The aim of this work is to enhance the detection and classification pipelines of an artificial intelligence (AI)-based decision support system (DSS) for diagnosing acanthamoeba keratitis (AK), a vision-threatening disease. The images used are taken with the in vivo confocal microscopy (IVCM) technique, a complementary tool for clinical assessment of the cornea that requires manual human analysis to support diagnosis. The DSS facilitates automated image analysis and currently aids in diagnosing AK. However, the accuracy of AK detection needs improvements in order to use it in clinical practice. To address this challenge, we utilize image brightness processing through multiscale retinex (MSR), and develop a custom-built image processing pipeline with deep learning model and rule-based strategies. The proposed pipeline replaces two deep learning models in original DSS, resulting in an overall accuracy improvement of 10.23% on average. Additionally, our improved pipeline not only enhances the original system’s ability to aid AK diagnosis, but also provides a versatile set of functions that can be used to create pipelines for detecting similar keratitis diseases.

Radio frequency interference (RFI) poses significant challenges for passive microwave radiometry used in climate studies and Earth science. Despite operating in protected frequency bands, microwave radiometers often encounter RFI from sources like air surveillance radars, 5G communications, and unmanned aerial vehicles. Traditional RFI detection methods rely on handcrafted algorithms designed for specific RFI types. This study proposes a deep learning (DL) approach, leveraging convolutional neural networks to detect various RFI types on a global scale. By learning directly from radiometer data, this data-driven method enhances detection accuracy and generalization. The DL framework processes raw moment data and Stokes parameters, dynamically labeled using quality flags, offering a robust and efficient solution for RFI detection. This approach demonstrates the potential for improved RFI mitigation in passive remote sensing applications.

L’allogreffe des cellules souches hématopoïétiques (CSH) dans les situations d’incompatibilité HLA partielle représente une option thérapeutique irremplaçable pour des patients nécessitant une greffe de cellules souches hématopoïétiques, en absence d’un donneur HLA-identique. Toutefois, le retard de la restauration du système immunitaire en particulier dans du compartiment lymphocytaire après greffe est l'une des complications majeures. Une nouvelle stratégie pour promouvoir la reprise de la thymopoïèse à partir des CSH provenant du donneur et d'accélérer la reconstitution cellulaire T chez des patients après greffe de CSH consiste en le transfert adoptif des progéniteurs T générés in vitro. L’identification de Notch1 comme le régulateur-clé du développement lymphocytaire T a permis l’établissement de systèmes de culture à base de ligands de Notch, qui permettent la génération efficace de progéniteurs lymphoïdes T in vitro. L'efficacité des progeniteurs T-lymphoïdes murins pour promouvoir la reconstitution des lymphocytes T a été bien démontrée dans des modèles de greffe chez la souris. De même, des progéniteurs T-lymphopoïétiques humains générés in vitro et greffés aux souris humanisées favorisent la reprise de la thymopoïèse. Pourtant, aucune donnée n’a encore démontré leur capacité à donner naissance à un compartiment lymphocytaire T périphérique. De plus, les systèmes de co-culture à base de ligand de Notch actuellement utilisés consistent en des lignées stromales murines génétiquement modifiées. Afin d'établir un système cliniquement applicable, il est donc indispensable d’établir des systèmes de culture qui soutiennent la génération de progéniteurs T en absence d’un support des cellules nourricières. Au cours de mon projet de thèse, j'ai développé un nouveau système de culture pour la génération des progéniteurs T-lymphopoïétiques humains T basé sur l’immobilisation du ligand de Notch Delta-like-4 (DL-4) sous sa forme protéique. La culture des progéniteurs hématopoïétiques CD34+ issue de sang en