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  1. 1 CFR 6.3 - Daily lists of parts affected.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 1 General Provisions 1 2011-01-01 2011-01-01 false Daily lists of parts affected. 6.3 Section 6.3 General Provisions ADMINISTRATIVE COMMITTEE OF THE FEDERAL REGISTER THE FEDERAL REGISTER INDEXES AND ANCILLARIES § 6.3 Daily lists of parts affected. (a) Each daily issue of the Federal Register shall carry...

  2. 1 CFR 6.3 - Daily lists of parts affected.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 1 General Provisions 1 2013-01-01 2012-01-01 true Daily lists of parts affected. 6.3 Section 6.3 General Provisions ADMINISTRATIVE COMMITTEE OF THE FEDERAL REGISTER THE FEDERAL REGISTER INDEXES AND ANCILLARIES § 6.3 Daily lists of parts affected. (a) Each daily issue of the Federal Register shall carry...

  3. 1 CFR 6.3 - Daily lists of parts affected.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 1 General Provisions 1 2012-01-01 2012-01-01 false Daily lists of parts affected. 6.3 Section 6.3 General Provisions ADMINISTRATIVE COMMITTEE OF THE FEDERAL REGISTER THE FEDERAL REGISTER INDEXES AND ANCILLARIES § 6.3 Daily lists of parts affected. (a) Each daily issue of the Federal Register shall carry...

  4. 1 CFR 6.3 - Daily lists of parts affected.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 1 General Provisions 1 2010-01-01 2010-01-01 false Daily lists of parts affected. 6.3 Section 6.3 General Provisions ADMINISTRATIVE COMMITTEE OF THE FEDERAL REGISTER THE FEDERAL REGISTER INDEXES AND ANCILLARIES § 6.3 Daily lists of parts affected. (a) Each daily issue of the Federal Register shall carry...

  5. 1 CFR 6.3 - Daily lists of parts affected.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 1 General Provisions 1 2014-01-01 2012-01-01 true Daily lists of parts affected. 6.3 Section 6.3 General Provisions ADMINISTRATIVE COMMITTEE OF THE FEDERAL REGISTER THE FEDERAL REGISTER INDEXES AND ANCILLARIES § 6.3 Daily lists of parts affected. (a) Each daily issue of the Federal Register shall carry...

  6. 1,2,3,3',4',6'-Hexaacetyl-4,6-O-benzyl-idenesucrose.

    PubMed

    Brito-Arias, Marco A; Soto-Ortega, Miguel; García-Báez, Efrén V

    2011-01-01

    In the title compound, C(31)H(38)O(17), the 1,3-dioxane and pyran-oside rings both show (4)C(1) chair conformations while for the d-fructofuran-oside moiety an envelop 3E conformation is observed. The phenyl ring is oriented almost perpendicular to the 1,3-dioxane ring [dihedral angle = 79.3 (2)°], and the acetate groups are equatorial for the pyran-oside ring and axial for the furan-oside ring. The analysis of potential hydrogen bonds shows both intra- and inter-molecular C-H⋯O contacts to be present. PMID:21523142

  7. 1,3,6,8-Tetraethynylpyrene and 1,3,6,8-tetrakis (trimethylsilylethynyl) pyrene: Photophysical properties in homogeneous media

    NASA Astrophysics Data System (ADS)

    Shyamala, T.; Sankararaman, S.; Mishra, Ashok K.

    2006-11-01

    The photophysical properties of two new tetra substituted derivatives of pyrene: 1,3,6,8-tetraethynylpyrene (TEP) and 1,3,6,8-tetrakis(trimethylsilylethynyl)pyrene (TEP-TMS) have been studied. Studies were done with respect to mirror image symmetry in the absorption and emission spectra and permissive or forbidden nature of S 0-S 1 transition, solvent sensitivity of the first and third vibronic bands and fluorescence anisotropy. Both the derivatives exhibited a strongly allowed S 0-S 1 transition, high fluorescence quantum yield, shorter fluorescence lifetime compared to pyrene and invariance of the vibronic band intensity ratio to solvent polarity. The behavior of the two pyrene derivatives validates the hypothesis "solvent polarity mediates vibronic coupling and therefore the emission band intensities, for forbidden S 0-S 1 transitions". The trimethylsilyl derivative (TEP-TMS) was characterized by a strong fluorescence in solid state. The tetraethynyl derivative (TEP) showed high fluorescence anisotropy comparable to the well-known anisotropy probe DPH in glycerol at 0 °C. The fluorescence intensities of TEP and TEP-TMS did not show any significant change in the temperature ranger 0-40 °C for a low viscous solvent like ethanol and in the range 0-60 °C in glycerol. Unlike pyrene, no excimer emission was observed even up to 10 -3 M for TEP and TEP-TMS.

  8. 1,1',4,5-tetrahydrotrispiro[1,3,2-diazaphosphole-2,2'-[1,3,5,2,4,6]triazatriphosphinine-4',6''-dibenzo[d,f][1,3,2]dioxaphosphepine-6',6'''-dibenzo[d,f][1,3,2]dioxaphosphepine

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The title compound 1,1',4,5-tetrahydrotrispiro[1,3,2-diazaphosphole-2,2'-[1,3,5,2,4,6]triazatriphosphinine-4',6''-dibenzo[d,f][1,3,2]dioxaphosphepine-6',6'''-dibenzo[d,f][1,3,2]dioxaphosphepine], C26H22N5O4P3, at 100°K has monoclinic (P21/c) symmetry and is achieved in a two step synthesis that does...

  9. Preparation of 3,3'-azobis(6-amino-1,2,4,5-tetrazine)

    DOEpatents

    Hiskey, Michael A.; Chavez, David E.; Naud, Darren

    2002-01-01

    The compound of the structure ##STR1## where a, b, c, d and e are 0 or 1 and a+b+c+d+e is from 0 to 5 is disclosed together with the species 3,3'-azobis(6-amino-1,2,4,5-tetrazine) and a process of preparing such compounds.

  10. ARTD1 Suppresses Interleukin 6 Expression by Repressing MLL1-Dependent Histone H3 Trimethylation.

    PubMed

    Minotti, Roberta; Andersson, Anneli; Hottiger, Michael O

    2015-09-01

    ADP-ribosyltransferase diphtheria-toxin like 1/poly(ADP-ribose) polymerase 1 (ARTD1/PARP1) is a chromatin-associated protein in the nucleus and plays an important role in different cellular processes such as regulation of gene transcription. ARTD1 has been shown to coregulate the inflammatory response by modulating the activity of the transcription factor nuclear factor κB (NF-κB), the principal regulator of interleukin 6 (IL-6), an important inflammatory cytokine implicated in a variety of diseases such as cancer. However, to what extent and how ARTD1 regulates IL-6 transcription has not been clear. Here, we show that ARTD1 suppresses lipopolysaccharide (LPS)-induced IL-6 expression in macrophages, without affecting the recruitment of the NF-κB subunit RelA to the IL-6 promoter and independent of its enzymatic activity. Interestingly, knockdown of ARTD1 did not alter H3 occupancy but increased LPS-induced trimethylation of histone 3 at lysine 4 (H3K4me3), a hallmark of transcriptionally active genes. We found that ARTD1 mediates its effect through the methyltransferase MLL1, by catalyzing H3K4me3 at the IL-6 promoter and forming a complex with NF-κB. These results demonstrate that ARTD1 modulates IL-6 expression by regulating the function of an NF-κB enhanceosome complex, which involves MLL1 and does not require ADP-ribosylation. PMID:26149390

  11. β-(13),(16)-Glucans: medicinal activities, characterization, biosynthesis and new horizons.

    PubMed

    Dalonso, Nicole; Goldman, Gustavo Henrique; Gern, Regina Maria Miranda

    2015-10-01

    Biological activities of medicinal mushrooms have been attributed to β-(13),(16)-glucans that are present in the cell wall of fungi and some plants. Antitumor, immunomodulatory, antimicrobial, antinociception, antiinflammatory, prebiotic, antioxidant, and antidiabetic are some of different properties already described for β-(13),(16)-glucans. Immune activation systems, including specific β-glucan receptors like Dectin-1, complement (CR3), and Toll (TLR), have been identified to clarify these biological effects. The β-(13)-glucans are synthesized by β-(13)-glucan synthase (GLS), an enzyme belonging to the glucosyltransferase group, which has a catalytic unit (FKS) and another regulatory (RHO). The mechanisms for adding β-(16) branches to the non-reducing ends of the β-(13)-glucan chains are unclear until now. Due to the biological importance of β-(13),(16)-glucan, it is necessary to understand the biochemical and molecular mechanisms of its synthesis, both to optimize the production of bioactive compounds and to develop antifungal drugs that interrupt this process. Therefore, the aim of this review is to gather information about the potential of β-(13),(16)-glucans, their methods of isolation, purification, and chemical characterization, as well as how these biomolecules are synthesized by fungi and what studies involving biotechnology or molecular biology have contributed to this subject. PMID:26252967

  12. Bicyclo[3.2.1]octa-3,6-dien-2-yl cation: a bishomoantiaromate.

    PubMed

    Volz, Heinrich; Shin, Jung-Hyu

    2006-03-17

    Antiaromatic compounds with a closed loop of 4n p-electrons are relatively unstable and often difficult to study. We report in this article the synthesis of alcohols 2-(4'-fluorophenyl)bicyclo[3.2.1]octan-2-ol 11, 2-(4'-fluorophenyl)bicyclo[3.2.1]oct-3-en-2-ol 12, and 2-(4'-fluorophenyl)bicyclo[3.2.1]octa-3,6-dien-2-ol 13 and their transformations into corresponding carbocations 14-16, respectively, in a superacidic medium (FSO3H/SO2ClF) at -120 degrees C. Cations 14-16 are characterized by NMR analysis (1H, 13C, 19F), and 15 and 16 are further characterized by quenching in NaOCH3/H3COH at -120 degrees C. The relative stabilities of 14-16 are determined experimentally by 19F NMR spectroscopy. Cation 16 is found to be experimentally less stable than cation 15 by 3.7 kcal/mol. DFT calculations (structure and energy: B3LYP/6-31G(d); NMR: B3LYP/6-311+G(2d,p)) are performed for alcohols 11-13 and bicyclo[3.2.1]octyl cations 6, 7, 9, 14-16, 26, 28, and 30. In the case of 11-16, data from DFT calculations is in good agreement with experimental data. Because 6,7-dimethylenebicyclo[3.2.1]oct-3-en-2-yl cation 26 is more stable than cation 7 by 1.69 kcal/mol, the inductive effect of sp(2)-hybridized carbon atoms C6 and C7 in carbocations 6 and 16 cannot be the reason for the destabilization of 6 relative to 7 and 16 relative to 15. Destabilization of 6 relative to 7 and 16 relative to 15 and the calculated NICS of 6 (+4.17 ppm) and 16(+3.3 ppm) document that 6 and 16 are bishomoantiaromates. PMID:16526766

  13. Synthesis of 1,3,4-thiadiazole, 1,3,4-thiadiazine, 1,3,6-thiadiazepane and quinoxaline derivatives from symmetrical dithiobiureas and thioureidoethylthiourea derivatives.

    PubMed

    Hassan, Alaa A; Mourad, Aboul-Fetouh; El-Shaieb, Kamal M; Abou-Zied, Ashraf H

    2005-01-01

    Reactions of N,N;-disubstituted hydrazinecarbothioamides 8a-c and substituted thioureidoethylthioureas 9a-c with 2,3,5,6-tetrachloro-1,4-benzoquinone (chloranil, 10a) and 2,3,5,6-tetrabromo-1,4-benzoquinone (bromanil, 10b) to form N,N;-disubstituted [1,3,4]thiadiazole-2,5-diamines 11a-c, 6,7-dichloro-3-substituted amino-1H-benzo[1,3,4]- thiadiazine-5,8-diones 12a-c, 2,3,7,8-tetrahalothianthrene-1,4,6,9-tetraones 13a,b, 5,6,8- trihalo-7-oxo-3,7-dihydro-2H-quinoxaline-1-carbothioic acid substituted amides 14a-c, 15a-c and 7-substituted imino-[1,3,6]thiadiazepane-3-thiones 16a-c are reported. Rationales for the observed conversions are presented. PMID:18007352

  14. Teachers Teaching Teachers (T3). Volume 6, Number 1

    ERIC Educational Resources Information Center

    Armstrong, Anthony, Ed.

    2010-01-01

    "Teachers Teaching Teachers" ("T3") focuses on coaches' roles in the professional development of teachers. Each issue also explores the challenges and rewards that teacher leaders encounter. This issue includes: (1) Collective Responsibility Makes All Teachers the Best (Stephanie Hirsh); (2) Tools: How Our School Measures up/Exploring Our…

  15. 3,3,6,6-Tetra-methyl-9-[6-(3,3,6,6-tetra-methyl-1,8-dioxo-2,3,4,5,6,7,8,9-octa-hydro-1H-xanthen-9-yl)pyridin-2-yl]-2,3,4,5,6,7,8,9-octa-hydro-1H-xanthene-1,8-dione.

    PubMed

    Abdelhamid, Antar A; Mohamed, Shaaban Kamel; Allahverdiyev, Mirze A; Gurbanov, Atash V; Ng, Seik Weng

    2011-04-01

    In the title mol-ecule, C(39)H(45)NO(6), the two tetra-methyl-octa-hydroxanthen-1,8-dione substituents are arranged approximately parallel to each other and approximately perpendicular to the plane of the pyridine ring. The six-membered xanthene rings adopt flattened boat conformations with the O and methine C atoms deviating from the plane of the other four atoms. PMID:21754076

  16. (3+1)-Incommensurately modulated crystal structure of Cs3ScSi6O15.

    PubMed

    Hejny, Clivia; Kahlenberg, Volker; Schmidmair, Daniela; Dabić, Predrag

    2016-02-01

    Single-crystal X-ray diffraction of Cs3ScSi6O15 shows the presence of main reflections and satellite reflections up to the fourth order along the c* direction. The (3+1)-dimensional incommensurately modulated structure was solved in superspace group X3m1(00gamma)0s0 [a = 13.861 (1), c = 6.992 (1) Å, V = 1163.4 (2) Å(3)] with a modulation wavevector q = 0.14153 (2)c*. Refinement of three modulation waves for positional and anisotropic displacement parameter values for all atoms converged to R(obs) values for all, main and satellite reflections of first, second and third order of 0.0200, 0.0166, 0.0181, 0.0214 and 0.0303, respectively. Cs3ScSi6O15 forms a mixed tetrahedral-octahedral framework with prominent six-membered rings of [SiO4]-tetrahedra interconnected by [ScO6]-octahedra. Apart from Sc, all atoms are strongly affected by positional modulation with maximum atomic displacements of up to 0.93 Å causing rigid polyhedral arrangements to perform tilt and twist movements relative to each other, such as a rotation of the Sc-octahedra around the 3-axis by over 38°. Cs has an irregular coordination environment; however, considering distances up to 3.5 Å, the bond-valence sum changes by no more than 0.02 as a function of t and thus overall kept at a level of ca 1.075. PMID:26830802

  17. Heteroadamantanes and their derivatives. V. Synthesis of 5-monosubstituted 6-oxo- and 6-hydroxy-1,3-diazaadamantanes

    SciTech Connect

    Kuznetsov, A.I.; Basargin, E.B.; Mamadu Hadi Ba; Yakushev, P.F.; Unkovskii, B.V.

    1986-05-20

    The difficulty obtainable 5-methyl- and 5-phenyl-6-oxo-1,3-diazaadamantanes are formed when methyl ethyl ketone and methyl benzyl ketone are heated with hexamethylenetetraamine and glacial acetic acid in 1-butanol by a modified Mannich reaction. Their reduction gave 5-methyl- and 5-phenyl-6-hydroxy-1,3-diazaadamantanes.

  18. 2-Azido-1-(3,6-dichloro-9H-fluoren-1-yl)ethanone

    PubMed Central

    Fun, Hoong-Kun; Chia, Tze Shyang; Kayarmar, Reshma; Dinesha; Nagaraja, G. K.

    2011-01-01

    In the title compound, C15H9Cl2N3O, an intra­molecular C—H⋯O inter­action generates an S(7) ring motif. The cyclo­penta-1,3-diene ring forms dihedral angles of 1.93 (6) and 2.78 (6)° with its attached benzene rings. In the crystal, mol­ecules are linked by C—H⋯N and C—H⋯O hydrogen bonds, thereby forming layers lying parallel to the ac plane. The crystal also features a π–π inter­action with a centroid–centroid distance of 3.5612 (6) Å. PMID:22058777

  19. Propellant Containing 3, 6bis(1h-1,2,3,4-Tetrazol-5-Ylamino)-1,2,4,5- Tetrazine Or Salt Thereof

    DOEpatents

    Hiskey, Michael A.; Chavez, David E.; Naud, Darren

    2003-12-02

    The compound 3,6-bis(1H-1,2,3,4-tetrazol-5-ylamino)-1,2,4,5-tetrazine and its salts are provided together with a propellant composition including an oxidizer, a binder and 3,6-bis(1H-1,2,3,4-tetrazol-5-ylamino)-1,2,4,5-tetrazine or its salts.

  20. 40 CFR 721.7280 - 1,3-Propanediamine, N,N′-1,2-ethanediylbis-, polymer with 2,4,6-trichloro-1,3,5-triazine...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...-ethanediylbis-, polymer with 2,4,6-trichloro-1,3,5-triazine, reaction products with N-butyl-2,2,6,6-tetramethyl...-, polymer with 2,4,6-trichloro-1,3,5-triazine, reaction products with N-butyl-2,2,6,6-tetramethyl-4..., reaction products with N-butyl-2,2,6,6-tetramethyl-4-piperidinamine (PMN P-89-632) is subject to...

  1. 40 CFR 721.7280 - 1,3-Propanediamine, N,N′-1,2-ethanediylbis-, polymer with 2,4,6-trichloro-1,3,5-triazine...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...-ethanediylbis-, polymer with 2,4,6-trichloro-1,3,5-triazine, reaction products with N-butyl-2,2,6,6-tetramethyl...-, polymer with 2,4,6-trichloro-1,3,5-triazine, reaction products with N-butyl-2,2,6,6-tetramethyl-4..., reaction products with N-butyl-2,2,6,6-tetramethyl-4-piperidinamine (PMN P-89-632) is subject to...

  2. 40 CFR 721.7280 - 1,3-Propanediamine, N,N′-1,2-ethanediylbis-, polymer with 2,4,6-trichloro-1,3,5-triazine...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...-ethanediylbis-, polymer with 2,4,6-trichloro-1,3,5-triazine, reaction products with N-butyl-2,2,6,6-tetramethyl...-, polymer with 2,4,6-trichloro-1,3,5-triazine, reaction products with N-butyl-2,2,6,6-tetramethyl-4..., reaction products with N-butyl-2,2,6,6-tetramethyl-4-piperidinamine (PMN P-89-632) is subject to...

  3. 40 CFR 721.7280 - 1,3-Propanediamine, N,N′-1,2-ethanediylbis-, polymer with 2,4,6-trichloro-1,3,5-triazine...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...-ethanediylbis-, polymer with 2,4,6-trichloro-1,3,5-triazine, reaction products with N-butyl-2,2,6,6-tetramethyl...-, polymer with 2,4,6-trichloro-1,3,5-triazine, reaction products with N-butyl-2,2,6,6-tetramethyl-4..., reaction products with N-butyl-2,2,6,6-tetramethyl-4-piperidinamine (PMN P-89-632) is subject to...

  4. Reactions of organyl and silyl alanes with 1,3,4,5,6-pentamethyl-2-aminoborazine.

    PubMed

    Fan, Maomin; Duesler, Eileen N; Nöth, Heinrich; Paine, Robert T

    2010-03-15

    The reactions of (Me(3)Si)(3)Al, Me(3)Al, Et(3)Al, and i-Bu(3)Al with 1,3,4,5,6-pentamethyl-2-aminoborazine have been examined. An amine alane adduct (Me(3)Si)(3)Al.NH(2)B(3)(Me)(2)N(3)Me(3) (1) and several elimination products [(Me(3)Si)(2)AlN(H)B(3)(Me)(2)N(3)Me(3)](2) (2), [(Me(3)SiAl)(4)(Me(3)SiN)(3)NH] (3), [Me(2)AlN(H) B(3)(Me)(2)N(3)Me(3)](2) (4), [Et(2)AlN(H) B(3)(Me)(2)N(3)Me(3)](2) (5), and [i-Bu(2)AlN(H) B(3)(Me)(2)N(3)Me(3)](2) (6) have been isolated. Compounds 1, 2, 4-6 have been spectroscopically characterized, and single crystal X-ray diffraction structure determinations have been completed for 1-4 and 6. The molecular chemistry provides insight into the reaction of Me(3)Al and 1,3,5-N-trimethyl-2,4,6-B-triaminoborazine that, upon pyrolysis, produces AlN/BN composite ceramic materials. PMID:20158196

  5. 49 CFR 177.841 - Division 6.1 and Division 2.3 materials.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 2 2011-10-01 2011-10-01 false Division 6.1 and Division 2.3 materials. 177.841... PUBLIC HIGHWAY Loading and Unloading § 177.841 Division 6.1 and Division 2.3 materials. (See also § 177... by other appropriate method, and the marking removed. (b) (c) Division 2.3 (poisonous gas)...

  6. Heterologous expression of C. elegans fat-1 decreases the n-6/n-3 fatty acid ratio and inhibits adipogenesis in 3T3-L1 cells

    SciTech Connect

    An, Lei; Pang, Yun-Wei; Gao, Hong-Mei; Tao, Li; Miao, Kai; Wu, Zhong-Hong; and others

    2012-11-23

    Highlights: Black-Right-Pointing-Pointer Expression of C. elegans fat-1 reduces the n-6/n-3 PUFA ratio in 3T3-L1 cells. Black-Right-Pointing-Pointer fat-1 inhibits the proliferation and differentiation of 3T3-L1 preadipocytes. Black-Right-Pointing-Pointer fat-1 reduces lipid deposition in 3T3-L1 adipocytes. Black-Right-Pointing-Pointer The lower n-6/n-3 ratio induces apoptosis in 3T3-L1 adipocytes. -- Abstract: In general, a diet enriched in polyunsaturated fatty acids (PUFAs) inhibits the development of obesity and decreases adipose tissue. The specific impacts of n-3 and n-6 PUFAs on adipogenesis, however, have not been definitively determined. Traditional in vivo and in vitro supplementation studies have yielded inconsistent or even contradictory results, which likely reflect insufficiently controlled experimental systems. Caenorhabditiselegans fat-1 gene encodes an n-3 fatty acid desaturase, and its heterologous expression represents an effective method both for altering the n-6/n-3 PUFA ratio and for evaluating the biological effects of n-3 and n-6 PUFAs. We sought to determine whether a reduced n-6/n-3 ratio could influence adipogenesis in 3T3-L1 cells. Lentivirus-mediated introduction of the fat-1 gene into 3T3-L1 preadipocytes significantly reduced the n-6/n-3 ratio and inhibited preadipocyte proliferation and differentiation. In mature adipocytes, fat-1 expression reduced lipid deposition, as measured by Oil Red O staining, and induced apoptosis. Our results indicate that a reduced n-6/n-3 ratio inhibits adipogenesis through several mechanisms and that n-3 PUFAs more effectively inhibit adipogenesis (but not lipogenesis) than do n-6 PUFAs.

  7. Inositol 1,3,4,6-tetrakisphosphate mobilizes calcium in Xenopus oocytes with high potency.

    PubMed Central

    Ivorra, I; Gigg, R; Irvine, R F; Parker, I

    1991-01-01

    Injection of Ins(1,3,4,6)P4 into Xenopus oocytes evoked Ca2(+)-dependent membrane currents with a potency 5-10 times less than Ins(1,4,5)P3, whereas Ins(1,3,4)P3 and Ins(1,3,4,5,6)P5 were almost ineffective. Responses to Ins(1,3,4,6)P4 arose through liberation of intracellular Ca2+ and through entry of extracellular Ca2+. These results, together with the observation that Ins(1,3,4,6)P4 facilitated responses to Ins(1,4,5)P3, suggests that both of these compounds may act on the same intracellular receptors. PMID:1991032

  8. 40 CFR 180.1086 - 3,7,11-Trimethyl-1,6,10-dodecatriene-1-ol and 3,7,11-trimethyl-2,6,10-dodecatriene-3-ol...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ....1086 3,7,11-Trimethyl-1,6,10-dodecatriene-1-ol and 3,7,11-trimethyl-2,6,10-dodecatriene-3-ol; exemption... 40 Protection of Environment 23 2010-07-01 2010-07-01 false 3,7,11-Trimethyl-1,6,10-dodecatriene-1-ol and 3,7,11-trimethyl-2,6,10-dodecatriene-3-ol; exemption from the requirement of a tolerance....

  9. Asymmetric synthesis of bicyclo[4.3.1]decadienes and bicyclo[3.3.2]decadienes via [6 + 3] trimethylenemethane cycloaddition with tropones.

    PubMed

    Trost, Barry M; McDougall, Patrick J; Hartmann, Olaf; Wathen, Peter T

    2008-11-12

    The cyanosubstituted trimethylenemethane donor undergoes palladium-catalyzed [6 + 3] cycloaddition with a variety of tropones to yield bicyclo[4.3.1]decadienes in excellent regio-, diastereo-, and enantioselectivity. Products of the Pd-TMM [6 + 3] cycloaddition participate in a thermal [3,3] sigmatropic rearrangement to yield bicyclo[3.3.2]decadienes in good yield. PMID:18937462

  10. Entry of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine into the rat brain

    SciTech Connect

    Riachi, N.J.; LaManna, J.C.; Harik, S.I.

    1989-06-01

    We studied blood-to-brain entry of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), 1-methyl-4-phenylpyridinium (MPP+) and butanol in anesthetized rats using the indicator-fractionation method with right atrial bolus injection. Minimal amounts of MPP+, which has low octanol/water partition coefficient, crossed the blood-brain barrier. MPTP and butanol, both of which have high octanol/water partition coefficients, were almost completely extracted by all regions of the brain on the first pass. The main difference between the MPTP and butanol tracers is that butanol rapidly left the brain with an exponential rate constant of 1.24 min-1, whereas MPTP was avidly retained by the brain with a washout rate constant of 0.10 min-1 (mean values for the four brain regions that we studied). Early retention of MPTP by the brain was not due to its rapid metabolism by monoamine oxidase because pargyline pretreatment did not affect this rate constant. However, 30 min after (/sup 3/H)MPTP injection, brain retention of the 3H tracer was reduced significantly by pargyline treatment, and the ratio of brain MPTP/MPP+ was increased markedly.

  11. 3,4,6-Trimethyl-1-phenyl-1H-pyrazolo­[3,4-b]pyridine

    PubMed Central

    Hamri, Salha; Hafid, Abderrafia; Zouihri, Hafid; Lazar, Saïd; Khouili, Mostafa

    2010-01-01

    In the title compound, C15H15N3, the 1H-pyrazolo­[3,4-b]pyridine system and the phenyl ring are each individually planar, with r.m.s. deviations of 0.017 (2) and 0.011 (2) Å, respectively; the dihedral angle between the two aromatic systems is 9.33 (10)°. The crystal packing is stabilized by offset π–π stacking between parallel pyrazolo­[3,4-b]pyridine ring systems [face-to-face distance = 3.449 (6) Å]. PMID:21588287

  12. 40 CFR 721.7280 - 1,3-Propanediamine, N,N′-1,2-ethanediylbis-, polymer with 2,4,6-trichloro-1,3,5-triazine...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...-ethanediylbis-, polymer with 2,4,6-trichloro-1,3,5-triazine, reaction products with N-butyl-2,2,6,6-tetramethyl... AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances § 721.7280 1,3-Propanediamine,...

  13. Regioselective synthesis of pyrimido[1,2-a][1,3,5]triazin-6-ones via reaction of 1-(6-oxo-1,6-dihydropyrimidin-2-yl)guanidines with triethylorthoacetate: observation of an unexpected rearrangement.

    PubMed

    Sachdeva, Nikhil; Dolzhenko, Anton V; Chui, Wai Keung

    2012-06-21

    A novel thermal rearrangement, involving pyrimidine ring opening and subsequent ring closure leading to recyclization of the system, was identified in the reaction of (6-oxo-1,6-dihydropyrimidin-2-yl)guanidines 3 (where NR(1)R(2) = NH(2), NH alkyl, NH aralkyl, NHCH(2)Ph(R)) with triethyl orthoacetate, affording 4-substituted-2-methyl-6H-pyrimido[1,2-a][1,3,5]triazin-6-ones 6 and their ring opened products. However, no such rearrangement was observed with (6-oxo-1,6-dihydropyrimidin-2-yl)guanidines 3 bearing a tertiary amino or anilino substituent (i.e. where NR(1)R(2) = N(CH(3))(2), indoline, morpholino, NHAr). As expected, 2-substituted-4-methyl-6H-pyrimido[1,2-a][1,3,5]triazin-6-ones 4 were obtained as the final products. Experimental structural determination and theoretical studies were carried out to get an understanding of the observed thermal rearrangement. In addition, an attempt to obtain similar pyrimido[1,2-a][1,3,5]triazin-6-ones using N,N-dimethylacetamide dimethyl acetal (DMA-DMA) as one carbon inserting synthon had furnished triazine ring annulated product 14 bearing N,N-dimethyl enamino substituent at position 4 as a result of further reaction with a second molecule of DMA-DMA. PMID:22581349

  14. Synthesis of 1,4,5,6-tetrahydropyridine derivatives starting from trans-3-chloro-1,3-alkadien-5-ones

    SciTech Connect

    Melikyan, G.G.; Atanesyan, K.A.; Aslanyan, G.Kh.; Tirakyan, M.R.; Khachatryan, L.A.; Badanyan, Sh.O.

    1987-10-01

    A method has been developed for the synthesis of 3-carbethoxy-2-methyl-6-(oxo-alkylidene)-1,4,5,6-tetrahydropyridines by reaction of trans-3-chloro-1,3-alkadien-5-ones with ethyl aminocrotonate. It is shown that the corresponding vinylacetylanic ketones are intermediate products of the reactions. PMR spectra in CCl/sub 4/ were obtained on a Perkin-Elmer R12B (60 MHz) spectrometer, with TMS as internal standard. /sup 13/C NMR spectra were recordeed on a Bruker WH-90 instrument (22.63 MHz) without suppression and with complete suppression of spin-spin coupling. IR spectra were recorded in CCl/sub 4/ on a UR-10 instrument, mass spectra were recorded on a MX-1303 spectrometer with electron ionization energy of 30 eV.

  15. 4,6-Dihy-droxy-4,6-dimethyl-1,3-diazinane-2-thione.

    PubMed

    Aliyeva, Khatira N; Maharramov, Abel M; Allahverdiyev, Mirze A; Gurbanov, Atash V; Brito, Iván

    2011-09-01

    In the title compound, C(6)H(12)N(2)O(2)S, the heterocyclic ring has a sofa conformation. The mol-ecular conformation is stabilized by an intra-molecular O-H⋯O hydrogen-bond inter-action with graph-set motif S(6). In the crystal, mol-ecules are linked by O-H⋯S, N-H⋯S and N-H⋯O hydrogen-bond inter-actions, forming an extended two-dimensional framework parallel to the ac plane. PMID:22058933

  16. Observations of the microwave emission of Venus from 1.3 to 3.6 cm.

    PubMed

    Steffes, P G; Klein, M J; Jenkins, J M

    1990-03-01

    Laboratory measurements of Steffes (1986) have suggested that the intensity and shape of the microwave spectrum of Venus might be especially sensitive to the subcloud abundance of constituents such as SO2 and gaseous H2SO4. It was likewise suggested that some variations of the shape of the emission spectrum might occur between 1.5 and 3 cm (10 to 20 GHz), a wavelength range which had previously only been sparsely observed. As a result, coordinated observations of Venus emission were conducted at four wavelengths between 1.35 cm (22.2 GHz) and 3.6 cm (8.42 GHz) using the 43-m NRAO antenna at Green Bank, West Virginia, and the 64-m antenna at NASA's Deep Space Communication Complex, Goldstone, California. In this paper, we report the methodology and results of these observations, and compare the results with other observations and with calculated emission spectra. We conclude that the observed emission spectrum is consistent with an average subcloud abundance of gaseous H2SO4 in equatorial and midlatitude regions which is approximately 5 ppm. It is suggested that additional measurements of atmospheric microwave opacity be made with the Pioneer-Venus Orbiter Radio Occultation experiment to search for temporal and spatial variations in gaseous H2SO4 abundance in the Venus atmosphere. An upper limit for the subcloud abundance of SO2 is also determined. PMID:11538401

  17. (16)- and (13)(16)-β-glucans from Lasiodiplodia theobromae MMBJ: Structural characterization and pro-inflammatory activity.

    PubMed

    Oliveira, Kassandra S M; Di Bastiani, Mirela; Cordeiro, Lucimara M C; Costa, Mírian F; Toledo, Karina A; Iacomini, Marcello; Babosa, Aneli M; Dekker, Robert F H; Nascimento, Valéria M G

    2015-11-20

    The chemical composition and structural characterization of exopolysaccharides from the fungus Lasiodiplodia theobromae MMBJ are described, and the immunomodulatory activity of a purified β-glucan was evaluated. L. theobromae MMBJ produced three different β-glucans. One, fraction PEPS, was a branched (13)(16)-β-glucan and was insoluble in cold water. The other two, fractions SEPS-005R and SEPS-10E, were characterized as linear (16)-β-glucans with molar mass of 1.8×10(6)Da and 7.0×10(3)Da, respectively. From a total of 2.2g/L of EPS produced by L. theobromae through submerged fermentation, 1.5g/L (67%) was of the branched (13)(16)-β-glucan, while 25% (w/w) were linear (16)-β-glucans. Tests conducted with macrophages showed that the high molar mass (16)-β-glucan fraction (SEPS-005R) induced a pro-inflammatory response pattern. PMID:26344312

  18. Human Cytomegalovirus IE1 Protein Disrupts Interleukin-6 Signaling by Sequestering STAT3 in the Nucleus

    PubMed Central

    Reitsma, Justin M.; Sato, Hiromi; Nevels, Michael

    2013-01-01

    In the canonical STAT3 signaling pathway, binding of agonist to receptors activates Janus kinases that phosphorylate cytoplasmic STAT3 at tyrosine 705 (Y705). Phosphorylated STAT3 dimers accumulate in the nucleus and drive the expression of genes involved in inflammation, angiogenesis, invasion, and proliferation. Here, we demonstrate that human cytomegalovirus (HCMV) infection rapidly promotes nuclear localization of STAT3 in the absence of robust phosphorylation at Y705. Furthermore, infection disrupts interleukin-6 (IL-6)-induced phosphorylation of STAT3 and expression of a subset of IL-6-induced STAT3-regulated genes, including SOCS3. We show that the HCMV 72-kDa immediate-early 1 (IE1) protein associates with STAT3 and is necessary to localize STAT3 to the nucleus during infection. Furthermore, expression of IE1 is sufficient to disrupt IL-6-induced phosphorylation of STAT3, binding of STAT3 to the SOCS3 promoter, and SOCS3 gene expression. Finally, inhibition of STAT3 nuclear localization or STAT3 expression during infection is linked to diminished HCMV genome replication. Viral gene expression is also disrupted, with the greatest impact seen following viral DNA synthesis. Our study identifies IE1 as a new regulator of STAT3 intracellular localization and IL-6 signaling and points to an unanticipated role of STAT3 in HCMV infection. PMID:23903834

  19. Preparation of 1,3,5-triamino-2,4,6-trinitrobenzene from 3,5-dichloroanisole

    DOEpatents

    Ott, D.G.; Benziger, T.M.

    1991-03-05

    Preparation of 1,3,5-triamino-2,4,6-trinitrobenzene (TATB) from 3,5-dichloroanisole is described. Nitration of 3,5-dichloroanisole under relatively mild conditions gave 3,5-dichloro-2,4,6-trinitroanisole in high yield and purity. Ammonolysis of this latter compound gave the desired TATB. Another route to TATB was through the treatment of the 3,5-dichloro-2,4,6-trinitroanisole with thionyl chloride and dimethylformamide to yield 1,3,5-trichloro-2,4,6-trinitrobenzene. Ammonolysis of this product produced TATB. 8 figures.

  20. The spectroscopic analysis of the v2 = 1, v5 = 1, and v3 = v6 = 1 infrared vibration system of H3SiI

    NASA Astrophysics Data System (ADS)

    Canè, Elisabetta; Villa, Mattia; Tamassia, Filippo; Fusina, Luciano; Bürger, Hans; Litz, Marion

    2016-06-01

    The ν2 (A1)/ν5 (E)/ν3 + ν6 (E) band system of H328SiI was investigated using Fourier transform infrared spectra recorded from 820 to 1100 cm- 1 at a resolution of 2.0 × 10- 3 cm- 1. In total, 11,903 transitions were assigned. Additional 1466 transitions reaching the v3 = v6 = 1 state were obtained from the ν3 + ν6 - ν6 and ν3 + ν6 - ν3 hot bands near 360 and 590 cm- 1, respectively. Moreover, 30 highly accurate CO2 laser sideband transitions of the rQ0 branch of ν5 (J.M. Frye, W. Schupita, and G. Magerl, J. Mol. Spectrosc. 128, 427 (1988)) were implemented in the data set with J max ″ = 140 and K max ″ = 21. To adequately reproduce the complex pattern of interacting levels the Hamiltonian employed included 14 off-diagonal terms. These comprise x,y Coriolis ro-vibration resonances, between ν2/ν5, ν2/ν3 + ν6 and ν5/ν3 + ν6, and the anharmonic Fermi resonance between ν5/ν3 + ν6. All these resonances strongly perturb the v2 = 1, v5 = 1, and v3 = v6 = 1 excited states whose rounded deperturbed vibrational term values are 904.5, 941.1, and 953.7 cm- 1, respectively. In addition, the Δl = Δk = ± 2 l-resonance was found to be active within the v3 = v6 = 1 state and between v5 = 1 and v3 = v6 = 1; the Δl = ± 2 , Δk = ∓ 1 l-resonance within the v5 = 1 state and between v5 = 1 and v3 = v6 = 1 was established, as well as the Δl = ± 1 , Δk = ∓ 2 α resonance between v2 = 1 and v5 = 1. A standard deviation of the fit, 0.48 × 10- 3 cm- 1, resulted which is ca. three times the estimated precision of experimental wavenumbers. Improved J-dependent ground state parameters of H3SiI were obtained by fitting 5420 combination differences, σ(fit) = 0.22 × 10- 3 cm- 1.

  1. Volumetric Properties of the Mixture Dimethyl carbonate C3H6O3 + C6H12O3 2,4,6-Trimethyl-1,3,5-trioxane (VMSD1111, LB4518_V)

    NASA Astrophysics Data System (ADS)

    Cibulka, I.; Fontaine, J.-C.; Sosnkowska-Kehiaian, K.; Kehiaian, H. V.

    This document is part of Subvolume C 'Binary Liquid Systems of Nonelectrolytes III' of Volume 26 'Heats of Mixing, Vapor-Liquid Equilibrium, and Volumetric Properties of Mixtures and Solutions' of Landolt-Börnstein Group IV 'Physical Chemistry'. It contains the Chapter 'Volumetric Properties of the Mixture Dimethyl carbonate C3H6O3 + C6H12O3 2,4,6-Trimethyl-1,3,5-trioxane (VMSD1111, LB4518_V)' providing data from direct low-pressure measurement of mass density at variable mole fraction and constant temperature, in the single-phase region(s).

  2. Volumetric Properties of the Mixture Dimethyl carbonate C3H6O3 + C6H12O3 2,4,6-Trimethyl-1,3,5-trioxane (VMSD1212, LB4519_V)

    NASA Astrophysics Data System (ADS)

    Cibulka, I.; Fontaine, J.-C.; Sosnkowska-Kehiaian, K.; Kehiaian, H. V.

    This document is part of Subvolume C 'Binary Liquid Systems of Nonelectrolytes III' of Volume 26 'Heats of Mixing, Vapor-Liquid Equilibrium, and Volumetric Properties of Mixtures and Solutions' of Landolt-Börnstein Group IV 'Physical Chemistry'. It contains the Chapter 'Volumetric Properties of the Mixture Dimethyl carbonate C3H6O3 + C6H12O3 2,4,6-Trimethyl-1,3,5-trioxane (VMSD1212, LB4519_V)' providing data by calculation of molar excess volume from low-pressure density measurements at variable mole fraction and constant temperature.

  3. Volumetric Properties of the Mixture Dimethyl carbonate C3H6O3 + C6H12O3 2,4,6-Trimethyl-1,3,5-trioxane (VMSD1511, LB4517_V)

    NASA Astrophysics Data System (ADS)

    Cibulka, I.; Fontaine, J.-C.; Sosnkowska-Kehiaian, K.; Kehiaian, H. V.

    This document is part of Subvolume C 'Binary Liquid Systems of Nonelectrolytes III' of Volume 26 'Heats of Mixing, Vapor-Liquid Equilibrium, and Volumetric Properties of Mixtures and Solutions' of Landolt-Börnstein Group IV 'Physical Chemistry'. It contains the Chapter 'Volumetric Properties of the Mixture Dimethyl carbonate C3H6O3 + C6H12O3 2,4,6-Trimethyl-1,3,5-trioxane (VMSD1511, LB4517_V)' providing data from direct measurement of low-pressure thermodynamic speed of sound at variable mole fraction and constant temperature, in the single-phase region(s).

  4. 3,3,6,6,9,9-Hexaethyl-1,2,4,5,7,8-hexaoxacyclononane at 296 K.

    PubMed

    Cerna, Jorge; Bernès, Sylvain; Cañizo, Adriana; Eyler, Nora

    2009-11-01

    The title molecule (diethyl ketone triperoxide, DEKTP), C(15)H(30)O(6), is a cyclic triperoxide closely related to triacetone triperoxide (TATP), one of the most unstable explosives known. However, the stability of DEKTP is ca 20-50 times greater than that of TATP. DEKTP crystallizes with two molecules in the asymmetric unit, with virtually identical geometry. The cyclononane core is stabilized in a twisted boat-chair conformation (approximate D(3) symmetry), very close to that previously described for TATP. The explanation for the safe thermal behaviour of DEKTP compared with TATP should thus not be sought in the molecular dimensions, but rather in the thermal decomposition kinetics. PMID:19893236

  5. Omega 3 but not omega 6 fatty acids inhibit AP-1 activity and cell transformation in JB6 cells

    PubMed Central

    Liu, Guangming; Bibus, Douglas M.; Bode, Ann M.; Ma, Wei-Ya; Holman, Ralph T.; Dong, Zigang

    2001-01-01

    Epidemiological and animal-based investigations have indicated that the development of skin cancer is in part associated with poor dietary practices. Lipid content and subsequently the derived fatty acid composition of the diet are believed to play a major role in the development of tumorigenesis. Omega 33) fatty acids, including docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), can effectively reduce the risk of skin cancer whereas omega 66) fatty acids such as arachidonic acid (AA) reportedly promote risk. To investigate the effects of fatty acids on tumorigenesis, we performed experiments to examine the effects of the ω3 fatty acids EPA and DHA and of the ω6 fatty acid AA on phorbol 12-tetradecanoate 13-acetate (TPA)-induced or epidermal growth factor (EGF)-induced transcription activator protein 1 (AP-1) transactivation and on the subsequent cellular transformation in a mouse epidermal JB6 cell model. DHA treatment resulted in marked inhibition of TPA- and EGF-induced cell transformation by inhibiting AP-1 transactivation. EPA treatment also inhibited TPA-induced AP-1 transactivation and cell transformation but had no effect on EGF-induced transformation. AA treatment had no effect on either TPA- or EGF-induced AP-1 transactivation or transformation, but did abrogate the inhibitory effects of DHA on TPA- or EGF-induced AP-1 transactivation and cell transformation in a dose-dependent manner. The results of this study demonstrate that the inhibitory effects of ω3 fatty acids on tumorigenesis are more significant for DHA than for EPA and are related to an inhibition of AP-1. Similarly, because AA abrogates the beneficial effects of DHA, the dietary ratio of ω6 to ω3 fatty acids may be a significant factor in mediating tumor development. PMID:11416221

  6. Microarray profiling of L1-overexpressing endothelial cells reveals STAT3 activation via IL-6/IL-6Rα axis

    PubMed Central

    Magrini, Elena; Cavallaro, Ugo; Bianchi, Fabrizio

    2015-01-01

    We recently identified a novel role for the L1 transmembrane glycoprotein (also known as L1CAM or CD171) in the regulation of tumor angiogenesis and vessels stabilization. L1 overexpression in cultured endothelial cells of the lung (luECs) exerted a pleiotropic effect in that it regulated proliferation, migration, tubulogenesis, vascular permeability, and endothelial-to-mesenchymal transition (EndMT). In addition, we provided strong evidence that antibody-mediated targeting of L1 may be an effective strategy for vessel normalization with the potential to increase efficacy of chemotherapeutic agents. High-throughput microarray expression profile revealed that L1 modulates the expression of hundreds of genes mainly involved in cell cycle regulation, DNA replication, cellular assembly, migration, development and organization. By using a ‘pathway-oriented’ analysis strategy we were able to identify a network of 105 genes modulated by L1 through the predicted activation of five transcription factors: STAT1, STAT2, STAT3, IRF7, and ATF4. Indeed, L1 overexpression resulted in the strong induction of STAT3 phosphorylation which was abolished by antibody-mediated neutralization of IL-6Rα. These results indicated that L1 promoted STAT3 activation via the IL-6/IL-6Rα axis. PMID:26484199

  7. Heteryladamantanes. Communication 5. Synthesis of 6-(1-adamantyl)-3-cyanopyridin-2(1H)-selenone and related selenophenopyridines

    SciTech Connect

    Apenova, E.E.; Sharanin, Yu.A.; Zolotarev, B.M.; Litvinov, V.P.

    1986-08-20

    Reaction of the sodium salt of 3-(1-adamantyl)-1-hydroxyprop-1-en-3-one with cyanoselenoacetamide led to the first synthesis of 6-(1-adamantyl)-3-cyanopyridine-2-(1H)-selenone. 2-Seleno substituted 6-(1-adamantyl)-3-cyanopyridines have been obtained by alkylation of pyridineselenone with RCH/sub 2/HAl. Cyclization in the presence of base gives 2-substituted 6-(1-adamantyl)-3-aminoselenopheno(2,3-b)pyridines. Under electron impact conditions 2-mercapto and 2-seleno substituted 6-(1-adamantyl)-3-cyanopyridines undergo cyclization to the corresponding substituted thieno- and selenophenopyridines. The sulfur-containing compounds do not show an ion peak corresponding to separation of the adamantyl and pyridyl rings, whereas such a process does occur in the case of the selenium analogs.

  8. Vicarious nucleophilic substitution to prepare 1,3-diamino-2,4,6-trinitrobenzene or 1,3,5-triamino-2,4,6-trinitrobenzene

    DOEpatents

    Mitchell, Alexander R.; Pagoria, Philip F.; Schmidt, Robert D.

    1996-01-01

    The present invention relates to a process to produce 1,3-diamino-2,4,6-trinitrobenzene (DATB) or 1,3,5-triamino-2,4,6,-trinitrobenzene (TATB) by: (a) reacting at ambient pressure and a temperature of between about 0.degree. and 50.degree. C. for between about 0.1 and 24 hr, a trinitroaromatic compound of structure V: ##STR1## wherein X, Y, and Z are each independently selected from --H, or --NH.sub.2, with the proviso that at least 1 or 2 of X, Y, and Z are hydrogen, with an amount effective to produce DATB or TATB of 1,1,1-trialkylhydrazinium halide wherein alkyl is selected from methyl, ethyl, propyl or butyl and halide is selected from chloride, bromide or iodide. in the presence of a strong base selected from sodium butoxide, potassium butoxide, potassium propoxide, sodium propoxide, sodium ethoxide, potassium ethoxide, sodium methoxide, potassium methoxide, and combinations thereof; in a solvent selected from the group consisting of methanol, ethanol, propanol, butanol, dimethylsulphoxide, N-methylpyrrolidone, hexamethylphosphoramide, dimethylformide, dimethylacetamide and mixtures thereof, provided that when alcohols are present primarily DATB and picramide is formed; and (b) isolating the DATB or TATB produced. DATB and TATB are useful specialty explosives. TATB is also used for the preparation of benzenehexamine, a starting material for the synthesis of novel materials (optical imaging devices, liquid crystals, ferromagnetic compounds).

  9. Mitochondria Targeted Peptides Protect Against 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine Neurotoxicity

    PubMed Central

    Yang, Lichuan; Zhao, Kesheng; Calingasan, Noel Y.; Luo, Guoxiong; Szeto, Hazel H.

    2009-01-01

    Abstract A large body of evidence suggests that mitochondrial dysfunction and oxidative damage play a role in the pathogenesis of Parkinson's disease (PD). A number of antioxidants have been effective in animal models of PD. We have developed a family of mitochondria-targeted peptides that can protect against mitochondrial swelling and apoptosis (SS peptides). In this study, we examined the ability of two peptides, SS-31 and SS-20, to protect against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) neurotoxicity in mice. SS-31 produced dose-dependent complete protection against loss of dopamine and its metabolites in striatum, as well as loss of tyrosine hydroxylase immunoreactive neurons in substantia nigra pars compacta. SS-20, which does not possess intrinsic ability in scavenging reactive oxygen species, also demonstrated significant neuroprotective effects on dopaminergic neurons of MPTP-treated mice. Both SS-31 and SS-20 were very potent (nM) in preventing MPP+ (1-methyl-4-phenylpyridinium)-induced cell death in cultured dopamine cells (SN4741). Studies with isolated mitochondria showed that both SS-31 and SS-20 prevented MPP+-induced inhibition of oxygen consumption and ATP production, and mitochondrial swelling. These findings provide strong evidence that these neuroprotective peptides, which target both mitochondrial dysfunction and oxidative damage, are a promising approach for the treatment of PD. Antioxid. Redox Signal. 11, 2095–2104. PMID:19203217

  10. 40 CFR 721.10594 - Hexanedioic acid, polymer with 2,2-dimethyl-1,3-propanediol, 1,6-hexanediol, hydrazine, 3-hydroxy...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...-dimethyl-1,3-propanediol, 1,6-hexanediol, hydrazine, 3-hydroxy-2-(hydroxymethyl)-2-methylpropanoic acid, 5...-hexanediol, hydrazine, 3-hydroxy-2-(hydroxymethyl)-2-methylpropanoic acid, 5-isocyanato-1-(isocyanatomethyl... hexanedioic acid, polymer with 2,2-dimethyl-1,3-propanediol, 1,6-hexanediol, hydrazine,...

  11. 40 CFR 721.10594 - Hexanedioic acid, polymer with 2,2-dimethyl-1,3-propanediol, 1,6-hexanediol, hydrazine, 3-hydroxy...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...-dimethyl-1,3-propanediol, 1,6-hexanediol, hydrazine, 3-hydroxy-2-(hydroxymethyl)-2-methylpropanoic acid, 5...-hexanediol, hydrazine, 3-hydroxy-2-(hydroxymethyl)-2-methylpropanoic acid, 5-isocyanato-1-(isocyanatomethyl... hexanedioic acid, polymer with 2,2-dimethyl-1,3-propanediol, 1,6-hexanediol, hydrazine,...

  12. 6-gingerol prevents adipogenesis and the accumulation of cytoplasmic lipid droplets in 3T3-L1 cells.

    PubMed

    Tzeng, Thing-Fong; Liu, I-Min

    2013-04-15

    6-Gingerol ((S)-5-hydroxy-1-(4-hydroxy-3-methoxyphenyl)-3-decanone) is one of the pungent constituents of Zingiber zerumbet (L) Smith (Zingiberaceae family). In this study, we investigated the effects of 6-gingerol on the inhibition of adipogenesis in 3T3-L1 cells. After treatment with 6-gingerol in differentiation medium for 4 or 8 days, the 3T3-L1 cells were lysed for experimental analysis. Cells were stained with Oil-Red-O to detect oil droplets in adipocytes. The 3T3-L1 cells were lysed and measured for triglyceride contents. The protein expression of adipogenesis-related transcription factor was evaluated by Western blot analysis. 6-Gingerol suppressed oil droplet accumulation and reduced the droplet size in a concentration (5-15 μg/ml)- and time-dependent manner. Treatment of 3T3-L1 cells with 6-gingerol reduced the protein levels of peroxisome proliferator-activated receptor (PPAR)γ and CCAAT/enhancer-binding protein (C/EBP)α. Additionally, the protein levels of fatty acid synthase (FAS) and adipocyte-specific fatty acid binding protein (aP2) decreased upon treatment with 6-gingerol. Meanwhile, 6-gingerol diminished the insulin-stimulated serine phosphorylation of Akt (Ser473) and GSK3β (Ser9). These results suggest that 6-gingerol effectively suppresses adipogenesis and that it exerts its role mainly through the significant down-regulation of PPARγ and C/EBPα and subsequently inhibits FAS and aP2 expression. 6-Gingerol also inhibited differentiation in 3T3-L1 cells by attenuating the Akt/GSK3β pathway. Our findings provide important insights into the mechanisms underlying the anti-adipogenic activity of 6-gingerol. PMID:23369342

  13. Vicarious nucleophilic substitution to prepare 1,3-diamino-2,4,6-trinitrobenzene or 1,3,5-triamino-2,4,6-trinitrobenzene

    DOEpatents

    Mitchell, A.R.; Pagoria, P.F.; Schmidt, R.D.

    1996-10-29

    The present invention relates to a process to produce 1,3-diamino-2,4,6-trinitrobenzene (DATB) or 1,3,5-triamino-2,4,6,trinitrobenzene (TATB) by: (a) reacting at ambient pressure and a temperature of between about 0 and 50 C for between about 0.1 and 24 hr, a trinitroaromatic compound of the structure shown within where X, Y, and Z are each independently selected from --H, or --NH{sub 2}, with the proviso that at least 1 or 2 of X, Y, and Z are hydrogen, with an amount effective to produce DATB or TATB, or 1,1,1-trialkylhydrazinium halide wherein alkyl is selected from methyl, ethyl, propyl or butyl and halide is selected from chloride, bromide or iodide, in the presence of a strong base selected from sodium butoxide, potassium butoxide, potassium propoxide, sodium propoxide, sodium ethoxide, potassium ethoxide, sodium methoxide, potassium methoxide, and combinations thereof; in a solvent selected from the group consisting of methanol, ethanol, propanol, butanol, dimethylsulfoxide, N-methylpyrrolidone, hexamethylphosphoramide, dimethylformide, dimethylacetamide and mixtures thereof, provided that when alcohols are present primarily DATB and picramide is formed; and (b) isolating the DATB or TATB produced. DATB and TATB are useful specialty explosives. TATB is also used for the preparation of benzenehexamine, a starting material for the synthesis of novel materials (optical imaging devices, liquid crystals, ferromagnetic compounds).

  14. The 6p3/2ns(J = 1,2) autoionizing states of barium

    NASA Astrophysics Data System (ADS)

    Li, S. B.; Dai, C. J.; Sun, W.; Xue, P.

    2001-06-01

    Using a three-step laser excitation scheme we have selectively excited the Ba 6p3/2ns(J = 1,2) autoionizing Rydberg states with different polarization configurations. The level energies and widths of Ba 6p3/2ns(J = 1) autoionizing states with n = 9-33 and 6p3/2ns(J = 2) autoionizing states with n = 9-20 are reported, most of which were observed for the first time. Their spectroscopic properties are discussed in detail. The experimental data are in good agreement with the theoretical analysis from the multichannel quantum defect theory.

  15. The ubiquitin E3 ligase TRAF6 exacerbates pathological cardiac hypertrophy via TAK1-dependent signalling

    PubMed Central

    Ji, Yan-Xiao; Zhang, Peng; Zhang, Xiao-Jing; Zhao, Yi-Chao; Deng, Ke-Qiong; Jiang, Xi; Wang, Pi-Xiao; Huang, Zan; Li, Hongliang

    2016-01-01

    Tumour necrosis factor receptor-associated factor 6 (TRAF6) is a ubiquitin E3 ligase that regulates important biological processes. However, the role of TRAF6 in cardiac hypertrophy remains unknown. Here, we show that TRAF6 levels are increased in human and murine hypertrophied hearts, which is regulated by reactive oxygen species (ROS) production. Cardiac-specific Traf6 overexpression exacerbates cardiac hypertrophy in response to pressure overload or angiotensin II (Ang II) challenge, whereas Traf6 deficiency causes an alleviated hypertrophic phenotype in mice. Mechanistically, we show that ROS, generated during hypertrophic progression, triggers TRAF6 auto-ubiquitination that facilitates recruitment of TAB2 and its binding to transforming growth factor beta-activated kinase 1 (TAK1), which, in turn, enables the direct TRAF6–TAK1 interaction and promotes TAK1 ubiquitination. The binding of TRAF6 to TAK1 and the induction of TAK1 ubiquitination and activation are indispensable for TRAF6-regulated cardiac remodelling. Taken together, we define TRAF6 as an essential molecular switch leading to cardiac hypertrophy in a TAK1-dependent manner. PMID:27249171

  16. 6-alkylthio-4-[1-(2,6-difluorophenyl)alkyl]-1H-[1,3,5]triazin-2-ones (ADATs): novel regulators of cell differentiation and proliferation.

    PubMed

    Sbardella, Gianluca; Bartolini, Sara; Castellano, Sabrina; Artico, Marino; Paesano, Nicola; Rotili, Dante; Spadafora, Corrado; Mai, Antonello

    2006-10-01

    Novel triazine analogues of 5-alkyl-2-alkylthio-6-[1-(2,6-difluorophenyl)alkyl]-3,4-dihydropyrimidin-4(3H)-ones (F(2)-DABOs), previously described by us as nonnucleoside HIV-1 reverse transcriptase inhibitors (NNRTIs), were tested for their antiproliferative and cytodifferentiating activity on the A-375 human melanoma cell line. Most of the tested derivatives were effective in decreasing cell proliferation, facilitating morphological differentiation, and reprogramming gene expression. All these effects were reversible upon withdrawal of RT inhibitors. Among the compounds tested, 3 f showed the highest antiproliferative effect, whereas compound 6 c, although not affecting cell proliferation, is endowed with a strong cytodifferentiating effect, which is probably related to a marked upregulation of the e-cad gene. These results support the potential of NNRTIs as valuable antitumor agents. PMID:16944545

  17. Absorption, distribution, and biotransformation of hexahydro-1,3,5-trinitro-1,3,5-triazine in B6C3F1 mice (Mus musculus).

    PubMed

    Pan, Xiaoping; Ochoa, Kelly M; Francisco, Michael J San; Cox, Stephen B; Dixon, Kenneth; Anderson, Todd A; Cobb, George P

    2013-06-01

    Absorption, distribution, and biotransformation are 3 critical aspects affecting toxicant action in animals. In the present study, B6C3F1 mice (Mus musculus) were exposed for 28 d to contaminated feed that contained 1 of 5 different hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) concentrations: 0 mg/kg, 0.5 mg/kg, 5 mg/kg, 50 mg/kg, and 500 mg/kg. The authors quantified RDX and its reductive transformation products hexahydro-1-nitroso-3,5-dinitro-1,3,5-triazine (MNX), hexahydro-1,3-dinitroso-5-nitro-1,3,5-triazine (DNX), and hexahydro-1,3,5-trinitroso-1,3,5-triazine (TNX) in the stomach, intestine, plasma, liver, and brain of these mice. Average RDX concentrations followed a dose-dependent pattern for all matrices tested. No controls had concentrations above limits of detection. Average RDX concentrations in tissues of exposed mice ranged from 11.1 ng/mL to 182 ng/mL, 25.6 ng/g to 3319 ng/g, 123 ng/g to 233 ng/g, 144 ng/g to 35 900 ng/g, and 51.1 ng/g to 2697 ng/g in the plasma, brain, liver, stomach, and intestine, respectively. A considerable amount of RDX was present in the brain, especially in the highest-exposure group. This is consistent with the widely observed central nervous system effects caused by γ-aminobutyric acid inhibition associated with RDX exposure. N-nitroso metabolites of RDX were also present in tested tissues in a dose-dependent pattern. Average MNX concentrations in the stomachs of mice exposed to RDX ranged from nondetectable in control exposures to 490 ng/g in the highest-exposure groups. In the brain, MNX accumulated at a maximum average concentration of 165.1 ng/g, suggesting the potential formation of MNX from RDX within the brain. At higher exposures, DNX and TNX were present in the stomach, plasma, and brain of mice. The presence of RDX metabolites at notable amounts in different tissues suggests that RDX can transform into its N-nitroso metabolites in vivo by an undefined mechanism. PMID:23423972

  18. Degradation of Extracellular β-(1,3)(1,6)-d-Glucan by Botrytis cinerea

    PubMed Central

    Stahmann, K.-Peter; Pielken, Petra; Schimz, Karl-Ludwig; Sahm, Hermann

    1992-01-01

    During growth on glucose, Botrytis cinerea produced extracellular β-(1,3)(1,6)-d-glucan (cinerean), which formed an adhering capsule and slime. After glucose was exhausted from the medium, cinereanase activity increased from <0.4 to 30 U/liter, effecting a striking loss in the viscosity of the culture. Cinerean was cleaved into glucose and gentiobiose. Gentiobiose was then hydrolyzed to glucose. While cinereanase activity was strongest in the culture supernatant, gentiobiase activity was located mainly in the cell wall fraction. The addition of extra glucose or cycloheximide prevented the cinerean degradation caused by an effect on cinereanase formation. Cinerean degradation was accompanied by microconidiation and sclerotium formation. B. cinerea was found to grow on cinerean with the latter as its single carbon and energy source. In this case, cinerean degradation occurred during hyphal growth, and no microconidiation or sclerotium formation was observed. Growth experiments with various carbon sources indicated that cinerean had a positive effect on the formation of cinerean-degrading enzymes. Images PMID:16348789

  19. Polymerase Bypass of N6-Deoxyadenosine Adducts Derived from Epoxide Metabolites of 1,3-Butadiene

    PubMed Central

    Kotapati, Srikanth; Wickramaratne, Susith; Esades, Amanda; Boldry, Emily J.; Dorr, Danae Quirk; Pence, Matthew G.; Guengerich, F. Peter; Tretyakova, Natalia Y.

    2015-01-01

    N 6-(2-Hydroxy-3-buten-1-yl)-2′-deoxyadenosine (N6-HB-dA I) and N6,N6-(2,3-dihydroxybutan-1,4-diyl)-2′-deoxyadenosine (N6,N6-DHB-dA) are exocyclic DNA adducts formed upon alkylation of the N6 position of adenine in DNA by epoxide metabolites of 1,3-butadiene (BD), a common industrial and environmental chemical classified as a human and animal carcinogen. Since the N6-H atom of adenine is required for Watson-Crick hydrogen bonding with thymine, N6-alkylation can prevent adenine from normal pairing with thymine, potentially compromising the accuracy of DNA replication. To evaluate the ability of BD-derived N6-alkyladenine lesions to induce mutations, synthetic oligodeoxynucleotides containing site-specific (S)-N6-HB-dA I and (R,R)-N6,N6-DHB-dA adducts were subjected to in vitro translesion synthesis in the presence of human DNA polymerases β, η, ι, and κ. While (S)-N6-HB-dA I was readily bypassed by all four enzymes, only polymerases η and κ were able to carry out DNA synthesis past (R,R)-N6,N6-DHB-dA. Steady-state kinetic analyses indicated that all four DNA polymerases preferentially incorporated the correct base (T) opposite (S)-N6-HB-dA I. In contrast, hPol β was completely blocked by (R,R)-N6,N6-DHB-dA, while hPol η and κ inserted A, G, C, or T opposite the adduct with similar frequency. HPLC-ESI-MS/MS analysis of primer extension products confirmed that while translesion synthesis past (S)-N6-HB-dA I was mostly error-free, replication of DNA containing (R,R)-N6,N6-DHB-dA induced significant numbers of A, C, and G insertions and small deletions. These results indicate that singly substituted (S)-N6-HB-dA I lesions are not miscoding, but exocyclic (R,R)-N6,N6-DHB-dA adducts are strongly mispairing, probably due to their inability to form stable Watson-Crick pairs with dT. PMID:26098310

  20. Synthesis and fluorescence emission properties of 1,3,6,8-tetraarylpyrenes

    NASA Astrophysics Data System (ADS)

    Hu, Jian-Yong; Feng, Xing; Tomiyasu, Hirotsugu; Seto, Nobuyuki; Rayhan, Ummey; Elsegood, Mark R. J.; Redshaw, Carl; Yamato, Takehiko

    2013-09-01

    Three types of stable pyrene-based highly fluorescence (blue) compounds, 1-, 1,6-bis, 1,8-bis and 1,3,6,8-tetrakis(7-tert-butylpyrenyl)pyrenes and 1,3,6,8-tetrakis[9,9-bis(3-methylbutyl)-9H-fluoren-2-yl]pyrene, were successfully synthesized via a Pd/Cu-catalysed Suzuki cross-coupling reaction of the corresponding bromopyrenes with 7-tert-butyl-1-pyrenylboronic ester or 2-[9,9-bis(3-methylbutyl)-9H-fluoren-2-yl]-4,4,5,5-tetramethyl[1,3,2]dioxaborolane, respectively. All compounds have good solubility in common organic solvents and high thermal stability with melting points up to 270 °C; the exceptions are the isomeric 1,6-bis-, and 1,8-bispyrenyl-substituted pyrenes. All products show high extinction coefficients of absorption (λmax ≈ 349-396 nm) and high quantum yields (λmax ≈ 432-465 nm; Φf ≈ 0.75-0.99) in dichloromethane solution, and emit strong fluorescence in the visible region ranging from deep-blue to pure-blue on increasing the number of substituents. This data suggests that such systems have promise as blue emitters in organic light-emitting device (OLED) applications (OLED = organic light emitting diode). Crystal structures were determined for 1,3,6,8-tetrakis [9,9-bis(3-methylbutyl)-9H-fluoren-2-yl] pyrene and 1,3,6,8-tetrakis(4-methoxyphenyl)pyrene.

  1. (+/-)-6-tert-butyl-8-hydroxymethyl-2-phenyl-4H-1,3-benzodioxin and 2,2,2',2',6,6'-hexamethyl-8,8'-methylenebis(4H-1,3-benzodioxin).

    PubMed

    Masci, Bernardo; Levi Mortera, Stefano; Varrone, Maurizio; Thuéry, Pierre

    2002-11-01

    Two compounds containing 1,3-benzodioxin groups are reported, namely (+/-)-6-tert-butyl-8-hydroxymethyl-2-phenyl-4H-1,3-benzodioxin, C(19)H(22)O(3), (I), and 2,2,2',2',6,6'-hexamethyl-8,8'-methylenebis(4H-1,3-benzodioxin), C(23)H(28)O(4), (II). The hydroxy groups of neighbouring molecules in (I) are hydrogen bonded to each other, giving rise to double-row chains. The molecule in (II) adopts a 'butterfly' conformation, with the O atoms in distal positions. In both compounds, the dioxin rings are in distorted half-chair conformations. PMID:12415170

  2. A toxological study of 3,6-BIS(3,5-Dimethyl-1-1-Pyrazolyl)1,2-Dihydro-1,2,4,5-Tetrazine

    SciTech Connect

    London, J.E.

    1993-03-01

    The acute oral LD[sub 30/50] values for 3,6-BIS(3,5-Dimethyl-1-Pyrazolyl)-1,2-Dihydro-1,2,4,5-Tetrazine BIS(DMP)DHT are greater than 5g/kg. According to classical guidelines, the material would be considered only slightly toxic or practically nontoxic in both rats and mice. The sensitization study in the guinea pig did not show BIS(DMP)SHT to have potential sensitizing effects. Skin application studies on the rabbit demonstrated the material was cutaneously nonirritating. This material was also nonirritating in the rabbit eye application studies.

  3. A toxological study of 3,6-BIS(3,5-Dimethyl-1-1-Pyrazolyl)1,2-Dihydro-1,2,4,5-Tetrazine

    SciTech Connect

    London, J.E.

    1993-03-01

    The acute oral LD{sub 30/50} values for 3,6-BIS(3,5-Dimethyl-1-Pyrazolyl)-1,2-Dihydro-1,2,4,5-Tetrazine BIS(DMP)DHT are greater than 5g/kg. According to classical guidelines, the material would be considered only slightly toxic or practically nontoxic in both rats and mice. The sensitization study in the guinea pig did not show BIS(DMP)SHT to have potential sensitizing effects. Skin application studies on the rabbit demonstrated the material was cutaneously nonirritating. This material was also nonirritating in the rabbit eye application studies.

  4. 6,6′-Dimethyl-2,2′-[1,3-diazinane-1,3-diyl­bis(methyl­ene)]diphenol

    PubMed Central

    Rivera, Augusto; González, Derly Marcela; Ríos-Motta, Jaime; Fejfarová, Karla; Dušek, Michal

    2012-01-01

    In the mol­ecule of the title compound, C20H26N2O2, the 1,3-diazinane ring adopts a slightly distorted chair conformation and the hy­droxy­benzyl substituents occupy equatorial positions on the N atoms of the heterocyclic ring. There are two intra­molecular O—H⋯N hydrogen bonds between the N atoms of the 1,3-diazinane ring and the hy­droxy groups of the aromatic rings, with an S(6) set-graph motif. However, the two observed intra­molecular hydrogen-bond distances were different. Considering that both N atoms experience the same chemical environment, it is surprising to see the difference in O⋯N distances [2.6771 (14) and 2.8123 (12) Å]. The crystal structure is further stabilized by a C—H⋯π interaction. PMID:22412589

  5. Syntheses and Properties of Homoleptic Carbonyl and Trifluorophosphane Niobates: [Nb(CO)(6)](-), [Nb(PF(3))(6)](-) and [Nb(CO)(5)](3)(-) (,)(1).

    PubMed

    Barybin, Mikhail V.; Ellis, John E.; Pomije, Marie K.; Tinkham, Mary L.; Warnock, Garry F.

    1998-12-14

    Reductive carbonylations of NbCl(4)(THF)(2), THF = tetrahydrofuran, mediated by sodium naphthalene in 1,2-dimethoxyethane, DME, or sodium anthracene in THF, provide [Nb(CO)(6)](-) as the tetraethylammonium salt in 60% or 70% isolated yields, respectively, the highest known for atmospheric pressure syntheses of this metal carbonyl. Corresponding reductions involving PF(3) give about 40% yields of [Et(4)N][Nb(PF(3))(6)], which in the past was only accessible by a photochemical route. Electrochemical data for [Nb(CO)(6)](-) and [Nb(PF(3))(6)](-) are compared and show that the PF(3) complex is almost 1 V more difficult to oxidize than the CO analogue. Protonation of [Nb(PF(3))(6)](-) by concentrated sulfuric acid yields a volatile, thermally unstable species, which has been shown by (1)H NMR and mass spectral studies to be the new niobium hydride, Nb(PF(3))(6)H. Previously unpublished (93)Nb and (13)C NMR studies corroborate prior claims that the sodium metal reduction of [Nb(CO)(6)](-) in liquid ammonia affords [Nb(CO)(5)](3)(-), the only known Nb(III-) species. The first details of this synthesis and those of [Nb(CO)(5)H](2)(-), [Nb(CO)(5)SnPh(3)](2)(-), [Nb(CO)(5)NH(3)](-), and [Nb(CO)(5)(CNtBu)](-) are presented. PMID:11670773

  6. Modelling of crystal structure of cis-1,2,3,6 and 3,4,5,6-tetrahydrophthalic anhydrides using lattice energy calculations.

    PubMed

    Fredj, A Ben; Day, G M

    2015-08-01

    Lattice energy calculations using a model potential were performed to model the crystal structures of cis-1,2,3,6- and 3,4,5,6-tetrahydrophthalic (THP) anhydrides. The optimized molecular models using the DFT method at the B3LYP/6-31G** level were found consistent with the available experimental evidence and allowed all differences observed in crystal packing between cis-1,2,3,6- and 3,4,5,6-THP anhydrides to be reproduced. Calculations provide evidence for the presence of dipole-dipole C=O⋯C=O intermolecular interactions and support the idea that the molecules distort from their ideal geometries, improving packing in both crystals. The search for minima in the lattice energy of both crystals amongst the more common space groups with Z' = 1, using a simulated annealing crystal structure prediction procedure followed by lattice energy minimization showed that the observed structure of 3,4,5,6-THP anhydride (Z' = 2) is the thermodynamically most stable, and allowed us to justify why 3,4,5,6-THP anhydride crystallizes in such a complex structure with 16 molecules in the unit cell. The computational model was successful in predicting the second observed form at 173 K for cis-1,2,3,6-THP anhydride as a polymorph, and could predict several hypothetical structures with Z' = 1 that appear competitive with the observed structures. The results of phonon estimates of zero point intermolecular vibrational energy and entropy suggest that crystal structures of cis-1,2,3,6-THP anhydride cannot be predicted solely on the basis of lattice energy; factors other than thermodynamics favor the observed structures. PMID:26224602

  7. The Akt1/IL-6/STAT3 pathway regulates growth of lung tumor initiating cells.

    PubMed

    Malanga, Donatella; De Marco, Carmela; Guerriero, Ilaria; Colelli, Fabiana; Rinaldo, Nicola; Scrima, Marianna; Mirante, Teresa; De Vitis, Claudia; Zoppoli, Pietro; Ceccarelli, Michele; Riccardi, Miriam; Ravo, Maria; Weisz, Alessandro; Federico, Antonella; Franco, Renato; Rocco, Gaetano; Mancini, Rita; Rizzuto, Antonia; Gulletta, Elio; Ciliberto, Gennaro; Viglietto, Giuseppe

    2015-12-15

    Here we report that the PI3K/Akt1/IL-6/STAT3 signalling pathway regulates generation and stem cell-like properties of Non-Small Cell Lung Cancer (NSCLC) tumor initiating cells (TICs). Mutant Akt1, mutant PIK3CA or PTEN loss enhances formation of lung cancer spheroids (LCS), self-renewal, expression of stemness markers and tumorigenic potential of human immortalized bronchial cells (BEAS-2B) whereas Akt inhibition suppresses these activities in established (NCI-H460) and primary NSCLC cells. Matched microarray analysis of Akt1-interfered cells and LCSs identified IL-6 as a critical target of Akt signalling in NSCLC TICs. Accordingly, suppression of Akt in NSCLC cells decreases IL-6 levels, phosphorylation of IkK and IkB, NF-kB transcriptional activity, phosphorylation and transcriptional activity of STAT3 whereas active Akt1 up-regulates them. Exposure of LCSs isolated from NSCLC cells to blocking anti-IL-6 mAbs, shRNA to IL-6 receptor or to STAT3 markedly reduces the capability to generate LCSs, to self-renew and to form tumors, whereas administration of IL-6 to Akt-interfered cells restores the capability to generate LCSs. Finally, immunohistochemical studies in NSCLC patients demonstrated a positive correlative trend between activated Akt, IL-6 expression and STAT3 phosphorylation (n = 94; p < 0.05). In conclusion, our data indicate that aberrant Akt signalling contributes to maintaining stemness in lung cancer TICs through a NF-kB/IL-6/STAT3 pathway and provide novel potential therapeutic targets for eliminating these malignant cells in NSCLC. PMID:26486080

  8. The Akt1/IL-6/STAT3 pathway regulates growth of lung tumor initiating cells

    PubMed Central

    Malanga, Donatella; De Marco, Carmela; Guerriero, Ilaria; Colelli, Fabiana; Rinaldo, Nicola; Scrima, Marianna; Mirante, Teresa; De Vitis, Claudia; Zoppoli, Pietro; Ceccarelli, Michele; Riccardi, Miriam; Ravo, Maria; Weisz, Alessandro; Federico, Antonella; Franco, Renato; Rocco, Gaetano; Mancini, Rita; Rizzuto, Antonia; Gulletta, Elio; Ciliberto, Gennaro; Viglietto, Giuseppe

    2015-01-01

    Here we report that the PI3K/Akt1/IL-6/STAT3 signalling pathway regulates generation and stem cell-like properties of Non-Small Cell Lung Cancer (NSCLC) tumor initiating cells (TICs). Mutant Akt1, mutant PIK3CA or PTEN loss enhances formation of lung cancer spheroids (LCS), self-renewal, expression of stemness markers and tumorigenic potential of human immortalized bronchial cells (BEAS-2B) whereas Akt inhibition suppresses these activities in established (NCI-H460) and primary NSCLC cells. Matched microarray analysis of Akt1-interfered cells and LCSs identified IL-6 as a critical target of Akt signalling in NSCLC TICs. Accordingly, suppression of Akt in NSCLC cells decreases IL-6 levels, phosphorylation of IkK and IkB, NF-kB transcriptional activity, phosphorylation and transcriptional activity of STAT3 whereas active Akt1 up-regulates them. Exposure of LCSs isolated from NSCLC cells to blocking anti-IL-6 mAbs, shRNA to IL-6 receptor or to STAT3 markedly reduces the capability to generate LCSs, to self-renew and to form tumors, whereas administration of IL-6 to Akt-interfered cells restores the capability to generate LCSs. Finally, immunohistochemical studies in NSCLC patients demonstrated a positive correlative trend between activated Akt, IL-6 expression and STAT3 phosphorylation (n = 94; p < 0.05). In conclusion, our data indicate that aberrant Akt signalling contributes to maintaining stemness in lung cancer TICs through a NF-kB/IL-6/STAT3 pathway and provide novel potential therapeutic targets for eliminating these malignant cells in NSCLC. PMID:26486080

  9. Modulation of CD6 function through interaction with Galectin-1 and -3.

    PubMed

    Escoda-Ferran, Cristina; Carrasco, Esther; Caballero-Baños, Miguel; Miró-Julià, Cristina; Martínez-Florensa, Mario; Consuegra-Fernández, Marta; Martínez, Vanesa G; Liu, Fu-Tong; Lozano, Francisco

    2014-08-25

    CD6 is a lymphocyte glycoprotein receptor that physically associates with the antigen-specific receptor complex at the center of the immunological synapse, where it interacts with its ligand CD166/ALCAM. The present work reports the carbohydrate-dependent interaction of CD6 and CD166/ALCAM with Galectin-1 and -3, two well-known soluble mammalian lectins. Both galectins interfered with superantigen-induced T cell proliferation and cell adhesion phenomena mediated by the CD6-CD166/ALCAM pair, while CD6 expression protected cells from galectin-induced apoptosis. The results suggest that interaction of Galectin-1 and -3 with CD6 and CD166/ALCAM might modulate some relevant aspects of T cell physiology. PMID:24945728

  10. Preparation of 1,3,5-triamino-2,4,6-trinitrobenzene of submicron particle size

    DOEpatents

    Rigdon, Lester P.; Moody, Gordon L.; McGuire, Raymond R.

