On Japanese adverbs of a speaker's subjective attitude

This thesis develops a prototype approach to lexicosyntactic categorisation and exemplifies the approach for a set of Japanese adverbs. The general proposals developed in this thesis should contribute to an understanding of lexical subcategorisation where substantial heterogeneity is an issue. In addition, the thesis advances Japanese lexicography by providing detailed analyses of the meaning and use of a number of specific lexical items. Loosely, the adverbs in the set express the speaker’s subjective a ttitu d e or a similar psychological perspective. The set (referred to as SSA adverbs) has approximately 30 members. A prototype subgrouping for this set is motivated and illustrated in detail on the basis of a combination of (and p a rtial convergence of) syntactic, semantic and pragmatic criteria and tests. The thesis demonstrates th a t simply establishing a uniform and discrete class of ‘sentence adverbs’ (characteristic of several earlier approaches) is not a realistic solution for elucidating the internal complexity of adverbs of this kind. The substantial heterogeneity among these items is more amenable to a subcategorisation based on multiple interrelated properties. These properties may vary in strength or salience depending on adverbs, giving rise to a prototype organisation. Chapters in the thesis are arranged in an inductive way. The members of the SSA adverb set are discussed according to criteria in sub-divisions, including detailed lexical analyses at each stage. A view of the internal organisation of SSA adverbs is reached stepby- step, with a final integration

PHENOTYPIC ANALYSIS OF MICE DEFICIENT FOR Ly6C1/Ly6C2

Ly6C comprises two homologous components of Ly6C1 and Ly6C2, and the expression of either of the Ly6C molecules defines unique functional subsets of monocytes. Ly6C is also expressed by other immune cell types, including Aire-expressing medullary thymic epithelial cells. Because the role of Ly6C expression in determining the functional subsets remains unclear, we generated mice deficient for both Ly6C1 and Ly6C2 with CRISPR-Cas9–mediated deletion. Mice deficient for Ly6C1/Ly6C2 showed no major alterations in the subsets and function of monocyte and other immune cells, including the cells involved in the dextran sulfate sodium salt–induced colitis model. By generating the mice deficient for Ly6C1 alone, we have also investigated the expression pattern of Ly6C1 and Ly6C2 in immune cells. Except for medullary thymic epithelial cells and CD4 single-positive T cells, immune cells predominantly expressed Ly6C2. Thus, despite the importance as a marker with a unique differential expression pattern, the Ly6C molecules have no major impact on determining the functional subsets and maintaining immune homeostasis

Aire suppresses CTLA-4 expression from the thymic stroma to control autoimmunity

Impaired production of thymic regulatory T cells (Tregs) is implicated in the development of Aire-dependent autoimmunity. Because Tregs require agonistic T cell receptor stimuli by self-antigens to develop, reduced expression of self-antigens from medullary thymic epithelial cells (mTECs) has been considered to play a major role in the reduced Treg production in Aire deficiency. Here, we show that mTECs abnormally express co-inhibitory receptor CTLA-4 if Aire is non-functional. Upon binding with CD80/CD86 ligands expressed on thymic dendritic cells (DCs), the ectopically expressed CTLA-4 from Aire-deficient mTECs removes the CD80/CD86 ligands from the DCs. This attenuates the ability of DCs to provide co-stimulatory signals and to present self-antigens transferred from mTECs, both of which are required for Treg production. Accordingly, impaired production of Tregs and organ-specific autoimmunity in Aire-deficient mice are rescued by the depletion of CTLA-4 expression from mTECs. Our studies illuminate the significance of mTEC-DC interaction coordinated by Aire for the establishment of thymic tolerance

Efficacy Of A Combination Of Transarterial Chemoembolization And Radiation Therapty For Patients With Hepatochellular Carcinoma Ineligible For Resection Or Radiofrequency Ablation.

