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COMBINATORIAL BIOSYNTHETIC DERIVATIZATION OF THE ANTITUMORAL AGENT GILVOCARCIN VShepherd, Micah Douglas 01 January 2011 (has links)
Gilvocarcin V (GV), the principal product of Streptomyces griseoflavus Gö 3592 and other Streptomyces spp., is the most prominent member of a distinct class of antitumor antibiotics that share a polyketide derived coumarin-based aromatic core. GV and other members of this class including polycarcin V from Streptomyces polyformus, often referred to as gilvocarcin-like aryl C-glycosides, are particularly interesting because of their potent bactericidal, virucidal and antitumor activities at low concentrations while maintaining low in vivo toxicity. Although the precise molecular mechanism of GV bioactivity is unknown, gilvocarcin V has been shown to undergo a photoactivated [2+2] cycloaddition of its vinyl side chain with thymine residues of DNA in near-UV or visible blue light. In addition, GV was shown to selectively crosslink histone H3 with DNA, thereby effectively disrupting normal cellular processes such as transcription. Furthermore, GVs ability to inhibit topoisomerase II has also been attributed as a mechanism of action for gilvocarcin V activity. The excellent antitumor activity, as well as an unprecedented structural architecture, has made GV an ideal candidate for biosynthetic studies toward the development of novel analogues with improved pharmacological properties. Previous biosynthetic research has identified several candidate genes responsible for key steps during the biosynthesis of gilvocarcin V including an oxygenase cascade leading to C-C bond cleavage, methylations, lactone formation, C-glycosylation and vinyl side chain formation.
In this study, we further examined two critical biosynthetic transformations essential for the bioactivity of gilvocarcin V, namely starter unit incorporation and C-glycosylation, through the following specific aims: 1) creation of functional chimeric C-glycosyltransferases through domain swapping of gilvocarcin-like glycosyltransferases and identification and evaluation of the donor substrate flexibility of PlcGT, the polycarcin V pathway specific C-glycosyltransferase; 2) creation of a library of O-methylated-L-rhamnose analogues of polycarcin V for structure activity relationship studies; 3) identification of the role of GilP and GilQ in starter unit specificity during gilvocarcin V biosynthesis; and 4) creation of a plasmid based approach in which selective gilvocarcin biosynthetic genes were utilized to produce important gilvocarcin intermediates for further in vivo and in vitro experimentation.
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Nouvelle approche de formulation des bétons drainants aux propriétés mécaniques et drainantes amélioréesKabagire Kibenga, Daddy January 2013 (has links)
Le béton drainant est généralement utilisé pour ses caractéristiques drainantes, d'ailleurs ces dernières décennies ont été marqué par une utilisation croissante du béton drainant aux États-Unis, à cause de l'adoption d'une loi spéciale sur la gestion des eaux de ruissèlement et de surface. Les applications les plus courantes sont: les aires de stationnements, les chaussées à faible trafic et les terrains de tennis. Cependant, le béton drainant possède des faibles propriétés mécaniques comparativement au béton conventionnel. Ceci est dû à sa porosité effective relativement importante. Le but principal pour le concepteur est alors de trouver un équilibre entre les propriétés mécaniques et drainantes conformément aux exigences voulues. Dans cette étude, un intérêt particulier est porté sur la méthode de formulation du béton drainant. La méthode proposée dans la littérature ne couvre pas tous les granulats et ne fournit pas de recommandations simples d'application pour faciliter la procédure de formulation. Dans la méthode proposée, la porosité inter-granulaire, déterminée via la compacité granulaire, est le paramètre principal pour la formulation des bétons drainant. Il est également question d'évaluer l'effet de différents paramètres de formulation ainsi que de l'effet de l'énergie de consolidation sur les propriétés drainantes et mécaniques des bétons drainants. Les échantillons de béton sont préparés en utilisant deux différents niveaux d'énergie de consolidation. Une modélisation à l'aide des plans d'expériences considérant trois paramètres les plus influents (Rapport E/C, le volume de pâte, et la teneur en agent réducteur d'eau) a permis de quantifier la contribution de chaque paramètres ainsi que leur interactions sur les différentes propriétés évaluées. Afin de faciliter l'approche de formulation des bétons drainants, le volume de pâte est exprimé en fonction du volume de vide inter-granulaire (V P /VVG ). L'effet des particules fines sur les propriétés mécaniques a également été évalué. Les