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Simple Summary: Since chronic inflammation has been found to increase the risk of many forms of cancer, we examined the expression of major genes that regulate inflammation in cancerous specimens from 469 patients with colorectal cancer. We found that these genes were overexpressed together with several other cancer-promoting genes in colorectal tumors. Our findings demonstrate that the development of colorectal cancer is tightly linked to the overexpression of genes that regulate inflammation. These genes and their products are molecular targets for cancer prevention and therapy. We examined the expression of major inflammatory genes, cyclooxygenase-1, 2 (COX1, COX2), arachidonate-5-lipoxygenase (ALOX5), and arachidonate-5-lipoxygenase activating protein (ALOX5AP) among 469 tumor specimens of colorectal cancer in The Cancer Genome Atlas (TCGA). Among 411 specimens without mutations in mismatch repair (MMR) genes, the mean expression of each of the inflammatory genes ranked above the 80th percentile, and the overall mean cyclooxygenase expression (COX1+COX2) ranked in the upper 99th percentile of all genes. Similar levels were observed for 58 cases with MMR mutations. Pearson correlation coefficients exceeding r = 0.70 were observed between COX and LOX mRNA levels with genes of major cell-signaling pathways involved in tumorigenesis (Src, JAK STAT, MAPK, PI3K). We observed a novel association (r = 0.78) between ALOX5 expression and a natural antisense transcript (NAT), RP11-67C2.2, a long non-coding mRNA gene, 462 base pairs in length that is located within the terminal intron of the ALOX5 gene on chromosome 10q11.21. Tumor-promoting genes highly correlated with the expression of COX1, COX2, ALOX5 and ALOX5AP are known to increase mitogenesis, mutagenesis, angiogenesis, cell survival, immunosuppression and metastasis in the inflammogenesis of colorectal cancer. These genes and the novel NAT, RP1167C2.2 are potential molecular targets for chemoprevention and therapy of colorectal cancer. [ABSTRACT FROM AUTHOR]

Rework that occurs late in the product life cycle is dramatically more expensive than design work performed early in the cycle. However, shifting traditional design work earlier in the design process so as to avoid rework later is difficult. A number of product development practices that have been characterized as a shift from developing a single-point design to developing a set of possible designs have proven effective at reducing development rework. This paper refines the definitions of such "set-based" development practices, which are aimed at early development phases, and shows how they can be applied to the systems engineering process in order to reduce or eliminate the root causes of rework. Examples from the Wright Brothers, Toyota, and several other companies are presented. [ABSTRACT FROM AUTHOR]

On July 4, 2005 at 05:44:34 UTC the Impactor spacecraft (s/c) impacted comet 9P/Tempel 1 with a relative speed of more than 10 km/s. The Flyby s/c captured the impact event, using both the medium resolution imager and the high resolution imager, and tracked the impact site for the entire observing period following impact. The objective of the Impactor s/c was to impact in an illuminated area viewable from the Flyby s/c and telemeter high-resolution context images of the impact site prior to impact. The Flyby s/c had two primary objectives: (1) capture the impact event in order to observe the ejecta plume expansion dynamics and (2) track the impact site for at least 800 s to observe the crater formation and capture high-resolution images of the fully developed crater. All of these objectives were met by estimating the trajectory of each spacecraft relative to 9P/Tempel 1 using the autonomous navigation system, precise attitude information from the attitude determination and control subsystem, and allowing each spacecraft to independently select the same impact site. This paper describes the challenges of targeting and tracking comet 9P/Tempel 1. © 2007 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]