The SuperCam Instrument Suite on the Mars 2020 Rover: Science Objectives and Mast-Unit Description

On the NASA 2020 rover mission to Jezero crater, the remote determination of the texture, mineralogy and chemistry of rocks is essential to quickly and thoroughly characterize an area and to optimize the selection of samples for return to Earth. As part of the Perseverance payload, SuperCam is a suite of five techniques that provide critical and complementary observations via Laser-Induced Breakdown Spectroscopy (LIBS), Time-Resolved Raman and Luminescence (TRR/L), visible and near-infrared spectroscopy (VISIR), high-resolution color imaging (RMI), and acoustic recording (MIC). SuperCam operates at remote distances, primarily 2-7 m, while providing data at sub-mm to mm scales. We report on SuperCam's science objectives in the context of the Mars 2020 mission goals and ways the different techniques can address these questions. The instrument is made up of three separate subsystems: the Mast Unit is designed and built in France; the Body Unit is provided by the United States; the calibration target holder is contributed by Spain, and the targets themselves by the entire science team. This publication focuses on the design, development, and tests of the Mast Unit; companion papers describe the other units. The goal of this work is to provide an understanding of the technical choices made, the constraints that were imposed, and ultimately the validated performance of the flight model as it leaves Earth, and it will serve as the foundation for Mars operations and future processing of the data.In France was provided by the Centre National d'Etudes Spatiales (CNES). Human resources were provided in part by the Centre National de la Recherche Scientifique (CNRS) and universities. Funding was provided in the US by NASA's Mars Exploration Program. Some funding of data analyses at Los Alamos National Laboratory (LANL) was provided by laboratory-directed research and development funds

Determinants of the access to remote specialised services provided by national sarcoma reference centres

BACKGROUND: Spatial inequalities in cancer management have been evidenced by studies reporting lower quality of care or/and lower survival for patients living in remote or socially deprived areas. NETSARC+ is a national reference network implemented to improve the outcome of sarcoma patients in France since 2010, providing remote access to specialized diagnosis and Multidisciplinary Tumour Board (MTB). The IGéAS research program aims to assess the potential of this innovative organization, with remote management of cancers including rare tumours, to go through geographical barriers usually impeding the optimal management of cancer patients. METHODS: Using the nationwide NETSARC+ databases, the individual, clinical and geographical determinants of the access to sarcoma-specialized diagnosis and MTB were analysed. The IGéAS cohort (n = 20,590) includes all patients living in France with first sarcoma diagnosis between 2011 and 2014. Early access was defined as specialised review performed before 30 days of sampling and as first sarcoma MTB discussion performed before the first surgery. RESULTS: Some clinical populations are at highest risk of initial management without access to sarcoma specialized services, such as patients with non-GIST visceral sarcoma for diagnosis [OR 1.96, 95% CI 1.78 to 2.15] and MTB discussion [OR 3.56, 95% CI 3.16 to 4.01]. Social deprivation of the municipality is not associated with early access on NETSARC+ remote services. The quintile of patients furthest away from reference centres have lower chances of early access to specialized diagnosis [OR 1.18, 95% CI 1.06 to 1.31] and MTB discussion [OR 1.24, 95% CI 1.10 to 1.40] but this influence of the distance is slight in comparison with clinical factors and previous studies on the access to cancer-specialized facilities. CONCLUSIONS: In the context of national organization driven by reference network, distance to reference centres slightly alters the early access to sarcoma specialized services and social deprivation has no impact on it. The reference networks' organization, designed to improve the access to specialized services and the quality of cancer management, can be considered as an interesting device to reduce social and spatial inequalities in cancer management. The potential of this organization must be confirmed by further studies, including survival analysis

CIBERER : Spanish national network for research on rare diseases: A highly productive collaborative initiative

Altres ajuts: Instituto de Salud Carlos III (ISCIII); Ministerio de Ciencia e Innovación.CIBER (Center for Biomedical Network Research; Centro de Investigación Biomédica En Red) is a public national consortium created in 2006 under the umbrella of the Spanish National Institute of Health Carlos III (ISCIII). This innovative research structure comprises 11 different specific areas dedicated to the main public health priorities in the National Health System. CIBERER, the thematic area of CIBER focused on rare diseases (RDs) currently consists of 75 research groups belonging to universities, research centers, and hospitals of the entire country. CIBERER's mission is to be a center prioritizing and favoring collaboration and cooperation between biomedical and clinical research groups, with special emphasis on the aspects of genetic, molecular, biochemical, and cellular research of RDs. This research is the basis for providing new tools for the diagnosis and therapy of low-prevalence diseases, in line with the International Rare Diseases Research Consortium (IRDiRC) objectives, thus favoring translational research between the scientific environment of the laboratory and the clinical setting of health centers. In this article, we intend to review CIBERER's 15-year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions toward the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to RD research

HGG-44. STRESSED TO DEATH: EGFRvIII EXPRESSION RENDERS GLIOBLASTOMA CELLS MORE SENSITIVE TO ER STRESS INDUCING CHEMOTHERAPEUTICS