    2001-01-01

    A method is disclosed for the preparation of very small particle size, relatively pure 1,3,5-triamino-2,4,6-trinitrobenzene (TATB). Particles of TATB prepared according to the disclosed method are of submicron size and have a surface area in the range from about 3.8 to 27 square meters per gram.

  11. Preparation of 1,3,5-triamo-2,4,6-trinitrobenzene of submicron particle size

    DOEpatents

    Rigdon, Lester P.; Moody, Gordon L.; McGuire, Raymond R.

    2001-05-01

    A method is disclosed for the preparation of very small particle size, relatively pure 1,3,5-triamino-2,4,6-trinitrobenzene (TATB). Particles of TATB prepared according to the disclosed method are of submicron size and have a surface area in the range from about 3.8 to 27 square meters per gram.

  12. 1-(6-Chloro-1,3-benzothia­zol-2-yl)hydrazine

    PubMed Central

    Fun, Hoong-Kun; Ooi, Chin Wei; Sarojini, B. K.; Mohan, B. J.; Narayana, B.

    2012-01-01

    The asymmetric unit of the title compound, C7H6ClN3S, consists of two crystallographically independent mol­ecules (A and B). The dihedral angle between the benzothia­zole ring system and the hydrazine group is 8.71 (6)° in mol­ecule A and 7.16 (6)° in mol­ecule B. The N—N—C—N and N—N—C—S torsion angles involving the hydrazine group are 170.89 (9) and −9.96 (13)°, respectively, in mol­ecule A and 172.50 (9) and −7.43 (13)°, respectively, in mol­ecule B. In the crystal, neighbouring mol­ecules are connected via pairs of N—H⋯N hydrogen bonds, generating R 2 2(8) ring motifs, and are connected further by N—H⋯N hydrogen bonds into sheets lying parallel to the ab plane. The crystal studied was an inversion twin, the refined ratio of the twin components being 0.50 (3):0.50 (3). PMID:22412583

  13. Glycinamide ribonucleotide synthase (EC 6.34.13)-aminoimidazole ribonucleotide synthase (EC 6.3.3.1) from Saccharomyces cerevisiae

    SciTech Connect

    Tret`yakov, O.Yu.; Ryzhova, T.A.; Smirnov, M.N.

    1995-12-01

    Here we report for the first time the isolation and properties of GAR synthase (E2)-AIR synthase (E5) (E2-E5) from the yeast Saccharomyces cerevisiae. A vector containing the S. cerevisiae ADE5,7 gene was used to obtain a yeast strain accumulating ADE5,7 coded E2-E5 in amounts equivalent to {approximately}20% of the total soluble protein. The pH optimum for E2 activity in forward reaction is 7.5, in the reverse reaction 7.5 - 8.5; the E5 activity optimum is at pH 8.0. The temperature optimum for E2 is 42{degrees}C (in the reverse reaction), 35{degrees}C for E5. Data on the pH and temperature stability of E2-E5 are presented. The E2 K{sub m} values are ({mu}M): 49 {+-}4 for glycine, 64 {+-}5 for PRA, 144 {+-} 10 for ATP, 21 {+-} 2 for GAR, 7 {+-} 1 for ADP, and 320 {+-} 30 for P{sub i}. The E5 K{sub m} values are ({mu}M): 80 {+-} 9 for GAM and 500 {+-} 52 for ATP. E2 and E5 are inactive in the absence of Mg{sup 2+}. E5 is K{sup +} -dependent. 2{prime}-dATP, GTP, ITP, UTP, and CTP are not substrates for E5, while AMP is a competitive E5 inhibitor relative to ATP (with K{sub i} = 700 {+-} 80 {mu}M). Hence, regulation of purine biosynthesis by one of its end products in S. cerevisiae occurs at the fifth stage of biosynthesis, supplementing the inhibition of the first enzyme. The molecular mass of the E2-E5 subunits is {approximately}87 kD. The native form is dimeric: the molecular masses of the enzyme determined by three different methods are 170, 175, and 200 kD. Short-term chymotrypsin treatment of E2-E5 cleaves the polypeptide chain, presumably in an interdomain region; as a result, E5 activity disappears while E2 activity is retained. 45 refs., 6 figs., 2 tabs.

  14. Structure of rabbit liver fructose 1,6-bisphosphatase at 2.3 A resolution.

    PubMed

    Weeks, C M; Roszak, A W; Erman, M; Kaiser, R; Jörnvall, H; Ghosh, D

    1999-01-01

    The three-dimensional structure of the R form of rabbit liver fructose 1,6-bisphosphatase (Fru-1,6-Pase; E.C. 3.1.3.11) has been determined by a combination of heavy-atom and molecular-replacement methods. A model, which includes 2394 protein atoms and 86 water molecules, has been refined at 2.3 A resolution to a crystallographic R factor of 0.177. The root-mean-square deviations of bond distances and angles from standard geometry are 0.012 A and 1.7 degrees, respectively. This structural result, in conjunction with recently redetermined amino-acid sequence data, unequivocally establishes that the rabbit liver enzyme is not an aberrant bisphosphatase as once believed, but is indeed homologous to other Fru-1,6-Pases. The root-mean-square deviation of the Calpha atoms in the rabbit liver structure from the homologous atoms in the pig kidney structure complexed with the product, fructose 6-phosphate, is 0.7 A. Fru-1,6-Pases are homotetramers, and the rabbit liver protein crystallizes in space group I222 with one monomer in the asymmetric unit. The structure contains a single endogenous Mg2+ ion coordinated by Glu97, Asp118, Asp121 and Glu280 at the site designated metal site 1 in pig kidney Fru-1,6-Pase R-form complexes. In addition, two sulfate ions, which are found at the positions normally occupied by the 6-phosphate group of the substrate, as well as the phosphate of the allosteric inhibitor AMP appear to provide stability. Met177, which has hydrophobic contacts with the adenine moiety of AMP in pig kidney T-form complexes, is replaced by glycine. Binding of a non-hydrolyzable substrate analog, beta-methyl-fructose 1,6-bisphosphate, at the catalytic site is also examined. PMID:10089399

  15. Determination of the lifetime of the Mercury 6/3/P-1 state

    NASA Technical Reports Server (NTRS)

    Halstead, J. A.; Reeves, R. R.

    1982-01-01

    A pulsed tunable dye laser was used for a high resolution experimental study of mercury fluorescence from the 6(3)P-1 state. The output of the dye laser was frequency doubled into the 253.7 nm region using a potassium pentaborate crystal. Exponential decays were separately observed for each of the five individual components of the hyperfine structure and the effects of the trapping of resonance radiation on the observed lifetime of the 6(3)P-1 state of mercury were investigated for each resolvable component. Within experimental error, the natural radiative lifetime of the 6(3)P-1 state was found to be independent of the hyperfine component irradiated and a value of 122 + or 2 nsec was obtained, consistent with results found by other methods.

  16. Determination of high mitochondrial membrane potential in spermatozoa loaded with the mitochondrial probe 5,5',6,6'tetrachloro-1,1',3,3'-tetraethylbenzimidazolyl-carbocyanine iodide (JC-1) using flow cytometry.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A flow cytometric method was developed to identify viable, energized sperm cells with high mitochondrial inner transmembrane potential (''m), > 80-100 mV using the mitochondrial probe 5, 5', 6, 6'-tetrachloro-1, 1', 3, 3'-tetraethylbenzimidazolylcarbocyanine iodide (JC-1) and the impermeant nuclear ...

  17. 5-(3,4-Dimethyl-benzyl-idene)-2,2-dimethyl-1,3-dioxane-4,6-dione.

    PubMed

    Zeng, Wu-Lan

    2011-06-01

    The title compound, C(15)H(16)O(4), was prepared by the reaction of 2,2-dimethyl-1,3-dioxane-4,6-dione and 3,4-dimethyl-benzaldehyde in ethanol. The 1,3-dioxane ring exhibits an envelope conformation. In the crystal, mol-ecules are linked by weak inter-molecular C-H⋯O hydrogen bonds, forming chains parallel to the b axis. PMID:21754745

  18. Two- and three-dimensional lanthanide-organic frameworks constructed using 1-hydro-6-oxopyridine-3-carboxylate and oxalate ligands.

    PubMed

    Liu, Cai-Ming; Xiong, Ming; Zhang, De-Qing; Du, Miao; Zhu, Dao-Ben

    2009-08-01

    6-Hydroxypyridine-3-carboxylic acid (6-HOPy-3-CO(2)H) reacts with Ln(2)O(3) (Ln = Nd, Sm, Eu, Gd) and oxalic acid (H(2)OX) under hydrothermal conditions to generate four novel lanthanide-organic coordination polymeric networks [Ln(2)(1H-6-Opy-3-CO(2))(2)(OX)(2)(H(2)O)(3)] x 2.5 H(2)O (Ln = Nd, 1; Sm, 2; 1H-6-Opy-3-CO(2)(-) = 1-hydro-6-oxopyridine-3-carboxylate) and [Ln(1H-6-Opy-3-CO(2))(OX)(H(2)O)(2)] x H(2)O (Ln = Eu, 3; Gd, 4). The new co-ligand 1H-6-Opy-3-CO(2)(-) anion was generated by the autoisomerization of the single deprotonated 6-HOPy-3-CO(2)(-) anion (from the enol form into the ketone one). 1 and 2 are isomorphous, they possess a three-dimensional architecture constructed from Ln(3+) ions bridged by oxalate anions and two types of 1H-6-Opy-3-CO(2)(-) bridges, showing a three-nodal (4,5)-connected topology (3.4(2).5(2).6(3).7.8)(2)(3.5(3).6(2))(2)(3(2).6.7(2).8) or a simplified uninodal 6-connected topology (3(3).4(6).5(5).6), both topologies are completely new; while only one type of 1H-6-Opy-3-CO(2)(-) bridge is used to construct the two-dimensional layer networks of 3 and 4 besides oxalate bridges, both complexes 3 and 4 are isostructural, exhibiting the honeycomb topology 6(3). The lanthanide contraction effect is believed to play a key role in directing the formation of a particular structure. A magnetic study of 1-3 indicated that the coupling interaction between Ln(3+) ions is weak. PMID:20449079

  19. Evolutionary dynamics of retrotransposable elements Rex1, Rex3 and Rex6 in neotropical cichlid genomes

    PubMed Central

    2013-01-01

    Background Transposable elements (TEs) have the potential to produce broad changes in the genomes of their hosts, acting as a type of evolutionary toolbox and generating a collection of new regulatory and coding sequences. Several TE classes have been studied in Neotropical cichlids; however, the information gained from these studies is restricted to the physical chromosome mapping, whereas the genetic diversity of the TEs remains unknown. Therefore, the genomic organization of the non-LTR retrotransposons Rex1, Rex3, and Rex6 in five Amazonian cichlid species was evaluated using physical chromosome mapping and DNA sequencing to provide information about the role of TEs in the evolution of cichlid genomes. Results Physical mapping revealed abundant TE clusters dispersed throughout the chromosomes. Furthermore, several species showed conspicuous clusters accumulation in the centromeric and terminal portions of the chromosomes. These TE chromosomal sites are associated with both heterochromatic and euchromatic regions. A higher number of Rex1 clusters were observed among the derived species. The Rex1 and Rex3 nucleotide sequences were more conserved in the basal species than in the derived species; however, this pattern was not observed in Rex6. In addition, it was possible to observe conserved blocks corresponding to the reverse transcriptase fragment of the Rex1 and Rex3 clones and to the endonuclease of Rex6. Conclusion Our data showed no congruence between the Bayesian trees generated for Rex1, Rex3 and Rex6 of cichlid species and phylogenetic hypothesis described for the group. Rex1 and Rex3 nucleotide sequences were more conserved in the basal species whereas Rex6 exhibited high substitution rates in both basal and derived species. The distribution of Rex elements in cichlid genomes suggests that such elements are under the action of evolutionary mechanisms that lead to their accumulation in particular chromosome regions, mostly in heterochromatins. PMID

  20. IN VITRO PERCUTANEOUS APPROACH OF SODIUM ARSENATE IN B6C3F1 MICE

    EPA Science Inventory

    Percutaneous absorption of sodium [73As] arsenate in female B6C3F1 mice was investigated in this study from various exposure conditions, including solid compound, aqueous solution (100 and 250 ul) and soil (= 23 mg/cm2). In vitro diffusion experiments were conducted for 24 hr usi...

  1. 1-(Piperidin-1-yl)-3-(2,4,6-trimethyl-phen-yl)propan-2-ol.

    PubMed

    Maharramov, Abel M; Khalilov, Ali N; Gurbanov, Atash V; Allahverdiyev, Mirze A; Ng, Seik Weng

    2011-01-01

    The title compound, C(17)H(27)NO, features a bufferfly-shaped substituted 2-propanol having an aromatic ring on the 1-carbon and a piperidine ring on the 3-carbon. The piperidine ring adopts a chair conformation and its N atom shows a trigonal coordination. In the crystal, the hy-droxy group inter-acts with the N atom of an inversion-related mol-ecule, generating an O-H⋯N hydrogen-bonded dimer. PMID:21522478

  2. Nasal Tumorigenesis in B6C3F1 Mice Following Intraperitoneal Diethylnitrosamine.

    PubMed

    Chen, Yung-Ju; Wallig, Matthew A; Jeffery, Elizabeth H

    2016-08-01

    Diethylnitrosamine (DEN) is a chemical broadly used in animal models as a hepatocarcinogen, reported to also cause pulmonary neoplasms in mice. The original objective was to evaluate the impact of a Western diet with or without 10% broccoli on DEN-induced on liver cancer. We administered DEN (45 mg/kg) intraperitoneally to young adult male B6C3F1 mice by 6 weekly injections and evaluated liver cancer 6 months after the DEN treatments. Here, we report unexpected primary tumorigenesis in nasal epithelium, independent of dietary treatment. More than 50% of DEN-treated B6C3F1 mice developed nasal neoplasm-related lesions, not reported previously in the literature. Only one of these neoplasms was visible externally prior to postmortem examination. Intraperitoneal DEN treatment used as a model for liver cancer can have a carcinogenic effect on the nasal epithelium in B6C3F1 mice, which should be carefully monitored in future liver cancer studies. PMID:27207684

  3. The ν1 + ν3 combination band of 238UF 6

    NASA Astrophysics Data System (ADS)

    McDowell, Robin S.; Reisfeld, Martin J.; Nereson, Norris G.; Krohn, Burton J.; Patterson, Chris W.

    1985-09-01

    The ν1 + ν3 band of 238UF 6 has been observed at Doppler-limited resolution between 1291.5 and 1297.2 cm -1 in a statically cooled longpath cell at 226 K. The frequencies of 21 transitions belonging to P(22, 28, 30), 14 belonging to R(12, 30, 31), and 28 belonging to the Q branch with 41 ≤ J ≤ 71, were measured with an accuracy of ±0.002 cm -1. In addition, 53 frequency differences were measured in the Q branch between lines having different J assignments from Q(14) to Q(76). Five spectroscopic constants were fitted to these 116 data points with a standard deviation of 0.0006 cm -1. The rotational constants have nearly the values expected from a consideration of ν1 and ν3 themselves, and there is little evidence for interaction of ν1 + ν3 with other levels.

  4. Conformational and Bonding Properties of 3,3-Dimethyl- and 6,6-Dimethyl-1,5-diazabicyclo[3.1.0]hexane: A Case Study Employing the Monte Carlo Method in Gas Electron Diffraction.

    PubMed

    Vishnevskiy, Yury V; Schwabedissen, Jan; Rykov, Anatolii N; Kuznetsov, Vladimir V; Makhova, Nina N

    2015-11-01

    Gas-phase structures of two isomers of dimethyl-substituted 1,5-diazabicyclo[3.1.0]hexanes, namely, 3,3-dimethyl- and 6,6-dimethyl-1,5-diazabicyclo[3.1.0]hexane molecules, have been determined by gas electron diffraction method. A new approach based on the Monte Carlo method has been developed and used for the analysis of precision and accuracy of the refined structures. It was found that at 57 °C 3,3-dimethyl derivative exists as a mixture of chair and boat conformers with abundances 68(8)% and 32(8)%, respectively. 6,6-Dimethyl-1,5-diazabicyclo[3.1.0]hexane at 50 °C has only one stable conformation with planar 5-ring within error limits. Theoretical calculations predict that the 6,6-dimethyl isomer is more stable in comparison to the 3,3-dimethyl isomer with energy difference 3-5 kcal mol(-1). In order to explain the relative stability and bonding properties of different structures the natural bond orbitals (NBO), atoms in molecules (AIM), and interacting quantum atoms (IQA) analyses were performed. PMID:26461037

  5. Spot test for 1,3,5-triamino-2,4,6-trinitrobenzene, TATB

    DOEpatents

    Harris, B.W.

    1984-11-29

    A simple, sensitive and specific spot test for 1,3,5-triamino-2,4,6-trinitrobenzene, TATB, is described. Upon the application of the composition of matter of the subject invention to samples containing in excess of 0.1 mg of this explosive, a bright orange color results. Interfering species such as TNT and Tetryl can be removed by first treating the sample with a solvent which does not dissolve the TATB, but readily dissolves these interfering explosives.

  6. Spot test for 1,3,5-triamino-2,4,6-trinitrobenzene, TATB

    DOEpatents

    Harris, Betty W.

    1986-01-01

    A simple, sensitive and specific spot test for 1,3,5-triamino-2,4,6-trinitrobenzene, TATB, is described. Upon the application of the composition of matter of the present invention to samples containing in excess of 0.1 mg of this explosive, a bright orange color results. Interfering species such as TNT and Tetryl can be removed by first treating the sample with a solvent which does not dissolve much of the TATB, but readily dissolves these explosives.

  7. Atomic and electronic structures of Si(1 1 1)-\\left(\\sqrt{\\mathbf{3}}\\times\\sqrt{\\mathbf{3}}\\right)\\text{R}\\mathbf{3}{{\\mathbf{0}}^{\\circ}} -Au and (6 × 6)-Au surfaces

    NASA Astrophysics Data System (ADS)

    Patterson, C. H.

    2015-12-01

    Si(1 1 1)-Au surfaces with around one monolayer of Au exhibit many ordered structures and structures containing disordered domain walls. Hybrid density functional theory (DFT) calculations presented here reveal the origin of these complex structures and tendency to form domain walls. The conjugate honeycomb chain trimer (CHCT) structure of the \\sqrt{3} -Au phase contains Si atoms with non-bonding surface states which can bind Au atoms in pairs in interstices of the CHCT structure and make this surface metallic. Si adatoms adsorbed on the \\sqrt{3} -Au surface induce a gapped surface through interaction with the non-bonding states. Adsorption of extra Au atoms in interstitial sites of the \\sqrt{3} -Au surface is stabilized by interaction with the non-bonding orbitals and leads to higher coverage ordered structures including the ≤ft(6× 6\\right) -Au phase. Extra Au atoms bound in interstitial sites of the \\sqrt{3} -Au surface result in top layer Si atoms with an SiAu4 butterfly wing configuration. The structure of a ≤ft(6× 6\\right) -Au phase, whose in-plane top atomic layer positions were previously determined by an electron holography technique (Grozea et al 1998 Surf. Sci. 418 32), is calculated using total energy minimization. The Patterson function for this structure is calculated and is in good agreement with data from an in-plane x-ray diffraction study (Dornisch et al 1991 Phys. Rev. B 44 11221). Filled and empty state scanning tunneling microscopy (STM) images are calculated for domain walls and the ≤ft(6× 6\\right) -Au structure. The ≤ft(6× 6\\right) -Au phase is 2D chiral and this is evident in computed and actual STM images. ≤ft(6× 6\\right) -Au and domain wall structures contain the SiAu4 motif with a butterfly wing shape. Chemical bonding within the Si-Au top layers of the \\sqrt{3} -Au and ≤ft(6× 6\\right) -Au surfaces is analyzed and an explanation for the SiAu4 motif structure is given.

  8. Application of RELAP5/MOD3.1 code to the LOFT test L3-6

    SciTech Connect

    Pylev, S.S.; Roginskaja, V.L.

    1998-02-01

    A calculation of LOFT Experiment L3-6, a small break equivalent to a 4-in diameter rupture in the cold leg of a four-loop commercial pressurized water reactor, has been performed to help validate RELAP5/MOD3.1 for this application. The version of the code to be used is SCDAP/RELAP5/MOD3.1.8d0. Three calculations were carried out in order to study the sensitivity to change break nozzle superheated discharge coefficient. Conducted comparative analysis of the LOFT L3-6 experiment shows on the whole a reasonable agreement between calculated data. Some discrepancies in the system pressure do not distort a picture of the transient. 6 refs.

  9. Pax6-dependence of Six3, Eya1 and Dach1 expression during lens and nasal placode induction.

    PubMed

    Purcell, Patricia; Oliver, Guillermo; Mardon, Graeme; Donner, Amy L; Maas, Richard L

    2005-12-01

    The Drosophila eyeless gene plays a central role in fly eye development and controls a subordinate regulatory network consisting of the so, eya and dac genes. All three genes have highly conserved mammalian homologs, suggesting possible conservation of this eye forming regulatory network. sine oculis (so) belongs to the so/Six gene family, and Six3 is prominently expressed in the developing mammalian eye. Eya1 and Dach1 are mammalian homologs of eya and dac, respectively, and although neither Eya1 nor Dach1 knockout mice express prenatal eye defects, possibilities exist for postnatal ocular phenotypes or for functional redundancy between related family members. To examine whether expression relationships analogous to those between ey, so, eya and dac exist in early mammalian oculogenesis, we investigated Pax6, Six3, Eya1 and Dach1 protein expression in murine lens and nasal placode development. Six3 expression in the pre-placode lens ectoderm is initially Pax6-independent, but subsequently both its expression and nuclear localization become Pax6-dependent. Six3, Dach1 and Eya1 nasal expression in pre-placode ectoderm are also initially Pax6-independent, but thereafter become Pax6-dependent. Pax6, Six3, Dach1 and Eya1 are all co-expressed in the developing ciliary marginal zone, a source of retinal stem cells in some vertebrates. An in vitro protein-protein interaction is detected between Six3 and Eya1. Collectively, these findings suggest that the Pax-Eya-Six-Dach network is at best only partly conserved during lens and nasal placode development. However, the findings do not rule out the possibility that such a regulatory network acts at later stages of oculogenesis. PMID:16024294

  10. The matricellular protein CCN6 (WISP3) decreases Notch1 and suppresses breast cancer initiating cells.

    PubMed

    Huang, Wei; Martin, Emily E; Burman, Boris; Gonzalez, Maria E; Kleer, Celina G

    2016-05-01

    Increasing evidence supports that the epithelial to mesenchymal transition (EMT) in breast cancer cells generates tumor initiating cells (TICs) but the contribution of the tumor microenvironment to these programs needs further elucidation. CCN6 (WISP3) is a secreted matrix-associated protein (36.9 kDa) of the CCN family (named after CTGF, Cyr61 and Nov) that is reduced or lost in invasive carcinomas of the breast with lymph node metastasis and in inflammatory breast cancer. CCN6 exerts breast cancer growth and invasion inhibitory functions, but the mechanisms remain to be defined. In the present study we discovered that ectopic CCN6 overexpression in triple negative (TN) breast cancer cells and in cells derived from patients is sufficient to induce a mesenchymal to epithelial transition (MET) and to reduce TICs. In vivo, CCN6 overexpression in the TIC population of MDA-MB-231 cells delayed tumor initiation, reduced tumor volume, and inhibited the development of metastasis. Our studies reveal a novel CCN6/Slug signaling axis that regulates Notch1 signaling activation, epithelial cell phenotype and breast TICs, which requires the conserved thrombospondin type 1 (TSP1) motif of CCN6. The relevance of these data to human breast cancer is highlighted by the finding that CCN6 protein levels are inversely correlated with Notch1 intracellular activated form (NICD1) in 69.5% of invasive breast carcinomas. These results demonstrate that CCN6 regulates epithelial and mesenchymal states transition and TIC programs, and pinpoint one responsible mechanism. PMID:26933820

  11. The contribution of TRPC1, TRPC3, TRPC5 and TRPC6 to touch and hearing

    PubMed Central

    Sexton, Jane E.; Desmonds, Terri; Quick, Kathryn; Taylor, Ruth; Abramowitz, Joel; Forge, Andy; Kros, Corné J.; Birnbaumer, Lutz; Wood, John N.

    2016-01-01

    Transient receptor potential channels have diverse roles in mechanosensation. Evidence is accumulating that members of the canonical subfamily of TRP channels (TRPC) are involved in touch and hearing. Characteristic features of TRP channels include their high structural homology and their propensity to form heteromeric complexes which suggests potential functional redundancy. We previously showed that TRPC3 and TRPC6 double knockout animals have deficits in light touch and hearing whilst single knockouts were apparently normal. We have extended these studies to analyse deficits in global quadruple TRPC1, 3, 5 and 6 null mutant mice. We examined both touch and hearing in behavioural and electrophysiological assays, and provide evidence that the quadruple knockout mice have larger deficits than the TRPC3 TRPC6 double knockouts. Mechano-electrical transducer currents of cochlear outer hair cells were however normal. This suggests that TRPC1, TRPC3, TRPC5 and TRPC6 channels contribute to cutaneous and auditory mechanosensation in a combinatorial manner, but have no direct role in cochlear mechanotransduction. PMID:26520460

  12. The contribution of TRPC1, TRPC3, TRPC5 and TRPC6 to touch and hearing.

    PubMed

    Sexton, Jane E; Desmonds, Terri; Quick, Kathryn; Taylor, Ruth; Abramowitz, Joel; Forge, Andy; Kros, Corné J; Birnbaumer, Lutz; Wood, John N

    2016-01-01

    Transient receptor potential channels have diverse roles in mechanosensation. Evidence is accumulating that members of the canonical subfamily of TRP channels (TRPC) are involved in touch and hearing. Characteristic features of TRP channels include their high structural homology and their propensity to form heteromeric complexes which suggests potential functional redundancy. We previously showed that TRPC3 and TRPC6 double knockout animals have deficits in light touch and hearing whilst single knockouts were apparently normal. We have extended these studies to analyse deficits in global quadruple TRPC1, 3, 5 and 6 null mutant mice. We examined both touch and hearing in behavioural and electrophysiological assays, and provide evidence that the quadruple knockout mice have larger deficits than the TRPC3 TRPC6 double knockouts. Mechano-electrical transducer currents of cochlear outer hair cells were however normal. This suggests that TRPC1, TRPC3, TRPC5 and TRPC6 channels contribute to cutaneous and auditory mechanosensation in a combinatorial manner, but have no direct role in cochlear mechanotransduction. PMID:26520460

  13. Crystal structure of 1,3-bis-(2,3-di-methyl-quinoxalin-6-yl)benzene.

    PubMed

    Diesendruck, Charles E; Rubin, Gabrielle; Bertke, Jeffery A; Gray, Danielle L; Moore, Jeffrey S

    2015-12-01

    The title compound, C26H22N4 (I), was synthesized by C-H iridium-catalyzed borylation followed by Suzuki coupling. The mol-ecular structure of (I) consists of a central benzene ring with 3-di-methyl-quinoxalin-6-yl groups at the 1 and 3 positions. These 2,3-di-methyl-quinoxalin-6-yl groups twist significantly out of the plane of the benzene ring. There are inter-molecular π-π inter-actions which result in a two-dimensional extended structure. The layers extend parallel to the ab plane and stack along the c axis. PMID:26870397

  14. Structure-activity study for (bis)ureidopropyl- and (bis)thioureidopropyldiamine LSD1 inhibitors with 3-5-3 and 3-6-3 carbon backbone architectures

    PubMed Central

    Nowotarski, Shannon L.; Pachaiyappan, Boobalan; Holshouser, Steven L.; Kutz, Craig J.; Li, Youxuan; Huang, Yi; Sharma, Shiv K.; Casero, Robert A.; Woster, Patrick M.

    2015-01-01

    Methylation at specific histone lysine residues is a critical post-translational modification that alters chromatin architecture, and dysregulated lysine methylation/demethylation is associated with the silencing of tumor suppressor genes. The enzyme lysine-specific demethylase 1 (LSD1) complexed to specific transcription factors catalyzes the oxidative demethylation of mono- and dimethyllysine 4 of histone H3 (H3K4me and H3K4me2 respectively). We have previously reported potent (bis)urea and (bis)thiourea LSD1 inhibitors that increase cellular levels of H3K4me and H3K4me2, promote the re-expression of silenced tumor suppressor genes and suppress tumor growth in vitro. Here we report the design additional (bis)urea and (bis)thiourea LSD1 inhibitors that feature 3-5-3 or 3-6-3 carbon backbone architectures. Three of these compounds displayed single-digit IC50 values in a recombinant LSD1 assay. In addition, compound 6d exhibited an IC50 of 4.2 μM against the Calu-6 human lung adenocarcinoma line, and 4.8 μM against the MCF7 breast tumor cell line, in an MTS cell viability assay. Following treatment with 6b–6d, Calu-6 cells exhibited a significant increase in the mRNA expression for the silenced tumor suppressor genes SFRP2, HCAD and p16, and modest increases in GATA4 message. The compounds described in this paper represent the most potent epigenetic modulators in this series, and have potential for use as antitumor agents. PMID:25725609

  15. BSND and ATP6V1G3: Novel Immunohistochemical Markers for Chromophobe Renal Cell Carcinoma

    PubMed Central

    Shinmura, Kazuya; Igarashi, Hisaki; Kato, Hisami; Koda, Kenji; Ogawa, Hiroshi; Takahashi, Seishiro; Otsuki, Yoshiro; Yoneda, Tatsuaki; Kawanishi, Yuichi; Funai, Kazuhito; Takayama, Tatsuya; Ozono, Seiichiro; Sugimura, Haruhiko

    2015-01-01

    Abstract Differentiating between chromophobe renal cell carcinoma (RCC) and other RCC subtypes can be problematic using routine light microscopy. This study aimed to identify novel immunohistochemical markers useful for a differential diagnosis between chromophobe RCC and other RCC subtypes. We selected 3 genes (including BSND and ATP6V1G3) that showed specific transcriptional expression in chromophobe RCC using expression data (n = 783) from The Cancer Genome Atlas (TCGA) database. A subsequent immunohistochemical examination of 186 RCCs obtained in our patient series resulted in a strong diffuse positivity of BSND and ATP6V1G3 proteins (both of which are involved in the regulation of membrane transport) in all the chromophobe RCC specimens (23/23 cases, 100%) but not in the clear cell RCC specimens (0/153 cases, 0%) or the papillary RCC specimens (0/10 cases, 0%). BSND and ATP6V1G3 protein expressions were also detected in renal oncocytoma (13/14 cases, 92.9%) and in the distal nephron, including the collecting duct, in the normal kidney. A computational analysis of TCGA data suggested that DNA methylation was involved in the differential expression pattern of both genes among RCC subtypes. Finally, an immunohistochemical analysis showed lung carcinomas were negative (0/85 cases, 0%) for the expression of both proteins. These results suggest that BSND and ATP6V1G3 are excellent novel immunohistochemical markers for differentiating between chromophobe RCC and other subtypes of RCC, including clear cell and papillary RCCs.

  16. BSND and ATP6V1G3: Novel Immunohistochemical Markers for Chromophobe Renal Cell Carcinoma.

    PubMed

    Shinmura, Kazuya; Igarashi, Hisaki; Kato, Hisami; Koda, Kenji; Ogawa, Hiroshi; Takahashi, Seishiro; Otsuki, Yoshiro; Yoneda, Tatsuaki; Kawanishi, Yuichi; Funai, Kazuhito; Takayama, Tatsuya; Ozono, Seiichiro; Sugimura, Haruhiko

    2015-06-01

    Differentiating between chromophobe renal cell carcinoma (RCC) and other RCC subtypes can be problematic using routine light microscopy. This study aimed to identify novel immunohistochemical markers useful for a differential diagnosis between chromophobe RCC and other RCC subtypes. We selected 3 genes (including BSND and ATP6V1G3) that showed specific transcriptional expression in chromophobe RCC using expression data (n = 783) from The Cancer Genome Atlas (TCGA) database. A subsequent immunohistochemical examination of 186 RCCs obtained in our patient series resulted in a strong diffuse positivity of BSND and ATP6V1G3 proteins (both of which are involved in the regulation of membrane transport) in all the chromophobe RCC specimens (23/23 cases, 100%) but not in the clear cell RCC specimens (0/153 cases, 0%) or the papillary RCC specimens (0/10 cases, 0%). BSND and ATP6V1G3 protein expressions were also detected in renal oncocytoma (13/14 cases, 92.9%) and in the distal nephron, including the collecting duct, in the normal kidney. A computational analysis of TCGA data suggested that DNA methylation was involved in the differential expression pattern of both genes among RCC subtypes. Finally, an immunohistochemical analysis showed lung carcinomas were negative (0/85 cases, 0%) for the expression of both proteins. These results suggest that BSND and ATP6V1G3 are excellent novel immunohistochemical markers for differentiating between chromophobe RCC and other subtypes of RCC, including clear cell and papillary RCCs. PMID:26091477

  17. Conformational Changes in Inositol 1,3,4,5,6-Pentakisphosphate 2-Kinase upon Substrate Binding

    PubMed Central

    Baños-Sanz, José Ignacio; Sanz-Aparicio, Julia; Whitfield, Hayley; Hamilton, Chris; Brearley, Charles A.; González, Beatriz

    2012-01-01

    Inositol 1,3,4,5,6-pentakisphosphate 2-kinase (IP5 2-K) catalyzes the synthesis of inositol 1,2,3,4,5,6-hexakisphosphate from ATP and IP5. Inositol 1,2,3,4,5,6-hexakisphosphate is implicated in crucial processes such as mRNA export, DNA editing, and phosphorus storage in plants. We previously solved the first structure of an IP5 2-K, which shed light on aspects of substrate recognition. However, failure of IP5 2-K to crystallize in the absence of inositide prompted us to study putative conformational changes upon substrate binding. We have made mutations to residues on a region of the protein that produces a clasp over the active site. A W129A mutant allowed us to capture IP5 2-K in its different conformations by crystallography. Thus, the IP5 2-K apo-form structure displays an open conformation, whereas the nucleotide-bound form shows a half-closed conformation, in contrast to the inositide-bound form obtained previously in a closed conformation. Both nucleotide and inositide binding produce large conformational changes that can be understood as two rigid domain movements, although local changes were also observed. Changes in intrinsic fluorescence upon nucleotide and inositide binding are in agreement with the crystallographic findings. Our work suggests that the clasp might be involved in enzyme kinetics, with the N-terminal lobe being essential for inositide binding and subsequent conformational changes. We also show how IP5 2-K discriminates between inositol 1,3,4,5-tetrakisphosphate and 3,4,5,6-tetrakisphosphate enantiomers and that substrate preference can be manipulated by Arg130 mutation. Altogether, these results provide a framework for rational design of specific inhibitors with potential applications as biological tools for in vivo studies, which could assist in the identification of novel roles for IP5 2-K in mammals. PMID:22745128

  18. Tank 241-AP-106, Grab samples, 6AP-98-1, 6AP-98-2 and 6AP-98-3 Analytical results for the final report

    SciTech Connect

    FULLER, R.K.

    1999-02-23

    This document is the final report for tank 241-AP-106 grab samples. Three grab samples 6AP-98-1, 6AP-98-2 and 6AP-98-3 were taken from riser 1 of tank 241-AP-106 on May 28, 1998 and received by the 222-S Laboratory on May 28, 1998. Analyses were performed in accordance with the ''Compatability Grab Sampling and Analysis Plan'' (TSAP) (Sasaki, 1998) and the ''Data Quality Objectives for Tank Farms Waste Compatability Program (DQO). The analytical results are presented in the data summary report. No notification limits were exceeded. The request for sample analysis received for AP-106 indicated that the samples were polychlorinated biphenyl (PCB) suspects. The results of this analysis indicated that no PCBs were present at the Toxic Substance Control Act (TSCA) regulated limit of 50 ppm. The results and raw data for the PCB analysis are included in this document.

  19. Final contamination assessment report, site 4-6, motor pool area. Version 3. 1. 19

    SciTech Connect

    Not Available

    1988-07-01

    This final report documents the phase I contamination survey of site 4-6, a vehicle maintenance area. A total of 36 borings, 1 soil grab sample, and 3 water samples yielded 169 samples. These samples were analyzed for volatile and semivolatile organics and metals. The following analytes were detected within or above their respective indicator ranges: C6H6, CHCl3, 11DClE, ETC6H6, CH2Cl2, TClEE, MEC6H5, 111TCE, TRClE, XYLEN, ALDRN, DBCP, CD, Cr, Cu, Pb, Zn, As, and Hg. Because the phase I survey has defined the general extent of potential contamination, no phase II program is planned at this time. However, ground water monitoring and the drilling of a limited number of borings near the fuel storage tanks are recommended. The volume of potentially contaminated material presented is estimated at 180,000 cubic yards. Appendices include chemical names, phase I chemical data, and comments and responses.

  20. Benchmarking ENDF/B-VII.1, JENDL-4.0 and JEFF-3.1.1 with MCNP6

    NASA Astrophysics Data System (ADS)

    van der Marck, Steven C.

    2012-12-01

    Recent releases of three major world nuclear reaction data libraries, ENDF/B-VII.1, JENDL-4.0, and JEFF-3.1.1, have been tested extensively using benchmark calculations. The calculations were performed with the latest release of the continuous energy Monte Carlo neutronics code MCNP, i.e. MCNP6. Three types of benchmarks were used, viz. criticality safety benchmarks, (fusion) shielding benchmarks, and reference systems for which the effective delayed neutron fraction is reported. For criticality safety, more than 2000 benchmarks from the International Handbook of Criticality Safety Benchmark Experiments were used. Benchmarks from all categories were used, ranging from low-enriched uranium, compound fuel, thermal spectrum ones (LEU-COMP-THERM), to mixed uranium-plutonium, metallic fuel, fast spectrum ones (MIX-MET-FAST). For fusion shielding many benchmarks were based on IAEA specifications for the Oktavian experiments (for Al, Co, Cr, Cu, LiF, Mn, Mo, Si, Ti, W, Zr), Fusion Neutronics Source in Japan (for Be, C, N, O, Fe, Pb), and Pulsed Sphere experiments at Lawrence Livermore National Laboratory (for 6Li, 7Li, Be, C, N, O, Mg, Al, Ti, Fe, Pb, D2O, H2O, concrete, polyethylene and teflon). The new functionality in MCNP6 to calculate the effective delayed neutron fraction was tested by comparison with more than thirty measurements in widely varying systems. Among these were measurements in the Tank Critical Assembly (TCA in Japan) and IPEN/MB-01 (Brazil), both with a thermal spectrum, two cores in Masurca (France) and three cores in the Fast Critical Assembly (FCA, Japan), all with fast spectra. The performance of the three libraries, in combination with MCNP6, is shown to be good. The results for the LEU-COMP-THERM category are on average very close to the benchmark value. Also for most other categories the results are satisfactory. Deviations from the benchmark values do occur in certain benchmark series, or in isolated cases within benchmark series. Such

  1. Benchmarking ENDF/B-VII.1, JENDL-4.0 and JEFF-3.1.1 with MCNP6

    SciTech Connect

    Marck, Steven C. van der

    2012-12-15

    Recent releases of three major world nuclear reaction data libraries, ENDF/B-VII.1, JENDL-4.0, and JEFF-3.1.1, have been tested extensively using benchmark calculations. The calculations were performed with the latest release of the continuous energy Monte Carlo neutronics code MCNP, i.e. MCNP6. Three types of benchmarks were used, viz. criticality safety benchmarks, (fusion) shielding benchmarks, and reference systems for which the effective delayed neutron fraction is reported. For criticality safety, more than 2000 benchmarks from the International Handbook of Criticality Safety Benchmark Experiments were used. Benchmarks from all categories were used, ranging from low-enriched uranium, compound fuel, thermal spectrum ones (LEU-COMP-THERM), to mixed uranium-plutonium, metallic fuel, fast spectrum ones (MIX-MET-FAST). For fusion shielding many benchmarks were based on IAEA specifications for the Oktavian experiments (for Al, Co, Cr, Cu, LiF, Mn, Mo, Si, Ti, W, Zr), Fusion Neutronics Source in Japan (for Be, C, N, O, Fe, Pb), and Pulsed Sphere experiments at Lawrence Livermore National Laboratory (for {sup 6}Li, {sup 7}Li, Be, C, N, O, Mg, Al, Ti, Fe, Pb, D2O, H2O, concrete, polyethylene and teflon). The new functionality in MCNP6 to calculate the effective delayed neutron fraction was tested by comparison with more than thirty measurements in widely varying systems. Among these were measurements in the Tank Critical Assembly (TCA in Japan) and IPEN/MB-01 (Brazil), both with a thermal spectrum, two cores in Masurca (France) and three cores in the Fast Critical Assembly (FCA, Japan), all with fast spectra. The performance of the three libraries, in combination with MCNP6, is shown to be good. The results for the LEU-COMP-THERM category are on average very close to the benchmark value. Also for most other categories the results are satisfactory. Deviations from the benchmark values do occur in certain benchmark series, or in isolated cases within benchmark series

  2. Membrane pore architecture of the CslF6 protein controls (1-3,1-4)-β-glucan structure

    PubMed Central

    Jobling, Stephen A.

    2015-01-01

    The cereal cell wall polysaccharide (1-3,1-4)-β-glucan is a linear polymer of glucose containing both β1-3 and β1-4 bonds. The structure of (1-3,1-4)-β-glucan varies between different cereals and during plant growth and development, but little is known about how this is controlled. The cellulose synthase–like CslF6 protein is an integral membrane protein and a major component of the (1-3,1-4)-β-glucan synthase. I show that a single amino acid within the predicted transmembrane pore domain of CslF6 controls (1-3,1-4)-β-glucan structure. A new mechanism for the control of the polysaccharide structure is proposed where membrane pore architecture and the translocation of the growing polysaccharide across the membrane control how the acceptor glucan is coordinated at the active site and thus the proportion of β1-3 and β1-4 bonds within the polysaccharide. PMID:26601199

  3. Correlational switching between 3{times}1 and 6{times}1 surface reconstructions on Si(111) with submonolayer Ag adsorption

    SciTech Connect

    Kempa, K.; Broido, D.A.; Weitering, H.H. |

    1996-07-01

    Electron correlations are strongly enhanced in low dimensional systems. Taking correlations as the dominant mechanism, we provide and explanation of the recently observed electrostatically enforced structural phase transition (3x1 to 6x1) on a Si(111) surface with sub-monolayer Ag adsorption.

  4. Heteroadamantanes and their derivatives. 6. Synthesis and mass-spectrometric investigation of 5-mono- and 5,6-disubstituted 6-oxo-1,3-diazaadamantanes

    SciTech Connect

    Kuznetsov, A.I.; Basargin, E.B.; Moskovkin, A.S.; Ba, M.Kh.; Miroshnichenko, I.V.; Botnikov, M.Ya.; Unkovskii, B.V.

    1986-06-01

    The corresponding 5-mono- and 5,7-disubstituted 6-oxo-1,3-diazaadamantanes were obtained with high yields by the condensation of mono- and ..cap alpha..,..cap alpha..'-disubstituted acetones with hexamethylenetetramine in the presence of glacial acetic acid, and their structures were confirmed by IR and PMR spectra. The behavior of the compounds under electron impact was studied, and the main fragmentation paths of their molecules were determined.

  5. Sensitivity of 2,6-Diamino-3, 5-Dinitropyrazine-1-Oxide

    SciTech Connect

    Tarver, C M; Urtiew, P A; Tran, T D

    2005-01-20

    The thermal and shock sensitivities of plastic bonded explosive formations based on 2,6-diamino-3,5-dinitropyrazine-1-oxide (commonly called LLM-105 for Lawrence Livermore Molecule No.105) are reported. The One Dimensional Time to Explosion (ODTX) apparatus was used to generate times to thermal explosion at various initial temperatures. A four-reaction chemical decomposition model was developed to calculate the time to thermal explosion versus inverse temperature curve. Three embedded manganin pressure gauge experiments were fired at different initial pressures to measure the pressure buildup and the distance required for transition to detonation. An Ignition and Growth reactive model was calibrated to this shock initiation data. LLM-105 exhibited thermal and shock sensitivities intermediate between those of triaminotrinitrobenzene (TATB) and octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazine (HMX).

  6. Studies of carcinogenicity of sodium chlorite in B6C3F1 mice

    SciTech Connect

    Yokose, Y.; Uchida, K.; Nakae, D.; Shiraiwa, K.; Yamamoto, K.; Konishi, Y.

    1987-12-01

    The carcinogenic activities of sodium chlorite in B6C3F1 mice were examined. Sodium chlorite was given at concentration of 0 (control), 0.025% (low dose), or 0.05% (high dose) in the drinking water of 150 female and 150 male mice for 80 weeks, after which time the animals were returned to distilled water without sodium chlorite. All mice were sacrificed 85 weeks from the beginning of the experiment. The incidence of tumor-bearing animals was 32% (control), 34% (low dose), and 26% (high dose) in female mice, and 46% (control), 57% (low dose), and 53% (high dose) in male mice. The types and incidence of neoplasms that occurred frequently in each group of both sexes were similar to those observed spontaneously in B6C3F1 mice. The incidence of lymphomas/leukemias in the high dose group of females (2%), however, was lower than that in the control group (15%). Furthermore, the incidence of pulmonary adenomas in the high dose group of males (12%) was higher than that in the control group (0%), but neither dose-related increases in the adenoma incidences nor increased incidences of the adenocarcinomas were observed. These results indicated no clear evidence of a carcinogenic potential of sodium chlorite in B6C3F1 mice.

  7. Child Proportional Scaling: Is 1/3 = 2/6 = 3/9 = 4/12?

    ERIC Educational Resources Information Center

    Boyer, Ty W.; Levine, Susan C.

    2012-01-01

    The current experiments examined the role of scale factor in children's proportional reasoning. Experiment 1 used a choice task and Experiment 2 used a production task to examine the abilities of kindergartners through fourth-graders to match equivalent, visually depicted proportional relations. The findings of both experiments show that accuracy…

  8. Atomic and electronic structures of Si(1 1 1)-(√3 x √3)R30°-Au and (6 × 6)-Au surfaces.

    PubMed

    Patterson, C H

    2015-12-01

    Si(1 1 1)-Au surfaces with around one monolayer of Au exhibit many ordered structures and structures containing disordered domain walls. Hybrid density functional theory (DFT) calculations presented here reveal the origin of these complex structures and tendency to form domain walls. The conjugate honeycomb chain trimer (CHCT) structure of the [Formula: see text]-Au phase contains Si atoms with non-bonding surface states which can bind Au atoms in pairs in interstices of the CHCT structure and make this surface metallic. Si adatoms adsorbed on the [Formula: see text]-Au surface induce a gapped surface through interaction with the non-bonding states. Adsorption of extra Au atoms in interstitial sites of the [Formula: see text]-Au surface is stabilized by interaction with the non-bonding orbitals and leads to higher coverage ordered structures including the [Formula: see text]-Au phase. Extra Au atoms bound in interstitial sites of the [Formula: see text]-Au surface result in top layer Si atoms with an SiAu4 butterfly wing configuration. The structure of a [Formula: see text]-Au phase, whose in-plane top atomic layer positions were previously determined by an electron holography technique (Grozea et al 1998 Surf. Sci. 418 32), is calculated using total energy minimization. The Patterson function for this structure is calculated and is in good agreement with data from an in-plane x-ray diffraction study (Dornisch et al 1991 Phys. Rev. B 44 11221). Filled and empty state scanning tunneling microscopy (STM) images are calculated for domain walls and the [Formula: see text]-Au structure. The [Formula: see text]-Au phase is 2D chiral and this is evident in computed and actual STM images. [Formula: see text]-Au and domain wall structures contain the SiAu4 motif with a butterfly wing shape. Chemical bonding within the Si-Au top layers of the [Formula: see text]-Au and [Formula: see text]-Au surfaces is analyzed and an explanation for the SiAu4 motif structure is given. PMID

  9. Metabolism of 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine by Mitochondrion-targeted Cytochrome P450 2D6

    PubMed Central

    Bajpai, Prachi; Sangar, Michelle C.; Singh, Shilpee; Tang, Weigang; Bansal, Seema; Chowdhury, Goutam; Cheng, Qian; Fang, Ji-Kang; Martin, Martha V.; Guengerich, F. Peter; Avadhani, Narayan G.

    2013-01-01

    1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a neurotoxic side product formed in the chemical synthesis of desmethylprodine opioid analgesic, which induces Parkinson disease. Monoamine oxidase B, present in the mitochondrial outer membrane of glial cells, catalyzes the oxidation of MPTP to the toxic 1-methyl-4-phenylpyridinium ion (MPP+), which then targets the dopaminergic neurons causing neuronal death. Here, we demonstrate that mitochondrion-targeted human cytochrome P450 2D6 (CYP2D6), supported by mitochondrial adrenodoxin and adrenodoxin reductase, can efficiently catalyze the metabolism of MPTP to MPP+, as shown with purified enzymes and also in cells expressing mitochondrial CYP2D6. Neuro-2A cells stably expressing predominantly mitochondrion-targeted CYP2D6 were more sensitive to MPTP-mediated mitochondrial respiratory dysfunction and complex I inhibition than cells expressing predominantly endoplasmic reticulum-targeted CYP2D6. Mitochondrial CYP2D6 expressing Neuro-2A cells produced higher levels of reactive oxygen species and showed abnormal mitochondrial structures. MPTP treatment also induced mitochondrial translocation of an autophagic marker, Parkin, and a mitochondrial fission marker, Drp1, in differentiated neurons expressing mitochondrial CYP2D6. MPTP-mediated toxicity in primary dopaminergic neurons was attenuated by CYP2D6 inhibitor, quinidine, and also partly by monoamine oxidase B inhibitors deprenyl and pargyline. These studies show for the first time that dopaminergic neurons expressing mitochondrial CYP2D6 are fully capable of activating the pro-neurotoxin MPTP and inducing neuronal damage, which is effectively prevented by the CYP2D6 inhibitor quinidine. PMID:23258538

  10. Radii and albedos of asteroids 1, 2, 3, 4, 6, 15, 51, 433, and 511

    NASA Technical Reports Server (NTRS)

    Cruikshank, D. P.; Morrison, D.

    1973-01-01

    The following radii (in kilometers) and visual geometric albedos are derived for nine asteroids from 10- and 20-micron radiometry: 1 Ceres (540, .06); 2 Pallas (275, .08); 3 Juno (125, .14); 4 Vesta (270, .21); 6 Hebe (110, .16); 15 Eunomia (135, .15); 51 Nemausa (80, .05); 433 Eros (12, .07); and 511 Davida (180, .04). Vesta has the highest albedo measured for an asteroid, while Davida, the lowest-albedo object in the sample, is one of the darkest known objects in the solar system. The median of all asteroid albedos measured to date is 0.1.-

  11. Translesion Synthesis across 1,N6-(2-Hydroxy-3-hydroxymethylpropan-1,3-diyl)-2′-deoxyadenosine (1,N6-γ-HMHP-dA) Adducts by Human and Archebacterial DNA Polymerases*

    PubMed Central

    Kotapati, Srikanth; Maddukuri, Leena; Wickramaratne, Susith; Seneviratne, Uthpala; Goggin, Melissa; Pence, Matthew G.; Villalta, Peter; Guengerich, F. Peter; Marnett, Lawrence; Tretyakova, Natalia

    2012-01-01

    The 1,N6-(2-Hydroxy-3-hydroxymethylpropan-1,3-diyl)-2′-deoxyadenosine (1,N6-γ-HMHP-dA) adducts are formed upon bifunctional alkylation of adenine nucleobases in DNA by 1,2,3,4-diepoxybutane, the putative ultimate carcinogenic metabolite of 1,3-butadiene. The presence of a substituted 1,N6-propano group on 1,N6-γ-HMHP-dA is expected to block the Watson-Crick base pairing of the adducted adenine with thymine, potentially contributing to mutagenesis. In this study, the enzymology of replication past site-specific 1,N6-γ-HMHP-dA lesions in the presence of human DNA polymerases (hpols) β, η, κ, and ι and archebacterial polymerase Dpo4 was investigated. Run-on gel analysis with all four dNTPs revealed that hpol η, κ, and Dpo4 were able to copy the modified template. In contrast, hpol ι inserted a single base opposite 1,N6-γ-HMHP-dA but was unable to extend beyond the damaged site, and a complete replication block was observed with hpol β. Single nucleotide incorporation experiments indicated that although hpol η, κ, and Dpo4 incorporated the correct nucleotide (dTMP) opposite the lesion, dGMP and dAMP were inserted with a comparable frequency. HPLC-ESI-MS/MS analysis of primer extension products confirmed the ability of bypass polymerases to insert dTMP, dAMP, or dGMP opposite 1,N6-γ-HMHP-dA and detected large amounts of −1 and −2 deletion products. Taken together, these results indicate that hpol η and κ enzymes bypass 1,N6-γ-HMHP-dA lesions in an error-prone fashion, potentially contributing to A→T and A→C transversions and frameshift mutations observed in cells following treatment with 1,2,3,4-diepoxybutane. PMID:22977231

  12. 3,3,6,6-Tetra­methyl-9-[6-(3,3,6,6-tetra­methyl-1,8-dioxo-2,3,4,5,6,7,8,9-octa­hydro-1H-xanthen-9-yl)pyridin-2-yl]-2,3,4,5,6,7,8,9-octa­hydro-1H-xanthene-1,8-dione

    PubMed Central

    Abdelhamid, Antar A.; Mohamed, Shaaban Kamel; Allahverdiyev, Mirze A.; Gurbanov, Atash V.; Ng, Seik Weng

    2011-01-01

    In the title mol­ecule, C39H45NO6, the two tetra­methyl­octa­hydroxanthen-1,8-dione substituents are arranged approximately parallel to each other and approximately perpendicular to the plane of the pyridine ring. The six-membered xanthene rings adopt flattened boat conformations with the O and methine C atoms deviating from the plane of the other four atoms. PMID:21754076

  13. MLK-3 activates the SAPK/JNK and p38/RK pathways via SEK1 and MKK3/6.

    PubMed Central

    Tibbles, L A; Ing, Y L; Kiefer, F; Chan, J; Iscove, N; Woodgett, J R; Lassam, N J

    1996-01-01

    Mixed lineage kinase-3 (MLK-3) is a 97 kDa serine/threonine kinase with multiple interaction domains, including a Cdc42 binding motif, but unknown function. Cdc42 and the related small GTP binding protein Rac1 can activate the SAPK/JNK and p38/RK stress-responsive kinase cascades, suggesting that MLK-3 may have a role in upstream regulation of these pathways. In support of this role, we demonstrate that MLK-3 can specifically activate the SAPK/JNK and p38/RK pathways, but has no effect on the activation of ERKs. Immunoprecipitated MLK-3 catalyzed the phosphorylation of SEK1 in vitro, and co-transfected MLK-3 induced phosphorylation of SEK1 and MKK3 at sites required for activation, suggesting direct regulation of these protein kinases. Furthermore, interactions between MLK-3 and SEK and MLK-3 and MKK6 were observed in co-precipitation experiments. Finally, kinase-dead mutants of MLK-3 blocked activation of the SAPK pathway by a newly identified mammalian analog of Ste20, germinal center kinase, but not by MEKK, suggesting that MLK-3 functions to activate the SAPK/JNK and p38/RK cascades in response to stimuli transduced by Ste20-like kinases. Images PMID:9003778

  14. High energy xLi2MnO3-(1-x)LiNi2/3Co1/6Mn1/6O2 composite cathode for advanced Li-ion batteries

    NASA Astrophysics Data System (ADS)

    Shojan, Jifi; Chitturi, Venkateswara Rao; Soler, Jess; Resto, Oscar; West, William C.; Katiyar, Ram S.

    2015-01-01

    Novel composite cathode materials, xLi2MnO3-(1-x)LiNi2/3Co1/6Mn1/6O2 (where x = 0.3, 0.5, and 0.7), were synthesized by sol-gel route and characterized by advanced techniques for rechargeable Li-ion battery applications. Phase purity of the composites was examined by XRD as well as Raman spectroscopy and the studies revealed good crystallinity and the formation of pure composite phases with monoclinic (C2/m) and hexagonal (R3m) crystal structures for Li2MnO3 and LiNi2/3Co1/6Mn1/6O2, respectively. Polyhedral agglomerates seen in the scanning and transmission electron microscopic images elucidated the better electrochemical properties of the composites. Valence states of transition metals in the composites were examined by X-ray photoelectron spectroscopy and the analysis suggested predominant oxidation states of Ni, Co, and Mn as 2+, 3+, and 4+, respectively. Galvanostatic charge-discharge tests, performed at different C-rates between 2.0 and 4.8 V, indicated high discharge capacity (∼250 mAh g-1), good rate capability, and excellent cycleability of the composite with x = 0.5 compared to the composites with x = 0.3 and 0.7. In-situ Raman spectroscopic studies revealed the activation of Li2MnO3 component in all composite cathode materials during the first cycle charging process with structural stability thereby enhancing performance of the composite with x = 0.5. These results demonstrated the feasibility of using 0.5Li2MnO3-0.5LiNi2/3Co1/6Mn1/6O2 composite as advanced cathode for high power Li-ion batteries.

  15. (E)-2,2-Dimethyl-5-(3-phenyl-allyl-idene)-1,3-dioxane-4,6-dione.

    PubMed

    Zeng, Wu-Lan

    2010-01-01

    The title compound, C(15)H(14)O(4), was prepared by the reaction of 2,2-dimethyl-1,3-dioxane-4,6-dione and (Z)-3-phenyl-acryl-aldehyde in ethanol. The dioxane ring is in a sofa conformation with the C atom bonded to the two methyl groups forming the flap. With the exception of the flap atom and the methyl group C atoms, all other non-H atoms are essentially planar, with an r.m.s. deviation of 0.067 (1) Å. The crystal structure is stabilized by weak inter-molecular C-H⋯O hydrogen bonds. PMID:21589113

  16. Differential Regulation of ERK1/2 and mTORC1 Through T1R1/T1R3 in MIN6 Cells

    PubMed Central

    Wauson, Eric M.; Guerra, Marcy L.; Dyachok, Julia; McGlynn, Kathleen; Giles, Jennifer; Ross, Elliott M.

    2015-01-01

    The MAPKs ERK1/2 respond to nutrients and other insulin secretagogues in pancreatic β-cells and mediate nutrient-dependent insulin gene transcription. Nutrients also stimulate the mechanistic target of rapamycin complex 1 (mTORC1) to regulate protein synthesis. We showed previously that activation of both ERK1/2 and mTORC1 in the MIN6 pancreatic β-cell-derived line by extracellular amino acids (AAs) is at least in part mediated by the heterodimeric T1R1/T1R3, a G protein-coupled receptor. We show here that AAs differentially activate these two signaling pathways in MIN6 cells. Pretreatment with pertussis toxin did not prevent the activation of either ERK1/2 or mTORC1 by AAs, indicating that Gi is not central to either pathway. Although glucagon-like peptide 1, an agonist for a Gs-coupled receptor, activated ERK1/2 well and mTORC1 to a small extent, AAs had no effect on cytosolic cAMP accumulation. Ca2+ entry is required for ERK1/2 activation by AAs but is dispensable for AA activation of mTORC1. Pretreatment with UBO-QIC, a selective Gq inhibitor, reduced the activation of ERK1/2 but had little effect on the activation of mTORC1 by AAs, suggesting a differential requirement for Gq. Inhibition of G12/13 by the overexpression of the regulator of G protein signaling domain of p115 ρ-guanine nucleotide exchange factor had no effect on mTORC1 activation by AAs, suggesting that these G proteins are also not involved. We conclude that AAs regulate ERK1/2 and mTORC1 through distinct signaling pathways. PMID:26168033

  17. 3-(1'-Cyclobutylspiro[4H-1,3-benzodioxine-2,4'-piperidine]-6-yl)-5,5-dimethyl-1,4-dihydropyridazin-6-one (CEP-32215), a new wake-promoting histamine H3 antagonist/inverse agonist.

    PubMed

    Hudkins, Robert L; Gruner, John A; Raddatz, Rita; Mathiasen, Joanne R; Aimone, Lisa D; Marino, Michael J; Bacon, Edward R; Williams, Michael; Ator, Mark A

    2016-07-01

    CEP-32215 is a new, potent, selective, and orally bioavailable inverse agonist of the histamine H3 receptor (H3R) with drug-like properties. High affinity in human (hH3R Ki = 2.0 ± 0.2 nM) and rat (rH3R Ki = 3.6 ± 0.7 nM) H3R radioligand binding assays was demonstrated. Potent functional antagonism (Kb = 0.3 ± 0.1 nM) and inverse agonism (EC50 = 0.6 ± 0.2 nM) were demonstrated in [(35)S]guanosine 5(')-O-(γ-thio)-triphosphate binding assays. Oral bioavailability and dose-related exposure was consistent among rat, dog, and monkey. After oral dosing, occupancy of H3R by CEP-32215 was estimated by the inhibition of ex vivo binding in rat cortical slices (ED50 = 0.1 mg/kg p.o.). Functional antagonism in brain was demonstrated by the inhibition of R-α-methylhistamine-induced drinking in the rat dipsogenia model (ED50 = 0.92 mg/kg). CEP-32215 significantly increased wake duration in the rat EEG model at 3-30 mg/kg p.o. Increased motor activity, sleep rebound or undesirable events (such as spike wave or seizure activity) was not observed following doses up to 100 mg/kg p.o., indicating an acceptable therapeutic index. CEP-32215 may have potential utility in the treatment of a variety of sleep disorders. This article is part of the Special Issue entitled 'Histamine Receptors'. PMID:26400408

  18. Structure activity optimization of 6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazines as Jak1 kinase inhibitors.

    PubMed

    Friedman, Michael; Frank, Kristine E; Aguirre, Ana; Argiriadi, Maria A; Davis, Heather; Edmunds, Jeremy J; George, Dawn M; George, Jonathan S; Goedken, Eric; Fiamengo, Bryan; Hyland, Deborah; Li, Bin; Murtaza, Anwar; Morytko, Michael; Somal, Gagandeep; Stewart, Kent; Tarcsa, Edit; Van Epps, Stacy; Voss, Jeffrey; Wang, Lu; Woller, Kevin; Wishart, Neil

    2015-10-15

    Previous work investigating tricyclic pyrrolopyrazines as kinase cores led to the discovery that 1-cyclohexyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazine (12) had Jak inhibitory activity. Herein we describe our initial efforts to develop orally bioavailable analogs of 12 with improved selectivity of Jak1 over Jak2. PMID:26372653

  19. The Henry reaction of (1R)-(1,4:3,6-dianhydro-D-mannitol-2-yl)-1,4:3,6-dianhydro-D-fructose 5,5'-dinitrate. Different reactive features of nitromethane to nitroethane.

    PubMed

    Liu, Feng-Wu; Wang, Zhen-Ji; Song, Xiao-Ping; Zhang, Sai-Yang; Liu, Hong-Min

    2009-12-14

    Henry reactions of a novel higher sugar derivative, (1R)-(1,4:3,6-dianhydro-D-mannitol-2-yl)-1,4:3,6-dianhydro-D-fructose 5,5'-dinitrate (Alternate nomenclature: (1R)-(isomannid-2-yl)-1,4:3,6-dianhydro-D-fructose 5,5'-dinitrate), with nitromethane and nitroethane were studied. The kinetic and thermodynamic reactions with nitromethane under different conditions were carried out to afford (2S)- and (2R)-beta-nitroalcohols, respectively. But when using nitroethane the reaction gave a (2S)-beta-nitroalcohol with an inverted configuration at vicinal carbon C-1. Two stereogenic centers were generated, and one was altered in the reaction. PMID:19880098

  20. Planetary brightness temperature measurements at 8.6 mm and 3.1 mm wavelengths.

    NASA Technical Reports Server (NTRS)

    Ulich, B. L.; Cogdell, J. R.; Davis, J. H.

    1973-01-01

    New measurements of the sun, moon, Mercury, Venus, Mars, Jupiter, and Saturn at 3.1- and 8.6-mm wavelengths are given. The temperatures reported for the planets at 3.1-mm wavelength are higher than previous measurements in this wavelength range and change the interpretation of some planetary spectra. For Mercury, it is found that the mean brightness temperature is independent of wavelength and that a temperature-dependent thermal conductivity is not required to match the observations. In the case of Mars, the spectrum is shown to rise in the millimeter region, as simple models predict. For Jupiter, the need to recalculate the spectrum with recent models is demonstrated. The flux density scale proposed by Dent (1972) has been revised according to a more accurate determination of the millimeter brightness temperature of Jupiter.

  1. Prediction of the age at onset in spinocerebellar ataxia type 1, 2, 3 and 6

    PubMed Central

    Tezenas du Montcel, Sophie; Durr, Alexandra; Rakowicz, Maria; Nanetti, Lorenzo; Charles, Perrine; Sulek, Anna; Mariotti, Caterina; Rola, Rafal; Schols, Ludger; Bauer, Peter; Dufaure-Garé, Isabelle; Jacobi, Heike; Forlani, Sylvie; Schmitz-Hübsch, Tanja; Filla, Alessandro; Timmann, Dagmar; van de Warrenburg, Bart P; Marelli, Cecila; Kang, Jun-Suk; Giunti, Paola; Cook, Arron; Baliko, Laszlo; Bela, Melegh; Boesch, Sylvia; Szymanski, Sandra; Berciano, José; Infante, Jon; Buerk, Katrin; Masciullo, Marcella; Di Fabio, Roberto; Depondt, Chantal; Ratka, Susanne; Stevanin, Giovanni; Klockgether, Thomas; Brice, Alexis; Golmard, Jean-Louis

    2014-01-01

    Background The most common spinocerebellar ataxias (SCA)—SCA1, SCA2, SCA3, and SCA6—are caused by (CAG)n repeat expansion. While the number of repeats of the coding (CAG)n expansions is correlated with the age at onset, there are no appropriate models that include both affected and preclinical carriers allowing for the prediction of age at onset. Methods We combined data from two major European cohorts of SCA1, SCA2, SCA3, and SCA6 mutation carriers: 1187 affected individuals from the EUROSCA registry and 123 preclinical individuals from the RISCA cohort. For each SCA genotype, a regression model was fitted using a log-normal distribution for age at onset with the repeat length of the alleles as covariates. From these models, we calculated expected age at onset from birth and conditionally that this age is greater than the current age. Results For SCA2 and SCA3 genotypes, the expanded allele was a significant predictor of age at onset (−0.105±0.005 and −0.056±0.003) while for SCA1 and SCA6 genotypes both the size of the expanded and normal alleles were significant (expanded: −0.049±0.002 and −0.090±0.009, respectively; normal: +0.013±0.005 and −0.029±0.010, respectively). According to the model, we indicated the median values (90% critical region) and the expectancy (SD) of the predicted age at onset for each SCA genotype according to the CAG repeat size and current age. Conclusions These estimations can be valuable in clinical and research. However, results need to be confirmed in other independent cohorts and in future longitudinal studies. ClinicalTrials.gov, number NCT01037777 and NCT00136630 for the French patients. PMID:24780882

  2. AGR-1 Fuel Compact 6-3-2 Post-Irradiation Examination Results

    SciTech Connect

    Paul demkowicz; jason Harp; Scott Ploger

    2012-12-01

    Destructive post-irradiation examination was performed on fuel Compact 6-3-2, which was irradiated in the AGR-1 experiment to a final compact average burnup of 11.3% FIMA and a time-average, volume-average temperature of 1070°C. The analysis of this compact was focused on characterizing the extent of fission product release from the particles and examining particles to determine the condition of the kernels and coating layers. The work included deconsolidation of the compact and leach-burn-leach analysis, visual inspection and gamma counting of individual particles, measurement of fuel burnup by several methods, metallurgical preparation of selected particles, and examination of particle cross-sections with optical microscopy. A single particle with a defective SiC layer was identified during deconsolidation-leach-burn-leach analysis, which is in agreement with previous measurements showing elevated cesium in the Capsule 6 graphite fuel holder associated with this fuel compact. The fraction of the compact europium inventory released from the particles and retained in the matrix was relatively high (approximately 6E-3), indicating release from intact particle coatings. The Ag-110m inventory in individual particles exhibited a very broad distribution, with some particles retaining =80% of the predicted inventory and others retaining less than 25%. The average degree of Ag-110m retention in 60 gamma counted particles was approximately 50%. This elevated silver release is in agreement with analysis of silver on the Capsule 6 components, which indicated an average release of 38% of the Capsule 6 inventory from the fuel compacts. In spite of the relatively high degree of silver release from the particles, virtually none of the Ag-110m released was found in the compact matrix, and presumably migrated out of the compact and was deposited on the irradiation capsule components. Release of all other fission products from the particles appears to be less than a single

  3. New 1-(3-nitrophenyl)-5,6-dihydro-4H-[1,2,4]triazolo[4,3-a][1,5]benzodiazepines: synthesis and computational study.

    PubMed

    Kosychova, Lidija; Karalius, Antanas; Staniulytė, Zita; Sirutkaitis, Romualdas Aleksas; Palaima, Algirdas; Laurynėnas, Audrius; Anusevičius, Žilvinas

    2015-01-01

    Triazole derivatives constitute an important group of heterocyclic compounds have have been the subject of extensive study in the recent past. These compounds have shown a wide range of biological and pharmacological activities. In this work, new fused tricyclic 1-(3-nitrophenyl)-5,6-dihydro-4H-[1,2,4]triazolo[4,3-a][1,5]-benzodiazepines have been synthesized by the thermal cyclization of N'-(2,3-dihydro-1H-1,5-benzodiazepin-4-yl)-3-nitrobenzohydrazides. After screening ethanol, toluene and 1-butanol as solvents, butanol-1 was found to be the best choice for the cyclization reaction in order to obtain the highest yields of tricyclic derivatives. The chemical structures of the synthesized compounds were elucidated by the analysis of their IR, 1H- and 13C-NMR spectral data. For tentative rationalization of the reaction processes, the global and local reactivity indices of certain compounds, taking part in the reaction pathway, were assessed by means of quantum mechanical calculations using the conceptual density functional theory (DFT) approach. This work could be useful for the synthesis of new heterocyclic compounds bearing a fused triazole ring. PMID:25822079

  4. Intracellular localization of human Ins(1,3,4,5,6)P5 2-kinase

    PubMed Central

    Brehm, Maria A.; Schenk, Tobias M. H.; Zhou, Xuefei; Fanick, Werner; Lin, Hongying; Windhorst, Sabine; Nalaskowski, Marcus M.; Kobras, Mario; Shears, Stephen B.; Mayr, Georg W.

    2007-01-01

    InsP6 is an intracellular signal with several proposed functions that is synthesized by IP5K [Ins(1,3,4,5,6)P5 2-kinase]. In the present study, we overexpressed EGFP (enhanced green fluorescent protein)–IP5K fusion proteins in NRK (normal rat kidney), COS7 and H1299 cells. The results indicate that there is spatial microheterogeneity in the intracellular localization of IP5K that could also be confirmed for the endogenous enzyme. This may facilitate changes in InsP6 levels at its sites of action. For example, overexpressed IP5K showed a structured organization within the nucleus. The kinase was preferentially localized in euchromatin and nucleoli, and co-localized with mRNA. In the cytoplasm, the overexpressed IP5K showed locally high concentrations in discrete foci. The latter were attributed to stress granules by using mRNA, PABP [poly(A)-binding protein] and TIAR (TIA-1-related protein) as markers. The incidence of stress granules, in which IP5K remained highly concentrated, was further increased by puromycin treatment. Using FRAP (fluorescence recovery after photobleaching) we established that IP5K was actively transported into the nucleus. By site-directed mutagenesis we identified a nuclear import signal and a peptide segment mediating the nuclear export of IP5K. PMID:17705785

  5. Suppression of Adipogenesis by 5-Hydroxy-3,6,7,8,3',4'-Hexamethoxyflavone from Orange Peel in 3T3-L1 Cells.

    PubMed

    Wang, Yu; Lee, Pei-Sheng; Chen, Yi-Fen; Ho, Chi-Tang; Pan, Min-Hsiung

    2016-09-01

    We reported previously that hydroxylated polymethoxyflavones (HPMFs) effectively suppressed obesity in high-fat-induced mouse. In this study, we further investigated the molecular mechanism of action of 5-hydroxy-3,6,7,8,3',4'-hexamethoxyflavone (5-OH-HxMF), one of major HPMFs in orange peel. Treatment of 5-OH-HxMF effectively inhibited lipid accumulation by 55-60% in a dose-dependent manner. The 5-OH-HxMF attenuated adipogenesis through downregulating adipogenesis-related transcription factors such as peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer-binding proteins (C/EBPs), as well as downstream target fatty acid synthase and acetyl-CoA carboxylase (ACC). 5-OH-HxMF activated adenosine monophosphate-activated protein kinase signaling and silent mating type information regulation 1 (SIRTUIN 1 or SIRT1) in 3T3-L1 adipocytes to decrease lipid accumulation. In addition, the inhibition rate of lipid accumulation was compared between 5-OH-HxMF and 3,5,6,7,8,3',4'-heptamethoxyflavone (HpMF). 5-OH-HxMF inhibited lipid accumulation 15-20% more than HpMF did, indicating that hydroxyl group at position 5 can be a key factor in the suppression of adipogenesis. PMID:27542074

  6. Parallel Synthesis of 1,6-Disubstituted-1,2,4-Triazin-3-Ones on Solid-Phase

    PubMed Central

    Hu, Miao; Huang, Wei; Giulianotti, Marc A.; Houghten, Richard A.; Yu, Yongping

    2013-01-01

    A parallel solid-phase synthesis of 1,6-disubstituted-1,2,4-triazin-3-ones from MBHA resin is described. The reduction of resin-bound nitrosamino acids provides hydrazines efficiently without affecting the amide bond. The trityl protected hydrazine is then reduced with borane, and cyclized with 1,1-carbonyldiimidazole. The desired products are cleaved from their solid support and obtained in good yield and purity. This methodology is of value for the rapid parallel preparation of these potentially bioactive molecules. PMID:23750635

  7. Inhalation pharmacokinetics of ethylbenzene in B6C3F1 mice

    SciTech Connect

    Charest-Tardif, G.; Tardif, R.; Krishnan, K. . E-mail: Kannan.krishnan@umontreal.ca

    2006-01-15

    The objective of the present study was to characterize the inhalation pharmacokinetics of ethylbenzene (EB) in male and female B6C3F1 mice following single and repeated exposures. Initially, groups of 28 male and female mice were exposed for 4 h to 75, 200, 500, or 1000 ppm in order to determine potential non-linearity in the kinetics of EB. Then, groups of male and female mice were exposed for 6 h to 75 ppm and 750 ppm (corresponding to the NTP exposures) for 1 or 7 consecutive days, to evaluate whether EB kinetics was altered during repeated exposures, The maximal blood concentration (C {sub max}; mean {+-} SD, n = 4) observed in female mice at the end of a 4-h exposure to 75, 200, 500, and 1000 ppm was 0.53 {+-} 0.18, 2.26 {+-} 0.38, 19.17 {+-} 2.74, and 82.36 {+-} 16.66 mg/L, respectively. The areas under the concentration vs. time curve (AUCs) following 4-h exposure to 75, 200, 500, and 1000 ppm were 88.5, 414.0, 3612.2, and 19,104.1 mg/L/min, respectively, in female mice, and 116.7, 425.7, 3148.3, and 16,039.1 mg/L/min in male mice. The comparison of C {sub max} and the kinetic profile of EB in mice exposed to 75 ppm suggests that they are similar between 1-day and 7-day exposures. However, at 750 ppm, the rate of EB elimination would appear to be greater after repeated exposures than single exposure, the pattern being evident in both male and female mice. Overall, the single and repeated exposure pharmacokinetic data collected in the present study suggest that EB kinetics is saturable at exposure concentrations exceeding 500 ppm (and therefore at 750 ppm used in the NTP mouse cancer bioassay) but is in the linear range at the lower concentration used in the bioassay (75 ppm). These data suggest that consideration of the nature and magnitude of non-linear kinetics and induction of metabolism during repeated exposures is essential for the conduct of a scientifically sound analysis of EB cancer dose-response data collected in B6C3F1 mice.

  8. Microstructural examination of V-(3-6%)Cr-(3-5%)Ti irradiated in the ATR-A1 experiment

    SciTech Connect

    Gelles, D.S.

    1998-09-01

    Microstructural examination results are reported for four heats of V-(3-6%)Cr-(3-5%)Ti irradiated in the ATR-A1 experiment to {approximately}4 dpa at {approximately}200 and 300 C to provide an understanding of the microstructural evolution that may be associated with degradation of mechanical properties. Fine precipitates were observed in high density intermixed with small defect clusters for all conditions examined following the irradiation. The irradiation-induced precipitation does not appear to be affected by preirradiation heat treatment or composition.

