La personnalisation de l’apprentissage dans les environnements informatiques pour l’apprentissage humain (EIAH) est un sujet de recherche qui est traité depuis de nombreuses années. Avec l’arrivée des cours en ligne ouverts et massifs (MOOC), la question de la personnalisation se pose de façon encore plus cruciale et de nouveaux défis se présentent aux chercheurs. En effet, le même MOOC peut être suivi par des milliers d’apprenants ayant des profils hétérogènes (connaissances, niveaux éducatif, objectifs, etc). Il devient donc nécessaire de tenir compte de cette hétérogénéité en présentant aux apprenants des contenus éducatifs adaptés à leurs profils afin qu’ils tirent parti au mieux du MOOC.D’un autre côté, de plus en plus de ressources éducatives libres (REL) sont partagées sur le web. Il est important de pouvoir réutiliser ces REL dans un contexte différent de celui pour lequel elles ont été créées. En effet, produire des REL de qualité est une activité coûteuse en temps et la rentabilisation des REL passe par leur réutilisation.Pour faciliter la découverte des REL, des schémas de métadonnées sont utilisés pour décrire les REL.Cependant, l’utilisation de ces schémas a amené à des entrepôts isolés de descriptions hétérogènes et qui ne sont pas interopérables. Afin de régler ce problème, une solution adoptée dans la littérature consiste à appliquer les principes des données ouvertes et liées (LOD) aux descriptions des REL.Dans le cadre de cette thèse, nous nous intéressons à la personnalisation des MOOC et à la réutilisation des REL.Nous proposons un système de recommandation qui fournit à un apprenant en train de suivre un MOOC des ressources externes qui sont des REL adaptées à son profil, tout en respectant les spécificités du MOOC suivi.Pour sélectionner les REL, nous nous intéressons à celles qui possèdent des descriptions insérées dans les LOD, stockées dans des entrepôts accessibles sur le web et offrant des moyens d’accès standardisés. Notre système de recommandation est implémenté dans une plateforme de MOOC, Open edX et il est évalué en utilisant une plateforme de micro-tâches. / For many years now, personalization in TEL is a major subject of intensive research. With the spreading of Massive Open Online Courses (MOOC), the personalization issue becomes more acute. Actually, any MOOC can be followed by thousands of learners with different educational levels, learning styles, preferences, etc. So, it is necessary to present pedagogical contents taking into account their heterogeneous profiles so that they can maximize their benefit from following the MOOC.At the same time, the amount of Open Educational Resources (OER) available on the web is permanently growing. These OERs have to be reused in contexts different from the initial ones for which they were created.Indeed, producing quality OER is costly and requires a lot of time. Then, different metadata schemas are used to describe OER. However, the use of these schemas has led to isolated repositories of heterogeneous descriptions which are not interoperable. In order to address this problem, a solution adopted in the literature is to apply Linked Open Principles (LOD) to OER descriptions.In this thesis, we are interested in MOOC personalization and OER reuse. We design a recommendation technique which computes a set of OERs adapted to the profile of a learner attending some MOOC. The recommended OER are also adapted to the MOOC specificities. In order to find OER, we are interested in those who have metadata respecting LOD principles and stored in repositories available on the web and offering standardized means of access. Our recommender system is implemented in the MOOC platform Open edX and assessed using a micro jobs platform.