Purpose: The local control rate of trans-arterial chemoembolization (TACE) for the patients with hepatocellular carcinoma (HCC) was unsatisfactory compared to resection or radiofrequency ablation (RFA). To increase the local control rate for tumors, we performed radiation therapy followed by TACE in our institution. The purpose of this study was to evaluate the efficacy and toxicity of the TACE and radiotherapy combination in HCC patients ineligible for resection or RFA. Material and Methods: Between January 2017 and April 2020, 33 patients with HCC ineligible for resection or RFA were treated with a combination of TACE and radiation therapy. Eight patients were initial cases, and 25 were recurrent or residual cases. A total dose of 40-60 Gy in 5-20 fractions was delivered to the 50-90% isodose line. Results: The median follow-up period was 16 months (range, 6-47 months); the objective response rate was 66.7%; and the 1- and 2-year overall survival rates, 72.7% and 62.5%, respectively. The objective response rate for HCCs <5 em was 79.2%; the 1- and 2-year overall survival rates, 91.7% and 62.5%, respectively; median progression-free survival, 13.5 months (range, 3-47 months), and the 1- and 2-year local progression-free survival rates, 95.8% and 85.7%, respectively. There was one case each of grade 2 radiation esophagitis and ascites after three months of irradiation. Conclusion: The combination of TACE and radiation therapy shows good local control and acceptable toxicity, particularly in HCCs <5 cm and may be a good treatment option

英国における日本語教育の再考―異文化理解をめぐる学習者及び日本語教師の意識調査から = Revisiting Japanese Language Education in the UK: A survey on learners’ and teachers’ perceptions regarding intercultural understanding

世界のグローバル化に伴い、以前にも増して異なる文化や価値観を持つ人々が共生するようになり、外国 語教育では単に言語を的確に使えるだけではなく、相手の文化を理解し、自己の文化との違いを受け入れる能力、つまり異文化間コミュニケーション能力（intercultural communicative competence, ICC）が求められるようになった（Byram et al. 2013）。英国の高等教育においても、人の移動が頻繁になりかつ世界情勢が不安定な中にあって、異文化に対する寛容性や関心の高い人材を育てるための教育がますます強く望まれるようになった（Bothwell 2016）。しかし、言語教育の実践では、未だに言語とコミュニケーションを中心とした授業が行われている場合が多い（Byram et al. 2013）。また、異文化間能力（intercultural competence, IC）は必ずしも自然に身につくわけではないとも言われており、意識的なトレーニングの必要性が唱えられている（Behrnd & Porzelt 2012)。本発表は、英国の日本語教育の現場においてどの程度 IC 及び ICC の養成が意識されているかに関する基礎的調査の報告である。英国で活躍している日本語教師（n=34）と日本語を専攻し、日本に留学した経験のある大学学部生（n=38）に彼らの動機や異文化理解に関する意識、日本語教師または話者としての社会的貢献について、オンラインアンケートを行い、詳細な記述を求めた。Byram（1997）の ICC モデルに照らし合わせて学生回答者のコメントを分析した結果、全体として“critical cultural awareness”の不足が目立った。自らを異文化に対する寛容性が高いと評価した学生が多かったものの、その根拠として挙げられた理由からは、異文化理解への自己認識にかなりの差が見られた。また、英国の大学の「多文化コミュニティー」としての側面に対する認識が高いとはいえないことが窺えた。一方教師は、英国の大学の「多文化コミュニティー」としての側面に対する認識は高く、日本語教育の実践の場が、異文化理解能力開発のために有益な教育効果をもたらすことを十分理解していることがデータから観察された。しかし、「多言語多文化社会を意識した教育を行っているか」という問いに対しては、具体的な教育実践に言及した回答が少なく、日本文化について紹介する際に自己の文化と照らし合わせて話し合う程度で IC 及び ICC の養成がカリキュラムに含まれている場合は少ないことが分かった。つまり、教師のビリーフと実践の間には乖離が見られた。以上の結果を踏まえ、英国における日本語教育の現場で IC 及び ICC を高めるために何ができるかを考えたい。= With the advance of globalisation we are living in an increasingly diverse society where people with different cultures and values coexist. Foreign language education has also taken a ‘cultural turn’ (Byram et al. 2013) by which, in addition to learning to use the target language accurately and appropriately, gaining intercultural communicative competence (ICC), i.e., understanding and accepting other cultures, has become a central theme. In the age of international mobility and instability, it became required in higher education in the UK to train students to be tolerant and be interested in other cultures (Bothwell 2016). In reality, however, language and communication continue to be the main focus in many language classrooms and ICC has not been integrated as one of the learning objectives (Byram et al. 2013). Studies have also shown that intercultural competence (IC) does not always develop naturally through the experience of studying abroad, and suggest the need for intercultural training prior to studying abroad (Behrnd & Porzelt 2012). This study is a fundamental research on the awareness of IC and ICC in Japanese Language education in the UK. An online questionnaire was administered to each group. The questions focused on their motives for teaching or learning Japanese, how they perceived IC and ICC and what they thought their contribution to society was. Some questions asked the participants to explain in detail and a total of 34 teachers and 38 university students, who are majoring in Japanese and have studied abroad in Japan, participated. The results from analysing the student questionnaire using Byram’s ICC Model (1997) showed that in general many of the students lacked “critical cultural awareness”. Although many of them thought that they were tolerant to other cultures, there was a big difference in their self-awareness to IC. The results also showed that many of the students did not recognize British Universities as a ‘multicultural society’. The results from analysing the teacher questionnaire showed that many recognized British Universities as a ‘multicultural society’ and fully understood that the classrooms of Japanese language education could improve IC and ICC effectively. However, to the question, ‘Are you teaching students to have an awareness of our multilingual or multicultural society?’ only a few teachers provided concrete examples of IC and ICC related teaching, and few curricula included the training of IC and ICC. That is, there was a separation of teachers’ belief and actual teaching. Based on the results above, we would like to consider what we can do in order to improve IC and ICC for Japanese language education in the UK

