Engineer education as citizenship education

Engineering and technology aim to lead a better life for people. But the meaning of “better” is highly contested in modern democratic societies where different citizens have different cultures and values. Engineers, as one of the citizens in such societies, are also living in multicultural and multi-value settings, and therefore they need to be responsible for such diversity when they engage in technological developments. Therefore, in engineering education, it is necessary to aim at not only acquiring the specialized technological knowledge but also cultivating citizenship. By citizenship, it refers to a set of abilities to communicate and care for people with respect by taking into account different opinions and expertise of others. Nevertheless, this has not been emphasized much in engineering education in Japan. For example, even in the class of engineering ethics, emphasis is placed more on the acquisition of textbook-based knowledge and virtue of problem cases, and less on abilities to discuss freely and gently. Then, in general education of NIT we have conducted a dialogue-based educational program where learners/students ask questions, listen together and discuss with others. This program is designed based upon so-called Philosophy for/with Children (P4C). Matthew Lipman, one of the founders of P4C, defined the primary aim of P4C as multidimensional- thinking: critical thinking, creative thinking, and caring thinking. In addition, this multidimensional- thinking may, according to many P4C scholars, have a potential of creating active citizenry. The discussion by P4C has three characteristics as follows: 1) People make a circle in the classroom and create a space where students can feel an emotional and intellectual “safety”. 2)Questions being discussed is proposed by students themselves based on their interests, not by teachers 3) Rather than rushing to reach a conclusion, students are asked to concentrate on listening to the differences between each other. This paper begins by explaining what P4C is and why/how P4C is suitable for citizenship education, and then the following sections show our P4C classes in NIT (Tokyo and Ube) and learner's responses. Finally, we claim that the “community of inquiry” created through P4C can prevent the “self- righteousness” of engineers

Development of an oxygen-sensitive degradable peptide probe for the imaging of hypoxia-inducible factor-1-active regions in tumors.

[Purpose]We aimed to develop a radiolabeled peptide probe for the imaging of hypoxia-inducible factor-1 (HIF-1)-active tumors. [Procedures]We synthesized the peptide probes that contain or lack an essential sequence of the oxygen-dependent degradation of HIF-1α in proteasomes ([123/125]I-DKOP30 or [125]I-mDKOP, respectively). The degradation of probes was evaluated in vitro using cell lysates containing proteasomes. In vivo biodistribution study, planar imaging, autoradiography, and comparison between probe accumulation and HIF-1 transcriptional activity were also performed. [Results]The [125]I-DKOP30 underwent degradation in a proteasome-dependent manner, while [125]I-mDKOP was not degraded. Biodistribution analysis showed [125]I-DKOP30 accumulation in tumors. The tumors were clearly visualized by in vivo imaging, and intratumoral distribution of [125]I-DKOP30 coincided with the HIF-1α-positive hypoxic regions. Tumoral accumulation of 125I-DKOP30 was significantly correlated with HIF-1-dependent luciferase bioluminescence, while that of [125]I-mDKOP was not. [Conclusion] [123]I-DKOP30 is a useful peptide probe for the imaging of HIF-1-active tumors

奈良における侵襲性GBS感染症における臨床的特徴と分子疫学的特徴(2007～2016年)

