs, ENIT, BP 37, Le belvédère, 1002 Tunis (Tunisia); Khemiri, N. [Université Tunis El Manar, Laboratoire de Photovoltaïque et Matériaux Semi-conducteurs, ENIT, BP 37, Le belvédère, 1002 Tunis (Tunisia); Kanzari, M. [Université Tunis El Manar, Laboratoire de Photovoltaïque et Matériaux Semi-conducteurs, ENIT, BP 37, Le belvédère, 1002 Tunis (Tunisia); Institut Préparatoire aux Etudes d’Ingénieurs de Tunis Montfleury, Université de Tunis (Tunisia)

2016-10-01

In this study, we report the structural and morphological properties of the new material Sn{sub 2}Sb{sub 6}S{sub 11} thin films prepared on glass substrates by vacuum thermal evaporation at various substrate temperatures (30, 60, 100, 140, 180 and 200 °C). Sn{sub 2}Sb{sub 6}S{sub 11} ingot was synthesized by the horizontal Bridgman technique. The structural properties of Sn{sub 2}Sb{sub 6}S{sub 11} powder were studied by X-ray diffraction (XRD), transmission electron microscopy (TEM) and Raman spectroscopy. The films were characterized for their structural properties by using XRD. All films were polycrystalline in nature. The variations of the structural parameters of the films with the substrate temperature were investigated. The results show that the crystallite sizes increase as the substrate temperature increases. The morphological properties of the films were analyzed by atomic force microscopy (AFM). The roughness and the topography of the surface of the films strongly depend on the substrate temperature. - Highlights: • Sn{sub 2}Sb{sub 6}S{sub 11} powder was successfully synthesized by the horizontal Bridgman technique. • Sn{sub 2}Sb{sub 6}S{sub 11} films were grown by thermal evaporation at different substrate temperatures. • Structural properties of Sn{sub 2}Sb{sub 6}S{sub 11} powder were investigated. • The effect of the substrate temperature on structural and morphological of Sn{sub 2}Sb{sub 6}S{sub 11} films properties was studied.
Le système de sûreté lyonnais selon les arrêtés du 6 décembre 1833

Directory of Open Access Journals (Sweden)

Amos Frappa

2010-01-01

Full Text Available Le 6 décembre 1833, le maire de Lyon Gabriel Prunelle adopte trois arrêtés instaurant un service de sûreté. Il s’agit de la seconde ville française à se doter d’un groupe de policiers spécialisé dans la recherche et l’arrestation des malfaiteurs. Un an plus tôt, le préfet de police Gisquet met à profit l’expérience de « la Rousse », surnom donné à la brigade de l’ancien bagnard Vidocq, pour équiper la capitale d’une telle structure. Le premier des textes du 6 décembre 1833 fixe les attributi...
Inositol pyrophosphates promote tumor growth and metastasis by antagonizing liver kinase B1

Science.gov (United States)

Rao, Feng; Xu, Jing; Fu, Chenglai; Cha, Jiyoung Y.; Gadalla, Moataz M.; Xu, Risheng; Barrow, James C.; Snyder, Solomon H.

2015-01-01

The inositol pyrophosphates, molecular messengers containing an energetic pyrophosphate bond, impact a wide range of biologic processes. They are generated primarily by a family of three inositol hexakisphosphate kinases (IP6Ks), the principal product of which is diphosphoinositol pentakisphosphate (IP7). We report that IP6K2, via IP7 synthesis, is a major mediator of cancer cell migration and tumor metastasis in cell culture and in intact mice. IP6K2 acts by enhancing cell-matrix adhesion and decreasing cell–cell adhesion. This action is mediated by IP7-elicited nuclear sequestration and inactivation of the tumor suppressor liver kinase B1 (LKB1). Accordingly, inhibitors of IP6K2 offer promise in cancer therapy. PMID:25617365
AdS5 solutions from M5-branes on Riemann surface and D6-branes sources

Energy Technology Data Exchange (ETDEWEB)

Bah, Ibrahima [Department of Physics and Astronomy, University of Southern California,Los Angeles, CA 90089 (United States); Institut de Physique Théorique, CEA/Saclay,91191 Gif-sur-Yvette (France)

2015-09-24

We describe the gravity duals of four-dimensional N=1 superconformal field theories obtained by wrapping M5-branes on a punctured Riemann surface. The internal geometry, normal to the AdS{sub 5} factor, generically preserves two U(1)s, with generators (J{sup +},J{sup −}), that are fibered over the Riemann surface. The metric is governed by a single potential that satisfies a version of the Monge-Ampère equation. The spectrum of N=1 punctures is given by the set of supersymmetric sources of the potential that are localized on the Riemann surface and lead to regular metrics near a puncture. We use this system to study a class of punctures where the geometry near the sources corresponds to M-theory description of D6-branes. These carry a natural (p,q) label associated to the circle dual to the killing vector pJ{sup +}+qJ{sup −} which shrinks near the source. In the generic case the world volume of the D6-branes is AdS{sub 5}×S{sup 2} and they locally preserve N=2 supersymmetry. When p=−q, the shrinking circle is dual to a flavor U(1). The metric in this case is non-degenerate only when there are co-dimension one sources obtained by smearing M5-branes that wrap the AdS{sub 5} factor and the circle dual the superconformal R-symmetry. The D6-branes are extended along the AdS{sub 5} and on cups that end on the co-dimension one branes. In the special case when the shrinking circle is dual to the R-symmetry, the D6-branes are extended along the AdS{sub 5} and wrap an auxiliary Riemann surface with an arbitrary genus. When the Riemann surface is compact with constant curvature, the system is governed by a Monge-Ampère equation.
Integrated readout of organic scintillator and ZnS:Ag/6LiF for segmented antineutrino detectors

International Nuclear Information System (INIS)

Kiff, Scott D.; Reyna, David; Monahan, James; Bowden, Nathaniel S.

2010-01-01

Antineutrino detection using inverse beta decay conversion has demonstrated the capability to measure nuclear reactor power and fissile material content for nuclear safeguards. Current efforts focus on aboveground deployment scenarios, for which highly efficient capture and identification of neutrons is needed to measure the anticipated antineutrino event rates in an elevated background environment. In this submission, we report on initial characterization of a new scintillation-based segmented design that uses layers of ZnS:Ag/ 6 LiF and an integrated readout technique to capture and identify neutrons created in the inverse beta decay reaction. Laboratory studies with multiple organic scintillator and ZnS:Ag/ 6 LiF configurations reliably identify 6 Li neutron captures in 60 cm-long segments using pulse shape discrimination.

α +d →6Li+γ astrophysical S factor and its implications for Big Bang nucleosynthesis

Science.gov (United States)

Grassi, A.; Mangano, G.; Marcucci, L. E.; Pisanti, O.

2017-10-01

The α +d →6Li +γ radiative capture is studied in order to predict the 6Li primordial abundance. Within a two-body framework, the α particle and the deuteron are considered the structureless constituents of 6Li. Five α +d potentials are used to solve the two-body problem: four of them are taken from the literature, only one having also a tensor component. A fifth model is here constructed in order to reproduce, besides the 6Li static properties as binding energy, magnetic dipole, and electric quadrupole moments, also the S -state asymptotic normalization coefficient (ANC). The two-body bound and scattering problem is solved with different techniques, in order to minimize the numerical uncertainty of the present results. The long-wavelength approximation is used, and therefore only the electric dipole and quadrupole operators are retained. The astrophysical S factor is found to be significantly sensitive to the ANC, but in all the cases in good agreement with the available experimental data. The theoretical uncertainty has been estimated of the order of few percent when the potentials which reproduce the ANC are considered, but increases up to ≃20 % when all five potential models are retained. The effect of this S -factor prediction on the 6Li primordial abundance is studied, using the public code PArthENoPE. For the five models considered here we find 6Li/H=(0.9 -1.8 ) ×10-14 , with the baryon density parameter in the 3-σ range of Planck 2015 analysis, Ωbh2=0.022 26 ±0.000 23 .
Structural characterization and electrochemical behavior of 45S5 bioglass coating on Ti6Al4V alloy for dental applications

Energy Technology Data Exchange (ETDEWEB)

López, M.M. Machado, E-mail: machadolopez23@gmail.com [Instituto de Investigaciones Metalúrgicas, Universidad Michoacana de San Nicolás de Hidalgo, C.U. Edificio “U”, C.P. 58000, Morelia, Michoacán, México (Mexico); Fauré, J. [Laboratoire Ingénierie et Sciences des Matériaux (LISM EA 4695) - Université de Reims Champagne-Ardenne, 21 rue Clément Ader, Reims, BP 138 Cedex 02, 51685 France (France); Cabrera, M.I. Espitia [Facultad de ingeniería Química, Universidad Michoacana de San Nicolás de Hidalgo, C.U. Edificio “D”, C.P. 58000, Morelia, Michoacán, México (Mexico); García, M.E. Contreras, E-mail: eucontre@umich.mx [Instituto de Investigaciones Metalúrgicas, Universidad Michoacana de San Nicolás de Hidalgo, C.U. Edificio “U”, C.P. 58000, Morelia, Michoacán, México (Mexico)

2016-04-15

Graphical abstract: - Highlights: • Bioglass 45S5 nanostructured films were obtained by colloidal electrophoretic deposition (CEDP) method, proposed in this work, on Ti6Al4 V substrates. • Ti6Al4 V corrosion resistance in Hank's solution was increased with bioglass 45S5 coating. • Crystalline phases of 45S5 bioglass xerogels were obtained and characterized by XRD. • The model of chemical anchoring between Ti6Al4 V and bioglass 45S5 is proposed. - Abstract: In the present work, 45S5 bioglass coatings were deposited on the Ti6Al4 V alloy substrate through the cathodic colloidal electrophoretic deposition process (CEDP) proposed in this work. The coatings were thermally treated at temperatures of 500, 600, 700, and 800 °C for 2 h, and their structure was characterized by FESEM and DRX. Nanostructure and phase evolution of the coatings and xerogels was followed as a function of temperature. The corrosion resistance of the Ti6Al4 V alloy and the 45S5/Ti6Al4 V coating was studied by means of Tafel extrapolation in Hank's solution, at 37 °C, simulating the conditions inside the mouth. The 45S5 bioglass coatings displayed an amorphous nanostructure at lower temperatures, and partial crystallization at higher temperatures. An increase in the corrosion resistance was observed in the 45S5/Ti6l4 V coating treated at 700 °C because it reduced the i{sub corr}, and there was a change in the E{sub corr} towards more noble values. A model of the chemical anchorage of the 45S5 bioglass coating on Ti6Al4 V was proposed.
Fabrication of magnetic Fe@ZnO_0_._6S_0_._4 nanocomposite for visible-light-driven photocatalytic inactivation of Escherichia coli

International Nuclear Information System (INIS)

Peng, Ziling; Wu, Dan; Wang, Wei; Tan, Fatang; Ng, Tsz Wai; Chen, Jianguo; Qiao, Xueliang; Wong, Po Keung

2017-01-01

Highlights: • Fe@ZnO_0_._6S_0_._4 was prepared by a facile two-step precipitation method. • Fe@ZnO_0_._6S_0_._4 exhibited high photocatalytic activity under LED lamp irradiation. • Fe@ZnO_0_._6S_0_._4 possessed good stability and reusability for bacterial inactivation. • Fe@ZnO_0_._6S_0_._4 could be easily collected from the reaction solution by a magnet. • The release rate of metal ions from nanocomposite was kept at a very low level. - Abstract: Bacterial inactivation by magnetic photocatalysts has now received growing interests due to the easy separation for recycle and reuse of photocatalysts. In this study, magnetic Fe@ZnO_0_._6S_0_._4 photocatalyst was prepared by a facile two-step precipitation method. Multiple techniques such as X-ray diffraction (XRD), transmission electron microscope (TEM), scanning electron microscope (SEM), X-ray photoelectron spectroscopy (XPS), UV–vis diffused reflectance spectra (UV-vis DRS) and vibrating sample magnetometer (VSM) were employed to characterize the structure, morphology and physicochemical properties of the photocatalyst. The as-obtained Fe@ZnO_0_._6S_0_._4 possessing magnetic property was easily collected from the reaction system by a magnet. Under white light-emitting-diode (LED) lamp irradiation, Fe@ZnO_0_._6S_0_._4 nanocomposite could completely inactivate 7-log of Escherichia coli K-12 within 5 h. More importantly, almost no decrease of photocatalytic efficiency in bacterial inactivation was observed even after five consecutive cycles, demonstrating Fe@ZnO_0_._6S_0_._4 exhibited good stability for reuse. The low released rate of Fe"2"+/Fe"3"+ and Zn"2"+ from Fe@ZnO_0_._6S_0_._4 composite further indicated the photocatalyst showed low cytotoxicity to bacterium and high stability under LED lamp irradiation. Facile preparation, high photocatalytic efficiency, good stability and reusability, and magnetic recovery property endow Fe@ZnO_0_._6S_0_._4 nanocomposite to be a promising photocatalytic material
Human herpesvirus-8 (HHV-8 sero-detection and HIV association in Kaposi's sarcoma (KS, non-KS tumors and non-neoplastic conditions

Directory of Open Access Journals (Sweden)

Pak Fatemeh

2008-06-01

Full Text Available Abstract Background The association of the human herpesvirus-8/Kaposi's sarcoma (KS-associated herpesvirus (HHV-8/KSHV serology with various malignancies in Tanzania is not currently well established while previous studies were based on either PCR or immunofluorescence assays [IFA] but not with a sensitive enzyme-linked immunosorbent assay (ELISA. Selected archival diagnostic biopsies (n = 184 and sera from indigenous patients with KS (n = 120, non-KS tumors (n = 24 and non-neoplastic lesions (n = 40 at Muhimbili National Hospital (MNH, Tanzania, were evaluated by diagnostic histopathology, immunohistology [anti-HHV-8 latency-associated nuclear antigen (LANA] and serology for HIV (ELISA and HHV-8 (IFA and ELISA. Results About 66.3% (n = 122 cases including AIDS-associated Kaposi's sarcoma (AKS (n = 93, reactive conditions (n = 28 and only one non-KS tumour were HIV positive. Endemic KS (EKS patients were mostly males (96.3%, 26/27 who were less (69.9%, 65/93 predominant in AIDS-associated (AKS. A high (89% percentage of patients with anti-HHV-8 antibodies was found in the cohort including the HIV positive (92% cases, males (81.2%, KS patients (93%, non-KS tumors (92%, and reactive conditions (75%. All HHV-8 seronegative KS cases were nodular stage whereas both sera and corresponding biopsies from early stage KS were HHV-8+. Assay sensitivity, positive predictive value (PPV and specificity were 98.6%, 93.5% and 16.7% for IFA and 93.5%, 98.6% and 50.0% for ELISA respectively. Conclusion HHV-8 seroprevalence at MNH appears high as expected among AKS cases and males but also in non-KS patients. ELISA showed a combination of high HHV-8 sensitivity as well as higher PPV and specificity than IFA which however, showed higher sensitivity. The apparent stage-dependent, inverted serum HHV-8 immunoreactivity supports a notion of viral immune-segregation during KS development. Routine HHV-8 screening should be considered particularly in patients at risk of
Structural phase transitions in BaMo6S8: Evidence for an incommensurate phase

International Nuclear Information System (INIS)

Jorgensen, J.D.; Hinks, D.G.; Hatch, D.M.; Putnam, R.M.

1986-01-01

The structure of BaMo 6 S 8 has been studied over the temperature range 19 K to 573 K by time-of-flight neutron powder diffraction. Below 175 K the data can be suitably refined in a triclinic, P1, cell with volume equal to the rhombohedral, R3, cell common to most Chevrel-phase structures. At temperatures immediately above 175 K, the rhombohedral, R3, Bragg peaks are broadened by satellite reflections which appear to be identical to those recently observed at low temperature in PbMo 6 S 8 and SnMo 6 S 8 . An abrupt change in the sign of the temperature dependence of the hexagonal c axis (∂c/∂T) signals the transition to an undistorted rhombohedral, R3, structure at temperatures above about 350 K. An extended Landau theory determines both continuous and discontinuous transitions from R3 induced by a single order parameter. Analysis of the order parameters inducing commensurate transitions imposes symmetry restrictions on the atomic displacements in the lower symmetry phases. The assumption of an R3 commensurate phase is not consistent with the bond lengths obtained for the distortions to the P1 (or P1) phase for any of the possible cells preserving order parameters. Thus the phase immediately above 175 K cannot be a commensurate R3 structure. This is consistent with experimental evidence. 25 refs., 11 figs., 8 tabs
TGF-beta1 modulates matrix metalloproteinase-13 expression in hepatic stellate cells by complex mechanisms involving p38MAPK, PI3-kinase, AKT, and p70S6k.

Science.gov (United States)

Lechuga, Carmen G; Hernández-Nazara, Zamira H; Domínguez Rosales, José-Alfredo; Morris, Elena R; Rincón, Ana Rosa; Rivas-Estilla, Ana María; Esteban-Gamboa, Andrés; Rojkind, Marcos

2004-11-01

Transforming growth factor-beta1 (TGF-beta1), the main cytokine involved in liver fibrogenesis, induces expression of the type I collagen genes in hepatic stellate cells by a transcriptional mechanism, which is hydrogen peroxide and de novo protein synthesis dependent. Our recent studies have revealed that expression of type I collagen and matrix metalloproteinase-13 (MMP-13) mRNAs in hepatic stellate cells is reciprocally modulated. Because TGF-beta1 induces a transient elevation of alpha1(I) collagen mRNA, we investigated whether this cytokine was able to induce the expression of MMP-13 mRNA during the downfall of the alpha1(I) collagen mRNA. In the present study, we report that TGF-beta1 induces a rapid decline in steady-state levels of MMP-13 mRNA at the time that it induces the expression of alpha1(I) collagen mRNA. This change in MMP-13 mRNA expression occurs within the first 6 h postcytokine administration and is accompanied by a twofold increase in gene transcription and a fivefold decrease in mRNA half-life. This is followed by increased expression of MMP-13 mRNA, which reaches maximal values by 48 h. Our results also show that this TGF-beta1-mediated effect is de novo protein synthesis-dependent and requires the activity of p38MAPK, phosphatidylinositol 3-kinase, AKT, and p70(S6k). Altogether, our data suggest that regulation of MMP-13 by TGF-beta1 is a complex process involving transcriptional and posttranscriptional mechanisms.
The role of the isolated 6s states in BiVO{sub 4} on the electronic and atomic structures

Energy Technology Data Exchange (ETDEWEB)

Ma, Jie; Wang, Lin-Wang [Joint Center for Artificial Photosynthesis and Materials Science Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720 (United States)

2014-10-27

BiVO{sub 4} is one of the most promising photoanodes for water-splitting applications. Similar to many d{sup 10} materials, where the full-shell d electrons are not directly involved in the bonding, the Bi 6s electrons form isolated low-energy bands in BiVO{sub 4}. By systematically altering the energy of the Bi 6s states, we find direct evidences that the isolated s states, through the s-p coupling, affect the BiVO{sub 4} properties, including valence band maximum position, charge density, and atomic structural distortion. We find that many good properties of BiVO{sub 4} for water splitting are related to the s-p coupling due to the existence of Bi 6s states. Based on this understanding, we propose that alloying Bi with Sb can enhance these properties, and hence improve the water-splitting efficiency.
Demonstration of immunogenic keratan sulphate in commercial chondroitin 6-sulphate from shark cartilage. Implications for ELISA assays

DEFF Research Database (Denmark)

Møller, H J; Møller-Pedersen, T; Damsgaard, T E

1995-01-01

The prototype monoclonal keratan sulphate (KS) antibody 5D4 that is widely used for detection of KS in tissues and biological fluids reacts strongly with commercial low grade shark cartilage chondroitin 6-sulphate. Characterization of the immunogenic material by chondroitinase ABC digestion, ELISA...... cartilage chondroitin 6-sulphate is an easy accessible source of immunogenic KS that can be used as a reference standard and as coating antigen in KS-ELISAs. The concentration of immunogenic KS in synovial fluid measured with an ELISA based solely on reagents of shark cartilage chondroitin 6-sulphate...... correlated well (r = 0.90) with the concentrations obtained with a traditional KS-ELISA that uses purified aggrecan as standard and coating antigen, and KS in both serum and synovial fluid could be measured with sufficient linearity....
S-phase induction by interleukin-6 followed by chemotherapy in patients with chronic lymphocytic leukemia and non-Hodgkin's lymphoma

DEFF Research Database (Denmark)

Brown, P D; Diamant, M; Jensen, P O

1999-01-01

Interleukin-6 (IL-6) has in vitro demonstrated growth regulatory effects on tumor cells from patients with chronic lymphocytic leukemia (CLL) and lymphoma. The proliferation rate of these cells is usually very low and this is thought to be one of the reasons for the lack of a curative potential....../kg and 10 micrograms/kg s.c. daily for 5 days followed by CHOP chemotherapy on the last day of rhIL-6 injection. Six patients had two treatment cycles. The proportion of cells in S-phase was determined by the bromodeoxyuridine labeling index (LI). Three patients achieved a partial remission, one patient had....../kg and 5 micrograms/kg respectively. Immunophenotypic assessment demonstrated that rhIL-6 increased the expression of CD20 in all CLL patients with a reversal after cessation of rhIL-6. We conclude that rhIL-6, in the dosage and schedule used in this study, did not increase the proportion of the cells in S...
Effects of pH, temperature, and chemical structure on the stability of S-(purin-6-yl)-L-cysteine: evidence for a novel molecular rearrangement mechanism to yield N-(purin-6-yl)-L-cysteine.

Science.gov (United States)

Elfarra, A A; Hwang, I Y

1996-01-01

The stability of S-(purin-6-yl)-L-cysteine (SPC), a kidney-selective prodrug of 6-mercaptopurine and a putative metabolite of 6-chloropurine, was investigated under various pH and temperature conditions. At room temperature, the half-life (t 1/2) of SPC at either highly acidic (pH 3.6) or basic conditions (pH 9.6) was longer than at neutral or slightly acidic or basic conditions (pH 5.7-8.75). The primary degradation product, N-(purin-6-yl)-L-cysteine (NPC), was isolated using Sephadex LH-20 chromatography and characterized by 1H NMR and FAB/MS after derivatization with 2-iodoacetic acid. These results reveal novel stability requirements and implicate the cysteinyl amino group and the purinyl N-1 nitrogen in the mechanism of SPC rearrangement to NPC. Further evidence for this hypothesis was provided by the findings that the stability of SPC in phosphate buffer (pH 7.4) at 37 degrees C was similar to that of S-(guanin-6-yl)-L-cysteine, whereas S-(purin-6-yl)-N-acetyl-L-cysteine and S-(purin-6-yl)glutathione which have their cysteine amino groups blocked were much more stable than SPC. S-(Purin-6-yl)-L-homocysteine (SPHC) was also more stable than SPC, possibly because the formation of a 6-membered ring transition state as would be expected with SPHC is kinetically less favored than the formation of a 5-membered ring transition state as would be expected with SPC. These results may explain previous in vivo metabolism results of SPC and its analogs and may contribute to a better understanding of stability of structurally related cysteine S-conjugates.
Experiment data report for LOFT Boron dilution Experiment L6-6

International Nuclear Information System (INIS)

Stitt, B.D.; Divine, J.M.

1982-06-01

Selected pertinent and uninterpreted data from the sixth anticipated transient experiment (Experiment L6-6) conducted in the Loss-of-Fluid Test (LOFT) facility are presented. Experiment L6-6 simulated a boron dilution accident by injecting demineralized water into the primary coolant system (PCS) at a rate of 0.47 L/s while the reactor was in a cold shutdown condition with the control rods withdrawn. System pressure was maintained at approximately 285 kPa throughout the experiment. The experiment was divided into two parts. In the first part, L6-6A, a recirculation flow of 4.7 L/s was maintained through the PCS and criticality was achieved 7416 +- 10 s after the initiation of the dilution flow. The second part, L6-6B, was identical to L6-6A except that a recirculation flow of 9.5 L/s was maintained and criticality occurred at 8058 +- 10 s
Antioxidant effects of betulin on porcine chondrocyte behavior in gelatin/C6S/C4S/HA modified tricopolymer scaffold

International Nuclear Information System (INIS)

Lin, Wen-Yang; Lin, Feng-Huei; Sadhasivam, S.; Savitha, S.

2010-01-01

The antioxidant effects of betulin on porcine chondrocytes cultured in gelatin/C6S/C4S/HA modified tricopolymer scaffold for a period of 4 weeks was investigated. The porous structure of the scaffold and cell attachment was observed by scanning electron microscopy (SEM). Biochemical measures of necrosis, cell proliferation, sulfated glycosaminoglycans (sGAG) content and extracellular matrix related gene expressions were quantitatively evaluated. The cell proliferation data showed good cellular viability in tricopolymer scaffold and increased optical density for total DNA demonstrated that the cells continued to proliferate inside the scaffold. The sGAG production indicated chondrogenic differentiation. Chondrocytes treated with betulin expressed transcripts encoding type II collagen, aggrecan, and decorin. To conclude, the substantiated results supported cell proliferation, production of extracellular matrix proteins and down-regulation of matrix metalloproteases and cytokine, in betulin treated scaffolds.
Antioxidant effects of betulin on porcine chondrocyte behavior in gelatin/C6S/C4S/HA modified tricopolymer scaffold

Energy Technology Data Exchange (ETDEWEB)

Lin, Wen-Yang; Lin, Feng-Huei [Institute of Biomedical Engineering, National Taiwan University, Taipei, Taiwan (China); Sadhasivam, S., E-mail: rahulsbio@yahoo.co.in [Institute of Biomedical Engineering, National Taiwan University, Taipei, Taiwan (China); Savitha, S. [Institute of Biomedical Engineering, National Taiwan University, Taipei, Taiwan (China)

2010-05-10

The antioxidant effects of betulin on porcine chondrocytes cultured in gelatin/C6S/C4S/HA modified tricopolymer scaffold for a period of 4 weeks was investigated. The porous structure of the scaffold and cell attachment was observed by scanning electron microscopy (SEM). Biochemical measures of necrosis, cell proliferation, sulfated glycosaminoglycans (sGAG) content and extracellular matrix related gene expressions were quantitatively evaluated. The cell proliferation data showed good cellular viability in tricopolymer scaffold and increased optical density for total DNA demonstrated that the cells continued to proliferate inside the scaffold. The sGAG production indicated chondrogenic differentiation. Chondrocytes treated with betulin expressed transcripts encoding type II collagen, aggrecan, and decorin. To conclude, the substantiated results supported cell proliferation, production of extracellular matrix proteins and down-regulation of matrix metalloproteases and cytokine, in betulin treated scaffolds.
Tumor necrosis factor receptor- associated factor 6 (TRAF6) regulation of development, function, and homeostasis of the immune system.

Science.gov (United States)

Walsh, Matthew C; Lee, JangEun; Choi, Yongwon

2015-07-01

Tumor necrosis factor receptor (TNFR)-associated factor 6 (TRAF6) is an adapter protein that mediates a wide array of protein-protein interactions via its TRAF domain and a RING finger domain that possesses non-conventional E3 ubiquitin ligase activity. First identified nearly two decades ago as a mediator of interleukin-1 receptor (IL-1R)-mediated activation of NFκB, TRAF6 has since been identified as an actor downstream of multiple receptor families with immunoregulatory functions, including members of the TNFR superfamily, the Toll-like receptor (TLR) family, tumor growth factor-β receptors (TGFβR), and T-cell receptor (TCR). In addition to NFκB, TRAF6 may also direct activation of mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase (PI3K), and interferon regulatory factor pathways. In the context of the immune system, TRAF6-mediated signals have proven critical for the development, homeostasis, and/or activation of B cells, T cells, and myeloid cells, including macrophages, dendritic cells, and osteoclasts, as well as for organogenesis of thymic and secondary lymphoid tissues. In multiple cellular contexts, TRAF6 function is essential not only for proper activation of the immune system but also for maintaining immune tolerance, and more recent work has begun to identify mechanisms of contextual specificity for TRAF6, involving both regulatory protein interactions, and messenger RNA regulation by microRNAs. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Protein kinase CK2 modulates IL-6 expression in inflammatory breast cancer

Energy Technology Data Exchange (ETDEWEB)

Drygin, Denis, E-mail: ddrygin@cylenepharma.com; Ho, Caroline B.; Omori, Mayuko; Bliesath, Joshua; Proffitt, Chris; Rice, Rachel; Siddiqui-Jain, Adam; O' Brien, Sean; Padgett, Claire; Lim, John K.C.; Anderes, Kenna; Rice, William G.; Ryckman, David

2011-11-11

Highlights: Black-Right-Pointing-Pointer We examine the potential cross-talk between CK2 and IL-6. Black-Right-Pointing-Pointer Inhibition of CK2 by siRNA or CX-4945 inhibits expression of IL-6 in models of IBC. Black-Right-Pointing-Pointer Treatment of IBC patient in the clinic with CX-4945 reduces her IL-6 plasma levels. Black-Right-Pointing-Pointer We demonstrate that CK2 is a potential therapeutic target for IL-6 driven diseases. -- Abstract: Inflammatory breast cancer is driven by pro-angiogenic and pro-inflammatory cytokines. One of them Interleukin-6 (IL-6) is implicated in cancer cell proliferation and survival, and promotes angiogenesis, inflammation and metastasis. While IL-6 has been shown to be upregulated by several oncogenes, the mechanism behind this phenomenon is not well characterized. Here we demonstrate that the pleotropic Serine/Threonine kinase CK2 is implicated in the regulation of IL-6 expression in a model of inflammatory breast cancer. We used siRNAs targeted toward CK2 and a selective small molecule inhibitor of CK2, CX-4945, to inhibit the expression and thus suppress the secretion of IL-6 in in vitro as well as in vivo models. Moreover, we report that in a clinical trial, CX-4945 was able to dramatically reduce IL-6 levels in plasma of an inflammatory breast cancer patient. Our data shed a new light on the regulation of IL-6 expression and position CX-4945 and potentially other inhibitors of CK2, for the treatment of IL-6-driven cancers and possibly other diseases where IL-6 is instrumental, including rheumatoid arthritis.
S-phase induction by interleukin-6 followed by chemotherapy in patients with refractory multiple myeloma

DEFF Research Database (Denmark)

de Nully Brown, P; Jensen, P O; Diamant, M

1998-01-01

.0 microg/kg (n = 6) by subcutaneous injection once daily for 5 days and chemotherapy was administered on the last day of rhIL-6 injection. The effect of rhIL-6 treatment on labeling index (LI) was heterogeneous, but no statistically significant change was noted for this particular group as a whole. In two......The plasma cell labeling index (PCLI) in patients with multiple myeloma (MM) is relatively low and this has been associated with the low rate of remission following chemotherapy. Interleukin-6 (IL-6) has been demonstrated to be a major growth factor of myeloma cells. In order to increase the S......-phase proportion of myeloma cells, which might increase the sensitivity to chemotherapy, we gave rhIL-6 followed by chemotherapy to 15 myeloma patients with refractory disease. A total of 25 treatment cycles were administered since ten patients had two cycles. The rhIL-6 dose was 2.5 (n = 3), 5.0 (n = 6) and 10...
Immunohistochemical Analysis of the Activation Status of the Akt/mTOR/pS6 Signaling Pathway in Oral Lichen Planus

Directory of Open Access Journals (Sweden)

Georgios Prodromidis

2013-01-01

Full Text Available Introduction. Aberrations of the Akt/mTOR/pS6 pathway have been linked to various types of human cancer, including oral squamous cell carcinoma (OSCC. The purpose of this study was to evaluate the activation status of Akt, mTOR, and pS6 in oral lichen planus (OLP in comparison with oral premalignant and malignant lesions and normal oral mucosa (NM. Materials and Methods. Immunohistochemistry for p-Akt, p-mTOR, and phospho-pS6 was performed in 40 OLP, 20 oral leukoplakias (OL, 10 OSCC, and 10 control samples of NM. Results. Nuclear p-Akt expression was detected in the vast majority of cases in all categories, being significantly higher in OL. Cytoplasmic p-Akt and p-mTOR staining was present only in a minority of OLP cases, being significantly lower compared to OL and OSCC. Phospho-pS6 showed cytoplasmic positivity in most OLP cases, which however was significantly lower compared to OL and OSCC. Conclusions. Overall, cytoplasmic p-Akt, p-mTOR, and phospho-pS6 levels appear to be significantly lower in OLP compared to OL and OSCC. However, the expression of these molecules in a subset of OLP cases suggests that activation of Akt/mTOR/pS6 may occur in the context of OLP, possibly contributing to the premalignant potential of individual cases.
Side-effects of protein kinase inhibitors on ion channels

Indian Academy of Sciences (India)

2013-11-06

Nov 6, 2013 ... with aberrant kinase activity, including cancers, arthritis and cardiovascular disorders. Several strategies .... family, the β-adrenergic receptor kinase (βARK), the ribosomal S6 ..... urinary bladder smooth muscle cells. While no ...
Phosphorylation of the Yeast Choline Kinase by Protein Kinase C

Science.gov (United States)

Choi, Mal-Gi; Kurnov, Vladlen; Kersting, Michael C.; Sreenivas, Avula; Carman, George M.

2005-01-01

The Saccharomyces cerevisiae CKI1-encoded choline kinase catalyzes the committed step in phosphatidylcholine synthesis via the Kennedy pathway. The enzyme is phosphorylated on multiple serine residues, and some of this phosphorylation is mediated by protein kinase A. In this work, we examined the hypothesis that choline kinase is also phosphorylated by protein kinase C. Using choline kinase as a substrate, protein kinase C activity was dose- and time-dependent, and dependent on the concentrations of choline kinase (Km = 27 μg/ml) and ATP (Km = 15 μM). This phosphorylation, which occurred on a serine residue, was accompanied by a 1.6-fold stimulation of choline kinase activity. The synthetic peptide SRSSS25QRRHS (Vmax/Km = 17.5 mM-1 μmol min-1 mg-1) that contains the protein kinase C motif for Ser25 was a substrate for protein kinase C. A Ser25 to Ala (S25A) mutation in choline kinase resulted in a 60% decrease in protein kinase C phosphorylation of the enzyme. Phosphopeptide mapping analysis of the S25A mutant enzyme confirmed that Ser25 was a protein kinase C target site. In vivo, the S25A mutation correlated with a decrease (55%) in phosphatidylcholine synthesis via the Kennedy pathway whereas an S25D phosphorylation site mimic correlated with an increase (44%) in phosphatidylcholine synthesis. Whereas the S25A (protein kinase C site) mutation did not affect the phosphorylation of choline kinase by protein kinase A, the S30A (protein kinase A site) mutation caused a 46% reduction in enzyme phosphorylation by protein kinase C. A choline kinase synthetic peptide (SQRRHS30LTRQ) containing Ser30 was a substrate (Vmax/Km = 3.0 mM−1 μmol min−1 mg−1) for protein kinase C. Comparison of phosphopeptide maps of the wild type and S30A mutant choline kinase enzymes phosphorylated by protein kinase C confirmed that Ser30 was also a target site for protein kinase C. PMID:15919656
Semiclassical equivalence of Green–Schwarz and pure–spinor/hybrid formulations of superstrings in AdS5 × S5 and AdS2 × S2 × T6

International Nuclear Information System (INIS)

Cagnazzo, Alessandra; Sorokin, Dmitri; Tseytlin, Arkady A; Wulff, Linus

2013-01-01

We demonstrate the equivalence between the worldsheet one-loop partition functions computed near classical string solutions in the Green–Schwarz and in the pure–spinor formulations of superstrings in AdS 5 × S 5 . While their bosonic sectors are the same in the conformal gauge, their fermionic sectors superficially appear to be very different (first versus second-derivative kinetic terms, presence versus absence of fermionic gauge symmetry). Still, we show that the quadratic fluctuation spectrum of 16 fermionic modes of the pure–spinor formulation is the same as in the Green–Schwarz superstring and the contribution of the extra ‘massless’ fermionic modes cancels against that of the pure–spinor ghosts. We also provide evidence for a similar semiclassical equivalence between the Green–Schwarz and the hybrid formulations of superstrings in AdS 2 × S 2 × T 6 by studying several particular examples of string solutions. (paper)

Etat nutritionnel des enfants âgés de 6 à 59 mois infectés par le VIH mais non traités aux ARV à Lubumbashi

Science.gov (United States)

Mwadianvita, Costa Kazadi; Kanyenze, Faustin Ngoy; Wembonyama, Cecile Watu; Mutomb, Florence Mujing A; Mupoya, Kalombo; Nkoy, Albert Mwembo–Tambwe A; Mwenze, Prosper Kalenga

2014-01-01

Introduction L'infection par le VIH provoque et/ou aggrave les déficits nutritionnels de l'enfant. Ce travail avait pour objectif d'analyser l’état nutritionnel des enfants infectés par le VIH à Lubumbashi. Méthodes Une étude transversale portant sur 83 enfants âgés de 6 à 60 mois s'est déroulée de mai 2010 à mai 2011 dans trois(3) centres de prise en charge des Personnes Vivant avec le VIH(PVV), notamment le Centre d'Excellence(CE) de l'hôpital Sendwe, le Centre Amo-Congo de la Kenya et le Centre de Référence de la Kenya. Les statistiques descriptives usuelles ont été utilisées. Résultats La prévalence de la malnutrition globale était de 60,2% (n = 50) dont 8,4% de malnutrition sévère. Le poids moyen était de 11,6±4,1 kg avec un minimum de 5 kg et un maximum de 22 kg. Le taux d'hémoglobine moyen était d'environ 9,8± 2,0 g/dl avec une prévalence globale de l'anémie (hémoglobine VIH. La survenue de l'anémie n’était pas associée au déficit nutritionnel (p = 0,6). Conclusion Ces résultats révèlent que l'infection à VIH modifie l’état nutritionnel des enfants à Lubumbashi avec 60,2% de malnutrition globale et 8,4% de retard de croissance. Les enfants au stade avancé de l'infection à VIH en sont plus affectés. PMID:25574336
6-Alkyl-, 6-aryl- or 6-hetaryl-7-deazapurine ribonucleosides as inhibitors of human or MTB adenosine kinase and potential antimycobacterial agents

Czech Academy of Sciences Publication Activity Database

Perlíková, Pavla; Konečný, P.; Nauš, Petr; Snášel, Jan; Votruba, Ivan; Džubák, P.; Pichová, Iva; Hajdúch, M.; Hocek, Michal

2013-01-01

Roč. 4, č. 11 (2013), s. 1497-1500 ISSN 2040-2503 R&D Projects: GA ČR GAP207/11/0344 EU Projects: European Commission(XE) 241587 - SYSTEMTB Grant - others:Operational Programme Research and Development for Innovations(XE) CZ.1.05/2.1.00/01.0030 Institutional support: RVO:61388963 Keywords : mycobacterium- tuberculosis * enzyme-inhibition * 6-(het)aryl-7-deazapurine ribonucleosides Subject RIV: CC - Organic Chemistry Impact factor: 2.626, year: 2013
Inhibition by anandamide of 6-hydroxydopamine-induced cell death in PC12 cells.

LENUS (Irish Health Repository)

Mnich, Katarzyna

2010-01-01

6-hydroxydopamine (6-OHDA) is a selective neurotoxin that is widely used to investigate cell death and protective strategies in models of Parkinson\\'s disease. Here, we investigated the effects of the endogenous cannabinoid, anandamide, on 6-OHDA-induced toxicity in rat adrenal phaeochromocytoma PC12 cells. Morphological analysis and caspase-3 activity assay revealed that anandamide inhibited 6-OHDA-induced apoptosis. The protection was not affected by antagonists of either cannabinoid receptors (CB(1) or CB(2)) or the vanilloid receptor TRPV1. Anandamide-dependent protection was reduced by pretreatment with LY294002 (inhibitor of phosphatidylinositol 3-kinase, PI3K) and unaffected by U0126 (inhibitor of extracellularly-regulated kinase). Interestingly, phosphorylation of c-Jun-NH2-terminal kinase (JNK) in cells exposed to 6-OHDA was strongly reduced by anandamide pre-treatment. Furthermore, 6-OHDA induced c-Jun activation and increased Bim expression, both of which were inhibited by anandamide. Together, these data demonstrate antiapoptotic effects of anandamide and also suggest a role for activation of PI3K and inhibition of JNK signalling in anandamide-mediated protection against 6-OHDA.
Time-dependent amplitude analysis of semileptonically-tagged $D^0 \\to K_S^0 \\pi^+ \\pi^-$ decays at LHCb

CERN Document Server

INSPIRE-00392459

2013-01-01

The hadronic decay $D^0 \\to K_S^0 \\pi^+ \\pi^-$ provides access to the measurement of the mixing parameters of the neutral D-meson system and allows to test for CP violation. A measurement of the mixing parameters $x_D$ and $y_D$ as well as of the parameters $|q/p|$ and $\\phi=arg(q,p)$, which govern indirect CP violation, will be performed based on a time-dependent amplitude-model analysis of the full LHCb dataset of 2011 and 2012 corresponding to an integrated luminosity of 3/fb.
Seroprevalence of Epstein-Barr virus infection in U.S. children ages 6-19, 2003-2010.

Directory of Open Access Journals (Sweden)

Jennifer Beam Dowd

Full Text Available BACKGROUND: Epstein-Barr virus (EBV is a common herpesvirus linked to infectious mononucleosis and multiple cancers. There are no national estimates of EBV seroprevalence in the United States. Our objective was to estimate the overall prevalence and sociodemographic predictors of EBV among U.S. children and adolescents aged 6-19. METHODS: We calculated prevalence estimates and prevalence ratios for EBV seroprevalence using data from the 2003-2010 U.S. National Health and Nutrition Examination Survey (NHANES for children aged 6-19 (n = 8417. Poisson regression was used to calculate multivariable-adjusted prevalence ratios across subgroup categories (sex, race/ethnicity, parental education, household income, household size, foreign-born, BMI, and household smoking. FINDINGS: Overall EBV seroprevalence was 66.5% (95% CI 64.3%-68.7%.. Seroprevalence increased with age, ranging from 54.1% (95% CI 50.2%-57.9% for 6-8 year olds to 82.9% (95% CI 80.0%-85.9% for 18-19 year olds. Females had slightly higher seroprevalence (68.9%, 95% CI 66.3%-71.6% compared to males (64.2%, 95% CI 61.7%-66.8%. Seroprevalence was substantially higher for Mexican-Americans (85.4%, 95% CI 83.1%-87.8% and Non-Hispanic Blacks (83.1%, 95% CI 81.1%-85.1% than Non-Hispanic Whites (56.9%, 95% CI 54.1%-59.8%. Large differences were also seen by family income, with children in the lowest income quartile having 81.0% (95% CI 77.6%-84.5% seroprevalence compared to 53.9% (95% CI 50.5%-57.3% in the highest income quartile, with similar results for parental education level. These results were not explained by household size, BMI, or parental smoking. Among those who were seropositive, EBV antibody titers were significantly higher for females, Non-Hispanic Blacks and Mexican-Americans, with no association found for socioeconomic factors. CONCLUSIONS: In the first nationally representative U.S. estimates, we found substantial socioeconomic and race/ethnic differences in the
Tangeretin and its metabolite 4'-hydroxytetramethoxyflavone attenuate EGF-stimulated cell cycle progression in hepatocytes; role of inhibition at the level of mTOR/p70S6K.

