Mars Atmosphere Resource Verification INsitu (MARVIN) - In Situ Resource Demonstration for the Mars 2020 Mission

The making of oxygen from resources in the Martian atmosphere, known as In Situ Resource Utilization (ISRU), has the potential to provide substantial benefits for future robotic and human exploration. In particular, the ability to produce oxygen on Mars for use in propulsion, life support, and power systems can provide significant mission benefits such as a reducing launch mass, lander size, and mission and crew risk. To advance ISRU for possible incorporation into future human missions to Mars, NASA proposed including an ISRU instrument on the Mars 2020 rover mission, through an announcement of opportunity (AO). The purpose of the the Mars Atmosphere Resource Verification INsitu or (MARVIN) instrument is to provide the first demonstration on Mars of oxygen production from acquired and stored Martian atmospheric carbon dioxide, as well as take measurements of atmospheric pressure and temperature, and of suspended dust particle sizes and amounts entrained in collected atmosphere gases at different times of the Mars day and year. The hardware performance and environmental data obtained will be critical for future ISRU systems that will reduce the mass of propellants and other consumables launched from Earth for robotic and human exploration, for better understanding of Mars dust and mitigation techniques to improve crew safety, and to help further define Mars global circulation models and better understand the regional atmospheric dynamics on Mars. The technologies selected for MARVIN are also scalable for future robotic sample return and human missions to Mars using ISRU

High-Level Production of Amorpha-4,11-Diene, a Precursor of the Antimalarial Agent Artemisinin, in Escherichia coli

BACKGROUND: Artemisinin derivatives are the key active ingredients in Artemisinin combination therapies (ACTs), the most effective therapies available for treatment of malaria. Because the raw material is extracted from plants with long growing seasons, artemisinin is often in short supply, and fermentation would be an attractive alternative production method to supplement the plant source. Previous work showed that high levels of amorpha-4,11-diene, an artemisinin precursor, can be made in Escherichia coli using a heterologous mevalonate pathway derived from yeast (Saccharomyces cerevisiae), though the reconstructed mevalonate pathway was limited at a particular enzymatic step. METHODOLOGY/ PRINCIPAL FINDINGS: By combining improvements in the heterologous mevalonate pathway with a superior fermentation process, commercially relevant titers were achieved in fed-batch fermentations. Yeast genes for HMG-CoA synthase and HMG-CoA reductase (the second and third enzymes in the pathway) were replaced with equivalent genes from Staphylococcus aureus, more than doubling production. Amorpha-4,11-diene titers were further increased by optimizing nitrogen delivery in the fermentation process. Successful cultivation of the improved strain under carbon and nitrogen restriction consistently yielded 90 g/L dry cell weight and an average titer of 27.4 g/L amorpha-4,11-diene. CONCLUSIONS/ SIGNIFICANCE: Production of >25 g/L amorpha-4,11-diene by fermentation followed by chemical conversion to artemisinin may allow for development of a process to provide an alternative source of artemisinin to be incorporated into ACTs

The behaviour of political parties and MPs in the parliaments of the Weimar Republic

Copyright @ 2012 The Authors. This is the author's accepted manuscript. The final published article is available from the link below.Analysing the roll-call votes of the MPs of the Weimar Republic we find: (1) that party competition in the Weimar parliaments can be structured along two dimensions: an economic left–right and a pro-/anti-democratic. Remarkably, this is stable throughout the entire lifespan of the Republic and not just in the later years and despite the varying content of votes across the lifespan of the Republic, and (2) that nearly all parties were troubled by intra-party divisions, though, in particular, the national socialists and communists became homogeneous in the final years of the Republic.Zukunftskolleg, University of Konstan

Municipal Wastewater Effluents as a Source of Listerial Pathogens in the Aquatic Milieu of the Eastern Cape Province of South Africa: A Concern of Public Health Importance

We evaluated the effluent quality of an urban wastewater treatment facility in South Africa and its impact on the receiving watershed for a period of 12 months. The prevalence and antimicrobial susceptibility of potential Listeria pathogens (L. ivanovii and L. innocua) and the physicochemical quality of the treated wastewater effluent was assessed, with a view to ascertain the potential health and environmental hazards of the discharged effluent. Total listerial density varied between 2.9 × 100 and 1.2 × 105 cfu/mL; free living Listeria species were more prevalent (84%), compared to Listeria species attached to planktons (59–75%). The treated effluent quality fell short of recommended standards for turbidity, dissolved oxygen, chemical oxygen demand, nitrite, phosphate and Listeria density; while pH, temperature, total dissolved solids and nitrate contents were compliant with target quality limits after treatment. The Listeria isolates (23) were sensitive to three (15%) of the 20 test antibiotics, and showed varying (4.5–91%) levels of resistance to 17 antibiotics. Of seven resistance gene markers assayed, only sulII genes were detected in five (22%) Listeria strains. The study demonstrates a potential negative impact of the wastewater effluent on the receiving environment and suggests a serious public health implication for those who depend on the receiving watershed for drinking and other purposes

Genome-Wide Association Study and Gene Expression Analysis Identifies CD84 as a Predictor of Response to Etanercept Therapy in Rheumatoid Arthritis

