Problem-based learning has long been recognized as an innovative and effective instructional strategy for enhancing problem-solving and critical skills, which are essential for 21st-century employability. Despite its recognized benefits, PBL adoption in K-12 education remains limited due to significant implementation challenges. This integrative literature review investigates PBL instructional strategies and teachers' experiences, focusing on their challenges and the types of problems used in K12 classrooms, while analyzing empirical studies from 2004 to 2024. The study findings reveal teachers' challenges in terms of problem design and development, scaffolding, technology integration, assessment, and promoting student collaboration, with time availability being a recurring concern. Again, teachers' implementation strategies are flexible but could, however, be summarized into (1) preparing learners for PBL, (2) an iterative cycle of activities, and (3) presentation and evaluation. The findings also revealed that design problems dominate the type of problems that are incorporated into K-12 PBL implementation studies. Beyond setting the foundation for future research in the area, this integrative review offers a deeper understanding related to PBL's application in K-12 settings, providing valuable insight for educational stakeholders. / Doctor of Philosophy / Problem-based learning (PBL) is a student-centered teaching method that supports the development of relevant problem-solving and critical-thinking skills which are critical for career success and employability in the 21st century. Although many studies have emphasized its effectiveness, it is not widely used in K-12 education. This limitation is attributed to different implementation challenges. This integrative literature review investigates PBL instructional strategies and teachers' experiences, focusing on their challenges and the types of problems used in K-12 classrooms, while analyzing empirical studies from 2004 to 2024. The study findings reveal teachers' challenges in terms of problem design and development, scaffolding, technology integration, assessment, and promoting student collaboration, with time availability being a recurring concern. Again, teachers' implementation strategies are flexible but could, however, be summarized into (1) preparing learners for PBL, (2) an iterative cycle of activities, and (3) presentation and evaluation. The findings also reveal that design problems dominate the type of problems that are incorporated into K-12 PBL implementation studies. Beyond setting the foundation for future research in this area, this integrative review offers a deeper understanding related to PBL's application in K-12 settings, providing valuable insight for educational stakeholders.

Le travail présenté dans cette thèse concerne l'étude de la notion de conversion inhérente à tous système de types dépendants. Plusieurs présentations de ces systèmes ont été étudiées pour des usages variés: typage, recherche de preuve, cohérence de logique... Chacune de ces représentation est accompagnée d'une notion d'égalité différente, suivant les besoins du moment. Mais il n'est pas certains que toutes ces représentations parlent en fin de compte d'une seule et même logique. Nous nous intéressons ici à une famille assez conséquente de systèmes de types, appelés Systèmes de Types Purs, et nous allons prouver que pour ces systèmes, toutes les représentations habituellement utilisées sont en fait équivalentes, c'est à dire qu'il existe des traductions constructives entre chacune de ces présentations. Ces traductions reposent toutes sur la manière de porter une égalité d'un système à l'autre. Ce travail se concentre donc sur les mécanismes de ces égalités, et prouve qu'il est possible de typer n'importe quelle égalité syntaxique en égalité sémantique, et ainsi qu'il est donc possible de passer d'un système à l'autre. L'intégralité de cette thèse a en outre été vérifiée et certifiée correcte à l'aide de l'assistant à la preuve Coq, qui a activement été utilisé tout au long de l'élaboration des preuves. ~

Xylella fastidiosa é uma bactéria com alta diversidade genética, sendo responsável por várias doenças, com destaque para a clorose variegada dos citros (CVC) e Pierce\'s disease (PD) em videira. O sucesso da transmissão dessa bactéria depende da colonização em biofilme no xilema da planta e no estomodeu de vetores, que são cigarrinhas (Hemiptera: Cicadellidae: Cicadellinae). O conhecimento sobre o mecanismo de transmissão desta bactéria vem de estudos com a subespécie fastidiosa de videira. Com relação à CVC, que tem a subespécie pauca como agente causal, observa-se eficiência de transmissão mais baixa que em videira, indicando que os mecanismos envolvidos no processo de transmissão podem variar entre subespécies da bactéria. Neste sentido, os objetivos desse trabalho foram: i) adaptar e validar um sistema de alimentação em dieta artificial para a aquisição e transmissão de estirpes de X. fastidiosa subsp. pauca por cigarrinhas; ii) aplicar a técnica estabelecida para investigar a eficiência de transmissão variando-se