109 Background: Since CPB may alter immune marker expression in key immunomodulatory populations such as myeloid-derived suppressor cells (MDSC) and CD8 + cytotoxic T lymphocytes (CTL), we evaluated PD1/PDL1 expression in longitudinal samples from mUC pts treated with CPB. Methods: Serial peripheral blood samples were collected from mUC pts who received CPB. PD1/PDL1 and VISTA expression was measured in MDSC (CD33 + HLADR − ) and CTL (CD8 + CD4 − ) from live peripheral blood mononuclear cells using flow cytometry. MDSC subsets were further defined as (G)ranulocytic (CD15 + CD14 − ), (M)onocytic (CD15 − CD14 + ), and (I)mmature (CD15 − CD14 − ). PD1/PDL1 and VISTA expression was presented as % of each MDSC subset or CTL. Wilcoxon signed-rank tests and mixed-model regression analyses were performed to assess changes in immune marker expression after CPB. Results: Of 30 CPB-treated pts with ≥ 2 blood samples for analysis, 21 received anti-PDL1 (20 atezolizumab/1 avelumab; [A]) and 9 received anti-PD1 (pembrolizumab [P]). Median age at diagnosis was 69.5 (4681), 77% men, 33% never smokers, 63% pure UC, 70% bladder primary, 20% prior intravesical BCG, 37% prior neoadjuvant chemotherapy, 63% prior cystectomy. Best overall responses to CPB were 3 PR/13 SD/5 PD (A) and 1 CR/1 PR/4 SD/3 PD (P). Successive doses of A correlated with decreased %PDL1 + M-MDSC, while those of P correlated with decreased %PD1 + M- and I- MDSC (Table). No significant changes in VISTA expression were detected. In 11 A-treated pts with samples before/after the 1st dose, %PDL1 + M- and I- MDSC decreased (median change −25.5 and −5.7; p = 0.02 and 0.03) and %PD1 + CTL increased (median change +2.4; p = 0.02) between 1st and 2nd samples. Conclusions: In this mUC pt cohort, distinct post-tx changes in %PD1/PDL1 in MDSC subsets and CTL occurred based on CPB (anti-PD1 vs anti-PDL1). Further analysis of correlations between CPB, immune marker expression, clinicopathologic factors, and outcomes is ongoing in a larger cohort. Mean absolute change in marker expression per dose in pts treated with CPB. [Table: see text]
Flow visualization was performed to give a physical insight with vortical structures of an axisymmetric impinging jet on a concave surface. High-speed imaging was employed to get clear images with a laser light sheet illumination. An axisymmetric jet is issued into quasi-ambient air through a straight pipe nozzle with fully-developed velocity profile. A regular vertical pattern of an axisymmetric jet was observed with different flow entrainment rate. While an impinged jet turns to convert a wall jet along a concave surface, the flow interaction between the large-scale toroidal vortex and the concave surface was observed in the transition between the stagnation and wall jet zone. The ring-shaped wall eddies induced from a pair of toroidal vortices were also appeared to diverge into the radial direction along the concave surface. As the jet Reynolds number increases, small-scale vortices can be developed to a large-scale toroidal vortex. The location in which a large-scale toroidal vortex strikes is generally identical to the location where the secondary peak in heat transfer occurs. The frequency of large scale toroidal vortex on concave surface is found to be nearly similar as that of wall jet on flat surface. As the nozzle-to-target spacing (L/D) increases, it becomes shorter due to the loss of jet momentum. The flow behavior of axisymmetric impinging jet on a concave surface can be helpful to design the internal passage cooling for gas turbine blade.
Rap1-guanosine triphosphate (GTP)-interacting adaptor molecule (RIAM) plays a critical role in actin reorganization and inside-out activation of integrins in lymphocytes and platelets. We investigated the role of RIAM in T cell receptor (TCR)-mediated signaling. Although phosphorylation of the kinase ZAP-70 and formation of a signalosome recruited to the adaptor protein LAT were unaffected, elimination of endogenous RIAM by short hairpin RNA impaired generation of inositol 1,4,5-trisphosphate, mobilization of intracellular calcium ions (Ca(2+)), and translocation of the transcription factor NFAT to the nucleus. The activation of Ras guanine nucleotide-releasing protein 1 was also impaired, which led to the diminished expression of the gene encoding interleukin-2. These events were associated with the impaired translocation of phosphorylated phospholipase C-gamma1 (PLC-gamma1) to the actin cytoskeleton, which was required to bring PLC-gamma1 close to its substrate phosphatidylinositol 4,5-bisphosphate, and were reversed by reconstitution of cells with RIAM. Thus, by regulating the localization of PLC-gamma1, RIAM plays a central role in TCR signaling and the transcription of target genes.
Meeting abstracts In order to induce significant tumor regression T cells must effectively recognize and kill target cells. Secretion of IFN-γ is considered a key effector function of activated CD8+ T cells via induction of apoptosis. Thus programming T cells to secrete high levels of IFN-γ after
Condensation behavior on a superhydrophobic microporous surface was visually compared with that on a plain surface in the water saturated at the pressures of 101.3 kPa (Tsat = 100 °C) and 3.2 kPa (Tsat = 25 °C). The microporous surface was formed by sintering copper powders with the average diameter of 50 µm on the bare copper surface, resulting in the coating thickness of approximately 250 µm. The microporous surface was coated with the polytetrafluoroethylene (PTFE) layer by the spray-coating method to change the wettability into superhydrophobic, which was verified from a measured apparent contact angle of above 150°. While dropwise condensation is observed on both bare and hydrophobic plain surfaces at Psat = 101.3 kPa, filmwise condensation is seen on the superhydrophilic plain surface. At the low saturation pressure of 3.2 kPa, condensation behavior on the bare plain surface is changed into the filmwise condensation with improved wettability. In contrast, on the microporous surface, the only superhydrophobic microporous surface shows dropwise condensation behavior, where the surface is considered at the Cassie-state. However, filmwise condensation behaviors are observed on both superhydrophilic and bare microporous surfaces due to the wicking into the pores.
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