Most engineering curricula in the United States include some form of major design project experiences for students, such as capstone courses or design-build-fly projects. Such courses are examples of project-based learning (PBL). Part of PBL is to prepare students—and future engineers—to deal with and prevent common project failures such as missing requirements, overspending, and schedule delays. <i>But how well are students performing once they join the workforce?</i> Unfortunately, despite our best efforts to prepare future engineers as best we can, the frequency of failures of complex projects shows no signs of decreasing. In 2020 only 53% of projects were on time, 59% within budget, and 69% met their goal, as reported by the Project Management Institute. If we want to improve success rates in industry projects, letting students get the most out of their PBL experience and be better prepared to deal with project failures before they join the workforce may be a viable starting point. <br><br>The overarching goal of this dissertation is to identify and suggest improvements to areas that PBL lacks when it comes to preparing students for failure, to investigate student behaviors that lead to project failures, and to improve these behaviors by providing helpful feedback to students. <br><br>To investigate the actions and behaviors that lead to events that cause failures in student projects, I introduced “crowd signals”, which are data collected directly from the students that are part of a project team. In total, I developed 49 survey questions that collect these crowd signals. To complete the first part of the dissertation, I conducted a first experiment with 28 student teams and their instructors in two aerospace engineering PBL courses at Purdue University. The student teams were working on aircraft designs or low-gravity experiments.<br><br><i>Does PBL provide sufficient opportunities for students to fail safely, and learn from the experience? How can we improve?</i> To identify areas that PBL may lack, I compared industry failure cause occurrence rates with similar rates from student teams in PBL courses, and then provided recommendations to PBL instructors. Failure causes refer to events that frequently preceded budget, schedule, or requirements failures in industry, and are identified from the literature. Through this analysis, I found that PBL does not prepare students sufficiently for situations where the failure cause missing a design aspect occurs. The failure cause is fundamentally linked to proper systems engineering: it represents a scenario where, for example, students failed to consider an important requirement during system development, or did not detect a design flaw, or component incompatibility. I provided four recommendations to instructors who want to give their students more opportunities to learn from this failure cause, so they are better prepared to tackle it as engineers. <br><br><i>Is crowdsourced information from project team members a good indicator of future failure occurrences in student projects?</i> I developed models that predict the occurrence of future budget, schedule, or requirements failures, using crowd signals and other information as inputs, and interpreted those models to get an insight on which student actions are likely to lead to project failures. The final models correctly predict, on average, 73.11±6.92% of budget outcomes, 75.27%±9.21% of schedule outcomes, and 76.71±6.90% of technical requirements outcomes. The previous status of the project is the only input variable that appeared to be important in all three final predictive models for all three metrics. Overall, crowdsourced information is a useful source of knowledge to assess likelihood of future failures in student projects. <br><br><i>Does targeted feedback that addresses the failure causes help reduce failures in student projects?</i> To improve student behaviors that lead to project failures, I used correlations between failure measures and the crowd signals as a guide to generate 35 feedback statements. To evaluate whether the feedback statements help reduce project failures in the student teams, I conducted a second experiment at Purdue University with 14 student teams and their instructors. The student teams were enrolled in aircraft design, satellite design, or propulsion DBT courses. The student teams were split in two treatment groups: teams that received targeted feedback (i.e., feedback that aimed to address the failure causes that the specific team is most prone to) and teams that received non-targeted feedback (i.e., feedback that is positive, but does not necessarily address the failure causes the specific team is most prone to). Through my analysis, I found that my targeted feedback does not reduce the failure occurrences in terms of any metrics, compared to the non-targeted feedback. However, qualitative evaluations from the students indicated that student teams who received targeted feedback made more changes to their behaviors and thought the feedback was more helpful, compared to the student teams who received non-targeted feedback.<br><br>

During the Second Intifada, Israel shocked the international community by becoming the first country in the world to publically announce an overt policy of targeted-killing. While utilized by Israel in previous conflicts, the Second Intifada was a turning point in Israeli history due to a series of dramatic changes introduced to its targeting policy which would sharply contrast those which were previously utilized. This diploma thesis analyzed thirty-eight cases of Israeli targeting operations conducted both before and during the Second Intifada to determine if the changes made to its policy during the Second Intifada resulted in more or less successful targeting operations compared to those conducted prior to this time period. The results of this study indicated that, following the introduction of the aforementioned policy changes, Israeli targeting operations during the Second Intifada were less successful than those conducted prior to this time period.

