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Electrothermal-chemical (ETC) propulsion with the control of a combustion process yet requires large electrical energies for an appreciable effect. Referring to the changed tendency of focusing ETC researches on the early ignition phase, the Agency for Defense Development (ADD), Korea, has been studying an electrothermal ignition for a 120-mm gun using a capillary plasma injector. Under the condition of a limited capillary geometry, design efforts with various liner materials have been done to achieve robust capillary discharges capable of transferring energies around 100 kJ. Electrical properties were estimated with the help of plasma theories and compared with experimental results. Experiments using a closed vessel and a gun-chamber simulator have been done to investigate the burning behaviors and the early phase of an electrothermal ignition, respectively. The closed vessel was designed for both a plasma and a conventional ignition. The burning rates could be obtained up to 70 MPa. The gun-chamber simulator was designed in the shape of the chamber of a 120-mm gun except for an acrylic chamber wall withstanding up to 30 MPa. Through prior tests using the closed vessel and the gun-chamber simulator, appropriate electrical energies and propellant have been selected. Firings of the full-scale 120-mm gun have been done using JA2 propellant. Electrical pulses of 1-2.5-ms duration in the energy from 20 to 120 kJ were applied. Aside from ignition capability, the results showed a possibility of a control on the peak pressure. Currently, ADD, Korea, continues the research to enhance the efficiency of the plasma injector, to compact the pulse forming network, and to investigate the electrothermal ignition properties of LOVA propellant. Index Terms--Capillary, electrothermal, propellant.

A low lymphocyte count puts immune‐compromised patients at risk of mortality. hIL‐7‐hyFc is a homodimeric interleukin‐7 (IL‐7), a potent T‐cell amplifier, fused to the hybridizing IgD/IgG4 immunoglobulin domain. We performed a randomized, double‐blind, placebo‐controlled, dose‐escalation, phase I study to assess the pharmacokinetic, pharmacodynamic, safety, tolerability, and immunogenicity profiles of hIL‐7‐hyFc administered s.c. and i.m. to healthy volunteers. Thirty subjects randomly received hIL‐7‐hyFc or its matching placebo in an 8:2 ratio at 20, 60 μg/kg s.c., or 60 μg/kg i.m. The hIL‐7‐hyFc was slowly absorbed and its terminal half‐life was 63.26 hours after i.m. administration. The hIL‐7‐hyFc increased absolute lymphocyte count, mostly in T‐cells, which peaked 3 weeks after administration and then lasted for several additional weeks. The hIL‐7‐hyFc was well‐tolerated after a single s.c. and i.m. administration. Injection site reaction was the most common treatment‐emergent adverse event, which resolved spontaneously without treatment. The hIL‐7‐hyFc can be developed into a beneficial treatment option for patients with compromised T‐cell immunity. This trial was registered at www.clinicaltrials.gov as #NCT02860715. [ABSTRACT FROM AUTHOR]

Objectives: Emerging oncotherapeutic strategies require the induction of an immunostimulatory tumor microenvironment (TME) containing numerous tumor‐reactive CD8+ T cells. Interleukin‐7 (IL‐7), a T‐cell homeostatic cytokine, induces an antitumor response; however, the detailed mechanisms underlying the contributions of the IL‐7 to TME remain unclear. Here, we aimed to investigate the mechanism underlying the induction of antitumor response by hybrid Fc‐fused long‐acting recombinant human IL‐7 (rhIL‐7‐hyFc) through regulation of both adaptive and innate immune cells in the TME. Methods: We evaluated rhIL‐7‐hyFc‐mediated antitumor responses in murine syngeneic tumor models. We analysed the cellular and molecular features of tumor‐infiltrating lymphocytes (TILs) and changes in the TME after rhIL‐7‐hyFc treatment. Furthermore, we evaluated the antitumor efficacy of rhIL‐7‐hyFc combined with chemotherapy and checkpoint inhibitors (CPIs). Results: Systemic delivery of rhIL‐7‐hyFc induced significant therapeutic benefits by expanding CD8+ T cells with enhanced tumor tropism. In tumors, rhIL‐7‐hyFc increased both tumor‐reactive and bystander CD8+ TILs, all of which displayed enhanced effector functions but less exhausted phenotypes. Moreover, rhIL‐7‐hyFc suppressed the generation of immunosuppressive myeloid cells in the bone marrow of tumor‐bearing mice, resulting in the immunostimulatory TME. Combination therapy with chemotherapy and CPIs, rhIL‐7‐hyFc elicited a strong antitumor response and even under a T lymphopenic condition by restoring CD8+ T cells. When combined with chemotherapy and CPIs, rhIL‐7‐hyFc administration enhanced antitumor response under intact andlymphopenic conditions by restoring CD8+ T cells. Conclusion: Taken together, these data demonstrate that rhIL‐7‐hyFc induces antitumor responses by generating T‐cell‐inflamed TME and provide a preclinical proof of concept of immunotherapy with rhIL‐7‐hyFc to enhance therapeutic responses in the clinic. [ABSTRACT FROM AUTHOR]

