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Study of [18F]MK-6240, a second-generation tau PET tracer, for the diagnosis and monitoring of Alzheimer’s disease and other tauopathies
No full textThis thesis evaluates [¹⁸F]MK-6240, a second-generation tau PET tracer, for its ability to detect and quantify tau pathology in Alzheimer’s disease and other tauopathies. It demonstrates that [¹⁸F]MK-6240 offers high specificity for AD-related tauopathy (3R/4R paired helical filaments), with limited off-target binding. A novel quantification method, the Extent of Tauopathy is developed and shown to correlate more strongly with cognitive impairment than traditional SUVr metrics. The study confirms that [¹⁸F]MK-6240 has great clinical potential in distinguishing AD from other neurodegenerative diseases and in tracking disease progression. These findings support its integration into diagnostic workflows and therapeutic trials targeting tau pathology.(BIFA - Sciences biomédicales et pharmaceutiques) -- UCL, 202
Enseignants en fin de carrière en école maternelle : exploration qualitative du modèle des exigences-ressources professionnelles
No full textContexte / objectif Le secteur éducatif fait face aujourd'hui à de nombreux défis, parmi lesquels une pénurie croissante d'enseignants. Ce phénomène s’explique par un faible nombre de nouvelles recrues, couplé à un taux élevé de départs, touchant aussi bien les enseignants en début de carrière que leurs collègues plus expérimentés. En effet, de plus en plus d'enseignants en fin de carrière quittent la profession avant l'âge de la retraite, aggravant ainsi les difficultés de recrutement et réduisant le vivier de compétences disponibles au sein des établissements scolaires. Pour remédier à cette pénurie et garantir un enseignement de qualité, il devient indispensable de se concentrer sur les besoins spécifiques de ces enseignants et d'explorer les moyens de les soutenir, notamment en renforçant leur bien-être au travail et en favorisant leur engagement dans la profession. Cette étude cherche à identifier les ressources institutionnelles et environnementales et les exigences quotidiennes propres à cette phase de carrière et à ce métier. Ce sujet, encore relativement peu exploré dans la littérature, intègre rarement le point de vue des enseignants en fin de carrière, malgré leur présence significative au sein du corps enseignant si l’on croit les indicateurs de la Belgique francophone. Méthodologie Cette étude inductive et phénoménologique vise à explorer en profondeur les expériences des participants, en s’appuyant sur un échantillonnage raisonné de cas informatifs et homogènes pour garantir des caractéristiques et perceptions communes. Vingt-quatre enseignantes en fin de carrière ont participé volontairement à deux entretiens semi-directifs espacés d’une semaine pour offrir une vision détaillée de leur parcours. Inspirée de la méthode en plusieurs étapes de Seidman, cette approche a permis d’ajuster chaque entretien en fonction des éléments recueillis précédemment. Une analyse thématique de contenu a ensuite été réalisée en vue d’approfondir les questions soulevées. Résultats Les enseignantes interrogées expriment des exigences multiples et simultanées liées à leur métier, notamment un rythme soutenu et l'imprévisibilité de leurs journées de travail, ce qui affecte sévèrement leurs perceptions professionnelles. La gestion de classe à long terme engendre une charge cognitive et émotionnelle importante, tandis que la surcharge administrative devient de plus en plus difficile à supporter avec l'âge. Les tâches connexes s'éloignent de leur mission principale, mais le sens qu'elles attribuent à leur métier et son rôle de service à la société offrent un certain réconfort. Le soutien de collègues et de la direction d'école, lorsqu'il est présent, favorise une évolution positive de leur carrière. Cependant, les participantes oscillent entre un équilibre précaire et un seuil critique face à ces exigences. Pour y faire face, certaines doivent accepter une détérioration de leur bien-être, ce qui les pousse parfois à prendre des arrêts de travail prolongés. Ces décisions entraînent des coûts non négligeables sur leur pension et génèrent un ressentiment face à un arrêt forcé d'un métier qu'elles exercent souvent depuis plus de trente ans. Conclusion L'équilibre professionnel, bien que souvent recherché, reste difficile à atteindre pour les enseignants. Les exigences de la profession, face à des ressources parfois insuffisantes, rendent complexe l'exercice du métier, en particulier lors de la dernière étape de carrière. Les résultats soulignent l'importance de prévenir l'effet de rupture ressenti par les enseignants en fin de carrière et de créer des réseaux de soutien anticipatifs et personnalisés. Prendre en compte le bien-être des enseignants est crucial pour réduire la rotation du personnel, menacée par un environnement éducatif instable, ce qui affecte la continuité pédagogique et le développement sain des enfants en éducation préscolaire. Des initiatives telles que des formations adaptées, des opportunités de mentorat, et des ajustements organisationnels pourraient contribuer à prolonger leur carrière et, par conséquent, à maintenir la stabilité et la qualité des équipes pédagogiques
Constitutive cGAS-STING activation in ALT+ cells
