AERO: Auroral Emission Radio Observer

Earth’s aurora has a deep complexity and richness that is of intense interest for our understanding of space physics, with many unknown or ill-defined features. Auroral radio emissions in the LF and HF frequency range allow radio remote sensing, leading to investigation of nonlinear wave processes and wave-particle interactions operating in a broad range of heliospheric, planetary and astrophysical plasmas. The Auroral Emission Radio Observer (AERO) is a one-year CubeSat mission in polar orbit that will significantly advance our knowledge by examining radio emissions from the auroral acceleration region in near-Earth space. AERO uses a unique electromagnetic vector sensor (VS) to study AKR at LF and HF frequencies (100 kHz – 5 MHz) with six orthogonal dipole and loop antennas giving angle of arrival and polarization information within a single unit. The mission will store many orbits of compressed data on board, then select download segments based either on summary spectrogram ground analysis or on automatic detection of bright auroral radio events. AERO is also a stepping stone to a novel spaceborne high capability remote sensing platform for diverse scientific targets such as radio emission from the solar corona and inner heliosphere, and anisotropic turbulence properties of interplanetary medium plasma

Design and Verification of a Clock System for Orbital Radio Interferometry

Radio interferometry using multiple small satellites will enable measurements with high angular resolution for remote sensing and astronomy. The NASA sponsored Auroral Emissions Radio Explorer (AERO) and Vector Interferometry Space Technology using AERO (VISTA) CubeSats will demonstrate orbital interferometry from 0.1 MHz to 15 MHz, frequencies which are largely blocked by the ionosphere. We report on the design and testing of a clock system for radio interferometry between these orbital receivers. We discuss the clock system design up to PCB fabrication, including requirements flow and major hardware trades. The performance of the timing components has been verified using a phase noise test set with a high-quality benchtop crystal. While these results are presented for the AERO-VISTA mission payload, they are more generally applicable to any orbital interferometry platform with multiple satellites

NASA Strategic Roadmap Summary Report

In response to the Vision, NASA commissioned strategic and capability roadmap teams to develop the pathways for turning the Vision into a reality. The strategic roadmaps were derived from the Vision for Space Exploration and the Aldrich Commission Report dated June 2004. NASA identified 12 strategic areas for roadmapping. The Agency added a thirteenth area on nuclear systems because the topic affects the entire program portfolio. To ensure long-term public visibility and engagement, NASA established a committee for each of the 13 areas. These committees - made up of prominent members of the scientific and aerospace industry communities and senior government personnel - worked under the Federal Advisory Committee Act. A committee was formed for each of the following program areas: 1) Robotic and Human Lunar Exploration; 2) Robotic and Human Exploration of Mars; 3) Solar System Exploration; 4) Search for Earth-Like Planets; 5) Exploration Transportation System; 6) International Space Station; 7) Space Shuttle; 8) Universe Exploration; 9) Earth Science and Applications from Space; 10) Sun-Solar System Connection; 11) Aeronautical Technologies; 12) Education; 13) Nuclear Systems. This document contains roadmap summaries for 10 of these 13 program areas; The International Space Station, Space Shuttle, and Education are excluded. The completed roadmaps for the following committees: Robotic and Human Exploration of Mars; Solar System Exploration; Search for Earth-Like Planets; Universe Exploration; Earth Science and Applications from Space; Sun-Solar System Connection are collected in a separate Strategic Roadmaps volume. This document contains memebership rosters and charters for all 13 committees

AERO & VISTA: Demonstrating HF Radio Interferometry with Vector Sensors

AERO (Auroral Emission Radio Observer) and VISTA (Vector Interferometry Space Technology using AERO) are recently selected NASA HTIDeS CubeSat missions for terrestrial auroral science and radio interferometric technology demonstration. The AERO and VISTA CubeSats both host vector sensing antenna systems providing advanced electromagnetic capabilities. Together, they will provide the first in-space demonstration of interferometric imaging, beamforming, and nulling using electromagnetic vector sensors at low frequencies (100 kHz –15 MHz). A key goal of the joint missions’ technology demonstration is to validate theoretical sensor performance modeling indicating that interferometric arrays composed of vector sensors will be able to maintain sensitivity even in the presence of terrestrial interference. If validated in flight, this capability would relax the requirement that space-based low frequency interferometers be placed far from the Earth (e.g. lunar orbit), and the closer communications range will significantly increase the data volume returned from space-based radio telescope systems. The two-spacecraft AERO+VISTA mission will address the auroral science goals of AERO (Erickson et al. 2018, SSC18) while adding three additional technology demonstration goals enabled by the second CubeSat, VISTA