AIRE illuminates the feature of medullary thymic epithelial cells in thymic carcinoma

Despite the clear distinction between cortical (cTECs) and medullary thymic epithelial cells (mTECs) in physiology, the cell of origin of thymic carcinomas (TCs) and other thymic epithelial tumors remained enigmatic. We addressed this issue by focusing on AIRE, an mTEC-specific transcriptional regulator that is required for immunological self-tolerance. We found that a large proportion of TCs expressed AIRE with typical nuclear dot morphology by immunohistochemistry. AIRE expression in TCs was supported by the RNA-seq data in the TCGA-THYM database. Furthermore, our bioinformatics approach to the recent single-cell RNA-seq data on human thymi has revealed that TCs hold molecular characteristics of multiple mTEC subpopulations. In contrast, TCs lacked the gene signatures for cTECs. We propose that TCs are tumors derived from mTECs

Dysregulated Aire expression and autoimmunity

Deficiency for AIRE/Aire in both humans and mice results in the development of organ-specific autoimmune disease. We tested whether augmented and/or dysregulated AIRE/Aire expression might be also prone to the breakdown of self-tolerance. To define the effect of augmented Aire expression on the development of autoimmunity, antigen-specific clonal deletion and production of clonotypic regulatory T cells (Tregs) in the thymus were examined using mice expressing two additional copies of Aire in a heterozygous state (3xAire-knockin mice: 3xAire-KI). We found that both clonal deletion of autoreactive T cells and production of clonotypic Tregs in the thymus from 3xAire-KI were impaired in a T-cell receptor-transgenic system. Furthermore, 3xAire-KI females showed higher scores of experimental autoimmune encephalomyelitis induced by myelin oligodendrocyte glycoprotein than wild-type littermates, suggesting that augmented Aire expression exacerbates organ-specific autoimmunity under disease-prone conditions. In humans, we found that one patient with amyopathic dermatomyositis showed CD3–CD19– cells expressing AIRE in the peripheral blood before the treatment but not during the remission phase treated with immunosuppressive drugs. Thus, not only loss of function of AIRE/Aire but also augmented and/or dysregulated expression of AIRE/Aire should be considered for the pathogenesis of organ-specific autoimmunity. We suggest that further analyses should be pursued to establish a novel link between organ-specific autoimmune disease and dysregulated AIRE expression in clinical settings

Assay of serum E2 concentration inpostmenopausal breast cancer patients using a high-sensitivity RIA method is generally useful

Background : Serum E2 must be monitored for aromatase inhibitor (AI) therapy, but conventional assays lack sensitivity. Subjects/Methods : Forty amenorrheic breast cancer patients scheduled for AI treatment but requiring hormonological confirmation of their menopausal status were studied. Serum E2 data generated by high-sensitivity RIA and by LC-MS/MS were analyzed for correlation. Results : RIA gave a higher E2 value than LC-MS/MS in 62% of cases, but there was a significant positive correlation. Patients whose E2 levels by RIA were≥2.5 pg/mL higher than those by LC-MS/MS (RIA-H group) and all other patients (RIA-N group) were compared. Both groups showed strong correlations between the two assay methods. With both methods patients with a high BMI had significantly elevated E2. Multiple regression analysis used age, age at menarche, number of births and BMI as explanatory variables. Significant variables were the BMI with LC-MS/MS, and both BMI and age with RIA. The RIA-H and RIA-N groups showed no difference in regard to the BMI, whereas the age was significantly lower in the RIA-H group. Summary : Serum E2 levels determined for postmenopausal women by RIA and LC-MS/MS generally correlated well. High-sensitivity RIA is a potentially useful clinical assay, but it overestimated serum E2 in some women