No full textStimulator of interferon genes (STING) is a pivotal mediator of anti-tumor immunity, activated downstream of cytoplasmic DNA recognition by cyclic GMP-AMP synthase (cGAS). In cells that employ the alternative lengthening of telomeres (ALT) pathway, extrachromosomal telomeric repeats (ECTRs) act as potent activators of the cGAS–STING pathway. Although ALT+ cells were previously thought to evade this pathway through epigenetic silencing, our findings reveal more nuanced adaptive mechanisms that involve the spatial regulation of STING and the clearance of immunostimulatory ECTR species. In the vast majority of ALT+ cells, ongoing ECTR production drives sustained 2′3′-cGAMP synthesis, directing STING to the Golgi apparatus for immune signaling before lysosomal degradation. Lysosomal degradation of STING relies largely on interferon regulatory factor 3 (IRF3), with minimal involvement of TANK-binding kinase 1 (TBK1), pointing at a novel role for IRF3 in STING trafficking in ALT+ cells. Another adaptive mechanism involves the removal of immunogenic cytoplasmic ECTRs through STING-mediated lysosomal degradation. These mechanisms likely cooperate to restrict chronic interferon signaling that might otherwise prevent ALT+ cancers from emerging. These findings refine our understanding of immune sensing in ALT+ cancers, revealing how ALT+ cells respond to continuous ECTR production and suggesting a potential therapeutic target to modulate the microenvironment of ALT+ tumors
Bimodal Spin Switch Emerging from Hybridized 2D MoS2/Ferromagnet Interfaces
No full textOver the past decade, MRAMs developments have focused on improving magnetic tunnel junctions while using magnetic electrodes with fixed properties as spin sources. Interestingly, 2D semiconductors offer interface tailoring opportunities for spin valve devices, with many atomically thin materials now available. However, integrating them with oxidation-prone spintronics materials remains a challenge. Here, spin devices are fabricated and evaluated with large-scale MoS2 directly grown on a monocrystallineferromagnetic spin source. While most spin transport experiments with 2D semiconductors focus on their isolated dielectric properties, the presented approach unlocks an additional spin manipulation opportunity from MoS2 hybridization with ferromagnetic electrodes. The experimental results show a substantial tunnel magnetoresistance (TMR) value of over 65%, an order of magnitude higher than previously observed for exfoliated 2D semiconductor-based devices. A non-monotonic dependence of the spin signal on the applied bias, including a sign reversal, is also uncovered, which is attributed to the modulation of the MoS2 band structure by the ferromagnetic electrode. Ab initio calculations support these findings by illustrating how the MoS2 band structure evolves upon hybridization, introducing a pronounced exchange-induced spin splitting and resulting in an unusual bimodal spin response. This study demonstrates the unique spin manipulation opportunities offered by 2D semiconductors unlocked by direct integration
Note-taking in a Dutch Medium Instruction (DMI) context at a French-speaking university: focus on language use in students’ notes
No full textTaking effective notes in academic settings is difficult, particularly for first-year students (van der Meer, 2012). However, taking notes improves academic achievement and recall after the lecture, making it a crucial academic skill. L2 note-taking, for example in the worldwide expanding English Medium Instruction (EMI) contexts, is even more challenging, but universities do usually not provide academic language support to help students to take notes in an L2 context (Siegel, 2022). Research on L2 note-taking strategies remains limited, particularly for languages other than English (LOTE), making Dutch Medium Instruction (DMI) contexts particularly interesting to analyse. This contribution focuses on the under-researched skill of note-taking in academic lectures given in a foreign language, focussing on a DMI context in French-speaking Belgium. The specific objective of the study was to analyse how diverse the language use in note-taking in a DMI context is according to the students' language profile and their previous educational background. We selected one DMI course taken by 85 first- and second-year students enrolled at the French-speaking university UCLouvain (campus Saint-Louis, Brussels, Belgium). A paper questionnaire was administered to the undergraduate students in order to determine their study background, language profile and educational background. Next, the handwritten and electronic notes that students took during two 2-hour class sessions were collected on a voluntary basis (n = 27). Finally, semi-structured interviews were conducted with students to discuss their language use and note-taking strategies in an L2 context in detail (n = 8). These 8 participants have been selected to ensure diversity in linguistic secondary school backgrounds: 2 students attended a French-speaking school, 2 students a French-speaking school with CLIL in Dutch, 1 student went to a French-speaking school with CLIL in Dutch for the first 3 years before switching to a French-speaking school without CLIL in Dutch for another 3 years, and 3 students attended a Dutch-speaking school. In this presentation, we focus on the questionnaire data, notes and parts of the interview data of the 8 students who have been interviewed. The data analysis of the eight interviewees, their questionnaires and background reveal that the diversity of language use in note-taking in a DMI context depends on