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

IKKα and IKKβ Each Function to Regulate NF-κB Activation in the TNF-Induced/Canonical Pathway

Activation of the transcription factor NF-kappaB by cytokines is rapid, mediated through the activation of the IKK complex with subsequent phosphorylation and degradation of the inhibitory IkappaB proteins. The IKK complex is comprised of two catalytic subunits, IKKalpha and IKKbeta, and a regulatory protein known as NEMO. Using cells from mice that are genetically deficient in IKKbeta or IKKalpha, or using a kinase inactive mutant of IKKbeta, it has been proposed that IKKbeta is critical for TNF-induced IkappaB phosphorylation/degradation through the canonical pathway while IKKalpha has been shown to be involved in the non-canonical pathway for NF-kappaB activation. These conclusions have led to a focus on development of IKKbeta inhibitors for potential use in inflammatory disorders and cancer.Analysis of NF-kappaB activation in response to TNF in MEFs reveals that IKKbeta is essential for efficient phosphorylation and subsequent degradation of IkappaB alpha, yet IKKalpha contributes to the NF-kappaB activation response in these cells as measured via DNA binding assays. In HeLa cells, both IKKalpha and IKKbeta contribute to IkappaB alpha phosphorylation and NF-kappaB activation. A kinase inactive mutant of IKKbeta, which has been used as evidence for the critical importance of IKKbeta in TNF-induced signaling, blocks activation of NF-kappaB induced by IKKalpha, even in cells that are deficient in IKKbeta.These results demonstrate the importance of IKKalpha in canonical NF-kappaB activation, downstream of cytokine treatment of cells. The experiments suggest that IKKalpha will be a therapeutic target in inflammatory disorders

The role of the NF-κB pathway in Her2-overexpressing breast cancer

Overexpression of the membrane-bound receptor tyrosine kinase Her2 (ErbB-2, EGFR2) occurs in approximately 30% of all breast cancers and typically correlates with poor prognosis. Overexpression of Her2 leads to activation of multiple downstream pathways including the MAPK, PI3K/Akt and NF-κB pathways. Her2 has been previously reported to activate the NF-κB pathway. However, the mechanism by which this occurs is poorly elucidated. In this report, we utilize an siRNA approach to investigate the role that the different Inhibitor of Kappa-B Kinase (IKK) subunits play in activation of NF-κB downstream of Her2. We show that IKKα plays a previously unreported role in NF-κB activation via the canonical pathway in Her2-overexpressing breast cancer cells. Furthermore, IKKα plays an important role in NF-κB regulated gene expression and induction of an invasive phenotype in these cells, independent of PI3K. This activation of NF-κB by Her2 also requires the NF-κB pathway kinase, TGF-β- activated kinase 1 (TAK1). Finally, we also show that inhibition of IKKα by siRNA leads to activation of SPARC, a member of the BM-40 family of genes which are often dysregulated in cancer. Activation of the NF-κB pathway can directly suppress expression of SPARC through a mechanism at the promoter of SPARC, proximal to the transcriptional start site. In summary, we present data elucidating the role and consequences of NF-κB activation in Her2-overexpressing breast cancer

Resolving Australian analogs for an Eocene Patagonian paleorainforest using leaf size and floristics

