2006 NASA Range Safety Annual Report

Throughout 2006, Range Safety was involved in a number of exciting and challenging activities and events, from developing, implementing, and supporting Range Safety policies and procedures-such as the Space Shuttle Launch and Landing Plans, the Range Safety Variance Process, and the Expendable Launch Vehicle Safety Program procedures-to evaluating new technologies. Range Safety training development is almost complete with the last course scheduled to go on line in mid-2007. Range Safety representatives took part in a number of panels and councils, including the newly formed Launch Constellation Range Safety Panel, the Range Commanders Council and its subgroups, the Space Shuttle Range Safety Panel, and the unmanned aircraft systems working group. Space based range safety demonstration and certification (formerly STARS) and the autonomous flight safety system were successfully tested. The enhanced flight termination system will be tested in early 2007 and the joint advanced range safety system mission analysis software tool is nearing operational status. New technologies being evaluated included a processor for real-time compensation in long range imaging, automated range surveillance using radio interferometry, and a space based range command and telemetry processor. Next year holds great promise as we continue ensuring safety while pursuing our quest beyond the Moon to Mars

Cloning and endogenous expression of a Eucalyptus grandis UDP-glucose dehydrogenase cDNA

UDP-glucose dehydrogenase (UGDH) catalyzes the oxidation of UDP-glucose (UDP-Glc) to UDP-glucuronate (UDP-GlcA), a key sugar nucleotide involved in the biosynthesis of plant cell wall polysaccharides. A full-length cDNA fragment coding for UGDH was cloned from the cambial region of 6-month-old E. grandis saplings by RT-PCR. The 1443-bp-ORF encodes a protein of 480 amino acids with a predicted molecular weight of 53 kDa. The recombinant protein expressed in Escherichia coli catalyzed the conversion of UDP-Glc to UDP-GlcA, confirming that the cloned cDNA encodes UGDH. The deduced amino acid sequence of the cDNA showed a high degree of identity with UGDH from several plant species. The Southern blot assay indicated that more than one copy of UGDH is present in Eucalyptus. These results were also confirmed by the proteomic analysis of the cambial region of 3- and 22-year-old E. grandis trees by 2-DE and LC-MS/MS, showing that at least two isoforms are present. The cloned gene is mainly expressed in roots, stem and bark of 6-month-old saplings, with a lower expression in leaves. High expression levels were also observed in the cambial region of 3- and 22-year-old trees. The results described in this paper provide a further view of the hemicellulose biosynthesis during wood formation in E. grandis

Evolution of Plant Nucleotide-Sugar Interconversion Enzymes

Nucleotide-diphospho-sugars (NDP-sugars) are the building blocks of diverse polysaccharides and glycoconjugates in all organisms. In plants, 11 families of NDP-sugar interconversion enzymes (NSEs) have been identified, each of which interconverts one NDP-sugar to another. While the functions of these enzyme families have been characterized in various plants, very little is known about their evolution and origin. Our phylogenetic analyses indicate that all the 11 plant NSE families are distantly related and most of them originated from different progenitor genes, which have already diverged in ancient prokaryotes. For instance, all NSE families are found in the lower land plant mosses and most of them are also found in aquatic algae, implicating that they have already evolved to be capable of synthesizing all the 11 different NDP-sugars. Particularly interesting is that the evolution of RHM (UDP-L-rhamnose synthase) manifests the fusion of genes of three enzymatic activities in early eukaryotes in a rather intriguing manner. The plant NRS/ER (nucleotide-rhamnose synthase/epimerase-reductase), on the other hand, evolved much later from the ancient plant RHMs through losing the N-terminal domain. Based on these findings, an evolutionary model is proposed to explain the origin and evolution of different NSE families. For instance, the UGlcAE (UDP-D-glucuronic acid 4-epimerase) family is suggested to have evolved from some chlamydial bacteria. Our data also show considerably higher sequence diversity among NSE-like genes in modern prokaryotes, consistent with the higher sugar diversity found in prokaryotes. All the NSE families are widely found in plants and algae containing carbohydrate-rich cell walls, while sporadically found in animals, fungi and other eukaryotes, which do not have or have cell walls with distinct compositions. Results of this study were shown to be highly useful for identifying unknown genes for further experimental characterization to determine their functions in the synthesis of diverse glycosylated molecules

Strategies for acquiring the phospholipid metabolite inositol in pathogenic bacteria, fungi and protozoa: making it and taking it

myo-Inositol (inositol) is an essential nutrient that is used for building phosphatidylinositol and its derivatives in eukaryotes and even in some eubacteria such as the mycobacteria. As a consequence, fungal, protozoan and mycobacterial pathogens must be able to acquire inositol in order to proliferate and cause infection in their hosts. There are two primary mechanisms for acquiring inositol. One is to synthesize inositol from glucose 6-phosphate using two sequentially acting enzymes: inositol-3-phosphate synthase (Ino1p) converts glucose 6-phosphate to inositol 3-phosphate, and then inositol monophosphatase (IMPase) dephosphorylates inositol 3-phosphate to generate inositol. The other mechanism is to import inositol from the environment via inositol transporters. Inositol is readily abundant in the bloodstream of mammalian hosts, providing a source from which many pathogens could potentially import inositol. However, despite this abundance of inositol in the host, some pathogens such as the bacterium Mycobacterium tuberculosis and the protist parasite Trypanosoma brucei must be able to make inositol de novo in order to cause disease (M. tuberculosis) or even grow (T. brucei). Other pathogens such as the fungus Candida albicans are equally adept at causing disease by importing inositol or by making it de novo. The role of inositol acquisition in the biology and pathogenesis of the parasite Leishmania and the fungus Cryptococcus are being explored as well. The specific strategies used by these pathogens to acquire inositol while in the host are discussed in relation to each pathogen's unique metabolic requirements

Costlets: A Generalized Approach to Cost Functions for Automated Optimization of IMRT Treatment Plans

We present the creation and use of a generalized cost function methodology based on costlets for automated optimization for conformal and intensity modulated radiotherapy treatment plans. In our approach, cost functions are created by combining clinically relevant “costlets”. Each costlet is created by the user, using an “evaluator” of the plan or dose distribution which is incorporated into a function or “modifier” to create an individual costlet. Dose statistics, dose-volume points, biological model results, non-dosimetric parameters, and any other information can be converted into a costlet. A wide variety of different types of costlets can be used concurrently. Individual costlet changes affect not only the results for that structure, but also all the other structures in the plan (e.g., a change in a normal tissue costlet can have large effects on target volume results as well as the normal tissue). Effective cost functions can be created from combinations of dose-based costlets, dose-volume costlets, biological model costlets, and other parameters. Generalized cost functions based on costlets have been demonstrated, and show potential for allowing input of numerous clinical issues into the optimization process, thereby helping to achieve clinically useful optimized plans. In this paper, we describe and illustrate the use of the costlets in an automated planning system developed and used clinically at the University of Michigan Medical Center. We place particular emphasis on the flexibility of the system, and its ability to discover a variety of plans making various trade-offs between clinical goals of the treatment that may be difficult to meet simultaneously.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47484/1/11081_2005_Article_2066.pd