Separation of 225Ra (t1/2 = 15 d) from its daughter isotope 225Ac (t1/2 = 10 d) is necessary to obtain pure 225Ac for cancer alpha-therapy. In this study, microscale separation of 225Ra from its daughter 225Ac using BioRad AG50X4 cation exchange resin was achieved with good reproducibility across microdevices, and ≥90% purity was achieved for 225Ac, which is comparable to conventional chromatography. These results indicate the potential for greater use of microfluidics for biomedical radiochemistry. The modularity of the system and its compatibility with different resins allows for quick and easy adaptation to the various needs of a separation campaign.

In the light of the ongoing loss of biodiversity at the global scale, monitoring grasslands is nowadays of utmost importance considering their functional relevance in terms of the ecosystem services that they provide. Here, guidelines of the European Union like the Fauna-Flora-Habitat Directive and the European Agricultural fund for Rural Development with its HNV indicators are crucial. Indeed, they form the legal framework for nature conservation and define grasslands as one of their conservation targets, whose status needs to be assessed and reported by all member states on a regular basis. In the light of these reporting requirements, the need for a harmonised and thorough grassland monitoring is highly demanding since most member states are still currently adopting intensive field surveys or photointerpretation with differing levels of detail for mapping habitat distribution. To this purpose, a cost-effective solution is offered by Earth Observation data for which specific grassland monitoring methodologies shall be then implemented which are capable of processing multitemporal acquisitions collected throughout the entire growing season. Although optical data are most suited for characterising vegetation in terms of spectral information content, they are actually subject to weather conditions (especially cloud coverage), which hinder the possibility of collecting enough information over the full phenological cycle. Furthermore, so far only few studies started employing high and very high resolution optical time series for grassland habitat monitoring since they have become available e.g., from the RapidEye satellites, only in the recent past. To overcome this limitation, SAR systems can be employed which provide imagery independent from weather or daytime conditions, hence enabling vegetation analysis by means of complete time series. Compared to optical data, radar imagery is less affected by the physical-chemical characteristics of the surface, but rather it is sensitive to structural features like geometry and roughness. However, in this context presently only very few techniques have been implemented, which are anyhow not suitable to be employed in an operational framework. Furthermore, to address the classification task, supervised approaches (which require in situ information for all the land-cover classes present in the study area) represent the most accurate methodological solution; nevertheless, collecting an exhaustive ground truth is generally expensive both in terms of time and economic costs and is not even feasible when the test site is remote. However, in many applications the end-users are generally only interested in very few specific targeted land-cover classes which, for instance, have high ecological value or are associated with support actions, subsidies or benefits from national or international institutions. The categorisation of specific grasslands and habitat types as those addressed in this thesis falls within such category of problems, which is defined in the literature as targeted land-cover classification. In this framework, a robust and effective targeted classification system for the automatic identification of grassland types by means of multi-temporal and multi-polarised SAR data has been developed within this thesis. In particular, the proposed system is composed of three main blocks: the preprocessing of the SAR image time series including the Kennaugh decomposition, the feature extraction including multi-temporal filtering and texture analysis, and the hierarchical targeted classification, which consist of two phases where first a one-class classifier is employed to outline the merger of all the grassland types of interest considered as a single information class and then a multi-class classifier is applied for discriminating the specific targeted classes within the areas identified as positive by the one-class classifier. To evaluate the capabilities of the proposed methodology, several experimental trials have been carried out over two test sites located in Southern Bavaria (Germany) and Mecklenburg Western-Pomerania (Germany) for which six diverse datasets have been derived from multitemporal series of dualpol TerraSAR-X as well as dual-/quadpol Radarsat-2 images. Four among the Natura 2000 habitat types of the Fauna-Flora-Habitat Directive as well all High Nature Value grassland types have been considered as targeted classes for this study. Overall, the proposed system proved to be robust and confirmed the effectiveness of employing multitemporal and multi-polarisation VHR SAR data for discriminating habitat types and High Nature Value grassland types, exhibiting high potential for future employment even at larger scales. In particular, it could be demonstrated that the proposed hierarchical targeted classification approach outperforms the available state-of-the-art methods and has a clear advantage with respect to the standard approaches in terms of robustness, reliability and transferability.