os sequence types (STs) de X. fastidiosa subsp. pauca e as espécies de cigarrinhas e iii) avaliar a importância da adesina XadA2 para a formação de biofilme por X. fastidiosa em superfície de polissacarídeos, bem como na aquisição e transmissão dessa bactéria pelos insetos. Verificou-se que o protocolo de aquisição usado para a entrega de células bacterianas da estirpe Temecula (subsp. fastidiosa) é transferível para estirpes da subsp. pauca. No entanto, diferentemente de fastidiosa, as estirpes de pauca testadas não necessitam interagir com o monômero de pectina (ácido galacturônico) para serem transmitidas para plantas. Com o sistema de aquisição in vitro, observou-se que todas as combinações STs de pauca e espécies de cigarrinhas resultaram na transmissão para plantas, indicando a ausência de especificidade de vetores. Todavia observaram-se diferenças nas taxas de aquisição e transmissão, que podem estar relacionadas com a interação inseto-ST. Em ensaios utilizando X. fastidiosa modificada com green fluorescent protein, incubada em meio de cultivo sem fonte de carbono e contendo asas como única fonte de carboidratos, verificou-se que a bactéria utiliza a quitina das asas para garantir a sobrevivência da colônia. Por meio de ensaios de bloqueio em asas, utilizando a adesina XadA2 e seu anticorpo específico como moléculas competidoras, foi possível observar que quando a adesina é bloqueada, há a redução significativa da formação de biofilme nas asas. Utilizando-se o sistema in vitro para a entrega de células de X. fastidiosa e do anticorpo para as cigarrinhas, observou-se diminuição da taxa de insetos infectivos, porém não houve diferença estatística nas taxas de transmissão. Esses resultados mostram que a adesina XadA2 é importante no início da colonização bacteriana no inseto e, juntamente com o método de aquisição in vitro adaptado nesse trabalho, estabelecem bases para estudos com outras estirpes ou subespécies de X. fastidiosa, e avaliação de outras proteínas-alvo visando o bloqueio da interação bactéria-vetor e, possivelmente, o controle das doenças. / Xylella fastidiosa is a bacterium with high genetic diversity, being responsible for several diseases, with emphasis on citrus variegated chlorosis (CVC) and Pierce\'s disease (PD) on grapevines. The success of the transmission of this bacterium depends on the biofilm colonization in the plant xylem and in the foregut of vectors, the sharpshooters (Hemiptera: Cicadellidae: Cicadellinae). The knowledge about the transmission mechanism of this bacterium comes from studies with the fastidiosa subspecies of grapevine. With regard to CVC, which has the subspecies pauca as causal agent, transmission efficiency is lower than in vine, indicating that the mechanisms involved in the transmission process may vary between subspecies of the bacterium. In this sense, the objectives of this work were: i) to adapt and validate an artificial diet feeding system for the acquisition and transmission of strains of X. fastidiosa subsp. pauca by sharpshooters; ii) apply the established technique to investigate the efficiency of transmission by varying the sequence types (STs) of X. fastidiosa subsp. pauca and sharpshooters and iii) to evaluate the importance of XadA2 adhesin for X. fastidiosa biofilm formation on the surface of polysaccharides, as well as on the acquisition and transmission of this bacterium by the insects. The acquisition protocol used for the delivery of Temecula strain bacterial cells (subspecies fastidiosa) was transferable to strains of the subspecies pauca. However, unlike fastidiosa, the tested pauca strains do not need to interact with the pectin monomer (galacturonic acid) to be transmitted to plants. With the in vitro acquisition system, it was observed that all STs pauca and sharpshooter species combinations resulted in the transmission to plants, indicating the absence of vector specificity. However, there were differences in acquisition and transmission rates, which may be related to the insect-ST interaction. In tests using X. fastidiosa modified with green fluorescent protein, incubated in culture medium without carbon source and containing wings as only source of carbohydrates, it was verified that the bacterium uses the chitin of the wings to guarantee the survival of the colony. With wing-blocking assays, using XadA2 adhesin and its specific antibody as competing molecules, it was possible to observe that when adhesin is blocked, there is a significant reduction of biofilm formation in the wings. Using the in vitro system for the delivery of X. fastidiosa cells and the antibody to the sharpshooters, a decrease in the rate of infective insects was observed, but there was no statistical difference in the rates of transmission. These results show that XadA2 adhesin is important at the beginning of bacterial colonization in the insect and, together with the in vitro acquisition method adapted in this work, establishes bases for studies with other strains or subspecies of X. fastidiosa, and evaluation of other target proteins to block bacterial-vector interaction and, possibly, to control of the diseases.

