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Minimal residual disease (MRD) is usually defined as the small number of cancer cells that remain in the body after treatment. The clinical significance of MRD kinetics is well recognized in treatment of hematologic malignancies, particularly acute lymphoblastic leukemia (ALL). Real time quantitative PCR targeting immunoglobulin (Ig) or T-cell receptor (TCR) rearrangement (PCR-MRD), as well as multiparametric flow cytometric analysis targeting antigen expression, are widely used in MRD detection. In this study, we devised an alternative method to detect MRD using droplet digital PCR (ddPCR), targeting somatic single nucleotide variants (SNVs). This ddPCR-based method (ddPCR-MRD) had sensitivity up to 1E-4. We assessed ddPCR-MRD at 26 time points from eight T-ALL patients, and compared it to the results of PCR-MRD. Almost all results were concordant between the two methods, but ddPCR-MRD detected micro-residual disease that was missed by PCR-MRD in one patient. We also measured MRD in stored ovarian tissue of four pediatric cancer patients, and detected 1E-2 of submicroscopic infiltration. Considering the universality of ddPCR-MRD, the methods can be used as a complement for not only ALL, but also other malignant diseases regardless of tumor-specific Ig/TCR or surface antigen patterns.

Translocations of retinoic acid receptor-α (RARA), typically PML–RARA, are a genetic hallmark of acute promyelocytic leukemia (APL). However, because a small fraction of APL lack translocations of RARA, we focused here on APL cases without RARA translocation to elucidate the molecular etiology of RARA-negative APL. We performed whole-genome sequencing, PCR, and FISH for five APL cases without RARA translocations. Four of five RARA-negative APL cases had translocations involving retinoic acid receptor-β (RARB) translocations, and TBL1XR1–RARB was identified as an in-frame fusion in three cases; one case had an RARB rearrangement detected by FISH, although the partner gene could not be identified. When transduced in cell lines, TBL1XR1–RARB homodimerized and diminished transcriptional activity for the retinoic acid receptor pathway in a dominant-negative manner. TBL1XR1–RARB enhanced the replating capacity of mouse bone marrow cells and inhibited myeloid maturation of human cord blood cells as PML–RARA did. However, the response of APL with RARB translocation to retinoids was attenuated compared with that of PML–RARA, an observation in line with the clinical resistance of RARB-positive APL to ATRA. Our results demonstrate that the majority of RARA-negative APL have RARB translocations, thereby forming a novel, distinct subgroup of APL. TBL1XR1–RARB as an oncogenic protein exerts effects similar to those of PML–RARA, underpinning the importance of retinoic acid pathway alterations in the pathogenesis of APL.Significance: These findings report a novel and distinct genetic subtype of acute promyelocytic leukemia (APL) by illustrating that the majority of APL without RARA translocations harbor RARB translocations. Cancer Res; 78(16); 4452–8. ©2018 AACR.

Supplementary Methods: IRB approval, Genomic analysis, Identification of translocations and determination of their breakpoints, Plasmids Construct, Cell line and reagent, Co-immunoprecipotation and immunoblotting analysis, Luciferase assay, Retrovirus production and transduction, FCM and Morphologic analysis, Human CB cell culture, and Colony replating assay. Supplementary Tables: Table 1. Clinical characteristics of RARA translocation negative APL cases. Table 2. BAC clones for FISH used in this study. Table 3. Primer sequences. Table 4. Somatic mutations observed in RARA-negative APL cases. Supplementary Figures: Figure 1. Morphologic feature and FISH analyisis for RARB translocations. Figure 2. Event-free survival of RARA-negative APL. Figure 3. Determination of TBL1XR1 mutated allele by allele-specific PCR. Figure 4. Constructs of TBL1XR1-RARB and other RARA fusions. Figure 5. Morphologic change in U937. Figure 6. Colony replating assay with mouse bone marrow. Figure 7. Colony replating assay with human cord blood.

Inconsistency in maturation of saccharinan kelp due to changes in the marine environment is a problem in terms of securing seedlings for aquaculture. In Hokkaido, the main producing area of Saccharina japonica, it has become a challenge to stably secure the parental algae of the species for aquaculture. When maturation was induced by short-day conditions in naturally collected S. japonica sporophytes as well as in the sporophytes collected from them and cultivated, sorus formation began in approximately 3 weeks and spread to 0.4%-16.8% on the upper side area and 23.2%-41.1% on the underside area after about 5 weeks, with the highest rates, 23.2%-59.5%, observed around the base part of the underside. Sorus formation began from the base and middle parts in the top-intact thalli and from the marginal part in the top-cut thalli. The released zoospore germlings grew steadily as aquaculture seedlings, and the blade width and wet weight of the seedlings collected in August and subjected to mariculture in November were significantly larger after approximately five and a half months compared to those of thalli cultivated using a conventional method (i.e. thalli collected just prior to the mariculture). Seedling production through maturation induction in sporophytes would be a feasible option for seedling production facilities and would be helpful for stably producing seedlings without the effect of the natural environment.

