Methodology for back-contamination risk assessment for a Mars sample return mission

The risk of back-contamination from Mars Surface Sample Return (MSSR) missions is assessed. The methodology is designed to provide an assessment of the probability that a given mission design and strategy will result in accidental release of Martian organisms acquired as a result of MSSR. This is accomplished through the construction of risk models describing the mission risk elements and their impact on back-contamination probability. A conceptual framework is presented for using the risk model to evaluate mission design decisions that require a trade-off between science and planetary protection considerations

Genomic diversity of bacteriophages infecting Microbacterium spp

The bacteriophage population is vast, dynamic, old, and genetically diverse. The genomics of phages that infect bacterial hosts in the phylum Actinobacteria show them to not only be diverse but also pervasively mosaic, and replete with genes of unknown function. To further explore this broad group of bacteriophages, we describe here the isolation and genomic characterization of 116 phages that infect Microbacterium spp. Most of the phages are lytic, and can be grouped into twelve clusters according to their overall relatedness; seven of the phages are singletons with no close relatives. Genome sizes vary from 17.3 kbp to 97.7 kbp, and their G+C% content ranges from 51.4% to 71.4%, compared to ~67% for their Microbacterium hosts. The phages were isolated on five different Microbacterium species, but typically do not efficiently infect strains beyond the one on which they were isolated. These Microbacterium phages contain many novel features, including very large viral genes (13.5 kbp) and unusual fusions of structural proteins, including a fusion of VIP2 toxin and a MuF-like protein into a single gene. These phages and their genetic components such as integration systems, recombineering tools, and phage-mediated delivery systems, will be useful resources for advancing Microbacterium genetics

Inhibition of Specific NF-κB Activity Contributes to the Tumor Suppressor Function of 14-3-3σ in Breast Cancer

14-3-3σ is frequently lost in human breast cancers by genetic deletion or promoter methylation. We have now investigated the involvement of 14-3-3σ in the termination of NF-κB signal in mammary cells and its putative role in cancer relapse and metastasis. Our results show that 14-3-3σ regulates nuclear export of p65-NF-κB following chronic TNFα stimulation. Restoration of 14-3-3σ in breast cancer cells reduces migration capacity and metastatic abilities in vivo. By microarray analysis, we have identified a genetic signature that responds to TNFα in a 14-3-3σ-dependent manner and significantly associates with different breast and other types of cancer. By interrogating public databases, we have found that over-expression of this signature correlates with poor relapse-free survival in breast cancer patients. Finally, screening of 96 human breast tumors showed that NF-κB activation strictly correlates with the absence of 14-3-3σ and it is significantly associated with worse prognosis in the multivariate analysis. Our findings identify a genetic signature that is important for breast cancer prognosis and for future personalized treatments based on NF-κB targeting

Increased IKKα Expression in the Basal Layer of the Epidermis of Transgenic Mice Enhances the Malignant Potential of Skin Tumors

Non-melanoma skin cancer is the most frequent type of cancer in humans. In this study we demonstrate that elevated IKKα expression in murine epidermis increases the malignancy potential of skin tumors. We describe the generation of transgenic mice overexpressing IKKα in the basal, proliferative layer of the epidermis and in the outer root sheath of hair follicles. The epidermis of K5-IKKα transgenic animals shows several alterations such as hyperproliferation, mislocalized expression of integrin-α6 and downregulation of the tumor suppressor maspin. Treatment of the back skin of mice with the mitogenic agent 12-O-tetradecanoylphorbol-13-acetate causes in transgenic mice the appearance of different preneoplastic changes such as epidermal atypia with loss of cell polarity and altered epidermal tissue architecture, while in wild type littermates this treatment only leads to the development of benign epidermal hyperplasia. Moreover, in skin carcinogenesis assays, transgenic mice carrying active Ha-ras (K5-IKKα-Tg.AC mice) develop invasive tumors, instead of the benign papillomas arising in wild type-Tg-AC mice also bearing an active Ha-ras. Therefore we provide evidence for a tumor promoter role of IKKα in skin cancer, similarly to what occurs in other neoplasias, including hepatocarcinomas and breast, prostate and colorectal cancer. The altered expression of cyclin D1, maspin and integrin-α6 in skin of transgenic mice provides, at least in part, the molecular bases for the increased malignant potential found in the K5-IKKα skin tumors

