Development of Formation Flying CubeSats and Operation Systems for the CANYVAL-C Mission: Launch and Lessons Learned

The CubeSat Astronomy NASA and Yonsei using Virtual telescope ALignment for Coronagraph (CANYVAL-C) is a technology demonstration mission that shows the concept of a virtual space telescope using two CubeSats in formation flying. The final goal of the mission is to obtain several images of the solar corona during an artificial solar eclipse created by the two CubeSats, Timon (1U CubeSat) and Pumbaa (2U CubeSat). To implement this mission, two CubeSats in formation flying and a ground segment have been developed. The CubeSats were constructed mainly with commercial off the shelf components, sharing the bus architecture. The payload of each CubeSat is a visible camera and an occulter to block the light from the photosphere of the Sun. The occulter is composed of tape measures and a black-colored polyimide film; the system size is smaller than 0.5U (10 × 10 × 5 cm3) while it stowed and enlarged to 0.75 × 0.75 m2 after spreading the film. The 3D-printed propulsion system is smaller than 0.5U and facilitates accurate positioning maneuvers of Pumbaa. The on-board computer has multi-task processing capabilities and a space-saving configuration which is integrated with the GNSS receiver and the UHF transceiver. The core technology for the mission implementation is the precise formation flying guidance, navigation, and control system with a cold-gas propulsion system and an inter-satellite link system. The specification of each CubeSat system was evaluated using numerical simulations and ground testing. To operate CubeSats, the ground segment was constructed with some components, including the UHF ground station (UGS), flight dynamics system (FDS), mission analysis and planning system (MAPS), and spacecraft operation system (SOS). Each component works under the environment of an integrated graphic user interface. In particular, the UGS handles the RF communication, data storage, and instrument control for tracking CubeSats. The FDS processes the navigation data to precisely estimate absolute position and velocity. Then, the MAPS determines the allowable mission schedule and parameter set for implementing maneuvers of each CubeSat. Using the MAPS, feasibility of the mission operation canbe ensured through numerical simulations based on the solutions from the FDS. Finally, the SOS is the interface system between each component, processing telemetry and generating telecommand. The CubeSats were launched on March 22, 2021, by Soyuz-2.1a with a Fregat stage

538 A.D. and the Transition from Pagan Roman Empire to Holy Roman Empire: Justinian’s Metamorphosis from Chief of Staffs to Theologian

The year 538 A.D. became the turning point in the history of the Roman Empire since so many aspects on political, administrative and economical levels were already switched off that when Justinian declared himself to be a theologian from this year and no longer a soldier, he crossed the barrier of his mandate between what is purely civil obligation and what is religious obligation, similarly to Constantine before, and entered in competition with the papal function and this role is evidence of Justinian’s ongoing caesaro-papism. The quest for unification of the empire by unification of the church, the fever for church-building projects with his wife Theodora, the persecution of enemies of the church and heretics, his disdain with the Sabbath although his second name was Sabbatini, his support for suppressing any eschatological fever in line with the church fathers and Oecumenius and yet trying to build the ‘Kingdom of God’ on earth, all this indicate the problem 538 was for the Roman Empire and the Catholic Church. Archaeological and historical original sources of Justinian and contemporaries of popes, biographer of Justinian and a commentator on Revelation (Oecumenius) are very revealing of these times and the shift or transition of what belonged to the Roman Empire handed over since 538 A.D. to the church and the papal function. The Code of Justinian was a persecuting instrument. Justinian upheld the supremacy of the papacy. He permitted through the Council of Orleans actions to be done on Sunday that Constantine prohibited like travel and preparation of food and cleaning the house. In Novellae CXLIV Justinian instituted a Seventh-day Sabbath persecution. He changed the times and laws ad hoc as his Novellae XLVI and coins of 538 A.D. (XII year) indicate. Private gatherings were persecuted. He had church-manual laws. Justinian studied Systematic Theology on the nature of Christ and wrote homiletical rules for preachers. He gave textcritical advice to Jews and condemned their doctrinal deviations. This theological hobby of the ruler of the once mighty Roman Empire was to be taken over by a more theological competent power that would eventually lead to papal-caesarism until the unsettling of this new aggrandizing paradigm in 1798 by Napoleon. The prophetic embedding of the 1260 days as “years” prophecies in both Daniel 7 and Revelation 12 definitely started in 538 A.D. contrary to W. Spicer’s (1918) suggestion of 533 or 538 as two alternative dates or any other dates suggested by other scholars in the history of interpretation in historicism. It is also not just a case of history of interpretation hermeneutics but data solidly supported by archaeology, iconography and original historical sources that coincides with the parameters provided by exegesis of the rest of the Books of Daniel and Revelation added with the exegesis of the detail of the passages under consideration. A necessary ingredient for the historical researcher remains to be the faith that God can predict the future and He did and that the data as well as the prophecies of the Biblical Text are evidence of that

Functional Ambivalence of Dendritic Cells: Tolerogenicity and Immunogenicity

Dendritic cells (DCs) are the most potent professional antigen-presenting cells (APCs) and inducers of T cell-mediated immunity. Although DCs play a central role in promoting adaptive immune responses against growing tumors, they also establish and maintain peripheral tolerance. DC activity depends on the method of induction and/or the presence of immunosuppressive agents. Tolerogenic dendritic cells (tDCs) induce immune tolerance by activating CD4+CD25+Foxp3+ regulatory T (Treg) cells and/or by producing cytokines that inhibit T cell activation. These findings suggest that tDCs may be an effective treatment for autoimmune diseases, inflammatory diseases, and infertility

TNF-α Induces Mitophagy in Rheumatoid Arthritis Synovial Fibroblasts, and Mitophagy Inhibition Alleviates Synovitis in Collagen Antibody-Induced Arthritis