Science.gov (United States)

Cheng, Z; Surichan, S; Ruparelia, K; Arroo, R; Boarder, M R

2011-04-01

The mechanisms by which the dietary compound tangeretin has anticancer effects may include acting as a prodrug, forming an antiproliferative product in cancer cells. Here we show that tangeretin also inhibits cell cycle progression in hepatocytes and investigate the role of its primary metabolite 4'-hydroxy-5,6,7,8-tetramethoxyflavone (4'-OH-TMF) in this effect. We used epidermal growth factor (EGF)-stimulated rat hepatocytes, with [(3)H]-thymidine incorporation into DNA as an index of progression to S-phase of the cell cycle, and Western blots for phospho-proteins involved in the cell signalling cascade. Incubation of tangeretin with microsomes expressing CYP1A, or with hepatocytes, generated a primary product we identified as 4'-OH-TMF. Low micromolar concentrations of tangeretin or 4'-OH-TMF gave a concentration-dependent inhibition of EGF-stimulated progression to S-phase while having little effect on cell viability. To determine whether time for conversion of tangeretin to an active metabolite would enhance the inhibitory effect we used long pre-incubations; this reduced the inhibitory effect, in parallel with a reduction in the concentration of tangeretin. The EGF-stimulation of hepatocyte cell cycle progression requires signalling through Akt/mTOR/p70S6K kinase cascades. The tangeretin metabolite 4'-OH-TMF selectively inhibited S6K phosphorylation in the absence of significant inhibition of upstream Akt activity, suggesting an effect at the level of mTOR. Tangeretin and 4'-OH-TMF both inhibit cell cycle progression in primary hepatocytes. The inhibition of p70S6K phosphorylation by 4'-OH-TMF raises the possibility that inhibition of the mTOR pathway may contribute to the anticancer influence of a flavonoid-rich diet. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.
Model-independent measurement of mixing parameters in $D^0 \\to K_S^0 \\pi^+ \\pi^-$ decays

CERN Document Server

Aaij, Roel; Adeva, Bernardo; Adinolfi, Marco; Affolder, Anthony; Ajaltouni, Ziad; Akar, Simon; Albrecht, Johannes; Alessio, Federico; Alexander, Michael; Ali, Suvayu; Alkhazov, Georgy; Alvarez Cartelle, Paula; Alves Jr, Antonio Augusto; Amato, Sandra; Amerio, Silvia; Amhis, Yasmine; An, Liupan; Anderlini, Lucio; Anderson, Jonathan; Andreassi, Guido; Andreotti, Mirco; Andrews, Jason; Appleby, Robert; Aquines Gutierrez, Osvaldo; Archilli, Flavio; d'Argent, Philippe; Artamonov, Alexander; Artuso, Marina; Aslanides, Elie; Auriemma, Giulio; Baalouch, Marouen; Bachmann, Sebastian; Back, John; Badalov, Alexey; Baesso, Clarissa; Baldini, Wander; Barlow, Roger; Barschel, Colin; Barsuk, Sergey; Barter, William; Batozskaya, Varvara; Battista, Vincenzo; Bay, Aurelio; Beaucourt, Leo; Beddow, John; Bedeschi, Franco; Bediaga, Ignacio; Bel, Lennaert; Bellee, Violaine; Belloli, Nicoletta; Belyaev, Ivan; Ben-Haim, Eli; Bencivenni, Giovanni; Benson, Sean; Benton, Jack; Berezhnoy, Alexander; Bernet, Roland; Bertolin, Alessandro; Bettler, Marc-Olivier; van Beuzekom, Martinus; Bien, Alexander; Bifani, Simone; Billoir, Pierre; Bird, Thomas; Birnkraut, Alex; Bizzeti, Andrea; Blake, Thomas; Blanc, Frédéric; Blouw, Johan; Blusk, Steven; Bocci, Valerio; Bondar, Alexander; Bondar, Nikolay; Bonivento, Walter; Borghi, Silvia; Borsato, Martino; Bowcock, Themistocles; Bowen, Espen Eie; Bozzi, Concezio; Braun, Svende; Britsch, Markward; Britton, Thomas; Brodzicka, Jolanta; Brook, Nicholas; Buchanan, Emma; Burr, Christopher; Bursche, Albert; Buytaert, Jan; Cadeddu, Sandro; Calabrese, Roberto; Calvi, Marta; Calvo Gomez, Miriam; Campana, Pierluigi; Campora Perez, Daniel; Capriotti, Lorenzo; Carbone, Angelo; Carboni, Giovanni; Cardinale, Roberta; Cardini, Alessandro; Carniti, Paolo; Carson, Laurence; Carvalho Akiba, Kazuyoshi; Casse, Gianluigi; Cassina, Lorenzo; Castillo Garcia, Lucia; Cattaneo, Marco; Cauet, Christophe; Cavallero, Giovanni; Cenci, Riccardo; Charles, Matthew; Charpentier, Philippe; Chefdeville, Maximilien; Chen, Shanzhen; Cheung, Shu-Faye; Chiapolini, Nicola; Chrzaszcz, Marcin; Cid Vidal, Xabier; Ciezarek, Gregory; Clarke, Peter; Clemencic, Marco; Cliff, Harry; Closier, Joel; Coco, Victor; Cogan, Julien; Cogneras, Eric; Cogoni, Violetta; Cojocariu, Lucian; Collazuol, Gianmaria; Collins, Paula; Comerma-Montells, Albert; Contu, Andrea; Cook, Andrew; Coombes, Matthew; Coquereau, Samuel; Corti, Gloria; Corvo, Marco; Couturier, Benjamin; Cowan, Greig; Craik, Daniel Charles; Crocombe, Andrew; Cruz Torres, Melissa Maria; Cunliffe, Samuel; Currie, Robert; D'Ambrosio, Carmelo; Dall'Occo, Elena; Dalseno, Jeremy; David, Pieter; Davis, Adam; De Aguiar Francisco, Oscar; De Bruyn, Kristof; De Capua, Stefano; De Cian, Michel; De Miranda, Jussara; De Paula, Leandro; De Simone, Patrizia; Dean, Cameron Thomas; Decamp, Daniel; Deckenhoff, Mirko; Del Buono, Luigi; Déléage, Nicolas; Demmer, Moritz; Derkach, Denis; Deschamps, Olivier; Dettori, Francesco; Dey, Biplab; Di Canto, Angelo; Di Ruscio, Francesco; Dijkstra, Hans; Donleavy, Stephanie; Dordei, Francesca; Dorigo, Mirco; Dosil Suárez, Alvaro; Dossett, David; Dovbnya, Anatoliy; Dreimanis, Karlis; Dufour, Laurent; Dujany, Giulio; Dupertuis, Frederic; Durante, Paolo; Dzhelyadin, Rustem; Dziurda, Agnieszka; Dzyuba, Alexey; Easo, Sajan; Egede, Ulrik; Egorychev, Victor; Eidelman, Semen; Eisenhardt, Stephan; Eitschberger, Ulrich; Ekelhof, Robert; Eklund, Lars; El Rifai, Ibrahim; Elsasser, Christian; Ely, Scott; Esen, Sevda; Evans, Hannah Mary; Evans, Timothy; Falabella, Antonio; Färber, Christian; Farley, Nathanael; Farry, Stephen; Fay, Robert; Ferguson, Dianne; Fernandez Albor, Victor; Ferrari, Fabio; Ferreira Rodrigues, Fernando; Ferro-Luzzi, Massimiliano; Filippov, Sergey; Fiore, Marco; Fiorini, Massimiliano; Firlej, Miroslaw; Fitzpatrick, Conor; Fiutowski, Tomasz; Fohl, Klaus; Fol, Philip; Fontana, Marianna; Fontanelli, Flavio; Forshaw, Dean Charles; Forty, Roger; Frank, Markus; Frei, Christoph; Frosini, Maddalena; Fu, Jinlin; Furfaro, Emiliano; Gallas Torreira, Abraham; Galli, Domenico; Gallorini, Stefano; Gambetta, Silvia; Gandelman, Miriam; Gandini, Paolo; Gao, Yuanning; García Pardiñas, Julián; Garra Tico, Jordi; Garrido, Lluis; Gascon, David; Gaspar, Clara; Gauld, Rhorry; Gavardi, Laura; Gazzoni, Giulio; Gerick, David; Gersabeck, Evelina; Gersabeck, Marco; Gershon, Timothy; Ghez, Philippe; Gianì, Sebastiana; Gibson, Valerie; Girard, Olivier Göran; Giubega, Lavinia-Helena; Gligorov, V.V.; Göbel, Carla; Golubkov, Dmitry; Golutvin, Andrey; Gomes, Alvaro; Gotti, Claudio; Grabalosa Gándara, Marc; Graciani Diaz, Ricardo; Granado Cardoso, Luis Alberto; Graugés, Eugeni; Graverini, Elena; Graziani, Giacomo; Grecu, Alexandru; Greening, Edward; Gregson, Sam; Griffith, Peter; Grillo, Lucia; Grünberg, Oliver; Gui, Bin; Gushchin, Evgeny; Guz, Yury; Gys, Thierry; Hadavizadeh, Thomas; Hadjivasiliou, Christos; Haefeli, Guido; Haen, Christophe; Haines, Susan; Hall, Samuel; Hamilton, Brian; Han, Xiaoxue; Hansmann-Menzemer, Stephanie; Harnew, Neville; Harnew, Samuel; Harrison, Jonathan; He, Jibo; Head, Timothy; Heijne, Veerle; Hennessy, Karol; Henrard, Pierre; Henry, Louis; van Herwijnen, Eric; Heß, Miriam; Hicheur, Adlène; Hill, Donal; Hoballah, Mostafa; Hombach, Christoph; Hulsbergen, Wouter; Humair, Thibaud; Hussain, Nazim; Hutchcroft, David; Hynds, Daniel; Idzik, Marek; Ilten, Philip; Jacobsson, Richard; Jaeger, Andreas; Jalocha, Pawel; Jans, Eddy; Jawahery, Abolhassan; Jing, Fanfan; John, Malcolm; Johnson, Daniel; Jones, Christopher; Joram, Christian; Jost, Beat; Jurik, Nathan; Kandybei, Sergii; Kanso, Walaa; Karacson, Matthias; Karbach, Moritz; Karodia, Sarah; Kecke, Matthieu; Kelsey, Matthew; Kenyon, Ian; Kenzie, Matthew; Ketel, Tjeerd; Khairullin, Egor; Khanji, Basem; Khurewathanakul, Chitsanu; Klaver, Suzanne; Klimaszewski, Konrad; Kochebina, Olga; Kolpin, Michael; Komarov, Ilya; Koopman, Rose; Koppenburg, Patrick; Kozeiha, Mohamad; Kravchuk, Leonid; Kreplin, Katharina; Kreps, Michal; Krocker, Georg; Krokovny, Pavel; Kruse, Florian; Krzemien, Wojciech; Kucewicz, Wojciech; Kucharczyk, Marcin; Kudryavtsev, Vasily; Kuonen, Axel Kevin; Kurek, Krzysztof; Kvaratskheliya, Tengiz; Lacarrere, Daniel; Lafferty, George; Lai, Adriano; Lambert, Dean; Lanfranchi, Gaia; Langenbruch, Christoph; Langhans, Benedikt; Latham, Thomas; Lazzeroni, Cristina; Le Gac, Renaud; van Leerdam, Jeroen; Lees, Jean-Pierre; Lefèvre, Regis; Leflat, Alexander; Lefrançois, Jacques; Lemos Cid, Edgar; Leroy, Olivier; Lesiak, Tadeusz; Leverington, Blake; Li, Yiming; Likhomanenko, Tatiana; Liles, Myfanwy; Lindner, Rolf; Linn, Christian; Lionetto, Federica; Liu, Bo; Liu, Xuesong; Loh, David; Longstaff, Iain; Lopes, Jose; Lucchesi, Donatella; Lucio Martinez, Miriam; Luo, Haofei; Lupato, Anna; Luppi, Eleonora; Lupton, Oliver; Lusiani, Alberto; Machefert, Frederic; Maciuc, Florin; Maev, Oleg; Maguire, Kevin; Malde, Sneha; Malinin, Alexander; Manca, Giulia; Mancinelli, Giampiero; Manning, Peter Michael; Mapelli, Alessandro; Maratas, Jan; Marchand, Jean François; Marconi, Umberto; Marin Benito, Carla; Marino, Pietro; Marks, Jörg; Martellotti, Giuseppe; Martin, Morgan; Martinelli, Maurizio; Martinez Santos, Diego; Martinez Vidal, Fernando; Martins Tostes, Danielle; Massafferri, André; Matev, Rosen; Mathad, Abhijit; Mathe, Zoltan; Matteuzzi, Clara; Mauri, Andrea; Maurin, Brice; Mazurov, Alexander; McCann, Michael; McCarthy, James; McNab, Andrew; McNulty, Ronan; Meadows, Brian; Meier, Frank; Meissner, Marco; Melnychuk, Dmytro; Merk, Marcel; Michielin, Emanuele; Milanes, Diego Alejandro; Minard, Marie-Noelle; Mitzel, Dominik Stefan; Molina Rodriguez, Josue; Monroy, Ignacio Alberto; Monteil, Stephane; Morandin, Mauro; Morawski, Piotr; Mordà, Alessandro; Morello, Michael Joseph; Moron, Jakub; Morris, Adam Benjamin; Mountain, Raymond; Muheim, Franz; Müller, Dominik; Müller, Janine; Müller, Katharina; Müller, Vanessa; Mussini, Manuel; Muster, Bastien; Naik, Paras; Nakada, Tatsuya; Nandakumar, Raja; Nandi, Anita; Nasteva, Irina; Needham, Matthew; Neri, Nicola; Neubert, Sebastian; Neufeld, Niko; Neuner, Max; Nguyen, Anh Duc; Nguyen, Thi-Dung; Nguyen-Mau, Chung; Niess, Valentin; Niet, Ramon; Nikitin, Nikolay; Nikodem, Thomas; Novoselov, Alexey; O'Hanlon, Daniel Patrick; Oblakowska-Mucha, Agnieszka; Obraztsov, Vladimir; Ogilvy, Stephen; Okhrimenko, Oleksandr; Oldeman, Rudolf; Onderwater, Gerco; Osorio Rodrigues, Bruno; Otalora Goicochea, Juan Martin; Otto, Adam; Owen, Patrick; Oyanguren, Maria Aranzazu; Palano, Antimo; Palombo, Fernando; Palutan, Matteo; Panman, Jacob; Papanestis, Antonios; Pappagallo, Marco; Pappalardo, Luciano; Pappenheimer, Cheryl; Parker, William; Parkes, Christopher; Passaleva, Giovanni; Patel, Girish; Patel, Mitesh; Patrignani, Claudia; Pearce, Alex; Pellegrino, Antonio; Penso, Gianni; Pepe Altarelli, Monica; Perazzini, Stefano; Perret, Pascal; Pescatore, Luca; Petridis, Konstantinos; Petrolini, Alessandro; Petruzzo, Marco; Picatoste Olloqui, Eduardo; Pietrzyk, Boleslaw; Pilař, Tomas; Pinci, Davide; Pistone, Alessandro; Piucci, Alessio; Playfer, Stephen; Plo Casasus, Maximo; Poikela, Tuomas; Polci, Francesco; Poluektov, Anton; Polyakov, Ivan; Polycarpo, Erica; Popov, Alexander; Popov, Dmitry; Popovici, Bogdan; Potterat, Cédric; Price, Eugenia; Price, Joseph David; Prisciandaro, Jessica; Pritchard, Adrian; Prouve, Claire; Pugatch, Valery; Puig Navarro, Albert; Punzi, Giovanni; Qian, Wenbin; Quagliani, Renato; Rachwal, Bartolomiej; Rademacker, Jonas; Rama, Matteo; Rangel, Murilo; Raniuk, Iurii; Rauschmayr, Nathalie; Raven, Gerhard; Redi, Federico; Reichert, Stefanie; Reid, Matthew; dos Reis, Alberto; Ricciardi, Stefania; Richards, Sophie; Rihl, Mariana; Rinnert, Kurt; Rives Molina, Vincente; Robbe, Patrick; Rodrigues, Ana Barbara; Rodrigues, Eduardo; Rodriguez Lopez, Jairo Alexis; Rodriguez Perez, Pablo; Roiser, Stefan; Romanovsky, Vladimir; Romero Vidal, Antonio; Ronayne, John William; Rotondo, Marcello; Rouvinet, Julien; Ruf, Thomas; Ruiz Valls, Pablo; Saborido Silva, Juan Jose; Sagidova, Naylya; Sail, Paul; Saitta, Biagio; Salustino Guimaraes, Valdir; Sanchez Mayordomo, Carlos; Sanmartin Sedes, Brais; Santacesaria, Roberta; Santamarina Rios, Cibran; Santimaria, Marco; Santovetti, Emanuele; Sarti, Alessio; Satriano, Celestina; Satta, Alessia; Saunders, Daniel Martin; Savrina, Darya; Schiller, Manuel; Schindler, Heinrich; Schlupp, Maximilian; Schmelling, Michael; Schmelzer, Timon; Schmidt, Burkhard; Schneider, Olivier; Schopper, Andreas; Schubiger, Maxime; Schune, Marie Helene; Schwemmer, Rainer; Sciascia, Barbara; Sciubba, Adalberto; Semennikov, Alexander; Serra, Nicola; Serrano, Justine; Sestini, Lorenzo; Seyfert, Paul; Shapkin, Mikhail; Shapoval, Illya; Shcheglov, Yury; Shears, Tara; Shekhtman, Lev; Shevchenko, Vladimir; Shires, Alexander; Siddi, Benedetto Gianluca; Silva Coutinho, Rafael; Silva de Oliveira, Luiz Gustavo; Simi, Gabriele; Sirendi, Marek; Skidmore, Nicola; Skwarnicki, Tomasz; Smith, Edmund; Smith, Eluned; Smith, Iwan Thomas; Smith, Jackson; Smith, Mark; Snoek, Hella; Sokoloff, Michael; Soler, Paul; Soomro, Fatima; Souza, Daniel; Souza De Paula, Bruno; Spaan, Bernhard; Spradlin, Patrick; Sridharan, Srikanth; Stagni, Federico; Stahl, Marian; Stahl, Sascha; Stefkova, Slavorima; Steinkamp, Olaf; Stenyakin, Oleg; Stevenson, Scott; Stoica, Sabin; Stone, Sheldon; Storaci, Barbara; Stracka, Simone; Straticiuc, Mihai; Straumann, Ulrich; Sun, Liang; Sutcliffe, William; Swientek, Krzysztof; Swientek, Stefan; Syropoulos, Vasileios; Szczekowski, Marek; Szumlak, Tomasz; T'Jampens, Stephane; Tayduganov, Andrey; Tekampe, Tobias; Teklishyn, Maksym; Tellarini, Giulia; Teubert, Frederic; Thomas, Christopher; Thomas, Eric; van Tilburg, Jeroen; Tisserand, Vincent; Tobin, Mark; Todd, Jacob; Tolk, Siim; Tomassetti, Luca; Tonelli, Diego; Topp-Joergensen, Stig; Torr, Nicholas; Tournefier, Edwige; Tourneur, Stephane; Trabelsi, Karim; Tran, Minh Tâm; Tresch, Marco; Trisovic, Ana; Tsaregorodtsev, Andrei; Tsopelas, Panagiotis; Tuning, Niels; Ukleja, Artur; Ustyuzhanin, Andrey; Uwer, Ulrich; Vacca, Claudia; Vagnoni, Vincenzo; Valenti, Giovanni; Vallier, Alexis; Vazquez Gomez, Ricardo; Vazquez Regueiro, Pablo; Vázquez Sierra, Carlos; Vecchi, Stefania; Velthuis, Jaap; Veltri, Michele; Veneziano, Giovanni; Vesterinen, Mika; Viaud, Benoit; Vieira, Daniel; Vieites Diaz, Maria; Vilasis-Cardona, Xavier; Volkov, Vladimir; Vollhardt, Achim; Volyanskyy, Dmytro; Voong, David; Vorobyev, Alexey; Vorobyev, Vitaly; Voß, Christian; de Vries, Jacco; Waldi, Roland; Wallace, Charlotte; Wallace, Ronan; Walsh, John; Wandernoth, Sebastian; Wang, Jianchun; Ward, David; Watson, Nigel; Websdale, David; Weiden, Andreas; Whitehead, Mark; Wilkinson, Guy; Wilkinson, Michael; Williams, Mark Richard James; Williams, Matthew; Williams, Mike; Williams, Timothy; Wilson, Fergus; Wimberley, Jack; Wishahi, Julian; Wislicki, Wojciech; Witek, Mariusz; Wormser, Guy; Wotton, Stephen; Wyllie, Kenneth; Xie, Yuehong; Xu, Zhirui; Yang, Zhenwei; Yu, Jiesheng; Yuan, Xuhao; Yushchenko, Oleg; Zangoli, Maria; Zavertyaev, Mikhail; Zhang, Liming; Zhang, Yanxi; Zhelezov, Alexey; Zhokhov, Anatoly; Zhong, Liang; Zucchelli, Stefano

2016-04-06

The first model-independent measurement of the charm mixing parameters in the decay $D^0 \\to K_S \\pi^+ \\pi^-$ is reported, using a sample of $pp$ collision data recorded by the LHCb experiment, corresponding to an integrated luminosity of 1.0 fb$^{-1}$ at a centre-of-mass energy of 7 TeV. The measured values are \\begin{eqnarray*} x &=& ( -0.86 \\pm 0.53 \\pm 0.17 ) \\times 10^{-2}, \\\\ y &=& ( +0.03 \\pm 0.46 \\pm 0.13 ) \\times 10^{-2}, \\end{eqnarray*} where the first uncertainties are statistical and include small contributions due to the external input for the strong phase measured by the CLEO collaboration, and the second uncertainties are systematic.
Superconducting properties, chemical compositions, and lattice parameters of Pb-, Sn- and (Pb1-xSnx)Mo6S8

International Nuclear Information System (INIS)

Sadakata, N.; Corderman, R.; Asano, T.; Cox, D.; Suenaga, M.; Foner, S.; McNiff, E.J. Jr.

1991-01-01

The values of critical temperatures for alloys of Pb- and SnMo 6 S 8 were shown to be lower than those of the respective pure Chevrel phases. Chemical compositional analysis of the compounds revealed that the decreased T c in the alloys are due to the off-stoichiometric compositions in the alloys. Although alloying slightly increased the values of the upper critical field H c2 over that for PbMo 6 S 8 , the H c2 values for these specimens were substantially lower than those which have been reported for PbMo 6 S 8 . Possible causes for these depressed values of H c2 are discussed
Oxygen concentration cell for the measurements of the standard molar Gibbs energy of formation of Nd6UO12(s)

International Nuclear Information System (INIS)

Sahu, Manjulata; Dash, Smruti

2011-01-01

The standard molar Gibbs energies of formation of Nd 6 UO 12 (s) have been measured using an oxygen concentration cell with yttria stabilized zirconia as solid electrolyte. Δ f G m o (T) for Nd 6 UO 12 (s) has been calculated using the measured and required thermodynamic data from the literature. The calculated Gibbs energy expression can be given as: Δ f G m o (Nd 6 UO 12 , s,T)/(± 2.3) kJmol -1 = -6660.1+1.0898 (T/K). (author)
The Bi{sup 3+} 6s and 6p electron binding energies in relation to the chemical environment of inorganic compounds

Energy Technology Data Exchange (ETDEWEB)

Awater, Roy H.P., E-mail: R.H.P.Awater@tudelft.nl; Dorenbos, Pieter

2017-04-15

This paper provides an overview and interpretation of the spectroscopic data of the Bi{sup 3+} activator ion in 117 different inorganic compounds. The energies of the metal-to-metal charge transfer and the interconfigurational transitions of Bi{sup 3+} were collected from the archival literature. Using these energies, in combination with the electron binding energies in the host conduction and valence band, the binding energies in the 6s ground state and 6p excited state were determined relative to the vacuum level. The locations of the Bi{sup 3+} energy levels within the forbidden gap of the host compound provides valuable insight in the physical properties of the Bi{sup 3+} activator ion in different compounds.
TRAF6 promotes myogenic differentiation via the TAK1/p38 mitogen-activated protein kinase and Akt pathways.

Directory of Open Access Journals (Sweden)

Fang Xiao

Full Text Available p38 mitogen-activated protein kinase (MAPK is an essential kinase involved in myogenic differentiation. Although many substrates of p38 MAPK have been identified, little is known about its upstream activators during myogenic differentiation. TRAF6 is known to function in cytokine signaling during inflammatory responses. However, not much is known about its role in myogenic differentiation and muscle regeneration. We showed here that TRAF6 and its intrinsic ubiquitin E3 ligase activity are required for myogenic differentiation. In mouse myoblasts, knockdown of TRAF6 compromised the p38 MAPK and Akt pathways, while deliberate activation of either pathway rescued the differentiation defect caused by TRAF6 knockdown. TAK1 acted as a key signal transducer downstream of TRAF6 in myogenic differentiation. In vivo, knockdown of TRAF6 in mouse muscles compromised the injury-induced muscle regeneration without impairing macrophage infiltration and myoblast proliferation. Collectively, we demonstrated that TRAF6 promotes myogenic differentiation and muscle regeneration via the TAK1/p38 MAPK and Akt pathways.
Sangivamycin-Like Molecule 6 (SLM6) exhibits potent anti-multiple myeloma activity through inhibition of cyclin-dependent kinase-9 (CDK9)

Science.gov (United States)

Dolloff, Nathan G.; Allen, Joshua E.; Dicker, David T.; Aqui, Nicole; Vogl, Dan; Malysz, Jozef; Talamo, Giampaolo; El-Deiry, Wafik S.

2012-01-01

Despite significant treatment advances over the past decade, multiple myeloma (MM) remains largely incurable. In this study we found that MM cells were remarkably sensitive to the death-inducing effects of a new class of sangivamycin-like molecules (SLMs). A panel of structurally related SLMs selectively induced apoptosis in MM cells but not other tumor or non-malignant cell lines at sub-micromolar concentrations. SLM6 was the most active compound in vivo, where it was well-tolerated and significantly inhibited growth and induced apoptosis of MM tumors. We determined that the anti-MM activity of SLM6 was mediated by direct inhibition of cyclin-dependent kinase 9 (CDK9), which resulted in transcriptional repression of oncogenes that are known to drive MM progression (c-Maf, cyclin D1, and c-Myc). Furthermore, SLM6 demonstrated superior in vivo anti-MM activity over the CDK inhibitor flavopiridol, which is currently in clinical trials for MM. These findings demonstrate that SLM6 is a novel CDK9 inhibitor with promising preclinical activity as an anti-MM agent. PMID:22964485
Nucleation behavior of melted Bi films at cooling rates from 101 to 104 K/s studied by combining scanning AC and DC nano-calorimetry techniques

International Nuclear Information System (INIS)

Xiao, Kechao; Vlassak, Joost J.

2015-01-01

Highlights: • We proposed a general data reduction scheme that combines scanning AC and DC calorimetry results for the study of reaction kinetics. • Calorimetry measurements at cooling rates ranging from 30 K/s to 20,000 K/s were achieved. • Upon initial melting, the Bi thin-film sample breaks up into thousands of isolated islands, and highly repeatable nucleation behavior is observed. • The nucleation rate of melted Bi is calculated, which can be well described by classical nucleation theory over a wide range of cooling rates. - Abstract: We study the nucleation behavior of undercooled liquid Bi at cooling rates ranging from 10 1 to 10 4 K/s using a combination of scanning DC and AC nano-calorimetry techniques. Upon initial melting, the Bi thin-film sample breaks up into silicon nitride-coated isolated islands. The number of islands in a typical sample is sufficiently large that highly repeatable nucleation behavior is observed, despite the stochastic nature of the nucleation process. We establish a data reduction technique to evaluate the nucleation rate from DC and AC calorimetry results. The results show that the driving force for the nucleation of melted Bi is well described by classical nucleation theory over a wide range of cooling rates. The proposed technique provides a unique and efficient way to examine nucleation kinetics with cooling rates over several orders of magnitude. The technique is quite general and can be used to evaluate reaction kinetics in other materials
Enantioselective synthesis of (+-polyzonimine, defensive monoterpene alkaloid produced by a milliped Polyzonium rosalbum, and determination of its S absolute configuration by Its conversion to (4S,5R,6S-(+-nitropolyzonamine

Directory of Open Access Journals (Sweden)

Takagi Yasuyo

2000-01-01

Full Text Available Asymmetric Michael addition of the enamine derived from 2,2-dimethylcyclopentanecarbox-aldehyde and (S-prolinol methyl ether to nitroethylene afforded the adduct of 75-76% ee, which finally yielded enantiomerically pure (+-polyzonimine, a nitrogen-containing spirocyclic compound isolated from the defensive glands of a milliped, Polyzonium rosalbum. By converting (+-polyzonimine into (4S,5R,6S-(+-nitropolyzonamine, the hitherto uncertain absolute configuration of the former was established as S.
Post-test analysis of semiscale tests S-UT-6 and S-UT-7 using TRAC PF1

International Nuclear Information System (INIS)

Boyack, B.E.

1983-01-01

A posttest study of Semiscale Tests S-UT-6 and S-UT-7 has been completed to assess TRAC-PFl predictions of pressurized water-reactor (PWR) small-break transients. The comparisons of the TRAC calculations and experimental results show that the correct qualitative influence of upper-head injection (UHI) was predicted. The major phenomenological difference predicted was the mode of core voiding. The data show a slow boiloff from the top of the core resulting in a dryout near the top of the core only. TRAC predicted a more extensive voiding with fluid forced from the bottom of the core by a pressure increase in the upper vessel plenum. The pressure increase was the primary consequence of a failure to predict a complete clearance of the seal in the intact-loop pump-suction upflow leg. Further review of the interphasic drag correlations, entrainment correlations, and critical-flow model is recommended. 20 figures
Synthetic peptides and ribosomal proteins as substrate for 60S ribosomal protein kinase from yeast cells

DEFF Research Database (Denmark)

Grankowski, N; Gasior, E; Issinger, O G

1993-01-01

Kinetic studies on the 60S protein kinase were conducted with synthetic peptides and ribosomal proteins as substrate. Peptide RRREEESDDD proved to be the best synthetic substrate for this enzyme. The peptide has a sequence of amino acids which most closely resembles the structure of potential...... phosphorylation sites in natural substrates, i.e., acidic ribosomal proteins. The superiority of certain kinetic parameters for 60S kinase obtained with the native whole 80S ribosomes over those of the isolated fraction of acidic ribosomal proteins indicates that the affinity of 60S kinase to the specific protein...
6d dual conformal symmetry and minimal volumes in AdS

Energy Technology Data Exchange (ETDEWEB)

Bhattacharya, Jyotirmoy; Lipstein, Arthur E. [Centre for Particle Theory & Department of Mathematical Sciences, Durham University,South Road, Durham DH1 3LE (United Kingdom)

2016-12-20

The S-matrix of a theory often exhibits symmetries which are not manifest from the viewpoint of its Lagrangian. For instance, powerful constraints on scattering amplitudes are imposed by the dual conformal symmetry of planar 4d N=4 super Yang-Mills theory and the ABJM theory. Motivated by this, we investigate the consequences of dual conformal symmetry in six dimensions, which may provide useful insight into the worldvolume theory of M5-branes (if it enjoys such a symmetry). We find that 6d dual conformal symmetry uniquely fixes the integrand of the one-loop 4-point amplitude, and its structure suggests a Lagrangian with more than two derivatives. On integrating out the loop momentum in 6−2ϵ dimensions, the result is very similar to the corresponding amplitude of N=4 super Yang-Mills theory. We confirm this result holographically by generalizing the Alday-Maldacena solution for a minimal area string in Anti-de Sitter space to a minimal volume M2-brane ending on a pillow-shaped surface in the boundary whose seams correspond to a null-polygon. This involves careful treatment of a prefactor which diverges as 1/ϵ, and we comment on its possible interpretation. We also study 2-loop 4-point integrands with 6d dual conformal symmetry and speculate on the existence of an all-loop formula for the 4-point amplitude.
Preferential Selectivity of Inhibitors with Human Tau Protein Kinase Gsk3 Elucidates Their Potential Roles for Off-Target Alzheimer’s Therapy

Directory of Open Access Journals (Sweden)

Jagadeesh Kumar Dasappa

2013-01-01

Full Text Available Alzheimer’s disease (AD is a neurodegenerative disorder characterized by the accumulation of amyloid beta peptides (A and neurofibrillary tangles (NFTs. The abnormal phosphorylation of tau leads to the formation of NFTs produced by the action of tau kinases, resulting in the loss of neurons and synapse, leading to dementia. Hence, tau kinases have become potential drug target candidates for small molecule inhibitors. With an aim to explore the identification of a common inhibitor, this investigation was undertaken towards analyzing all 10 tau kinases which are implicated in phosphorylation of AD. A set of 7 inhibitors with varied scaffolds were collected from the Protein Data Bank (PDB. The analysis, involving multiple sequence alignment, 3D structural alignment, catalytic active site overlap, and docking studies, has enabled elucidation of the pharmacophoric patterns for the class of 7 inhibitors. Our results divulge that tau protein kinases share a specific set of conserved structural elements for the binding of inhibitors and ATP, respectively. The scaffold of 3-aminopyrrolidine (inhibitor 6 exhibits high preferential affinity with GSK3. Surprisingly, the PDB does not contain the structural details of GSK3 with this specific inhibitor. Thus, our investigations provide vital clues towards design of novel off-target drugs for Alzheimer’s.
Regulatory role of tumor necrosis factor receptor-associated factor 6 in breast cancer by activating the protein kinase B/glycogen synthase kinase 3β signaling pathway.

Science.gov (United States)

Shen, Hongyu; Li, Liangpeng; Yang, Sujin; Wang, Dandan; Zhou, Siying; Chen, Xiu; Tang, Jinhai

2017-08-01

Tumor necrosis factor receptor-associated factor 6 (TRAF6) is an endogenous adaptor of innate and adaptive immune responses, and serves a crucial role in tumor necrosis factor receptor and toll‑like/interleukin‑1 receptor signaling. Although studies have demonstrated that TRAF6 has oncogenic activity, its potential contributions to breast cancer in human remains largely uninvestigated. The present study examined the expression levels and function of TRAF6 in breast carcinoma (n=32) and adjacent healthy (n=25) tissue samples. Compared with adjacent healthy tissues, TRAF6 protein expression levels were significantly upregulated in breast cancer tissues. Reverse transcription‑quantitative polymerase chain reaction analysis revealed a significant upregulation of the cellular proliferative marker Ki‑67 and proliferation cell nuclear antigen expression levels in breast carcinoma specimens. Furthermore, protein expression levels of the accessory molecule, transforming growth factor β‑activated kinase 1 (TAK1), were significantly increased in breast cancer patients, as detected by western blot analysis. As determined by MTT assay, TRAF6 exerted profoundly proliferative effects in the MCF‑7 breast cancer cell line; however, these detrimental effects were ameliorated by TAK1 inhibition. Notably, protein kinase B (AKT)/glycogen synthase kinase (GSK)3β phosphorylation levels were markedly upregulated in breast cancer samples, compared with adjacent healthy tissues. In conclusion, an altered TRAF6‑TAK1 axis and its corresponding downstream AKT/GSK3β signaling molecules may contribute to breast cancer progression. Therefore, TRAF6 may represent a potential therapeutic target for the treatment of breast cancer.
ZnO nanorods/ZnS.(1,6-hexanediamine)0.5 hybrid nanoplates hierarchical heteroarchitecture with improved electrochemical catalytic properties for hydrazine

Science.gov (United States)

Wu, Zhengcui; Wu, Yaqin; Pei, Tonghui; Wang, Huan; Geng, Baoyou

2014-02-01

Novel hierarchical heteronanostructures of ZnO nanorods/ZnS.(HDA)0.5 (HDA = 1,6-hexanediamine) hybrid nanoplates on a zinc substrate are successfully synthesized on a large scale by combining hydrothermal growth (for ZnO nanorods) and liquid chemical conversion (for ZnS.(HDA)0.5 nanoplates) techniques. The formation of ZnS.(HDA)0.5 hybrid nanoplates branches takes advantage of the preferential binding of 1,6-hexanediamine on specific facets of ZnS, which makes the thickening rate much lower than the lateral growth rate. The ZnS.(HDA)0.5 hybrid nanoplates have a layered structure with 1,6-hexanediamine inserted into interlayers of wurtzite ZnS through the bonding of nitrogen. The number density and thickness of the secondary ZnS.(HDA)0.5 nanoplates can be conveniently engineered by variation of the sulfur source and straightforward adjustment of reactant concentrations such as 1,6-hexanediamine and the sulfur source. The fabricated ZnO/ZnS.(HDA)0.5 heteronanostructures show improved electrochemical catalytic properties for hydrazine compared with the primary ZnO nanorods. Due to its simplicity and efficiency, this approach could be similarly used to fabricate varieties of hybrid heterostructures made of materials with an intrinsic large lattice mismatch.Novel hierarchical heteronanostructures of ZnO nanorods/ZnS.(HDA)0.5 (HDA = 1,6-hexanediamine) hybrid nanoplates on a zinc substrate are successfully synthesized on a large scale by combining hydrothermal growth (for ZnO nanorods) and liquid chemical conversion (for ZnS.(HDA)0.5 nanoplates) techniques. The formation of ZnS.(HDA)0.5 hybrid nanoplates branches takes advantage of the preferential binding of 1,6-hexanediamine on specific facets of ZnS, which makes the thickening rate much lower than the lateral growth rate. The ZnS.(HDA)0.5 hybrid nanoplates have a layered structure with 1,6-hexanediamine inserted into interlayers of wurtzite ZnS through the bonding of nitrogen. The number density and thickness of the

Mitogen activated protein kinase 6 and MAP kinase phosphatase 1 are involved in the response of Arabidopsis roots to L-glutamate.

Science.gov (United States)

López-Bucio, Jesús Salvador; Raya-González, Javier; Ravelo-Ortega, Gustavo; Ruiz-Herrera, León Francisco; Ramos-Vega, Maricela; León, Patricia; López-Bucio, José; Guevara-García, Ángel Arturo

2018-03-01

The function and components of L-glutamate signaling pathways in plants have just begun to be elucidated. Here, using a combination of genetic and biochemical strategies, we demonstrated that a MAPK module is involved in the control of root developmental responses to this amino acid. Root system architecture plays an essential role in plant adaptation to biotic and abiotic factors via adjusting signal transduction and gene expression. L-Glutamate (L-Glu), an amino acid with neurotransmitter functions in animals, inhibits root growth, but the underlying genetic mechanisms are poorly understood. Through a combination of genetic analysis, in-gel kinase assays, detailed cell elongation and division measurements and confocal analysis of expression of auxin, quiescent center and stem cell niche related genes, the critical roles of L-Glu in primary root growth acting through the mitogen-activated protein kinase 6 (MPK6) and the dual specificity serine-threonine-tyrosine phosphatase MKP1 could be revealed. In-gel phosphorylation assays revealed a rapid and dose-dependent induction of MPK6 and MPK3 activities in wild-type Arabidopsis seedlings in response to L-Glu. Mutations in MPK6 or MKP1 reduced or increased root cell division and elongation in response to L-Glu, possibly modulating auxin transport and/or response, but in a PLETHORA1 and 2 independent manner. Our data highlight MPK6 and MKP1 as components of an L-Glu pathway linking the auxin response, and cell division for primary root growth.
S100A6 is a negative regulator of the induction of cardiac genes by trophic stimuli in cultured rat myocytes

International Nuclear Information System (INIS)

Tsoporis, J.N.; Marks, A.; Haddad, A.; O'Hanlon, D.; Jolly, S.; Parker, T.G.

2005-01-01

S100A6 (calcyclin), a member of the S100 family of EF-hand Ca 2+ binding proteins, has been implicated in the regulation of cell growth and proliferation. We have previously shown that S100B, another member of the S100 family, is induced postinfarction and limits the hypertrophic response of surviving cardiac myocytes. We presently report that S100A6 expression is also increased in the periinfarct zone of rat heart postinfarction and in cultured neonatal rat myocytes by treatment with several trophic agents, including platelet-derived growth factor (PDGF), the α 1 -adrenergic agonist phenylephrine (PE), and angiotensin II (AII). Cotransfection of S100A6 in cultured neonatal rat cardiac myocytes inhibits induction of the cardiac fetal gene promoters skeletal α-actin (skACT) and β-myosin heavy chain (β-MHC) by PDGF, PE, AII, and the prostaglandin F 2α (PGF 2α ), induction of the S100B promoter by PE, and induction of the α-MHC promoter by triiodothyronine (T3). By contrast, S100B cotransfection selectively inhibited only PE induction of skACT and β-MHC promoters. Fluorescence microscopy demonstrated overlapping intracellular distribution of S100B and S100A6 in transfected myocytes and in postinfarct myocardium but heterodimerization of the two proteins could not be detected by co-immunoprecipitation. We conclude that S100A6 may function as a global negative modulator of differentiated cardiac gene expression comparable to its putative role in cell cycle progression of dividing cells
Üks kuningas En-metena raidkiri (En-metena E1.9.5.3.). Kas esimene teadaolev sõprusleping muistses Lähis-Idas? / Vladimir Sazonov

Index Scriptorium Estoniae

Sazonov, Vladimir, 1979-

2015-01-01

Üks raidkiri varadünastilise perioodi III perioodist on eriline, kuna nimetab "sõprust" või olemuslikult võimalikku "sõpruspakti" kahe Sumeri valitseja vahel. Tegemist on Lagaši kuninga El-metena raidkirjaga. Esmakordselt on tekst avaldatud eesti keeles. Juttu on sõprusest Lagaši kuninga E-metena ja Uruki vürsti Lugal-kiğine-dudu vahel. En-metena isikust. Sündmuste rekontruktsioonist pärast En-metena surma Lagašis 2340. a. paiku e. Kr. Uruki ja Uri valitsejast Lugal-kiğine-dudu'st
Activation of the interleukin-6/Janus kinase/STAT3 pathway in pleomorphic adenoma of the parotid gland

DEFF Research Database (Denmark)

Andreasen, Simon; Therkildsen, Marianne Hamilton; Grauslund, Morten

2015-01-01

The interleukin-6 (IL-6)/Janus kinase (JAK)/signal transducer and activator of transcription 3 (STAT3) pathway is of crucial importance in promoting tumorigenesis in several malignant tumors but may also be active in benign tumors, e.g., of pleomorphic adenoma (PA). In this study we characterize ...
Reversible and irreversible magnetization of the Chevrel-phase superconductor PbMo6S8

International Nuclear Information System (INIS)

Zheng, D.N.; Ramsbottom, H.D.; Hampshire, D.P.