présence de DL-4 immobilisé permet la génération d’un grand nombre de cellules ayant un phénotype de progéniteurs thymiques précoces (early thymic progenitor: ETP) et de prothymocytes (proT). Les cellules ETP et ProT ainsi générées expriment à des niveaux élevés des gènes impliqués dans le développement lymphocytaire précoce (i.e. pTa, Rag1, IL7Ra et BCL11b). Elles montrent des signes de réarrangement du récepteur des cellules T (TCR) similaires à leurs homologues thymiques. Par des expériences de dilution limite sur une co-culture OP9/DL-1 secondaire, j’ai pu montrer que les progéniteurs générés sur DL-4 possédaient un potentiel lymphoïde T très augmenté, qui pourrait être entièrement attribué aux sous populations ETP et ProT. Suite à leur transfert dans des souris NOD/SCID/γc-/-, les progéniteurs lymphoïde T générés par exposition a DL-4 sont capable de migrer dans le thymus, d’y poursuivre des étapes ultérieures de leur développement et d’accélérer la différentiation T intra thymique ainsi que l’émergence des lymphocytes T mature, polyclonaux et fonctionnels en périphérie. Dans une approche de co-transplantation, qui se rapproche des conditions cliniques envisagées, j’ai simultanément injecté dans le même récipient des progéniteurs générées sur DL-4 et des cellules CD34+ non traitées (d’un 2èm donneur HLA-incompatible). Cette procédure a permis une reconstitution des lymphocytes T encore plus rapide et plus. Etant donné que les progéniteurs T générées sur DL-4 et les cellules CD34+ non-traitées étaient issue de deux donneurs avec un HLA différent, cette expérience a permis de montrer que les progéniteurs préalablement exposés à DL-4 reconstituaient spécifiquement les compartiments lymphoïdes T alors que les autres lignées hématopoïétiques provenaient des progéniteurs CD34+ non-traités... / Human leukocyte antigen (HLA)-mismatched haematopoietic stem cell transplantation (HSCT) represents an important therapeutic option for patients lacking suitable donors. Delayed posttransplant immune recovery constitutes one of its major complications and is most pronounced in the T cellular compartment. A novel strategy to promote de novo thymopoiesis from donor derived HSCs and to accelerate T cellular reconstitution in patients after HSCT consists in the adoptive transfer of in vitro generated T cell progenitor cells. Identification of Notch1 as the key regulator of early T-lineage development has allowed the generation of Notch ligand-based culture systems, which provide a powerful tool to generate T-lymphoid progenitors in vitro. The efficacy of murine T-lymphoid progenitors to promote T cell reconstitution has been well demonstrated in conventional mouse models. In consistency, in vitro-generated human T cell progenitors were demonstrated to promote thymic recovery in humanized mice. Yet, positive effects of in vitro generated human T cell precursors on peripheral T cell reconstitution have not been demonstrated. Moreover currently used Notch-based co-culture systems consist of genetically modified murine cell lines. With view to establishing a clinically applicable system, feeder-cell-free Notch-ligand culture systems for the generation of T-lymphopoietic progenitors are warranted. During my PhD project I developed a new culture system based on the immobilized Notch ligand Delta-like-4 (DL-4). Exposure of human CD34+ cord blood cells to immobilized DL-4 enabled the in vitro generation of high number of T cell progenitors, which harboured the phenotype of immature early thymic progenitor cells (ETP) and prothymocytes (proT). ETP and proT cell generated during DL-4 culture upregulated essential genes involved in early T-lymphoid development (i.e. IL7Rα, PTα, RAG1 and BCL11b) and had undergone stage-specific recombination of the T cell receptor (TCR) locus in a similar way as in native human thymopoiesis. In limiting dilution analysis after secondary OP9/DL-1 co-culture, DL-4 progenitors displayed a highly increased T-lymphoid potential, which could be entirely attributed to the ETP and proT subset. When transferred into NOD/SCID/γc-/- mice, DL-4 primed T cell progenitors migrated to the thymus and