Mitophagy is a selective form of autophagy that removes damaged mitochondria. Increasing evidence indicates that dysregulated mitophagy is implicated in numerous autoimmune diseases, but the role of mitophagy in rheumatoid arthritis (RA) has not yet been reported. The aim of the present study was to determine the roles of mitophagy in patient-derived RA synovial fibroblasts (RASFs) and in the collagen antibody-induced arthritis mouse model. We measured the mitophagy marker PTEN-induced putative kinase 1 (PINK1) in RASFs treated with tumor necrosis factor-α (TNF-α) using Western blotting and immunofluorescence. Arthritis was induced in PINK1−/− mice by intraperitoneal injection of an anti-type II collagen antibody cocktail and lipopolysaccharide. RA severity was assessed by histopathology. PINK1 expression and damaged mitochondria increased in TNF-α treated RASFs via increased intracellular levels of reactive oxygen species. PINK1 knockdown RASFs decreased cellular migration and invasion functions. In addition, PINK1−/− mice with arthritis exhibited markedly reduced swelling and inflammation relative to wild-type mice with arthritis. Taken together, these findings suggest that regulation of PINK1 expression in RA could represent a potential therapeutic and diagnostic target for RA

TGF-β/IL-7 Chimeric Switch Receptor-Expressing CAR-T Cells Inhibit Recurrence of CD19-Positive B Cell Lymphoma

Chimeric antigen receptor (CAR)-T cells are effective in the treatment of hematologic malignancies but have shown limited efficacy against solid tumors. Here, we demonstrated an approach to inhibit recurrence of B cell lymphoma by co-expressing both a human anti-CD19-specific single-chain variable fragment (scFv) CAR (CD19 CAR) and a TGF-β/IL-7 chimeric switch receptor (tTRII-I7R) in T cells (CD19 CAR-tTRII-I7R-T cells). The tTRII-I7R was designed to convert immunosuppressive TGF-β signaling into immune-activating IL-7 signaling. The effect of TGF-β on CD19 CAR-tTRII-I7R-T cells was assessed by western blotting. Target-specific killing by CD19 CAR-tTRII-I7R-T cells was evaluated by Eu-TDA assay. Daudi tumor-bearing NSG (NOD/SCID/IL2Rγ-/-) mice were treated with CD19 CAR-tTRII-I7R-T cells to analyze the in vivo anti-tumor effect. In vitro, CD19 CAR-tTRII-I7R-T cells had a lower level of phosphorylated SMAD2 and a higher level of target-specific cytotoxicity than controls in the presence of rhTGF-β1. In the animal model, the overall survival and recurrence-free survival of mice that received CD19 CAR-tTRII-I7R-T cells were significantly longer than in control mice. These findings strongly suggest that CD19 CAR-tTRII-I7R-T cell therapy provides a new strategy for long-lasting, TGF-β-resistant anti-tumor effects against B cell lymphoma, which may lead ultimately to increased clinical efficacy

Synthetic TGF-β Signaling Agonist-Treated Dendritic Cells Induce Tolerogenicity and Antirheumatic Effects

The newly synthesized compound TGF-β signaling agonist (T74) is a small molecule associated with the TGF-β receptor signaling pathway. Tolerogenic dendritic cells (tDCs) have been used to examine immunosuppressive and anti-inflammatory effects in multiple autoimmune disease models. The aim of this study was to investigate whether treatment of DCs with T74 has an antirheumatic effect in a mouse model of collagen-induced arthritis (CIA). Bone marrow-derived cells were obtained from DBA/1J mice and differentiated into DCs. T74-treated DCs (T74-DCs) were generated by treating bone marrow-derived DCs with LPS, type II collagen, and T74. T74-DCs expressed lower levels of surface molecules and inflammatory cytokines associated with antigen presentation and T cell stimulation. The ability of T74-DCs to differentiate effector T cells was lower than that of T74-untreated DCs (NT-DCs), but T74-DCs increased the regulatory T (Treg) cell differentiation in vitro. DBA/1J mice received two subcutaneous (s.c.) injections of type II collagen to establish CIA. Mice then received two s.c. injections of T74-DCs or NT-DCs. Joint inflammation was ameliorated in the paws of T74-DC-treated mice. Additionally, Treg populations in T74-DC-treated mice were higher than in NT-DC-treated or PBS-treated CIA mice. Taken together, these results demonstrate that T74 induces tolerance in DCs, and that T74-mediated DCs exert antirheumatic effects via induction of Tregs

Enpp2 Expression by Dendritic Cells Is a Key Regulator in Migration

Enpp2 is an enzyme that catalyzes the conversion of lysophosphatidylcholine (LPC) to lysophosphatidic acid (LPA), which exhibits a wide variety of biological functions. Here, we examined the biological effects of Enpp2 on dendritic cells (DCs), which are specialized antigen-presenting cells (APCs) characterized by their ability to migrate into secondary lymphoid organs and activate naïve T-cells. DCs were generated from bone marrow progenitors obtained from C57BL/6 mice. Enpp2 levels in DCs were regulated using small interfering (si)RNA or recombinant Enpp2. Expression of Enpp2 in LPS-stimulated mature (m)DCs was high, however, knocking down Enpp2 inhibited mDC function. In addition, the migratory capacity of mDCs increased after treatment with rmEnpp2; this phenomenon was mediated via the RhoA-mediated signaling pathway. Enpp2-treated mDCs showed a markedly increased capacity to migrate to lymph nodes in vivo. These findings strongly suggest that Enpp2 is necessary for mDC migration capacity, thereby increasing our understanding of DC biology. We postulate that regulating Enpp2 improves DC migration to lymph nodes, thus improving the effectiveness of cancer vaccines based on DC