Anti-tumor necrosis factor alpha (anti-TNF) biologic therapy is a widely used treatment for rheumatoid arthritis (RA). It is unknown why some RA patients fail to respond adequately to anti-TNF therapy, which limits the development of clinical biomarkers to predict response or new drugs to target refractory cases. To understand the biological basis of response to anti-TNF therapy, we conducted a genome-wide association study (GWAS) meta-analysis of more than 2 million common variants in 2,706 RA patients from 13 different collections. Patients were treated with one of three anti-TNF medications: etanercept (n = 733), infliximab (n = 894), or adalimumab (n = 1,071). We identified a SNP (rs6427528) at the 1q23 locus that was associated with change in disease activity score (ΔDAS) in the etanercept subset of patients (P = 8×10-8), but not in the infliximab or adalimumab subsets (P>0.05). The SNP is predicted to disrupt transcription factor binding site motifs in the 3′ UTR of an immune-related gene, CD84, and the allele associated with better response to etanercept was associated with higher CD84 gene expression in peripheral blood mononuclear cells (P = 1×10-11 in 228 non-RA patients and P = 0.004 in 132 RA patients). Consistent with the genetic findings, higher CD84 gene expression correlated with lower cross-sectional DAS (P = 0.02, n = 210) and showed a non-significant trend for better ΔDAS in a subset of RA patients with gene expression data (n = 31, etanercept-treated). A small, multi-ethnic replication showed a non-significant trend towards an association among etanercept-treated RA patients of Portuguese ancestry (n = 139, P = 0.4), but no association among patients of Japanese ancestry (n = 151, P = 0.8). Our study demonstrates that an allele associated with response to etanercept therapy is also associated with CD84 gene expression, and further that CD84 expression correlates with disease activity. These findings support a model in which CD84 genotypes and/or expression may serve as a useful biomarker for response to etanercept treatment in RA patients of European ancestry. © 2013 Cui et al

Studying the Salt Dependence of the Binding of σ70 and σ32 to Core RNA Polymerase Using Luminescence Resonance Energy Transfer

The study of protein-protein interactions is becoming increasingly important for understanding the regulation of many cellular processes. The ability to quantify the strength with which two binding partners interact is desirable but the accurate determination of equilibrium binding constants is a difficult process. The use of Luminescence Resonance Energy Transfer (LRET) provides a homogeneous binding assay that can be used for the detection of protein-protein interactions. Previously, we developed an LRET assay to screen for small molecule inhibitors of the interaction of σ70 with theβ' coiled-coil fragment (amino acids 100–309). Here we describe an LRET binding assay used to monitor the interaction of E. coli σ70 and σ32 with core RNA polymerase along with the controls to verify the system. This approach generates fluorescently labeled proteins through the random labeling of lysine residues which enables the use of the LRET assay for proteins for which the creation of single cysteine mutants is not feasible. With the LRET binding assay, we are able to show that the interaction of σ70 with core RNAP is much more sensitive to NaCl than to potassium glutamate (KGlu), whereas the σ32 interaction with core RNAP is insensitive to both salts even at concentrations >500 mM. We also find that the interaction of σ32 with core RNAP is stronger than σ70 with core RNAP, under all conditions tested. This work establishes a consistent set of conditions for the comparison of the binding affinities of the E.coli sigma factors with core RNA polymerase. The examination of the importance of salt conditions in the binding of these proteins could have implications in both in vitro assay conditions and in vivo function

Physics Opportunities with the 12 GeV Upgrade at Jefferson Lab

This white paper summarizes the scientific opportunities for utilization of the upgraded 12 GeV Continuous Electron Beam Accelerator Facility (CEBAF) and associated experimental equipment at Jefferson Lab. It is based on the 52 proposals recommended for approval by the Jefferson Lab Program Advisory Committee.The upgraded facility will enable a new experimental program with substantial discovery potential to address important topics in nuclear, hadronic, and electroweak physics.Comment: 64 page

Rethinking megafauna

Concern for megafauna is increasing among scientists and non-scientists. Many studies have emphasized that megafauna play prominent ecological roles and provide important ecosystem services to humanity. But, what precisely are “megafauna”? Here we critically assess the concept of megafauna and propose a goal-oriented framework for megafaunal research. First, we review definitions of megafauna and analyze associated terminology in the scientific literature. Second, we conduct a survey among ecologists and paleontologists to assess the species traits used to identify and define megafauna. Our review indicates that definitions are highly dependent on the study ecosystem and research question, and primarily rely on ad hoc size-related criteria. Our survey suggests that body size is crucial, but not necessarily sufficient, for addressing the different applications of the term megafauna. Thus, after discussing the pros and cons of existing definitions, we propose an additional approach by defining two function-oriented megafaunal concepts: “keystone megafauna” and “functional megafauna”, with its variant “apex megafauna”. Assessing megafauna from a functional perspective could challenge the perception that there may not be a unifying definition of megafauna that can be applied to all eco-evolutionary narratives. In addition, using functional definitions of megafauna could be especially conducive to cross-disciplinary understanding and cooperation, improvement of conservation policy and practice, and strengthening of public perception. As megafaunal research advances, we encourage scientists to unambiguously define how they use the term “megafauna” and to present the logic underpinning their definition

Focused Ion Beam Microfabrication

Contains an introduction, reports on seven research projects and a list of publications.Defense Advanced Research Projects Agency/U.S. Army Research Office Contract DAAL03-88-K-0108National Science Foundation Grant ECS 89-21728U.S. Army Research Office Contract DAAL03-87-K-0126U.S. Navy - Naval Research Laboratory/Micrion Agreement M08774SEMATEC