• Premise of the study: The diverse early Eocene flora from Laguna del Hunco (LH) in Patagonia, Argentina has many nearest living relatives (NLRs) in Australasia but few in South America, indicating the differential survival of an ancient, trans‐Antarctic rainforest biome. To better understand this significant biogeographic pattern, we used detailed comparisons of leaf size and floristics to quantify the legacy of LH across a large network of Australian rainforest‐plot assemblages. • Methods: We applied vein scaling, a new method for estimating the original areas of fragmented leaves. We then compared leaf size and floristics at LH with living Australian assemblages and tabulated the climates of those where NLRs occur, along with additional data on climatic ranges of “ex‐Australian” NLRs that survive outside of Australia. • Key results: Vein scaling estimated areas as accurately as leaf‐size classes. Applying vein scaling to fossil fragments increased the grand mean area of LH by 450 mm2, recovering more originally large leaves. The paleoflora has a majority of microphyll leaves, comparable to leaf litter in subtropical Australian forests, which also have the greatest floristic similarity to LH. Tropical Australian assemblages also share many taxa with LH, and ex‐Australian NLRs mostly inhabit cool, wet montane habitats no longer present in Australia. • Conclusions: Vein scaling is valuable for improving the resolution of fossil leaf‐size distributions by including fragmented specimens. The legacy of LH is evident not only in subtropical and tropical Australia but also in tropical montane Australasia and Southeast Asia, reflecting the disparate histories of surviving Gondwanan lineages.Fil: Merkhofer, Lisa. State University of Pennsylvania; Estados UnidosFil: Wilf, Peter. State University of Pennsylvania; Estados UnidosFil: Haas, M. Tyler. State University of Pennsylvania; Estados UnidosFil: Kooyman, Robert M.. Macquarie University; AustraliaFil: Sack, Lawren. University of California at Los Angeles; Estados UnidosFil: Scoffoni, Christine. University of California at Los Angeles; Estados UnidosFil: Cúneo, Néstor Rubén. Museo Paleontológico Egidio Feruglio; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Risk-based prioritization of the Idaho National Engineering Laboratory Environmental Programs

This paper describes an application of a formal prioritization system to help the Idaho National Engineering Laboratory (INEL) allocate funds for environmental projects. The system, known as the Laboratory Integration and Prioritization System (LIPS), was jointly developed by Los Alamos National Laboratory (LANL), Lawrence Livermore National Laboratory (LLNL), Sandia National Laboratories (SNL), and the US Department of Energy (DOE). LIPS is based on a formal approach for multi-criteria decision-making known as multiattribute utility analysis. The system is designed to provide a logical, practical, and equitable means for estimating and comparing the benefits to be obtained from funding project work

IKKα and IKKβ each function to regulate NF-κB activation in the TNF-induced/canonical pathway

Background: Activation of the transcription factor NF-κB by cytokines is rapid, mediated through the activation of the IKK complex with subsequent phosphorylation and degradation of the inhibitory IκB proteins. The IKK complex is comprised of two catalytic subunits, IKKα and IKKβ, and a regulatory protein known as NEMO. Using cells from mice that are genetically deficient in IKKβ or IKKα, or using a kinase inactive mutant of IKKβ, it has been proposed that IKKβ is critical for TNF-induced IκB phosphorylation/degradation through the canonical pathway while IKKα has been shown to be involved in the non-canonical pathway for NF-κB activation. These conclusions have led to a focus on development of IKKβ inhibitors for potential use in inflammatory disorders and cancer. Methodology: Analysis of NF-κB activation in response to TNF in MEFs reveals that IKKβ is essential for efficient phosphorylation and subsequent degradation of IκBα, yet IKKα contributes to the NF-κB activation response in these cells as measured via DNA binding assays. In HeLa cells, both IKKα and IKKβ contribute to IκBα phosphorylation and NF-κB activation. A kinase inactive mutant of IKKβ, which has been used as evidence for the critical importance of IKKβ in TNF-induced signaling, blocks activation of NF-κB induced by IKKα, even in cells that are deficient in IKKβ. Conclusions: These results demonstrate the importance of IKKα in canonical NF-κB activation, downstream of cytokine treatment of cells. The experiments suggest that IKKα will be a therapeutic target in inflammatory disorders

