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  • 1
    ISSN: 1573-904X
    Keywords: allometric scaling ; interspecies scaling ; pharmacokinetics ; clearance ; in vitro models ; bosentan
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. The goal of this study was to find a rational and reliable method of using animal data to predict the clearance of metabolised drugs in humans. Methods. One such approach is to use in vitro liver models (e.g. hepatocytes and microsomes) to determine the relative capacities of the various animal species and humans to metabolise the test compound. These data can then be combined with the in vivo clearances in animals, to calculate the in vivo clearance in humans using allometric scaling techniques. In this study, this approach was evaluated with a new endothelin receptor antagonist, bosentan, which is eliminated mainly through metabolism and is characterized by very large interspecies differences in clearance. Therefore, this compound provided a stringent test of our new extrapolation method for allometric scaling. Results. The results obtained with bosentan showed that adjusting the in vivo clearance in the different animal species for the relative rates of metabolism in vitro gave a far better prediction of human clearance than an empirical correcting factor (brain weight). Conclusions. This approach provided a more rational basis for predicting the clearance of metabolised compounds in humans.
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  • 2
    ISSN: 1476-5535
    Keywords: Microtiter fermentation ; Lovastatin ; Polyketide ; Strain improvement ; Screening
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: Summary A lovastatin-hyperproducing culture ofAspergillus terreus was shown to produce several co-metabolites extracted from whole broth. The predominant co-metabolite was the benzophenone, sulochrin, reported to arise from a polyketide biosynthetic pathway. This compound was targeted for elimination by classical mutagenesis and screening. A surface culture method employing microtiter, plates was used to ferment mutants for the primary screen. Qualitative determinations of lovastatin and sulochrin production were achieved by high-performance thin-layer chromatography. A mutant, strain AH6, which produced lovastatin titers equivalent to the parent culture and no detectable sulochrin was isolated. In addition, a lovastatin-hyperproducing mutant designated CB4 was capable of producing 16% more lovastatin and 30% less sulochrin than the parent culture in shake flask fermentations. In a pilot-scale 250-gallon fermentation, strain CB4 gave a 20% increase in lovastatin titer while producing 83% less sulochrin than the parent culture.
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  • 3
    Electronic Resource
    Electronic Resource
    Weinheim : Wiley-Blackwell
    Zeitschrift für anorganische Chemie 430 (1977), S. 227-233 
    ISSN: 0044-2313
    Keywords: Chemistry ; Inorganic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Description / Table of Contents: Imidodiphosphoric Acid EstersImidodiphosphoryl tetrachloride reacts with aliphatic alcohols (C1-C3) as well as with sodium phenolate to form tetraalkylesters or tetraphenylesters of the imidodiphosphoric acid, resp. The tetraalkylesters (alkyl = methyl, ethyl, n-propyl) are also formed by reaction of trichlorphosphazene phosphoryldichloride, Cl3P=N—POCl2, with the corresponding alcohols. The purification of the esters can be reached by destillation of their silyl derivatives followed by desilylation. The esters are associated by intermolecular O…H…O hydrogen bonds.
    Notes: Imidodiphosphoryltetrachlorid reagiert mit Alkanolen (C1-C3) zu den Tetraalkylestern und mit Natriumphenolat zum Tetraphenylester der Imidodiphosphorsäure. Die Tetraalkylester (Alkyl = Methyl, Äthyl, n-Propyl) werden auch bei der Umsetzung von Trichlorphosphazenphosphoryldichlorid, Cl3P=N—POCl2, mit den entsprechenden Alkoholen gebildet. Die Reinigung der Ester gelingt durch Destillation ihrer Silylderivate und deren anschließender Desilylierung. Die Ester sind über intermolekulare O … H … O-Wasserstoffbrücken assoziiert.
