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Anti-PD-1 antibody decreases tumour-infiltrating regulatory T cells
Background There are many types of therapies for cancer. In these days, immunotherapies, especially immune checkpoint inhibitors, are focused on. Though many types of immune checkpoint inhibitors are there, the difference of effect and its mechanism are unclear. Some reports suggest the response rate of anti-PD-1 antibody is superior to that of anti-PD-L1 antibody and could potentially produce different mechanisms of action. On the other hand, Treg also express PD-1; however, their relationship remains unclear. Methods In this study, we used osteosarcoma cell lines in vitro and osteosarcoma mouse model in vivo. In vitro, we analyzed the effect of IFN gamma for expression of PD-L1 on the surface of cell lines by flowcytometry. In vivo, murine osteosarcoma cell line LM8 was subcutaneously transplanted into the dorsum of mice. Mouse anti-PD-1 antibody was intraperitoneally administered. we analysed the effect for survival of anti-PD-1 antibody and proportion of T cells in the tumour by flowcytometry. Results We discovered that IFN gamma increased PD-L1 expression on the surface of osteosarcoma cell lines. In assessing the relationship between anti-PD-1 antibody and Treg, we discovered the administration of anti-PD-1 antibody suppresses increases in tumour volume and prolongs overall survival time. In the tumour microenvironment, we found that the administration of anti-PD-1 antibody decreased Treg within the tumour and increased tumour-infiltrating lymphocytes. Conclusions Here we clarify for the first time an additional mechanism of anti-tumour effect-as exerted by anti-PD-1 antibody decreasing Treg- we anticipate that our findings will lead to the development of new methods for cancer treatment.ArticleBMC CANCER. 20(1):25 (2020)journal articl
Direct simulation of phase delay effects on induced-charge electro-osmosis under large ac electric fields
The standard theory of induced-charge electro-osmosis (ICEO) often overpredicts experimental values of ICEO velocities. Using a nonsteady direct multiphysics simulation technique based on the coupled Poisson-Nernst-Planck and Stokes equations for an electrolyte around a conductive cylinder subject to an ac electric field, we find that a phase delay effect concerning an ion response provides a fundamental mechanism for electrokinetic suppression. A surprising aspect of our findings is that the phase delay effect occurs even at much lower frequencies (e.g., 50 Hz) than the generally believed charging frequency of an electric double layer (typically, 1 kHz) and it can decrease the electrokinetic velocities in one to several orders. In addition, we find that the phase delay effect may also cause a change in the electrokinetic flow directions (i.e., flow reversal) depending on the geometrical conditions. We believe that our findings move toward a more complete understanding of complex experimental nonlinear electrokinetic phenomena.ArticlePHYSICAL REVIEW E.94(2):022609(2016)journal articl
Visualization of Flows around a Wide Au-Coated Beam in Valving Motion Understood as AC Electroosmosis
Recently, bio-inspired devices have attracted much attention. In particular, elastic valves using AC electroosmosis (ACEO) hold promise for the development of artificial cilia in future microfluidic applications because of their simplicity and high-performance multi-functionality. However, direct evidence of ACEO-driven large valving motion has not been obtained yet. In this study, we report experiments that a wide Au-coated plastic-film beam shows large valving motion in water. By visualizing the flow fields during the motion, we show that the large valving motion of the wide Au-coated beam is understood to be due to ACEO occurring at the edge of the beam. Furthermore, we found that the wide beam was elevated largely by the effect of the vortex flow (understood to be the flow due to ACEO at the beam edge) and the incoming lift flow into the rearward region of the valve. We believe that our findings contribute significantly to realizing new artificial cilia.ArticleJOURNAL OF THE PHYSICAL SOCIETY OF JAPAN.89(4):044401(2020)journal articl
A low-frequency IL4R locus variant in Japanese patients with intravenous immunoglobulin therapy-unresponsive Kawasaki disease