résultats 'de cette étude montrent que les propriétés déterminées à partir de la courbe granulométrique ne suffisent pas pour prédire la porosité inter-granulaire des granulats utilisés. Les résultats ont également montré que la formulation des bétons drainants est réalisable avec des rapports V P /GVG compris entre 30 à 60%. Cependant, le rapport VP /VVG optimal trouvé est situé à environ 50%. Par ailleurs, les résultats montrent que les propriétés mécaniques ne dépendent pas de la taille des granulats, mais elles sont fonction de la distribution granulométriques et de la quantité des éléments fins des granulats. L'analyse des résultats obtenus sur les bétons étudiés dans le programme montre que la porosité requise pour obtenir une perméabilité minimale de 1 mm/sec est de 19%. Les modèles statistiques établis sont fiables et peuvent être utilisé pour décrire l'influence des paramètres étudiés (rapport E/C, VP /VVG , agent réducteur d'eau) sur les propriétés drainantes et mécaniques du béton drainant. La validation des modèles est réalisée à l'aide des points centraux et des mélanges de la première phase se trouvant dans le domaine expérimental. Ces modèles sont exploités pour tracer les iso-réponses qui peuvent servir de guide de sélection de matériau pour faciliter la formulation des bétons drainants. Les modèles statistiques montrent que le rapport V P /VVG est le paramètre le plus influent parmi les paramètres étudiés. D'autre part, il est observé que le rapport E/C a une influence significative sur les propriétés mécaniques, En effet, une augmentation du rapport E/C améliore les propriétés mécaniques. [symboles non conformes]
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The Politics of Protection: The Forgotten History of Georgia Feminists and Doe v. BoltonMcGee, Alexandra 11 August 2015 (has links)
In this thesis, I will argue that Doe v. Bolton, 410 U.S. 179 (1973), a United States Supreme Court case originating in Georgia, enabled all women access to abortion, including groups of marginalized women previously denied this right. An examination of the background of Doe uncovers the roles played by Georgia feminists and the medical community. By comparing Doe v. Bolton with the concurrent Supreme Court case of Roe v. Wade, I will shed light on the history of abortion in America as well as continuing divisions over abortion access in America today.
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Förändringen av MARPOL Annex V år 2013 : Hur den implementerats och upplevts ombordRönnblom, Jenny, Sigurdh, Oskar January 2014 (has links)
Första januari år 2013 trädde den senaste versionen av MARPOL Annex V i kraft. Denna studie har genom en litteraturstudie samt intervjuer med nautiska befäl sökt svar på vilka förändringar som skedde, hur dem implementerats ombord samt hur förändringarna upplevts av sjöfarare. Syftet med studien var att bidra med en pusselbit till bilden av hur avfallssortering utövas till sjöss samt hur arbetet med det upplevs. Litteraturstudien kom fram till att den stora skillnaden är att papper, glas, metall samt aska inte längre får slängas i havet. Inom specialområde får endast matavfall destruerat genom avfallskvarn slängas överbord. Intervjuerna visade att respondenterna inte påverkats nämnvärt av förändringarna då de redan tidigare följt strängare riktlinjer och regelverk för avfallshantering. Den mest betydande arbetsuppgiften för avfallsansvarigt befäl ombord är att underrätta övrig besättning om hur avfall skall hanteras. Dock efterfrågas av samtliga befäl ytterligare internationell lagstiftning riktat mot hamnar för en global likformighet för att underlätta arbetet som annars kan ses som krångligt och omotiverat. / The first of January 2013 came an updated version of MARPOL Annex V. This research has been made with a literature study and interviews with nautical officers searched for answers to what changes have been made, how they are implemented on board and how the changes experienced by seafarers. The purpose of this study was to contribute how the waste handling works onboard, how waste sorting exercise at sea and how the work is perceived. The literature study found that the major difference is that paper, glass, metal and ashes can no longer be thrown in the sea. Food waste inside special areas must have been processed through a food waste disposer before thrown overboard. The interviews showed that respondents are not significantly affected by the changes as they have already followed a more strict version of the regulations for waste disposal. The most important task for the waste responsible officer on board is to inform the rest of the crew on how waste should be managed onboard. All the respondents ask for international legislation directed at ports of a global uniformity in order to facilitate the work that otherwise might be viewed as burdensome and unjustified.