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  • 4
    ISSN: 0044-2313
    Keywords: Chemistry ; Inorganic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Description / Table of Contents: Investigations on the Phosphorylation of Imidodiphosphoryl DerivativesDerivatives of esters and octaalkylamides of imidodiphosphoric acid, {[X2P(O)]2N}Y (X = OR, NR2; Y = H, Na, SiMe3, MgBr), react with phosphorus(V) chlorides exclusively under formation of O-phosphorylated products. No derivatives of nitridotriphosphoric acid are formed. O-Diethoxyphosphorylated phosphazenes, X2P(O)—N=PX2-O—P(O)(OEt)2, are obtained by using diethoxyphosphoryl chloride, (EtO)2P(O)Cl. Octaalkylamides react with PCl5 to form tetrachlorophosphonium compounds containing the PCl4 group chelate-like surrounded by the octaalkyl imidodiphosphoryl tetramide anion. The product of the reaction of octaalkyl imidodiphosphoryl tetramide sodium and POCl3 seems to have an analogous constitutions.
    Notes: Derivate von Estern und Octaalkylamiden der Imidodiphosphorsäure, {[X2P(O)]2N}Y (X = OR, NR2; Y = H, Na, SiMe3, MgBr), reagieren mit Phosphor(V)-chloriden ausschließlich unter Bildung O-phosphorylierter Produkte. Es entstehen keine Derivate der Nitridotriphosphorsäure. Mit Diäthoxyphosphorylchlorid, (EtO)2P(O)Cl, bilden sich O-Diäthoxyphosphorylierte Phosphazene, X2P(O)—N=PX2-O—P(O)(OEt)2. Die Octaalkylamide reagieren mit PCl5 zu Tetrachlorophosphoniumverbindungen, in denen die PCl4-Gruppe vom Octaalkylimidodiphosphoryltetramid-Anion chelatartig umgeben ist (IV). Eine analoge Konstitution scheint das Reaktionsprodukt von Octaäthylimidodiphosphoryltetramid-Natrium mit POCl3 zu haben.
    Additional Material: 2 Tab.
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  • 5
    ISSN: 0044-2313
    Keywords: Chemistry ; Inorganic Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Description / Table of Contents: On the Constitution of the Trimethylsilyl Derivatives of Imidodiphosphoryl CompoundsEsters and dialkylamides of the imidodiphosphoric acid react with hexamethyl-disilazane to form trimethylsilyl derivatives. 1H-, 29Si-, and 31P-NMR data show the trimethylsilyl group to be bond to oxygen with rapid reversible exchange between both phosphoryloxygen atoms.
    Notes: Ester und Dialkylamide der Imidodiphosphorsäure reagieren mit Hexamethyldisilazan zu den Trimethylsilylderivaten. Aus 1H-, 29Si- und 31P-NMR-Daten folgt, daß die Trimethylsilylgruppe über Sauerstoff gebunden ist und einem schnellen reversiblen Austausch zwischen den beiden Phosphorylsauerstoffatomen unterliegt.
    Additional Material: 1 Tab.
