From Bakke to Grutter and Gratz: The Supreme Court as a Policymaking Institution

Finding the best means for ensuring equal opportunities for women and minorities has long been controversial and initial efforts to do so were addressed by executive orders, and later the historic Civil Rights Act of 1964. However, this paper argues, since its initial Bakke decision in 1978, it is the Supreme Court that has set policy in this area. In the twenty-five years between that decision and the recent Gratz and Grutter decisions, the court has shifted in its stance, in many cases declaring unconstitutional what it once sanctioned. That shift has not resulted from changes in laws or new amendments to the Constitution, nor can it be seen as reflecting public opinion, as that is not clear-cut. Rather, affirmative action policy has reflected the ideological stances of the justices sitting at the time a decision was rendered. The paper concludes with an assessment as to what this means for a democracy. Copyright 2004 by The Policy Studies Association..

Public Administration for the Twenty-First Century

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Development of a Targeted Gene Vector Platform Based on Simian Adenovirus Serotype 24▿

Efforts to develop adenovirus vectors suitable for genetic interventions in humans have identified three major limitations of the most frequently used vector prototype, human adenovirus serotype 5 (Ad5). These limitations—widespread preexisting anti-Ad5 immunity in humans, the high rate of transduction of normal nontarget tissues, and the lack of target-specific gene delivery—justify the exploration of other Ad serotypes as vector prototypes. In this paper, we describe the development of an alternative vector platform using simian Ad serotype 24 (sAd24). We found that sAd24 virions formed unstable complexes with blood coagulation factor X and, because of that, transduced the liver and other organs at low levels when administered intravenously. The overall pattern of biodistribution of sAd24 particles was similar, however, to that of Ad5, and the intravenously injected sAd24 was cleared by Kupffer cells, leading to their depletion. We modified the virus's fiber protein to design a Her2-specific derivative of sAd24 capable of infecting target human tumor cells in vitro. In the presence of neutralizing anti-Ad5 antibodies, Her2-mediated infection with targeted sAd24 compared favorably to that with the Ad5-derived vector. When used to target Her2-expressing tumors in animals, this fiber-modified vector achieved a higher level of gene transfer to metastasis-containing murine lungs than to tumor-free lungs. In aggregate, these studies provide important insights into sAd24 biology, identify its advantages and limitations as a vector prototype, and are thus essential for further development of an sAd24-based gene delivery platform