Objectif: Environ 30% des patients ayant un cancer du rein métastatique présentent d’emblée des résistances aux agents de thérapie ciblée. Les autres patients développent des résistances thérapeutiques à plus long terme. Une amélioration de la capacité du clinicien à prédire la réponse thérapeutique avant l’initiation du traitement pourrait améliorer le pronostic des patients. Le but de notre projet a été de développer un modèle de xénogreffes dérivées de patients afin d’évaluer la sensibilité des cellules tumorales de chaque patient aux différents agents de thérapie ciblée, avant d’initier un traitement.Méthodes: La membrane chorio-allantoïque de l’embryon de poulet a servi de base à notre modèle. Dans une première phase de notre travail, une xénogreffe de cellules tumorales rénales humaines en suspension a été réalisée afin de vérifier que les caractéristiques histologiques et phénotypiques des tumeurs d’origine étaient conservées dans les xénogreffes réalisées sur notre modèle. Dans une seconde étape, des fragments tissulaires de tumeurs rénales de 5 patients opérés pour néphrectomie cytoréductive dans notre centre hospitalier étaient prélevés et greffés sur notre modèle (>60/patient). Différents agents dethérapie ciblée étaient testés sur les xénogreffes ainsi réalisées.Résultats : Les caractéristiques histo-pathologiques et phénotypiques des tumeurs rénales d’origine étaient conservées après xénogreffes. Il existait une hétérogénéité spatiale intra-tumorale en termes de sensibilité aux différents agents de thérapie ciblée. Il existait également un polymorphisme nucléotidique au sein des différentes régions de chaque tumeur rénale.Conclusion : Ce modèle de xénogreffes rénales dérivées de patients est utile pour l’évaluation de la sensibilité aux agents de thérapie ciblée des cellules tumorales en amont de la prise en charge thérapeutique. Ce modèle permet au clinicien de personnaliser le traitement de chaque patient ayant un cancer du rein métastatique, avant la mise en route d’un traitement systémique. Une évaluation prospective de notre modèle pourrait permettre de mieux appréhender les potentielles retombées cliniques liées à son utilisation. / Objective: Approximately 30% of patients with metastatic renal cancer are resistant to targeted therapy agents. The other patients will eventually develop long-term therapeutic resistances. An improvement in the clinician's ability to predict therapeutic response before treatment initiation could improve patients' prognosis. The aim of our projet was to develop a patient-derived xenograft models to be able to test the sensibility of each patient's renal tumor cells to the different available targeted therapy agent prior to treatment.Methods: The chicken embryo chorioallantoic membrane has been the base of our model. In a first phase of our work, a xenograft of human kidney tumor cells has been carried out in order to verify that the histologic and phenotypic characteristics of the original tumors were preserved in the xenografts performed on our model. As a second step, fragments of the kidney tumor speciments of 5 patients undergoing cytoreductive nephrectomy in our hospital center were grafted on our model (> 60/patient). Different targeted therapy agents were tested on the xenografts we performed.Results: The histopathologic and phenotypic characteristics of the original renal tumors were preserved in our xenografts. There was intra-tumor spatial heterogeneity in terms of sensitivity in different targeted therapy agents. There was also a nucleotide polymorphism within the different regions of each renal tumor.Conclusion: This patient-derived renal xenograft model could be useful prior to treatment for the evaluation of each patients'renal tumor cells to the different available targeted therapy agents. This model could make it possible to personalize the treatment of each metastatic kidney cancer patient, prior to systemic treatment. A prospective evaluation of our model could help assess the potential clinical benefits of its use.