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  • 6
    Publication Date: 2014-05-15
    Description: Organic Letters DOI: 10.1021/ol500776j
    Print ISSN: 1523-7060
    Electronic ISSN: 1523-7052
    Topics: Chemistry and Pharmacology
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  • 7
    Publication Date: 1999-01-01
    Print ISSN: 0009-8558
    Electronic ISSN: 1471-8030
    Topics: Geosciences
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  • 8
    Publication Date: 1999-09-01
    Print ISSN: 0009-8558
    Electronic ISSN: 1471-8030
    Topics: Geosciences
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  • 9
    Publication Date: 2014-05-17
    Description: The new mineral mössbauerite (IMA2012–049), $${\mathrm{Fe}}_{6}^{3+}$$ O 4 (OH) 8 [CO 3 ]·3H 2 O, is a member of the fougèrite group of the hydrotalcite supergroup. Thus, it has a layered double hydroxide-type structure, in which brucite-like layers [ $${\mathrm{Fe}}_{6}^{3+}$$ O 4 (OH) 8 ] 2+ are intercalated with $${\mathrm{CO}}_{3}^{2-}$$ anions and water molecules. Mössbauerite is the fully oxidized analogue of fougèrite and trébeurdenite, related to them chemically by the exchange of (Fe 3+ O 2– ) with (Fe 2+ OH – ). Mössbauerite, intimately intergrown with trébeurdenite, was discovered in intertidal gleys from Mont Saint-Michel Bay, France, along with quartz, feldspars and clay minerals. Mössbauerite is formed by the oxidation of the other members of the fougèrite group. Like them, it occurs as μm-scale platelets in gleys with restricted access to atmospheric O and decomposes rapidly when exposed to air. Identification and characterization of these minerals has relied on an electrochemical study of synthetic analogues and Mössbauer spectroscopy, which inspired the name of the new mineral. Unlike fougèrite and trébeurdenite, which are blue-green, pure synthetic mössbauerite is orange in colour. Detailed optical and other physical properties could not be determined because of the small platelet size and instability. The hardness is probably 2–3, by analogy with other members of the supergroup and the density, calculated from unit-cell parameters, is 2.950 g/cm 3 . Synchrotron X-ray data indicate that the natural material is a nanoscale intergrowth of 2 T and 3 T polytypes; the latter probably has the 3 T 7 stacking sequence. The corresponding maximum possible space group symmetries are P 3I m 1 and P 3 m 1. Unit-cell parameters for the 3T cell are a = 3.032(7) Å, c = 22.258(4) = 3 x 7.420 Å and Z = 1/2. Mössbauer spectroscopy at 78 K indicates that two distinct Fe 3+ environments exist in a 2:1 ratio. These are interpreted to be ordered within each layer, but without the development of a three-dimensional superlattice. Mössbauerite undergoes gradual magnetic ordering at 70–80 K to a ferromagnetic state, below which it splits into three sextets S 1m , S 2m and S 3m , as measured at 15 K, and shows the same intensity ratio: 1/2:1/6:1/3 as the three doublets for fougèrite D 1f , D 2f , D 3f in the paramagnetic state at 78 K. This suggests that there is also short-range coupling of interlayer carbonate anions with respect to the octahedral layers and that the 2D long-range order of carbonates in interlayers remains unchanged.
    Print ISSN: 0026-461X
    Electronic ISSN: 1471-8022
    Topics: Geosciences
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  • 10
    Publication Date: 2018-01-01
    Description: Developing low cost and effective phosphate adsorbents is crucial to prevent eutrophication of natural waters. Here, phosphate removal by a natural and abundant shale from the Ivory Coast was investigated in both batch and column experiments with special attention devoted to understand the adsorption process. Batch experiments were carried out to assess the influence of initial phosphate concentration, sorbent dosage, contact time, and pH on phosphate removal. The phosphate removal efficiency increased with increased shale dosage while phosphate uptake decreased. Aqueous Ca, Mg, Al, and Fe species concentrations decreased in the presence of phosphate. Additionally, phosphate uptake strongly decreased with pH increases in the range 2 — 11, but then increased at pH 12. The kinetics were well described using a pseudo-second order model, and Langmuir adsorption isotherms were used for the equilibrium surface reactions. Adsorption to nanoparticles of goethite was hypothesized to be the major phosphate removal mechanism in the pH range 4 — 10. Column experiments with a flow rate of 1 mL min–1 and an initial phosphate concentration of 25 mg L–1 showed a breakthrough point at a V/Vp value of ~17, where V is the volume of phosphate solution added to the column and Vp is the pore volume. A V/Vp value of ~17 corresponded to a phosphate uptake of 0.17 mg/g, which was in agreement with the batch experiments. Column experiments revealed a strong correlation between the aqueous concentrations of Ca, Mg, Al, and Fe species and phosphate removal and, thus, suggest that phosphate removal by the shale occurred by aqueous dissolution/precipitation.
    Print ISSN: 0009-8604
    Electronic ISSN: 1552-8367
    Topics: Geosciences
    Published by Clay Minerals Society
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