accelerated intrathymic T cell differentiation and emergence of functional, mature and polyclonal αβ T cells in the periphery. In a co-transplantation approach, which more closely mimics a clinical setting, DL-4 progenitors and untreated CD34+ cells from HLA-disparate donors were simultaneously injected in the same recipient. This procedure allowed even more rapid and more robust T cell reconstitution. HLA-tracking of the distinct graft sources further showed, that DL-4 progenitors specifically reconstituted the T-lymphoid compartments. This work provides further evidence for the ability of in vitro-generated human T cell progenitors to promote de novo thymopoiesis and shows for the first time, that these cells accelerate peripheral T cell reconstitution in humanized mice. The availability of the efficient feeder-cell-free DL-4 culture technique represents an important step towards the future clinical exploitation translation of in vitro generated T-lymphoid progenitor cells to improve posttransplant immune reconstitution / Die Wiederherstellung der T-lymphozytären Immunität nach T-Zell depletierter hämatopoetischer Stammzelltransplantation (HSZT) ist ein langwieriger Prozess. Eine potentielle Strategie zur Beschleunigung der Neubildung von T-Zellen aus den transplantierten Stammzellen besteht in der Gabe von T-lymphozytären Vorläuferzellen. Die Entdeckung von Notch1 als wichtigster Regulator der frühen T-Zell-Entwicklung hat zur Etablierung Notchligand-basierter Zellkulturen geführt, mit deren Hilfe T-lymphoide Vorläuferzellen aus hämatopoetischen Stammzellen in vitro gebildet werden können. Das therapeutische Potential dieses Zelltyps wurde eindrucksvoll in konventionellen, syngenen und allogenen Maustransplantationsmodellen belegt, in denen nach Injektion in vitro generierter, muriner T-Vorläuferzellen eine Verbesserung der Neubesiedlung des Thymus sowie eine beschleunigte Wiederherstellung der T-zellulären Immunität erreicht werden konnte. Notchbasierte Co-Kultursysteme wurden ebenfalls für die invitro Herstellung humaner T-lymphoider Vorläuferzellen verwendet. Das in-vivo Potential humaner T Vorläuferzellen ist bislang jedoch nur lückenhaft charakterisiert: Zwar konnte gezeigt werden, dass humane T-Vorläuferzellen den hypoplastischen Thymus von immundefizienten NOD/SCID/γc-/- Mäusen besiedeln können. Ihre Wirksamkeit, die Wiederherstellung eines funktionellen, peripheren T-Zellkompartiments zu beschleunigen, gelang bislang jedoch nicht. Darüber hinaus werden Notchliganden in derzeit verwendeten Kultursystemen von genetisch modifizierten, murinen Stromazellen präsentiert. Die Entwicklung stromazellfreier, proteinbasierter Notchligand-Kultursysteme ist daher von grosser Bedeutung für eine mögliche therapeutische Nutzung in vitro generierter T-Vorläuferzellen. Durch Immobilisierung von Notchligand Delta-like 4 (DL-4) habe ich im Rahmen meines PhD Projekts ein stromazellfreies Kultursystem zur Züchtung T-zellulärer Vorläuferzellen aus humanen CD34+ Nabelschnurblutzellen etabliert. In DL-4 Kultur generierte Zellen besitzen phänotypische und molekulare Eigenschaften von frühen thymischen Vorläuferzellen (ETP) und Prothymocyten (proT). ETP und proT Zellen aus DL-4 Kulturen exprimieren wesentliche Geneder frühen T-Zellentstehung (z.B. IL7Ra, PTa, RAG1 und BCL11b). Die entwicklungsstadiumspezifischen TCR-Rekombinationsprozesse in DL-4 Zellen erfolgen nach dem gleichen Muster wie in der nativen Thymusentstehung. Die in DL4 Kultur generierten T-Vorläuferzellen können sich in reife T-Zellen weiterentwickeln und durchlaufen die weitere T-Zelldifferenzierung innerhalb kürzerer Zeit als native CD34+ hämatopoetische Vorläuferzellen. 