Lunar Resource Assessment: an Industry Perspective

The goals of the U.S. space program are to return to the Moon, establish a base, and continue onward to Mars. To accomplish this in a relatively short time frame and to avoid the high costs of transporting materials from the Earth, resources on the Moon will need to be mined. Oxygen will be one of the most important resources, to be used as a rocket propellant and for life support. Ilmenite and lunar regolith have both been considered as ores for the production of oxygen. Resource production on the Moon will be a very important part of the U.S. space program. To produce resources we must explore to identify the location of ore or feedback and calculate the surface and underground reserves. Preliminary resource production tests will provide the information that can be used in final plant design. Bechtel Corporation's experience in terrestrial engineering and construction has led to an interest in lunar resource assessment leading to the construction of production facilities on the Moon. There is an intimate link between adequate resource assessment to define feedstock quantity and quality, material processing requirements, and the successful production of lunar oxygen. Although lunar resource assessment is often viewed as a research process, the engineering and production aspects are very important to consider. Resource production often requires the acquisition of different types, scales, or resolutions of data than that needed for research, and it is needed early in the exploration process. An adequate assessment of the grade, areal extent, and depth distribution of the resources is a prerequisite to mining. The need for a satisfactory resource exploration program using remote sensing techniques, field sampling, and chemical and physical analysis is emphasized. These data can be used to define the ore for oxygen production and the mining, processing facilities, and equipment required

Development and Validation of a Model for Hydrogen Reduction of JSC-1A

Hydrogen reduction of lunar regolith has been proposed as a viable technology for oxygen production on the moon. Hydrogen reduces FeO present in the lunar regolith to form metallic iron and water. The water may be electrolyzed to recycle the hydrogen and produce oxygen. Depending upon the regolith composition, FeO may be bound to TiO2 as ilmenite or it may be dispersed in glassy substrates. Some testing of hydrogen reduction has been conducted with Apollo-returned lunar regolith samples. However, due to the restricted amount of lunar material available for testing, detailed understanding and modeling of the reduction process in regolith have not yet been developed. As a step in this direction, hydrogen reduction studies have been carried out in more detail with lunar regolith simulants such as JSC-1A by NASA and other organizations. While JSC-1A has some similarities with lunar regolith, it does not duplicate the wide variety of regolith types on the moon, for example, it contains almost no ilmenite. Nonetheless, it is a good starting point for developing an understanding of the hydrogen reduction process with regolith-like material. In this paper, a model utilizing a shrinking core formulation coupled with the reactor flow is described and validated against experimental data on hydrogen reduction of JSC-1A

Impact of Epistasis and Pleiotropy on Evolutionary Adaptation

Evolutionary adaptation is often likened to climbing a hill or peak. While this process is simple for fitness landscapes where mutations are independent, the interaction between mutations (epistasis) as well as mutations at loci that affect more than one trait (pleiotropy) are crucial in complex and realistic fitness landscapes. We investigate the impact of epistasis and pleiotropy on adaptive evolution by studying the evolution of a population of asexual haploid organisms (haplotypes) in a model of N interacting loci, where each locus interacts with K other loci. We use a quantitative measure of the magnitude of epistatic interactions between substitutions, and find that it is an increasing function of K. When haplotypes adapt at high mutation rates, more epistatic pairs of substitutions are observed on the line of descent than expected. The highest fitness is attained in landscapes with an intermediate amount of ruggedness that balance the higher fitness potential of interacting genes with their concomitant decreased evolvability. Our findings imply that the synergism between loci that interact epistatically is crucial for evolving genetic modules with high fitness, while too much ruggedness stalls the adaptive process.Comment: 20 pages, 8 figures, plus 10 supporting figure

An Evolutionary Reduction Principle for Mutation Rates at Multiple Loci

A model of mutation rate evolution for multiple loci under arbitrary selection is analyzed. Results are obtained using techniques from Karlin (1982) that overcome the weak selection constraints needed for tractability in prior studies of multilocus event models. A multivariate form of the reduction principle is found: reduction results at individual loci combine topologically to produce a surface of mutation rate alterations that are neutral for a new modifier allele. New mutation rates survive if and only if they fall below this surface - a generalization of the hyperplane found by Zhivotovsky et al. (1994) for a multilocus recombination modifier. Increases in mutation rates at some loci may evolve if compensated for by decreases at other loci. The strength of selection on the modifier scales in proportion to the number of germline cell divisions, and increases with the number of loci affected. Loci that do not make a difference to marginal fitnesses at equilibrium are not subject to the reduction principle, and under fine tuning of mutation rates would be expected to have higher mutation rates than loci in mutation-selection balance. Other results include the nonexistence of 'viability analogous, Hardy-Weinberg' modifier polymorphisms under multiplicative mutation, and the sufficiency of average transmission rates to encapsulate the effect of modifier polymorphisms on the transmission of loci under selection. A conjecture is offered regarding situations, like recombination in the presence of mutation, that exhibit departures from the reduction principle. Constraints for tractability are: tight linkage of all loci, initial fixation at the modifier locus, and mutation distributions comprising transition probabilities of reversible Markov chains.Comment: v3: Final corrections. v2: Revised title, reworked and expanded introductory and discussion sections, added corollaries, new results on modifier polymorphisms, minor corrections. 49 pages, 64 reference

