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Despite the therapeutic success of immune checkpoint blockade (ICB) therapy against multiple tumors, many patients still do not benefit from ICB. In particular, high-grade brain tumors, such as glioblastoma multiforme (GBM), have a very low response rate to ICB, resulting in several failed clinical trials. This low response rate might be caused by a lack of understanding of the unique characteristics of brain immunity. To overcome this knowledge gap, macroscopic studies of brain immunity are needed. We use single cell RNA sequencing to analyze the immune landscape of the tumor microenvironment (TME) under anti-PD-1 antibody treatment in a murine GBM model. We observe that CD8 T cells show a mixed phenotype overall that includes reinvigoration and re-exhaustion states. Furthermore, we find that CCL5 induced by anti-PD- 1 treatment might be related to an increase in the number of anti-inflammatory macrophages in the TME. Therefore, we hypothesize that CCL5-mediated recruitment of anti-inflammatory macrophages may be associated with re-exhaustion of CD8 T cells in the TME. We compare our observations in the murine GBM models with publicly available data from human patients with recurrent GBM. Our study provides critical information for the development of novel immunotherapies to overcome the limitations of anti-PD-1 therapy. [ABSTRACT FROM AUTHOR]

Adoptive transfer of γδ T cells is a novel immunotherapeutic approach to glioblastoma. Few recent studies have shown the efficacy of γδ T cells against glioblastoma, but no previous studies have identified the ligand-receptor interactions between γδ T cells and glioblastoma cells. Here, we identify those ligand-receptor interactions and provide a basis for using γδ T cells to treat glioblastoma. Vγ9Vd2 T cells were generated from peripheral blood mononuclear cells of healthy donors using artificial antigen presenting cells. MICA, ULBP, PVR and Nectin-2 expression in 10 patient-derived glioblastoma (PDG) cells were analyzed. The in vitro cytokine secretion from the γδ T cells and their cytotoxicity toward the PDG cells were also analyzed. The in vivo anti-tumor effects were evaluated using a U87 orthotopic xenograft glioblastoma model. Expression of ligands and cytotoxicity of the γδ T cells varied among the PDG cells. IFN-γ and Granzyme B secretion levels were significantly higher when γδ Tcells were co-cultured with high-susceptible PDG cells than when they were co-cultured with low-susceptible PDG cells. Cytotoxicity correlated significantly with the expression levels of DNAM-1 ligands of the PDG cells. Blocking DNAM-1 resulted in a decrease in γδ T cell-mediated cytotoxicity and cytokine secretion. Intratumoral injection of γδ T cells showed anti-tumor effects in an orthotopic mouse model. Allogenic γδ T cells showed potent anti-tumor effects on glioblastoma in a DNAM-1 axis dependent manner. Our findings will facilitate the development of clinical strategies using γδ T cells for glioblastoma treatment. [ABSTRACT FROM AUTHOR]

A compact infrared space telescope called MIRIS (Multi-purpose Infra-Red Imaging System) was developed by the Korea Astronomy and Space Science Institute (KASI), and launched onboard the Science and Technology Satellite-3 of Korea (STSAT-3) in 2013 November. The main mission of MIRIS is the Paschen-α emission line survey along the Galactic plane and the cosmic infrared background (CIB) observation, particularly around the north ecliptic pole region. For these missions, a wide field of view (3:67 × 3:67°) with an angular resolution of 51.6" and wavelength coverage from 0.9 ~ 2.0 µm have been adopted for MIRIS, having optical components consisting of a 80 mm main lens and four other lenses with F/2 focal ratio optics. The opto-mechanical system was carefully designed to minimize any effects from shock during the launch process and thermal variation. Also, the telescope was designed to use a passive cooling technique to maintain the temperature around 200 K in order to reduce thermal noise. A micro Stirling cooler was used to cool down the Teledyne PICNIC infrared array to 90 K, which was equipped in a dewar with four filters for infrared passbands of I, H, and Paschen-a and a dual-band continuum line filter. MIRIS system was integrated into the STSAT-3 as its primary payload and successfully passed required tests in the laboratory, such as thermal-vacuum, vibration, and shock tests. MIRIS is now operating in sun synchronous orbits for initial tests and has observed its first images successfully. [ABSTRACT FROM AUTHOR]

We present a study on four new star clusters discovered in the halo of the intriguing dwarf irregular galaxy NGC 6822 from a wide-field survey covering 3° x 3° area carried out with MegaCam at the Canada-France-Hawaii Telescope. The star clusters have extended structures with half-light radii Rh ≈ 7.5-14.0 pc, larger than typical Galactic globular clusters and other known globular clusters in NGC 6822. The integrated colors and color-magnitude diagrams of resolved stars suggest that the new star clusters are 2-10 Gyr old and relatively metal poor with Z = 0.0001-0.004 based on the comparison with theoretical models. The projected distance of each star cluster from the galaxy center ranges from 10'.7(≈1.5 kpc) to 77' (≈11 kpc), far beyond the optical body of the galaxy. Interestingly, the new star clusters are aligned along the elongated old stellar halo of NGC 6822, which is almost perpendicular to the H I gas distribution where young stellar populations exist. We also find that the colors and half-light radii of the new clusters are correlated with the galactocentric distance: clusters farther from the galaxy center are larger and bluer than those closer to the galaxy center. We discuss the stellar structure and evolution of NGC 6822 implied by these new extended star clusters in the halo. We also discuss the current status of observational and theoretical understandings regarding the origin of extended star clusters in NGC 6822 and other galaxies. [ABSTRACT FROM AUTHOR]

In this brief, a new adaptive neurocontrol algorithm for a single-input-single-output (SISO) strict-feedback nonlinear system is proposed. Most of the previous adaptive neural control algorithms for strict-feedback nonlinear systems were based on the backstepping scheme, which makes the control law and stability analysis very complicated. The main contribution of the proposed method is that it demonstrates that the state-feedback control of the strict-feedback system can be viewed as the output-feedback control problem of the system in the normal form. As a result, the proposed control algorithm is considerably simpler than the previous ones based on backstepping. Depending heavily on the universal approximation property of the neural network (NN), only one NN is employed to approximate the lumped uncertain system nonlinearity. The Lyapunov stability of the NN weights and filtered tracking error is guaranteed in the semiglobal sense. [ABSTRACT FROM AUTHOR]

Presents information on a study which examined the applicability of fuzzy logic to modeling a plasma etch process. Methodology; Results; Discussion.