  9. 40 CFR 721.9750 - 2-Chloro-4,6-bis(substituted)-1,3,5-triazine, dihydrochloride.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false 2-Chloro-4,6-bis(substituted)-1,3,5... New Uses for Specific Chemical Substances § 721.9750 2-Chloro-4,6-bis(substituted)-1,3,5-triazine... identified generically as 2-chloro-4,6-bis(substituted)-1,3,5-triazine, dihydrochloride (PMN P-91-659)...

  10. Rational design, synthesis, anti-HIV-1 RT and antimicrobial activity of novel 3-(6-methoxy-3,4-dihydroquinolin-1(2H)-yl)-1-(piperazin-1-yl)propan-1-one derivatives.

    PubMed

    Chander, Subhash; Wang, Ping; Ashok, Penta; Yang, Liu-Meng; Zheng, Yong-Tang; Murugesan, Sankaranarayanan

    2016-08-01

    In the present study, fifteen novel 3-(6-methoxy-3,4-dihydroquinolin-1(2H)-yl)-1-(piperazin-1-yl)propan-1-one (6a-o) derivatives were designed as inhibitor of HIV-1 RT using ligand based drug design approach and in-silico evaluated for drug-likeness properties. Designed compounds were synthesized, characterized and in-vitro evaluated for RT inhibitory activity against wild HIV-1 RT strain. Among the tested compounds, four compounds (6a, 6b, 6j and 6o) exhibited significant inhibition of HIV-1 RT (IC50⩽10μg/ml). All synthesized compounds were also evaluated for anti-HIV-1 activity as well as cytotoxicity on T lymphocytes, in which compounds 6b and 6l exhibited significant anti-HIV activity (EC50 values 4.72 and 5.45μg/ml respectively) with good safety index. Four compounds (6a, 6b, 6j and 6o) found significantly active against HIV-1 RT in the in-vitro assay were in-silico evaluated against two mutant RT strains as well as one wild strain. Further, titled compounds were evaluated for in-vitro antibacterial (Escherichia coli, Pseudomonas putida, Staphylococcus aureus and Bacillus cereus) and antifungal (Candida albicans and Aspergillus niger) activities. PMID:27288643

  11. Chemically induced Parkinson's disease: intermediates in the oxidation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine to the 1-methyl-4-phenyl-pyridinium ion

    SciTech Connect

    Chacon, J.N.; Chedekel, M.R.; Land, E.J.; Truscott, T.G.

    1987-04-29

    Various unstable intermediate oxidation states have been postulated in the metabolic activation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine to the 1-methyl-4-phenyl pyridinium ion. We now report the first direct observation of these free radical intermediates by pulse radiolysis and flash photolysis. Studies are described of various reactions of such species, in particular with dopamine whose autoxidation to dopamine quinone is reported to be potentiated by 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine.

  12. CX3CL1-CX3CR1 Interaction Increases the Population of Ly6C(-)CX3CR1(hi) Macrophages Contributing to Unilateral Ureteral Obstruction-Induced Fibrosis.

    PubMed

    Peng, Xiaogang; Zhang, Jing; Xiao, Zhicheng; Dong, Yanjun; Du, Jie

    2015-09-15

    Chemokines modulate inflammatory responses that are prerequisites for kidney injury. The specific role of monocyte-associated CX3CR1 and its cognate ligand CX3CL1 in unilateral ureteral obstruction (UUO)-induced kidney injury remains unclear. In this study, we found that UUO caused a CCR2-dependent increase in numbers of Ly6C(hi) monocytes both in the blood and kidneys and of Ly6C(-)CX3CR1(+) macrophages in the obstructed kidneys of mice. Using CX3CR1(gfp/+) knockin mice, we observed a rapid conversion of infiltrating proinflammatory Ly6C(+)CX3CR1(1o) monocytes/macrophages to anti-inflammatory Ly6C(-)CX3CR1(hi) macrophages. CX3CR1 deficiency affected neither monocyte trafficking nor macrophage differentiation in vivo upon renal obstruction, but CX3CR1 expression in monocytes and macrophages was required for increases in fibrosis in the obstructed kidneys. Mechanistically, CX3CL1-CX3CR1 interaction increases Ly6C(-)CX3CR1(hi) macrophage survival within the obstructed kidneys. Therefore, CX3CL1 and CX3CR1 may represent attractive therapeutic targets in obstructive nephropathy. PMID:26254342

  13. Chronic bioassays of chlorinated humic acids in B6C3F1 mice

    SciTech Connect

    van Duuren, B.L.; Melchionne, S.; Seidman, I.; Pereira, M.A.

    1986-11-01

    Humic acids (Fluka), chlorinated to carbon:chlorine (C:Cl) ratios of 1:1 and 1:0.3, were administered to B6C3F1 mice, 50 males and 50 females per group, in the drinking water at a total organic carbon (TOC) level of 0.5 g/L. The mice were 6 to 8 weeks old at the beginning of the bioassays. The doses used were based on short-term (8 weeks) evaluations for toxicity, palatability, and weight gain. The chronic bioassays included the following control groups: unchlorinated humic acids (0.5 g/L), no-treatment (100 males and 100 females), dibromoethane (DBE, 2.0 mM in drinking water; positive control) and 0.44% sodium chloride in drinking water, i.e., at the same concentration as those receiving chlorinated humic acids. The chlorinated humic acids were prepared freshly and chemically assayed once per week. All chemicals were, with the exception of DBE, administered for 24 months; DBE was administered for 18 months. The volumes of solutions consumed were measured once weekly. All treatment groups showed normal weight gain except the DBE group. No markedly significant increases in tumor incidences were evident in any of the organs and tissues examined in the chlorinated humic acid groups compared to unchlorinated humic acids and the no-treatment control groups. DBE caused the expected high incidence of squamous carcinomas of the forestomach. The chlorinated humic acids tested contained direct-acting alkylating agents, based on their reactivity with p-nitrobenzylpyridine (PNBP), and showed mutagenic activity in S. typhimurium.

  14. Synthesis and in vitro anticancer evaluation of some 4,6-diamino-1,3,5-triazine-2-carbohydrazides as Rad6 ubiquitin conjugating enzyme inhibitors.

    PubMed

    Kothayer, Hend; Spencer, Sebastian M; Tripathi, Kaushlendra; Westwell, Andrew D; Palle, Komaraiah

    2016-04-15

    Series of 4-amino-6-(arylamino)-1,3,5-triazine-2-carbohydrazides (3a-e) and N'-phenyl-4,6-bis(arylamino)-1,3,5-triazine-2-carbohydrazides (6a-e), for ease of readership, we will abbreviate our compound names as 'new triazines', have been synthesized, based on the previously reported Rad6B-inhibitory diamino-triazinylmethyl benzoate anticancer agents TZ9 and 4-amino-N'-phenyl-6-(arylamino)-1,3,5-triazine-2-carbohydrazides. Synthesis of the target compounds was readily accomplished in two steps from either bis-aryl/aryl biguanides via reaction of phenylhydrazine or hydrazinehydrate with key 4-amino-6-bis(arylamino)/(arylamino)-1,3,5-triazine-2-carboxylate intermediates. These new triazine derivatives were evaluated for their abilities to inhibit Rad6B ubiquitin conjugation and in vitro anticancer activity against several human cancer cell lines: ovarian (OV90 and A2780), lung (H1299 and A549), breast (MCF-7 and MDA-MB231) and colon (HT29) cancer cells by MTS assays. All the 10 new triazines exhibited superior Rad6B inhibitory activities in comparison to selective Rad6 inhibitor TZ9 that was reported previously. Similarly, new triazines also showed better IC50 values in survival assays of various tumor cell lines. Particularly, new triazines 6a-c, exhibited lower IC50 (3.3-22μM) values compared to TZ9. PMID:26965855

  15. 5,6-Dehydrokawain from Alpinia zerumbet promotes osteoblastic MC3T3-E1 cell differentiation.

    PubMed

    Kumagai, Momochika; Mishima, Takashi; Watanabe, Akio; Harada, Teppei; Yoshida, Izumi; Fujita, Kazuhiro; Watai, Masatoshi; Tawata, Shinkichi; Nishikawa, Keisuke; Morimoto, Yoshiki

    2016-07-01

    Bone homeostasis is maintained by balancing bone formation and bone resorption, but an imbalance between them is associated with various bone-related diseases such as osteoporosis and rheumatoid arthritis. We found that 5,6-dehydrokawain (DK) and dihydro-5,6-dehydrokawain (DDK), which were isolated as promising compounds from Alpinia zerumbet rhizomes, promote differentiation of osteoblastic MC3T3-E1 cells. DK and DDK increased the alkaline phosphatase activity and matrix mineralization of MC3T3-E1 cells. DK exerts larger effects than DDK. The gene expression of runt-related transcription factor 2 and osterix, which are essential transcription factors in the early period of osteoblast differentiation, was significantly increased by DK treatment. The mRNA level of distal-less homeobox 5 was also enhanced by DK treatment, and DK activated the p38 mitogen-activated protein kinase pathway. Therefore, DK may have clinical potential for preventing osteoporosis, and could be considered as a potential anabolic therapeutic agent. PMID:26940726

  16. Low-field magnetization studies in the reentrant superconductor ErRh/sub 1. 1/Sn/sub 3. 6/

    SciTech Connect

    Andres, K.; Remeika, J.P.; Espinosa, G.P.; Cooper, A.S.

    1981-02-01

    Absolute static magnetization measurements in fields as low as 0.1 Oe in a single crystal of ErRh/sub 1.1/Sn/sub 3.6/ show a clear Meissner effect at the superconducting transition. In the superconducting state, the magnetization shows reversible type-II behavior above a field of 6 Oe, and a thermodynamic critical field H/sub 0/=20 +- 5 Oe can be deduced from the data. The previously reported reduction in H/sub c/2 upon cooling towards the ferromagnetic Curie temperature (T/sub C/=0.46 K) can be explained entirely as being due to the increasing paramagnetic induction in the sample. A search for a coexistence region of superconductivity and ferromagnetism below T/sub C/ indicates that such a region must be smaller than 0.03 K.

  17. Smc5/6 Mediated Sumoylation of the Sgs1-Top3-Rmi1 Complex Promotes Removal of Recombination Intermediates.

    PubMed

    Bonner, Jaclyn N; Choi, Koyi; Xue, Xiaoyu; Torres, Nikko P; Szakal, Barnabas; Wei, Lei; Wan, Bingbing; Arter, Meret; Matos, Joao; Sung, Patrick; Brown, Grant W; Branzei, Dana; Zhao, Xiaolan

    2016-07-12

    Timely removal of DNA recombination intermediates is critical for genome stability. The DNA helicase-topoisomerase complex, Sgs1-Top3-Rmi1 (STR), is the major pathway for processing these intermediates to generate conservative products. However, the mechanisms that promote STR-mediated functions remain to be defined. Here we show that Sgs1 binds to poly-SUMO chains and associates with the Smc5/6 SUMO E3 complex in yeast. Moreover, these interactions contribute to the sumoylation of Sgs1, Top3, and Rmi1 upon the generation of recombination structures. We show that reduced STR sumoylation leads to accumulation of recombination structures, and impaired growth in conditions when these structures arise frequently, highlighting the importance of STR sumoylation. Mechanistically, sumoylation promotes STR inter-subunit interactions and accumulation at DNA repair centers. These findings expand the roles of sumoylation and Smc5/6 in genome maintenance by demonstrating that they foster STR functions in the removal of recombination intermediates. PMID:27373152

  18. Control of Paip1-eukayrotic translation initiation factor 3 interaction by amino acids through S6 kinase.

    PubMed

    Martineau, Yvan; Wang, Xiaoshan; Alain, Tommy; Petroulakis, Emmanuel; Shahbazian, David; Fabre, Bertrand; Bousquet-Dubouch, Marie-Pierre; Monsarrat, Bernard; Pyronnet, Stéphane; Sonenberg, Nahum

    2014-03-01

    The simultaneous interaction of poly(A)-binding protein (PABP) with eukaryotic translation initiation factor 4G (eIF4G) and the mRNA 3' poly(A) tail promotes translation initiation. We previously showed that the interaction of PABP-interacting protein 1 (Paip1) with PABP and eukaryotic translation initiation factor 3 (eIF3; via the eIF3g subunit) further stimulates translation. Here, we demonstrate that the interaction of eIF3 with Paip1 is regulated by amino acids through the mTORC1 signaling pathway. The Paip1-eIF3 interaction is impaired by the mTORC1 inhibitors, rapamycin and PP242. We show that ribosomal protein S6 kinases 1 and 2 (S6K1/2) promote the interaction of eIF3 with Paip1. The enhancement of Paip1-eIF3 interaction by amino acids is abrogated by an S6K inhibitor or shRNA against S6K1/2. S6K1 interacts with eIF3f and, in vitro, phosphorylates eIF3. Finally, we show that S6K inhibition leads to a reduction in translation by Paip1. We propose that S6K1/2 phosphorylate eIF3 to stimulate Paip1-eIF3 interaction and consequent translation initiation. Taken together, these data demonstrate that eIF3 is a new translation target of the mTOR/S6K pathway. PMID:24396066

  19. 2-Amino-6-methyl-4,5,6,7-tetra-hydro-1-benzothio-phene-3-carbonitrile.

    PubMed

    Ziaulla, Mohamed; Banu, Afshan; Begum, Noor Shahina; Panchamukhi, Shridhar I; Khazi, I M

    2011-01-01

    In the title compound, C(10)H(12)N(2)S, one of the C atoms of the cyclo-hexene ring (at position 6) and the methyl group attached to it are disordered over two sets of sites in a 0.650 (3):0.350 (3) ratio. The cyclo-hexene ring in both the major and minor occupancy conformers adopts a half-chair conformation. The thio-phene ring is essentially planar (r.m.s. deviation = 0.05 Å). In the crystal, N-H⋯N hydrogen bonds involving the amino groups result in inversion dimers with R(2) (2)(12) graph-set motif. Further N-H⋯N hydrogen bonds involving the amino and carbonitrile groups generate zigzag chains along the a axis. PMID:21522444

  20. Fundamental Kinetics Database Utilizing Shock Tube Measurements (Volumes 1, 2, 3, 4, and Volume 6)

    DOE Data Explorer

    Davidson, D. F.; Hanson, R. K

    The data from shock tube experiments generally takes three forms: ignition delay times, species concentration time-histories and reaction rate measurements. Volume 1 focuses on ignition delay time data measured and published by the Shock Tube Group in the Mechanical Engineering Department of Stanford University. The cut-off date for inclusion into this volume was January 2005. Volume 2 focuses on species concentration time-histories and was cut off December 2005. The two volumes are in PDF format and are accompanied by a zipped file of supporting data. Volume 3 was issued in 2009. Volume 4, Ignition delay times measurements came out in May, 2014, along with Reaction Rates Measurements, Vol 6. Volume 5 is not available at this time.

  1. A Versatile Synthesis of 1,3,5-Triamino-2,4,6-Trinitrobenzene (TATB)

    SciTech Connect

    Mitchell, A R; Pagoria, P F; Schmidt, R D; Coburn, M D; Lee, G S; Hsu, P C

    2006-04-06

    A safe and versatile synthesis of high-purity 1,3,5-triamino-2,4,6-trinitrobenzene (TATB) based on vicarious nucleophilic substitution (VNS) chemistry has now been achieved. The starting material can be selected from a variety of inexpensive nitroarenes obtained from commercial suppliers (4-nitroaniline, picric acid) or U.S. stockpiles (ammonium picrate, TNT). The use of picric acid and ammonium picrate (Explosive D) is preferred as both compounds are directly converted to picramide in the presence of ammonium salts (diammonium hydrogen phosphate, ammonium carbamate) in sulfolane at elevated temperature. The picramide resulting from this process is directly converted to TATB using an optimized VNS reaction employing inexpensive hydroxylamine as the nucleophilic aminating reagent. A crucial element in our synthesis is a novel and efficient purification of TATB.

  2. Preliminary toxicology study of 3,6-diamino-1,2,4,5-tetrazine

    SciTech Connect

    London, J.E.

    1993-03-01

    The calculated acute oral LD 30/50 (lethal dose for 50% of the animals occurring within 30 days after compound administration) value for 3,6-diamino-1,2,4,5-tetrazine (DATZ) was 863 mg/kg in rats. According to classical guidelines, DATZ would be considered slightly to moderately toxic for rats. The calculated acute oral LD {sub 30/50} value was 2,288 mg/kg in mice and would be considered slightly to moderately toxic for mice. Skin application studies using rabbits demonstrated DATZ to be a nonirritant. The eye study using rabbits disclosed DATZ to be a very mild irritant. The sensitization study using guinea pigs did not show DATZ to have potential sensitizing properties.

  3. Preliminary toxicology study of 3,6-diamino-1,2,4,5-tetrazine

    SciTech Connect

    London, J.E.

    1993-03-01

    The calculated acute oral LD 30/50 (lethal dose for 50% of the animals occurring within 30 days after compound administration) value for 3,6-diamino-1,2,4,5-tetrazine (DATZ) was 863 mg/kg in rats. According to classical guidelines, DATZ would be considered slightly to moderately toxic for rats. The calculated acute oral LD [sub 30/50] value was 2,288 mg/kg in mice and would be considered slightly to moderately toxic for mice. Skin application studies using rabbits demonstrated DATZ to be a nonirritant. The eye study using rabbits disclosed DATZ to be a very mild irritant. The sensitization study using guinea pigs did not show DATZ to have potential sensitizing properties.

  4. Limited treatment with beta-1,3/1,6-glucan improves production values of broiler chickens challenged with Escherichia coli.

    PubMed

    Huff, G R; Huff, W E; Rath, N C; Tellez, G

    2006-04-01

    The development of antibiotic-resistant bacteria has led to a need for alternatives to antibiotics for growth promotion and disease prevention in poultry production. The helical polysaccharide beta-1,3/1,6-glucan is derived from the cell wall of Saccharomyces cervisiae and has immunomodulating activities. The objective of this study was to determine the ability of 2 supplementation programs with a commercial beta-1,3/1,6-glucan product to protect broiler chicks from experimental respiratory challenge with Escherichia coli. Chicks were housed in battery-brooders from 1 d of age and fed a standard starter diet or the same diet containing 20 g/ton (22 ppm) of purified beta-1,3/1,6-glucan either continuously (BG25d) or for only the first 7 d prior to challenge (BG7d). At d 7 one-half of the birds were inoculated in the thoracic air sac with 800 cfu of a serotype O2, nonmotile strain of E. coli. All surviving birds were necropsied at d 25. Body weight of survivors and feed conversion efficiency were protected from the adverse effects of E. coli challenge by BG7d but not by BG25d. Mortality was nominally decreased from 63% (control) to 53% in BG25d and 47% in BG7d, but these decreases were not significant. The relative weights of the liver and heart were increased, and the bursa of Fabricius relative weights were decreased by E. coli challenge, and these effects were modulated by beta-glucan treatment. Despite positive effects of BG7d in E. coli-challenged birds, the BW of nonchallenged birds was decreased by BG7d and BG25d. These results suggest that supplementation of broiler diets with beta-1,3/1,6-glucan may be valuable for decreasing production losses due to E. coli respiratory disease, but that the immune stimulation provided may also result in decreased production values under experimental battery conditions or for birds raised in an environment with minimal disease challenges. PMID:16615344

  5. Czochralski growth and scintillation properties of Li6LuxY1-x(BO3)3:Ce3+ single crystals

    NASA Astrophysics Data System (ADS)

    Fawad, U.; Kim, H. J.; Park, H.; Kim, Sunghwan; Khan, Sajid

    2016-01-01

    We report on Czochralski growth of Ce3+-doped mixed crystals of Li6Lu(BO3)3 (LLBO) and Li6Y(BO3)3 (LYBO) i.e. Li6LuxY1-x(BO3)3 (x=0.0, 0.5, 1.0) (LLYBO). Problems faced during the growth process and the techniques to overcome them are discussed. Single phase of the grown crystals is confirmed by powder X-ray diffraction (XRD) analysis. The grown crystals are characterized for their scintillation properties such as energy resolution, light yield, fluorescent decay time and α/β ratio under γ-rays and α-particles excitation. The X-ray induced luminescence is measured for the grown crystals.

  6. Sonochemical synthesis of 1,3,5-triamino-2,4,6-trinitrobenzene (TATB)

    SciTech Connect

    Lee, Kien-Yin

    1996-05-01

    The synthesis of 1,3,5-triamino-2,4,6-trinitrobenzene (TATB) from trichlorotrinitrobenzene (TCTNB) in toluene and ammonium hydroxide solution under the influence of ultrasonic waves was investigated. When the two-phase reaction mixture was irradiated with high intensity ultrasound at ambient temperature, fine-particle TATB (FP-TATB) was produced. This sonochemically produced TATB powder is lemon color in appearance and was analyzed to have the same explosive properties as reported in the literature. That is, it is insensitive to impact stimuli, and thermally stable. The median particle diameter of FP-TATB was calculated to be around 14 {mu}m, and the powder can be pressed to a density of 1.82 g/cm{sup 3} without a binder. The amination process is simple and requires neither the monitoring of the ammonia gas pressure nor the controlling of the reaction temperature during amination reaction, and we anticipate no problem in large scale production of FP-TATB.

  7. Analysis of the Rotational Spectra of 2,3,4,5,6-PENTAFLUOROTOLUENE and 1-CHLORO-2,3,4,5,6-PENTAFLUOROBENZENE

    NASA Astrophysics Data System (ADS)

    Osthoff, Ashley A.; Peebles, Rebecca A.; Peebles, Sean A.; Grubbs, Garry S. Grubbs, II; Cooke, Stephen A.; Pate, Brooks H.; Neill, Justin L.; Muckle, Matt T.

    2009-06-01

    The microwave spectra of two substituted pentafluorobenzenes have been obtained. 2,3,4,5,6-Pentafluorotoluene was measured using the FTMW spectrometer at Eastern Illinois University and the chirped-pulse FTMW spectrometer at University of North Texas. The heavy atom structure has been obtained from the assigned ^{13}C transitions and is in reasonable agreement with ab initio calculations at the MP2/6-311++G(2d, 2p) level. The ground state rotational constants are A = 1036.61253(10) MHz, B = 1030.94126(10) MHz, and C = 516.92062(9) MHz, and the single dipole moment component is μ_b = 1.98(17) D. Very small splittings for many of the assigned transitions and multiple, as yet unassigned, lines were presumably due to excited torsional states of the methyl group. In a related study, the microwave spectrum of 1-chloro-2,3,4,5,6-pentafluorobenzene was obtained for both the ^{35}Cl and the ^{37}Cl isotopologues using the chirped-pulse microwave spectrometer at University of Virginia. The preliminary ground state rotational constants for this compound are A = 1028.5403(14) MHz, B = 751.8198(3) MHz and C = 434.3533(4) MHz for ^{35}Cl and A = 1028.5435(7) MHz, B = 734.4786(2) MHz and C = 428.5082(2) MHz for ^{37}Cl. Initial fits of the nuclear quadrupole coupling constants give χ_{aa} = -79.512(15) MHz, χ_{bb} = 43.593(8) MHz, χ_{cc} = 35.92(2) MHz for the ^{35}Cl species and χ_{aa} = -62.68(2) MHz, χ_{bb} = 34.38(4) MHz, χ_{cc} = 28.29(17) MHz for the ^{37}Cl species. These results will be compared with pentafluorotoluene to observe the effects on the structure of the benzene ring when substituting a chlorine atom for a methyl group.

  8. 26 CFR 1.752-6 - Partnership assumption of partner's section 358(h)(3) liability after October 18, 1999, and...

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...(h)(3) liability after October 18, 1999, and before June 24, 2003. 1.752-6 Section 1.752-6 Internal... Partnership assumption of partner's section 358(h)(3) liability after October 18, 1999, and before June 24... assumptions of liabilities occurring after October 18, 1999, and before June 24, 2003. (2) Election to...

  9. 40 CFR 721.9750 - 2-Chloro-4,6-bis(substituted)-1,3,5-triazine, dihydrochloride.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...-triazine, dihydrochloride. 721.9750 Section 721.9750 Protection of Environment ENVIRONMENTAL PROTECTION... New Uses for Specific Chemical Substances § 721.9750 2-Chloro-4,6-bis(substituted)-1,3,5-triazine... identified generically as 2-chloro-4,6-bis(substituted)-1,3,5-triazine, dihydrochloride (PMN P-91-659)...

  10. 26 CFR 1.752-6 - Partnership assumption of partner's section 358(h)(3) liability after October 18, 1999, and...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... debt obligation of $50 and a fixed or contingent obligation of $100 that is not a liability to which...(h)(3) liability after October 18, 1999, and before June 24, 2003. 1.752-6 Section 1.752-6 Internal... of partner's section 358(h)(3) liability after October 18, 1999, and before June 24, 2003. (a)...

  11. 15-Lipoxygenase-1 suppression of colitis-associated colon cancer through inhibition of the IL-6/STAT3 signaling pathway.

    PubMed

    Mao, Fei; Xu, Min; Zuo, Xiangsheng; Yu, Jiang; Xu, Weiguo; Moussalli, Micheline J; Elias, Elias; Li, Haiyan S; Watowich, Stephanie S; Shureiqi, Imad

    2015-06-01

    The IL-6/signal transducer and activator of transcription 3 (STAT3) pathway is a critical signaling pathway for colitis-associated colorectal cancer (CAC). Peroxisome proliferator-activated receptor (PPAR)-δ, a lipid nuclear receptor, up-regulates IL-6. 15-Lipoxygenase-1 (15-LOX-1), which is crucial to production of lipid signaling mediators to terminate inflammation, down-regulates PPAR-δ. 15-LOX-1 effects on IL-6/STAT3 signaling and CAC tumorigenesis have not been determined. We report that intestinally targeted transgenic 15-LOX-1 expression in mice inhibited azoxymethane- and dextran sodium sulfate-induced CAC, IL-6 expression, STAT3 phosphorylation, and IL-6/STAT3 downstream target (Notch3 and MUC1) expression. 15-LOX-1 down-regulation was associated with IL-6 up-regulation in human colon cancer mucosa. Reexpression of 15-LOX-1 in human colon cancer cells suppressed IL-6 mRNA expression, STAT3 phosphorylation, IL-6 promoter activity, and PPAR-δ mRNA and protein expression. PPAR-δ overexpression in colonic epithelial cells promoted CAC tumorigenesis in mice and increased IL-6 expression and STAT3 phosphorylation, whereas concomitant 15-LOX-1 expression in colonic epithelial cells (15-LOX-1-PPAR-δ-Gut mice) suppressed these effects: the number of tumors per mouse (mean ± sem) was 4.22 ± 0.68 in wild-type littermates, 6.67 ± 0.83 in PPAR-δ-Gut mice (P = 0.026), and 2.25 ± 0.25 in 15-LOX-1-PPAR-δ-Gut mice (P = 0.0006). Identification of 15-LOX-1 suppression of PPAR-δ to inhibit IL-6/STAT3 signaling-driven CAC tumorigenesis provides mechanistic insights that can be used to molecularly target CAC. PMID:25713055

  12. All-cis 1,2,3,4,5,6-hexafluorocyclohexane is a facially polarized cyclohexane

    NASA Astrophysics Data System (ADS)

    Keddie, Neil S.; Slawin, Alexandra M. Z.; Lebl, Tomas; Philp, Douglas; O'Hagan, David

    2015-06-01

    The highest-energy stereoisomer of 1,2,3,4,5,6-hexafluorocyclohexane, in which all of the fluorines are ‘up’, is prepared in a 12-step protocol. The molecule adopts a classic chair conformation with alternate C-F bonds aligned triaxially, clustering three highly electronegative fluorine atoms in close proximity. This generates a cyclohexane with a high molecular dipole (μ = 6.2 D), unusual in an otherwise aliphatic compound. X-ray analysis indicates that the intramolecular Fax···Fax distances (˜2.77 Å) are longer than the vicinal Fax···Feq­ distances (˜2.73 Å) suggesting a tension stabilizing the chair conformation. In the solid state the molecules pack in an orientation consistent with electrostatic ordering. Our synthesis of this highest-energy isomer demonstrates the properties that accompany the placement of axial fluorines on a cyclohexane and the unusual property of a facially polarized ring in organic chemistry. Derivatives have potential as new motifs for the design of functional organic molecules or for applications in supramolecular chemistry design.

  13. Peripheral Blood CCR4+CCR6+ and CXCR3+CCR6+ CD4+ T Cells Are Highly Permissive to HIV-1 Infection

    PubMed Central

    Gosselin, Annie; Monteiro, Patricia; Chomont, Nicolas; Diaz-Griffero, Felipe; Said, Elias A.; Fonseca, Simone; Wacleche, Vanessa; El-Far, Mohamed; Boulassel, Mohamed-Rachid; Routy, Jean-Pierre; Sekaly, Rafick-Pierre; Ancuta, Petronela

    2015-01-01

    There is limited knowledge on the identity of primary CD4+ T cell subsets selectively targeted by HIV-1 in vivo. In this study, we established a link between HIV permissiveness, phenotype/homing potential, and lineage commitment in primary CD4+ T cells. CCR4+CCR6+, CCR4+CCR6−, CXCR3+CCR6+, and CXCR3+CCR6− T cells expressed cytokines and transcription factors specific for Th17, Th2, Th1Th17, and Th1 lineages, respectively. CCR4+CCR6+ and CXCR3+CCR6+ T cells expressed the HIV coreceptors CCR5 and CXCR4 and were permissive to R5 and X4 HIV replication. CCR4+CCR6− T cells expressed CXCR4 but not CCR5 and were permissive to X4 HIV only. CXCR3+CCR6− T cells expressed CCR5 and CXCR4 but were relatively resistant to R5 and X4 HIV in vitro. Total CCR6+ T cells compared with CCR6− T cells harbored higher levels of integrated HIV DNA in treatment-naive HIV-infected subjects. The frequency of total CCR6+ T cells and those of CCR4+CCR6+ and CXCR3+CCR6+ T cells were diminished in chronically infected HIV-positive subjects, despite viral-suppressive therapy. A high-throughput analysis of cytokine profiles identified CXCR3+CCR6+ T cells as a major source of TNF-α and CCL20 and demonstrated a decreased TNF-α/IL-10 ratio in CXCR3+CCR6− T cells. Finally, CCR4+CCR6+ and CXCR3+CCR6+ T cells exhibited gut- and lymph node-homing potential. Thus, we identified CCR4+CCR6+ and CXCR3+CCR6+ T cells as highly permissive to HIV replication, with potential to infiltrate and recruit more CCR6+ T cells into anatomic sites of viral replication. It is necessary that new therapeutic strategies against HIV interfere with viral replication/persistence in discrete CCR6+ T cell subsets. PMID:20042588

  14. Time-resolved spectroscopy of the Mercury 6 3P1 state

    NASA Technical Reports Server (NTRS)

    Halstead, J. A.; Reeves, R. R.

    1981-01-01

    The time-resolved fluorescence was observed from the Hg 6 3P1 state under the influence of the earth's magnetic field and with applied fields of up to 14 G. Modulation of the fluorescence decay signal was observed as a function of both time and space and can be interpreted in terms of a classical precession of the excited atom about the magnetic field or as quantum beats resulting from interference between coherently populated Zeeman sublevels. This modulation was studied for each of the five resolvable components of the hyperfine structure separately. The fluorescence from the even isotopes was determined to be almost completely modulated while the fluorescence from the odd isotopes was only partially modulated. The frequency of modulation of the fluorescence from the mercury-202 isotope was observed as a function of the applied magnetic field and a value for the Lande factor of 1.46 + or - 0.03 was obtained. This is within experimental error of the accepted value of 1.486. In addition, the frequency of modulation as a function of applied magnetic field was determined for each of the three resolvable components with more than one contributing isotopic hyperfine line. An investigation of the effect of radiation trapping on the degree modulation was also made.

  15. Reanalysis of the photoassociation spectrum of 133Cs2 (6P3/2) 1g state

    NASA Astrophysics Data System (ADS)

    Ma, Jie; Li, Yu-Qing; Wu, Ji-Zhou; Fan, Qun-Chao; Feng, Hao; Sun, Wei-Guo; Xiao, Lian-Tuan; Jia, Suo-Tang

    2013-08-01

    Reanalysis of the photoassociation spectrum of the weakly binding (6S1/2 + 6P3/2) 1g133Cs2 levels, reported in the previous study [J. Mol. Spectro. 255 (2009) 106], is performed by using a Lu—Fano graph coupled to the improved LeRoy—Bernstein formula including two additional modified terms. A more accurate coefficient (c3) is obtained for the leading long-range potential (-c3/R3) of a diatomic molecule.

  16. Affinity-matured recombinant immunotoxin targeting gangliosides 3′-isoLM1 and 3′,6'-isoLD1 on malignant gliomas

    PubMed Central

    Piao, Hailan; Kuan, Chien-Tsun; Chandramohan, Vidya; Keir, Stephen T; Pegram, Charles N; Bao, Xuhui; Månsson, Jan-Eric; Pastan, Ira H; Bigner, Darell D

    2013-01-01

    About 60 percent of glioblastomas highly express the gangliosides 3′-isoLM1 and 3′,6′-isoLD1 on the cell surface, providing ideal targets for brain tumor immunotherapy. A novel recombinant immunotoxin, DmAb14m-(scFv)-PE38KDEL (DmAb14m-IT), specific for the gangliosides 3′-isoLM1 and 3′,6′-isoLD1, was constructed with improved affinity and increased cytotoxicity for immunotherapeutic targeting of glioblastoma. We isolated an scFv parental clone from a previously established murine hybridoma, DmAb14, that is specific to both 3′-isoLM1 and 3′,6′-isoLD1. We then performed in vitro affinity maturation by CDR hotspot random mutagenesis. The binding affinity and specificity of affinity-matured DmAb14m-IT were measured by surface-plasmon resonance, flow cytometry, and immunohistochemical analysis. In vitro cytotoxicity of DmAb14m-IT was measured by protein synthesis inhibition and cell death assays in human cell lines expressing gangliosides 3′-isoLM1 and 3′,6′-isoLD1 (D54MG and D336MG) and xenograft-derived cells (D2224MG). As a result, the KD of DmAb14m-IT for gangliosides 3′-isoLM1 and 3′,6′-isoLD1 was 2.6 × 10−9M. Also, DmAb14m-IT showed a significantly higher internalization rate in cells expressing 3′-isoLM1 and 3′,6′-isoLD1. The DmAb14m-IT IC50 was 80 ng/mL (1194 pM) on the D54MG cell line, 5 ng/ml (75 pM) on the D336MG cell line, and 0.5 ng/ml (7.5 pM) on the D2224MG xenograft-derived cells. There was no cytotoxicity on ganglioside-negative HEK293 cells. Immunohistochemical analysis confirmed the specific apparent affinity of DmAb14m-IT with 3′-isoLM1 and 3′,6′-isoLD1. In conclusion, DmAb14m-IT showed specific binding affinity, a significantly high internalization rate, and selective cytotoxicity on glioma cell lines and xenograft-derived cells expressing 3′-isoLM1 and 3′,6′-isoLD1, thereby displaying robust therapeutic potential for testing the antitumor efficacy of DmAb14m-IT at the preclinical level and

  17. e-Cadherin in 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-Induced Parkinson Disease

    PubMed Central

    Cataldi, Samuela; Codini, Michela; Hunot, Stéphane; Légeron, François-Pierre; Ferri, Ivana; Siccu, Paola; Sidoni, Angelo; Ambesi-Impiombato, Francesco Saverio; Beccari, Tommaso; Curcio, Francesco; Albi, Elisabetta

    2016-01-01

    Today a large number of studies are focused on clarifying the complexity and diversity of the pathogenetic mechanisms inducing Parkinson disease. We used 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a neurotoxin that induces Parkinson disease, to evaluate the change of midbrain structure and the behavior of the anti-inflammatory factor e-cadherin, interleukin-6, tyrosine hydroxylase, phosphatase and tensin homolog, and caveolin-1. The results showed a strong expression of e-cadherin, variation of length and thickness of the heavy neurofilaments, increase of interleukin-6, and reduction of tyrosine hydroxylase known to be expression of dopamine cell loss, reduction of phosphatase and tensin homolog described to impair responses to dopamine, and reduction of caveolin-1 known to be expression of epithelial-mesenchymal transition and fibrosis. The possibility that the overexpression of the e-cadherin might be implicated in the anti-inflammatory reaction to MPTP treatment by influencing the behavior of the other analyzed molecules is discussed. PMID:27194825

  18. Myelotoxicity induced in female B6C3F1 mice by inhalation of methyl isocyanate

    SciTech Connect

    Hong, H.L.; Bucher, J.R.; Canipe, J.; Boorman, G.A.

    1987-06-01

    The effects of a 4-day inhalation exposure (6 hr/day) to 0, 1, and 3 ppm methyl isocyanate (MIC) on bone marrow parameters in female mice were examined at 5, 8, and 21 days following exposure. The MIC exposure was associated with myelotoxicity as evidenced by hypocellularity, suppression of pluripotent stem cells (CFU-S), granulocyte-macrophage progenitors (CFU-GM) and erythroid precursors (CFU-E) in both dose groups. Hematopoietic parameters returned to normal by 21 days in the 1 ppm dose group, but not in the 3 ppm dose group. This indicates that the alterations in the bone marrow parameters persist for a relatively long period at dose levels where there are little or no changes in body weight, clinical pathology, or immunological parameters, suggesting that the bone marrow may be a sensitive endpoint for MIC exposure in mice. MIC is a highly reactive chemical that appears to exert its effect directly on the lining epithelium of the nasal cavity and major airways; there was no histological evidence of a systemic effect. The pathogenesis of the bone marrow depression is unknown; however, there were chronic bronchitis and bronchial fibrosis in the 3 ppm dose group. One possible explanation is that the cell injury induced in the lung is associated with the release of inhibitory factors for hematopoiesis, as the rodent lung is a potent source of both stimulatory and inhibitory growth factors for bone marrow progenitor cells. A second possibility is that the thymic atrophy found in MIC-exposed mice might be related to myelotoxicity. The pathogenesis of myelotoxicity in MIC exposure and its relationship with pulmonary injury require further study.

  19. 5,5'-Di-tert-butyl-2,2'-dihydroxy-3,3'-methylenedibenzaldehyde and 6,6'-di-tert-butyl-8,8'-methylenebis(spiro[4H-1,3-benzodioxin-2,1'-cyclohexane]).

    PubMed

    Masci, Bernardo; Mortera, Stefano Levi; Seralessandri, Luca; Thuéry, Pierre

    2004-02-01

    Two related compounds containing p-tert-butyl-o-methylene-linked phenol or phenol-derived subunits are described, namely 5,5'-di-tert-butyl-2,2'-dihydroxy-3,3'-methylenedibenzaldehyde, C(23)H(28)O(4), (I), and 6,6'-di-tert-butyl-8,8'-methylenebis(spiro[4H-1,3-benzodioxin-2,1'-cyclohexane]), C(35)H(48)O(4), (II). Both compounds adopt a 'butterfly' shape, with the two phenol or phenol-derived O atoms in distal positions. Phenol and aldehyde groups in (I) are involved in intramolecular hydrogen bonds and the two dioxin rings in (II) are in distorted half-chair conformations. PMID:14767128

  20. Cyclophosphazenic cryptands: serendipitous architectures from aminolysis of N 3P 3C1 6 by 4,11-dioxatetradecane-1,14-diamine

    NASA Astrophysics Data System (ADS)

    Zanin, Bruno; Scheidecker, Sylvie; Sournies, François; Labarrel, Jean-François

    1991-06-01

    The reaction "at rest" (i.e. without any magnetic stirring) of N 3P 3C1 6 with the 4,11-dioxatetra- decane-1,14-diamine (coded as 30603) in a heterogeneous medium (interface process) of toluene and a saturated water solution of sodium carbonate leads stereospecifically to a trans monocyclo- phosphazenic 19-crown-ether species ( trans-ANSA 30603). In the same conditions, shortest oxodiamines yield pure SPIRO loop configurations. The same reaction gives stereoselectively the bridged BINO (30603) architecture as soon as the reactional medium (homogeneous or hetero- geneous) is stirred. The trans-ANSA (30603) is preferred to the cis one by 4 kcal mol -1 and then it appears as the common configuration which may be expected upon reaction "at rest" of very long oxodiamines on N 3P 3C1 6. The specific behaviour of 30603 is elucidated in terms of geomet- rical and electronic peculiarities of the oxodiamine in question.

  1. The crystal structures of m,o-Ce3Pt4Sn6 and Ce1-xPt6Al13+2x

    NASA Astrophysics Data System (ADS)

    Paschinger, Werner; Yubuta, Kunio; Saiga, Yuta; Takabatake, Toshiro; Giester, Gerald; Rogl, Peter

    2016-05-01

    The crystal structures of two novel ternary compounds, Ce3Pt4Sn6 and Ce1-xPt6Al13+2x (x = 0.207), have been derived by direct methods from X-ray single crystal data. Whereas Ce1-xPt6Al13+2x is of a new structure type (a = 1.42224(2) nm, c = 0.87367(1) nm, space group P 6 bar 2 m), Ce3Pt4Sn6 was found to crystallize in two different crystal modifications, (i) a monoclinic variant (a = 0.93682(2) nm, b = 0.46145(1) nm, c = 1.40434(3) nm, β = 99.635(1)°, space group P21/m), which is isotypic with the Y3Pt4Ge6-type and (ii) an orthorhombic modification (a = 2.76394(4) nm, b = 0.460588(7) nm, c = 0.93530(1) nm, space group Pnma), which crystallizes with the ordered Pr3Pt4Ge6-type. For the monoclinic arrangement m-Ce3Pt4Sn6 an intrinsically defect growth pattern was found - it grows in two related motifs (opposite directions of pentagonal units) in the ratio of 90% : 10% ensuring a stoichiometric composition. TEM observation directly revealed intrinsic building defects detected by single crystal X-ray diffraction for m-Ce3Pt4Sn6. Diffuse streaks in electron diffraction and inhomogeneous contrasts in a high resolution TEM image indicate the existence of a random stacking sequence between two related motifs.

  2. Determination of high mitochondrial membrane potential in spermatozoa loaded with the mitochondrial probe 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolyl-carbocyanine iodide (JC-1) by using fluorescence-activated flow cytometry.

    PubMed

    Guthrie, H David; Welch, Glenn R

    2008-01-01

    A flow cytometric method was developed to identify viable, energized sperm cells with high mitochondrial inner transmembrane potential (Deltapsi(m)), >80-100 mV using the mitochondrial probe 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolylcarbocyanine iodide (JC-1) and the impermeant nuclear stain propidium iodine (PI). This flow cytometric method is described in detail here. When in contact with membranes possessing a high Deltapsi(m), JC-1 forms aggregates (J(agg)) that are fluorescent at 590 nm in response to 488 nm excitation. We found that the reactive oxygen species generator, menadione reduced sperm motility and reduced Deltapsi(m) in a dose responsive fashion that was closely correlated with the loss of motility. PMID:19082941

  3. Anti-parkinsonian effects of octacosanol in 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine-treated mice☆

    PubMed Central

    Wang, Tao; Liu, Yanyong; Yang, Nan; Ji, Chao; Chan, Piu; Zuo, Pingping

    2012-01-01

    Our previous research showed that octacosanol exerted its protective effects in 6-hydroxydopamine-induced Parkinsonian rats. The goal of this study was to investigate whether octacosanol would attenuate neurotoxicity in 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP)-treated C57BL/6N mice and its potential mechanism. Behavioral tests, tyrosine hydroxylase immunohistochemistry and western blot were used to investigate the effects of octacosanol in a mouse model of Parkinson's disease. Oral administration of octacosanol (100 mg/kg) significantly improved behavioral impairments in mice treated by MPTP and markedly ameliorated morphological appearances of tyrosine hydroxylase-positive neuronal cells in the substantia nigra. Furthermore, octacosanol blocked MPTP-induced phosphorylation of p38MAPK and JNK, but not ERK1/2. These findings implicated that the protective effects afforded by octacosanol might be mediated by blocking the phosphorylation of p38MAPK and JNK on the signal transduction in vivo. Considering its excellent tolerability, octacosanol might be considered as a candidate agent for clinical application in treating Parkinson's disease. PMID:25722698

  4. Interpretation of 3D void measurements with Tripoli4.6/JEFF3.1.1 Monte Carlo code

    SciTech Connect

    Blaise, P.; Colomba, A.

    2012-07-01

    The present work details the first analysis of the 3D void phase conducted during the EPICURE/UM17x17/7% mixed UOX/MOX configuration. This configuration is composed of a homogeneous central 17x17 MOX-7% assembly, surrounded by portions of 17x17 1102 assemblies with guide-tubes. The void bubble is modelled by a small waterproof 5x5 fuel pin parallelepiped box of 11 cm height, placed in the centre of the MOX assembly. This bubble, initially placed at the core mid-plane, is then moved in different axial positions to study the evolution in the core of the axial perturbation. Then, to simulate the growing of this bubble in order to understand the effects of increased void fraction along the fuel pin, 3 and 5 bubbles have been stacked axially, from the core mid-plane. The C/E comparison obtained with the Monte Carlo code Tripoli4 for both radial and axial fission rate distributions, and in particular the reproduction of the very important flux gradients at the void/water interfaces, changing as the bubble is displaced along the z-axis are very satisfactory. It demonstrates both the capability of the code and its library to reproduce this kind of situation, as the very good quality of the experimental results, confirming the UM-17x17 as an excellent experimental benchmark for 3D code validation. This work has been performed within the frame of the V and V program for the future APOLL03 deterministic code of CEA starting in 2012, and its V and V benchmarking database. (authors)

  5. Acrylonitrile is a multisite carcinogen in male and female B6C3F1 mice.

    PubMed

    Ghanayem, Burhan I; Nyska, Abraham; Haseman, Joseph K; Bucher, John R

    2002-07-01

    Acrylonitrile is a heavily produced unsaturated nitrile, which is used in the production of synthetic fibers, plastics, resins, and rubber. Acrylonitrile is a multisite carcinogen in rats after exposure via gavage, drinking water, or inhalation. No carcinogenicity studies of acrylonitrile in a second animal species were available. The current studies were designed to assess the carcinogenicity of acrylonitrile in B6C3F1 mice of both sexes. Acrylonitrile was administered by gavage at 0, 2.5, 10, or 20 mg/kg/day, 5 days per week, for 2 years. Urinary thiocyanate and N-acetyl-S-(2-cyanoethyl)-L-cysteine were measured as markers of exposure to acrylonitrile. In general, there were dose-related increases in urinary thiocyanate and N-acetyl-S-(2-cyanoethyl)-L-cysteine concentrations in all dosed groups of mice and at all time points. Survival was significantly (p < 0.001) reduced in the top dose (20 mg/kg) group of male and female mice relative to controls. The incidence of forestomach papillomas and carcinomas was increased in mice of both sexes in association with an increase in forestomach epithelial hyperplasia. The incidence of Harderian gland adenomas and carcinomas was also markedly increased in the acrylonitrile-dosed groups. In female mice, the incidence of benign or malignant granulosa cell tumors (combined) in the ovary in the 10 mg/kg dose group was greater than that in the vehicle control group, but because of a lack of dose response, this was considered an equivocal finding. In addition, the incidences of atrophy and cysts in the ovary of the 10 and 20 mg/kg dose groups were significantly increased. The incidences of alveolar/bronchiolar adenoma or carcinoma (combined) were significantly increased in female mice treated with acrylonitrile at 10 mg/kg/day for 2 years. This was also considered an equivocal result. In conclusion, these studies demonstrated that acrylonitrile causes multiple carcinogenic effects after gavage administration to male and female B6

  6. Inhalation toxicology and carcinogenicity of 1,3-butadiene in B6C3F1 mice following 65 weeks of exposure.

    PubMed Central

    Melnick, R L; Huff, J E; Roycroft, J H; Chou, B J; Miller, R A

    1990-01-01

    1,3-Butadiene, a large-production volume chemical used mainly in the manufacture of synthetic rubber, was found to induce multiple-organ carcinogenicity in male and female B6C3F1 mice at exposure concentrations (625 and 1250 ppm) equivalent to and below the OSHA standard of 1000 ppm. Since this study was terminated after 60 weeks of exposure because of reduced survival due to fatal tumors, and because dose-response relationships for 1,3-butadiene-induced neoplastic and nonneoplastic lesions were not clearly established, a second long-term inhalation study of 1,3-butadiene in B6C3F1 mice was conducted at lower exposure concentrations, ranging from 6.25 to 625 ppm. Both the histopathological findings from animals dying through week 65 and the results of evaluations of animals exposed for 40 and 65 weeks are presented in this report. Exposure to 1,3-butadiene caused a regenerative anemia at concentrations of 62.5 ppm and higher. Testicular atrophy was induced at 625 ppm, and ovarian atrophy was observed at 20 ppm and higher. During the first 50 weeks of the study, lymphocytic lymphoma was the major cause of death of mice exposed to 625 ppm 1,3-butadiene. Neoplasms of the heart, forestomach, lung, Harderian gland, mammary gland, ovary, and liver were frequently observed in 1,3-butadiene-exposed mice that died between week 40 and week 65 of the study. Studies in which exposure to 1,3-butadiene was stopped after limited periods were also included to assess the relationship between exposure levels and duration of exposures on the outcome of 1,3-butadiene-induced carcinogenicity. In these studies, lymphocytic lymphomas were induced in male mice exposed to 625 ppm 1,3-butadiene for only 13 weeks. The incidence of lymphocytic lymphoma in male mice exposed to 625 ppm 1,3-butadiene for 26 weeks was two times that in mice exposed to 625 ppm for 13 weeks. However, when the exposure concentration was reduced by half to 312 ppm and the exposure duration extended to 52 weeks, the

  7. Synthesis and structure of a 1,6-hexyldiamine heptaborate, [H{sub 3}N(CH{sub 2}){sub 6}NH{sub 3}][B{sub 7}O{sub 10}(OH){sub 3}

    SciTech Connect

    Yang Sihai; Li Guobao Tian Shujian; Liao Fuhui; Xiong Ming; Lin Jianhua

    2007-08-15

    A new 1,6-hexyldiamine heptaborate, [H{sub 3}N(CH{sub 2}){sub 6}NH{sub 3}][B{sub 7}O{sub 10}(OH){sub 3}] (1), has been solvothermally synthesized and characterized by single-crystal X-ray diffraction, FTIR, elemental analysis, and thermogravimetric analysis. Compound 1 crystallizes in monoclinic system, space group P2{sub 1}/n with a=8.042(2) A, b=20.004(4) A, c=10.103(2) A, and {beta}=90.42(3) deg. The anionic [B{sub 7}O{sub 10}(OH){sub 3}]{sub n}{sup 2n-} layers are interlinked via hydrogen bonding to form a 3D supramolecular network containing large channels, in which the templated [H{sub 3}N(CH{sub 2}){sub 6}NH{sub 3}]{sup 2+} cations are located. - Graphical abstract: A layered 1,6-hexyldiamine heptaborate, [H{sub 3}N(CH{sub 2}){sub 6}NH{sub 3}][B{sub 7}O{sub 10}(OH){sub 3}], was solvothermally synthesized at 150 deg. C. It is a layer borate and crystallized in monoclinic space group P2{sub 1}/n with a=8.042(2) A, b=20.004(4) A, c=10.103(2) A, {beta}=90.42(3) deg.

  8. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine inhibits proton motive force in energized liver mitochondria

    SciTech Connect

    Singh, Y.; Bhatnagar, R.; Sidhu, G.S.; Batra, J.K.; Krishna, G. )

    1989-05-15

    It is known that 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), which induces Parkinson's-like disease in primates and humans, depletes hepatocytes of ATP and subsequently causes cell death. Incubation of rat liver mitochondria with MPTP and 1-methyl-4-phenyl pyridinium ion (MPP+) significantly inhibited incorporation of {sup 32}Pi into ATP. MPTP and MPP+ inhibited the development of membrane potential and pH gradient in energized rat liver mitochondria, suggesting that reduction of the proton motive force may have reduced ATP synthesis. Since deprenyl, an inhibitor of monoamine oxidase, prevented the formation of MPP+ and inhibited the decrease in membrane potential caused by MPTP, but not that caused by MPP+, these effects of MPTP, as well as cell death, probably were mediated by MPP+. This mechanism may play a role in the specific loss of dopaminergic neurons resulting in MPTP-induced Parkinson's disease.

  9. Synthesis and antimalarial activity of 3,3-spiroanellated 5,6-disubstituted 1,2,4-trioxanes.

    PubMed

    Maurya, Ranjani; Soni, Awakash; Anand, Devireddy; Ravi, Makthala; Raju, Kanumuri S R; Taneja, Isha; Naikade, Niraj K; Puri, S K; Wahajuddin; Kanojiya, Sanjeev; Yadav, Prem P

    2013-02-14

    Novel 3,3-spiroanellated 5-aryl, 6-arylvinyl-substituted 1,2,4-trioxanes 19-34 have been synthesized and appraised for their antimalarial activity against multidrug-resistant Plasmodium yoelii nigeriensis in Swiss mice by oral route at doses ranging from 96 mg/kg × 4 days to 24 mg/kg × 4 days. The most active compound of the series (compound 25) provided 100% protection at 24 mg/kg × 4 days, and other 1,2,4-trioxanes 22, 26, 27, and 30 also showed promising activity. In this model, β-arteether provided 100 and 20% protection at 48 mg/kg × 4 days and 24 mg/kg × 4 days, respectively, by oral route. Compound 25 displayed a similar in vitro pharmacokinetic profile to that of reference drug β-arteether. The activity results demonstrated the importance of an aryl moiety at the C-5 position on the 1,2,4-trioxane pharmacophore. PMID:24900640

  10. Crystal structure of 1-methyl-3-([2,2-dimethyl-4,6-dioxo-1,3-dioxane-5-ylidene]methyl)urea

    SciTech Connect

    Habibi, A. Ghorbani, H. S.; Bruno, G.; Rudbari, H. A.; Valizadeh, Y.

    2013-12-15

    The crystal structure of 1-Methyl-3-([2,2-dimethyl-4,6-dioxo-1,3-dioxane-5-ylidene]methyl)urea (C{sub 9}H{sub 12}N{sub 2}O{sub 5}) has been determined by single crystal X-ray diffraction analysis. The crystals are monoclinic, a = 5.3179(2), b = 18.6394(6), c =10.8124(3) Å, β = 100.015(2)°, Z = 4, sp. gr. P2{sub 1}/c, R = 0.0381 for 2537 reflections with I > 2σ(I). Except for C(CH{sub 3}){sub 2} group, the molecule is planar. The structure is stabilized by inter- and intramolecular N-H...O hydrogen bonds and weak C-H...O interactions.

  11. Anticonvulsant and Neurotoxicity of Some Novel 1-([1,3,4]thiadiazino[6,5- b]indol-3-yl Semicarbazides.

    PubMed

    Deshmukh, Ravitas; Thakur, Alok S; Jha, Arvind K; Kumar, Sudhir P

    2015-01-01

    In the present study a series of new N(4)-(4-substituted benzylidene)-N(1)-([1,3,4]thiadiazino [6,5-b]indol-3-yl)semicarbazide (1-6), N(4)-([1,3,4]thiadiazino[6,5-b]indol-3-yl)-N(1)-(1-(4-substituted phenyl)ethylidene)semicarbazide (7-10), N(4)-([1,3,4]thiadiazino[6,5-b]indol-3-yl)-N(1)-((4-substituted phenyl)(phenyl)methylene) semicarbazide. (11-14) have been synthesized from isatin and thiosemicarbazide through multiple steps to meet structural necessities for the anticonvulsant activity. All the newly prepared compounds were characterized by spectral techniques like FT-IR, (1)H and (13)C NMR, EI-MS and elemental analysis. All the newly synthesized compounds were investigated for the anticonvulsant activity against maximal electroshock induced seizures (MES) and subcutaneous pentylenetetrazole (scPTZ) models and their neurotoxicity were also evaluated by rotarod test. The results obtained showed that 64% of the compounds showed protection in the MES test and 36% of the compounds showed protection in ScPTZ test. Some of the compounds also showed good activity after oral administration. Among the synthesized compounds, compound 14 was shown to be the most active compound showing activity at 100 and 300 mg/kg in MES and ScPTZ test with prolonged duration of action. In the present study, semicarbazones of hydroxy containing carbonyl compounds were depicted to be the potent molecule with low neurotoxicity and prolong duration of action on oral administration. The result of the present study may be used for the future development of novel anticonvulsants with broad spectrum of anticonvulsant activity. PMID:26100150

  12. Evaluation of the oral subchronic toxicity of AHTN (7-Acetyl-1,1,3,4,4,6-hexamethyl-1,2,3,4-tetrahydronaphthalene) in the rat.

    PubMed

    Api, Anne Marie; Smith, Robert L; Pipino, Sandra; Marczylo, Timothy; De Matteis, Francesco

    2004-05-01

    7-Acetyl-1,1,3,4,4,6-hexamethyl-1,2,3,4-tetrahydronaphthalene (AHTN) is used as a fragrance material in a wide variety of consumer products. Because of its widespread exposure, a 90-day oral feeding study, with 4-week recovery periods for selected rats, was conducted. AHTN was added to the diet of rats at levels calculated to result in mean daily doses of 1.5, 5, 15 or 50 mg AHTN/kg body weight/day. On completion of the treatment period, 3 males and 3 females from each of the high dose groups and controls were maintained for a treatment free period of 4 weeks. There were no adverse effects revealed upon clinical examination or following extensive histopathological examinations. Histopathological examination of the prostate, seminal vesicles, mammary gland and testes of males and ovaries, mammary gland, uterus and vagina of females, undertaken on all animals in all test groups, revealed no evidence of hormonal effects of AHTN. A statistically significant decrease in body weight gain was observed in both sexes in the high dose group only. Statistically significant effects were observed in hematology and blood chemistry, although these effects were all within the range for historical controls and were not proportional to dose. A green to dark brown coloration in the livers and mesenteric lymph nodes was also seen in high dose animals. At the end of the treatment-free period, the color change was almost completely reversed; one high dose male still had green colored lymph nodes, but the liver appeared normal. A green coloration of the lacrimal glands in females, but not males, was also seen in 8/12, 4/15 and in 1 female given 50, 15 and 5 mg/kg body weight/day, respectively. This green color was still present in 2/3 of the high dose females after the treatment-free period. Microscopic examination of unstained sections of frozen livers under UV illumination did not reveal any fluorescence that might have been consistent with porphyrin accumulation. These findings were

  13. 3-ALKYL-1-BUTANOL ATTRACTANTS FOR FRUGIVOROUS PEST INSECTS, PATENT NO. 6.224.890

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Compositions and lures are described which provide 3-alkyl-1-butanol vapors and vapor blends of 3-alkyl-1-butanol with one or more compounds selected from the group consisting of acetic acid, ammonia, putrescine and mixtures which function as highly effective attractants for frugivorous pest flies e...

  14. Equations of state of 2,6-diamino-3,5-dinitropyrazine-1-oxide

    NASA Astrophysics Data System (ADS)

    Gump, Jared C.; Stoltz, Chad A.; Mason, Brian P.; Freedman, Benjamin G.; Ball, Jason R.; Peiris, Suhithi M.

    2011-10-01

    2,6-diamino-3,5-dinitropyrazine-1-oxide (LLM-105) is an energetic ingredient that has an impact sensitivity close to that of TATB, yet a calculated energy content close to HMX. Reported tests of formulated LLM-105 reveal that it is a good candidate for a new insensitive high-performance explosive. As use of LLM-105 increases, thermodynamic parameters and phase stability will need to be determined for accurate modeling. In order to accomplish this goal, isothermal equations of state of LLM-105 at static high-pressure and temperature were investigated using synchrotron angle-dispersive x-ray diffraction and diamond anvil cells. Data at ambient temperature, 100 °C (373 K), and 180 °C (453 K) were used to obtain isothermal equations of state, and data at ambient pressure were used to obtain the volume thermal expansion coefficient. At ambient temperature, 100 °C (373 K), and 180 °C (453 K) no phase change was evident up to the highest measured pressure; and at ambient pressure, LLM-105 was stable up to 240 °C (513 K) and thermally decomposed by 260 °C (533 K).

  15. Natural product-based 6-hydroxy-2 3 4 6-tetrahydropyrrolo[1 2-a]pyrimidinium Scaffold as a new antifungal template

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Synthetic analogues of the marine-derived class of natural products phloeodictines have been prepared and exhibited potent in vitro fungicidal activities against a broad array of fungal pathogens including drug-resistant strains. The 6-hydroxy-2,3,4,6-tetrahydropyrrolo[1,2-a] pyrimidinium structura...

  16. 40 CFR 721.6160 - Piperazinone, 1,1′,1″-[1,3,5- triazine-2,4,6-triyltris[(cyclohexylimino)-2,1-ethanediyl

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    .... Requirements as specified in § 721.80(q). (b) Specific requirements. The provisions of subpart A of this part... workplace. Requirements as specified in § 721.63 (a)(4), (a)(5)(iv) through (vii), (a)(6)(i), (b... § 721.72 (a), (b), (c), (d) (e) (concentration set at 1.0 percent), (f), (g)(1)(iv), (g)(1)(vi),...

  17. 40 CFR 721.6160 - Piperazinone, 1,1′,1″-[1,3,5- triazine-2,4,6-triyltris[(cyclohexylimino)-2,1-ethanediyl

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    .... Requirements as specified in § 721.80(q). (b) Specific requirements. The provisions of subpart A of this part... workplace. Requirements as specified in § 721.63 (a)(4), (a)(5)(iv) through (vii), (a)(6)(i), (b... § 721.72 (a), (b), (c), (d) (e) (concentration set at 1.0 percent), (f), (g)(1)(iv), (g)(1)(vi),...

  18. Benzophenanthridines. V. Investigation of the Rodionov-Suvorov scheme. Synthesis of 3,3-diethoxycarbonyl-2-(3,4-dimethoxyphenyl)-6,7-dimethoxy-1-tetralone

    SciTech Connect

    Kyong, D.H.; Sladkov, V.I.; Suvorov, N.N.

    1988-02-20

    Triethyl 1,3-bis(3,4-dimethoxyphenyl)propane-1,2,2-tricarboxylate was synthesized by the alkylation of the lithium enolate of ethyl homoveratrate with /alpha/-bromo(3,4-dimethoxybenzyl)malonic ester. It was converted by intramolecular acylation, catalyzed by BF/sub 3/ /times/ OEt/sub 2/, into the ACD synthon for the total synthesis of benzo(c)-phenanthridine alkaloids by the Rodionov-Suvorov scheme, i.e., 3,3-diethoxy-carbonyl-2-(3,4-dimethoxyphenyl)-6,7-dimethoxy-1-tetralone. The structure of the synthesized substances agrees well with the data from elemental analysis and IR, /sup 1/H NMR, and mass spectra.

  19. Cdc6 degradation requires phosphodegron created by GSK-3 and Cdk1 for SCFCdc4 recognition in Saccharomyces cerevisiae

    PubMed Central

    Al-Zain, Amr; Schroeder, Lea; Sheglov, Alina; Ikui, Amy E.

    2015-01-01

    To ensure genome integrity, DNA replication takes place only once per cell cycle and is tightly controlled by cyclin-dependent kinase (Cdk1). Cdc6p is part of the prereplicative complex, which is essential for DNA replication. Cdc6 is phosphorylated by cyclin-Cdk1 to promote its degradation after origin firing to prevent DNA rereplication. We previously showed that a yeast GSK-3 homologue, Mck1 kinase, promotes Cdc6 degradation in a SCFCdc4-dependent manner, therefore preventing rereplication. Here we present evidence that Mck1 directly phosphorylates a GSK-3 consensus site in the C-terminus of Cdc6. The Mck1-dependent Cdc6 phosphorylation required priming by cyclin/Cdk1 at an adjacent CDK consensus site. The sequential phosphorylation by Mck1 and Clb2/Cdk1 generated a Cdc4 E3 ubiquitin ligase–binding motif to promote Cdc6 degradation during mitosis. We further revealed that Cdc6 degradation triggered by Mck1 kinase was enhanced upon DNA damage caused by the alkylating agent methyl methanesulfonate and that the resulting degradation was mediated through Cdc4. Thus, Mck1 kinase ensures proper DNA replication, prevents DNA damage, and maintains genome integrity by inhibiting Cdc6. PMID:25995377

  20. Toxicokinetics of acrylamide and glycidamide in B6C3F{sub 1} mice

    SciTech Connect

    Doerge, Daniel R. . E-mail: ddoerge@nctr.fda.gov; Young, John F.; McDaniel, L. Patrice; Twaddle, Nathan C.; Churchwell, Mona I.

    2005-02-01

    Acrylamide (AA) is a widely studied industrial chemical that is neurotoxic, mutagenic to somatic and germ cells, and carcinogenic in rodents. The recent discovery of AA at ppm levels in a wide variety of commonly consumed foods has energized research efforts worldwide to define toxic mechanisms, particularly toxicokinetics and bioavailability. This study compares the toxicokinetics of AA and its epoxide metabolite glycidamide (GA) in serum and tissues of male and female B6C3F1 mice following acute dosing by intravenous, gavage, and dietary routes at 0.1 mg/kg AA or intravenous and gavage dosing with an equimolar amount of GA. AA was rapidly absorbed from oral dosing, was widely distributed to tissues, was efficiently converted to GA, and increased levels of GA-DNA adducts were observed in liver after complete elimination from serum. GA dosing also resulted in rapid absorption, wide distribution to tissues, and produced liver DNA adduct levels that were approximately 40% higher than those from an equimolar dose of AA. While oral administration was found to attenuate AA bioavailability to 23% from the diet and to 32-52% from aqueous gavage, a first-pass effect or other kinetic change resulted in higher relative internal exposure to GA when compared to the intravenous route. A similar effect on relative GA exposure was also evident as the administered dose was reduced, which suggests that as dosing rate decreases, the conversion of AA to GA is more efficient. These findings are critical to the assessment of genotoxicity of AA at low doses in the food supply, which appears to depend on total exposure to GA.

  1. Palladium-Catalyzed 6-Endo Selective Alkyl-Heck Reactions: Access to 5-Phenyl-1,2,3,6-tetrahydropyridine Derivatives.

    PubMed

    Dong, Xu; Han, Ying; Yan, Fachao; Liu, Qing; Wang, Ping; Chen, Kexun; Li, Yueyun; Zhao, Zengdian; Dong, Yunhui; Liu, Hui

    2016-08-01

    A new type of palladium-catalyzed 6-endo-selective alkyl-Heck reaction of unactivated alkyl iodides has been described. This strategy provides efficient access to a variety of 5-phenyl-1,2,3,6-tetrahydropyridine derivatives, which are important structural motifs for bioactive molecules. This process displays a broad substrate scope with excellent 6-endo selectivity. Mechanistic investigations reveal that this alkyl-Heck reaction performs via a hybrid palladium-radical process. PMID:27409716

  2. Effects of β-(1,3-1,6)-D-glucan on irritable bowel syndrome-related colonic hypersensitivity.

    PubMed

    Asano, Teita; Tanaka, Ken-ichiro; Suemasu, Shintaro; Ishihara, Tomoaki; Tahara, Kayoko; Suzuki, Toshio; Suzuki, Hidekazu; Fukudo, Shin; Mizushima, Tohru

    2012-04-01

    Irritable bowel syndrome (IBS) is a gastrointestinal disorder characterized by chronic abdominal pain associated with altered bowel habits. Since the prevalence of IBS is very high and thus, involves elevated health-care costs, treatment of this condition by methods other than prescribed medicines could be beneficial. β-(1,3)-D-glucan with β-(1,6) branches (β-glucan) has been used as a nutritional supplement for many years. In this study, we examined the effect of β-glucan on fecal pellet output and visceral pain response in animal models of IBS. Oral administration of β-glucan suppressed the restraint stress- or drug-induced fecal pellet output. β-Glucan also suppressed the visceral pain response to colorectal distension. These results suggest that β-glucan could be beneficial for the treatment and prevention of IBS. PMID:22430139

  3. 3-[3-(3-florophenyl-2-propyn-1-ylthio)-1, 2, 5-thiadiazol-4-yl]-1, 2, 5, 6-tetrahydro-1- methylpyridine oxalate, a novel xanomeline derivative, improves neural cells proliferation and survival in adult mice

    PubMed Central

    Zhang, Xiaoliang; Gong, Qiang; Zhang, Shuang; Wang, Lin; Hu, Yinghe; Shen, Haiming; Dong, Suzhen

    2012-01-01

    The present study analyzed the influence of 3-[3-(3-florophenyl-2-propyn-1-ylthio)-1, 2, 5-thiadiazol-4-yl]-1, 2, 5, 6-tetrahydro-1-methylpyridine oxalate (EUK1001), a novel xanomeline derivative of the M1/M4 receptor agonist, on hippocampal neurogenesis in adult C57BL6 mice. Results showed that 15-day EUK1001 treatment via intraperitoneal injection promoted neural cell proliferation in the dentate gyrus, although cell differentiation did not change. The majority of bromodeoxyuridine-positive cells co-expressed the immature neuronal marker doublecortin. In addition, the level of neurogenesis in the subventricular zone was not altered. Brain-derived neurotrophic factor mRNA expression was up-regulated following EUK1001 treatment, but no change was observed in expression of camp-responsive element binding protein 1, paired box gene 6, vascular endothelial growth factor alpha, neurogenic differentiation factor 1, and wingless-related mouse mammary tumor virus integration site 3A mRNA. These experimental findings indicated that EUK1001 enhanced proliferation and survival of hippocampal cells, possibly by increasing brain-derived neurotrophic factor expression. PMID:25806054

  4. Suggestions for Teaching Mathematics Using Laboratory Approaches Grades 1-6. 3. Geometry. Experimental Edition.

    ERIC Educational Resources Information Center

    New York State Education Dept., Albany. Bureau of Elementary Curriculum Development.

    This guide describes activities and materials which can be used in a mathematics laboratory approach to a basic mathematics program for grades 1-6. Thirty-five activities pertaining to geometric concepts are described in terms of purpose, suggested grade levels, materials needed, and procedures. Some concepts included in the guide are: basic…

  5. Synthesis and QSAR study of novel 6-chloro-3-(2-Arylmethylene-1-methylhydrazino)-1,4,2-benzodithiazine 1,1-dioxide derivatives with anticancer activity.

    PubMed

    Sławiński, Jarosław; Żołnowska, Beata; Brzozowski, Zdzisław; Kawiak, Anna; Belka, Mariusz; Bączek, Tomasz

    2015-01-01

    A series of new 6-chloro-3-(2-arylmethylene-1-methylhydrazino)-1,4,2-benzodithiazine 1,1-dioxide derivatives were effectively synthesized from N-methyl-N-(6-chloro-1,1-dioxo-1,4,2-benzodithiazin-3-yl)hydrazines. The intermediate compounds as well as the products, were evaluated for their cytotoxic effects toward three human cancer cell lines. All compounds shown moderate or weak cytotoxic effects against the tested cancer cell lines, but selective cytotoxic effects were observed. Compound 16 exhibited the most potent cytotoxic activity against the HeLa cell line, with an IC50 value of 10 µM, while 14 was the most active against the MCF-7 and HCT-116 cell lines, affording IC50 values of 15 µM and 16 µM, respectively. The structure-activity relationship was evaluated based on QSAR methodology. The QSAR MCF-7 model indicated that natural charge on carbon atom C13 and energy of highest occupied molecular orbital (HOMO) are highly involved in cytotoxic activity against MCF-7 cell line. The cytotoxic activity of compounds against HCT-116 cell line is dependent on natural charge on carbon atom C13 and electrostatic charge on nitrogen atom N10. The obtained QSAR models could provide guidelines for further development of novel anticancer agents. PMID:25834988

  6. The ribonucleotidyl transferase USIP-1 acts with SART3 to promote U6 snRNA recycling

    PubMed Central

    Rüegger, Stefan; Miki, Takashi S.; Hess, Daniel; Großhans, Helge

    2015-01-01

    The spliceosome is a large molecular machine that serves to remove the intervening sequences that are present in most eukaryotic pre-mRNAs. At its core are five small nuclear ribonucleoprotein complexes, the U1, U2, U4, U5 and U6 snRNPs, which undergo dynamic rearrangements during splicing. Their reutilization for subsequent rounds of splicing requires reversion to their original configurations, but little is known about this process. Here, we show that ZK863.4/USIP-1 (U Six snRNA-Interacting Protein-1) is a ribonucleotidyl transferase that promotes accumulation of the Caenorhabditis elegans U6 snRNA. Endogenous USIP-1–U6 snRNA complexes lack the Lsm proteins that constitute the protein core of the U6 snRNP, but contain the U6 snRNP recycling factor SART3/B0035.12. Furthermore, co-immunoprecipitation experiments suggest that SART3 but not USIP-1 occurs also in a separate complex containing both the U4 and U6 snRNPs. Based on this evidence, genetic interaction between usip-1 and sart-3, and the apparent dissociation of Lsm proteins from the U6 snRNA during spliceosome activation, we propose that USIP-1 functions upstream of SART3 to promote U6 snRNA recycling. PMID:25753661

  7. DIETHYLDITHIOCARBAMATE POTENTIATES THE NEUROTOXICITY OF IN VIVO 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE AND OF IN VITRO 1-METHYL-4-PHENYLPYRIDINIUM

    EPA Science Inventory

    Diethyldithiocarbamic acid (DDC), a dithiocarbamate, potentiates the neurotoxicity of 1-methyl-r-pheny-1,2,3,6-tetrahydropyridine (MPTP) in vivo and of its major metabolite, 1,-methyl-4-phenylpyridinium (MPP+), in bovine adrenal medullary (BAM) cells maintained in culture. ale C5...

  8. The effect of cesium carbonate on 1-(3-methoxycarbonyl)propyl-1-phenyl[6,6]C61 aggregation in films

    SciTech Connect

    Lindemann, William R.; Wang, Wenjie; Fungura, Fadzai; Shinar, Joseph; Shinar, Ruth; Vaknin, David

    2014-11-11

    Surface-pressure isotherms, X-ray reflectivity, and X-ray near-total reflection fluorescence were used to study the properties of 1-(3-methoxycarbonyl)propyl-1-phenyl[6,6]C61 (PCBM) that was pre-mixed with cesium carbonate and spread as a film at the air-water interface. The pre-mixed PCBM with cesium carbonate demonstrated a strikingly strong effect on the organization of the film. Whereas films formed from pure PCBM solution were rough due to strong inter-molecular interactions, the films formed from the mixture were much smoother. This indicates that the cesium carbonate moderates the inter-molecular interactions among PCBM molecules, hinting that the cesium diffusion observed in inverted organic photovoltaics and the likely ensuing ionic Cs-PCBM interaction decrease aggregation tendency of PCBM. As a result, this implies that the use of cesium salts affects the morphology of the organic layer and consequently improves the efficiency of these devices.

  9. The effect of cesium carbonate on 1-(3-methoxycarbonyl)propyl-1-phenyl[6,6]C61 aggregation in films

    DOE PAGESBeta

    Lindemann, William R.; Wang, Wenjie; Fungura, Fadzai; Shinar, Joseph; Shinar, Ruth; Vaknin, David

    2014-11-11

    Surface-pressure isotherms, X-ray reflectivity, and X-ray near-total reflection fluorescence were used to study the properties of 1-(3-methoxycarbonyl)propyl-1-phenyl[6,6]C61 (PCBM) that was pre-mixed with cesium carbonate and spread as a film at the air-water interface. The pre-mixed PCBM with cesium carbonate demonstrated a strikingly strong effect on the organization of the film. Whereas films formed from pure PCBM solution were rough due to strong inter-molecular interactions, the films formed from the mixture were much smoother. This indicates that the cesium carbonate moderates the inter-molecular interactions among PCBM molecules, hinting that the cesium diffusion observed in inverted organic photovoltaics and the likely ensuingmore » ionic Cs-PCBM interaction decrease aggregation tendency of PCBM. As a result, this implies that the use of cesium salts affects the morphology of the organic layer and consequently improves the efficiency of these devices.« less

  10. Molecular level investigation of 2,2,6,6-tetramethyl-3,5-heptanedione on Si(1 0 0)-2 × 1: Spectroscopic and computational studies

    NASA Astrophysics Data System (ADS)

    Perrine, Kathryn A.; Skliar, Dimitri B.; Willis, Brian G.; Teplyakov, Andrew V.

    2008-07-01

    The molecular level chemistry of 2,2,6,6-tetramethyl-3,5-heptanedione (dpmH) has been investigated on a Si(1 0 0)-2 × 1 surface. The dpmH compound is a β-diketone, whose deprotonated form is used as a ligand in chemical precursors for metal-organic chemical vapor deposition (MOCVD). A combination of multiple internal reflection Fourier-transform infrared spectroscopy (MIR-FTIR), temperature programmed desorption (TPD), Auger electron spectroscopy (AES) and density functional theory (DFT) were employed to analytically detect and monitor surface species under different thermal conditions. Upon adsorption at cryogenic temperatures dpmH was shown to be present in the enolic form, while primarily OH dissociation and [2 + 2] carbonyl cycloaddition were revealed at room temperature. Upon heating from room temperature to 900 K, isobutene evolution into the gas phase was found to be a minor reaction pathway. The remainder of dpmH decomposes on the surface to release hydrogen into the gas phase.