Aurora: A Software Radio for Electromagnetic Vector Sensors in Space

The AERO (Auroral Emission Radio Observer) and VISTA (Vector Interferometry Space Technology using AERO) missions will advance auroral radio science and radio interferometry technology. AERO is intended to qualify and validate electromagnetic vector sensor technology in space while also answering key scientific questions about the nature and sources of auroral radio emissions. These questions cannot be addressed from the ground due to shielding by the ionosphere. VISTA, together with AERO, will provide the first demonstration of interferometric imaging, beamforming, and nulling using electromagnetic vector sensors at low frequencies (100 kHz – 15 MHz) using Space based sensors. A key component of the AERO-VISTA joint mission is the Aurora software radio system which forms the primary mission payload when combined with an electromagnetic vector sensor antenna (VSA). This radio combines the analog, digital, and signal processing necessary to detect and digitize the signals associated with the radio aurora. We provide a detailed discussion of the radio design, implementation, and performance results from early testing of our engineering model units

Superparamagnetic Iron Oxide Nanoparticles Labeling of Bone Marrow Stromal (Mesenchymal) Cells Does Not Affect Their “Stemness”

Superparamagnetic iron oxide nanoparticles (SPION) are increasingly used to label human bone marrow stromal cells (BMSCs, also called “mesenchymal stem cells”) to monitor their fate by in vivo MRI, and by histology after Prussian blue (PB) staining. SPION-labeling appears to be safe as assessed by in vitro differentiation of BMSCs, however, we chose to resolve the question of the effect of labeling on maintaining the “stemness” of cells within the BMSC population in vivo. Assays performed include colony forming efficiency, CD146 expression, gene expression profiling, and the “gold standard” of evaluating bone and myelosupportive stroma formation in vivo in immuncompromised recipients. SPION-labeling did not alter these assays. Comparable abundant bone with adjoining host hematopoietic cells were seen in cohorts of mice that were implanted with SPION-labeled or unlabeled BMSCs. PB+ adipocytes were noted, demonstrating their donor origin, as well as PB+ pericytes, indicative of self-renewal of the stem cell in the BMSC population. This study confirms that SPION labeling does not alter the differentiation potential of the subset of stem cells within BMSCs

Regulation of thymocyte positive selection and motility by GIT2

Thymocytes are highly motile cells that migrate under the influence of chemokines in distinct thymic compartments as they mature. The motility of thymocytes is tightly regulated; however, the molecular mechanisms that control thymocyte motility are not well understood. Here we report that G protein–coupled receptor kinase-interactor 2 (GIT2) was required for efficient positive selection. Notably, Git2−/− double-positive thymocytes showed greater activation of the small GTPase Rac, actin polymerization and migration toward the chemokines CXCL12 (SDF-1) and CCL25 in vitro. By two-photon laser-scanning microscopy, we found that the scanning activity of Git2−/− thymocytes was compromised in the thymic cortex, which suggests GIT2 has a key role in regulating the chemokine-mediated motility of double-positive thymocytes.National Institutes of Health (U.S.) (R01AI064227)Leukemia & Lymphoma Society of Americ

Glutaminolysis and fumarate accumulation integrate immunometabolic and epigenetic programs in trained immunity

