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The Advancement of Targeted Alpha Therapy and the Role of Click Chemistry Therein
No full textInternational audienceRecent years have seen a swift rise in the use of α-emitting radionuclides such as 225Ac and 223Ra as various radiopharmaceuticals to treat (micro)metastasized tumors. They have shown remarkable effectiveness in clinical practice owing to the highly cytotoxic α-particles that are emitted, which have a very short range in tissue, causing mainly double-stranded DNA breaks. However, it is essential that both chelation and targeting strategies are optimized for their successful translation to clinical application, as α-emitting radionuclides have distinctly different features compared to β−-emitters, including their much larger atomic radius. Furthermore, upon α-decay, any daughter nuclide irrevocably breaks free from the targeting molecule, known as the recoil effect, dictating the need for faster targeting to prevent healthy tissue toxicity. In this review we provide a brief overview of the current status of targeted α-therapy and highlight innovations in α-emitter-based chelator design, focusing on the role of click chemistry to allow for fast complexation to biomolecules at mild labeling conditions. Finally, an outlook is provided on different targeting strategies and the role that pre-targeting can play in targeted alpha therapy
How influenza A virus NS1 impedes transcription of the host cell’s messenger RNAs
No full textResearch highlightInternational audienceHow influenza virus non-structural protein NS1 inhibits the activity of nuclear speckles, these liquid-liquid phase separation complexes that control the transcription and posttranscriptional regulation of cellular gene
The counter-rotating mechanism makes a substantial contribution to balance-movement coordination during the anticipatory period of gait initiation
No full textInternational audienceMaintaining balance during gait initiation is essential for mobility and functional independence. The transition from a postural state to steady-state gait relies on two mechanisms to accelerate the whole-body centre of mass (WBCoM): moving centre of pressure (CoP); and counter-rotating segments to modulate internal whole-body angular momentum (HM). While the moving CoP mechanism is well-understood and known to generate mechanical instability, the role of the counter-rotating mechanism is less clear. Therefore, the present study quantified the contribution of the counter-rotating mechanism and explored its coordination with the moving CoP mechanism during the anticipatory period of gait initiation. Based on a sample of 13 healthy participants, we computed the time evolution of CoP, HM, the coefficient of cancellation (i.e., the extend to which segmental angular momenta counterbalance each other), and the relative contribution of each mechanism to WBCoM acceleration. We tested whether the contribution of the counter-rotating mechanism was significantly different from zero using a Statistical Parametric Mapping t-test. In the frontal plane, the counter-rotating mechanism did not appear to play a substantial role. However, in the sagittal plane, we found that: (1) the period of mechanical instability was longer than the period that have been identified based on the moving CoP mechanism alone; (2) rotational instability was reduced in anticipation of unipedal support; and (3) the counter-rotating mechanism significantly contributed to WBCoM forward acceleration. Overall, our findings emphasise the critical role of the counter-rotating mechanism in the sagittal plane for balance-movement coordination. Considering the counter-rotating mechanism appears important for understanding, assessing, and developing interventions for individuals with balance impairments
Integrative models of psychopathology and psychotherapy: A PRISMA-based scoping review
No full textInternational audienceIntroductionSince the 1970s there has been increasing interest in integrative approaches to psychopathology. Within this framework, numerous models have been developed. The aim of this manuscript is to inventory these models, provide a critical evaluation of them, and offer recommendations for their further development.MethodWe conducted a scoping review based on PRISMA guidelines. The search strategy included keywords related to psychotherapy and/or psychopathology, one keyword related to models or conceptualizations, and one keyword associated with the integrative notion. The selected studies focused exclusively on integrative models of psychopathology and/or psychotherapy. The research was carried out using PsycInfo, PubMed, and EMBASE databases.ResultsA total of 61 manuscripts were included in the systematic review. We identified a broad range of conceptual proposals, which can be categorized into three main types of models: 1) Models proposing a general framework for understanding psychopathology, 2) Models focusing on common factors in psychotherapy and 3) Models suggesting that a specific psychotherapy is inherently integrative.ConclusionsMany of these identified models face criticism for their lack of clear methodological development, limited empirical evidence, and/or