  11. The effect of cesium carbonate on 1-(3-methoxycarbonyl)propyl-1-phenyl[6,6]C{sub 61} aggregation in films

    SciTech Connect

    Lindemann, William R.; Wang, Wenjie; Shinar, Joseph; Vaknin, David; Fungura, Fadzai; Shinar, Ruth

    2014-11-10

    Surface-pressure versus molecular area isotherms, X-ray reflectivity, and X-ray near-total reflection fluorescence were used to study the properties of 1-(3-methoxycarbonyl)propyl-1-phenyl[6,6]C{sub 61} (PCBM) that was pre-mixed with cesium carbonate and spread as a film at the air-water interface. The pre-mixed PCBM with cesium carbonate demonstrated a strikingly strong effect on the organization of the film. Whereas films formed from pure PCBM solution were rough due to strong inter-molecular interactions, the films formed from the mixture were much smoother. This indicates that the cesium carbonate moderates the inter-molecular interactions among PCBM molecules, hinting that the cesium diffusion observed in inverted organic photovoltaic structures and the likely ensuing ionic Cs-PCBM interaction decrease aggregation tendency of PCBM. This implies that the use of cesium salts affects the morphology of the organic layer and consequently improves the efficiency of these devices.

  12. Comparison of charge modulations in La1.875Ba0.125CuO4 and YBa2Cu3O6.6

    NASA Astrophysics Data System (ADS)

    Thampy, V.; Blanco-Canosa, S.; García-Fernández, M.; Dean, M. P. M.; Gu, G. D.; Först, M.; Loew, T.; Keimer, B.; Le Tacon, M.; Wilkins, S. B.; Hill, J. P.

    2013-07-01

    A charge modulation has recently been reported in (Y,Nd)Ba2Cu3O6+x [G. Ghiringhelli , ScienceSCIEAS0036-807510.1126/science.1223532 337, 821 (2012)]. Here we report Cu L3 edge soft x-ray scattering studies comparing the lattice modulation associated with the charge modulation in YBa2Cu3O6.6 with that associated with the well-known charge and spin stripe order in La1.875Ba0.125CuO4. We find that the correlation length in the CuO2 plane is isotropic in both cases, and is 259±9 Å for La1.875Ba0.125CuO4 and 55±15 Å for YBa2Cu3O6.6. Assuming weak interplanar correlations of the charge ordering in both compounds, we conclude that the order parameters of the lattice modulations in La1.875Ba0.125CuO4 and YBa2Cu3O6.6 are of the same order of magnitude.

  13. Synthesis and antimicrobial evaluation of novel 4-amino-6-(1,3,4-oxadiazolo/1,3,4-thiadiazolo)-pyrimidine derivatives.

    PubMed

    Shetty, Poornima; Praveen, B M; Raghavendra, M; Manjunath, K; Cheruku, Srinivas

    2016-05-01

    A series of novel 4-amino-6-(1,3,4-oxadiazolo/1,3,4-thiadiazolo)-pyrimidine derivatives of biological interest were prepared by sequential amination, hydrazide formation, and hydrazine carbothioamidination followed by cyclization. All the synthesized compounds (6a-6h and 7a-7f) were screened for antibacterial and antifungal activity. From this group, compound 7f (MIC (μg/mL μg/mL )/Inhibition (mm): 6.25/23-30) showed good antibacterial and antifungal activity. Reagents and conditions: (a) Ethyl acetoacetate, 60% NaH, 1,4-dioxane, 60°C, 6 h; (b) DIPEA, 1,4-dioxane, 100°C, 14 h; (c) NH2NH2 ⋅ H2O, EtOH, reflux, 14 h; (d) Tolyl isothiocyanatobenzene, DMF, RT, 2 h; (e) (if X = O) EDC⋅ HCl, TEA, DMF, RT, 14 h; (f) (if X = S) Conc. H2O4, RT, 14h. PMID:26498121

  14. Microscale Synthesis of 1-Bromo-3-Chloro-5-Iodobenzene: An Improved Deamination of 4-Bromo-2-Chloro-6-Iodoaniline

    ERIC Educational Resources Information Center

    Pelter, Michael W.; Pelter, Libbie S. W.; Colovic, Dusanka; Strug, Regina

    2004-01-01

    The sequence of microscale mixing of 1-bromo-3-chloro-5-iodobenzene along with reductive deamination of 4-bromo-2-chloro-6-iodoaniline is described. This novel deamination approach is beneficial in final product separation and higher product output.

  15. The metabolism of gamma-2,3,4,5,6-pentachlorocyclohex-1-ene and gamma-hexachlorocyclohexane in rats.

    PubMed

    Grover, P L; Sims, P

    1965-08-01

    1. After intraperitoneal administration, gamma-hexachlorocyclohexane (Gammexane) and gamma-2,3,4,5,6-pentachlorocyclohex-1-ene were converted by rats into 2,3,5- and 2,4,5-trichlorophenol, which were excreted as free phenols and as sulphuric acid and glucuronic acid conjugates. 2. Derivatives of 2,4,5-trichlorophenol and 2,4,5-trichlorophenyl glucosiduronic acid and 2,4-dichlorophenylmercapturic acid were isolated from the urine as metabolites of gamma-2,3,4,5,6-pentachlorocyclohex-1-ene. 3. The phenolic metabolites of gamma-hexachlorocyclohexane and gamma-2,3,4,5,6-pentachlorocyclohex-1-ene isolated from urine were similar to those of 1,2,4-trichlorobenzene, which indicates that the two latter compounds are intermediates in gamma-hexachlorocyclohexane metabolism in rats. PMID:4158352

  16. Immunotoxicity of nitrobenzene in female B6C3F1 mice.

    PubMed

    Burns, L A; Bradley, S G; White, K L; McCay, J A; Fuchs, B A; Stern, M; Brown, R D; Musgrove, D L; Holsapple, M P; Luster, M I

    1994-01-01

    Nitrobenzene (NBZ) is primarily employed as an oxidizing agent in the synthesis of analine and benzene compounds. It produces myelotoxic effects and effects on erythrocytes in both animal models and man. Reported hepatosplenomegaly and effects on the bone marrow are indicators that NBZ may be immunotoxic. In these studies, female B6C3F1 mice were exposed to 30, 100 and 300 mg/kg of NBZ in corn oil by gavage for 14 consecutive days. To assess the immunotoxic potential of NBZ, body and organ weights were determined and selected immunologic and host resistance responses were studied. In these studies, the liver and spleen appeared to be the primary target organs. Both liver and spleen weights were dose dependently increased. Gross histopathologic examinations revealed significant changes in the spleen, consisting of severe congestion of the red pulp areas with erythrocytes and reticulocytes. Serum chemistry profiles showed increases in alanine aminotransferase and aspartate aminotransferase activities, indicating liver toxicity. Hematologic studies showed a decrease in erythrocyte number and a concomitant increase in mean corpuscular hemoglobin and mean corpuscular volume. A dose-dependent increase in peripheral reticulocytes was also seen. DNA synthesis was enhanced, as was the number of formed elements and the number of monocyte/granulocyte stem cells in the bone marrow of treated mice. IgM responses were decreased and the phagocytic activity of macrophages in the liver was dose dependently increased with a concomitant decrease in the activities in the spleen and lung. Other immunological parameters examined were unchanged. Host resistance to microbial or viral infection was not markedly altered by NBZ; however, there were trends towards increased susceptibility where T-cell function contributes to host defense. These data indicate that NBZ-induced hemolysis and liver injury are linked to the observed alterations in bone marrow activity. PMID:7988385

  17. Tank 241-AP-106, grab samples, 6AP-96-1 through 6AP-96-3 analytical results for the final report

    SciTech Connect

    Esch, R.A., Westinghouse Hanford

    1996-12-11

    This document is the final report for tank 241-AP-106 grab samples. This document presents the analytical results for three samples (6AP-96-1, 6AP-96-2 and 6AP-96-3) taken from riser 1 @ 150{degrees} of tank 241-AP-1 06 on September 12, 1996. Analyses were performed in accordance with the Compatibility Grab Sampling and Analysis Plan (TSAP) (Sasaki, 1996) and the Data Quality Objectives for Tank Farms Waste Compatibility Program (DQO) (Fowler, 1995).

  18. Validating Geant4 Versions 7.1 and 8.3 Against 6.1 for BaBar

    SciTech Connect

    Banerjee, Swagato; Brown, David N.; Chen, Chunhui; Cote, David; Dubois-Felsmann, Gregory P.; Gaponenko, Igor; Kim, Peter C.; Lockman, William S.; Neal, Homer A.; Simi, Gabriele; Telnov, Alexandre V.; Wright, Dennis H.; /SLAC

    2011-11-08

    Since 2005 and 2006, respectively, Geant4 versions 7.1 and 8.3 have been available, providing: improvements in modeling of multiple scattering; corrections to muon ionization and improved MIP signature; widening of the core of electromagnetic shower shape profiles; newer implementation of elastic scattering for hadronic processes; detailed implementation of Bertini cascade model for kaons and lambdas, and updated hadronic cross-sections from calorimeter beam tests. The effects of these changes in simulation are studied in terms of closer agreement of simulation using Geant4 versions 7.1 and 8.3 as compared to Geant4 version 6.1 with respect to data distributions of: the hit residuals of tracks in BABAR silicon vertex tracker; the photon and K{sub L}{sup 0} shower shapes in the electromagnetic calorimeter; the ratio of energy deposited in the electromagnetic calorimeter and the flux return of the magnet instrumented with a muon detection system composed of resistive plate chambers and limited-streamer tubes; and the muon identification efficiency in the muon detector system of the BABAR detector.

  19. Process for manufacturing bis(2-methoxyethyl)-2,3,6,7-tetracyano-1,4,5,8,9,10-hexazaanthracene

    SciTech Connect

    Rasmussen, Paul George; Lawton, Richard Graham

    2014-06-03

    A process to manufacture substituted tetracyano-hexaazatricyclics with the substitutions occurring at the 9 and 10 hydrogens. The process begins with 2,3-dichloro-5,6-dicyanopyrazine, which is reacted to form the desired tetracyano-hexaazatricyclic. Different process embodiments enable different reaction paths to the desired tetracyano-hexaazatricyclic. Different tetracyano-hexaazatricyclic embodiments include bis(2-methoxyethyl)-2,3,6,7-tetracyano-1,4,5,8,9,10-hexazaanthracene and bis(2-methoxyethoxyethyl)-2,3,6,7-tetracyano-1,4,5,8,9,10-hexazaanthracen- e.

  20. A protective lipidomic biosignature associated with a balanced omega-6/omega-3 ratio in fat-1 transgenic mice.

    PubMed

    Astarita, Giuseppe; McKenzie, Jennifer H; Wang, Bin; Strassburg, Katrin; Doneanu, Angela; Johnson, Jay; Baker, Andrew; Hankemeier, Thomas; Murphy, James; Vreeken, Rob J; Langridge, James; Kang, Jing X

    2014-01-01

    A balanced omega-6/omega-3 polyunsaturated fatty acid (PUFA) ratio has been linked to health benefits and the prevention of many chronic diseases. Current dietary intervention studies with different sources of omega-3 fatty acids (omega-3) lack appropriate control diets and carry many other confounding factors derived from genetic and environmental variability. In our study, we used the fat-1 transgenic mouse model as a proxy for long-term omega-3 supplementation to determine, in a well-controlled manner, the molecular phenotype associated with a balanced omega-6/omega-3 ratio. The fat-1 mouse can convert omega-6 to omega-3 PUFAs, which protect against a wide variety of diseases including chronic inflammatory diseases and cancer. Both wild-type (WT) and fat-1 mice were subjected to an identical diet containing 10% corn oil, which has a high omega-6 content similar to that of the Western diet, for a six-month duration. We used a multi-platform lipidomic approach to compare the plasma lipidome between fat-1 and WT mice. In fat-1 mice, an unbiased profiling showed a significant increase in the levels of unesterified eicosapentaenoic acid (EPA), EPA-containing cholesteryl ester, and omega-3 lysophosphospholipids. The increase in omega-3 lipids is accompanied by a significant reduction in omega-6 unesterified docosapentaenoic acid (omega-6 DPA) and DPA-containing cholesteryl ester as well as omega-6 phospholipids and triacylglycerides. Targeted lipidomics profiling highlighted a remarkable increase in EPA-derived diols and epoxides formed via the cytochrome P450 (CYP450) pathway in the plasma of fat-1 mice compared with WT mice. Integration of the results of untargeted and targeted analyses has identified a lipidomic biosignature that may underlie the healthful phenotype associated with a balanced omega-6/omega-3 ratio, and can potentially be used as a circulating biomarker for monitoring the health status and the efficacy of omega-3 intervention in humans. PMID

  1. Vicarious nucleophilic substitution using 4-amino-1,2,4-triazole, hydroxylamine or O-alkylhydroxylamine to prepare 1,3-diamino-2,4,6-trinitrobenzene or 1,3,5-triamino-2,4,6-trinitrobenzene

    DOEpatents

    Mitchell, Alexander R.; Pagoria, Philip F.; Schmidt, Robert D.

    1997-01-01

    The present invention relates to a process to produce 1,3-diamino-2,4,6-trinitrobenzene (DATB) or 1,3,5-triamino-2,4,6,-trinitrobenzene (TATB) by: (a) reacting at ambient pressure and a temperature of between about 0.degree. and 50.degree. C. for between about 0.1 and 24 hr, a trinitroaromatic compound of structure V: ##STR1## wherein X, Y, and Z are each independently selected from the group consisting of --H and --NH.sub.2, with the proviso that at least 1 or 2 of X, Y, and Z are hydrogen; with an effective amount of 1-amino-1,2,4-triazole, hydroxylamine or O-alkylhydroxamine to produce DATB or TATB; in the presence of a strong base selected from sodium butoxide, potassium butoxide, potassium propoxide, sodium propoxide, sodium ethoxide, potassium ethoxide, sodium methoxide, potassium methoxide, and combinations thereof; in a solvent selected from the group consisting of methanol, ethanol, propanol, butanol, dimethylsulphoxide, N-methylpyrrolidone, hexamethylphosphoramide, dimethylformide, dimethylacetamide and mixtures thereof, provided that when alcohols are present or when hydroxylamine or its O-alkyl derivatives replace ATA primarily DATB is formed; and (b) isolating the DATB or TATB produced. DATB and TATB are important and useful specialty explosives and intermediates for other materials.

  2. 4,6-Dihy­droxy-4,6-dimethyl-1,3-diazinane-2-thione

    PubMed Central

    Aliyeva, Khatira N.; Maharramov, Abel M.; Allahverdiyev, Mirze A.; Gurbanov, Atash V.; Brito, Iván

    2011-01-01

    In the title compound, C6H12N2O2S, the heterocyclic ring has a sofa conformation. The mol­ecular conformation is stabilized by an intra­molecular O—H⋯O hydrogen-bond inter­action with graph-set motif S(6). In the crystal, mol­ecules are linked by O—H⋯S, N—H⋯S and N—H⋯O hydrogen-bond inter­actions, forming an extended two-dimensional framework parallel to the ac plane. PMID:22058933

  3. 40 CFR 721.9790 - Benzenesulfonic acid, 2,2′-(1,2-ethenediyl)bis[5-[[4-[bis(2-hydroxypropyl) amino]- 6-[(3...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...); Benzenesulfonic acid, 5- -6- -1,3,5-triazin-2-yl]amino]-2- -6- -1,3,5-triazin-2-yl]amino]-2-sulfophenyl]ethenyl...); Benzenesulfonic acid, 5- -6- -1,3,5-triazin-2-yl]amino]-2- -6- -1,3,5-triazin-2-yl]amino]-2-sulfophenyl]ethenyl...); Benzenesulfonic acid, 5- -6- -1,3,5-triazin-2-yl]amino]-2- -6-......

  4. 40 CFR 721.9790 - Benzenesulfonic acid, 2,2′-(1,2-ethenediyl)bis[5-[[4-[bis(2-hydroxypropyl) amino]- 6-[(3...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...); Benzenesulfonic acid, 5- -6- -1,3,5-triazin-2-yl]amino]-2- -6- -1,3,5-triazin-2-yl]amino]-2-sulfophenyl]ethenyl...); Benzenesulfonic acid, 5- -6- -1,3,5-triazin-2-yl]amino]-2- -6- -1,3,5-triazin-2-yl]amino]-2-sulfophenyl]ethenyl...); Benzenesulfonic acid, 5- -6- -1,3,5-triazin-2-yl]amino]-2- -6-......

  5. 40 CFR 721.9790 - Benzenesulfonic acid, 2,2′-(1,2-ethenediyl)bis[5-[[4-[bis(2-hydroxypropyl) amino]- 6-[(3...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...); Benzenesulfonic acid, 5- -6- -1,3,5-triazin-2-yl]amino]-2- -6- -1,3,5-triazin-2-yl]amino]-2-sulfophenyl]ethenyl...); Benzenesulfonic acid, 5- -6- -1,3,5-triazin-2-yl]amino]-2- -6- -1,3,5-triazin-2-yl]amino]-2-sulfophenyl]ethenyl...); Benzenesulfonic acid, 5- -6- -1,3,5-triazin-2-yl]amino]-2- -6-......

  6. On the reactivity of 6-acetyl-7-(2-dimethylaminovinyl)pyrazolo[1,5-a]pyrimidines with 1,3- and 1,4-bisnucleophiles.

    PubMed

    Chimichi, Stefano; Boccalini, Marco; Selleri, Silvia; Costagli, Camilla; Guerrini, Gabriella; Viola, Giampietro

    2008-02-21

    Reaction of 6-acetyl-7-(2-dimethylaminovinyl)pyrazolo[1,5-a]pyrimidine 1 with 1,3- and 1,4-bisnucleophiles has been investigated; obtainment of new polycyclic heterocyclic derivatives is reported. A convenient procedure leading to new pyrazolo[1,5-a]quinazolines is described; a modest bioactivity of these compounds against two human tumor cell lines was also ascertained. PMID:18264575

  7. 5-(4-Fluoro-benzyl-idene)-2,2-dimethyl-1,3-dioxane-4,6-dione.

    PubMed

    Zeng, Wu-Lan

    2010-01-01

    The title compound, C(13)H(11)FO(4), was prepared by the reaction of 2,2-dimethyl-1,3-dioxane-4,6-dione and 4-fluoro-benz-alde-hyde in ethanol. The 1,3-dioxane ring adopts an envelope conformation. The crystal structure is stabilized by weak inter-molecular C-H⋯O hydrogen bonds. PMID:21588707

  8. 40 CFR 721.805 - Benzenamine, 4,4′-[1,3-phenylenebis(1-methylethyl idene)]bis[2,6-dimethyl-.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... workplace. Requirements as specified in § 721.63 (a)(1), (a)(3), (a)(4), (a)(5)(iv) through (a)(5)(xv), (a)(6)(i), (a)(6)(ii), (b) (concentration set at 0.1 percent), and (c). (ii) Hazard communication... subject to reporting. (1) The chemical substance benzenamine, 4,4′- bis[2,6-dimethyl- (CAS Registry...

  9. Vicarious nucleophilic substitution using 4-amino-1,2,4-triazole, hydroxylamine or O-alkylhydroxylamine to prepare 1,3-diamino-2,4,6-trinitrobenzene or 1,3,5-triamino-2,4,6-trinitrobenzene

    DOEpatents

    Mitchell, A.R.; Pagoria, P.F.; Schmidt, R.D.

    1997-05-27

    The present invention relates to a process to produce 1,3-diamino-2,4,6-trinitrobenzene (DATB) or 1,3,5-triamino-2,4,6,trinitrobenzene (TATB) by: (a) reacting at ambient pressure and a temperature of between about 0 and 50 C for between about 0.1 and 24 hr, a trinitroaromatic compound of the structure shown where X, Y, and Z are each independently selected from the group consisting of -H and -NH{sub 2}, with the proviso that at least 1 or 2 of X, Y, and Z are hydrogen; with an effective amount of 1-amino-1,2,4-triazole, hydroxylamine or O-alkylhydroxamine to produce DATB or TATB; in the presence of a strong base selected from sodium butoxide, potassium butoxide, potassium propoxide, sodium propoxide, sodium ethoxide, potassium ethoxide, sodium methoxide, potassium methoxide, and combinations thereof; in a solvent selected from the group consisting of methanol, ethanol, propanol, butanol, dimethylsulphoxide, N-methylpyrrolidone, hexamethylphosphoramide, dimethylformide, dimethylacetamide and mixtures thereof, provided that when alcohols are present or when hydroxylamine or its O-alkyl derivatives replace ATA primarily DATB is formed; and (b) isolating the DATB or TATB produced. DATB and TATB are important and useful specialty explosives and intermediates for other materials.

  10. Prevention of the nigrostriatal toxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine by inhibitors of 3,4-dihydroxyphenylethylamine transport.

    PubMed

    Mayer, R A; Kindt, M V; Heikkila, R E

    1986-10-01

    The 3,4-dihydroxyphenylethylamine (DA, dopamine) uptake inhibitors GBR 13,069, amfonelic acid, WIN-35,065-2, WIN-35,428, nomifensine, mazindol, cocaine, McN-5908, McN-5847, and McN-5292 were effective in preventing [3H]DA and [3H]1-methyl-4-phenylpyridinium (MPP+) uptake in rat and mouse neostriatal tissue slices. These DA uptake inhibitors also were effective in attenuating the MPP+-induced release of [3H]DA in vitro. 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration to mice (6 X 25 mg/kg i.p.) resulted in a large (70-80%) decrement in neostriatal DA. WIN-35,428 (5 mg/kg), GBR 13,069 (10 mg/kg), McN-5292 (5 mg/kg), McN-5908 (2 mg/kg), and amfonelic acid (2 mg/kg), when administered intraperitoneally 30 min prior to each MPTP injection, fully protected against MPTP-induced neostriatal damage. Other DA uptake inhibitors showed partial protection in vivo at the doses selected. Desmethylimipramine did not prevent [3H]MPP+ uptake or MPP+-induced release of [3H]DA in vitro, and did not protect against MPTP neurotoxicity in vivo. These results support the hypothesis put forth previously by others that the active uptake of MPP+ by dopaminergic neurons is necessary for toxicity. PMID:3489072

  11. Identification of a cryptic type III polyketide synthase (1,3,6,8-tetrahydroxynaphthalene synthase) from Streptomyces peucetius ATCC 27952.

    PubMed

    Ghimire, Gopal Prasad; Oh, Tae-Jin; Liou, Kwangkyoung; Sohng, Jae Kyung

    2008-10-31

    We identified a 1,134-bp putative type III polyketide synthase from the sequence analysis of Streptomyces peucetius ATCC 27952, named Sp-RppA, which is characterized as 1,3,6,8-tetrahydroxynaphthalene synthase and shares 33% identity with SCO1206 from S. coelicolor A3(2) and 32% identity with RppA from S. griseus. The 1,3,6,8-tetrahydroxynaphthalene synthase is known to catalyze the sequential decarboxylative condensation, intramolecular cyclization, and aromatization of an oligoketide derived from five units of malonyl-CoA to give 1,3,6,8-tetrahydroxynaphthalene, which spontaneously oxidizes to form 2,5,7-trihydroxy-1,4-naphthoquinone (flaviolin). In this study, we report the in vivo expression and in vitro synthesis of flaviolin from purified gene product (Sp-RppA). PMID:18612244

  12. ARF6–JIP3/4 regulate endosomal tubules for MT1-MMP exocytosis in cancer invasion

    PubMed Central

    Marchesin, Valentina; Castro-Castro, Antonio; Lodillinsky, Catalina; Castagnino, Alessia; Cyrta, Joanna; Bonsang-Kitzis, Hélène; Fuhrmann, Laetitia; Irondelle, Marie; Infante, Elvira; Montagnac, Guillaume; Reyal, Fabien; Vincent-Salomon, Anne

    2015-01-01

    Invasion of cancer cells into collagen-rich extracellular matrix requires membrane-tethered membrane type 1–matrix metalloproteinase (MT1-MMP) as the key protease for collagen breakdown. Understanding how MT1-MMP is delivered to the surface of tumor cells is essential for cancer cell biology. In this study, we identify ARF6 together with c-Jun NH2-terminal kinase–interacting protein 3 and 4 (JIP3 and JIP4) effectors as critical regulators of this process. Silencing ARF6 or JIP3/JIP4 in breast tumor cells results in MT1-MMP endosome mispositioning and reduces MT1-MMP exocytosis and tumor cell invasion. JIPs are recruited by Wiskott-Aldrich syndrome protein and scar homologue (WASH) on MT1-MMP endosomes on which they recruit dynein–dynactin and kinesin-1. The interaction of plasma membrane ARF6 with endosomal JIPs coordinates dynactin–dynein and kinesin-1 activity in a tug-of-war mechanism, leading to MT1-MMP endosome tubulation and exocytosis. In addition, we find that ARF6, MT1-MMP, and kinesin-1 are up-regulated in high-grade triple-negative breast cancers. These data identify a critical ARF6–JIP–MT1-MMP–dynein–dynactin–kinesin-1 axis promoting an invasive phenotype of breast cancer cells. PMID:26504170

  13. ARF6-JIP3/4 regulate endosomal tubules for MT1-MMP exocytosis in cancer invasion.

    PubMed

    Marchesin, Valentina; Castro-Castro, Antonio; Lodillinsky, Catalina; Castagnino, Alessia; Cyrta, Joanna; Bonsang-Kitzis, Hélène; Fuhrmann, Laetitia; Irondelle, Marie; Infante, Elvira; Montagnac, Guillaume; Reyal, Fabien; Vincent-Salomon, Anne; Chavrier, Philippe

    2015-10-26

    Invasion of cancer cells into collagen-rich extracellular matrix requires membrane-tethered membrane type 1-matrix metalloproteinase (MT1-MMP) as the key protease for collagen breakdown. Understanding how MT1-MMP is delivered to the surface of tumor cells is essential for cancer cell biology. In this study, we identify ARF6 together with c-Jun NH2-terminal kinase-interacting protein 3 and 4 (JIP3 and JIP4) effectors as critical regulators of this process. Silencing ARF6 or JIP3/JIP4 in breast tumor cells results in MT1-MMP endosome mispositioning and reduces MT1-MMP exocytosis and tumor cell invasion. JIPs are recruited by Wiskott-Aldrich syndrome protein and scar homologue (WASH) on MT1-MMP endosomes on which they recruit dynein-dynactin and kinesin-1. The interaction of plasma membrane ARF6 with endosomal JIPs coordinates dynactin-dynein and kinesin-1 activity in a tug-of-war mechanism, leading to MT1-MMP endosome tubulation and exocytosis. In addition, we find that ARF6, MT1-MMP, and kinesin-1 are up-regulated in high-grade triple-negative breast cancers. These data identify a critical ARF6-JIP-MT1-MMP-dynein-dynactin-kinesin-1 axis promoting an invasive phenotype of breast cancer cells. PMID:26504170

  14. Expression of Functional Human Sialyltransferases ST3Gal1 and ST6Gal1 in Escherichia coli

    PubMed Central

    Ortiz-Soto, Maria Elena; Seibel, Jürgen

    2016-01-01

    Sialyltransferases (STs) are disulfide-containing, type II transmembrane glycoproteins that catalyze the transfer of sialic acid to proteins and lipids and participate in the synthesis of the core structure oligosaccharides of human milk. Sialic acids are found at the outermost position of glycostructures, playing a key role in health and disease. Sialylation is also essential for the production of recombinant therapeutic proteins (RTPs). Despite their importance, availability of sialyltransferases is limited due to the low levels of stable, soluble and active protein produced in bacterial expression systems, which hampers biochemical and structural studies on these enzymes and restricts biotechnological applications. We report the successful expression of active human sialyltransferases ST3Gal1 and ST6Gal1 in commercial Escherichia coli strains designed for production of disulfide-containing proteins. Fusion of hST3Gal1 with different solubility enhancers and substitution of exposed hydrophobic amino acids by negatively charged residues (supercharging-like approach) were performed to promote solubility and folding. Co-expression of sialyltransferases with the chaperon/foldases sulfhydryl oxidase, protein disulfide isomerase and disulfide isomerase C was explored to improve the formation of native disulfide bonds. Active sialyltransferases fused with maltose binding protein (MBP) were obtained in sufficient amounts for biochemical and structural studies when expressed under oxidative conditions and co-expression of folding factors increased the yields of active and properly folded sialyltransferases by 20%. Mutation of exposed hydrophobic amino acids increased recovery of active enzyme by 2.5-fold, yielding about 7 mg of purified protein per liter culture. Functionality of recombinant enzymes was evaluated in the synthesis of sialosides from the β-d-galactoside substrates lactose, N-acetyllactosamine and benzyl 2-acetamido-2-deoxy-3-O

  15. Interruption of electronically excited Xe dimer formation by the photoassociation of Xe(6s[3/2]2)-Xe(5p6 1S0) thermal collision pairs

    NASA Astrophysics Data System (ADS)

    Galvin, T. C.; Wagner, C. J.; Eden, J. G.

    2016-06-01

    The diatomic collisional intermediate responsible for the formation of an electronically excited molecule by teratomic recombination has been observed in both the spectral and temporal domains by laser spectroscopy. We report experiments demonstrating thermal Xe(6s[3/2]2)-Xe(5p6 1S0) atomic collision pairs to be the immediate precursor to the formation of Xe 2∗ ( a 3 Σu + , A 1 Σu +) by the three body process: Xe∗(6s) + 2Xe ⟶ Xe 2∗ + Xe, where the asterisk denotes an excited electronic state. Photoassociating Xe(6s)-Xe atomic pairs by free ⟵ free transitions of the collision complex interrupts the production of the electronically excited Xe dimer, thereby suppressing Xe2 spontaneous emission in the vacuum ultraviolet (VUV, λ ˜ 172 nm, A 1 Σu + → X 1 Σg +). Intercepting Xe(6s)-Xe pairs before the complex is stabilized by the arrival of the third atom in the teratomic collision process selectively depletes the pair population in a specific Franck-Condon region determined by the probe laser wavelength (λ). Measurements of the variation of VUV emission suppression with λ provide a spectral signature of the [Xe(6s[3/2]2) - Xe(1S0)]∗ complex and map the probe laser wavelength onto the thermal energy (ɛ″) of the incoming collision pairs.

  16. Constitutive androstane receptor activation by 2,4,6-triphenyldioxane-1,3 suppresses the expression of the gluconeogenic genes.

    PubMed

    Kachaylo, Ekaterina M; Yarushkin, Andrei A; Pustylnyak, Vladimir O

    2012-03-15

    The constitutive androstane receptor (CAR, NR1I3) has a central role in detoxification processes, regulating the expression of a set of genes involved in metabolism. The dual role of NR1I3 as both a xenosensor and as a regulator of endogenous energy metabolism has recently been accepted. Here, we investigated the mechanism of transcriptional regulation of the glucose metabolising genes phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) by the cis isomer of 2,4,6-triphenyldioxane-1,3 (cisTPD), a highly effective NR1I3 activator in rat liver. It was shown that expression of the gluconeogenic genes PEPCK and G6Pase was repressed by cisTPD treatment under fasting conditions. Western-blot analysis demonstrated a clear reduction in the intensity of PEPCK and G6Pase immunobands from the livers of cisTPD-treated animals relative to bands from the livers of control animals. Chromatin immunoprecipitation assays demonstrated that cisTPD prevents the binding of FOXO1 to the insulin response sequences in the PEPCK and G6Pase gene promoters in rat liver. Moreover, cisTPD-activated NR1I3 inhibited NR2A1 (HNF-4) transactivation by competing with NR2A1 for binding to the NR2A1-binding element (DR1-site) in the gluconeogenic gene promoters. Thus, our results are consistent with the hypothesis that the cisTPD-activated NR1I3 participates in the regulation of the gluconeogenic genes PEPCK and G6Pase. PMID:22296760

  17. IL-6 modulates hepatocyte proliferation via induction of HGF/p21{sup cip1}: Regulation by SOCS3

    SciTech Connect

    Sun Rui; Jaruga, Barbara; Kulkarni, Shailin; Sun Haoyu; Gao Bin . E-mail: bgao@mail.nih.gov

    2005-12-30

    The precise role of IL-6 in liver regeneration and hepatocyte proliferation is controversial and the role of SOCS3 in liver regeneration remains unknown. Here we show that in vitro treatment with IL-6 inhibited primary mouse hepatocyte proliferation. IL-6 induced p21{sup cip1} protein expression in primary mouse hepatocytes. Disruption of the p21{sup cip1} gene abolished the inhibitory effect of IL-6 on cell proliferation. Co-culture with nonparenchymal liver cells diminished IL-6 inhibition of hepatocyte proliferation, which was likely due to IL-6 stimulation of nonparenchymal cells to produce HGF. Finally, IL-6 induced higher levels of p21{sup cip1} protein expression and a slightly stronger inhibition of cell proliferation in SOCS3{sup +/-} mouse hepatocytes compared to wild-type hepatocytes, while liver regeneration was enhanced and prolonged in SOCS3{sup +/-} mice. Our findings suggest that IL-6 directly inhibits hepatocyte proliferation via a p21{sup cip1}-dependent mechanism and indirectly enhances hepatocyte proliferation via stimulating nonparenchymal cells to produce HGF. SOCS3 negatively regulates liver regeneration.

  18. Synthesis, structural characterization and biological activity of fluorinated Schiff-bases of the type [C6H4-1-(OH)-3-(CHdbnd NArF)

    NASA Astrophysics Data System (ADS)

    Avila-Sorrosa, Alcives; Hernández-González, Jorge Ignacio; Reyes-Arellano, Alicia; Toscano, Rubén A.; Reyes-Martínez, Reyna; Roberto Pioquinto-Mendoza, J.; Morales-Morales, David

    2015-04-01

    A series of fluorinated imines of the type [C6H4-1-(OH)-3-(CHdbnd NArF)]; ArFdbnd C6H4-4-F (1), C6H3-2,3-F2 (2), C6H3-3,5-F2 (3), C6H2-2,4,6-F3 (4), C6H4-3-CF3 (5), C6H3-3,5-(CF3)2 (6), were synthesized and fully characterized including single crystal X-ray diffraction analyses of compounds [C6H4-1-(OH)-3-(CHdbnd NC6H4-4-F)] (1), [C6H4-1-(OH)-3-(CHdbnd NC6H3-3,5-F2)] (3), [C6H4-1-(OH)-3-(CHdbnd NC6H4-3-CF3)] (5). Further analyses of these results allowed the identification of the predominant non-covalent interactions and supramolecular arrangements in the solid state. Exploration of the anti-bacterial activity against both gram-positive and gram-negative bacteria showed those compounds including F or CF3 substituents at the meta positions i.e. [C6H4-1-(OH)-3-(CHdbnd NC6H3-3,5-F2)] (3), [C6H4-1-(OH)-3-(CHdbnd NC6H4-3-CF3)] (5), [C6H4-1-(OH)-3-(CHdbnd NC6H3-3,5-(CF3)2)] (6), to be the best when their activity is compared versus ampicillin.

  19. Purified rat liver DT-diaphorase potentiates the mutagenicity of 1,3-, 1,6- and 1,8-dinitropyrene

    SciTech Connect

    Hajos, A.K.D.; Winston, G.W. )

    1991-03-11

    The effect of highly purified rat liver cytosolic DT-diaphorase on the mutagenicity of 1,3-, 1,6- and 1,8-dinitropyrene (DNP) was studied in the Ames Salmonella typhimurium mutagenicity assay. DT-diaphorase over the range of 0 - 0.78 {mu}g/plate increased the mutagenicity of all three DNP in S. typhimurium TA 98 to a maximum of 3-fold. In the nitroreductase-deficient strain, TA98NR, 1,6- and 1,8-DNP were activated to a lesser extent in the presence of equal amounts of DT-diaphorase as compared to TA98. The mutagenicity of 1,3-DNP was markedly lowered in TA98NR and DT-diaphorase did not increase the mutagenicity of this toxicant except at the highest level utilized. DT-diaphorase was found to activate 1,6-, but not 1,3-DNP to mutagenic intermediates in TA98 18DNP{sub 6}, a strain deficient in O-acetyltransferase activity. The results suggest that DT-diaphorase not only catalyzes reduction of the parent DNP but also that of partially reduced metabolites generated from that DNP. This may result in increased formation of the penultimate mutagenic species. Thus, while DT-diaphorase is commonly viewed as having antimutagenic properties with certain compounds the opposite appears to be true for DNP.

  20. Human fructose-1,6-bisphosphatase gene (FBP1): Exon-intron organization, localization to chromosome bands 9q22.2-q22.3, and mutation screening in subjects with fructose-1,6-bisphosphatase deficiency

    SciTech Connect

    El-Maghrabi, M.R.; Jiang, W.

    1995-06-10

    Fructose-1,6-bisphosphatase (EC 3.1.3.11) is a key regulatory enzyme of gluconeogenesis that catalyzes the hydrolysis of fructose-1,6-bisphosphate to generate fructose-6-phosphate and inorganic phosphate. Deficiency of fructose-1,6-bisphosphatase is associated with fasting hypoglycemia and metabolic acidosis because of impaired gluconeogenesis. We have cloned and characterized the human liver fructose-1,6-bisphosphatase gene (FBP1). FBP1, localized to chromosome bands 9q22.2-q22.3 by fluorescence in situ hybridization, consists of seven exons that span > 31 kb, and the six introns are in the same position as in the rat gene. FBP1 was screened for mutations in two subjects with fructose-1,6-bisphosphatase deficiency. Four nucleotide substitutions were identified, two of which were silent mutations in the codons for Ala-216 (GCT {yields} GCC) and Gly-319 (GGG {yields} GGA). The other substitutions were in intron 3, a C {yields} T substitution 7 nucleotides downstream from the splice donor site, and in the promoter region, an A {yields} T substitution 188 nucleotides upstream from the start of transcription. These nucleotide substitutions were also found in normal unaffected subjects and thus are not the cause of fructose-1,6-bisphosphatase deficiency in the two subjects studied. The molecular basis of hepatic fructose-1,6-bisphosphatase deficiency in these subjects remains undetermined but could result from unidentified mutations in the promoter that decrease expression or from mutations in another gene that indirectly lead to decreased fructose-1,6-bisphosphatase activity. 18 refs., 3 figs., 3 tabs.

  1. Allelic variation of the Tas1r3 taste receptor gene selectively affects taste responses to sweeteners: evidence from 129.B6-Tas1r3 congenic mice.

    PubMed

    Inoue, Masashi; Glendinning, John I; Theodorides, Maria L; Harkness, Sarah; Li, Xia; Bosak, Natalia; Beauchamp, Gary K; Bachmanov, Alexander A

    2007-12-19

    The Tas1r3 gene encodes the T1R3 receptor protein, which is involved in sweet taste transduction. To characterize ligand specificity of the T1R3 receptor and the genetic architecture of sweet taste responsiveness, we analyzed taste responses of 129.B6-Tas1r3 congenic mice to a variety of chemically diverse sweeteners and glucose polymers with three different measures: consumption in 48-h two-bottle preference tests, initial licking responses, and responses of the chorda tympani nerve. The results were generally consistent across the three measures. Allelic variation of the Tas1r3 gene influenced taste responsiveness to nonnutritive sweeteners (saccharin, acesulfame-K, sucralose, SC-45647), sugars (sucrose, maltose, glucose, fructose), sugar alcohols (erythritol, sorbitol), and some amino acids (D-tryptophan, D-phenylalanine, L-proline). Tas1r3 genotype did not affect taste responses to several sweet-tasting amino acids (L-glutamine, L-threonine, L-alanine, glycine), glucose polymers (Polycose, maltooligosaccharide), and nonsweet NaCl, HCl, quinine, monosodium glutamate, and inosine 5'-monophosphate. Thus Tas1r3 polymorphisms affect taste responses to many nutritive and nonnutritive sweeteners (all of which must interact with a taste receptor involving T1R3), but not to all carbohydrates and amino acids. In addition, we found that the genetic architecture of sweet taste responsiveness changes depending on the measure of taste response and the intensity of the sweet taste stimulus. Variation in the T1R3 receptor influenced peripheral taste responsiveness over a wide range of sweetener concentrations, but behavioral responses to higher concentrations of some sweeteners increasingly depended on mechanisms that could override input from the peripheral taste system. PMID:17911381

  2. Multiphoton ionization studies of clusters of immiscible liquids. II. C6H6- (H2O)n, n=3-8 and (C6H6)2- (H2O)1,2

    NASA Astrophysics Data System (ADS)

    Garrett, Aaron W.; Zwier, Timothy S.

    1992-03-01

    Resonant two-photon ionization (R2PI) time-of-flight mass spectroscopy is used to record S0-S1 spectra of the neutral complexes C6H6-(H2O)n with n=3-8 and (C6H6)2-(H2O)1,2. Due to limitations imposed by the size of these clusters, a number of vibronic level arguments are used to constrain the gross features of the geometries of these clusters. Among the spectral clues provided by the data are the frequency shifts of the transitions, their van der Waals structure, the fragmentation of the photoionized clusters, and the complexation-induced origin intensity and 610 splitting. In the 1:3 cluster, simple arguments are made based on the known structures of the 1:1 and 1:2 clusters which lead to the conclusion that all three water molecules reside on the same side of the benzene ring. Three structures for the 1:3 cluster are proposed which are consistent with the available data. Of these, only one is also consistent with the remarkable similarity of the 1:4 and 1:5 spectra to those of the 1:3 cluster. This structure involves a cyclic water trimer in which one of the water molecules is near the sixfold axis in a π hydrogen-bonded configuration. This structure is then expanded in the 1:4 and 1:5 clusters to incorporate the fourth and fifth water molecules in cyclic structures which place the additional water molecules far from the benzene ring without disturbing the interaction of the other water molecules with the benzene ring. For 1:n clusters with n≥6, subtle and then significant changes are observed in the spectra which indicate changes in the way the water cluster interacts with the benzene ring. This development occurs at precisely the water cluster size which calculations predict that cagelike water cluster structures will begin to compete and eventually be favored over large cyclic structures. Finally, cursory scans of the 2:1 cluster show that this cluster also fragments efficiently upon photoionization by loss of a single water molecule and that it possesses a

  3. Synthesis of Novel Pyrido[4,3-e][1,2,4]triazino[3,2-c][1,2,4]thiadiazine 6,6-dioxide Derivatives with Potential Anticancer Activity.

    PubMed

    Sławiński, Jarosław; Grzonek, Aleksandra; Żołnowska, Beata; Kawiak, Anna

    2015-01-01

    A series of novel 3-/2,3-substituted pyrido[4,3-e][1,2,4]triazino[3,2-c][1,2,4]thiadiazine 6,6-dioxides 4-28 have been synthesized by the reaction of 3-amino-2-(4-thioxo-1,4-dihydropyridin-3-yl-sulfonyl)guanidine with either 2-oxoalkanoic acids and its esters, or phenylglyoxylic hydrates in glacial acetic acid. Some of them exhibited reasonable or moderate anticancer activity toward human cancer cell lines, HCT-116, MCF-7 and HeLa. The structure of this novel heterocyclic ring system was confirmed by ¹D-NMR and ²D-NMR spectroscopic data including COSY, ROESY and HMBC, elemental analyses and MS spectrometry. PMID:26729078

  4. 1α,25 dihydroxi-vitamin D{sub 3} modulates CDK4 and CDK6 expression and localization

    SciTech Connect

    Irazoqui, Ana P.; Heim, Nadia B.; Boland, Ricardo L.; Buitrago, Claudia G.

    2015-03-27

    We recently reported that the vitamin D receptor (VDR) and p38 MAPK participate in pro-differentiation events triggered by 1α,25(OH){sub 2}-vitamin D{sub 3} [1,25D] in skeletal muscle cells. Specifically, our studies demonstrated that 1,25D promotes G0/G1 arrest of cells inducing cyclin D3 and cyclin dependent kinases inhibitors (CKIs) p21{sup Waf1/Cip1} and p27{sup Kip1} expression in a VDR and p38 MAPK dependent manner. In this work we present data indicating that cyclin-dependent kinases (CDKs) 4 and 6 also play a role in the mechanism by which 1,25D stimulates myogenesis. To investigate VDR involvement in hormone regulation of CDKs 4 and 6, we significantly reduced its expression by the use of a shRNA against mouse VDR, generating the skeletal muscle cell line C2C12-VDR. Investigation of changes in cellular cycle regulating proteins by immunoblotting showed that the VDR is involved in the 1,25D –induced CDKs 4 and 6 protein levels at 6 h of hormone treatment. CDK4 levels remains high during S phase peak and G0/G1 arrest while CDK6 expression decreases at 12 h and increases again al 24 h. The up-regulation of CDKs 4 and 6 by 1,25D (6 h) was abolished in C2C12 cells pre-treated with the ERK1/2 inhibitor, UO126. Moreover, CDKs 4 and 6 expression induced by the hormone nor was detected when α and β isoforms of p38 MAPK were inhibited by compound SB203580. Confocal images show that there is not co-localization between VDR and CDKs at 6 h of hormone treatment, however CDK4 and VDR co-localizates in nucleus after 12 h of 1,25D exposure. Of relevance, at this time 1,25D promotes CDK6 localization in a peri-nuclear ring. Our data demonstrate that the VDR, ERK1/2 and p38 MAPK are involved in the control of CDKs 4 and 6 by 1,25D in skeletal muscle cells sustaining the operation of a VDR and MAPKs –dependent mechanism in hormone modulation of myogenesis. - Highlights: • 1,25D modulates CDKs 4 and 6 expression in skeletal muscle cells. • CDK4 co

  5. 4-Amino-2,8-dimethyl-6H-pyrimido[1,2-a][1,3,5]triazin-6-one1

    PubMed Central

    Sachdeva, Nikhil; Dolzhenko, Anton V.; Tan, Geok Kheng; Koh, Lip Lin; Chui, Wai Keung

    2010-01-01

    In the title compound, C8H9N5O, the mean planes through the pyrimidine and triazine rings form a dihedral angle of 2.83 (16)°. The amino group adopts a trigonal-planar configuration and forms an intra­molecular resonance-assisted N—H⋯O=C hydrogen bond with the carbonyl group. In the crystal, mol­ecules are linked via inter­molecular N—H⋯N hydrogen bonds into chains of C 2 2(6)[R 2 2(6)] motif. The molecules form two types of sheet parallel to (201) and (01), respectively. PMID:21588357

  6. 26 CFR 1.411(d)-3 - Section 411(d)(6) protected benefits.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ..., provisions relating to years of service and compensation. (ii) Amendments effective with the same applicable... section, a plan amendment that satisfies the applicable requirements under 29 CFR 2530.203-2(c) (rules... of a participant's highest 3 consecutive years of compensation. As of January 1, 2007, Participant...

  7. JAK1 Activates STAT3 Activity in Non-Small-Cell Lung Cancer cells and IL-6 Neutralizing Antibodies can Suppress JAK1-STAT3 Signaling

    PubMed Central

    Song, Lanxi; Rawal, Bhupendra; Nemeth, Jeffrey A.; Haura, Eric B.

    2014-01-01

    Members of the signal transducer and activator of transcription (STAT) family of transcription factors are potential targets for the treatment and prevention of cancers including non-small-cell lung cancer. STAT proteins can be phosphorylated and activated by diverse upstream kinases including cytokine receptors and tyrosine kinases. We examined STAT protein activation in lung cancer cell lines including those with activating mutations in the EGFR and examined upstream kinases responsible for STAT3 phosphorylation and activation using small molecules, antibodies, and RNA interference. We found more pronounced STAT3 activation in cells with activating EGFR mutations yet inhibition of EGFR activity had no effect on STAT3 activation. Inhibition of JAK1 with small molecules or RNA interference resulted in loss of STAT3 tyrosine phosphorylation and inhibition of cell growth. An interleukin-6 neutralizing antibody, siltuximab (CNTO 328) could inhibit STAT3 tyrosine phosphorylation in a cell-dependent manner. Siltuximab could completely inhibit STAT3 tyrosine phosphorylation in H1650 cells and this resulted in inhibition of lung cancer cell growth in vivo. Combined EGFR inhibition with erlotinib and siltuximab resulted in dual inhibition of both tyrosine and serine STAT3 phosphorylation, more pronounced inhibition of STAT3 transcriptional activity, and translated into combined effects on lung cancer growth in a mouse model. Our results suggest that JAK1 is responsible for STAT3 activation in lung cancer cells, and that indirect attacks on JAK1-STAT3 using an IL-6 neutralizing antibody with or without EGFR inhibition can inhibit lung cancer growth in lung cancer subsets. PMID:21216930

  8. Interleukin-6-Specific Activation of the C/EBPδ Gene in Hepatocytes Is Mediated by Stat3 and Sp1

    PubMed Central

    Cantwell, Carrie A.; Sterneck, Esta; Johnson, Peter F.

    1998-01-01

    C/EBPδ (CCAAT/enhancer binding protein δ) has been implicated as a regulator of acute-phase response (APR) genes in hepatocytes. Its expression increases dramatically in liver during the APR and can be induced in hepatic cell lines by interleukin-6 (IL-6), an acute-phase mediator that activates transcription of many APR genes. Here we have investigated the mechanism by which C/EBPδ expression is regulated by IL-6 in hepatoma cells. C/EBPδ promoter sequences to −125 bp are sufficient for IL-6 inducibility of a reporter gene and include an APR element (APRE) that is essential for IL-6 responsiveness. DNA binding experiments and transactivation assays demonstrate that Stat3, but not Stat1, interacts with this APRE. Two Sp1 sites, one of which is adjacent to the APRE, are required for IL-6 induction and transactivation by Stat3. Thus, Stat3 and Sp1 function cooperatively to activate the C/EBPδ promoter. Replacement of the APRE with Stat binding elements (SBEs) from the ICAM-1 or C/EBPβ promoter, both of which recognize both Stat1 and Stat3, confers responsiveness to gamma interferon, a cytokine that selectively activates Stat1. Sequence comparisons suggest that the distinct Stat binding specificities of the C/EBPδ and C/EBPβ SBEs are determined primarily by a single base pair difference. Our findings indicate that the cytokine specificity of C/EBPδ gene expression is governed by the APRE sequence. PMID:9528783

  9. 1,3-Dichloro-2-propanol induced hyperlipidemia in C57BL/6J mice via AMPK signaling pathway.

    PubMed

    Lu, Jing; Huang, Guoren; Hu, Sizhuo; Wang, Zhenning; Guan, Shuang

    2014-02-01

    1,3-Dichloro-2-propanol (1,3-DCP) is a well-known contaminant that has been detected in a wide range of foods. Dietary intake represents the greatest source of exposure to 1,3-DCP. In the study, we first found 1,3-DCP could induce hyperlipidemia in C57BL/6J mice below 1 mg/kg/day. We investigated serum lipid profile, liver total cholesterol (TC) and triglyceride (TG), histopathology of Liver and adipose tissue. The results showed 1,3-DCP dose dependently increased serum TG, TC and low-density lipoprotein cholesterol (LDL-C), decreased serum high-density lipoprotein cholesterol (HDL-C), increased relative liver weight, liver TG and TC, relative adipose tissue weight and enlarged the size of adipose cells. Because AMPK signal pathway is important in the process of lipid metabolism, we further investigated the effects of 1,3-DCP on AMPK signaling pathway in murine models. The results showed that 1,3-DCP (0.1-1 mg/kg/day) decreased p-AMPK/tAMPK ratio, p-ACC/tACC ratio, PPARα expression, but increased FAT, SREBP1, HMGCR and FAS expression. These observations indicated that 1,3-DCP induced hyperlipidemia in C57BL/6J mice at least partially through regulating AMPK signaling pathway. PMID:24333398

  10. Novel C6-substituted 1,3,4-oxadiazinones as potential anti-cancer agents

    PubMed Central

    Jung, Yujin; Yun, Hye Jeong; Min, Hye-Young; Lee, Ho Jin; Pham, Phuong Chi; Moon, Jayoung; Kwon, Dah In; Lim, Bumhee; Suh, Young-Ger; Lee, Jeeyeon; Lee, Ho-Young

    2015-01-01

    The insulin-like growth factor 1 receptor (IGF-1R) is a membrane receptor tyrosine kinase over-expressed in a number of tumors. However, combating resistance is one of the main challenges in the currently available IGF-1R inhibitor-based cancer therapies. Increased Src activation has been reported to confer resistance to anti-IGF-1R therapeutics in various tumor cells. An urgent unmet need for IGF-1R inhibitors is to suppress Src rephosphorylation induced by current anti-IGF-1R regimens. In efforts to develop effective anticancer agents targeting the IGF-1R signaling pathway, we explored 2-aryl-1,3,4-oxadiazin-5-ones as a novel scaffold that is structurally unrelated to current tyrosine kinase inhibitors (TKIs). The compound, LL-2003, exhibited promising antitumor effects in vitro and in vivo; it effectively suppressed IGF-1R and Src and induced apoptosis in various non-small cell lung cancer cells. Further optimizations for enhanced potency in cellular assays need to be followed, but our strategy to identify novel IGF-1R/Src inhibitors may open a new avenue to develop more efficient anticancer agents. PMID:26515601

  11. 1,1′,4,5-Tetra­hydro­tri­spiro­[1,3,2-di­aza­phosphole-2,2′-[1,3,5,2,4,6]tri­aza­triphosphinine-4′,6′′-dibenzo[d,f][1,3,2]dioxaphosphepine-6′,6′′′-dibenzo[d,f][1,3,2]dioxaphosphepine] acetone monosolvate

    PubMed Central

    Fontenot, Krystal R.; Easson, Michael W.; Fronczek, Frank R.; Condon, Brian D.

    2013-01-01

    The title compound, C26H22N5O4P3·C3H6O, has been achieved in a two-step synthesis that does not require chromatography. This mol­ecule contains a seven-membered spiro­cyclic ring at two P-atom positions and a five-membered ring containing new P—N bonds at the other P-atom position. Endocyclic torsion angles about the central biphenyl C—C bonds are −41.5 (3) and −44.4 (3)°, and P—N bonds of the central P3N3 ring are within the range 1.5665 (17)–1.6171 (17) Å, while the P—O distances are in the range 1.5940 (14)–1.6041 (14) Å. One N—H group makes an inter­molecular N—H⋯N hydrogen bond, forming centrosymmetric dimers, while the other N—H group makes an N—H⋯O hydrogen bond to the acetone solvent mol­ecule. The crystal was a two-component non-merohedral twin with ratio 0.811/0.189. PMID:24427109

  12. Mechanism and regioselectivity of the reversible Diels-Alder cycloaddition of 2-methyl-1,3 butadiene with C48B6N6 heterofullerene: a DFT approach.

    PubMed

    Zahedi, Ehsan

    2014-09-01

    A theoretical study of the mechanism and regioslectivity of Diels-Alder [4+2] cycloaddition reactions between 2-methyl-1,3 butadiene and hetero bonds of the most stable isomer of C48B6N6 heterofullerene have been studied at the B3LYP/6-31G(*) level. Three heterobond pathways BC, BN and NC including two regioisomers for each one are considered by different approaches. All studied reactions have normal electron demand nature and corresponding regioisomers are produced via asynchronous processes. Predicted regioselectivities using electronic and energetic results are in complete agreement with each other and show that BC heterobond pathway is more active than others and regioisomer 16 is the major. The local reactivity difference values (Rk) show that all reaction sites at C48B6N6 present ambiphilic activation while reaction sites at 2-methyl-1,3 butadiene show nucleophilic activation. Therefore, it is predictable that C48B6N6 should present electrophilic nature. Plotting of ΔRk and Δs values of six studied channels toward corresponding activation Gibbs free energies showed that the regioisomeric channel with lower ΔRk and Δs values is faster and vice versa. PMID:25203975

  13. VUV spectroscopy of complex fluoride systems Na0.4(Y1-xREx)0.6F2.2 (RE3+ = Nd3+, Tm3+)

    NASA Astrophysics Data System (ADS)

    Makhov, V. N.; Uvarova, T. V.; Kirm, M.; Vielhauer, S.

    2016-05-01

    Emission and excitation spectra as well as luminescence decay kinetics of complex non-stoichiometric fluoride crystals Na0.4(Y1-xNdx)0.6F2.2 (x = 0.005, 0.05, 0.2, 1) and Na0.4(Y1-xTmx)0.6F2.2 (x = 0.0005, 0.01, 0.05, 0.1) have been studied in the VUV spectral range at liquid-helium (T ∼ 10 K) temperatures. It has been shown that these crystals show intense broad-band VUV luminescence due to the interconfiguration 5d-4f transitions in Nd3+ and Tm3+ ions. Remarkable concentration quenching is observed for Nd3+ 5d-4f luminescence whereas fast (spin-allowed) 5d-4f luminescence of Tm3+ shows no concentration quenching for the studied doping level up to 10%. The spin-allowed 5d-4f luminescence of Tm3+ in these crystals was found to be rather weak compared to spin-forbidden 5d-4f luminescence because of efficient nonradiative relaxation from higher-energy 5d states of Tm3+ to the lowest-energy 5d level responsible for spin-forbidden 5d-4f luminescence. The studied fluoride systems can be considered as promising active media for the development of VUV solid state lasers with optical pumping.

  14. cAMP/PKA enhances interleukin-1β-induced interleukin-6 synthesis through STAT3 in glial cells.

    PubMed

    Tanabe, Kumiko; Kozawa, Osamu; Iida, Hiroki

    2016-01-01

    We previously reported that interleukin (IL)-1β induces IL-6 synthesis via activation of the IκB/NFκB pathway, p38 mitogen-activated protein (MAP) kinase, stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK), and signal transducer and activator of transcription (STAT)3, but not p44/p42 MAP kinase in rat glioma cell line, C6 cells and that cAMP enhances the IL-6 synthesis. However, the details behind enhancement of IL-1β-induced IL-6 synthesis by cAMP remain to be elucidated. In the present study, we investigated the exact mechanism of cAMP underlying the amplification of IL-1β-induced IL-6 synthesis in C6 cells. 8-Bromo cAMP significantly enhanced IL-1β-induced STAT3 phosphorylation without affecting phosphorylation of IκB, p38 MAP kinase or SAPK/JNK. In addition, we found that forskolin, a direct activator of adenylyl cyclase, significantly enhanced IL-1β-induced STAT3 phosphorylation. Janus family of tyrosine kinase (JAK) inhibitor I markedly suppressed the amplification by 8-bromo cAMP of IL-1β-induced IL-6 release. IL-1β induced JAK2 phosphorylation, and FLLL32, a specific JAK2 inhibitor, significantly reduced IL-1β-stimulated IL-6 release. 4-Cyano-3-methylisoquinoline, an inhibitor of protein kinase A (PKA), significantly attenuated the enhancing effect of 8-bromo cAMP on IL-1β-induced STAT3 phosphorylation. 8-Bromo cAMP markedly induced JAK2 phosphorylation. PKA siRNA transfection reduced enhancement of IL-1β-induced IL-6 release by 8-bromo cAMP. In conclusion, our results strongly suggest that the adenylyl cyclase/cAMP/PKA pathway upregulates IL-1β-induced IL-6 synthesis through enhancement of the JAK2/STAT3 pathway in C6 glioma cells. PMID:26527061

  15. Immunomodulatory and neuroprotective effects of ginsenoside Rg1 in the MPTP(1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) -induced mouse model of Parkinson's disease.

    PubMed

    Zhou, Ting-ting; Zu, Guo; Wang, Xi; Zhang, Xiao-gang; Li, Shao; Liang, Zhan-hua; Zhao, Jie

    2015-12-01

    Ginsenoside Rg1, one of the biologically active ingredients of ginseng, has been considered to be a candidate neuroprotective drug. The objective of the study was to study the protective effects of Rg1 through the peripheral and central inflammation in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease (PD) mouse model. Rg1 treatment protected TH-positive cells in the SNpc region from MPTP toxicity measured with immunofluoresence. The protein expression levels of TH in the SNpc region of MPTP-induced mice following treatment with Rg1 were higher than MPTP-induced mice which were tested with Western blot. The ratio of CD3(+)CD4(+) to CD3(+)CD8(+) T cells and CD4(+)CD25(+)Foxp3(+) regulatory T cells in the blood increased in MPTP-induced mice following treatment with Rg1 which were detected by flow cytometry analysis. Moreover, Rg1 reduced the serum concentrations of proinflammatory cytokines TNF-α, IFN-γ, IL-1β and IL-6 which were tested with enzyme-linked immunosorbent assay (ELISA). In addition, Rg1 inhibited the activation of microglia and reduced the infiltration of CD3(+) T cells into the SNpc region which were measured by immunofluorescence. Our results indicated that Rg1 may represent a promising drug for the treatment of PD via the regulation of the peripheral and central inflammation. PMID:26548343

  16. A retro-evolution study of CDP-6-deoxy-D-glycero-L-threo-4-hexulose-3-dehydrase (E1) from Yersinia pseudotuberculosis: implications for C-3 deoxygenation in the biosynthesis of 3,6-dideoxyhexoses.

    PubMed

    Wu, Qingquan; Liu, Yung-Nan; Chen, Huawei; Molitor, Erich J; Liu, Hung-wen

    2007-03-27

    CDP-6-deoxy-l-threo-d-glycero-4-hexulose-3-dehydrase (E1), which catalyzes C-3 deoxygenation of CDP-4-keto-6-deoxyglucose in the biosynthesis of 3,6-dideoxyhexoses, shares a modest sequence identity with other B6-dependent enzymes, albeit with two important distinctions. It is a rare example of a B6-dependent enzyme that harbors a [2Fe-2S] cluster, and a highly conserved lysine that serves as an anchor for PLP in most B6-dependent enzymes is replaced by histidine at position 220 in E1. Since alteration of His220 to a lysine residue may produce a putative progenitor of E1, the H220K mutant was constructed and tested for the ability to process the predicted substrate, CDP-4-amino-4,6-dideoxyglucose, using PLP as the coenzyme. Our data showed that H220K-E1 has no dehydrase activity, but can act as a PLP-dependent transaminase. However, the reaction is not catalytic since PLP cannot be regenerated during turnover. Reported herein are the results of this investigation and the implications for the role of His220 in the catalytic mechanism of E1. PMID:17323931

  17. Dextromethorphan prevents the diethyldithiocarbamate enhancement of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine toxicity in mice.

    PubMed

    Vaglini, Francesca; Pardini, Carla; Bonuccelli, Ubaldo; Maggio, Roberto; Corsini, Giovanni U

    2003-05-30

    In this report we show that dextromethorphan, a non-opioid cough suppressant, prevents the neurodegeneration of dopaminergic neurons in the substantia nigra of mice treated with diethyldithiocarbamate (DDC) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). This effect is further substantiated by the assessment of dopamine (DA) content in the striatum of these animals. Dextromethorphan does not attenuate the striatal DA fall induced by MPTP alone but completely prevents DDC-induced enhancement after the combined treatment. Moreover, a study of DA metabolites has confirmed this neuroprotective property. The striatal levels of serotonin, which were studied as a control neuronal marker, did not change with any of the treatments administered. Furthermore, we show that dextromethorphan reduces the toxicity of glutamate against dopamine neurons in mesencephalic cell cultures. In line with previous data suggesting that dextromethorphan can prevent neuronal damage, our observations supply new evidence regarding the possibility of this compound being of therapeutic use in neurodegenerative diseases. PMID:12738074

  18. 5-Demethylnobiletin and 5-Acetoxy-6,7,8,3',4'-pentamethoxyflavone Suppress Lipid Accumulation by Activating the LKB1-AMPK Pathway in 3T3-L1 Preadipocytes and High Fat Diet-Fed C57BL/6 Mice.

    PubMed

    Tung, Yen-Chen; Li, Shiming; Huang, Qingrong; Hung, Wei-Lun; Ho, Chi-Tang; Wei, Guor-Jien; Pan, Min-Hsiung

    2016-04-27

    Polymethoxyflavones (PMFs) and hydroxylated polymethoxyflavones (HPMFs), such as nobiletin (Nob) and 5-demethylnobiletin (5-OH-Nob), are unique flavonoids that are found exclusively in citrus peels. Nobiletin has been shown to suppress adipogenesis in vitro, but the antiadipogenic activity of 5-OH-Nob has not been investigated. Both nobiletin and 5-OH-Nob have poor aqueous solubility and low oral bioavailability. We employed chemical modification to produce the acetyl derivative of 5-OH-Nob, that is, 5-acetyloxy-6,7,8,3',4'-pentamethoxyflavone (5-Ac-Nob), to improve its bioavailability and bioactive efficiency. We found that 5-Ac-Nob reduced triacylglycerol (TG) content to a greater extent than 5-OH-Nob in 3T3-L1 preadipocytes. Orally administered 5-Ac-Nob resulted in a significant reduction in body weight, intra-abdominal fat, plasma and liver TG levels, and plasma cholesterol level in high fat diet-induced obese male C57BL/6J mice. The 5-Ac-Nob treatment decreased lipid accumulation by triggering the adenosine 5'-monophosphate-activated protein kinase (AMPK) pathway to alter transcriptional factors or lipogenesis-related enzymes in vivo and in vitro. PMID:27041493

  19. Hierarchical cobalt-formate framework series with (4{sup 12}⋅6{sup 3})(4{sup 9}⋅6{sup 6}){sub n} (n = 13) topologies exhibiting slow dielectric relaxation and weak ferromagnetism

    SciTech Connect

    Shang, Ran; Chen, Sa; Hu, Ke-Li; Jiang, Ze-Chun; Wang, Bing-Wu; Wang, Zhe-Ming E-mail: gaosong@pku.edu.cn; Gao, Song E-mail: gaosong@pku.edu.cn; Kurmoo, Mohamedally

    2014-12-01

    The employment of linear di-, tri-, and tetra-ammoniums has generated a hierarchy in the binodal (4{sup 12}⋅6{sup 3})(4{sup 9}⋅6{sup 6}){sub n} topologies with n = 1, 2, and 3, respectively, for the cobalt formate frameworks with increasing length of the cavities to match the ammoniums. This indicates the length-directing effect of the polyammoniums. The dynamic movements of polyammoniums between favored sites or orientations within the cavities lead to slow dielectric relaxations. All materials are spin-canted antiferromagnets in low temperatures and show reduced spontaneous magnetizations from di- and tri-, to tetra-ammoniums, because of the increased number of unique Co ions or the antiferromagnetically coupled sublattices.

  20. Synthesis and photosensitivity characterizations of 9-(6-bromo-4-oxo-4H-chromen-3-yl)-3,4,6,7-tetrahydro-3,3,6,6-tetramethyl-2H-xanthene-1,8-(5H,9H)-dione(BOCTTX)

    NASA Astrophysics Data System (ADS)

    Ibrahim, Magdy A.; Farag, A. A. M.; Roushdy, N.; El-Gohary, Nasser M.

    2016-02-01

    Condensation reaction of 6-bromochromone-3-carboxaldehyde (1) with dimedone afforded 9-(6-bromo-4-oxo-4H-chromen-3-yl)-3,4,6,7-tetrahydro-3,3,6,6-tetramethyl-2H-xanthene-1,8-(5H,9H)-dione (3, BOCTTX). Structure of BOCTTX was deduced based on its correct elemental analysis and spectral data (IR, 1H NMR, 13C NMR and mass spectra). Thin films of BOCTTX were prepared in this study by using spin coating technique. X-ray diffraction, scanning electron microscope analysis were studied for study the crystal and morphology characterization of BOCTTX. The results indicate that BOCTTX has a polycrystalline nature with monoclinic structure. From differential scanning calorimetry, BOCTTX is found to be thermally stable up to 583 K and the chemical structure plays an important role in the thermal decomposition process. The optical absorption of the film was studied in the UV-Vis spectral range and the value of two allowed energy gaps of 2.2 and 3.3 eV. Current-voltage characteristics of BOCTTX based devices were studied in dark and under various illumination intensities in the range 20-100 mW/cm2. Electrical and photoelectrical parameters were studied as a function of light intensity. The obtained results exhibits photoconductivity cauterization and suggest that the diode can be used as a photodiode in optoelectronic sensor application.

  1. A Review of Subsurface Behavior of Plutonium and Americium at the 200-PW-1/3/6 Operable Units

    SciTech Connect

    Cantrell, Kirk J.; Riley, Robert G.

    2008-01-31

    This report begins with a brief summary of the history and current status of 200-PW-1/3/6 OUs in section 2.0. This is followed by a description of our concentual model of Pu/Am migration at the 200-PW-1/3/6 OUs, during both past artificial recharge conditions and current natural recharge condictions (section 3.0). Section 4.0 discusses data gaps and information needs. The final section (section 5.0) provides recommendations for futher work to address the data gaps and information needs identified in section 4.0.

  2. 40 CFR 721.5260 - 1,3,6-Naphthalenetrisulfonic acid, 7-[[2-[(aminocarbonyl)amino]- 4-[[4-[[2-[2-(ethenylsulfonyl...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...- - 4- ethyl]amino]- 6-fluoro-1,3,5-triazin-2-yl]amino]phenyl]azo], trisodium salt. 721.5260 Section 721...,3,6-Naphthalenetrisulfonic acid, 7- - 4- ethyl]amino]- 6-fluoro-1,3,5-triazin-2-yl]amino]phenyl]azo... substance identified as 1,3,6-Naphthalenetrisulfonic acid, 7- -4-......

  3. 40 CFR 721.5260 - 1,3,6-Naphthalenetrisulfonic acid, 7-[[2-[(aminocarbonyl)amino]- 4-[[4-[[2-[2-(ethenylsulfonyl...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...- - 4- ethyl]amino]- 6-fluoro-1,3,5-triazin-2-yl]amino]phenyl]azo], trisodium salt. 721.5260 Section 721...,3,6-Naphthalenetrisulfonic acid, 7- - 4- ethyl]amino]- 6-fluoro-1,3,5-triazin-2-yl]amino]phenyl]azo... substance identified as 1,3,6-Naphthalenetrisulfonic acid, 7- -4-......

  4. Inositol 1,3,4,5,6-Pentakisphosphate 2-Kinase from Maize: Molecular and Biochemical Characterization[OA

    PubMed Central

    Sun, Yuejin; Thompson, Mark; Lin, Gaofeng; Butler, Holly; Gao, Zhifang; Thornburgh, Scott; Yau, Kerrm; Smith, Doug A.; Shukla, Vipula K.

    2007-01-01

    Inositol 1,3,4,5,6-pentakisphosphate 2-kinase, an enzyme encoded by the gene IPK1, catalyzes the terminal step in the phytic acid biosynthetic pathway. We report here the isolation and characterization of IPK1 cDNA and genomic clones from maize (Zea mays). DNA Southern-blot analysis revealed that ZmIPK1 in the maize genome constitutes a small gene family with two members. Two nearly identical ZmIPK1 paralogs, designated as ZmIPK1A and ZmIPK1B, were identified. The transcripts of ZmIPK1A were detected in various maize tissues, including leaves, silks, immature ears, seeds at 12 d after pollination, midstage endosperm, and maturing embryos. However, the transcripts of ZmIPK1B were exclusively detected in roots. A variety of alternative splicing products of ZmIPK1A were discovered in maize leaves and seeds. These products are derived from alternative acceptor sites, alternative donor sites, and retained introns in the transcripts. Consequently, up to 50% of the ZmIPK1A transcripts in maize seeds and leaves have an interrupted open reading frame. In contrast, only one type of splicing product of ZmIPK1B was detected in roots. When expressed in Escherichia coli and subsequently purified, the ZmIPK1 enzyme catalyzes the conversion of myo-inositol 1,3,4,5,6-pentakisphosphate to phytic acid. In addition, it is also capable of catalyzing the phosphorylation of myo-inositol 1,4,6-trisphosphate, myo-inositol 1,4,5,6-tetrakisphosphate, and myo-inositol 3,4,5,6-tetrakisphosphate. Nuclear magnetic resonance spectroscopy analysis indicates that the phosphorylation product of myo-inositol 1,4,6-trisphosphate is inositol 1,2,4,6-tetrakisphosphate. Kinetic studies showed that the Km for ZmIPK1 using myo-inositol 1,3,4,5,6-pentakisphosphate as a substrate is 119 μm with a Vmax at 625 nmol/min/mg. These data describing the tissue-specific accumulation and alternative splicing of the transcripts from two nearly identical ZmIPK1 paralogs suggest that maize has a highly sophisticated

  5. Homochiral 3D metal-organic frameworks from chiral 1D rods: 6-way helical packing.

    PubMed

    Shin, Sung Min; Moon, Dohyun; Jeong, Kyung Seok; Kim, Jaheon; Thallapally, Praveen K; Jeong, Nakcheol

    2011-09-01

    The chiral 3D MOFs resulted from the packing of chiral 1D SBBs were studied. It was demonstrated that the final packing pattern is sensitively dependent on the dimension of SBBs. In addition, we were able to identify a new plywood-like network from ligand 2H(2) exhibiting an unprecedented six-way chiral helical packing motif, which extends the list of invariant rod packings. PMID:21773637

  6. NTP Toxicology and Carcinogenesis Studies of 1,3-Butadiene (CAS No. 106-99-0) in B6C3F1 Mice (Inhalation Studies).

    PubMed

    1984-08-01

    1,3-Butadiene is used as an intermediate in the production of elastomers, polymers, and other chemicals. Of the 1,3-butadiene used in 1978, 44% was used to manufacture styrene-butadiene rubber (a substitute for natural rubber, produced by copolymerization of 1,3-butadiene with styrene), and 19% was used to produce polybutane elastomer (a substance that increases resistance of tire products to wear, heat degradation, and blowouts). Chloroprene monomer, derived from 1,3-butadiene, is used exclusively to manufacture neoprene elastomers for non-tire and latex applications. Commercial nitrile rubber, used largely in rubber hoses, seals, and gaskets for automobiles, is a copolymer of 1,3-butadiene and acrylonitrile. Acrylonitrile- butadiene- styrene resins, usually containing 20%-30% 1,3-butadiene by weight, are used to make parts for automobiles and appliances. Other polymer uses include specialty polybutadiene polymers, thermoplastic elastomers, nitrile barrier resins, and K resins(R). 1,3-Butadiene is used as an intermediate in the production of a variety of industrial chemicals, including two fungicides, captan and captofol. It is approved by the U.S. Food and Drug Administration for use in the production of adhesives used in articles for packaging, transporting, or holding food; in components of paper and paperboard that are in contact with dry food; and as a modifier in the production of semigrid and rigid vinyl chloride plastic food-contact articles. No information was located on the levels of monomer or on its elution rate from any of the commercially available polymers. It is not known if unreacted 1,3-butadiene migrated from packaging materials. Male and female B6C3F1 mice were exposed to air containing 1,3-butadiene (greater than 99% pure) at concentrations of 0-8,000 ppm in 15-day and 14-week inhalation studies. In the 15-day studies, survival was unaffected by dose, and no pathologic effects were observed; slight decreases in mean body weight occurred at the

  7. Benzoxaborole antimalarial agents. Part 4. Discovery of potent 6-(2-(alkoxycarbonyl)pyrazinyl-5-oxy)-1,3-dihydro-1-hydroxy-2,1-benzoxaboroles.

    PubMed

    Zhang, Yong-Kang; Plattner, Jacob J; Easom, Eric E; Jacobs, Robert T; Guo, Denghui; Sanders, Virginia; Freund, Yvonne R; Campo, Brice; Rosenthal, Philip J; Bu, Wei; Gamo, Francisco-Javier; Sanz, Laura M; Ge, Min; Li, Liang; Ding, Jie; Yang, Yin

    2015-07-01

    A series of 6-hetaryloxy benzoxaborole compounds was designed and synthesized for a structure-activity relationship (SAR) investigation to assess the changes in antimalarial activity which result from 6-aryloxy structural variation, substituent modification on the pyrazine ring, and optimization of the side chain ester group. This SAR study discovered highly potent 6-(2-(alkoxycarbonyl)pyrazinyl-5-oxy)-1,3-dihydro-1-hydroxy-2,1-benzoxaboroles (9, 27-34) with IC50s = 0.2-22 nM against cultured Plasmodium falciparum W2 and 3D7 strains. Compound 9 also demonstrated excellent in vivo efficacy against P. berghei in infected mice (ED90 = 7.0 mg/kg). PMID:26067904

  8. Benzoxaborole Antimalarial Agents. Part 4. Discovery of Potent 6-(2-(Alkoxycarbonyl)pyrazinyl-5-oxy)-1,3-dihydro-1-hydroxy-2,1-benzoxaboroles

    PubMed Central

    2016-01-01

    A series of 6-hetaryloxy benzoxaborole compounds was designed and synthesized for a structure–activity relationship (SAR) investigation to assess the changes in antimalarial activity which result from 6-aryloxy structural variation, substituent modification on the pyrazine ring, and optimization of the side chain ester group. This SAR study discovered highly potent 6-(2-(alkoxycarbonyl)pyrazinyl-5-oxy)-1,3-dihydro-1-hydroxy-2,1-benzoxaboroles (9, 27–34) with IC50s = 0.2–22 nM against cultured Plasmodium falciparum W2 and 3D7 strains. Compound 9 also demonstrated excellent in vivo efficacy against P. berghei in infected mice (ED90 = 7.0 mg/kg). PMID:26067904

  9. Natural Product-Based 6-Hydroxy-2,3,4,6-tetrahydropyrrolo[1,2-a]pyrimidinium Scaffold as a New Antifungal Template

    PubMed Central

    2011-01-01

    Synthetic analogues of the marine-derived class of natural products phloeodictines have been prepared and exhibited potent in vitro fungicidal activities against a broad array of fungal pathogens including drug-resistant strains. The 6-hydroxy-2,3,4,6-tetrahydropyrrolo[1,2-a]pyrimidinium structural moiety with a C12 to C16 aliphatic side chain at C-6 has been shown to be the antifungal pharmacophore and may serve as a new antifungal template for further lead optimization. PMID:21743827

  10. 3-(2-Fluoro-phen-yl)-6-(phenoxy-meth-yl)-1,2,4-triazolo[3,4-b][1,3,4]thia-diazole.

    PubMed

    Holm, Melanie; Schollmeyer, Dieter; Laufer, Stefan

    2008-01-01

    The crystal structure of the title compound, C(16)H(11)FN(4)OS, was synthesized in the course of our studies on 1,2,4-triazolo[3,4-b][1,3,4]thia-diazo-les as inhibitors of p38 mitogen-activated protein kinase (MAPK). The three-dimensional data obtained were used to generate a three-dimensional pharmacophore model for in silico database screening. The dihedral angles between the central heterocylic system and the fluoro-phenyl and phenyl rings are 20.21 (3) and 5.43 (1)°, respectively; the dihedral angle between the two benzene rings is 15.80 (4)°. PMID:21202091

  11. Illegitimate RAG-mediated recombination events are involved in IKZF1 Δ3-6 deletion in BCR-ABL1 lymphoblastic leukaemia.