本研究は、美術系造形教育へ三次元デジタイズ技術を取り入れていくことを目的としている。複数種類の機器を導入して実験と教材開発を行い、各機器の特性、価格のバランスを含めて、実際の授業への導入実現性、継続性を分析していく。 5年計画の2年目にあたる本研究では、3Dスキャン4機種の運用実験に加えて、実際の授業でのシステムを利用した演習を行った。Photo Booth型システムでは、3Dメッシュとテクスチャの生成から、オートリギングとアニメーション設定を行った。また、一眼レフ型システムを構築して、複数種類の対象物を用いてスキャン実験を行った。, The goal of this project is to integrate 3D digitizing technologies into the curriculum of art educational institutions. We conduct experiments and develop teaching materials with several types of equipment. Based on the comparison between the characteristics of each equipment and its price, we analyze the feasibility and sustainability using the system in the classroom. In the second year of the five-year plan, we conducted operational experiments of four 3D scanning systems and exercises using this system in the classroom. Using Photo Booth system, students generated 3D mesh and texture, and then set up auto-rigging and animation. In addition, we built a SLR (Single-lens reflex camera) system and conducted scanning experiments with multiple types of objects.

We aimed to examine the effects of cannabidiol (CBD)-containing hemp oil without delta-9-tetrahydrocannabinol (THC) as a supplemental treatment for canine atopic dermatitis (CAD), as well as its adverse effects, and effects on concurrent drug use in dogs.In this retrospective case series, 8 dogs with CAD were diagnosed by veterinary dermatologists certified by the Japanese Society of Veterinary Dermatology.The medical records of dogs supplemented with CBD-containing hemp oil were evaluated with respect to signalment, physical examination, plasma C-reactive protein concentrations, pharmacologic management, the CAD Extent and Severity Index (4th iteration), and the Pruritus Visual Analog Scale.Overall, CBD, used as a supplement in combination with other drugs, was well-tolerated over a wide dose range and decreased the occurrence of pruritus in dogs with CAD when ingested twice a day.This study provides the first report of supplementation with CBD without THC that was effective in controlling pruritic behavior in dogs with CAD.Further controlled studies are required to investigate the dose range, efficacy, and safety.Effets du cannabidiol sans delta-9-tétrahydrocannabinol sur la dermatite atopique canine : évaluation rétrospective de huit cas.Nous avons cherché à examiner les effets de l’huile de chanvre contenant du cannabidiol (CBD) sans delta-9-tétrahydrocannabinol (THC) en tant que traitement complémentaire de la dermatite atopique canine (CAD), ainsi que ses effets indésirables et ses effets sur les médicaments concomitants utilisés chez le chien.Dans cette étude rétrospective de cas, huit chiens atteints de CAD ont été diagnostiqués par des dermatologues vétérinaires certifiés par la Société japonaise de dermatologie vétérinaire.Les dossiers médicaux des chiens supplémentés avec de l’huile de chanvre contenant du CBD ont été évalués en ce qui concerne le signalement, l’examen physique, les concentrations plasmatiques de protéine C-réactive, la gestion pharmacologique, l’indiceDans l’ensemble, le CBD, utilisé comme supplément en association avec d’autres médicaments, a été bien toléré sur une large gamme de doses et a diminué l’apparition de prurit chez les chiens atteints de CAD lorsqu’il est ingéré deux fois par jour.Cette étude fournit le premier rapport de supplémentation en CBD sans THC efficace pour contrôler le comportement prurigineux chez les chiens atteints de CAD.D’autres études contrôlées sont nécessaires pour étudier la gamme de doses, l’efficacité et l’innocuité.(Traduit par D

本研究は、美術系造形教育へ三次元デジタイズ技術を取り入れていくことを目的としている。複数種類の機器を導入して実験と教材開発を行い、各機器の特性、価格のバランスを含めて、実際の授業への導入実現性、継続性を分析していく。 5 年計画の初年度では、Photo Booth 型、Hand Held 型、赤外線360 度カメラ型の3 種の機器を導入した。それぞれ、システム開発、運用実験、教材開発を進めた。特に、赤外線360 度カメラ型では、学生の卒業作品に利用することができた。夜の大学全体を三次元スキャンすることで、ウェブ上で体験できる作品「バーチャルナイトユニバーシティ」が完成した。, The goal of this project is to integrate 3D digitizing technologies into the curriculum of art educational institutions. We conduct experiments and develop teaching materials with several types of equipment. Based on the comparison between the characteristics of each equipment and its price, we analyze the feasibility and sustainability using the system in the classroom. In the first year of the five-year plan, we introduced three types of equipment: Photo Booth, Hand Held, and Infrared 360-degree camera. For each equipment, we developed systems and teaching materials, and conducted operational experiments. In particular, the infrared 360-degree camera was used for the students’ graduation project. By scanning the entire university at night, the student has created “Virtual Night University” that can be experienced on the web.

