1,811 research outputs found
Studies on the pro-oxidant chemistry of flavonoids
No full textThere is currently much interest in the development of functional foods aiming at the prevention of the development of some diseases, for example cancer, by the introduction of selected natural substances at elevated levels into the diet. The rationale for this approach is based especially on epidemiological data that indicate that food items containing such chemicals may reduce the risk of these diseases in humans. Epidemiological studies indicate, for example, that diets rich in fruit and vegetables protect against a variety of diseases, including heart diseases and certain forms of cancer. However, identification of the actual ingredient in a specific diet responsible for the beneficial health effects remains an important bottleneck for translating observational epidemiology to development of a functional food ingredient. The protection against cancer afforded by fruit and vegetables has been attributed to antioxidant micronutrients such as vitamin C, beta-carotene and vitamin E, which may act at many sites, including the stomach, intestine, lung and bladder. However, present scientific attention is focusing as well on the significance of other minor dietary components, notably the flavonoids as protectants against disease. Flavonoids are widespread in nature and are found in considerable quantities in fruits, vegetables, seeds, peel and tubers. The average Western diet may provide up to 1 g of flavonoids per day. Numerous in vitro studies show that flavonoids are potent antioxidants and metal chelators. Their potential as anti-inflammatory, antiallergic and antiviral compounds has also attracted attention. These studies provide the basis for the present rapidly increasing interest for the use of flavonoids as functional food ingredients. As a result increased human exposure to flavonoids can be expected in the near future. In shops and at the internet, food and food supplements based on (iso)flavonoids as functional ingredients are marketed. This, although hard scientific data supporting the health claims as well as data allowing a balanced risk-benefit evaluation are lacking. For flavonoids increased future human exposure regimens induce the question on their pro-oxidant chemistry. There is considerable evidence that some flavonoids are mutagenic in both bacterial and mammalian experimental systems. A high incidence of gastric cancer in some human populations has been linked to consumption of wine containing potentially mutagenic flavonoids (Tamura et al. , Proc. Natl. Acad. Sci. USA. 77, 4961-4965, 1980, Hoey et al. , Am. J. Epidemiol., 113, 669-974, 1981). Relatively little is understood about either the toxicity or protection afforded by flavonoids in humans.Since flavonoid quinone/quinone methides have been suggested as the major metabolites responsible for the possible pro-oxidant toxicity and mutagenicity of flavonoids, characterisation of flavonoid quinone chemistry is of importance. However, little information is available on the structure and reactivity of these flavonoid oxidation products. Therefore, the objective of this thesis was to investigate the pro-oxidant chemistry of flavonoids and to perform structure activity studies on the chemical behaviour of 3',4'-dihydroxyflavonoids with special emphasis on the nature and reactivity of the quinone/quinone methide type metabolites formed. Using the GSH trapping method, HPLC, LC/MS, MALDI-TOF, 1H NMR, 13C NMR and quantum mechanical computer calculations the quinone/quinone methide chemistry of a series of 3',4'-dihydroxyflavonoids could be characterised.The results provide insight in structure-activity-relationships for the pro-oxidant chemistry of these electrophilic quinone/quinone methide flavonoid metabolites. The results obtained also reveal an unexpected pH-dependent electrophilic behaviour of B ring catechol flavonoids. Furthermore the results of this thesis also reveal, for the first time, evidence for the pro-oxidative chemistry of quercetin in a cellular in vitro model. The formation of these glutathionyl-flavonoid adducts provides evidence for the actual pro-oxidative formation of reactive quinone type metabolites from B ring catechol flavonoids in the selected cellular in vitro model using melanoma cells. Oxidation of the catechols to quinones and their isomeric quinone methides generates potent electrophiles that could alkylate DNA. Interestingly, the structural requirements essential for good antioxidant activity match the requirements essential for pro-oxidant action and quinone methide formation. Altogether, the pro-oxidant behaviour of flavonoids and their quinone/quinone methides are far from straight forward and need to be re-evaluated especially in the framework of the risk-benefit evaluation of the use of these flavonoids as functional food ingredients and/or food supplements.SamenvattingEr is momenteel veel interesse voor de ontwikkeling van functionele voedingsmiddelen (functional foods), met als doel het voorkomen van het ontstaan van ziekten zoals bijvoorbeeld kanker, via het in verhoogde mate introduceren van geselecteerde natuurlijke bestanddelen in het dieet. De basis voor deze aanpak wordt momenteel met name gevonden in epidemiologische studies die laten zien dat diëten rijk aan specifieke voedselcomponenten of ingrediënten de kans op bepaalde ziekten bij de mens verlagen. Zo geven epidemiologische studies bijvoorbeeld aan dat diëten die rijk zijn aan fruit en groenten beschermen tegen een aantal