13 Darüber hinaus können DL-4 generierte T-Vorläuferzellen nach Xenotransplantation den hypoplastischen Thymus von immundefizienten NOD/SCID/γc-/- Mäusen besiedeln, intrathymische T-Zellentwicklung begünstigen und die Neubildung reifer und funktionaler TZellen in der Peripherie beschleunigen. Zur Simulation einer klinischen Anwendung führte ich weiterhin Co-Transplantationen mit DL-4 Vorläuferzellen und unbehandelten CD34+ Zellen in gleiche Empfänger durch und konnte hiermit eine weitere Verbesserung der Immunrekonstitution erzielen. Durch Verwendung HLA-divergenter Spender in diesen Versuchen konnte ich zeigen, dass DL-4 Zellen sich vornehmlich in T-Zellen weiterentwickelten, während die restlichen Blutzellreihen von unbehandelten CD34-poitiven Zellen gebildet wurden. Im Rahmen dieses Projekts konnte ich mit einem für die klinische Anwendung geeigneten Kulturmodell wichtige präklinische Belege für das therapeutische Potential in vitro generierter TVorläuferzellen erbringen. Diese Arbeit bildet somit eine wichtige Grundlage für eine zukünftige klinische Anwendung von T-Vorläuferzellen zur Verbesserung der T-Zell-Immunität nach HSZT

In computer science, an ontology is a machine-processable representation of knowledge about some domain. Ontologies are encoded in ontology languages, such as the Web Ontology Language (OWL) based on Description Logics (DLs). An ontology is a set of logical statements, called axioms. Some axioms make universal statements, e.g. all fathers are men, while others record data, i.e. facts about specific individuals, e.g. Bob is a father. A set of universal statements is called TBox, as it encodes terminology, i.e. schema-level conceptual relationships, and a set of facts is called ABox, as it encodes instance-level assertions. Ontologies are extensively developed and widely used in domains such as biology and medicine. Manual engineering of a TBox is a difficult task that includes modelling conceptual relationships of the domain and encoding those relationships in the ontology language, e.g. OWL. Hence, it requires the knowledge of domain experts and skills of ontology engineers combined together. In order to assist engineering of TBoxes and potentially automate it, acquisition (or induction) of axioms from data has attracted research attention and is usually called Ontology Learning (OL). This thesis investigates the problem of OL from general principles. We formulate it as General Terminology Induction that aims at acquiring general, expressive TBox axioms (called general terminology) from data. The thesis addresses and investigates in depth two main questions: how to rigorously evaluate the quality of general TBox axioms and how to efficiently construct them. We design an approach for General Terminology Induction and implement it in an algorithm called DL-Miner. We extensively evaluate DL-Miner, compare it with other approaches, and run case studies together with domain experts to gain insight into its potential applications. The thesis should be of interest to ontology developers seeking automated means to facilitate building or enriching ontologies. In addition, as our experiments show, DL-Miner can deliver valuable insights into the data, i.e. can be useful for data analysis and debugging.

This study explores how education and the medieval intellectual and pedagogical discipline of 'grammatical' developed in Iceland during the medieval period, defined roughly from the official conversion to Christianity c.1000 to the Reformation c.1550, The first chapter deals with social, institutional, and financial aspects of teaching and learning in medieval Iceland, surveying key figures and places, but also arguing that more attention shoulder be paid to the costs of learning and the effect of that on poor students. The second chapter addresses Latin education, discussing the importance of Latinity in medieval Iceland and the types of education that would involve Latin. It also addresses the idea of bilingual education and suggests ways in which extant venacular writings can provide evidence for how Latin was taught and learned using the vernacular, using the model of Old English bilingual education. Finally, the third chapter addresses vernacular topics of learning, focusing on the development of a venacular \(grammatical\) which is focused on the interpretation and normalization of Old Norse texts, rather than the understanding and use of Latin. Discussing these three components of educational history together is fundamental to understanding the intellectual and pedagogical dynamics behind the extant medieval Icelandic textual corpus.