Background An atypical form of Burkitt leukemia/lymphoma (BL), BL with a phenotype of precursor B-cells (preBLL), is listed in the WHO Classification. Recent reports suggested that preBLL and classical BL could be distinguished by the differences in IG-MYC translocation architecture and an additional mutated genes profile. The characteristics of classical BL are IG-MYC by aberrant somatic hypermutation or class switch recombination, and BL-specific gene mutations such as MYC, ID3, and CCND3. Meanwhile, preBLL is characterized by IG-MYC due to aberrant VDJ recombination and mutations in NRAS and KRAS. However, it is not clear whether all preBLL cases can be differentiated. This report investigated the molecular characteristics of an infant preBLL case, with a more advanced stage of maturity than typical preBLL. Case The patient showed BL-like morphology with IGH-MYC rearrangement. In the immunophenotyping, CD20 and surface immunoglobulin were negative, whereas other markers were consistent with BL. To evaluate the genetic contribution, we performed whole-exome sequencing. The breakpoint analysis revealed the IG-MYC occurred due to an aberrant VDJ recombination. Meanwhile, additional somatic mutations were detected in FBXO11, one of the mutant genes specific to BL. In the analysis of the specimen in complete remission, mutation in KRAS, frequently mutated in preBLL, was detected with low frequency, suggesting somatic mosaicism. Conclusion The present case showed the characteristics of both typical preBLL and classical BL. Because preBLL includes atypical cases such as the present case, further studies are required to elucidate preBLL features.

Background Lymphoblastic lymphoma (LBL) and acute lymphoblastic leukemia (ALL) are categorized as the same entity under precursor lymphoid neoplasms in the World Health Organization classification. However, compared to B-cell ALL, the molecular genetic makeup of B-cell LBL remains to be understood, mainly due to its rarity. We performed whole exome sequencing (WES) on seven patients with TCF3-PBX1-positive B-cell LBL. Methods WES was performed using DNA extracted from tumor specimens and paired blood samples at remission for six patients, and tumor-only analysis was performed for one patient whose remission sample was not available. For one patient, a relapsed sample was also analyzed. Results KMT2D variants and 6q LOH were found as recurrent alterations. Somatic variants of KMT2D were identified in three of the seven patients. Of note, the two patients with heterozygous nonsense variant of KMT2D were at stage III, without bone marrow infiltration. 6q LOH was also identified in two others, out of the seven patients. The common 6q deleted region of the two patients ranged from 6q12 to 6q16.3. Both patients had bone marrow infiltration. Analysis of recurrent case also revealed that the relapsed clone might be derived from a minor clone of the bone marrow at diagnosis. Conclusion In this study, through WES for seven patients with TCF3-PBX1-positive B-LBL, we identified KMT2D mutations and 6q LOH as recurrent alterations. In order to elucidate the relationship between these recurrent alterations and disease specificity or outcomes, further studies comparing with TCF3-PBX1-positive B-ALL are required.

Purpose: Primary central nervous system (CNS) rhabdomyosarcomais a rare mesenchymal tumor predominantly seen in children and associated with a poor outcome. We report a case of primary CNS rhabdomyosarcoma with PAX3-NCOA2 fusion and presenta systematic meta-review of primary CNS rhabdomyosarcoma to characterize this rare tumor.Methods: We present the case of a 6-year-old boy with primary CNS rhabdomyosarcoma in the posterior fossa. In a systematic meta-review, we compare the demographic data of primary CNS rhabdomyosarcoma with data of rhabdomyosarcoma at all sites from the SEER database and analyze clinical factors associated with survival outcome.Results: Our patient underwent gross total resectionand receivedvincristine, actinomycin-D, cyclophosphamide with early introduction of concurrent focal radiation and remained alive with no evidence of disease for 2 years after the end of therapy. Histopathological review revealed embryonal-type rhabdomyosarcoma, and whole-transcriptome analysis revealed PAX3 (EX6)-NCOA2 (EX12) fusion. In all, 77 cases of primary CNS rhabdomyosarcoma were identified through the meta-review. The demographic data of primary CNS rhabdomyosarcoma were similar to dataof rhabdomyosarcoma at all sites. Overall and event-free survival outcomes were available for 64 and 56 patients, respectively, with a 3-year OS of 29.5%and a 3-year EFS of 26.2%. The group that received trimodal treatment exhibited better survival outcomes, with a 3-year OS of 57.4%and a 3-year EFS of 46.3%.Conclusions: Primary CNS rhabdomyosarcoma shares common histological, molecular, and demographic features with non-CNS rhabdomyosarcoma. A trimodal treatment approach with early introduction of radiation therapy may result in favorable survival outcomes.

The effect of genetic variation on second malignant neoplasms (SMNs) remains unclear. First, we identified the pathogenic germline variants in cancer-predisposing genes among 15 children with SMNs after childhood leukemia/lymphoma using whole-exome sequencing. Because the prevalence was low, we focused on the association between SMNs and NUDT15 in primary acute lymphoblastic leukemia (ALL) cases. NUDT15 is one of the 6-mercaptopurine (6-MP) metabolic genes, and its variants are common in East Asian individuals. The prevalence of NUDT15 hypomorphic variants was higher in patients with SMNs (n = 14; 42.9%) than in the general population in the gnomAD database (19.7%; P = .042). In the validation study with a cohort of 438 unselected patients with ALL, the cumulative incidence of SMNs was significantly higher among those with (3.0%; 95% confidence interval [CI], 0.6% to 9.4%) than among those without NUDT15 variants (0.3%; 95% CI, 0.0% to 1.5%; P = .045). The 6-MP dose administered to patients with ALL with a NUDT15 variant was higher than that given to those without SMNs (P = .045). The 6-MP–related mutational signature was observed in SMN specimens after 6-MP exposure. In cells exposed to 6-MP, a higher level of 6-MP induced DNA damage in NUDT15-knockdown induced pluripotent stem cells. Our study indicates that NUDT15 variants may confer a risk of SMNs after treatment with 6-MP in patients with ALL.

