Comparative genomics and phylogenetics of the vertebrate CYP3 family

CYP3A verstoffwechselt mehr als 50% aller gegenwärtig in der Therapie eingesetzten Wirkstoffe, die häufig an klinisch relevanten Arzneimitttel-Wechselwirkungen beteiligt sind. Das Verständnis über die Bedeutung und die Regulation von einzelnen CYP3A Genen in der Pharmakologie und Physiologie ist unvollständig. Wir untersuchten die Evolution des CYP3 Genlokus über einen Zeitraum von 450 Millionen Jahre mittels genomischer Sequenzen von 16 Tierarten. Neue CYP3 Unterfamilien (CYP3B, C und D) entstanden über eine beschleunigte Evolution aus CYP3A Vorstufen von Clupeocephala Spezies. Ausgeprägte funktionelle Unterschiede traten zwischen CYP3A in Säugern und Clupeocephala CYP3 auf. Alle amnioten CYP3A Gene entwickelten sich aus zwei CYP3A Urgenen. Aufgrund der Entstehung von Säugern mit Plazenta ging eines von ihnen verloren während das andere eine neue genomische Umgebung infolge einer Translokation erlangte. In Primaten unterzog sich CYP3A mit mehreren Genduplikationen, Deletionen, Pseudogenisierung und Genkonversionen einer raschen evolutionären Veränderung. Die Entwicklung von CYP3A in Schmalnasenaffen (Alte Welt Affen, große Menschenaffen und Menschen) unterschieden sich wesentlich von Neue Welt Primaten (z.B. gewöhnlichen Krallenaffen) und Feuchtnasenaffen (z.B. Galago). Stellvertretend für die CYP3A Protein-codierende Sequenz entdeckten wir zwei frühe Episoden von besonders starker positiver Selektion: (1) auf CYP3A7 in der frühen hominoiden Evolution, welche im fetalen Zeitraum von einer Einschränkung der hepatischen Expression begleitet war, und (2) auf humanes CYP3A4 im Anschluss an die Teilung der Abstammungslinie in Schimpansen und Mensch. In Übereinstimmung mit diesen Befunden beeinflussen drei von vier positiv ausgewählten Aminosäuren, die in früheren biochemischen CYP3A Studien untersucht wurden, die Aktivität und Regioselektivität. Es ist somit naheliegend, dass CYP3A7 und CYP3A4 katalytische Funktionen erworben haben können, die besonders wichtig waren für die Evolution von Hominoiden und Menschen. Die Charakterisierung von CYP3A Promotoren in Primaten zeigte eine Anreicherung von ER6 Elementen in CYP3A Promotoren von Primaten und einen Trend in Richtung Erhöhung der ER6 Enstehung entlang den Abstammungslinien, die zu humanen und Schimpansen CYP3A4 führten. Die steigende Anzahl an ER6 Elementen kann durch die ausgeprägte CYP3A4 Induzierbarkeit und Expressionsvariabilität im Menschen verursacht sein.

Our world...

[v.1] The new-world life.--[v.2] The new-world religion.

Our world ...

[v.1] The new world-life.--[v.2] The new world-religion.

Narratives of New Netherland, 1609-1664 /

Anthology of contemporary accounts of the Dutch period in New York.

The fortune hunter, or, The adventures of a man about town : a novel of New York society /

Wright, L.H. Amer. fiction, 1774-1850 (2nd ed.),

A pictorial geography of the world : comprising a system of universal geography, popular and scientific, including a physical, political, and statistical account of the Earth and its various divisions, with numerous sketches from recent travels : and illustrated by more than twelve hundred engravings of manners, costumes, curiosities, cities, edifices, ruins, beasts, birds, fishes, reptiles, trees, plants, fruits, etc : with a copious index answering the purpose of a gazetteer /

Added illustrated t.p.

The World tomorrow.

Subtitle varies slightly.

A World that Counts: Mobilising the Data Revolution for Sustainable Development

In September 2015, the UN Member States are expected to commit to an ambitious new set of global goals for a new era of sustainable development. Achieving them will require an unprecedented joint effort on the part of governments at every level, civil society and the private sector, and millions of individual choices and actions. To be realised, the SDGs will require a monitoring and accountability framework and a plan for implementation. A commitment to realise the opportunities of the data revolution should be firmly embedded into the action plan for the SDGs, to support those countries most in need of resources, and to set the world on track for an unprecedented push towards a new world of data for change.