restricted applicability to psychotherapeutic interventions. Future models should aim to address these limitations in order to advance the fieldIntroductionDepuis les années 1970, l’intérêt pour les approches intégratives de la psychopathologie n’a cessé de croître. Dans ce cadre, de nombreux modèles ont été développés. L’objectif de ce manuscrit est d’en dresser un inventaire, d’en proposer une évaluation critique et de formuler des recommandations pour leur développement futur.MéthodeNous avons réalisé une revue exploratoire selon les lignes directrices PRISMA. La stratégie de recherche comprenait des mots-clés liés à la psychothérapie et/ou à la psychopathologie, un mot-clé relatif aux modèles ou aux conceptualisations, ainsi qu’un mot-clé associé à la notion d’intégration. Les études sélectionnées portaient exclusivement sur les modèles intégratifs de la psychopathologie et/ou de la psychothérapie. La recherche a été effectuée dans les bases de données PsycInfo, PubMed et EMBASE.RésultatsAu total, 61 manuscrits ont été inclus dans la revue systématique. Nous avons identifié un large éventail de propositions conceptuelles, pouvant être classées en trois grandes catégories de modèles : 1) les modèles proposant un cadre général de compréhension de la psychopathologie, 2) Les modèles mettant l’accent sur les facteurs communs en psychothérapie et 3) Les modèles suggérant qu’une psychothérapie spécifique est intrinsèquement intégrative.ConclusionsNombre de ces modèles font l’objet de critiques en raison de leur manque de développement méthodologique clair, de preuves empiriques limitées et/ou de leur applicabilité restreinte aux interventions psychothérapeutiques. Les modèles futurs devraient s’attacher à surmonter ces limites afin de faire progresser le domaine
Du diplôme de langue au levier d’influence : les enjeux politiques du DELF
No full textInternational audienc
Analysis of edge termination techniques for GaN power devices: TCAD-based modeling and review of current developments
No full textInternational audienceEdge termination techniques play a crucial role in enhancing the breakdown voltage (BV) and managing electric field distribution in GaN-based power devices. This review explores six key termination methods—field plate (FP), mesa, bevel, trench, ion implantation, and guard ring (GR)—with a focus on their performance, fabrication complexity, and insights derived from TCAD simulations. FP and trench terminations excel in high-voltage applications due to their superior electric field control but are accompanied by significant fabrication challenges. Mesa and bevel terminations, while simpler and cost-effective, are more suited for medium-voltage applications. Ion implantation and GR techniques strike a balance, offering customizable parameters for improved BV performance. TCAD simulations provide a robust framework for analyzing these techniques, highlighting optimal configurations and performance trade-offs. The choice of edge termination depends on the specific application, balancing BV requirements with manufacturing feasibility. This review offers a comprehensive comparison, emphasizing the critical role of simulations in guiding the selection and design of edge termination techniques for GaN power devices
Sovereign credit rating and resource-backed loans in African countries
No full textDuring the past two decades, the number of African countries receiving a sovereign credit rating has increased exponentially compared to the previous period.In fact, faced with the drying up of conventional financing and the growing need for development finance, many African countries are turning to the eurobond market, which considers the sovereign credit rating as a credible signal of the sovereign's ability to pay their debt. At the same time, resource-rich African countries have resorted to resource-back loans from other developing nations -essentially China, whose principle is to use the natural resource endowments of the countries as collateral or payment in kind. Using the entropy balancing method, the purpose of this paper is to test whether African sovereigns resorting to resource-backed loans have on average a lower credit score compared to others. After performing a set of robustness checks, the study shows that the resource-backed loan has a negative and statistically significant impact on the sovereign credit rating for African countries.</div
A new XML conversion process for mensural music encoding : CMME_to_MEI (via Verovio)