IntroductionGiven an increasing use of dipeptidyl peptidase-4 (DPP-4) inhibitors to treat patients with type 2 diabetes mellitus in the real-world setting, we conducted a prospective observational study (Japan-based Clinical Research Network for Diabetes Registry: J-BRAND Registry) to elucidate the safety and efficacy profile of long-term usage of alogliptin.Research design and methodsWe registered 5969 patients from April 2012 through September 2014, who started receiving alogliptin (group A) or other classes of oral hypoglycemic agents (OHAs; group B), and were followed for 3 years at 239 sites nationwide. Safety was the primary outcome. Symptomatic hypoglycemia, pancreatitis, skin disorders of non-extrinsic origin, severe infections, and cancer were collected as major adverse events (AEs). Efficacy assessment was the secondary outcome and included changes in hemoglobin A1c (HbA1c), fasting blood glucose, fasting insulin and urinary albumin.ResultsOf the registered, 5150 (group A: 3395 and group B: 1755) and 5096 (3358 and 1738) were included for safety and efficacy analysis, respectively. Group A patients mostly (>90%) continued to use alogliptin. In group B, biguanides were the primary agents, while DPP-4 inhibitors were added in up to ~36% of patients. The overall incidence of AEs was similar between the two groups (42.7% vs 42.2%). Kaplan-Meier analysis revealed the incidence of cancer was significantly higher in group A than in group B (7.4% vs 4.8%, p=0.040), while no significant incidence difference was observed in the individual cancer. Multivariate Cox regression analysis revealed that the imbalanced patient distribution (more elderly patients in group A than in group B), but not alogliptin usage per se, contributed to cancer development. The incidence of other major AE categories was with no between-group difference. Between-group difference was not detected, either, in the incidence of microvascular and macrovascular complications. HbA1c and fasting glucose decreased significantly at the 0.5-year visit and nearly plateaued thereafter in both groups.ConclusionsAlogliptin as a representative of DPP-4 inhibitors was safe and durably efficacious when used alone or with other OHAs for patients with type 2 diabetes in the real world setting.

Translocations of retinoic acid receptor-α (RARA), typically PML–RARA, are a genetic hallmark of acute promyelocytic leukemia (APL). However, because a small fraction of APL lack translocations of RARA, we focused here on APL cases without RARA translocation to elucidate the molecular etiology of RARA-negative APL. We performed whole-genome sequencing, PCR, and FISH for five APL cases without RARA translocations. Four of five RARA-negative APL cases had translocations involving retinoic acid receptor-β (RARB) translocations, and TBL1XR1–RARB was identified as an in-frame fusion in three cases; one case had an RARB rearrangement detected by FISH, although the partner gene could not be identified. When transduced in cell lines, TBL1XR1–RARB homodimerized and diminished transcriptional activity for the retinoic acid receptor pathway in a dominant-negative manner. TBL1XR1–RARB enhanced the replating capacity of mouse bone marrow cells and inhibited myeloid maturation of human cord blood cells as PML–RARA did. However, the response of APL with RARB translocation to retinoids was attenuated compared with that of PML–RARA, an observation in line with the clinical resistance of RARB-positive APL to ATRA. Our results demonstrate that the majority of RARA-negative APL have RARB translocations, thereby forming a novel, distinct subgroup of APL. TBL1XR1–RARB as an oncogenic protein exerts effects similar to those of PML–RARA, underpinning the importance of retinoic acid pathway alterations in the pathogenesis of APL. Significance: These findings report a novel and distinct genetic subtype of acute promyelocytic leukemia (APL) by illustrating that the majority of APL without RARA translocations harbor RARB translocations. Cancer Res; 78(16); 4452–8. ©2018 AACR.

Herein, we propose methods that use three-dimensional trajectory data (one-dimensional time × two-dimensional space) acquired from probe vehicles to detect damaged spots on roads caused by natural disasters. Detecting road damages immediately after a disaster is essential to ensure quick and safe evacuations, rescue and relief operations, and efficient road repairs. However, road damages are currently monitored only by closed-circuit television, administrators patrolling the roads, and reports from users of the roads. Consequently, the number of locations that are being monitored is limited, and damage detection is delayed. Our proposed methods automatically estimate the locations of widespread damages on general roads. After analyzing and extracting the features of probe data obtained during a disaster, our proposed methods were verified using the data of past disasters. Our methods can identify anomalous vehicle behaviors and indicate various possibilities for detecting road damages.