1995-01-01

Magnetic measurements have been carried out on the hot-isostatically-pressed Chevrel-phase superconductor PbMo 6 S 8 at temperatures from 4.2 K to T c and for magnetic fields up to 12 T. The results show that for the PbMo 6 S 8 compound there is a wide magnetically reversible region, between the irreversibility field B irr and the upper critical field B c2 , on the isothermal magnetic hysteresis curves. The B irr (T) line, i.e., the irreversibility line, was found to obey a power-law expression: B irr =B * (1-T/T c ) α with α∼1.5. Magnetic relaxation measurements revealed that the flux-creep effect in the material studied is substantial and is greater than those observed in conventional metallic alloys, but smaller than in high-temperature superconductors. The existence of the irreversibility line and pronounced flux-creep effect in PbMo 6 S 8 is attributed to the short coherence length of the material. From the reversible magnetization data, the values of the penetration depth, the coherence length, and the critical fields are obtained together with the Ginzburg-Landau parameter κ. At 4.2 K, the critical current density J c is 10 9 A m -2 at zero field, and decreases to 2x10 8 A m -2 at 10 T. Pinning force curves measured at different temperatures obey a Kramer-scaling law of the form: F p (=J c xB)∝b 1/2 (1-b) 2 , which indicates that the J c is limited by one predominant flux-pinning mechanism
Demonstration of immunogenic keratan sulphate in commercial chondroitin 6-sulphate from shark cartilage. Implications for ELISA assays

DEFF Research Database (Denmark)

Møller, H J; Møller-Pedersen, T; Damsgaard, T E

1995-01-01

The prototype monoclonal keratan sulphate (KS) antibody 5D4 that is widely used for detection of KS in tissues and biological fluids reacts strongly with commercial low grade shark cartilage chondroitin 6-sulphate. Characterization of the immunogenic material by chondroitinase ABC digestion, ELISA...... inhibition studies, immunoblotting and HPLC analyses confirmed the presence of substantial amounts of KS, probably as a large proteoglycan (> 120 kDa). Commercial and heterogenic glycosaminoglycan preparations therefore must be used with great caution in immunological analyses. On the other hand the shark...... cartilage chondroitin 6-sulphate is an easy accessible source of immunogenic KS that can be used as a reference standard and as coating antigen in KS-ELISAs. The concentration of immunogenic KS in synovial fluid measured with an ELISA based solely on reagents of shark cartilage chondroitin 6-sulphate...
Quasirelativistic calculation of 4s24p5, 4s24p44d and 4s4p6 configuration spectroscopic parameters for the W39+ ion

International Nuclear Information System (INIS)

Bogdanovich, P; Karpuškienė, R; Kisielius, R

2015-01-01

The ab initio quasirelativistic Hartree–Fock method developed specifically for the calculation of spectral parameters of heavy atoms and highly charged ions is used to derive spectral data for the 4s 2 4p 5 , 4s 2 4p 4 4d and 4s4p 6 configurations of the multicharged tungsten ion W 39+ . The relativistic effects are taken into account in the Breit–Pauli approximation for the quasirelativistic Hartree–Fock radial orbitals. The configuration interaction method is applied to include the electron correlation effects. Produced data are compared with existing experimental measurements and theoretical calculations. (paper)
Tangeretin and its metabolite 4′-hydroxytetramethoxyflavone attenuate EGF-stimulated cell cycle progression in hepatocytes; role of inhibition at the level of mTOR/p70S6K

Science.gov (United States)

Cheng, Z; Surichan, S; Ruparelia, K; Arroo, R; Boarder, MR

2011-01-01

BACKGROUND AND PURPOSE The mechanisms by which the dietary compound tangeretin has anticancer effects may include acting as a prodrug, forming an antiproliferative product in cancer cells. Here we show that tangeretin also inhibits cell cycle progression in hepatocytes and investigate the role of its primary metabolite 4′-hydroxy-5,6,7,8-tetramethoxyflavone (4′-OH-TMF) in this effect. EXPERIMENTAL APPROACH We used epidermal growth factor (EGF)-stimulated rat hepatocytes, with [3H]-thymidine incorporation into DNA as an index of progression to S-phase of the cell cycle, and Western blots for phospho-proteins involved in the cell signalling cascade. KEY RESULTS Incubation of tangeretin with microsomes expressing CYP1A, or with hepatocytes, generated a primary product we identified as 4′-OH-TMF. Low micromolar concentrations of tangeretin or 4′-OH-TMF gave a concentration-dependent inhibition of EGF-stimulated progression to S-phase while having little effect on cell viability. To determine whether time for conversion of tangeretin to an active metabolite would enhance the inhibitory effect we used long pre-incubations; this reduced the inhibitory effect, in parallel with a reduction in the concentration of tangeretin. The EGF-stimulation of hepatocyte cell cycle progression requires signalling through Akt/mTOR/p70S6K kinase cascades. The tangeretin metabolite 4′-OH-TMF selectively inhibited S6K phosphorylation in the absence of significant inhibition of upstream Akt activity, suggesting an effect at the level of mTOR. CONCLUSIONS AND IMPLICATIONS Tangeretin and 4′-OH-TMF both inhibit cell cycle progression in primary hepatocytes. The inhibition of p70S6K phosphorylation by 4′-OH-TMF raises the possibility that inhibition of the mTOR pathway may contribute to the anticancer influence of a flavonoid-rich diet. PMID:21198542
(S)-homo-AMPA, a specific agonist at the mGlu6 subtype of metabotropic glutamic acid receptors

DEFF Research Database (Denmark)

Ahmadian, H; Nielsen, B; Bräuner-Osborne, Hans

1997-01-01

of the spectroscopic configurational assignments. The activities of 6 and 7 at ionotropic EAA (iGlu) receptors and at mGlu1-7 were studied. (S)-Homo-AMPA (6) was shown to be a specific agonist at mGlu6 (EC50 = 58 +/- 11 microM) comparable in potency with the endogenous mGlu agonist (S)-glutamic acid (EC50 = 20 +/- 3......Our previous publication (J. Med. Chem. 1996, 39, 3188-3194) described (RS)-2-amino-4-(3-hydroxy-5-methylisoxazol-4-yl)butyric acid (Homo-AMPA) as a highly selective agonist at the mGlu6 subtype of metabotropic excitatory amino acid (EAA) receptors. Homo-AMPA has already become a standard agonist...... microM). Although Homo-AMPA did not show significant effects at iGlu receptors, (R)-Homo-AMPA (7), which was inactive at mGlu1-7, turned out to be a weak N-methyl-D-aspartic acid (NMDA) receptor antagonist (IC50 = 131 +/- 18 microM)....
PAK6 Phosphorylates 14-3-3γ to Regulate Steady State Phosphorylation of LRRK2

Directory of Open Access Journals (Sweden)

Laura Civiero

2017-12-01

Full Text Available Mutations in Leucine-rich repeat kinase 2 (LRRK2 are associated with Parkinson's disease (PD and, as such, LRRK2 is considered a promising therapeutic target for age-related neurodegeneration. Although the cellular functions of LRRK2 in health and disease are incompletely understood, robust evidence indicates that PD-associated mutations alter LRRK2 kinase and GTPase activities with consequent deregulation of the downstream signaling pathways. We have previously demonstrated that one LRRK2 binding partner is P21 (RAC1 Activated Kinase 6 (PAK6. Here, we interrogate the PAK6 interactome and find that PAK6 binds a subset of 14-3-3 proteins in a kinase dependent manner. Furthermore, PAK6 efficiently phosphorylates 14-3-3γ at Ser59 and this phosphorylation serves as a switch to dissociate the chaperone from client proteins including LRRK2, a well-established 14-3-3 binding partner. We found that 14-3-3γ phosphorylated by PAK6 is no longer competent to bind LRRK2 at phospho-Ser935, causing LRRK2 dephosphorylation. To address whether these interactions are relevant in a neuronal context, we demonstrate that a constitutively active form of PAK6 rescues the G2019S LRRK2-associated neurite shortening through phosphorylation of 14-3-3γ. Our results identify PAK6 as the kinase for 14-3-3γ and reveal a novel regulatory mechanism of 14-3-3/LRRK2 complex in the brain.
Case study of atmospheric correction on CCD data of HJ-1 satellite based on 6S model

International Nuclear Information System (INIS)

Xue, Xiaoiuan; Meng, Oingyan; Xie, Yong; Sun, Zhangli; Wang, Chang; Zhao, Hang

2014-01-01

In this study, atmospheric radiative transfer model 6S was used to simulate the radioactive transfer process in the surface-atmosphere-sensor. An algorithm based on the look-up table (LUT) founded by 6S model was used to correct (HJ-1) CCD image pixel by pixel. Then, the effect of atmospheric correction on CCD data of HJ-1 satellite was analyzed in terms of the spectral curves and evaluated against the measured reflectance acquired during HJ-1B satellite overpass, finally, the normalized difference vegetation index (NDVI) before and after atmospheric correction were compared. The results showed: (1) Atmospheric correction on CCD data of HJ-1 satellite can reduce the ''increase'' effect of the atmosphere. (2) Apparent reflectance are higher than those of surface reflectance corrected by 6S model in band1∼band3, but they are lower in the near-infrared band; the surface reflectance values corrected agree with the measured reflectance values well. (3)The NDVI increases significantly after atmospheric correction, which indicates the atmospheric correction can highlight the vegetation information
Role of adenosine 5'-monophosphate-activated protein kinase in interleukin-6 release from isolated mouse skeletal muscle

DEFF Research Database (Denmark)

Glund, Stephan; Treebak, Jonas Thue; Long, Yun Chau

2009-01-01

IL-6 is released from skeletal muscle during exercise and has consequently been implicated to mediate beneficial effects on whole-body metabolism. Using 5-aminoimidazole-4-carboxamide-1-beta-4-ribofuranoside (AICAR), a pharmacological activator of 5'-AMP-activated protein kinase (AMPK), we tested......-type mice was also incubated with the AMPK activator A-769662. Incubation of mouse glycolytic extensor digitorum longus and oxidative soleus muscle for 2 h was associated with profound IL-6 mRNA production and protein release, which was suppressed by AICAR (P ... the hypothesis that AMPK modulates IL-6 release from isolated muscle. Skeletal muscle from AMPKalpha2 kinase-dead transgenic, AMPKalpha1 knockout (KO) and AMPKgamma3 KO mice and respective wild-type littermates was incubated in vitro, in the absence or presence of 2 mmol/liter AICAR. Skeletal muscle from wild...
High-pressure anisotropic distortion of Pb3Bi2S6

DEFF Research Database (Denmark)

Olsen, Lars Arnskov; Balic Zunic, Tonci; Makovicky, Emil

2008-01-01

The compound Pb3Bi2S6 is investigated by X-ray diffraction on single crystals in a diamond-anvil cell between 0.0001 and 10.5 GPa. It undergoes a first-order phase transition at hydrostatic pressure between 3.7 and 4.9 Gpa. The space group symmetry changes from Bbmm to Pbnm, and the unit......-cell volume decreases by 4%. The transition is strongly anisotropic, with a contraction along one of the crystal axes by 16% and expansion along another one by 14%. This is a piezoplastic phase transition, a displacive pressure-induced phase transition with systematic shearing of atomic planes and a migration...
MX: Milestone II. Final Environmental Impact Statement. Volume 6. Public Comments

Science.gov (United States)

1978-10-06

8217VPaoli, molyore, ’leming# Daily, Otis, AKrun, Brus , LcKley, "ray, Jos, Id~lia, and Vernon. Thjen tncrc are a nuuber ul CceUCeerleS in tebween witl Ourialz...KS Public Comments VI - 5-101 Grace Eastin Yuma, CO M. H. Eaton Oakley, KS Mr. Dan R. Ebener Dubuque, IA Mr. Tom Eberhart Burlington, CO Elizabeth ...Russell Springs, KS Burlington, CO Rebecca L. Smith Mrs. Elizabeth StevensWinona, KS Potter, NE * r. Ronald L. Smith Mr. Wesley L. Stevens Winona, KS
Fisetin targets phosphatidylinositol-3-kinase and induces apoptosis of human B lymphoma Raji cells

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Ji Yeon Lim

2015-01-01

Full Text Available Aberrant regulation of phosphatidylinositol-3-kinases (PI3Ks is known to be involved in the progression of cancers. PI3K-binding flavonoids such as quercetin and myricetin have been shown to inhibit PI3K activity, but the direct targeting of fisetin to PI3K has not been established. Here, we carried out an in silico investigation of fisetin binding to PI3K and determined fisetin’s inhibitory activity in enzymatic and cell-based assays. In addition, fisetin induced apoptosis in human Burkitt’s lymphoma Raji cells by inhibiting both PI3Ks and mammalian target of rapamycin (mTOR. Our results indicate that fisetin may serve as a natural backbone for the development of novel dual inhibitors of PI3Ks and mTOR for the treatment of cancer.
Computer Animation with Adobe Flash Professional Cs6 in Newton’s Law

Science.gov (United States)

Aji, S. D.; Hudha, M. N.; Huda, C.; Gufran, G.

2018-01-01

The purpose of this research is to develop computer-based physics learning media with Adobe Flash Professional CS6 on Newton’s Law of physics subject for senior high school (SMA / MA) class X. Type of research applied is Research and Development with ADDIE development model covering 5 stages: Analysis (Analysis), Design (Design), Development (Production), Implementation (Implementation) and Evaluation (Evaluation). The results of this study were tested toward media experts, media specialists, physics teachers, and students test results with media outcomes that are declared very feasible.
Regulation by S-nitrosylation of the Calvin-Benson cycle fructose-1,6-bisphosphatase in Pisum sativum

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Antonio Jesús Serrato

2018-04-01

Full Text Available Redox regulation is of great importance in chloroplasts. Many chloroplast enzymes, such as those belonging to the Calvin-Benson cycle (CBC, have conserved regulatory cysteines which form inhibitory disulphide bridges when physiological conditions become unfavourable. Amongst these enzymes, cFBP1, the CBC fructose-1,6-bisphosphatase (FBPase isoform, is well known to be redox activated by thioredoxin f through the reduction of a disulphide bridge involving Cys153 and Cys173. Moreover, data obtained during recent years point to S-nitrosylation as another redox post-translational modification putatively regulating an increasing number of plant enzymes, including cFBP1. In this study we have shown that the Pisum sativum cFBP1 can be efficiently S-nitrosylated by GSNO and SNAP, triggering the formation of the regulatory disulphide. Using in vivo experiments with P. sativum we have established that cFBP1 S-nitrosylation only occurs during the light period and we have elucidated by activity assays with Cys-to-Ser mutants that this enzyme may be inactivated through the S-nitrosylation of Cys153. Finally, in the light of the new data, we have proposed an extended redox-regulation model by integrating the S-nitrosylation and the TRX f-mediated regulation of cFBP1. Keywords: S-nitrosylation, GSNO, Redox regulation, Fructose-1,6-bisphosphatase, Pisum sativum, Calvin-Benson cycle
Measurement of the Branching Ratios of D+ and D+s Hadronic Decays to Four-Body Final States Containing a KS

Science.gov (United States)

Link, J. M.; Reyes, M.; Yager, P. M.; Anjos, J. C.; Bediaga, I.; Göbel, C.; Magnin, J.; Massafferi, A.; de Miranda, J. M.; Pepe, I. M.; Dos Reis, A. C.; Simão, F. R.; Carrillo, S.; Casimiro, E.; Sánchez-Hernández, A.; Uribe, C.; Vázquez, F.; Cinquini, L.; Cumalat, J. P.; O'Reilly, B.; Ramirez, J. E.; Vaandering, E. W.; Butler, J. N.; Cheung, H. W.; Gaines, I.; Garbincius, P. H.; Garren, L. A.; Gottschalk, E.; Kasper, P. H.; Kreymer, A. E.; Kutschke, R.; Bianco, S.; Fabbri, F. L.; Sarwar, S.; Zallo, A.; Cawlfield, C.; Kim, D. Y.; Rahimi, A.; Wiss, J.; Gardner, R.; Chung, Y. S.; Kang, J. S.; Ko, B. R.; Kwak, J. W.; Lee, K. B.; Park, H.; Alimonti, G.; Boschini, M.; Caccianiga, B.; D'Angelo, P.; Dicorato, M.; Dini, P.; Giammarchi, M.; Inzani, P.; Leveraro, F.; Malvezzi, S.; Menasce, D.; Mezzadri, M.; Milazzo, L.; Moroni, L.; Pedrini, D.; Pontoglio, C.; Prelz, F.; Rovere, M.; Sala, A.; Sala, S.; Davenport, T. F.; Agostino, L.; Arena, V.; Boca, G.; Bonomi, G.; Gianini, G.; Liguori, G.; Merlo, M.; Pantea, D.; Ratti, S. P.; Riccardi, C.; Segoni, I.; Viola, L.; Vitulo, P.; Hernandez, H.; Lopez, A. M.; Mendez, H.; Mendez, L.; Mirles, A.; Montiel, E.; Olaya, D.; Paris, A.; Quinones, J.; Rivera, C.; Xiong, W.; Zhang, Y.; Wilson, J. R.; Cho, K.; Handler, T.; Engh, D.; Hosack, M.; Johns, W. E.; Nehring, M.; Sheldon, P. D.; Stenson, K.; Webster, M.; Sheaff, M.

2001-10-01

We have studied hadronic four-body decays of D+ and D+s mesons with a KS in the final state using data recorded during the 1996-1997 fixed-target run of the Fermilab high energy photoproduction experiment FOCUS. We report a new branching ratio measurement of Γ(D+-->KSK- π+π+)/Γ(D+-->KSπ+π+π-) = 0.0768+/-0.0041+/-0.0032. We make the first observation of three new decay modes with branching ratios Γ(D+-->KSK+π+π- )/Γ(D+-->KSπ+π+π-) = 0.0562+/-0.0039+/-0.0040, Γ(D+-->KSK+K- π+)/Γ(D+-->KSπ+π+π-) = 0.0077+/-0.0015+/-0.0009, and Γ(D+s-->KSK+π+π- )/Γ(D+s-->KSK- π+π+) = 0.586+/-0.052+/-0.043, where in each case the first error is statistical and the second error is systematic.
Planarizing cytosine: The S1 state structure, vibrations, and nonradiative dynamics of jet-cooled 5,6-trimethylenecytosine

Science.gov (United States)

Trachsel, Maria A.; Lobsiger, Simon; Schär, Tobias; Blancafort, Lluís; Leutwyler, Samuel

2017-06-01

We measure the S0 → S1 spectrum and time-resolved S1 state nonradiative dynamics of the "clamped" cytosine derivative 5,6-trimethylenecytosine (TMCyt) in a supersonic jet, using two-color resonant two-photon ionization (R2PI), UV/UV holeburning, and ns time-resolved pump/delayed ionization. The experiments are complemented with spin-component scaled second-order approximate coupled cluster (SCS-CC2), time-dependent density functional theory, and multi-state second-order perturbation-theory (MS-CASPT2) ab initio calculations. While the R2PI spectrum of cytosine breaks off ˜500 cm-1 above its 000 band, that of TMCyt extends up to +4400 cm-1 higher, with over a hundred resolved vibronic bands. Thus, clamping the cytosine C5-C6 bond allows us to explore the S1 state vibrations and S0 → S1 geometry changes in detail. The TMCyt S1 state out-of-plane vibrations ν1', ν3', and ν5' lie below 420 cm-1, and the in-plane ν11', ν12', and ν23' vibrational fundamentals appear at 450, 470, and 944 cm-1. S0 → S1 vibronic simulations based on SCS-CC2 calculations agree well with experiment if the calculated ν1', ν3', and ν5' frequencies are reduced by a factor of 2-3. MS-CASPT2 calculations predict that the ethylene-type S1 ⇝ S0 conical intersection (CI) increases from +366 cm-1 in cytosine to >6000 cm-1 in TMCyt, explaining the long lifetime and extended S0 → S1 spectrum. The lowest-energy S1 ⇝ S0 CI of TMCyt is the "amino out-of-plane" (OPX) intersection, calculated at +4190 cm-1. The experimental S1 ⇝ S0 internal conversion rate constant at the S1(v'=0 ) level is kI C=0.98 -2.2 ṡ1 08 s-1, which is ˜10 times smaller than in 1-methylcytosine and cytosine. The S1(v'=0 ) level relaxes into the T1(3π π *) state by intersystem crossing with kI S C=0.41 -1.6 ṡ1 08 s-1. The T1 state energy is measured to lie 24 580 ±560 cm-1 above the S0 state. The S1(v'=0 ) lifetime is τ =2.9 ns, resulting in an estimated fluorescence quantum yield of Φf l=24 %. Intense
Aggregation of Ribosomal Protein S6 at Nucleolus Is Cell Cycle-Controlled and Its Function in Pre-rRNA Processing Is Phosphorylation Dependent.

Science.gov (United States)

Zhang, Duo; Chen, Hui-Peng; Duan, Hai-Feng; Gao, Li-Hua; Shao, Yong; Chen, Ke-Yan; Wang, You-Liang; Lan, Feng-Hua; Hu, Xian-Wen

2016-07-01

Ribosomal protein S6 (rpS6) has long been regarded as one of the primary r-proteins that functions in the early stage of 40S subunit assembly, but its actual role is still obscure. The correct forming of 18S rRNA is a key step in the nuclear synthesis of 40S subunit. In this study, we demonstrate that rpS6 participates in the processing of 30S pre-rRNA to 18S rRNA only when its C-terminal five serines are phosphorylated, however, the process of entering the nucleus and then targeting the nucleolus does not dependent its phosphorylation. Remarkably, we also find that the aggregation of rpS6 at the nucleolus correlates to the phasing of cell cycle, beginning to concentrate in the nucleolus at later S phase and disaggregate at M phase. J. Cell. Biochem. 117: 1649-1657, 2016. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Pathogenesis and micro-anatomic characterization of a cell-adapted mutant foot-and-mouth disease virus in cattle: Impact of the Jumonji C-domain containing protein 6 (JMJD6) and route of inoculation.

Science.gov (United States)

Lawrence, Paul; Pacheco, Juan; Stenfeldt, Carolina; Arzt, Jonathan; Rai, Devendra K; Rieder, Elizabeth

2016-05-01

A companion study reported Jumonji-C domain containing protein 6 (JMJD6) is involved in an integrin- and HS-independent pathway of FMDV infection in CHO cells. JMJD6 localization was investigated in animal tissues from cattle infected with either wild type A24-FMDV (A24-WT) or mutant FMDV (JMJD6-FMDV) carrying E95K/S96L and RGD to KGE mutations in VP1. Additionally, pathogenesis of mutant JMJD6-FMDV was investigated in cattle through aerosol and intraepithelial lingual (IEL) inoculation. Interestingly, JMJD6-FMDV pathogenesis was equivalent to A24-WT administered by IEL route. In contrast, JMJD6-FMDV aerosol-infected cattle did not manifest signs of FMD and animals showed no detectable viremia. Immunofluorescent microscopy of post-mortem tissue revealed JMJD6-FMDV exclusively co-localized with JMJD6(+) cells while A24-WT was occasionally found in JMJD6(+) cells. In vitro, chemical uptake inhibitors demonstrated JMJD6-FMDV entered cells via clathrin-coated pit endocytosis. In vivo, JMJD6-FMDV exhibited preference for JMJD6(+) cells, but availability of this alternative receptor likely depends on route of inoculation. Copyright © 2016. Published by Elsevier Inc.
Cytotoxic Activity of 3,6-Dihydroxyflavone in Human Cervical Cancer Cells and Its Therapeutic Effect on c-Jun N-Terminal Kinase Inhibition

Directory of Open Access Journals (Sweden)

Eunjung Lee

2014-08-01

Full Text Available Previously we have shown that 3,6-dihydroxyflavone (3,6-DHF is a potent agonist of the human peroxisome proliferator-activated receptor (hPPAR with cytotoxic effects on human cervical cancer cells. To date, the mechanisms by which 3,6-DHF exerts its antitumor effects on cervical cells have not been clearly defined. Here, we demonstrated that 3,6-DHF exhibits a novel antitumor activity against HeLa cells with IC50 values of 25 μM and 9.8 μM after 24 h and 48 h, respectively. We also showed that the anticancer effects of 3,6-DHF are mediated via the toll-like receptor (TLR 4/CD14, p38 mitogen-activated protein kinase (MAPK, Jun-N terminal kinase (JNK, extracellular-signaling regulated kinase (ERK, and cyclooxygenase (COX-2 pathways in lipopolysaccharide (LPS-stimulated RAW264.7 cells. We found that 3,6-DHF showed a similar IC50 (113 nM value to that of the JNK inhibitor, SP600125 (IC50 = 118 nM in a JNK1 kinase assay. Binding studies revealed that 3,6-DHF had a strong binding affinity to JNK1 (1.996 × 105 M−1 and that the 6-OH and the carbonyl oxygen of the C ring of 3,6-DHF participated in hydrogen bonding interactions with the carbonyl oxygen and the amide proton of Met111, respectively. Therefore, 3,6-DHF may be a candidate inhibitor of JNKs, with potent anticancer effects.
A-RAF kinase functions in ARF6 regulated endocytic membrane traffic.

Directory of Open Access Journals (Sweden)

Elena Nekhoroshkova

Full Text Available BACKGROUND: RAF kinases direct ERK MAPK signaling to distinct subcellular compartments in response to growth factor stimulation. METHODOLOGY/PRINCIPAL FINDINGS: Of the three mammalian isoforms A-RAF is special in that one of its two lipid binding domains mediates a unique pattern of membrane localization. Specific membrane binding is retained by an N-terminal fragment (AR149 that corresponds to a naturally occurring splice variant termed DA-RAF2. AR149 colocalizes with ARF6 on tubular endosomes and has a dominant negative effect on endocytic trafficking. Moreover actin polymerization of yeast and mammalian cells is abolished. AR149/DA-RAF2 does not affect the internalization step of endocytosis, but trafficking to the recycling compartment. CONCLUSIONS/SIGNIFICANCE: A-RAF induced ERK activation is required for this step by activating ARF6, as A-RAF depletion or inhibition of the A-RAF controlled MEK-ERK cascade blocks recycling. These data led to a new model for A-RAF function in endocytic trafficking.
Acoustic and elastic properties of Sn2P2S6 crystals

International Nuclear Information System (INIS)

Mys, O; Martynyuk-Lototska, I; Vlokh, R; Grabar, A

2009-01-01

We present the results concerned with acoustic and elastic properties of Sn 2 P 2 S 6 crystals. The complete matrices of elastic stiffness and compliance coefficients are determined in both the crystallographic coordinate system and the system associated with eigenvectors of the elastic stiffness tensor. The acoustic slowness surfaces are constructed and the propagation and polarization directions of the slowest acoustic waves promising for acousto-optic interactions are determined on this basis. The acoustic obliquity angle and the deviation of polarization of the acoustic waves from purely transverse or longitudinal states are quantitatively analysed.
Acoustic and elastic properties of Sn(2)P(2)S(6) crystals.

Science.gov (United States)

Mys, O; Martynyuk-Lototska, I; Grabar, A; Vlokh, R

2009-07-01

We present the results concerned with acoustic and elastic properties of Sn(2)P(2)S(6) crystals. The complete matrices of elastic stiffness and compliance coefficients are determined in both the crystallographic coordinate system and the system associated with eigenvectors of the elastic stiffness tensor. The acoustic slowness surfaces are constructed and the propagation and polarization directions of the slowest acoustic waves promising for acousto-optic interactions are determined on this basis. The acoustic obliquity angle and the deviation of polarization of the acoustic waves from purely transverse or longitudinal states are quantitatively analysed.
Fabrication of magnetic Fe@ZnO0.6S0.4 nanocomposite for visible-light-driven photocatalytic inactivation of Escherichia coli

Science.gov (United States)

Peng, Ziling; Wu, Dan; Wang, Wei; Tan, Fatang; Ng, Tsz Wai; Chen, Jianguo; Qiao, Xueliang; Wong, Po Keung

2017-02-01

Bacterial inactivation by magnetic photocatalysts has now received growing interests due to the easy separation for recycle and reuse of photocatalysts. In this study, magnetic Fe@ZnO0.6S0.4 photocatalyst was prepared by a facile two-step precipitation method. Multiple techniques such as X-ray diffraction (XRD), transmission electron microscope (TEM), scanning electron microscope (SEM), X-ray photoelectron spectroscopy (XPS), UV-vis diffused reflectance spectra (UV-vis DRS) and vibrating sample magnetometer (VSM) were employed to characterize the structure, morphology and physicochemical properties of the photocatalyst. The as-obtained Fe@ZnO0.6S0.4 possessing magnetic property was easily collected from the reaction system by a magnet. Under white light-emitting-diode (LED) lamp irradiation, Fe@ZnO0.6S0.4 nanocomposite could completely inactivate 7-log of Escherichia coli K-12 within 5 h. More importantly, almost no decrease of photocatalytic efficiency in bacterial inactivation was observed even after five consecutive cycles, demonstrating Fe@ZnO0.6S0.4 exhibited good stability for reuse. The low released rate of Fe2+/Fe3+ and Zn2+ from Fe@ZnO0.6S0.4 composite further indicated the photocatalyst showed low cytotoxicity to bacterium and high stability under LED lamp irradiation. Facile preparation, high photocatalytic efficiency, good stability and reusability, and magnetic recovery property endow Fe@ZnO0.6S0.4 nanocomposite to be a promising photocatalytic material for bacterial inactivation.
Komunikační strategie ve vazbě na CSR ve firmě THIMM Obaly, k.s.

OpenAIRE

Deutschová, Veronika

2014-01-01

Diplomová práce zachycuje koncepci CSR v podnikové strategii společnosti THIMM Obaly, k.s. včetně uvedení teoretických východisek. Analyzuje a hodnotí stávající úroveň komunikace o aktivitách CSR. Výstup práce představuje návrh komunikační strategie, který umožní efektivní naplňování programu CSR pro zvolenou společnost. This diploma thesis gives a comprehensive survey of the CSR concept in corporate strategy in the limited partnership company THIMM Obaly. Theoretical bases are included. T...
Knockdown of human serine/threonine kinase 33 suppresses human small cell lung carcinoma by blocking RPS6/BAD signaling transduction.

Science.gov (United States)

Sun, E L; Liu, C X; Ma, Z X; Mou, X Y; Mu, X A; Ni, Y H; Li, X L; Zhang, D; Ju, Y R

2017-01-01

Small cell lung cancer (SCLC) is characterized by rapid growth rate and a tendency to metastasize to distinct sites of patients' bodies. The human serine/threonine kinase 33 (STK33) gene has shown its potency as a therapeutic target for prevention of lung carcinomas including non-small cell lung cancer (NSCLC), but its function in the oncogenesis and development of SCLC remains unrevealed. In the current study, it was hypothesized that STK33 played a key role in the proliferation, survival, and invasion of SCLC cells. The expression of STK33 in human SCLC cell lines NCI-H466 and DMS153 was inhibited by specific shRNA. The cell proliferation, cell apoptosis, and cell invasion of the cells were assessed with a series of in vitro assays. To explore the mechanism through which STK33 gene exerted its function in the carcinogenesis of SCLC cells, the effect of STK33 knockdown on the activity of S6K1/RPS6/BAD signaling was detected. Then the results were further confirmed with STK33 inhibitor ML281 and in vivo assays. The results demonstrated that inhibition of STK33 in SCLC cells suppressed the cell proliferation and invasion while induced cell apoptosis. Associated with the change in the phenotypic features, knockdown of STK33 also decreased the phosphorylation of RPS6 and BAD while increased the expression of cleaved caspase 9, indicating that apoptosis induced by STK33 suppression was mediated via mitochondrial pathway. Similar to the results of STK33 knockdown, incubating NCI-H466 cells with STK33 inhibitor also reduced the cell viability by suppressing RPS6/BAD pathways. Additionally, STK33 knockdown also inhibited tumor growth and RPS6/BAD activity in mice models. Findings outlined in our study were different from that in NSCLC to some extent: knockdown of STK33 in SCLC cells induced the apoptosis through mitochondrial pathway but independent of S6K1 function, inferring that the function of STK33 might be cancer type specific.
Unique dielectric features of a ceramic-semiconductor nanocomposite MgNb2O6 + 0.25Zn0.5Cd0.5S

Science.gov (United States)

Pukazhselvan, D.; Selvaraj, Nivas Babu; Bdikin, Igor; Saravanan, R. Sakthi Sudar; Jakka, Suresh Kumar; Soares, M. J.; Fagg, Duncan Paul

2017-12-01

The present communication deals with the optical/dielectric characteristics of MgNb2O6 + 0.25Zn0.5Cd0.5S nanocomposite (10-30 nm) mixture. Zn0.5Cd0.5S (size ∼10 nm) was synthesized by microwave assisted solvo-thermal method. Monophase magnesium niobate (MN) nanoparticles (10-20 nm) were synthesized in a single step by mechanochemical treatment of MgO + Nb2O5 under dry N2 atmosphere. The nanocomposite, MgNb2O6 + 0.25Zn0.5Cd0.5S, was prepared by mechanical admixing of MgNb2O6 and Zn0.5Cd0.5S taken in 4:1 molar ratio. The photoluminescence study shows violet, yellow and orange-red emissions by the MgNb2O6 + 0.25Zn0.5Cd0.5S composite. The observed dielectric constant value (ε) for MgNb2O6 + 0.25Zn0.5Cd0.5S is only 4.7, which is ∼5 times smaller than the ε value of MgNb2O6 while a dielectric loss for the composite being closer to zero ensures promising commercial applications.
Specific IgE to peanut 2S albumin Ara h 7 has a discriminative ability comparable to Ara h 2 and 6.

Science.gov (United States)

Blankestijn, M A; Otten, H G; Suer, W; Weimann, A; Knol, E F; Knulst, A C

2018-01-01

Little is known on the clinical relevance of peanut 2S albumin Ara h 7. To investigate the discriminative ability of Ara h 7 in peanut allergy and assess the role of cross-reactivity between Ara h 2, 6 and Ara h 7 isoforms. Sensitization to recombinant peanut storage proteins Ara h 1, 2, 3, 6, and 7 was assessed using a line blot in sera from 40 peanut-tolerant and 40 peanut-allergic patients, based on food challenge outcome. A dose-dependent ELISA inhibition experiment was performed with recombinant Ara h 2, 6 and Ara h 7 isoforms. For Ara h 7.0201, an area under the ROC curve was found of 0.83, comparable to Ara h 2 (AUC 0.81) and Ara h 6 (AUC 0.85). Ara h 7 intensity values strongly correlated with those from Ara h 2 and 6 (r s = 0.81). Of all patients sensitized to 2S albumins Ara h 2, 6, or 7, the majority was co-sensitized to all three (n = 24, 68%), although mono-sensitization to either 2S albumin was also observed in selected patients (Ara h 2: n = 6, 17%; Ara h 6: n = 2, 6%; Ara h 7: n = 2, 6%). Binding to Ara h 7.0101 could be strongly inhibited by Ara h 7.0201, but not the other way around. Specific IgE against Ara h 7.0201 has a predictive ability for peanut allergy similar to Ara h 2 and 6 and possesses unique IgE epitopes as well as epitopes shared between the other Ara h 7 isoform and Ara h 2 and 6. While co-sensitization to all three 2S albumins is most common, mono-sensitization to either Ara h 2, 6, or 7 occurs in selected patients, leading to a risk of misdiagnosis when testing for a single 2S albumin. © 2017 John Wiley & Sons Ltd.
Cocoa Procyanidins Suppress Transformation by Inhibiting Mitogen-activated Protein Kinase Kinase*S⃞

Science.gov (United States)

Kang, Nam Joo; Lee, Ki Won; Lee, Dong Eun; Rogozin, Evgeny A.; Bode, Ann M.; Lee, Hyong Joo; Dong, Zigang

2008-01-01

Cocoa was shown to inhibit chemically induced carcinogenesis in animals and exert antioxidant activity in humans. However, the molecular mechanisms of the chemopreventive potential of cocoa and its active ingredient(s) remain unknown. Here we report that cocoa procyanidins inhibit neoplastic cell transformation by suppressing the kinase activity of mitogen-activated protein kinase kinase (MEK). A cocoa procyanidin fraction (CPF) and procyanidin B2 at 5 μg/ml and 40 μm, respectively, inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced neoplastic transformation of JB6 P+ mouse epidermal (JB6 P+) cells by 47 and 93%, respectively. The TPA-induced promoter activity and expression of cyclooxygenase-2, which is involved in tumor promotion and inflammation, were dose-dependently inhibited by CPF or procyanidin B2. The activation of activator protein-1 and nuclear factor-κB induced by TPA was also attenuated by CPF or procyanidin B2. The TPA-induced phosphorylation of MEK, extracellular signal-regulated kinase, and p90 ribosomal s6 kinase was suppressed by CPF or procyanidin B2. In vitro and ex vivo kinase assay data demonstrated that CPF or procyanidin B2 inhibited the kinase activity of MEK1 and directly bound with MEK1. CPF or procyanidin B2 suppressed JB6 P+ cell transformation induced by epidermal growth factor or H-Ras, both of which are known to be involved in MEK/ERK signal activation. In contrast, theobromine (up to 80 μm) had no effect on TPA-induced transformation, cyclooxygenase-2 expression, the transactivation of activator protein-1 or nuclear factor-κB, or MEK. Notably, procyanidin B2 exerted stronger inhibitory effects compared with PD098059 (a well known pharmacological inhibitor of MEK) on MEK1 activity and neoplastic cell transformation. PMID:18519570
Role of interleukin-6 and pentraxin 3 as an early marker in Peyronie’s disease

Directory of Open Access Journals (Sweden)

Arda Atar

2017-04-01

Full Text Available Inflammation is mechanistically involved in the development of Peyronie’s disease (PD. The aim of this study is to assess the relevance of serum pentraxin 3 (PTX3 and interleukin-6 (IL-6 concentrations in PD. The study enrolled 40 patients with PD in the acute phase and 40 healthy controls. Plasma PTX3 and IL-6 concentrations were evaluated in 40 patients in the acute phase of PD and 40 healthy controls by enzyme-linked immunosorbent assay. Serum concentrations of both PTX3 and IL-6 were significantly higher in the PD patients than in the control group (p=0.001 and p=0.001, respectively. There was a significant correlation between concentration of PTX3 and painful erections. IL-6 concentrations were significantly higher in patients with erectile dysfunction. IL-6 and PTX3 levels showed no correlation with age, serum C-reactive protein, degree of curvature, and disease duration. IL-6 trans-signaling and PTX3 amplification at the site of inflammation could have a role in pathophysiological mechanisms of PD. Biological drugs may be used for treatment during the acute phase of the disease based on this mechanism.
Impact parameter analysis of proton-antiproton elastic scattering from √s=7.6 GeV to √s=546 GeV

International Nuclear Information System (INIS)

Fearnley, T.

1985-09-01

The proton-antiproton elastic profile function GAMMA (b) and inelastic overlap function Gsub(in)(b) are calculated from a coherent set of proton-antiproton elastic scattering data at Psub(L)=30 and 50 GeV/c (√s=7.6 and 9.8 GeV), and at √s=53 and 546 GeV. The energy dependence of Gsub(in)(b) is studied in the low energy regime and in the high energy regime. The increase of the inelastic cross section from 50 GeV/c to 30 GeV/c and from √s=53 GeV to √s=546 GeV is found to originate from a peripheral increase of Gsub(in) around 1 fm, accompanied by a non-negligible central increase. The proton-antiproton collision at √s=53 GeV is shown to be slightly less absorptive centrally than pp at this energy, while it is more absorptive peripherally around 1.2 fm. The inelastic overlap functions strongly disagree with the predictions of geometrical scaling and factorizing eikonal models, both in the low energy regime psub(L)=30-50 GeV/c and in the high energy regime √s=53-546 GeV
The Protein Kinase SmSnRK2.6 Positively Regulates Phenolic Acid Biosynthesis in Salvia miltiorrhiza by Interacting with SmAREB1.

Science.gov (United States)

Jia, Yanyan; Bai, Zhenqing; Pei, Tianlin; Ding, Kai; Liang, Zongsuo; Gong, Yuehua

2017-01-01

Subclass III members of the sucrose non-fermenting-1-related protein kinase 2 (SnRK2) play essential roles in both the abscisic acid signaling and abiotic stress responses of plants by phosphorylating the downstream ABA-responsive element (ABRE)-binding proteins (AREB/ABFs). This comprehensive study investigated the function of new candidate genes, namely SmSnRK2.3 , SmSnRK2.6 , and SmAREB1 , with a view to breeding novel varieties of Salvia miltiorrhiza with improved stress tolerance stresses and more content of bioactive ingredients. Exogenous ABA strongly induced the expression of these genes. PlantCARE predicted several hormones and stress response cis -elements in their promoters. SmSnRK2.6 and SmAREB1 showed the highest expression levels in the leaves of S. miltiorrhiza seedlings, while SmSnRK2.3 exhibited a steady expression in their roots, stems, and leaves. A subcellular localization assay revealed that both SmSnRK2.3 and SmSnRK2.6 were located in the cell membrane, cytoplasm, and nucleus, whereas SmAREB1 was exclusive to the nucleus. Overexpressing SmSnRK2.3 did not significantly promote the accumulation of rosmarinic acid (RA) and salvianolic acid B (Sal B) in the transgenic S. miltiorrhiza hairy roots. However, overexpressing SmSnRK2.6 and SmAREB1 increased the contents of RA and Sal B, and regulated the expression levels of structural genes participating in the phenolic acid-branched and side-branched pathways, including SmPAL1 , SmC4H , Sm4CL1 , SmTAT , SmHPPR , SmRAS , SmCHS , SmCCR , SmCOMT , and SmHPPD . Furthermore, SmSnRK2.3 and SmSnRK2.6 interacted physically with SmAREB1. In summary, our results indicate that SmSnRK2.6 is involved in stress responses and can regulate structural gene transcripts to promote greater metabolic flux to the phenolic acid-branched pathway, via its interaction with SmAREB1 , a transcription factor. In this way, SmSnRK2.6 contributes to the positive regulation of phenolic acids in S. miltiorrhiza hairy roots.
The Protein Kinase SmSnRK2.6 Positively Regulates Phenolic Acid Biosynthesis in Salvia miltiorrhiza by Interacting with SmAREB1

Directory of Open Access Journals (Sweden)

Yanyan Jia

2017-08-01

Full Text Available Subclass III members of the sucrose non-fermenting-1-related protein kinase 2 (SnRK2 play essential roles in both the abscisic acid signaling and abiotic stress responses of plants by phosphorylating the downstream ABA-responsive element (ABRE-binding proteins (AREB/ABFs. This comprehensive study investigated the function of new candidate genes, namely SmSnRK2.3, SmSnRK2.6, and SmAREB1, with a view to breeding novel varieties of Salvia miltiorrhiza with improved stress tolerance stresses and more content of bioactive ingredients. Exogenous ABA strongly induced the expression of these genes. PlantCARE predicted several hormones and stress response cis-elements in their promoters. SmSnRK2.6 and SmAREB1 showed the highest expression levels in the leaves of S. miltiorrhiza seedlings, while SmSnRK2.3 exhibited a steady expression in their roots, stems, and leaves. A subcellular localization assay revealed that both SmSnRK2.3 and SmSnRK2.6 were located in the cell membrane, cytoplasm, and nucleus, whereas SmAREB1 was exclusive to the nucleus. Overexpressing SmSnRK2.3 did not significantly promote the accumulation of rosmarinic acid (RA and salvianolic acid B (Sal B in the transgenic S. miltiorrhiza hairy roots. However, overexpressing SmSnRK2.6 and SmAREB1 increased the contents of RA and Sal B, and regulated the expression levels of structural genes participating in the phenolic acid-branched and side-branched pathways, including SmPAL1, SmC4H, Sm4CL1, SmTAT, SmHPPR, SmRAS, SmCHS, SmCCR, SmCOMT, and SmHPPD. Furthermore, SmSnRK2.3 and SmSnRK2.6 interacted physically with SmAREB1. In summary, our results indicate that SmSnRK2.6 is involved in stress responses and can regulate structural gene transcripts to promote greater metabolic flux to the phenolic acid-branched pathway, via its interaction with SmAREB1, a transcription factor. In this way, SmSnRK2.6 contributes to the positive regulation of phenolic acids in S. miltiorrhiza hairy roots.
The Protein Kinase RSK Family - Roles in Prostate Cancer

National Research Council Canada - National Science Library

Lannigan, Deborah

2006-01-01

The Ser/Thr protein kinase p90-kDa ribosomal S6 kinase (RSK) is an important downstream effector of mitogen-activated protein kinase but its roles in prostate cancer have not been previously examined...
IL-6 stabilizes Twist and enhances tumor cell motility in head and neck cancer cells through activation of casein kinase 2.