Tanto as incubadoras como as aceleradoras são organizações especializadas no suporte de empreendimentos em fases iniciais, em especial, aqueles intensivos em inovação conhecidos como startups. Apesar da grande disseminação dessas organizações, há poucas informações na literatura que evidenciem as suas diferenças e as contribuições na jornada do empreendedorismo inovador. Assim, o objetivo principal deste estudo é comparar a diferença entre as propostas de valor das aceleradoras e das incubadoras a partir da percepção das startups que tenham sido tanto incubadas como aceleradas. Entre os objetivos específicos temos: discutir possíveis relações entre as aceleradoras e as incubadoras de negócios; apresentar a evolução das incubadoras e os fatores que induziram o surgimento das aceleradoras, descrevendo os diferentes arquétipos e as implicações que essas organizações têm no ecossistema de empreendedorismo; apresentar o cenário nacional do fenômeno de aceleração e de incubação. O levantamento de dados contará com duas etapas: análise documental de fontes de dados secundárias e estudos de caso com uso de técnica de entrevista e questionário semiestruturado. A análise documental foi feita a partir de banco de dados de artigos científicos, dados oficiais de governos, fundações, revistas e páginas web especializadas e editais de chamamento das próprias organizações. A análise documental fornecerá o retrato de como as incubadoras e as aceleradoras se promovem no ecossistema como organizações importantes no apoio às startups. Em seguida, através de abordagem exploratória descritiva e qualitativa, foram realizadas entrevistas com roteiros semiestruturados com fundadores de startups que foram incubadas e aceleradas, para compreender o valor que cada um desses processos forneceu ao desenvolvimento dessas empresas. Concluiu-se que existe uma dissonância entre o valor percebido pelas startups e o que as incubadoras e as aceleradoras promovem. Também foi possível identificar que a busca por recursos pelas startups tende a não seguir um processo linear, capturando as melhores oportunidades que estejam disponíveis no momento. Por fim, esta pesquisa é um passo exploratório para trazer novas evidências do fenômeno das startups e dos diferentes instrumentos que as constroem. Sugerem-se encaminhamentos que possam preencher lacunas na literatura a respeito dos fenômenos citados, indicando a necessidade de estudos futuros que adensem o conhecimento desse fenômeno. / Both incubators and acelerators are specialized organizations to support early-stage ventures, especially innovation-intensive ones known as startups. Despite the great spread of these organizations, there is a few information in the literature that show their differences and contributions in the journey of innovative entrepreneurship. The main objective of this study is comparing the difference between value porposition of accelerators and incubators from the perception of startups that have been both incubated and accelerated. The specific objectives are: to discuss possible relationships between accelerators and incubators; to present the evolution of the incubators and the factors that led to the emergence of the accelerators, describing the different accelerators archetypes and the implications in entrepreneurship ecosystem; to present the national scenario of acceleration and incubation. The data collection stage had two stages: documentary analysis of secondary data sources; and the case study using interview technique through semi-structured questionnaire. The documentary analysis was made from a database of scientific articles, official data from governments, foundations, journals and specialized web pages and incubators and accelerators calls for proposals. Documentary analysis provided a picture of how incubators and accelerators are promoted to the ecosystem and startups. Then, through a descriptive and qualitative exploratory approach, interviews were conducted with semistructured scripts with founders of startups that were incubated and accelerated to understand the value that each of these processes provided to the development of these companies. It was concluded that there is a dissonance between what the incubators and the accelerators promote and the value perceived by the startups, they are not