BACKGROUND Genetic hallmark of atypical teratoid/rhabdoid tumor (AT/RT) is loss-of-function variants or deletions in SMARCB1 gene on 22q11.2 chromosome, which is common to extracranial malignant rhabdoid tumors (MRT). Previous studies demonstrated that approximately one-thirds of AT/RT and extracranial MRT patients harbored germline SMARCB1 variants as the rhabdoid tumor predisposing syndrome. We studied herein intensive analysis of the SMARCB1 gene in AT/RT and extracranial MRT patients focusing on prevalence of germline genetic variants. PROCEDURE: In total, 16 patients were included. Both tumor-derived DNA and germline DNA were obtained from all patients. First, screening for SMARCB1 alterations in the tumor specimens was done by direct sequencing, ddPCR and SNP array analysis. Then, analysis of germline DNA samples focusing on the genomic abnormalities detected in the paired tumors in each case was performed. RESULTS In eight of 16 cases (50%), genomic alterations observed in the tumor-derived DNA were also detected in the germline DNA. It is worth noting that three patients had germline mosaicism. Two of three patients had mosaic deletion, including SMARCB1 region, and the average copy number of the deleted region in the SMARCB1 gene in the germline was 1.60 and 1.76. For another patient, the fraction of SMARCB1 variants in normal cells was as low as 1.7%. CONCLUSIONS Approximately half the MRT cases in this study had SMARCB1 germline alterations. Considering the presence of low-frequency mosaicisms which conventional methods might overlook, inherited germline variants in predisposition genes are more important than previously assumed for the pathogenesis of pediatric cancers.

Enantioselective α-allylation of α-substituted β-ketoesters with simple allyl alcohols was successfully performed by synergistic catalysis with the catalyst combination of a chiral primary amino acid and an achiral palladium complex without additional promotors like acids or bases. The allylation reaction and generation of a chiral quaternary carbon stereocenter proceeded smoothly to produce α,α-disubstituted β-ketoesters in high yields (91-99%) with high enantioselectivities (90-99% ee).

本稿は科学研究費助成事業16K00731「地域博物館の有する骨格標本を3D プリンターを用いて活用する手法の開発と実践」及び、その成果発表としての「動物のからだ展」の実施報告である。研究においては美術・デザイン系大学の取り組みとして、地域の自然史博物館や動物園資料館に収蔵されている骨格標本のデジタルデータ化と3D プリンターを用いたレプリカ制作、及びそれらを展示、教育目的として活用する一連の試みを実践した。3D スキャンの手法としてはフォトグラメトリーを採用している。フォトグラメトリーのデータ取得において、館外への持ち出しが難しい貴重な標本については、撮影条件を整えるのが困難な出張先においても成功率を高めるノウハウも確立した。本稿においてはそれらについても報告している。 「動物のからだ展」ではこれまでに無い試みとして、美術と博物の垣根を越え、人工物である美術作品や標本のレプリカを同じ会場で比較して展示をしている。多くの展示・発表の機会も創出し、「動物のからだ展」では9 日間で2,700 名の動員を得た。, This report is the implementation report of Grants-in-Aid for Scientific Research 16K00731 "Development and practice of a method to use skeletal specimens owned by the natural history museum with a 3D printer" and "Animal Body Exhibition” of the research's result announcement. In this research , as a study of art design university, we did digitalization of skeletal specimens and replica production using 3D printer. The replicas were produced using skeletal specimens stored in the museum of natural history and the zoo's museum, and those collected by ourselves. I adopted photogrammetry as a method of 3D scanning. It is very difficult to acquire data of valuable samples that are difficult to take out outside because it is difficult to set up the imaging conditions. We have also established a way to increase the success rate of data acquisition under such difficult shooting conditions. In “Animal Body Exhibition”, we made an unprecedented attempt. We display replicas of works of art and specimens, which are artefacts, across the boundaries of art and museums at the same venue. At the “Animal Body Exhibition”, 2,700 people were mobilized on the 9days.

Intensive analysis of the SMARCB1 gene in malignant rhabdoid tumors (MRT) revealed eight of 16 patients with constitutional genetic variants. Three patients had mosaicism of deletion/variant of the SMARCB1 gene, which conventional methods might overlook. The prevalence of cancer predisposition in MRT may thus be higher than previously reported.

Maritime Autonomous Surface Ship (MASS) has been developed recently, and demonstration projects have been carried out internationally. Considering the full autonomous level is unlikely to be addressed shortly, remote control centre and Remote Operator (RO) will play a vital role in the MASS system. Although competence of watchkeeping at the ship&rsquo, s bridge is inevitable for RO to avoid ship accidents caused by human errors, international requirements have not been introduced yet. This paper presents a way to develop the regulatory framework on the competence of RO based on the International Convention on Standards of Training, Certification and Watchkeeping for Seafarers (STCW) by exploring the concept of Situation Awareness (SA). Goal-Based Gap Analysis (GBGA) is constructed based on the human-behaviour model and the required information for SA. A case study through the mini focus group discussion with interviews by a total of three (3) veteran instructors of training ships is conducted utilising the information including the results of previous demonstration projects on the remote control. The results show the relationship between required information and ship sense, shortage of these factors when RO is operating, additional competence and possible regulatory requirements for RO. The findings support the usefulness of GBGA and pave the way to develop a regulatory framework for RO further.