Directory of Open Access Journals (Sweden)

Ying-Wen Su

Full Text Available BACKGROUND: Squamous cell carcinoma of the head and neck (SCCHN is the seventh most common cancer worldwide. Unfortunately, the survival of patients with SCCHN has not improved in the last 40 years, and thus new targets for therapy are needed. Recently, elevations in serum level of interleukin 6 (IL-6 and expression of Twist in tumor samples were found to be associated with poor clinical outcomes in multiple types of cancer, including SCCHN. Although Twist has been proposed as a master regulator of epithelial-mesenchymal transition and metastasis in cancers, the mechanisms by which Twist levels are regulated post-translationally are not completely understood. Tumor progression is characterized by the involvement of cytokines and growth factors and Twist induction has been connected with a number of these signaling pathways including IL-6. Since many of the effects of IL-6 are mediated through activation of protein phosphorylation cascades, this implies that Twist expression must be under a tight control at the post-translational level in order to respond in a timely manner to external stimuli. METHODOLOGY/PRINCIPAL FINDINGS: Our data show that IL-6 increases Twist expression via a transcription-independent mechanism in many SCCHN cell lines. Further investigation revealed that IL-6 stabilizes Twist in SCCHN cell lines through casein kinase 2 (CK2 phosphorylation of Twist residues S18 and S20, and that this phosphorylation inhibits degradation of Twist. Twist phosphorylation not only increases its stability but also enhances cell motility. Thus, post-translational modulation of Twist contributes to its tumor-promoting properties. CONCLUSIONS/SIGNIFICANCE: Our study shows Twist expression can be regulated at the post-translational level through phosphorylation by CK2, which increases Twist stability in response to IL-6 stimulation. Our findings not only provide novel mechanistic insights into post-translational regulation of Twist but also suggest
Syntheses and structural characterization of non-centrosymmetric Na{sub 2}M{sub 2}M'S{sub 6} (M, M′=Ga, In, Si, Ge, Sn, Zn, Cd) sulfides

Energy Technology Data Exchange (ETDEWEB)

Yohannan, Jinu P.; Vidyasagar, Kanamaluru, E-mail: kvsagar@iitm.ac.in

2016-06-15

Seven new non-centrosymmetric Na{sub 2}M{sub 2}M’S{sub 6} sulfides, namely, Na{sub 2}Sn{sub 2}ZnS{sub 6}(1){sub ,} Na{sub 2}Ga{sub 2}GeS{sub 6}(2), Na{sub 2}Ga{sub 2}SnS{sub 6}(3-α), Na{sub 2}Ga{sub 2}SnS{sub 6}(3-β){sub ,} Na{sub 2}Ge{sub 2}ZnS{sub 6}(4){sub ,} Na{sub 2}Ge{sub 2}CdS{sub 6}(5){sub ,} Na{sub 2}In{sub 2}SiS{sub 6}(6) and Na{sub 2}In{sub 2}GeS{sub 6}(7), were synthesized by high temperature solid state reactions and structurally characterized by single crystal X-ray diffraction. They crystallize in non-centrosymmetric Fdd2 and Cc space groups and their three-dimensional [M{sub 2}M′S{sub 6}]{sup 2-}framework structures consist of MS{sub 4} and M′S{sub 4} tetrahedra corner-connected to one another in either orderly or disordered fashion. Sodium ions reside in the tunnels of the anionic framework. Compounds 1, 2 and 3-α have the structure of known Li{sub 2}Ga{sub 2}GeS{sub 6}, whereas compounds 6 and 7 are isostructural with known Li{sub 2}In{sub 2}GeS{sub 6} compound. Isostructural compounds 4 and 5 represent a new structural variant. Compounds 3-α and its new monoclinic structural variant 3-β have disordered structural framework. All of them are wide band gap semiconductors. Na{sub 2}Ga{sub 2}GeS{sub 6}(2), Na{sub 2}Ga{sub 2}SnS{sub 6}(3), Na{sub 2}Ge{sub 2}ZnS{sub 6}(4) and Na{sub 2}In{sub 2}GeS{sub 6}(7) compounds are found to be second-harmonic generation (SHG) active. Compounds 1, 2 and 3-α melt congruently. - Graphical abstract: Na{sub 2}Ga{sub 2}GeS{sub 6}, Na{sub 2}Ga{sub 2}SnS{sub 6}, Na{sub 2}Ge{sub 2}ZnS{sub 6}, Na{sub 2}In{sub 2}GeS{sub 6}, Na{sub 2}Sn{sub 2}ZnS{sub 6}, Na{sub 2}Ge{sub 2}CdS{sub 6} and Na{sub 2}In{sub 2}SiS{sub 6} have non-centrosymmetric structures and the first four compounds are SHG active. Display Omitted - Highlights: • Seven new Na{sub 2}M{sub 2}M′S{sub 6} compounds with non-centrosymmetric structures were synthesized. • They are wide band gap semiconductors. • Na{sub 2}Ga{sub 2}GeS{sub 6}, Na{sub 2
Synthesis, structural, electronic and linear electro-optical features of new quaternary Ag{sub 2}Ga{sub 2}SiS{sub 6} compound

Energy Technology Data Exchange (ETDEWEB)

Piasecki, M., E-mail: m.piasecki@ajd.czest.pl [Institute of Physics, Jan Dlugosz University, Armii Krajowej 13/15, PL-42-201 Czestochowa (Poland); Myronchuk, G.L. [Department of Solid State Physics, Lesya Ukrainka Eastern European National University, 13 Voli Ave., Lutsk 43025 (Ukraine); Parasyuk, O.V. [Department of Inorganic and Physical Chemistry, Lesya Ukrainka Eastern European National University, 13 Voli Ave., Lutsk 43025 (Ukraine); Khyzhun, O.Y. [Frantsevych Institute for Problems of Materials Science, National Academy of Sciences of Ukraine, 3 Krzhyzhanivsky St., Kyiv 03142 (Ukraine); Fedorchuk, A.O. [Department of Inorganic and Organic Chemistry, Lviv National University of Veterinary Medicine and Biotechnologies, 50 Pekarska Street, Lviv 79010 (Ukraine); Pavlyuk, V.V. [Department of Inorganic Chemistry, Ivan Franko National University of Lviv, 6 Kyryla and Mefodiya St., 79005 Lviv (Ukraine); Institute of Chemistry, Environment Protection and Biotechnology, Jan Dlugosz University, al. Armii Krajowej 13/15, 42-200 Czestochowa (Poland); Kozer, V.R.; Sachanyuk, V.P. [Department of Inorganic and Physical Chemistry, Lesya Ukrainka Eastern European National University, 13 Voli Ave., Lutsk 43025 (Ukraine); El-Naggar, A.M. [Physics Department, Faculty of Science, Ain Shams University, Abassia, Cairo 11566 (Egypt); Research Chair of Exploitation of Renewable Energy Applications in Saudi Arabia, Physics & Astronomy Department, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451 (Saudi Arabia); Albassam, A.A. [Research Chair of Exploitation of Renewable Energy Applications in Saudi Arabia, Physics & Astronomy Department, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451 (Saudi Arabia); Jedryka, J.; Kityk, I.V. [Faculty of Electrical Engineering, Czestochowa University Technology, Armii Krajowej 17, Czestochowa (Poland)

2017-02-15

For the first time phase equilibria and phase diagram of the AgGaS{sub 2}–SiS{sub 2} system were successfully explored by differential thermal and X-ray phase analysis methods. Crystal structure of low-temperature (LT) modification of Ag{sub 2}Ga{sub 2}SiS{sub 6} (LÐ Ñž- Ag{sub 2}Ga{sub 2}SiS{sub 6}) was studied by X-ray powder method and it belongs to tetragonal space group I-42d, with unit cell parameters a=5.7164(4) Å, c=9.8023(7) Å, V=320.32(7) Å{sup 3}. Additional details regarding the crystal structure exploration are available at the web page Fachinformationszentrum Karlsruhe. X-ray photoelectron core-level and valence-band spectra were measured for pristine LÐ Ñž- Ag{sub 2}Ga{sub 2}SiS{sub 6} crystal surface. In addition, the X-ray photoelectron valence-band spectrum of LÐ Ñž-Ag{sub 2}Ga{sub 2}SiS{sub 6} was matched on a common energy scale with the X-ray emission S Kβ{sub 1,3} and Ga Kβ{sub 2} bands, which give information on the energy distribution of the S 3p and Ga 4p states, respectively. The presented X-ray spectroscopy results indicate that the valence S p and Ga p atomic states contribute mainly to the upper and central parts of the valence band of LÐ Ñž-Ag{sub 2}Ga{sub 2}SiS{sub 6}, respectively, with a less significant contribution also to other valence-band regions. Band gap energy was estimated by measuring the quantum energy in the spectral range of the fundamental absorption. We have found that energy gap Eg is equal to 2.35 eV at 300 K. LT-Ag{sub 2}Ga{sub 2}SiS{sub 6} is a photosensitive material and reveals two spectral maxima on the curve of spectral photoconductivity spectra at λ{sub max1} =590 nm and λ{sub max2} =860 nm. Additionally, linear electro-optical effect of LT-Ag{sub 2}Ga{sub 2}SiS{sub 6} for the wavelengths of a cw He-Ne laser at 1150 nm was explored. - Graphical abstract: Manuscript present the technology of growth and investigation of properties a new quaternary compound Ag{sub 2}Ga{sub 2}SiS{sub 6
El estrés docente: elaboración de la escala ed-6 para su evaluación. [ Educational stress: elaboration of ed-6 scale for its assesment

Directory of Open Access Journals (Sweden)

Santiago Morán-Suárez

2005-02-01

Full Text Available The educational stress is an investigation topic that monopolizes or great number of studies. In the work that here is presented, the psychometrics properties of the scale ED-6 are analyzed. This scale was elaborated ad hoc to measure the stress or educational discomfort of face to their use in a wider frame of investigations on this phenomenon. As he/she will be able to be proven, the results show a reliability and acceptable validity, being conformed for 77 ítems and 6 dimensions: Anxiety, Depression, Pressures, Beliefs, Amotivation and Bad confrontation. It is expected that its use in future investigations is of great profit. El estrés docente es un tema de investigación que acapara un gran número de estudios. En el trabajo que aquí se presenta, se analizan las propiedades psicométricas de la escala ED-6,elaborada ad hoc para medir el estrés o malestar docente de cara a su utilización en un marco más amplio de investigaciones sobre este fenómeno. Como se podrá comprobar, los resultados muestran una fiabilidad y validez aceptable, quedando conformada por 77 ítems y 6 dimensiones: Ansiedad, Depresión, Presiones, Creencias, Desmotivación y Mal afrontamiento. Se espera que su uso en futuras investigaciones resulte de gran provecho

Critical current density and upper critical field of the PbMo6S8 Chevrel phase

International Nuclear Information System (INIS)

Seeber, B.; Decroux, M.; Fischer, O.

1988-01-01

A detailed discussion of critical current density and upper critical field for PbMo 6 S 8 (PMS) is given. It is shown that PMS bulk as well as wire samples can be prepared with sufficient quality to observe the scaling law for the volume pinning force. Using the scaling law an estimation for the critical current density as a function of field and temperature was made. The study also indicates that a substantial improvement of the critical current density can be expected by optimizing the upper critical field without changing the microstructure. It is shown that the availability of high quality samples of EuMo 6 S 8 , to which PMS is similar, makes it possible to study separately the different physical parameters which determine the upper critical field in PMS
Fabrication of magnetic Fe@ZnO{sub 0.6}S{sub 0.4} nanocomposite for visible-light-driven photocatalytic inactivation of Escherichia coli

Energy Technology Data Exchange (ETDEWEB)

Peng, Ziling [State Key Laboratory of Material Processing and Die & Mould Technology, Huazhong University of Science and Technology, Wuhan 430074, Hubei (China); Wu, Dan [School of Life Sciences, The Chinese University of Hong Kong, Shatin, NT, Hong Kong Special Administrative Region (China); Wang, Wei, E-mail: weiwang@hust.edu.cn [State Key Laboratory of Material Processing and Die & Mould Technology, Huazhong University of Science and Technology, Wuhan 430074, Hubei (China); Tan, Fatang [State Key Laboratory of Material Processing and Die & Mould Technology, Huazhong University of Science and Technology, Wuhan 430074, Hubei (China); Ng, Tsz Wai [School of Life Sciences, The Chinese University of Hong Kong, Shatin, NT, Hong Kong Special Administrative Region (China); Chen, Jianguo; Qiao, Xueliang [State Key Laboratory of Material Processing and Die & Mould Technology, Huazhong University of Science and Technology, Wuhan 430074, Hubei (China); Wong, Po Keung, E-mail: pkwong@cuhk.edu.hk [School of Life Sciences, The Chinese University of Hong Kong, Shatin, NT, Hong Kong Special Administrative Region (China)

2017-02-28

Highlights: • Fe@ZnO{sub 0.6}S{sub 0.4} was prepared by a facile two-step precipitation method. • Fe@ZnO{sub 0.6}S{sub 0.4} exhibited high photocatalytic activity under LED lamp irradiation. • Fe@ZnO{sub 0.6}S{sub 0.4} possessed good stability and reusability for bacterial inactivation. • Fe@ZnO{sub 0.6}S{sub 0.4} could be easily collected from the reaction solution by a magnet. • The release rate of metal ions from nanocomposite was kept at a very low level. - Abstract: Bacterial inactivation by magnetic photocatalysts has now received growing interests due to the easy separation for recycle and reuse of photocatalysts. In this study, magnetic Fe@ZnO{sub 0.6}S{sub 0.4} photocatalyst was prepared by a facile two-step precipitation method. Multiple techniques such as X-ray diffraction (XRD), transmission electron microscope (TEM), scanning electron microscope (SEM), X-ray photoelectron spectroscopy (XPS), UV–vis diffused reflectance spectra (UV-vis DRS) and vibrating sample magnetometer (VSM) were employed to characterize the structure, morphology and physicochemical properties of the photocatalyst. The as-obtained Fe@ZnO{sub 0.6}S{sub 0.4} possessing magnetic property was easily collected from the reaction system by a magnet. Under white light-emitting-diode (LED) lamp irradiation, Fe@ZnO{sub 0.6}S{sub 0.4} nanocomposite could completely inactivate 7-log of Escherichia coli K-12 within 5 h. More importantly, almost no decrease of photocatalytic efficiency in bacterial inactivation was observed even after five consecutive cycles, demonstrating Fe@ZnO{sub 0.6}S{sub 0.4} exhibited good stability for reuse. The low released rate of Fe{sup 2+}/Fe{sup 3+} and Zn{sup 2+} from Fe@ZnO{sub 0.6}S{sub 0.4} composite further indicated the photocatalyst showed low cytotoxicity to bacterium and high stability under LED lamp irradiation. Facile preparation, high photocatalytic efficiency, good stability and reusability, and magnetic recovery property endow Fe@ZnO{sub 0.6
Energies, fine structures, and transitions of the core-excited sextet states "6S"e","o(n) and "6P"e","o(n) (n=1–5) of B-like ions

International Nuclear Information System (INIS)

Sun, Yan; Liu, Dong Dong; Mei, Mao Fei; Zhang, Chun Mei; Han, Chong; Hu, Feng; Gou, Bing Cong

2015-01-01

A comprehensive theoretical study of atomic characteristics of energy levels and transitions for the core-excited "6S"e","o(n) and "6P"e","o(n) (n=1–5) states of the boron isoelectronic sequence (Z=6–14) are investigated by the Rayleigh–Ritz variation method and multi-configuration interaction wavefunctions. The relativistic corrections and mass polarization effects are included by first-order perturbation theory. The configuration structures of the high-lying sextet series "6S"e","o(n) and "6P"e","o(n) (n=1–5) of the B-like ions are assigned. The transition rates and wavelengths for the electric dipole transitions "6S"e","o(n)—"6P"o","e(n) (n=1–5) of the B-like ions are calculated and compared with currently available theoretical and experimental data. Furthermore, the radiative transition rates and wavelengths for the important dipole transitions are discussed with the increase of nuclear charge number Z. The calculations will provide useful data for identification of spectral lines arising from the solar atmosphere and the experimental study in future work. - Highlights: • Energy and transition data of core-excited sextet states of B-like ions are studied. • Relativistic corrections, mass polarization effects are included in the calculation. • Radiative rates and transition wavelengths are discussed with the increase of Z. • Variation trend of transition rates and wavelengths are present with the n increase. • Some energy levels and transition data are reported for the first time.
SIRT6 stabilizes DNA-dependent protein kinase at chromatin for DNA double-strand break repair

DEFF Research Database (Denmark)

McCord, Ronald A; Michishita, Eriko; Hong, Tao

2009-01-01

-PKcs) to chromatin in response to DNA damage and stabilizes DNA-PKcs at chromatin adjacent to an induced site-specific DSB. Abrogation of these SIRT6 activities leads to impaired resolution of DSBs. Together, these findings elucidate a mechanism whereby regulation of dynamic interaction of a DNA repair factor......-dependent protein kinase) and promotes DNA DSB repair. In response to DSBs, SIRT6 associates dynamically with chromatin and is necessary for an acute decrease in global cellular acetylation levels on histone H3 Lysine 9. Moreover, SIRT6 is required for mobilization of the DNA-PK catalytic subunit (DNA......, and SIRT6 knockout cells exhibit genomic instability and DNA damage hypersensitivity. However, the molecular mechanisms underlying these defects are not fully understood. Here, we show that SIRT6 forms a macromolecular complex with the DNA double-strand break (DSB) repair factor DNA-PK (DNA...
Ventilation components according to DIN 1946-6. Messages from the C.A.T.S. Academy; Lueftungskomponenten nach DIN 1946-6. Mitteilungen aus der C.A.T.S.-Academy

Energy Technology Data Exchange (ETDEWEB)

Nadler, Norbert [CSE Nadler, Oranienburg (Germany)

2011-07-01

On the one hand, the buildings are performed tightly according to the building regulations, on the other hand a minimum of air change is to be ensured. The former demand for air change by manual opening of the windows is no longer accepted. The calculation method of the regulation DIN 1946-6 enables both the establishment of a ventilation concept as well as an interpretation of the ventilation components. A critical evaluation of the regulation and the demands of practice result in necessary amendments which result in requirements of the appropriate software. The implementation of these requirements exemplary is demonstrated on the basis od the new C.A.T.S. ventilation.
Beam-foil lifetime measurements for some 5d10 nl and 5d96s6p levels of Pb IV

International Nuclear Information System (INIS)

Pinnington, E.H.; Ansbacher, W.; Tauheed, A.; Kernahan, J.A.

1991-01-01

The beam-foil technique was used to measure the lifetimes of the 5d 10 5f, 5g, 6d, 6h, 7p, 7d, 8s and 5d 9 6s6p (2) 0 , (3) 0 , (6) 0 , (14) 0 , (17) 0 levels of Pb IV. Correlated decay-curve analyses were used to correct for the effects of cascading in the case of the 5d 10 5f, 5g, 6d, and 7p levels. The numerical Coulomb approximation was used to calculate comparison values for the 5d 10 nl levels. The need for a more rigorous calculation for specific levels is discussed. (12 refs., fig., tab.)
Deficiency in LRP6-Mediated Wnt Signaling Contributes to Synaptic Abnormalities and Amyloid Pathology in Alzheimer’s Disease

OpenAIRE

Liu, Chia-Chen; Tsai, Chih-Wei; Deak, Ferenc; Rogers, Justin; Penuliar, Michael; Sung, You Me; Maher, James N.; Fu, Yuan; Li, Xia; Xu, Huaxi; Estus, Steven; Hoe, Hyang-Sook; Fryer, John D.; Kanekiyo, Takahisa; Bu, Guojun

2014-01-01

Alzheimer’s disease (AD) is an age-related neurological disorder characterized by synaptic loss and dementia. The low-density lipoprotein receptor-related protein 6 (LRP6) is an essential co-receptor for Wnt signaling and its genetic variants have been linked to AD risk. Here we report that neuronal LRP6-mediated Wnt signaling is critical for synaptic function and cognition. Conditional deletion of Lrp6 gene in mouse forebrain neurons leads to age-dependent deficits in synaptic integrity and ...
Structures of Staphylococcus aureus D-tagatose-6-phosphate kinase implicate domain motions in specificity and mechanism.

Science.gov (United States)

Miallau, Linda; Hunter, William N; McSweeney, Sean M; Leonard, Gordon A

2007-07-06

High resolution structures of Staphylococcus aureus d-tagatose-6-phosphate kinase (LacC) in two crystal forms are herein reported. The structures define LacC in apoform, in binary complexes with ADP or the co-factor analogue AMP-PNP, and in a ternary complex with AMP-PNP and D-tagatose-6-phosphate. The tertiary structure of the LacC monomer, which is closely related to other members of the pfkB subfamily of carbohydrate kinases, is composed of a large alpha/beta core domain and a smaller, largely beta "lid." Four extended polypeptide segments connect these two domains. Dimerization of LacC occurs via interactions between lid domains, which come together to form a beta-clasp structure. Residues from both subunits contribute to substrate binding. LacC adopts a closed structure required for phosphoryl transfer only when both substrate and co-factor are bound. A reaction mechanism similar to that used by other phosphoryl transferases is proposed, although unusually, when both substrate and co-factor are bound to the enzyme two Mg(2+) ions are observed in the active site. A new motif of amino acid sequence conservation common to the pfkB subfamily of carbohydrate kinases is identified.
Leber's hereditary optic neuropathy is associated with mitochondrial ND6 T14502C mutation

Energy Technology Data Exchange (ETDEWEB)

Zhao, Fuxin [School of Ophthalmology and Optometry, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China); Zhejiang Provincial Key Laboratory of Medical Genetics, School of Life Sciences, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China); Guan, Minqiang [Zhejiang Provincial Key Laboratory of Medical Genetics, School of Life Sciences, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China); Zhou, Xiangtian [School of Ophthalmology and Optometry, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China); Yuan, Meixia; Liang, Ming [School of Ophthalmology and Optometry, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China); Zhejiang Provincial Key Laboratory of Medical Genetics, School of Life Sciences, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China); Liu, Qi [Zhejiang Provincial Key Laboratory of Medical Genetics, School of Life Sciences, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China); Liu, Yan; Zhang, Yongmei [School of Ophthalmology and Optometry, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China); Zhejiang Provincial Key Laboratory of Medical Genetics, School of Life Sciences, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China); Yang, Li [Division of Human Genetics, Cincinnati Children' s Hospital Medical Center, Cincinnati, OH 45229 (United States); Tong, Yi [School of Ophthalmology and Optometry, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China); The First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian 350005 (China); Wei, Qi-Ping; Sun, Yan-Hong [Department of Ophthalmology, Dongfang Hospital, Beijing University of Chinese Medicine and Pharmacology, Beijing 100078 (China); Qu, Jia, E-mail: jqu@wzmc.net [School of Ophthalmology and Optometry, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China); Zhejiang Provincial Key Laboratory of Medical Genetics, School of Life Sciences, Wenzhou Medical College, Wenzhou, Zhejiang 325003 (China); and others

2009-11-20

We report here the clinical, genetic, and molecular characterization of three Chinese families with Leber's hereditary optic neuropathy (LHON). There were variable severity and age of onset in visual impairment among these families. Strikingly, there were extremely low penetrances of visual impairment in these Chinese families. Sequence analysis of complete mitochondrial genomes in these pedigrees showed the homoplasmic T14502C (I58V) mutation, which localized at a highly conserved isoleucine at position 58 of ND6, and distinct sets of mtDNA polymorphisms belonging to haplogroups M10a, F1a1, and H2. The occurrence of T14502C mutation in these several genetically unrelated subjects affected by visual impairment strongly indicates that this mutation is involved in the pathogenesis of visual impairment. Here, mtDNA variants I187T in the ND1, A122V in CO1, S99A in the A6, and V254I in CO3 exhibited an evolutionary conservation, indicating a potential modifying role in the development of visual impairment associated with T14502C mutation in those families. Furthermore, nuclear modifier gene(s) or environmental factor(s) may play a role in the phenotypic manifestation of the LHON-associated T14502C mutation in these Chinese families.
Parental Predictors of Children’s Shame and Guilt at Age 6 in a Multi-Method, Longitudinal Study

Science.gov (United States)

Parisette-Sparks, Alyssa; Bufferd, Sara J.; Klein, Daniel N.

2015-01-01

Objective Shame and guilt are self-conscious emotions that begin to develop early in life and are associated with various forms of psychopathology. However, little is known about the factors that contribute to these emotions in young children. Specifically, no longitudinal studies to date have examined a range of parent factors that shape the expression of children’s shame and guilt. The current multi-method, longitudinal study sought to determine whether parenting style, parental psychopathology, and parents’ marital satisfaction assessed when children were age 3 predict expressions of shame and guilt in children at age 6. Method A large community sample of families (N = 446; 87.4% Caucasian) with three-year-old children (45.7% female) was recruited through commercial mailing lists. Parent variables were assessed when children were age 3 with mother- and father-report questionnaires and a diagnostic interview. Children’s expressions of shame and guilt were observed in the laboratory at age 6. Results Fathers’, but not mothers’, history of depression and permissive parenting assessed when children were age 3 predicted children’s expressions of shame and guilt when children were age 6; parents’ marital dissatisfaction also predicted children’s shame and guilt. Conclusions These findings suggest that parents, and fathers in particular, contribute to expressions of self-conscious emotions in children. These data on emotional development may be useful for better characterizing the risk and developmental pathways of psychopathology. PMID:26538055
Assessment of serum enzymatic markers of cardiomyocytes injury in female dogs submitted to ketamine S(+, atropin and xylazine association Mensuração da atividade sérica de marcadores de lesão cardíaca em cadelas anestesiadas com cetamina S(+, atropina e xilazina

Directory of Open Access Journals (Sweden)

Leandro Guimarães Franco

2009-02-01

Full Text Available PURPOSE: To assessment of the aspartate aminotransferase (AST, creatine kinase (CK and creatine kinase isoenzyme fraction MB (CK-MB serum activity in female dogs anesthetized with ketamine S (+, atropine and xylazine in several associations. METHODS: Twenty three healthy female dogs randomly distributed in four groups named as GI (n=6, GII (n=6, GIII (n=6 and GIV (n=5 were treated respectively with atropine and ketamine S(+ (0.04mg/kg; 10 mg/kg; ketamine S(+ (10 mg/kg; atropine, xylazine and ketamine S(+ (0.04mg/kg; 1.1 mg/kg; 10 mg/kg and xylazine and ketamine S(+ (1.1 mg/kg; 10 mg/kg. AST, CK and CK-MB serum activity measurement before pre-medication (M0 and one, two, three, six, 12, 24, 36 hours after. RESULTS: There was no significant change in AST, CK e CK-MB serum activity among groups. However, CK serum activity in relation to moments within the groups was increased in all groups over the time in spite of treatment, except GI. In relation to CK-MB activity, in the moments within the group, it was observed an increase compared to baseline in all groups. CONCLUSION: Creatine kinase and creatine kinase fraction MB isoenzyme showed changes in their mean values remained higher than baseline for a longer time in GIII and GIV.OBJETIVO: Determinar a atividade sérica de AST, CK e CK-MB em cadelas anestesiadas com cetamina S (+, atropina e xilazina em diferentes associações. MÉTODOS: Vinte e três cadelas saudáveis foram distribuídas ao acaso em quarto grupos denominados GI (n=6, GII (n=6, GIII (n=6 e GIV (n=5 tratados respectivamente com atropina e cetamina S (+ (0,04mg/kg; 10 mg/kg; cetamina S (+ (10 mg/kg; atropina, xilazina e cetamina S (+ (0,04mg/kg; 1,1 mg/kg; 10 mg/kg exilazina e cetamina S (+ (1,1 mg/kg; 10 mg/kg. A atividade sérica de AST, CK e CK-MB foi determinada antes da pré-medicação (M0 e uma, duas, três seis, 12, 24 e 36 horas após M0. RESULTADOS: Não foram encontradas mudanças significativas na atividade sérica de
Effects of Butyltins (BTs) on Mitogen-Activated-Protein Kinase Kinase Kinase (MAP3K) and Ras Activity in Human Natural Killer Cells

Science.gov (United States)

Celada, Lindsay J.; Whalen, Margaret M.

2013-01-01

Butyltins (BTs) contaminate the environment and are found in human blood. BTs, tributyltin (TBT) and dibutyltin (DBT), diminish the cytotoxic function and levels of key proteins of human natural killer (NK) cells. NK cells are an initial immune defense against tumors, virally-infected cells and antibody-coated cells and thus critical to human health. The signaling pathways that regulate NK cell functions include mitogen-activated protein kinases (MAPKs). Studies have shown that exposure to BTs leads to the activation of specific MAPKs and MAPK kinases (MAP2Ks) in human NK cells. MAP2K kinases (MAP3Ks) are upstream activators of MAP2Ks, which then activate MAPKs. The current study examined if BT-induced activation of MAP3Ks was responsible for MAP2K and thus, MAPK activation. This study examines the effects of TBT and DBT on the total levels of two MAP3Ks, c-Raf and ASK1, as well as activating and inhibitory phosphorylation sites on these MAP3Ks. In addition, the immediate upstream activator of c-Raf, Ras, was examined for BT-induced alterations. Our results show significant activation of the MAP3K, c-Raf, in human NK cells within 10 minutes of TBT exposure and the MAP3K, ASK1, after one hour exposures to TBT. In addition, our results suggest that both TBT and DBT are impacting the regulation of c-Raf. PMID:24038145
Non-intubated uniportal left-lower lobe upper segmentectomy (S6).

Science.gov (United States)

Galvez, Carlos; Navarro-Martinez, Jose; Bolufer, Sergio; Sesma, Julio; Lirio, Francisco; Galiana, Maria; Rivera, Maria Jesus

2017-01-01

Worldwide accepted indications of anatomical segmentectomies are mainly early stage primary adenocarcinomas, pulmonary metastasis and benign conditions. Their performance through uniportal VATS has become more and more popular due to the less invasiveness of the whole procedure under this approach. Recently, many efforts have focused on non-intubated spontaneously breathing management of lobectomies and anatomical segmentectomies, although specific selection criteria and main advantages are not completely standardized. In a 62-year-old thin man with two pulmonary residual metastasis from sigma adenocarcinoma, after chemotherapy plus antiangiogenic treatment, we indicated a single-incision video-assisted left-lower lobe (LLL) upper segmentectomy (S6) under spontaneous breathing and intercostal blockade. Total operation time was 240 minutes. Chest tube was removed at 24 hours and the patient was discharge on postoperative day 2 without any complication. Non-intubated uniportal VATS is a safe and reasonable approach for lung-sparing resections in selected patients, although more evidence is required for selecting which patients can benefit more over standard intubated procedures.
Bacillus subtilis Two-Component System Sensory Kinase DegS Is Regulated by Serine Phosphorylation in Its Input Domain

DEFF Research Database (Denmark)

Jers, Carsten; Kobir, Ahasanul; Søndergaard, Elsebeth Oline

2011-01-01

Bacillus subtilis two-component system DegS/U is well known for the complexity of its regulation. The cytosolic sensory kinase DegS does not receive a single predominant input signal like most two-component kinases, instead it integrates a wide array of metabolic inputs that modulate its activity......S phosphorylation can be carried out by at least two B. subtilis Hanks-type kinases in vitro, and this stimulates the phosphate transfer towards DegU. The consequences of this process were studied in vivo, using phosphomimetic (Ser76Asp) and non-phosphorylatable (Ser76Ala) mutants of DegS. In a number...
BI-D1870 is a specific inhibitor of the p90 RSK (ribosomal S6 kinase) isoforms in vitro and in vivo

DEFF Research Database (Denmark)

Sapkota, Gopal P; Cummings, Lorna; Newell, Felicity S

2007-01-01

), which then mediate many of the physiological processes that are regulated by these extracellular agonists. It can be difficult to assess the individual functions of each AGC kinase because their substrate specificities are similar. Here we describe the small molecule BI-D1870, which inhibits RSK1, RSK2......, RSK3 and RSK4 in vitro with an IC(50) of 10-30 nM, but does not signi-ficantly inhibit ten other AGC kinase members and over 40 other protein kinases tested at 100-fold higher concentrations. BI-D1870 is cell permeant and prevents the RSK-mediated phorbol ester- and EGF (epidermal growth factor......)-induced phosphoryl-ation of glycogen synthase kinase-3beta and LKB1 in human embry-onic kidney 293 cells and Rat-2 cells. In contrast, BI-D1870 does not affect the agonist-triggered phosphorylation of substrates for six other AGC kinases. Moreover, BI-D1870 does not suppress the phorbol ester- or EGF...
Rho Kinase ROCK2 Mediates Acid-Induced NADPH Oxidase NOX5-S Expression in Human Esophageal Adenocarcinoma Cells.

Directory of Open Access Journals (Sweden)

Jie Hong

Full Text Available Mechanisms of the progression from Barrett's esophagus (BE to esophageal adenocarcinoma (EA are not fully understood. We have shown that NOX5-S may be involved in this progression. However, how acid upregulates NOX5-S is not well known. We found that acid-induced increase in NOX5-S expression was significantly decreased by the Rho kinase (ROCK inhibitor Y27632 in BE mucosal biopsies and FLO-1 EA cells. In addition, acid treatment significantly increased the Rho kinase activity in FLO-1 cells. The acid-induced increase in NOX5-S expression and H2O2 production was significantly decreased by knockdown of Rho kinase ROCK2, but not by knockdown of ROCK1. Conversely, the overexpression of the constitutively active ROCK2, but not the constitutively active ROCK1, significantly enhanced the NOX5-S expression and H2O2 production. Moreover, the acid-induced increase in Rho kinase activity and in NOX5-S mRNA expression was blocked by the removal of calcium in both FLO-1 and OE33 cells. The calcium ionophore A23187 significantly increased the Rho kinase activity and NOX5-S mRNA expression. We conclude that acid-induced increase in NOX5-S expression and H2O2 production may depend on the activation of ROCK2, but not ROCK1, in EA cells. The acid-induced activation of Rho kinase may be mediated by the intracellular calcium increase. It is possible that persistent acid reflux present in BE patients may increase the intracellular calcium, activate ROCK2 and thereby upregulate NOX5-S. High levels of reactive oxygen species derived from NOX5-S may cause DNA damage and thereby contribute to the progression from BE to EA.
Multi-lobulation of the nucleus in prolonged S phase by nuclear expression of Chk tyrosine kinase.

Science.gov (United States)

Nakayama, Yuji; Yamaguchi, Naoto

2005-04-01

Chk tyrosine kinase phosphorylates Src-family tyrosine kinases and suppresses their kinase activity. We recently showed that Chk localizes to the nucleus as well as the cytoplasm and inhibits cell proliferation. To investigate the role of nuclear Chk in proliferation, various Chk mutants were constructed and expressed. Nuclear localization of Chk-induced dynamic multi-lobulation of the nucleus and prolonged S phase of the cell cycle. The N-terminal domain of Chk and a portion of its kinase domain but not the kinase activity were responsible for induction of the multi-lobulation. Cell sorting analysis revealed that nuclear multi-lobulated cells were enriched in late S phase. Multi-lobulated nuclei were surrounded with lamin B1 that was particularly concentrated in concave regions of the nuclei. Furthermore, treatment with nocodazole or taxol disrupted multi-lobulation of the nucleus. These results suggest that nuclear multi-lobulation in late S phase, which is dependent on polymerization and depolymerization of microtubules, may be involved in nuclear Chk-induced inhibition of proliferation.
Multi-lobulation of the nucleus in prolonged S phase by nuclear expression of Chk tyrosine kinase

International Nuclear Information System (INIS)

Nakayama, Yuji; Yamaguchi, Naoto

2005-01-01

Chk tyrosine kinase phosphorylates Src-family tyrosine kinases and suppresses their kinase activity. We recently showed that Chk localizes to the nucleus as well as the cytoplasm and inhibits cell proliferation. To investigate the role of nuclear Chk in proliferation, various Chk mutants were constructed and expressed. Nuclear localization of Chk-induced dynamic multi-lobulation of the nucleus and prolonged S phase of the cell cycle. The N-terminal domain of Chk and a portion of its kinase domain but not the kinase activity were responsible for induction of the multi-lobulation. Cell sorting analysis revealed that nuclear multi-lobulated cells were enriched in late S phase. Multi-lobulated nuclei were surrounded with lamin B1 that was particularly concentrated in concave regions of the nuclei. Furthermore, treatment with nocodazole or taxol disrupted multi-lobulation of the nucleus. These results suggest that nuclear multi-lobulation in late S phase, which is dependent on polymerization and depolymerization of microtubules, may be involved in nuclear Chk-induced inhibition of proliferation
Nitric oxide switches on glycolysis through the AMP protein kinase and 6-phosphofructo-2-kinase pathway

OpenAIRE

Almeida Parra, Ángeles; Moncada, Salvador; Bolaños Hernández, Juan Pedro

2004-01-01

El óxido nítrico activa la glucolisis en los astrocitos a través de una cascada de señalización en la que interviene la AMP kinasa, que fosforila (y activa) la fosfofructokinasa-2, enzima responsable de la biosíntesis de fructosa-2, 6-bisfosfato, efector alostérico positivo de la fosfofructokinasa-1. Este mecanismo es citoprotector.
IL-6, Antioxidant Capacity and Muscle Damage Markers Following High-Intensity Interval Training Protocols.

Science.gov (United States)

Cipryan, Lukas

2017-02-01

The aim of this study was to investigate changes of interleukin-6 (IL-6), total antioxidant capacity (TAC) and muscle damage markers (creatine kinase (CK), myoglobin and lactate dehydrogenase (LDH)) in response to three different high-intensity interval training (HIIT) protocols of identical external work. Twelve moderately-trained males participated in the three HIIT trials which consisted of a warm-up, followed by 12 min of 15 s, 30 s or 60 s HIIT sequences with the work/rest ratio 1. The biochemical markers of inflammation, oxidative stress and muscle damage were analysed POST, 3 h and 24 h after the exercise. All HIIT protocols caused an immediate increase in IL-6, TAC, CK, myoglobin and LDH. The most pronounced between-trials differences were found for the POST-exercise changes in IL-6 (Effect size ± 90% confidence interval: 1.51 ± 0.63, 0.84 ± 0.34 and 1.80 ± 0.60 for the 15s/15s, 30s/30s and 60s/60s protocol, respectively) and myoglobin (1.11 ± 0.29, 0.45 ± 0.48 and 1.09 ± 0.22 for the 15s/15s, 30s/30s and 60s/60s protocol, respectively). There were no substantial between-trial differences in other biochemical variables. In conclusion, the 15s/15s and 60s/60s protocols might be preferred to the 30s/30s protocols in order to maximize the training stimulus.

Fructose 2,6-bisphosphate and its phosphorothioate analogue. Comparison of their hydrolysis and action on glycolytic and gluconeogenic enzymes.

OpenAIRE

Rider, M H; Kuntz, D A; Hue, L

1988-01-01

Purified chicken liver 6-phosphofructo-2-kinase/fructose 2,6-bisphosphatase was phosphorylated either from fructose 2,6-bis[2-32P]phosphate or fructose 2-phosphoro[35S]thioate 6-phosphate. The turnover of the thiophosphorylated enzyme intermediate as well as the overall phosphatase reaction was four times faster than with authentic fructose 2,6-bisphosphate. Fructose 2-phosphorothioate 6-phosphate was 10-100-fold less potent than authentic fructose 2,6-bisphosphate in stimulating 6-phosphofru...
Express and low-cost microwave synthesis of the ternary Chevrel phase Cu{sub 2}Mo{sub 6}S{sub 8} for application in rechargeable magnesium batteries

Energy Technology Data Exchange (ETDEWEB)

Murgia, Fabrizio; Antitomaso, Philippe; Stievano, Lorenzo; Monconduit, Laure [Institut Charles Gerhardt de Montpellier (ICGM, UMR 5253CNRS Université de Montpellier), 2, Place Eugène Bataillon, CC1502, 34095 Montpellier cedex 5 (France); Réseau sur le Stockage Electrochimique de l' Energie (RS2E,FR 3459CNRS), 33, Rue Saint-Leu, 80039 Amiens cedex (France); Berthelot, Romain, E-mail: romain.berthelot@umontpellier.fr [Institut Charles Gerhardt de Montpellier (ICGM, UMR 5253CNRS Université de Montpellier), 2, Place Eugène Bataillon, CC1502, 34095 Montpellier cedex 5 (France); Réseau sur le Stockage Electrochimique de l' Energie (RS2E,FR 3459CNRS), 33, Rue Saint-Leu, 80039 Amiens cedex (France)

2016-10-15

The ternary Chevrel phase Cu{sub 2}Mo{sub 6}S{sub 8} was successfully synthetized using a simple and cost-effective solid-state microwave-assisted reaction. While solid-state routes require days of high-temperature treatment under inert atmosphere, highly pure and crystalline Cu{sub 2}Mo{sub 6}S{sub 8} could be obtained in only 400 s from this precursor, the Chevrel binary phase Mo{sub 6}S{sub 8} was then obtained by copper removal through acidic leaching, and was evaluated as a positive electrode material for Mg-battery. The electrochemical performance in half-cell configuration shows reversible capacity exceeding 80 mAh/g, which is comparable to previous works carried out with materials synthesized by conventional high-temperature solid-state routes. - Graphical abstract: Ultrafast micro-wave synthesis of Chevrel phase Cu{sub 2}Mo{sub 6}S{sub 8} towards Mo{sub 6}S{sub 8} as positive electrode of Mg-battery. - Highlights: • Chevrel phase Cu{sub 2}Mo{sub 6}S{sub 8} is synthesized by fast microwave-assisted solid-state reaction. • Highly-pure and well-crystalline Cu{sub 2}Mo{sub 6}S{sub 8} is obtained. • Mo{sub 6}S{sub 8} obtained from leaching is tested as a positive electrode for Mg batteries.
The human papillomavirus type 16 E6 oncoprotein activates mTORC1 signaling and increases protein synthesis.

