537 research outputs found

    Synthesis of A83586C/citropeptin hybrid and synthetic studies toward azinothricin

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    The Azinothricin family of cyclodepsipeptides are a class of antitumour antibiotics whose antitumour properties are attributed to their ability to selectively repress the expression of genes essential for the progression of the cell cycle from G1 to S phase. They have been shown to inhibit E2F transcription factors, which are critical regulators of mammalian cellular proliferation. This biological observation has made them a potentially important new therapeutic target for the control of proliferative diseases, such as cancer. An asymmetric total synthesis of an A83586C-citropeptin hybrid is presented in this thesis, along with a synthetic route to the azinothricin cyclodepsipeptide. The A83586C- citropeptin hybrid will serve as a useful intracellular probe that will provide valuable insights into the mechanism of the antitumour action of this class, which may contribute to a greater understanding of cancer biology. The cyclodepsipeptide components of these molecules have been assembled via a 2+2+2 -fragment condensation strategy and a HATU-mediated macrolactamisation. In the case of the A83586C-citropeptin hybrid, a chemoselective coupling was performed between the fully elaborated N-hydroxybenzotriazole activated ester and the citropeptin cyclodepsipeptide

    Optimal and Efficient Crossover Designs for Test-Control Study When Subject Effects are Random

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    I study crossover designs based on the criteria of A- and MV- optimality under the model with random subject effects, for the purpose of comparing several test treatments with a standard control treatment. Optimal and efficient designs are proposed, and their efficiencies are also evaluated. A family of totally balanced test-control incomplete crossover designs based on a function of the ratio of the subject effect variance to the error variance are shown to be highly efficient and robust. The results have interesting connections with those in Hedayat and Yang (2005) and Hedayat, Stufken, and Yang (2006). Constructions of efficient designs are also studied

    Typical relations between Ci and Rj.

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    <p>Typical relations between Ci and Rj.</p

    Dependence index between the reason and result events at different states.

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    <p>Dependence index between the reason and result events at different states.</p

    Comparison of algorithms for the fault indicator.

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    <p>Comparison of algorithms for the fault indicator.</p

    Data volume control experiment.

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    <p>Data volume control experiment.</p

    Three-story building structure.

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    <p>Three-story building structure.</p

    Contrastive chart of data volume.

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    <p>Contrastive chart of data volume.</p

    Causality index map.

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    <p>Causality index map.</p
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