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Identifying Drugs Associated With Parkinson's Disease Risk Using Machine Learning
No full textInternational audienceABSTRACT Machine learning (ML)–based methods have been proposed as a potential approach for identifying candidate drugs to be repurposed as disease‐modifying treatments for Parkinson's disease (PD). We applied an ML‐based signal detection method to identify drugs associated with PD and evaluated the method's generalizability. An algorithm combining subsampling and lasso logistic regression was implemented in a case–control study of 12 257 PD cases and 81 103 matched controls identified in Finnish registers. Drug exposure was defined at the subgroup and drug substance levels of the Anatomical Therapeutic Chemical (ATC) classification, considering the frequency of dispensation over 2 years, starting 10 years before the index date (8‐year lag). Three subgroups and two individual drugs were associated with reduced PD risk. Inhalant anticholinergics, in particular tiotropium bromide, showed the most robust signal. Other signals included antimalarial drugs (aminoquinolines) and the antibiotic subgroup lincosamides. Several drugs were associated with increased PD risk, as expected. In addition to direct pharmacological effects, observed associations could be due to treatment of prodromal symptoms of PD, increased comorbidity in individuals later diagnosed with PD or a combination of these factors. These results support the feasibility of the approach. Associations of decreased PD risk observed should be further investigated in view of drug repurposing
Microbial growth rate is a stronger predictor of soil organic carbon than carbon use efficiency
No full textInternational audienc
Changes in compliance with cardiovascular medication after a breast cancer diagnosis: a latent class trajectory analysis using French nationwide data
No full textInternational audienc
Catégories dérivées, surfaces et localisation
No full textThis doctoral dissertation studies the localization of the topological Fukaya category of a graded marked surface, as defined by Haiden-Katzarkov-Kontsevich, at a collection of compatible spherical objects. Geometrically, such a collection corresponds to a set of disjoint graded simple closed curves on the surface. We seek to motivate the idea that the localized category can play the role of a topological Fukaya category for the singular surface obtained by contracting the corresponding simple closed curves. In the first chapter we recall classical results of the representation theory of gentle algebras and introduce the relevant concepts regarding A∞-categories, before presenting the construction of the topological Fukaya category of a graded marked surface. Some aspects of the geometric model for the bounded derived category of a gentle algebra are also presented. In the second chapter we define a class of algebras given by quivers with relations, that we call pinched gentle algebras. Based on a similar result for gentle algebras, we show that graded pinched gentle quivers are in one-to-one correspondence with marked surfaces with conical singularities endowed with a graded simple admissible dissection. We then study a differential graded (DG) enhancement of the localization of the perfect derived category of a gentle algebra by a subcategory generated by a collection of compatible spherical objects. We show that each pinched gentle algebra arises as the endomorphism ring of a formal generator of such a DG quotient. In order to show the formality, we use a spectral sequence on the morphism spaces of a DG quotient and describe its first page in a general way. Finally, using a result of Gyenge, we deduce that the derived category of a pinched gentle algebra sits in a recollement similar to the one obtained by Chang-Jin-Schroll for the localization at a collection of compatible arcs. The third chapter essentially generalizes the results of the second one by enlarging the class of formal generators obtained for localizations of topological Fukaya categories by compatible spherical objects. More precisely, a generalization of the class of pinched gentle algebras is given, as well as a generalization of the notion of admissible dissection of a marked surface with conical singularities. The one-to-one correspondence between these objects, given in the second chapter, is then described in this new generality. We then study a A∞-enhancement of the triangulated quotient and show that each pinched gentle algebra