Science.gov (United States)

Spangle, Jennifer M; Münger, Karl

2010-09-01

The mammalian target of rapamycin (mTOR) kinase acts as a cellular rheostat that integrates signals from a variety of cellular signal transduction pathways that sense growth factor and nutrient availability as well as intracellular energy status. It was previously reported that the human papillomavirus type 16 (HPV16) E6 oncoprotein may activate the S6 protein kinase (S6K) through binding and E6AP-mediated degradation of the mTOR inhibitor tuberous sclerosis complex 2 (TSC2) (Z. Lu, X. Hu, Y. Li, L. Zheng, Y. Zhou, H. Jiang, T. Ning, Z. Basang, C. Zhang, and Y. Ke, J. Biol. Chem. 279:35664-35670, 2004; L. Zheng, H. Ding, Z. Lu, Y. Li, Y. Pan, T. Ning, and Y. Ke, Genes Cells 13:285-294, 2008). Our results confirmed that HPV16 E6 expression causes an increase in mTORC1 activity through enhanced phosphorylation of mTOR and activation of downstream signaling pathways S6K and eukaryotic initiation factor binding protein 1 (4E-BP1). However, we did not detect a decrease in TSC2 levels in HPV16 E6-expressing cells. We discovered, however, that HPV16 E6 expression causes AKT activation through the upstream kinases PDK1 and mTORC2 under conditions of nutrient deprivation. We show that HPV16 E6 expression causes an increase in protein synthesis by enhancing translation initiation complex assembly at the 5' mRNA cap and an increase in cap-dependent translation. The increase in cap-dependent translation likely results from HPV16 E6-induced AKT/mTORC1 activation, as the assembly of the translation initiation complex and cap-dependent translation are rapamycin sensitive. Lastly, coexpression of the HPV16 E6 and E7 oncoproteins does not affect HPV16 E6-induced activation of mTORC1 and cap-dependent translation. HPV16 E6-mediated activation of mTORC1 signaling and cap-dependent translation may be a mechanism to promote viral replication under conditions of limited nutrient supply in differentiated, HPV oncoprotein-expressing proliferating cells.
Alignment creation in atomic ensembles by elastic electron scattering; the case of 138Ba(...6s6p 1P1) atoms

International Nuclear Information System (INIS)

Trajmar, S.; Kanik, I.; LeClair, L.R.; Khakoo, M.A.; Bray, I.; Fursa, D.; Csanak, G.

1998-01-01

We describe some of our results from a joint experimental and theoretical program concerning elastic electron scattering by 138 Ba(...6s6p 1 P 1 ) atoms. From the experimental results, we derived various scattering parameters and magnetic sublevel specific differential elastic scattering cross sections at impact energy (E 0 ) of 20.0 eV and at scattering angles (θ) of 10deg, 15deg, and 20deg. The same parameters and cross sections were calculated by the convergent close coupling (CCC) approximation and compared to the experimental results. An excellent agreement, found for the two sets of data, gave us confidence in the CCC method and allowed us to extend the angular and energy ranges for the purpose of generating integral elastic scattering cross sections needed for the deduction of the alignment creation cross sections. (J.P.N.)
Microextração em fase sólida de 6-pentil-α-pirona produzida por fermentação em estado sólido Solid-phase microextraction of 6-pentyl-α-pyrone produced by solid-state fermentation

Directory of Open Access Journals (Sweden)

Aline de Souza Ramos

2009-09-01

Full Text Available A substância 6-pentil-α-pirona (6-PP é uma lactona com aroma característico de coco e uso aprovado pela agência americana Food and Drug Administration (FDA. O presente trabalho teve como objetivo ajustar as condições de microextração em fase sólida em headspace para a quantificação por cromatografia gasosa de 6-PP produzida pelo fungo Trichoderma harzianum a partir do pó da casca de coco verde. Para isto, foi realizado um estudo em que soluções padronizadas de 6-PP foram adicionadas ao pó da casca de coco verde. A substância foi extraída por uma fibra de polidimetilsiloxano. Agitação e adição de solução de NaCl a 25% (p/v resultaram em melhor reprodutibilidade nas análises. Um planejamento composto central foi empregado para estudar três fatores: temperatura de extração, tempo de condicionamento e tempo de extração. Boas respostas foram obtidas com a temperatura de 79 °C e tempo de extração de 29 minutos. O efeito da variável tempo de condicionamento não foi significativo e foi fixado em 2 minutos. Após o desenvolvimento do método analítico, este foi empregado para determinar a produção de 6-PP por fermentação em estado sólido realizada por Trichoderma harzianum e com o uso de pó da casca de coco verde como suporte para o processo.The lactone 6-pentyl-a-pyrone (6-PP is a coconut-like aroma compound approved by the American agency Food and Drug Administration (FDA for food use. The aim of the present study was to improve the extraction conditions of headspace solid-phase microextraction coupled with gas chromatography to quantify the 6-PP produced by Trichoderma harzianum using green coir dust. To achieve this purpose, standard solutions of 6-PP were added to green coir dust. The compound was extracted by a polydimethylsiloxane fiber. Agitation and addition of a 25% NaCl solution (w/v resulted in better reproducibility. A central composite design was applied to study three factors: extraction
Trehalose-6-phosphate and SnRK1 kinases in plant development and signaling: the emerging picture

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Sonia eGazzarrini

2014-04-01

Full Text Available Carbohydrates, or sugars, regulate various aspects of plant growth through modulation of cell division and expansion. Besides playing essential roles as sources of energy for growth and as structural components of cells, carbohydrates also regulate the timing of expression of developmental programs. The disaccharide trehalose is used as an energy source, as a storage and transport molecule for glucose, and as a stress-responsive compound important for cellular protection during stress in all kingdoms. Trehalose, however, is found in very low amounts in most plants, pointing to a signaling over metabolic role for this non-reducing disaccharide. In the last decade, trehalose-6-phosphate (T6P, an intermediate in trehalose metabolism, has been shown to regulate embryonic and vegetative development, flowering time, meristem determinacy and cell fate specification in plants. T6P acts as a global regulator of metabolism and transcription promoting plant growth and triggering developmental phase transitions in response to sugar availability. Among the T6P targets are members of the Sucrose-non-fermenting1-Related Kinase1 (SnRK1 family, which are sensors of energy availability and inhibit plant growth and development during metabolic stress to maintain energy homeostasis. In this review, we will discuss the opposite roles of the sugar metabolite T6P and the SnRK1 kinases in the regulation of developmental phase transitions in response to carbohydrate levels. We will focus on how these two global regulators of metabolic processes integrate environmental cues and interact with hormonal signaling pathways to modulate plant development.
Investigation of $K_{L,S} \\rightarrow \\pi^{+}\\pi^{-}e^{+}e^{-}$ decays

CERN Document Server

Lai, A; Arcidiacono, R; Barr, G; Becker, H G; Bevan, A; Biino, C; Bizzeti, A; Bocquet, G; Calvetti, M; Cartiglia, N; Casali, R; Ceccucci, Augusto; Cenci, P; Cerri, C; Cheshkov, C; Chollet, J C; Chèze, J B; Cirilli, M; Clemencic, M; Cogan, J; Collazuol, G; Contalbrigo, M; Costantini, F; Cundy, Donald C; Dalpiaz, Pietro; De Beer, M; Debu, P; Doble, Niels T; Dosanjh, R S; Duclos, J; Eppard, M; Falaleev, V P; Fantechi, R; Fayard, Louis; Fischer, G; Formica, A; Fox, H; Frabetti, P L; Gaponenko, A N; Gatignon, L; Gershon, T J; Gianoli, A; Giudici, Sergio; Gonidec, A; Gorini, B; Govi, G; Grafström, P; Granier de Cassagnac, R; Graziani, G; Hay, B; Holder, M; Holtz, K; Iacopini, E; Iconomidou-Fayard, L; Imbergamo, E; Jeitler, Manfred; Kalmus, George Ernest; Kalter, A; Kekelidze, V D; Khristov, P Z; Kleinknecht, K; Knowles, I; Koch, U; Kubischta, Werner; Köpke, L; Lazzeroni, C; Lenti, M; Lopes da Silva, P; Lubrano, P; Luitz, S; Madigozhin, D T; Maier, A; Mannelli, I; Marchetto, F; Markytan, Manfred; Marouelli, P; Marras, D; Martin, V; Martini, M; Masetti, L; Mazzucato, E; Menichetti, E; Mestvirishvili, A; Mikulec, I; Munday, D J; Nappi, A; Nassalski, J P; Needham, M D; Neuhofer, Günther; Norton, A; Ocariz, J; Olaiya, E; Palestini, S; Panzer-Steindel, B; Parker, M A; Pellmann, I A; Pepé, M; Pernicka, Manfred; Peters, A; Petrucci, F; Peyaud, B; Piccini, M; Pierazzini, G M; Potrebenikov, Yu K; Rondio, Ewa; Sacco, R; Savrié, M; Schmidt, S; Schué, Yu; Schönharting, V; Sozzi, M; Szleper, M; Tatishvili, G T; Taureg, Hans; Taurok, Anton; Turlay, René; Unal, G; Vallage, B; Velasco, M; Veltri, M; Wahl, H; Walker, A; Wanke, R; White, T O; Widhalm, L; Wingerter-Seez, I; Winhart, A; Wislicki, W; Wittgen, M; Wotton, S A; Wronka, S; Zinchenko, A I; Ziolkowski, M

2003-01-01

The K_L -> pi+pi-e+e- and K_S -> pi+pi-e+e- decay modes have been studied in detail using the NA48 detector at CERN SPS. Based on the data collected during the 1998 and 1999 run periods, a sample of 1162 K_L -> pi+pi-e+e- candidates has been observed with an expected background level of 36.9 events, yielding the branching ratio measurement BR(K_L -> pi+pi-e+e-)=(3.08+-0.20)x10^-7. The distribution of events in the sin\\phicos\\phi variable, where \\phi is the angle between the pi+pi- and the e+e- decay planes in the kaon centre of mass, is found to exhibit a large CP-violating asymmetry with the value A_\\phi(14.2+-3.6)%. For the K_S -> pi+pi-e+e- decay channel, 621 candidates have been identified in the 1999 data sample with an estimated background contribution of 0.7 event. The corresponding branching ratio has been determined to be BR(K_S -> pi+pi-e+e-)=(4.71+-0.32)x10^-5. The combined value of this measurement with the published 1998 result id BR(K_S -> pi+pi-e+e-)=4.69+-0.30)x10^-5. No asymmetry is observed ...
Brominated flame retardants, tetrabromobisphenol A and hexabromocyclododecane, activate mitogen-activated protein kinases (MAPKs) in human natural killer cells.

Science.gov (United States)

Cato, Anita; Celada, Lindsay; Kibakaya, Esther Caroline; Simmons, Nadia; Whalen, Margaret M

2014-12-01

Natural killer (NK) cells provide a vital surveillance against virally infected cells, tumor cells, and antibody-coated cells through the release of cytolytic mediators and gamma interferon (IFN-γ). Hexabromocyclododecane (HBCD) is a brominated flame retardant used primarily in expanded (EPS) and extruded (XPS) polystyrene foams for thermal insulation in the building and construction industry. Tetrabromobisphenol A (TBBPA) is used both as a reactive and an additive flame retardant in a variety of materials. HBCD and TBBPA contaminate the environment and are found in human blood samples. In previous studies, we have shown that other environmental contaminants, such as the dibutyltin (DBT) and tributyltin (TBT), decrease NK lytic function by activating mitogen-activated protein kinases (MAPKs) in the NK cells. HBCD and TBBPA also interfere with NK cell(s) lytic function. The current study evaluates whether HBCD and/or TBBPA have the capacity to activate MAPKs and MAPK kinases (MAP2Ks). The effects of concentrations of HBCD and TBBPA that inhibited lytic function on the phosphorylation state and total levels of the MAPKs (p44/42, p38, and JNK) and the phosphorylation and total levels of the MAP2Ks (MEK1/2 and MKK3/6) were examined. Results indicate that exposure of human NK cells to 10-0.5 μM HBCD or TBBPA activate MAPKs and MAP2Ks. This HBCD and TBBPA-induced activation of MAPKs may leave them unavailable for activation by virally infected or tumor target cells and thus contributes to the observed decreases in lytic function seen in NK cells exposed to HBCD and TBBPA.
Molecular dissection of the interaction between the SH3 domain and the SH2-Kinase Linker region in PTK6.

Science.gov (United States)

Kim, Han Ie; Jung, Jinwon; Lee, Eun-Saem; Kim, Yong-Chul; Lee, Weontae; Lee, Seung-Taek

2007-11-03

PTK6 (also known as Brk) is an intracellular tyrosine kinase that contains SH3, SH2, and tyrosine kinase catalytic (Kinase) domains. The SH3 domain of PTK6 interacts with the N-terminal half of the linker (Linker) region between the SH2 and Kinase domains. Site-directed mutagenesis and surface plasmon resonance studies showed that a tryptophan residue (Trp44) in the SH3 domain and proline residues in the Linker region, in the order of Pro177, Pro175, and Pro179, contribute to the interaction. The three-dimensional modeled structure of the SH3-Linker complex was in agreement with the biochemical data. Disruption of the intramolecular interaction between the SH3 domain and the Linker region by mutation of Trp44, Pro175, Pro177, and Pro179 markedly increased the catalytic activity of PTK6 in HEK 293 cells. These results demonstrate that Trp44 in the SH3 domain and Pro177, Pro175, and Pro179 in the N-terminal half of the Linker region play important roles in the SH3-Linker interaction to maintain the protein in an inactive conformation along with the phosphorylated Tyr447-SH2 interaction.
36 CFR 801.6 - Coordination with requirements under the National Environmental Policy Act (42 U.S.C. 4321 et seq.).

Science.gov (United States)

2010-07-01

... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false Coordination with requirements under the National Environmental Policy Act (42 U.S.C. 4321 et seq.). 801.6 Section 801.6 Parks... OF THE URBAN DEVELOPMENT ACTION GRANT PROGRAM § 801.6 Coordination with requirements under the...
IL-6 Impairs Myogenic Differentiation by Downmodulation of p90RSK/eEF2 and mTOR/p70S6K Axes, without Affecting AKT Activity

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Michele Pelosi

2014-01-01

Full Text Available IL-6 is a multifaceted pleiotropic cytokine, which is produced by a variety of cell types and targets different cells and tissues. In physiological conditions, IL-6 can be locally and transiently produced by skeletal muscle and plays an important role in muscle homeostasis. Circulating IL-6 levels are normally very low or undetectable but are dramatically increased in several pathologic conditions. In this study, we aimed to define the potential molecular mechanisms underlying the effects of IL-6 on myogenic program. We explored the molecular mechanisms through which exogenous IL-6, or the conditioned medium from the murine C-26 adenocarcinoma cells (a cellular model that secretes high levels of IL-6 and induces cancer cachexia in mice, interferes with the myogenic program. Our study revealed that IL-6 induces the activation of the Stat3 signaling and promotes the downmodulation of the p90RSK/eEF2 and mTOR/p70S6K axes, while it does not affect the activation of AKT. We thus identified potential molecular mediators of the inhibitory effects of IL-6 on myogenic program.
2,6,9-Trisubstituted purines as CRK3 kinase inhibitors with antileishmanial activity in vitro

Czech Academy of Sciences Publication Activity Database

Řezníčková, Eva; Popa, Alexandr; Gucký, Tomáš; Zatloukal, Marek; Havlíček, Libor; Bazgier, Václav; Berka, K.; Jorda, Radek; Popa, Igor; Nasereddin, A.; Jaffe, Ch. L.; Kryštof, Vladimír; Strnad, Miroslav

2015-01-01

Roč. 25, č. 11 (2015), s. 2298-2301 ISSN 0960-894X R&D Projects: GA MŠk(CZ) LO1204 Institutional support: RVO:61389030 Keywords : Purine * Cyclin-dependent kinase * Leishmania Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.486, year: 2015
Chemical and structural changes in polyamide based organic–inorganic hybrid materials upon incorporation of SeS{sub 2}O{sub 6}{sup 2−} precursor

Energy Technology Data Exchange (ETDEWEB)

Krylova, V.; Dukstienė, N.; Žalenkienė, S. [Department of Physical and Inorganic Chemistry, Kaunas University of Technology, Radvilenu st. " 1" 9" , LT-50254, Kaunas (Lithuania); Baltrusaitis, J., E-mail: job314@lehigh.edu [Department of Chemical and Biomolecular Engineering, Lehigh University, B336 Iacocca Hall, 111 Research Drive, Bethlehem, PA 18015 (United States)

2017-01-15

Highlights: • We investigated deposited and diffused K{sub 2}SeS{sub 2}O{sub 6} into polyamide 6 (PA 6). • AAS showed Se:S molar ratio = 1:2 within the PA. • Various decomposition products were detected within the polymer. • Measured bandgap shifted towards lower light absorption energies. - Abstract: Composite organic-inorganic functional materials are of significant importance in various applications of science and technology. In this work, physicochemical characterization of such composite materials obtained after the exposure of polyamide PA 6 to K{sub 2}SeS{sub 2}O{sub 6} precursor solution was performed. Chalcogenized polymer surface was characterized using X-ray diffraction, infrared, and UV–vis spectroscopies while their bulk chemical analysis was performed using atomic absorption spectroscopy. Crystallite size was not found to change with the exposure to K{sub 2}SeS{sub 2}O{sub 6} precursor but PA 6 chain–chain separation decreased. Importantly, infrared and X-ray analyses showed chemical bonding taking place between the PA 6 and SeS{sub 2}O{sub 6}{sup 2−} ions via −NH− functional group. A distinct change in bandgap, E{sub g}, value was observed in UV–vis spectra due to the presence of SeS{sub 2}O{sub 6}{sup 2−}, SeSO{sub 3}{sup 2−} and Se{sub 2}S{sub 2}O{sub 6}{sup 2−} ions formed via decomposition of the precursor material in acidic medium. After extended 4 h chalcogenation a distinct absorption due to the elemental selenium was also observed as obtained from Tauc plots.
Near-infrared colorimetry of J6 Himalia and S9 Phoebe - A summary of 0.3- to 2.2-micron reflectances

Science.gov (United States)

Degewij, J.; Cruikshank, D. P.; Hartmann, W. K.

1980-01-01

VJHK measurements of J6 Himalia and S9 Phoebe, using the new NASA IRTF telescope, show that these objects have carbonaceous chondritic type colors in the 0.5- to 2.2-micron region. For Phoebe, this is in contrast to the JHK colors published by Cruikshank (1980), which indicated that the satellite's surface was unlike the material found on asteroids and on the dark side of Iapetus. J6 is known to have a low albedo from thermal infrared studies (Cruikshank, 1977), and the new VJHK observations of S9 imply that it also has a low albedo. The H and K reflectances of S9 are slightly lower than those of J6, suggesting some slight difference in surface composition or a contamination by foreign material. The conjectured low albedo of S9 can be tested with measurements in the thermal infrared.
Crystal structures of (RS-N-[(1R,2S-2-benzyloxy-1-(2,6-dimethylphenylpropyl]-2-methylpropane-2-sulfinamide and (RS-N-[(1S,2R-2-benzyloxy-1-(2,4,6-trimethylphenylpropyl]-2-methylpropane-2-sulfinamide: two related protected 1,2-amino alcohols

Directory of Open Access Journals (Sweden)

Matthew R. Carbone

2014-11-01

Full Text Available The title compounds, C22H31NO2S, (1, and C23H33NO2S, (2, are related protected 1,2-amino alcohols. They differ in the substituents on the benzene ring, viz. 2,6-dimethylphenyl in (1 and 2,4,6-trimethylphenyl in (2. The plane of the phenyl ring is inclined to that of the benzene ring by 28.52 (7° in (1 and by 44.65 (19° in (2. In the crystal of (1, N—H...O=S and C—H...O=S hydrogen bonds link molecules, forming chains along [100], while in (2, similar hydrogen bonds link molecules into chains along [010]. The absolute structures of both compounds were determined by resonance scattering.
A SERS protocol as a potential tool to access 6-mercaptopurine release accelerated by glutathione-S-transferase.

Science.gov (United States)

Wang, Ying; Sun, Jie; Yang, Qingran; Lu, Wenbo; Li, Yan; Dong, Jian; Qian, Weiping

2015-11-21

The developed method for monitoring GST, an important drug metabolic enzyme, could greatly facilitate researches on relative biological fields. In this work, we have developed a SERS technique to monitor the absorbance behaviour of 6-mercaptopurine (6-MP) and its glutathione-S-transferase (GST)-accelerated glutathione (GSH)-triggered release behaviour on the surface of gold nanoflowers (GNFs), using the GNFs as excellent SERS substrates. The SERS signal was used as an indicator of absorbance or release of 6-MP on the gold surface. We found that GST can accelerate GSH-triggered release behaviour of 6-MP from the gold surface. We speculated that GST catalyzes nucleophilic GSH to competitively bind with the electrophilic substance 6-MP. Experimental results have proved that the presented SERS protocol can be utilized as an effective tool for accessing the release of anticancer drugs.
Multifunctional Effects of Mangosteen Pericarp on Cognition in C57BL/6J and Triple Transgenic Alzheimer’s Mice

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Hei-Jen Huang

2014-01-01

Full Text Available Mangosteen- (Garcinia mangostana- based nutraceutical compounds have long been reported to possess multiple health-promoting properties. The current study investigated whether mangosteen pericarp (MP could attenuate cognitive dysfunction. First, we found that treatment with MP significantly reduced the cell death and increased the brain-derived neurotrophic factor (BDNF level in an organotypic hippocampal slice culture (OHSC. We then investigated the effects of age and MP diet on the cognitive function of male C57BL/6J (B6 mice. After 8-month dietary supplementation, the MP diet (5000 ppm significantly attenuated the cognitive impairment associated with anti-inflammation, increasing BDNF level and decreasing p-tau (phospho-tau S202 in older B6 mice. We further applied MP dietary supplementation to triple transgenic Alzheimer’s disease (3×Tg-AD mice from 5 to 13 months old. The MP diet exerted neuroprotective, antioxidative, and anti-inflammatory effects and reduced the Aβ deposition and p-tau (S202/S262 levels in the hippocampus of 3×Tg-AD mice, which might further attenuate the deficit in spatial memory retrieval. Thus, these results revealed that the multifunctional properties of MP might offer a promising supplementary diet to attenuate cognitive dysfunction in AD.
Divergent actions of the pyrethroid insecticides S-bioallethrin, tefluthrin, and deltamethrin on rat Nav1.6 sodium channels

International Nuclear Information System (INIS)

Tan Jianguo; Soderlund, David M.

2010-01-01

We expressed rat Na v 1.6 sodium channels in combination with the rat β 1 and β 2 auxiliary subunits in Xenopus laevis oocytes and evaluated the effects of the pyrethroid insecticides S-bioallethrin, deltamethrin, and tefluthrin on expressed sodium currents using the two-electrode voltage clamp technique. S-Bioallethrin, a type I structure, produced transient modification evident in the induction of rapidly decaying sodium tail currents, weak resting modification (5.7% modification at 100 μM), and no further enhancement of modification upon repetitive activation by high-frequency trains of depolarizing pulses. By contrast deltamethrin, a type II structure, produced sodium tail currents that were ∼ 9-fold more persistent than those caused by S-bioallethrin, barely detectable resting modification (2.5% modification at 100 μM), and 3.7-fold enhancement of modification upon repetitive activation. Tefluthrin, a type I structure with high mammalian toxicity, exhibited properties intermediate between S-bioallethrin and deltamethrin: intermediate tail current decay kinetics, much greater resting modification (14.1% at 100 μM), and 2.8-fold enhancement of resting modification upon repetitive activation. Comparison of concentration-effect data showed that repetitive depolarization increased the potency of tefluthrin ∼ 15-fold and that tefluthrin was ∼ 10-fold more potent than deltamethrin as a use-dependent modifier of Na v 1.6 sodium channels. Concentration-effect data from parallel experiments with the rat Na v 1.2 sodium channel coexpressed with the rat β 1 and β 2 subunits in oocytes showed that the Na v 1.6 isoform was at least 15-fold more sensitive to tefluthrin and deltamethrin than the Na v 1.2 isoform. These results implicate sodium channels containing the Na v 1.6 isoform as potential targets for the central neurotoxic effects of pyrethroids.
Measurement of D{sub s}{sup +} and D{sub s}{sup *+} Production in B Meson Decays and from Continuum e{sup +}e{sup -} Annihilations at {radical}s=10.6 GeV.

Energy Technology Data Exchange (ETDEWEB)

Ganzhur, Sergey

2001-07-30

New precise measurements of D{sub s}{sup +} and D*{sub s}{sup +} meson production from B mesons and q{bar q} continuum events near the {Upsilon}(4S) resonance are presented in this paper. Using the BABAR data recorded in 1999 and 2000 of 20.8 fb{sup -1} on-resonance and 2.6 fb{sup -1} off-resonance, we measure the inclusive branching fractions (B {yields} D{sub s}{sup +}) = (10.93 {+-} 0.19 {+-} 0.58 {+-} 2.73)% and (B {yields} D*{sub s}{sup +}) = (7.94 {+-} 0.82 {+-} 0.72 {+-} 1.99)%, where the first error is statistical, the second is the systematic error, and the third is the error due to the D{sub s}{sup +} {yields} {pi}{sup +} branching fraction uncertainty. The branching fractions (B {yields} D{sup (*)}{sub s}{sup +} {bar D}(*)) = (5.07 {+-} 0.09 {+-} 0.34 {+-} 1.27)% and (B {yields} D*{sub s}{sup +} {bar D}(*)) = (4.07 {+-} 0.42 {+-} 0.53 {+-} 1.02)% have been determined from the measured D{sup (*)}{sub s}{sup +} momentum spectra.
The Ste20 Family Kinases MAP4K4, MINK1, and TNIK Converge to Regulate Stress-Induced JNK Signaling in Neurons.

Science.gov (United States)

Larhammar, Martin; Huntwork-Rodriguez, Sarah; Rudhard, York; Sengupta-Ghosh, Arundhati; Lewcock, Joseph W

2017-11-15

The c-Jun- N -terminal kinase (JNK) signaling pathway regulates nervous system development, axon regeneration, and neuronal degeneration after acute injury or in chronic neurodegenerative disease. Dual leucine zipper kinase (DLK) is required for stress-induced JNK signaling in neurons, yet the factors that initiate DLK/JNK pathway activity remain poorly defined. In the present study, we identify the Ste20 kinases MAP4K4, misshapen-like kinase 1 (MINK1 or MAP4K6) and TNIK Traf2- and Nck-interacting kinase (TNIK or MAP4K7), as upstream regulators of DLK/JNK signaling in neurons. Using a trophic factor withdrawal-based model of neurodegeneration in both male and female embryonic mouse dorsal root ganglion neurons, we show that MAP4K4, MINK1, and TNIK act redundantly to regulate DLK activation and downstream JNK-dependent phosphorylation of c-Jun in response to stress. Targeting MAP4K4, MINK1, and TNIK, but not any of these kinases individually, is sufficient to protect neurons potently from degeneration. Pharmacological inhibition of MAP4Ks blocks stabilization and phosphorylation of DLK within axons and subsequent retrograde translocation of the JNK signaling complex to the nucleus. These results position MAP4Ks as important regulators of the DLK/JNK signaling pathway. SIGNIFICANCE STATEMENT Neuronal degeneration occurs in disparate circumstances: during development to refine neuronal connections, after injury to clear damaged neurons, or pathologically during disease. The dual leucine zipper kinase (DLK)/c-Jun- N -terminal kinase (JNK) pathway represents a conserved regulator of neuronal injury signaling that drives both neurodegeneration and axon regeneration, yet little is known about the factors that initiate DLK activity. Here, we uncover a novel role for a subfamily of MAP4 kinases consisting of MAP4K4, Traf2- and Nck-interacting kinase (TNIK or MAP4K7), and misshapen-like kinase 1 (MINK1 or MAP4K6) in regulating DLK/JNK signaling in neurons. Inhibition of

ARF6, PI3-kinase and host cell actin cytoskeleton in Toxoplasma gondii cell invasion

International Nuclear Information System (INIS)

Vieira da Silva, Claudio; Alves da Silva, Erika; Costa Cruz, Mario; Chavrier, Philippe; Arruda Mortara, Renato

2009-01-01

Toxoplasma gondii infects a variety of different cell types in a range of different hosts. Host cell invasion by T. gondii occurs by active penetration of the host cell, a process previously described as independent of host actin polymerization. Also, the parasitophorous vacuole has been shown to resist fusion with endocytic and exocytic pathways of the host cell. ADP-ribosylation factor-6 (ARF6) belongs to the ARF family of small GTP-binding proteins. ARF6 regulates membrane trafficking and actin cytoskeleton rearrangements at the plasma membrane. Here, we have observed that ARF6 is recruited to the parasitophorous vacuole of tachyzoites of T. gondii RH strain and it also plays an important role in the parasite cell invasion with activation of PI3-kinase and recruitment of PIP 2 and PIP 3 to the parasitophorous vacuole of invading parasites. Moreover, it was verified that maintenance of host cell actin cytoskeleton integrity is important to parasite invasion.
Spin-triplet excitons and anisotropy effects in the S=12 gapped antiferromagnet BaCuSi2O6

International Nuclear Information System (INIS)

Zvyagin, S.A.; Wosnitza, J.; Krzystek, J.; Stern, R.; Jaime, M.; Sasago, Y.; Uchinokura, K.

2007-01-01

BaCuSi 2 O 6 can be regarded as an almost ideal realization of an S=12 system of weakly interacting spin dimers with spin-singlet ground state and gapped excitation spectrum. We argue that the fine structure observed in low-temperature EPR spectra of BaCuSi 2 O 6 is a fingerprint of triplet excitations (excitons). Analyzing the angular dependence of the exciton modes allows us to precisely calculate the zero-field splitting within the triplet states and, correspondingly, the anisotropy parameter, D=0.07cm -1 . The proposed procedure can be applied for studying anisotropy effects in a large number of S=12 gapped quantum antiferromagnets with dimerized or alternating spin structure
In situ reverse transcription-PCR for monitoring gene expression in individual Methanosarcina mazei S-6 cells

DEFF Research Database (Denmark)

Lange, Marianne; Tolker-Nielsen, Tim; Molin, Søren

2000-01-01

An in situ reverse transcription-PCR protocol for detecting specific mRNA in Methanosarcina mazei S-6 is described. This method allowed us to detect heat shock-induced increases in the intracellular levels of the transcript of the universal stress gene dnaK. The cell walls of paraformaldehyde...
Microglia P2Y6 receptor is related to Parkinson’s disease through neuroinflammatory process

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Xiaodong Yang

2017-02-01

Full Text Available Abstract Background Microglia in the central nervous system (CNS were reported to play crucial role in neurodegeneration. Previous studies showed that P2Y6 receptor (P2Y6R mainly contributed to microglia activation and phagocytosis in CNS. However, the level of P2Y6R in Parkinson’s disease (PD patients is unclear. Therefore, we measured the level of P2Y6R in PD patients and speculated whether it could be a potential biomarker for PD. Given on the basis that P2Y6R was higher in PD patients, we further explored the mechanisms underlying P2Y6R in the pathogenesis of PD. Methods We tested the expression level of P2Y6R in the peripheral blood mononuclear cells (PBMCs among 145 PD patients, 170 healthy controls, and 30 multiple system atrophy (MSA patients. We also used a lipopolysaccharide (LPS-stimulated microglial cell culture model to investigate (i the effects of LPS on P2Y6R expression with western blot and RT-PCR, (ii the effects of LPS on UDP expression using HPLC, (iii the effects of UDP/P2Y6R signaling on cytokine expression using western blot, RT-PCR, and ELISA, and (iv the signaling pathways activated by the P2Y6R involved in the neuroinflammation. Results Expression levels of P2Y6R in PD patients were higher than healthy controls and MSA patients. P2Y6R could be a good biomarker of PD. P2Y6R was also upregulated in LPS-treated BV-2 cells and involved in proinflammatory cytokine release through an autocrine loop based on LPS-triggered UDP secretion and accelerated neuroinflammatory responses through the ERK1/2 pathway. Importantly, blocking UDP/P2Y6R signaling could reverse these pathological processes. Conclusions P2Y6R may be a potential clinical biomarker of PD. Blocking P2Y6R may be a potential therapeutic approach to the treatment of PD patients through inhibition of microglia-activated neuroinflammation.
Upper Extremity Multifocal Neuropathy in a 10-Year-Old Boy Associated With NS6S Disaccharide Antibodies.

Science.gov (United States)

Edelman, Frederick; Naddaf, Elie; Waclawik, Andrew J

2015-06-01

We present a 10-year-old boy with a predominantly motor multifocal neuropathy with demyelinating and axonal changes with sensory involvement, affecting only one upper extremity. Laboratory studies revealed an elevated titer of immunoglobulin M (IgM) antibodies against the NS6S antigen. He responded to treatment with high dose intravenous immunoglobulins. Focal or multifocal immune-mediated neuropathies are not common in children and may be underdiagnosed. © The Author(s) 2014.
[4,6-Dimethylpyrimidine-2(1H)-thione-κS]iodidobis(triphenylphosphane-κP)copper(I)

Science.gov (United States)

Pakawatchai, Chaveng; Wattanakanjana, Yupa; Choto, Patcharanan; Nimthong, Ruthairat

2012-01-01

In the mononuclear title complex, [CuI(C6H8N2S)(C18H15P)2], the CuI ion is in a slightly distorted tetrahedral coordination geometry formed by two P atoms from two triphenylphosphane ligands, one S atom from a 4,6-dimethylpyrimidine-2(1H)-thione ligand and one iodide ion. There is an intramolecular N—H⋯I hydrogen bond. In the crystal, π–π stacking interactions [centroid–centroid distance = 3.594 (1) Å] are observed. PMID:22719327
Crystallization and preliminary X-ray diffraction analysis of inositol 1,3,4,5,6-pentakisphosphate kinase from Arabidopsis thaliana

International Nuclear Information System (INIS)

Baños-Sanz, Jose Ignacio; Villate, Maider; Sanz-Aparicio, Julia; Brearley, Charles Alistair; González, Beatriz

2009-01-01

Inositol 1,3,4,5,6-pentakisphosphate kinase from A. thaliana has been expressed in E. coli, purified and crystallized and diffraction data have been collected to 2.3 Å resolution. Two heavy-atom crystal derivatives are under study. Inositol 1,3,4,5,6-pentakisphosphate kinase (IP 5 2-K) is an enzyme involved in inositol metabolism that synthesizes IP 6 (inositol 1,2,3,4,5,6-hexakisphosphate) from inositol 1,3,4,5,6-pentakisphosphate (IP 5 ) and ATP. IP 6 is the major phosphorus reserve in plants, while in mammals it is involved in multiple cellular events such as DNA editing and chromatin remodelling. In addition, IP 6 is the precursor of other highly phosphorylated inositols which also play highly relevant roles. IP 5 2-K is the only enzyme that phosphorylates the 2-OH axial position of the inositide and understanding its molecular mechanism of substrate specificity is of great interest in cell biology. IP 5 2-K from Arabidopsis thaliana has been expressed in Escherichia coli as two different fusion proteins and purified. Both protein preparations yielded crystals of different quality, always in the presence of IP 6 . The best crystals obtained for X-ray crystallographic analysis belonged to space group P2 1 2 1 2 1 , with unit-cell parameters a = 58.124, b = 113.591, c = 142.478 Å. Several diffraction data sets were collected for the native enzyme and two heavy-atom derivatives using a synchrotron source
IL6 induces TAM resistance via kinase-specific phosphorylation of ERα in OVCA cells.

Science.gov (United States)

Wang, Yue; Niu, Xiu Long; Guo, Xiao Qin; Yang, Jing; Li, Ling; Qu, Ye; Xiu Hu, Cun; Mao, Li Qun; Wang, Dan

2015-06-01

About 40-60% of ovarian cancer (OVCA) cases express ERα, but only a small proportion of patients respond clinically to anti-estrogen treatment with estrogen receptor (ER) antagonist tamoxifen (TAM). The mechanism of TAM resistance in the course of OVCA progression remains unclear. However, IL6 plays a critical role in the development and progression of OVCA. Our recent results indicated that IL6 secreted by OVCA cells may promote the resistance of these cells to TAM via ER isoforms and steroid hormone receptor coactivator-1. Here we demonstrate that both exogenous (a relatively short period of treatment with recombinant IL6) and endogenous IL6 (generated as a result of transfection with a plasmid encoding sense IL6) increases expression of pERα-Ser118 and pERα-Ser167 in non-IL6-expressing A2780 cells, while deleting endogenous IL6 expression in IL6-overexpressing CAOV-3 cells (by transfection with a plasmid encoding antisense IL6) reduces expression of pERα-Ser118 and pERα-Ser167, indicating that IL6-induced TAM resistance may also be associated with increased expression of pERα-Ser118 and pERα-Ser167 in OVCA cells. Results of further investigation indicate that IL6 phosphorylates ERα at Ser118 and Ser167 by triggering activation of MEK/ERK and phosphotidylinositol 3 kinase/Akt signaling, respectively, to activate the ER pathway and thereby induce OVCA cells resistance to TAM. These results indicate that IL6 secreted by OVCA cells may also contribute to the refractoriness of these cells to TAM via the crosstalk between ER and IL6-mediated intracellular signal transduction cascades. Overexpression of IL6 not only plays an important role in OVCA progression but also promotes TAM resistance. Our results indicate that TAM-IL6-targeted adjunctive therapy may lead to a more effective intervention than TAM alone. © 2015 Society for Endocrinology.
(4bS,8aS-1-Isopropyl-4b,8,8-trimethyl-4b,5,6,7,8,8a,9,10-octahydrophenanthren-2-yl acetate

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Radouane Oubabi

2014-03-01

Full Text Available The hemisynthesis of the title compound, C22H32O2, was carried out through direct acetylation reaction of the naturally occurring diterpene totarol [systematic name: (4bS,8aS-4b,8,8-trimethyl-1-propan-2-yl-5,6,7,8a,9,10-hexahydrophenanthren-2-ol]. The molecule is built up from three fused six membered rings, one saturated and two unsaturated. The central unsaturated ring has a half-chair conformation, whereas the other unsaturated ring displays a chair conformation. The absolute configuration is deduced from the chemical pathway. The value of the Hooft parameter [−0.10 (6] allowed this absolute configuration to be confirmed.
Amplitude Analysis and Measurement of the Time-dependent CP Asymmetry of B0 to KsKsKs Decays

Energy Technology Data Exchange (ETDEWEB)

Lees, J.P.

2012-04-11

We present the first results on the Dalitz-plot structure and improved measurements of the time-dependent CP-violation parameters of the process B{sup 0} {yields} K{sub S}{sup 0}K{sub S}{sup 0}K{sub S}{sup 0} obtained using 468 x 10{sup 6} B{bar B} decays collected with the BABAR detector at the PEP-II asymmetric-energy B factory at SLAC. The Dalitz-plot structure is probed by a time-integrated amplitude analysis that does not distinguish between B{sup 0} and {bar B}{sup 0} decays. We measure the total inclusive branching fraction {Beta}(B{sup 0} {yields} K{sub S}{sup 0}K{sub S}{sup 0}K{sub S}{sup 0}) = (6.19 {+-} 0.48 {+-} 0.15 {+-} 0.12) x 10{sup -6}, where the first uncertainty is statistical, the second is systematic, and the third represents the Dalitz-plot signal model dependence. We also observe evidence for the intermediate resonant states f{sub 0}(980), f{sub 0}(1710), and f{sub 2}(2010). Their respective product branching fractions are measured to be (2.70{sub -1.19}{sup +1.25} {+-} 0.36 {+-} 1.17) x 10{sup -6}, (0.50{sub -0.24}{sup +0.46} {+-} 0.04 {+-} 0.10) x 10{sup -6}, and (0.54{sub -0.20}{sup +0.21} {+-} 0.03 {+-} 0.52) x 10{sup -6}. Additionally, we determine the mixing-induced CP-violation parameters to be S = -0.94{sub -0.21}{sup +0.24} {+-} 0.06 and C = -0.17 {+-} 0.18 {+-} 0.04, where the first uncertainty is statistical and the second is systematic. These values are in agreement with the standard model expectation.
1-Pb/s (32 SDM/46 WDM/768 Gb/s) C-band Dense SDM Transmission over 205.6-km of Single-mode Heterogeneous Multi-core Fiber using 96-Gbaud PDM-16QAM Channels

DEFF Research Database (Denmark)

Kobayashi, Takayuki; Nakamura, M.; Hamaoka, F.

2017-01-01

We demonstrate the first 1-Pb/s unidirectional inline-amplified transmission over 205.6-km of single-mode 32-core fiber within C-band only. 96-Gbaud LDPC-coded PDM-16QAM channels with FEC redundancy of 12.75% realize high-aggregate spectral efficiency of 217.6 b/s/Hz...
E6 variants of human papillomavirus 18 differentially modulate the protein kinase B/phosphatidylinositol 3-kinase (akt/PI3K) signaling pathway

International Nuclear Information System (INIS)

Contreras-Paredes, Adriana; Cruz-Hernandez, Erick de la; Martinez-Ramirez, Imelda; Duenas-Gonzalez, Alfonso; Lizano, Marcela

2009-01-01

Intra-type genome variations of high risk Human papillomavirus (HPV) have been associated with a differential threat for cervical cancer development. In this work, the effect of HPV18 E6 isolates in Akt/PKB and Mitogen-associated protein kinase (MAPKs) signaling pathways and its implication in cell proliferation were analyzed. E6 from HPV types 16 and 18 are able to bind and promote degradation of Human disc large (hDlg). Our results show that E6 variants differentially modulate hDlg degradation, rebounding in levels of activated PTEN and PKB. HPV18 E6 variants are also able to upregulate phospho-PI3K protein, strongly correlating with activated MAPKs and cell proliferation. Data was supported by the effect of E6 silencing in HPV18-containing HeLa cells, as well as hDlg silencing in the tested cells. Results suggest that HPV18 intra-type variations may derive in differential abilities to activate cell-signaling pathways such as Akt/PKB and MAPKs, directly involved in cell survival and proliferation
Studying the Specific Activity of the Amide Form of HLDF-6 Peptide using the Transgenic Model of Alzheimer’s Disease

Science.gov (United States)

Bogachouk, A. P.; Storozheva, Z. I.; Telegin, G. B.; Chernov, A. S.; Proshin, A. T.; Sherstnev, V. V.; Zolotarev, Yu. A.; Lipkin, V. M.