    PubMed

    Dong, Y; Liu, F; Wu, C; Li, S; Zhao, X; Zhang, P; Jiao, J; Yu, X; Ji, Y; Zhang, M

    2016-09-01

    Breakpoint cluster region-Abelson murine leukaemia viral oncogene homologue 1 (BCR-ABL1), encoded by the Philadelphia (Ph) chromosome, is the characteristic of chronic myeloid leukaemia (CML) and a subset of acute lymphoblastic leukaemia (ALL). We demonstrated that expression of the Ik6 transcript, which lacked exons 3-6, was observed exclusively in BCR-ABL1(+) B ALL and lymphoid blast crisis CML (BC-CML) patients harbouring the IKZF1 Δ3-6 deletion. To confirm the hypothesis that illegitimate recombination activating gene protein (RAG)-mediated recombination events are involved in IKZF1 Δ3-6 deletion in BCR-ABL1 lymphoblastic leukaemia, we first demonstrated that the expression rates of RAG1 and RAG2, collectively called RAG, were higher in ALL and BC-CML (lymphoid). Notably, analysis of relationships among RAG, BCR-ABL1 and Ikaros 6 (Ik6) showed that Ik6 can be generated only if RAG and BCR-ABL1 are co-existing. The sequencing data showed that the deleted segments of introns 2 and 6 contained cryptic recombination signal sequences (cRSSs) and frequently had non-template nucleotides inserted between breakpoints. Furthermore, we used chromatin immunoprecipitation (ChIP) technology and demonstrated that the sequences directly flanking IKZF1 Δ3-6 deletion breakpoints have significantly higher levels of histone H3 lysine 4 trimethylation (H3K4me3) modifications. Overall, RAG expression, good-quality cRSS and a specific chromatin modification, H3K4me3, satisfy the conditions of RAG's off-target effects on IKZF1. Our work provides evidence for RAG-mediated IKZF1 Δ3-6 deletion. Our results raise the prospect that RAG is a valuable biomarker in disease surveillance. Dissecting the contribution of RAG should not only provide valuable mechanistic insights, but will also lead to a new therapeutic direction. PMID:27198500

  12. Structural and computational characterization of 4‧,4‧,6‧,6‧-tetrachloro-3-(2-methoxyethyl)-3H,4H-spiro-1,3,2-benzoxaza phosphinine-2,2‧- [1,3,5,2,4,6] triazatriphosphinine

    NASA Astrophysics Data System (ADS)

    Işıklan, Muhammet; Yıldırım, Erdem Kamil; Atiş, Murat; Sonkaya, Ömer; Çoşut, Bünyemin

    2016-08-01

    In this study a new monospirocyclic phosphazene derivative, 4‧,4‧,6‧,6‧-tetrachloro-3-(2-methoxyethyl)-3H,4H-spiro [1,3,2-benzoxazaphosphinine-2,2‧- [1,3,5,2,4,6] triazatriphosphinine] (SP1) was synthesized from the reaction of hexachlorocyclotriphosphazene (N3P3Cl6) with N/O donor-type, 2-{[(2-Metoxyethyl) amino]methyl}phenol. The structural investigations of the compound were verified by elemental analyses, MS, FTIR, 1H, 13C, 31P NMR spectroscopy and the single crystal X-ray diffraction analysis. The structural and spectroscopic data of the molecule in the ground state were calculated by using density functional method (DFT) using 6-311++G (d, p) basis set. The complete assignments of all vibrational modes were performed on the basis of the total energy distributions (TED). Isotropic chemical shifts (31P, 1H and 13C NMR) were calculated using the gauge-invariant atomic orbital (GIAO) method. Theoretical calculations of bond parameters, harmonic vibration frequencies and nuclear magnetic resonance are in good agreement with experimental results. The electrophilic and nucleophilic attack centers in SP1 were predicted with the local softness values (sk+, and sk-) of individual atoms and it is confirmed that P atoms of the PCl2 groups are nucleophilic attack centers.

  13. 6-Bromo-2-methyl­sulfanyl-1,3-benzo­thia­zole

    PubMed Central

    Dobrowolski, Michał A.; Struga, Marta; Szulczyk, Daniel

    2011-01-01

    The title mol­ecule, C8H6BrNS2, is almost planar with a dihedral angle of 0.9 (1)° between the benzene and thia­zole rings. The values of the geometry-based index of aromaticity (HOMA) and the nucleus-independent chemical shift (NICS) for the two cyclic fragments of the title mol­ecule are 0.95 and −9.61, respectively, for the benzene ring, and 0.69 and −7.71, respectively, for the thia­zole ring. They show that the benzene ring exhibits substanti­ally higher cyclic π-electron delocalization than the thia­zole ring. Comparison with other similar benzothia­zole fragments reveals a similar trend. PMID:22199926

  14. The spectroscopic analysis of the v2=1, v5=1, and v3=v6=1 infrared vibration system of H3SiI.

    PubMed

    Canè, Elisabetta; Villa, Mattia; Tamassia, Filippo; Fusina, Luciano; Bürger, Hans; Litz, Marion

    2016-06-01

    The ν2 (A1)/ν5 (E)/ν36 (E) band system of H3(28)SiI was investigated using Fourier transform infrared spectra recorded from 820 to 1100cm(-1) at a resolution of 2.0×10(-3)cm(-1). In total, 11,903 transitions were assigned. Additional 1466 transitions reaching the v3=v6=1 state were obtained from the ν366 and ν363 hot bands near 360 and 590cm(-1), respectively. Moreover, 30 highly accurate CO2 laser sideband transitions of the (r)Q0 branch of ν5 (J.M. Frye, W. Schupita, and G. Magerl, J. Mol. Spectrosc. 128, 427 (1988)) were implemented in the data set with Jmax(″)=140andKmax(″)=21. To adequately reproduce the complex pattern of interacting levels the Hamiltonian employed included 14 off-diagonal terms. These comprise x,y Coriolis ro-vibration resonances, between ν2/ν5, ν2/ν36 and ν5/ν36, and the anharmonic Fermi resonance between ν5/ν36. All these resonances strongly perturb the v2=1, v5=1, and v3=v6=1 excited states whose rounded deperturbed vibrational term values are 904.5, 941.1, and 953.7cm(-1), respectively. In addition, the Δl=Δk=±2 l-resonance was found to be active within the v3=v6=1 state and between v5=1 and v3=v6=1; the Δl=±2,Δk=∓1 l-resonance within the v5=1 state and between v5=1 and v3=v6=1 was established, as well as the Δl=±1,Δk=∓2 α resonance between v2=1 and v5=1. A standard deviation of the fit, 0.48×10(-3)cm(-1), resulted which is ca. three times the estimated precision of experimental wavenumbers. Improved J-dependent ground state parameters of H3SiI were obtained by fitting 5420 combination differences, σ(fit)=0.22×10(-3)cm(-1). PMID:26978785

  15. The IL-6 family of cytokines modulates STAT3 activation by desumoylation of PML through SENP1 induction

    SciTech Connect

    Ohbayashi, Norihiko; Kawakami, Shiho; Muromoto, Ryuta; Togi, Sumihito; Ikeda, Osamu; Kamitani, Shinya; Sekine, Yuichi; Honjoh, Tsutomu; Matsuda, Tadashi

    2008-07-11

    Post-translational modification by small ubiquitin-like modifier (SUMO) plays an important role in the regulation of different signaling pathways and is involved in the formation of promyelocytic leukemia (PML) protein nuclear bodies following sumoylation of PML. In the present study, we found that IL-6 induces desumoylation of PML and dissociation between PML and SUMO1 in hepatoma cells. We also found that IL-6 induces mRNA expression of SENP1, a member of the SUMO-specific protease family. Furthermore, wild-type SENP1 but not an inactive SENP1 mutant restored the PML-mediated suppression of STAT3 activation. These results indicate that the IL-6 family of cytokines modulates STAT3 activation by desumoylation and inactivation PML through SENP1 induction.

  16. Spectrofluorimetric determination of nitric oxide at trace levels with 5,6-diamino-1,3-naphthalene disulfonic acid.

    PubMed

    Zhang, Xian; Wang, Hong; Liang, Shu-Cai; Zhang, Hua-Shan

    2002-03-01

    Based on the selective reaction that 5,6-diamino-1,3-naphthalene disulfonic acid (DANDS) traps nitric oxide (NO) in the presence of dioxygen to yield the highly fluorescent form, 1-[H]-naphthotriazole-6,8-disulfonic acid in moderately alkaline medium, a new spectrofluorimetric method for the determination of NO has been reported. The method offered the advantage of specificity, sensitivity and a simple protocol for the direct detection of NO in aqueous solution. The linear calibration range for NO was 0.04-1.44 mumoll(-1) with a 3sigma detection limit of 0.6 nmoll(-1). The proposed method has been used to monitor the release of NO from S-nitrosocysteine, a NO-releasing agent. PMID:18968522

  17. HEPATOCARCINOGENICITY OF CHLORAL HYDRATE, 2-CHLOROACETALDEHYDE, AND DICHLOROACETIC ACID IN THE MALE B6C3F1 MOUSE

    EPA Science Inventory

    Chloral hydrate (CH) and 2-chloroacetaldehyde (CAA) have been identified as chlorination by-products in drinking water. oth chemicals are genotoxic, but their carcinogenic potential had not been adequately tested. hese bioassays were conducted using male B6C3F1 mice exposed to 1 ...

  18. New Pyrazolo[1',5':1,6]pyrimido[4,5-d]pyridazin-4(3H)-ones Fluoroderivatives as Human A1 Adenosine Receptor Ligands.

    PubMed

    Graziano, Alessia; Giovannoni, Maria Paola; Cilibrizzi, Agostino; Crocetti, Letizia; Piaz, Vittorio Dal; Vergelli, Claudia; Trincavelli, Maria Letizia; Martini, Claudia; Giacomelli, Chiara

    2012-09-01

    In this paper we report the synthesis and biological evaluation of a new series of pyrazolo[1',5':1,6]pyrimido[4,5-d]pyridazin-4(3H)-ones as human A1 adenosine receptor ligands. The tricyclic scaffold was modified at position 6 and 9 by introducing small alkyl chains and substituted phenyls. The most interesting compounds showed Ki for A1 in the submicromolar range (0.105-0.244 µM) and the most interesting term (compound 4c) combined an appreciable affinity for A1 (Ki = 0.132 µM) with a good selectivity toward A2A (43% inhibition at 10 µM) and A3 (46% inhibition at 10 µM). PMID:24061322

  19. 40 CFR 721.5260 - 1,3,6-Naphthalenetrisulfonic acid, 7-[[2-[(aminocarbonyl)amino]- 4-[[4-[[2-[2-(ethenylsulfonyl...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...,3,6-Naphthalenetrisulfonic acid, 7- - 4- ethyl]amino]- 6-fluoro-1,3,5-triazin-2-yl]amino]phenyl]azo... substance identified as 1,3,6-Naphthalenetrisulfonic acid, 7- -4- ethyl]amino]-6-fluoro-1,3,5-triazin-2-yl... 40 Protection of Environment 32 2013-07-01 2013-07-01 false 1,3,6-Naphthalenetrisulfonic acid,...

  20. 40 CFR 721.5260 - 1,3,6-Naphthalenetrisulfonic acid, 7-[[2-[(aminocarbonyl)amino]- 4-[[4-[[2-[2-(ethenylsulfonyl...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...,3,6-Naphthalenetrisulfonic acid, 7- - 4- ethyl]amino]- 6-fluoro-1,3,5-triazin-2-yl]amino]phenyl]azo... substance identified as 1,3,6-Naphthalenetrisulfonic acid, 7- -4- ethyl]amino]-6-fluoro-1,3,5-triazin-2-yl... 40 Protection of Environment 32 2012-07-01 2012-07-01 false 1,3,6-Naphthalenetrisulfonic acid,...

  1. 40 CFR 721.5260 - 1,3,6-Naphthalenetrisulfonic acid, 7-[[2-[(aminocarbonyl)amino]- 4-[[4-[[2-[2-(ethenylsulfonyl...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...,3,6-Naphthalenetrisulfonic acid, 7- - 4- ethyl]amino]- 6-fluoro-1,3,5-triazin-2-yl]amino]phenyl]azo... substance identified as 1,3,6-Naphthalenetrisulfonic acid, 7- -4- ethyl]amino]-6-fluoro-1,3,5-triazin-2-yl... 40 Protection of Environment 31 2014-07-01 2014-07-01 false 1,3,6-Naphthalenetrisulfonic acid,...

  2. Aminopeptidase A activity of the murine B-lymphocyte differentiation antigen BP-1/6C3.

    PubMed Central

    Wu, Q; Li, L; Cooper, M D; Pierres, M; Gorvel, J P

    1991-01-01

    The predicted amino acid sequence of the cDNA encoding the murine B-lymphocyte differentiation antigen BP-1/6C3 suggested that it is a member of the zinc-dependent metalloprotease family, possibly an aminopeptidase related to aminopeptidase N [microsomal aminopeptidase; alpha-aminoacyl-peptide hydrolase (microsomal), EC 3.4.11.2]. In the present studies, we examined the enzymatic activity of this antigen. From brush border preparations of the small intestine, a rich source of many endopeptidases and exopeptidases, the BP-1 antibody selectively removed aminopeptidase A [APA; L-alpha-aspartyl(L-alpha-glutamyl)-peptide hydrolase, EC 3.4.11.7] activity. The APA activity of a panel of cell lines correlated in linear fashion with cell-surface levels of the BP-1/6C3 antigen. APA activity was demonstrated for the BP-1/6C3 antigen immunopurified from the pre-B-cell membrane. This activity was enhanced by alkaline earth metals such as Ca2+ and was abrogated by amastatin and angiotensin, which are known competitive inhibitors of APA. The data indicate that the murine BP-1/6C3 antigen is active APA, an enzyme that catalyzes specifically the removal of unsubstituted, N-terminal glutamic acid and aspartic acid residues from peptides. Images PMID:1988965

  3. DnaJ-1 and karyopherin α3 suppress degeneration in a new Drosophila model of Spinocerebellar Ataxia Type 6.

    PubMed

    Tsou, Wei-Ling; Hosking, Ryan R; Burr, Aaron A; Sutton, Joanna R; Ouyang, Michelle; Du, Xiaofei; Gomez, Christopher M; Todi, Sokol V

    2015-08-01

    Spinocerebellar ataxia type 6 (SCA6) belongs to the family of CAG/polyglutamine (polyQ)-dependent neurodegenerative disorders. SCA6 is caused by abnormal expansion in a CAG trinucleotide repeat within exon 47 of CACNA1A, a bicistronic gene that encodes α1A, a P/Q-type calcium channel subunit and a C-terminal protein, termed α1ACT. Expansion of the CAG/polyQ region of CACNA1A occurs within α1ACT and leads to ataxia. There are few animal models of SCA6. Here, we describe the generation and characterization of the first Drosophila melanogaster models of SCA6, which express the entire human α1ACT protein with a normal or expanded polyQ. The polyQ-expanded version of α1ACT recapitulates the progressively degenerative nature of SCA6 when expressed in various fly tissues and the presence of densely staining aggregates. Additional studies identify the co-chaperone DnaJ-1 as a potential therapeutic target for SCA6. Expression of DnaJ-1 potently suppresses α1ACT-dependent degeneration and lethality, concomitant with decreased aggregation and reduced nuclear localization of the pathogenic protein. Mutating the nuclear importer karyopherin α3 also leads to reduced toxicity from pathogenic α1ACT. Little is known about the steps leading to degeneration in SCA6 and the means to protect neurons in this disease are lacking. Invertebrate animal models of SCA6 can expand our understanding of molecular sequelae related to degeneration in this disorder and lead to the rapid identification of cellular components that can be targeted to treat it. PMID:25954029

  4. Integrin α3β1 regulates kidney collecting duct development via TRAF6-dependent K63-linked polyubiquitination of Akt

    PubMed Central

    Yazlovitskaya, Eugenia M.; Tseng, Hui-Yuan; Viquez, Olga; Tu, Tianxiang; Mernaugh, Glenda; McKee, Karen K.; Riggins, Karen; Quaranta, Vito; Pathak, Amrita; Carter, Bruce D.; Yurchenco, Peter; Sonnenberg, Arnoud; Böttcher, Ralph T.; Pozzi, Ambra; Zent, Roy

    2015-01-01

    The collecting system of the kidney develops from the ureteric bud (UB), which undergoes branching morphogenesis, a process regulated by multiple factors, including integrin–extracellular matrix interactions. The laminin (LM)-binding integrin α3β1 is crucial for this developmental program; however, the LM types and LM/integrin α3β1–dependent signaling pathways are poorly defined. We show that α3 chain–containing LMs promote normal UB branching morphogenesis and that LM-332 is a better substrate than LM-511 for stimulating integrin α3β1–dependent collecting duct cell functions. We demonstrate that integrin α3β1–mediated cell adhesion to LM-332 modulates Akt activation in the developing collecting system and that Akt activation is PI3K independent but requires decreased PTEN activity and K63-linked polyubiquitination. We identified the ubiquitin-modifying enzyme TRAF6 as an interactor with the integrin β1 subunit and regulator of integrin α3β1–dependent Akt activation. Finally, we established that the developmental defects of TRAF6- and integrin α3–null mouse kidneys are similar. Thus K63-linked polyubiquitination plays a previously unrecognized role in integrin α3β1–dependent cell signaling required for UB development and may represent a novel mechanism whereby integrins regulate signaling pathways. PMID:25808491

  5. Sperm-head morphology study in B6C3F1 mice following inhalation exposure to 1,3-butadiene: Final technical report

    SciTech Connect

    Hackett, P.L.; McClanahan, B.J.; Brown, M.G.; Buschbom, R.L.; Clark, M.L.; Decker, J.R.; Evanoff, J.J.; Rommereim, R.L.; Rowe, S.E.; Westerberg, R.B.

    1988-04-01

    The present report describes the results of a study of the morphology of epididymal sperm heads of B6C3F1 mice that were exposed to varying concentrations of 1,3-butadiene. During the fifth post-exposure week, the animals were killed and examined for gross lesions of the reproductive tract; suspensions of the epididymal sperm were prepared for morphologic evaluations. No mortality was observed in any of the inhalation exposure groups. Transient toxic signs, including piloerection and dyspnea, were evident during a 20- to 30-minute period following exposure to 5000 ppM. Mean values for body weights and weight gains of the mice exposed to 1,3-butadiene were not significantly different from control values. A concentration-related increase in the incidence of sperm-head abnormalities was evident and the percentage of sperm heads that were morphologically abnormal was significantly higher in mice exposed to 1000 and 5000 ppM than in the controls. 23 refs., 2 figs., 6 tabs.

  6. Local relaxation around [6]Cr3+ in synthetic pyrope knorringite garnets, [8]Mg3[6](Al1-X CrX3+)2[4]Si3O12, from electronic absorption spectra

    NASA Astrophysics Data System (ADS)

    Taran, M. N.; Langer, K.; Abs-Wurmbach, I.; Frost, D. J.; Platonov, A. N.

    2004-12-01

    Pyrope-knorringite garnets, Mg3(Al1-X Cr3+X)2Si3O12 with X=0.25, 0.50, and 1.00, were synthesized between 9 and 16 GPa and 1300 and 1600 °C, using multianvil high-pressure techniques. The garnets with X=0.25 and 0.50 are fine-grained, pink and violet in color. The end-member knorringites with X=1.00 are black when compact and gray when coarse-grained. The fine powder is greenish gray in natural light and pale pink under a tungsten lamp. Powder remission spectra in the wavenumber range 30 000 10 000 cm-1 on finely powdered crystals were measured by two different methods: (I.) by the use of a small integrating sphere for small samples or (II.) microscope-spectrometric measurement using diffusely reflected radiation from a 45° illuminated microsample. Both methods yielded similar diffuse reflectance spectra. The following crystal-field parameters of [6]Cr3+ were determined for garnets with X=0.25, 0.50, 1.00: 10 Dq=17 856, 17 596, 17 286 cm-1; and B=654, 677, 706 cm-1; nephelauxetic ratio β=(Bfield/Bfree)= 0.71, 0.74, 0.77. The β-values indicate decreasing covalency of the Cr O bond with increasing Cr content. The 10 Dq value for together with the mean Cr O distance in end-member knorringite, 1.96 Å (Novak and Gibbs 1971), were used to calculate from the spectral data, local mean Cr O distances (Langer 2001a) as a function of composition. The results indicate relatively strong local site relaxation with a value of ɛ=0.77.

  7. Refrigeration of the 18.3 GHz C_3H_2 Transition in Dark Clouds G1.6-0.25

    NASA Technical Reports Server (NTRS)

    Kuiper, T. B. H.; Whiteoak, J. B.; Peng, R. -S.; Peters, W. L., III; Reynolds, J. E.

    1993-01-01

    We have observed the 1_(10)-1_(01) (18.3 GHz) transition of orthocyclopropenylidene, C_(-3)H_(-2), at 24 positions in the unusual dense cloud G1.6- 0.025. Except for one position, the transition is refrigerated, a phenomenon which has not been seen in this transition before.

  8. 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE (MPTP)-INDUCED DAMAGE OF STRIATAL DOPAMINERGIC FIBERS ATTENUATES SUBSEQUENT ASTROCYTE RESPONSE TO MPTP

    EPA Science Inventory

    Acute administration of the dopaminergic neurotoxicant, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to the C57B1/6 mouse caused a rapid decrease in the amount of striatal tyrosine hydroxylase (TH), a marker of dopaminergic neurons, followed by a large increase in the astr...

  9. 5-(4-Hy-droxy-benzyl-idene)-2,2-dimethyl-1,3-dioxane-4,6-dione.

    PubMed

    Zeng, Wu-Lan

    2010-01-01

    The title compound, C(13)H(12)O(5), was prepared by the reaction of 2,2-dimethyl-1,3-dioxane-4,6-dione and 4-hy-droxy-benz-alde-hyde in ethanol. The 1,3-dioxane ring is in a distorted boat conformation. In the crystal, inversion dimers linked by pairs of O-H⋯O hydrogen bonds generate R(2) (2)(20) rings. PMID:21588666

  10. Automated fluorous-assisted solution-phase synthesis of β-1,2-, 1,3-, and 1,6-mannan oligomers.

    PubMed

    Tang, Shu-Lun; Pohl, Nicola L B

    2016-07-22

    Automated solution-phase syntheses of β-1,2-, 1,3-, and 1,6-mannan oligomers have been accomplished by applying a β-directing C-5 carboxylate strategy. Fluorous-tag-assisted purification after each reaction cycle allowed the synthesis of short β-mannan oligomers with limited loading of glycosyl donor-as low as 3.0 equivalents for each glycosylation cycle. This study showed the capability of the automated solution-phase synthesis protocol for synthesizing various challenging glycosides, including use of a C-5 ester as a protecting group that could be converted under reductive conditions to a hydroxymethyl group for chain extension. PMID:27155895

  11. Advanced power assessment for Czech lignite. Task 3.6, Volume 1

    SciTech Connect

    Sondreal, E.A.; Mann, M.D.; Weber, G.W.; Young, B.C.

    1995-12-01

    The US has invested heavily in research, development, and demonstration of efficient and environmentally acceptable technologies for the use of coal. The US has the opportunity to use its leadership position to market a range of advanced coal-based technologies internationally. For example, coal mining output in the Czech Republic has been decreasing. This decrease in demand can be attributed mainly to the changing structure of the Czech economy and to environmental constraints. The continued production of energy from indigenous brown coals is a major concern for the Czech Republic. The strong desire to continue to use this resource is a challenge. The Energy and Environmental Research Center undertook two major efforts recently. One effort involved an assessment of opportunities for commercialization of US coal technologies in the Czech Republic. This report is the result of that effort. The technology assessment focused on the utilization of Czech brown coals. These coals are high in ash and sulfur, and the information presented in this report focuses on the utilization of these brown coals in an economically and environmentally friendly manner. Sections 3--5 present options for utilizing the as-mined coal, while Sections 6 and 7 present options for upgrading and generating alternative uses for the lignite. Contents include Czech Republic national energy perspectives; powering; emissions control; advanced power generation systems; assessment of lignite-upgrading technologies; and alternative markets for lignite.

  12. Structures of Exocyclic R,R- and S,S-N6,N6-(2,3-Dihydroxybutan-1,4-diyl)-2′-Deoxyadenosine Adducts Induced by 1,2,3,4-Diepoxybutane

    PubMed Central

    2015-01-01

    1,3-Butadiene (BD) is an industrial and environmental chemical present in urban air and cigarette smoke, and is classified as a human carcinogen. It is oxidized by cytochrome P450 to form 1,2,3,4-diepoxybutane (DEB); DEB bis-alkylates the N6 position of adenine in DNA. Two enantiomers of bis-N6-dA adducts of DEB have been identified: R,R-N6,N6-(2,3-dihydroxybutan-1,4-diyl)-2′-deoxyadenosine (R,R-DHB-dA), and S,S-N6,N6-(2,3-dihydroxybutan-1,4-diyl)-2′-deoxyadenosine (S,S-DHB-dA) [SeneviratneU., AntsypovichS., DorrD. Q., DissanayakeT., KotapatiS., and TretyakovaN. (2010) Chem. Res. Toxicol.23, 1556−156720873715]. Herein, the R,R-DHB-dA and S,S-DHB-dA adducts have been incorporated into the 5′-d(C1G2G3A4C5X6A7G8A9A10G11)-3′:5′-d(C12T13T14C15T16T17G18T19C20C21G22)-3′ duplex [X6 = R,R-DHB-dA (R6) or S,S-DHB-dA (S6)]. The structures of the duplexes were determined by molecular dynamics calculations, which were restrained by experimental distances obtained from NMR data. Both the R,R- and S,S-DHB-dA adducts are positioned in the major groove of DNA. In both instances, the bulky 3,4-dihydroxypyrrolidine rings are accommodated by an out-of-plane rotation about the C6-N6 bond of the bis-alkylated adenine. In both instances, the directionality of the dihydroxypyrrolidine ring is evidenced by the pattern of NOEs between the 3,4-dihydroxypyrrolidine protons and DNA. Also in both instances, the anti conformation of the glycosyl bond is maintained, which combined with the out-of-plane rotation about the C6-N6 bond, allows the complementary thymine, T17, to remain stacked within the duplex, and form one hydrogen bond with the modified base, between the imine nitrogen of the modified base and the T17 N3H imino proton. The loss of the second Watson–Crick hydrogen bonding interaction at the lesion sites correlates with the lower thermal stabilities of the R,R- and S,S-DHB-dA duplexes, as compared to the corresponding unmodified duplex. The reduced base stacking at the

  13. Fusion of the TBL1XR1 and HMGA1 genes in splenic hemangioma with t(3;6)(q26;p21)

    PubMed Central

    PANAGOPOULOS, IOANNIS; GORUNOVA, LUDMILA; BJERKEHAGEN, BODIL; LOBMAIER, INGVILD; HEIM, SVERRE

    2016-01-01

    RNA-sequencing of a splenic hemangioma with the karyotype 45~47,XX,t(3;6)(q26;p21) showed that this translocation generated a chimeric TBL1XR1-HMGA1 gene. This is the first time that this tumor has been subjected to genetic analysis, but the finding of an acquired clonal chromosome abnormality in cells cultured from the lesion and the presence of the TBL1XR1-HMGA1 fusion in them strongly favor the conclusion that splenic hemangiomas are of a neoplastic nature. Genomic PCR confirmed the presence of the TBL1XR1-HMGA1 fusion gene, and RT-PCR together with Sanger sequencing verified the presence of the fusion transcripts. The molecular consequences of the t(3;6) would be substantial. The cells carrying the translocation would retain only one functional copy of the wild-type TBL1XR1 gene while the other, rearranged allele could produce a putative truncated form of TBL1XR1 protein containing the LiSH and F-box-like domains. In the TBL1XR1-HMGA1 fusion transcript, furthermore, untranslated exons of HMGA1 are replaced by the first 5 exons of the TBL1XR1 gene. The result is that the entire coding region of HMGA1 comes under the control of the TBL1XR1 promoter, bringing about dysregulation of HMGA1. This is reminiscent of similar pathogenetic mechanisms involving high mobility genes in benign connective tissue tumors such as lipomas and leiomyomas. PMID:26708416

  14. The juxtamembrane domain in ETV6/FLT3 is critical for PIM-1 up-regulation and cell proliferation

    SciTech Connect

    Vu, Hoang Anh; Xinh, Phan Thi; Kano, Yasuhiko; Tokunaga, Katsushi; Sato, Yuko

    2009-06-05

    We recently reported that the ETV6/FLT3 fusion protein conferred interleukin-3-independent growth on Ba/F3 cells. The present study has been conducted to assess role of the juxtamembrane domain of FLT3 for signal transduction and cell transformation. The wild-type ETV6/FLT3 fusion protein in transfected cells was a constitutively activated tyrosine kinase that led to up-regulation of PIM-1 and activations of STAT5, AKT, and MAPK. Deletion of the juxtamembrane domain abrogated interleukin-3-independent growth of the transfected cells and PIM-1 up-regulation, whereas it retained compatible levels of phosphorylations of STAT5, AKT, and MAPK. Further deletion of N-terminal region of the tyrosine kinase I domain of FLT3 completely abolished these phosphorylations. Our data indicate that the juxtamembrane domain of FLT3 in ETV6/FLT3 fusion protein is critical for cell proliferation and PIM-1 up-regulation that might be independent of a requirement for signaling through STAT5, MAPK, and AKT pathways.

  15. Bis[2,6-bis­(3,5-dimethyl-1H-pyrazol-1-yl)pyridine]di-μ3-iodido-diiodidotetra­copper(I)

    PubMed Central

    Jia, Chun-Xiao

    2011-01-01

    In the title centrosymmetric tetra­nuclear complex, [Cu4I4(C15H17N5)2], the two distinct CuI atoms adopt similar tetra­hedral arrangements, each being ligated by two I atoms, and two N atoms from one 2,6-bis­(3,5-dimethyl-1H-pyrazol-1-yl)pyridine ligand. In the crystal, there are no hydrogen bonds present, and only very weak π–π inter­actions are observed [centroid–centroid distance = 3.985 (4) Å], which connect neighbouring tetra­nuclear units into a chain motif along the b axis. PMID:22090844

  16. Triple Benzannulation of Naphthalene via a 1,3,6-Naphthotriyne Synthetic Equivalent. Synthesis of Dibenz[a,c]anthracene.

    PubMed

    Mannes, Philip Z; Onyango, Evans O; Gribble, Gordon W

    2015-11-01

    A new synthesis of dibenzo[a,c]anthracene (4) is described that features the generation, from tetrabromo-bis-triflate 1 and phenyllithium, of a 1,3,6-naphthotriyne (2) synthetic equivalent that is trapped with 3 equiv of furan to form Diels-Alder tris-adduct 3. A subsequent two-step deoxygenation of 3 represents the first synthesis of dibenz[a,c]anthracene (4) that involves a tandem aryne Diels-Alder cycloaddition-deoxygenation strategy. PMID:26452053

  17. cis-1,3,4,6-Tetranitrooctahydroimidazo-[4,5-d]imidazole (BCHMX), its properties and initiation reactivity.

    PubMed

    Klasovitý, Dusan; Zeman, Svatopluk; Růzicka, Ales; Jungová, Marcela; Rohác, Michal

    2009-05-30

    Using the (15)N NMR chemical shifts of nitrogen atoms in nitramino groups of cis-1,3,4,6-tetranitrooctahydroimidazo-[4,5-d]imidazole (bicyclo-HMX or BCHMX) and additional 10 nitramines, we have assessed its reactivity in detonation, under the influence of impact, and by action of electric spark. It is stated that the thermal stability of BCHMX is higher than that of 1,3,5-trinitro-1,3,5-triazinane (RDX). The longest NN bond in the BCHMX molecule (1.412(4)A) is the cause for its higher impact reactivity, which is at the level of that of penterythritol tetranitrate (PETN). In the experimentally determined detonation velocity, BCMX can be slightly better performing than RDX. From the standpoint of friction sensitivity, BCHMX is similar to 1,3,5,7-tetranitro-1,3,5,7-tetrazocane (HMX). Attention was also focused on the solubility-temperature dependence of BCHMX in acetone, acetonitrile, ethyl acetate, dimethyl sulfoxide, tetrahydrofurane, and nitromethane. X-ray crystallographic study of BCHMX (C(4)H(6)N(8)O(8), M(r)=294.17), has been carried out at the temperature of 150K with the following results: a=8.5430(8), b=6.9480(6), c=8.7780(8)A, alpha=90.0(7) degrees , beta=102.452(11) degrees , gamma=90.0(9) degrees , V=508.777(8)A(3), Z=2, D(x)=1.920 g cm(-3), lambda(Mo Ka)=0.71073A, micro=0.169 cm(-1), F(000)=856, final R=0.0414 for 1254 independent observed reflections. In the BCHMX crystal there were found more short contacts in the molecular crystal of BCHMX data of Gilardi creating extensive supramolecular architecture. PMID:18926628

  18. Dichloro[(1E,1'E)-1,1'-(pyridine-2,6-diyl)diethanone bis(O-methyloxime)-kappa(3)N(1),N(2),N(6)]copper(II).

    PubMed

    Ozdemir, Namik; Dinçer, Muharrem; Dayan, Osman; Cetinkaya, Bekir

    2006-07-01

    In the title compound, [CuCl(2)(C(11)H(15)N(3)O(2))], the Cu(II) ion is five-coordinated in a strongly distorted trigonal-bipyramidal arrangement, with the two methyloxime N atoms located in the apical positions, and the pyridine N and the Cl atoms located in the basal plane. The two axial Cu-N distances are almost equal (mean 2.098 A) and are substantially longer than the equatorial Cu-N bond [1.9757 (15) A]. It is observed that the N(oxime)-M-N(pyridine) bond angle for five-membered chelate rings of 2,6-diacetylpyridine dioxime complexes is inversely related to the magnitude of the M-N(pyridine) bond. The structure is stabilized by intra- and intermolecular C-H...Cl hydrogen bonds which involve the methyl H atoms, except for one of the two acetylmethyl groups. PMID:16823201

  19. Structural, magnetic and magnetocaloric properties of layered perovskite La1.1Bi0.3Sr1.6Mn2O7

    NASA Astrophysics Data System (ADS)

    Oubla, M.; Lamire, M.; Boutahar, A.; Lassri, H.; Manoun, B.; Hlil, E. K.

    2016-04-01

    The La1.1Bi0.3Sr1.6Mn2O7 sample was synthesized by coprecipitation method. Its structure has been characterized by X-ray powder diffraction. The diffraction patterns are consistent with the I4/mmm symmetry, with tetragonal lattice parameters a=3.8750±0.0001 Å and c=20.0456±0.0002 Å. Magnetic measurements have shown a ferromagnetic like ordering with second order magnetic phase transition to paramagnetic states. The magnetic entropy change caused by a magnetic field, (-∆Smax), was estimated on the basis of the Maxwell relation. The maximum magnetic entropy change (-∆Smax) and the relative cooling power (RCP) are, 1.65 J kg-1K-1 and 134.4 J kg-1 respectively, for a 5 T magnetic field change at 340 K.

  20. Structure at 1.6 Å resolution of the protein from gene locus At3g22680 from Arabidopsis thaliana

    SciTech Connect

    Allard, Simon T. M.; Bingman, Craig A.; Johnson, Kenneth A.; Wesenberg, Gary E.; Bitto, Eduard; Jeon, Won Bae; Phillips, George N. Jr

    2005-07-01

    The crystal structure of the 18 kDa At3g22680 gene product from A. thaliana was determined at 1.6 Å resolution. At3g22680 shows no structural homology to any other known proteins and represents a new fold in protein conformational space. The gene product of At3g22680 from Arabidopsis thaliana codes for a protein of unknown function. The crystal structure of the At3g22680 gene product was determined by multiple-wavelength anomalous diffraction and refined to an R factor of 16.0% (R{sub free} = 18.4%) at 1.60 Å resolution. The refined structure shows one monomer in the asymmetric unit, with one molecule of the non-denaturing detergent CHAPS (3-[(3-cholamidopropyl)dimethylammonio]-1-propane sulfonate) tightly bound. Protein At3g22680 shows no structural homology to any other known proteins and represents a new fold in protein conformation space.

  1. Structural Basis of Species-Dependent Differential Affinity of 6-Alkoxy-5-Aryl-3-Pyridinecarboxamide Cannabinoid-1 Receptor Antagonists

    PubMed Central

    Iyer, Malliga R.; Cinar, Resat; Liu, Jie; Godlewski, Grzegorz; Szanda, Gergö; Puhl, Henry; Ikeda, Stephen R.; Deschamps, Jeffrey; Lee, Yong-Sok; Steinbach, Peter J.

    2015-01-01

    6-Alkoxy-5-aryl-3-pyridincarboxamides, including the brain-penetrant compound 14g [5-(4-chlorophenyl)-6-(cyclopropylmethoxy)-N-[(1R,2R)-2-hydroxy-cyclohexyl]-3-pyridinecarboxamide] and its peripherally restricted analog 14h [5-(4-chlorophenyl)-N-[(1R,2R)-2-hydroxycyclohexyl]-6-(2-methoxyethoxy)-3-pyridinecarboxamide], have been recently introduced as selective, high-affinity antagonists of the human cannabinoid-1 receptor (hCB1R). Binding analyses revealed two orders of magnitude lower affinity of these compounds for mouse and rat versus human CB1R, whereas the affinity of rimonabant is comparable for all three CB1Rs. Modeling of ligand binding to CB1R and binding assays with native and mutant (Ile105Met) hCB1Rs indicate that the Ile105 to Met mutation in rodent CB1Rs accounts for the species-dependent affinity of 14g and 14h. Our work identifies Ile105 as a new pharmacophore component for developing better hCB1R antagonists and invalidates rodent models for assessing the antiobesity efficacy of 14g and 14h. PMID:26013543

  2. Synthesis and Biological Evaluation of New 3-Phenyl-1-[(4-arylpiperazin-1-yl)alkyl]-piperidine-2,6-diones

    PubMed Central

    Bielenica, Anna; Kossakowski, Jerzy; Struga, Marta; Dybała, Izabela; Loddo, Roberta; Ibba, Cristina; La Colla, Paolo

    2011-01-01

    A set of 13 alkyl derivatives of 3-phenylpiperidine-2,6-dione were synthesized. Newly obtained compounds were investigated in vitro against HIV-1 and other selected viruses. The benzyl 3f and fluorophenyl 3g derivatives showed moderate protection against CVB-2 and the compound 3g also against HSV-1. Derivatives were tested also for their antibacterial and antifungal activity. The molecular structures of 3a and 3d were determined by an X-ray analysis. PMID:21773062

  3. Synthesis and cytotoxicity testing of novel 2-(3-substituted-6-chloro-1,1-dioxo-1,4,2-benzodithiazin-7-yl)-3-phenyl-4(3H)-quinazolinones.

    PubMed

    Pomarnacka, Elzbieta; Maruszak, Magdalena; Langowska, Karolina; Reszka, Przemyslaw; Bednarski, Patrick J

    2008-08-01

    A new series of thirteen 2-[3-(substituted amino)-6-chloro-1,1-dioxo-1,4,2-benzodithiazin-7-yl]-3-phenyl-4(3H)-quinazolinones 4-16 were prepared in order to evaluate their cytotoxic activity against 12 human cancer cell lines. The bioassay indicated that the quinazolinone derivatives 5, 8-12, 15, and 16 possess cancer-cell growth-inhibitory properties. Compounds 5 and 12 showed a high level of selectivity for certain cell lines. The most active compounds 9, 10, 15, and 16 showed moderate antiproliferative activity and were approximately 4-fold less potent than cisplatin. PMID:18618486

  4. Relativistic multireference Fock-space coupled-cluster calculation of the forbidden 6s{sup 2} {sup 1}S{sub 0}{yields}6s5d {sup 3}D{sub 1} magnetic-dipole transition in ytterbium

    SciTech Connect

    Sur, Chiranjib; Chaudhuri, Rajat K.

    2007-07-15

    We report the forbidden 6s{sup 2} {sup 1}S{sub 0}{yields}6s5d {sup 3}D{sub 1} magnetic-dipole transition amplitude computed using multireference Fock-space coupled-cluster theory. Our computed transition matrix element (1.34x10{sup -4}){mu}{sub B} is in excellent agreement with the experimental value (1.33x10{sup -4}){mu}{sub B}. This value in combination with other known quantities will be helpful in determining the parity-nonconserving amplitude for the 6s{sup 2} {sup 1}S{sub 0}{yields}6s5d {sup 3}D{sub 1} transition in atomic Yb. To our knowledge, this calculation is the most accurate to date, and can be very important in the search for physics beyond the standard model. We further report the 6s6p {sup 3}P{sub 0}{yields}6s6p {sup 1}P{sub 1} and 6s5d {sup 3}D{sub 1}{yields}6s6p {sup 3}P{sub 0} transition matrix elements, which are also in good agreement with the earlier theoretical estimates.

  5. Protective effects of 6-hydroxy-1-methylindole-3-acetonitrile on cisplatin-induced oxidative nephrotoxicity via Nrf2 inactivation.

    PubMed

    Moon, Ji Hee; Shin, Ji-Sun; Kim, Jong-Bin; Baek, Nam-In; Cho, Young-Wuk; Lee, Yong Sup; Kay, Hee Yeon; Kim, Soo-dong; Lee, Kyung-Tae

    2013-12-01

    We previously demonstrated the ethanol extract of the roots of Brassica rapa protects against cisplatin-induced nephrotoxicity by attenuating oxidative stress. Here, we investigated the nephroprotective effects of 6-hydroxy-1-methylindole-3-acetonitrile (6-HMA), which was isolated from the roots of B. rapa, on cisplatin-induced toxicity in renal epithelial LLC-PK1 cells and in rats with acute renal injury. Pretreatment of LLC-PK1 cells with 6-HMA ameliorated cisplatin-induced cytotoxicity caused by oxidative stress, as was demonstrated by reductions in the levels of reactive oxygen species (ROS) and malondialdehyde (MDA) and increased levels of glutathione (GSH). In addition, 6-HMA inhibited cisplatin-induced heme oxygenase-1 (HO-1) expression, possibly due to the suppression of the nuclear translocation and binding activity of NF-E2-related factor 2 (Nrf2). Furthermore, 6-HMA administered rats showed lower levels of blood urea nitrogen (BUN), creatinine, and urinary lactate dehydrogenase (LDH) than cisplatin alone-treated rats in cisplatin-induced renal injury model. Moreover, 6-HMA inhibited the cisplatin-induced formation of MDA and GSH depletion and increased the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione reductase (GR). Taken together, these findings indicate 6-HMA is a major active constituent from the roots of B. rapa to have a protective effect against cisplatin-induced nephrotoxicity by attenuating oxidative stress. PMID:23989062

  6. EPR and polarography of nitroazoles. 6. 3-Nitro-1,2,4-triazoles

    SciTech Connect

    Vakul'skaya, T.I.; Rakhmatulina, T.N.; Pevzner, M.S.; Kofman, T.P.; Lopyrev, V.A.

    1987-09-01

    The electrochemical reduction of eight 3-nitro-1,2,4-triazole derivatives in acetonitrile was investigated by polarography and EPR spectroscopy. Two different signals were recorded in the EPR spectra in the electrochemical reduction of derivative I. The first signal shows up at the potentials of the second wave with a hyperfine structure corresponding to coupling of an unpaired electron with five nitrogen atoms and to a symmetrical distribution of the spin density as shown. Electrochemical generation of the ion radicals was realized in special electrochemical cells that had been previously deoxygenated by successive freezing and thawing of solutions in vacuo and were then filled with argon purified over potassium-sodium alloy.

  7. Whole genomic analyses of asymptomatic human G1P[6], G2P[6] and G3P[6] rotavirus strains reveal intergenogroup reassortment events and genome segments of artiodactyl origin.

    PubMed

    Ghosh, Souvik; Urushibara, Noriko; Chawla-Sarkar, Mamta; Krishnan, Triveni; Kobayashi, Nobumichi

    2013-06-01

    Although P[6] group A rotaviruses (RVA) cause diarrhoea in humans, they have been also associated with endemics of predominantly asymptomatic neonatal infections. Interestingly, strains representing the endemic and asymptomatic P[6] RVAs were found to possess one of the four common human VP7 serotypes (G1-G4), and exhibited little antigenic/genetic differences with the VP4 proteins/VP4 encoding genome segments of P[6] RVAs recovered from diarrhoeic children, raising interest on their complete genetic constellations. In the present study, we report the overall genetic makeup and possible origin of three such asymptomatic human P[6] RVA strains, RVA/Human-tc/VEN/M37/1982/G1P2A[6], RVA/Human-tc/SWE/1076/1983/G2P2A[6] and RVA/Human-tc/AUS/McN13/1980/G3P2A[6]. G1P[6] strain M37 exhibited an unusual genotype constellation (G1-P[6]-R1-C1-M1-A1-N1-T2-E1-H1), not reported previously, and was found to originate from possible intergenogroup reassortment events involving acquisition of a DS-1-like NSP3 encoding genome segment by a human Wa-like RVA strain. On the other hand, G2P[6] strain 1076 exhibited a DS-1-like genotype constellation, and was found to possess several genome segments (those encoding VP1, VP3, VP6 and NSP4) of possible artiodactyl (ruminants) origin on a human RVA genetic backbone. The whole genome of G3P[6] strain McN13 was closely related to that of asymptomatic human Wa-like G3P[6] strain RV3, and both strains shared unique amino acid changes, which might have contributed to their attenuation. Taken together, the present study provided insights into the origin and complex genetic diversity of P[6] RVAs possessing the common human VP7 genotypes. This is the first report on the whole genomic analysis of a G1P[6] RVA strain. PMID:23347969

  8. High-lying bound Rydberg states of excited Hg(6s6p {sup 3}P{sub 1}) atoms from two-color resonance ionization mass spectroscopy

    SciTech Connect

    Bisling, Peter; Dederichs, Jan; Neidhart, Bernd; Weitkamp, Claus

    1998-12-16

    Mercury isotopes are investigated with two-color resonance ionization mass spectroscopy (RIMS). Isotope shifts, hyperfine structure splittings, and the lifetime of the intermediate 6s6p {sup 3}P{sub 1} state are determined by RIMS. Ion yields at the threshold region in various static electric fields are measured in order to determine an extrapolated ionization energy value at zero field strength. New energy values for high-lying bound 6s nd {sup 3}D (21

  9. Socs1 and Socs3 degrades Traf6 via polyubiquitination in LPS-induced acute necrotizing pancreatitis

    PubMed Central

    Zhou, X; Liu, Z; Cheng, X; Zheng, Y; Zeng, F; He, Y

    2015-01-01

    Mechanisms involved in inflammatory development during acute pancreatitis (AP) are largely vague, especially in the transformation of acute edematous pancreatitis (AEP) into acute necrotizing pancreatitis (ANP). This current study aims to investigate the functions of Traf6 in different AP models in vitro and in vivo, and to identify the possible regulatory mechanism in the progression of inflammation from mild to severe. Our data revealed that the level of Traf6 expression was significantly increased in the mild AP induced by caerulein, and the upregulation of Traf6 played a protective role in acinar cells against caerulein-induced apoptosis. In contrast, only Traf6 protein but not mRNA was downregulated in the severe ANP induced by combination treatment of caerulein and LPS. Mechanistic studies showed that LPS upregulated the levels of Socs1 and Socs3 expressions in acinar cells, Socs1 and Socs3 interacted Traf6 directly and degraded Traf6 protein via polyubiquitination, thereby counteracted the protective function of Traf6. In vivo study further showed that combination treatment of caerulein and LPS failed to induce an ANP model in the TLR4 knockout mice, and the level of Traf6 expression in the pancreatic tissues remained the same as that from the acute edematous pancreatitis (AEP) mouse. Taken together, our study reveals that Traf6 functioned as a protective factor in the progression of AP, and LPS-induced Socs1 and Socs3 exacerbate mild AP to severe AP, which provides evidence for developing a new therapeutic target to combat AP. PMID:26633718

  10. IL-6/STAT3 axis initiated CAFs via up-regulating TIMP-1 which was attenuated by acetylation of STAT3 induced by PCAF in HCC microenvironment.

    PubMed

    Zheng, Xin; Xu, Meng; Yao, Bowen; Wang, Cong; Jia, Yuli; Liu, Qingguang

    2016-09-01

    Aberrant tumor microenvironment is involved closely in tumor initiation and progression, in which cancer associated fibroblasts (CAFs) play a pivotal role. Both IL-6/STAT3 signaling and TIMP-1 have been found to modulate the crosstalk between tumor cells and CAFs in tumor microenvironment, however, the underlying mechanism remains unclear. Here, we showed that IL-6/STAT3 signaling was activated aberrantly in HCC tissues and correlated with poor post-surgical outcome. The in vitro experiments confirmed that activation of IL-6/STAT3 pathway enhanced TIMP-1 expression directly via phosphorylated STATs (p-STAT3)-binding with TIMP-1 promoter in Huh7 cells. Furthermore, activation of IL-6/STAT3 pathway in HCC cells was shown to induce the transformation from normal liver fibroblasts (LFs) to CAFs via up-regulating TIMP-1 expression. Co-culture with CAFs promoted the growth of Huh7 cells both in vitro and in vivo. Finally, by co-Immunoprecipitation and immunoblotting assessments, PCAF, a well-known acetyltransferase, was revealed to acetylate cytoplasmic STAT3 protein directly and regulate TIMP-1 expression negatively in Huh7 cells. In summary, this investigation indicated that there was a positive IL-6/TIMP-1 feedback loop controlling the crosstalk between HCC cells and its neighbouring fibroblasts. The data here also identified that PCAF repressed TIMP-1 expression via acetylation of STAT3. In conclusion, this investigation demonstrated that CAFs promoted HCC growth via IL-6/STAT3/AKT pathway and TIMP-1 over-expression driven by IL-6/STAT3 pathway in HCC cells brought in more CAFs through activating LFs. Finally, PCAF could block this positive feedback by acetylating STAT3 in HCC cells. PMID:27297362

  11. New observation and combined analysis of the Cs{sub 2} 0{sub g}{sup −}, 0{sub u}{sup +}, and 1{sub g} states at the asymptotes 6S{sub 1/2} + 6P{sub 1/2} and 6S{sub 1/2} + 6P{sub 3/2}

    SciTech Connect

    Ma, Jie; Liu, Wenliang; Wu, Jizhou; Jia, Suotang; Yang, Jinxin; Dai, Xingcan; Sun, Weiguo; Ivanov, Valery S.; Skublov, Alexei S.; Sovkov, Vladimir B.

    2014-12-28

    We report on new observations of the photoassociation spectroscopy of ultracold cesium molecules using a highly sensitive detection technique and a combined analysis with all observed electronic states. The technique is achieved by directly modulating the frequency of the trapping lasers of a magneto-optical trap. New observations of the Cs{sub 2}0{sub g}{sup −}, 0{sub u}{sup +}, and 1{sub g} states at the asymptotes 6S{sub 1/2} + 6P{sub 1/2} and 6S{sub 1/2} + 6P{sub 3/2} are reported. The spectral range is extended to the red detuning of 112 cm{sup −1} below the 6S{sub 1/2} + 6P{sub 3/2} dissociation limit. Dozens of vibrational levels of the ultracold Cs{sub 2}0{sub g}{sup −}, 0{sub u}{sup +}, and 1{sub g} states are observed for the first time. The available experimental binding energies of these states are analyzed simultaneously in a framework of the generalized LeRoy–Bernstein theory and the almost degenerate perturbation theory by Marinescu and Dalgarno [Phys. Rev. A: At., Mol., Opt. Phys. 52, 311 (1995)]. The unique atomic-related parameter c{sub 3} governing the dispersion forces of all the molecular states is estimated as (10.29 ± 0.05) a.u.

  12. Metal Nitrides Grown from Ca/Li Flux: Ca6Te3N2 and New Nitridoferrate(I) Ca6(LixFe1-x)Te2N3.

    PubMed

    Dickman, Matthew J; Latturner, Susan E

    2016-08-24

    Two new tellurium-containing nitrides were grown from reactions in molten calcium and lithium. The compound Ca6Te3N2 crystallizes in space group R3̅c (a = 12.000(3)Å, c = 13.147(4)Å; Z = 6); its structure is an anti-type of rinneite (K3NaFeCl6) and 2H perovskite related oxides such as Sr3Co2O6. The compound Ca6(LixFe1-x)Te2N3 where x ≈ 0.48 forms in space group P42/m (a = 8.718(3)Å, c = 6.719(2)Å; Z = 2) with a new stuffed anti-type variant of the Tl3BiCl6 structure. Band structure calculations and easily observable red/green dichroic behavior indicate that Ca6Te3N2 is a highly anisotropic direct band gap semiconductor (Eg = 2.5 eV). Ca6(LixFe1-x)Te2N3 features isolated linear N-Fe-N units with iron in the rare Fe(1+) state. The magnetic behavior of the iron site was characterized by magnetic susceptibility measurements, which indicate a very high magnetic moment (5.16μB) likely due to a high degree of spin-orbit coupling. Inherent disorder at the Fe/Li mixed site frustrates long-range communication between magnetic centers. PMID:27479366

  13. 40 CFR 721.9750 - 2-Chloro-4,6-bis(substituted)-1,3,5-triazine, dihydrochloride.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false 2-Chloro-4,6-bis(substituted)-1,3,5-triazine, dihydrochloride. 721.9750 Section 721.9750 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) TOXIC SUBSTANCES CONTROL ACT SIGNIFICANT NEW USES OF CHEMICAL SUBSTANCES Significant New Uses for Specific Chemical Substances...

  14. Immunotoxicological Profile of Chloroform in Female B6c3f1 Mice When Administered In Drinking Water

    EPA Science Inventory

    Chloroform can be formed as a disinfection by-product during water chlorination, one of the primary modalities for purifying municipal water supplies for human consumption. The goal of this study was to characterize the immunotoxic effects of chloroform in female B6C3F1 mice when...

  15. Registration of the maize germplasm CRW3(S1)C6 with resistance to western corn rootworm

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Maize germplasm CRW3(S1)C6 is a synthetic population developed with resistance to western corn rootworm (WCR) by the USDA-ARS Plant Genetics Research Unit in cooperation with the Missouri Agricultural Experiment Station at the University of Missouri-Columbia. The corn rootworm is one of the most se...

  16. RTVP-1 promotes mesenchymal transformation of glioma via a STAT-3/IL-6-dependent positive feedback loop

    PubMed Central

    Giladi, Nis David; Ziv-Av, Amotz; Lee, Hae Kyung; Finniss, Susan; Cazacu, Simona; Xiang, Cunli; Ben-Asher, Hiba Waldman; deCarvalho, Ana; Mikkelsen, Tom; Poisson, Laila; Brodie, Chaya

    2015-01-01

    Glioblastomas (GBMs), the most aggressive primary brain tumors, exhibit increased invasiveness and resistance to anti-tumor treatments. We explored the role of RTVP-1, a glioma-associated protein that promotes glioma cell migration, in the mesenchymal transformation of GBM. Analysis of The Cancer Genome Atlas (TCGA) demonstrated that RTVP-1 expression was higher in mesenchymal GBM and predicted tumor recurrence and poor clinical outcome. ChiP analysis revealed that the RTVP-1 promoter binds STAT3 and C/EBPβ, two master transcription factors that regulate mesenchymal transformation of GBM. In addition, IL-6 induced RTVP-1 expression in a STAT3-dependent manner. RTVP-1 increased the migration and mesenchymal transformation of glioma cells. Similarly, overexpression of RTVP-1 in human neural stem cells induced mesenchymal differentiation, whereas silencing of RTVP-1 in glioma stem cells (GSCs) decreased the mesenchymal transformation and stemness of these cells. Silencing of RTVP-1 also increased the survival of mice bearing GSC-derived xenografts. Using gene array analysis of RTVP-1 silenced glioma cells we identified IL-6 as a mediator of RTVP-1 effects on the mesenchymal transformation and migration of GSCs, therefore acting in a positive feedback loop by upregulating RTVP-1 expression via the STAT3 pathway. Collectively, these results implicate RTVP-1 as a novel prognostic marker and therapeutic target in GBM. PMID:26267319

  17. Synthesis and anti-inflammatory activity of 5-(6-methyl-2-substituted 4-pyrimidinyloxymethyl)-1,3,4-oxadiazole-2-thiones and their 3-morpholinomethyl derivatives.

    PubMed

    Jakubkiene, Virginija; Burbuliene, Milda Malvina; Mekuskiene, Giedrute; Udrenaite, Emilija; Gaidelis, Povilas; Vainilavicius, Povilas

    2003-04-01

    The synthesis of 5-(6-methyl-2-substituted 4-pyrimidinyloxymethyl)-2,3-dihydro-1,3,4-oxadiazole-2-thiones and their 3-morpholinomethyl derivatives and the results of anti-inflammatory activity in vivo are described. Most of the tested compounds exhibited anti-inflammatory activity and some of them were more active than acetylsalicylic acid. PMID:12727542

  18. Stark parameters irregularities of Xe II lines obtained by transitions from ({sup 3}P{sub 1})6plevels

    SciTech Connect

    Mar, S.; Pelaez, R. J.; Rodriguez, F.; Aparicio, J. A.

    2008-10-22

    Stark widths and shifts of some Xe II lines belonging to the supermultiplets with upper levels ({sup 3}P{sub 1})6p were measured using a pulsed discharge lamp. Plasma parameters, i.e. electron density and temperature, in this experiment were in the range from 0.2 to 1.4x10{sup 23} m{sup -3} and from 18000 to 23000 K, respectively. Lines obtained by transitions from levels ({sup 3}P{sub 1})6p show some strong intra-supermultiplet irregularities in their Stark widths and shifts. These results and the measurements obtained in previous works were used here to analyse the main irregularities that can appear in the case of Xe II. This study may be very useful for obtaining Stark parameters of non-measured lines, using the known parameters of other lines belonging to similar transitions.

  19. 40 CFR 721.9790 - Benzenesulfonic acid, 2,2′-(1,2-ethenediyl)bis[5-[[4-[bis(2-hydroxypropyl) amino]- 6-[(3...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...-ethenediyl)bis - 6- -1,3,5-triazin-2-yl]amino]-, disodium salt, compd. with 2,2â²,2â³-nitrilo-tris (1:2); Benzenesulfonic acid, 5- -6- -1,3,5-triazin-2-yl]amino]-2- -6- -1,3,5-triazin-2-yl]amino]-2-sulfophenyl]ethenyl...-ethenediyl)bis - 6- -1,3,5-triazin-2-yl]amino]-, disodium salt, compd. with......

  20. 40 CFR 721.9790 - Benzenesulfonic acid, 2,2′-(1,2-ethenediyl)bis[5-[[4-[bis(2-hydroxypropyl) amino]- 6-[(3...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...-ethenediyl)bis - 6- -1,3,5-triazin-2-yl]amino]-, disodium salt, compd. with 2,2â²,2â³-nitrilo-tris (1:2); Benzenesulfonic acid, 5- -6- -1,3,5-triazin-2-yl]amino]-2- -6- -1,3,5-triazin-2-yl]amino]-2-sulfophenyl]ethenyl...-ethenediyl)bis - 6- -1,3,5-triazin-2-yl]amino]-, disodium salt, compd. with......

  1. Crystal structure of 3-de-oxy-3-nitro-methyl-1,2;5,6-di-O-iso-propyl-idene-α-d-allo-furan-ose.

    PubMed

    Lugiņina, Jevgeņija; Rjabovs, Vitālijs; Stepanovs, Dmitrijs

    2016-03-01

    The title compound, C13H21NO7 {systematic name: (3aR,5S,6R,6aR)-5-[(R)-2,2-dimethyl-1,3-dioxolan-4-yl]-2,2-dimethyl-6-(nitro-meth-yl)tetra-hydro-furo[2,3-d][1,3]dioxole}, consists of a substituted 2,2-di-methyl-tetra-hydro-furo[2,3-d][1,3]dioxolane skeleton. The furan-ose ring A adopts a (o)T 4 conformation. The fused dioxolane ring B and the substituent dioxolane ring C also have twisted conformations. There are no strong hydrogen bonds in the crystal structure: only weak C-H⋯O contacts are present, which link the mol-ecules to form a three-dimensional structure. PMID:27006795

  2. Ly6Chigh Monocytes Protect against Kidney Damage during Sepsis via a CX3CR1-Dependent Adhesion Mechanism.

    PubMed

    Chousterman, Benjamin G; Boissonnas, Alexandre; Poupel, Lucie; Baudesson de Chanville, Camille; Adam, Julien; Tabibzadeh, Nahid; Licata, Fabrice; Lukaszewicz, Anne-Claire; Lombès, Amélie; Deterre, Philippe; Payen, Didier; Combadière, Christophe

    2016-03-01

    Monocytes have a crucial role in both proinflammatory and anti-inflammatory phenomena occurring during sepsis. Monocyte recruitment and activation are orchestrated by the chemokine receptors CX3CR1 and CCR2 and their cognate ligands. However, little is known about the roles of these cells and chemokines during the acute phase of inflammation in sepsis. Using intravital microscopy in a murine model of polymicrobial sepsis, we showed that inflammatory Ly6C(high) monocytes infiltrated kidneys, exhibited altered motility, and adhered strongly to the renal vascular wall in a chemokine receptor CX3CR1-dependent manner. Adoptive transfer of Cx3cr1-proficient monocyte-enriched bone marrow cells into septic Cx3cr1-depleted mice prevented kidney damage and promoted mouse survival. Modulation of CX3CR1 activation in septic mice controlled monocyte adhesion, regulated proinflammatory and anti-inflammatory cytokine expression, and was associated with the extent of kidney lesions such that the number of lesions decreased when CX3CR1 activity increased. Consistent with these results, the pro-adhesive I249 CX3CR1 allele in humans was associated with a lower incidence of AKI in patients with sepsis. These data show that inflammatory monocytes have a protective effect during sepsis via a CX3CR1-dependent adhesion mechanism. This receptor might be a new therapeutic target for kidney injury during sepsis. PMID:26160897

  3. Synthesis of 4-((1E, 6E)-7-(4-hydroxy-3-methoxyphenyl)-3, 5-dioxohepta-1, 6-dienyl)-2-methoxyphenyl 4-fluorobenzoate, a novel monoester derivative of curcumin, its experimental and theoretical (DFT) studies

    NASA Astrophysics Data System (ADS)

    Srivastava, Sangeeta; Gupta, Preeti; Amandeep; Singh, Ranvijay Pratap

    2016-04-01

    Curcumin (1), isolated as a major component from the chloroform extract of Curcuma longa was converted to its ester derivative 4-((1E, 6E)-7-(4-hydroxy-3-methoxyphenyl)-3,5-dioxohepta-1,6-dienyl)-2-methoxyphenyl 4-fluorobenzoate (2). The compound has been characterized with the help of 1H, 13C NMR, UV, IR and mass spectrometry. The molecular geometry of synthesized compound was calculated in ground state by Density functional theory (DFT/B3LYP) using 6-31G (d,p) basis set. 1H and 13C NMR chemical shifts were calculated in ground state by using Gauge-Including Atomic Orbital (GIAO) approach and these values were correlated with experimental observations. The electronic properties such as HOMO and LUMO energies were calculated using time dependent Density Functional Theory (TD-DFT). Stability of the molecule as a result of hyper conjugative interactions and electron delocalization were analysed using Natural bond orbital (NBO) analysis. Intramolecular interactions were analysed by AIM (Atom in molecule) approach. Global reactivity descriptors were calculated to study the reactive site within molecule. The vibrational wavenumbers were calculated using DFT method and assigned with the help of potential energy distribution (PED). First hyperpolarizability values have been calculated to describe the nonlinear optical (NLO) property of the synthesized compounds. Molecular electrostatic potential (MEP) analysis has also been carried out.

  4. Functional characterization of barley betaglucanless mutants demonstrates a unique role for CslF6 in (1,3;1,4)-β-D-glucan biosynthesis

    PubMed Central

    Taketa, Shin; Yuo, Takahisa; Tonooka, Takuji; Tsumuraya, Yoichi; Inagaki, Yoshiaki; Haruyama, Naoto; Larroque, Oscar; Jobling, Stephen A.

    2012-01-01

    (1,3;1,4)-β-D-glucans (mixed-linkage glucans) are found in tissues of members of the Poaceae (grasses), and are particularly high in barley (Hordeum vulgare) grains. The present study describes the isolation of three independent (1,3;1,4)-β-D-glucanless (betaglucanless; bgl) mutants of barley which completely lack (1,3;1,4)-β-D-glucan in all the tissues tested. The bgl phenotype cosegregates with the cellulose synthase like HvCslF6 gene on chromosome arm 7HL. Each of the bgl mutants has a single nucleotide substitution in the coding region of the HvCslF6 gene resulting in a change of a highly conserved amino acid residue of the HvCslF6 protein. Microsomal membranes isolated from developing endosperm of the bgl mutants lack detectable (1,3;1,4)-β-D-glucan synthase activity indicating that the HvCslF6 protein is inactive. This was confirmed by transient expression of the HvCslF6 cDNAs in Nicotiana benthamiana leaves. The wild-type HvCslF6 gene directed the synthesis of high levels of (1,3;1,4)-β-D-glucans, whereas the mutant HvCslF6 proteins completely lack the ability to synthesize (1,3;1,4)-β-D-glucans. The fine structure of the (1,3;1,4)-β-D-glucan produced in the tobacco leaf was also very different from that found in cereals having an extremely low DP3/DP4 ratio. These results demonstrate that, among the seven CslF and one CslH genes present in the barley genome, HvCslF6 has a unique role and is the key determinant controlling the biosynthesis of (1,3;1,4)-β-D-glucans. Natural allelic variation in the HvCslF6 gene was found predominantly within introns among 29 barley accessions studied. Genetic manipulation of the HvCslF6 gene could enable control of (1,3;1,4)-β-D-glucans in accordance with the purposes of use. PMID:21940720

  5. 2-(4-Chlorobenzyl)-6-arylimidazo[2,1-b][1,3,4]thiadiazoles: synthesis, cytotoxic activity and mechanism of action.

    PubMed

    Kumar, Sujeet; Hegde, Mahesh; Gopalakrishnan, Vidya; Renuka, Vinaya Kumar; Ramareddy, Sureshbabu A; De Clercq, Erik; Schols, Dominique; Gudibabande Narasimhamurthy, Anil Kumar; Raghavan, Sathees C; Karki, Subhas S

    2014-09-12

    The cytotoxic activity of a new series of 2-(4'-chlorobenzyl)-5,6-disubstituted imidazo[2,1-b][1,3,4]thiadiazoles against different human and murine cancer cell lines is reported. Among the tested compounds, two derivatives namely 2-(4-chlorobenzyl)-6-(2-oxo-2H-chromen-3-yl)imidazo[2,1-b][1,3,4]thiadiazole-5-carbaldehyde 4i and 2-(4-chlorobenzyl)-6-(2-oxo-2H-chromen-3-yl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl thiocyanate 5i emerged as the most potent against all the cell lines. To investigate the mechanism of action, we selected compounds 4i for cell cycle study, analysis of mitochondrial membrane potential and Annexin V-FITC flow cytometric analysis and DNA fragmentation assay. Results showed that 4i induced cytotoxicity by inducing apoptosis without arresting the cell cycle. PMID:25064346

  6. Correlation of infrared reflectance ratios at 2.3 microns/1.6 micron and 1.1 micron/1.6 micron with delta O-18 values delineating fossil hydrothermal systems in the Idaho batholith

    NASA Technical Reports Server (NTRS)

    Gillespie, A. R.; Criss, R. E.

    1983-01-01

    Reflectance ratios from laboratory spectra and airborne multispectral images are found to be strongly correlated with delta O-18 values of granite rocks in the Idaho batholith. The correlation is largely a result of interactions between hot water and rock, which lowered the delta O-18 values of the rocks and produced secondary hydrous material. Maps of the ratio of reflectivities at 2.3 and 1.6 microns should delineate fossil hydrothermal systems and provide estimates of alteration intensity. However, hydrous minerals produced during deuteric alteration or weathering cannot be unambiguously distinguished in remotely sensed images from the products of propylitic alteration without the use of narrow-band scanners. The reflectivity at 1.6 micron is strongly correlated with rock density and may be useful in distinguishing rock types in granitic terranes.

  7. Acute Effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or Paraquat on Core Temperature in C57BL/6J Mice

    PubMed Central

    Jiao, Yun; Dou, Yuchen; Lockwood, Georgina; Pani, Amar; Jay Smeyne, Richard

    2015-01-01

    Abstract Background: MPTP and paraquat are two compounds that have been used to model Parkinson’s disease in mice. Previous studies in two non-traditional strains of mice have shown that a single dose of MPTP can induce changes in body temperature, while the effects of paraquat have not been examined. Examination of body temperature is important since small fluctuations in an animal’s core temperature can significantly affect drug metabolism, and if significant enough can even culminate in an animal’s death. Objective: To determine how external heating can alter the survival of C57BL/6J mice following MPTP administration. Methods: In this study, we examine the effects of MPTP (4×20 mg/kg, 2 hours apart) and paraquat (2×10 mg/kg/week for 3 weeks) on core temperature of C57BL/6J mice. Correlations of purine and catecholamine levels were also done in mice treated with MPTP. Results: We find that MPTP induces a significant hypothermia in C57BL/6J mice that reduces their core temperature below the limit of fatal hypothermia. Unlike MPTP, paraquat did not induce a significant hypothermia. Placement of animals on heating pads significantly abrogates the loss of core temperature. In both heated and non-heated conditions, mice treated with MPTP showed a significant depletion of ATP within 2 hours of administration in both striatum and SN that started to recover 2 hours after MPTP administration was complete. Striatal DA and DOPAC are significantly reduced starting 4–6 hours after MPTP. Conclusions: The fatal hypothermic effects of MPTP can be abrogated through use of external heating. PMID:25633843

  8. Duplication of segment 1p21 following paternal insertional translocation, ins(6;1)(q25;p13.3p22.1)

    PubMed Central

    Utkus, A.; Sorokina, I.; Kucinskas, V.; Rothlisberger, B.; Balmer, D.; Brecevic, L.; Schinzel, A.

    1999-01-01

    A moderately mentally retarded 3 year old boy showed minor anomalies including a prominent forehead and flat occiput, exophthalmos, large and prominent ears, high arched palate, umbilical hernia, sacral dimple, and irregular position of the toes. Cardiac sonography disclosed a chorda running through the left ventricle. Cytogenetic investigation of the family showed a balanced insertional translocation of segment 1p13→p22 into distal 6q in the father which had led, through unbalanced segregation, to duplication of 1p13.3→p22.1 in the proband. Familial duplication of such a small interstitial segment of 1p has not been reported previously, and the paucity of abnormal physical findings in the proband compared to previous patients with a similar aberration is remarkable. 


Keywords: chromosome duplication 1p; dual colour FISH; unbalanced insertional translocation PMID:9950373

  9. Fluorine for Hydrogen Exchange in the Hydrofluorobenzene Derivatives C6HxF(6-x), where x = 2, 3, 4 and 5 by Monomeric [1,2,4-(Me3C)3C5H2]2CeH; The Solid State Isomerization of [1,2,4-(Me3C)3C5H2]2Ce(2,3,4,5-C6HF4) to [1,2,4-(Me3C)3C5H2]2Ce(2,3,4,6-C6HF4)

    SciTech Connect

    Andersen, Richard; Werkema, Evan L.; Andersen, Richard A.

    2008-04-21

    The reaction between monomeric bis(1,2,4-tri-t-butylcyclopentadienyl)cerium hydride, Cp'2CeH, and several hydrofluorobenzene derivatives is described. The aryl derivatives that are the primary products, Cp'2Ce(C6H5-xFx) where x = 1,2,3,4, are thermally stable enough to be isolated in only two cases, since all of them decompose at different rates to Cp'2CeF and a fluorobenzyne; the latter is trapped by either solvent when C6D6 is used or by a Cp'H ring when C6D12 is the solvent. The trapped products are identified by GCMS analysis after hydrolysis. The aryl derivatives are generated cleanly by reaction of the metallacycle, Cp'((Me3C)2C5H2C(Me2)CH2)Ce, with a hydrofluorobenzene and the resulting arylcerium products, in each case, are identified by their 1H and 19F NMR spectra at 20oC. The stereochemical principle that evolves from these studies is that the thermodynamic isomer is the one in which the CeC bond is flanked by two ortho-CF bonds. This orientation is suggested to arise from the negative charge that is localized on the ipso-carbon atom due to Co(delta+)-Fo(delta-) polarization. The preferred regioisomer is determined by thermodynamic rather than kinetic effects; this is illustrated by the quantitative, irreversible solid-state conversion at 25oC over two months of Cp'2Ce(2,3,4,5-C6HF4) to Cp'2Ce(2,3,4,6-C6HF4), an isomerization that involves a CeC(ipso) for C(ortho)F site exchange.

  10. State-Specific Reactions of Cu(+)((1)S,(3)D) with SF6 and SF5Cl.

    PubMed

    Taylor, William S; Redmon, Xavier S; Scheuter, Benjamin A

    2016-04-21

    State-specific reactions of Cu(+)((1)S,(3)D) were carried out in a selected ion drift cell apparatus with SF6 and SF5Cl. Copper ions were prepared in a glow discharge utilizing Ne as the working gas. Analysis of Cu(+) states using ion mobility mass spectrometry (IMS) indicated the presence of both Cu(+)(3d(10)) and Cu(+)(3d(9)4s(1)) configurations attributable to the (1)S ground and (3)D first excited states of this metal ion, respectively. State-specific product formation in reactions of these ions with the two neutral substrates of interest here was determined using IMS along with both known and calculated energetic requirements for product formation. These experiments indicate that Cu(+)((1)S) associates with both SF6 and SF5Cl; however, the process is approximately four times as efficient with the latter neutral under these conditions. Association is also observed as a minor product between Cu(+)((3)D) and both neutral reactants. Inefficient formation of SF3(+) occurs as the sole bimolecular product from SF6 via Cu(+)((3)D). In contrast, Cu(+)((3)D) reacts with SF5Cl in rapid parallel bimolecular processes yielding SF3(+) and CuCl(+). These results also indicate that CuCl(+) initiates additional higher-order processes which result in SF5(+) and SF4Cl(+). The energetics associated with the formation of SF3(+) suggest that a copper halide neutral byproduct must also be formed, requiring a more complex mechanism than simple dissociative charge-transfer. PMID:27014999

  11. Coexpression with Auxiliary β Subunits Modulates the Action of Tefluthrin on Rat Nav1.6 and Nav1.3 Sodium Channels

    PubMed Central

    Tan, Jianguo; Choi, Jin Sung; Soderlund, David M.

    2011-01-01

    We expressed the rat Nav1.3 and Nav1.6 sodium channel α subunit isoforms in Xenopus oocytes either alone or with the rat β1 and β2 auxiliary subunits in various combinations and assessed the sensitivity of the expressed channels to resting and use-dependent modification by the pyrethroid insecticide tefluthrin using the two-electrode voltage clamp technique. Coexpression with the β1 and β2 subunits, either individually or in combination, did not affecting the resting sensitivity of Nav1.6 channels to tefluthrin. Modification by tefluthrin of Nav1.6 channels in the absence of β subunits was not altered by the application of trains of high-frequency depolarizing prepulses. By contrast, coexpression of the Nav1.6 channel with the β1 subunit enhanced the extent of channel modification twofold following repeated depolarization. Coexpression of Nav1.6 with the β2 subunit also slightly enhanced modification following repeated depolarization, but coexpression of Nav1.6 with both β subunits caused enhanced modification following repeated depolarization that was indistinguishable from that found with Nav1.61 channels. In contrast to Nav1.6, the resting modification by tefluthrin of Nav1.3 channels expressed in the absence of β subunits was reduced by repeated depolarization. However, tefluthrin modification of the Nav1.3 α subunit expressed with both β subunits was enhanced 1.7-fold by repeated depolarization, thereby confirming that β subunit modulation of use-dependent effects was not confined to the Nav1.6 isoform. These results show that the actions of pyrethroids on mammalian sodium channels in the Xenopus oocyte expression system are determined in part by the interactions of the sodium channel α subunit with the auxiliary β subunits that are part of the heteromultimeric sodium channel complexes found in neurons and other excitable cells. PMID:22577241

  12. 2,3,5,6-Tetra­methoxy­piperazine-1,4-dicarbaldehyde

    PubMed Central

    Moosavi, Sayed Mojtaba; Taheri, Amir

    2009-01-01

    The asymmetric unit of the title compound, C10H18N2O6, contains two halves of two independent centrosymmetric mol­ecules with almost identical conformations. Weak inter­molecular C—H⋯O hydrogen bonds consolidate the crystal packing. PMID:21577809

  13. 3,3,3′,3′-Tetra­methyl-6,6′-bis­[(pyridin-4-yl)meth­oxy]-1,1′-spiro­biindane ­monohydrate

    PubMed Central

    Zhang, Ya-Jie; Sun, Yan; Gao, Shu-Mei; Jiang, Xiao-Qing; Deng, Yu-Heng

    2012-01-01

    The asymmetric unit in the title compound, C33H34N2O2·H2O, consists of a V-shaped mol­ecule and a water mol­ecule to which it is hydrogen bonded. The angle between the mean planes of the two spiro-connected indane groups is 77.06 (5)°. The two five-membered rings of the indane groups have envelope conformations with the methyl­ene atoms adjacent to the spiro C atom forming the flaps. They have deviations from the mean plane of the other four atoms in the rings of 0.374 (4) and 0.362 (4) Å. In the crystal, molecules are linked to form inversion dimers via O—H⋯N hydrogen bonds involving the pyridine N atoms and the solvent water mol­ecule. The dimers are linked into a chain along the b axis by π–π stacking inter­actions between a pyridine ring and its centrosymmetrically related ring in an adjacent dimer. The centroid–centroid distance between the planes is 3.7756 (17) Å, the perpendicular distance is 3.4478 (11) Å and the offset is 1.539 Å. PMID:22719546

  14. 6-[6-(Pyridin-2-yl)-1,2,4,5-tetra­zin-3-yl]pyridin-3-amine monohydrate

    PubMed Central

    Broichhagen, Johannes; Klingl, Yvonne E.; Trauner, Dirk; Mayer, Peter

    2016-01-01

    The packing of the title compound, C12H9N7·H2O, is dominated by hydrogen bonding and π-stacking. Layers parallel to [010] are established by hydrogen bonds involving all amine donor functions and one of the water donor functions, while the remaining water donor function enables the stacking of the layers along [10-1], which is accompanied by π-stacking. In the molecule, the plane of the central tetra­zine ring forms angles of 5.33 (7) and 19.84 (8)° with the adjacent 3-amine-pyridine and pyridine rings, respectively. PMID:26958397

  15. Encapsulation of haloalkane 1-(3-chlorophenyl)-4-(3-chloropropyl)-piperazinium in symmetrical α,α',δ,δ'-tetramethyl-cucurbit[6]uril.

