100 research outputs found
Calibration of the channel that determines the omega-hydroxylation regiospecificity of cytochrome P4504A1 - Catalytic oxidation of 12-halododecanoic acids
The fatty acid omega-hydroxylation regiospecificity of CYP4 enzymes may result from presentation of the terminal carbon to the oxidizing species via a narrow channel that restricts access to the other carbon atoms. To test this hypothesis, the oxidation of 12-iodo-, 12-bromo-, and 12-chlorododecanoic acids by recombinant CYP4A1 has been examined. Although all three 12-halododecanoic acids bind to CYP4A1 with similar dissociation constants, the 12-chloro and 12-bromo fatty acids are oxidized to 12-hydroxydodecanoic acid and 12-oxododecanoic acid, whereas the 12-iodo analogue is very poorly oxidized. Incubations in (H2O)-O-18 show that the 12-hydroxydodecanoic acid oxygen derives from water, whereas that in the aldehyde derives from O-2. The alcohol thus arises from oxidation of the halide to an oxohalonium species that is hydrolyzed by water, whereas the aldehyde arises by a conventional carbon hydroxylation-elimination mechanism. No irreversible inactivation of CYP4A1 is observed during 12-halododecanoic acid oxidation. Control experiments show that CYP2E1, which has an omega-1 regiospecificity, primarily oxidizes 12-halododecanoic acids to the omega-aldehyde rather than alcohol product. Incubation of CYP4A1 with 12,12-[H-2](2)-12-chlorododecanoic acid causes a 2-3-fold increase in halogen versus carbon oxidation. The fact that the order of substrate oxidation (Br > Cl >> I) approximates the inverse of the intrinsic oxidizability of the halogen atoms is consistent with presentation of the halide terminus via a channel that accommodates the chloride and bromide but not iodide atoms, which implies an effective channel diameter greater than 3.90 angstrom but smaller than 4.30 angstrom
Intercultural ethics: questions of methods in language and intercultural communication
This paper explores how questions of ethics and questions of method are intertwined and unavoidable in any serious study of language and intercultural communication. It argues that the focus on difference and solution orientations to intercultural conflict has been a fundamental driver for theory, data collection and methods in the field. These approaches, the paper argues, have created a considerable consciousness raising industry, with methods, trainings and ‘critical incidents’, which ultimately focus intellectual energy in areas which may be productive in terms of courses and publications but which have a problematic basis in their ethical terrain.
Dieser Artikel untersucht wie ethische und methodische Fragen nicht nur ineinander greifen, sondern in keiner ernstzunehmenden Studie ueber Sprache und interkulturelle Kommunikation ausgelassen werden duerfen. Es wird hier argumentiert, dass der Schwerpunkt auf Verschiedenheit und Problemorientierung im interkulturellen Konflikt einen wesentlichen Einfluss auf theoretische Entwicklungen, Datenerhebung und Methoden in diesem Bereich hatte. Dieser Artikel legt auch dar, wie diese Ansaetze eine betraechtliche ‘Bewusstseinsbildungs – Branche' erzeugt haben, mit Methoden, Trainings, und ‘kritischen Interaktionssituationen’, welche letztendlich allen intellektuellen Arbeitseifer auf Bereiche konzentriert hat, die zwar ertragreich sind in Bezug auf Kurse und Publikationen, jedoch eine problematische Grundlage im ethischen Bereich aufweisen
Healthcare in the news media: The privileging of private over public
This article reports on a discourse analysis of the representation of healthcare in the print news media, and the way this representation shapes perspectives of healthcare. We analysed news items from six major Australian newspapers over a three-year time period. We show how various framing devices promote ideas about a crisis in the current public healthcare system, the existence of a precarious balance between the public and private health sectors, and the benefits of private healthcare. We employ Bourdieu’s concepts of field and capital to demonstrate the processes through which these devices are employed to conceal the power relations operating in the healthcare sector, to obscure the identity of those who gain the most from the expansion of private sector medicine, and to indirectly increase health inequalities
Breaking the furniture in erotic narrative: Towards a history of desire (18th and 19th century French literature)
The structure of division: Objectivity and myth in Roger Martin du Gard's Les 'Thibault'
The substance of desire: Towards a thematic history of the aphrodisiac in nineteenth-century French fiction
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