2017-01-01

The neuroprotective and nootropic activities of the amide form (AF) of the HLDF-6 peptide (TGENHR-NH2) were studied in transgenic mice of the B6C3-Tg(APPswe,PSEN1de9)85Dbo (Tg+) line (the animal model of familial Alzheimer’s disease (AD)). The study was performed in 4 mouse groups: group 1 (study group): Tg+ mice intranasally injected with the peptide at a dose of 250 μg/kg; group 2 (active control): Tg+ mice intranasally injected with normal saline; group 3 (control 1): Tg- mice; and group 4 (control 2): C57Bl/6 mice. The cognitive functions were evaluated using three tests: the novel object recognition test, the conditioned passive avoidance task, and the Morris water maze. The results testify to the fact that the pharmaceutical substance (PhS) based on the AF of HLDF-6 peptide at a dose of 250 μg/kg administered intranasally efficiently restores the disturbed cognitive functions in transgenic mice. These results are fully consistent with the data obtained in animal models of Alzheimer’s disease induced by the injection of the beta-amyloid (βA) fragment 25-35 into the giant-cell nucleus basalis of Meynert or by co-injection of the βA fragment 25-35 and ibotenic acid into the hippocampus, and the model of ischemia stroke (chronic bilateral occlusion of carotids, 2VO). According to the overall results, PhS based on AF HLDF-6 was chosen as an object for further investigation; the dose of 250 μg/kg was used as an effective therapeutic dose. Intranasal administration was the route for delivery. PMID:29104777
Design principles of the yeast G1/S switch.

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Xiaojing Yang

2013-10-01

Full Text Available A hallmark of the G1/S transition in budding yeast cell cycle is the proteolytic degradation of the B-type cyclin-Cdk stoichiometric inhibitor Sic1. Deleting SIC1 or altering Sic1 degradation dynamics increases genomic instability. Certain key facts about the parts of the G1/S circuitry are established: phosphorylation of Sic1 on multiple sites is necessary for its destruction, and both the upstream kinase Cln1/2-Cdk1 and the downstream kinase Clb5/6-Cdk1 can phosphorylate Sic1 in vitro with varied specificity, cooperativity, and processivity. However, how the system works as a whole is still controversial due to discrepancies between in vitro, in vivo, and theoretical studies. Here, by monitoring Sic1 destruction in real time in individual cells under various perturbations to the system, we provide a clear picture of how the circuitry functions as a switch in vivo. We show that Cln1/2-Cdk1 sets the proper timing of Sic1 destruction, but does not contribute to its destruction speed; thus, it acts only as a trigger. Sic1's inhibition target Clb5/6-Cdk1 controls the speed of Sic1 destruction through a double-negative feedback loop, ensuring a robust all-or-none transition for Clb5/6-Cdk1 activity. Furthermore, we demonstrate that the degradation of a single-phosphosite mutant of Sic1 is rapid and switch-like, just as the wild-type form. Our mathematical model confirms our understanding of the circuit and demonstrates that the substrate sharing between the two kinases is not a redundancy but a part of the design to overcome the trade-off between the timing and sharpness of Sic1 degradation. Our study provides direct mechanistic insight into the design features underlying the yeast G1/S switch.
Arsenite induces cell transformation by reactive oxygen species, AKT, ERK1/2, and p70S6K1

International Nuclear Information System (INIS)

Carpenter, Richard L.; Jiang, Yue; Jing, Yi; He, Jun; Rojanasakul, Yon; Liu, Ling-Zhi; Jiang, Bing-Hua

2011-01-01

Highlights: ► Chronic exposure to arsenite induces cell proliferation and transformation. ► Arsenite-induced transformation increases ROS production and downstream signalings. ► Inhibition of ROS levels via catalase reduces arsenite-induced cell transformation. ► Interruption of AKT, ERK, or p70S6K1 inhibits arsenite-induced cell transformation. -- Abstract: Arsenic is naturally occurring element that exists in both organic and inorganic formulations. The inorganic form arsenite has a positive association with development of multiple cancer types. There are significant populations throughout the world with high exposure to arsenite via drinking water. Thus, human exposure to arsenic has become a significant public health problem. Recent evidence suggests that reactive oxygen species (ROS) mediate multiple changes to cell behavior after acute arsenic exposure, including activation of proliferative signaling and angiogenesis. However, the role of ROS in mediating cell transformation by chronic arsenic exposure is unknown. We found that cells chronically exposed to sodium arsenite increased proliferation and gained anchorage-independent growth. This cell transformation phenotype required constitutive activation of AKT, ERK1/2, mTOR, and p70S6K1. We also observed these cells constitutively produce ROS, which was required for the constitutive activation of AKT, ERK1/2, mTOR, and p70S6K1. Suppression of ROS levels by forced expression of catalase also reduced cell proliferation and anchorage-independent growth. These results indicate cell transformation induced by chronic arsenic exposure is mediated by increased cellular levels of ROS, which mediates activation of AKT, ERK1/2, and p70S6K1.
Canted ferrimagnetism and giant coercivity in the nonstoichiometric double perovskite L a2N i1.19O s0.81O6

Science.gov (United States)

Feng, Hai L.; Reehuis, Manfred; Adler, Peter; Hu, Zhiwei; Nicklas, Michael; Hoser, Andreas; Weng, Shih-Chang; Felser, Claudia; Jansen, Martin

2018-05-01

The nonstoichiometric double perovskite oxide L a2N i1.19O s0.81O6 was synthesized by solid-state reaction and its crystal and magnetic structures were investigated by powder x-ray and neutron diffraction. L a2N i1.19O s0.81O6 crystallizes in the monoclinic double perovskite structure (general formula A2B B'O6 ) with space group P 21/n , where the B site is fully occupied by Ni and the B ' site by 19% Ni and 81% Os atoms. Using x-ray absorption spectroscopy an O s4.5 + oxidation state was established, suggesting the presence of about 50% paramagnetic O s5 + (5 d3 , S =3 /2 ) and 50% nonmagnetic O s4 + (5 d4 , Jeff=0 ) ions at the B ' sites. Magnetization and neutron diffraction measurements on L a2N i1.19O s0.81O6 provide evidence for a ferrimagnetic transition at 125 K. The analysis of the neutron data suggests a canted ferrimagnetic spin structure with collinear N i2 + -spin chains extending along the c axis but a noncollinear spin alignment within the a b plane. The magnetization curve of L a2N i1.19O s0.81O6 features a hysteresis with a very high coercive field, HC=41 kOe , at T =5 K , which is explained in terms of large magnetocrystalline anisotropy due to the presence of Os ions together with atomic disorder. Our results are encouraging to search for rare-earth-free hard magnets in the class of double perovskite oxides.
K.S. Maniam, Jhumpa Lahiri, Shirley Lim: A Reflection of Culture and Identity

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Hardev Kaur Jujar Singh

2012-07-01

Full Text Available “I do not want my house to be walled in on all sides and my windows to be stuffed. I want the culture of all lands to be blown about my house as freely as possible. But I refuse to be blown off my feet by any”—Mahatma Gandhi. With these sayings by Gandhiji, one will be able to understand why, even in a borderless world where the diffusion of races and culture happens all the time, and many would simply accept without restraint, the cultures and identity of their adopted land, there remain some writers who, despite being part of a new land, are still deeply influenced by their motherland and various aspects of life that are distinctive and peculiar to their motherland. The writers concerned in this paper are K.S Maniam, Shirley Lim and Jhumpa Lahiri. All these writers have nationalities not of their motherland, but somehow, their writings are usually immersed with the thoughts and culture of their motherland. In this study, we will examine the strong influences imbedded in these writers of the culture of their motherland despite being in their new land. We will also portray how some of the characters assimilate in their new land, whereas some still have a sense of belonging towards their motherland.
I/asterisk/ /6s 4P/ collisional quenching - Application to the IF 491-nm laser

Science.gov (United States)

Hutchison, S. B.; Verdeyen, J. T.; Eden, J. G.

1981-01-01

Measurements of the rate constants for quenching of the excited I (6s 4P) states by Ar, Xe, CF39I, UF6, and NF3 are described. Each rate constant is determined by recording the exponential time decay of the excited IF or excited I2 (342 nm) fluorescence in the afterglow of the e-beam-excited plasmas containing Ar, CF3I, NF3, and the desired quenching gas. In addition, further experimental evidence in support of neutral channel formation of excited IF in e-beam-pumped Ar/CF3I/NF3 mixtures is presented. Details of the experimental apparatus and gas handling procedures are given, and the kinetics model developed to interpret the experimental data is described.
Hydrothermal synthesis of CdS/Bi{sub 2}MoO{sub 6} heterojunction photocatalysts with excellent visible-light-driven photocatalytic performance

Energy Technology Data Exchange (ETDEWEB)

Feng, Yi; Yan, Xu; Liu, Chunbo; Hong, Yuanzhi; Zhu, Lin; Zhou, Mingjun; Shi, Weidong, E-mail: swd1978@ujs.edu.cn

2015-10-30

Graphical abstract: - Highlights: • The novel CdS/Bi{sub 2}MoO{sub 6} heterojunction were synthesized for the first time via a two-step hydrothermal process. • The CdS/Bi{sub 2}MoO{sub 6} heterojunction exhibited an excellent visible-light-driven photocatalytic activity for RhB degradation. • The photocatalytic activity of this heterojunction also evaluated by TC, MB degradation. • The mechanism of this photocatalysis system was firstly proposed. - Abstract: A novel CdS/Bi{sub 2}MoO{sub 6} heterojunction photocatalysts were successfully prepared via two-step hydrothermal methods. The prepared samples were characterized by various physicochemical techniques, such as XRD, SEM, TEM, HRTEM, XPS, UV–vis and PL. The obtained samples exhibited highly photocatalytic activity toward the degradation of the different kinds of organic dyes and tetracycline in aqueous solution under visible light irradiation (λ > 420 nm). The optimum photocatalytic efficiency of CdS-2 sample for the degradation rhodamine B (RhB) was about 25.3 and 3.7 times higher than that of individual CdS and Bi{sub 2}MoO{sub 6}, respectively. In addition, the possible photocatalytic mechanism was analyzed by different active species trapping experiments. The results indicated that the h{sup +} and ·O{sub 2}{sup −} were the main active species for the photocatalytic degradation of RhB. Moreover, the prepared sample shows good stability and recyclability properties which are beneficial for its practical application.
Lymphocyte-specific protein tyrosine kinase (Lck) interacts with CR6-interacting factor 1 (CRIF1) in mitochondria to repress oxidative phosphorylation

International Nuclear Information System (INIS)

Vahedi, Shahrooz; Chueh, Fu-Yu; Chandran, Bala; Yu, Chao-Lan

2015-01-01

of intramitochondrial translational machinery, in Jurkat further supports the role of mitochondrial Lck as a negative regulator of CRIF1 through competitive binding. This is the first report demonstrating the role of mitochondrial Lck in metabolic reprogramming of leukemic cells. Mechanistically, it is distinct from other reported mitochondrial protein tyrosine kinases. In a kinase-independent manner, mitochondrial Lck interferes with mitochondrial translational machinery through competitive binding to CRIF1. These findings may reveal novel approaches in cancer therapy by targeting cancer cell metabolism. The online version of this article (doi:10.1186/s12885-015-1520-6) contains supplementary material, which is available to authorized users

Radiation damage in SmS, SmSsub(1-x)Psub(x) and SmB6

International Nuclear Information System (INIS)

Morillo, J.; Bordier, G.; de Novion, C.H.; Senateur, J.P.; Jun, J.

1984-08-01

Large conductivity increases under 21 K electron or neutron irradiations are observed in SmS and SmSsub(1-x)Psub(x). It is shown that they are related to Sm defects. A possible mechanism is 4f electron delocalization around radiation defects. In SmB 6 , the low temperature resistivity increase desappears under 21 K irradiation. The thermal stability of the defects is also investigated up to room temperature
Identification of a major IP5 kinase in Cryptococcus neoformans confirms that PP-IP5/IP7, not IP6, is essential for virulence

OpenAIRE

Li, Cecilia; Lev, Sophie; Saiardi, Adolfo; Desmarini, Desmarini; Sorrell, Tania C.; Djordjevic, Julianne T.

2016-01-01

Fungal inositol polyphosphate (IP) kinases catalyse phosphorylation of IP3 to inositol pyrophosphate, PP-IP5/IP7, which is essential for virulence of Cryptococcus neoformans. Cryptococcal Kcs1 converts IP6 to PP-IP5/IP7, but the kinase converting IP5 to IP6 is unknown. Deletion of a putative IP5 kinase-encoding gene (IPK1) alone (ipk1?), and in combination with KCS1 (ipk1?kcs1?), profoundly reduced virulence in mice. However, deletion of KCS1 and IPK1 had a greater impact on virulence attenua...
Phosphatidylinositol 4-kinases: Function, structure, and inhibition

International Nuclear Information System (INIS)

Boura, Evzen; Nencka, Radim

2015-01-01

The phosphatidylinositol 4-kinases (PI4Ks) synthesize phosphatidylinositol 4-phosphate (PI4P), a key member of the phosphoinositide family. PI4P defines the membranes of Golgi and trans-Golgi network (TGN) and regulates trafficking to and from the Golgi. Humans have two type II PI4Ks (α and β) and two type III enzymes (α and β). Recently, the crystal structures were solved for both type II and type III kinase revealing atomic details of their function. Importantly, the type III PI4Ks are hijacked by +RNA viruses to create so-called membranous web, an extensively phosphorylated and modified membrane system dedicated to their replication. Therefore, selective and potent inhibitors of PI4Ks have been developed as potential antiviral agents. Here we focus on the structure and function of PI4Ks and their potential in human medicine
Phosphatidylinositol 4-kinases: Function, structure, and inhibition

Energy Technology Data Exchange (ETDEWEB)

Boura, Evzen, E-mail: boura@uochb.cas.cz; Nencka, Radim, E-mail: nencka@uochb.cas.cz

2015-10-01

The phosphatidylinositol 4-kinases (PI4Ks) synthesize phosphatidylinositol 4-phosphate (PI4P), a key member of the phosphoinositide family. PI4P defines the membranes of Golgi and trans-Golgi network (TGN) and regulates trafficking to and from the Golgi. Humans have two type II PI4Ks (α and β) and two type III enzymes (α and β). Recently, the crystal structures were solved for both type II and type III kinase revealing atomic details of their function. Importantly, the type III PI4Ks are hijacked by +RNA viruses to create so-called membranous web, an extensively phosphorylated and modified membrane system dedicated to their replication. Therefore, selective and potent inhibitors of PI4Ks have been developed as potential antiviral agents. Here we focus on the structure and function of PI4Ks and their potential in human medicine.
A 6-bit 4 GS/s pseudo-thermometer segmented CMOS DAC

Science.gov (United States)

Yijun, Song; Wenyuan, Li

2014-06-01

A 6-bit 4 GS/s, high-speed and power-efficient DAC for ultra-high-speed transceivers in 60 GHz band millimeter wave technology is presented. A novel pseudo-thermometer architecture is proposed to realize a good compromise between the fast conversion speed and the chip area. Symmetrical and compact floor planning and layout techniques including tree-like routing, cross-quading and common-centroid method are adopted to guarantee the chip is fully functional up to near-Nyquist frequency in a standard 0.18 μm CMOS process. Post simulation results corroborate the feasibility of the designed DAC, which canperform good static and dynamic linearity without calibration. DNL errors and INL errors can be controlled within ±0.28 LSB and ±0.26 LSB, respectively. SFDR at 4 GHz clock frequency for a 1.9 GHz near-Nyquist sinusoidal output signal is 40.83 dB and the power dissipation is less than 37 mW.
A 6-bit 4 GS/s pseudo-thermometer segmented CMOS DAC

International Nuclear Information System (INIS)

Song Yijun; Li Wenyuan

2014-01-01

A 6-bit 4 GS/s, high-speed and power-efficient DAC for ultra-high-speed transceivers in 60 GHz band millimeter wave technology is presented. A novel pseudo-thermometer architecture is proposed to realize a good compromise between the fast conversion speed and the chip area. Symmetrical and compact floor planning and layout techniques including tree-like routing, cross-quading and common-centroid method are adopted to guarantee the chip is fully functional up to near-Nyquist frequency in a standard 0.18 μm CMOS process. Post simulation results corroborate the feasibility of the designed DAC, which canperform good static and dynamic linearity without calibration. DNL errors and INL errors can be controlled within ±0.28 LSB and ±0.26 LSB, respectively. SFDR at 4 GHz clock frequency for a 1.9 GHz near-Nyquist sinusoidal output signal is 40.83 dB and the power dissipation is less than 37 mW. (semiconductor integrated circuits)
Significant sE-Selectin levels reduction after 6 months of anti-TNF-α therapy in non-diabetic patients with moderate-to-severe psoriasis.

Science.gov (United States)

Genre, Fernanda; Armesto, Susana; Corrales, Alfonso; López-Mejías, Raquel; Remuzgo-Martínez, Sara; Pina, Trinitario; Ubilla, Begoña; Mijares, Verónica; Martín-Varillas, José Luis; Rueda-Gotor, Javier; Portilla, Virginia; Dierssen-Sotos, Trinidad; González-López, Marcos Antonio; González-Vela, María Del Carmen; Blanco, Ricardo; Llorca, Javier; Hernández, José Luis; González-Gay, Miguel Ángel

2017-12-01

Psoriasis patients have high risk of atherosclerosis, characterized by endothelial dysfunction. We aimed to study the association of the endothelial activation biomarkers monocyte chemoattractant protein 1 (MCP-1), soluble (s) E-selectin and P-selectin with disease activity and severity in psoriasis patients treated with anti-TNF-α therapy. Also, to evaluate the relationship of metabolic syndrome features with these biomarkers and the effect of anti-TNF-α therapy on these molecules. Twenty-nine consecutive non-diabetic patients with moderate-to-severe psoriasis who underwent 6 months of anti-TNF-α-adalimumab therapy were studied. Metabolic and clinical evaluation was performed prior to anti-TNF-α treatment (time 0) and 6 months later. MCP-1, sE-selectin and sP-selectin serum levels were determined by ELISA. Dyslipidemic and obese patients showed higher MCP-1 levels at month 6 from the onset of anti-TNF-α therapy (p = .05 and .01, respectively). sE-selectin positively correlated with pro-inflammatory molecules such as asymmetric dimethylarginine, sP-selectin and resistin at baseline and month 6 (p psoriasis. Adalimumab therapy led to a reduction in sE-selectin levels, supporting the beneficial effect of anti-TNF-α therapy on mechanisms associated with the development of atherosclerosis in psoriasis.
Comparative action spectra for pyrimidine dimer formation in Cloudman S91 mouse melanoma and EMT6 mouse mammary carcinoma cells

Energy Technology Data Exchange (ETDEWEB)

Hill, H Z [New Jersey, Medical School, Newark (USA); Setlow, R B [Brookhaven National Lab., Upton, NY (USA)

1982-05-01

Pyrimidine dimer formation in melanotic mouse melanoma cells, Cloudman S91H-, and in mouse mammary carcinoma cells, EMT6, was compared as a function of wavelength by irradiating equal numbers of cells from the two cell lines simultaneously. More dimers were formed in EMT6 than in S91H- by light of wavelengths less than 289nm, while light of higher wavelengths caused equivalent dimer formation, as measured by the Micrococcus luteus UV-endonuclease assay. The cells of S91H- are lightly melanotic, yet shielding at lower wavelengths is considerable. It is speculated that melanin pigmentation arose by selection during an evolutionary period when UV-C light reaching the earth's surface was significantly greater than it is today.
Some features and results of thermal neutron background measurements with the [ZnS(Ag)+{sup 6}LiF] scintillation detector

Energy Technology Data Exchange (ETDEWEB)

Kuzminov, V.V.; Alekseenko, V.V.; Barabanov, I.R.; Etezov, R.A.; Gangapshev, A.M.; Gavrilyuk, Yu.M.; Gezhaev, A.M.; Kazalov, V.V. [Institute for Nuclear Research, 117312 Moscow (Russian Federation); Khokonov, A.Kh. [Kh.M. Berbekov Kabardino-Balkarian State University, 360004 (Russian Federation); Panasenko, S.I. [V.N. Karazin Kharkiv National University, 61022 Kharkiv (Ukraine); Ratkevich, S.S., E-mail: ssratk@gmail.com [V.N. Karazin Kharkiv National University, 61022 Kharkiv (Ukraine)

2017-01-01

Features of a thermal neutron test detector with thin scintillator [ZnS(Ag)+{sup 6}LiF] are described. Background of the detector and its registration efficiency were defined as a result of measurements. The thermal neutron flux at different locations, and for different conditions around the Baksan Neutrino Observatory are reported. - Highlights: • This paper describes tests of a thermal neutron detector based on a thin scintillator ZnS(Ag) with {sup 6}LiF. • The results are a measurement of the background neutron flux from the detector and the detector's efficiency. • The thermal neutron flux at different locations, and for different conditions around the Baksan Neutrino Observatory are reported.
Summation of the high orders of perturbation theory for the parity nonconcerving E1-amplitude of 6s-7s-transition in Caesium atom

International Nuclear Information System (INIS)

Dzyuba, V.A.; Flambaum, V.V.; Sushkov, O.P.

1989-01-01

Three dominating subsequences of diagrams in the correlation correction to amplitude are summed: screening of the electron-electron interaction, particle-hole interaction and the iterations of the self-energy. The result of calculations is: E1(6s-7s)=(0.91±0.01)x10 -11 iea B (-Q W /N), Q W is the weak charge of nucleus, N is the number of neutrons. The calculations give the following value of the Weinberg angle: sin 2 Θ W =0.226±0.007(exp.)±0.004(theor.). 30 refs.; 7 figs.; 3 tabs
The first quinary rare earth thiophosphates. Cs{sub 5}Ln{sub 3}X{sub 3}(P{sub 2}S{sub 6}){sub 2}(PS{sub 4}) (Ln = La, Ce, X = Br, Cl) and the quasi-quaternary Cs{sub 10}Y{sub 4}Cl{sub 10}(P{sub 2}S{sub 6}){sub 3}

Energy Technology Data Exchange (ETDEWEB)

Schoop, Leslie Mareike; Eger, Roland; Nuss, Juergen; Pielnhofer, Florian [Max Planck Institute for Solid State Research, Stuttgart (Germany); Lotsch, Bettina Valeska [Max Planck Institute for Solid State Research, Stuttgart (Germany); Nanosystems Initiative Munich (NIM) and Center for Nanoscience, Muenchen (Germany)

2017-12-13

We report the first examples of quinary rare earth thiophosphates with a fully ordered cation and anion distribution, Cs{sub 5}Ln{sub 3}X{sub 3}(P{sub 2}S{sub 6}){sub 2}(PS{sub 4}), (Ln = La, Ce and X = Br, Cl) as well as the quasi-quaternary Cs{sub 10}Y{sub 4}Cl{sub 10}(P{sub 2}S{sub 6}){sub 3}. These four new compounds crystallize in three different, unknown structure types. The yellowish, transparent, brittle Cs{sub 5}Ce{sub 3}Br{sub 3}(P{sub 2}S{sub 6}){sub 2}(PS{sub 4}) crystallizes in the orthorhombic space group Pnma (no. 62) with a = 13.276(3), b = 14.891(3), c = 19.593(4) Aa, and V = 3873(1) Aa{sup 3} in a novel structure type. Colorless crystals of Cs{sub 5}La{sub 3}Br{sub 3}(P{sub 2}S{sub 6}){sub 2}(PS{sub 4}) and Cs{sub 5}La{sub 3}Cl{sub 3}(P{sub 2}S{sub 6}){sub 2}(PS{sub 4}) are isotypic and were obtained in the monoclinic space group P2{sub 1}/m (no. 11) with a = 9.715(2), b = 14.310(3), c = 13.685(3) Aa, β = 100.16(3) and V = 1873(1) Aa{sup 3} and a = 9.513(2), b = 14.182(3), c = 13.699(3) Aa, β = 99.39(3) and V = 1823(1) Aa{sup 3}, respectively. Both structures contain isolated hexathiohypodiphosphate(IV) [P{sub 2}S{sub 6}]{sup 4-} and thiophosphate [PS{sub 4}]{sup 3-} units that are arranged alternately in layers. Cs{sub 10}Y{sub 4}Cl{sub 10}(P{sub 2}S{sub 6}){sub 3} crystallizes in colorless transparent platelets in the orthorhombic space group Pnnm (no. 58) with a = 13.153(3), b = 28.964(6), c = 7.780(2) Aa, and V = 2964(1) Aa{sup 3}. The structure is composed of isolated [P{sub 4/2}S{sub 6}]{sup 4-} octahedra containing four half occupied P positions surrounded octahedrally by sulfur. We show with Raman scattering that this disordered thiophosphate anion shows a Raman spectrum that is distinct from spectra published for other literature-known thiophosphate anions. (copyright 2017 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)
Critical currents and flux-pinning properties in PbMo6S8 superconductors

International Nuclear Information System (INIS)

Noto, K.; Hamasaki, K.; Komata, T.; Saito, T.; Watanabe, K.; Yamashita, T.

1986-01-01

We report on recent investigations of the fabrication of PbMo 6 S 8 tapes prepared using an electro-plating and diffusion technique. Measurement of critical currents was carried out in either 16.5 T superconducting magnet, or 20.5 T (HM-3) and 23 T (HM-2) hybrid magnets in High Field Laboratory for Superconducting Materials RIISOM, Tohoku University in Japan. After optimal reaction the critical temperature measured by a resistive method reaches about 14.5 K, and a transition width was less than 0.5 K. Critical current densities are relatively high in a low magnetic field, and reached 1X10 4 A/cm 2 in a 15 T magnetic field at 4.2 K. However, J /SUB c/ 's in a strong magnetic field above 15 T are still insufficient for practical applications. In some of these samples pinning force densities were found to obey a simple scaling law, and in most cases the scaling is not obey. Poor J /SUB c/ -B characteristics in a strong magnetic field may be due to inhomogeneities of this compound
Safety test No. S-6, launch pad abort sequential test Phase II: solid propellant fire

International Nuclear Information System (INIS)

Snow, E.C.

1975-08-01

In preparation for the Lincoln Laboratory's LES 8/9 space mission, a series of tests was performed to evaluate the nuclear safety capability of the Multi-Hundred Watt (MHW) Radioisotope Thermoelectric Generator (RTG) to be used to supply power for the satellite. One such safety test is Test No. S-6, Launch Pad Abort Sequential Test. The objective of this test was to subject the RTG and its components to the sequential environments characteristic of a catastrophic launch pad accident to evaluate their capability to contain the 238 PuO 2 fuel. This sequence of environments was to have consisted of the blast overpressure and fragments, followed by the fireball, low velocity impact on the launch pad, and solid propellant fire. The blast overpressure and fragments were subsequently eliminated from this sequence. The procedures and results of Phase II of Test S-6, Solid Propellant Fire are presented. In this phase of the test, a simulant Fuel Sphere Assembly (FSA) and a mockup of a damaged Heat Source Assembly (HSA) were subjected to single proximity solid propellant fires of approximately 10-min duration. Steel was introduced into both tests to simulate the effects of launch pad debris and the solid rocket motor (SRM) casing that might be present in the fire zone. (TFD)
(3R,6R,12R,20S,24S-3,6,12-Triacetyl-20,24-epoxydammarane-3,6,12,25-tetraol

Directory of Open Access Journals (Sweden)

Qing-Guo Meng

2011-01-01

Full Text Available The title compound, C36H58O8, was prepared from 20(S-protopanaxatriol, which was degraded from Panax quinquefolium saponin with sodium in glycerine, extracted and seperated by flash chromatography. Three six-membered rings are in chair conformations, the five-membered ring is in an envelope form and the tetrahydrofuran ring has a conformation intermediate between half-chair and envelope. In the crystal, molecules are linked by O—H...O hydrogen bonds, and C—H...O contacts also occur. The absolute structure was assigned on the basis of the synthesis.
Plasticity of the PAS domain and a potential role for signal transduction in the histidine kinase DcuS

NARCIS (Netherlands)

Etzkorn, M.; Kneuper, H.; Dünnwald, P.; Vijayan, V.; Krämer, J.; Griesinger, C.; Becker, S.; Unden, G.; Baldus, M.

2008-01-01

The mechanistic understanding of how membrane-embedded sensor kinases recognize signals and regulate kinase activity is currently limited. Here we report structure-function relationships of the multidomain membrane sensor kinase DcuS using solidstate NMR, structural modeling and mutagenesis.
Time dependent analysis and amplitude analysis of B0 → Ks0Ks0Ks0 decays with the BaBar experiment

International Nuclear Information System (INIS)

Sitt, S.

2010-09-01

Two independent analyses of the decay channel B 0 → K s 0 K s 0 K s 0 have been performed on a data sample of 468 millions of BB-bar pairs recorded by the BABAR detector at the PEP-II B factory at SLAC National Laboratory. The first analysis is a phase-space-integrated time-dependent analysis to extract the CP violation parameters S and C from the two sub-modes B 0 → 3K s 0 (π + π - ) and B 0 → 2K s 0 (π + π - )K s 0 (π 0 π 0 ) simultaneously and to compare them to the charmonium measurements. The result is: S = -0.94+0.24-0.21±0.06 and C = -0.17+0.18-0.18±0.04, where the first uncertainty is statistical and the second is systematical. The result is compatible within uncertainties with the Standard Model prediction and the charmonium modes measurements. The second analysis is a time-integrated amplitude (or Dalitz plot) analysis to extract the inclusive branching fraction and the branching fractions of the resonant modes that contribute to the decay. The result of the first amplitude analysis of this decay channel is: B(B 0 → K s 0 K s 0 K s 0 ) equal to (6.18 ± 0.47 ± 0.14 ± 0.06)*10 -6 ; B(B 0 → f 0 (980)K s 0 with f 0 (980) → K s 0 K s 0 ) equal to (2.69+1.25-1.18±0.35±1.87)*10 -6 ; B(B 0 → f 0 (1710)K s 0 with f 0 (1710) → K s 0 K s 0 ) equal to (0.50+0.46-0.23±0.04±0.12)*10 -6 ; B(B 0 → f 2 (2010)K s 0 with f 2 (2010) → K s 0 K s 0 ) equal to (0.54+0.21-0.20±0.03±0.44)*10 -6 ; B(B 0 → Nonresonant with K s 0 K s 0 K s 0 ) equal to (13.31+2.23-2.30±0.55±2.77)*10 -6 ; B(B 0 → χ c0 K s 0 with χ c0 → K s 0 K s 0 ) equal to (0.46+0.25-0.16±0.01±0.19)*10 -6 ; where the first uncertainty is statistical, the second is systematical and the third corresponds to Dalitz plot model uncertainties. No significant contribution of the controversial f X (1500) resonance has been found. (author)
Secretion of soluble vascular endothelial growth factor receptor 1 (sVEGFR1/sFlt1 requires Arf1, Arf6, and Rab11 GTPases.

Directory of Open Access Journals (Sweden)

Jae-Joon Jung

Full Text Available The soluble form of vascular endothelial growth factor receptor 1 (sVEGFR-1/sFlt1 is generated by alternative splicing of the FLT1 gene. Secretion of sFlt1 from endothelial cells plays an important role in blood vessel sprouting and morphogenesis. However, excess sFlt1 secretion is associated with diseases such as preeclampsia and chronic kidney disease. To date, the secretory transport process involved in the secretion of sFlt1 is poorly understood. In the present study, we investigated the itinerary of sFlt1 trafficking along the secretory pathway. To understand the timecourse of sFlt1 secretion, endothelial cells stably expressing sFlt1 were metabolically radiolabeled with [(35S]-methionine and cysteine. Our results indicate that after initial synthesis the levels of secreted [(35S]-sFlt1 in the extracellular medium peaks at 8 hours. Treatment with brefeldin A (BFA, a drug which blocks trafficking between the endoplasmic reticulum (ER and the Golgi complex, inhibited extracellular release of sFlt1 suggesting that ER to Golgi and intra-Golgi trafficking of sFlt1 are essential for its secretion. Furthermore, we show that ectopic expression of dominant-negative mutant forms of Arf1, Arf6, and Rab11 as well as siRNA-mediated knockdown of these GTPases block secretion of sFlt1 during normoxic and hypoxic conditions suggesting role for these small GTPases. This work is the first to report role of regulatory proteins involved in sFlt1 trafficking along the secretory pathway and may provide insights and new molecular targets for the modulation of sFlt-1 release during physiological and pathological conditions.
Increased Plasma Cathepsin S at the Time of Percutaneous Transluminal Angioplasty is Associated with 6-Months’ Restenosis of the Femoropopliteal Artery

Directory of Open Access Journals (Sweden)

Mijovski Mojca Bozic

2018-01-01

Full Text Available Background: We tested the hypothesis that increased levels of cathepsin S and decreased levels of cystatin C in plasma at the time of percutaneous transluminal angioplasty (PTA are associated with the occurrence of 6-months’ restenosis of the femoropopliteal artery (FPA. Methods: 20 patients with restenosis and 24 matched patients with patent FPA after a 6-months follow-up were in - cluded in this study. They all exhibited disabling claudication or critical limb ischemia and had undergone technically successful PTA. They were all receiving statins and ACE in hi - bitors (or angiotensin II receptor antagonist before the PTA and the therapy did not change throughout the observational period. Plasma concentrations of C-reactive protein were < 10 mg/L and of creatinine within the reference range at the time of the PTA. Plasma concentration and activity of cathepsin S, together with its potent inhibitor cystatin C, were measured the day before and the day after the PTA. Results: The increased plasma concentration and activity of cathepsin S at the time of PTA was associated with the occurrence of 6-months’ restenosis of FPA, independently of established risk factors (lesion complexity, infrapopliteal run-off vessels, type of PTA, age, gender, smoking, diabetes, lipids and of cystatin C. Plasma cystatin C concentration was not associated with restenosis and did not correlate with cathepsin S activity and concentration in the plasma. Conclusion: Increased level of plasma cathepsin S at the time of PTA is associated with 6-months’ restenosis of PTA, independently of established risk factors.
V0 production in p+A collisions at √(s)=41.6 GeV

International Nuclear Information System (INIS)

Abt, I.; Kisel, I.; Adams, M.; Cruse, C.; Ehret, K.; Funcke, M.; Schwenninger, B.; Wegener, D.; Agari, M.; Bauer, C.; Braeuer, M.; Hofmann, W.; Jagla, T.; Knoepfle, K.T.; Pleier, M.A.; Reeves, K.; Sanchez, F.; Schmelling, M.; Schwingenheuer, B.; Sciacca, F.; Albrecht, H.; Aplin, S.J.; Bagaturia, Y.; Egorytchev, V.; Emeliyanov, D.; Flammer, J.; Goloubkov, D.; Golubkov, Y.; Hohlmann, M.; Lewendel, B.; Lomonosov, B.; Masciocchi, S.; Medinnis, M.; Mevius, M.; Michetti, A.; Negodaev, M.; Noerenberg, M.; Nunez Pardo de Vera, M.T.; Padilla, C.; Ressing, D.; Riu, I.; Rybnikov, V.; Schmidt, B.; Schwarz, A.S.; Soezueer, L.; Somov, A.; Somov, S.; Spengler, J.; Wurth, R.; Aleksandrov, A.; Bohm, G.; Gellrich, A.; Hernandez, J.M.; Mankel, R.; Nowak, S.; Schreiner, A.; Schwanke, U.; Walter, M.; Amaral, V.; Amorim, A.; Bastos, J.; Batista, J.; Carvalho, J.; Silva, L.; Wolters, H.; Aushev, V.; Prystupa, S.; Pugatch, V.; Vassiliev, Yu.; Balagura, V.; Bobchenko, B.; Bogatyrev, A.; Danilov, M.; Essenov, S.; Fominykh, B.; Golutvin, A.; Gouchtchine, O.; Guilitsky, Yu.; Igonkina, O.; Khasanov, F.; Kvaratskheliia, T.; Matchikhilian, I.; Mikhailov, Yu.; Mizuk, R.; Popov, V.; Rostovtseva, I.; Tikhomirov, I.; Titov, M.; Zaitsev, Yu.; Zhelezov, A.; Bargiotti, M.; Bertin, A.; Bruschi, M.; De Castro, S.; Fabbri, L.; Faccioli, P.; Giacobbe, B.; Grimaldi, F.; Massa, I.; Piccinini, M.; Poli, M.; Semprini-Cesari, N.; Spighi, R.; Villa, M.; Vitale, A.; Zoccoli, A.; Barsukova, O.; Belkov, A.; Belkov, Ar.; Belotelov, I.; Golutvin, I.; Karpenko, N.; Kiryushin, Yu.; Lanyov, A.; Solunin, S.; Bauer, T.S.; Hulsbergen, W.; Sbrizzi, A.; Boecker, M.; Buchholz, P.; Husemann, U.; Keller, S.; Walenta, A.H.; Werthenbach, U.; Bruinsma, M.; Ouchrif, M.; Buran, T.; Danielsen, K.M.; Ould-Saada, F.; Pylypchenko, Y.; Conde, P.; Dam, M.; Groth-Jensen, J.; Hansen, J.D.; Klinkby, E.; Muresan, R.; Petersen, B.A.; Xella-Hansen, S.; Deppe, H.; Dreis, H.B.; Eisele, F.; Feuerstack-Raible, M.; Gradl, S.; Gradl, W.; Hott, T.; Kessler, J.; Krauss, C.; Rick, H.; Uwer, U.; Dong, X.; Jiang, C.; Zheng, Z.; Garrido, Ll.; Peralta, D.; Glaess, J.; Maenner, R.; Wurz, A.; Gorbounov, I.; Zeuner, T.; Gorisek, A.; Kupper, S.; Pestotnik, R.; Staric, M.; Zivko, T.; Goulart, D.C.; Schwartz, A.J.; Ispiryan, M.; Lau, K.; Pyrlik, J.; Subramania, H.S.; Kapitza, H.; Symalla, M.; Eldik, C. van; Karabekyan, S.; Pernack, R.; Schroeder, H.; Zimmermann, R.; Kolanoski, H.; Kruecker, D.; Lohse, T.; Medin, G.; Nedden, M. zur; Stegmann, C.; Korpar, S.; Kreuzer, P.; Krizan, P.; Stanovnik, A.; Pose, D.; Robmann, P.; Shuvalov, S.; Spiridonov, A.; Tsakov, I.; Vukotic, I.; Wahlberg, H.; Wang, J.J.; Zavertyaev, M.