Invasive Streptococcus agalactiae (GBS) infections are increasingly common among neonates and the elderly. Therefore, GBS surveillance for better antibiotic treatment and prophylaxis strategies are needed. We retrospectively evaluated the clinical aspects of invasive infections and the phenotypic and genetic diversity of infectious isolates from Nara, Japan, collected between 2007 and 2016, by using information from hospital records. GBS strains collected from the blood and cerebrospinal fluid cultures were evaluated for capsular types, multi-locus sequence typing (MLST), antibiotic susceptibility, antibiotics resistance gene, and pulsed-field gel electrophoresis. Forty GBS isolates (10 from children and 30 from adults) were analyzed, and the distribution of molecular serotype and allelic profiles varied between children and adults. We found the rates of early-onset disease in neonates with birth complications to be higher than that of previous reports, indicating that there could be relevance between complications at birth and early-onset disease. Standard antibiotic prophylaxis strategies may need to be reconsidered in patients with birth complications. In adults, the mean age of the patients was 68 years (male: 63%). Primary bacteremia was the most common source of infection. In the neonates, six had early-onset diseases and four had late-onset diseases. The most frequently identified strains were molecular serotype Ia ST23 (40%) and molecular serotype Ib ST10 (20%) in children and molecular serotype Ib ST10 (17%), molecular serotype VI ST1 (13%), and molecular serotype V ST1 (13%) in adults. Levofloxacin-resistant molecular serotype Ib strains and molecular serotypes V and VI ST1 were common causes of GBS infection in adults but were rarely found in children. Furthermore, pulsed-field gel electrophoresis in our study showed that specific clone isolates, that tend to have antibiotics resistance were widespread horizontally for a decade. Continuous surveillance and molecular investigation are warranted to identify the transmission route and improve antibiotic treatment strategies.博士（医学）・甲第773号・令和3年3月15日Copyright: © 2020 Hirai et al. This is an open access article distributed under the terms of the Creative Commons Attribution License(https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Non-Invasive Prenatal Genetic Testing (NIPT) Leading to Prenatal Diagnosis of Trisomy 21 Mosaicism and 18q Deletion Syndrome: Two Cases

NIPT is non-definitive testing to estimate the possibility that fetuses have trisomy 21, trisomy 18, or trisomy 13. However, in NIPT-positive and indeterminate cases, rare chromosomal disease may become apparent, requiring advanced genetic considerations and counseling skills. We experienced two such cases, a trisomy 21 mosaicism case triggered by NIPT-positive status and 18q deletion syndrome triggered by NIPT-indeterminate status. These cases have two clinical implications for NIPT. First, it was revealed that trisomy mosaicism might be found in NIPT-positive cases that have lower Z-Scores than those inferred from the fraction of fetal cfDNA in the case of standard trisomy. Second, it is possible that microdeletion syndrome could be the reason for an indeterminate NIPT result. Today’s genetic counseling requires more expertise in ethics and communication as well as genetic science because NIPT can lead to totally unexpected results

Squamous cell carcinoma in an esophageal diverticulum below the aortic arch

AbstractINTRODUCTIONEsophageal diverticula frequently arise from pharyngoesophageal transition area, tracheal bifurcation and epiphrenic region. Carcinoma arising from esophageal diverticulum is rarely seen. We report a patient with a squamous cell carcinoma arising within an esophageal diverticulum below the aortic arch.PRESENTATION OF CASEA 70-year-old man was diagnosed to have a squamous cell carcinoma of the vocal cord with enlarged lymph nodes in the neck, as well as a squamous cell carcinoma arising within an esophageal diverticulum below the aortic arch. There have been no reported cases of esophageal cancer arising from a diverticulum below the aortic arch. Preoperative radiotherapy for the esophageal cancer and pharyngeal cancer was given, followed by surgery. The excised specimen of the esophageal diverticulum and its external appearance revealed that it lacked muscle fibers, with a type 0-IIa lesion arising from the diverticulum. Microscopic examination showed three lymph nodes at the superior mediastinum were positive for malignancy. Bilateral pleural dissemination was detected 7 months after esophagectomy.DISCUSSIONCancer arising from an esophageal diverticulum is mainly found at an advanced stage because of delayed diagnosis. The absence of muscularis propia may lead to early invasion. Thus, cancers within an esophageal diverticulum are considered to be at a more advanced stage than similar cancers arising elsewhere.CONCLUSIONFor detecting of cancer arising from an esophageal diverticulum, a high index of awareness is important. Delay in diagnosis makes surgical management difficult

A study on evaluation method of advanced transport information system based on discrete choice analysis