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From Colonies to Nation: Locating the Historical Legitimacy of the American Charter School MovementGoodridge, Shane Michael 25 April 2013 (has links)
From colonies to nation, this work identifies and emphasizes the influence of interdependent communal relationships on the ascent of the charter school movement. These ideals were made manifest in colonial social covenants that were then compromised by the conformist republican mandate of the common school. These ideals were recovered incrementally as education was affected by broader historical forces, most notably the implementation of court-sanctioned racial apartheid during the Plessy era, the reaction to the underwhelming impact of Brown, and, beginning in the 1980s, the rise of legislation that prepared the way for charter schools. Moreover, this work challenges the assumption that charter schools have proven popular with American citizens due solely to promises of superior academic results. Alternatively, this work suggests that charter schools have prospered because they have challenged the state monopoly in K-12 education, and have thus returned balance to the dynamic between the individual and the state. Finally, this work troubles the idea that charter schools are balkanizing American education, suggesting that the right of citizens to form charter schools, in an effort to sustain unique communities, justifies and is in fact endorsed by the American metanarrative. Research on American charter schools lacks a coherent historical framework. This work provides the charter school movement with an historical narrative that argues for the movement’s legitimacy based on its consistency with the American Republic’s founding philosophy. / Graduate / 0323 / 0337 / 0520 / smg32@duke.edu
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Crown-magnate relations in the personal rule of James V, 1528-1542Cameron, James S. January 1995 (has links)
In terms of general interest, James V has suffered by comparison with his more famous father, James IV, and his internationally renowned daughter, Mary Queen of Scots. Yet his reign is an important one, embracing the establishment of the court of session, the beginnings of Protestantism in some areas of Scotland, and the growth of royal power to such an extent that the king could leave the country for nine months in 1536-37 without fear of rebellion. Studies of royal finance, of some aspects of the growth of the legal profession, and of religious dissent have already been undertaken; and the politics of the minority of James V has also been the subject of recent research. This thesis aims to demonstrate that the politics practised in the personal rule differed little in kind from those practised by earlier adult Stewart monarchs. The approach has been to examine the major political events of the period, the attitude of the king, the impact of royal policy upon his magnates, and the careers of some of those magnates. For too long James V has been judged to have been a vindictive and irrational king, motivated largely by greed. The assumption has been that he antagonised most of his leading magnates and met his just deserts when they refused to support him in 1542. A different view is offered here. Essentially, many of James' later policies were shaped by the events of 1528-29 when he assumed his royal authority in person. For the rest, his approach closely resembles that of his supposedly more popular father. There were some individual magnates who suffered financially by the application of legalistic sharp practice. But the conclusion is that this king did not lose the support of the majority, even at the end.
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Varozės profilaktika ir gydymas kvapiaisiais augalais / Varroatosis prophylaxis and treatment with redolent plantsGražulytė, Agnė 05 March 2014 (has links)
Baigiamojo darbo tikslas: ištirti kvapiųjų augalų įtaką varozės profilaktikai ir gydymui.
