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Subsequent to the recent formulation and adoption of safety criteria for reactor cooling systems, there appeared the need for an independent evaluation of the safety and reliability of the K-Reactor cooling system in terms of these criteria. The primary, secondary and last-ditch cooling systems of this reactor involve a strong inter-dependence between electrical and hydraulic components of the water plant. Because of the complexity of inter-relationships between these components, the analysis was divided into two parallel studies which were accomplished during the simmer of 1959. F. D. Robbins has presented his analysis of the electrical power and control system in HW-61887. This report deals with an engineering analysis of the hydraulic and mechanical aspects of the reliability and safety of the K-Reactor Cooling System. The system, as described in this report, is that which existed during the simmer of 1959, prior to modification under Project CG-775 (now Project CG-883).

The synthesis of substituted 3-(5-imidazo[2,1-b]thiazolylmethylene)-2-indolinones and analogues is reported. Their cytotoxic activity was evaluated according to protocols available at the National Cancer Institute (NCI), Bethesda, MD. The action of selected compounds was examined for potential inhibition of tubulin assembly in comparison with the potent colchicine site agent combretastatin A-4. The most potent compounds also strongly and selectively inhibited the phosphorylation of the oncoprotein kinase Akt in cancer cells. The effect of the most interesting compounds was examined on the growth of HT-29 colon cancer cells. These compounds caused the cells to arrest in the G2/M phase of the cell cycle, as would be expected for inhibitors of tubulin assembly.

The synthesis of new substituted E-3-(3-indolylmethylene)1,3-dihydroindol-2-ones is reported. The antitumor activity was evaluated according to protocols available at the National Cancer Institute (NCI), Bethesda, MD. Structure-activity relationships are discussed. The action of selected compounds was investigated in MCF-7 breast cancer cells. The ability of these derivatives to inhibit cellular proliferation was accompanied by increased level of p53 and its transcriptional targets p21 and Bax, interference in the cell cycle progression with cell accumulation in the G2/M phase, and lastly activation of apoptosis.

The synthesis of new antitumor 6-substituted imidazothiazole guanylhydrazones is described. Moreover, a series of compounds with a different basic chain at the 5 position were prepared. Finally, the replacement of the thiazole ring in the imidazothiazole system was also considered. All the new compounds prepared were submitted to the NCI cell line screen for evaluation of their antitumor activity. A few selected compounds were submitted to additional biological studies concerning effects on the cell cycle, apoptosis, and mitochondria.