being able to identify enough characteristics that distinguish them. The reason for it is the diversity of the needs and demands of the startups, different models of accelerators and incubators are formulated that, in many cases, overlap in the benefits offered. It was also possible to identify that the search for resources by startups, whether radical or disruptive startups, does not follow a linear process, capturing the best opportunities available in the ecosystem through a minimally tactical and selective approach. In order to contribute to the understanding of the growing formation of organizations supporting startups, such as incubators and accelerators, and considering the findings of this research, a tool was suggested to define the types of these organizations, loosely termed \"startup guiders\". This tool analyzes three basic dimensions: business model, value proposition and stage of intervention in the development of early-stages ventures. Finally, this research is an exploratory step in bringing new evidence of the phenomenon of startups and of the different instruments that construct them. It is suggested that there be gaps in the literature regarding the mentioned phenomena, indicating the need for future studies that increase the knowledge of this phenomenon.

Dans le cadre des théories stables, il a été prouvé qu'une courbe pseudolinéaire était toujours, spécifiquement, linéaire (ce qui correspond dans ce cadre également à localement modulaire): on peut alors caractériser la géométrie de l'ensemble associé, qui est soit projective (avec le type associé à la courbe non-trivial et modulaire), soit affine (quand le type est non-modulaire) sur un corps gauche; lorsque le type associé est trivial, la géométrie est dégénérée. Cela nous permet donc de déduire de la simple pseudolinéarité d'un type la structure de l'ensemble sous-jacent: cette thèse étend ce résultat au cadre des théories simples, ce qui nous permettra à nouveau de détermé de la théorie), mais en se restreignant au cas où k < 4 / In the context of stable theories, it has been proven that a plane curve which is pseudolinear must be linear; it is then possible to deduce the geometry of the associated set, which is either projective (when the type associated to the plane curve is non-trivial and modular), or affine (when the type is non-modular) on a division ring; if the associated type is trivial, the geometry is degenerate. This means we can infer, from a type's pseudolinearity, the structure of the underlying set; this thesis extends this result to the context of simple theories, allowing us to determine the set's geometry (with several differences to account for the fact that the theory is simple and not stable) if we restrict ourselves to k < 4

Le vieillissement musculaire (sarcopénie) conduit inéluctablement à une perte d'autonomie, et à une moindre capacité à lutter contre les agressions métaboliques. Or, les mécanismes mis en jeu sont complexes et restent mal connus. Ainsi, au cours de cette thèse, une étude protéomique comparative a été développée afin d'identifier de nouveaux biomarqueurs potentiels de la sarcopénie chez la femme âgée post-ménopausée, et 73 protéines exprimées différentiellement dans le muscle âga ont été identifiées. En plus des altérations du muscle squelettique, l'âge est connu comme étant un facteur favorisant l'apparition du syndrome métabolique (SM), facteur de risque pour les maladies cardiovasculaires et le diabète de type II. Cependant, les effets du SM sur le muscle squelettique des personnes âgées sont peu décrits dans la littérature. Des marquages immunohistologiques ont été réalisés à partir de biopsies du muscle vastus lateralis provenant de personnes jeunes (25 ans) et âgées avec ou sans SM (75 ans), afin de décrire les altérations structurales et fonctionnelles du muscle squelettique liées à l'âge et au MS. Les résultats montrent une atrophie des fibres de type II ayant une déformation accrue lors du vieillissement. Chez les personnes âgées atteintes de SM, l'aire des fibres est augmentée par rapport aux personnes âgées contrôles, et une forte diminution de l'activité cytochrome c oxydase a été observée. De plus, le vieillissement et plus particulièrement le SM sont associés à une forte accumulation de lipides intramusculaires. Enfin, alors