2009-01-01

Inclusive doubly differential cross sections d 2 σ pA /dx F dp T 2 as a function of Feynman-x(x F ) and transverse momentum (p T ) for the production of K S 0 , Λ and anti Λ in proton-nucleus interactions at 920 GeV are presented. The measurements were performed by HERA-B in the negative x F range (-0.12 F T =1.6 GeV/c. Results for three target materials: carbon, titanium and tungsten are given. The ratios of production cross sections are presented and discussed. The Cronin effect is clearly observed for all three V 0 species. The atomic number dependence is parameterized as σ pA =σ pN .A α where σ pN is the proton-nucleon cross section. The measured values of α are all near one. The results are compared with EPOS 1.67 and PYTHIA 6.3. EPOS reproduces the data to within ∼20% except at very low transverse momentum. (orig.)
Expression, purification, crystallization and preliminary diffraction studies of the mammalian DAG kinase homologue YegS from Escherichia coli

International Nuclear Information System (INIS)

Bakali H, M. Amin; Nordlund, Pär; Hallberg, B. Martin

2006-01-01

The overexpression, crystallization and preliminary diffraction analysis of E. coli YegS are reported. yegS is a gene encoding a 32 kDa cytosolic protein with unknown function but with strong sequence homology to a family of structurally uncharacterized eukaryotic non-protein kinases: diacylglycerol kinases, sphingosine kinases and ceramide kinases. Here, the overexpression, crystallization and preliminary diffraction analysis of Escherichia coli YegS are reported. The crystals belong to space group P2 1 , with unit-cell parameters a = 42.4, b = 166.1, c = 48.5 Å, β = 96.97°. The presence of a dimer in the asymmetric unit was estimated to give a Matthews coefficient (V M ) of 2.5 Å 3 Da −1 and a solvent content of 50.8%(v/v). Single-wavelength diffraction data were collected to a resolution of 1.9 Å using synchrotron radiation

Construction of an all-solid-state artificial Z-scheme system consisting of Bi2WO6/Au/CdS nanostructure for photocatalytic CO2 reduction into renewable hydrocarbon fuel

Science.gov (United States)

Wang, Meng; Han, Qiutong; Li, Liang; Tang, Lanqin; Li, Haijin; Zhou, Yong; Zou, Zhigang

2017-07-01

An all-solid-state Bi2WO6/Au/CdS Z-scheme system was constructed for the photocatalytic reduction of CO2 into methane in the presence of water vapor. This Z-scheme consists of ultrathin Bi2WO6 nanoplates and CdS nanoparticles as photocatalysts, and a Au nanoparticle as a solid electron mediator offering a high speed charge transfer channel and leading to more efficient spatial separation of electron-hole pairs. The photo-generated electrons from the conduction band (CB) of Bi2WO6 transfer to the Au, and then release to the valence band (VB) of CdS to recombine with the holes of CdS. It allows the electrons remaining in the CB of CdS and holes in the VB of Bi2WO6 to possess strong reduction and oxidation powers, respectively, leading the Bi2WO6/Au/CdS to exhibit high photocatalytic reduction of CO2, relative to bare Bi2WO6, Bi2WO6/Au, and Bi2WO6/CdS. The depressed hole density on CdS also enhances the stability of the CdS against photocorrosion.
101 sõbraga leedi / Jaan Mettik

Index Scriptorium Estoniae

Mettik, Jaan

2007-01-01

Virve Roosti toalilleraamatutest. Vt. samas: Kuidas sündis Virve Roosti viimane teos "Toalilleraamat. 101 rohelist sõpra?" ; Miks peab lillesõbra raamaturiiulis olema vähemalt üks Virve Roosti toalilleraamat?
High level waste storage tank farms/242-A evaporator Standards/Requirements Identification Document (S/RID), Volume 6

Energy Technology Data Exchange (ETDEWEB)

1994-04-01

The High-Level Waste Storage Tank Farms/242-A Evaporator Standards/Requirements Identification Document (S/RID) is contained in multiple volumes. This document (Volume 6) outlines the standards and requirements for the sections on: Environmental Restoration and Waste Management, Research and Development and Experimental Activities, and Nuclear Safety.
High level waste storage tank farms/242-A evaporator Standards/Requirements Identification Document (S/RID), Volume 6

International Nuclear Information System (INIS)

1994-04-01

The High-Level Waste Storage Tank Farms/242-A Evaporator Standards/Requirements Identification Document (S/RID) is contained in multiple volumes. This document (Volume 6) outlines the standards and requirements for the sections on: Environmental Restoration and Waste Management, Research and Development and Experimental Activities, and Nuclear Safety
Legal medical consideration of Alzheimer’s disease patients’ dysgraphia and cognitive dysfunction a 6 month follow up

Directory of Open Access Journals (Sweden)

Onofri E

2016-03-01

Full Text Available Emanuela Onofri,1 Marco Mercuri,1 Trevor Archer,2 Max Rapp-Ricciardi,2 Serafino Ricci1 1Department of Anatomy, Histology, Legal Medicine and Orthopaedics, Sapienza University of Rome, Rome, Italy; 2Department of Psychology, University of Gothenburg, Gothenburg, Sweden Background: The purpose of this study was to investigate the ability of Alzheimer’s disease (AD patients to express intentions and desires, and their decision-making capacity. This study examines the findings from a 6-month follow-up of our previous results in which 30 patients participated. Materials and methods: The patient’s cognition was examined by conducting the tests of 14 questions and letter-writing ability over a period of 19 days, and it was repeated after 6 months. The difference between these two cognitive measures (PQ1 before–PQ2 before, tested previously and later the writing test, was designated DΔ before. The test was repeated after 6 months, and PQ1 after–PQ2 after was designated DΔ after. Results: Several markedly strong relationships between dysgraphia and other measures of cognitive performance in AD patients were observed. The most aged patients (over 86 years, despite less frequency, maintain the cognitive capacity manifested in the graphic expressions. A document, written by an AD patient presents an honest expression of the patient’s intention if that document is legible, clear, and comprehensive. Conclusion: The identification of impairment/deficits in writing and cognition during different phases of AD may facilitate the understanding of disease progression and identify the occasions during which the patient may be considered sufficiently lucid to make decisions. Keywords: cognition, intentions, unfit to plead, consent
Warped AdS{sub 6}×S{sup 2} in Type IIB supergravity II: global solutions and five-brane webs

Energy Technology Data Exchange (ETDEWEB)

D’Hoker, Eric; Gutperle, Michael; Uhlemann, Christoph F. [Mani L. Bhaumik Institute for Theoretical Physics,Department of Physics and Astronomy, University of California Los Angeles,475 Portola Plaza, Los Angeles, CA 90095 (United States)

2017-05-23

Motivated by the construction of holographic duals to five-dimensional superconformal quantum field theories, we obtain global solutions to Type IIB supergravity invariant under the superalgebra F(4) on a space-time of the form AdS{sub 6}×S{sup 2} warped over a two-dimensional Riemann surface Σ. In earlier work, the general local solutions were expressed in terms of two locally holomorphic functions A{sub ±} on Σ and global solutions were sketched when Σ is a disk. In the present paper, the physical regularity conditions on the supergravity fields required for global solutions are implemented on A{sub ±} for arbitrary Σ. Global solutions exist only when Σ has a non-empty boundary ∂Σ. The differentials ∂A{sub ±} are allowed to have poles only on ∂Σ and each pole corresponds to a semi-infinite (p,q) five-brane. The construction for the disk is carried out in detail and the conditions for the existence of global solutions are articulated for surfaces with more than one boundary and higher genus.
Validation of MATRA-S Low Flow Predictions Using PNL 2x6 Mixed Convection Test

Energy Technology Data Exchange (ETDEWEB)

Seo, Kyong-Won; Kwon, Hyuk; Kim, Seong-Jin; Hwang, Dae-Hyun [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

2015-10-15

The MATRA-S, a subchannel analysis code has been used to thermal-hydraulic design of SMART core. As the safety enhancement is getting important more and more, some features of the MATRA-S code are required to be validated in order to be applied to nonnominal operating conditions in addition to its applicability to reactor design under normal operating conditions. The MATRA-S code has two numerical schemes, SCHEME for implicit application and XSCHEM for explicit one. The implicit scheme had been developed under assumptions that the axial flow is larger enough than the crossflow. Under certain conditions, especially low flow and low pressure operating conditions, this implicit SCHEME oscillates or becomes unstable numerically and then MATRA-S fails to obtain good solution. These demerits were known as common in implicit schemes of many COBRA families. Efforts have been exerted to resolve these limitations in SCHEME of the MATRA-S such as a once through marching scheme against the multi-pass marching scheme and an adaptive multi-grid method. These remedies can reduce the numerically unstable range for SCHEME but some unstable regions still remain. The XSCHEM, an explicit scheme of MATRA-S was validated using the PNL 2x6 rod bundle flow transient test. The explicit scheme agreed with implicit scheme for steady state calculations. And it showed its capability to predict low flow conditions such as negative flow and recirculation flow.
Toxicological evaluation of 6'-sialyllactose (6'-SL) sodium salt.

Science.gov (United States)

Gurung, Rit Bahadur; Kim, Dae Hee; Kim, Lila; Lee, Albert W; Wang, Zhenhua; Gao, Yonglin

2018-06-01

We performed a series of toxicity studies on the safety of 6'-sialyllactose (6'-SL) sodium salt as a food ingredient. 6'-SL sodium salt, up to a maximum dose of 5000 μg/plate, did not increase the number of revertant colonies in five strains of Salmonella typhimurium in the presence or absence of S9 metabolic activation. A chromosomal aberration assay (using Chinese hamster lung cells) found no clastogenic effects at any concentration of 6'-SL sodium salt in the presence or absence of S9 metabolic activation. An in vivo bone marrow micronucleus test in Kunming mice showed no clastogenic activities with 6'-SL sodium salt doses up to 2000 mg/kg body weight (bw). In an acute toxicity study, the mean lethal dose of 6'-SL sodium salt was greater than 20 g/kg bw in rats. In a 13-week subchronic toxicity investigation, no effects were found at doses up to 5.0 g/kg bw of 6'-SL sodium salt in food consumption, body weight, clinical signs, blood biochemistry and hematology, urinalysis, or ophthalmic and histological macroscopic examination of organs. The no-observed-adverse-effect level (NOAEL) was 5.0 g/kg bw/day in rats. Copyright © 2018 Elsevier Inc. All rights reserved.
Rational synthesis of high nuclearity Mo/Fe/S clusters: the reductive coupling approach in the convenient synthesis of (Cl(4)-cat)(2)Mo(2)Fe(6)S(8)(PR(3))(6) [R = Et, (n)Pr, (n)Bu] and the new [(Cl(4)-cat)(2)Mo(2)Fe(2)S(3)O(PEt(3))(3)Cl]-1/2(Fe(PEt(3))(2)(MeCN)(4)) and (Cl(4)-cat)(2)Mo(2)Fe(3)S(5)(PEt(3))(5) clusters.

Science.gov (United States)

Han, J; Koutmos, M; Ahmad, S A; Coucouvanis, D

2001-11-05

A general method for the synthesis of high nuclearity Mo/Fe/S clusters is presented and involves the reductive coupling of the (Et(4)N)(2)[(Cl(4)-cat)MoOFeS(2)Cl(2)] (I) and (Et(4)N)(2)[Fe(2)S(2)Cl(4)] (II) clusters. The reaction of I and II with Fe(PR(3))(2)Cl(2) or sodium salts of noncoordinating anions such as NaPF(6) or NaBPh(4) in the presence of PR(3) (R = Et, (n)Pr, or (n)Bu) affords (Cl(4)-cat)(2)Mo(2)Fe(6)S(8)(PR(3))(6) [R = Et (IIIa), (n)Pr (IIIb), (n)Bu (IIIc)], Fe(6)S(6)(PEt(3))(4)Cl(2) (IV) and (PF(6))[Fe(6)S(8)(P(n)Pr(3))(6)] (V) as byproducts. The isolation of (Et(4)N)[Fe(PEt(3))Cl(3)] (VI), NaCl, and SPEt(3) supports a reductive coupling mechanism. Cluster IV and V also have been synthesized by the reductive self-coupling of compound II. The reductive coupling reaction between I and II by PEt(3) and NaPF(6) in a 1:1 ratio produces the (Et(4)N)(2)[(Cl(4)-cat)Mo(L)Fe(3)S(4)Cl(3)] clusters [L = MeCN (VIIa), THF (VIIb)]. The hitherto unknown [(Cl(4)-cat)(2)Mo(2)Fe(2)S(3)O(PEt(3))(3)Cl](+) cluster (VIII) has been isolated as the 2:1 salt of the (Fe(PEt(3))(2)(MeCN)(4))(2+) cation after the reductive self-coupling reaction of I in the presence of Fe(PEt(3))(2)Cl(2). Cluster VIII crystallizes in the monoclinic space group P2(1)/c with a = 11.098(3) A, b = 22.827(6) A, c = 25.855(6) A, beta = 91.680(4) degrees, and Z = 4. The formal oxidation states of metal atoms in VIII have been assigned as Mo(III), Mo(IV), Fe(II), and Fe(III) on the basis of zero-field Mössbauer spectra. The Fe(PEt(3))(2)(MeCN)(4) cation of VIII is also synthesized independently, isolated as the BPh(4)(-) salt (IX), and has been structurally characterized. The reductive coupling of compound I also affords in low yield the new (Cl(4)-cat)(2)Mo(2)Fe(3)S(5)(PEt(3))(5) cluster (X) as a byproduct. Cluster X crystallizes in the monoclinic space group P2(1)/n with a = 14.811(3) A, b = 22.188(4) A, c = 21.864(4) A, beta = 100.124(3) degrees, and Z = 4 and the structure shows very short Mo
Effects of 6-methyl-uracil upon the phagocytic activity in mice following whole-body X-irradiation or 2,4,6,-triethyleneimino-s-triazine treatment

International Nuclear Information System (INIS)

Raake, W.; Tempel, K.

1977-01-01

1. Phagocytic activity measured by means of the intravasal clearence of a soot dispersion in male NMRI-mice was increased six to ten days after whole-body X-irradiation (640 R) and decreased during the same period after i.v. administration of 2,4,6-triethyleneimino-s-triazine (TEM 2.0 mg/kg). 2. By means of 6-methyl-uracil food admixtures (200 to 400 ppm during 2 or 3 weeks) or by repeated intravenous injections of a N-methyl-D-glucosamine-6-methyluracil complex (62.5 to 250 mg/kg daily during five days), a significant augmentation of the phagocytic index being related to time and dosage was obtained in otherwise untreated mice. Comparable results were seen using cytidine and cytidine-5'-phosphate, whereas guanosine-5'-phosphate remained ineffective. 3. Whilst stimulating effects of 6-methyl-uracil or its N-methyl-D-glucosamine complex on X-irradiated mice were suspended, an increase up to supernormal values of the phagocytic index was produced by the pyrimidine base in animals treated with TEM. In accordance to this the survival rate of lethally X-irradiated mice (960 R) could not be increased; with animals given lethal TEM-doses, however, a significantly increased survival rate was obtained. 4. The present investigations as well as former biochemical analyses confirm the assumption that 6-methyluracil produces its regeneration effects, to some extent at least, by specific pathways influencing the reticuloendothelium. Different results from X-irradiated and TEM-treated mice are referring to the different points of attack of the two noxa. (orig.) [de
Management of Sjogren’s Syndrome Patient: A Case Report of Prosthetic Rehabilitation with 6-Year Follow-Up

Directory of Open Access Journals (Sweden)

Marcos de Mendonça Invernici

2014-01-01

Full Text Available Completely and partially edentulous patients with Sjogren’s syndrome (SS experience severe hyposalivation, xerostomia, and considerable difficulty in using tissue-supported prosthesis. This clinical paper describes the management, treatment, and 6-year follow-up of a patient diagnosed with SS type II, who uses corticosteroids and antihyperglycemic drugs. The patient received restorative, periodontal, and surgical treatments followed by implant-supported fixed prosthesis. Radiographic evaluation and probing depth showed gingival health and no bone loss after 6 years. Treatment with implant-retained dental prosthesis greatly increased comfort and function, offering an alternative to patients with SS.
Antiproliferative activity of olomoucine II, a novel 2,6,9-trisubstituted purine cyclin-dependent kinase inhibitor

Czech Academy of Sciences Publication Activity Database

Kryštof, Vladimír; McNae, I. W.; Walkinshaw, M. D.; Fischer, P.M.; Müller, P.; Vojtešek, B.; Orság, Martin; Havlíček, Libor; Strnad, Miroslav

2005-01-01

Roč. 62, č. 15 (2005), s. 1763-1771 ISSN 1420-682X R&D Projects: GA ČR GP204/03/D231 Institutional research plan: CEZ:AV0Z50380511 Keywords : olomoucine II * roscovitine * cyclin-dependent kinase inhibitor Subject RIV: CE - Biochemistry Impact factor: 4.582, year: 2005
Atomic layer deposition of molybdenum disulfide films using MoF ₆ and H ₂ S

Energy Technology Data Exchange (ETDEWEB)

Mane, Anil U. [Energy Systems Division, Argonne National Laboratory, 9700 S. Cass Ave., Argonne, Illinois 60439; Letourneau, Steven [Micron School of Materials Science and Engineering, Boise State University, 1910 University Dr., Boise, Idaho 83725; Mandia, David J. [Energy Systems Division, Argonne National Laboratory, 9700 S. Cass Ave., Argonne, Illinois 60439; Liu, Jian [Department of Chemistry, Northwestern University, 2145 Sheridan Rd., Evanston, Illinois 60208; Libera, Joseph A. [Energy Systems Division, Argonne National Laboratory, 9700 S. Cass Ave., Argonne, Illinois 60439; Lei, Yu [Energy Systems Division, Argonne National Laboratory, 9700 S. Cass Ave., Argonne, Illinois 60439; Peng, Qing [Energy Systems Division, Argonne National Laboratory, 9700 S. Cass Ave., Argonne, Illinois 60439; Graugnard, Elton [Micron School of Materials Science and Engineering, Boise State University, 1910 University Dr., Boise Idaho 83725; Elam, Jeffrey W. [Energy Systems Division, Argonne National Laboratory, 9700 S. Cass Ave, Argonne, Illinois 60439

2018-01-01

Molybdenum sulfide films were grown by atomic layer deposition on silicon and fused silica substrates using molybdenum hexafluoride (MoF6) and hydrogen sulfide at 200 degrees C. In situ quartz crystal microbalance (QCM) measurements confirmed linear growth at 0.46 angstrom/cycle and self-limiting chemistry for both precursors. Analysis of the QCM step shapes indicated that MoS2 is the reaction product, and this finding is supported by x-ray photoelectron spectroscopy measurements showing that Mo is predominantly in the Mo(IV) state. However, Raman spectroscopy and x-ray diffraction measurements failed to identify crystalline MoS2 in the as-deposited films, and this might result from unreacted MoFx residues in the films. Annealing the films at 350 degrees C in a hydrogen rich environment yielded crystalline MoS2 and reduced the F concentration in the films. Optical transmission measurements yielded a bandgap of 1.3 eV. Finally, the authors observed that the MoS2 growth per cycle was accelerated when a fraction of the MoF6 pulses were substituted with diethyl zinc. Published by the AVS
Presidendi sõnavõistlusele laekus 2030 sõna

Index Scriptorium Estoniae

2010-01-01

President Toomas Hendrik Ilvese algatatud sõnaloomevõistluse tulemustest. Ilmunud ka: Eesti Päevaleht 6. okt. 2010, lk. 6, pealk.: Sõnausel osales tuhandeid inimesi; Virumaa Teataja 6. okt. 2010, lk. 3, pealk.: President Ilvese sõnaus oli menukas; Põhjarannik 6. okt. 2010, lk. 7; Lääne Elu 7. okt. 2010, lk. 2; Vaba Eesti Sõna 7. okt. 2010, lk. 3, pealk.: Presidendi sõnavõistlusele laekus üle 2000 sõna; Meie Maa 7. okt. 2010, lk. 3, pealk.: Presidendi sõnavõistlusel lõi kaasa 11 saarlast; Eesti Elu 8. okt. 2010, lk. 7, pealk.: Sõnavõistlusele laekus 2030 sõna
Sphingosine kinase 1 deficiency confers protection against hyperoxia-induced bronchopulmonary dysplasia in a murine model: role of S1P signaling and Nox proteins.

Science.gov (United States)

Harijith, Anantha; Pendyala, Srikanth; Reddy, Narsa M; Bai, Tao; Usatyuk, Peter V; Berdyshev, Evgeny; Gorshkova, Irina; Huang, Long Shuang; Mohan, Vijay; Garzon, Steve; Kanteti, Prasad; Reddy, Sekhar P; Raj, J Usha; Natarajan, Viswanathan

2013-10-01

Bronchopulmonary dysplasia of the premature newborn is characterized by lung injury, resulting in alveolar simplification and reduced pulmonary function. Exposure of neonatal mice to hyperoxia enhanced sphingosine-1-phosphate (S1P) levels in lung tissues; however, the role of increased S1P in the pathobiological characteristics of bronchopulmonary dysplasia has not been investigated. We hypothesized that an altered S1P signaling axis, in part, is responsible for neonatal lung injury leading to bronchopulmonary dysplasia. To validate this hypothesis, newborn wild-type, sphingosine kinase1(-/-) (Sphk1(-/-)), sphingosine kinase 2(-/-) (Sphk2(-/-)), and S1P lyase(+/-) (Sgpl1(+/-)) mice were exposed to hyperoxia (75%) from postnatal day 1 to 7. Sphk1(-/-), but not Sphk2(-/-) or Sgpl1(+/-), mice offered protection against hyperoxia-induced lung injury, with improved alveolarization and alveolar integrity compared with wild type. Furthermore, SphK1 deficiency attenuated hyperoxia-induced accumulation of IL-6 in bronchoalveolar lavage fluids and NADPH oxidase (NOX) 2 and NOX4 protein expression in lung tissue. In vitro experiments using human lung microvascular endothelial cells showed that exogenous S1P stimulated intracellular reactive oxygen species (ROS) generation, whereas SphK1 siRNA, or inhibitor against SphK1, attenuated hyperoxia-induced S1P generation. Knockdown of NOX2 and NOX4, using specific siRNA, reduced both basal and S1P-induced ROS formation. These results suggest an important role for SphK1-mediated S1P signaling-regulated ROS in the development of hyperoxia-induced lung injury in a murine neonatal model of bronchopulmonary dysplasia. Copyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.
Electrochemical behavior of 45S5 bioactive ceramic coating on Ti6Al4V alloy for dental applications

Science.gov (United States)

Machado López, M. M.; Espitia Cabrera, M. I.; Faure, J.; Contreras García, M. E.

2016-04-01

Titanium and its alloys are widely used as implant materials because of their mechanical properties and non-toxic behavior. Unfortunately, they are not bioinert, which means that they can release ions and can only fix the bone by mechanical anchorage, this can lead to the encapsulation of dense fibrous tissue in the body. The bone fixation is required in clinical conditions treated by orthopedic and dental medicine. The proposal is to coat metallic implants with bioactive materials to establish good interfacial bonds between the metal substrate and bone by increasing bioactivity. Bioactive glasses, ceramics specifically 45 S5 Bioglass, have drawn attention as a serious functional biomaterial because osseointegration capacity. The EPD method of bioglass gel precursor was proposed in the present work as a new method to obtain 45S5/Ti6A14V for dental applications. The coatings, were thermally treated at 700 and 800°C and presented the 45 S5 bioglass characteristic phases showing morphology and uniformity with no defects, quantification percentages by EDS of Si, Ca, Na, P and O elements in the coating scratched powders, showed a good proportional relationship demonstrating the obtention of the 45S5 bioglass. The corrosion tests were carried out in Hank's solution. By Tafel extrapolation, Ti6Al4V alloy showed good corrosion resistance in Hank's solution media, by the formation of a passivation layer on the metal surface, however, in the system 45S5/Ti6Al4V there was an increase in the corrosion resistance; icon-, Ecorr and corrosion rate decreased, the mass loss and the rate of release of ions, were lower in this system than in the titanium alloy without coating.
Synthesis and characterization of MoS2/Ti composite coatings on Ti6Al4V prepared by laser cladding

Science.gov (United States)

Yang, Rongjuan; Liu, Zongde; Wang, Yongtian; Yang, Guang; Li, Hongchuan

2013-02-01

The MoS2/Ti composite coating with sub-micron grade structure has been prepared on Ti6Al4V by laser method under argon protection. The morphology, microstructure, microhardness and friction coefficient of the coating were examined. The results indicated that the molybdenum disulfide was decomposed during melting and resolidification. The phase organization of composite coating mainly consisted of ternary element sulfides, molybdenum sulfides and titanium sulfides. The friction coefficient of and the surface roughness the MoS2/Ti coating were lower than those of Ti6Al4V. The composite coating exhibits excellent adhesion to the substrates, less surface roughness, good wear resistance and harder surface.
Pre-45s rRNA promotes colon cancer and is associated with poor survival of CRC patients.

Science.gov (United States)

Tsoi, H; Lam, K C; Dong, Y; Zhang, X; Lee, C K; Zhang, J; Ng, S C; Ng, S S M; Zheng, S; Chen, Y; Fang, J; Yu, J

2017-11-02

One characteristic of cancer cells is the abnormally high rate of cell metabolism to sustain their enhanced proliferation. However, the behind mechanism of this phenomenon is still elusive. Here we find that enhanced precursor 45s ribosomal RNA (pre-45s rRNA) is one of the core mechanisms in promoting the pathogenesis of colorectal cancer (CRC). Pre-45s rRNA expression is significantly higher in primary CRC tumor tissues samples and cancer cell lines compared with the non-tumorous colon tissues, and is associated with tumor sizes. Knockdown of pre-45s rRNA inhibits G1/S cell-cycle transition by stabilizing p53 through inducing murine double minute 2 (MDM2) and ribosomal protein L11 (RpL11) interaction. In addition, we revealed that high rate of cancer cell metabolism triggers the passive release of calcium ion from endoplasmic reticulum to the cytoplasm. The elevated calcium ion in the cytoplasm activates the signaling cascade of calcium/calmodulin-dependent protein kinase II, ribosomal S6 kinase (S6K) and ribosomal S6K (CaMKII-S6K-UBF). The activated UBF promotes the transcription of rDNA, which therefore increases pre-45s rRNA. Disruption of CaMKII-S6K-UBF axis by either RNAi or pharmaceutical approaches leads to reduction of pre-45s rRNA expression, which subsequently suppresses cell proliferation in colon cancer cells by causing cell-cycle arrest. Knockdown of APC activates CaMKII-S6K-UBF cascade and thus enhances pre-45s rRNA expression. Moreover, the high expression level of pre-45s rRNA is associated with poor survival of CRC patients in two independent cohorts. Our study identifies a novel mechanism in CRC pathogenesis mediated by pre-45s rRNA and a prognostic factor of pre-45s rRNA in CRC patients.
Toxicological evaluation of the flavour ingredient N-(1-((4-amino-2,2-dioxido-1H-benzo[c][1,2,6]thiadiazin-5-yloxy-2-methylpropan-2-yl-2,6-dimethylisonicotinamide (S2218

Directory of Open Access Journals (Sweden)

Donald S. Karanewsky

Full Text Available A toxicological evaluation of N-(1-((4-amino-2,2-dioxido-1H-benzo[c][1,2,6]thiadiazin-5-yloxy-2-methylpropan-2-yl-2,6-dimethylisonicotinamide (S2218; CAS 1622458-34-7, a flavour with modifying properties, was completed for the purpose of assessing its safety for use in food and beverage applications. S2218 exhibited minimal oxidative metabolism in vitro, and in rat pharmacokinetic studies, the compound was poorly orally bioavailable and rapidly eliminated. S2218 was not found to be mutagenic in an in vitro bacterial reverse mutation assay, and was found to be neither clastogenic nor aneugenic in an in vitro mammalian cell micronucleus assay. In subchronic oral toxicity studies in male and female rats, the NOAEL was 140 mg/kg bw/day (highest dose tested for S2218 sulfate salt (S8069 when administered as a food ad-mix for 13 consecutive weeks. Furthermore, S2218 sulfate salt demonstrated a lack of maternal toxicity, as well as adverse effects on fetal morphology at the highest dose tested, providing a NOAEL of 1000 mg/kg bw/day for both maternal toxicity and embryo/fetal development when administered orally during gestation to pregnant rats. Keywords: Flavours with modifying properties, S2218, FEMA GRAS, Subchronic toxicological evaluation, Genetic toxicological evaluation, Developmental toxicity evaluation
Standard Missile-6 (SM-6)

Science.gov (United States)

2016-12-01

attack or Anti-Ship Cruise Missiles in flight. The SM-6 ERAM program is an evolutionary, capabilities based acquisition program that will use spiral ...Prior SAR Total O&S Estimates - Dec 2014 SAR 460.3 Programmatic/Planning Factors 0.0 Cost Estimating Methodology 0.0 Cost Data Update 0.0 Labor Rate

Alkali metals in addition to acidic pH activate the EvgS histidine kinase sensor in Escherichia coli.

Science.gov (United States)

Eguchi, Yoko; Utsumi, Ryutaro

2014-09-01

Two-component signal transduction systems (TCSs) in bacteria perceive environmental stress and transmit the information via phosphorelay to adjust multiple cellular functions for adaptation. The EvgS/EvgA system is a TCS that confers acid resistance to Escherichia coli cells. Activation of the EvgS sensor initiates a cascade of transcription factors, EvgA, YdeO, and GadE, which induce the expression of a large group of acid resistance genes. We searched for signals activating EvgS and found that a high concentration of alkali metals (Na(+), K(+)) in addition to low pH was essential for the activation. EvgS is a histidine kinase, with a large periplasmic sensor region consisting of two tandem PBPb (bacterial periplasmic solute-binding protein) domains at its N terminus. The periplasmic sensor region of EvgS was necessary for EvgS activation, and Leu152, located within the first PBPb domain, was involved in the activation. Furthermore, chimeras of EvgS and PhoQ histidine kinases suggested that alkali metals were perceived at the periplasmic sensor region, whereas the cytoplasmic linker domain, connecting the transmembrane region and the histidine kinase domain, was required for low-pH perception. Copyright © 2014, American Society for Microbiology. All Rights Reserved.
cap alpha. -transfer reactions /sup 27/Al(/sup 6/Li, d)/sup 31/P, /sup 29/Si(/sup 6/Li, d)/sup 33/S and /sup 31/P(/sup 6/Li, d)/sup 35/Cl at 36 MeV. [Angular distributions, EFR DWBA, spectroscopic strengths

Energy Technology Data Exchange (ETDEWEB)

Eswaran, M A; Gove, H E; Cook, R; Sikora, B [Rochester Univ., NY (USA). Nuclear Structure Research Lab.

1979-08-13

The ..cap alpha..-transfer reactions /sup 27/Al(/sup 6/Li,d)/sup 31/P,/sup 29/Si(/sup 6/Li,d) /sup 33/S and /sup 31/P(Li,d)/sup 35/Cl have been studied at a /sup 6/Li energy of 36 MeV. Absolute cross sections and angular distributions have been measured and an exact finite-range distorted-wave Born approximation analysis assuming a direct cluster transfer has been used to extract from the data ..cap alpha..-particle spectroscopic strengths for levels populated in /sup 31/P, /sup 33/S and /sup 35/Cl in three reactions respectively. The results show that in the case of most of the low-lying excited states of /sup 31/P a single value of L of the transferred ..cap alpha..-particle contributes, though a multiplicity of L-values are allowed by angular momentum selection rules. It is also found that the ..cap alpha..-particle spectroscopic strength of the ground state of /sup 31/P is a factor of 2 more than the strengths of the ground states of /sup 33/S and /sup 35/Cl. The ..cap alpha..-spectroscopic strengths of ground states of these, as well as other odd-A s-d shell nuclei, are compared with the presently available shell model calculations.
Facile synthesis of MoS{sub 2}/Bi{sub 2}WO{sub 6} nanocomposites for enhanced CO{sub 2} photoreduction activity under visible light irradiation

Energy Technology Data Exchange (ETDEWEB)

Dai, Weili, E-mail: wldai81@126.com [Key Laboratory of Jiangxi Province for Persistant Pollutants Control and Resources Recycle, Nanchang Hangkong University, Nanchang 330063, Jiangxi (China); Yu, Juanjuan [Key Laboratory of Jiangxi Province for Persistant Pollutants Control and Resources Recycle, Nanchang Hangkong University, Nanchang 330063, Jiangxi (China); Deng, Yiqiang, E-mail: dyq3211@126.com [College of Chemical Engineering, Guangdong University of Petrochemical Technology, Maoming 525000 Guangdong (China); Hu, Xu; Wang, Tengyao; Luo, Xubiao [Key Laboratory of Jiangxi Province for Persistant Pollutants Control and Resources Recycle, Nanchang Hangkong University, Nanchang 330063, Jiangxi (China)

2017-05-01

Highlights: • MoS{sub 2}/Bi{sub 2}WO{sub 6} nanocomposites (MB) were fabricated by a facile two-step approach. • MoS{sub 2} was first used as a cocatalyst coupling with Bi{sub 2}WO{sub 6} for CO{sub 2} photoreduction. • MoS{sub 2} significantly enhanced the photoelectric properties and photoactivity. • The CO{sub 3}{sup 2−}, HCO{sub 3}{sup −} and H{sub 2}CO{sub 3} in CO{sub 2} solution actually act as the reactive substrates. - Abstract: A novel composite material, MoS{sub 2}/Bi{sub 2}WO{sub 6}, has been fabricated via a facile two-step approach. The few layered MoS{sub 2} as a cocatalyst has intimate interactions with the hierarchical flower-like Bi{sub 2}WO{sub 6} microspheres, which boosts the visible light harvesting and charge transferring, and promotes the separation of electron-hole pairs, thus leading to the superior photocatalytic activity. It was found that the as-synthesized MoS{sub 2}/Bi{sub 2}WO{sub 6} nanocomposites exhibited significantly enhanced performance for the photoreduction of CO{sub 2} into hydrocarbons, i.e. methanol and ethanol, as compared with pure Bi{sub 2}WO{sub 6}. The yields of methanol and ethanol obtained over the composite with optimal content of MoS{sub 2} (0.4 wt%) were 36.7 and 36.6 μmol gcat{sup −1} after 4 h of visible light irradiation, respectively, which were 1.94 times higher than that over pure Bi{sub 2}WO{sub 6}. Furthermore, the mechanism of CO{sub 2} photoreduction was also investigated. It indicates that the CO{sub 3}{sup 2−}, HCO{sub 3}{sup −} and H{sub 2}CO{sub 3} generated in CO{sub 2} aqueous solution would be the reactive substrates during the photoreduction reaction, proving the thermodynamic feasibility of CO{sub 2} photoreduction. This work demonstrated that MoS{sub 2} is a very promising candidate for development of highly active photocatalysts, and supplied a facile and simple strategy for designing environmentally benign, cheap non-noble metal, and highly efficient semiconductor
Comments on the symmetry of AdS6 solutions in string/M-theory and Killing spinor equations

Directory of Open Access Journals (Sweden)

Hyojoong Kim

2016-09-01

Full Text Available It was recently pointed out in [1] that AdS6 solutions in IIB theory enjoy an extended symmetry structure and the consistent truncation to D=4 internal space leads to a nonlinear sigma model with target SL(3,R/SO(2,1. We continue to study the purely bosonic D=4 effective action, and elucidate how the addition of scalar potential term still allows Killing spinor equations in the absence of gauge fields. In particular, the potential turns out to be a single diagonal component of the coset representative. Furthermore, we perform a general analysis of the integrability conditions of Killing spinor equations and establish that the effective action can be in fact generalized to arbitrary sizes and signatures, e.g. with target SL(n,R/SO(p,n−p and the scalar potential expressible by a single diagonal component of the coset representative. We also comment on a similar construction and its generalizations of effective D=5 purely bosonic non-linear sigma model action related to AdS6 in M-theory.
Functional characterization of human RSK4, a new 90-kDa ribosomal S6 kinase, reveals constitutive activation in most cell types

DEFF Research Database (Denmark)

Dümmler, Bettina A; Hauge, Camilla; Silber, Joachim

2005-01-01

characterization of a predicted new human RSK homologue, RSK4. We showed that RSK4 is a predominantly cytosolic protein with very low expression and several characteristics of the RSK family kinases, including the presence of two functional kinase domains and a C-terminal docking site for ERK. Surprisingly......, however, in all cell types analyzed, endogenous RSK4 was maximally (constitutively) activated under serum-starved conditions where other RSKs are inactive due to their requirement for growth factor stimulation. Constitutive activation appeared to result from constitutive phosphorylation of Ser232, Ser372...
Practical enrichment technique for 33S (34S)

International Nuclear Information System (INIS)

McInteer, B.B.; Lyman, J.L.; Nilsson, A.C.; Quigley, G.P.

1982-01-01

The successful preparation of a macroscopic sample of enriched 33 S by laser-induced molecular dissociation is reported. Approach was to induce isotopically selective dissociation of SF 6 with CO 2 -laser pulses and to separate the remaining SF 6 from the sulfur-containing reaction products by cryogenic distillation. A 200 Hz, 0.75 J/pulse laser was used for photolysis of low-pressure (less than 1 torr) gas mixtures. The mixture of SF 6 and scavenger recirculated continuously throughout the irradiation chamber where the laser pulses selectively dissociated 32 SF 6 to give the final products: SF 4 or SOF 2 . The unreacted SF 6 was enriched in the heavier isotopes: 33 S, 34 S, and 36 S. A 1.3-g sample of SF 6 was collected with a 33 S enrichment factor of 1.96 and a 34 S enrichment factor of 2.25. A similar size sample of depleted ( 32 S) sulfur compounds was also collected. A scavenger was necessary to ensure high yield, and moist hydrogen was found to be best for our conditions. Removal of hydrogen fluoride was also necessary to prevent severe corrosion and to maintain high isotopic selectivity. 6 figures
Measurement of $CP$ violation and constraints on the CKM angle $\\gamma$ in $B^{\\pm}\\rightarrow D K^{\\pm}$ with $D \\rightarrow K_S^0 \\pi^+ \\pi^-$ decays

CERN Document Server

Aaij, Roel; Adinolfi, Marco; Affolder, Anthony; Ajaltouni, Ziad; Albrecht, Johannes; Alessio, Federico; Alexander, Michael; Ali, Suvayu; Alkhazov, Georgy; Alvarez Cartelle, Paula; Alves Jr, Antonio; Amato, Sandra; Amerio, Silvia; Amhis, Yasmine; An, Liupan; Anderlini, Lucio; Anderson, Jonathan; Andreassen, Rolf; Andreotti, Mirco; Andrews, Jason; Appleby, Robert; Aquines Gutierrez, Osvaldo; Archilli, Flavio; Artamonov, Alexander; Artuso, Marina; Aslanides, Elie; Auriemma, Giulio; Baalouch, Marouen; Bachmann, Sebastian; Back, John; Badalov, Alexey; Balagura, Vladislav; Baldini, Wander; Barlow, Roger; Barschel, Colin; Barsuk, Sergey; Barter, William; Batozskaya, Varvara; Bay, Aurelio; Beaucourt, Leo; Beddow, John; Bedeschi, Franco; Bediaga, Ignacio; Belogurov, Sergey; Belous, Konstantin; Belyaev, Ivan; Ben-Haim, Eli; Bencivenni, Giovanni; Benson, Sean; Benton, Jack; Berezhnoy, Alexander; Bernet, Roland; Bettler, Marc-Olivier; van Beuzekom, Martinus; Bien, Alexander; Bifani, Simone; Bird, Thomas; Bizzeti, Andrea; Bjørnstad, Pål Marius; Blake, Thomas; Blanc, Frédéric; Blouw, Johan; Blusk, Steven; Bocci, Valerio; Bondar, Alexander; Bondar, Nikolay; Bonivento, Walter; Borghi, Silvia; Borgia, Alessandra; Borsato, Martino; Bowcock, Themistocles; Bowen, Espen Eie; Bozzi, Concezio; Brambach, Tobias; van den Brand, Johannes; Bressieux, Joël; Brett, David; Britsch, Markward; Britton, Thomas; Brodzicka, Jolanta; Brook, Nicholas; Brown, Henry; Bursche, Albert; Busetto, Giovanni; Buytaert, Jan; Cadeddu, Sandro; Calabrese, Roberto; Calvi, Marta; Calvo Gomez, Miriam; Camboni, Alessandro; Campana, Pierluigi; Campora Perez, Daniel; Carbone, Angelo; Carboni, Giovanni; Cardinale, Roberta; Cardini, Alessandro; Carranza-Mejia, Hector; Carson, Laurence; Carvalho Akiba, Kazuyoshi; Casse, Gianluigi; Cassina, Lorenzo; Castillo Garcia, Lucia; Cattaneo, Marco; Cauet, Christophe; Cenci, Riccardo; Charles, Matthew; Charpentier, Philippe; Chen, Shanzhen; Cheung, Shu-Faye; Chiapolini, Nicola; Chrzaszcz, Marcin; Ciba, Krzystof; Cid Vidal, Xabier; Ciezarek, Gregory; Clarke, Peter; Clemencic, Marco; Cliff, Harry; Closier, Joel; Coco, Victor; Cogan, Julien; Cogneras, Eric; Collins, Paula; Comerma-Montells, Albert; Contu, Andrea; Cook, Andrew; Coombes, Matthew; Coquereau, Samuel; Corti, Gloria; Corvo, Marco; Counts, Ian; Couturier, Benjamin; Cowan, Greig; Craik, Daniel Charles; Cruz Torres, Melissa Maria; Cunliffe, Samuel; Currie, Robert; D'Ambrosio, Carmelo; Dalseno, Jeremy; David, Pascal; David, Pieter; Davis, Adam; De Bruyn, Kristof; De Capua, Stefano; De Cian, Michel; De Miranda, Jussara; De Paula, Leandro; De Silva, Weeraddana; De Simone, Patrizia; Decamp, Daniel; Deckenhoff, Mirko; Del Buono, Luigi; Déléage, Nicolas; Derkach, Denis; Deschamps, Olivier; Dettori, Francesco; Di Canto, Angelo; Dijkstra, Hans; Donleavy, Stephanie; Dordei, Francesca; Dorigo, Mirco; Dosil Suárez, Alvaro; Dossett, David; Dovbnya, Anatoliy; Dujany, Giulio; Dupertuis, Frederic; Durante, Paolo; Dzhelyadin, Rustem; Dziurda, Agnieszka; Dzyuba, Alexey; Easo, Sajan; Egede, Ulrik; Egorychev, Victor; Eidelman, Semen; Eisenhardt, Stephan; Eitschberger, Ulrich; Ekelhof, Robert; Eklund, Lars; El Rifai, Ibrahim; Elsasser, Christian; Ely, Scott; Esen, Sevda; Falabella, Antonio; Färber, Christian; Farinelli, Chiara; Farley, Nathanael; Farry, Stephen; Fay, Robert; Ferguson, Dianne; Fernandez Albor, Victor; Ferreira Rodrigues, Fernando; Ferro-Luzzi, Massimiliano; Filippov, Sergey; Fiore, Marco; Fiorini, Massimiliano; Firlej, Miroslaw; Fitzpatrick, Conor; Fiutowski, Tomasz; Fontana, Marianna; Fontanelli, Flavio; Forty, Roger; Francisco, Oscar; Frank, Markus; Frei, Christoph; Frosini, Maddalena; Fu, Jinlin; Furfaro, Emiliano; Gallas Torreira, Abraham; Galli, Domenico; Gallorini, Stefano; Gambetta, Silvia; Gandelman, Miriam; Gandini, Paolo; Gao, Yuanning; Garofoli, Justin; Garra Tico, Jordi; Garrido, Lluis; Gaspar, Clara; Gauld, Rhorry; Gavardi, Laura; Geraci, Angelo; Gersabeck, Evelina; Gersabeck, Marco; Gershon, Timothy; Ghez, Philippe; Gianelle, Alessio; Giani', Sebastiana; Gibson, Valerie; Giubega, Lavinia-Helena; Gligorov, V.V.; Göbel, Carla; Golubkov, Dmitry; Golutvin, Andrey; Gomes, Alvaro; Gordon, Hamish; Gotti, Claudio; Grabalosa Gándara, Marc; Graciani Diaz, Ricardo; Granado Cardoso, Luis Alberto; Graugés, Eugeni; Graziani, Giacomo; Grecu, Alexandru; Greening, Edward; Gregson, Sam; Griffith, Peter; Grillo, Lucia; Grünberg, Oliver; Gui, Bin; Gushchin, Evgeny; Guz, Yury; Gys, Thierry; Hadjivasiliou, Christos; Haefeli, Guido; Haen, Christophe; Haines, Susan; Hall, Samuel; Hamilton, Brian; Hampson, Thomas; Han, Xiaoxue; Hansmann-Menzemer, Stephanie; Harnew, Neville; Harnew, Samuel; Harrison, Jonathan; Hartmann, Thomas; He, Jibo; Head, Timothy; Heijne, Veerle; Hennessy, Karol; Henrard, Pierre; Henry, Louis; Hernando Morata, Jose Angel; van Herwijnen, Eric; Heß, Miriam; Hicheur, Adlène; Hill, Donal; Hoballah, Mostafa; Hombach, Christoph; Hulsbergen, Wouter; Hunt, Philip; Hussain, Nazim; Hutchcroft, David; Hynds, Daniel; Idzik, Marek; Ilten, Philip; Jacobsson, Richard; Jaeger, Andreas; Jalocha, Pawel; Jans, Eddy; Jaton, Pierre; Jawahery, Abolhassan; Jing, Fanfan; John, Malcolm; Johnson, Daniel; Jones, Christopher; Joram, Christian; Jost, Beat; Jurik, Nathan; Kaballo, Michael; Kandybei, Sergii; Kanso, Walaa; Karacson, Matthias; Karbach, Moritz; Kelsey, Matthew; Kenyon, Ian; Ketel, Tjeerd; Khanji, Basem; Khurewathanakul, Chitsanu; Klaver, Suzanne; Kochebina, Olga; Kolpin, Michael; Komarov, Ilya; Koopman, Rose; Koppenburg, Patrick; Korolev, Mikhail; Kozlinskiy, Alexandr; Kravchuk, Leonid; Kreplin, Katharina; Kreps, Michal; Krocker, Georg; Krokovny, Pavel; Kruse, Florian; Kucharczyk, Marcin; Kudryavtsev, Vasily; Kurek, Krzysztof; Kvaratskheliya, Tengiz; La Thi, Viet Nga; Lacarrere, Daniel; Lafferty, George; Lai, Adriano; Lambert, Dean; Lambert, Robert W; Lanciotti, Elisa; Lanfranchi, Gaia; Langenbruch, Christoph; Langhans, Benedikt; Latham, Thomas; Lazzeroni, Cristina; Le Gac, Renaud; van Leerdam, Jeroen; Lees, Jean-Pierre; Lefèvre, Regis; Leflat, Alexander; Lefrançois, Jacques; Leo, Sabato; Leroy, Olivier; Lesiak, Tadeusz; Leverington, Blake; Li, Yiming; Liles, Myfanwy; Lindner, Rolf; Linn, Christian; Lionetto, Federica; Liu, Bo; Liu, Guoming; Lohn, Stefan; Longstaff, Iain; Lopes, Jose; Lopez-March, Neus; Lowdon, Peter; Lu, Haiting; Lucchesi, Donatella; Luo, Haofei; Lupato, Anna; Luppi, Eleonora; Lupton, Oliver; Machefert, Frederic; Machikhiliyan, Irina V; Maciuc, Florin; Maev, Oleg; Malde, Sneha; Manca, Giulia; Mancinelli, Giampiero; Mapelli, Alessandro; Maratas, Jan; Marchand, Jean François; Marconi, Umberto; Marin Benito, Carla; Marino, Pietro; Märki, Raphael; Marks, Jörg; Martellotti, Giuseppe; Martens, Aurelien; Martín Sánchez, Alexandra; Martinelli, Maurizio; Martinez Santos, Diego; Martinez Vidal, Fernando; Martins Tostes, Danielle; Massafferri, André; Matev, Rosen; Mathe, Zoltan; Matteuzzi, Clara; Mazurov, Alexander; McCann, Michael; McCarthy, James; McNab, Andrew; McNulty, Ronan; McSkelly, Ben; Meadows, Brian; Meier, Frank; Meissner, Marco; Merk, Marcel; Milanes, Diego Alejandro; Minard, Marie-Noelle; Moggi, Niccolò; Molina Rodriguez, Josue; Monteil, Stephane; Moran, Dermot; Morandin, Mauro; Morawski, Piotr; Mordà, Alessandro; Morello, Michael Joseph; Moron, Jakub; Morris, Adam Benjamin; Mountain, Raymond; Muheim, Franz; Müller, Katharina; Muresan, Raluca; Mussini, Manuel; Muster, Bastien; Naik, Paras; Nakada, Tatsuya; Nandakumar, Raja; Nasteva, Irina; Needham, Matthew; Neri, Nicola; Neubert, Sebastian; Neufeld, Niko; Neuner, Max; Nguyen, Anh Duc; Nguyen, Thi-Dung; Nguyen-Mau, Chung; Nicol, Michelle; Niess, Valentin; Niet, Ramon; Nikitin, Nikolay; Nikodem, Thomas; Novoselov, Alexey; Oblakowska-Mucha, Agnieszka; Obraztsov, Vladimir; Oggero, Serena; Ogilvy, Stephen; Okhrimenko, Oleksandr; Oldeman, Rudolf; Onderwater, Gerco; Orlandea, Marius; Otalora Goicochea, Juan Martin; Owen, Patrick; Oyanguren, Maria Arantza; Pal, Bilas Kanti; Palano, Antimo; Palombo, Fernando; Palutan, Matteo; Panman, Jacob; Papanestis, Antonios; Pappagallo, Marco; Parkes, Christopher; Parkinson, Christopher John; Passaleva, Giovanni; Patel, Girish; Patel, Mitesh; Patrignani, Claudia; Pazos Alvarez, Antonio; Pearce, Alex; Pellegrino, Antonio; Pepe Altarelli, Monica; Perazzini, Stefano; Perez Trigo, Eliseo; Perret, Pascal; Perrin-Terrin, Mathieu; Pescatore, Luca; Pesen, Erhan; Petridis, Konstantin; Petrolini, Alessandro; Picatoste Olloqui, Eduardo; Pietrzyk, Boleslaw; Pilař, Tomas; Pinci, Davide; Pistone, Alessandro; Playfer, Stephen; Plo Casasus, Maximo; Polci, Francesco; Poluektov, Anton; Polycarpo, Erica; Popov, Alexander; Popov, Dmitry; Popovici, Bogdan; Potterat, Cédric; Powell, Andrew; Prisciandaro, Jessica; Pritchard, Adrian; Prouve, Claire; Pugatch, Valery; Puig Navarro, Albert; Punzi, Giovanni; Qian, Wenbin; Rachwal, Bartolomiej; Rademacker, Jonas; Rakotomiaramanana, Barinjaka; Rama, Matteo; Rangel, Murilo; Raniuk, Iurii; Rauschmayr, Nathalie; Raven, Gerhard; Reichert, Stefanie; Reid, Matthew; dos Reis, Alberto; Ricciardi, Stefania; Richards, Alexander; Rihl, Mariana; Rinnert, Kurt; Rives Molina, Vincente; Roa Romero, Diego; Robbe, Patrick; Rodrigues, Ana Barbara; Rodrigues, Eduardo; Rodriguez Perez, Pablo; Roiser, Stefan; Romanovsky, Vladimir; Romero Vidal, Antonio; Rotondo, Marcello; Rouvinet, Julien; Ruf, Thomas; Ruffini, Fabrizio; Ruiz, Hugo; Ruiz Valls, Pablo; Sabatino, Giovanni; Saborido Silva, Juan Jose; Sagidova, Naylya; Sail, Paul; Saitta, Biagio; Salustino Guimaraes, Valdir; Sanchez Mayordomo, Carlos; Sanmartin Sedes, Brais; Santacesaria, Roberta; Santamarina Rios, Cibran; Santovetti, Emanuele; Sapunov, Matvey; Sarti, Alessio; Satriano, Celestina; Satta, Alessia; Savrie, Mauro; Savrina, Darya; Schiller, Manuel; Schindler, Heinrich; Schlupp, Maximilian; Schmelling, Michael; Schmidt, Burkhard; Schneider, Olivier; Schopper, Andreas; Schune, Marie Helene; Schwemmer, Rainer; Sciascia, Barbara; Sciubba, Adalberto; Seco, Marcos; Semennikov, Alexander; Senderowska, Katarzyna; Sepp, Indrek; Serra, Nicola; Serrano, Justine; Sestini, Lorenzo; Seyfert, Paul; Shapkin, Mikhail; Shapoval, Illya; Shcheglov, Yury; Shears, Tara; Shekhtman, Lev; Shevchenko, Vladimir; Shires, Alexander; Silva Coutinho, Rafael; Simi, Gabriele; Sirendi, Marek; Skidmore, Nicola; Skwarnicki, Tomasz; Smith, Anthony; Smith, Edmund; Smith, Eluned; Smith, Jackson; Smith, Mark; Snoek, Hella; Sokoloff, Michael; Soler, Paul; Soomro, Fatima; Souza, Daniel; Souza De Paula, Bruno; Spaan, Bernhard; Sparkes, Ailsa; Spradlin, Patrick; Stagni, Federico; Stahl, Sascha; Steinkamp, Olaf; Stenyakin, Oleg; Stevenson, Scott; Stoica, Sabin; Stone, Sheldon; Storaci, Barbara; Stracka, Simone; Straticiuc, Mihai; Straumann, Ulrich; Stroili, Roberto; Subbiah, Vijay Kartik; Sun, Liang; Sutcliffe, William; Swientek, Krzysztof; Swientek, Stefan; Syropoulos, Vasileios; Szczekowski, Marek; Szczypka, Paul; Szilard, Daniela; Szumlak, Tomasz; T'Jampens, Stephane; Teklishyn, Maksym; Tellarini, Giulia; Teubert, Frederic; Thomas, Christopher; 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Williams, Mike; Wilson, Fergus; Wimberley, Jack; Wishahi, Julian; Wislicki, Wojciech; Witek, Mariusz; Wormser, Guy; Wotton, Stephen; Wright, Simon; Wu, Suzhi; Wyllie, Kenneth; Xie, Yuehong; Xing, Zhou; Xu, Zhirui; Yang, Zhenwei; Yuan, Xuhao; Yushchenko, Oleg; Zangoli, Maria; Zavertyaev, Mikhail; Zhang, Feng; Zhang, Liming; Zhang, Wen Chao; Zhang, Yanxi; Zhelezov, Alexey; Zhokhov, Anatoly; Zhong, Liang; Zvyagin, Alexander