Tokyo Institute of TechnologyTokyo Institute of Technolog

Transcriptional factors associated with epithelial-mesenchymal transition in choroidal neovascularization

Purpose: To investigate the transcriptional factors associated with epithelial-mesenchymal transition (EMT) in choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD). Methods: Paraffin sections of CNV obtained from patients with AMD (n=12) were stained for transcriptional factors related to EMT, i.e., Snail, Slug, SIP1, and Twist. As a control, postmortem sections of ocular normal tissue were used. Furthermore, using a human retinal pigment epithelial (RPE) cell line (ARPE-19), reverse transcription–polymerase chain reaction (RT–PCR) and immunofluorescence microscopy were performed to explore the cellular localization and expression levels of EMT-associated transcriptional factors upon cytokine stimulation. Results: Of 12 specimens, 11 CNV tissues (91.6%) showed staining for Snail localized in cellular nuclei, particularly in those of RPE cells. Snail was strongly co-localized with α-smooth muscle antigen (SMA) in RPE cells. In contrast, postmortem human retina showed no Snail staining in RPE cells. Other transcriptional factors, Slug, Twist and SIP1 were not detected in CNV or normal human retina. In ARPE-19 cells, RT–PCR and immunofluorescence microscopy showed that Snail mRNA was upregulated by transforming growth factor (TGF)-β and VEGF stimulation. Furthermore, TGF-β induced relocalization of Snail to the nucleus in RPE cells. Conclusions: The current data indicate that Snail is a major transcriptional factor for EMT changes of RPE cells in human CNV

プラスミド性キノロン耐性遺伝子を保有するIMP-6産生腸内細菌科細菌でのイノカラムサイズ効果の比較

Almost all cases of carbapenemase-producing Enterobacteriaceae infections in Japan are caused by blaIMP-positive Enterobacteriaceae (especially blaIMP-6) and infections caused by other types of carbapenemase-producing Enterobacteriaceae are quite rare. We examined drug resistance genes co-harboring with blaIMP-6 and their inoculum size effects. We screened β-lactamase genes, plasmid-mediated quinolone resistance (PMQR) genes, and aminoglycoside-modifying enzyme genes by PCR and performed sequencing for 14 blaIMP-6-positive Enterobacteriaceae. Further, all PMQR-positive isolates were submitted to conjugation and inoculum effect evaluation. Our data showed that 13 of the 14 isolates harbored CTX-M-2 and one co-harbored CTX-M-2 and CTX-M-1 as extended-spectrum β-lactamases. All isolates carried one or more PMQRs; aac(6’)-Ib-cr was the most prevalent (92.8%), and was followed by oqxA (64.3%), qnrS (50%), oqxAB (21.4%), and qnrB (14.3%). However, Klebsiella pneumoniae contains chromosomal OqxAB. Inoculum size effects were significant in all strains for meropenem, 13 strains for imipenem, 7 for levofloxacin, and 3 for amikacin. We observed that 11 of the experimental strains (100%), 8 strains (72.7%), and 1 strain showed inoculum size effects for meropenem, imipenem, and amikacin, respectively. However, four strains harbored qnr genes and two strains harbored qnr genes and QRDR mutations concurrently; no inoculum size effect was seen for levofloxacin. The blaIMP-6-positive Enterobacteriaceae that we studied was found to harbor at least one plasmid-mediated drug resistance gene. The inoculum size effect for carbapenems was thought to be mainly due to IMP-6-type metallo-β-lactamase; however qnrB and qnrS also had a minimal impact on the inoculum size effect for levofloxacin.博士（医学）・乙第1463号・令和2年6月30日Copyright: © 2019 Ogawa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License(https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

スルフォラファンはNrf2 活性化作用を介し抗酸化ストレス作用、アセトアルデヒド代謝作用およびLPS/TLR4 シグナル経路を阻害することで四塩化炭素およびエタノール投与により誘発されるアルコール肝線維症を改善する