L’avènement du séquençage haut débit a mis en lumière l’hétérogénéité des cancers du sein qui peuvent être groupés en fonction d’altérations moléculaires spécifiques qui sont pour certaines à la base de thérapies ciblées dans le cadre de la médecine personnalisée. Néanmoins de nombreuses complications viennent compromettre le succès thérapeutique de ces approches. En effet, l’une des thérapies ciblées les plus efficaces développées récemment, les inhibiteurs de CDK4/6, sont prescrits chez tous les patients HR+/HER aux stades avancés de la maladie alors même qu’aucun biomarqueur n’a pour l’heure été identifié. Ainsi les données pharmacodynamiques et les marqueurs pronostics font cruellement défaut pour ces patients. Afin d’identifier de tels marqueurs, nous avons conduit une étude clinique « fenêtre d’opportunité » incluant 100 patients à un stade précoce de la maladie. L’analyse en IHC et les études de profilage expression génomique des tumeurs a permis de montrer qu’une courte exposition au palbociclib, un inhibiteur de CDK4/6 induisait un arrêt du cycle cellulaire révélé par une diminution de phospho-Rb et Ki67. Cette corrélation entre diminution du phospho-Rb et la diminution de la prolifération suggère d’ailleurs son utilisation comme biomarqueur de la réponse au palbociclib. Une analyse sur puce à cDNA a permis d’identifier un panel de gènes régulateurs de la prolifération (MKI67, TOP2A, BIRC5) et de la machinerie du cycle cellulaire (PLK1, FOXM1) modulé par le palbociclib. Bien que nous n’ayons pu identifier de marqueurs de résistance au palbociclib en condition basale, nous avons observé des niveaux élevés de CCNE chez les patients traités résistants au palbociclib. Cette donnée a été confirmée chez les patients aux stades avancés de la maladie dans le cadre d’une étude menée en collaboration avec un groupe britannique. D’autres données obtenues en collaboration avec une équipe de l’université Vanderbilt, ont par ailleurs permis de suggérer une contribution des inhibiteurs de CDK4/6 à la réversion de la résistances aux hormonothérapie en inhibant l’expression les gènes cibles du facteur de transcription E2F4. Pour finir, les activités biologiques et cliniques des différents inhibiteurs de CDK4/6 disponibles n’étant pas exactement identiques, un second essai clinique « fenêtre d’opportunité » nous a permis de mettre en évidence un profil de toxicité distinct de l’abemaciclib et de montrer que, contrairement au palbociclib, l’abemaciclib montre une efficacité lorsqu’il est utilisé seul. Une des explications possible de ces différentes activités serait un spectre d’action de l’abemaciclib ciblant plus efficacement la CDK9, même si l’impact clinique associé n’a pas été examiné en détail et qu’une comparaison rigoureuse de l’activité de ces deux inhibiteurs de CDK n’a pas encore été réalisée. / New sequencing methods have revealed that breast cancer is heterogeneous and characterized by different subgroups harboring specific molecular alterations for which targeted therapies have been developed with the hope of implementing personalized medicine. However, this approach has been proven far too simplistic. Indeed, one of the latest and more efficient targeted therapies to be developed in breast cancer are the CDK4/6 inhibitors, approved for all HR+/HER2- advanced breast cancers. So far, and despite the significant number of patients treated with these drugs, no biomarkers of efficacy have been identified and no clear information about pharmacodynamics have been presented. In order to determine biomarkers of efficacy and pharmacodynamics of palbociclib, the first approved CDK4/6 inhibitor, we conducted a window of opportunity clinical trial in 100 early breast cancer patients. IHC and GE analyses identified that a short period of palbociclib treatment was able to induce cell cycle arrest as determined by decreased phospho-Rb expression and this was accompanied by a profound decrease in proliferation as determined by lnKi67<1 after treatment, with a correlation between changes in proliferation and changes in phospho-Rb, suggesting that early decrease in phospho-Rb could be linked to sensitivity to this drug. Microarray analyses identified that palbociclib modulates genes involved in proliferation (such as MKI67, TOP2A, BIRC5) and cell cycle (such as PLK1, FOXM1). Despite we were not able to identify baseline biomarkers of resistance to this treatment, we observed that levels of CCNE remained high in palbociclib-resistant patients. This finding was further validated in collaboration with an-UK research group who had conducted biomarker research in the advanced setting. Moreover, our data helped also to determine in a different collaboration with Vanderbilt University, that CDK/6 inhibitors might contribute to reverse endocrine resistance generated by activation of genes linked to the E2F4 transcription factor. Finally, as preclinical and clinical data suggest some diversity between different CDK4/6 inhibitors, we decided to conduct a second window of opportunity trial with a second CDK4/6 inhibitor, abemaciclib, who has shown different toxicity profile and, unlike palbociclib, significant efficacy as single-agent. One suggested explanation could be due to a higher impact on CDK9, although its clinical impact has not been determined and no comparison between these two drugs has been performed.

