Summary of Space Environment Magnetometer and Particle Replacement Experiment (SEMPRE) Study

As part of the GOES-R series follow on architecture study following the NOAA Satellite Observing System Architecture (NSOSA) study, a study team evaluated the feasibility of accommodating the GOES in-situ instruments (Magnetometer and Particle Detectors) on a dedicated spacecraft with no impact to the overall baseline mission cost assuming two large observatories. The accommodations cost on a primary operational type observatory are non-negligible requiring: a large non-magnetic boom to reduce the impact of the spacecraft interference on the magnetometer; and strict contamination control and magnetic cleanliness to prevent magnetic contamination near the magnetometers. These, along with the additional interface complexities greatly increase the cost of larger spacecraft by extending integration time with a large marching army. By contrast, a dedicated mission provides flexibility in location and refresh rate not afforded when these sensors are launched as secondary payloads. This study performed an informal industry survey of small form-factor instruments currently flying or in process of being developed. The study identified three potential particle detector suites and multiple magnetometers that will satisfy the requirements while having low enough volume and mass to allow accommodation on a rideshare class spacecraft. Using the largest of the identified particle detector suites, the Goddard Space Flight Center Mission Design Lab developed a design for a rideshare spacecraft that will accommodate the particle detector suite and magnetometer. The cost of the spacecraft, based on multiple cost models, is comparable to the cost of accommodating the magnetometer and particle detector suite on two (East and West) larger main observatories

GOES-17 Advanced Baseline Imager Performance Recovery Summary

The 17th Geostationary Operational Environmental Satellite (GOES-17) was launched on 1 March 2018. The Advanced Baseline Imager (ABI) is the primary instrument on the GOES-R series for weather and environmental monitoring. The GOES-17 ABI (flight model 2) experienced a degradation in its thermal system that limits ABI's ability to shed solar heat load. This limitation resulted in significant reduction in performance after initial turn on with only 3 of 16 spectral channels expected to be available for much of the year. A combined government/vendor team was tasked with optimizing the operation of ABI to recapture as much performance as possible. By modifying the operational configuration and sensor parameters, the team was able to regain over 97% imaging capability.This was accomplished by taking advantage of the considerably flexible nature of ABI's design to adapt its configuration to the new reality and improve capabilities for many of ABI's subsystems. The significant differences in operational configuration, sensor parameter optimization, and algorithm optimization will be discussed as well as their impact on performance and data availability

Oncogenic transformation in the absence of Xrcc4 targets peripheral B cells that have undergone editing and switching

Nonhomologous end-joining (NHEJ) repairs DNA double-strand breaks (DSBs) during V(D)J recombination in developing lymphocytes and during immunoglobulin (Ig) heavy chain (IgH) class switch recombination (CSR) in peripheral B lymphocytes. We now show that CD21-cre–mediated deletion of the Xrcc4 NHEJ gene in p53-deficient peripheral B cells leads to recurrent surface Ig-negative B lymphomas (“CXP lymphomas”). Remarkably, CXP lymphomas arise from peripheral B cells that had attempted both receptor editing (secondary V[D]J recombination of Igκ and Igλ light chain genes) and IgH CSR subsequent to Xrcc4 deletion. Correspondingly, CXP tumors frequently harbored a CSR-based reciprocal chromosomal translocation that fused IgH to c-myc, as well as large chromosomal deletions or translocations involving Igκ or Igλ, with the latter fusing Igλ to oncogenes or to IgH. Our findings reveal peripheral B cells that have undergone both editing and CSR and show them to be common progenitors of CXP tumors. Our studies also reveal developmental stage-specific mechanisms of c-myc activation via IgH locus translocations. Thus, Xrcc4/p53-deficient pro–B lymphomas routinely activate c-myc by gene amplification, whereas Xrcc4/p53-deficient peripheral B cell lymphomas routinely ectopically activate a single c-myc copy

Oncogenic transformation in the absence of Xrcc4 targets peripheral B cells that have undergone editing and switching

Nonhomologous end-joining (NHEJ) repairs DNA double-strand breaks (DSBs) during V(D)J recombination in developing lymphocytes and during immunoglobulin (Ig) heavy chain (IgH) class switch recombination (CSR) in peripheral B lymphocytes. We now show that CD21-cre–mediated deletion of the Xrcc4 NHEJ gene in p53-deficient peripheral B cells leads to recurrent surface Ig-negative B lymphomas (“CXP lymphomas”). Remarkably, CXP lymphomas arise from peripheral B cells that had attempted both receptor editing (secondary V[D]J recombination of Igκ and Igλ light chain genes) and IgH CSR subsequent to Xrcc4 deletion. Correspondingly, CXP tumors frequently harbored a CSR-based reciprocal chromosomal translocation that fused IgH to c-myc, as well as large chromosomal deletions or translocations involving Igκ or Igλ, with the latter fusing Igλ to oncogenes or to IgH. Our findings reveal peripheral B cells that have undergone both editing and CSR and show them to be common progenitors of CXP tumors. Our studies also reveal developmental stage-specific mechanisms of c-myc activation via IgH locus translocations. Thus, Xrcc4/p53-deficient pro–B lymphomas routinely activate c-myc by gene amplification, whereas Xrcc4/p53-deficient peripheral B cell lymphomas routinely ectopically activate a single c-myc copy

Immunoregulatory Mechanisms Underlying Prevention of Colitis-Associated Colorectal Cancer by Probiotic Bacteria

Background: Inflammatory bowel disease (IBD) increases the risk of colorectal cancer. Probiotic bacteria produce immunoregulatory metabolites in vitro such as conjugated linoleic acid (CLA), a polyunsaturated fatty acid with potent anticarcinogenic effects. This study aimed to investigate the cellular and molecular mechanisms underlying the efficacy of probiotic bacteria in mouse models of cancer. Methodology/Principal Findings: The immune modulatory mechanisms of VSL#3 probiotic bacteria and CLA were investigated in mouse models of inflammation-driven colorectal cancer. Colonic specimens were collected for histopathology, gene expression and flow cytometry analyses. Immune cell subsets in the mesenteric lymph nodes (MLN), spleen and colonic lamina propria lymphocytes (LPL) were phenotypically and functionally characterized. Mice treated with CLA or VSL#3 recovered faster from the acute inflammatory phase of disease and had lower disease severity in the chronic, tumor-bearing phase of disease. Adenoma and adenocarcinoma formation was also diminished by both treatments. VSL#3 increased the mRNA expression of TNF-a, angiostatin and PPAR c whereas CLA decreased COX-2 levels. Moreover, VSL#3-treated mice had increased IL-17 expression in MLN CD4+ T cells and accumulation of Treg LPL and memory CD4+ T cells. Conclusions/Significance: Both CLA and VSL#3 suppressed colon carcinogenesis, although VSL#3 showed greater anticarcinogeni