CSP Hybrid Space Computing for STP-H5/ISEM on ISS

The Space Test Program (STP) at the Department of Defense (DoD) supports the development, evaluation, and advancement of new technologies needed for the future of spaceflight. STP-Houston provides opportunities for DoD and civilian space agencies to perform on-orbit research and technology demonstrations from the International Space Station (ISS). The STP-H5/ISEM (STP-Houston 5, ISS SpaceCube Experiment Mini) payload is scheduled for launch on the upcoming SpaceX 10 mission and will feature new technologies, including a hybrid space computer developed by the NSF CHREC Center, working closely with the NASA SpaceCube Team, known as the CHREC Space Processor (CSP). In this paper, we present the novel concepts behind CSP and the CSPv1 flight technologies on the ISEM mission. The ISEM-CSP system was subjected to environmental testing, including a thermal vacuum test, a vibration test, and two radiation tests, and results were encouraging and are presented. Primary objectives for ISEM-CSP are highlighted, which include processing, compression, and downlink of terrestrial-scene images for display on Earth, and monitoring of upset rates in various subsystems to provide environmental information for future missions. Secondary objectives are also presented, including experiments with features for fault-tolerant computing, reliable middleware services, FPGA partial reconfiguration, device virtualization, and dynamic synthesis

The Ecosystems SAR (EcoSAR) an Airborne P-band Polarimetric InSAR for the Measurement of Vegetation Structure, Biomass and Permafrost

EcoSAR is a new synthetic aperture radar (SAR) instrument being developed at the NASA/ Goddard Space Flight Center (GSFC) for the polarimetric and interferometric measurements of ecosystem structure and biomass. The instrument uses a phased-array beamforming architecture and supports full polarimetric measurements and single pass interferometry. This Instrument development is part of NASA's Earth Science Technology Office Instrument Incubator Program (ESTO IIP)

The Science Performance of JWST as Characterized in Commissioning

This paper characterizes the actual science performance of the James Webb Space Telescope (JWST), as determined from the six month commissioning period. We summarize the performance of the spacecraft, telescope, science instruments, and ground system, with an emphasis on differences from pre-launch expectations. Commissioning has made clear that JWST is fully capable of achieving the discoveries for which it was built. Moreover, almost across the board, the science performance of JWST is better than expected; in most cases, JWST will go deeper faster than expected. The telescope and instrument suite have demonstrated the sensitivity, stability, image quality, and spectral range that are necessary to transform our understanding of the cosmos through observations spanning from near-earth asteroids to the most distant galaxies.Comment: 5th version as accepted to PASP; 31 pages, 18 figures; https://iopscience.iop.org/article/10.1088/1538-3873/acb29

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Innate and Adaptive Immunity in Aging and Alzheimer’s Disease

Alzheimer’s Disease is the most common form of dementia and is the fifth-leading cause of death in people age 65 and older. Unfortunately, no cure currently exists, and the few treatment options may temporarily relieve symptoms but have limited long-term effectiveness. Recent genome-wide association studies (GWAS) have unearthed a strong link between immune-related genes and AD risk. Both the innate and adaptive immune system have been implicated in the progression of AD, and much of the neuroinflammation that exists in this disease is thought to be related to an age-related decline in immune function. Microglia, the innate immune cells of the brain, become a large source of dysfunctional inflammation as they become chronically activated by the amyloid-beta (Aβ) plaques and tau tangles that aggregate in the AD brain. The protective functions of microglia are known to decline with age, yet it is still unclear what separates healthy and pathogenic aging of these cells. T cells, which typically exist in small numbers in the healthy brain, infiltrate the parenchyma in large numbers in response to AD-related inflammation. The mechanisms that recruit T cells to the brain and the effects that these cells have on pathology remain understudied, especially for CD8+ and γδ T cell subpopulations.Chapter 1 of this dissertation explores the interaction of infiltrating T cells with amyloid plaques and tau tangles in AD model mice. In this study, we examined T cells from bone marrow transplantation studies and from immune-intact AD model mice using flow cytometry, immunohistochemistry, and single-cell RNA sequencing. We found evidence of significant infiltration of multiple T cell phenotypes in AD model mice, with CD8+ effector memory T cells forming the largest population. We also found clonal expansion of T cells from mice that developed Aβ pathology or Aβ and tau pathology, but not in mice with tau pathology alone, suggesting that early recruitment and clonal expansion of T cells is primarily amyloid-driven. These experiments provide an important resource for future investigations into the role of CD8+ T cells in AD.Chapter 2 of this dissertation describes the creation of a model of premature aging in human iPSC- derived microglia, which was developed to facilitate research into human-specific age-related dysfunction in microglia. To create an aged phenotype in iPSCs, we induced homozygous genetic knockout of ERCC1, a critical DNA repair enzyme that causes progeroid diseases in patients with near-total loss of ERCC1 expression. In vitro assays and single-cell RNA sequencing of xenotransplanted microglia reveal signs of immune dysfunction, early senescence, and an increase in pro-inflammatory interferon signaling in ERCC1 KO microglia that may indicate a more aged phenotype. While further examination of this model is required, ERCC1 KO in iPSCs provides a platform for testing age-related microglial dysfunction in AD and other neuroinflammatory diseases

Running for exercise mitigates age-related deterioration of walking economy.

Impaired walking performance is a key predictor of morbidity among older adults. A distinctive characteristic of impaired walking performance among older adults is a greater metabolic cost (worse economy) compared to young adults. However, older adults who consistently run have been shown to retain a similar running economy as young runners. Unfortunately, those running studies did not measure the metabolic cost of walking. Thus, it is unclear if running exercise can prevent the deterioration of walking economy.To determine if and how regular walking vs. running exercise affects the economy of locomotion in older adults.15 older adults (69 ± 3 years) who walk ≥ 30 min, 3x/week for exercise, "walkers" and 15 older adults (69 ± 5 years) who run ≥ 30 min, 3x/week, "runners" walked on a force-instrumented treadmill at three speeds (0.75, 1.25, and 1.75 m/s). We determined walking economy using expired gas analysis and walking mechanics via ground reaction forces during the last 2 minutes of each 5 minute trial. We compared walking economy between the two groups and to non-aerobically trained young and older adults from a prior study.Older runners had a 7-10% better walking economy than older walkers over the range of speeds tested (p = .016) and had walking economy similar to young sedentary adults over a similar range of speeds (p =  .237). We found no substantial biomechanical differences between older walkers and runners. In contrast to older runners, older walkers had similar walking economy as older sedentary adults (p =  .461) and ∼ 26% worse walking economy than young adults (p<.0001).Running mitigates the age-related deterioration of walking economy whereas walking for exercise appears to have minimal effect on the age-related deterioration in walking economy