En l'absence d'une autorité de nommage centrale sur le Web de données, il est fréquent que différents graphes de connaissances utilisent des noms (IRIs) différents pour référer à la même entité. Chaque fois que plusieurs noms sont utilisés pour désigner la même entité, les faits owl:sameAs sont nécessaires pour déclarer des liens d’identité et améliorer l’exploitation des données disponibles. De telles déclarations d'identité ont une sémantique logique stricte, indiquant que chaque propriété affirmée à un nom sera également déduite à l'autre et vice versa. Bien que ces inférences puissent être extrêmement utiles pour améliorer les systèmes fondés sur les connaissances tels que les moteurs de recherche et les systèmes de recommandation, l'utilisation incorrecte de l'identité peut avoir des effets négatifs importants dans un espace de connaissances global comme le Web de données. En effet, plusieurs études ont montré que owl:sameAs est parfois incorrectement utilisé sur le Web des données. Cette thèse étudie le problème de liens d’identité erronés ou inappropriés qui sont exprimés par des liens owl:sameAs et propose des solutions différentes mais complémentaires. Premièrement, elle présente une ressource contenant la plus grande collection de liens d’identité collectés du LOD Cloud, avec un service Web à partir duquel les données et leur clôture transitive peuvent être interrogées. Une telle ressource a à la fois des impacts pratiques (elle aide les utilisateurs à trouver différents noms pour la même entité), ainsi qu'une valeur analytique (elle révèle des aspects importants de la connectivité du LOD Cloud). En outre, en s’appuyant sur cette collection de 558 millions liens d’identité, nous montrons comment des mesures de réseau telles que la structure de communauté du réseau owl:sameAs peuvent être utilisées afin de détecter des liens d’identité éventuellement erronées. Pour cela, nous attribuons un degré d'erreur pour chaque lien owl:sameAs en fonction de la densité de la ou des communautés dans lesquelles elles se produisent et de leurs caractéristiques symétriques. L'un des avantages de cette approche est qu'elle ne repose sur aucune connaissance supplémentaire. Finalement, afin de limiter l'utilisation excessive et incorrecte du owl:sameAs, nous définissons une nouvelle relation pour représenter l'identité de deux instances d’une classe dans un contexte spécifique (une sous-partie de l’ontologie). Cette relation d'identité s'accompagne d'une approche permettant de détecter automatiquement ces liens, avec la possibilité d'utiliser certaines contraintes expertes pour filtrer des contextes non pertinents. La détection et l’exploitation des liens d’identité contextuels détectés sont effectuées sur deux graphes de connaissances pour les sciences de la vie, construits en collaboration avec des experts du domaine de l’institut national de la recherche agronomique (INRA). / In the absence of a central naming authority on the Web of data, it is common for different knowledge graphs to refer to the same thing by different names (IRIs). Whenever multiple names are used to denote the same thing, owl:sameAs statements are needed in order to link the data and foster reuse. Such identity statements have strict logical semantics, indicating that every property asserted to one name, will also be inferred to the other, and vice versa. While such inferences can be extremely useful in enabling and enhancing knowledge-based systems such as search engines and recommendation systems, incorrect use of identity can have wide-ranging effects in a global knowledge space like the Web of data. With several studies showing that owl:sameAs is indeed misused for different reasons, a proper approach towards the handling of identity links is required in order to make the Web of data succeed as an integrated knowledge space. This thesis investigates the identity problem at hand, and provides different, yet complementary solutions. Firstly, it presents the largest dataset of identity statements that has been gathered from the LOD Cloud to date, and a web service from which the data and its equivalence closure can be queried. Such resource has both practical impacts (it helps data users and providers to find different names for the same entity), as well as analytical value (it reveals important aspects of the connectivity of the LOD Cloud). In addition, by relying on this collection of 558 million identity statements, we show how network metrics such as the community structure of the owl:sameAs graph can be used in order to detect possibly erroneous identity assertions. For this, we assign an error degree for each owl:sameAs based on the density of the community(ies) in which they occur, and their symmetrical characteristics. One benefit of this approach is that it does not rely on any additional knowledge. Finally, as a way to limit the excessive and incorrect use of owl:sameAs, we define a new relation for asserting the identity of two ontology instances in a specific context (a sub-ontology). This identity relation is accompanied with an approach for automatically detecting these links, with the ability of using certain expert constraints for filtering irrelevant contexts. As a first experiment, the detection and exploitation of the detected contextual identity links are conducted on two knowledge graphs for life sciences, constructed in a mutual effort with domain experts from the French National Institute of Agricultural Research (INRA).

A new enzyme activity assay has been developed for the target N8-acetylspermidine deacetylase, a not-well-studied but essential enzyme in the polyamine interconversion and reutilization pathway. The enzyme assay, based on mass spectrometric detection of a specific reaction product following sample introduction by flow injection, was shown to have a sensitivity of smaller than 1 micromolar and typical RSD of 3-10%. The linear range for analyte was from 1 μM to 100 μM, with R2 > 0.992. The new assay avoids the use of radio labels. Sample preparation is straightforward, and high specificity is provided by the selected reaction monitoring, SRM, using a triple quadrupole mass spectrometer. Acetylputrescine was used for the first time as the substrate for the assay of N8-acetylspermidine deacetylase in lieu of N8 -acetylspermidine. The crude enzyme extracted from rat liver had an apparent Km value of 80.6 μM for acetylputrescine and a Vmax of 1.1 nmol mg-1 min-1. Enzyme extracted from frozen rat liver was compared with that from fresh rat liver. Frozen rat liver extraction had similar kinetics parameters with the fresh preparation and had a specific activity of 0.8 nmol mg-1 min-1. N8-acetylspermidine deacetylase was partially purified by protein precipitation and gell filtration chromatography. Affinity chromatography was tentatively applied for further isolation of the enzyme, but was not yet successful.

京都大学 / 0048 / 新制・課程博士 / 博士(農学) / 甲第19770号 / 農博第2166号 / 新制||農||1040(附属図書館) / 学位論文||H28||N4986(農学部図書室) / 32806 / 京都大学大学院農学研究科食品生物科学専攻 / (主査)教授 河田 照雄, 教授 保川 清, 教授 橋本 渉 / 学位規則第4条第1項該当 / Doctor of Agricultural Science / Kyoto University / DGAM

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Linked verse is a communicative and dynamic poetic form in which a series of verses are usually composed by several poets. It existed in both China and Japan and was fully explored by Han Yu’s circle and Bashō’s school, respectively. This thesis is a comparative study of the lian ju (Chinese linked verse) by Han Yu’s circle and the haikai (Japanese popular linked verse) by Bashō’s school, with focus on the arts of linking, the most important and interesting aspect of this unique poetic form. This study begins with a broad introduction and comparison of the two literary groups and their linked verse compositions. Representing the highest level of linked verse compositions in China and Japan, Han’s lian ju and Bashō’s haikai share some similarities. Yet whereas the former never outshone individual poetry in terms of influence and popularity, the latter dominated the entire poetic field, at least in Bashō’s day. In the second chapter, I investigate how the verses are linked. In terms of linking techniques, Han Yu’s circle basically used “close link,” including “word link” and “content link,” which does not exceed the range of the Chinese poetic tradition. In contrast, Bashō’s school valued the “distant link,” which is usually beyond expectation and needs analysis and imagination. In both cases, the linking is usually a combination of “complementary linking” and “competitive linking.” However, the competitive atmosphere prevails in the former while the complementary characteristic is represented more often in the latter. The third chapter continues the topic of linking, but it focuses on how the verses in a sequence are integrated as a whole. The verses in a lian ju sequence share a topic and are organized as in traditional individual poetry. In a haikai sequence, however, verses with different topics and images are disciplined by detailed rules. Finally, I compare the styles of the two schools. Both of them created a “new” poetic style by searching for the “old.” Nevertheless, the content of their poetry and their ways of composing poetry are very different.

This thesis describes the development of a way to study the N8 - acetylspermidine deacetylase enzyme activity. The method created in this thesis emphasizes sensitivity, accuracy and safety. In this study, HeLa cells were cultured and extracted to yield a crude N8 - acetylspermidine deacetylase enzyme mixture. By measuring the decrease of N8 - acetylspermidine and the increase of spetmidine, N8 -acetylspermidine deacetylase enzyme activity can be determined using either a Varian 1200L LC/MS/MS or an API 3000 LC-ES (+)/MS/MS. An acetylation-derivatization method was developed because N8 -acetylspermidine and spermidine are hard to purify from a biological sample since they are not retained on a CIS solid phase extraction column or on a RP HPLC (high performance liquid chromatography) reverse phase column due to their small molecular weight and high polarity. The quantitation of N8 -acetylspem1indine over the range 2ng/ul to 5pg/ul was fit by linear regression as y = 1.064x + 0.218 with an R-squared value of 0.9996, where y is the peak area of the fragment-ion SRM (selected reaction monitoring: m/z: 188/114) chromatograms from N8 -acetylspermindine and x is the concentration of N8 - acetylspermindine. Acetylation of spermidine (SPD) and N8-acetylspermidine (N8AcSPD) with d6-acetic anhydride produces the d9 labeled triacetylated derivative of SPD and d6 labled triacetylated spermidine derivative of N8AcSPD. These triacetylated forms are retained on a C18 column. MS/MS gives characteristic m/z fragment ions for the derivatized species: N8AcSPD (278 to 215), NlAcSPD (278 to 218) and SPD (281 to 218). The fragment-ion SRM (selected reaction monitoring) chromatograms are used for the quantitation. A plot of peak area ratios for known mixtures of N8AcSPD and total SPD versus the molar ratios of N8AcSPD and total SPD was found to fit a linear regression line withy= 0.705x + 0.035 with an R-squared value of 0.9919. Quantitation of d6- and dg-tri-acetylspermidine by LC/MS/MS is possible at the low levels of materials found in cell extracts since the separation method results in a lower limit of quantitation. This approach enables the study of N8 - acetylspermidine deacetylase enzyme activity.