自然はときに人間の想像をはるかに越えた、不思議な「カタチ」を作り出す。地球上に生息するあらゆる生き物はそれぞれ個性的な独自の形を持っているが、昆虫の形態の多様性は特に群を抜いているといえるだろう。 本稿はそうした昆虫のなかでも特に特異かつ美しい形態を特徴とするツノゼミ「マルヨツコブツノゼミ」について、展示で使用するための模型の受注から制作、展示を行うまでの一連の流れや技法、考え方について記録したものである。 「マルヨツコブツノゼミ」は全長が1センチ足らずの微細な昆虫であり、形の面白さで大変人気のある種類である。 その小ささのため肉眼での観察は困難であり、研究者から依頼を受けて拡大模型を制作することになった。 制作にあたっては、デジタル造形や3Dプリントを活用した。デジタル彫刻を博物館での展示模型制作に活用するという試みは芸術と科学技術が交差する学際分野である芸術工学にとってふさわしい題材であると考えている。, Nature sometimes creates a mysterious "shape" that goes far beyond human imagination. Every living thing that lives on the earth has its own unique form, but it can be said that the diversity of insect form is particularly outstanding. In this article, I describe a series of work flow, techniques, and ideas from the receipt of orders for models to be used in exhibitions, production, and exhibition about treehoppers "Bocydium globulare" which is characterized by a particularly unique and beautiful form. Treehoppers "Bocydium globulare" is a small insect whose total length is less than a centimeter and it’s a very popular type due to the interestingness of the shape. Because of its small size, it was difficult to observe with the naked eye, and it was decided to produce an enlarged model upon receiving a request from a researcher. I used digital modeling and 3D print for model creation. I believe that trying to using digital sculpting for exhibit model at museums is a suitable subject for design, which is a composite region where art and science and technology intersect.

Translocations of retinoic acid receptor-α (

Lung lesions often appear in patients with sarcoidosis; however, miliary opacities are rare. We herein report the case of a 40-year-old woman with pulmonary sarcoidosis who presented with dyspnea on exertion. Subsequent computed tomography showed miliary opacities, and the presence of granulomas was confirmed by a transbronchial lung biopsy. Glucocorticoid therapy was initiated and the symptoms and miliary opacities rapidly improved. Although miliary sarcoidosis is uncommon, physicians should consider sarcoidosis in addition to tuberculosis, malignancy, and pneumoconiosis when presented with miliary opacities.

A 63-year-old man employed in a hard metal manufacturing company for 40 years presented with a chronic dry cough and exertional dyspnea 20 years after the onset of recurrent exanthemas. A chest radiograph revealed bilateral reticular shadows in the upper lung field. Pathological specimens in which tungsten was detected were obtained via a transbronchial lung biopsy. Patch tests were positive for cobalt and other metals. The patient was diagnosed with hard metal lung disease (HMLD) concurrent with contact dermatitis and treated with corticosteroids. This case suggests that allergies to metal may play a role in the onset of HMLD.

Background: Secondary or subsequent malignant neoplasms (SMNs) are one of the most serious late complications in children and adolescents after treatment for acute lymphoblastic leukemia (ALL). Several studies have reported that excess dosing of 6-mercaptopurine (6-MP) therapy and polymorphisms of 6-MP metabolizing enzyme coding gene might influence the risk of SMNs. Recently, nucleoside diphosphate-linked moiety X-type motif 15 (NUDT15) variants have been identified as a cause of high sensitivity to 6-MP, which reflects a high sensitivity to 6MP in East Asians. Therefore, we investigated an association between NUDT15 genotype and incidence of SMNs in pediatric ALL. Methods: Germline samples including bone marrow samples, peripheral blood samples and buccal swab samples during remission were obtained from 13 cases who suffered from SMN after childhood ALL. The prevalence of major NUDT15 non-functional alleles (*2 and *3), which is categorized intermediate or poor metabolizer of 6-MP in Clinical Pharmacogenetics Implementation Consortium Guideline (Relling M et al. Clin Pharmacol Ther 2019), was evaluated by using Sanger sequencing and/or whole exome sequencing. The NUDT15 variants prevalence in SMN patients with primary ALL was compared to those without SMN, who were registered in the TCCSG L04-16 study, which was conducted by the Tokyo Children's Cancer Study Group (TCCSG). Results: Patients' profiles and NUDT15 genotypes were summarized in table 1. Median ages at diagnoses of ALL and SMNs were 4 (1-15) and 13 (5-44) years, respectively. Median duration between ALL and SMNs was 8 (1-30) years. SMNs included acute myeloblastic leukemia (AML) / myelodysplastic syndrome (MDS) (n = 8), brain tumor (n = 1), basal cell carcinoma (n = 1), bladder cancer (n = 1), Ewing sarcoma (n = 1) and osteosarcoma (n = 1). Among the 13 SMN cases, six patients (46.2%) possessed NUDT15 non-functional alleles. The SMNs of these cases included AML / MDS (n = 4), bladder cancer (n = 1) and osteosarcoma (n = 1). Among them, 3 patients, whose SMNs were AML, bladder cancer and osteosarcoma, were treated with radiation therapy against primary ALL. All NUDT15 genotypes were heterozygous variants (3 were *1/*2 and 3 were *1/*3) and seemed to be intermediate metabolizers. In patients without known SMNs in TCCSG ALL L04-16 cohort study, 73 of 437 (16.7%) possessed NUDT15 non-functional alleles. Three of them had bi-allelic variants (2 cases were *3/*3, 1 case was *2/*3), and the others were all heterozygous. The prevalence of NUDT15 non-functional alleles was significantly higher in SMNs compared to that of non-SMN cases (P = 0.012). Conclusion: Our study indicated the NUDT15 hypomorphic variant alleles could be a risk of SMNs after ALL treatment with 6-MP. NUDT15 heterozygotic variants carriers are generally tolerable of 6-MP, and are usually treated with normal or slightly low-dose of 6-MP. However, our results suggested that standard adjustment of 6-MP in maintenance therapy might cause potential overdose of 6-MP for cases with NUDT15 variants, leading to increased risk of SMNs. To certify it, a higher number of study samples and somatic samples analysis of 6-MP induced SMNs are required. To obtain the best long-term event-free survival probability, it might be necessary to reduce the risk of SMNs development without compromising therapeutic effect by further optimal adjustment of 6-MP dose (or alternative agents). Disclosures No relevant conflicts of interest to declare.