L’identification de la notion de driver oncogene et le développement de molécules capables de cibler leur activité a entrainé d’importants changements dans le traitement des cancers CBNPC.L’EGFR est un récepteur transmembranaire à activité TK (Tyrosine Kinase) permettant latransmission de signaux extracellulaires jusqu’au sein de la cellule grâce à l’activation de voies de signalisations. Parmis ces voies de signalisation on retrouve les voies de prolifération et de survie cellulaire. Des mutations activatrices dans le domaine TK confèrent à ce dernier un rôle de driver oncogene. Dans ce domaine l’EGFR a joué un rôle avant gardiste. Ainsi de nombreuses molécules ciblant l’activité de l’EGFR muté (EGFR-TKI, gefitinib) ont été développées. L’utilisation de ces molécules en clinique a représenté une vraie révolution dans la prise en charge des patients. Cependant ces derniers développent inéluctablement des mécanismes de résistance. L’analyse transcriptomique de modèles ayant acquis une résistance aux EGFR-TKI a mis en évidence une dérégulation de l’expression des transcrits. Par ailleurs des résultats del’équipe ont montré que l’expression des protéines SR (facteurs d’épissage impliqués dans la régulation de nombreux transcrits) était dérégulée dans les CBNPC. Sur la base de ces résultats nous avons émis l’hypothèse que l’épissage alternatif des transcrits médié par les protéines SR pourrait jouer un rôle dans la résistance acquise par les tumeurs pulmonaires en réponse aux EGFR-TKI.Au sein du laboratoire des clones résistants ont été générés après exposition chroniqueau gefitinib de modèles cellulaires d’adénocarcinomes pulmonaires exprimant une mutation activatrice de l’EGFR.Nous avons tout d’abord mis en évidence une accumulation de l’expression de SRSF2 dans les clones résistants comparativement à la lignée sensible. Dans deux clones résistants au gefitinib, issus de la lignée d’adénocarcinome pulmonaire sensible PC9 exprimant un EGFR mutant Del19, nous montrons que la neutralisation de la protéine SRSF2 sensibilise les clones à l’apoptose induite par le gefitinib. Une analyse RNA-seq nous a permis d’identifier Atg16L1 comme un acteur potentiel de la resensibilisation à l’apoptose médiée par SRSF2. La neutralisation de SRSF2 entraine une modulation de l’épissage de l’exon8 de la protéine Atg16L1 en réponse à un traitement au gefitinib. Et la neutralisation de l’expression des transcrits ARN d’ATG16L1 comportant l’exon8 sensibilise les clones résistant à l’apoptose induite par le gefitinib. Ce switch d’épissage entraine une modulation de l’activité autophagique des cellules en réponse au gefitinib. Nous montrons qu’une expression majoritaire des transcrits comportant l’exon 8 favorise une inhibition de l’autophagie en réponse au gefitinib. De plus les modèlesrésistants pour lesquels on observait une resensibilisation à l’apoptose suite à une neutralisation des transcrits contenant l’exon 8, conservent leur phénotype de résistance lorsque dans ces mêmes conditions l’activité autophagique est inhibée. L’ensemble de ces travaux met en avant l’existence d’un switch d’épissage de la protéine Atg16L1 au niveau de son exon 8 contribuant à une inactivation de l’autophagie corrélée avec un phénotype de résistance à l’apoptose en réponse à un traitement par EGFR-TKI. Enfin SRSF2 participerait à la modulation de cet épissage en réponse à un traitement au gefitinib. / Identifying what is a driver oncogene and developping small molecules that are able to targetits activity led to drastic changes in NSCLC treatments. EGFR is a transmembrane receptorwith Tyrosine Kinase (TK) activity allowing signal transmission from the environment towardsthe inner of the cell by signaling pathways activation. Among those signaling pathways arefound survival and proliferation pathways. Activating mutations make EGFR a driver onco-gene, which was the first protein to be identified as such. Hence numerous chemical compoundtargeting mutated EGFR (EGFR-TKI, gefitinib) have been developped. Their use in clinicsrepresent a huge improvement for patients care. However resistance mechanisms ultimatelyoccur. Transcriptomic analyses of acquired resistant models to EGFR-TKI have shown thattheir RNA transcripts expression is abnormal. Moreover results from the team have demons-trated that SR proteins (splicing factor) expression