Alcoholic liver disease (ALD)-related fibrosis results from a variety of mechanisms including the accumulation of acetaldehyde, reactive oxygen species, and hepatic overload of endogenous lipopolysaccharide (LPS). Alcohol cessation is the therapeutic mainstay for patients with all stages of ALD, whereas pharmacological strategies for liver fibrosis have not been established. Sulforaphane, a phytochemical found in cruciferous vegetables, activates nuclear factor erythroid 2-related factor 2 (Nrf2) and exerts anticancer, antidiabetic, and antimicrobial effects; however, few studies investigated its efficacy in the development of ALD-related fibrosis. Herein, we investigated the effect of sulforaphane on acetaldehyde metabolism and liver fibrosis in HepaRG and LX-2 cells, human hepatoma and hepatic stellate cell lines, respectively, as well as in a mouse model of alcoholic liver fibrosis induced by ethanol plus carbon tetrachloride (EtOH/CCl₄). Sulforaphane treatment induced the activity of acetaldehyde-metabolizing mitochondrial aldehyde dehydrogenase in HepaRG cells and suppressed the acetaldehyde-induced proliferation and profibrogenic activity in LX-2 cells with upregulation of Nrf2-regulated antioxidant genes, including HMOX1, NQO1, and GSTM3. Moreover, sulforaphane attenuated the LPS/toll-like receptor 4-mediated sensitization to transforming growth factor-β with downregulation of NADPH oxidase 1 (NOX1) and NOX4. In EtOH/CCl₄-treated mice, oral sulforaphane administration augmented hepatic acetaldehyde metabolism. Additionally, sulforaphane significantly inhibited Kupffer cell infiltration and fibrosis, decreased fat accumulation and lipid peroxidation, and induced Nrf2-regulated antioxidant response genes in EtOH/CCl₄-treated mice. Furthermore, sulforaphane treatment blunted hepatic exposure of gut-derived LPS and suppressed hepatic toll-like receptor 4 signaling pathway. Taken together, these results suggest sulforaphane as a novel therapeutic strategy in ALD-related liver fibrosis.博士（医学）・甲第811号・令和4年3月15日© 2020 Elsevier Inc. All rights reserved

レンバチニブは実験的肝線維症において肝星細胞の活性化と類洞毛細血管化を阻害することにより肝線維化を抑制する。

Molecular targeted agents are pharmacologically used to treat liver fibrosis and have gained increased attention. The present study examined the preventive effect of lenvatinib on experimental liver fibrosis and sinusoidal capillarization as well as the in vitro phenotypes of hepatic stellate cells. LX-2, a human stellate cell line, was used for in vitro studies. In vivo liver fibrosis was induced in F344 rats using carbon tetrachloride by intraperitoneal injection for 8 weeks, and oral administration of lenvatinib was started two weeks after initial injection of carbon tetrachloride. Lenvatinib restrained proliferation and promoted apoptosis of LX-2 with suppressed phosphorylation of extracellular signal-regulated kinase 1/2 and AKT. It also down-regulated COL1A1, ACTA2 and TGFB1 expressions by inhibiting the transforming growth factor-β1/Smad2/3 pathway. Treatment with lenvatinib also suppressed platelet-derived growth factor-BB-stimulated proliferation, chemotaxis and vascular endothelial growth factor-A production, as well as basic fibroblast growth factor-induced LX-2 proliferation. In vivo study showed that lenvatinib attenuated liver fibrosis development with reduction in activated hepatic stellate cells and mRNA expression of profibrogenic markers. Intrahepatic neovascularization was ameliorated with reduced hepatic expressions of Vegf1, Vegf2 and Vegfa in lenvatinib-treated rats. Collectively, these results suggest the potential use of lenvatinib as a novel therapeutic strategy for liver fibrosis.博士（医学）・甲第812号・令和4年3月15日© 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License(https://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited