Type I and type II interferons (IFNs) bind to different cell surface receptors but activate overlapping signal transduction pathways. We examined the effects of a type I IFN (IFN-alphacon1) and a type II IFN (IFN-gamma1b) on gene expression in A549 cells and demonstrate that there is a common set of genes modulated by both IFNs as well as a set of genes specifically regulated by each, reflecting the activation of different signaling pathways. In particular, IFN-gamma induced many more genes of the signaling pathways, apoptosis, and cytokine interactions than did IFN-alpha. Even with genes induced by both IFNs there were distinctive quantitative differences in expression. IFN-gamma1b plays a major role in the induction and regulation of the complement pathway. Previous work has shown a synergistic antiviral and antiproliferative effect of type I and type II IFNs in cell culture and in the treatment of tumors in mice. We demonstrate that a majority of genes showed an additive effect of IFN-alphacon1 and IFN-gamma1b, but a subset of genes is synergistically induced; these include ISG20, MX2, OAS2, and other genes known to be involved in the antiviral response, TRAIL (TNFSF10) and caspases involved in apoptosis and chemokine genes RANTES, CXCL10, and CXCL11. Greater than additive transcription of some of these genes in the presence of both IFNs was confirmed by real-time kinetic RT-PCR. Elevated induction of many of these genes may be sufficient to explain the synergistic antiviral and antitumor effects of this combination of IFNs in vivo.
The effect of anatase, rutile, and amorphous TiO 2 nanoparticles on the combustion of solid rocket propellant was investigated. Each additive increased the burning rate of propellant strands by 30%. Typical fast-burning propellants are unstable due to oversensitivity to pressure variations, but the anatase additive yielded propellants with high yet stable burning rates over a broad pressure range. Anatase nanoparticles also catalyzed the high-temperature decomposition of ammonium perchlorate, a key component of solid propellant.
Recent advances in nanostructured fuels and oxidizers may lead to high-performance energetic materials for propulsion, but these nanoparticulates present serious challenges due to their inherent instability and safety hazards and difficulty of manufacture. In this paper, we develop an alternate route, the use of nanoscale metal-oxides to catalyze reactions between micrometer-scale energetic constituents. Methods to synthesize TiO 2 -based nanoparticles that are highly active toward energetic reactions and effectively incorporate them into energetic composites are reported. Activity was maximized by tuning the physical and chemical properties of the nano-TiO 2 dispersion in the composite. An 81% increase in combustion rate was achieved with a nanoparticle loading of 1 wt %, making energetically active nano-TiO 2 a viable material for advanced propulsion, without the hazards and difficulties of competing technologies.
A statistical Taguchi L8 matrix was used to conduct a multiparameter study of the use of nanoscale additives in composite solid propellants. The additives studied were TiO 2 (titania) and CeO 2 (ceria). The other parameters involved in the experiment were the oxidizer loading and distribution, additive percentage and size, additive size (nano-scale or mm-scale), and the mixing method. Four baseline propellants without additives were also produced for comparison. The propellants were tested from 3.45 to 13.78 MPa in a strand bomb, and burning rate curves were determined for all formulas. By analyzing the Taguchi matrix, the sensitivity of each parameter according to the pressure sensitivity and burning rate of the propellant was calculated. The dominant factors depend on whether the additive is needed for modifying the pressure index or the absolute value of the burning rate. In general, the effectiveness of the additives was most influenced by oxidizer percentage, oxidizer size distribution, and additive type. The amount of additive, mixing method, and additive size all had relatively minor impacts on the effectiveness of the additives.
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