A study of the effective output activities : An application of “Large Grammar” and ways of making occasion.

英語は人と人とをつなぐコミュニケーションツールである。英語学習の醍醐味は自分が発信した英語が伝わり相手の英語を理解できた喜びにもある。新型コロナウイルスの影響でコミュニケーション活動が制限されるなか教師は英語でつながる喜びをどのように生徒に伝えるかまたどのようなアウトプット活動が生徒の英語による表現力の向上に効果があるのか鳥取大学地域学部の足立和美が提唱するLarge Grammarの手法を取り入れながら活動の場の工夫について考えてきた。ここでは各学年で取り組んできた実践を紹介する。English is one of the communication tools used by humans, and this is the very reason why English learners take pleasure in making themselves understood in English and understanding others’ English. However, under the current situation in which new corona virus has spread globally, communicative activities using English in lessons have been limited in terms of amount of time and method of classes. This essay presents what Tottori University Junior High School has carried out, using methods of Large Grammar by ADACHI Kazumi of Tottori University, in English classes of each grade year, thinking about what kind of communication activities can be practiced, whether they can help develop students’ ability in expressing themselves, and finally how teachers can give students chances to feel the joy of communication with others in English

Junior high school output activities based on the "Large Grammar" method : Using English as a communication tool.

英語科では， 学習した英語を用いて実際にコミュニケーションが行えることを目標として日常的にアウトプット活動を実践している。具体的な活動の一つとしては， 共同研究者である鳥取大学地域学部の足立和美が提唱するLarge Grammar の手法による活動を用いて即興でのアウトプットの場面を各学年の授業に取り入れている。本研究では， その理論と各学年での活動事例を紹介する。生徒一人ひとりが課題に向かって「主体的に」「対話的に」「深く」考え，英語で他者と繋がっていくためには， どのような活動が考えられるだろうか。「個」の学びを深めるために， 各学年で行ってきたやりくりを紹介する。 / At Tottori University junior high school we practice output activities on a daily basis in our English classes with the aim of enhancing students’ ability to communicate in English. These activities, using the Large Grammar method proposed by one of the authors, Kazumi Adachi, rely on improvised output. In this paper, we introduce the theory of Large Grammar, then give examples of activities used in each grade. We are aiming for activities that encourage students to think "voluntarily", "interactively" and "deeply" about the task. We also want them to connect with others in English. We will introduce the attempts that we have made in each grade to deepen students individual learning

An All-Recombinant Protein-Based Culture System Specifically Identifies Hematopoietic Stem Cell Maintenance Factors.

Hematopoietic stem cells (HSCs) are considered one of the most promising therapeutic targets for the treatment of various blood disorders. However, due to difficulties in establishing stable maintenance and expansion of HSCs in vitro, their insufficient supply is a major constraint to transplantation studies. To solve these problems we have developed a fully defined, all-recombinant protein-based culture system. Through this system, we have identified hemopexin (HPX) and interleukin-1α as responsible for HSC maintenance in vitro. Subsequent molecular analysis revealed that HPX reduces intracellular reactive oxygen species levels within cultured HSCs. Furthermore, bone marrow immunostaining and 3D immunohistochemistry revealed that HPX is expressed in non-myelinating Schwann cells, known HSC niche constituents. These results highlight the utility of this fully defined all-recombinant protein-based culture system for reproducible in vitro HSC culture and its potential to contribute to the identification of factors responsible for in vitro maintenance, expansion, and differentiation of stem cell populations

Spatiotemporal T790M Heterogeneity in Individual Patients with EGFR-Mutant Non–Small-Cell Lung Cancer after Acquired Resistance to EGFR-TKI

IntroductionEpidermal growth factor receptor (EGFR) mutation T790M accounts for approximately half of acquired resistances to EGFR-tyrosine kinase inhibitor (TKI). Because T790M is mediated by TKI exposure, its penetration and “on–off” may affect T790M status.MethodsWe retrospectively reviewed T790M status and clinical course of patients who had undergone multiple rebiopsies after acquired resistance to EGFR-TKI.ResultsOf 145 patients with EGFR-mutant NSCLC receiving rebiopsy after acquired resistance, 30 underwent multiple site rebiopsies, and 24 received repeated rebiopsies at the same lesion. In 22 patients who underwent rebiopsies from both central nervous system (CNS; 20 cerebrospinal fluids [CSF] and 2 brain tumoral tissues) and thoracic lesions (7 lung tissues, 14 pleural effusions, and 1 lymph node), 12 were thoracic-T790M-positive. Of these 12 patients, 10 were CNS-T790M-negative, despite exhibiting thoracic-T790M-positive. All 10 thoracic-T790M-negatives were CNS-T790M-negative. Three patients revealed a spatial heterogeneous T790M status among their thoracic lesions. In 24 patients receiving repeated rebiopsies at the same lesion (12 lung tissues, 6 CSFs, and 6 pleural effusions), T790M status of lung lesions varied in five patients after TKI-free interval. In all five patients whose T790M status changed from positive to negative, EGFR-TKI rechallenge was effective. In three of these five patients, after further TKI exposure, T790M status changed from negative to positive again. There was also a patient whose CSF T790M status changed from negative to positive after high-dose erlotinib therapy.ConclusionsT790M status in an individual patient can be spatiotemporally heterogeneous because of selective pressure from EGFR-TKI

Making Peer Relationship in the Play Session of 5-year-old Children : A Preliminary Study