    PubMed

    Xiao, Xin; Gao, Zhong-Zheng; Shan, Cheng-Long; Tao, Zhu; Zhu, Qian-Jiang; Xue, Sai-Feng; Liu, Jing-Xin

    2015-04-14

    Complexation of haloalkane 1-(3-chlorophenyl)-4-(3-chloropropyl)-piperazinium (PZ(+)) dihydrochloride with symmetrical α,α',δ,δ'-tetramethyl-cucurbit[6]uril (TMeQ[6]) has been investigated using NMR spectroscopy, MALDI-TOF mass spectrometry, isothermal titration calorimetry (ITC), and X-ray crystallography. Our data indicate that the chloropropyl group of PZ(+) resides within the cavity of TMeQ[6] in both aqueous solution and the solid state, generating a highly stable inclusion complex PZ(+)@TMeQ[6]. In aqueous solution, the formation of the inclusion complex PZ(+)@TMeQ[6] benefits from the ion-dipole interactions between the guest PZ(+) and the host TMeQ[6]. While in the solid state, hydrogen-bonding interactions also play an important role in stabilizing the inclusion complex PZ(+)@TMeQ[6]. PMID:25746008

  16. Static and dynamic properties of the quasi-1D Heisenberg antiferromagnets AgVP 2S 6 ( S=1) and AgCrP 2S 6 ( S = 3/2)

    NASA Astrophysics Data System (ADS)

    Payen, C.; Mutka, H.; Soubeyroux, J. L.; Molinié, P.; Colombet, P.

    1992-02-01

    Differences in behaviour between the two quasi-1D Heisenberg antiferromagnets AgVP 2S 6 ( S=1) and AgCrP 2S 6 ( S = 3/2) have been evidenced by susceptibility measurements, neutron powder diffraction and inelastic neutron scattering. The results obtained for the S=1 compound are consistent with Haldane's conjecture as well as existing numerical results. The S = 3/2 compound behaves conventionally above the 3D ordering temperature ( TN=20 K).

  17. IL-17A synergistically enhances TNFα-induced IL-6 and CCL20 production in 3T3-L1 adipocytes.

    PubMed

    Shinjo, Takanori; Iwashita, Misaki; Yamashita, Akiko; Sano, Tomomi; Tsuruta, Mitsudai; Matsunaga, Hiroaki; Sanui, Terukazu; Asano, Tomoichiro; Nishimura, Fusanori

    2016-08-19

    Interleukin-17A (IL-17A) is known to induce inflammatory responses and to be involved in the pathogenesis of not only autoimmune diseases, but also several metabolic and infectious diseases. In this study, IL-17A is shown to induce IL-6 expression in 3T3-L1 mature adipocytes. Interestingly, we found that IL-17A synergistically amplified TNFα-induced secretion of IL-6 and upregulation of IL-17RA expression in 3T3-L1 adipocytes. Its synergistic effects on IL-6 production were inhibited by pre-treatment with inhibitors of IκBα and JNK. Furthermore, IL-17A cooperatively enhanced LPS-mediated IL-6 production in 3T3-L1 adipocytes co-cultured with RAW264.7 macrophages. In addition, IL-17A also enhanced CCL20 production in 3T3-L1 adipocytes stimulated with TNFα or co-cultured with LPS-stimulated RAW macrophages. In high-fat diet-fed mouse epididymal adipose tissues, IL-17RA and RORγt mRNA levels were significantly increased and the serum level of CCL20 was also upregulated. Taken together, these data show that, in adipose tissues, IL-17A contributes to exacerbating insulin resistance-enhancing IL-6 production and promotes the infiltration of Th17 cells in cooperation with TNFα; these findings represent a novel hypothesis for the association between IL-17A-producing cells and type 2 diabetes. PMID:27311858

  18. Synthesis, click reaction, molecular structure, spectroscopic and DFT computational studies on 3-(2,6-bis(trifluoromethyl)phenoxy)-6-(prop-2-yn-1-yloxy)phthalonitrile

    NASA Astrophysics Data System (ADS)

    Hasan, Muhammad; Shalaby, Mona

    2016-06-01

    The compound 3-(2,6-bis(trifluoromethyl)phenoxy)-6-(prop-2-yn-1-yloxy)phthalonitrile has been synthesized and confirmed by different characterization techniques such as elemental analysis, IR, UV-vis spectroscopy, and X-ray single-crystal determination. The molecular geometry from X-ray determination of this compound in the ground state has been compared using the Hartree-Fock (HF) and density functional theory (DFT) with the 6-31G(d) basis set. This compound reacted with sugar azide via click reaction to form triazol ring. The synergy between carbohydrate molecule and fluorinated organic compound achieved novel synthetic pathways, properties, and applications in chemistry science.

  19. 6-Chloro-1-methyl­indoline-2,3-dione

    PubMed Central

    Liu, Hua Quan; Tang, Wei; Wang, De Cai; Ou-yang, Ping Kai

    2012-01-01

    The title mol­ecule, C9H6ClNO2, is essentially planar: the maximum deviation from the mean plane of the indoline ring is 0.020 (2) Å and the substituents do not deviate by more than 0.053 (2) Å from this plane. C—H⋯O hydrogen bonds help to consolidate the crystal structure. PMID:22259426

  20. New Insights into the Structure of (13,16)-β-D-Glucan Side Chains in the Candida glabrata Cell Wall

    PubMed Central

    Lowman, Douglas W.; West, Lara J.; Bearden, Daniel W.; Wempe, Michael F.; Power, Trevor D.; Ensley, Harry E.; Haynes, Ken; Williams, David L.; Kruppa, Michael D.

    2011-01-01

    β-glucan is a (13)-β-linked glucose polymer with (16)-β-linked side chains and a major component of fungal cell walls. β-glucans provide structural integrity to the fungal cell wall. The nature of the (16)-β-linked side chain structure of fungal (13,16)-β-D-glucans has been very difficult to elucidate. Herein, we report the first detailed structural characterization of the (16)-β-linked side chains of Candida glabrata using high-field NMR. The (16)-β-linked side chains have an average length of 4 to 5 repeat units spaced every 21 repeat units along the (13)-linked polymer backbone. Computer modeling suggests that the side chains have a bent curve structure that allows for a flexible interconnection with parallel (13)-β-D-glucan polymers, and/or as a point of attachment for proteins. Based on these observations we propose new approaches to how (16)-β-linked side chains interconnect with neighboring glucan polymers in a manner that maximizes fungal cell wall strength, while also allowing for flexibility, or plasticity. PMID:22096604

  1. Direct Observation of the 6S1 / 2 to 5D3 / 2 Electric Quadrupole Transition in Barium-138

    NASA Astrophysics Data System (ADS)

    Kleczewski, Adam; Hoffman, Matt; Magnuson, Eric; Blinov, Boris; Fortson, Norval

    2011-05-01

    The 6S1 / 2 to 5D3 / 2 electric quadrupole transition at 2051 nm in Ba+ plays an important role in a number of proposed experiments.,, We present the results of the first narrow laser spectroscopy performed on this transition. 2051 nm light is generated by a diode pumped solid state Tm,Ho:YLF laser. The laser is frequency stabilized to a high finesse cavity made from ultra-low expansion glass. In order to take advantage of higher performing optics and detectors available at shorter wavelengths, the 2051 nm light is frequency doubled using a periodically poled lithium niobate crystal inside a bow-tie enhancement cavity before being sent to the reference cavity. Using this laser system we observed Rabi oscillations on the 6S1 / 2 to 5D3 / 2 transition and demonstrated a laser-ion coherence time of 3 ms. This work is supported by NSF Grant PHY-0906494.

  2. Duplication of segment 1p21 following paternal insertional translocation, ins(6;1)(q25;p13.3p22.1).

    PubMed

    Utkus, A; Sorokina, I; Kucinskas, V; Röthlisberger, B; Balmer, D; Brecevic, L; Schinzel, A

    1999-01-01

    A moderately mentally retarded 3 year old boy showed minor anomalies including a prominent forehead and flat occiput, exophthalmos, large and prominent ears, high arched palate, umbilical hernia, sacral dimple, and irregular position of the toes. Cardiac sonography disclosed a chorda running through the left ventricle. Cytogenetic investigation of the family showed a balanced insertional translocation of segment 1p13-->p22 into distal 6q in the father which had led, through unbalanced segregation, to duplication of 1p13.3-->p22.1 in the proband. Familial duplication of such a small interstitial segment of 1p has not been reported previously, and the paucity of abnormal physical findings in the proband compared to previous patients with a similar aberration is remarkable. PMID:9950373

  3. 6,7-Dimethoxy-2-{2-[4-(1H-1,2,3-triazol-1-yl)phenyl]ethyl}-1,2,3,4-tetrahydroisoquinolines as superior reversal agents for P-glycoprotein-mediated multidrug resistance.

    PubMed

    Liu, Baomin; Qiu, Qianqian; Zhao, Tianxiao; Jiao, Lei; Li, Yunman; Huang, Wenlong; Qian, Hai

    2015-02-01

    P-glycoprotein (P-gp)-mediated multidrug resistance (MDR) is a major obstacle for successful cancer chemotherapy. Based on our previous study, 17 novel compounds with the 6,7-dimethoxy-2-{2-[4-(1H-1,2,3-triazol-1-yl)phenyl]ethyl}-1,2,3,4-tetrahydroisoquinoline scaffold were designed and synthesized. Among them, 2-[(1-{4-[2-(6,7-dimethoxy-3,4-dihydroisoquinolin-2(1H)-yl)ethyl]phenyl}-1H-1,2,3-triazol-4-yl)methoxy]-N-(p-tolyl)benzamide (compound 7 h) was identified as a potent modulator of P-gp-mediated MDR, with high potency (EC50 =127.5 ± 9.1 nM), low cytotoxicity (TI>784.3), and long duration (>24 h) in reversing doxorubicin (DOX) resistance in K562/A02 cells. Compound 7 h also enhanced the effects of other MDR-related cytotoxic agents (paclitaxel, vinblastine, and daunorubicin), increased the accumulation of DOX and blocked P-gp-mediated rhodamine 123 efflux function in K562/A02 MDR cells. Moreover, 7 h did not have any effect on cytochrome (CYP3A4) activity. These results indicate that 7 h is a relatively safe modulator of P-gp-mediated MDR that has good potential for further development. PMID:25470220

  4. STAT3 and STAT6 Signaling Pathways Synergize to Promote Cathepsin Secretion from Macrophages via IRE1α Activation.

    PubMed

    Yan, Dongyao; Wang, Hao-Wei; Bowman, Robert L; Joyce, Johanna A

    2016-09-13

    Tumor-associated macrophages play critical roles during tumor progression by promoting angiogenesis, cancer cell proliferation, invasion, and metastasis. Cysteine cathepsin proteases, produced by macrophages and cancer cells, modulate these processes, but it remains unclear how these typically lysosomal enzymes are regulated and secreted within the tumor microenvironment. Here, we identify a STAT3 and STAT6 synergy that potently upregulates cathepsin secretion by macrophages via engagement of an unfolded protein response (UPR) pathway. Whole-genome expression analyses revealed that the TH2 cytokine interleukin (IL)-4 synergizes with IL-6 or IL-10 to activate UPR via STAT6 and STAT3. Pharmacological inhibition of the UPR sensor IRE1α blocks cathepsin secretion and blunts macrophage-mediated cancer cell invasion. Similarly, genetic deletion of STAT3 and STAT6 signaling components impairs tumor development and invasion in vivo. Together, these findings demonstrate that cytokine-activated STAT3 and STAT6 cooperate in macrophages to promote a secretory phenotype that enhances tumor progression in a cathepsin-dependent manner. PMID:27626662

  5. Benzene-1,2,4,5-tetra-carb-oxy-lic acid bis-(1,3,7-trimethyl-2,3,6,7-tetra-hydro-1H-purine-2,6-dione).

    PubMed

    Arman, Hadi D; Tiekink, Edward R T

    2013-01-01

    The asymmetric unit of the title co-crystal, C10H6O8·2C8H10N4O2, comprises a centrosymmetric benzene-1,2,4,5-tetra-carb-oxy-lic acid (LH4) mol-ecule and a mol-ecule of caffeine in a general position. LH4 is nonplanar, with the dihedral angles between the ring and pendent carb-oxy-lic acid groups being 44.22 (7) and 49.74 (7)°. By contrast, the caffeine mol-ecule is planar (r.m.s. deviation = 0.040 Å). Supra-molecular layers parallel to (-1-10) are sustained by carb-oxy-lic acid O-H⋯O(carbon-yl) and O-H⋯N(imidazole) hydrogen bonds, as well as by meth-yl-carbonyl C-H⋯O inter-actions. These stack via π-π inter-actions between the benzene and imidazole rings [inter-centroid distance = 3.4503 (10) Å]. PMID:24427071

  6. Synthesis and structure elucidation of potential 6-oxygenated metabolites of (22R)-6alpha,9alpha-difluoro-11beta,21-dihydroxy-1 6alpha,17alpha-propyl methylenedioxypregn-4-ene-3,20-dione, and related glucocorticosteroids.

    PubMed

    Thalén, A; Wickström, L I

    2000-01-01

    (22R)-6alpha,9alpha-Difluoro-11beta,21-dihydroxy-16 alpha,17alpha-propylmethylenedioxypregn-4-ene-3,20-dione (rofleponide) is a synthetic glucocorticosteroid with high affinity for the rat thymus glucocorticoid receptor and a very high biotransformation rate demonstrated through incubation with a human liver S9 subcellular fraction. Because oxidation in the 6-position is an important metabolic pathway of glucocorticosteroids, the potential 6beta-hydroxy and 6-oxo metabolites of rofleponide were synthesized to be used as reference compounds. Three alternative routes were used to reach the 6-hydroxy compound: (a) a one-step procedure involving allylic oxidation of rofleponide by selenium dioxide, (b) selenium dioxide oxidation of the corresponding 1,4-diene followed by selective 1,2-hydrogenation using Wilkinson's catalyst, and (c) autoxidation of a 3-methoxypregna-3,5-diene derivative. All three routes proceeded stereospecifically. Routes (a) and (c) gave approximately the same overall yield of the 6beta-hydroxy epimer, whereas the overall yield from route (b) was much lower, primarily because of incomplete 1,2-hydrogenation. The 6-oxo compound was prepared through Pfitzner/Moffat oxidation of the 6-hydroxy compound. The stereochemistry of the 6-hydroxy substituent is discussed on the basis of 1H-NMR spectroscopy and supplementary 2D NOESY experiments. PMID:10624832

  7. Lack of antagonism of 2,3,7,8-tetrachlorodibenzo-p-dioxin's (TCDDs) induction of cytochrome P4501A1 (CYP1A1) by the putative selective aryl hydrocarbon receptor modulator 6-alkyl-1,3,8-trichlorodibenzofuran (6-MCDF) in the mouse hepatoma cell line Hepa-1c1c7.

    PubMed

    Fretland, Adrian J; Safe, Stephen; Hankinson, Oliver

    2004-11-20

    Regulation of gene expression by the aryl hydrocarbon (AHR) receptor is a much-studied pathway of molecular toxicology. Activation of AHR by the xenobiotic ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is hypothesized as the mechanism by which TCDD exerts its toxic and carcinogenic effects. Paradoxically, some studies have shown that TCDD acts as an antiestrogen. This has led to the hypothesis that so-called selective aryl hydrocarbon receptor modulators (SAhRMs), AHR ligands that retain the antiestrogenic effects but lack the transcriptional effects of TCDD associated with toxicity, may be utilized as cancer chemotherapeutics in conjunction with other antiestrogenic compounds such as tamoxifen. The present study attempts to further define the molecular mechanism of action of the putative SAhRMs, 6-alkyl-1,3,8-trichlorodibenzofuran (6-MCDF), and diindolylmethane (DIM), focusing particularly on the former. We tested 6-MCDF and DIM for the recruitment of AHR and RNA polymerase II (pol II) to the regulatory region of the AHR responsive gene, cytochrome P4501A1 (CYP1A1), using the chromatin immunoprecipitation (ChIP) assay in the mouse hepatoma cell line Hepa-1c1c7 (Hepa-1). We also tested the level of CYP1A1 induction in Hepa-1 cells using quantitative real-time PCR. We show no difference in the recruitment of AHR or pol II to the regulatory region of CYP1A1 in response to TCDD, 6-MCDF, or co-treatment with both TCDD and 6-MCDF. Our results also show no antagonism of CYP1A1 induction with co-treatment of Hepa-1 cells with TCDD and 6-MCDF. These data suggest that 6-MCDF exhibits agonist activity with respect to induction of CYP1A1 in the Hepa-1 cell line. PMID:15535986

  8. 2,2-Dimethyl-5-(2,3,4-trimeth-oxy-benzyl-idene)-1,3-dioxane-4,6-dione.

    PubMed

    Zeng, Wu-Lan

    2011-08-01

    The title compound, C(16)H(18)O(7), was prepared by the reaction of 2,2-dimethyl-1,3-dioxane-4,6-dione and 2,3,4-trimeth-oxy-benzaldehyde. The 1,3-dioxane ring is in a slightly distorted boat conformation. The crystal structure is stabilized by weak inter-molecular C-H⋯O hydrogen bonds. PMID:22090981

  9. Volumetric Properties of the Mixture Thiolane 1,1-dioxide C4H8O2S + C6H14O4 3,6-Dioxaoctane-1,8-diol (VMSD1111, LB5084_V)

    NASA Astrophysics Data System (ADS)

    Cibulka, I.; Fontaine, J.-C.; Sosnkowska-Kehiaian, K.; Kehiaian, H. V.

    This document is part of Subvolume C 'Binary Liquid Systems of Nonelectrolytes III' of Volume 26 'Heats of Mixing, Vapor-Liquid Equilibrium, and Volumetric Properties of Mixtures and Solutions' of Landolt-Börnstein Group IV 'Physical Chemistry'. It contains the Chapter 'Volumetric Properties of the Mixture Thiolane 1,1-dioxide C4H8O2S + C6H14O4 3,6-Dioxaoctane-1,8-diol (VMSD1111, LB5084_V)' providing data from direct low-pressure measurement of mass density at variable mole fraction and constant temperature, in the single-phase region(s).

  10. Volumetric Properties of the Mixture Thiolane 1,1-dioxide C4H8O2S + C6H14O4 3,6-Dioxaoctane-1,8-diol (VMSD1212, LB5088_V)

    NASA Astrophysics Data System (ADS)

    Cibulka, I.; Fontaine, J.-C.; Sosnkowska-Kehiaian, K.; Kehiaian, H. V.

    This document is part of Subvolume C 'Binary Liquid Systems of Nonelectrolytes III' of Volume 26 'Heats of Mixing, Vapor-Liquid Equilibrium, and Volumetric Properties of Mixtures and Solutions' of Landolt-Börnstein Group IV 'Physical Chemistry'. It contains the Chapter 'Volumetric Properties of the Mixture Thiolane 1,1-dioxide C4H8O2S + C6H14O4 3,6-Dioxaoctane-1,8-diol (VMSD1212, LB5088_V)' providing data by calculation of molar excess volume from low-pressure density measurements at variable mole fraction and constant temperature.

  11. Formation of 6-methyl-1,4-dihydronaphthalene in the reaction of the p-tolyl radical with 1,3-butadiene under single-collision conditions.

    PubMed

    Parker, Dorian S N; Dangi, Beni B; Kaiser, Ralf I; Jamal, Adeel; Ryazantsev, Mikhail; Morokuma, Keiji

    2014-12-26

    Crossed molecular beam reactions of p-tolyl (C7H7) plus 1,3-butadiene (C4H6), p-tolyl (C7H7) plus 1,3-butadiene-d6 (C4D6), and p-tolyl-d7 (C7D7) plus 1,3-butadiene (C4H6) were carried out under single-collision conditions at collision energies of about 55 kJ mol(-1). 6-Methyl-1,4-dihydronaphthalene was identified as the major reaction product formed at fractions of about 94% with the monocyclic isomer (trans-1-p-tolyl-1,3-butadiene) contributing only about 6%. The reaction is initiated by barrierless addition of the p-tolyl radical to the terminal carbon atom of the 1,3-butadiene via a van der Waals complex. The collision complex isomerizes via cyclization to a bicyclic intermediate, which then ejects a hydrogen atom from the bridging carbon to form 6-methyl-1,4-dihydronaphthalene through a tight exit transition state located about 27 kJ mol(-1) above the separated products. This is the dominant channel under the present experimental conditions. Alternatively, the collision complex can also undergo hydrogen ejection to form trans-1-p-tolyl-1,3-butadiene; this is a minor contributor to the present experiment. The de facto barrierless formation of a methyl-substituted aromatic hydrocarbons by dehydrogenation via a single event represents an important step in the formation of polycyclic aromatic hydrocarbons (PAHs) and their partially hydrogenated analogues in combustion flames and the interstellar medium. PMID:25407848

  12. 4,6-Dimeth­oxy­pyrimidin-2-amine–2-(1H-indol-3-yl)acetic acid (1/1)

    PubMed Central

    Ebenezer, Samuel; Muthiah, Packianathan Thomas

    2010-01-01

    In the title co-crystal C6H9N3O2·C10H9NO2, the 4,6-dimeth­oxy­pyrimidin-2-amine mol­ecule inter­acts with the carboxyl group of the 2-(1H-indol-3-yl)acetic acid mol­ecule through N—H⋯O and O—H⋯N hydrogen bonds, forming a cyclic hydrogen-bonded R 2 2(8) motif, which is further linked by an N—H⋯N hydrogen bond, forming a supra­molecular chain along the c axis. Neighboring chains are inter­linked via C—H⋯O hydrogen bonds, forming a supra­molecular ladder PMID:21587607

  13. Specific, reversible inactivation of phosphofructokinase by fructose-1,6-bisphosphatase. Involvement of adenosine 5'-triphosphate, oleate, and 3-phosphoglycerate.

    PubMed

    Proffitt, R T; Sankaran, L

    1976-06-29

    Optimal conditions necessary for the reversible inactivation of crystalline rabbit muscle phosphofructokinase by homogeneous rabbit liver fructose-1,6-bisphosphatase have been studied. At higher enzyme levels (to 530 mug/ml of phosphofructokinase) the two proteins were mixed and incubated in a pH 7.5 buffer composed of 50 mM Tris-HC1, 2 mM potassium phosphate, and 0.2 mM dithiothreitol. Aliquots were removed at various times and assayed for enzyme activity. A time dependent inactivation of phosphofructokinase caused by 1-2.3 times its weight of fructose-1,6-bisphosphatase was observed at 30, 23, and 0 degree C. This inactivation did not require the presence of adenosine 5'-triphosphate or Mg2+ in the incubation mixture, but an adenosine 5'-triphosphate concentration of 2.7 mM or greater was required in the assay to keep phosphofructokinase in an inactive form. A mixture of activators (inorganic phosphate, (NH4)2SO4, and adenosine 5'-monophosphate), when added to the assay cuvette, restored nearly all of the expected enzyme activity. Incubations with other proteins, including aldolase, at concentrations equal to or greater than the effective quantity of fructose-1,6-bisphosphatase had no inhibitory effect on phosphofructokinase activity. Removal of tightly bound fructose 1,6-bisphosphate from phosphofructokinase could not explain this inactivation, since several analyses of crystalline phosphofructokinase averaged less than 0.1 mol of fructose 1,6-bisphosphate/320 000 g of enzyme. Furthermore, the inactivation occurred in the absence of Mg2+ where the complete lack of fructose-1-6-bisphosphatase activity was confirmed directly. At lower phosphofructokinase concentrations (0.2-2 mug/ml) the inactivation was studied directly in the assay cuvette. Higher ratios of fructose-1,6-bisphosphatase to phosphofructokinase were necessary in these cases, but oleate and 3-phosphoglycerate acted synergistically with lower amounts of fructose-1,6-bisphosphatase to cause

  14. N-heterocyclic carbene gold(I) catalyzed transformation of N-tethered 1,5-bisallenes to 6,7-dimethylene-3-azabicyclo[3.1.1]heptanes.

    PubMed

    Kim, Soo Min; Park, Ji Hoon; Kang, Youn Kyung; Chung, Young Keun

    2009-01-01

    Tying up loose ends: The reaction of bisallenes tethered with N-(p-tolylsulfonamide) in the presence of a cationic gold N-heterocyclic carbene catalyst gave new cycloisomerization products, 6,7-dimethyleneazabicyclo[3.1.1]heptanes, in high yields (see scheme; IPr = N,N'-bis(2,6-diisopropylphenyl)imidazol-2-ylidene). PMID:19437519

  15. 2-Amino-4-methyl-4,5,6,7-tetrahydro-1-benzothiophene-3-carbonitrile.

    PubMed

    Khan, Ashraf Y; Fathima, Nikhath; Kalashetti, Mallikarjun B; Begum, Noor Shahina; Khazi, I M

    2012-10-01

    In the title compound, C(10)H(12)N(2)S, the thio-phene ring is essentially planar (r.m.s. deviation = 0.0290 Å). The two C atoms of the cyclo-hexene ring (at positions 6 and 7) are disordered over two sets of sites in a 0.810 (5):0.190 (5) ratio. The cyclo-hexene rings in both the major and minor occupancy conformers adopt a half-chair conformation. In the crystal, there are two types of N-H⋯N inter-action. One of these results in centrosymmetric head-to-head dimers corresponding to an R(2) (2)(12) graph-set motif and the other forms a 20-membered macrocyclic ring involving six mol-ecules. PMID:23125792

  16. Hydrogen Sulfide Attenuates Inflammatory Hepcidin by Reducing IL-6 Secretion and Promoting SIRT1-Mediated STAT3 Deacetylation

    PubMed Central

    Xin, Hong; Wang, Minjun; Tang, Wenbo; Shen, Zhuqing; Miao, Lei; Wu, Weijun; Li, Chengyi; Wang, Xiling; Xin, Xiaoming

    2016-01-01

    Abstract Aims: Anemia of inflammation is quite prevalent in hospitalized patients with poor prognosis. Concerns about the effectiveness and safety of iron supplementation have arisen, driving the demand for alternative therapies. Induction of hepatic hepcidin, the master hormone of iron homeostasis, causes anemia under inflammatory conditions. Previous studies indicated that hydrogen sulfide (H2S), the third gasotransmitter and a well-known regulator of inflammation, may inhibit the secretion of inflammatory cytokines. We thus investigated the effect of H2S on inflammatory hepcidin induction. Results: H2S suppressed lipopolysaccharide (LPS)-induced hepcidin production and regulated iron homeostasis in mice by decreasing serum interleukin-6 (IL-6) and Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) activation; similar results were obtained in Huh7 cells exposed to conditioned medium from LPS-challenged THP-1 macrophages. Intriguingly, we found H2S also attenuated hepcidin levels in Huh7 cells and mouse primary hepatocytes in a sirtuin 1 (SIRT1)-dependent manner. By promoting SIRT1 expression and stabilizing SIRT1-STAT3 interactions, H2S ameliorated IL-6-induced STAT3 acetylation, resulting in reduced hepcidin production. Inhibition and silencing of SIRT1 diminished H2S-mediated suppression of hepcidin, as opposed to SIRT1 activation and overexpression. Consistent results were observed in vivo. Furthermore, knockout of cystathionine γ-lyase (CSE), an endogenous H2S synthase, exaggerated inflammatory hepcidin expression in mice. Innovation: For the first time, we elucidated the effects and possible mechanisms of H2S on inflammatory hepcidin and established a novel regulatory link between SIRT1 and hepcidin. Conclusion: Our work demonstrates that H2S attenuates inflammation-induced hepatic hepcidin via multipathways and suggests new treatment strategies for anemia of inflammation. Antioxid. Redox Signal. 24, 70–83. PMID:26154696

  17. Fluorescence in situ hybridization mapping of the mouse platelet endothelial cell adhesion molecule-1 (PECAM1) to mouse chromosome 6, region F3-G1

    SciTech Connect

    Xie, Yong; Muller, W.A.

    1996-10-15

    Human platelet/endothelial cell adhesion molecule-1 (PECAM1), an important member of the immunoglobulin gene superfamily, is widely distributed on cells of the vascular system and mediates cellular interactions through both homophilic and heterophilic adhesive mechanisms. The function of PECAM1 in vitro has begun to be understood, but its function in vivo is yet to be established. To study the function of PECAM1 in vivo, its mouse counterpart was identified and its cDNA gene isolated and characterized. In this study, the mouse chromosomal localization was determined for the mouse gene encoding Pecam. Fluorescence in situ hybridization was used to map the Pecam gene on mouse chromosome 6, region F3-G1. 12 refs., 2 figs.

  18. 1,3-Diallyl-1H-anthra[1,2-d]imidazole-2,6,11(3H)-trione

    PubMed Central

    Afrakssou, Zahra; Rodi, Youssef Kandri; Zouihri, Hafid; Essassi, El Mokhtar; Ng, Seik Weng

    2010-01-01

    In the title compound, C21H16N2O3, the fused-ring system (r.m.s. deviation = 0.067 Å) is slightly buckled at the carbonyl C atom of the anthracenyl ring system [deviation = 0.177 (1) Å] that is closer to an allyl substituent. The two allyl units lie on the same side of the fused-ring plane but are oriented in opposite directions, with N—C—C—C torsion angles of 126.9 (2) and 116.7 (2)°. In the crystal, the mol­ecules are linked into chains propagating along the b axis by C—H⋯O hydrogen bonds. PMID:21588049

  19. Cu(I)-catalyzed regio- and stereoselective [6 + 3] cycloaddition of azomethine ylides with tropone: an efficient asymmetric access to bridged azabicyclo[4.3.1]decadienes.

    PubMed

    Teng, Huai-Long; Yao, Lu; Wang, Chun-Jiang

    2014-03-12

    An unprecedented Cu(I)-catalyzed asymmetric [6 + 3] cycloaddition of tropone with azomethine ylides was reported, which performs well over a broad scope of substrates and offers a unique and facile access to the synthetically useful bridged azabicyclo[4.3.1]decadiene derivatives in good yields with high levels of diastereoselectivities and enantioselectivities under mild conditions. PMID:24564408

  20. 2,2-Dimethyl-5-(2-nitro-benzyl-idene)-1,3-dioxane-4,6-dione.

    PubMed

    García-Álvarez, Fernando; Romero, Nancy; Lobato-García, Carlos E; Terán, Joel L; Mendoza, Angel

    2013-01-01

    The asymmetric unit of the title compound, C13H11NO6, contains two mol-ecules in both of which the six-membered 1,3-dioxane-4,6-dione ring shows a screw-boat conformation. The dihedral angles between the best planes through the six-membered rings are 47.8 (2) and 49.8 (2)°. In the crystal, C-H⋯O inter-actions link the mol-ecules, building a supramolecular sheet parallel to the c axis. PMID:23476434

  1. Dissolution and sorption of hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) and 2,4,6-trinitrotoluene (TNT) residues from detonated mineral surfaces.

    PubMed

    Jaramillo, Ashley M; Douglas, Thomas A; Walsh, Marianne E; Trainor, Thomas P

    2011-08-01

    Composition B (Comp B) is a commonly used military formulation composed of the toxic explosive compounds 2,4,6-trinitrotoluene (TNT), and hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX). Numerous studies of the temporal fate of explosive compounds in soils, surface water and laboratory batch reactors have been conducted. However, most of these investigations relied on the application of explosive compounds to the media via aqueous addition and thus these studies do not provide information on the real world loading of explosive residues during detonation events. To address this we investigated the dissolution and sorption of TNT and RDX from Comp B residues loaded to pure mineral phases through controlled detonation. Mineral phases included nontronite, vermiculite, biotite and Ottawa sand (quartz with minor calcite). High Performance Liquid Chromatography and Attenuated Total Reflectance Fourier Transform Infrared spectroscopy were used to investigate the dissolution and sorption of TNT and RDX residues loaded onto the mineral surfaces. Detonation resulted in heterogeneous loading of TNT and RDX onto the mineral surfaces. Explosive compound residues dissolved rapidly (within 9 h) in all samples but maximum concentrations for TNT and RDX were not consistent over time due to precipitation from solution, sorption onto mineral surfaces, and/or chemical reactions between explosive compounds and mineral surfaces. We provide a conceptual model of the physical and chemical processes governing the fate of explosive compound residues in soil minerals controlled by sorption-desorption processes. PMID:21601233

  2. Technical Support Document for Version 3.6.1 of the COMcheck Software

    SciTech Connect

    Bartlett, Rosemarie; Connell, Linda M.; Gowri, Krishnan; Halverson, Mark A.; Lucas, Robert G.; Richman, Eric E.; Schultz, Robert W.; Winiarski, David W.

    2009-09-29

    This technical support document (TSD) is designed to explain the technical basis for the COMcheck software as originally developed based on the ANSI/ASHRAE/IES Standard 90.1-1989 (Standard 90.1-1989). Documentation for other national model codes and standards and specific state energy codes supported in COMcheck has been added to this report as appendices. These appendices are intended to provide technical documentation for features specific to the supported codes and for any changes made for state-specific codes that differ from the standard features that support compliance with the national model codes and standards.

  3. 78 FR 67142 - HHCB (1,3,4,6,7,8-Hexahydro-4,6,6,7,8,8,-hexamethylcyclopenta[γ]-2-benzopyran) TSCA Risk...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-08

    ...) chemical risk assessment, ``TSCA Workplan Chemical Risk Assessment for HHCB.'' EPA will hold three peer... technical information contact: Stan Barone, Jr., Risk Assessment Division (7403M), Office of Pollution.... Background On January 9, 2013, EPA published a document in the Federal Register (78 FR 1856) (FRL-9375-1)...

  4. Arabidopsis inositol 1,3,4-trisphosphate 5/6 kinase 2 is required for seed coat development.

    PubMed

    Tang, Yong; Tan, Shutang; Xue, Hongwei

    2013-07-01

    Inositol 1,3,4-trisphosphate 5/6 kinase (ITPK) phosphorylates inositol 1,3,4-trisphosphate to form inositol 1,3,4,5-tetrakisphosphate and inositol 1,3,4,6-tetrakisphosphate which can be finally transferred to inositol hexaphosphate (IP₆) and play important roles during plant growth and development. There are 4 putative ITPK members in Arabidopsis. Expression pattern analysis showed that ITPK2 is constitutively expressed in various tissues. A T-DNA knockout mutant of ITPK2 was identified and scanning electron microscopy (SEM) analysis showed that the epidermis structure of seed coat was irregularly formed in seeds of itpk2-1 mutant, resulting in the increased permeability of seed coat to tetrazolium salts. Further analysis by gas chromatography coupled with mass spectrometry of lipid polyester monomers in cell wall confirmed a dramatic decrease in composition of suberin and cutin, which relate to the permeability of seed coat and the formation of which is accompanied with seed coat development. These results indicate that ITPK2 plays an essential role in seed coat development and lipid polyester barrier formation. PMID:23595027

  5. Health for Development. Farm House Dialogue (6th, Ota, Nigeria, September 1-3, 1989).

    ERIC Educational Resources Information Center

    Africa Leadership Forum.

    This document summarizes discussions at an invitational workshop on health care development in Nigeria. The discussion centered on the need for cooperation among government service-delivery agencies and on the need to improve general national economic conditions. The following broad topics were discussed: (1) the history of health care during the…

  6. Catalytic transformations of vinylthiiranes by tungsten carbonyl complexes. A new route to 3,6-dihydro-1,2-dithiins

    SciTech Connect

    Adams, R.D.; Perrin, J.L.

    1999-04-28

    W(CO){sub 5}(NCMe) has been found to transform vinylthiirane and a series of methyl-substituted vinylthiiranes into a series of 3,6-dihydro-1,2-dithiin compounds. Two equivalents of the vinylthiirane are required, and 1 equiv of a butadiene is formed by the transfer of its sulfur atom to the second vinylthiirane, which is then transformed into the dihydrodithiin. The formation of 3,6-dihydro-1,2-dithiin proceeds at 15 turnovers/h at 25 C using vinylthiirane as the catalyst. The catalyst is long-lived (up to 2,000 turnovers have been obtained without loss of activity) and relatively insensitive to air. Methyl substituents on the vinyl group increase the rate of reaction while methyl substituents on the thiirane ring slow it considerably. The introduction of phosphine ligands to the catalyst also leads to significant increases in the rate of reaction. The dithiin complex W(CO){sub 5}({ovr SSCH{sub 2}CH{double_bond}CHC}H{sub 2}) was isolated from the catalytic reactions and was structurally characterized. The dihydrodithiin is coordinated to the tungsten atom through one of its two sulfur atoms. This product was shown to be a species in the catalytic cycle. A mechanism involving a vinylthiirane intermediate that undergoes spontaneous ring opening, followed by addition of a second vinylthiirane to the terminal carbon of the chain, elimination of 1 equiv of butadiene, and formation of a sulfur-sulfur bond leading to the compound above is proposed. The vinylthiirane intermediate is regenerated by ligand substitution which releases the dihydrodithiin product. 3,6-dihydro1,2-dithiin readily polymerizes when its pure form is exposed to visible light. If the polymerization is interrupted at an early stage, 1,2,7,8-tetrathiacyclododeca-4,10-diene, a dimer, can be isolated. The dimer was obtained in 5.6% yield and was structurally characterized crystallographically.

  7. Formation of inositol 1,3,4,6-tetrakisphosphate during angiotensin II action in bovine adrenal glomerulosa cells

    SciTech Connect

    Balla, T.; Guillemette, G.; Baukal, A.J.; Catt, K.J.

    1987-10-14

    Angiotensin II stimulates the formation of several inositol polyphosphates in cultured bovine adrenal glomerulosa cells prelabelled with (/sup 3/H) inositol. Analysis by high performance anion exchange chromatography of the inositol-phosphate compounds revealed the existence of two additional inositol tetrakisphosphate (InsP4) isomers in proximity to Ins-1,3,4,5-P4, the known phosphorylation product of Ins-1,4,5-trisphosphate and precursor of Ins-1,3,4-trisphosphate. Both of these new compounds showed a slow increase after stimulation with angiotensin II. The structure of one of these new InsP4 isomers, which is a phosphorylation product of Ins-1,3,4-P3, was deduced by its resistance to periodate oxidation to be Ins-1,3,4,6-P4. The existence of multiple cycles of phosphorylation-dephosphorylation reactions for the processing of Ins-1,4,5-P4 may represent a new aspect of the inositol-lipid related signalling mechanism in agonist-activated target cells.

  8. The thermodynamic properties of 4,5,9,10-tetrahydropyrene and 1,2,3,6,7,8-hexahydropyrene

    SciTech Connect

    Chirico, R.D.; Knipmeyer, S.E.; Nguyen, A.; Smith, N.K.; Steele, W.V.

    1992-12-01

    Measurements leading to the calculation of the ideal-gas thermodynamic properties are reported for 4,5,9,10-tetrahydropyrene and 1,2,3,6,7,8-hexahydropyrene. Experimental methods included combustion calorimetry, adiabatic heat-capacity calorimetry, vibrating-tube densitometry, comparative ebulliometry, inclined-piston gauge manometry, and differential-scanning calorimetry (d.s.c.). Critical properties were estimated for both materials based on the measurement results. Entropies, enthalpies, and Gibbs energies of formation were derived for the ideal gases for selected temperatures between 380 K and 700 K. The property-measurement results reported here for 4,5,9,10-tetrahydropyrene and 1,2,3,6,7,8-hexahydropyrene are the first for these important intermediates in the pyrene/H{sub 2} hydrogenation reaction network.

  9. Polarized Raman spectroscopy of corrugated MBE grown GaAs (6¯3¯1¯) homoepitaxial films

    NASA Astrophysics Data System (ADS)

    Espinosa-Vega, L. I.; Rodriguez, A. G.; Cruz-Hernandez, E.; Martinez-Veliz, I.; Rojas-Ramirez, J.; Ramirez-Lopez, M.; Nieto-Navarro, J.; Lopez-Lopez, M.; Mendez-Garcia, V. H.

    2013-09-01

    In this work, we present a Raman scattering study of GaAs layers grown on (6¯3¯1¯)-oriented substrates by molecular beam epitaxy. A set of samples whose morphology sustained different corrugation order were grown by MBE by varying the growth parameters such as temperature and As/Ga flux ratio. We employed polarized Raman spectroscopy using the backscattering configurations Z(XX) Z¯, Z(XY) Z¯ and Z(YY)Z¯. According to the calculated dipole selection rules both TO and LO phonons are allowed for backscattering from a perfect GaAs (6¯3¯1¯) crystal, but with the intensity of the TO phonon much larger than that of the LO phonon. However, it is found that the selection rules differ for corrugated samples. Besides, the TO/LO phonon resonances intensity ratio and the LO peak asymmetry depend on the corrugation order of the samples.

  10. New example of spontaneous resolution among aryl glycerol ethers: 3-(2,6-dichlorophenoxy)propane-1,2-diol

    NASA Astrophysics Data System (ADS)

    Bredikhina, Zemfira A.; Kurenkov, Alexey V.; Zakharychev, Dmitry V.; Krivolapov, Dmitry B.; Bredikhin, Alexander A.

    2016-08-01

    Using a set of simple tests, based on the properties of ideal conglomerate phase diagrams, it has been suggested to the conglomerate-formative nature of 3-(2,6-dichlorophenoxy)-propane-1,2-diol 1. Additional arguments have been drawn during the study of a single crystal X-ray diffraction study of the compound. The crystal packing details have been evaluated and discussed. Racemic 1 have been resolved into individual (S)- and (R)-components by a preferential crystallization procedure.

  11. Synthesis of Substituted 2,3,5,6-tetraarylbenzo(1,2-b:5,4-b')difurans

    NASA Technical Reports Server (NTRS)

    Abdul-Aziz, Mahmoud; Auping, Judith V.; Meador, Michael A.

    1995-01-01

    A series of substituted 2,3,5,6-tetraarylbenzo(l,2-b:5,4-b')difurans 1 was synthesized. This synthesis is based upon the photocyclization of 2,5-dibenzoylresorcinol dibenzyl ethers to the corresponding tetrahydrobenzo(1,2-b:5,4-b')difurans. Treatment of the photoproducts with methanesulfonyl chloride in pyridine afforded 1 in overall yields ranging from 30-72%. A number of these compounds have high fluorescence quantum yields (of phi(sub f) = 0.76-0.90), and their fluorescence spectra exhibit large solvatochromic shifts. These compounds may be suitable for use as fluorescent probes.

  12. Direct activation of RIP3/MLKL-dependent necrosis by herpes simplex virus 1 (HSV-1) protein ICP6 triggers host antiviral defense

    PubMed Central

    Wang, Xing; Li, Yun; Liu, Shan; Yu, Xiaoliang; Li, Lin; Shi, Cuilin; He, Wenhui; Li, Jun; Xu, Lei; Hu, Zhilin; Yu, Lu; Yang, Zhongxu; Chen, Qin; Ge, Lin; Zhang, Zili; Zhou, Biqi; Jiang, Xuejun; Chen, She; He, Sudan

    2014-01-01

    The receptor-interacting kinase-3 (RIP3) and its downstream substrate mixed lineage kinase domain-like protein (MLKL) have emerged as the key cellular components in programmed necrotic cell death. Receptors for the cytokines of tumor necrosis factor (TNF) family and Toll-like receptors (TLR) 3 and 4 are able to activate RIP3 through receptor-interacting kinase-1 and Toll/IL-1 receptor domain-containing adapter inducing IFN-β, respectively. This form of cell death has been implicated in the host-defense system. However, the molecular mechanisms that drive the activation of RIP3 by a variety of pathogens, other than the above-mentioned receptors, are largely unknown. Here, we report that human herpes simplex virus 1 (HSV-1) infection triggers RIP3-dependent necrosis. This process requires MLKL but is independent of TNF receptor, TLR3, cylindromatosis, and host RIP homotypic interaction motif-containing protein DNA-dependent activator of IFN regulatory factor. After HSV-1 infection, the viral ribonucleotide reductase large subunit (ICP6) interacts with RIP3. The formation of the ICP6–RIP3 complex requires the RHIM domains of both proteins. An HSV-1 ICP6 deletion mutant failed to cause effective necrosis of HSV-1–infected cells. Furthermore, ectopic expression of ICP6, but not RHIM mutant ICP6, directly activated RIP3/MLKL-mediated necrosis. Mice lacking RIP3 exhibited severely impaired control of HSV-1 replication and pathogenesis. Therefore, this study reveals a previously uncharacterized host antipathogen mechanism. PMID:25316792

  13. Adsorption-desorption of 2,4,6-trinitrotoluene and hexahydro-1,3,5-trinitro-1,3,5-triazine in soils

    SciTech Connect

    Xue, S.K.; Selim, H.M.; Iskandar, I.K.

    1995-11-01

    This study studied the adsorption-desorption behavior of TNT (2, 4, 6-trinitrotoluene) and RDX (hexahydro-1,3,5-trinitro-1,3,5-triazine) in a bentonite/sand reference material (Swy-1 montmorillonite clay mixed with acid-washed sand) and two selected soils (Norwood and Kolin). Release of TNT,RDX, and other compounds from a contaminated soil obtained from the Louisiana Army Ammunition Plant (AAP) site was also investigated. The kinetics of TNT and RDX retention were measured using batch methods for a range of input concentrations. For RDX, the adsorption isotherms were distinctly linear. The TNT adsorption isotherm for bentonite/sand mixture appeared linear and was described equally well using linear, Freundlich, Langmuir, and a modified Langmuir model. For the Norwood and Kolin soils, TNT adsorption isotherms exhibited distinct nonlinearity and the Freundlich model provided the best fit. As indicated by the K{sub d} values, TNT exhibited stronger retention or affinity to all soils and the bentonite/sand mixture than for RDX. The RDX retention data indicated little time-dependent behavior. The TNT retention data indicated a continued decrease in TNT concentration with time in the Norwood and Kolin soils. This was possibly caused by the formation and subsequent adsorption of transformation products because transformation products, such as amino nitro toluene compounds, were identified during batch experiments. For the bentonite/sand mixture, TNT retention was rapid initially and reached apparent equilibrium within 1 day. Unlike Kolin and Norwood soils, there was no hysteretic behavior of TNT adsorption-desorption by the bentonite/sand mixture and a mass balance suggested fully reversible retention mechanisms. 15 refs., 13 figs., 2 tabs.

  14. Considerations on Daylight Operation of 1.6-VERSUS 3.7-µm Channel on NOAA and Metop Satellites.

    NASA Astrophysics Data System (ADS)

    Rosenfeld, Daniel; Cattani, Elsa; Melani, Samantha; Levizzani, Vincenzo

    2004-06-01

    The transition from the Advanced Very High Resolution Radiometer (AVHRR)/2 to AVHRR/3 on NOAA polar orbiters was associated with a switching from daylight operations of the 3.7- to 1.6-µm wave band, while retaining 3.7 µm for nighttime operations. Investigations of the daylight applicability of the two channels suggest that the 1.6-µm wave band for daylight operations does not prove to be the better choice, at least for cloud applications. The 3.7-µm wave band is much less affected by surface contamination, and measures more faithfully and unambiguously the particle effective radius near cloud tops. The 1.6-µm radiation penetrates deeper into the cloud, supplying an integrated signal throughout the inner portions of the cloud, including surface contribution. Therefore, a synergetic use of the two wave bands can provide an improved retrieval of cloud microstructure and precipitation than from any of the channels alone. However, when one channel must be selected for the AVHRR/3, 3.7 µm performs much better for these applications. Both wave bands identify equally well microphysical features in the anvils of severe storms. For other applications, such as detection of ice and snow over vegetated surfaces and desert dust aerosols, the 1.6-µm wave band does not present clear advantages with respect to 3.7 µm, except that it can be used directly as is, whereas the 3.7-µm wave band has to be corrected for the thermal emission and water vapor absorption. Anyway, the Moderate Resolution Imaging Spectroradiometer (MODIS) can be used instead for the applications to the relatively slowly changing surface properties, while prioritizing the AVHRR for the faster varying atmospheric applications. Finally, the 3.7-mm wave band is more effective in detecting fog, fires, and hot spots. All these factors need to be considered by the operators of AVHRR/3 making a justifiable choice of the channels for the maximum benefit of the user community.

  15. Structural and Enzymatic Characterization of Os3BGlu6, a Rice β-Glucosidase Hydrolyzing Hydrophobic Glycosides and (13)- and (1→2)-Linked Disaccharides1[C][W][OA

    PubMed Central

    Seshadri, Supriya; Akiyama, Takashi; Opassiri, Rodjana; Kuaprasert, Buabarn; Cairns, James Ketudat

    2009-01-01

    Glycoside hydrolase family 1 (GH1) β-glucosidases play roles in many processes in plants, such as chemical defense, alkaloid metabolism, hydrolysis of cell wall-derived oligosaccharides, phytohormone regulation, and lignification. However, the functions of most of the 34 GH1 gene products in rice (Oryza sativa) are unknown. Os3BGlu6, a rice β-glucosidase representing a previously uncharacterized phylogenetic cluster of GH1, was produced in recombinant Escherichia coli. Os3BGlu6 hydrolyzed p-nitrophenyl (pNP)-β-d-fucoside (kcat/Km = 67 mm−1 s−1), pNP-β-d-glucoside (kcat/Km = 6.2 mm−1 s−1), and pNP-β-d-galactoside (kcat/Km = 1.6 mm−1s−1) efficiently but had little activity toward other pNP glycosides. It also had high activity toward n-octyl-β-d-glucoside and β-(13)- and β-(1→2)-linked disaccharides and was able to hydrolyze apigenin β-glucoside and several other natural glycosides. Crystal structures of Os3BGlu6 and its complexes with a covalent intermediate, 2-deoxy-2-fluoroglucoside, and a nonhydrolyzable substrate analog, n-octyl-β-d-thioglucopyranoside, were solved at 1.83, 1.81, and 1.80 Å resolution, respectively. The position of the covalently trapped 2-F-glucosyl residue in the enzyme was similar to that in a 2-F-glucosyl intermediate complex of Os3BGlu7 (rice BGlu1). The side chain of methionine-251 in the mouth of the active site appeared to block the binding of extended β-(1→4)-linked oligosaccharides and interact with the hydrophobic aglycone of n-octyl-β-d-thioglucopyranoside. This correlates with the preference of Os3BGlu6 for short oligosaccharides and hydrophobic glycosides. PMID:19587102

  16. 2,6-Diphenylthiazolo[3,2-b][1,2,4]triazoles as telomeric G-quadruplex stabilizers.

    PubMed

    El Bakali, Jamal; Klupsch, Frédérique; Guédin, Aurore; Brassart, Bertrand; Fontaine, Gaëlle; Farce, Amaury; Roussel, Pascal; Houssin, Raymond; Bernier, Jean-Luc; Chavatte, Philippe; Mergny, Jean-Louis; Riou, Jean-François; Hénichart, Jean-Pierre

    2009-07-01

    The design and synthesis of 2,6-diphenylthiazolo[3,2-b][1,2,4]triazoles characterized by a large aromatic building block bearing cationic side chains are reported. These molecules are evaluated as telomeric G-quadruplex stabilizers and for their selectivity towards duplex DNA by competition experiments. Two compounds (14a, 19) were found active with high selectivity for telomeric G-quadruplex over duplex DNA. PMID:19473838

  17. Enzyme-Linked Immunosorbent Assay Specific for (16) Branched, (13)-β-d-Glucan Detection in Environmental Samples

    PubMed Central

    Milton, Donald K.; Alwis, K. Udeni; Fisette, Leslie; Muilenberg, Michael

    2001-01-01

    (13)-β-d-Glucans have been recognized as a potential causative agent responsible for bioaerosol-induced respiratory symptoms observed in both indoor and occupational environments. A specific enzyme immunoassay was developed to quantify (16) branched, (13)-β-d-glucans in environmental samples. The assay was based on the use of a high-affinity receptor (galactosyl ceramide) specific for (13)-β-d-glucans as a capture reagent and a monoclonal antibody specific for fungal cell wall β-d-glucans as a detector reagent. The assay was highly specific for (16) branched, (13)-β-d-glucans (such as that from Saccharomyces cerevisiae) and did not show any response at 200 ng/ml to curdlan, laminarin, pustulan, dextran, mannan, carboxymethyl cellulose, and endotoxins. The detection level was 0.8 ng/ml for baker's yeast glucan and Betafectin. A coefficient of variation of 7.8% was obtained for (13)-β-d-glucans in house dust samples. Metal working fluids spiked with (13)-β-d-glucans inhibited the glucan assay. Because the assay is specific for (16) branched, (13)-β-d-glucans and is sensitive and reproducible, it will be useful for the investigation of health effects from exposure to this class of biologically active molecules. PMID:11722887

  18. Efficacy of a novel, orally active GSK-3 inhibitor 6-Methyl-N-[3-[[3-(1-methylethoxy)propyl]carbamoyl]-1H-pyrazol-4-yl]pyridine-3-carboxamide in tau transgenic mice.

    PubMed

    Uno, Yumiko; Iwashita, Hiroki; Tsukamoto, Tetsuya; Uchiyama, Noriko; Kawamoto, Tomohiro; Kori, Masakuni; Nakanishi, Atsushi

    2009-11-01

    Neurofibrillary tangles (NFTs) composed of hyperphosphorylated and aggregated tau are common pathological characteristics in Alzheimer's disease (AD) and other tauopathies. Aberrant tau phosphorylation is an early and pivotal event in the pathogenesis of tauopathies, and since GSK-3 is a key factor implicated in aberrant tau phosphorylation, GSK-3 inhibition is expected to suppress tauopathy disease progression. In the present study, we report the efficacy of a newly discovered small molecule GSK-3 inhibitor, 6-methyl-N-[3-[[3-(1-methylethoxy)propyl]carbamoyl]-1H-pyrazol-4-yl]pyridine-3-carboxamide (compound A), to inhibit tau phosphorylation and to reduce the amount of pathological aggregated tau in JNPL3 mice that overexpress a mutant form of human tau. Compound A is a highly potent and selective inhibitor of GSK-3 with an IC(50) of 2 nM, with at least 230-fold lower potency against 27 other kinases. Oral administration of compound A resulted in a significant reduction of tau phosphorylation at several GSK-3 directed sites. Furthermore, chronic oral administration of compound A markedly reduced aggregated tau in old JNPL3 mice. These results suggest that a novel, orally active GSK-3 inhibitor, compound A, has potency in the prevention of tau pathology. PMID:19698704

  19. The synthesis and structure of gemini QASs of 1,4:3,6-dianhydro-L-iditol

    NASA Astrophysics Data System (ADS)

    Sikora, Karol; Nowacki, Andrzej; Sikorski, Artur; Dmochowska, Barbara

    2015-12-01

    New, efficient, straightforward method of synthesizing quaternary diammonium salts of 1,4:3,6-dianhydro-L-iditol have been developed. This paper presents the synthesis and structural analysis of diammonium (gemini) salts, including their X-ray diffraction analysis, wherein the linking structure of nitrogen atoms consists of two fused furanoid rings. 1,4:3,6-dianhydro-2,5-di-O-triflyl-D-mannitol and four tertiary amines, i.e., 4-(N,N-dimethylamino)pyridine (DMAP), pyridine, trimethylamine and N,N-dimethyloctylamine, were used for the synthesis. All the syntheses were carried out under mild conditions by the direct nucleophilic displacement of the O-triflil group by the amine. Walden inversion of configuration at C2 and C5 atoms has occurred during the reaction, giving products with L-ido configuration. Furthermore, NMR and X-ray conformational analysis of 1,4:3,6-dianhydrohexitol residue was done. In most cases furanoid rings adopt the twisted conformation both in the crystal and in solution.

  20. Optical Zeeman spectroscopy of the [17.6]2-X3Δ1(1,0) band system of tungsten monocarbide, WC

    NASA Astrophysics Data System (ADS)

    Wang, Fang; Steimle, Timothy C.

    2011-09-01

    The Zeeman effect in the [17.6]2-X3Δ1(1,0) band system of tungsten monocarbide, WC, has been recorded and analyzed. Magnetic tuning of the spectral features recorded at high resolution (full width at half maximum ≅ 35 MHz) and at field strengths of 1101 and 2230 G are accurately modeled using an effective Zeeman Hamiltonian. The observed spectra were fit to produce gel -factors for the X3Δ1(υ = 0) and [17.6]2(υ = 1) states. The observed gel-factors are discussed in terms of the proposed electronic state distribution.

  1. An exceptionally simple method of preparation of biradicals. 2. Low-temperature fluorescence spectra and ambient temperature laser-induced fluorescence spectra of 1,3-, 1,6-, 2,6-, and 2,7-naphthoquinodimethane

    SciTech Connect

    Biewer, M.C.; Biehn, C.R.; Platz, M.S. ); Despres, A.; Migirdicyan, E. )

    1991-01-16

    1,3-, 1,6-, 2,6-, and 2,7-naphthoquinodimethane have been obtained by photolysis (254 nm) of bis(chloromethyl)naphthalenes in glassy media at 77 K or in solution at ambient temperature by KrF (249 nm) laser flash photolysis. These species are detected and characterized by fluorescence spectroscopy.

  2. Investigation of cyano-bridged coordination nanoparticles Gd(3+)/[Fe(CN)6](3-)/D-mannitol as T1-weighted MRI contrast agents.

    PubMed

    Perrier, M; Gallud, A; Ayadi, A; Kennouche, S; Porredon, C; Gary-Bobo, M; Larionova, J; Goze-Bac, Ch; Zanca, M; Garcia, M; Basile, I; Long, J; de Lapuente, J; Borras, M; Guari, Y

    2015-07-28

    Cyano-bridged Gd(3+)/[Fe(CN)6](3-) coordination polymer nanoparticles of 3-4 nm stabilized with D-mannitol presenting a high r1 relaxivity value of 11.4 mM(-1) s(-1) were investigated in vivo as contrast agents (CA) for Magnetic Resonance Imaging (MRI). They allow an increase of the MR image contrast and can act as an efficient intravascular T1 CA with a relatively long blood-circulation lifetime (60 min) without specific toxicity. PMID:25967733

  3. Some Topological Cycle Indices for the Full Non-Rigid Group 1, 3, 5-triamino-2, 4, 6-trinitrobenzene

    NASA Astrophysics Data System (ADS)

    Ghaforiadl, N.; Moghani, A.

    2010-11-01

    The dominant subgroups of an arbitrary finite group has been proposed by S. Fujita who applied his results to enumerate isomers of molecules. The full non-rigid group of 1,3,5-triamino-2,4,6-trinitronebzene is isomorphism to the wreath product of the symmetric groups S2 and S3 i.e. S2 wr S3 introduced by K. Balasubramanian (see Chem. Phy. Letter 398, 15-21, 2004), wr stands wreath product. Let Gi and Gj be any subgroups of an arbitrary finite group G, a subduced representation denoted by G(/Gi)↓Gj as a subgroup of the coset representation G(/Gi) that contains only the elements associated with the elements of Gj. A topological cycle index introduced by Fujita is called unit subduced cycle index denoted by USCI is defined Z(G(/Gi)↘Gj,sd) = Πg∈ΩSdg(ij) where Ω is a transversal for the double coset decompositions concerning Gi and Gj for i,j = 1,2,…|Ω| and sdg(ij) = |Gi|/|g-1Gig∩Gj. In this paper at first, we find the markaracter table for the matured full non-rigid group 1,3,5-triamino-2,4,6-trinitrobenzene and then, via GAP program the topological indices i.e. USCIs for the above molecule are computed.

  4. 1-(Piperidin-1-yl)-3-(2,4,6-trimethyl­phen­yl)propan-2-ol

    PubMed Central

    Maharramov, Abel M.; Khalilov, Ali N.; Gurbanov, Atash V.; Allahverdiyev, Mirze A.; Ng, Seik Weng

    2011-01-01

    The title compound, C17H27NO, features a bufferfly-shaped substituted 2-propanol having an aromatic ring on the 1-carbon and a piperidine ring on the 3-carbon. The piperidine ring adopts a chair conformation and its N atom shows a trigonal coordination. In the crystal, the hy­droxy group inter­acts with the N atom of an inversion-related mol­ecule, generating an O—H⋯N hydrogen-bonded dimer. PMID:21522478

  5. High nitrogen explosives. Part 2. Dibenzo-1,3a,4,6a-tetraazapentalenes and benzo-1 2,3,4-tetrazine-1,3-dioxides. Progress report, February 1994-June 1995

    SciTech Connect

    Altmann, K.L.; Merwin, L.H.; Norris, W.P.; Wilson, W.S.; Gilardi, R.

    1996-08-01

    High nitrogen materials are sought as a potentially dense, powerful but insensitive explosive and propellant ingredients. Elucidation of the structure and chemistry of dibenzo-1 ,3a,4,6a-tetraazapentalenes has continued, with particular attention to a putative C12N12O12 derivative initially prepared at the University of New Orleans. This research contributed substantially to identification of the actual o-quinone hydrate structure, and explanation of the apparently anomalous explosive insensitivity of the material. Synthesis of the novel 5,7-dinitrobenzo-1, 2,3,4-tetrazine-1,3-dioxide has been repeated, its structure has been confirmed, and preliminary evaluation of its explosive sensitivity has been completed.

  6. BOREAS RSS-16 AIRSAR CM Images: Integrated Processor Version 6.1 Level-3b

    NASA Technical Reports Server (NTRS)

    Hall, Forrest G. (Editor); Nickeson, Jaime (Editor); Saatchi, Susan; Newcomer, Jeffrey A.; Strub, Richard; Irani, Fred

    2000-01-01

    The BOREAS RSS-16 team used satellite and aircraft SAR data in conjunction with various ground measurements to determine the moisture regime of the boreal forest. RSS-16 assisted with the acquisition and ordering of NASA JPL AIRSAR data collected from the NASA DC-8 aircraft. The NASA JPL AIRSAR is a side-looking imaging radar system that utilizes the SAR principle to obtain high resolution images that represent the radar backscatter of the imaged surface at different frequencies and polarizations. The information contained in each pixel of the AIRSAR data represents the radar backscatter for all possible combinations of horizontal and vertical transmit and receive polarizations (i.e., HH, HV, VH, and VV). Geographically, the data cover portions of the BOREAS SSA and NSA. Temporally, the data were acquired from 12-Aug-1993 to 31-Jul-1995. The level-3b AIRSAR CM data are in compressed Stokes matrix format, which has 10 bytes per pixel. From this data format, it is possible to synthesize a number of different radar backscatter measurements. The data are stored in binary image-format files. The data files are available on a CD-ROM (see document number 20010000884), or from the Oak Ridge National Laboratory (ORNL) Distributed Active Archive Center (DAAC).

  7. Human Cytomegalovirus Immediate-Early 1 Protein Rewires Upstream STAT3 to Downstream STAT1 Signaling Switching an IL6-Type to an IFNγ-Like Response

    PubMed Central

    Lukas, Simone; Zenger, Marion; Reitberger, Tobias; Danzer, Daniela; Übner, Theresa; Munday, Diane C.; Paulus, Christina

    2016-01-01

    The human cytomegalovirus (hCMV) major immediate-early 1 protein (IE1) is best known for activating transcription to facilitate viral replication. Here we present transcriptome data indicating that IE1 is as significant a repressor as it is an activator of host gene expression. Human cells induced to express IE1 exhibit global repression of IL6- and oncostatin M-responsive STAT3 target genes. This repression is followed by STAT1 phosphorylation and activation of STAT1 target genes normally induced by IFNγ. The observed repression and subsequent activation are both mediated through the same region (amino acids 410 to 445) in the C-terminal domain of IE1, and this region serves as a binding site for STAT3. Depletion of STAT3 phenocopies the STAT1-dependent IFNγ-like response to IE1. In contrast, depletion of the IL6 receptor (IL6ST) or the STAT kinase JAK1 prevents this response. Accordingly, treatment with IL6 leads to prolonged STAT1 instead of STAT3 activation in wild-type IE1 expressing cells, but not in cells expressing a mutant protein (IE1dl410-420) deficient for STAT3 binding. A very similar STAT1-directed response to IL6 is also present in cells infected with a wild-type or revertant hCMV, but not an IE1dl410-420 mutant virus, and this response results in restricted viral replication. We conclude that IE1 is sufficient and necessary to rewire upstream IL6-type to downstream IFNγ-like signaling, two pathways linked to opposing actions, resulting in repressed STAT3- and activated STAT1-responsive genes. These findings relate transcriptional repressor and activator functions of IE1 and suggest unexpected outcomes relevant to viral pathogenesis in response to cytokines or growth factors that signal through the IL6ST-JAK1-STAT3 axis in hCMV-infected cells. Our results also reveal that IE1, a protein considered to be a key activator of the hCMV productive cycle, has an unanticipated role in tempering viral replication. PMID:27387064

  8. Human Cytomegalovirus Immediate-Early 1 Protein Rewires Upstream STAT3 to Downstream STAT1 Signaling Switching an IL6-Type to an IFNγ-Like Response.

    PubMed

    Harwardt, Thomas; Lukas, Simone; Zenger, Marion; Reitberger, Tobias; Danzer, Daniela; Übner, Theresa; Munday, Diane C; Nevels, Michael; Paulus, Christina

    2016-07-01

    The human cytomegalovirus (hCMV) major immediate-early 1 protein (IE1) is best known for activating transcription to facilitate viral replication. Here we present transcriptome data indicating that IE1 is as significant a repressor as it is an activator of host gene expression. Human cells induced to express IE1 exhibit global repression of IL6- and oncostatin M-responsive STAT3 target genes. This repression is followed by STAT1 phosphorylation and activation of STAT1 target genes normally induced by IFNγ. The observed repression and subsequent activation are both mediated through the same region (amino acids 410 to 445) in the C-terminal domain of IE1, and this region serves as a binding site for STAT3. Depletion of STAT3 phenocopies the STAT1-dependent IFNγ-like response to IE1. In contrast, depletion of the IL6 receptor (IL6ST) or the STAT kinase JAK1 prevents this response. Accordingly, treatment with IL6 leads to prolonged STAT1 instead of STAT3 activation in wild-type IE1 expressing cells, but not in cells expressing a mutant protein (IE1dl410-420) deficient for STAT3 binding. A very similar STAT1-directed response to IL6 is also present in cells infected with a wild-type or revertant hCMV, but not an IE1dl410-420 mutant virus, and this response results in restricted viral replication. We conclude that IE1 is sufficient and necessary to rewire upstream IL6-type to downstream IFNγ-like signaling, two pathways linked to opposing actions, resulting in repressed STAT3- and activated STAT1-responsive genes. These findings relate transcriptional repressor and activator functions of IE1 and suggest unexpected outcomes relevant to viral pathogenesis in response to cytokines or growth factors that signal through the IL6ST-JAK1-STAT3 axis in hCMV-infected cells. Our results also reveal that IE1, a protein considered to be a key activator of the hCMV productive cycle, has an unanticipated role in tempering viral replication. PMID:27387064

  9. 5-(2,6-difluorobenzyl)oxymethyl-5-methyl-3-(3-methylthiophen-2-yl)- 1,2-isoxazoline as a useful rice herbicide.

    PubMed

    Hwang, In Taek; Kim, Hyoung Rae; Jeon, Dong Ju; Hong, Kyung Sik; Song, Jong Hwan; Cho, Kwang Yun

    2005-11-01

    5-(2,6-difluorobenzyl)oxymethyl-5-methyl-3-(3-methylthiophen-2-yl)-1,2-isoxazoline derivative was synthesized, and its herbicidal activity was assessed under glasshouse and flooded paddy conditions. 5-(2,6-Difluorobenzyl)oxymethyl-5-methyl-3-(3-methylthiophen-2-yl)-1,2-isoxazoline demonstrated good rice selectivity and potent herbicidal activity against annual weeds at 125 g of a.i. ha(-1) under greenhouse conditions. Soil application of this compound showed complete control of barnyard-grass to the fourth leaf stage at 250 g of a.i. ha(-1). Field trials indicated that this compound controlled annual weeds rapidly with a good tolerance on transplanted rice seedlings by post-emergence and soil application. This compound showed a low mammalian and environmental toxicity in various toxicological tests. PMID:16248565

  10. 40 CFR 721.8950 - Chromate(3-), bis[3-[[6-amino-1,4-dihydro-2-[[[4-[(2-hydroxy-1-naphthalenyl)azo] phenyl]sulfonyl...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...]amino]-4-(oxo-.kappa.O)-5-pyrimidinyl]azo-.kappaN1]-4-hydroxy-.kappa.O)-5-nitrobenzenesulfonato(3... substance identified as chromate(3-), bis phenyl]sulfonyl]amino]-4-(oxo-.kappa.O)-5-pyrimidinyl]azo-.kappaN1... Significant New Uses for Specific Chemical Substances § 721.8950 Chromate(3-), bis...

  11. 40 CFR 721.8950 - Chromate(3-), bis[3-[[6-amino-1,4-dihydro-2-[[[4-[(2-hydroxy-1-naphthalenyl)azo] phenyl]sulfonyl...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...]amino]-4-(oxo-.kappa.O)-5-pyrimidinyl]azo-.kappaN1]-4-hydroxy-.kappa.O)-5-nitrobenzenesulfonato(3... substance identified as chromate(3-), bis phenyl]sulfonyl]amino]-4-(oxo-.kappa.O)-5-pyrimidinyl]azo-.kappaN1... Significant New Uses for Specific Chemical Substances § 721.8950 Chromate(3-), bis...

  12. Anisotropic magnetodielectric coupling behavior of Ca3Co1.4Rh0.6O6 due to geometrically frustrated magnetism

    NASA Astrophysics Data System (ADS)

    Basu, Tathamay; Iyer, Kartik K.; Singh, Kiran; Mukherjee, K.; Paulose, P. L.; Sampathkumaran, E. V.

    2014-09-01

    We have investigated the magnetic, dielectric, and magnetodielectric (MDE) behavior of a geometrically frustrated spin-chain system, Ca3Co1.4Rh0.6O6 (related to Ca3CoRhO6), in the single crystalline form for different orientations. The results bring out that the magnetic behavior of this compound is by itself interesting in the sense that this compound exhibits an anisotropic glassy-like magnetic behavior with a huge frequency (ν) dependence of ac susceptibility (χ) peak for an orientation along the spin-chain in the range of 30-60 K; this behavior is robust to applications of large external magnetic fields (H) unlike in canonical spin-glasses. The temperature dependence of dielectric constant also shows strong ν-dependence with similar robustness to H. The isothermal H-dependent dielectric results at low temperatures establish anisotropic MDE coupling. It is intriguing to note that there is a "step" roughly at one-third of saturation values as in the case of isothermal magnetization curves for same temperatures (for orientation along spin-chain), a correlation hitherto unrealized for geometrically frustrated systems.

  13. Identification and pharmacological characterization of 3,6-diazabicyclo[3.1.1]heptane-3-carboxamides as novel ligands for the α4β2 and α63β2β3 nicotinic acetylcholine receptors (nAChRs).

    PubMed

    Strachan, Jon-Paul; Kombo, David C; Mazurov, Anatoly; Heemstra, Ronald; Bhatti, Balwinder S; Akireddy, Rao; Murthy, Srinivasa; Miao, Lan; Jett, John E; Speake, Jason; Bencherif, Merouane

    2014-10-30

    We have synthesized a novel series of compounds, 3,6-diazabicyclo[3.1.1]heptane-3-carboxamides, targeting both the α4β2 and α63β2β3 nAChRs. Members of the obtained chemical library are partial or full agonists at both the high sensitivity (α4)2(β2)3 and α63β2β3 nAChRs. 3-(Cyclopropylcarbonyl)-3,6-diazabicyclo[3.1.1]heptane (TC-8831 or compound 7 herein) demonstrated a safe in vitro pharmacological profile and the potential for reducing or preventing L-dopa-induced dyskinesias (LID) in several in vivo animal models [1-4]. In vivo metabolism studies in rat and in vitro metabolism studies in liver microsomes from human, rat, dog and monkey showed TC-8831 to be relatively stable. In vivo pharmacokinetic analysis in the rat confirmed brain penetration, with an average brain:plasma ratio of approximately 0.3 across time points from 0.5 to 4 h. Docking into homology models predicted alternative binding modes for TC-8831 and highlighted the importance of the cationic center, hydrogen-bond acceptor, and hydrophobic aliphatic features in promoting binding affinity to both nAChRs. Pharmacophore elucidation confirmed the importance of these key interactions. QSAR modeling suggested that binding affinity is primarily driven by ligand shape, relative positive charge distribution onto the molecular surface, and molecular flexibility. Of the two subtypes, ligand binding to α6β2β3 appears to be more sensitive to bulkiness and flexibility. PMID:25147147

  14. Development of doxorubicin-induced chronic cardiotoxicity in the B6C3F{sub 1} mouse model

    SciTech Connect

    Desai, Varsha G.; Herman, Eugene H.; Moland, Carrie L.; Branham, William S.; Lewis, Sherry M.; Davis, Kelly J.; George, Nysia I.; Lee, Taewon; Kerr, Susan; Fuscoe, James C.

    2013-01-01

    Serum levels of cardiac troponins serve as biomarkers of myocardial injury. However, troponins are released into the serum only after damage to cardiac tissue has occurred. Here, we report development of a mouse model of doxorubicin (DOX)-induced chronic cardiotoxicity to aid in the identification of predictive biomarkers of early events of cardiac tissue injury. Male B6C3F{sub 1} mice were administered intravenous DOX at 3 mg/kg body weight, or an equivalent volume of saline, once a week for 4, 6, 8, 10, 12, and 14 weeks, resulting in cumulative DOX doses of 12, 18, 24, 30, 36, and 42 mg/kg, respectively. Mice were sacrificed a week following the last dose. A significant reduction in body weight gain was observed in mice following exposure to a weekly DOX dose for 1 week and longer compared to saline-treated controls. DOX treatment also resulted in declines in red blood cell count, hemoglobin level, and hematocrit compared to saline-treated controls after the 2nd weekly dose until the 8th and 9th doses, followed by a modest recovery. All DOX-treated mice had significant elevations in cardiac troponin T concentrations in plasma compared to saline-treated controls, indicating cardiac tissue injury. Also, a dose-related increase in the severity of cardiac lesions was seen in mice exposed to 24 mg/kg DOX and higher cumulative doses. Mice treated with cumulative DOX doses of 30 mg/kg and higher showed a significant decline in heart rate, suggesting drug-induced cardiac dysfunction. Altogether, these findings demonstrate the development of DOX-induced chronic cardiotoxicity in B6C3F{sub 1} mice. -- Highlights: ► 24 mg/kg was a cumulative cardiotoxic dose of doxorubicin in male B6C3F{sub 1} mice. ► Doxorubicin-induced hematological toxicity was in association with splenomegaly. ► Doxorubicin induced severe testicular toxicity in B6C3F{sub 1} male mice.

  15. Synthesis of 2,6-dicarbethoxy-3,5-diaryltetrahydro-1,4-thiazine-1,1-dioxide derivatives as potent anticonvulsant agents.

    PubMed

    Edayadulla, Naushad; Ramesh, Penugonda

    2015-12-01

    An efficient synthesis of 2,6-dicarbethoxy-3,5-diaryltetrahydro-1,4-thiazine-1,1-dioxide derivatives has been achieved under aqueous medium for the first time in good to excellent yields. All the synthesized compounds were tested for anticonvulsant activity using the maximal electroshock (MES), subcutaneous pentylenetetrazole (scPTZ) screens, which are the most broadly employed seizure models for early identification of candidate anticonvulsants. Their neurotoxicity was determined applying the rotarod test. Seven compounds 4a, 4d, 4f, 4h, 4o, 4p and 4q showed promising anticonvulsant activities in both models employed for anticonvulsant evaluation. The most active compound 4d showed the MES-induced seizures with ED50 value of 10.2 mg/kg and TD50 value of 288.6 mg/kg after intraperitoneal injection to mice, which provided compound 4d with a protective index (TD50/ED50) of 28.3 in the MES test. PMID:26519928

  16. β-1,3/1,6-Glucan alleviated intestinal mucosal barrier impairment of broiler chickens challenged with Salmonella enterica serovar Typhimurium.

