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Surface Plasmon Enhanced Fluorescence Spectroscopy (SPFS) has been used to monitor the hybridization reaction of fluorophore-labeled 15mer target oligonucleotides from solution to probe DNA previously immobilized on plasma-polymerized allylamine films (ppA). The surfaces were treated with 254 nm UV light to covalently link the probe DNA to the ppA films. Since strong unspecific adsorption would occur between target DNA and unreacted amino groups on the polymer surface, any remaining reactive moieties in the polymer film were neutralized by rinsing the substrate surface with succinic anhydride after probe adsorption and before target hybridization. The SPFS data were utilized to determine hybridization affinity constants (KA) for complementary targets (MM0) as well as mismatch 1 (MM1) and mismatch 2 (MM2) hybridization reactions. Complementary target (MM0) DNA hybridization was shown to have a significantly higher KA than that MM1 and MM2. The three-dimensional network of the ppA appears to allow a similar hybridization mechanism in comparison to the more conventional two-dimensional systems.

The present work describes the fabrication, characterization, and optimization of NH2-derivatized polymer coatings prepared by pulsed-plasma polymerization for applications as adhesion layers in DNA immobilization. Fourier transform infrared spectroscopy and surface plasmon resonance spectroscopy were used to study (i) polymer matrix properties and (ii) oligonucleotide/DNA binding. The successful DNA attachment on amine functionalized surfaces was found to depend on the macromolecular architecture of the plasma films and on the amine group densities. Pulsed and continuous wave plasma polymers deposited at similar equivalent power showed comparable immobilization properties, while low duty cycle plasma-polymerized films showed a higher sensitivity toward DNA binding than high duty cycle plasma-deposited films. The stabilities of the various films in buffer solution and their reactivities as they were affected by variations in pH have been investigated.

CD33 is expressed by acute myeloid leukemia (AML) cells in >80% of patients but not by normal hematopoietic stem cells, suggesting that elimination of CD33⁺ cells may be therapeutically beneficial. A conjugate of a calicheamicin hydrazide derivative attached via hydrazone formation to the oxidized carbohydrates of the anti-CD33 murine antibody P67.6 had been chosen for use in AML prior to humanization of this antibody. However, the CDR-grafted humanized P67.6 could not be used to make the carbohydrate conjugate because of the unexpected sensitivity of this antibody to periodate oxidation. Exploration of a series of bifunctional linkers resulted in a new class of calicheamicin conjugates, termed the hybrid conjugates, that allows for the attachment of the calicheamicin to lysines but incorporates the site of hydrolytic release, a hydrazone, previously shown to be required for activity. The optimized conjugate chosen for clinical trials, gemtuzumab ozogamicin (“gem-ozo”, Mylotarg, formerly designated CMA-676), was significantly more potent and selective than the carbohydrate conjugate it replaced. It was selectively cytotoxic to HL-60 leukemia cells in tissue culture with an IC50 in the low to sub-pg cal/mL range (cal = calicheamicin equivalents). Doses of gem-ozo as low as 50 μg cal/kg given three times to mice bearing HL-60 xenografts routinely resulted in long-term, tumor-free survivors, while a nonbinding control conjugate was relatively inactive. Gem-ozo at a concentration of 2 to 10 ng cal/mL selectively inhibited leukemia colony formation by marrow cells from a significant proportion of AML patients. Gem-ozo has also shown significant activity against AML in Phase II trials and is the first antibody-targeted chemotherapeutic agent approved by the FDA.

The Atmospheric Fluidized Bed Coal Combustor Program will develop the technology for a fluidized bed coal combustion system to provide a source of high temperature air for process heating and power generation with gas turbines in industrial plants. The gas turbine has the advantages of a higher ratio of electric power output to exhaust heat load and a higher exhaust temperature than do steam turbines in cogeneration applications. The program is directed toward systems in the size range of 5 to 50 MW(e) and is sponsored by the Department of Energy. A study of industrial energy use has been completed that indicates a large potential market for gas turbine cogeneration systems. Conceptual design studies have been done for typical industrial’ installations, and some of these results are presented. The conceptual design of a 300 kW(e) test unit has been completed. A number of furnace design firms have been invited to submit their own designs for a 1500 kW(t) (5 × 106 Btu/hr) combustor, from which a final selection will be made. The design of the balance of the test system will proceed in parallel with the combustor design. An engineering design study has been completed by AiResearch Division of Garrett Corporation in which the modifications required to adapt an existing AiResearch 831-200 gas turbine to this cycle for both open and closed cycle operation were determined. Development and testing have been conducted in the areas of fluidization, heat transfer, tube corrosion and coal feeding. Results from heat transfer, tube corrosion, and coal feeding tests are presented.

For more than two and a half years we have been watching the evolution of a gigantic conflict involving the peoples of the greater part of Europe and Asia, our near neighbor Canada, and far off Australia. In these fateful days our sober thoughts search for a lesson from which we may profit. Our nation has been profoundly stirred by the horrors of this war, and it is not surprising that, being thus deeply stirred by the dangers of a general war conflagration, patriotic impulse searches for a method of expressing itself. Individuals and organized groups of individuals are coming forward, offering their skill and their services. But if we are without a clear understanding of the fundamental needs of the situation, if we are without a sympathetic exchange of purpose, if we are without a definition of requirements, the result will not aid our military and naval services, but