Background: Kawasaki disease (KD) is a systemic vasculitis which may be associated with coronary artery aneurysms. A notable risk factor for the development of coronary artery aneurysms is resistance to intravenous immunoglobulin (IVIG) therapy, which comprises standard treatment for the acute phase of KD. The cause of IVIG resistance in KD is largely unknown; however, the contribution of genetic factors, especially variants in immune-related genes, has been suspected. Methods: To explore genetic variants related to IVIG-unresponsiveness, we designated KD patients who did not respond to both first and second courses of IVIG therapy as IVIG-unresponsive patients. Using genomic DNA from 30 IVIG-unresponsive KD patients, we performed pooled genome sequencing targeting 39 immune-related cytokine receptor genes. Results: The single nucleotide variant (SNV), rs563535954 (located in the IL4R locus), was concentrated in IVIG-unresponsive KD patients. Individual genotyping showed that the minor allele of rs563535954 was present in 4/33 patients with IVIG-unresponsive KD, compared with 20/1063 individuals in the Japanese genome variation database (odds ratio = 7.19, 95% confidence interval 2.43-21.47). Furthermore, the minor allele of rs563535954 was absent in 42 KD patients who responded to IVIG treatment (P = 0.0337), indicating that a low-frequency variant, rs563535954, is associated with IVIG-unresponsiveness in KD patients. Although rs563535954 is located in the 3'-untranslated region of IL4R, there was no alternation in IL4R expression associated with the mior allele of rs563535954. However, IVIG-unresponsive patients that exhibited the minor allele of rs563535954 tended to be classified into the low-risk group (based on previously reported risk scores) for prediction of IVIG-resistance. Therefore, IVIG-unresponsiveness associated with the minor allele of rs563535954 might differ from IVIG-unresponsiveness associated with previous risk factors used to evaluate IVIG-unresponsiveness in KD. Conclusion: These findings suggest that the SNV rs563535954 could serve as a predictive indicator of IVIG-unresponsiveness, thereby improving the sensitivity of risk scoring systems, and may aid in prevention of coronary artery lesions in KD patients.ArticlePEDIATRIC RHEUMATOLOGY.17:34(2019)journal articl
花の絵の系譜の読解的鑑賞 : ヒューホ・ファン・デル・フース「ポルティナーリ祭壇画」と尾形光琳「燕子花図屛風」の東西比較を含む鑑賞題材の提案
本稿では,『中学校学習指導要領』第6節美術がB鑑賞領域の指導事項とする,「美術を通した国際理解」に立脚し,ヒューホ・ファン・デル・フース「ポルティナーリ祭壇画」,その中央図下部を彩る花の情景と,群舞的な美と壮麗さを併せ持つ尾形光琳「燕子花図屛風」の読解的鑑賞に関する多角的検討を試みる。その際,前者では,キリスト教図像学に基本則る図像学的読解を適用した読み取りを確認し,後者は,絵の背後に隠れる『伊勢物語』第九段〈三河国八橋〉に照明を当て,物語と在原業平の歌とを絵に還流させ,言語と視覚的イメージの合一的状態から絵を読み直してみた。かかる教材研究的段階を経,二作の読解と東西比較を主要活動に位置付ける8段階の授業計画を提起し,それを以て本稿の結部とした。今後の最重要課題は,提起事項の臨床的分析であり,検証授業の実現を模索したい。Article美術教育学研究.49(1):89-96(2017)journal articl
CELLULAR STRATIFIED SPACES
Book chapterCombinatorial and Toric Homotopy: 305-435(2017)boo
Forest in situ observations using unmanned aerial vehicle as an alternative of terrestrial measurements
Background: Lately, terrestrial point clouds have drawn attention as a new data source for in situ forest investigations. So far, terrestrial laser scanning (TLS) has the highest data quality among all terrestrial point cloud data in terms of geometric accuracy and level of detail (IEEE Transact Geosci Remote Sens 53: 5117-5132, 2015). The TLS point clouds processed by automated algorithms can provide certain individual tree parameters at close to required accuracy in practical applications. However, all terrestrial point clouds face a general challenge, which is the occlusions of upper tree crowns. An emerging technology called unmanned-aerial-vehicle (UAV) - borne laser scanning (ULS) potentially combines the strengths of above and under canopy surveys. Results: The performance of ULS are evaluated in 22 sample plots of various forest stand conditions in a boreal forest. The forest parameter estimates are benchmarked through a comparison with state-of-the-art terrestrial mechanisms from both static terrestrial and mobile laser scanning. The results show that in easy forest stand conditions, the performance of ULS point cloud is comparable with the terrestrial solutions. Conclusions: This study gives the first strict evaluation of ULS in situ observations in varied forest conditions. The study also acts as a benchmarking of available active remote sensing techniques for forest in situ mensuration. The results indicate that the current off-the-shelf ULS has an excellent tree height/tops measurement performance. Although the geometrical accuracy of the ULS data, especially at the stem parts, does not yet reach the level of other terrestrial point clouds, the unbeatable high mobility and fast data acquisition make the ULS a very attractive option in forest investigations.ArticleFOREST ECOSYSTEMS.6:20(2019)journal articl
DEVELOPMENT OF SMART PRECISION FOREST IN CONIFER PLANTATION IN JAPAN USING LASER SCANNING DATA
Currently, the authors are planning to launch a consortium effort toward Japan’s first smart precision forestry project using laser data and to develop this technology throughout the country. Smart precision forestry information gathered using the Nagano model (laser scanning from aircraft, drone, and backpack) is being developed to improve the sophistication of forest information, reduce labor-intensive work, maintain sustainable timber productivity, and facilitate supply chain management by laser sensing information in collaboration with industry, academia, and government. In this paper, we outline the research project and the technical development situation of unmanned aerial vehicle laser scanning.ArticleThe International Archives of the Photogrammetry, Remote Sensing and Spatial Information Sciences.XLII-3/W3:95-100(2017)journal articl