Idea Creation: Function Synthesis Approach with Simplification and Evaluation

AbstractProduct engineer is being required to design attractive products in a short product development cycle from stakeholder. And, its attraction is influenced a great deal by idea creation in a conceptual design phase of this cycle. On the other hand, K. Yoshioka and H. Hasegawa proposed the FSA (Function Synthesis Approach) to create a combination of a large number of functions in a short period of time. FSA become a conceptual design support tool that combines the PSO (Particle Swarm Optimization) and the particle method of USIT. However, FSA is only to outputting combination of large numbers of functions. For this reason, there is a need to provide a way to support the conceptual design process systematically. Therefore, this paper proposes a method to systematically support the conceptual design process from the output of the FSA. This systematic process is consisted from two phases. First, the design solution is built by combination of large number of function via using axiomatic design and function structure method. Next, it is evaluated by using UCP (Use Case Points) method. And, this paper described these phases via example to the refrigerator

Large-scale stem cell production system by newly designed bioreactor

Large scale cell production system is required in drug discovery and cell based therapy. However there are technically challenges in maintaining high quality and low cost for practical biomanufacturing industry. 3D suspension culture is one of attractive process, especially static culture is ultimate free from shear force. Utilizing static 3D suspension culture, automated closed system is newly designed and demonstrated expansion culture over several subcultures. Cell growth curves of this system and conventional manual method have good accordance. The system is also compatible with good scalability for scale up and scale out use. Please click Additional Files below to see the full abstract

Mapping of the 2018 Heavy Rain Disaster in the Southern Part of Hiroshima Prefecture

これまでに発生した土砂災害，洪水，地震，津波などの災害の様子を示した地図をディザスターマップ（災害記録地図）と呼ぶことを提案し，その一例として平成30年7月豪雨直後から行った災害を記録する活動内容を報告した。平成30年7月豪雨によって広島県南部では多数の斜面崩壊が発生し，甚大な被害が生じた。広島大学の調査団を中心に，豪雨直後からその後約1年半に渡り，災害の情報を整理し，被害の様子を記録するディザスターマップの作成を行ってきた。具体的には地理情報システム（GIS）を用いて斜面崩壊の発生状況を示す地図や，被災の様子を記録した写真を撮影位置に配置した地図の作成である。本稿ではこのようなディザスターマップの作成経緯や内容などの記述に加え，今後の防災教育などにおいてのこれらの地図の活用の可能性について予察的な考察を行った。本稿では，過去のすべての災禍を「古災害」（paleo-disaster）と呼ぶことを提案した。ディザスターマップの作成を含め，過去の災禍についてそれぞれの広がりや履歴が明らかにされる研究が進展することを期待したい。A massive disaster, including a large number of slope movements and the flooding of large rivers, was triggered by record-breaking torrential rain in July 2018 over a broad area of western Japan. Severe damage in the southern part of Hiroshima prefecture was mainly caused by the debris flow, with a total of 108 people reported killed or missing. The geographer group for “the Hiroshima University Disaster Investigation Team for July Torrential Rain of 2018” recorded the distribution of slope movements as geographical data and prepared detailed maps on the geographic information system (GIS) since just after its initiation. The authors also created “disaster maps” with photographs of locations of slope movements, broken artificial features, and floods taken in the field were depicted in Higashihiroshima City, where the largest number of slope movements occurred in Hiroshima prefecture. In this paper, we described the process of making these maps and their contents, and the possibility of utilizing them for disaster prevention education. We also proposed referring to all past disasters as “paleo-disaster” to progress the research that reveals the distribution and history of past disasters

Dual effects of FGFR inhibition in lung fibrosis

[Rationale] Fibroblast growth factors (FGF) are major factors associated with the pathogenesis of pulmonary fibrosis. Nintedanib, a tyrosine kinase inhibitor targeting several growth factor receptors including the FGF receptor (FGFR), has been approved for the treatment of idiopathic pulmonary fibrosis (IPF). On the other hand, recent reports suggest that FGF are required for epithelial recovery. In this study, we focused on FGF signaling to both fibroblasts and alveolar epithelial cells (AECs), and examined the effect of a pan-FGFR blocker on experimental pulmonary fibrosis in mice. [Methods] The effects of BGJ398, a pan-FGFR inhibitor, on the migration and proliferation of fibroblasts and AECs were assessed using transwell migration or 3H-thymidine incorporation assays. The expression of FGFR was analyzed using immunoblot or flow cytometry. We also investigated the effect of BGJ398 on the pulmonary fibrosis induced by bleomycin in mice. [Results] Both lung fibroblasts and AECs expressed FGFRs. BGJ398 significantly inhibited the proliferation and migration of lung fibroblasts stimulated with FGF2. BGJ398 also reduced the proliferation of AECs in response to FGF2. Although the administration of BGJ398 ameliorated pulmonary fibrosis in bleomycin-treated mice, it increased mortality due to alveolar injury and inhibition of AEC regeneration. [Conclusions] These data suggest that the total inhibition of FGFR signaling can suppress lung fibrosis by inhibiting fibroblast activities, although alveolar injury is simultaneously caused

Anti-fibrotic efficacy of nintedanib in pulmonary fibrosis via the inhibition of fibrocyte activity

Background: Nintedanib, a tyrosine kinase inhibitor that is specific for platelet-derived growth factor receptors (PDGFR), fibroblast growth factor receptors (FGFR), and vascular endothelial growth factor receptors (VEGFR), has recently been approved for idiopathic pulmonary fibrosis. Fibrocytes are bone marrow-derived progenitor cells that produce growth factors and contribute to fibrogenesis in the lungs. However, the effects of nintedanib on the functions of fibrocytes remain unclear. Methods: Human monocytes were isolated from the peripheral blood of healthy volunteers. The expression of growth factors and their receptors in fibrocytes was analyzed using ELISA and Western blotting. The effects of nintedanib on the ability of fibrocytes to stimulate lung fibroblasts were examined in terms of their proliferation. The direct effects of nintedanib on the differentiation and migration of fibrocytes were also assessed. We investigated whether nintedanib affected the accumulation of fibrocytes in mouse lungs treated with bleomycin. Results: Human fibrocytes produced PDGF, FGF2, and VEGF-A. Nintedanib and specific inhibitors for each growth factor receptor significantly inhibited the proliferation of lung fibroblasts stimulated by the supernatant of fibrocytes. Nintedanib inhibited the migration and differentiation of fibrocytes induced by growth factors in vitro. The number of fibrocytes in the bleomycin-induced lung fibrosis model was reduced by the administration of nintedanib, and this was associated with anti-fibrotic effects. Conclusions: These results support the role of fibrocytes as producers of and responders to growth factors, and suggest that the anti-fibrotic effects of nintedanib are at least partly mediated by suppression of fibrocyte function

Repeated Enterocutaneous Fistula in a Munchausen Syndrome Patient

Munchausen syndrome is a rare type of mental disorder in which the patient fakes illness to gain attention and sympathy. Patients may lie about symptoms, make themselves appear sick, or make themselves purposely unwell. We describe a case of repeated enterocutaneous fistula in Munchausen syndrome. A 53-year-old Japanese male was admitted to our hospital for the treatment of a high-flow enterocutaneous fistula. Surgery was performed two times, but the fistula recurred each time. Chopsticks with blood on them were coincidentally detected in the trash in the patient’s room. It was revealed that the enterocutaneous fistula was caused by self-mutilation. A psychiatrist was consulted, and the patient was diagnosed with Munchausen syndrome. The psychiatrist initiated treatment and the patient admitted the self-harm. His prolonged wound site was closed and he was able to be discharged. There has been no recurrence of the self-harm as of this writing, 3 years later. The treatment of Munchausen syndrome is difficult and early detection is important

Development, validation, and comparison of gene analysis methods for detecting EGFR mutation from non-small cell lung cancer patients-derived circulating free DNA

The feasibility and required sensitivity of circulating free DNA (cfDNA)-based detection methods in second-line epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) treatment are not well elucidated. We examined T790M and other activating mutations of EGFR by cfDNA to assess the clinical usability. In 45 non-small cell lung cancer (NSCLC) patients harboring activating EGFR mutations, cfDNAs were prepared from the plasma samples. EGFR mutations in cfDNA were detected using highly sensitive methods and originally developed assays and these results were compared to tissue-based definitive diagnoses. The specificity of each cfDNA-based method ranged 96–100% whereas the sensitivity ranged 56–67%, indicating its low pseudo-positive rate. In EGFR-TKI failure cohort, 41–46% samples were positive for T790M by each cfDNA-based method, which was comparable to re-biopsy tissue-based T790M positive rates in literature. The concordance of the results for each EGFR mutation ranged from 83–95%. In eight patients, the results of the cfDNA-based assays and re-biopsy-derived tissue-based test were compared. The observed overall agreement ranged in 50–63% in T790M, and in 63–100% in activating EGFR mutations. In this study, we have newly developed three types of assay which have enough sensitivity to detect cfDNA. We also detected T790M in 44% of patients who failed prior EGFR-TKI treatment, indicating that cfDNA-based assay has clinical relevance for detecting acquired mutations of EGFR

Clinical features and outcome of acute exacerbation of interstitial pneumonia associated with connective tissue disease.

Acute exacerbation (AE) of interstitial lung disease is reported to be developed in not only idiopathic pulmonary fibrosis but also connective tissue disease-associated interstitial pneumonia (CTD-IP). As the significance of AE of CTD-IP has not been so widely recognized, its clinical feature is not fully elucidated. In the present study, we investigated the incidence, clinical features and outcome of AE of CTD-IP. We retrospectively reviewed admitted cases in our department with medical record from 2011 to 2015. Among 155 patients with CTD-IP, 10 (6.5%) cases developed AE (6 rheumatoid arthritis, 2 polymyositis/dermatomyositis, 1 systemic lupus erythematosus, 1 Sjögren syndrome), and one died of AE within 30 days. Median survival time after the onset of AE was 169 days in all 10 patients. The treatment with immunosuppressant just before AE onset might improve the prognosis of AE. The median survival time after the onset of AE was significantly longer in patients showing good response to corticosteroid compared with those with poor response to corticosteroid (805 days and 45 days, respectively) (p<0.05), suggesting that there are some cases in CTD-IP, showing the good response to corticosteroid even when AE was complicated

Development of disaster prevention education video and teaching materials on the theme of local natural disasters: Joint research between Higashi-Hiroshima City and Hiroshima University triggered by the heavy rains in western Japan in July 2018

In this paper, we introduce the production of a disaster prevention education video based on the natural disasters of Higashi-Hiroshima City, and the proposal of lessons using the video through joint research between Higashi-Hiroshima City and Hiroshima University. Introducing the efforts of this project would be help develop disaster prevention education materials in other areas. The project was adopted in early June 2019 and continued for 9 months. The materials are intended for the upper grades of elementary school. The contents are as follows: disaster prevention education video, lesson plan using video, worksheets for lesson, debris flow distribution map, and disaster photos caused by the 2018 heavy rain in each elementary school district, and City hazard map. The video was created by collecting interviews with local residents, movies and photographs of flood monuments, debris flow, public assistance, and local-organized assistance. From the questionnaire results for the video to junior high school students, the video’s content was highly evaluated. It is suggested that it is necessary to raise awareness of disaster prevention by giving lessons based on local natural disasters such as the materials.本論文の内容の一部は，2020年度地理科学学会秋季学術大会で口頭発表しました

Influence of the Great East Japan Earthquake and the Fukushima Daiichi nuclear disaster on the birth weight of newborns in Fukushima Prefecture: Fukushima Health Management Survey

Objective: The Great East Japan Earthquake and Fukushima Daiichi nuclear disaster occurred on 11 March 2011. We investigated the incidence of SGA (small for gestational age) in the Fukushima Prefecture in newborns delivered by women who were pregnant at the time of the disasters and identified any risk factors for SGA. Methods: Subjects were women who were pregnant at the time of the disasters. Questionnaires were sent to the women who lived in the Hamadori area (seaside and near to the nuclear power plant) at the time of the disasters as well as to a control group of women who lived outside the Hamadori area. The incidence of SGA was compared. Logistic regression analysis was performed to identify the risk factors for SGA. Results: In total, 325(5.6%) women had infants with SGA. Neither area nor the trimester of pregnancy at the time of the disasters influenced the incidence of SGA. Pregnancy-induced hypertension (PIH) was higher in the SGA group. PIH was found to be an independent risk factor for SGA. Conclusion: We found no evidence that the Great East Japan Earthquake and the Fukushima Daiichi nuclear disaster increased the incidence of SGA in the Fukushima Prefecture