    PubMed

    Shao, Yujing; Guo, Yuming; Wang, Zhong

    2013-07-01

    This study investigated the protective effect of β-1,3/1,6-glucan on gut morphology, intestinal epithelial tight junctions, and bacterial translocation of broiler chickens challenged with Salmonella enterica serovar Typhimurium. Ninety Salmonella-free Arbor Acre male broiler chickens were randomly divided into 3 groups: negative control group (NC), Salmonella Typhimurium-infected positive group (PC), and the Salmonella Typhimurium-infected group with dietary 100 mg/kg of β-1,3/1,6-glucan supplementation (T) to determine the effect of β-1,3/1,6-glucan on intestinal barrier function. Salmonella Typhimurium challenge alone significantly decreased villus height (P < 0.001), villus height/crypt depth ratio (P < 0.05), and the number of goblet cells (P < 0.001) in the jejunum at 14 d postinfection (dpi), but significantly increased the number of intestinal secretory IgA (sIgA)-expressing cells at 14 dpi (P < 0.01) and total sIgA levels in the jejunum at 7 (P < 0.05) and 14 dpi (P < 0.01) compared with the unchallenged birds (NC). Dietary β-1,3/1,6-glucan supplementation not only significantly increased villus height, villus height/crypt depth ratio, and the number of goblet cells (P < 0.01), but also increased the number of sIgA-expressing cells (P < 0.05) and sIgA content in the jejunum at 14 dpi (P < 0.01) in birds challenged with Salmonella Typhimurium in comparison with Salmonella Typhimurium challenge alone. β-1,3/1,6-Glucan addition had significant inhibitory effects (P < 0.05) on cecal Salmonella colonization levels and liver Salmonella invasion of the Salmonella Typhimurium-infected birds compared with the PC group. Intestinal tight junction proteins claudin-1, claudin-4, and occludin mRNA expression in the jejunum at 14 dpi was significantly decreased by Salmonella Typhimurium challenge alone (P < 0.01) compared with that of the NC group, whereas β-1,3/1,6-glucan supplementation significantly increased claudin-1 and occludin mRNA expression (P < 0.01) at

  17. Elevated oxidative stress in skin of B6C3F1 mice affects dermal exposure to metal working fluid.

    PubMed

    Shvedova, A A; Kisin, E; Kisin, J; Castranova, V; Kommineni, C

    2000-09-01

    Metal working fluids (MWFs) are widely used in industry for metal cutting, drilling, shaping, lubricating, and milling. Potential for dermal exposure to MWFs exists for a large number of men and women via aerosols and splashing during the machining operations. It has been reported earlier that occupational exposure to MWFs causes allergic and irritant contact dermatitis. Previously, we showed that dermal exposure of female and male B6C3F1 mice to 5% MWFs for 3 months resulted in accumulation of mast cells and elevation of histamine in the skin. Topical exposure to MWF also resulted in elevated oxidative stress in the liver of both sexes and the testes in males. The goal of this study was to evaluate the interaction between oxidative stress in the skin and topical application of MWF. Oxidative stress in skin ofB6C3F1 mice of both sexes was generated by intradermal injection ofthe hydrogen peroxide (H2O2) -producing enzyme, glucose oxidase with polyethylene glycol (GOD+PEG). In mice given GOD+PEG, topical treatment with MWF (200 microl, 30%, for 1, 3, or 7 days) resulted in a mixed inflammatory cell response, accumulation of peroxidative products, and reduction of GSH content in the skin. Such changes were not observed with MWF treatment alone. These data indicate that oxidative stress can enhance dermal inflammation caused by occupational exposure to MWF. PMID:11693944

  18. Experimental investigations of material models for Ti-6A1-4V and 2024-T3

    SciTech Connect

    Leseur, D

    1999-05-03

    This report describes studies of the deformation and failure behavior of Ti-6Al-4V and 2024-T3 aluminum. Data was obtained at high strain rates and large strains using the split Hopkinson pressure bar technique. This information, plus additional data from the literature, was used to critically evaluate the ability of the Johnson Cook material model to represent the deformation and failure response of Ti-6AMV and 2024-T3 under conditions relevant to simulations of engine containment and the influence of uncontained engine debris on aircraft structures. This model is being used in the DYNA3D finite element code, which is being developed/validated for evaluating aircraft/engine designs relative to the federal airworthiness standards and for improving mitigation/containment technology. The results of the experimental work reported here were used to define a new set of material constants for the strength component of the Johnson Cook model for Ti-6Al-4V and 2024-T3. The capabilities and limitations of the model are reviewed. The model can accurately represent the stress-strain response of the materials. The major concern with the Johnson Cook material model is its ability to accurately represent the stress - strain rate response at strain rates greater than 10{sup 3}-10{sup 4} s{sup {minus}1}. Additional work is also needed to adequately account for failure via shear localization, which was the dominant failure mode at high strain rates in both materials. Failure modeling in both Ti-6Al-N and 2024-T3 will be considered further in future reports.

  19. Synthesis, characterization and cholinesterase enzymes inhibitory activity of 1-[3-methyl-5-(2,6,6-trimethyl-cyclohex-1-enyl)-4,5-dihydro-pyrazol-1-yl]-ethanone

    NASA Astrophysics Data System (ADS)

    Mehdi, Sayed Hasan; Ghalib, Raza Murad; Hashim, Rokiah; da Silva, M. Fátima C. Guedes; Sulaiman, Othman; Murugaiyah, Vikneswaran; Marimuthu, Mani Maran; Naqvi, Mehnaz

    2013-10-01

    The crystal structure of the title compound, 1-[3-methyl-5-(2,6,6-trimethyl-cyclohex-1-enyl)-4,5-dihydro-pyrazol-1-yl]-ethanone has been determined by single crystal X-ray diffraction. It crystallizes in the orthorhombic space group P212121. The FTIR as well as the 1H and 13C NMR spectra of the compound were also recorded and briefly discussed. Compound 1 demonstrated good inhibitory activity against butyrylcholinesterase (BChE; IC50 = 46.42 μM) comparable to physostigmine. However it showed moderate inhibitory activity against acetylcholinesterase (AChE; IC50 = 157.31 μM). It showed moderate inhibitory activity against acetylcholinesterase and selective inhibitory activity towards butyrylcholinesterase enzyme.

  20. Multiscale distribution of oxygen puddles in 1/8 doped YBa2Cu3O6.67

    PubMed Central

    Ricci, Alessandro; Poccia, Nicola; Campi, Gaetano; Coneri, Francesco; Caporale, Alessandra Stella; Innocenti, Davide; Burghammer, Manfred; Zimmermann, Martin v.; Bianconi, Antonio

    2013-01-01

    Despite intensive research a physical explanation of high Tc superconductors remains elusive. One reason for this is that these materials have generally a very complex structure making useless theoretical models for a homogeneous system. Little is known on the control of the critical temperature by the space disposition of defects because of lack of suitable experimental probes. X-ray diffraction and neutron scattering experiments used to investigate y oxygen dopants in YBa2Cu3O6+y lack of spatial resolution. Here we report the spatial imaging of dopants distribution inhomogeneity in YBa2Cu3O6.67 using scanning nano X-ray diffraction. By changing the X-ray beam size from 1 micron to 300 nm of diameter, the lattice inhomogeneity increases. The ordered oxygen puddles size distribution vary between 6–8 nm using 1 × 1 μm2 beam, while it is between 5–12 nm with a fat tail using the 300 × 300 nm2 beam. The increased inhomogeneity at the nanoscale points toward a network of superconducting puddles made of ordered oxygen interstitials. PMID:23924946

  1. Establishment of M1 multipolarity of a 6.5 (micro)2n resonance in 172Yb at E(gamma) = 3.3 MeV

    SciTech Connect

    Schiller, A; Voinov, A; Algin, E; Becker, J A; Bernstein, L A; Garrett, P E; Guttormsen, M; Nelson, R O; Rekstad, J; Siem, S

    2004-02-04

    Two-step-cascade spectra in {sup 172}Yb have been measured after thermal neutron capture. they are compared to calculations based on experimental values of the level density and radiative strength function (RSF) obtained from the {sup 173}Yb(3{sup 3}He,{alpha}{gamma}){sup 172}Yb reaction. The multipolarity of a 6.5(15) {mu}{sub N}{sup 2} resonance at E{sub {gamma}} = 3.3(1) MeV in the RSF is determined to be M1 by this comparison.

  2. 40 CFR 721.9078 - 6-Methoxy-1H-benz[de]isoquinoline-2 [3H]-dione derivative (generic).

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false 6-Methoxy-1H-benz isoquinoline-2... New Uses for Specific Chemical Substances § 721.9078 6-Methoxy-1H-benz isoquinoline-2 -dione... substance identified generically as 6-methoxy-1H-benz isoquinoline-2 -dione derivative (PMN P-00-1205)...

  3. 1-(6-Methyl-3-phenyl-2-sulfanyl­idene-1,2,3,4-tetra­hydro­pyrimidin-5-yl)ethanone

    PubMed Central

    Garibov, Emin N.; Gojayeva, Sevinj S.; Allahverdiyev, Mirze A.; Gurbanov, Atash V. Gurbanov; Brito, Iván

    2012-01-01

    In the title compound, C13H14N2OS, four C atoms of the phenyl ring are disordered over two sets of sites in a 0.60 (3):0.40 (3) ratio. The heterocyclic ring is essentially planar (r.m.s. deviation = 0.017 Å) and forms dihedral angles of 82.0 (2) and 79.3 (3)°, respectively, with the major and minor occupancy components of the phenyl ring. The crystal packing features N—H⋯O hydrogen bonds, which link the mol­ecules into C(6) chains running parallel to the b axis. PMID:22346918

  4. 1-(6-Methyl-3-phenyl-2-sulfanyl-idene-1,2,3,4-tetra-hydro-pyrimidin-5-yl)ethanone.

    PubMed

    Garibov, Emin N; Gojayeva, Sevinj S; Allahverdiyev, Mirze A; Gurbanov, Atash V Gurbanov; Brito, Iván

    2012-02-01

    In the title compound, C(13)H(14)N(2)OS, four C atoms of the phenyl ring are disordered over two sets of sites in a 0.60 (3):0.40 (3) ratio. The heterocyclic ring is essentially planar (r.m.s. deviation = 0.017 Å) and forms dihedral angles of 82.0 (2) and 79.3 (3)°, respectively, with the major and minor occupancy components of the phenyl ring. The crystal packing features N-H⋯O hydrogen bonds, which link the mol-ecules into C(6) chains running parallel to the b axis. PMID:22346918

  5. 40 CFR 721.10716 - Phenol, 2,6-dimethyl-, homopolymer, ether with 2,2',3,3',5,5'-hexamethyl[1,1'-biphenyl]-4,4'-diol...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Phenol, 2,6-dimethyl-, homopolymer... Phenol, 2,6-dimethyl-, homopolymer, ether with 2,2',3,3',5,5'-hexamethyl -4,4'-diol (2:1),bis ether. (a... phenol, 2,6-dimethyl-, homopolymer, ether with 2,2',3,3',5,5'-hexamethyl -4,4'-diol (2:1),bis ether...

  6. Insight into the pseudo π-hole interactions in the M3H6(NCF)n (M = C, Si, Ge, Sn, Pb; n = 1, 2, 3) complexes.

    PubMed

    Li, Wei; Zeng, Yanli; Li, Xiaoyan; Sun, Zheng; Meng, Lingpeng

    2016-09-21

    For cyclopropane and its derivatives M3H6 (M = C, Si, Ge, Sn, Pb), "pseudo π-hole" regions above and below the M-M-M three-membered ring have been discovered, and pseudo π-hole interactions between M3H6 and F-CN have been designed and investigated by MP2/aug-cc-pVTZ and MP2/aug-cc-pVTZ-pp calculations. To investigate the enhancing effects of FN halogen bonds on the pseudo π-hole interactions, the termolecular and tetramolecular complexes M3H6(NCF)n (n = 2, 3) were constructed. Energy decomposition analysis shows that the dispersion term contributes the most among the three attractive components in the C3H6(NCF)n (n = 1, 2, 3) complexes while in the Si3H6(NCF)n and Ge3H6(NCF)n complexes, the electrostatic term has the largest contribution. The electrostatic and polarization energies have more effect than the dispersion energy for the enhancement of the FN halogen bond on the pseudo π-hole interactions. With the increase in the number of NCF units from 1 to 3, the VS,min values outside the nitrogen atom of NCF become increasingly negative, the electric field of the lone pair of nitrogen becomes greater and causes a further increase of electron density outside the nitrogen atom and a further decrease of electron density outside the pseudo π-hole region, resulting in a stronger pseudo π-hole interaction. PMID:27545836

  7. 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...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 25 2013-07-01 2013-07-01 false S-Abscisic Acid, (S)-5-(1-hydroxy-2,6,6-trimethyl-4-oxo-1-cyclohex-2-enyl)-3-methyl-penta-(2Z,4E)-dienoic Acid; exemption from the...-enyl)-3-methyl-penta-(2Z,4E)-dienoic Acid; exemption from the requirement of a tolerance. An...

  8. 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...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 23 2010-07-01 2010-07-01 false S-Abscisic Acid, (S)-5-(1-hydroxy-2,6,6-trimethyl-4-oxo-1-cyclohex-2-enyl)-3-methyl-penta-(2Z,4E)-dienoic Acid; exemption from the...-enyl)-3-methyl-penta-(2Z,4E)-dienoic Acid; exemption from the requirement of a tolerance. An...

  9. 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...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 25 2012-07-01 2012-07-01 false S-Abscisic Acid, (S)-5-(1-hydroxy-2,6,6-trimethyl-4-oxo-1-cyclohex-2-enyl)-3-methyl-penta-(2Z,4E)-dienoic Acid; exemption from the...-enyl)-3-methyl-penta-(2Z,4E)-dienoic Acid; exemption from the requirement of a tolerance. An...

  10. 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...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 24 2011-07-01 2011-07-01 false S-Abscisic Acid, (S)-5-(1-hydroxy-2,6,6-trimethyl-4-oxo-1-cyclohex-2-enyl)-3-methyl-penta-(2Z,4E)-dienoic Acid; exemption from the...-enyl)-3-methyl-penta-(2Z,4E)-dienoic Acid; exemption from the requirement of a tolerance. An...

  11. Theoretical studies on the electronic structures and photoelectron spectra of tri-rhenium oxide clusters: Re3On- and Re3On (n = 1-6)

    NASA Astrophysics Data System (ADS)

    Zhou, Qi; Gong, Wei-Chao; Xie, Lu; Zheng, Cun-Gong; Zhang, Wei; Wang, Bin; Zhang, Yong-Fan; Huang, Xin

    2014-01-01

    Density functional theory (DFT) calculations are performed to study the structural and electronic properties of tri-rhenium oxide clusters Re3On-/0 (n = 1-6). Generalized Koopmans' theorem is applied to predict the vertical detachment energies (VDEs) and simulate the photoelectron spectra (PES). Theoretical calculations at the B3LYP level are carried out to search for the global minima for both the anions and the neutrals. For the anions, the first two O atoms prefer the same corner position of a Re3 triangle. Whereas, Re3O3- possesses a C2v symmetry with one bridging and two terminal O atoms. The next three O atoms (n = 4-6) are adding sequentially on the basis of Re3O3- motif, i.e., adding one terminal O atom for Re3O4-, one terminal and one bridging O atoms for Re3O5-, and one terminal and two bridging O atoms for Re3O6-, respectively. Their corresponding neutral species are similar to the anions in geometry except Re3O4 and Re3O5. Molecular orbital analyses are employed to investigate the chemical bonding and structural evolution in these tri-rhenium oxide clusters.

  12. Thermally stable compositions including 2,4,8,10-tetranitro-5H-pyrido[3',2':4,5][1,2,3]triazolo[1,2-a]benzotriazo- l-6-ium, inner salt

    DOEpatents

    Hiskey, Michael A.; Huynh, My Hang

    2010-01-26

    An explosive formulation including 2,4,8,10-tetranitro-5H-pyrido[3',2':4,5][1,2,3]triazolo[1,2-a]benzotriazo- l-6-ium, inner salt and a high temperature binder is disclosed together with a process of preparing 2,4,8,10-tetranitro-5H-pyrido[3',2':4,5][1,2,3]triazolo[1,2-a]benzotriazo- l-6-ium, inner salt.

  13. Polarization degrees of 3p 2P3/2-3s 2S1/2 transition in O5+(1s 23p) produced in collisions of O6+ with He and H2

    NASA Astrophysics Data System (ADS)

    Zhao, Y. Q.; Liu, L.; Xue, P.; Wang, J. G.; Janev, R. K.

    2010-09-01

    Electron capture processes in collisions of O6+ with ground state He and H2 are investigated using the two-centre atomic orbital close-coupling method. Total and state-selective one-electron capture cross sections are obtained for collision energies between 0.5 and 300 keV/u. The comparison with the available experimental state-selective capture data in the overlapping energy range (0.5-100 keV/u for O6++He and 0.5-8 keV/u for O6++H2) shows a good overall agreement. The polarization degrees of 3p 2P3/2-3s 2S1/2 radiation from O5+(3p 2P3/2) produced in O6++He and O6++H2 collisions are calculated from the magnetic substate-selective cross sections with inclusion of cascade contributions from higher n = 4 and n = 5 states. Good agreement is obtained with the experimental data available in the energy range 3-8 keV/u. Below ~10 keV/u, the polarization degrees of O5+(3p 2P3/2) in both collision systems exhibit an oscillatory structure and above this energy they steadily increase with the increase of collision energy, reaching the values of about 0.37 at 300 keV/u. The energy behaviour of the polarization degree of O5+(3p 2P3/2) in the O6++He collision system is determined almost exclusively by the direct electron capture to 3p0 and 3p1 states of O5+, while in the case of the O6++H2 collision system in the energy region below ~40 keV/u it is strongly affected by the cascade contributions from the 4l states, which are the dominant capture states in this system.

  14. Investigation of cyano-bridged coordination nanoparticles Gd3+/[Fe(CN)6]3-/d-mannitol as T1-weighted MRI contrast agents

    NASA Astrophysics Data System (ADS)

    Perrier, M.; Gallud, A.; Ayadi, A.; Kennouche, S.; Porredon, C.; Gary-Bobo, M.; Larionova, J.; Goze-Bac, Ch.; Zanca, M.; Garcia, M.; Basile, I.; Long, J.; de Lapuente, J.; Borras, M.; Guari, Y.

    2015-07-01

    Cyano-bridged Gd3+/[Fe(CN)6]3- coordination polymer nanoparticles of 3-4 nm stabilized with d-mannitol presenting a high r1 relaxivity value of 11.4 mM-1 s-1 were investigated in vivo as contrast agents (CA) for Magnetic Resonance Imaging (MRI). They allow an increase of the MR image contrast and can act as an efficient intravascular T1 CA with a relatively long blood-circulation lifetime (60 min) without specific toxicity.Cyano-bridged Gd3+/[Fe(CN)6]3- coordination polymer nanoparticles of 3-4 nm stabilized with d-mannitol presenting a high r1 relaxivity value of 11.4 mM-1 s-1 were investigated in vivo as contrast agents (CA) for Magnetic Resonance Imaging (MRI). They allow an increase of the MR image contrast and can act as an efficient intravascular T1 CA with a relatively long blood-circulation lifetime (60 min) without specific toxicity. Electronic supplementary information (ESI) available: Experimental details and procedures, toxicological data, physical characterization. See DOI: 10.1039/c5nr01557j

  15. Semaphorin 3E Initiates Antiangiogenic Signaling through Plexin D1 by Regulating Arf6 and R-Ras▿ †

    PubMed Central

    Sakurai, Atsuko; Gavard, Julie; Annas-Linhares, Yuliya; Basile, John R.; Amornphimoltham, Panomwat; Palmby, Todd R.; Yagi, Hiroshi; Zhang, Fan; Randazzo, Paul A.; Li, Xuri; Weigert, Roberto; Gutkind, J. Silvio

    2010-01-01

    Recent studies revealed that a class III semaphorin, semaphorin 3E (Sema3E), acts through a single-pass transmembrane receptor, plexin D1, to provide a repulsive cue for plexin D1-expressing endothelial cells, thus providing a highly conserved and developmentally regulated signaling system guiding the growth of blood vessels. We show here that Sema3E acts as a potent inhibitor of adult and tumor-induced angiogenesis. Activation of plexin D1 by Sema3E causes the rapid disassembly of integrin-mediated adhesive structures, thereby inhibiting endothelial cell adhesion to the extracellular matrix (ECM) and causing the retraction of filopodia in endothelial tip cells. Sema3E acts on plexin D1 to initiate a two-pronged mechanism involving R-Ras inactivation and Arf6 stimulation, which affect the status of activation of integrins and their intracellular trafficking, respectively. Ultimately, our present study provides a molecular framework for antiangiogenesis signaling, thus impinging on a myriad of pathological conditions that are characterized by aberrant increase in neovessel formation, including cancer. PMID:20385769

  16. CHARACTERIZATION OF THE ASTROCYTE RESPONSE TO INJURY USING THE DOPAMINERGIC NEUROTOXICANT, 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE

    EPA Science Inventory

    The amount of glial fibrillary acidic protein (GFAP), an astrocyte protein, increases following injury of the CNS. e used a radioimmunoassay of GFAP to characterize the astrocytic response to injury resulting from exposure to the dopaminergic neurotoxicant, 1-methyl-1,2,3,6-tetra...

  17. (1,3;1,4)-β-Glucan Biosynthesis by the CSLF6 Enzyme: Position and Flexibility of Catalytic Residues Influence Product Fine Structure.

    PubMed

    Dimitroff, George; Little, Alan; Lahnstein, Jelle; Schwerdt, Julian G; Srivastava, Vaibhav; Bulone, Vincent; Burton, Rachel A; Fincher, Geoffrey B

    2016-04-01

    Cellulose synthase-like F6 (CslF6) genes encode polysaccharide synthases responsible for (1,3;1,4)-β-glucan biosynthesis in cereal grains. However, it is not clear how both (1,3)- and (1,4)-linkages are incorporated into a single polysaccharide chain and how the frequency and arrangement of the two linkage types that define the fine structure of the polysaccharide are controlled. Through transient expression in Nicotiana benthamiana leaves, two CSLF6 orthologs from different cereal species were shown to mediate the synthesis of (1,3;1,4)-β-glucans with very different fine structures. Chimeric cDNA constructs with interchanged sections of the barley and sorghum CslF6 genes were developed to identify regions of the synthase enzyme responsible for these differences. A single amino acid residue upstream of the TED motif in the catalytic region was shown to dramatically change the fine structure of the polysaccharide produced. The structural basis of this effect can be rationalized by reference to a homology model of the enzyme and appears to be related to the position and flexibility of the TED motif in the active site of the enzyme. The region and amino acid residue identified provide opportunities to manipulate the solubility of (1,3;1,4)-β-glucan in grains and vegetative tissues of the grasses and, in particular, to enhance the solubility of dietary fibers that are beneficial to human health. PMID:26967377

  18. Unexpected ring-closure products derived from 3-(2-allylanilino)-3-phenylacrylate esters: crystal and molecular structures of 3-acetyl-8-allyl-6-methyl-2-phenylquinolin-4-yl acetate and (2RS)-2,8-dimethyl-4-phenyl-1,2-dihydro-6H-pyrrolo[3,2,1-ij]quinolin-6-one.

    PubMed

    Luque, Adriana L; Sanabria, Carlos M; Palma, Alirio; Cobo, Justo; Glidewell, Christopher

    2016-08-01

    The reactions of two 3-(2-allylanilino)-3-phenylacrylate esters with acetic anhydride and with strong acids has revealed a richly diverse reactivity providing a number of unexpected products. Thus, acetylation of ethyl 3-(2-allylanilino)-3-phenylacrylate, (Ia), or ethyl 3-(2-allyl-4-methylanilino)-3-phenylacrylate, (Ib), with acetic anhydride yields not only the expected acetylated esters, (II), as the major products but also the unexpected polysubstituted quinolines 3-acetyl-8-allyl-2-phenylquinolin-4-yl acetate, (IIIa), and 3-acetyl-8-allyl-6-methyl-2-phenylquinolin-4-yl acetate, (IIIb), as minor products. Subsequent reaction of the major product ethyl 2-[(2-allyl-4-methylanilino)(phenyl)methylidene]-3-oxobutanoate, (IIb), with concentrated sulfuric acid did not provide the expected 3-acetylquinoline derivative, but instead two unexpected products, namely ethyl 4-ethyl-2-phenyl-1,4-dihydroquinoline-3-carboxylate, (IV), and ethyl 3-acetyl-4-ethyl-2-phenyl-3,4-dihydroquinoline-3-carboxylate, (V), in yields of 39 and 22%, respectively. The reaction of (Ib) with Eaton's reagent gave both the quinoline (Z)-6-methyl-2-phenyl-8-(prop-1-en-1-yl)quinolin-4(1H)-one, (VI), and the unexpected tricyclic product (2RS)-2,8-dimethyl-4-phenyl-1,2-dihydro-6H-pyrrolo[3,2,1-ij]quinolin-6-one, (VII), in yields of 71 and 12%, respectively. The products (II)-(VII) have all been fully characterized spectroscopically and the crystal structures of two of the unexpected products, i.e. (IIIb) (C23H21NO3) and (VII) (C19H17NO), are reported here. The formation of compounds (IV), (V) and (VII) all require an isomerization of the initial allyl substituent, with migration of the C=C double bond from the terminal site to the internal site. In (IIIb), the two acetyl substituents are oriented such that the intramolecular distance between the two carbonyl O atoms is only 3.243 (2) Å, and in (VII), the five-membered ring adopts a twisted half-chair conformation. The molecules of compound (IIIb

  19. Silibinin negatively contributes to primary cilia length via autophagy regulated by histone deacetylase 6 in confluent mouse embryo fibroblast 3T3-L1 cells.

    PubMed

    Xu, Qian; Liu, Wei; Liu, Xiaoling; Liu, Weiwei; Wang, Hongju; Yao, Guodong; Zang, Linghe; Hayashi, Toshihiko; Tashiro, Shin-Ichi; Onodera, Satoshi; Ikejima, Takashi

    2016-09-01

    Primary cilium is a cellular antenna, signalling as a sensory organelle. Numerous pathological manifestation is associated with change of its length. Although the interaction between autophagy and primary cilia has been suggested, the role of autophagy in primary cilia length is largely unknown. In this study the primary cilia were immunostained and observed by using confocal fluorescence microscopy, and we found that silibinin, a natural flavonoid, shortened the length of primary cilia, meanwhile it also induced autophagy in 3T3-L1 cells. This study was designed to investigate the significance of silibinin-induced autophagy in primary ciliary structure in confluent mouse embryo fibroblast 3T3-L1 cells. Either blocking the autophagic flux with pre-treatment with the autophagy inhibitor, 3-methyladenine (3-MA), or transfection of siRNA targeting LC3 inhibited the reduction of cilia length caused by silibinin exposure. Autophagy induced by silibinin decreased expressions of the cilia-associated proteins, such as IFT88, KIF3a and Ac-tubulin, while 3-MA restored it, indicating that autophagy induced by silibinin led to a reduction of primary cilia length. Histone deacetylase 6 (HDAC6), which was suggested as a mediator of autophagy, was up-regulated by silibinin in a time-dependent manner. In addition, 3T3-L1 cells treated with siRNA against HDAC6 had a reduced autophagic level and were protected from silibinin-induced cilia shortening. Taken together, we conclude that the HDAC6-mediated autophagy negatively regulates primary cilia length during silibinin treatment and has the potential to serve as a therapeutic target for primary cilia-associated ciliopathies. These findings thus provide new information about the potential link between autophagy and primary cilia. PMID:27435857

  20. Selective solid-phase microextraction of explosives using fibers coated with the La (III) complex of p-di (4,4,5,5,6,6,6-hepafluoro-1,3-hexanediony) benzene

    SciTech Connect

    Harvey, Scott D.

    2008-12-12

    This research demonstrates enhanced capture of explosives on polydimethylsiloxane (PDMS) solid-phase microextraction (SPME) fibers coated with a metal beta-diketonate polymer, [La(III) complex of p-di(4,4,5,5,6,6,6-heptafluoro-1,3-hexanedionyl)benzene, La(dihed)], compared to PDMS control fibers. SPME sampling was performed in an explosives bunker where the concentration of 2,4,6-trinitrotoluene (TNT) was estimated at less than 3 parts-per-trillion (v/v). Analysis by gas chromatography/mass spectrometry showed an approximate ten-fold enhancement in the quantity of 2,4-dinitrotoluene captured on La(dihed) over the control fiber. La(dihed) sampling also resulted in a strong signal for TNT, whereas this explosive was well below the detection limit (1 pg on fiber) on the control fiber.

  1. Novel 3-Amino-6-chloro-7-(azol-2 or 5-yl)-1,1-dioxo-1,4,2-benzodithiazine Derivatives with Anticancer Activity: Synthesis and QSAR Study.

    PubMed

    Pogorzelska, Aneta; Sławiński, Jarosław; Brożewicz, Kamil; Ulenberg, Szymon; Bączek, Tomasz

    2015-01-01

    A series of new 3-amino-6-chloro-7-(azol-2 or 5-yl)-1,1-dioxo-1,4,2-benzodithiazine derivatives 5a-j have been synthesized and evaluated in vitro for their antiproliferative activity at the U.S. National Cancer Institute. The most active compound 5h showed significant cytotoxic effects against ovarian (OVCAR-3) and breast (MDA-MB-468) cancer (10% and 47% cancer cell death, respectively) as well as a good selectivity toward prostate (DU-145), colon (SW-620) and renal (TK-10) cancer cell lines. To obtain a deeper insight into the structure-activity relationships of the new compounds 5a-j QSAR studies have been applied. Theoretical calculations allowed the identification of molecular descriptors belonging to the RDF (RDF055p and RDF145m in the MOLT-4 and UO-31 QSAR models, respectively) and 3D-MorSE (Mor32m and Mor16e for MOLT-4 and UO-31 QSAR models) descriptor classes. Based on these data, QSAR models with good robustness and predictive ability have been obtained. PMID:26690109

  2. 40 CFR 721.8940 - Chromate(3-), bis[3-[[6-amino-1,4-dihydro-2-[[[4-[(2-hydroxy-1-naphthalenyl)azo] phenyl]sulfonyl...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...] amino]-4-(oxo-.kappa.O)-5- pyrimidinyl]azo-.kappaN1] -4-hydroxy-.kappa.O)-5-nitrobenzenesulfonato(3... Specific Chemical Substances § 721.8940 Chromate(3-), bis phenyl]sulfonyl] amino]-4-(oxo-.kappa.O)-5...-), bis phenyl] sulfonyl]amino]-4-(oxo-.kappa.O)-5-pyrimidinyl]azo-.kappaN1]...

  3. 40 CFR 721.8940 - Chromate(3-), bis[3-[[6-amino-1,4-dihydro-2-[[[4-[(2-hydroxy-1-naphthalenyl)azo] phenyl]sulfonyl...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...] amino]-4-(oxo-.kappa.O)-5- pyrimidinyl]azo-.kappaN1] -4-hydroxy-.kappa.O)-5-nitrobenzenesulfonato(3... Specific Chemical Substances § 721.8940 Chromate(3-), bis phenyl]sulfonyl] amino]-4-(oxo-.kappa.O)-5...-), bis phenyl] sulfonyl]amino]-4-(oxo-.kappa.O)-5-pyrimidinyl]azo-.kappaN1]...

  4. Synthesis and characterization of p-type conductivity dopant 2-(3-(adamantan-1-yl)propyl)-3,5,6-trifluoro-7,7,8,8-tetracyanoquinodimethane

    SciTech Connect

    Rainbolt, James E.; Koech, Phillip K.; Polikarpov, Evgueni; Swensen, James S.; Cosimbescu, Lelia; Von Ruden, Amber L.; Wang, Liang; Sapochak, Linda S.; Padmaperuma, Asanga B.; Gaspar, Daniel J.

    2013-01-22

    We report the synthesis and characterization of 2-(3-(adamantan-1-yl)propyl)-3,5,6-trifluoro-7,7,8,8-tetracyanoquinodimethane (F3TCNQ-Ad1), a substituted analog of 2,3,5,6-tetrafluoro-7,7,8,8-tetracyanoquinodimethane (F4TCNQ), designed for p-type conductivity doping. The dopant is designed as a model for substituted alternatives to F4TCNQ that maintain similar electronic properties with the goal of engineering dopants with superior fabrication characteristics over F4TCNQ. We describe the design strategy for F3TCNQ-Ad1 based on molecular modeling predictions that substitution of a single fluorine atom of F4TCNQ has little effect on the electronic properties of the molecule. Photophysical and electrochemical characterization reveal that the adamantyl substituent in F3TCNQ-Ad1 does not significantly alter the electronic properties of the substituted dopant relative to F4TCNQ. Unfortunately, F3TCNQ-Ad1 degrades under standard sublimation conditions, preventing sublimation deposition processing. Instead, hole-only devices were made via solution-processing of the p-doped films with the structure glass/ITO/2.3 x103Å PVK:(MTDATA:dopant)/2.0x102Å Au/1.0x103Å Al, where dopant is either F4TCNQ or F3TCNQ-Ad1. We demonstrate that F3TCNQ-Ad1 increased the conductivity of the films by at least 1,000 times compared to an undoped device.

  5. Down-Regulation of the CSLF6 Gene Results in Decreased (1,3;1,4)-β-d-Glucan in Endosperm of Wheat1[C][W

    PubMed Central

    Nemeth, Csilla; Freeman, Jackie; Jones, Huw D.; Sparks, Caroline; Pellny, Till K.; Wilkinson, Mark D.; Dunwell, Jim; Andersson, Annica A.M.; Åman, Per; Guillon, Fabienne; Saulnier, Luc; Mitchell, Rowan A.C.; Shewry, Peter R.

    2010-01-01

    (1,3;1,4)-β-d-Glucan (β-glucan) accounts for 20% of the total cell walls in the starchy endosperm of wheat (Triticum aestivum) and is an important source of dietary fiber for human nutrition with potential health benefits. Bioinformatic and array analyses of gene expression profiles in developing caryopses identified the CELLULOSE SYNTHASE-LIKE F6 (CSLF6) gene as encoding a putative β-glucan synthase. RNA interference constructs were therefore designed to down-regulate CSLF6 gene expression and expressed in transgenic wheat under the control of a starchy endosperm-specific HMW subunit gene promoter. Analysis of wholemeal flours using an enzyme-based kit and by high-performance anion-exchange chromatography after digestion with lichenase showed decreases in total β-glucan of between 30% and 52% and between 36% and 53%, respectively, in five transgenic lines compared to three control lines. The content of water-extractable β-glucan was also reduced by about 50% in the transgenic lines, and the Mr distribution of the fraction was decreased from an average of 79 to 85 × 104 g/mol in the controls and 36 to 57 × 104 g/mol in the transgenics. Immunolocalization of β-glucan in semithin sections of mature and developing grains confirmed that the impact of the transgene was confined to the starchy endosperm with little or no effect on the aleurone or outer layers of the grain. The results confirm that the CSLF6 gene of wheat encodes a β-glucan synthase and indicate that transgenic manipulation can be used to enhance the health benefits of wheat products. PMID:20089768

  6. Palbociclib treatment of FLT3-ITD+ AML cells uncovers a kinase-dependent transcriptional regulation of FLT3 and PIM1 by CDK6.

    PubMed

    Uras, Iris Z; Walter, Gina J; Scheicher, Ruth; Bellutti, Florian; Prchal-Murphy, Michaela; Tigan, Anca S; Valent, Peter; Heidel, Florian H; Kubicek, Stefan; Scholl, Claudia; Fröhling, Stefan; Sexl, Veronika

    2016-06-01

    Up to 30% of patients with acute myeloid leukemia have constitutively activating internal tandem duplications (ITDs) of the FLT3 receptor tyrosine kinase. Such mutations are associated with a poor prognosis and a high propensity to relapse after remission. FLT3 inhibitors are being developed as targeted therapy for FLT3-ITD(+) acute myeloid leukemia; however, their use is complicated by rapid development of resistance, which illustrates the need for additional therapeutic targets. We show that the US Food and Drug Administration-approved CDK4/6 kinase inhibitor palbociclib induces apoptosis of FLT3-ITD leukemic cells. The effect is specific for FLT3-mutant cells and is ascribed to the transcriptional activity of CDK6: CDK6 but not its functional homolog CDK4 is found at the promoters of the FLT3 and PIM1 genes, another important leukemogenic driver. There CDK6 regulates transcription in a kinase-dependent manner. Of potential clinical relevance, combined treatment with palbociclib and FLT3 inhibitors results in synergistic cytotoxicity. Simultaneously targeting two critical signaling nodes in leukemogenesis could represent a therapeutic breakthrough, leading to complete remission and overcoming resistance to FLT3 inhibitors. PMID:27099147

  7. Palbociclib treatment of FLT3-ITD+ AML cells uncovers a kinase-dependent transcriptional regulation of FLT3 and PIM1 by CDK6

    PubMed Central

    Uras, Iris Z.; Walter, Gina J.; Scheicher, Ruth; Bellutti, Florian; Prchal-Murphy, Michaela; Tigan, Anca S.; Valent, Peter; Heidel, Florian H.; Kubicek, Stefan; Scholl, Claudia; Fröhling, Stefan

    2016-01-01

    Up to 30% of patients with acute myeloid leukemia have constitutively activating internal tandem duplications (ITDs) of the FLT3 receptor tyrosine kinase. Such mutations are associated with a poor prognosis and a high propensity to relapse after remission. FLT3 inhibitors are being developed as targeted therapy for FLT3-ITD+ acute myeloid leukemia; however, their use is complicated by rapid development of resistance, which illustrates the need for additional therapeutic targets. We show that the US Food and Drug Administration–approved CDK4/6 kinase inhibitor palbociclib induces apoptosis of FLT3-ITD leukemic cells. The effect is specific for FLT3-mutant cells and is ascribed to the transcriptional activity of CDK6: CDK6 but not its functional homolog CDK4 is found at the promoters of the FLT3 and PIM1 genes, another important leukemogenic driver. There CDK6 regulates transcription in a kinase-dependent manner. Of potential clinical relevance, combined treatment with palbociclib and FLT3 inhibitors results in synergistic cytotoxicity. Simultaneously targeting two critical signaling nodes in leukemogenesis could represent a therapeutic breakthrough, leading to complete remission and overcoming resistance to FLT3 inhibitors. PMID:27099147

  8. Map3k1, Il6st, Gzmk, and Hspb3 gene coexpression network in the mechanism of freezing reaction in mice.

    PubMed

    Kondaurova, Elena M; Naumenko, Vladimir S; Sinyakova, Nadezda A; Kulikov, Alexander V

    2011-02-01

    Freezing reaction (catalepsy) is a natural passive defensive strategy in animals. An exaggerated form of catalepsy is a symptom of grave brain dysfunction. Catalepsy in mice was shown to be linked to the Map3k1, Il6st, Gzmk, and Hspb3 genes as potential candidates for a high predisposition to catalepsy. The study sought to test the hypothesis of an association between catalepsy and expression of these genes in the brain. Thegenes' mRNA levels were measured in the hypothalamus, hippocampus, frontal cortex, striatum, and midbrain of catalepsy-resistant AKR/J strain and catalepsy-prone strains CBA/Lac, ASC (antidepressant-sensitive cataleptic) and the congenic line AKR.CBA-D13M76C. No association between expression of any investigated genes and predisposition to catalepsy was found. At the same time, multivariate analysis revealed interactions among the expressions of Map3k1, Il6st, Gzmk, and Hspb3 genes in the brain structures. A factor analysis of all variables produced two independent factors explaining 76.2% of the total variance. The catalepsy-resistant AKR strain was distinguished from the catalepsy-prone strains CBA, ASC, and AKR.CBA-D13M76C by factor 1. It was suggested that a high predisposition to catalepsy in mice can be defined by the Map3k1, Il6st, Gzmk, and Hspb3 genes' coexpression network. PMID:21162133

  9. Synthesis, structural characterization and theoretical approach of 3-(2,6-dichlorobenzyl)-5-methyl-N-nitro-1,3,5-oxadiazinan-4-imine.

    PubMed

    Ni, Haiwei; Zhang, Yu; Zhang, Fang; Zhao, Jianying; Wu, Liubi; Chu, Xiaozhong

    2015-03-01

    3-(2,6-Dichlorobenzyl)-5-methyl-N-nitro-1,3,5-oxadiazinan-4-imine (DNOI) was synthesized and characterized by X-ray diffraction, FT-IR, FT-Raman and UV-Vis spectra. The X-ray diffraction study showed that DNOI has a one dimensional configuration, due to the intermolecular C9H⋯O1 and N4H⋯O2 hydrogen bonds. The benzene ring and the oxadiazine rings are tilted with respect to each other by 63.07° (C3N1C5C6). Vibrational spectra and electronic spectra measurements were made for the compound. Optimized geometrical structure and harmonic vibrational frequencies were computed with DFT (B3LYP, B3P86, and M062X) methods using 6-311++G(d,p) basis set. Assignments of the observed spectra were proposed. The equilibrium geometries computed by all of the methods were compared with X-ray diffraction results. The absorption spectra of the title compound were computed both in gas phase and in CH3OH solution using TD-B3LYP/6-311++G(d,p) and PCM-B3LYP/6-311++G(d,p) approaches, respectively. The calculated results provide a good description of positions of the bands maxima in the observed electronic spectrum. Temperature dependence of thermodynamic parameters in the range of 100-1000K were determined, entropy, heat capacity and enthalpy changes were increasing with temperature increasing, while for Gibbs free energy is decreasing with temperature increasing. The bond orbital occupancies, contribution from parent natural bond orbital (NBO), the natural atomic hybrids was calculated and discussed. PMID:25541404

  10. (E)-2-(3-Chloro­benzyl­idene)-5,6-dimeth­oxy-2,3-dihydro-1H-inden-1-one

    PubMed Central

    Ali, Mohamed Ashraf; Ismail, Rusli; Tan, Soo Choon; Yeap, Chin Sing; Fun, Hoong-Kun

    2010-01-01

    In the title compound, C18H15ClO3, the dihydro­indenone group makes a dihedral angle of 8.56 (6)° with the bezene ring. In the crystal, the mol­ecules are inter­connected into a three-dimensional network via inter­molecular C—H⋯O hydrogen bonds. Weak C—H⋯π and π⋯π [centroid–centroid distances 3.6598 (9)–3.6913 (9) Å] inter­actions are also observed. PMID:21589046

  11. Miscoding properties of 1,N{sup 6}-ethanoadenine, a DNA adduct derived from reaction with antitumor agent 1,3-bis(2-chloroethyl)-1-nitrosourea

    SciTech Connect

    Hang, Bo; Guliaev, Anton B.; Chenna, Ahmed; Singer, B.

    2003-03-05

    1,N{sup 6}-Ethanoadenine (EA) is an exocyclic adduct formed from DNA reaction with the antitumor agent, 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). To understand the role of this adduct in the mechanism of mutagenicity or carcinogenicity by BCNU, an oligonucleotide with a site-specific EA was synthesized using phosphoramidite chemistry. We now report the in vitro miscoding properties of EA in translesion DNA synthesis catalyzed by mammalian DNA polymerases (pols) {alpha}, {beta}, {eta} and {iota}. These data were also compared with those obtained for the structurally related exocyclic adduct, 1,N{sup 6}-ethenoadenine ({var_epsilon}A). Using a primer extension assay, both pols {alpha} and {beta} were primarily blocked by EA or {var_epsilon}A with very minor extension. Pol {eta} a member of the Y family of polymerases, was capable of catalyzing a significant amount of bypass across both adducts. Pol {eta} incorporated all four nucleotides opposite EA and {var_epsilon}A, but with differential preferences and mainly in an error-prone manner. Human pol {iota}, a paralog of human pol {eta}, was blocked by both adducts with a very small amount of synthesis past {var_epsilon}A. It incorporated C and, to a much lesser extent, T, opposite either adduct. In addition, the presence of an A adduct, e.g. {var_epsilon}A, could affect the specificity of pol {iota} toward the template T immediately 3 feet to the adduct. In conclusion, the four polymerases assayed on templates containing an EA or {var_epsilon}A showed differential bypass capacity and nucleotide incorporation specificity, with the two adducts not completely identical in influencing these properties. Although there was a measurable extent of error-free nucleotide incorporation, all these polymerases primarily misincorporated opposite EA, indicating that the adduct, similar to {var_epsilon}A, is a miscoding lesion.

  12. A DFT study of the [3 + 2] versus [4 + 2] cycloaddition reactions of 1,5,6-trimethylpyrazinium-3-olate with methyl methacrylate.

    PubMed

    Domingo, Luis R; Sáez, Jose A; Joule, John A; Rhyman, Lydia; Ramasami, Ponnadurai

    2013-02-15

    The reaction between 1,5,6-trimethylpyrazinium-3-olate and methyl methacrylate (MMA) yielding a lactone-lactam has been studied using the DFT method at the B3LYP/6-31G(d) level. It is concluded that formation of the lactone-lactam is a domino process involving three consecutive reactions: (i) a 1,3-dipolar cycloaddition (13DC) reaction between the pyrazinium-3-olate and MMA yielding a [3 + 2] cycloadduct (CA); (ii) a skeletal rearrangement, which converts the [3 + 2] CA into a formal [4 + 2] CA, possessing a diazabicyclo[2.2.2]octane structure; and finally, (iii) an S(N)2 reaction, promoted by halide anion, with concomitant nucleophilic attack of the created carboxylate anion on an iminium carbon with formation of the lactone ring present in the lactone-lactam. Analysis of the four competitive channels associated with the 13DC reaction indicates that this cycloaddition takes place with complete endo stereoselectivity and 6 regioselectivity, yielding [3 + 2] CA. The subsequent skeletal rearrangement also takes place in an elementary step via a non-concerted mechanism. Electron localization function bonding analysis makes it possible to establish that the bicyclo[2.2.2]octane skeleton present in the lactone-lactam complex structure is not attained via a Diels-Alder reaction between pyrazinium-3-olate and MMA. PMID:23342990

  13. Effects of dietary supplementation of coriander oil, in canola oil diets, on the metabolism of [1-(14)C] 18:3n-3 and [1-(14)C] 18:2n-6 in rainbow trout hepatocytes.

    PubMed

    Randall, K M; Drew, M D; Øverland, M; Østbye, T-K; Bjerke, M; Vogt, G; Ruyter, B

    2013-09-01

    The aim of this study was to investigate the effects of petroselinic acid, found in coriander oil, on the ability of rainbow trout hepatocytes to increase the production of eicosapentaenoic acid (20:5n-3; EPA) and docosahexaenoic acid (22:6n-3; DHA) from [1-(14)C] α-linolenic acid (18:3n-3; ALA) and to reduce the production of arachidonic acid (20:4n-6; ARA) from [1-(14)C] 18:2n-6. Addition of coriander oil increased the production of 22:6n-3, from [1-(14)C] 18:3n-3, at the 0.5 and 1.0% inclusion levels and reduced the conversion of [1-(14)C] 18:2n-6 to 20:4n-6. β-Oxidation was significantly increased at the 1.5% inclusion level for [1-(14)C] 18:2n-6, however β-oxidation for [1-(14)C] 18:3n-3 only showed an increasing trend. Acetate, a main breakdown product of fatty acids (FA) via peroxisomal β-oxidation, decreased three-fold for [1-(14)C] 18:2n-6 and nearly doubled for [1-(14)C] 18:3n-3 when coriander was added at a 1.5% inclusion level. Acyl coenzyme A oxidase (ACO) enzyme activity showed no significant differences between treatments. Relative gene expression of ∆6 desaturase decreased with addition of coriander oil compared to the control. The addition of petroselinic acid via coriander oil to vegetable oil (VO) based diets containing no fishmeal (FM) or fish oil (FO), significantly increased the production of anti-inflammatory precursor 22:6n-3 (P=0.011) and decreased pro-inflammatory precursor 20:4n-6 (P=0.023) in radiolabelled hepatocytes of rainbow trout. PMID:23867781

  14. 4-(4-fluoro-3-phenoxyphenyl)-6-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carbonitrile and the 6-(4-methylphenyl)- analogue.

    PubMed

    Chopra, Deepak; Mohan, T P; Vishalakshi, B; Guru Row, T N

    2006-09-01

    The crystal structures of the title compounds, viz. C24H14F2N2O2, (I), and C25H17FN2O2, (II), respectively, have been determined in order to unravel the role of an ordered F atom in generating stable supramolecular assemblies. On changing the substitution from fluorine to a methyl group, C-H...F interactions are replaced by C-H...pi interactions, revealing the importance of such weak interactions when present alongside N-H...O and C-H...O hydrogen bonds. The dihedral angle between the planes of the 4-fluorophenyl ring and the pyridine ring is 26.8 (1) degrees in (I), while that between the planes of the 4-methylphenyl and pyridine rings is 29.5 (1) degrees in (II). PMID:16954636

  15. Repeated dose toxicity and relative potency of 1,2,3,4,6,7-hexachloronaphthalene (PCN 66) 1,2,3,5,6,7-hexachloronaphthalene (PCN 67) compared to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) for induction of CYP1A1, CYP1A2 and thymic atrophy in female Harlan Sprague-Dawley rats

    PubMed Central

    Hooth, Michelle J.; Nyska, Abraham; Fomby, Laurene M.; Vasconcelos, Daphne Y.; Vallant, Molly; DeVito, Michael J.; Walker, Nigel J.

    2012-01-01

    In this study we assessed the relative toxicity and potency of the chlorinated naphthalenes 1,2,3,4,6,7-hexachloronaphthalene (PCN 66) and 1,2,3,5,6,7-hexachloronaphthalene (PCN 67) relative to that of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Chemicals were administered in corn oil:acetone (99:1) by gavage to female Harlan Sprague-Dawley rats at dosages of 0 (vehicle), 500, 1500, 5000, 50000 and 500000 ng/kg (PCN 66 and PCN 67) and 1, 3, 10, 100, and 300 ng/kg (TCDD) for 2 weeks. Histopathologic changes were observed in the thymus, liver and lung of TCDD treated animals and in the liver and thymus of PCN treated animals. Significant increases in CYP1A1 and CYP1A2 associated enzyme activity were observed in all animals exposed to TCDD, PCN 66 and PCN 67. Dose response modeling of CYP1A1, CYP1A2 and thymic atrophy gave ranges of estimated relative potencies, as compared to TCDD, of 0.0015-0.0072, for PCN 66 and 0.00029-0.00067 for PCN 67. Given that PCN 66 and PCN 67 exposure resulted in biochemical and histopathologic changes similar to that seen with TCDD, this suggests that they should be included in the WHO Toxic Equivalency Factor (TEF) scheme, although the estimated relative potencies indicate that these hexachlorinated naphthalenes should not contribute greatly to the overall human body burden of dioxin-like activity. PMID:22813907

  16. Photoluminescence of A- and B-site Eu3+-substituted (SrxBa1-x)2CaWyMo1-yO6 phosphors

    NASA Astrophysics Data System (ADS)

    Sletnes, M.; Lindgren, M.; Valmalette, J. C.; Wagner, N. P.; Grande, T.; Einarsrud, M.-A.

    2016-05-01

    The photoluminescence of two series of A- and B-site Eu3+ substituted (SrxBa1-x)2CaWyMo1-yO6 double perovskite phosphor materials, (SrxBa1-x)1.96Eu0.02K0.02CaWyMo1-yO6 and (SrxBa1-x)2Ca0.96Eu0.02Li0.02WyMo1-yO6 (x and y=0, 0.25, 0.50, 0.75, and 1), were studied systematically as a function of stoichiometry and crystal structure. The Eu3+ lattice sites controlled by co-doping with either K or Li were confirmed by Raman spectroscopy. The variation in integrated emission intensity and emission colour over the experimental matrix was examined using statistical tools, and the observed trends were rationalized based on the physical and electronic structure of the phosphors. Phosphors with Eu on B-site with maximum Sr content had remarkably higher emission intensities than all other materials, but the emission was more orange than red due to domination of the 5D0-7F1 (595 nm) transition of Eu3+. The relative intensities of the 5D0-7F2 (615 nm) and 5D0-7F1 transitions of Eu3+, and thus the red-shift of the emission, decreased linearly with increasing Sr content in the A-site Eu-substituted phosphors, and reached a maximum for Sr1.96Eu0.02K0.02CaW0.25Mo0.75O6. A maximum external quantum efficiency of 17% was obtained for the phosphor Sr2Ca0.7Eu0.15Li0.15W0.5Mo0.5O6 with Eu on B-site.

  17. Promotion of hepatic preneoplastic lesions in male B6C3F{sub 1} mice by unleaded gasoline

    SciTech Connect

    Standeven, A.M.; Wolf, D.C.; Goldsworthy, T.L.

    1995-07-01

    In previous studies, unleaded gasoline (UG) vapor was found to be a liver tumor promotor and hepatocarcinogen in female mice, but UG was not a hepatocarcinogen in male mice. However, UG vapor had similar transient mitogenic effects in nonlesioned liver of both male and female mice under the conditions of the cancer bioassay. We used an initiation-promotion protocol to determine whether UG vapor acts as a liver tumor promoter in male mice and to examine proliferative effects that may be critical to tumor development. Twelve-day-old male B6C3F{sub 1} mice were injected with N-nitrosodiethylamine (DEN; 5 mg/kg, intraperitoneally) or vehicle. Starting at 5-7 weeks of age, mice were exposed by inhalation 6 hr/day, 5 days/week for 16 weeks to 0 or 2046 ppm of PS-6 blend UG. UG treatment caused a significant 2.3-fold increase in the number of macroscopic hepatic masses in DEN-initiated mice, whereas no macroscopic masses were observed in noninitiated mice. To study hepatocyte proliferative effects of UG, we treated mice with 5-bromo-2`-deoxyuridine (BrdU) via osmotic pump for 3 days before necropsy and measured hepatocyte BruU labeling index (LI) in AHF and nonlesioned liver. UG did not significantly affect BrdU LI in nonlesioned liver. However, hepatocyte LI in AHF was about 30% higher in DEN/UG-treated mice relative to mice treated with DEN alone. These data show that UG vapor promotes AHF in male mice and that liver tumor promotion is associated with a selective increase in hepatocyte proliferation in AHF. UG acts as a liver tumor promoter in both male and female mice, and these findings contrast with the lack of hepatocarcinogenicity of UG in male mice in a cancer bioassy. 36 refs., 1 fig., 3 tabs.

  18. Characterization of UDP-N-acetylglucosamine:alpha-6-d-mannoside beta-1,6-N-acetylglucosaminyltransferase V from a human hepatoma cell line Hep3B.

    PubMed

    Park, C; Jin, U H; Lee, Y C; Cho, T J; Kim, C H

    1999-07-15

    UDP-N-acetylglucosamine:alpha-6-d-mannoside beta-1, 6-N-acetylglucosaminyltransferase V (GlcNAcT-V) has been purified from cell extracts of the human hepatoma cell line, Hep3B, with 8.7% recovery. The purified enzymes had molecular masses of about 67 and 65 kDa on denaturated and natural conditions, respectively. The values of pI was 5.9. The GlcNAcT-V, when resolved by SDS-PAGE, was positive for Schiff staining, suggesting that the enzyme is glycoprotein. When GlcN,GlcN-biant-PA and UDP-GlcNAc were used as substrates, the enzyme displayed a temperature optimum of around 50 degrees C and optimum an pH of 6.5. The enzyme was stable in response to incubation from pH 4.5 to pH 10.5 at 4 degrees C for 24 h. The presence of UDP-GlcNAc and GlcN,GlcN-bi-PA protected the enzyme from heat inactivation, the extent depending upon the substrate concentration. The activity of the enzyme was stimulated by Mn2+ ion; however, it was inhibited by Fe3+. The enzyme activity was inhibited by another series of NDP-sugars including ADP-, CDP-, GDP-, and TDP-GlcNAc. Studies on the activity of the enzyme toward a variety of pyridylaminated sugars showed that the enzyme is most active toward biantennary (GlcN,GlcN-bi-PA) sugars. The enzymes had apparent Km values of 1.28 and 5.8 mM for GlcN,GlcN-bi-PA and UDP-GlcNAc, respectively. In order to isolate the GlcNAcT-V gene, PCR primers of GNN-1 and GNN-8 were designed and the amplified PCR product carrying the gene was cloned and sequenced. Nucleotide sequence analysis showed a 2220-bp open reading frame encoding a 740-amino-acid protein. This was almost same as the previously reported human sequences, except for some sequence differences in three amino acids. The three amino acid changes were as follows: 375V --> L, 555T --> R, and 592A --> G. These studies represent the detailed characterization of a purified GlcNAcT-V from human hepatoma cell Hep3B. PMID:10395745

  19. Comparison of Renal Amyloid and Hyaline Glomerulopathy in B6C3F1 Mice: An NTP Retrospective Study.

    PubMed

    Hoane, Jessica S; Johnson, Crystal L; Morrison, James P; Elmore, Susan A

    2016-07-01

    Due to potential misdiagnosis of hyaline glomerulopathy (HG) for amyloidosis, a retrospective study of B6C3F1 mice from the National Toxicology Program (NTP) archives was undertaken to determine whether HG had occurred in prior NTP studies and, if so, whether these 2 glomerular lesions could be routinely discriminated. Kidney slides from 7 amyloid-positive control mice, 2 HG-positive control mice, 3 normal or negative control mice, and 41 potential HG mice (with renal-only deposits previously diagnosed as amyloid) were evaluated using hematoxylin and eosin (H&E), periodic acid Schiff (PAS), Congo red (CR), and Masson's trichrome (MT) stains. Utilizing these techniques, HG was reliably distinguished from amyloidosis. All 41 potential HG mice had glomerular deposits histochemically inconsistent with amyloid; the deposits were PAS positive and CR negative. Four of the 41 mice were selected for transmission electron microscopy of the glomerular deposits; ultrastructurally, the deposits in these animals were consistent with HG and not amyloid. Our findings indicate that HG is a spontaneous lesion in B6C3F1 mice of low occurrence, is commonly misdiagnosed as amyloidosis, and is more likely than amyloid to cause glomerular deposits in mice without evidence of deposits in other tissues. Also, HG can be distinguished from amyloid on H&E evaluation; however, the distinction is improved with use of PAS or CR staining and/or ultraviolet evaluation. PMID:27000376

  20. Enantiomers of myo-inositol-1,3,4-trisphosphate and myo-inositol-1,4,6 -trisphosphate: stereospecific recognition by cerebellar and platelet myo-inositol-1,4,5-trisphosphate receptors.

    PubMed

    Murphy, C T; Bullock, A J; Lindley, C J; Mills, S J; Riley, A M; Potter, B V; Westwick, J

    1996-11-01

    The naturally occurring tetrakisphosphate myo-inositol-1,3,4, 6-tetrakisphosphate [Ins(1,3,4,6)P4] was able to release Ca2+ from the intracellular stores of permeabilized rabbit platelets but was 40-fold less potent than D-myo-inositol-1,4,5-trisphosphate [Ins(1,4,5)P3]. The Ca2+ releasing activity of Ins(1,3,4,6)P4 was rationalized by envisaging two alternative receptor binding orientations in which the vicinal D-1,6-bisphosphate of Ins(1,3,4,6)P4 mimics the D-4,5-bisphosphate in the Ins(1,4,5)P3 binding conformation. This rationalization predicted that Ins(1,4,5)P3 regioisomers [i.e, D-myo-inositol -1,4,6-trisphosphate [D-Ins(1,4,6)P3] and D-myo-inositol-1,3,6 -trisphosphate [D-Ins(1,3,6)P3

  1. Local spin susceptibility of the S=(1)/(2) kagome lattice in ZnCu3(OD)6Cl2

    NASA Astrophysics Data System (ADS)

    Imai, T.; Fu, M.; Han, T. H.; Lee, Y. S.

    2011-07-01

    We report a single-crystal D2 NMR investigation of the nearly ideal spin S=1/2 kagome lattice ZnCu3(OD)6Cl2. We successfully identify D2 NMR signals originating from the nearest neighbors of Cu2+ defects occupying Zn sites. From the D2 Knight-shift measurements, we demonstrate that weakly interacting Cu2+ spins at these defects cause the large Curie-Weiss enhancement toward T=0 commonly observed in the bulk susceptibility data. We estimate the intrinsic spin susceptibility of the kagome planes by subtracting defect contributions, and explore several scenarios.

  2. LD50 value, phototoxicity and convulsion induction test of the new quinolone antibacterial agent (S)-10-[(S)-(8-amino-6-azaspiro[3,4]octan-6-yl)]-9-fluoro-2, 3-dihydro-3-methyl-7-oxo-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carboxyl ic acid hemihydrate in laboratory animals.

    PubMed

    Shimoda, K; Akahane, K; Nomura, M; Kato, M

    1996-06-01

    (S)-10-[(S)-(8-Amino-6-azaspiro[3,4]octan-6-yl)]-9-fluoro-2, 3-dihydro-3-methyl-7-oxo-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carboxyli c acid hemihydrate (CAS 151390-79-3, DV-7751a) a new quinolone antibacterial agent, was examined for LD50 value, phototoxicity and convulsion inducing potential in laboratory animals. A single oral administration of DV-7751a induced soft stool in rats at 1000 and 2000 mg/ kg and in monkeys at 250 mg/kg and vomiting in monkeys at 500 mg/kg or more. A single intravenous administration caused a decrease in locomotor activity, respiratory depression, convulsion, pulmonary edema and death in rats and mice. The LD50 values with oral administration were more than 2000 mg/ kg for rats and mice and more than 250 mg/kg for monkeys, and those with intravenous administration were 164.3 mg/kg for rats of both sexes at an injection rate of 2 ml/min, 118.8 mg/kg for male rats and 104 to 125 mg/kg for female rats at 0.5 ml/min, and 184.7 mg/kg for male mice and 187.4 mg/kg for female mice. DV-7751a showed very weak phototoxicity in mice after single oral administration of 600 mg/kg, followed by UVA irradiation, but no convulsion after oral administration of 200 or 1000 mg/kg in combination with 4-biphenylacetic acid at 400 mg/kg. PMID:8767355

  3. Two orders of magnitude reduction in the temperature dependent resistivity of Ga1-xMnxAs grown on (6 3 1) GaAs insulating substrates

    NASA Astrophysics Data System (ADS)

    Rangel-Kuopp, Victor-Tapio; Martinez-Velis, Isaac; Gallardo-Hernandez, Salvador; Lopez-Lopez, Maximo

    2013-12-01

    The temperature dependent van der Pauw (T-Pauw) technique was used to investigate the resistivity of three Ga1-xMnxAs layers grown on (6 3 1) GaAs semi-insulating substrates. The samples had Mn concentration of 3.52×l020 cm-3, 5.05×1020 cm-3 and 1.12×l021 cm-3, corresponding to Mn cell effusion temperature TMn of 700 °C, 715 °C and 745 °C, respectively. They were compared to samples grown under the same conditions but on (0 0 1) GaAs semi-insulating substrates. For the sample grown at TMn=700 °C on a (6 3 1) substrate, a two orders of magnitude decrease in the resistivity is observed, when compared with the sample grown on a (0 0 1) substrate. For the sample grown at TMn=715 °C the decrease is approximately four times, while for the sample grown at TMn=745 °C the decrease is approximately forty times. We plotted the resistivities as a function of temperature in Arrhenius plots, where we extracted two activation energies, the smallest one between 6 and 11 meV, and the largest one between 25 and 183 meV. Both activation energies increased as TMn increased. These results are in agreement with SIMS analysis where we observed that manganese concentration in the (6 3 1) orientation growth is around two order of magnitude larger than in the samples grown in the (0 0 1) orientation substrate.

  4. Detection of 1,N6-etheno-2'-deoxyadenosine and 3,N4-etheno-2'-deoxycytidine occurring endogenously in DNA.

    PubMed

    Watson, W P; Aston, J P; Barlow, T; Crane, A E; Potter, D; Brown, T

    1999-01-01

    1,N6-Etheno-2'-deoxyadenosine (epsilon dA) and 3,N4-etheno-2'-deoxycytidine (epsilon dC) are DNA adducts formed by a number of genotoxic chemicals, including vinyl chloride. They are also formed endogenously in tissue DNA, probably from a reactive metabolite of lipid peroxidation. Both the qualitative and quantitative detection of endogenous adducts is important in order to place adduct formation by chemicals such as vinyl chloride in the context of this natural background level. Methods with sufficient sensitivity are therefore being developed to measure the natural background of epsilon dA and epsilon dC adducts. We have developed a high-performance liquid chromatography (HPLC)-32P-postlabelling method to measure epsilon dA and epsilon dC at alkylation frequencies of 1 adduct in 10(7)-10(8) nucleotides in 10-microgram samples of DNA. In HPLC-32P-postlabelling analysis of liver DNA from control Wistar rats, epsilon dA and epsilon dC were determined at levels of 1 adduct in 8.1 x 10(7) and 1 adduct in 1.8 x 10(7) nucleotides, respectively. The levels of epsilon dA and epsilon dC measured in liver DNA of animals exposed orally to five daily doses of 50 mg/kg body weight vinyl chloride were found by this method to be 1 adduct in 2.9 x 10(7) and 1 adduct in 1.4 x 10(7) nucleotides, respectively. In contrast, in a direct labelling study, radiolabelled epsilon dA and epsilon dC were not detected in liver DNA of rats exposed for 6 h by nose-only inhalation to [1,2-14C]vinyl chloride at up to 45 ppm v/v. Immunochemical procedures are also being developed for recognizing etheno adducts. Thus, a monoclonal antibody raised to protein conjugates of epsilon dC showed high selectivity in the recognition of this DNA adduct. When the antibody was immobilized on a solid support and used in an immunoenrichment procedure to purify epsilon dC from a large excess of normal nucleotides, one epsilon dC adduct from about 10(8) normal nucleotides could be resolved. Coupling the

  5. Regulation of HPV16 E6 and MCL1 by SF3B1 inhibitor in head and neck cancer cells

    PubMed Central

    Gao, Yang; Trivedi, Sumita; Ferris, Robert L.; Koide, Kazunori

    2014-01-01

    ABT-737 inhibits the anti-apoptotic proteins B-cell lymphoma 2 (BCL-2) and BCL-XL. Meayamycin B switches the splicing pattern of myeloid cell leukemia factor 1 (MCL1) pre-mRNA. Specifically, inhibition of splicing factor 3B subunit 1 (SF3B1) with meayamycin B promotes the generation of the proapoptotic, short splicing variant (MCL1-S) and diminishes the antiapoptotic, long variant (MCL1-L). This action was previously associated with the cytotoxicity of meayamycin B in non-small cell lung carcinoma cell lines. ABT-737 induced apoptosis in response to an ablation of MCL1-L by meayamycin B. In this study, we further exploited this synergistic combination in head and neck squamous cell carcinoma (HNSCC), up to 90% of which overexpress MCL1 and BCL-XL. In a panel of seven HNSCC cell lines, the combination of meayamycin B and ABT-737 rapidly triggered a Bax/Bak-mediated apoptosis that overcame the resistance from HPV16-positive HNSCC against each agent alone. Both RT-PCR and Western blotting showed that meayamycin B up-regulated MCL1-S and down-regulated MCL1-L. Significantly, we discovered that SF3B1 was involved in the splicing of oncogenic HPV16 E6 to produce non-oncogenic HPV16 E6*, indicating that SF3B1 may inhibit HPV16-induced tumorigenesis. PMID:25139387

  6. Photoelectrochemical cells based on ternary compounds CuIn{sub 2n+1}Se{sub 3n+2} (n = 3-6)

    SciTech Connect

    Rud, V. Yu. Rud, Yu. V.; Bodnar, I. V.; Gorbachev, D. V.; Ushakova, T. N.

    2009-03-15

    Single crystals of ternary CuIn{sub 2n+1}Se{sub 3n+2} semiconductors with the composition index n = 3, 5, 6 were grown for the first time using the direct crystallization method. It was shown that these crystals have hexagonal symmetry and close unit cell parameters. Photoelectrochemical cells based on CuIn{sub 2n+1}Se{sub 3n+2} and In{sub 2}Se{sub 3} single crystals were fabricated. Their photosensitivity spectra were measured for the first time, which were used to determine the nature of interband transitions and the band gap. The weak dependence of the parameters of the band's spectrum and unit cell of these semiconductors at n {>=} 2 was attributed to the features of the interatomic interaction in such phases. It was concluded that new CuIn{sub 2n+1}Se{sub 3n+2} semiconductors can be used in broadband photoconverters of optical radiations.

  7. The Glycerol-3-Phosphate Acyltransferase GPAT6 from Tomato Plays a Central Role in Fruit Cutin Biosynthesis1[OPEN

    PubMed Central

    Petit, Johann; Mauxion, Jean-Philippe; Tai, Fabienne Wong Jun; Fich, Eric A.; Joubès, Jérôme; Rothan, Christophe

    2016-01-01

    The thick cuticle covering and embedding the epidermal cells of tomato (Solanum lycopersicum) fruit acts not only as a protective barrier against pathogens and water loss but also influences quality traits such as brightness and postharvest shelf-life. In a recent study, we screened a mutant collection of the miniature tomato cultivar Micro-Tom and isolated several glossy fruit mutants in which the abundance of cutin, the polyester component of the cuticle, was strongly reduced. We employed a newly developed mapping-by-sequencing strategy to identify the causal mutation underlying the cutin deficiency in a mutant thereafter named gpat6-a (for glycerol-3-phosphate acyltransferase6). To this end, a backcross population (BC1F2) segregating for the glossy trait was phenotyped. Individuals displaying either a wild-type or a glossy fruit trait were then pooled into bulked populations and submitted to whole-genome sequencing prior to mutation frequency analysis. This revealed that the causal point mutation in the gpat6-a mutant introduces a charged amino acid adjacent to the active site of a GPAT6 enzyme. We further showed that this mutation completely abolished the GPAT activity of the recombinant protein. The gpat6-a mutant showed perturbed pollen formation but, unlike a gpat6 mutant of Arabidopsis (Arabidopsis thaliana), was not male sterile. The most striking phenotype was observed in the mutant fruit, where cuticle thickness, composition, and properties were altered. RNA sequencing analysis highlighted the main processes and pathways that were affected by the mutation at the transcriptional level, which included those associated with lipid, secondary metabolite, and cell wall biosynthesis. PMID:27208295

  8. Three-step laser excitation of the 6p3/2ns, nd, ng autoionizing Rydberg levels via the 6p5f 1/2[5/2]2 level of lead

    NASA Astrophysics Data System (ADS)

    Ahad, A.; Nadeem, A.; Bhatti, S. A.; Baig, M. A.

    2005-03-01

    Odd parity autoionizing Rydberg levels of atomic lead in the energy region above the 6p1/2 ionization threshold have been investigated using three-step laser excitation in conjunction with an atomic beam apparatus. The 6p3/2ns (J = 1, 2), 6p3/2nd (J = 1, 2, 3) and 6p3/2ng (J = 2, 3) levels have been observed from the 6p5f 1/2[5/2]2 intermediate level. Energy values and FWHM of forty levels belonging to the 6p3/2ns, 6p3/2nd and 6p3/2ng configurations are presented. Six levels based on the 6p3/2ng (5, 13 ≤n ≤15) configurations and three levels attached to the 6p3/28d configuration are reported for the first time. The present study of the low-lying autoionizing levels attached to the 6p3/25g (J = 2, 3) configuration completes the series adjacent to the 6p1/2 limit.

  9. 100 MW 1.6-μm Pr+3:LaCl3 Propulsion Laser Pumped by a Nuclear-Pumped He/Ar/Xe Laser

    NASA Astrophysics Data System (ADS)

    Boody, Frederick P.

    2003-05-01

    A 20 kHz, 100-MW average power, pulsed 1.6-μm Pr+3:LaCl3 up-conversion laser for space propulsion, pumped at high intensity by a continuous 212-MW, 2.026-μm He/Ar/Xe nuclear-pumped laser, is proposed. 1.6 μm falls within the 1.72 μm > λ > 1.53 μm atmospheric transmission window and is sufficiently distant from 1.4 μm to be relatively eye safe. The high pulse rate minimizes dribble and thus maximizes specific impulse. The nuclear-pumped laser is also a steady-state nuclear reactor. The Pr+3:LaCl3 solid-state laser combines the many small beams produced by the reactor-laser with high beam quality. It consists of an array of face-pumped thin disks at Brewster's angle, face-cooled by high-pressure turbulent helium. The inhomogeneities introduced by the disk array are corrected by using a double pass geometry with a phase-conjugate mirror, as suggested by Magda. The fraction of the pump energy extracted from the Pr+3:LaCl3 laser is 47% at a pump intensity of 2×105 W/cm2. The He/Ar/Xe laser is 0.4% efficient, giving an overall efficiency of 0.2%, equivalent to ~0.8% if electrically pumped.

  10. Density functional theory and Raman spectroscopy applied to structure and vibrational mode analysis of 1,1',3,3'-tetraethyl-5,5',6,6'-tetrachloro- benzimidazolocarbocyanine iodide and its aggregate.

    PubMed

    Aydin, Metin; Dede, Özge; Akins, Daniel L

    2011-02-14

    We have measured electronic and Raman scattering spectra of 1,1',3,3'-tetraethyl-5,5',6,6'-tetrachloro-benzimidazolocarbocyanine iodide (TTBC) in various environments, and we have calculated the ground state geometric and spectroscopic properties of the TTBC cation in the gas and solution phases (e.g., bond distances, bond angles, charge distributions, and Raman vibrational frequencies) using density functional theory. Our structure calculations have shown that the ground state equilibrium structure of a cis-conformer lies ∼200 cm(-1) above that of a trans-conformer and both conformers have C(2) symmetry. Calculated electronic transitions indicate that the difference between the first transitions of the two conformers is about 130 cm(-1). Raman spectral assignments of monomeric- and aggregated-TTBC cations have been aided by density functional calculations at the same level of the theory. Vibrational mode analyses of the calculated Raman spectra reveal that the observed Raman bands above 700 cm(-1) are mainly associated with the in-plane deformation of the benzimidazolo moieties, while bands below 700 cm(-1) are associated with out-of-plane deformations of the benzimidazolo moieties. We have also found that for the nonresonance excited experimental Raman spectrum of aggregated-TTBC cation, the Raman bands in the higher-frequency region are enhanced compared with those in the nonresonance spectrum of the monomeric cation. For the experimental Raman spectrum of the aggregate under resonance excitation, however, we find new Raman features below 600 cm(-1), in addition to a significantly enhanced Raman peak at 671 cm(-1) that are associated with out-of-plane distortions. Also, time-dependent density functional theory calculations suggest that the experimentally observed electronic transition at ∼515 nm (i.e., 2.41 eV) in the absorption spectrum of the monomeric-TTBC cation predominantly results from the π → π∗ transition. Calculations are further interpreted

  11. (1)H NMR-based metabolomics study on a goldfish model of Parkinson's disease induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).

    PubMed

    Lu, Zhaoguang; Wang, Junsong; Li, Minghui; Liu, Qingwang; Wei, Dandan; Yang, Minghua; Kong, Lingyi

    2014-11-01

    A goldfish (Carassius auratus) model of Parkinson's disease (PD) was constructed by a single dose of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) according to previously reported methods. Global metabolite changes in brain of the MPTP induced goldfish model of PD were investigated. (1)H NMR-based metabolomics combined with various statistical methods such as orthogonal partial least squares discriminant analysis (OPLS-DA) and two-dimensional statistical total correlation spectroscopy (2D-STOCSY) found significant increase of leucine, isoleucine, valine, alanine, alanylalanine, creatinine, myo-inositol, 18:2 fatty acid, total fatty acids, arachic alcohol, taurine and significant decrease of N-acetylaspartate, (phospho)creatine, (phospho)choline, betaine, glutamine, 3-hexenedioate, acetamide, malonate, isocitrate, scyllo-inositol, phosphatidylcholines, cholesterols, n-3 fatty acids, polyunsaturated fatty acids (PUFAs) in brain of MPTP induced PD goldfish. These disturbed metabolite levels were involved in oxidative stress, energy failure, neuronal cell injury and death, consistent with those observed in clinical PD patients, and rodents and primates model of PD, indicating that the acute MPTP model of goldfish was an ideal and valuable model for PD research. In addition, several unusual metabolites in brain were significantly changed between MPTP induced PD and control goldfish, which might also play an important role in the pathogenesis of PD. This study also demonstrated the applicability and potential of (1)H NMR-based metabolomics approach for evaluation of animal models of disease induced by chemicals, such as MPTP-induced PD goldfish. PMID:25242684

  12. Exendin-4 Protects MIN6 Cells from t-BHP-Induced Apoptosis via IRE1-JNK-Caspase-3 Signaling

    PubMed Central

    Chen, Wen-Jia; Wang, Lin-Xi; Wang, Yan-Ping; Chen, Zhou; Liu, Xiao-Ying; Liu, Xiao-Hong; Liu, Li-Bin

    2012-01-01

    Objectives. This study aimed to explore the effect of exendin-4 on t-BHP-induced apoptosis in pancreatic β cells and the mechanism of action. Methods. Murine MIN6 pancreatic β cells were treated with exendin-4 in the presence or absence of tert-butyl hydroperoxide (t-BHP). Cell survival was assessed by MTT staining. The percentage of apoptotic cells was determined by fluorescence microscopy analysis after Hoechst/PI staining and flow cytometric assay after Annexin V-FITC/PI staining. The activity of caspase-3 was determined using a caspase-3 activity kit. Expression of P-IRE1α, IRE1α, C-Jun N-terminal kinase (JNK), P-JNK, C-JUN, and P-C-JUN was detected by western blotting. Results. Exendin-4 was found to inhibit t-BHP-induced apoptosis in pancreatic β-cells by downregulating caspase-3 activity. Exendin-4 also inhibited the endoplasmic reticulum transmembrane protein IRE1, the apoptosis-related signaling molecule JNK, and c-Jun activation. Conclusions. Our findings suggest that exendin-4 ultimately reduces t-BHP-induced β-cell apoptosis. IRE1-JNK-c-Jun signaling is involved in the exendin-4-mediated modulation of β-cell apoptosis. PMID:22518128

  13. 1,2,3-Triazolium-Based Poly(2,6-Dimethyl Phenylene Oxide) Copolymers as Anion Exchange Membranes.

