Immunotherapy of Neuroblastoma: Facts and Hopes

While the adoption of multimodal therapy including surgery, radiation, and aggressive combination-chemotherapy has improved outcomes for many children with high-risk neuroblastoma, we appear to have reached a plateau in what can be achieved with cytotoxic therapies alone. Most children with cancer, including high-risk neuroblastoma, do not benefit from treatment with immune-checkpoint-inhibitors (ICI) that have revolutionized the treatment of many highly immunogenic adult solid tumors. This likely reflects the low tumor mutation burden as well as the downregulated MHC-I that characterizes most high-risk neuroblastomas. For these reasons, neuroblastoma represents an immunotherapeutic challenge that may be a model for the creation of effective immunotherapy for other "cold" tumors in children and adults that do not respond to ICI. The identification of strong expression of the disialoganglioside, GD2, on the surface of nearly all neuroblastoma cells provided a target for immune recognition by anti-GD2 mAbs which recruit Fc-receptor-expressing innate immune cells that mediate cytotoxicity or phagocytosis. Adoption of anti-GD2 antibodies into both upfront and relapse treatment protocols has dramatically increased survival rates and altered the landscape for children with high-risk neuroblastoma. This review describes how these approaches have been expanded to additional combinations and forms of immunotherapy that have already demonstrated clear clinical benefit. We also describe the efforts to identify additional immune targets for neuroblastoma. Finally we summarize newer approaches being pursued that may well help both innate and adaptive immune cells, endogenous or genetically engineered, to more effectively destroy neuroblastoma cells, in order to better induce complete remission and prevent recurrence

Minority women officers in the Navy: past, present, and future prospects

This thesis is exploratory in nature and looks at the history, current status, and prospects of minority women in the officer corps of the U.S. Navy. The recruiting, promotion, and retention of these women is compared to that of whites, using information provided by the Defense Manpower Data Center and other sources. Research focuses on the period from 1972 through 1990. Overall, the study shows a very positive trend occurring for minority women, especially blacks, with steadily increasing representation in the officer corps. However, potential problem areas are found in the distribution of minority women across occupations and in their related prospects for advancement. In addition, evidence suggests that future participation by minority women may be adversely influenced by the planned reduction of Navy personnel. Several recommendations for further research are made, including the longitudinal tracking of minority women through their promotional flowpoints,http://archive.org/details/minoritywomenoff00turnLieutenant, United States NavyApproved for public release; distribution is unlimited

Status of Kilowatt-Class Stirling Power Conversion Using a Pumped NaK Loop for Thermal Input

Free-piston Stirling power conversion has been identified as a viable option for potential Fission Surface Power (FSP) systems on the Moon and Mars. Proposed systems consist of two or more Stirling convertors, in a dual-opposed configuration, coupled to a low-temperature uranium-dioxide-fueled, liquid-metal-cooled reactor. To reduce developmental risks associated with liquid-metal loop integration, a test rig has been built to evaluate the performance of a pair of 1-kW free-piston Stirling convertors using a pumped sodium-potassium (NaK) loop for thermal energy input. Baseline performance maps have been generated at the Glenn Research Center (GRC) for these 1-kW convertors operating with an electric heat source. Each convertor was then retrofitted with a custom-made NaK heater head and integrated into a pumped NaK system at the Marshall Space Flight Center (MSFC). This paper documents baseline testing at GRC as well as the progress made in integrating the Stirling convertors into the pumped NaK loop

Strain Coupled Domains in BaTiO3(111)-CoFeB Heterostructures

Domain pattern transfer from ferroelectric to ferromagnetic materials is a critical step for the electric field control of magnetism and has the potential to provide new schemes for low-power data storage and computing devices. Here we investigate domain coupling in BaTiO$_3$(111)/CoFeB heterostructures by direct imaging in a wide-field Kerr microscope. The magnetic easy axis is found to locally change direction as a result of the underlying ferroelectric domains and their polarisation. By plotting the remanent magnetisation as a function of angle in the plane of the CoFeB layer, we find that the magnetic easy axes in adjacent domains are angled at 60$^\circ$ or 120$^\circ$, corresponding to the angle of rotation of the polarisation from one ferroelectric domain to the next, and that the magnetic domain walls may be charged or uncharged depending on the magnetic field history. Micromagnetic simulations show that the properties of the domain walls vary depending on the magnetoelastic easy axis configuration and the charged or uncharged nature of the wall. The configuration where the easy axis alternates by 60$^\circ$ and a charged wall is initialised exhibits the largest change in domain wall width from 192 nm to 119 nm as a function of in-plane magnetic field. Domain wall width tuning provides an additional degree of freedom for devices that seek to manipulate magnetic domain walls using strain coupling to ferroelectrics.Comment: 7 pages, 8 figure