arises as the endomorphism ring of a formal generator. The computation of the formality is done this time by means of a homotopy transfer of A∞-structure. This construction allows us to associate to a graded marked surfaces with conical singularities S, endowed with an admissible dissection A, a category F_A(S) which generates the perfect derived category of a pinched gentle algebra. An immediate consequence of the equivalences given in the smooth case by Haiden-Katzarkov-Kontsevich is that the Morita equivalence class of F_A(S) is independent of A. We give two bases for pinched gentle algebras along the way, one of which is obtained using Bergman's Diamond Lemma. The last section provides an example of a non-Krull-Schmidt triangulated category containing two silting objects having a different number of indecomposable summands.Cette thèse étudie la localisation des catégories de Fukaya topologique de surfaces marquées graduées, telles que définies par Haiden-Katzarkov-Kontsevich, en une collection d'objets sphériques compatibles. Géométriquement, une telle collection correspond à une famille de courbes fermées simples graduées disjointes sur la surface. Nous chercherons à motiver l'idée que la catégorie localisée peut jouer le rôle d'une catégorie de Fukaya topologique pour la surface singulière obtenue en contractant les courbes fermées simples correspondantes. Dans le premier chapitre, nous rappelons des résultats classiques de la théorie des représentations des algèbres aimables et introduisons les concepts qui nous seront utiles pour les catégories A∞, avant de présenter la construction de la catégorie de Fukaya topologique d'une surface marquée graduée. Certains aspects du modèle géométrique pour la catégorie dérivée bornée d'une algèbre aimable sont également présentés. Dans le deuxième chapitre, nous définissons une classe d'algèbres données par carquois et relations, que nous appelons algèbres aimables contractées. En se basant sur un résultat similaire pour les algèbres aimables, nous montrons que les carquois gradués contractées sont en bijection avec les surfaces marquées avec singularités coniques munies d'une dissection graduée admissible simple. Nous étudions ensuite un enrichissement différentiel gradué (DG) de la localisation de la catégorie dérivée parfaite d'une algèbre aimable par une sous-catégorie engendrée par une collection d'objets sphériques compatibles. Nous montrons que chaque algèbre aimable contractée peut-être réalisé comme anneau d'endomorphisme d'un générateur formel d'un tel quotient DG. Afin de montrer la formalité, nous utilisons une suite spectrale sur les espaces de morphisme d'un quotient DG et nous décrivons sa première page en toute généralité. Enfin, nous déduisons d'un résultat de Gyenge le fait que la catégorie dérivée d'une algèbre aimable contractée prend place dans un recollement similaire à celui obtenu par Chang-Jin-Schroll pour les localisations en une collection d'arcs compatibles. Le troisième chapitre est essentiellement une généralisation des résultats du second, en élargissant la classe des générateurs formels obtenus pour les localisations de catégories de Fukaya topologiques par des objets sphériques compatibles. Plus précisément, une généralisation de la classe des algèbres aimables contractées est donnée, ainsi qu'une généralisation de la notion de dissection admissible d'une surface marquée avec singularités coniques. La bijection entre ces deux classes d'objets, établie au chapitre deux, est alors décrite dans cette nouvelle généralité. Nous étudions ensuite un enrichissement A∞ du quotient triangulé et montrons que chaque algèbre aimable contractée peut-être réalisé comme anneau d'endomorphisme d'un générateur formel. Le calcul de la formalité est effectué cette fois-ci au moyen d'un transfert d'homotopie de structure A∞. Cette construction nous permet d'associer à une surface graduée marquée avec singularités coniques S munie d'une dissection admissible A, une catégorie F_A(S) qui engendre la catégorie dérivée parfaite d'une algèbre aimable contractée. Une conséquence immédiate des équivalences données dans le cas lisse par Haiden-Katzarkov-Kontsevich est que la classe d'équivalence de Morita de F_A(S) est indépendante de A. Nous donnons au passage deux bases pour les algèbres aimables contractées, l'une étant obtenue par une application du lemme du diamant de Bergman. La dernière section donne un exemple de catégorie triangulée non-Krull-Schmidt contenant deux objets bousculants ayant un nombre différent de composantes directes indécomposables