En la actualidad, en el ámbito sanitario y, en concreto, en el dominio farmacoterapéutico existen múltiples sistemas de información (SI). Cada uno de estos SI representan el conocimiento sobre los medicamentos de formas diversas. Pero, en la práctica, para poder utilizarlos, los profesionales de la salud (médicos, enfermeras y farmacéuticos) deben de conocer el contenido y la forma de acceder a cada uno de estos SI, para obtener la información que apoye su toma de decisión sobre la terapéutica farmacológica. Para ello, los profesionales deben de invertir un tiempo, del que muchas veces no disponen, y demorar la atención directa. El reto está en que los SI sean capaces de compartir la información entre ellos, es decir, en resolver los problemas de interoperabilidad semántica. Para conseguir la interoperabilidad entre SI se han propuesto, como una opción, las tecnologías semánticas y, entre ellas, las ontologías. Las ontologías son un tipo de representación del conocimiento, basado en conceptos, que facilita la compresión del significado y del contexto de la información. A partir de estas premisas y del vacío detectado en la representación de los medicamentos, el trabajo presentado, en esta Tesis doctoral, aborda la definición de una propuesta metodológica y tecnológica para la construcción de la Ontología Farmacoterapéutica e Información para el Seguimiento, OntoFIS. La propuesta metodológica aplicada emplea el modelo de datos UML y OWL DL para el modelado de OntoFIS. La propuesta tecnológica se fundamenta en el uso de un plug-in para las transformaciones directas entre el diagrama de clases UML y el modelo de datos OWL DL. Estas propuestas pueden ser aplicadas a cualquier otro escenario y facilitan la reutilización de los diseños de aplicaciones Web para la obtención de ontologías. La aportación más significativa es que, la ontología construida, contribuye a resolver el problema de la carencia de una fuente de conocimiento específica en lengua castellana. La ontología OntoFIS está poblada con casi 55.000 instancias. Entre éstas destacan, por su valor terminológico, las correspondientes a las denominaciones de los medicamentos comercializados en España (17.204), los componentes farmacológicos (19.627), los nombres genéricos de principios activos (4.456), las denominaciones de grupos químicos (3.200) y las denominaciones de uso terapéutico (1.380). Asimismo, el modelo de conocimiento representado en OntoFIS, a partir de los resultados de la evaluación obtenidos, permite hacer inferencias, respecto al conocimiento del dominio farmacoterapéutico, válidas, consistentes y ajustadas a las necesidades de los profesionales de la salud.

Tese de Mestrado Integrado. Engenharia Mecânica. Faculdade de Engenharia. Universidade do Porto. 2012

Weiterbildung, also organisiertes Lernen nach dem Abschluss der ersten Bildungsphase, erfolgt zu großen Teilen im betrieblichen Kontext. Dort ist Weiterbildung nicht das primäre Ziel, sondern findet als beigeordnete Bildung statt. Vor diesem Hintergrund wurde im Rahmen des Promotionsvorhabens das Spannungsfeld von pädagogischen und ökonomischen Zielvorstellungen im Kontext betrieblicher Weiterbildung betrachtet. Der Fokus lag auf der betrieblichen Programmplanung, als Untersuchungsgegenstand wurde der Prozess der Bedarfserschließung gewählt. Dabei wurde das Ziel verfolgt, Gestaltungsspielräume sichtbar zu machen, um so den Einfluss pädagogischer Zielvorstellungen in der betrieblichen Weiterbildung zu stärken. Das Promotionsvorhaben ist im Rahmen eines DFG-Projekts entstanden und umfasst neben der vorliegenden Dissertationsschrift drei bereits veröffentlichte Einzelarbeiten (von Hippel/Röbel 2016, Röbel 2016, Röbel 2017, siehe Anhang). Datengrundlage sind drei vergleichende Unternehmensfallstudien in Großunternehmen aus verschiedenen Branchen (Gesundheit, Einzelhandel, Energie). In der vorliegenden Dissertationsschrift wird erstens das Promotionsvorhaben in den aktuellen Theorie- und Forschungstand eingeordnet. Dabei werden neben erwachsenenpädagogischen Arbeiten auch Ansätze aus der Wirtschaftsethik berücksichtigt. Zweitens wird die Gesamtkonzeption vorgestellt und der Beitrag der Einzelarbeiten erläutert. Drittens werden im Sinne einer abschließenden Diskussion Muster der Bedarfserschließung