The use of Linked Data to model and visualize complex information entails usability challenges and opportunities to improve the user experience. This study seeks to enhance the user experience of a product information tool which is developed with Linked Data approach. The research was carried out in an industrial setting and follows the case study paradigm. It consists of 1) user research and literature review to define design requirements, 2) prototyping, and 3) usability testing. The user research produced a list of user experience issues which were in turn translated into design requirements by reflecting on related research and following the user's needs and goals. The design requirements formed the design elements which are embedded into the development of low- and high-fidelity prototypes. Next, usability evaluation of the final high-fidelity prototype examined the extent to which the design decisions could optimize the Linked Data visualization. The results show that several design decisions, such as adding interaction dynamics and the use of rich color representation, could indeed improve it. Also, in terms of general information and visual notation, the shift from UML diagram to node-links diagram received positive feedback from the users. But both node-links diagram and UML diagram received similar scores for the effectiveness and efficiency. / Användningen av Linked Data i syfte att modellera och visualisera komplex information medför både utmaningar och möjligheter för förbättringar när det kommer till användarupplevelsen. Denna studie strävar efter att förbättra användarupplevelsen av ett produktinformationsverktyg som utvecklats med Linked Data-tekniker. Studien är en fallstudie som genomfördes i en industriell miljö och består av: 1) användarundersökning och litteraturöversikt för att definiera designkrav, 2) prototyputveckling, och 3) användbarhetstester. Användarundersökningen resulterade i en lista av problem relaterade till användarupplevelsen, vilken i sin tur översattes till designkrav genom reflektioner kring både tidigare forskning och användarnas behov och mål. De identifierade designkraven utgjorde sedan grunden för de designelement som inkluderades i utvecklingen av High and Low-fidelity-prototyper. Därefter utvärderades i vilken utsträckning de nya designelementen i den slutgiltiga High-fidelity-prototypen kunde förbättra datavisualiseringen. Resultaten visar att designbeslut som att inkludera interaktionsdynamik och rik färgrepresentation kan förbättra användarvänligheten av systemet. Även om både tillvägagångssätt som UML-diagram och Node-Link-diagram fick likartade resultat när det kom till effektivitet, gav skiftet från UML-diagram till Node-Link-diagram en mer positiv respons från användarna när det kom till generell information och visuell notation.

The development of Massively Parallel Sequencing (MPS) has enabled more accurate and less time-consuming DNA sequencing. Although MPS technologies are theoretically applicable to all samples and species, the majority of studies on microorganisms have been conducted on those able to be isolated and cultivated in laboratories. In the field of metagenomics, DNA from uncultivated environmental samples is analyzed. Whole genome sequencing of such complex samples poses difficult computational challenges due to the characteristics of metagenomic data, where one major challenge lies in determining the true origin of high similarity reads. In addition, the short-range information acquired from MPS reveals little about how reads from DNA sequencing fit together. Consequently, producing genome drafts from reads generated by MPS remains difficult. Here, the linked-read sequencing technology DB-Seq has been applied to bacterial samples in order to assess its potential in metagenomics. Specifically, its performance in retaining long-range information in de novo whole genome assembly has been tested. The results obtained in this initial study show great potential of DB-Seq in genome assembly, with significantly more contiguous results than conventional methods generate. / Utvecklingen av Massiv Parallel Sekvensering (MPS) har möjliggjort mer korrekt och mindre tidskrävande DNA sekvensering. Trots att MPS teoretiskt sett kan appliceras på alla provtyper och arter, har majoriteten av de studier som utförts på mikroorganismer varit fokuserade på de som kan isoleras och odlas i laboratorium. Inom ämnet metagenomik analyseras DNA från orörda miljöprover. Helgenomssekvensering av sådana prover ger upphov till komplicerade utmaningar för data-analys, där ett av de största problemen är att bestämma ursprunget av snarlika sekvenseringsresultat. Ytterligare komplikationer uppstår på grund av den data som erhålls från MPS, då denna ej ger information om hur sekvenseringsdata bör placeras i förhållande till varandra. Följdaktligen är det svårt att producera hopsatta genom utifrån MPS-data. I detta projekt har "linked-read"-sekvenseringsteknologin DB-Seq applicerats på bakterieprover för att undersöka metodens potential i metagenomik. Specifikt har metodens förmåga att bibehålla information om ursprungspositionen av sekvenseringsdata testats i de novo sammansättning av genom. De erhållna resultaten i denna förstagångsstudie tyder på stor potential för DB-Seq i genomsammansättning, med signifikant mer sammanhängande resultatsekvenser än vad konventionella metoder uppvisar.