Pentafluoroethyl Sulfoximine Reagent for the Photocatalytic Pentafluoroethylation–Difunctionalization of Styrene Derivatives
No full textInternational audienc
Compared SIMS and NanoSIMS Analyses of Duplex Oxide Layers Growth After Sequential Oxidation Tests Using Oxygen Isotope Tracers
No full textInternational audienceAbstract A precise methodology for determining the growth mode of oxide layers on metallic materials at high temperatures is proposed. The approach combines sequential isotopic oxidation tests (using 16 O and 18 O isotopes) with secondary ion mass spectrometry (SIMS and nanoSIMS) analyses. NanoSIMS provides high-resolution localisation of oxygen diffusion pathways and oxide growth zones. However, its limited accessibility and specialised instrumentation can pose practical constraints. In contrast, dynamic SIMS offers broader accessibility and the ability to directly quantify oxygen isotope ratios across depth profiles. The detection of both conventional atomic (O − ) and diatomic (O 2 − ) oxygen signals in dynamic SIMS analysis proved highly effective in offering insights on oxide growth mode, closely replicating nanoSIMS results. The diatomic signal analysis complements the atomic signal data by improving the understanding of oxidant transport within the oxide layer. The methodology was validated through its application to a Co-10Cr alloy oxidised at 900 °C in O 2, under sequential exposures to 16 O and 18 O isotopes. Both SIMS and nanoSIMS revealed the formation of a duplex oxide layer, consisting of an outer layer formed by outward Co cation diffusion and an inner layer growing by inward oxygen penetration, particularly in the grain-boundary regions of the outer oxide layer. The alloy is proposed to oxidise according to the Available Space Model
Reconstitution comparée des écosystèmes Weichselien et Saalien Supérieur en Europe de l’ouest et du sud
No full textInternational audienc
Extension of the Total Carbon Column Observing Network (TCCON) over the Eastern Mediterranean and Middle East: the Nicosia site in Cyprus
No full textInternational audienceAbstract. Long-term greenhouse gas (GHG) measurements are essential for understanding the carbon cycle, detecting trends in atmospheric composition, and assessing the efficiency of climate change mitigation strategies. However, observational gaps over large geographic areas such as the Eastern Mediterranean and Middle East (EMME), a well-known regional GHG hotspot, are likely to increase uncertainties in estimations of their sources and sinks. Here, we describe a new Total Carbon Column Observing Network (TCCON) observatory for solar absorption spectroscopy measurements that has been operating in Nicosia, Cyprus, since September 2019. The site helps bridge a regional observational gap in the EMME, a strategic location at the crossroads of air masses from Europe, Asia, and Africa. Using near-infrared (NIR, InGaAs detector) solar absorption spectra, TCCON-Nicosia measures total column average dry-air mole fractions (Xgas) of key trace gases, including carbon dioxide (CO2), methane (CH4), nitrous oxide (N2O), carbon monoxide (CO), hydrogen fluoride (HF), water vapor (H2O), and semi-heavy water (HDO). These continuous observations, spanning more than 4 years, are presented along with a description of the quality control procedures, compliant with the TCCON standards, to ensure total column atmospheric data with minimal errors. In 2023, observations were extended into the mid-infrared (MIR) spectral region with the addition of a liquid-nitrogen-cooled InSb (LN2-InSb) detector enabling the retrieval of additional trace gases such as formaldehyde (HCHO), carbonyl sulfide (OCS), nitrogen monoxide (NO), nitrogen dioxide (NO2), and ethane (C2H6), herewith further contributing to the global Network for the Detection of Atmospheric Composition Change (NDACC). To tie the TCCON Nicosia with the WMO reference scale, an AirCore (AC) campaign conducted in June 2020 over Cyprus provided vertical in situ profiles, which were converted into total column quantities (AC.Xgas) and compared to TCCON observations (Xgas). The TCCON/in situ comparison showed agreement well within their respective uncertainty budget
Vanadium thiocarboxylate metal–organic frameworks as efficient photocatalysts for photooxidative desulfurization
No full textInternational audienceNew vanadium-carboxythiolate MOFs were synthesized, structurally characterized and evaluated as photocatalysts for photooxidative desulfurization