Induction of trained immunity (innate immune memory) is mediated by activation of immune and metabolic pathways that result in epigenetic rewiring of cellular functional programs. Through network-level integration of transcriptomics and metabolomics data, we identify glycolysis, glutaminolysis, and the cholesterol synthesis pathway as indispensable for the induction of trained immunity by ß-glucan in monocytes. Accumulation of fumarate, due to glutamine replenishment of the TCA cycle, integrates immune and metabolic circuits to induce monocyte epigenetic reprogramming by inhibiting KDM5 histone demethylases. Furthermore, fumarate itself induced an epigenetic program similar to ß-glucan-induced trained immunity. In line with this, inhibition of glutaminolysis and cholesterol synthesis in mice reduced the induction of trained immunity by ß-glucan. Identification of the metabolic pathways leading to induction of trained immunity contributes to our understanding of innate immune memory and opens new therapeutic avenues.Netherlands Organization for Scientific Research (NWO). B.N. is supported by an NHMRC (Australia) CJ Martin Early Career Fellowship. N.P.R. Netherlands Heart Foundation (2012T051). N.P.R. and M.G.N. received a H2020 grant (H2020-PHC-2015-667873-2) from the European Union (grant agreement 667837). Fundação para a Ciência e Tecnologia, FCT (IF/00735/2014 to A.C., IF/00021/2014 to R.S., RECI/BBB-BQB/0230/2012 to L.G.G., and SFRH/BPD/96176/2013 to C. Cunha). The NMR spectrometers are part of the National NMR Facility supported by FCT (RECI/BBB-BQB/0230/2012). The research leading to these results received funding from the Fundação para a Ciência e Tecnologia (FCT), cofunded by Programa Operacional Regional do Norte (ON.2—O Novo Norte); from the Quadro de Referência Estratégico Nacional (QREN) through the Fundo Europeu de Desenvolvimento Regional (FEDER) and from the Projeto Estratégico – LA 26 – 2013–2014 (PEst-C/SAU/LA0026/2013). NIH (DK43351 and DK097485) and Helmsley Trust. D.L.W. is supported, in part, by the NIH (GM53522, GM083016, GM119197, and C06RR0306551

Cancer stem cell metabolism: A potential target for cancer therapy

© 2016 The Author(s). Cancer Stem cells (CSCs) are a unipotent cell population present within the tumour cell mass. CSCs are known to be highly chemo-resistant, and in recent years, they have gained intense interest as key tumour initiating cells that may also play an integral role in tumour recurrence following chemotherapy. Cancer cells have the ability to alter their metabolism in order to fulfil bio-energetic and biosynthetic requirements. They are largely dependent on aerobic glycolysis for their energy production and also are associated with increased fatty acid synthesis and increased rates of glutamine utilisation. Emerging evidence has shown that therapeutic resistance to cancer treatment may arise due to dysregulation in glucose metabolism, fatty acid synthesis, and glutaminolysis. To propagate their lethal effects and maintain survival, tumour cells alter their metabolic requirements to ensure optimal nutrient use for their survival, evasion from host immune attack, and proliferation. It is now evident that cancer cells metabolise glutamine to grow rapidly because it provides the metabolic stimulus for required energy and precursors for synthesis of proteins, lipids, and nucleic acids. It can also regulate the activities of some of the signalling pathways that control the proliferation of cancer cells. This review describes the key metabolic pathways required by CSCs to maintain a survival advantage and highlights how a combined approach of targeting cellular metabolism in conjunction with the use of chemotherapeutic drugs may provide a promising strategy to overcome therapeutic resistance and therefore aid in cancer therapy

Thrombospondin-2 and SPARC/osteonectin are critical regulators of bone remodeling

Thrombospondin-2 (TSP2) and osteonectin/BM-40/SPARC are matricellular proteins that are highly expressed by bone cells. Mice deficient in either of these proteins show phenotypic alterations in the skeleton, and these phenotypes are most pronounced under conditions of altered bone remodeling. For example, TSP2-null mice have higher cortical bone volume and are resistant to bone loss associated with ovariectomy, whereas SPARC-null mice have decreased trabecular bone volume and fail to demonstrate an increase in bone mineral density in response to a bone-anabolic parathyroid hormone treatment regimen. In vitro, marrow stromal cell (MSC) osteoprogenitors from TSP2-null mice have increased proliferation but delayed formation of mineralized matrix. Similarly, in cultures of SPARC-null MSCs, osteoblastic differentiation and mineralized matrix formation are decreased. Overall, both TSP2 and SPARC positively influence osteoblastic differentiation. Intriguingly, both of these matricellular proteins appear to impact MSC fate through mechanisms that could involve the Notch signaling system. This review provides an overview of the role of TSP2 and SPARC in regulating bone structure, function, and remodeling, as determined by both in vitro and in vivo studies