students’ language profile and educational background. Overall, all students mainly use the target language when taking notes. Students who have Dutch as mother tongue, who attended a French-speaking secondary school with CLIL in Dutch or a Dutch-speaking secondary school feel more comfortable with note-taking in Dutch. But all students who do not have Dutch as mother tongue, regardless of previous secondary school background, use other languages as soon as the pace of the course is too intense. Furthermore, diversity of language use in note-taking also depends on the lecturer’s language use during class. This study offers novel insights in the under-researched context of L2 note-taking at university level in a DMI context. In addition, the findings offer pertinent suggestions on how to enhance students’ note-taking skills within the setting of DMI courses. The suggestions are also applicable to university courses in other foreign languages
Docosapentaenoic (22:5 n-6) and docosahexaenoic (22:6 n-3) acids exhibit highly lipogenic properties in rainbow trout preadipocytes
No full textDietary polyunsaturated fatty acids are essential for fish health. Adipose tissue is the major tissue for fatty acid storage in rainbow trout (Oncorhynchus mykiss), and its development and function can be impacted by the fatty acids themselves. In the present study, the effects of seven fatty acids, oleic (OA, 18:1 n-9), α-linolenic (ALA, 18:3 n-3), eicosapentaenoic (EPA, 20:5 n-3), docosahexaenoic (DHA, 22:6 n-3), linoleic (LA, 18:2 n-6), arachidonic (AA, 20:4 n-6), and docosapentaenoic (DPA, 22:5 n-6) acids, on adipogenesis were investigated in primary cultures of rainbow trout preadipocytes. In terms of lipid accumulation, DPA and DHA appeared to be the most lipogenic fatty acids, while all treatments modified the fatty acid composition of the cellular phospholipids and neutral lipids. The fatty acid of interest added to the culture medium was the most abundant in preadipocytes, while the first bioconversion products were detected in lower amounts. In terms of transcriptional effects, DPA increased the expression of the early transcription factor CCAAT/enhancer binding protein δ, while DHA upregulated the expression of genes involved in neutral lipid synthesis, notably lipoprotein lipase, fatty acid transport protein 1 and glycerol-3-phosphate dehydrogenase. Both fatty acids decreased the expression of fatty acid synthase. These results highlight that DPA and DHA exert a significant effect on lipid deposition in rainbow trout preadipocytes, potentially through different pathways, and confirm that fatty acids have major impacts on preadipocyte lipid metabolism and adipogenesis
18FDG PET/CT is sensitive but not specific for malignancy: two cases of disseminated tuberculosis mimicking metastatic cancer on imaging and clinical presentation
No full textIntroduction: 18Fluorodeoxyglucose positron emission tomography/computed tomography (18FDG PET/CT) scan is widely used in the evaluation of suspected tumoral processes. In addition to its oncological applications, it is also employed in the diagnosis and follow-up of various conditions, including multiorgan tuberculosis. Case description: We report a case series of two young patients with exclusive extrapulmonary disseminated tuberculosis that mimicked a neoplastic process both clinically and on 18FDG PET/CT imaging. Initially, both patients were admitted to the oncology unit with a presumed diagnosis of cancer. However, following an exhaustive work-up, a definitive diagnosis of tuberculosis was established via histopathological and microbiological analysis. Conclusion: These cases underscore the importance of considering disseminated tuberculosis as a differential diagnosis during oncologic evaluations, especially in patients from endemic regions, and highlight the potential psychological impact of prematurely labelling a condition as cancer
Photocatalytic Synthesis of Substituted 2-Aryl Morpholines via Diastereoselective Annulation
No full textMorpholines are prevalent in medicinal chemistry due to their favorable pharmacokinetic properties and widespread presence in FDA-approved drugs. Existing methods for morpholine synthesis often require prefunctionalized or protected reagents, limiting their versatility and efficiency. Here, we present a photocatalytic, diastereoselective annulation strategy for the synthesis of morpholines directly from readily available starting materials. This method employs a visible-light-activated photocatalyst, Lewis acid, and Brønsted acid to achieve high yields and stereoselectivity. It also provides access to diverse substitution patterns, including challenging tri- and tetra-substituted morpholines. Mechanistic studies reveal that the reaction proceeds through the formation of a radical cation intermediate, with triflic acid playing critical roles in protonating the substrate, preserving the photocatalyst, and preventing product oxidation. Beyond morpholines, this strategy is extended to piperidines, pyrrolidines, and other privileged nitrogen heterocycles. Our findings provide a modular approach for constructing complex, medicinally valuable scaffolds, advancing both synthetic and medicinal chemistry
Hoe word je slim?
No full textsur le Nicolas Jean Népomucène Wa(c)ken et Luxembourg, BnL, Ms 168/2
et version française : Leçons du passé. Quatre siècles de notes d'étudiants à l'Université de Louvain (1425-1797) https://pul.uclouvain.be/book/?GCOI=2930310015334