APRICOT: A Dataset of Physical Adversarial Attacks on Object Detection

Physical adversarial attacks threaten to fool object detection systems, but reproducible research on the real-world effectiveness of physical patches and how to defend against them requires a publicly available benchmark dataset. We present APRICOT, a collection of over 1,000 annotated photographs of printed adversarial patches in public locations. The patches target several object categories for three COCO-trained detection models, and the photos represent natural variation in position, distance, lighting conditions, and viewing angle. Our analysis suggests that maintaining adversarial robustness in uncontrolled settings is highly challenging, but it is still possible to produce targeted detections under white-box and sometimes black-box settings. We establish baselines for defending against adversarial patches through several methods, including a detector supervised with synthetic data and unsupervised methods such as kernel density estimation, Bayesian uncertainty, and reconstruction error. Our results suggest that adversarial patches can be effectively flagged, both in a high-knowledge, attack-specific scenario, and in an unsupervised setting where patches are detected as anomalies in natural images. This dataset and the described experiments provide a benchmark for future research on the effectiveness of and defenses against physical adversarial objects in the wild.Comment: 23 pages, 14 figures, 3 tables. Updated version as accepted to ECCV 202

Her2 activates NF-κB and induces invasion through the canonical pathway involving IKKα

The membrane bound receptor tyrosine kinase Her2 is overexpressed in approximately 30% of human breast cancers which correlates with poor prognosis. Her2-induced signaling pathways include MAPK and PI3K/Akt, of which the latter has been shown to be critical for Her2+ breast cancer cell growth and survival. Additionally, the NF-κB pathway has been shown to be activated downstream of Her2 overexpression, however the mechanisms leading to this activation are not currently clear. Using Her2+/ER- breast cancer cells, we show that Her2 activates NF-κB through the canonical pathway which, surprisingly, involves IKKα. Knockdown of IKKα led to a significant decrease in transcription levels of multiple NF-κB-regulated cytokine and chemokine genes. siRNA-mediated knockdown of IKKα resulted in a decrease in cancer cell invasion, but had no effect on cell proliferation. Inhibition of the PI3K/Akt pathway had no effect on NF-κB activation, but significantly inhibited cell proliferation. Our study suggests different roles for the NF-κB and PI3K pathways downstream of Her2, leading to changes in invasion and proliferation of breast cancer cells. Additionally this work indicates the importance of IKKα as a mediator of Her2-induced tumor progression

An Integrated Multicriteria Decision-Making Approach for Evaluating Nuclear Fuel Cycle Systems for Long-term Sustainability on the Basis of an Equilibrium Model: Technique for Order of Preference by Similarity to Ideal Solution, Preference Ranking Organization Method for Enrichment Evaluation, and Multiattribute Utility Theory Combined with Analytic Hierarchy Process

The focus on the issues surrounding spent nuclear fuel and lifetime extension of old nuclear power plants continues to grow nowadays. A transparent decision-making process to identify the best suitable nuclear fuel cycle (NFC) is considered to be the key task in the current situation. Through this study, an attempt is made to develop an equilibrium model for the NFC to calculate the material flows based on 1 TWh of electricity production, and to perform integrated multicriteria decision-making method analyses via the analytic hierarchy process technique for order of preference by similarity to ideal solution, preference ranking organization method for enrichment evaluation, and multiattribute utility theory methods. This comparative study is aimed at screening and ranking the three selected NFC options against five aspects: sustainability, environmental friendliness, economics, proliferation resistance, and technical feasibility. The selected fuel cycle options include pressurized water reactor (PWR) once-through cycle, PWR mixed oxide cycle, or pyroprocessing sodium-cooled fast reactor cycle. A sensitivity analysis was performed to prove the robustness of the results and explore the influence of criteria on the obtained ranking. As a result of the comparative analysis, the pyroprocessing sodium-cooled fast reactor cycle is determined to be the most competitive option among the NFC scenarios.ope

NF-κB, stem cells and breast cancer: the links get stronger

Self-renewing breast cancer stem cells are key actors in perpetuating tumour existence and in treatment resistance and relapse. The molecular pathways required for their maintenance are starting to be elucidated. Among them is the transcription factor NF-κB, which is known to play critical roles in cell survival, inflammation and immunity. Recent studies indicate that mammary epithelial NF-κB regulates the self-renewal of breast cancer stem cells in a model of Her2-dependent tumourigenesis. We will describe here the NF-κB-activating pathways that are involved in this process and in which progenitor cells this transcription factor is actually activated