Chitosan (CS) is a man-made sugar based biopolymer derived from chitin, the second most abundant natural polymer after cellulose. Chitin is sourced from crustacean species such as shrimps and crabs. The chemical structure of chitin contains N-Acetyl D-glucosamine monomer units which forms CS upon deacetylation. In CS, ?-(1-4) linked D-glucosamine units are randomly distributed. Approximately 75% - 80% sugar units contains primary amine groups in commercially available low molecular weight CS. Biodegradability, low toxicity, mucoadhesive and transfecting properties of CS polymer are attractive for applications as oral and nasal drug delivery systems. Chitosan polymer is water insoluble at neutral pH. To solubilize CS, dilute mineral acid (such as hydrochloric acid and nitric acid) or organic acid (such as acetic acid) is often used. CS contains both hydroxyl and primary amine groups in its structure. In acidic solution, the amine functional groups become protonated (positively charged). Positively charged CS remains stable only in low pH condition due to electrostatic repulsion of charged polymer segments. Therefore, by using a suitable anionic (negatively charged) cross-linker, stable CS particles (such as nanoparticles and microspheres) can be prepared. This is popularly known as ionic gelation method. Extensive studies have been done on the synthesis of drug loaded CS particles where particle integrity is maintained by ionic gelation using tripolyphosphate (TPP, an anionic cross-linker). Drug encapsulated CS-TPP composite particles are shown to maintain biodegradability and biocompatibility. The CS-TPP composite particles exhibits very limited dispersibility at neutral pH conditions specifically in neutral buffered conditions. A number of biomedical applications (including systemic drug formulations) however demands buffer-stable CS composite particles for achieving optimal therapeutic outcome. To overcome the above dispersibility issues, CS polymer and CS particles units have been chemically modified using water soluble motifs (such as water soluble polymer or ligands). This approach is very cumbersome and usually involves multiple purification steps. Chemical modification of natural CS chain introduces risks of compromising biodegradability and biocompatibility. Therefore, there is a strong need for developing a straightforward method of making water soluble CS and CS particles. Chapter 1 of this dissertation presents an overview of the CS polymer, various applications of CS polymers, methods of making CS polymers and CS particles, current limitations of synthesis methods for preparing stable chitosan particles at neutral pH conditions and finally delineates the scope of the proposed research work. Chapter 2 describes development of chemo-hydrothermal synthesis method for producing water soluble CS polymer and water dispersible CS composite particles. In this method, a chemical (depolymerizing agent) is used to treat CS polymer in a hydrothermal (high temperature and high pressure) condition. Two types of depolymerizing agents have been used, an inorganic acid (e.g. hydrochloric acid, HCl) and a bicarboxylic organic acid (e.g. tartaric acid, TA). In both cases, 100% depolymerized CS polymer was obtained. Chemical characteristics of the depolymerized CS were comparable to acid solubilized CS. CS polymer exhibits weak fluorescence. Interestingly, hydrothermally depolymerized CS shows strong fluorescence properties irrespective of the nature of depolymerizing agent used. TA not only depolymerized CS but also formed CS-TA composite particulate structures in solution via self-assembly. The CS-TA composite particles are stable in a wide pH range from 5 to 11. Detailed spectroscopic and microscopic studies have been done to understand the basic mechanism of particle formation and increase in fluorescence properties (i.e. structure-property relationship). Usefulness of CS-TA in solubilizing water-insoluble cargos (such as fluorescein isothiocyanate, FITC) has been demonstrated. Chapter 3 is focused on hydrothermal synthesis of mixed-valence copper (Cu) oxide loaded CS-TA composite particles and their characterization. Crystalline Cu oxide nanoparticles were coated with the CS-TA layer. Water dispersibility of Cu oxide greatly improved upon coating with CS-TA material. To demonstrate catalytic activity of Cu-oxide loaded CS-TA film in sequestering carbon dioxide (CO2), an electrochemical setup was used. Electrochemical reduction of CO2 was successfully demonstrated. It was observed that CS-TA environment not only maintained catalytic properties of Cu oxide but also allowed solution processing of Cu-oxide film onto the electrode surface. Chapter 4 discusses a convenient method of making monodispersed water dispersible Cu loaded chitosan nanoparticles (Cu-CS) using HCl depolymerized CS polymer. The purpose of this study was to investigate if there was any improvement in antibacterial properties of Cu-CS nanoparticles prepared using hydrothermally treated CS polymer. Interestingly, it was observed that the antibacterial efficacy of Cu was not compromised in Cu-CS nanoparticles. Moreover, the materials exhibited improvement in antibacterial efficacy against both Gram-negative and Gram-positive bacteria species. A plausible mechanism has been proposed to explain antibacterial results. Chapter 5 summarizes major findings of this dissertation research and presents future research directions.