Cette thèse est consacrée à l’analyse de l’espace chimique des composés antipaludiques. L’analyse est faite à l’aide de la méthode des cartes topographiques génératrices (GTM). Un nouveau concept des cartes universelles est introduit et discuté en détail dans cette thèse : ce sont des cartes qui sont capables d’accommoder plusieurs jeux de données et les propriétés associées simultanément. Trois types des cartes sont construits et analysés : les cartes locales, globales et universelles. Elles sont toutes compétentes à la prédiction des composés actifs contre le parasite, ainsi qu’à l’analyse de l’espace chimique. Elles nous permettent d’étudier le recouvrement des données issues des sources différentes, de détecter des terra incognita de l’espace chimique, identifier des zones correspondantes aux différents mécanismes d’action, et révéler des incohérences d’annotations des données. / This thesis is dedicated to the concept of the analysis of chemical space, and the application of thatconcept to antimalarial compounds. The analysis of the chemical space of antimalarial compoundshere is done with the aid of the Generative Topographic Mapping (GTM) method. A concept ofUniversal GTM maps is developed and discussed in detail in this thesis: these are maps that areable to accommodate different datasets and associated properties. Three types of maps are builtand analyzed: local, global, and universal. All these maps perform well in predicting compoundsactive against the parasite, as well as in the analysis of chemical space: they help us to study theoverlap of data coming from different sources, detect terra incognita of the antimalarial space,delineate zones corresponding to various mechanisms of action, as well as highlight theinconsistencies in data annotations.

Cette thèse est dédiée à l’analyse systématique de l’espace chimique, et des relations structure-activité (SAR) en particulier. L’ouvrage présente des nouveaux protocoles d’analyse combinant des méthodes classiques et originales, dans le but d’analyser les SAR à l’échelle globale ainsi que locale. L’analyse globale des espaces chimiques repose sur la recherche des motifs structuraux privilégiés par cartographie topographique générative (GTM), ainsi que par analyse classique des « châssis » moléculaires. La cartographie a été ensuite couplée avec l’analyse de réseaux chimiques (CSN), permettant une transition de la vue globale vers l’analyse locale de SAR. L’optimisation mutiobjectif des propriétés de potentiels médicaments a été adressé par la méthode « star coordinates ». L’analyse locale des SAR inclut des nouvelles stratégies pour prédire les discontinuités dans le paysage structure-activité biologique, et une étude de l’impact de la structure sur l’ionisation des molécules. Des matrices SAR ont servi pour monitorer le progrès dans l’optimisation de nouveaux principes actifs. / This thesis presents studies devoted to aid in systematic analysis of chemical spaces, focusing on mining and visualization of structure-activity relationships (SARs). It reports some new analysis protocols, combining both existing and on-purpose developed novel methodology to address both large-scale and local SAR analysis. Large-scale analysis featured both generative topographic mapping (GTM)-based extraction of privileged structural motifs and scaffold analysis. GTM was combined with chemical space network (CSN) to develop a visualization tool providing global-local views of SAR in large data sets. We also introduce star coordinates (STC) to visualize multi-property space and prioritize drug-like subspaces. Local SAR monitoring includes new strategies to predict activity cliffs using support vector machine models and a study of structural modifications on ionization state of compounds. The SAR matrix methodology was applied to objectively evaluate SAR progression during lead optimization.

This thesis contributes to the debate on the link between a transitive verb corresponding to 'need' and the verb of possession in the world’s languages. Specifically, I analyze data mainly from Ewe and three Ghana-Togo Mountain (GTM) languages; Likpe, Tafi, and Logba. First, I report that Ewe expresses predicative possession using a wide range of structures. Prominent among these structures is an intransitive locative construction in which the possessee c-commands the possessor. This characterization situates Ewe in the B-languages group of the have/be dichotomy. Second, I demonstrate, drawing on compelling pieces of evidence from object shift in nominalization, object shift in inceptive aspectual constructions, object extraction in wh-movement, and the nominative-accusative paradigm, that Ewe has a transitive verb 'hiã' corresponding to 'need'. These facts pose a challenge to Harves and Kayne’s (2012) claim that all languages that have a transitive verb corresponding to need are languages that have an accusative-Case-assigning verb of possession. Third, I have shown that predicative possessees are not licensed in like manner as transitive objects, contra Halpert and Diercks’ (2012) prediction that all languages that have a transitive verb corresponding to 'need' are languages in which predicative possessees are licensed in the same manner as transitive objects. Fourth, I show that data from the three GTM languages also pose a challenge to the predictions in Harves & Kayne (2012) and Halpert & Diercks (2016). Finally, I suggest that the presence or absence of a transitive verb corresponding to 'need' is not necessarily contingent on a transitive verb of possession, and therefore, the optionality of a transitive 'need' in H-languages should be extended to B-languages.

