Imaging interferometers for analysis of Thomson scattered spectra

Polarization interferometers have some potential efficiency advantages for imaging Thomson scattering spectral analysis. In this article we present a number of designs for high-efficiency imaging polarization interferometers for Thomson scattering spectral analysis. The use of high-efficiency crystal polarizing beamsplitters (both displacement and angle) results in low-loss complementary passbands (no edge losses), simple imaging systems, and wide field of view. The efficiency and relative merits of both multiple-filter and dispersive-type configurations are being assessed before installation on the JT-60U ruby-laser Thomson scattering system. Light is transferred from the viewing port via a linear array of optical fiber bundles which will be imaged through the interferometer onto the photocathode of an intensified charge coupled device camera. Because of the broadband nature of the Thomson light, the optical delays required to Fourier analyze the spectrum are quite small. This leads to compact multicolor or dispersive systems based on combinations of Wollaston and Savart splitters and traditional waveplates.This work is supported in part by the Grant-in-Aid for Scientific Research in Priority Area “Advanced diagnostics for burning plasma” from the Japanese Ministry of Education, Culture, Sports, Science and Technology No. 1803501

Current issues and perspectives in PD-1 blockade cancer immunotherapy

Programmed cell death 1 (PD-1) signal receptor blockade has revolutionized the field of cancer therapy. Despite their considerable potential for treating certain cancers, drugs targeting PD-1 still present two main drawbacks: the substantial number of unresponsive patients and/or patients showing recurrences, and side effects associated with the autoimmune response. These drawbacks highlight the need for further investigation of the mechanisms underlying the therapeutic effects, as well as the need to develop novel biomarkers to predict the lack of treatment response and to monitor potential adverse events. Combination therapy is a promising approach to improve the efficacy of PD-1 blockade therapy. Considering the increasing number of patients with cancer worldwide, solving the above issues is central to the field of cancer immunotherapy. In this review, we discuss these issues and clinical perspectives associated with PD-1 blockade cancer immunotherapy

Endocervical glandular neoplasia associated with lobular endocervical glandular hyperplasia is HPV-independent and correlates with carbonic anhydrase-IX expression: a Gynaecological Oncology Group Study.

BackgroundLobular endocervical glandular hyperplasia (LEGH) is a rare lesion of the uterine cervix. It has been proposed that LEGH may represent a precursor lesion to a group of mucinous adenocarcinoma with gastric phenotype (GA) that is independent of high-risk human papillomavirus (H-HPV) infection. Carbonic anhydrase-IX (CA-IX) is highly expressed in conventional glandular lesions (CGLs). However, expression of CA-IX in LEGH or GA has not been studied.MethodsIn all, 12 CGLs, 7 LEGHs, 6 LEGHs with coexisting adenocarcinoma in situ (AIS, 3) and GA (3) were identified from Japanese women with a cytological diagnosis of atypical glandular cells of undetermined significance. Immunostaining was used to detect CA-IX and p16(INK)4(a) (hereafter termed p16) protein expression in the tissues and CA-IX protein expression in the Papanicolaou smears (PSs). Polymerase chain reaction was used to detect H-HPV DNA in liquid-based cytology.ResultsOut of 12 (83%) CGLs, 10 were positive with H-HPV and high levels of CA-IX expression were seen in all (100%) cases. P16 protein expression was observed in 11 out of 12 (92%) cases. None of the LEGHs, LEGHs with AIS or GA were positive for H-HPV and only 8 out of 13 (62%) showed focal weak (1+) p16 expression. In contrast, all cases (100%) exhibited strong CA-IX protein expression.ConclusionOur study suggests that there are different molecular mechanisms of carcinogenesis resulting in CGLs vs LEGHs associated with AIS or GA. There is also a possible link between LEGHs and GAs. Furthermore, CA-IX expression may serve as a useful biomarker for the detection of GAs in the absence of H-HPV infection