The words of God: Religious texts and the Counter -Reformation in the Spanish world

This dissertation analyzes a variety of religious texts such as catechisms, confession manuals, ecclesiastical legislation, saints' lives, and sermons to determine the definitions of orthodoxy held by the Spanish clergy and the origins of such visions. The conclusion posited by this research was that there was a definite continuity between the process of Catholic reform in Spain and the process of Catholic expansion into the New World in that the objectives and concerns of the Spanish clergy in Europe and the New World were very similar. This dissertation also analyzes sources that predated the Council of Trent and demonstrates that within the Iberian context the Council of Trent cannot be used as a starting date for the attempts at Catholic reform. In essence, this work concludes the Spanish clergy's activities were influenced by humanist concepts of models and model behaviour which is reflected in their attempt to form model Catholics in Spain and the New World and in their impulse to produce written texts as standards. ^

The Undersea World of the Sound Department: the Construction of Sonic Conventions in Sub-aqua Screen Environments

The availability of new underwater cameras and sub-aqua diving gear in the immediate post-war era opened up exciting possibilities for both narrative and documentary filmmakers. While the visual elements of this new world could now be more easily captured on film, the sound elements of the sub-aqua environment remained more elusive. What did, or should, this undersea world sound like? This article examines the use of sound in the sub-aqua scenes of both fictional and documentary films in the 1950s and asks questions about the methods used in the sonification of these worlds. Comparing the operation of underwater sound and human hearing with the production and post-production strategies used by filmmakers, I seek to identify the emergence of a sound convention and its implications for issues of cinematic realism. Central to this convention is the manipulation of sonic frequencies. The sound strategies adopted also raise questions about the malleability of viewer perspective and sound-image relationship in terms of a realist mode of address. Linked to this is the use of sound to enhance audience experience on an affective level. As well as underpinning cinematic realism, these new sound environments offered fresh experiences to audiences seeking new reasons to visit the cinema in an era of widening forms of entertainment.

New silk road : trade and investment. perspectives for eu and new partnerships

China has already given a fundamental contribution to the present globalization process and have also highly benefited from it by integrating becoming the final stage of the Global Chains Production networks in Asia. This process in China was the result of a survival economic strategy that saw in the attraction of Foreign Direct Investment in intensive low cost workmanship oriented to exports, a fundamental condition to overpass it´s millenary delay. This strategy accepted that the add value that remain in China, although very small was very important to give jobs to millions of Chinese and take them out of the absolute poverty line where they were in 1978 when Deng Xiao Ping launch the 4 Modernizations and the Open Door Policies. Other policies token during the first 30 years of the China Economic Reform, like the Grasp the Big Let Go the Small, the Socialist Market Economy, the Go West and the Go Global were equally important transforming Chinese economy in the second world biggest one. This first globalization stage had its big push in 2001 when China joined the WTO we can say that a new world economic order had begun in that date, placing China in the center of the world.

Perpetuating Racism: Legal Education, Race and Social Justice

By presenting the results of a content analysis of Australian undergraduate legal education, this paper examines the extent to which issues of race, ethnicity, discrimination, and multiculturalism feature within this component of the moral, ethical, and professional development of legal professionals. It will demonstrate that instead of encouraging a deep, critical and contextual understanding of such issues, legal education provides a relatively superficial one, which has important implications for the role that legal professionals play in overcoming injustices such as institutional racism, and the kinds of social reform that they are likely to undertake.

Discourse practice gaps in work life balance : comparative case studies in the Australian construction industry

Perspectives on work-life balance (WLB) reflected in political, media and organisational discourse, would maintain that WLB is on the agenda because of broad social, economic and political factors (Fleetwood 2007). In contrast, critical scholarship which examines work-life balance (WLB) and its associated practices maintains that workplace flexibility is more than a quasi-functionalist response to contemporary problems faced by individuals, families or organisations. For example, the literature identifies where flexible work arrangements have not lived up to expectations of a panacea for work-home conflicts, being characterised as much by employer-driven working conditions that disadvantage workers and constrain balance, as they are by employee friendly practices that enable it (Charlesworth 1997). Further, even where generous organisational work-life balance policies exist, under-utilisation is an issue (Schaefer et al, 2007). Compounding these issues is that many employees perceive their paid work as becoming more intense, pressured and demanding (Townsend et al 2003).

Speaking to each other at last? the ghost of tv past, present and to come...

John Hartley discusses TV past, present and future and concludes that 'This brave new world does have a couple of dystopian elements. One is that no-one knows how to fund non-universal TV production. Another is that any future 'imagined community' will have to get used to the fact that most people aren't inside it.