Plastic never fully disappears, but instead breaks into smaller pieces referred to as microplastics (< 5 mm length). Microplastics are common worldwide, and more studies are needed to understand the accumulation and diversity of microplastics found in various environments. In this study, six locations were sampled for one year in the Guana River Estuary, a partially impounded system with heavily urbanized headwaters. This study was conducted in conjunction with the Guana Tolomato Matanzas National Estuarine Research Reserve (GTM NERR) and the Florida Fish and Wildlife Conservation Commission (FWC) at their water sampling stations. The objectives of this study were to investigate: 1) distribution patterns across sample sites over time, 2) the color, size, and shape of microplastics found, and 3) polymer composition. Water samples were collected from surface waters in 1-L bottles, with five replicates at each site. Sampling occurred once a month, at the beginning of each month from August 2020-August 2021. Samples were analyzed for abundance and characteristics of microplastics using a dissecting microscope and the polymer composition was determined using Fourier-transform infrared spectroscopy. No pattern was found in the distribution of microplastics from north to south or over time. Variations in plastic color, size, and polymer composition suggests that there are multiple sources of pollution into the Guana River Estuary.

Cette étude considère des systèmes où non seulement la structure moléculaire, mais les conditions expérimentales sont impliquées. Les structures chimiques ont été codées par des descripteurs locaux ISIDA MA ou ISIDA CGR, ciblant spécifiquement les centres actifs et leur environnement le plus proche. Les descripteurs locaux ont été combinés avec les paramètres spécifiques des conditions expérimentales, codant ainsi un objet chimique particulier. La méthodologie a été appliquée avec succès pour la modélisation QSPR des paramètres thermodynamiques et cinétiques des interactions intermoléculaires (liaisons halogène et hydrogène), des équilibres tautomères et des réactions chimiques (cycloaddition et SN1). La méthode GTM a été appliquée pour la première fois pour la modélisation et la visualisation de données chimiques mixtes. La méthode sépare avec succès les groupes de données à la fois en raison des structures et des conditions. / This work describes original approaches for predictive chemoinformatics modeling of molecular interactions and reactions as a function of the structures of interacting partners and of the chemical environment (experimental conditions). Chemical structures have been encoded by local ISIDA MA-based or CGR-based descriptors, specifically targeting the active centers and their closest environment. The local descriptors have been combined with the specific parameters of experimental conditions, thereby encoding a particular chemical object. The methodology has been successfully applied for QSPR modeling of thermodynamic and kinetic parameters of intermolecular interactions (halogen and hydrogen bonds), tautomeric equilibria and chemical reactions (cycloaddition and SN1). GTM method has been applied for the first time for QSPR modeling and visualization of mixed chemical data. This method successfully separates data clusters on account of both chemical structures and experimental conditions.

This thesis is a description of some aspects of the grammar of Sɛlɛɛ, a Ghana-Togo-Mountain (GTM) language, based on my own fieldwork. The thesis consists of an introduction and five papers. Paper (I), Noun classes in Sεlεε, describes the noun class system of Sɛlɛɛ. It consists of eight noun class prefixes, four marking singular and four plural. They are paired in irregular ways to form eight genders (singular-plural pairs). Nouns agree with determiners, numerals and interrogative qualifiers within the noun phrase and can be indexed on the predicate. Nouns are allocated to classes/genders based partly on semantic notions. Paper (II), Sεlεε (with Francesca Di Garbo), details the morphological encoding of diminution in Sɛlɛɛ either by the suffixes -bi, -bii, -mii, -e or -nyi alone or in combination with noun class shift. Augmentation is not expressed morphologically. Paper (III), The tense and aspect system of Sεlεε: A preliminary analysis, shows that Sɛlɛɛ, unlike most Kwa languages, has a rather elaborate tense system encompassing present, hodiernal, pre-hodiernal and future tenses. The aspectual categories are progressive, habitual and perfect. Both categories often amalgamate with first person singular subject clitics. Paper (IV), Standard negation in Sεlεε, deals with the negation of declarative verbal main clauses. This is primarily encoded by a high tone, sometimes combined with segmental morphemes, portmanteau negative tense-aspect morphemes and vowel lengthening. Each tense-aspect category has at least one particular negation strategy. Paper (V), Unravelling temperature terms in Sεlεε (with Francesca Di Garbo), investigates the grammatical constructions employed for temperature evaluations. Personal feeling is only encoded via subjects, while ambient and tactile evaluations are construed attributively and predicatively. A comparison of Selee and other GTM languages revealed similar noun morphologies but very different verbal morphologies. / <p>At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 2: Unpublished book chapter. Paper 3: Manuscript. Paper 4: In press. Paper 5: Unpublished book chapter.</p>