Effect of Vitronectin Bound to Insulin-Like Growth Factor-I and Insulin-Like Growth Factor Binding Protein-3 on Porcine Enamel Organ-Derived Epithelial Cells

The aim of this paper was to determine whether the interaction between IGF, IGFBP, and VN modulates the functions of porcine EOE cells. Enamel organs from 6-month-old porcine third molars were dissociated into single epithelial cells and subcultured on culture dishes pretreated with VN, IGF-I, and IGFBP-3 (IGF-IGFBP-VN complex). The subcultured EOE cells retained their capacity for ameloblast-related gene expression, as shown by semiquantitative reverse transcription-polymerase chain reaction. Amelogenin expression was detected in the subcultured EOE cells by immunostaining. The subcultured EOE cells were then seeded onto collagen sponge scaffolds in combination with fresh dental mesenchymal cells and transplanted into athymic rats. After 4 weeks, enamel-dentin-like complex structures were present in the implanted constructs. These results show that EOE cells cultured on IGF-IGFBP-VN complex differentiated into ameloblasts-like cells that were able to secrete amelogenin proteins and form enamel-like tissues in vivo. Functional assays demonstrated that the IGF/IGFBP/VN complex significantly enhanced porcine EOE cell proliferation and tissue forming capacity for enamel. This is the first study to demonstrate a functional role of the IGF-IGFBP-VN complex in EOE cells. This application of the subculturing technique provides a foundation for further tooth-tissue engineering and for improving our understanding of ameloblast biology

Long-range heteronuclear J-coupling constants in esters: Implications for 13C metabolic MRI by side-arm parahydrogen-induced polarization

Side-arm parahydrogen induced polarization (PHIP-SAH) presents a cost-effective method for hyperpolarization of 13C metabolites (e.g. acetate, pyruvate) for metabolic MRI. The timing and efficiency of typical spin order transfer methods including magnetic field cycling and tailored RF pulse sequences crucially depends on the heteronuclear J coupling network between nascent parahydrogen protons and 13C, post-parahydrogenation of the target compound. In this work, heteronuclear nJHC (1 < n ≤ 5) couplings of acetate and pyruvate esters pertinent for PHIP-SAH were investigated experimentally using selective HSQMBC-based pulse sequences and numerically using DFT simulations. The CLIP-HSQMBC technique was used to quantify 2/3-bond JHC couplings, and 4/5-bond JHC ≲ 0.5 Hz were estimated by the sel-HSQMBC-TOCSY approach. Experimental and numerical (DFT-simulated) nJHC couplings were strongly correlated (P < 0.001). Implications for 13C hyperpolarization by magnetic field cycling, and PH-INEPT and ESOTHERIC type spin order transfer methods for PHIP-SAH were assessed, and the influence of direct nascent parahydrogen proton to 13C coupling when compared with indirect homonuclear TOCSY-type transfer through intermediate (non-nascent parahydrogen) protons was studied by the density matrix approach

ショウガッコウ ガイコクゴ キョウカカ ニ トモナウ ヨム シドウ ノ アリカタ : テッキ ニ テキセツナ シドウ オ

2020年度から施行される新学習指導要領が公示され，小学校高学年から「読む」「書く」の文字指導が導入されることになった。しかしながら，小学校から開始することになった理由やその指導法などは明確に示されているとは言い難い。本稿では，生得的な言語習得能力の低下やメタ認知能力の上昇がおこる発達段階であること，英語と書記体系が異なる日本語を母語とすることから学習初期から「聞く」「読む」の大量のインプットが必要なこと，「音」と「文字」との乖離を防ぐためにも初期段階からの文字指導が必要なことから，文字指導を小学校から開始するのが『適期』であると明確に示す。さらに，読むための『適切』な指導法として，ホール・ランゲージ的なトップダウン・アプローチと，ルールの積み上げ的なボトムアップ・アプローチを融合させた「バランスト・アプローチ」を推奨し，小学校中学年から中学校までの，段階的に「読む」力をつける系統立てたプログラムを提案する