1. Introduction Sjogren's syndrome (SjS) is a systemic chronic autoimmune disease that targets the exocrine glands, predominantly the salivary glands and lacrimal glands, resulting in xerostomia (dry mouth) and keratoconjunctivitis [...], Sjogren's syndrome (SjS) is a complex chronic autoimmune disease of unknown etiology which primarily targets the exocrine glands, resulting in eventual loss of secretory function. The disease can present as either primary SjS or secondary SjS, the latter of which occurs concomitantly with another autoimmune disease such as rheumatoid arthritis, systemic lupus erythematosus, scleroderma, or primary biliary cirrhosis. Current advancements in therapeutic prevention and treatment for SjS are impeded by lack of understanding in the pathophysiological and clinical progression of the disease. Development of appropriate mouse models for both primary and secondary SjS is needed in order to advance knowledge of this disease. This paper details important features, advantages, and pitfalls of current animal models of SjS, including spontaneous, transgenic, knockout, immunization, and transplantation chimera mouse models, and emphasizes the need for a better model in representing the human SjS phenotype.

Pollen presents a powerful model for studying mechanisms of precise formation and deposition of extracellular structures. Deposition of the pollen wall exine leads to the generation of species-specific patterns on pollen surface. In most species, exine does not develop uniformly across the pollen surface, resulting in the formation of apertures–openings in the exine that are species-specific in number, morphology and location. A long time ago, it was proposed that number and positions of apertures might be determined by the geometry of tetrads of microspores–the precursors of pollen grains arising via meiotic cytokinesis, and by the number of last-contact points between sister microspores. We have tested this model by characterizing Arabidopsis mutants with ectopic apertures and/or abnormal geometry of meiotic products. Here we demonstrate that contact points per se do not act as aperture number determinants and that a correct geometric conformation of a tetrad is neither necessary nor sufficient to generate a correct number of apertures. A mechanism sensitive to pollen ploidy, however, is very important for aperture number and positions and for guiding the aperture factor INP1 to future aperture sites. In the mutants with ectopic apertures, the number and positions of INP1 localization sites change depending on ploidy or ploidy-related cell size and not on INP1 levels, suggesting that sites for aperture formation are specified before INP1 is brought to them. [ABSTRACT FROM AUTHOR]

The immune system plays an important role in maintaining body homeostasis. Recent studies on the immune-enhancing effects of ginseng saponins have revealed more diverse mechanisms of action. Maillard reaction that occurs during the manufacturing processes of red ginseng produces a large amount of Amadori rearrangement compounds (ARCs), such as arginyl-fructose (AF). The antioxidant and anti-hyperglycemic effects of AF have been reported. However, the possible immune enhancing effects of non-saponin ginseng compounds, such as AF, have not been investigated. In this study the effects of AF and AF-enriched natural product (Ginofos, GF) on proliferation of normal mouse splenocytes were evaluated in vitro and male BALB/c mice models. The proliferation of splenocytes treated with mitogens (concanavalin A, lipopolysaccharide) were further increased by addition of AF (p < 0.01) or GF (p < 0.01), in a dose dependent manner. After the 10 days of oral administration of compounds, changes in weights of spleen and thymus, serum immunoglobulin, and expression of cytokines were measured as biomarkers of immune-enhancing potential in male BALB/c mice model. The AF or GF treated groups had higher weights of the thymus (0.94 ± 0.25 and 0.86 ± 0.18, p < 0.05, respectively) than that of cyclophosphamide treated group (0.59 ± 0.18). This result indicates that AF or AF-enriched extract (GF) increased humoral immunity against CY-induced immunosuppression. In addition, immunoglobulin contents and expression of cytokines including IgM (p < 0.01), IgG (p < 0.05), IL-2 (p < 0.01), IL-4 (p < 0.01), IL-6 (p < 0.01), and IFN-γ (p < 0.05) were also significantly increased by supplementation of AF or GF. These results indicate that AF has immune enhancing effects by activation of adaptive immunity via increase of expression of immunoglobulins and cytokines such as IgM, IgG, IL-2, IL-4, IL-6 and thereby proliferating the weight of thymus. Our findings provide a pharmacological rationale for AF-enriched natural products such as ginseng and red ginseng that can possibly have immune-enhancement potential and should be further evaluated. [ABSTRACT FROM AUTHOR]

Novel engineered T cells containing chimeric antigen receptors (CAR-T cells) that combine the benefits of antigen recognition and T cell response have been developed, and their effect in the anti-tumor immunotherapy of patients with relapsed/refractory leukemia has been dramatic. Thus, CAR-T cell immunotherapy is rapidly emerging as a new therapy. However, it has limitations that prevent consistency in therapeutic effects in solid tumors, which accounts for over 90% of all cancer patients. Here, we review the literature regarding various obstacles to CAR-T cell immunotherapy for solid tumors, including those that cause CAR-T cell dysfunction in the immunosuppressive tumor microenvironment, such as reactive oxygen species, pH, O2, immunosuppressive cells, cytokines, and metabolites, as well as those that impair cell trafficking into the tumor microenvironment. Next-generation CAR-T cell therapy is currently undergoing clinical trials to overcome these challenges. Therefore, novel approaches to address the challenges faced by CAR-T cell immunotherapy in solid tumors are also discussed here. [ABSTRACT FROM AUTHOR]