Global Conservation Priorities for Marine Turtles

Where conservation resources are limited and conservation targets are diverse, robust yet flexible priority-setting frameworks are vital. Priority-setting is especially important for geographically widespread species with distinct populations subject to multiple threats that operate on different spatial and temporal scales. Marine turtles are widely distributed and exhibit intra-specific variations in population sizes and trends, as well as reproduction and morphology. However, current global extinction risk assessment frameworks do not assess conservation status of spatially and biologically distinct marine turtle Regional Management Units (RMUs), and thus do not capture variations in population trends, impacts of threats, or necessary conservation actions across individual populations. To address this issue, we developed a new assessment framework that allowed us to evaluate, compare and organize marine turtle RMUs according to status and threats criteria. Because conservation priorities can vary widely (i.e. from avoiding imminent extinction to maintaining long-term monitoring efforts) we developed a “conservation priorities portfolio” system using categories of paired risk and threats scores for all RMUs (n = 58). We performed these assessments and rankings globally, by species, by ocean basin, and by recognized geopolitical bodies to identify patterns in risk, threats, and data gaps at different scales. This process resulted in characterization of risk and threats to all marine turtle RMUs, including identification of the world's 11 most endangered marine turtle RMUs based on highest risk and threats scores. This system also highlighted important gaps in available information that is crucial for accurate conservation assessments. Overall, this priority-setting framework can provide guidance for research and conservation priorities at multiple relevant scales, and should serve as a model for conservation status assessments and priority-setting for widespread, long-lived taxa

A decision analysis of an exploratory studies facility

An Exploratory Studies Facility (ESF) is planned to support the characterization of a potential site for a high-level nuclear waste repository at Yucca Mountain, NV. The selection of a design for the ESF is a critical decision, because the ESF design may affect the accuracy of characterization testing and subsequent repository design. The assist the design process, a comparative evaluation was conducted to rank 34 alternative relied on techniques from formal decision analysis, including decision trees and multiattribute utility analysis (MUA). The results helped to identify favorable design features and convinced the Department of Energy to adopt the top-ranked option as the preferred ESF design

Probability encoding of hydrologic parameters for basalt. Elicitation of expert opinions from a panel of three basalt waste isolation project staff hydrologists

The present study implemented a probability encoding method to estimate the probability distributions of selected hydrologic variables for the Cohassett basalt flow top and flow interior, and the anisotropy ratio of the interior of the Cohassett basalt flow beneath the Hanford Site. Site-speciic data for these hydrologic parameters are currently inadequate for the purpose of preliminary assessment of candidate repository performance. However, this information is required to complete preliminary performance assessment studies. Rockwell chose a probability encoding method developed by SRI International to generate credible and auditable estimates of the probability distributions of effective porosity and hydraulic conductivity anisotropy. The results indicate significant differences of opinion among the experts. This was especially true of the values of the effective porosity of the Cohassett basalt flow interior for which estimates differ by more than five orders of magnitude. The experts are in greater agreement about the values of effective porosity of the Cohassett basalt flow top; their estimates for this variable are generally within one to two orders of magnitiude of each other. For anisotropy ratio, the expert estimates are generally within two or three orders of magnitude of each other. Based on this study, the Rockwell hydrologists estimate the effective porosity of the Cohassett basalt flow top to be generally higher than do the independent experts. For the effective porosity of the Cohassett basalt flow top, the estimates of the Rockwell hydrologists indicate a smaller uncertainty than do the estimates of the independent experts. On the other hand, for the effective porosity and anisotropy ratio of the Cohassett basalt flow interior, the estimates of the Rockwell hydrologists indicate a larger uncertainty than do the estimates of the independent experts

Probability encoding of hydrologic parameters for basalt. Elicitation of expert opinions from a panel of five consulting hydrologists

The Columbia River basalts underlying the Hanford Site in Washington State are being considered as a possible location for a geologic repository for high-level nuclear waste. To investigate the feasibility of a repository at this site, the hydrologic parameters of the site must be evaluated. Among hydrologic parameters of particular interest are the effective porosity of the Cohassett basalt flow top and flow interior and the vertical-to-horizontal hydraulic conductivity, or anisotropy ratio, of the Cohassett basalt flow interior. The Cohassett basalt flow is the prime candidate horizon for repository studies. Site-specific data for these hydrologic parameters are currently inadequate for the purpose of preliminary assessment of candidate repository performance. To obtain credible, auditable, and independently derived estimates of the specified hydrologic parameters, a panel of five nationally recognized hydrologists was assembled. Their expert judgments were quantified during two rounds of Delphi process by means of a probability encoding method developed to estimate the probability distributions of the selected hydrologic variables. The results indicate significant differences of expert opinion for cumulative probabilities of less than 10% and greater than 90%, but relatively close agreement in the middle ranges of values. The principal causes of the diversity of opinion are believed to be the lack of site-specific data and the absence of a single, widely accepted, conceptual or theoretical basis for analyzing these variables

Decision analysis of Hanford underground storage tank waste retrieval systems

A decision analysis approach has been proposed for planning the retrieval of hazardous, radioactive, and mixed wastes from underground storage tanks. This paper describes the proposed approach and illustrates its application to the single-shell storage tanks (SSTs) at Hanford, Washington