In this study, 32 5-year-olds were observed during controlled play sessions, where four same-sex children unfamiliar to each other played together with two adults guiding their play. Sessions were first begun with parents of children, and included separation from parents, Japanese traditional play, two-times unattended free play, and interviews immediately after play. There children were measured and rated by observers in extent they participated in the play. On separation, children coded if they accepted dismissal of their parents. In Japanese traditional play, children were rated their achievement for taking two different roles, a leading role, and a herd-like role. Additionally they were measured in their amounts of locomotion during the unattended play. The results showed several tendencies about children’s participation to play. First, their locomotion during the unattended play generally increased from the first unattended play to the second, suggesting that they adjusted their behavior during the session. Moreover, their increment was related to the descriptions on the groups by an adult who had guided their play; groups whose increment of locomotion was relatively large had the description that the group consisted of one leading child and children who followed him or her, and the other groups did not. Secondly, their achievement for the leading role in the traditional play was correlated with positive impressions of that play stated by children on interviews, but the herd role was not, although those two different types of roles were correlated. These results are discussed in terms of the possibility to measure children's attendance at groups quantitatively and objectively

How Sensitive Are Epidermal Growth Factor Receptor–Tyrosine Kinase Inhibitors for Squamous Cell Carcinoma of the Lung Harboring EGFR Gene–Sensitive Mutations?

Introduction:Epidermal growth factor receptor (EGFR) mutations are found mostly in adenocarcinoma, and rarely in squamous cell carcinoma (SQC). Little is known about SQC harboring EGFR mutations.Methods:Between April 2006 and October 2010, we investigated the incidence of EGFR activating mutations in SQC of the lung using the peptide nucleic acid-locked nucleic acid polymerase chain reaction clamp method. The efficacy of EGFR-tyrosine kinase inhibitors (TKIs) was retrospectively evaluated in patients with EGFR-mutated SQC. Further pathologic analyses were performed using immunohistochemistry.Results:Thirty-three of 249 patients with SQC (13.3%) had EGFR mutations, including exon 19 deletion (19 of 33 patients, 58%), L858R point mutation in exon 21 (12 of 33, 36%), and G719S point mutation in exon 18 (2 of 33, 6%). Twenty of these 33 patients received EGFR-TKI therapy, and five of these 20 responded to EGFR-TKIs with a response rate of 25.0% (95% confidence interval [CI], 8.7%–49.1%). The patients’ median progression-free survival and median overall survival were 1.4 months (95% CI, 0.7–5.8 months) and 14.6 months (95% CI, 2.9–undeterminable months), respectively. Approximately one third of the EGFR-mutated SQC patients achieved progression-free survival for longer than 6 months. Some of these patients had high carcinoembryonic antigen levels or a history of never smoking, or were positive for thyroid transcription factor-1.Conclusions:Although EGFR-TKIs seem to be generally less effective in EGFR-mutated SQC than in EGFR-mutated adenocarcinoma, some EGFR-mutated SQC patients can obtain clinical benefit from EGFR-TKIs. To better identify these patients, not only EGFR mutation status, but also clinical factors and pathologic findings should be taken into consideration

Controlling genetic heterogeneity in gene-edited hematopoietic stem cells by single-cell expansion

Gene editing using engineered nucleases frequently produces unintended genetic lesions in hematopoietic stem cells (HSCs). Gene-edited HSC cultures thus contain heterogeneous populations, the majority of which either do not carry the desired edit or harbor unwanted mutations. In consequence, transplanting edited HSCs carries the risks of suboptimal efficiency and of unwanted mutations in the graft. Here, we present an approach for expanding gene-edited HSCs at clonal density, allowing for genetic profiling of individual clones before transplantation. We achieved this by developing a defined, polymer-based expansion system and identifying long-term expanding clones within the CD201 +CD150 +CD48 -c-Kit +Sca-1 +Lin - population of precultured HSCs. Using the Prkdc scid immunodeficiency model, we demonstrate that we can expand and profile edited HSC clones to check for desired and unintended modifications, including large deletions. Transplantation of Prkdc-corrected HSCs rescued the immunodeficient phenotype. Our ex vivo manipulation platform establishes a paradigm to control genetic heterogeneity in HSC gene editing and therapy

Isolation and characterization of a cDNA encoding a Translin-like protein, TRAX

AbstractTranslin is a DNA binding protein which specifically binds to consensus sequences at breakpoint junctions of chromosomal translocations in many cases of lymphoid malignancies. To investigate its functional significance at such recombination hotspots, we examined whether Translin interacts with other proteins using a yeast two-hybrid system and identified an associated 33 kd protein partner, TRAX, with extensive amino acid homology. The TRAX protein was established to contain bipartite nuclear targeting sequences in its N-terminal region, suggesting a possible role in the selective nuclear transport of Translin protein lacking any nuclear targeting motifs

Scenario description for multi-agent simulation

Making it easier to design interactions between agents and humans is essential for realizing multi-agent simulations of social phenomena such as group dynamics. To realize large-scale social simulations, we have developed the scenario description languages Q and IPC (Interaction Pattern Card); they enable experts in the application domain (often not computing professionals) to easily create complex scenarios. We have also established a four-step process for creating scenarios: 1) defining a vocabulary, 2) describing scenarios, 3) extracting interaction patterns, and 4) integrating real and virtual experiments. In order to validate the scenario description languages and the four-step process, we ran a series of evacuation simulations based on the proposed languages and process. We successfully double-check the result of the previous controlled experiment done in a real environment