beschrieben und Bildung als pädagogische Zielvorstellung diskutiert. / Adult education and training to a large extent take place as workplace learning (in the sense of employer-sponsored learning). Workplace learning by definition takes place in institutions with other primary goals than the provision of Adult Education. Against this background, the doctoral thesis has explored the relation of educational and economic objectives in the context of workplace learning. The focus was on program planning. The processes of needs assessment were chosen as object of investigation. The aim was to make leeways for decision-making visible in order to strengthen the influence of pedagogical objectives in workplace learning. The dissertation project was developed during a research project funded by the German Research Foundation (DFG). It comprises three publications (all already published) as well as the present text. The data base consists of three comparative case studies in large companies from various sectors (health, retail, energy). In this paper, first of all the state of research relevant to the dissertation project is presented. Besides recurring to adult education theory and research, approaches from the discipline of business ethics are introduced. Second, the overall concept of the dissertations project is presented and the contribution of the individual publications is explained. Thirdly, as a final discussion, patterns of need-assessment are described and the idea of Bildung is discussed as an educational objective.

網路環境的轉變與網路社群網站的盛行，不但改變網路使用者的使用習慣，亦是發揮學習社群力量的時機。數位圖書館自發展以來，累積優質而豐富的典藏內容，強調多元讀者服務，並精進個人化服務與檢索功能，但針對讀者學習社群的經營則顯得不足且忽略發展可以輔助學習社群經營的機制，致使數位圖書館無法成為讀者長期駐足，甚至留下學習心得、交互分享學習成果及良性互動討論數位圖書館典藏內容的園地。 本研究以「提升使用者駐足於學習社群平台之意願」與「促進數位圖書館資源之利用」為目標，促成一個基於數位圖書館典藏內容為經營基礎之學習社群。發展有效的社群經營機制，營造學習者願意參與、交互分享學習成果及良性互動討論的優質學習環境，並支援數位圖書館資源的有效利用。 利用知識論壇(Knoewledge Forum)作為社群學習的討論平台，本研究透過準實驗研究法，從數位圖書館資源與學習社群之結合所促成的學習活動中，探討學習社群的互動歷程與知識建構情況。透過統計分析歸結出適合於發展有效輔助數位圖書館資源應用之學習社群經營工具與機制，提高學習社群的參與以及數位圖書館資源支援學習的機會與價值。 研究結果顯示：1. 研究活動歷程中，相較各階段互動機制，推薦機制與激勵機制對於學習社群參與具有較明顯的助益；2. 數位圖書館資源融入學習社群，有助主題資源與概念多面向的知識討論與擴張；3. 數位圖書館資源融入學習社群過程中，領域專家引導有助於資源的利用。 / As the rapid changes of on-line environment and prevalence of social networking websites, not only has the on-line users’ behavior changed, but also it implies the perfect time to develop better learning community with the advantages of technology innovation. Taking the Digital library (DL) as example, it has been developed into the perfect portal with accumulation of high quality information with and reader-centered services, including personalized information services and searching functions. However, comparing with other social networking sites, DL has been considered less value on building on readers’ learning communities, or not suitable sites to share information or communicate with other readers. The purpose of the study is to promote people cohesiveness at the web-based learning community platform and to improve the usage of digital library resources. Based on the advantage of web-based learning communities, the study analyzes the possible models and outcomes for learning communities on DL. In addition, the study attempts to survey ways to make better environment for readers actively interacting with others more; moreover, utilizing the digital libraries to construct knowledge. Taking the “Knowledge Forum” as web-based learning community platform, the study adopted the quasi-experimental methodology to investigate the social networks and knowledge construction behavior of the learning community on DL. The statistics analysis scheme was employed to evaluate the specific model of community building for web-based learning, and its effectiveness for promoting DL as learning support. The results of this study are concluded as following. First, compared with other methods for community building, the recommendation and motivation system are more beneficial for participation on web-based learning community. Second, integrating the resources of DL with web-based learning community is helpful for the diversity of subject topics and concepts in on-line discussion. Third, academic field experts for subject matter discussion are helpful for better DL resources utilization during the process of web-based learning.