que peu de différences ont été observées chez les personnes âgées contrôles, le contenu en capillaire est fortement altéré chez les individus atteints de SM. Par la suite, une étude protéomique comparative a permis d'identifier 42 biomarqueurs potentiellement impliqués dans le vieillissement musculaire et/ou dans le syndrome métabolique. L'ensemble des résultats obtenus au cours de cette thèse devrait permettre d'améliorer notre compréhension des facteurs impliqués dans le développement de la sarcopénie, et pourrait permettre d'identifier à la fois de nouvelles voies de régulation et suggérer des cibles thérapeutiques potentielles. / Muscle aging (sarcopenia) contributes to both loss of autonomy and decreased capacity to prevent metabolic aggressions, but the mechanisms involved are complex and remain unclear. Therefore in this thesis, we have undertaken a top-down differential proteomic approach to reveal novel potential biomarkers of sarcopenia, and 73 differentially expressed proteins were identified. In addition to alterations of skeletal muscle, aging favors metabolic syndrome (MS), a risk factor for cardiovascular disease and type II diabetes. However, the effects of MS on skeletal muscle in old individuals have poorly been investigated. Immunohistochemical studies were performed with vastus lateralis muscle biopsies from young (25 years) and old (75 years) men with and without MS, to reveal the importance of age-dependent and MS-associated modifications on fiber-type characteristics. An atrophy of type-II fibers and altered fiber shape characterized muscle aging in lean healthy men. In contrast, increased cross sectional area of fibers, and reduced cytochrome c oxidase activity in all fiber types characterized MS, even in active elderly men. Moreover, aging and particularly MS were associated with accumulation of intramyocellular lipid droplets. Finally, while few differences were observed in lean healthy men, the capillary supply was strongly altered in old men with MS. Thereafter, a differential proteomic approach identified 42 potential biomarkers implicated in muscle aging and/or in metabolic syndrome. Overall the results obtained in this thesis may improve our understanding of the factors influencing sarcopenia, and may both identify new regulatory pathways and provide potential therapeutical targets.

MLF est un système de types combinant le polymorphisme implicite de seconde classe de ML avec le polymorphisme de première classe mais explicite du Système F. Nous proposons une représentation des types de MLF qui superpose un graphe acyclique orienté du premier ordre (encodant la structure du type avec partage) et un arbre inversé (encodant la structure de lieurs du type). Cela permet une définition simple et directe de l'instance sur les types, qui se décompose en une instance sur la structure du type, des opérations simples sur l'arbre de lieurs, et un contrôle acceptant ou rejetant ces opérations. En utilisant cette représentation, nous présentons un algorithme d'unification sur les types de MLF ayant une complexité linéaire.<br /><br />Nous étendons ensuite les types graphiques en un système de contraintes graphiques permettant l'inférence de types à la fois pour ML et MLF. Nous proposons quelques transformations préservant la sémantique de ces contraintes, et donnons une stratégie pour utiliser ces transformations afin de résoudre les contraintes de typage. Nous montrons que l'algorithme résultant a une complexité optimale pour l'inférence de types dans MLF, et que, comme pour ML, cette complexité est linéaire sous des hypothèses raisonnables.<br /><br />Enfin, nous présentons une version à la Church de MLF, appelée xMLF, dans laquelle tous les paramètres de fonctions, toutes les abstractions de type et toutes les instantiations de types sont explicites. Nous donnons des règles de réduction pour réduire les instantiations de types. Le système obtenu est confluent lorsque la réduction forte est autorisée, et vérifie la propriété de réduction du sujet. Nous montrons aussi le lemme de progression pour des stratégies faibles de réduction, dont l'appel par nom et l'appel par valeur en restreignant ou non le polymorphisme aux valeurs. Nous proposons un encodage de MLF dans xMLF qui préserve les types, ce qui assure la sureté de MLF.

