Free products of coarsely convex spaces and the coarse Baum-Connes conjecture

The first author and Oguni introduced a wide class of metric spaces, called coarsely convex spaces. It includes Gromov hyperbolic metric spaces, CAT(0) spaces, systolic complexes, proper injective metric spaces. We introduce the notion of free products of metric spaces and show that free products of symmetric geodesic coarsely convex spaces are also symmetric geodesic coarsely convex spaces. As an application, it follows that free products of symmetric geodesic coarsely convex spaces satisfy the coarse Baum-Connes conjecture.Comment: 27 pages, 9 figure

横断的・総合的な幼稚園教育教員養成プログラムの構築研究

本研究では，別冊『－平成30年度広島大学大学院教育学研究科共同研究プロジェクト－横断的・総合的な幼稚園教育教員養成プログラムの構築研究論文集』を作成し，紙幅の都合で本報告書に掲載できなかった調査・研究の成果を掲載した

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Yellow nail syndrome with massive chylothorax after esophagectomy: A case report

Yellow nail syndrome (YNS) is a rare condition characterized by the triad of yellow nails, lymphedema, and respiratory manifestations. Diuretics and thoracic drainage are often not effective in YNS, and the most effective treatments are pleurodesis and decortication/pleurectomy. A 66-year-old man was admitted to our hospital for YNS after esophagectomy with gastric tube reconstruction for esophageal cancer. The patient presented with yellow nails and lymphedema. Chest X-rays and computed tomography showed massive pleural effusions and ascites that were both chylous. The patient was considered to have YNS that became apparent after surgery. He recovered with diuretics and a low-fat diet without pleurodesis and decortication/pleurectomy. Thoracic surgery can exacerbate the functional impairment of lymphatic drainage in patients with asymptomatic and undiagnosed YNS, and can lead to further development of YNS-related clinical symptoms. Despite relatively massive chylothorax following thoracic surgery, chylothorax related to YNS could be successfully controlled with conservative treatment without pleurodesis and decortication/pleurectomy

Chemical Bonding in Polarised Push-Pull Ethylenes

1,1‐Diamino‐2,2‐bis(triflyl)ethylenes with both twisted and planar structures around the partial “C=C” bond were synthesised. Bonding properties in these compounds were analysed by an experimental approach using high‐resolution X‐ray diffraction data treated with X‐ray wavefunction refinement (XWR). In the twisted compound, a dominant contribution of the charge‐separated resonance structure was revealed. On the contrary, the nearly planar compound still showed π‐bonding character, however, with a considerable contribution of the charge‐separated resonance structure

Roles of Interleukin-6 and Parathyroid Hormone-Related Peptide in Osteoclast Formation Associated with Oral Cancers : Significance of Interleukin-6 Synthesized by Stromal Cells in Response to Cancer Cells

We investigated the roles of interleukin-6 (IL-6) and parathyroid hormone-related peptide (PTHrP) in oral squamous cell carcinoma (OSCC)-induced osteoclast formation. Microarray analyses performed on 43 human OSCC specimens revealed that many of the specimens overexpressed PTHrP mRNA, but a few overexpressed IL-6 mRNA. Immunohistochemical analysis revealed that IL-6 was expressed not only in cancer cells but also in fibroblasts and osteoclasts at the tumor-bone interface. Many of the IL-6-positive cells coexpressed vimentin. Conditioned medium (CM) derived from the culture of oral cancer cell lines (BHY, Ca9-22, HSC3, and HO1-u-1) stimulated Rankl expression in stromal cells and osteoclast formation. Antibodies against both human PTHrP and mouse IL-6 receptor suppressed Rankl in ST2 cells and osteoclast formation induced by CM from BHY and Ca9-22, although the inhibitory effects of IL6 antibody were greater than those of PTHrP antibody. CM derived from all of the OSCC cell lines effectively induced IL-6 expression in stromal cells, and the induction was partially blocked by anti-PTHrP antibody. Xenografts of HSC3 cells onto the periosteal region of the parietal bone in athymic mice presented histology and expression profiles of RANKL and IL-6 similar to those observed in bone-invasive human OSCC specimens. These results indicate that OSCC provides a suitable microenvironment for osteoclast formation not only by producing IL-6 and PTHrP but also by stimulating stromal cells to synthesize IL-6