Material Studies Related to the Use of NaK Heat Exchangers Coupled to Stirling Heater Heads

NASA has been supporting design studies and technology development that could provide power to an outpost on the Moon, Mars, or an asteroid. Technology development efforts have included fabrication and evaluation of components used in a Stirling engine power conversion system. Destructive material evaluation was performed on a NaK shell heat exchanger that was developed by the NASA Glenn Research Center (GRC) and integrated with a commercial 1 kWe Stirling convertor from Sunpower Incorporated. The NaK Stirling test demonstrated Stirling convertor electrical power generation using a pumped liquid metal heat source under thermal conditions that represent the heat exchanger liquid metal loop in a Fission Power Systems (FPS) reactor. The convertors were operated for a total test time of 66 hr at a maximum temperature of 823 K. After the test was completed and NaK removed, the heat exchanger assembly was sectioned to evaluate any material interactions with the flowing liquid metal. Several dissimilar-metal braze joint options, crucial for the heat exchanger transfer path, were also investigated. A comprehensive investigation was completed and lessons learned for future heat exchanger development efforts are discussed

EORNA, a barley gene and transcript abundance database

A high-quality, barley gene reference transcript dataset (BaRTv1.0), was used to quantify gene and transcript abundances from 22 RNA-seq experiments, covering 843 separate samples. Using the abundance data we developed a Barley Expression Database (EORNA*) to underpin a visualisation tool that displays comparative gene and transcript abundance data on demand as transcripts per million (TPM) across all samples and all the genes. EORNA provides gene and transcript models for all of the transcripts contained in BaRTV1.0, and these can be conveniently identified through either BaRT or HORVU gene names, or by direct BLAST of query sequences. Browsing the quantification data reveals cultivar, tissue and condition specific gene expression and shows changes in the proportions of individual transcripts that have arisen via alternative splicing. TPM values can be easily extracted to allow users to determine the statistical significance of observed transcript abundance variation among samples or perform meta analyses on multiple RNA-seq experiments. * Eòrna is the Scottish Gaelic word for Barley.</p

Lateral Load Testing of the Advanced Stirling Convertor (ASC-E2) Heater Head

Free-piston Stirling convertors are fundamental to the development of NASA s next generation of radioisotope power system, the Advanced Stirling Radioisotope Generator (ASRG). The ASRG will use General Purpose Heat Source (GPHS) modules as the energy source and Advanced Stirling Convertors (ASCs) to convert heat into electrical energy, and is being developed by Lockheed Martin under contract to the Department of Energy. Achieving flight status mandates that the ASCs satisfy design as well as flight requirements to ensure reliable operation during launch. To meet these launch requirements, GRC performed a series of quasi-static mechanical tests simulating the pressure, thermal, and external loading conditions that will be experienced by an ASC E2 heater head assembly. These mechanical tests were collectively referred to as lateral load tests since a primary external load lateral to the heater head longitudinal axis was applied in combination with the other loading conditions. The heater head was subjected to the operational pressure, axial mounting force, thermal conditions, and axial and lateral launch vehicle acceleration loadings. To permit reliable prediction of the heater head s structural performance, GRC completed Finite Element Analysis (FEA) computer modeling for the stress, strain, and deformation that will result during launch. The heater head lateral load test directly supported evaluation of the analysis and validation of the design to meet launch requirements. This paper provides an overview of each element within the test and presents assessment of the modeling as well as experimental results of this task

Fact sheet: Using a terrestrial ecosystem survey to estimate the historical density of ponderosa pine trees in northern Arizona

The Terrestrial Ecosystem Survey (TES) delineates ecosystems according to their climate, geology, soils, and potential natural vegetation (U.S. Forest Service 1986). Land managers and planners can use this information to help interpret site suitability for natural regeneration, reforestation, and revegetation potential as well as site suitability for road building, range and timber, range structures (watering sources), and other land uses. However, the TES can be used for other purposes as Ganey and Benoit (2002) demonstrated in their report about identifying potential habitat for Mexican spotted owl on national forest lands. Similarly, Bell and colleagues (2009) used the TES and its specific survey units (TESU) to analyze the characteristics of the Woolsey plots in northern Arizona - plots the Forest Service established in the early 1900s to examine tree regeneration. In our study, we identified historic ponderosa pine densities on various TES mapping units and then correlated our findings with what the TESU predicted we should find