A mechanistic study was carried out for the asymmetric Michael addition reaction of malonates to enones catalyzed by a primary amino acid lithium salt to elucidate the origin of the asymmetric induction. A primary beta-amino acid salt catalyst, O-TBDPS beta-homoserine lithium salt, exhibited much higher enantioselectivity than that achieved with the corresponding catalysts derived from alpha- and gamma-amino acids for this reaction. Detailed studies of the transition states with DFT calculations revealed that the lithium cation and carboxylate group of the beta-amino acid salt catalyst have important roles in achieving high enantioselectivity in the Michael addition reaction of malonates to enones. (C) 2013 Elsevier Ltd. All rights reserved.

Pulmonary Mycobacterium abscessus infection is resistant to many antibiotics and is difficult to treat. We retrospectively analyzed the clinical characteristics of pulmonary infection due to M. abscessus. Eleven cases diagnosed as having pulmonary M. abscessus infection at Osaka Red Cross Hospital from January. 2008, to June, 2012 were enrolled in this study. The average age of the 11 cases was 63 years (all were females). Nine cases showed underlying diseases, comprising 5 cases with Mycobacterium avium complex lung infection, 3 with old pulmonary tuberculosis, and 3 with bronchiectasis. The radiological examination revealed that 10 cases showed the small nodular type, 7 showed the bronchiectatic type, 4 showed a cavity lesion and 4 showed infiltrative shadows. A microbiological definite diagnosis was made from sputum in 10 cases and bronchial lavage fluid in one. As treatment for M. abscessus pulmonary infection, combined multi-drug chemotherapy was carried out in 7 of the 11 cases. No patients were successfully treated with antibiotics alone, whereas 4 patients had no exacerbation of radiological findings without any treatment. One patient received antibiotics including clarithromycin, amikacin and levofloxacin for 2 to 12 months following surgical excision and her sputum cultures have been maintained as negative over the long-term. During the study, none of the 11 patients were known to have died. In this study, we found that M. abscessus pulmonary infection is more common among females, and is found frequently in patients with M. avium complex lung infection. We also found that the clinical course of M. abscessus pulmonary infection was different among patients. We think this is because M. abscessus was shown to comprise three closely related species. M. abscessus is extremely difficult to eradicate, and surgical resection of localized disease or the main lesion or cavity may be significantly effective in preventing the progression of disease.

日本各地に存在する自然史博物館や動物園資料館は、その地域の野生動物や、かつて飼育されていた動物のさまざまな標本を整理、保管しておくという重要な役割を担っている。しかし、収集する資料は膨大な数にのぼるため、それらを標本としてまとめ、整理する作業が間に合っていないという現状がある。学芸員や資料館の担当者からはこうした資料を整え、研究者以外の一般の人や芸術、デザインの関係者に対しても広く公開し、地域の生き物への興味や理解の推進や絵画や立体、工芸などの作品制作に役立てたいと願う声も聞かれる。また、こうした地域博物館の有する学術資源としての標本を、病院で長期の入院治療を受けている子供たちや、被災地などにおいて活用する、出張ミュージアムなどのアウトリーチ活動も盛んに行われはじめている。 本研究では、こうした学術資源のうち、動物の「手」の骨格標本を題材として選び、3D スキャンなどのデジタル技術を用いてレプリカを作成、活用や考察の道を探る。, In various parts of Japan Natural History Museums and Zoos play important role of organizing and storing various specimens of formerly bred wild animals. However, since the amount of collected documents is enormous, often it cannot be properly made into specimen and organized. Curators and museum staff hope these materials, published openly for regular or arts and design related people, could promote understanding and interest in community, and drive creation of various reproductive works like paintings or sculptures. In addition, these science resources owned by regional museums are being used in outreach activities such as traveling Museum for children taking long term hospital treatments, or disaster struck areas. The goal of this study, is using selected skeletal specimens of the hand of animals to create a replica using digital technology such as 3D scanning, as well as exploring its practical uses.