    PubMed

    Liu, Lei; He, Shuqing; Zhang, Shufang; Zhang, Min; Guiver, Michael D; Li, Nanwen

    2016-02-01

    Anion exchange membranes (AEMs) based on 1,2,3-triazolium (TAM) were prepared from commercial poly(2,6-dimethyl phenylene oxide) (PPO) via "click chemistry" and subsequent N-alkylation. Flexible and tough membranes with various ion exchange capacities (IECs) were obtained by casting the polymers from NMP solutions. Although the resulting TAM-functionalized PPOs (PPO-TAM) membranes exhibited incomplete ion exchange in 1 M NaOH or NaHCO3 for 24 h even at elevated temperature, the highest hydroxide conductivities of the membranes were above 20 mS/cm at room temperature, which is comparable to many reported AEMs. Alkaline stability tests indicate that the PPO-TAM membranes showed a better alkaline stability than that of membranes containing imidazolium groups in 1 M NaOH at 80 °C, but still require further improvements in long-term stability for alkaline fuel cell application. An investigation of alkaline stability of model compounds demonstrated the instability of TAM cations under alkaline conditions could contribute to the deprotonation of benzylic methylene, C4 and C5 position on the triazolium ring. These results suggests that the alkaline stability of 1,2,3-triazolium cation could be improved by the introduction of substituents at the C4, C5 positions and benzylic methylene, and also provide insight and directions for organic cation designs for AEM application by the facile synthetic strategy of "click chemistry". PMID:26820176

  14. 27 CFR 6.3 - Application.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2012-04-01 2012-04-01 false Application. 6.3 Section 6.3 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS âTIED-HOUSEâ Scope of Regulations § 6.3 Application. (a) General. This part applies...

  15. 45 CFR 3.6 - Nondiscrimination.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 45 Public Welfare 1 2011-10-01 2011-10-01 false Nondiscrimination. 3.6 Section 3.6 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION CONDUCT OF PERSONS AND TRAFFIC ON THE NATIONAL INSTITUTES OF HEALTH FEDERAL ENCLAVE General § 3.6 Nondiscrimination. A person may not discriminate...

  16. 45 CFR 3.6 - Nondiscrimination.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 45 Public Welfare 1 2013-10-01 2013-10-01 false Nondiscrimination. 3.6 Section 3.6 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION CONDUCT OF PERSONS AND TRAFFIC ON THE NATIONAL INSTITUTES OF HEALTH FEDERAL ENCLAVE General § 3.6 Nondiscrimination. A person may not discriminate...

  17. 45 CFR 3.6 - Nondiscrimination.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 45 Public Welfare 1 2012-10-01 2012-10-01 false Nondiscrimination. 3.6 Section 3.6 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION CONDUCT OF PERSONS AND TRAFFIC ON THE NATIONAL INSTITUTES OF HEALTH FEDERAL ENCLAVE General § 3.6 Nondiscrimination. A person may not discriminate...

  18. 45 CFR 3.6 - Nondiscrimination.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 45 Public Welfare 1 2010-10-01 2010-10-01 false Nondiscrimination. 3.6 Section 3.6 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION CONDUCT OF PERSONS AND TRAFFIC ON THE NATIONAL INSTITUTES OF HEALTH FEDERAL ENCLAVE General § 3.6 Nondiscrimination. A person may not discriminate...

  19. 45 CFR 3.6 - Nondiscrimination.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 45 Public Welfare 1 2014-10-01 2014-10-01 false Nondiscrimination. 3.6 Section 3.6 Public Welfare Department of Health and Human Services GENERAL ADMINISTRATION CONDUCT OF PERSONS AND TRAFFIC ON THE NATIONAL INSTITUTES OF HEALTH FEDERAL ENCLAVE General § 3.6 Nondiscrimination. A person may not discriminate...

  20. 27 CFR 6.3 - Application.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2013-04-01 2013-04-01 false Application. 6.3 Section 6.3 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY ALCOHOL âTIED-HOUSEâ Scope of Regulations § 6.3 Application. (a) General. This part applies only to transactions between industry...

  1. 27 CFR 6.3 - Application.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2011-04-01 2011-04-01 false Application. 6.3 Section 6.3 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS âTIED-HOUSEâ Scope of Regulations § 6.3 Application. (a) General. This part applies only to transactions between industry...

  2. 27 CFR 6.3 - Application.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Application. 6.3 Section 6.3 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY LIQUORS âTIED-HOUSEâ Scope of Regulations § 6.3 Application. (a) General. This part applies only to transactions between industry...

  3. 27 CFR 6.3 - Application.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2014-04-01 2014-04-01 false Application. 6.3 Section 6.3 Alcohol, Tobacco Products and Firearms ALCOHOL AND TOBACCO TAX AND TRADE BUREAU, DEPARTMENT OF THE TREASURY ALCOHOL âTIED-HOUSEâ Scope of Regulations § 6.3 Application. (a) General. This part applies only to transactions between industry...

  4. Paeoniflorin suppresses IL-6/Stat3 pathway via upregulation of Socs3 in dendritic cells in response to 1-chloro-2,4-dinitrobenze.

    PubMed

    Shi, Dongmei; Wang, Qiong; Zheng, Hailin; Li, Dongmei; Shen, Yongnian; Fu, Hongjun; Li, Tianhang; Mei, Huan; Lu, Guixia; Qiu, Ying; Chen, Guanzhi; Liu, Weida

    2016-09-01

    Mounting evidence has suggested that inflammation is associated with IL-6/Stat3 pathway in dendritic cells (DCs) and Th17 cells, which are critical for development of allergic contact dermatitis (ACD). Paeoniflorin (PF) has been clinically proved to be effective in the treatment of inflammatory skin diseases such as ACD. We have previously demonstrated the effect of PF on DCs stimulated with 1-chloro-2,4-dinitrobenze (DNCB) and naïve CD4(+)CD45RA(+) T cells for Th17 cell differentiation. However, whether PF down-regulates IL-6/Stat3 in DCs and Th17 cells remains to be explored. In this study, we show clearly that PF markedly decreases IL-6/Stat3 in DCs stimulated with DNCB at both gene and protein levels compared with control DCs in vitro. Meanwhile, PF up-regulates suppressor of cytokine signaling 3 (Socs3). Such decreased expression of IL-6/Stat3 is abolished in DCs that were transfected with Socs3 short interfering RNA (siRNA). When mice CD4(+)CD45 RA(+) T cells were co-cultured with PF-treated DCs stimulated with/without DNCB, the gene expression of the Th17 cell markers such as retinoic acid-related orphan nuclear hormone receptor γt (RORγt), IL-17A, and IL-23R decreased, in accordance with the less secretions of IL-17 and IL-23 in vitro and in vivo. Finally, the suppressed Th17 differentiation induced by PF can be abolished by additional recombinant mouse IL-6. Our results suggest that the anti-inflammatory mechanisms introduced by depletion of Socs3 expression or inactivation of the negative regulator such as Socs3 may represent a promising strategy for the prevention of ACD. PMID:27236299

  5. 40 CFR 721.8940 - Chromate(3-), bis[3-[[6-amino-1,4-dihydro-2-[[[4-[(2-hydroxy-1-naphthalenyl)azo] phenyl]sulfonyl...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Chromate(3-), bis phenyl]sulfonyl... Specific Chemical Substances § 721.8940 Chromate(3-), bis phenyl]sulfonyl] amino]-4-(oxo-.kappa.O)-5... substance and significant new uses subject to reporting. (1) The chemical substance identified as...

  6. 40 CFR 721.8940 - Chromate(3-), bis[3-[[6-amino-1,4-dihydro-2-[[[4-[(2-hydroxy-1-naphthalenyl)azo] phenyl]sulfonyl...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Chromate(3-), bis phenyl]sulfonyl... Specific Chemical Substances § 721.8940 Chromate(3-), bis phenyl]sulfonyl] amino]-4-(oxo-.kappa.O)-5... substance and significant new uses subject to reporting. (1) The chemical substance identified as...

  7. 40 CFR 721.8940 - Chromate(3-), bis[3-[[6-amino-1,4-dihydro-2-[[[4-[(2-hydroxy-1-naphthalenyl)azo] phenyl]sulfonyl...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Chromate(3-), bis phenyl]sulfonyl... Specific Chemical Substances § 721.8940 Chromate(3-), bis phenyl]sulfonyl] amino]-4-(oxo-.kappa.O)-5... substance and significant new uses subject to reporting. (1) The chemical substance identified as...

  8. 2-pyrazinylnitrene and 4-pyrimidylnitrene. Ring expansion to 1,3,5-triazacyclohepta-1,2,4,6-tetraene and ring opening to (2-Isocyanovinyl)carbodiimide.

    PubMed

    Addicott, Chris; Wong, Ming Wah; Wentrup, Curt

    2002-11-29

    Tetrazolo[1,5-a]pyrazine/2-azidopyrazine 9T/9A undergo photolysis in Ar matrix at cryogenic temperatures to yield 1,3,5-triazacyclohepta-1,2,4,6-tetraene 21 as the first observable intermediate, and 1-cyanoimidazole 11 and (2-isocyanovinyl)carbodiimide 22 as the final products. The latter tautomerizes to 2-(isocyanovinyl)cyanamide 23 on warming to 40 K. The same intermediate 21 and the same final products are obtained on matrix photolysis of the isomeric tetrazolo[1,5-c]pyrimidine/4-azidopyrimidine 24T/24A. These photolysis results as well as those of the previously reported thermal ring contraction of (15)N-labeled 2-pyrazinyl- and 4-pyrimidylnitrenes to 1-cyanoimidazoles can all be rationalized in terms of selective ring opening of 21 or nitrine 10 to a nitrile ylide zwitterion 28 prior to formation of the final products, 11 and 22. The results are supported by high-level ab initio and DFT calculations (CASPT2-CASSCF(6,6), G3(MP2), and B3LYP/6-31+G) of the energies and IR spectra of the intermediates and products. PMID:12444636

  9. Design, synthesis, and biological evaluation of 1,9-diheteroarylnona-1,3,6,8-tetraen-5-ones as a new class of anti-prostate cancer agents.

    PubMed

    Zhang, Xiaojie; Wang, Rubing; Perez, German Ruiz; Chen, Guanglin; Zhang, Qiang; Zheng, Shilong; Wang, Guangdi; Chen, Qiao-Hong

    2016-10-01

    In search of more effective chemotherapeutics for the treatment of castration-resistant prostate cancer and inspired by curcumin analogues, twenty five (1E,3E,6E,8E)-1,9-diarylnona-1,3,6,8-tetraen-5-ones bearing two identical terminal heteroaromatic rings have been successfully synthesized through Wittig reaction followed by Horner-Wadsworth-Emmons reaction. Twenty-three of them are new compounds. The WST-1 cell proliferation assay was employed to assess their anti-proliferative effects toward both androgen-sensitive and androgen-insensitive human prostate cancer cell lines. Eighteen out of twenty-five synthesized compounds possess significantly improved potency as compared with curcumin. The optimal compound, 78, is 14- to 23-fold more potent than curcumin in inhibiting prostate cancer cell proliferation. It can be concluded from our data that 1,9-diarylnona-1,3,6,8-tetraen-5-one can serve as a new potential scaffold for the development of anti-prostate cancer agents and that pyridine-4-yls and quinolin-4-yl act as optimal heteroaromatic rings for the enhanced potency of this scaffold. Two of the most potent compounds, 68 and 75, effectively suppress PC-3 cell proliferation by activating cell apoptosis and by arresting cell cycle in the G0/G1 phase. PMID:27543391

  10. Synthesis, structural characterization, docking, lipophilicity and cytotoxicity of 1-[(1R)-1-(6-fluoro-1,3-benzothiazol-2-yl)ethyl]-3-alkyl carbamates, novel acetylcholinesterase and butyrylcholinesterase pseudo-irreversible inhibitors.

    PubMed

    Pejchal, Vladimír; Štěpánková, Šárka; Pejchalová, Marcela; Královec, Karel; Havelek, Radim; Růžičková, Zdeňka; Ajani, Haresh; Lo, Rabindranath; Lepšík, Martin

    2016-04-01

    In the current study, sixteen novel derivatives of (R)-1-(6-fluorobenzo[d]thiazol-2-yl)ethanamine were synthesized as acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitors. Chemical structures together with purity of the synthesized compounds were substantiated by IR, (1)H, (13)C, (19)F NMR, high resolution mass spectrometry and elemental analysis. The optical activities were confirmed by optical rotation measurements. The synthesized compounds were evaluated for their AChE and BChE inhibitory activities. In addition, the cytotoxicity of the most active compounds was investigated against human cell lines employing XTT tetrazolium salt reduction assay and xCELLigence system allowing a label-free assessment of the cells proliferation. Our results demonstrated that the inhibitory mechanism was confirmed to be pseudo-irreversible, in line with previous studies on carbamates. Compounds indicated as 3b, 3d, 3l and 3n showed the best AChE inhibitory activity of all the evaluated compounds and were up to tenfold more potent than standard drug rivastigmine. The binding mode was determined using state-of-the-art covalent docking and scoring methodology. The obtained data clearly demonstrated that 3b, 3d, 3l and 3n benzothiazole carbamates possess high inhibitory activity against AChE and BChE and concurrently negligible cytotoxicity. In conclusion, our results indicate, that these derivatives could be promising in an effective therapeutic intervention for Alzheimer's disease. PMID:26947959

  11. 26,27-Hexafluoro-1,25-dihydroxyvitamin D3 (F6-1,25(OH)2D3) prevents osteoporosis induced by immobilization combined with ovariectomy in the rat.

    PubMed

    Okumura, H; Yamamuro, T; Higuchi, S; Harada, M; Takamura, T; Otomo, S; Aihara, H; Ikekawa, N; Kobayashi, T

    1990-05-01

    The effect of 26,27-hexafluoro-1,25-dihydroxyvitamin D3 (F6-1,25(OH)2D3) on experimental osteoporosis in the rat induced by a combination of immobilization and ovariectomy was evaluated. F6-1,25(OH)2D3 increased the femur score and the photo-density. The administration of F6-1,25(OH)2D3 also significantly increased the dry weight, the ash weight and the ash content of the bone. Both F6-1,25(OH)2D3 and 1 alpha(OH)D3 showed a nearly dose-dependent effect and significant inhibition of the decrease of bone mass. Histomorphometry revealed a significant decrease of resorption by the administration of F6-1,25(OH)2D3. Bone formation rate in the F6-1,25(OH)2D3 treated group significantly decreased compared with the vehicle group. In conclusion, the pharmacological effective dose of F6-1,25(OH)2D3 was considered to prevent the osteoporotic decrease of bone mass by suppressing the elevated bone turnover. PMID:2350614

  12. Penicibilaenes A and B, sesquiterpenes with a tricyclo[6.3.1.0(1,5)]dodecane skeleton from the marine isolate of Penicillium bilaiae MA-267.

    PubMed

    Meng, Ling-Hong; Li, Xiao-Ming; Liu, Yang; Wang, Bin-Gui

    2014-12-01

    Penicibilaenes A (1) and B (2), two sesquiterpenes possessing a tricyclo[6.3.1.0(1,5)]dodecane skeleton, were characterized from Penicillium bilaiae MA-267, a fungus obtained from the rhizospheric soil of the mangrove plant Lumnitzera racemosa. The lack of some key COSY and NOESY correlations made the structure elucidation of compound 1 difficult, which was solved by a X-ray crystallographic study. Compounds 1 and 2 exhibited selective activity against the plant pathogenic fungus Colletotrichum gloeosporioides (MIC = 1.0 and 0.125 μg/mL, respectively). PMID:25408229

  13. Synthesis, X-ray structure analysis and density functional study of an unusual anhydrous 5,6-dimethylbenzo-1,3-imidazolium(H3) chloride

    NASA Astrophysics Data System (ADS)

    Tamasi, Gabriella; Carpini, Alice; Valensin, Daniela; Cini, Renzo

    2015-01-01

    The heteroaromatic base 5,6-dimethylbenzo-1,3-imidazole (DMBI) proved to be a Brönsted base in an anhydrous ethanol solution, which contained fac,trans-[Ru(CO)3Cl2]2 at 55 °C in air when the DMBI:Ru molar ratio was 2:1. The reaction produced colorless anhydrous single crystals of {(HDMBI)+Cl-}, C9H11ClN2, which were collected and analyzed using X-ray diffraction (XRD) techniques. A network of N-H⋯Cl hydrogen bond type interactions linking the protonated hetero-aromatic base to the chloride anions (bridging bases) stabilizes the crystal and mimics the N-H⋯Cl- interactions that play important roles in CCl channel biological systems. The shortest N⋯Cl contact distance and corresponding N-H⋯Cl angle are 3.073(3) Å and 173(3)°, respectively. The packing is also assisted by weaker C-H⋯Cl- hydrogen bond-type interactions and an extensive network of π⋯π stacking interactions involving HDMBI+ cations. Density functional calculations at the B3LYP/6-31G∗∗ and /6-311++G∗∗ levels for models of fragments of the crystal structure allowed for the evaluation of geometric parameters, hydrogen bond-type interaction formation energies, and infrared parameters for {(HDMBI)+Cl-} and {(HDMBI)+⋯Cl-⋯(HDMBI)+}.

  14. Ninety-day study of inhaled 1,3,5-trichloro-2,4,6-trinitrobenzene in rats

    SciTech Connect

    Johnson, J.S.

    1982-05-28

    Male and female rats were exposed to 2, 10, and 20 mg/m/sup 3/ of 1,3,5-Trichloro-2,4,6-Trinitrobenzene (TCTNB) dust for six hrs daily, five days a week, for up to 13 weeks. After 13 weeks of exposure, animals were sacrificed and examined for changes in blood constituents, internal organs, and tissues resulting from TCTNB exposure. Mortality at the high dose level was 37%, with deaths occurring in weeks 1-6. There was no mortality in either the middle-level or low-level exposure groups. In all decedents, signs of respiratory distress were observed in the days before death, and marked pathologic changes in the lung were observed at necropsy. Some pulmonary disease was observed in animals sacrificed at four weeks and, to a lesser extent, in those surviving to the scheduled 13-week sacrifice. Small increases in total erythrocyte counts and hematocrit were observed at four and 13 weeks in treated animals, but no other appreciable hematologic changes were apparent. Weekly body weights remained unaffected by TCTNB exposure. Additional groups of male and female rats were exposed once for six hrs and subsequently challenged twice to see if the mode of death was related to sensitization to TCTNB, but no deaths occurred.

  15. Laser induced third harmonic generation in δ-Bi1-xNdxB3O6 nanocomposites

    NASA Astrophysics Data System (ADS)

    Chrunik, By M.; Ebothé, J.; Aloufy, A. K.; Majchrowski, A.; Jaroszewicz, L. R.; Kityk, I. V.

    2016-04-01

    A possibility of optically operated third harmonic generation (THG) in polymer nanocomposites based on orthorhombic δ-Bi1-xNdxB3O6 powders (where x=0.025÷0.100) is presented. The nanoparticles were fabricated using polymeric precursor method. The particles were acoustically milled and then they were embedded into polyvinyl alcohol (PVA) photopolymer matrix. After solidification the additional photoinducing treatment was performed by two coherent 1064 nm Nd:YAG laser beams. The angle between the photoinducing beams and their polarization was varied in order to achieve the maximum of THG. THG efficiency was monitored immediately after Nd:YAG laser treatment at different temperatures. The photoinduced THG was explored versus the Nd3+ content and temperature. Origin of the effect is discussed within a framework of phenomenological description.

  16. Synthesis, structure elucidation, DNA-PK and PI3K and anti-cancer activity of 8- and 6-aryl-substituted-1-3-benzoxazines.

    PubMed

    Morrison, Rick; Al-Rawi, Jasim M A; Jennings, Ian G; Thompson, Philip E; Angove, Michael J

    2016-03-01

    The synthesis of 6-aryl, 8- aryl, and 8-aryl-6-chloro-2-morpholino-1,3-benzoxazines with potent activity against PI3K and DNA-PK is described. Synthesis of thirty one analogues was facilitated by an improved synthesis of 3-bromo-2-hydroxybenzoic acid 13 by de-sulphonation of 3-bromo-2-hydroxy-5-sulfobenzoic acid 12 en route to 2-methylthio-substituted-benzoxazine intermediates 17-19. From this series, compound 20k (LTURM34) (dibenzo[b,d]thiophen-4-yl) (IC50 = 0.034 μM) was identified as a specific DNA-PK inhibitor, 170 fold more selective for DNA-PK activity compared to PI3K activity. Other compounds of the series show markedly altered selectivity for various PI3K isoforms including compound 20i (8-(naphthalen-1-yl) a potent and quite selective PI3Kδ inhibitor (IC50 = 0.64 μM). Finally, nine compounds were evaluated and showed antiproliferative activity against an NCI panel of cancer cell lines. Compound 20i (8-(naphthalen-1-yl) showed strong anti-proliferative activity against A498 renal cancer cells that warrants further investigation. PMID:26854431

  17. Design, synthesis, and characterization of (1-(4-aryl)- 1H-1,2,3-triazol-4-yl)methyl, substituted phenyl-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylates against Mycobacterium tuberculosis.

    PubMed

    Venugopala, Katharigatta N; Dharma Rao, G B; Bhandary, Subhrajyoti; Pillay, Melendhran; Chopra, Deepak; Aldhubiab, Bandar E; Attimarad, Mahesh; Alwassil, Osama Ibrahim; Harsha, Sree; Mlisana, Koleka

    2016-01-01

    The novel (1-(4-aryl)-1H-1,2,3-triazol-4-yl)methyl, substituted phenyl-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate derivatives were synthesized by the click reaction of the dihydropyrimidinones, bearing a terminal alkynyl group, with various substituted aryl azides at room temperature using a catalytic amount of Cu(OAc)2 and sodium ascorbate in a 1:2 ratio of acetone and water as a solvent. The newly synthesized compounds were characterized by a number of spectroscopic techniques, such as infrared, liquid chromatography-mass spectrometry, (1)H, and (13)C nuclear magnetic resonance along with single crystal X-ray diffraction. The current procedure for the synthesis of 1,2,3-triazole hybrids with dihydropyrimidinones is appropriate for the synthesis of a library of analogs 7a-l and the method accessible here is operationally simple and has excellent yields. The title compounds 7a-l were evaluated for their in vitro antitubercular activity against H37RV and multidrug-resistant strains of Mycobacterium tuberculosis by resazurin microplate assay plate method and it was found that compound 7d was promising against H37RV and multidrug-resistant strains of M. tuberculosis at 10 and 15 μg/mL, respectively. PMID:27601885

  18. Design, synthesis, and characterization of (1-(4-aryl)- 1H-1,2,3-triazol-4-yl)methyl, substituted phenyl-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylates against Mycobacterium tuberculosis

    PubMed Central

    Venugopala, Katharigatta N; Dharma Rao, G B; Bhandary, Subhrajyoti; Pillay, Melendhran; Chopra, Deepak; Aldhubiab, Bandar E; Attimarad, Mahesh; Alwassil, Osama Ibrahim; Harsha, Sree; Mlisana, Koleka

    2016-01-01

    The novel (1-(4-aryl)-1H-1,2,3-triazol-4-yl)methyl, substituted phenyl-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate derivatives were synthesized by the click reaction of the dihydropyrimidinones, bearing a terminal alkynyl group, with various substituted aryl azides at room temperature using a catalytic amount of Cu(OAc)2 and sodium ascorbate in a 1:2 ratio of acetone and water as a solvent. The newly synthesized compounds were characterized by a number of spectroscopic techniques, such as infrared, liquid chromatography-mass spectrometry, 1H, and 13C nuclear magnetic resonance along with single crystal X-ray diffraction. The current procedure for the synthesis of 1,2,3-triazole hybrids with dihydropyrimidinones is appropriate for the synthesis of a library of analogs 7a-l and the method accessible here is operationally simple and has excellent yields. The title compounds 7a-l were evaluated for their in vitro antitubercular activity against H37RV and multidrug-resistant strains of Mycobacterium tuberculosis by resazurin microplate assay plate method and it was found that compound 7d was promising against H37RV and multidrug-resistant strains of M. tuberculosis at 10 and 15 μg/mL, respectively. PMID:27601885

  19. Two-hour methyl isocyanate inhalation and 90-day recovery study in B6C3F1 mice

    SciTech Connect

    Boorman, G.A.; Uraih, L.C.; Gupta, B.N.; Bucher, J.R.

    1987-06-01

    B6C3F1 mice were exposed by inhalation to 0, 3, 10, and 30 ppm methyl isocyanate for 2 hr followed by a 90-day recovery period. Sixteen of eight (20%) male mice in the 30 ppm group died following exposure. There were no other unscheduled deaths in the mice. Five mice/sex/group were examined at 2 hr or at 1, 3, 7, 14, 28, 49, or 91 days following exposure. Chemical-related changes were restricted to the respiratory system. At 30 ppm there were extensive necrosis and erosion of the respiratory and olfactory epithelium in the nasal cavity. Severe necrosis and epithelial erosion were also found in the trachea and main bronchi. Regeneration of the mucosal epithelium occurred rapidly in the nasal cavity and airways. In the turbinates, mild incomplete olfactory epithelial regeneration persisted to day 91 in the male mice. Intraluminal fibrotic projections covered by respiratory epithelium and bronchial fibrosis were found in the major airways of the 30 ppm male and female mice by day 7. The intraluminal fibrosis persisted to day 91. In males with severe bronchial fibrosis, chronic alveolitis and atelectasis were found. In mice exposed to 3 or 10 ppm, persistent pulmonary changes were not found. These studies indicate that methyl isocyanate inhalation at or near lethal concentrations can cause persistent fibrosis of the major bronchi in mice.

  20. The interactions of 2,3,7,8-tetrachlorodibenzo-p-dioxin(TCDD) and 6-methyl-1,3,8-trichlorodibenzofuran (MCDF) in TCDD-induced porphyria

    SciTech Connect

    Yao, Cheng Catsby.

    1989-01-01

    Halogenated aryl hydrocarbon(HAH)-induced porphyria is caused by alteration of porphyrin metabolism and results in the accumulation of hepatic and urinary porphyrins. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (75 {mu}/kg) caused significant increases of hepatic porphyrin levels in C57BL/6 male, female and ovariectomized female, and C57BL/10 male mice 3 weeks after treatment. In contrast, 6-methyl-1,3,8-trichlorodibenzofuran (MCDF) was inactive at a dose of 750 {mu}mol/kg. Cotreatment with MCDF (750 {mu}mol/kg) and 2,3,7,8-TCDD (75 {mu}g/kg) resulted in partial antagonism of 2,3,7,8-TCDD-induced porphyrin accumulation in female but not in male mice. In female C57BL/6 mice, 2,3,7,8-TCDD-induced porphyria was accompanied by the induction of hepatic microsomal aryl hydrocarbon hydroxylase (AHH) and ethoxyresorufin O-deethylase (EROD) activities and the inhibition of uroporphyrinogen decarboxylase (UROD) activity. MCDF (750 {mu}mol/kg) did not significantly affect these enzyme activities. In coadministration studies, MCDF partially antagonized 2,3,7,8-TCDD-induced hepatic porphyrin accumulation but did not affect the activities of hepatic AHH, EROD or UROD. These results demonstrate that the induction of the monooxygenase enzyme activities and the inhibition of UROD activity by 2,3,7,8-TCDD and the development of porphyria are not coordinately regulated in C57BL/6 female mice. In cultured chick embryo hepatocytes, 2,3,7,8-TCDD caused a significant increase in porphyrin levels and induced AHH and EROD activities. MCDF and Aroclor 1254 partially antagonized the 2,3,7,8-TCDD induced AHH and EROD activities but not the porphyrin accumulation.

  1. Theoretical determination of anisotropic thermal conductivity for crystalline 1,3,5-triamino-2,4,6-trinitrobenzene (TATB)

    NASA Astrophysics Data System (ADS)

    Kroonblawd, Matthew P.; Sewell, Thomas D.

    2013-08-01

    Bond stretching and three-center angle bending potentials have been developed to extend an existing rigid-bond 1,3,5-triamino-2,4,6-trinitrobenzene molecular dynamics force field [D. Bedrov, O. Borodin, G. D. Smith, T. D. Sewell, D. M. Dattelbaum, and L. L. Stevens, J. Chem. Phys. 131, 224703 (2009), 10.1063/1.3264972] for simulations requiring fully flexible molecules. The potentials were fit to experimental vibrational spectra and electronic structure predictions of vibrational normal modes using a combination of zero kelvin eigenmode analysis for the isolated molecule and power spectra for the isolated molecule and crystal. A reverse non-equilibrium molecular dynamics method [F. Müller-Plathe, J. Chem. Phys. 106, 6082 (1997), 10.1063/1.473271] was used to obtain the room temperature, atmospheric pressure thermal conductivity along three directions in a well-defined, non-orthogonal basis. The thermal conductivity was found to be significantly anisotropic with values 1.13 ± 0.07, 1.07 ± 0.07, and 0.65 ± 0.03 W m-1 K-1 for directions nominally parallel to the a, b, and c lattice vectors, respectively.

  2. Carcinogenicity study of GSM and DCS wireless communication signals in B6C3F1 mice.

    PubMed

    Tillmann, Thomas; Ernst, Heinrich; Ebert, Sven; Kuster, Niels; Behnke, Wolfgang; Rittinghausen, Susanne; Dasenbrock, Clemens

    2007-04-01

    The purpose of this study using a total of 1170 B6C3F1 mice was to detect and evaluate possible carcinogenic effects in mice exposed to radio-frequency-radiation (RFR) from Global System for Mobile Communication (GSM) and Digital Personal Communications System (DCS) handsets as emitted by handsets operating in the center of the communication band, that is, at 902 MHz (GSM) and 1747 MHz (DCS). Restrained mice were exposed for 2 h per day, 5 days per week over a period of 2 years to three different whole-body averaged specific absorption rate (SAR) levels of 0.4, 1.3, 4.0 mW/g bw (SAR), or were sham exposed. Regarding the organ-related tumor incidence, pairwise Fisher's test did not show any significant increase in the incidence of any particular tumor type in the RF exposed groups as compared to the sham exposed group. Interestingly, while the incidences of hepatocellular carcinomas were similar in EMF and sham exposed groups, in both studies the incidences of liver adenomas in males decreased with increasing dose levels; the incidences in the high dose groups were statistically significantly different from those in the sham exposed groups. Comparison to published tumor rates in untreated mice revealed that the observed tumor rates were within the range of historical control data. In conclusion, the present study produced no evidence that the exposure of male and female B6C3F1 mice to wireless GSM and DCS radio frequency signals at a whole body absorption rate of up to 4.0 W/kg resulted in any adverse health effect or had any cumulative influence on the incidence or severity of neoplastic and non-neoplastic background lesions, and thus the study did not provide any evidence of RF possessing a carcinogenic potential. PMID:17019729

  3. Synthesis, spectral features and biological activity of some novel hetarylazo dyes derived from 6-amino-1,3-dimethyluracil

    NASA Astrophysics Data System (ADS)

    Yousefi, Hessamoddin; Yahyazadeh, Asieh; Yazdanbakhsh, Mohammad Reza; Rassa, Mehdi; Moradi-e-Rufchahi, Enayat O.'llah

    2012-05-01

    A series of hetarylazoaminouracil dyes were prepared by coupling of 6-amino-1,3-dimethyluracil with eight diazotized heterocyclic amines in nitrosyl sulphuric acid. The prepared azo dyes were characterized by UV-Vis, FT-IR, 13C NMR, 1H NMR spectroscopic techniques and elemental analysis. The solvatochromism of dyes was evaluated with respect to wavelength of maximum absorption (λmax) in seven solvents with different polarities: acetic acid, methanol, water, chloroform, acetonitrile, dimethyl sulfoxide and dimethyl formamide. The effects of acid, base and concentration of the dye on the visible absorption spectra were also reported. In addition, the antimicrobial activity of the synthesized dyes was evaluated on Escherichia coli, Bacillus subtilis, Micrococcus leuteus and Pseudomonas aeruginosa.

  4. Interleukin-6 influences stress-signalling by reducing the expression of the mTOR-inhibitor REDD1 in a STAT3-dependent manner.

    PubMed

    Pinno, Jessica; Bongartz, Hannes; Klepsch, Oliver; Wundrack, Nicole; Poli, Valeria; Schaper, Fred; Dittrich, Anna

    2016-08-01

    Interleukin 6 (IL-6) is a pleiotropic cytokine and a strong activator of Mammalian Target of Rapamycin (mTOR). In contrast, mTOR activity is negatively regulated by Regulated in Development and DNA Damage Responses 1 (REDD1). Expression of REDD1 is induced by cellular stressors such as glucocorticoids and DNA damaging agents. We show that the expression of basal as well as stress-induced REDD1 is reduced by IL-6. The reduction of REDD1 expression by IL-6 is independent of proteasomal or caspase-mediated degradation of REDD1 protein. Instead, induction of REDD1 mRNA is reduced by IL-6. The regulation of REDD1 expression by IL-6 is independent of Phosphatidylinositide-3-Kinase (PI3K) and Mitogen-Activated Protein Kinase (MAPK) signalling but depends on the expression and activation of Signal Transducer and Activator of Transcription 3 (STAT3). Furthermore, the reduction of basal REDD1 expression by IL-6 correlates with IL-6-induced activation of mTOR signalling. Inhibition of STAT3 activation blocks IL-6-induced mTOR activation. In summary, we present a novel STAT3-dependent mechanism of both IL-6-induced activation of mTOR and IL-6-dependent reversion of stress-induced inhibition of mTOR activity. PMID:27094713

  5. Structural stabilization of transthyretin by a new compound, 6-benzoyl-2-hydroxy-1H-benzo[de]isoquinoline-1,3(2H)-dione.

    PubMed

    Yokoyama, Takeshi; Takaki, Shun; Chosa, Keisuke; Sato, Takashi; Suico, Mary Ann; Teranishi, Yuriko; Shuto, Tsuyoshi; Mizuguchi, Mineyuki; Kai, Hirofumi

    2015-12-01

    Familial amyloid polyneuropathy (FAP) is a genetic, adult-onset, neurodegenerative disorder caused by amyloid formation of transthyretin (TTR), a thyroxine-binding protein. Mutation in TTR causes a propensity of TTR tetramer to dissociate to monomer, which is the first step to amyloidosis. Thus, a drug that can stabilize the tetramer structure will have therapeutic benefit. Here, by virtual screening and biochemical assays, we identified small molecule 6-benzoyl-2-hydroxy-1H-benzo[de]isoquinoline-1,3(2H)-dione (L6) that can prevent the dissociation of TTR to monomer. X-ray crystallography reveals that L6 binds to the T4 binding pocket of TTR. These findings show that L6 is a candidate TTR stabilizer. PMID:26639444

  6. Electrochemical characterization of MC3T3-E1 cells cultured on γTiAl and Ti-6Al-4V alloys.

    PubMed

    Bueno-Vera, J A; Torres-Zapata, I; Sundaram, P A; Diffoot-Carlo, N; Vega-Olivencia, C A

    2015-12-01

    Electrochemical impedance spectroscopy (EIS) was used to study the behavior of MC3T3-E1 cells cultured in an αMEM+FBS solution on two Ti-based alloys (Ti-6Al-4V and γTiAl) for 4, 7 and 14 days. EIS measurements were carried out at an open-circuit potential in a 1 mHz to 100 kHz frequency range. Results indicate a general increase in impedance on the Ti alloy surfaces with cells as a function of time. Bode plots indicate changes corresponding to the passive oxide film, adsorption of proteins and cell tissue on surfaces with the passage of time. Normal cellular activity based on the polygonal morphology, with long and fine cytoplasmic prolongations of the cells on Ti-6Al-4V and γTiAl was observed from SEM images. Similarly, mineralization nodules corresponding to cell differentiation associated with the osseogenetic process were observed confirmed by Alizarin Red S staining. Immunofluorescence analysis to detect the presence of collagen Type I showed an increase in the segregation of collagen as a function of time. The impedance values obtained from EIS testing are indicative of the corrosion protection offered to the Ti alloy substrates by the cell layer. This study shows that γTiAl has better corrosion resistance than that of Ti-6Al-4V in the αMEM+FBS environment in the presence of MC3T3-E1 cells. PMID:26145813

  7. Solid-state thermochromism and phase transitions of charge transfer 1,3-diamino-4,6-dinitrobenzene dyes.

    PubMed

    Lee, Jong Hoon; Naumov, Pance; Chung, Ihn Hee; Lee, Sang Cheol

    2011-09-01

    The lower 1,3-bis(hydroxyalkylamino) homologues of the strong intramolecular X-type charge transfer (CT) system 1,3-diamino-4,6-dinitrobenzene (DADNB) exhibit reversible color change in the solid state from yellow at room temperature (RT) to orange and red at high temperature (HT). To investigate the structural prerequisites for occurrence of this phenomenon, we prepared 10 new derivatives of DADNB where the hydroxyalkyl arms at the amino groups were replaced with substituents having different electronic and steric profiles. Two of the new materials exhibit sharp and reversible thermochromic change in the solid state: when heated, the bis(aminoethyl) derivative (DADNB-1) undergoes color change from orange-red to brown, while one of the three polymorphs of the bisphenyl product (DADNB-2) changes its color from red to yellow. The physicochemical analysis and the crystal structures of seven of these compounds, one of which is trimorphic, confirmed that both phenomena are due to solid-solid phase transitions. The brown high-temperature phase of DADNB-1 presents the first example where the absorption is shifted beyond the red region. Form C of DADNB-2 is the first material of this group that exhibits "negative" thermochromism, where the high-temperature phase absorbs at lower wavelength than the low-temperature one. The results demonstrate the potentials of these simple and easily accessible organic molecular materials for thermal switching of the optical properties by utility of intermolecular interactions to modulate the intramolecular CT. PMID:21790159

  8. Multiple-site carcinogenicity of benzene in Fischer 344 rats and B6C3F1 mice.

    PubMed Central

    Huff, J E; Haseman, J K; DeMarini, D M; Eustis, S; Maronpot, R R; Peters, A C; Persing, R L; Chrisp, C E; Jacobs, A C

    1989-01-01

    Toxicology and carcinogenesis studies of benzene (CAS No. 71-43-2; greater than 99.7% pure) were conducted in groups of 60 F344/N rats and 60 B6C3F1 mice of each sex for each of three exposure doses and vehicle controls. These composite studies on benzene were designed and conducted because of large production volume and widespread human exposure, because of the epidemiologic association with leukemia, and because previous experiments were considered inadequate or inconclusive for determining carcinogenicity in laboratory animals. Using the results from 17-week studies, doses for the 2-year studies were selected based on clinical observations (tremors in higher dosed mice), on clinical pathologic findings (lymphoid depletion in rats and leukopenia in mice), and on body weight effects. Doses of 0, 50, 100, or 200 mg/kg body weight benzene in corn oil were administered by gavage to male rats, 5 days per week, for 103 weeks. Doses of 0, 25, 50, or 100 mg/kg benzene in corn oil were administered by gavage to female rats and to male and female mice for 103 weeks. Ten animals in each of the 16 groups were killed at 12 months, and necropsies were performed. Hematologic profiles were performed at 3-month intervals. For the 2-year studies, mean body weights of the top dose groups of male rats and of both sexes of mice were lower than those of the controls. Survivals of the top dose group of rats and mice of each sex were reduced; however, at week 92 for rats and week 91 for mice, survival was greater than 60% in all groups; most of the dosed animals that died before week 103 had neoplasia. Compound-related nonneoplastic or neoplastic effects on the hematopoietic system, Zymbal gland, forestomach, and adrenal gland were found both for rats and mice. Further, the oral cavity was affected in rats, and the lung, liver, Harderian gland, preputial gland, ovary, and mammary gland were affected in mice. Under the conditions of these 2-year gavage studies, there was clear evidence

  9. Synthesis of 6-(2-Methoxynaphthyl)-2,3-dihydro-1,2,4-triazine-3-thione as a New Reagent for Spectrophotometric Determination of Copper

    PubMed Central

    Ghanbari, Hutan; Souri, Effat; Shamsa, Fazel; Amini, Mohsen

    2014-01-01

    A simple, sensitive, accurate, and green spectrophotometric method for the determination of Cu(II) using newly synthesized reagent, 6-(2-methoxynaphthyl)-2,3-dihydro-1,2,4-triazine-3-thione (MNDTT), has been developed. MNDTT was synthesized based on the acylation of methoxy naphthalene and reaction of the product with amyl nitrite, which upon reaction with thiosemicarbazide yielded 6-(2-meyhoxynaphthyl)-2,3-dihydro-1,2,4-triazine-3-thione. MNDTT produces a dark red complex with copper in methanol according to the 1 : 2 stoichiometry. Beer's law was obeyed over the concentration range of 2.5–20 µg/mL with r2 = 0.992. The limit of detection and limit of quantification were 0.33 and 1.10 µg/mL, respectively. Within-day and between-day precision values were less than 3.68%. Finally, the method has been applied to a dental alloy (110-plus) successfully and the results were compared with atomic absorption method. The results showed that there was no significant difference between the two methods (P > 0.05). PMID:24639872

  10. Solubility of (1 leads to 3)-beta-D/(1 leads to 6)-beta-D-glucan in fungal walls: importance of presumed linkage between glucan and chitin.

    PubMed

    Sietsma, J H; Wessels, J G

    1981-07-01

    In Saccharomyces cerevisiae, Neurospora crassa, Aspergillus nidulans and Coprinus cinereus most of the alkali-insoluble (1 leads to 3)-beta-D/(1 leads to 6)-beta-D-glucan of the wall can be extracted with dimethyl sulphoxide. The same fraction, and in Saccharomyces cerevisiae a small additional fraction, can be extracted by a destructive procedure involving 40% NaOH at 100 degrees C. The small fraction of the glucan which resists this treatment becomes soluble after a subsequent treatment with HNO2 indicating that it is covalently linked to chitin in the wall. In contrast, in Schizophyllum commune and Agaricus bisporus, nearly all the (1 leads to 3)-beta-D/(1 leads to 6)-beta-D-glucan appears to be held insoluble by linkage to chitin. PMID:6460846

  11. 40 CFR 721.5283 - Cobaltate (5-), bis[4-[[6-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amio]-1-hydroxy-3-sulfo-2...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Cobaltate (5-), bis -1-hydroxy-3-sulfo... Substances § 721.5283 Cobaltate (5-), bis -1-hydroxy-3-sulfo-2-naphthalenyl]azo]-3-hydroxy-7-nitro-1... chemical substance identified as cobaltate (5-), bis...

  12. 40 CFR 721.5283 - Cobaltate (5-), bis[4-[[6-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amio]-1-hydroxy-3-sulfo-2...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Cobaltate (5-), bis -1-hydroxy-3-sulfo... Substances § 721.5283 Cobaltate (5-), bis -1-hydroxy-3-sulfo-2-naphthalenyl]azo]-3-hydroxy-7-nitro-1... chemical substance identified as cobaltate (5-), bis...

  13. 40 CFR 721.5283 - Cobaltate (5-), bis[4-[[6-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amio]-1-hydroxy-3-sulfo-2...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...-2-naphthalenyl]azo]-3-hydroxy-7-nitro-1-naphthalenesulfonato(4-)]-, pentasodium. 721.5283 Section... Substances § 721.5283 Cobaltate (5-), bis -1-hydroxy-3-sulfo-2-naphthalenyl]azo]-3-hydroxy-7-nitro-1... chemical substance identified as cobaltate (5-), bis...

  14. 40 CFR 721.5283 - Cobaltate (5-), bis[4-[[6-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amio]-1-hydroxy-3-sulfo-2...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...-2-naphthalenyl]azo]-3-hydroxy-7-nitro-1-naphthalenesulfonato(4-)]-, pentasodium. 721.5283 Section... Substances § 721.5283 Cobaltate (5-), bis -1-hydroxy-3-sulfo-2-naphthalenyl]azo]-3-hydroxy-7-nitro-1... chemical substance identified as cobaltate (5-), bis...

  15. 40 CFR 721.5283 - Cobaltate (5-), bis[4-[[6-[(4-amino-6-chloro-1,3,5-triazin-2-yl)amio]-1-hydroxy-3-sulfo-2...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...-2-naphthalenyl]azo]-3-hydroxy-7-nitro-1-naphthalenesulfonato(4-)]-, pentasodium. 721.5283 Section... Substances § 721.5283 Cobaltate (5-), bis -1-hydroxy-3-sulfo-2-naphthalenyl]azo]-3-hydroxy-7-nitro-1... chemical substance identified as cobaltate (5-), bis...

  16. Crystal structure of N-(1-acetyl-3-chloro-1H-indazol-6-yl)-4-meth-oxy-benzene-sulfonamide.

    PubMed

    Hakmaoui, Yassine; Rakib, El Mostapha; Gamouh, Ahmed; Saadi, Mohamed; El Ammari, Lahcen

    2015-12-01

    In the title compound, C16H14ClN3O4S, the six-membered ring of the indazole group is connected to a sulfonamide group. The indazole system is essentially planar, with the greatest deviation from the mean plane being 0.007 (2) Å. The dihedral angle between the two six-membered rings is 74.99 (9)°. The crystal structure exhibits inversion dimers in which mol-ecules are linked by pairs of N-H⋯O and C-H⋯O hydrogen bonds. PMID:26870524

  17. Labeled 1,N6-ethenoadenosine and 3,N4-ethenocytidine in hepatic RNA of mice given[ethyl-1,2(-3)H or ethyl-1(-14)C]ethyl carbamate (urethan).

    PubMed

    Ribovich, M L; Miller, J A; Miller, E C; Timmins, L G

    1982-01-01

    Injection of a single dose of[ethyl-1,2(-3)H]or[ethyl-1(-14C]- ethyl carbamate into 12-day old male[C57BL/6 x C3H/He]F1 mice or of[ethyl-1,2(-3H]ethyl carbamate into adult male A/Jax mice resulted in the formation of labeled 1,N6-ethenoadenosine and 3,N4-ethenocytidine adducts in the hepatic RNA. These adducts were characterized by comigration on h.p.l.c. of 3H or 14C in enzymatic hydrolysates of the RNA with synthetic standards. Both the ethenoadenosine and ethenocytidine were further characterized by their conversion to acetylated products that comigrated with acetylated synthetic standards. The ethenoadenosine was also converted by anhydrous trifluoroacetic acid to a product that comigrated with synthetic 1,N6-ethenoadenine. The levels of adducts in the hepatic RNA 12 h after a single injection of 0.5-0.6 mg of ethyl carbamate/g body weight were 6-10 and 2-3 pmol/mg RNA of ethenoadenosine and ethenocytidine, respectively. No labeled ethenoadenosine or ethenocytidine could be detected in the hepatic RNA of mice given[1-14C]ethanol, an enzymatic hydrolysis product of ethyl carbamate. These data indicate that ethyl carbamate may be metabolically activated by dehydrogenation to vinyl carbamate and subsequent epoxidation of the latter compound as previously proposed. Vinyl carbamate epoxide may form etheno derivatives in a manner analogous to that demonstrated for chloroethylene oxide, an electrophilic metabolite of vinyl chloride. Vinyl carbamate has been shown to have the same spectrum of tumor induction as ethyl carbamate but to be much more active than the latter carcinogen. PMID:6178529

  18. 2,6-Dihy-droxy-4-oxo-2-(pyridin-1-ium-3-yl)-4H-1,3,2-benzodioxaborinin-2-ide 0.67-hydrate.

    PubMed

    Garcia-Grajeda, Blanca A; Höpfl, Herbert; Guerrero-Alvarez, Jorge A; Campos-Gaxiola, José J; Cruz-Enríquez, Adriana

    2014-04-01

    The asymmetric unit of the title compound, C12H10BNO5·0.67H2O, contains three independent pyridinylboronic acid esters adopting zwitterionic forms and two water mol-ecules. The six-membered heterocyclic rings in the boronic esters have half-chair conformations and the deviations of the B atoms from the boronate mean planes range from 0.456 (3) to 0.657 (3) Å. All of the B atoms have tetra-hedral coordination environments, with B-O and B-C bond lengths of 1.446 (4)-1.539 (3) and 1.590 (5)-1.609 (5) Å, respectively. In the crystal, the ester and water mol-ecules are linked into a three-dimensional network by a large number of O-H⋯O, N-H⋯O and C-H⋯O hydrogen bonds. The crystal packing is further accomplished by π-π inter-actions, with centroid-centroid distances of 3.621 (4)-3.787 (4) Å. PMID:24826112

  19. 2,6-Dihy­droxy-4-oxo-2-(pyridin-1-ium-3-yl)-4H-1,3,2-benzodioxaborinin-2-ide 0.67-hydrate

    PubMed Central

    Garcia-Grajeda, Blanca A.; Höpfl, Herbert; Guerrero-Alvarez, Jorge A.; Campos-Gaxiola, José J.; Cruz-Enríquez, Adriana

    2014-01-01

    The asymmetric unit of the title compound, C12H10BNO5·0.67H2O, contains three independent pyridinylboronic acid esters adopting zwitterionic forms and two water mol­ecules. The six-membered heterocyclic rings in the boronic esters have half-chair conformations and the deviations of the B atoms from the boronate mean planes range from 0.456 (3) to 0.657 (3) Å. All of the B atoms have tetra­hedral coordination environments, with B—O and B—C bond lengths of 1.446 (4)–1.539 (3) and 1.590 (5)–1.609 (5) Å, respectively. In the crystal, the ester and water mol­ecules are linked into a three-dimensional network by a large number of O—H⋯O, N—H⋯O and C—H⋯O hydrogen bonds. The crystal packing is further accomplished by π–π inter­actions, with centroid–centroid distances of 3.621 (4)–3.787 (4) Å. PMID:24826112

  20. Immunomodulatory effects of black cohosh (Actaea racemosa) extract in female B6C3F1/N mice

    PubMed Central

    Smith, Matthew J.; Germolec, Dori R.; Frawley, Rachel P.; White, Kimber L.

    2013-01-01

    Black cohosh extracts (BCE; Actaea racemosa) are being used worldwide as an alternative to hormone replacement therapy for the management of menstrual and menopausal symptoms, yet the effects of BCE on the immune system are largely unknown. Female B6C3F1/N mice were treated daily with BCE (0, 62.5, 125, 250, 500, or 1000 mg/kg) for 28 days by oral gavage. Liver weights were significantly increased (26%–32%) at the 1000 mg/kg dose. Dose-related increases in mean corpuscular volume and mean corpuscular hemoglobin were observed. Decreasing trends were observed in all thymic T cell populations, with the most notable dose-responsive effects on immature thymocytes. In the spleen, dose-related decreases were observed in all cell phenotypes evaluated, reaching the level of statistical significance at the 1000 mg/kg BCE dose. Splenic natural killer (NK) cell numbers were significantly decreased at all BCE doses, with the exception of absolute NK numbers at the 125 mg/kg dose. No effects were observed on T-dependent antibody responses of the humoral immune system, including the antibody-forming cell response to sheep erythrocytes (sRBC) and IgM antibody levels to both sRBC and keyhole limpet hemocyanin. Cytotoxic T cell (TCTL) activity was increased, as was the mixed leukocyte response in one of two studies. Anti-CD3 mediated proliferation and the delayed-type hypersensitivity response were unaffected. No effects were observed on innate immunity or on bone marrow cellularity and colony-forming units. Overall, BCE exposure in B6C3F1/N mice for 28 days at doses up to 1000 mg/kg had minimal immune effects, with the exception of an increased TCTL response. PMID:23571075

  1. Immunomodulatory effects of black cohosh (Actaea racemosa) extract in female B6C3F1/N mice.

    PubMed

    Smith, Matthew J; Germolec, Dori R; Frawley, Rachel P; White, Kimber L

    2013-06-01

    Black cohosh extracts (BCE; Actaea racemosa) are being used worldwide as an alternative to hormone replacement therapy for the management of menstrual and menopausal symptoms, yet the effects of BCE on the immune system are largely unknown. Female B6C3F1/N mice were treated daily with BCE (0, 62.5, 125, 250, 500, or 1000mg/kg) for 28 days by oral gavage. Liver weights were significantly increased (26-32%) at the 1000mg/kg dose. Dose-related increases in mean corpuscular volume and mean corpuscular hemoglobin were observed. Decreasing trends were observed in all thymic T cell populations, with the most notable dose-responsive effects on immature thymocytes. In the spleen, dose-related decreases were observed in all cell phenotypes evaluated, reaching the level of statistical significance at the 1000mg/kg BCE dose. Splenic natural killer (NK) cell numbers were significantly decreased at all BCE doses, with the exception of absolute NK numbers at the 125mg/kg dose. No effects were observed on T-dependent antibody responses of the humoral immune system, including the antibody-forming cell response to sheep erythrocytes (sRBC) and IgM antibody levels to both sRBC and keyhole limpet hemocyanin. Cytotoxic T cell (TCTL) activity was increased, as was the mixed leukocyte response in one of two studies. Anti-CD3 mediated proliferation and the delayed-type hypersensitivity response were unaffected. No effects were observed on innate immunity or on bone marrow cellularity and colony-forming units. Overall, BCE exposure in B6C3F1/N mice for 28 days at doses up to 1000mg/kg had minimal immune effects, with the exception of an increased TCTL response. PMID:23571075

  2. Activation of native TRPC1/C5/C6 channels by endothelin-1 is mediated by both PIP3 and PIP2 in rabbit coronary artery myocytes

    PubMed Central

    Saleh, Sohag N; Albert, Anthony P; Large, William A

    2009-01-01

    We investigate activation mechanisms of native TRPC1/C5/C6 channels (termed TRPC1 channels) by stimulation of endothelin-1 (ET-1) receptor subtypes in freshly dispersed rabbit coronary artery myocytes using single channel recording and immunoprecipitation techniques. ET-1 evoked non-selective cation channel currents with a unitary conductance of 2.6 pS which were not inhibited by either ETA or ETB receptor antagonists, respectively BQ-123 and BQ788, when administered separately. However, in the presence of both antagonists, ET-1-evoked channel activity was abolished indicating that both ETA and ETB receptor stimulation activate this conductance. Stimulation of both ETA and ETB receptors evoked channel activity which was inhibited by the protein kinase C (PKC) inhibitor chelerythrine and by anti-TRPC1 antibodies indicating that activation of both receptor subtypes causes TRPC1 channel activation by a PKC-dependent mechanism. ETA receptor-mediated TRPC1 channel activity was selectively inhibited by phosphoinositol-3-kinase (PI-3-kinase) inhibitors wortmannin (50 nm) and PI-828 and by antibodies raised against phosphoinositol-3,4,5-trisphosphate (PIP3), the product of PI-3-kinase-mediated phosphorylation of phosphatidylinositol 4,5-bisphosphate (PIP2). Moreover, exogenous application of diC8-PIP3 stimulated PKC-dependent TRPC1 channel activity. These results indicate that stimulation of ETA receptors evokes PKC-dependent TRPC1 channel activity through activation of PI-3-kinase and generation of PIP3. In contrast, ETB receptor-mediated TRPC1 channel activity was inhibited by the PI-phospholipase C (PI-PLC) inhibitor U73122. 1-Oleoyl-2-acetyl-sn-glycerol (OAG), an analogue of diacylglycerol (DAG), which is a product of PI-PLC, also activated PKC-dependent TRPC1 channel activity. OAG-induced TRPC1 channel activity was inhibited by anti-phosphoinositol-4,5-bisphosphate (PIP2) antibodies and high concentrations of wortmannin (20 μm) which depleted tissue PIP2 levels. In

  3. Final report for tank 241-AP-101, grab samples 1AP-95-1, 1AP-95-2, 1AP-95-3, 1AP-95-4, 1AP-95-5, and 1AP-95-6

    SciTech Connect

    Esch, R.A.

    1996-03-04

    Six supernate grab samples (1AP-95-1 through 6) and one field blank (1AP-95-7) were taken from tank 241-AP-101, on Nov. 10 and 13, 1995. Analyses were performed in support of the Safety Screening and the Waste Compatibility Safety programs. All analytical results were within the action limits stated in the TSAP.

  4. PLEURAL EFFECTS OF INDIUM PHOSPHIDE IN B6C3F1 MICE: NONFIBROUS PARTICULATE INDUCED PLEURAL FIBROSIS

    PubMed Central

    Kirby, Patrick J.; Shines, Cassandra J.; Taylor, Genie J.; Bousquet, Ronald W.; Price, Herman C.; Everitt, Jeffrey I.; Morgan, Daniel L.

    2010-01-01

    The mechanism(s) by which chronic inhalation of indium phosphide (InP) particles causes pleural fibrosis is not known. Few studies of InP pleural toxicity have been conducted because of the challenges in conducting particulate inhalation exposures, and because the pleural lesions developed slowly over the 2-year inhalation study. The authors investigated whether InP (1 mg/kg) administered by a single oropharyngeal aspiration would cause pleural fibrosis in male B6C3F1 mice. By 28 days after treatment, protein and lactate dehydrogenase (LDH) were significantly increased in bronchoalveolar lavage fluid (BALF), but were unchanged in pleural lavage fluid (PLF). A pronounced pleural effusion characterized by significant increases in cytokines and a 3.7-fold increase in cell number was detected 28 days after InP treatment. Aspiration of soluble InCl3 caused a similar delayed pleural effusion; however, other soluble metals, insoluble particles, and fibers did not. The effusion caused by InP was accompanied by areas of pleural thickening and inflammation at day 28, and by pleural fibrosis at day 98. Aspiration of InP produced pleural fibrosis that was histologically similar to lesions caused by chronic inhalation exposure, and in a shorter time period. This oropharyngeal aspiration model was used to provide an initial characterization of the progression of pleural lesions caused by InP. PMID:19995279

  5. Crystal structure of 1,3-bis­(2,3-di­methyl­quinoxalin-6-yl)benzene

    PubMed Central

    Diesendruck, Charles E.; Rubin, Gabrielle; Bertke, Jeffery A.; Gray, Danielle L.; Moore, Jeffrey S.

    2015-01-01

    The title compound, C26H22N4 (I), was synthesized by C—H iridium-catalyzed borylation followed by Suzuki coupling. The mol­ecular structure of (I) consists of a central benzene ring with 3-di­methyl­quinoxalin-6-yl groups at the 1 and 3 positions. These 2,3-di­methyl­quinoxalin-6-yl groups twist significantly out of the plane of the benzene ring. There are inter­molecular π–π inter­actions which result in a two-dimensional extended structure. The layers extend parallel to the ab plane and stack along the c axis. PMID:26870397

  6. 2,2-Dimethyl-5-[(pyridin-2-yl-amino)-methyl-idene]-1,3-dioxane-4,6-dione.

    PubMed

    Shi, Jian-You; Li, Jin-Qi; Tong, Rong-Sheng; Lin, He; Lu, Chen

    2011-01-01

    In the title compound, C(12)H(12)N(2)O(4), the dihedral angle between the pyridine and enamine planes is 3.5 (3)°, while the angle between the dioxanedione (seven atoms) and enamine planes is 4.6 (3)°. The dioxane ring approximates an envelope conformation. PMID:21522947

  7. INDUCTION OF CYP1A1 AD CYP1B1 AND FORMATION OF DNA ADDUCTS IN C57BL/6, BALB/C, AND F1 MICE FOLLOWING IN UTERO EXPOSURE TO 3-METHYLCHOLANTHRENE

    EPA Science Inventory

    Fetal mice are more sensitive to chemical carcinogens than are adults. Previous studies from our laboratory demonstrated differences in the mutational spectrum induced in the Ki-ras gene from lung tumors isolated from [D2 x B6D2F1]F2 mice and Balb/c mice treated in utero with 3�m...

  8. Compositional dependence of the crystal symmetry of Eu3+-doped (SrxBa1-x)2CaWyMo1-yO6 phosphors

    NASA Astrophysics Data System (ADS)

    Sletnes, M.; Valmalette, J. C.; Grande, T.; Einarsrud, M.-A.

    2016-01-01

    Two series of A-site and B-site Eu3+ doped (SrxBa1-x)2CaWyMo1-yO6 double perovskite phosphor materials were prepared via a modified Pechini sol-gel route; (SrxBa1-x)1.96Eu0.02K0.02CaWyMo1-yO6 and (SrxBa1-x)2Ca0.96Eu0.02Li0.02WyMo1-yO6 (x and y=0, 0.25, 0.50, 0.75, 1). The Sr/Ba ratio was the main determinant for the crystal symmetry of the series, while variation in the W/Mo ratio did influence the crystal symmetry significantly. The crystal structure evolved with Sr/Ba ratio from cubic Fm 3 bar m for x=0, via tetragonal I 4 / m for x=0.25, to monoclinic P 21 / n for x≥0.5, as verified by Rietveld refinement of X-ray diffractograms as well as by Raman spectroscopy. The reported boundaries for the compositionally induced phase transitions are in very good agreement with reported optical properties.

  9. Genistein modulation of streptozotocin diabetes in male B6C3F1 mice can be induced by diet

    SciTech Connect

    Guo, Tai L.; Wang, Yunbiao; Xiong, Tao; Ling, Xiao; Zheng, Jianfeng

    2014-11-01

    Diet and phytoestrogens affect the development and progression of diabetes. The objective of the present study was to determine if oral exposure to phytoestrogen genistein (GE) by gavage changed blood glucose levels (BGL) through immunomodulation in streptozotocin (STZ)-induced diabetic male B6C3F1 mice fed with three different diets. These three diets were: NTP-2000 diet (NTP), soy- and alfalfa-free 5K96 diet (SOF) and high fat diet (HFD) with 60% of kcal from fat, primarily rendered fat of swine. The dosing regimen for STZ consisted of three 100 mg/kg doses (i.p.): the first dose was administered at approximately 2 weeks following the initiation of daily GE (20 mg/kg) gavage, and the second dose was on day 19 following the first dose, and the third dose was on day 57 following the first dose. In mice on the NTP diet, GE treatment decreased BGL with statistical significances observed on days 33 and 82 following the first STZ injection. In mice fed the HFD diet, GE treatment produced a significant decrease and a significant increase in BGL on days 15 and 89 following the first STZ injection, respectively. In mice fed the SOF diet, GE treatment had no significant effects on BGL. Although GE treatment affected phenotypic distributions of both splenocytes (T cells, B cells, natural killer cells and neutrophils) and thymocytes (CD4/CD8 and CD44/CD25), and their mitochondrial transmembrane potential and generation of reactive oxygen species, indicators of cell death (possibly apoptosis), GE modulation of neutrophils was more consistent with its diabetogenic or anti-diabetic potentials. The differential effects of GE on BGL in male B6C3F1 mice fed with three different diets with varied phytoestrogen contents suggest that the estrogenic properties of this compound may contribute to its modulation of diabetes. - Highlights: • Diets affected streptozotocin-induced diabetes in male B6C3F1 mice. • Genistein modulation of streptozotocin diabetes can be induced by diet.

  10. Multiple seismo-anomalies associated with the M6.1 Ludian earthquake on August 3, 2014

    NASA Astrophysics Data System (ADS)

    Zeng, Xiaoping; Lin, Yunfang; Chen, Weisheng; Bai, Zhiqiang; Liu, Jann-Yenq; Chen, Chieh-Hung

    2015-12-01

    Multiple geophysical parameters including groundwater level, water temperature, water radon, crustal deformation, electromagnetic waves and total electron contents (TEC) in the ionosphere, are examined together to investigate pre-earthquake anomalous phenomena associated with the Mw6.1 Ludian earthquake on August 3, 2014. Cross-parameter comparison eliminates anomalies that are detected in one parameter only and examine earthquake-related phenomena in various fields, simultaneously. Retrieved anomalies show that abnormal decreases of water temperature and radon concentration related to anomalous uplift of groundwater levels appeared about 1-8 days before the earthquake even without contributions from rain. Significant step-like changes are observed from data recorded by strainmeters on July 31 and are consistent with water-related anomalies in timing. No significant anomalies can be found from electromagnetic data through the preliminary observation. In contrast, TEC appeared positive anomalies 1-3 days before the Ludian earthquake. Although causal mechanisms of the TEC anomalies from stressed rocks are not fully understood, multiple-parameter examination can increase credibility of determination regarding pre-earthquake phenomena.

  11. Corporations Give Record $1.6 Billion to Colleges and Universities in 1984-85; Total Giving Reaches $6.3 Billion.

    ERIC Educational Resources Information Center

    CFAE Newsletter, 1986

    1986-01-01

    Findings from the publication, "Voluntary Support of Education 1984-85," are summarized. The survey report includes contributions to 1,114 colleges and universities. Highlights of findings show that: total estimated voluntary support was $6.32 billion in 1984-1985; for the first time, corporations contributed more than any other donor group ($1.57…

  12. Investigations on the synthesis and properties of new derivatives of ethyl 3H-2-imino-7-methyl-4-oxopyrido [3,2-e]-1,3-thiazine-6-carboxylate and isomeric compounds.

    PubMed

    Sladowska, H; Zawisza, T

    1982-04-01

    Condensation of diethyl 2-chloro-6-methylpyridine-3,5-dicarboxylate (IV) with thiourea and alkyl or alkenyl N-mono- and N,N'-disubstituted thioureas gives mainly the corresponding derivatives of ethyl 3H-2-imino-7-methyl-4-oxopyrido [3,2-e]-1,3-thiazine-6-carboxylate (VI-XII). As by-products isomeric derivatives of ethyl 7-methyl-4-oxo-2-thioxo-1,2,3,4-tetrahydropyrido [2,3-d) pyrimidine-6-carboxylate (XIII-XVIII) are formed. PMID:7084447

  13. Impact of T1r3 and Trpm5 on carbohydrate preference and acceptance in C57BL/6 mice.

    PubMed

    Zukerman, Steven; Glendinning, John I; Margolskee, Robert F; Sclafani, Anthony

    2013-06-01

    Knockout (KO) mice missing the sweet taste receptor subunit T1r3 or the signaling protein Trpm5 have greatly attenuated sweetener preferences but learn to prefer sucrose in 24-h tests. Here, we examined 24-h preferences of T1r3 KO, Trpm5 KO, and C57BL/6J wild-type (WT) mice for glucose, fructose, galactose, and corn starch. Unlike glucose, fructose has little postoral reward effect in WT mice, whereas conflicting data have been obtained with galactose. Naïve KO mice were initially indifferent to dilute glucose solutions (0.5-4%) but exhibited strong preferences for 8-32% concentrations. In a second test, they strongly preferred (~90%) all glucose concentrations although they drank less sugar than WT mice. Naïve KO mice were indifferent to 0.5-8% fructose and avoided 16-32% fructose. However, the glucose-experienced KO mice displayed significant preferences for all fructose solutions. Naïve KO mice preferred only 8% galactose, whereas WT mice preferred 4-16% galactose, and all mice avoided 32% galactose. Galactose experience enhanced the preference for this sugar in KO and WT mice. Naïve T1r3 KO and WT mice displayed similar preferences for 0.5-32% corn starch, which were enhanced by starch experience. Naïve Trpm5 KO mice did not prefer starch but did so after 1-bottle starch experience. The results confirm the sweet taste deficits of T1r3 KO and Trpm5 KO mice but demonstrate their ability to develop strong glucose and milder galactose preferences attributed to the postoral actions of these sugars. The acquired preference for the non-sweet flavor properties of glucose generalized to those of fructose. The findings further demonstrate that although Trpm5 (but not T1r3) signaling is essential for starch preference, Trpm5 KO mice can learn to prefer starch based on its postoral effects. PMID:23547138

  14. Biosynthesis of a 3,6-dideoxyhexose: crystallization and X-ray diffraction of CDP-6-deoxy-l-threo-d-glycero-4-hexulose-3-dehydrase (E{sub 1}) for ascarylose biosynthesis

    SciTech Connect

    Smith, Peter; Lin, Ava; Szu, Ping-hui; Liu, Hung-wen; Tsai, Shiou-Chuan

    2006-03-01

    E{sub 1} dehydrase, which is important in the biosynthesis of the 3,6-dideoxy sugar ascarylose and is the only known PMP-containing enzyme to carry out one-electron chemistry, has been crystallized and diffracted to 1.9 Å. CDP-6-deoxy-l-threo-d-glycero-4-hexulose-3-dehydrase (E{sub 1}), along with its reductase (E{sub 3}), catalyzes the unusual C-3 deoxygenation of CDP-6-deoxy-l-threo-d-glycero-4-hexulose to form CDP-3,6-dideoxy-l-threo-d-glycero-4-hexulose in CDP-ascarylose biosynthesis [Chen et al. (1996 ▶), Biochemistry, 35, 16412–16420]. This dimeric [2Fe–2S] protein, cloned from the bacteria Yersinia pseudotuberculosis, is currently the only known example of an enzyme that uses a vitamin B{sub 6}-derived pyridoxamine 5′-phosphate (PMP) cofactor to carry out one-electron chemistry [Agnihotri & Liu (2001 ▶), Bioorg. Chem.29, 234–257]. It also exhibits a [2Fe–2S] cluster-binding motif (C-X{sub 57}-C-X{sub 1}-C-X{sub 7}-C) which has not been observed previously [Agnihotri et al. (2004 ▶), Biochemistry, 43, 14265–14274] The recombinant 97.7 kDa dimer was crystallized in the trigonal space group P3{sub 2}, with unit-cell parameters a = b = 97.37, c = 142.2 Å, α = β = 90, γ = 120°. A data set has been collected to 1.9 Å resolution. A full MAD data set was also collected at the iron absorption edge that diffracted to 2.0 Å.

  15. Trichloroethylene-Induced Gene Expression and DNA Methylation Changes in B6C3F1 Mouse Liver

    PubMed Central

    Tong, Jian; Chen, Tao

    2014-01-01

    Trichloroethylene (TCE), widely used as an organic solvent in the industry, is a common contaminant in air, soil, and water. Chronic TCE exposure induced hepatocellular carcinoma in mice, and occupational exposure in humans was suggested to be associated with liver cancer. To understand the role of non-genotoxic mechanism(s) for TCE action, we examined the gene expression and DNA methylation changes in the liver of B6C3F1 mice orally administered with TCE (0, 100, 500 and 1000 mg/kg b.w. per day) for 5 days. After 5 days TCE treatment at a dose level of 1000 mg/kg b.w., a total of 431 differentially expressed genes were identified in mouse liver by microarray, of which 291 were up-regulated and 140 down-regulated. The expression changed genes were involved in key signal pathways including PPAR, proliferation, apoptosis and homologous recombination. Notably, the expression level of a number of vital genes involved in the regulation of DNA methylation, such as Utrf1, Tet2, DNMT1, DNMT3a and DNMT3b, were dysregulated. Although global DNA methylation change was not detected in the liver of mice exposed to TCE, the promoter regions of Cdkn1a and Ihh were found to be hypo- and hypermethylated respectively, which correlated negatively with their mRNA expression changes. Furthermore, the gene expression and DNA methylation changes induced by TCE were dose dependent. The overall data indicate that TCE exposure leads to aberrant DNA methylation changes, which might alter the expression of genes involved in the TCE-induced liver tumorgenesis. PMID:25549359

  16. 6,7-Dihydroxyisoindolin-1-one and 7,8-Dihydroxy-3,4-Dihydroisoquinolin- 1(2H)-one Based HIV-1 Integrase Inhibitors.

    PubMed

    Zhao, Xue Zhi; Metifiot, Mathieu; Smith, Steven J; Maddali, Kasthuraiah; Marchand, Christophe; Hughes, Stephen H; Pommier, Yves; Burke, Terrence R

    2016-01-01

    Integrase (IN) is an essential viral enzyme required for HIV-1 replication, which has been targeted by anti-AIDS therapeutics. Integrase strand transfer inhibitors (INSTIs) represent a new class of antiretroviral agents developed for the treatment of HIV-1 infections. Important structural features that are shared by many INSTIs include a coplanar arrangement of three heteroatoms that chelate two catalytic Mg(2+) ions in the IN active site and a linked halophenyl ring that binds in the hydrophobic pocket formed by the complex of IN with viral DNA. We recently reported bicyclic 6,7-dihydroxyoxoisoindolin-1-one-based IN inhibitors. In the current study, we modified these inhibitors in three ways. First, we increased the spacer length between the metalchelating triad and the halophenyl group. Second, we replaced the indoline [5,6] bicycle with a fused dihydroxyisoquinolinones [6,6] ring system. Finally, we prepared bis-6,7-dihydroxyisoindolin-1-one-4-sulfonamides as dimeric HIV-1 IN inhibitors. These new analogues showed low micromolar inhibitory potency in in vitro HIV-1 integrase assays. PMID:26268341

  17. Synthesis and Antimicrobial Activity of Bis-[4-methoxy-3-(6-aryl-7H-[1,2,4]triazolo[3,4-b][1,3,4]-thiadiazin-3-yl)phenyl]methanes and Bis-[(triazolo[3,4-b]thiadiazipin-3-yl)phenyl]methanes.

    PubMed

    Srinivas, Avula

    2016-01-01

    A series of novel Bis-[4-methoxy-3-(6-aryl-7H-[1,2,4]tria zolo[3,4-b][1,3,4]-thiadiazin-3-yl)phenyl]methanes and Bis-[(triazolo[3,4-b]thiadiazipin-3-yl)phenyl]methanes ( 5a-e & 6a-e ) has been synthesized and characterized by IR, (1)H NMR, (13)C NMR, MS and elemental analysis. All the newly synthesized compounds were screened for their antibacterial activity against Bacillus subtilis, Staphylococcus aureus, Klobsinella aerogenes and Chromobacteriumviolaceum and antifungal activity against Candida albicans, Aspergillus fumigatus, Trichophyton rubrum and Trichophyton mentagrophytes. Compounds 5b, 5d,5e, 6b, 6c and 6e exhibited potent activity against the test bacteria and fungi, and emerged as potential molecules for further development. PMID:26970802

  18. Density functional theory study of high-pressure effect on crystalline 4,4',6,6'-tetra(azido)hydrazo-1,3,5-triazine.

    PubMed

    Wang, Fang; Du, Hong-Chen; Liu, Hui; Gong, Xue-Dong

    2012-08-15

    Periodic density functional theory calculations are performed to study the hydrostatic compression effects on the structure, electronic, and thermodynamic properties of the energetic polyazide 4,4',6,6'-tetra(azido)hydrazo-1,3,5-triazine (TAHT) in the range of 0-100 GPa. At the ambient pressure, the local density approximation/Ceperley-Alder exchange-correlation potential parameterized by Perdew and Zunger relaxed crystal structure compares well with the experimental results. The predicted heat of sublimation is 38.68 kcal/mol, and the evaluated condensed phase of formation (414.04 kcal/mol) approximates to the experimental value. The detonation velocity and detonation pressure for the solid TAHT are calculated to be 7.44 km/s and 23.71 GPa, respectively. When the pressure is exerted less than 35 GPa, the crystal structure and geometric parameters change slightly. However, at 36 GPa, the molecular structure, band structure, and density of states change abnormally because of the azide-tetrazole transformation that has not been observed in gas phase or polar solvents. The azido group cyclizes to form a five-membered tetrazole ring that is coplanar with the riazine ring and contributes to a larger conjunction system. As the pressure augments further to 80 GPa, the hydrogen transfer is found and a new covalent bond H2-N9 is formed. In the studied pressure range, the band gap decreases generally except for some breaks due to the molecular transformation and drops to nearly zero at 100 GPa, which means the electronic character of the crystal changes toward a metallic system. An analysis of the electronic structure shows that an applied pressure increases the impact sensitivity of TAHT. PMID:22622667

  19. Carboxylate ligands induced structural diversity of zinc(II) coordination polymers based on 3,6-bis(imidazol-1-yl)carbazole: Syntheses, structures and photocatalytic properties

    NASA Astrophysics Data System (ADS)

    Cheng, Hong-Jian; Tang, Hui-Xiang; Shen, Ya-Li; Xia, Nan-Nan; Yin, Wen-Yu; Zhu, Wei; Tang, Xiao-Yan; Ma, Yun-Sheng; Yuan, Rong-Xin

    2015-12-01

    Solvothermal reactions of Zn(NO3)2·6H2O with 3,6-bis(1-imidazolyl)carbazole (3,6-bmcz) and 1,4-benzenedicarboxylic acid (1,4-H2bdc), p-phenylenediacetic acid (p-H2pda), benzophenone-4,4-dicarboxylic acid (H2bpda) afforded three coordination polymers [Zn(1,4-bdc)(3,6-bmcz)]n (1), {[Zn(p-pda)(3,6-bmcz)]·1.5H2O}n (2) and {[Zn(bpda)(3,6-bmcz)]·0.25H2O}n (3). Complexes 1-3 were characterized by elemental analysis, IR, powder X-ray diffraction, and single-crystal X-ray diffraction. Complex 1 shows 3D structure with 2D nets inclined polycatenation. Complexes 2 and 3 possess an extended 3D supramolecular architecture based on their respective 2D layers through hydrogen-bonding interactions and the π···π stacking interactions. The solid state luminescent and optical properties of 1-3 at ambient temperature were also investigated. A comparative study on their photocatalytic activity toward the degradation of methylene blue in polluted water was explored.

  20. A simple and efficient approach to the synthesis of endo and exo bicyclo[6.1.0]nona-3,5-diene-9-carboxaldehyde.

    PubMed

    Ghandi, Mehdi; Mashayekhi, Gholamreza

    2007-01-01

    Monobromination of 1,5-cyclooctadiene, followed by cyclopropanation with ethyl diazoacetate, led to the formation of endo and exo ethyl 4,5-dibromobicyclo[6.1.0]nonane-9-carboxylates 3a and 3b. Bis-dehydrobromination of 3a and 3b using 1,8-diazabicyclo[5,4,0]undec-7-ene (DBU) afforded the endo and exo ethyl bicyclo[6.1.0]nona-3,5-diene-9-carboxylates 4a and 4b. Reduction of these compounds to the corresponding alcohols 5a and 5b and subsequent oxidation with pyridinium chlorochromate (PCC) resulted in the formation of the target compounds endo and exo bicyclo[6.1.0]nona-3,5-diene-9-carboxaldehydes 6a and 6b. PMID:17978767