This research identifies shared strengths of Scrum and Kanban, such as iterative and incremental work and effective workload management, which are particularly beneficial in startup contexts characterized by high uncertainty. By systematically comparing the fundamental elements of both methodologies, the study delineates key dimensions and components that inform the development of a hybrid approach. This study aimed to explore which components of Kanban and Scrum are best suited for navigating uncertainty and ambiguity in a fast-paced environment. To achieve this objective, our first research question delves into the productive attributes of both Scrum and Kanban methods, laying the groundwork for our investigation. Additionally, we sought to identify the key factors driving adaptations in the application of these methods within software startups, as well as pinpoint the highlighted concepts and elements that can be effectively utilized. This formed the basis of our second research question, with the ultimate aim of developing a hybrid model that integrates the most beneficial aspects of both methodologies, thus addressing the challenges posed by uncertainty and rapid change in the initial phase of the study. We employed a mixed-methods approach, utilizing a literature review, survey, and case study analysis. The theoretical foundation was established through a comprehensive review of existing literature on Scrum and Kanban, supported by the construction of a comparative mind map. Survey data was collected from industry professionals to gather insights into the practical application of these methodologies. Additionally, a case study was conducted to provide a deeper understanding of the challenges and successes in implementing agile practices within a startup environment. Through our research, we identified key dimensions and components of Scrum and Kanban relevant to software startups, including values, principles/practices, team structure, events/cadences, and artifacts. By analyzing survey responses and conducting in-depth interviews, we gained valuable insights into the strengths and limitations of each methodology. Moreover, our case study provided real-world examples of the challenges faced and strategies employed in a startup setting. The findings suggest that while Scrum and Kanban offer distinct strengths, a hybrid approach integrating both methodologies can better address the dynamic needs of software startups. The proposed hybrid model emphasizes flexibility and adaptability, allowing startups to tailor practices to their specific context while leveraging the strengths of Scrum and Kanban. Overall, this research contributes to a deeper understanding of how startups can navigate agile transformation and achieve success in a competitive market.

Cette thèse est consacrée à la cartographie de l’espace chimique ; son but est d’établir les bases d’un outil donnant une vision d’ensemble d’un jeu de données, comprenant prédiction d’activité, visualisation, et comparaison de grandes librairies. Dans cet ouvrage, nous introduisons des modèles prédictifs QSAR (relations quantitatives structure à activité) avec de nouvelles définitions de domaines d’applicabilité, basés sur la méthode GTM (generative topographic mapping), introduite par C. Bishop et al. Une partie de cette thèse concerne l’étude de grandes librairies de composés chimiques grâce à la méthode GTM incrémentale. Nous introduisons également une nouvelle méthode « Stargate GTM », ou S-GTM, permettant de passer de l’espace des descripteurs chimiques à celui des activités et vice versa, appliquée à la prédiction de profils d’activité ou aux QSAR inverses. / This thesis is dedicated to the cartography of chemical space; our goal is to establish the foundations of a tool offering a complete overview of a chemical dataset, including visualization, activity prediction, and comparison of very large datasets. In this work, we introduce new QSAR models (quantitative structure-activity relationship) based on the GTM method (generative topographic mapping), introduced by C. Bishop et al. A part of this thesis is dedicated to the visualization and analysis of large chemical libraries using the incremental version of GTM. We also introduce a new method coined “Stargate GTM” or S-GTM, which allows us to travel from the space of chemical descriptors to activity space and vice versa; this approach was applied to activity profile prediction and inverse QSAR.

Geotechnical monitoring (GTM) is an essential part of the observation method. In the principle it is the measurement and monitoring of preselected magnitudes – their changing values in the course of the constructing process and their partial evaluation. On the measured values basis the correctness of designed structures and technological processes is verified, optionally new technical and organizational measures are adopted in order to guarantee the continuous and safe constructing course. The main goal of the dissertation is to analyze the current state of the problematics and evaluate the methods of GTM in underground structures with low overburden, including suggestions and recommendations for procedures. In the framework of knowledge, practical experience and data analysis, the basic types and procedures of monitoring elements of underground structures with low overburden will be defined.

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