ziekten zoals hartziekten en bepaalde vormen van kanker. Echter, het identificeren van de belangrijke ingrediënten in het betreffende dieet die het gezondheidsbevorderende effect tot stand brengen is een knelpunt voor het vertalen van de resultaten uit de epidemiologie naar de ontwikkeling van een functioneel voedingsingrediënt.De bescherming tegen kanker door groenten en fruit is toegeschreven aan antioxidanten zoals vitamine C, beta-caroteen en vitamine E, die op vele plaatsen in het lichaam, zoals de maag, darmen, long en de blaas actief zijn. Wetenschappelijk wordt momenteel veel aandacht besteed aan het mogelijke belang van andere belangrijke dieet componenten, zoals flavonoïden, als beschermende ingrediënten tegen ziekte. Flavonoïden komen in de natuur veel voor, en worden met name in hoge concentraties gevonden in fruit, groenten, knollen en zaden. Het gemiddelde Westerse dieet bevat ongeveer 1 gram aan flavonoïden per dag.Vele in vitro studies tonen aan dat flavonoïden goede antioxidanten en metaal chelatoren zijn. Daarnaast hebben ze anti-inflammatoire, anti-allergische en anti-virale eigenschappen die van belang worden geacht. Deze bevindingen verschaffen de basis voor de momenteel snel groeiende interesse om flavonoïden te gebruiken als functionele voedingsingrediënten. Als gevolg hiervan zou er in de nabije toekomst een toename in de opname van flavonoïden via het dieet verwacht kunnen worden. In winkels en via het internet worden voedingsmiddelen en voedingssupplementen gebaseerd op (iso)flavonoïden als functionele voedingsingrediënten verkocht. Dit, terwijl zowel de wetenschappelijke onderbouwing voor de gezondheidsclaims als gegevens die een gebalanceerde "risk-benefit" analyse mogelijk maken, nog ontbreken. In het geval van verhoogde toekomstige blootstelling van mensen aan flavonoïden worden voor de risk-benefit evaluatie vragen van belang rond hun mogelijk pro-oxidatieve chemisch gedrag. Er zijn aanwijzingen dat sommige flavonoïden mutageen zijn in zowel bacteriële als zoogdier in vitro test systemen. Een verhoogde mate aan maagkanker in bepaalde humane populaties is in verband gebracht met de consumptie van wijn met daarin mogelijk mutagene flavonoïden (Tamura et al. , Proc. Natl. Acad. Sci. USA. 77, 4961-4965, 1980, Hoey et al. , Am. J. Epidem., 113, 669-974, 1981). Alles samenvattend is er eigenlijk weinig bekend van de schadelijke maar ook van de gezondheidsbevorderende effecten van flavonoïden.Omdat flavonoid chinon/chinon methides genoemd zijn als de belangrijkste metabolieten die verantwoordelijk zouden zijn voor de mogelijke pro-oxidatieve toxiciteit en mutageniteit van flavonoïden, is karakterisering van deze pro-oxidant chemie van flavonoïden van belang. Echter er is weinig bekend over de structuur en de reactiviteit van deze flavonoid oxidatie producten. Daarom was het doel van deze studie de pro-oxidant chemie van flavonoïden te onderzoeken en een structuur-activiteits studie uit te voeren naar het chemische gedrag van 3',4'-dihydroxyflavonoïden. Daarbij werd speciale aandacht besteed aan de aard en reactiviteit van de gevormde chinon/chinon methide metabolieten. Met behulp van de GSH-trapping methode, HPLC, LC/MS, MALDI-TOF, 1H-NMR, 13C-NMR en kwantum-chemische computerberekeningen kon de chinon/chinon methide chemie van een serie 3',4'-dihydroxyflavonoiden gekarakteriseerd worden.De verkregen resultaten geven inzicht in de structuur-activteits relaties voor de pro-oxidatieve chemie van de electrofiele chinon /chinon methides metabolieten van de flavonoïden. De resultaten laten ook een onverwacht effect zien van de pH op het electrofiele gedrag van de B-ring catechol flavonoïden. Bovendien laten de resultaten van het proefschrift zien dat zelfs onder reducerende omstandigheden in een cellulair in vitro model (melanoma cellen) de pro-oxidatieve chemie van quercetine van belang kan zijn. Met name de vorming van glutathion-flavonoid conjugaten is een bewijs dat in het gekozen cellulaire model de pro-oxidatieve vorming van reactieve flavonoid chinon/ chinon methide metabolieten is opgetreden. Oxidatie van de catecholen naar chinonen en hun isomere chinon methides genereert electrofielen die DNA kunnen alkyleren. Van belang is dat de structurele randvoorwaarden die een flavonoid een goede antioxidant maken gelijk blijken te zijn aan de structurele kenmerken die essentieel zijn voor pro-oxidant gedrag en chinon methide vorming.Al met al is de pro-oxidant chemie van flavonoïden en van hun chinon /chinon methides verre van recht toe recht aan gebleken en zou de pro-oxidatieve chemie en de toxiciteit van de flavonoïden in het kader van hun gebruik als functional food ingredienten beter onderzocht en afgewogen moeten worden, rekening houdend met hun mogelijk gezondheidsbevorderende effecten
Photograph of a bust of the author Tasma
No full textPhotograph of a bust of the author Tasma (Jessie Catherine Couvreur). Pencilled on verso of photo 'Tasma - enlargement of an original lent to H.M. Green? by Mrs Erdos, a neice of Tasma
Isogeometric analysis for multi-patch structured Kirchhoff–Love shells