No full textInternational audienceThe Ricercar Lab — the musicological research team at the Center for advanced Studies in the Renaissance at the University of Tours — has decided to make available in open access, thanks to the support of the French digital infrastructure Biblissima, a large corpus of about 3500 XML files of 15th-c. music. This corpus was produced by the German musicologist Clemens Goldberg who encoded since 2010 onwards the musical content of 34 major 15th-c. music manuscripts and other complementary files, in order to offer on his foundation's website PDF files of complete collections of works by Du Fay, Binchois, Okeghem, Busnoys and most of their major contemporaries, focusing on their secular output. This corpus was encoded in an XML format named CMME (Computerized Mensural Music Editing), specifically conceived for mensural music by Theodor Dumitrescu in the 2000s, together with editorial and publication tools which have not been updated since then. This article focuses on the development of a set of conversion tools for these CMME files to meet more up-to-date standards of music encoding, namely MEI. A workshop was organised in September 2024 at the Campus Condorcet in Paris, gathering experts with a wide range of knowledge on mensural music notation, XML formats and programming. A converter was developped directly in the open-source rendering library Verovio, allowing the conversion from CMME to MEI mensural. A conversion to MEI CMN was implemented afterwards, enabling to load these files in common engraving softwares such as MuseScore with minimal loss of information. With the availability of a direct import of CMME-XML into Verovio, the corpus of existing CMME files gets a new life. Furthermore, since the stand-alone CMME editor still works fine and no alternative is available yet for native MEI, the converter offers a new pipeline for encoding and editing mensural music
Adaptation factors of SalmonellaTyphimurium, 1,4,[5],12:i:-and Dublin serovars to disinfection in the pig/pork and dairy industries : characterization of strain diversity and mechanisms of persistence: SalmoBOND
No full textInternational audienceBiocides are routinely used in food processing industries to control microbial contamination. Despite their proven effectiveness, some Salmonella spp. strains exhibit environmental persistence, surviving and reappearing even after stringent sanitation measures. Various tolerance mechanisms and adaptative pathways have been described for Enterobacteriaceae, particularly in foodborne pathogens. However, the specific mechanisms of Salmonella adaptation to these environments and the genetic determinants associated with its persistence despite cleaning and disinfection remain unclear. The current study aims 1/to decipher the increased potential of Salmonella strains for biocides tolerance and biofilm formation, and 2/develop a fast molecular tool to identify the strains with high survival potential. The genomic and phenotypical diversity of three distinct serovars of Salmonella (Typhimurium, its monophasic variant and Dublin) will be examined using a collection of 935 strains isolated in France between 2017 and 2024 from both the pig/pork and dairy production chains. Genes known as involved in biocides tolerance and biofilm production will be identified and characterized. Building on these results, a representative panel of 300 strains will be selected to investigate their phenotypic response to biocides in biofilm models, close to conditions undergone by bacteria on food processing chains. Finally, Association Studies will be conducted to identify possible new genetic markers involved in strain adaptation in food processing plants. The results will shed light on the potential presence of persistent Salmonella strains (Typhimurium, 1,4,[5],12:i:-, and Dublin) which are prevalent in the French pig/pork and dairy product sectors. This study will identify and describe genes implicated in persistence within the Salmonella populations of both sectors. The genetic markers identified will then be used to develop a molecular tool detecting strains capable of surviving in food processing plants. This test will assist the food industry in decision-making to improve sanitation measures and control Salmonella in the pig/pork and dairy product industries
Balance analysis of autistic children during beam walking
No full textInternational audienceAutism Spectrum Disorder (ASD) is characterised by persistent deficits in communication and social interaction, as well as restricted, repetitive patterns of behaviour, interests, or activities. Although not included among the diagnostic criteria, motor disorders are also part of the clinical phenotype of ASD, and their origins are largely under-researched (Mosconi et al., 2015). Among these motor disorders, specificities in postural control and gait initiation have been identified (Benchekri et al., 2023), suggesting that balance mechanisms are impacted by ASD. Walking on a narrow beam requires the ability to maintain balance with a reduced base of support (BoS) along the medio-lateral (ML) direction. When balance is challenged, humans can use various strategies to increase stability, such as increasing the size of the BoS to enhance the whole-body centre of mass (CoM) shifts and/or rotating segments to modulate whole-body angular momentum (AM) (Hof, 2007). To rely on the “extend the BoS” strategy is limited when walking on a beam. Authors have shown that the main stabilisation strategy during this type of task focuses on regulating the AM of different body parts (Chiovetto et al., 2018) and also that a significant active control is required to stabilise motion especially along the ML axis (Bauby & Kuo, 2000). Assuming that children with ASD exhibit unique balance characteristics in motor tasks, it is important to explore the extent of their particularities by analysing their performance during challenging balance tasks such as beam walking