Human leukocyte antigen (HLA)-mismatched haematopoietic stem cell transplantation (HSCT) represents an important therapeutic option for patients lacking suitable donors. Delayed posttransplant immune recovery constitutes one of its major complications and is most pronounced in the T cellular compartment. A novel strategy to promote de novo thymopoiesis from donor derived HSCs and to accelerate T cellular reconstitution in patients after HSCT consists in the adoptive transfer of in vitro generated T cell progenitor cells. Identification of Notch1 as the key regulator of early T-lineage development has allowed the generation of Notch ligand-based culture systems, which provide a powerful tool to generate T-lymphoid progenitors in vitro. The efficacy of murine T-lymphoid progenitors to promote T cell reconstitution has been well demonstrated in conventional mouse models. In consistency, in vitro-generated human T cell progenitors were demonstrated to promote thymic recovery in humanized mice. Yet, positive effects of in vitro generated human T cell precursors on peripheral T cell reconstitution have not been demonstrated. Moreover currently used Notch-based co-culture systems consist of genetically modified murine cell lines. With view to establishing a clinically applicable system, feeder-cell-free Notch-ligand culture systems for the generation of T-lymphopoietic progenitors are warranted. During my PhD project I developed a new culture system based on the immobilized Notch ligand Delta-like-4 (DL-4). Exposure of human CD34+ cord blood cells to immobilized DL-4 enabled the in vitro generation of high number of T cell progenitors, which harboured the phenotype of immature early thymic progenitor cells (ETP) and prothymocytes (proT). ETP and proT cell generated during DL-4 culture upregulated essential genes involved in early T-lymphoid development (i.e. IL7Rα, PTα, RAG1 and BCL11b) and had undergone stage-specific recombination of the T cell receptor (TCR) locus in a similar way as in native human thymopoiesis. In limiting dilution analysis after secondary OP9/DL-1 co-culture, DL-4 progenitors displayed a highly increased T-lymphoid potential, which could be entirely attributed to the ETP and proT subset. When transferred into NOD/SCID/γc-/- mice, DL-4 primed T cell progenitors migrated to the thymus and accelerated intrathymic T cell differentiation and emergence of functional, mature and polyclonal αβ T cells in the periphery. In a co-transplantation approach, which more closely mimics a clinical setting, DL-4 progenitors and untreated CD34+ cells from HLA-disparate donors were simultaneously injected in the same recipient. This procedure allowed even more rapid and more robust T cell reconstitution. HLA-tracking of the distinct graft sources further showed, that DL-4 progenitors specifically reconstituted the T-lymphoid compartments. This work provides further evidence for the ability of in vitro-generated human T cell progenitors to promote de novo thymopoiesis and shows for the first time, that these cells accelerate peripheral T cell reconstitution in humanized mice. The availability of the efficient feeder-cell-free DL-4 culture technique represents an important step towards the future clinical exploitation translation of in vitro generated T-lymphoid progenitor cells to improve posttransplant immune reconstitution