Epidermal growth factor receptor (EGFR) is often overexpressed and/or mutated cancer. The most common mutation is EGFRvIII and has been found to correlate with tumor aggressiveness and poor outcome. In glioblastoma (GBM) expression of EGFRvIII is linked to cell-signaling pathways required for increased cell proliferation, cancer stem-cell self-renewal and tumor invasiveness. Although the mechanisms by which EGFRvIII confers increased tumorigenecity are not fully understood, recent evidence suggests that endoplasmic reticulum (ER) proteostasis plays a key role in tumor aggressiveness and resistance to therapy. Here we sought to determine the role of EGFRvIII expression on GBM ER stressed-induced cell death. U87 and U87 EGFRviii expressing cells were exposed to the following ER stress inducers: 2-deoxy-D-glucose (2-DG, 0.5mM), velcade (10nM), tunicamycin (0.05ug/ml) or withaferin A (WA, 1uM) and viability determined by MTS assay. EGFRvIII expressing cells were approximately 2-fold more sensitive to these ER stress inducers; viability of 2-DG, velcade, tunicamycin and WA treated U87 cells was 71.1 + 3.6%, 92.5 + 2.7%, 55.3 + 3.8% and 77.2 + 6%, respectfully, verses 24.5 + 1.1%, 46.8 + 3, 22.7 + 2.1% and 19.5%, respectfully in EGFRvIII expressing U87 cells. Western blot analysis demonstrated higher levels of ER stress markers, GRP78 and CHOP. Effective mediation of ER stress is necessary for cancer cells to maintain uncontrolled growth and enhanced protein production. However this dependence provides a target for treatment intervention. Our data suggests that patients whose tumors express EGFRvIII may benefit from ER stress inducing chemotherapies

E-Cigarettes: A Review of New Trends in Cannabis Use

The emergence of electronic cigarettes (e-cigs) has given cannabis smokers a new method of inhaling cannabinoids. E-cigs differ from traditional marijuana cigarettes in several respects. First, it is assumed that vaporizing cannabinoids at lower temperatures is safer because it produces smaller amounts of toxic substances than the hot combustion of a marijuana cigarette. Recreational cannabis users can discretely “vape” deodorized cannabis extracts with minimal annoyance to the people around them and less chance of detection. There are nevertheless several drawbacks worth mentioning: although manufacturing commercial (or homemade) cannabinoid-enriched electronic liquids (e-liquids) requires lengthy, complex processing, some are readily on the Internet despite their lack of quality control, expiry date, and conditions of preservation and, above all, any toxicological and clinical assessment. Besides these safety problems, the regulatory situation surrounding e-liquids is often unclear. More simply ground cannabis flowering heads or concentrated, oily THC extracts (such as butane honey oil or BHO) can be vaped in specially designed, pen-sized marijuana vaporizers. Analysis of a commercial e-liquid rich in cannabidiol showed that it contained a smaller dose of active ingredient than advertised; testing our laboratory-made, purified BHO, however, confirmed that it could be vaped in an e-cig to deliver a psychoactive dose of THC. The health consequences specific to vaping these cannabis preparations remain largely unknown and speculative due to the absence of comprehensive, robust scientific studies. The most significant health concerns involve the vaping of cannabinoids by children and teenagers. E-cigs could provide an alternative gateway to cannabis use for young people. Furthermore, vaping cannabinoids could lead to environmental and passive contamination

Harangue faicte en l'assemblée generale des trois Estatz de France, le second jour d'avril, par le... Duc de Feria... : avec la lettre de sa majesté catholique... : ensemble la responce de... Cardinal de Pellevé...

[Actos reales. 1593-01-02

THE ROLE OF SOLVENT QUALITY AND OF COMPETITIVE ADSORPTION ON THE EFFICIENCY OF SUPERPLASTICIZERS IN ALKALI-ACTIVATED SLAG PASTES

The loss of dispersing ability by polycarboxylates ether superplasticizers in alkali-activated slag cements has been widely reported. However, no clear-cut explanation of this phenomenon can be found to date. Therefore, the behaviour of poly(methacrylate-g-poly(ethylene glycol)) superplasticizers in NaOH or Na2CO3 -activated slag pastes was investigated. The observed loss of efficiency of the polymer was not due to a specific property of the slag particles, nor to structural degradation of the polymer in the alkaline solutions. Actually, the ionic strength of the activating solution decreased the solvent quality and changed the polymer conformation, leading to a deterioration of the steric repulsion brought by the side-chains. Moreover, in the Na2CO3 -activated systems, the adsorption behaviour of the polymers was also significantly altered. Here, this was not caused by a low calcium concentration or by a preferential adsorption of the superplasticizer on calcite crystallites. The most plausible explanation was a competitive adsorption with CO32- ions

The contribution of ketone bodies to glycolytic inhibition for the treatment of adult and pediatric glioblastoma