It is said that the age of globalization of Japan started at 15century like other Western countries. It was the beginning of world-wide dispersal of the Japanese in history such as the trade by Wako ships to the Southeast Asia (Befu Harumi 2002). Since then, Japan entered the age of isolation by the Tokugawa Shogunate and closed the door for other countries except for the Dutch. The new age began after the American Black ships came to Japan at the end of 19th century. Japan accepted the foreign culture, especially western culture which was the aspiration of the Japanese in those days enthusiastically. However, it was through the experience of the overseas migration and the dispatch as soldiers at war and colonization that the general Japanese lived in and learned from the foreign culture directly.This paper considers ethnic relations and harmonious coexistence through cross-cultural marriage between Japanese and Indonesian nationals in the anthropological perspective. We asked how the couples crossed the cultural difference and how they obtained the harmony by maintaining their ethnicity in their daily life.The Japanese do not always recognize their ethnicity or culture in their daily life and are not aware of multiplicity of cultures in Japan. Once they meet with other culture, they start to recognize how to understand and how to live with other culture and people more seriously.I focus on the cross-cultural marriage because we can learn the process of learning, negotiating and understanding other culture and ethnicity based on the concrete data.

This study investigated the differences in dose–volume parameters for the breast and normal tissues during TomoDirectTM (TD) intensity-modulated radiation therapy (IMRT), TD-3D conformal radiotherapy (3DCRT) and 3DCRT plans, all using two beams, and analyzed treatment outcomes of two-beam TD-IMRT for breast cancer after breast-conserving surgery. Between August 2011 and January 2015, 152 patients were treated using two-beam TD-IMRT with 50 Gy/25 fractions. Among them, 20 patients with left-sided breast cancer were randomly chosen, and two-beam TD-IMRT, TD-3DCRT and 3DCRT plans were created for each patient. The homogeneity and conformity indices and various dose–volume parameters for the planning target volume and OARs were evaluated. Clinical outcomes were evaluated at 3 years. Toxicities were evaluated using the Common Terminology Criteria for Adverse Events version 4.0. TD-IMRT and TD-3DCRT showed better whole-breast coverage than 3DCRT (P

Highly enantioselective Michael addition of malonates to enones was achieved using a mixed catalyst consisting of a primary β-amino acid, O-TBDPS (S)-β-homoserine, and its lithium salt. Various cyclic and acyclic enones were converted into 1,5-ketoesters in high yields (up to 92%) with high enantioselectivity (up to 97% ee) under mild reaction conditions. Details of synthesis of the catalyst, optimization of the reaction conditions for the Michael addition reaction, and a plausible reaction mechanism are described.

An educational practice entitled “Breaking Away from Shallow Learning Habits” of the Faculty of Engineering, Niigata University is adopted as “Good Practice (GP) of Education” by The Ministry of Education, Culture, Sports, Science and Technology. This practice consists of a new introductory educational program for freshmen entitled “Introduction to Engineering Literacy” , as well as improvement of other lectures/experimentations/exercises for design education. “Introduction to Engineering Literacy” of The Department of Chemistry and Chemical Engineering, is programmed to let the students make “failure” (discrepancy from the knowledge obtained from the textbooks) in experiments, let them propose improvement, and let them conduct the same experiment again after the improvement, so that the freshmen can experience a PDCA (Plan-Do-Check-Action) cycle.

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant neoplasia syndrome characterized by the occurrence of tumors in the parathyroid glands, pancreas, and anterior pituitary. Approximately 30-40% of MEN1 patients also have adrenal lesions, such as hyperplasia, benign adenoma, and adrenocortical carcinoma. Most of the cases are hormonally silent. We describe the case of a 60-year-old man with bilateral macronodular adrenal lesions, in addition to parathyroid tumors, multiple insulinomas, and non-functioning pituitary microadenoma. Endocrinological tests revealed subclinical hypercortisolism; midnight cortisol level rose slightly (8.0 µg/dL), although basal plasma ACTH and cortisol levels were within the normal range (19.5 pg/mL and 12.0 µg/dL, respectively). One and 8 mg dexamethasone suppression tests showed cortisol levels of 2.3 and 9.8 µg/dL, respectively. (131)I-adosterol scintigraphy under dexamethasone suppression revealed bilateral adrenal uptake with right-sided predominance. The histological features of the removed right adrenal gland were consistent with ACTH-independent macronodular adrenal hyperplasia (AIMAH): immunoreactivity of 17α-hydroxylase was predominantly observed in the small compact cells, while that of 3β-hydroxysteroid dehydrogenase was exclusively expressed in the large clear cells. The glucose-dependent insulinotropic polypeptide (GIP) receptor was expressed at high levels in compact cells, suggesting that GIP is responsible for the development of AIMAH. Unilateral small adrenal lesions were detected in the patient's 2 children, who also presented with MEN1 symptoms. Genetic abnormalities in the MEN1, p27, and p18 genes were not found, however, the present case may provide a clue to the understanding of the etiology of MEN1 and AIMAH.