is deregulated in NSCLC. Based on thoseresults we hypothesized that SRSF2 mediated alternative splicing of mRNA could be involvedin resistance mechanims acquired by lung carcinoma in response to EGFR-TKIThe lab developped resistant clones by chronic exposure to gefitinib of EGFR mutated lungadenocarcinoma cellular models.We first observed the accumulation of the expression of SRSF2 protein in resistant clonescompared to the sensitive cell line. Secondly, sensitivity to gefitinib induced apoptosis of twoclones was resored when neutralising SRSF2. A RNA-seq analysis led us to identify Atg16L1 aspotentially being involved in the SRSF2-mediated sensitization to gefitinib-induced apoptosis.SRSF2 neutralisation modulates Atg16L1 splicing in response to gefitinib. Neutralisation ofExon 8 containing transcripts of Atg16L1 sensitizes resistant clones to gefitinib induced apop-tosis. This alternative splicing switch modulates autophagic activity of the cells in reponseto gefitinib. We have shown that exon8 containing transcripts favor autophagy inhibition inreponse to gefitinib. This work emphasize the role of Atg16L1 alternative splicing switch ofexon8 in autophagy inhibition and its correlation with a resistant phenotype in response toEGFR-TKI. SRSF2 may participate in the modulation of this alternative splicing switch inreponse to gefitinib.

La détection de potentielles cibles secondaires ou off-targets d’un ligand donné requiert la détermination de son site d’interaction et la recherche de sites d’interaction similaires sur d’autres protéines. Dans le but de mener à bien cette étude, nous avons développé PatchSearch : cet outil compare un patch requête, correspondant à un site d’interaction, avec la surface d’une cible potentielle. L’algorithme employé s’appuie sur une méthode originale de recherche de quasi-cliques dans un graphe produit : cette approche identifie des groupes d’atomes du patch appariés avec ceux de la surface ciblée avec des propriétés physico-chimiques conservées et dans des configurations proches. Nous montrons que PatchSearch trouve des patches qui correspondent à ceux qui sont connus sur les surfaces ciblées. De plus, les résultats de l’application de PatchSearch sur des protéines flexibles indiquent que l’approche des quasi-cliques permet de retrouver à la fois les parties rigides et flexibles des patches,contrairement à la recherche classique de cliques. Enfin, les performances de Patch-Search sont équivalentes à celles des autres outils de comparaison de sites de liaison.Nous avons également appliqué PatchSearch sur des off-targets de médicaments impliqués dans le traitement de cancers. Nos expériences suggèrent l’utilisation de PatchSearch dans la recherche des éventuelles off-targets d’un médicament. / Detection of putative off-targets for a ligand requires to search for some similarbinding sites onto other proteins surface. In order to achieve this goal, we developeda tool named PatchSearch. This program compares a query patch, whichcontains the binding site, with the surface a potentially targeted protein. Patch-Search’s algorithm is based on an original method searching for some quasi-cliquesin a graph product, which identifies some atoms both in the patch and in the surfacewith conserved physicochemical properties and in similar configurations. Weshow that PatchSearch efficiently finds known patches on protein surfaces. Moreover,application of PatchSearch on flexible proteins shows that, unlike the classiccliques approach, quasi-cliques method allows to find both rigid and flexible partsof the patches. PatchSearch gets similar results compared to the other binding sitecomparison tools. We also applied PatchSearch to find patches binding polypharmacologicaldrugs involved in cancer treatment, in order to identify them on knownoff targets. Our experiments suggest to employ PatchSearch in off-targets detectionprocess.

リポジトリの登録にあたっては、Peer reviewされた最終版のみ可能であり、その際には下記の出版社のウェブサイトのアドレスを記載することが求められる。当該論文は2014年6月の出版であり、12ヶ月を経過していることから、公開には差し支えはない。http://clincancerres.aacrjournals.org/content/20/12/3087.full / 京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第19617号 / 医博第4124号 / 新制||医||1015(附属図書館) / 32653 / 京都大学大学院医学研究科医学専攻 / (主査)教授 小川 誠司, 教授 野田 亮, 教授 伊達 洋至 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

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