Glioblastoma (GBM) remains one of the most lethal primary brain tumors in children and adults. Targeting tumor metabolism has emerged as a promising-targeted therapeutic strategy for GBM and characteristically resistant GBM stem-like cells (GSCs). Gene expression data was obtained from the online patient-histology database, GlioVis. GSC mitochondria morphology was examined by TEM. Cell viability and effect on GSC self-renewal was determined via MTS assay and neurosphere assay, respectively. Proteins were evaluated by Western Blot. Enzymes necessary for ketone catabolism (BDH1, OXCT1 and ACAT1) are significantly downregulated in adult and pediatric GBM. GSC mitochondrial ultrastructure suggested defects in oxidative phosphorylation. Treatment of both GBM and GSC cell lines resulted in dose-dependent decreases in viability in response to glycolytic inhibitor 2-deoxy-D-glucose (2-DG), and ketone body Acetoacetate (AA), but not β-hydroxybutyrate (βHB). AA induced apoptosis was confirmed by western blot analysis, indicating robust caspase activation and PARP cleavage. AA reduced neurosphere formation at concentrations as low as 1 mM. Combined treatment of low dose 2-DG (50 μM) with AA resulted in more cell death than either treatment alone. The effect was greater than additive at low concentrations of AA, reducing viability approximately 50% at 1 mM AA. AA was found to directly upregulate mitochondrial uncoupling protein 2 (UCP2), which may explain this potential drug synergism via multi-faceted inhibition of the glycolytic pathway. Targeting the metabolic pathway of GBM via glycolytic inhibition in conjunction with ketogenic diet or exogenous ketone body supplementation warrants further investigation as a promising adjunctive treatment to conventional therapy

Abstract B41: Withaferin A promotes ROS-mediated differentiation of neuroblastoma

Abstract Background: Neuroblastoma (NB), the most common extra-cranial solid tumor in children, originates from the precursor neuroblasts of the sympathetic nervous system. NB accounts for approximately 7-10% of childhood cancers and 15% of childhood cancer death. Despite an aggressive treatment regimen, the 5-year survival for high risk NB remains less than 50%. The differentiation of NB cells into mature cells represents a promising strategy for NB therapy. Currently, retinoids are the most commonly used differentiating agents. However, their use can be limited due to intrinsic or acquired resistance, as well as toxicity. We sought to evaluate the potential of the natural product withaferin A (WA), a steroidal lactone derived from the medicinal plant Withania somnifera, to induce NB cell differentiation. Methods: For differentiation studies NB cell lines (NB1691, SMS-KCNR, SH-SY5Y and the primary cell line SVBM15) were exposed to WA (100-500nM) for 7-10 days and evaluated by light microscopy, immunocytochemistry and western blot analysis. NB stem-like cell lines were generated by culturing NB1691 and SVBM15 cells in neurosphere media. To determine the IC50 (concentration needed to reduce viability by 50%), NB stem-like cell lines were exposed to increasing concentrations of WA and viability was assessed at 72 hours using MTS assay. Reactive oxygen species (ROS) were detected using CM-H2DFDA and ROS induction was inhibited with N-acetyl-L- Cysteine (NAC). To determine WA effect on neurosphere formation, NB cells were plated in 96-well plates at 50 cells/well. Cells were grown in increasing concentrations of WA and spheres were counted at 14 days. Results: WA promoted morphologic alterations (neurite outgrowth) and growth inhibition in a dose dependent manner. Immunocytochemistry and western blot analysis indicated an increase in neuronal markers including neurofilament, β-tubulin and MAP2, as well as a decrease in the stem cell markers BMi-1 and musashi. WA promoted ROS induction, which could be prevented with NAC pretreatment. NAC prevented WA-induced morphological changes and inhibited WA-induced changes in stem cell and differentiation marker expression. WA induced NB stem-like cell death in a dose dependent manner (IC50 of NB1691=1.05 μM; SVBM15=1.06 μM), and significantly inhibited neurosphere formation at concentrations as low as 50nM, which did not exhibit cytotoxicity in regular cell culture conditions. Conclusion: Withania somnifera has been used for centuries and is commonly used in ayurvedic medicine. WA has been shown to affect multiple pathways important for cancer progression and induce anti-cancer effects in breast, prostate and pancreatic cancers. Our data indicates that WA induces NB stem-like cell death, and promotes ROS-mediated NB cell differentiation. Differentiation therapy aims at reducing the risk of the tumor regrowth following high-dose chemotherapy and stem cell transplant in patients classified as high-risk. WA holds great promise as a novel alternative NB treatment strategy for children with persistent minimal residual disease. Citation Format: Gregor A. Rodriguez, Claudia P. Zapata, Anthony Sanchez, Nicolas A. De Cordoba, Beatriz E. Hawkins, Nadia G. Myrthil, Sarah A. Samuels, Amelia Bahamonde, Steven Vanni, Regina M. Graham. Withaferin A promotes ROS-mediated differentiation of neuroblastoma. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Pediatric Cancer Research: From Mechanisms and Models to Treatment and Survivorship; 2015 Nov 9-12; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Res 2016;76(5 Suppl):Abstract nr B41.</jats:p