A model-dependent amplitude analysis of $B^{\\pm} \\rightarrow D K^{\\pm}$ with $D \\rightarrow K_S^0 \\pi^+ \\pi^-$ decays is performed using proton-proton collision data, corresponding to an integrated luminosity of $1$ fb$^{-1}$, recorded by LHCb at a centre-of-mass energy of $7$ TeV in $2011$. Values of the $CP$ violation observables $x_{\\pm}$ and $y_{\\pm}$, which are sensitive to the CKM angle $\\gamma$, are measured to be \\begin{align*} x_- &= +0.027 \\pm 0.044 ^{+0.010}_{-0.008} \\pm 0.001, \\\\ y_- &= +0.013 \\pm 0.048 ^{+0.009}_{-0.007} \\pm 0.003, \\\\ x_+ &= -0.084 \\pm 0.045 \\pm 0.009 \\pm 0.005, \\\\ y_+ &= -0.032 \\pm 0.048 ^{+0.010}_{-0.009} \\pm 0.008, \\end{align*} where the first uncertainty is statistical, the second systematic and the third arises from the uncertainty of the $D \\rightarrow K_S^0 \\pi^+ \\pi^-$ amplitude model. The value of $\\gamma$ is determined to be $(84^{+49}_{-42})^\\circ$, including all sources of uncertainty. Neutral $D$ meson mixing is found to have negligible effect.
Measurement of $CP$ violation and constraints on the CKM angle $\\gamma$ in $B^{\\pm}\\rightarrow D K^{\\pm}$ with $D \\rightarrow K_S^0 \\pi^+ \\pi^-$ decays

CERN Document Server

Aaij, Roel; Adinolfi, Marco; Affolder, Anthony; Ajaltouni, Ziad; Albrecht, Johannes; Alessio, Federico; Alexander, Michael; Ali, Suvayu; Alkhazov, Georgy; Alvarez Cartelle, Paula; Alves Jr, Antonio; Amato, Sandra; Amerio, Silvia; Amhis, Yasmine; An, Liupan; Anderlini, Lucio; Anderson, Jonathan; Andreassen, Rolf; Andreotti, Mirco; Andrews, Jason; Appleby, Robert; Aquines Gutierrez, Osvaldo; Archilli, Flavio; Artamonov, Alexander; Artuso, Marina; Aslanides, Elie; Auriemma, Giulio; Baalouch, Marouen; Bachmann, Sebastian; Back, John; Badalov, Alexey; Balagura, Vladislav; Baldini, Wander; Barlow, Roger; Barschel, Colin; Barsuk, Sergey; Barter, William; Batozskaya, Varvara; Bay, Aurelio; Beaucourt, Leo; Beddow, John; Bedeschi, Franco; Bediaga, Ignacio; Belogurov, Sergey; Belous, Konstantin; Belyaev, Ivan; Ben-Haim, Eli; Bencivenni, Giovanni; Benson, Sean; Benton, Jack; Berezhnoy, Alexander; Bernet, Roland; Bettler, Marc-Olivier; van Beuzekom, Martinus; Bien, Alexander; Bifani, Simone; Bird, Thomas; Bizzeti, Andrea; Bjørnstad, Pål Marius; Blake, Thomas; Blanc, Frédéric; Blouw, Johan; Blusk, Steven; Bocci, Valerio; Bondar, Alexander; Bondar, Nikolay; Bonivento, Walter; Borghi, Silvia; Borgia, Alessandra; Borsato, Martino; Bowcock, Themistocles; Bowen, Espen Eie; Bozzi, Concezio; Brambach, Tobias; van den Brand, Johannes; Bressieux, Joël; Brett, David; Britsch, Markward; Britton, Thomas; Brodzicka, Jolanta; Brook, Nicholas; Brown, Henry; Bursche, Albert; Busetto, Giovanni; Buytaert, Jan; Cadeddu, Sandro; Calabrese, Roberto; Calvi, Marta; Calvo Gomez, Miriam; Camboni, Alessandro; Campana, Pierluigi; Campora Perez, Daniel; Carbone, Angelo; Carboni, Giovanni; Cardinale, Roberta; Cardini, Alessandro; Carranza-Mejia, Hector; Carson, Laurence; Carvalho Akiba, Kazuyoshi; Casse, Gianluigi; Cassina, Lorenzo; Castillo Garcia, Lucia; Cattaneo, Marco; Cauet, Christophe; Cenci, Riccardo; Charles, Matthew; Charpentier, Philippe; Chen, Shanzhen; Cheung, Shu-Faye; Chiapolini, Nicola; Chrzaszcz, Marcin; Ciba, Krzystof; Cid Vidal, Xabier; Ciezarek, Gregory; Clarke, Peter; Clemencic, Marco; Cliff, Harry; Closier, Joel; Coco, Victor; Cogan, Julien; Cogneras, Eric; Collins, Paula; Comerma-Montells, Albert; Contu, Andrea; Cook, Andrew; Coombes, Matthew; Coquereau, Samuel; Corti, Gloria; Corvo, Marco; Counts, Ian; Couturier, Benjamin; Cowan, Greig; Craik, Daniel Charles; Cruz Torres, Melissa Maria; Cunliffe, Samuel; Currie, Robert; D'Ambrosio, Carmelo; Dalseno, Jeremy; David, Pascal; David, Pieter; Davis, Adam; De Bruyn, Kristof; De Capua, Stefano; De Cian, Michel; De Miranda, Jussara; De Paula, Leandro; De Silva, Weeraddana; De Simone, Patrizia; Decamp, Daniel; Deckenhoff, Mirko; Del Buono, Luigi; Déléage, Nicolas; Derkach, Denis; Deschamps, Olivier; Dettori, Francesco; Di Canto, Angelo; Dijkstra, Hans; Donleavy, Stephanie; Dordei, Francesca; Dorigo, Mirco; Dosil Suárez, Alvaro; Dossett, David; Dovbnya, Anatoliy; Dujany, Giulio; Dupertuis, Frederic; Durante, Paolo; Dzhelyadin, Rustem; Dziurda, Agnieszka; Dzyuba, Alexey; Easo, Sajan; Egede, Ulrik; Egorychev, Victor; Eidelman, Semen; Eisenhardt, Stephan; Eitschberger, Ulrich; Ekelhof, Robert; Eklund, Lars; El Rifai, Ibrahim; Elsasser, Christian; Ely, Scott; Esen, Sevda; Falabella, Antonio; Färber, Christian; Farinelli, Chiara; Farley, Nathanael; Farry, Stephen; Fay, Robert; Ferguson, Dianne; Fernandez Albor, Victor; Ferreira Rodrigues, Fernando; Ferro-Luzzi, Massimiliano; Filippov, Sergey; Fiore, Marco; Fiorini, Massimiliano; Firlej, Miroslaw; Fitzpatrick, Conor; Fiutowski, Tomasz; Fontana, Marianna; Fontanelli, Flavio; Forty, Roger; Francisco, Oscar; Frank, Markus; Frei, Christoph; Frosini, Maddalena; Fu, Jinlin; Furfaro, Emiliano; Gallas Torreira, Abraham; Galli, Domenico; Gallorini, Stefano; Gambetta, Silvia; Gandelman, Miriam; Gandini, Paolo; Gao, Yuanning; Garofoli, Justin; Garra Tico, Jordi; Garrido, Lluis; Gaspar, Clara; Gauld, Rhorry; Gavardi, Laura; Geraci, Angelo; Gersabeck, Evelina; Gersabeck, Marco; Gershon, Timothy; Ghez, Philippe; Gianelle, Alessio; Giani', Sebastiana; Gibson, Valerie; Giubega, Lavinia-Helena; Gligorov, Vladimir; Göbel, Carla; Golubkov, Dmitry; Golutvin, Andrey; Gomes, Alvaro; Gordon, Hamish; Gotti, Claudio; Grabalosa Gándara, Marc; Graciani Diaz, Ricardo; Granado Cardoso, Luis Alberto; Graugés, Eugeni; Graziani, Giacomo; Grecu, Alexandru; Greening, Edward; Gregson, Sam; Griffith, Peter; Grillo, Lucia; Grünberg, Oliver; Gui, Bin; Gushchin, Evgeny; Guz, Yury; Gys, Thierry; Hadjivasiliou, Christos; Haefeli, Guido; Haen, Christophe; Haines, Susan; Hall, Samuel; Hamilton, Brian; Hampson, Thomas; Han, Xiaoxue; Hansmann-Menzemer, Stephanie; Harnew, Neville; Harnew, Samuel; Harrison, Jonathan; Hartmann, Thomas; He, Jibo; Head, Timothy; Heijne, Veerle; Hennessy, Karol; Henrard, Pierre; Henry, Louis; Hernando Morata, Jose Angel; van Herwijnen, Eric; Heß, Miriam; Hicheur, Adlène; Hill, Donal; Hoballah, Mostafa; Hombach, Christoph; Hulsbergen, Wouter; Hunt, Philip; Hussain, Nazim; Hutchcroft, David; Hynds, Daniel; Idzik, Marek; Ilten, Philip; Jacobsson, Richard; Jaeger, Andreas; Jalocha, Pawel; Jans, Eddy; Jaton, Pierre; Jawahery, Abolhassan; Jing, Fanfan; John, Malcolm; Johnson, Daniel; Jones, Christopher; Joram, Christian; Jost, Beat; Jurik, Nathan; Kaballo, Michael; Kandybei, Sergii; Kanso, Walaa; Karacson, Matthias; Karbach, Moritz; Kelsey, Matthew; Kenyon, Ian; Ketel, Tjeerd; Khanji, Basem; Khurewathanakul, Chitsanu; Klaver, Suzanne; Kochebina, Olga; Kolpin, Michael; Komarov, Ilya; Koopman, Rose; Koppenburg, Patrick; Korolev, Mikhail; Kozlinskiy, Alexandr; Kravchuk, Leonid; Kreplin, Katharina; Kreps, Michal; Krocker, Georg; Krokovny, Pavel; Kruse, Florian; Kucharczyk, Marcin; Kudryavtsev, Vasily; Kurek, Krzysztof; Kvaratskheliya, Tengiz; La Thi, Viet Nga; Lacarrere, Daniel; Lafferty, George; Lai, Adriano; Lambert, Dean; Lambert, Robert W; Lanciotti, Elisa; Lanfranchi, Gaia; Langenbruch, Christoph; Langhans, Benedikt; Latham, Thomas; Lazzeroni, Cristina; Le Gac, Renaud; van Leerdam, Jeroen; Lees, Jean-Pierre; Lefèvre, Regis; Leflat, Alexander; Lefrançois, Jacques; Leo, Sabato; Leroy, Olivier; Lesiak, Tadeusz; Leverington, Blake; Li, Yiming; Liles, Myfanwy; Lindner, Rolf; Linn, Christian; Lionetto, Federica; Liu, Bo; Liu, Guoming; Lohn, Stefan; Longstaff, Iain; Lopes, Jose; Lopez-March, Neus; Lowdon, Peter; Lu, Haiting; Lucchesi, Donatella; Luo, Haofei; Lupato, Anna; Luppi, Eleonora; Lupton, Oliver; Machefert, Frederic; Machikhiliyan, Irina V; Maciuc, Florin; Maev, Oleg; Malde, Sneha; Manca, Giulia; Mancinelli, Giampiero; Mapelli, Alessandro; Maratas, Jan; Marchand, Jean François; Marconi, Umberto; Marin Benito, Carla; Marino, Pietro; Märki, Raphael; Marks, Jörg; Martellotti, Giuseppe; Martens, Aurelien; Martín Sánchez, Alexandra; Martinelli, Maurizio; Martinez Santos, Diego; Martinez Vidal, Fernando; Martins Tostes, Danielle; Massafferri, André; Matev, Rosen; Mathe, Zoltan; Matteuzzi, Clara; Mazurov, Alexander; McCann, Michael; McCarthy, James; McNab, Andrew; McNulty, Ronan; McSkelly, Ben; Meadows, Brian; Meier, Frank; Meissner, Marco; Merk, Marcel; Milanes, Diego Alejandro; Minard, Marie-Noelle; Moggi, Niccolò; Molina Rodriguez, Josue; Monteil, Stephane; Moran, Dermot; Morandin, Mauro; Morawski, Piotr; Mordà, Alessandro; Morello, Michael Joseph; Moron, Jakub; Morris, Adam Benjamin; Mountain, Raymond; Muheim, Franz; Müller, Katharina; Muresan, Raluca; Mussini, Manuel; Muster, Bastien; Naik, Paras; Nakada, Tatsuya; Nandakumar, Raja; Nasteva, Irina; Needham, Matthew; Neri, Nicola; Neubert, Sebastian; Neufeld, Niko; Neuner, Max; Nguyen, Anh Duc; Nguyen, Thi-Dung; Nguyen-Mau, Chung; Nicol, Michelle; Niess, Valentin; Niet, Ramon; Nikitin, Nikolay; Nikodem, Thomas; Novoselov, Alexey; Oblakowska-Mucha, Agnieszka; Obraztsov, Vladimir; Oggero, Serena; Ogilvy, Stephen; Okhrimenko, Oleksandr; Oldeman, Rudolf; Onderwater, Gerco; Orlandea, Marius; Otalora Goicochea, Juan Martin; Owen, Patrick; Oyanguren, Maria Arantza; Pal, Bilas Kanti; Palano, Antimo; Palombo, Fernando; Palutan, Matteo; Panman, Jacob; Papanestis, Antonios; Pappagallo, Marco; Parkes, Christopher; Parkinson, Christopher John; Passaleva, Giovanni; Patel, Girish; Patel, Mitesh; Patrignani, Claudia; Pazos Alvarez, Antonio; Pearce, Alex; Pellegrino, Antonio; Pepe Altarelli, Monica; Perazzini, Stefano; Perez Trigo, Eliseo; Perret, Pascal; Perrin-Terrin, Mathieu; Pescatore, Luca; Pesen, Erhan; Petridis, Konstantin; Petrolini, Alessandro; Picatoste Olloqui, Eduardo; Pietrzyk, Boleslaw; Pilař, Tomas; Pinci, Davide; Pistone, Alessandro; Playfer, Stephen; Plo Casasus, Maximo; Polci, Francesco; Poluektov, Anton; Polycarpo, Erica; Popov, Alexander; Popov, Dmitry; Popovici, Bogdan; Potterat, Cédric; Powell, Andrew; Prisciandaro, Jessica; Pritchard, Adrian; Prouve, Claire; Pugatch, Valery; Puig Navarro, Albert; Punzi, Giovanni; Qian, Wenbin; Rachwal, Bartolomiej; Rademacker, Jonas; Rakotomiaramanana, Barinjaka; Rama, Matteo; Rangel, Murilo; Raniuk, Iurii; Rauschmayr, Nathalie; Raven, Gerhard; Reichert, Stefanie; Reid, Matthew; dos Reis, Alberto; Ricciardi, Stefania; Richards, Alexander; Rihl, Mariana; Rinnert, Kurt; Rives Molina, Vincente; Roa Romero, Diego; Robbe, Patrick; Rodrigues, Ana Barbara; Rodrigues, Eduardo; Rodriguez Perez, Pablo; Roiser, Stefan; Romanovsky, Vladimir; Romero Vidal, Antonio; Rotondo, Marcello; Rouvinet, Julien; Ruf, Thomas; Ruffini, Fabrizio; Ruiz, Hugo; Ruiz Valls, Pablo; Sabatino, Giovanni; Saborido Silva, Juan Jose; Sagidova, Naylya; Sail, Paul; Saitta, Biagio; Salustino Guimaraes, Valdir; Sanchez Mayordomo, Carlos; Sanmartin Sedes, Brais; Santacesaria, Roberta; Santamarina Rios, Cibran; Santovetti, Emanuele; Sapunov, Matvey; Sarti, Alessio; Satriano, Celestina; Satta, Alessia; Savrie, Mauro; Savrina, Darya; Schiller, Manuel; Schindler, Heinrich; Schlupp, Maximilian; Schmelling, Michael; Schmidt, Burkhard; Schneider, Olivier; Schopper, Andreas; Schune, Marie Helene; Schwemmer, Rainer; Sciascia, Barbara; Sciubba, Adalberto; Seco, Marcos; Semennikov, Alexander; Senderowska, Katarzyna; Sepp, Indrek; Serra, Nicola; Serrano, Justine; Sestini, Lorenzo; Seyfert, Paul; Shapkin, Mikhail; Shapoval, Illya; Shcheglov, Yury; Shears, Tara; Shekhtman, Lev; Shevchenko, Vladimir; Shires, Alexander; Silva Coutinho, Rafael; Simi, Gabriele; Sirendi, Marek; Skidmore, Nicola; Skwarnicki, Tomasz; Smith, Anthony; Smith, Edmund; Smith, Eluned; Smith, Jackson; Smith, Mark; Snoek, Hella; Sokoloff, Michael; Soler, Paul; Soomro, Fatima; Souza, Daniel; Souza De Paula, Bruno; Spaan, Bernhard; Sparkes, Ailsa; Spradlin, Patrick; Stagni, Federico; Stahl, Sascha; Steinkamp, Olaf; Stenyakin, Oleg; Stevenson, Scott; Stoica, Sabin; Stone, Sheldon; Storaci, Barbara; Stracka, Simone; Straticiuc, Mihai; Straumann, Ulrich; Stroili, Roberto; Subbiah, Vijay Kartik; Sun, Liang; Sutcliffe, William; Swientek, Krzysztof; Swientek, Stefan; Syropoulos, Vasileios; Szczekowski, Marek; Szczypka, Paul; Szilard, Daniela; Szumlak, Tomasz; T'Jampens, Stephane; Teklishyn, Maksym; Tellarini, Giulia; Teubert, Frederic; Thomas, Christopher; Thomas, Eric; van Tilburg, Jeroen; Tisserand, Vincent; Tobin, Mark; Tolk, Siim; Tomassetti, Luca; Tonelli, Diego; Topp-Joergensen, Stig; Torr, Nicholas; Tournefier, Edwige; Tourneur, Stephane; Tran, Minh Tâm; Tresch, Marco; Tsaregorodtsev, Andrei; Tsopelas, Panagiotis; Tuning, Niels; Ubeda Garcia, Mario; Ukleja, Artur; Ustyuzhanin, Andrey; Uwer, Ulrich; Vagnoni, Vincenzo; Valenti, Giovanni; Vallier, Alexis; Vazquez Gomez, Ricardo; Vazquez Regueiro, Pablo; Vázquez Sierra, Carlos; Vecchi, Stefania; Velthuis, Jaap; Veltri, Michele; Veneziano, Giovanni; Vesterinen, Mika; Viaud, Benoit; Vieira, Daniel; Vieites Diaz, Maria; Vilasis-Cardona, Xavier; Vollhardt, Achim; Volyanskyy, Dmytro; Voong, David; Vorobyev, Alexey; Vorobyev, Vitaly; Voß, Christian; Voss, Helge; de Vries, Jacco; Waldi, Roland; Wallace, Charlotte; Wallace, Ronan; Walsh, John; Wandernoth, Sebastian; Wang, Jianchun; Ward, David; Watson, Nigel; Websdale, David; Whitehead, Mark; Wicht, Jean; Wiedner, Dirk; Wilkinson, Guy; Williams, Matthew; Williams, Mike; Wilson, Fergus; Wimberley, Jack; Wishahi, Julian; Wislicki, Wojciech; Witek, Mariusz; Wormser, Guy; Wotton, Stephen; Wright, Simon; Wu, Suzhi; Wyllie, Kenneth; Xie, Yuehong; Xing, Zhou; Xu, Zhirui; Yang, Zhenwei; Yuan, Xuhao; Yushchenko, Oleg; Zangoli, Maria; Zavertyaev, Mikhail; Zhang, Feng; Zhang, Liming; Zhang, Wen Chao; Zhang, Yanxi; Zhelezov, Alexey; Zhokhov, Anatoly; Zhong, Liang; Zvyagin, Alexander

2014-01-01

A model-dependent amplitude analysis of $B^{\\pm} \\rightarrow D K^{\\pm}$ with $D \\rightarrow K_S^0 \\pi^+ \\pi^-$ decays is performed using proton-proton collision data, corresponding to an integrated luminosity of $1$ fb$^{-1}$, recorded by LHCb at a centre-of-mass energy of $7$ TeV in $2011$. Values of the $CP$ violation observables $x_{\\pm}$ and $y_{\\pm}$, which are sensitive to the CKM angle $\\gamma$, are measured to be \\begin{align*} x_- &= +0.027 \\pm 0.044 ^{+0.010}_{-0.008} \\pm 0.001, \\\\ y_- &= +0.013 \\pm 0.048 ^{+0.009}_{-0.007} \\pm 0.003, \\\\ x_+ &= -0.084 \\pm 0.045 \\pm 0.009 \\pm 0.005, \\\\ y_+ &= -0.032 \\pm 0.048 ^{+0.010}_{-0.009} \\pm 0.008, \\end{align*} where the first uncertainty is statistical, the second systematic and the third arises from the uncertainty of the $D \\rightarrow K_S^0 \\pi^+ \\pi^-$ amplitude model. The value of $\\gamma$ is determined to be $(84^{+49}_{-42})^\\circ$, including all sources of uncertainty. Neutral $D$ meson mixing is found to have negligible effect.
Reliable 6 PEP LTPS device for AMOLED's

Science.gov (United States)

Chou, Cheng-Wei; Wang, Pei-Yun; Hu, Chin-Wei; Chang, York; Chuang, Ching-Sang; Lin, Yusin

2013-09-01

This study presents a TFT structure which has less photo process and higher cost competitiveness in AMOLED display markets. A novel LTPS based 6 masks TFT structure for bottom emission AMOLED display is demonstrated in this paper. High field effect mobility (PMOS < 80 cm2/Vs ) and high reliability (PBTS △Vth< 0.02V @ 50oC VG=15V 10ks) was accomplished without the high temperature and rapid thermal annealing (RTA) activation process. Furthermore, a 14-inch AMOLED TV was achieved on the proposed 6-pep TFT backplane using the Gen. 3.5 mass production factory.
Experimental infection of chickens and turkeys with Mycoplasma gallisepticum reference strain S6 and North Carolina field isolate RAPD type B.

Science.gov (United States)

Sanei, B; Barnes, H J; Vaillancourt, J P; Leyc, D H

2007-03-01

During an epidemic of mycoplasmosis in chicken and turkey flocks in North Carolina between 1999 and 2001, isolates of Mycoplasma gallisepticum (MG) from affected flocks were characterized by random amplification of polymorphic DNA (RAPD), and eight distinct RAPD types were identified. MG RAPD type B accounted for more than 90% of the isolates and was associated with moderate-to-severe clinical signs and mortality. The virulence of MG RAPD type B for chickens and turkeys was compared with sham-inoculated negative controls and MG S6 (a virulent strain)-inoculated positive controls. Clinical signs occurred in chickens and turkeys inoculated with either MG RAPD type B or MG S6. However, they were not as frequent or severe as those seen in naturally affected flocks, and there was no mortality in the experimental groups. Based on gross and microscopic findings, MG RAPD type B was equal to or more virulent than MG S6. All MG-inoculated birds were culture and PCR positive at 7 and 14 days postinoculation (PI). Among serological tests, the serum plate agglutination test was positive for the majority of chickens and turkeys (58%-100%) infected with either strain of MG at both 7 and 14 days PI. The hemagglutination inhibition test was negative for all birds at 7 days PI and positive for a few chickens (8%-17%) and several turkey sera (40%-60%) at 14 days PI. Only a single serum was positive by enzyme-linked immunosorbent assay (an MG S6-infected turkey) at 14 days PI.
Facile synthesis of some novel 2-substituted-4,6-diarylpyrimidines using 4 ' -hydroxy-3 ' ,5 ' -dinitrochalcones and S-benzylthiouronium chloride

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K. L. Ameta

2012-01-01

Full Text Available Various 4'-hydroxy-3',5'-dinitro substituted chalcones 1 and S-benzylthiouronium chloride (SBT 2 in the presence of DMF-organic bases (morpholine/ pyrrolidine/ piperidine gave 4,6-diaryl-2-(4-morpholinyl / 1-pyrrolidinyl /1-piperidinyl- pyrimidines 4, 5 and 6 in a facile one-pot conversion. In an another attempt reactants 1 and 2 yielded intermediate 2-benzylthiopyrimidines 3, in presence of DMF, which on treatment with heterocyclic secondary amines gave products 4, 5 and 6 in an alternate two-step process.
Synthesis and characterization of MoS2/Ti composite coatings on Ti6Al4V prepared by laser cladding

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Rongjuan Yang

2013-02-01

Full Text Available The MoS2/Ti composite coating with sub-micron grade structure has been prepared on Ti6Al4V by laser method under argon protection. The morphology, microstructure, microhardness and friction coefficient of the coating were examined. The results indicated that the molybdenum disulfide was decomposed during melting and resolidification. The phase organization of composite coating mainly consisted of ternary element sulfides, molybdenum sulfides and titanium sulfides. The friction coefficient of and the surface roughness the MoS2/Ti coating were lower than those of Ti6Al4V. The composite coating exhibits excellent adhesion to the substrates, less surface roughness, good wear resistance and harder surface.
Ks0 and Lambda production in pp interactions at √s = 0.9 and 7 TeV measured with the ATLAS detector at the LHC

International Nuclear Information System (INIS)

Aad, G.; Abbott, B.; Abdallah, J.; Abdelalim, A.A.; Abdesselam, A.; Abdinov, O.; Abi, B.; Abolins, M.; Abramowicz, H.; Abreu, H.; Acerbi, E.; Acharya, B.S.; Adams, D.L.; Addy, T.N.; Adelman, J.; Aderholz, M.; Adomeit, S.; Adragna, P.; Adye, T.; Aefsky, S.; Aguilar-Saavedra, J.A.

2012-01-01

The production of K S 0 and Λ hadrons is studied in pp collision data at √s = 0.9 and 7 TeV collected with the ATLAS detector at the LHC using a minimum-bias trigger. The observed distributions of transverse momentum, rapidity, and multiplicity are corrected to hadron level in a model-independent way within well-defined phase-space regions. The distribution of the production ratio of Λ - to Λ baryons is also measured. The results are compared with various Monte Carlo simulation models. Although most of these models agree with data to within 15% in the KS0 distributions, substantial disagreements are found in the Λ distributions of transverse momentum.
Isolation of Notoamide S and Enantiomeric 6-epi-Stephacidin A from the Fungus Aspergillus amoenus: Biogenetic Implications

DEFF Research Database (Denmark)

Kato, Hikaru; Nakahara, Takashi; Sugimoto, Kayo

2015-01-01

Notoamide S has been hypothesized to be a key biosynthetic intermediate for characteristic metabolites stephacidin A, notoamide B, and versicolamide B in Aspergillus sp. but has not yet been isolated. The isolation of notoamide S and an enantiomeric mixture of 6-epi-stephacidin A enriched with th...
Cryo-EM Structure of the Archaeal 50S Ribosomal Subunit in Complex with Initiation Factor 6 and Implications for Ribosome Evolution

Science.gov (United States)

Greber, Basil J.; Boehringer, Daniel; Godinic-Mikulcic, Vlatka; Crnkovic, Ana; Ibba, Michael; Weygand-Durasevic, Ivana; Ban, Nenad

2013-01-01

Translation of mRNA into proteins by the ribosome is universally conserved in all cellular life. The composition and complexity of the translation machinery differ markedly between the three domains of life. Organisms from the domain Archaea show an intermediate level of complexity, sharing several additional components of the translation machinery with eukaryotes that are absent in bacteria. One of these translation factors is initiation factor 6 (IF6), which associates with the large ribosomal subunit. We have reconstructed the 50S ribosomal subunit from the archaeon Methanothermobacter thermautotrophicus in complex with archaeal IF6 at 6.6 Å resolution using cryo-electron microscopy (EM). The structure provides detailed architectural insights into the 50S ribosomal subunit from a methanogenic archaeon through identification of the rRNA expansion segments and ribosomal proteins that are shared between this archaeal ribosome and eukaryotic ribosomes but are mostly absent in bacteria and in some archaeal lineages. Furthermore, the structure reveals that, in spite of highly divergent evolutionary trajectories of the ribosomal particle and the acquisition of novel functions of IF6 in eukaryotes, the molecular binding of IF6 on the ribosome is conserved between eukaryotes and archaea. The structure also provides a snapshot of the reductive evolution of the archaeal ribosome and offers new insights into the evolution of the translation system in archaea. PMID:22306461
Photoabsorption and S 2p photoionization of the SF6 molecule: resonances in the excitation energy range of 200-280 eV.

Science.gov (United States)

Stener, M; Bolognesi, P; Coreno, M; O'Keeffe, P; Feyer, V; Fronzoni, G; Decleva, P; Avaldi, L; Kivimäki, A

2011-05-07

Photoabsorption and S 2p photoionization of the SF(6) molecule have been studied experimentally and theoretically in the excitation energy range up to 100 eV above the S 2p ionization potentials. In addition to the well-known 2t(2g) and 4e(g) shape resonances, the spin-orbit-resolved S 2p photoionization cross sections display two weak resonances between 200 and 210 eV, a wide resonance around 217 eV, a Fano-type resonance around 240 eV, and a second wide resonance around 260 eV. Calculations based on time-dependent density functional theory allow us to assign the 217-eV and 260-eV features to the shape resonances in S 2p photoionization. The Fano resonance is caused by the interference between the direct S 2p photoionization channel and the resonant channel that results from the participator decay of the S 2s(-1)6t(1u) excited state. The weak resonances below 210-eV photon energy, not predicted by theory, are tentatively suggested to originate from the coupling between S 2p shake-up photoionization and S 2p single-hole photoionization. The experimental and calculated angular anisotropy parameters for S 2p photoionization are in good agreement.
A 6.25 Gb/s equalizer in 0.18 μm CMOS technology for high-speed SerDes

International Nuclear Information System (INIS)

Zhang Mingke; Hu Qingsheng

2013-01-01

This paper presents a 0.18 μm CMOS 6.25 Gb/s equalizer for high speed backplane communication. The proposed equalizer is a combined one consisting of a one-tap feed-forward equalizer (FFE) and a two-tap half-rate decision feedback equalizer (DFE) in order to cancel both pre-cursor and post-cursor ISI. By employing an active-inductive peaking circuit for the delay line, the bandwidth of the FFE is increased and the area cost is minimized. CML-based circuits such as DFFs, summers and multiplexes all help to improve the speed of DFEs. Measurement results illustrate that the equalizer operates well when equalizing 6.25 Gb/s data is passed over a 30-inch channel with a loss of 22 dB and consumes 55.8 mW with the supply voltage of 1.8 V. The overall chip area including pads is 0.3 × 0.5 mm 2 . (semiconductor integrated circuits)
Interleukin-6 overexpression induces pulmonary hypertension.

Science.gov (United States)

Steiner, M Kathryn; Syrkina, Olga L; Kolliputi, Narasaish; Mark, Eugene J; Hales, Charles A; Waxman, Aaron B

2009-01-30

Inflammatory cytokine interleukin (IL)-6 is elevated in the serum and lungs of patients with pulmonary artery hypertension (PAH). Several animal models of PAH cite the potential role of inflammatory mediators. We investigated role of IL-6 in the pathogenesis of pulmonary vascular disease. Indices of pulmonary vascular remodeling were measured in lung-specific IL-6-overexpressing transgenic mice (Tg(+)) and compared to wild-type (Tg(-)) controls in both normoxic and chronic hypoxic conditions. The Tg(+) mice exhibited elevated right ventricular systolic pressures and right ventricular hypertrophy with corresponding pulmonary vasculopathic changes, all of which were exacerbated by chronic hypoxia. IL-6 overexpression increased muscularization of the proximal arterial tree, and hypoxia enhanced this effect. It also reproduced the muscularization and proliferative arteriopathy seen in the distal arteriolar vessels of PAH patients. The latter was characterized by the formation of occlusive neointimal angioproliferative lesions that worsened with hypoxia and were composed of endothelial cells and T-lymphocytes. IL-6-induced arteriopathic changes were accompanied by activation of proangiogenic factor, vascular endothelial growth factor, the proproliferative kinase extracellular signal-regulated kinase, proproliferative transcription factors c-MYC and MAX, and the antiapoptotic proteins survivin and Bcl-2 and downregulation of the growth inhibitor transforming growth factor-beta and proapoptotic kinases JNK and p38. These findings suggest that IL-6 promotes the development and progression of pulmonary vascular remodeling and PAH through proproliferative antiapoptotic mechanisms.
Atomic radii for atoms with the 6s shell outermost: The effective atomic radius and the van der Waals radius from 55Cs to 80Hg

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Hiroshi Tatewaki

2015-06-01

Full Text Available We consider, for atoms from 55Cs to 80Hg, the effective atomic radius (rear, which is defined as the distance from the nucleus at which the magnitude of the electric field is equal to that in He at one half of the equilibrium bond length of He2. The values of rear are about 50% larger than the mean radius of the outermost occupied orbital of 6s, . The value of rear decreases from 55Cs to 56Ba and undergoes increases and decreases with rising nuclear charge from 57La to 70Y b. In fact rear is understood as comprising two interlaced sequences; one consists of 57La, 58Ce, and 64Gd, which have electronic configuration (4fn−1(5d1(6s2, and the remaining atoms have configuration (4fn(6s2. The sphere defined by rear contains 85%–90% of the 6s electrons. From 71Lu to 80Hg the radius rear also involves two sequences, corresponding to the two configurations 5dn+16s1 and 5dn6s2. The radius rear according to the present methodology is considerably larger than rvdW obtained by other investigators, some of who have found values of rvdW close to .
Protective Effects of Sonic Hedgehog Against Ischemia/Reperfusion Injury in Mouse Skeletal Muscle via AKT/mTOR/p70S6K Signaling

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Qiu Zeng

2017-10-01

Full Text Available Background/Aims: Skeletal muscle ischemia/reperfusion (I/R injury is a common and severe disease. Sonic hedgehog (Shh plays a critical role in post-natal skeletal muscle regeneration. In the present study, the role of Shh in skeletal muscle I/R injury and the mechanisms involved were investigated. Methods: The expression of Shh, AKT/mTOR/p70S6K and apoptosis pathway components were evaluated following tourniquet-induced skeletal muscle I/R injury. Then, mice were subjected to systemic administration of cyclopamine or one-shot treatment of a plasmid encoding the human Shh gene (phShh to examine the effects of Shh on I/R injury. Moreover, mice were subjected to systemic administration of NVP-BEZ235 to investigate the role of the AKT/mTOR/p70S6K pathway in Shh-triggered skeletal muscle protection. Results: We found that the levels of Shh, AKT/mTOR/p70S6K pathway components and Cleaved Caspase 3 and the Bax/Bcl2 ratio initially increased and then decreased at different time points post-I/R injury. Moreover, Shh protected skeletal muscle against I/R injury by alleviating muscle destruction, reducing interstitial fibrosis and inhibiting apoptosis, and these protective effects were abrogated when the AKT/mTOR/p70S6K pathway was inhibited. Conclusion: Collectively, these data suggest that Shh signaling exerts a protective role through the AKT/mTOR/p70S6K signaling pathway during skeletal muscle I/R injury. Thus, Shh signaling may be a therapeutic target for protecting skeletal muscle from I/R injury.

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