Dans une première partie, nous définissons un nouveau langage à base fonctionnelle et avec récursion généralisée, en utilisant le système de types avec degrés de Boudol pour éliminer les récursions dangereuses. Ce langage est ensuite étendu par des enregistrements récursifs, puis par des mixins, permettant ainsi de mêler totalement les paradigmes fonctionnels et objets. Nous présentons également une implémentation, MlObj, ainsi que la machine abstraite servant à son exécution.<br /><br />Dans une deuxième partie, nous présentons un nouvel algorithme d'inférence pour les systèmes de types avec intersection, dans le cadre d'une extension du lambda-calcul. Après avoir prouvé sa correction, nous étudions sa généralisation aux références et à la récursion, nous le comparons aux algorithmes d'inférence déjà existants, notamment à celui de Système I, et nous montrons qu'il devient décidable à rang fini.

Les assistants de preuve basés sur des théories des types dépendants sont de plus en plus utilisé comme un outil pour développer programmes certifiés. Un exemple réussi est l'assistant de preuves Coq, fondé sur le Calcul des Constructions Inductives (CCI). Coq est un langage de programmation fonctionnel dont un expressif système de type qui permet de préciser et de démontrer des propriétés des programmes dans une logique d'ordre supérieur. Motivé par le succès de Coq et le désir d'améliorer sa facilité d'utilisation, dans cette thèse nous étudions certaines limitations des implémentations actuelles de Coq et sa théorie sous-jacente, CCI. Nous proposons deux extension de CCI que partiellement resourdre ces limitations et que on peut utiliser pour des futures implémentations de Coq. Nous étudions le problème de la terminaison des fonctions récursives. En Coq, la terminaison des fonctions récursives assure la cohérence de la logique sous-jacente. Les techniques actuelles assurant la terminaison de fonctions récursives sont fondées sur des critères syntaxiques et leurs limitations apparaissent souvent dans la pratique. Nous proposons une extension de CCI en utilisant un mécanisme basé sur les type pour assurer la terminaison des fonctions récursives. Notre principale contribution est une preuve de la normalisation forte et la cohérence logique de cette extension. Nous étudions les définitions par filtrage dans le CCI. Avec des types dépendants, il est possible d'écrire des définitions par filtrage plus précises, par rapport à des langages de programmation fonctionnels Haskell et ML. Basé sur le succès des langages de programmation avec types dépendants, comme Epigram et Agda, nous développons une extension du CCI avec des fonctions similaires.

We introduce abortable and query-abortable object types intended for implementation in asynchronous shared-memory systems with low contention. Implementations of such types behave like ordinary objects when accessed sequentially, but may abort operations when accessed concurrently. An aborted operation may or may not take effect, i.e., cause a state transition, and it returns no indication of which possibility occurred. Since this uncertainty can be problematic, a query-abortable type supports a QUERY operation that each process can use to determine its last non-QUERY operation on the object that caused a state transition, and the response associated with this state transition. Our research is closely related to obstruction-free implementations (introduced by Herlihy, Luchangco and Moir) and responsive obstruction-free implementations (introduced by Attiya, Guerraoui and Kouznetsov). Like abortable and query-abortable types, these implementations may exhibit degraded behaviour in the face of contention. We show that abortable registers--registers strictly weaker than safe registers--can be used to obtain obstruction-free and responsive obstruction-free implementations for any type. We present universal constructions for abortable and query-abortable types that are novel and efficient in the number of registers used. Specifically, they are based on a simple timestamping mechanism for detecting concurrent executions, and, in systems with n processes, use only n abortable registers or only O(n^2) single-reader, single-writer abortable registers. The timestamping mechanism we introduce is based on the inc&read counter type and appears to be interesting in its own right. As a generalization, we study the k-inc&read counter types, for k>0. We also identify a potential problem with correctness properties based on step contention: with such properties, the composition of correct object implementations may result in an implementation that is not correct. In other words, implementations defined in terms of step contention are not always composable. To avoid this problem, we introduce a property based on interval contention, namely non-triviality, to define the correct behaviour of abortable and query-abortable object implementations.