Analysis of cancer metabolism with high-throughput technologies

<p>Abstract</p> <p>Background</p> <p>Recent advances in genomics and proteomics have allowed us to study the nuances of the Warburg effect – a long-standing puzzle in cancer energy metabolism – at an unprecedented level of detail. While modern next-generation sequencing technologies are extremely powerful, the lack of appropriate data analysis tools makes this study difficult. To meet this challenge, we developed a novel application for comparative analysis of gene expression and visualization of RNA-Seq data.</p> <p>Results</p> <p>We analyzed two biological samples (normal human brain tissue and human cancer cell lines) with high-energy, metabolic requirements. We calculated digital topology and the copy number of every expressed transcript. We observed subtle but remarkable qualitative and quantitative differences between the citric acid (TCA) cycle and glycolysis pathways. We found that in the first three steps of the TCA cycle, digital expression of aconitase 2 (<it>ACO2</it>) in the brain exceeded both citrate synthase (<it>CS</it>) and isocitrate dehydrogenase 2 (<it>IDH2</it>), while in cancer cells this trend was quite the opposite. In the glycolysis pathway, all genes showed higher expression levels in cancer cell lines; and most notably, digital gene expression of glyceraldehyde-3-phosphate dehydrogenase (<it>GAPDH</it>) and enolase (<it>ENO</it>) were considerably increased when compared to the brain sample.</p> <p>Conclusions</p> <p>The variations we observed should affect the rates and quantities of ATP production. We expect that the developed tool will provide insights into the subtleties related to the causality between the Warburg effect and neoplastic transformation. Even though we focused on well-known and extensively studied metabolic pathways, the data analysis and visualization pipeline that we developed is particularly valuable as it is global and pathway-independent.</p

Point Mutations in c-Myc Uncouple Neoplastic Transformation from Multiple Other Phenotypes in Rat Fibroblasts

Deregulation of c-Myc (Myc) occurs in many cancers. In addition to transforming various cell types, Myc also influences additional transformation-associated cellular phenotypes including proliferation, survival, genomic instability, reactive oxygen species production, and metabolism. Although Myc is wild type in most cancers (wtMyc), it occasionally acquires point mutations in certain lymphomas. Some of these mutations confer a survival advantage despite partially attenuating proliferation and transformation. Here, we have evaluated four naturally-occurring or synthetic point mutations of Myc for their ability to affect these phenotypes, as well as to promote genomic instability, to generate reactive oxygen species and to up-regulate aerobic glycolysis and oxidative phosphorylation. Our findings indicate that many of these phenotypes are genetically and functionally independent of one another and are not necessary for transformation. Specifically, the higher rate of glucose metabolism known to be associated with wtMyc deregulation was found to be independent of transformation. One mutation (Q131R) was greatly impaired for nearly all of the studied Myc phenotypes, yet was able to retain some ability to transform. These findings indicate that, while the Myc phenotypes examined here make additive contributions to transformation, none, with the possible exception of increased reliance on extracellular glutamine for survival, are necessary for achieving this state

Phylostratigraphic tracking of cancer genes suggests a link to the emergence of multicellularity in metazoa

Background: Phylostratigraphy is a method used to correlate the evolutionary origin of founder genes (that is, functional founder protein domains) of gene families with particular macroevolutionary transitions. It is based on a model of genome evolution that suggests that the origin of complex phenotypic innovations will be accompanied by the emergence of such founder genes, the descendants of which can still be traced in extant organisms. The origin of multicellularity can be considered to be a macroevolutionary transition, for which new gene functions would have been required. Cancer should be tightly connected to multicellular life since it can be viewed as a malfunction of interaction between cells in a multicellular organism. A phylostratigraphic tracking of the origin of cancer genes should, therefore, also provide insights into the origin of multicellularity. Results: We find two strong peaks of the emergence of cancer related protein domains, one at the time of the origin of the first cell and the other around the time of the evolution of the multicellular metazoan organisms. These peaks correlate with two major classes of cancer genes, the 'caretakers', which are involved in general functions that support genome stability and the 'gatekeepers', which are involved in cellular signalling and growth processes. Interestingly, this phylogenetic succession mirrors the ontogenetic succession of tumour progression, where mutations in caretakers are thought to precede mutations in gatekeepers. Conclusions: A link between multicellularity and formation of cancer has often been predicted. However, this has not so far been explicitly tested. Although we find that a significant number of protein domains involved in cancer predate the origin of multicellularity, the second peak of cancer protein domain emergence is, indeed, connected to a phylogenetic level where multicellular animals have emerged. The fact that we can find a strong and consistent signal for this second peak in the phylostratigraphic map implies that a complex multi-level selection process has driven the transition to multicellularity