Apibūdinimas: varozė – parazitinė bičių liga, kuri pridaro daug žalos bitininkystei bei sodininkystės, žemdirbystės industrijoms. Varozės gydymui naudojami įvairūs gydymo būdai, tačiau nei vienas neveikia 100 proc.
Baigiamojo darbo metodikos: Bandymas atliktas Jurbarko ir Prienų rajono bitynuose 2013 m. Tyrimo metu nustatytas varozės, askosferozės, viduriavimo, puvinių paplitimas 52 bičių šeimose. Tirta erkių populiacijos dinamika, kintant bičių šeimų stiprumui. Nustatytas ligos poveikis bičių kūnelių sausųjų medžiagų cheminei sudėčiai, medaus cheminei sudėčiai, bičių produktyvumui. Tirtas kvapiųjų augalų (sėjamosios petražolės, paprastojo čiobrelio, valgomojo krieno, pipirmėtės, juodojo serbento, paprastojo apynio) poveikis erkėms, jų nimfoms. Bičių kūnelių SM baltymai, riebalai ir medaus cheminė sudėtis nustatyta Lietuvos žemdirbystės instituto agrocheminių tyrimų laboratorijoje. Atliekant eksperimentą su kvapiaisiais augalais, parinkta vienodo stiprumo bei rasės 12 bičių šeimų, šios suskirstytos į 2 grupes (kontrolinę ir bandomąją). Kvapieji augalai buvo susmulkinti ir po 300 g paskleisti viršutinėje avilio dalyje – kas 4 dienas jie keisti ir stebėta, kiek erkių nukrito į erkėgaudį.
Pagrindiniai tiriamojo darbo rezultatai: Tyrimais nustatyta, kad daugiausiai erkių, nimfų nukrito nuo paprastųjų apynių žiedų (bandomojoje grupėje į erkėgaudžius nukrito 82,35 proc. (P<0,05) erkių daugiau... [toliau žr. visą tekstą] / The aim and methods: The test was performed in apiaries of Jurbarkas and Prienai district, in 2013. During the time of the research varosis, chalk brood (askosferosis), diarrhea, rot prevalence were determined in 52 bees families. Mite population dynamics, varying strength of bees families was analysed. Influence of the disease for bees bodies dry matter (DM), chemical composition (protein, fat), honey chemical composition, bees productivity was determined. Aromatic herbs influence (parsley, plain thyme, eatable horseradish, peppermint, black currant, plain hop) for mites, their nymphs was analysed. Bees bodies DM protein, fat and chemical composition of honey determined in Agrochemical Laboratory of the Lithuanian Research Centre for Agriculture. Performing experiment with aromatic herbs, 12 bees families of equal strength, race were selected, these were divided into 2 groups (control and experimental). Aromatic herbs were granulated and spread in 300 g, in the upper part of the hive, they were changed in every 4 days, quantity of mites dropped into mite catcher was observed.
The main results of the research work: According to data of the research, the largest quantity of mites, nymphs dropped from plain hop flowers (82.35 percent (P<0.05) more mites dropped into mite catchers in experimental group, than in control group) also from black currant leaves (81.82 percent (P<0.05) more mites in experimental group, than in control group), the least quantity,-from parsley (50.00... [to full text]
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Die Kontrolle von Vertrauenspersonen im Strafprozess /Doka, Siiri Ann. January 2008 (has links)
Universiẗat, Diss.--Bielefeld, 2007.
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Die verdeckte Ermittlungstätigkeit der Strafverfolgungsbehörden durch die Zusammenarbeit mit V-Personen und Informanten /Ellbogen, Klaus. January 2004 (has links) (PDF)
Univ., Diss.-2004--Potsdam, 2003. / Literaturverz. S. [271] - 297.
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Eine attische schwarzfigurige Vasengattung und die Darstellung des Komos im VI. Jahrhundert.Greifenhagen, Adolf. January 1900 (has links)
Königsberg, Phil. Diss. v. 22. Juni 1929.
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