No full textWe present an isogeometric method for Kirchhoff–Love shell analysis of shell structures with geometries composed of multiple patches and which possibly possess extraordinary vertices, i.e. vertices with a valency different to four. The proposed isogeometric shell discretisation is based on the one hand on the approximation of the mid-surface by a particular class of multi-patch surfaces, called analysis-suitable G1 (Collin et al., 2016), and on the other hand on the use of the globally C1-smooth isogeometric multi-patch spline space (Farahat et al., 2023). We use our developed technique within an isogeometric Kirchhoff–Love shell formulation (Kiendl et al., 2009) to study linear and non-linear shell problems on multi-patch structures. Thereby, the numerical results show the great potential of our method for efficient shell analysis of geometrically complex multi-patch structures which cannot be modelled without the use of extraordinary vertices.Funding Information: The authors wish to thank the anonymous reviewers for their comments that helped to improve the paper. A. Farahat and M. Kapl have been supported by the Austrian Science Fund (FWF) through the project P 33023-N. H.M. Verhelst is grateful for the funding from Delft University of Technology. J. Kiendl has received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program (grant agreement No 864482). Additionally, the authors are grateful for the support from the developers of the Geometry + Simulation Modules, in particular from A. Mantzaflaris (Inria Sophia Antipolis-Méditerranée). Funding Information: The authors wish to thank the anonymous reviewers for their comments that helped to improve the paper. A. Farahat and M. Kapl have been supported by the Austrian Science Fund (FWF) through the project P 33023-N . H.M. Verhelst is grateful for the funding from Delft University of Technology . J. Kiendl has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant agreement No 864482 ). Additionally, the authors are grateful for the support from the developers of the Geometry + Simulation Modules, in particular from A. Mantzaflaris (Inria Sophia Antipolis-Méditerranée).Numerical AnalysisShip Hydromechanics and Structure
Samuel H.M. Byers; Poet; Author; Diplomat; Oskaloosa; Iowa; Mahaska County; Iowa
No full textThis is a photograph taken of Samuel H.M. Byers at the onset of the Civil War in 1861. Byers served in the Union Army during the Civil War and gained a great deal of inspiration for his poetic writing during the war. Byers's most famous work is a poem entitled "Sherman's March to the Sea" recapping events that took place during this famous piece of American history. Byers is also credited with writing the state song of Iowa, played to the melody of "O, Christmas Tree". After gaining fame and fortune from his writing, Byers pursued a career in diplomacy, serving in the U.S. Consulate in Switzerland and Italy. Byers then came back to the U.S., living out the remainder of his days in Los Angeles, California. Byers died in 1933, at the age 95
L'Image Du Buddha Dans L'Art Lao
No full textText and photos of Buddha images in LaosL'Image Du Buddha Dans L'Art Lao. Vientiane: H.M. Demain, 197
Thermally-enhanced oil recovery from stranded fields: Synergy potential for geothermal and oil exploitation
No full textAccepted author manuscriptReservoir EngineeringApplied Geolog
Cure of codfish and herrings; Extracts for a work on the cure of codfish and herring
No full textUseful Hints on the Cure of Codfish and HerringsAt head of title: Official; "(Extracts from), reprinted, by permission, by H.M. inspectors for Irish Fisheries", "... having obtained the permission from Newfoundland Fisheries Commission ..." --page
Trustworthy 100-Year Digital Objects: Durable Encoding for When It's Too Late to Ask
No full textHow can an author store digital information so that it will be reliably intelligible, even years later when he is no longer available to answer questions? Methods that might work are not good enough; what is preserved today should be reliably intelligible whenever someone wants it. Prior proposals fail because they generally confound saved data with irrelevant details of today’s information technology—details that are difficult to define, extract, and save completely and accurately.
We use a virtual machine to represent and eventually to render any data whatsoever. We focus on a case of intermediate difficulty—an executable procedure—and identify a variant for every other data type.
This solution might be more elaborate than needed to render some text, image, audio, or video data. Simple data can be preserved as representations using well-known standards. We sketch practical methods for files ranging from simple structures to those containing computer programs, treating simple cases here and deferring complex cases for future work. Enough of the complete solution is known to enable practical aggressive preservation programs today.
Questioning the Borders of Contemporary US Fiction: H.M. Naqvi’s “Home Boy”, 9/11 and the American Novel
No full textThis essay investigates the margins of twentieth-century American novel in the light of the increasingly deterritorialized status of US culture and literature – a literature whose borders need to be reconfigured not only in terms of reception, but of creation as well. In particular, the essay focuses on the Pakistani-born author H.M. Naqvi and his first novel, Home Boy (2009) – part immigrant narrative, part Bildungsroman, part 9/11 novel. Rooting Home Boy deep in the American grain and at the same time investigating the construction of Otherness through the protagonist’s “inoutsider” status and perspective, Naqvi explores the potential and the limits of what can be considered as “performative Americaness,” defined not by genealogic or geographical belonging, but by cultural and literary affiliations in the politically and socially unstable scenario of the post-national worl
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