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3. establish mechanisms of self-renewal in human ESCs and to evaluate the role of Myc. Although distinct differences exist between murine and human ESCs, it is likely that common modes of self-renewal regulation will exist. To understand self-renewal of hESCs, we will use information obtained from the mouse ESC model system (Specific Aims 1,2). This information will be crucial for our understanding of human ESC biology and in harnessing their therapeutic potential. The following hESC lines from the NIH Human Embryonic Stem Cell Registry will be used in these studies; BG01, TEO3 and WAO1.

A subset of anogenital HPVs, the 'high risk' HPVs including HPV-16 and 18 genotypes, are associated with greater than 95% of cervical carcinomas. Two genes of the high-risk anogenital human papillomaviruses (HPV), E6 and E7, are implicated in cervical carcinogenesis owing to their selective and continued expression in those cancers. E6 and E7 proteins possess multiple biochemical activities including but not limited to their capacities to inactivate tumor suppressor genes p53 and pRB, respectively.

We hypothesize that the interactions of Crx and these CIPs regulate transcription of target genes in specific types of photoreceptors. In this renewal application, we propose to test this hypothesis using both in vivo and in vitro approaches. In Aim #1, we will focus on two specific CIPs, the nuclear receptor Nr2e3 and the zinc-finger transcription factor Sp4 and characterize their interactions with Crx in vivo using co-immunoprecipitation and coexpression studies in the mouse retina. We will also use cell transfections to determine if these interactions have functional significance on the transcription of rod- or cone-specific genes, such as opsins and the gene products identified in Aim #2.

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Mathematical techniques of theoretical physics by Julian V. Noble


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