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Sea surface temperature (SST) is characterized by abundant warm and cold structures that influence the overlying atmospheric boundary layer dynamics through two different mechanisms. First, turbulence and large eddies in the lower troposphere are affected by atmospheric stability, which can be modified by local SST, resulting in enhanced vertical mixing and larger surface winds over warmer waters. Second, the thermodynamic adjustment of air density to the underlying SST structures and the subsequent changes in atmospheric pressure drive secondary circulations. This paper aims to disentangle the effects of these processes and explore the environmental conditions that favor them. Two main environmental variables are considered: the large-scale air–sea temperature difference (proxy for stability) and wind speed. Using 5 years of daily reanalyses data, we investigate the 10-m wind response to SST structures. Based on linear regression between wind divergence and SST derivatives, we show that both mechanisms operate over a large spectrum of conditions. Ten-meter wind divergence is strongly impacted by the local SST via its effect on vertical mixing for midwind regimes in slightly unstable to near-neutral conditions, whereas the secondary circulation is important in two distinct regimes: low wind speed with a slightly unstable air column and high background wind speed with a very unstable air column. The first regime is explained by the prolonged Lagrangian time that the air parcel stays over an SST structure while the second one is related to strong heat fluxes at the air–sea interface, which greatly modify the marine atmospheric boundary layer properties. Location and frequency of the environmentally favorable conditions are discussed, as well as the response in low-cloud cover and rainfall. Significance Statement The main objective of this study is to explore the wind response to thermal structures at the sea surface under different environmental conditions using the latest atmospheric reanalysis. Recent literature suggests that fine-scale air–sea interactions affect a large spectrum of atmospheric dynamics, from seasonal to weather-type regimes. It is thus important to characterize the atmospheric response to ocean surface variability. Our findings describe the environmental conditions for which the two main physical processes through which the atmosphere responds to sea surface temperature structures are active the most and can guide the development of high-resolution observing missions and campaigns in specific geographical locations and seasons to retrieve data that can be used to improve parameterization in models.

Background: This study aimed to investigate renal replacement therapy (RRT) practices in a representative nationwide sample of French intensive care units (ICUs). Methods: From July 1 to October 5 2021, 67 French ICUs provided data regarding their ICU and RRT implementation. We used an online questionnaire to record general data about each participating ICU, including the type of hospital, number of beds, staff ratios, and RRT implementation. Each center then prospectively recorded RRT parameters from 5 consecutive acute kidney injury (AKI) patients, namely the indication, type of dialysis catheter used, type of catheter lock used, type of RRT (continuous or intermittent), the RRT parameters initially prescribed (dose, blood flow, and duration), and the anticoagulant agent used for the circuit. Results: A total of 303 patients from 67 ICUs were analyzed. Main indications for RRT were oligo-anuria (57.4%), metabolic acidosis (52.1%), and increased plasma urea levels (47.9%). The commonest insertion site was the right internal jugular (45.2%). In 71.0% of cases, the dialysis catheter was inserted by a resident. Ultrasound guidance was used in 97.0% and isovolumic connection in 90.1%. Citrate, unfractionated heparin, and saline were used as catheter locks in 46.9%, 24.1%, and 21.1% of cases, respectively. Conclusions: Practices in French ICUs are largely compliant with current national guidelines and international literature. The findings should be interpreted in light of the limitations inherent to this type of study.

International audience; In the sub-Antarctic region, climate change is particularly rapid, while their freshwater ecosystems, such as ponds, host plant species with limited spatial distributions. These particular systems and their plant communities remain however poorly known and the context of their changing habitat calls for deeper insights into these systems. We performed an extensive survey of 45 ponds over three locations of the Iles Kerguelen during the winter and summer seasons of two years, which included the measurement of 12 abiotic parameters and the assessment of the plant community composition. Overall, our results showed that Iles Kerguelen ponds are shallow freshwater ecosystems harbouring species-poor plant communities with high even- ness, of which structure did not vary among the sampled locations. Three different habitats were identified among ponds in relation with nutrient supply by marine animals, which ultimately influenced plant community structure and cover. We highlight that these habitats are mostly determined by water depth, nutrients, and temperature (mean and variance). Present plant community composition was more strongly correlated with plant community composition in the previous year than with abiotic conditions. Overall, this study provides new knowledge on the aquatic plant communities and the functioning of Iles Kerguelen freshwater ecosystems, which can serve as a basis for future studies dealing with the impact of climate change in the sub-Antarctic region.

Background: Conventional chemotherapeutic treatment of colorectal cancer has a low efficacity because of its high toxicity. Several studies identified natural compounds as potential antitumor agents by inducing cancer cell cycle arrest or apoptosis and by exhibiting a potential synergy in drug combination therapy. Natural compounds derived from plants represent an important source of pharmacologic agents toward several diseases. For example, the Tunisian Thymelaeaceae plants, are used in folk medicine for the treatment of different pathologies such as diabetes and hypertension. Objective: The Thymelaea hirsuta L. extracts were evaluated for their anti-tumoral activities and their adjuvant potential that could be used in conventional colorectal cancer therapy. Methods: Fractionation of total methanolic extract from the plant leaves provided 4 fractions using vacuum liquid chromatography. The cytotoxic activities of these fractions were tested toward colorectal cancer cells. Results: Ethyl acetate fraction (E2 fraction) induced cell cycle arrest and apoptosis by activating caspase-3. E2 fraction inhibited cell invasion by reducing integrin 5 expression and FAK phosphorylation. Moreover, E2 fraction potentialized colorectal cancer cells to 5-FU treatment. Conclusion: The selected plant Thymelaea hirsuta is the source of natural compounds that inhibited cell growth and invasion and induced cell cycle arrest in colorectal cancer cells. The most interesting result was their potential synergy in 5-FU combination treatment. Further analysis will identify the active compounds and confirm their role in chemotherapeutic treatment by sensitizing colorectal cancer cell to anti-cancer drug.

Background: In patients with metastatic breast cancer (mBC), Circulating Tumor Cells (CTC) counts have a strong prognostic impact on progression free survival (PFS) and overall survival (OS). Changes 4 weeks after the start of a new line of therapy, inform on treatment efficacy. Despite improvements in systemic treatment, metastatic BC remains mainly uncurable with alteration of health-related quality of life (HRQOL) during the course of the disease. The aim of this work was to assess impact of clinical factors and biological factors as CTC on HRQOL. Methods: The French cohort COMET is a prospective study including first line HER2 negative patients receiving weekly paclitaxel and bevacizumab according to EMA approved combination. The aim of this cohort was to evaluate clinical, biological and radiological parameters associated with patients’ outcome (CTC, CEC, serum markers, ctDNA, pharmacogenomic polymorphisms, metabolomic parameters, visceral fat assessed by initial CTscan, serum estradiol level, and quality of life). HRQOL was assessed at baseline, at every cycle until progression and then every 3 months up to death using the EORTC QLQ-C30 questionnaire and its breast cancer specific module, the EORTC QLQ-BR23. Five dimensions of HRQOL were analyzed for the primary analyses: Global health status (GHS), physical functioning (PF), Emotional functioning (EF), fatigue (FA) and pain (PA). Time until definitive deterioration (TUDD) in HRQOL was defined as the interval between inclusion and the first decrease in HRQOL score ≥ 5 compared to baseline HRQOL score with no further improvement or in case of death. CTC counts were determined using the standard CellSearch system [Menarini Silicon Biosystems]. Results: Out of 510 patients included in COMET study, 432 patients with available HRQOL data were analyzed in this study. At baseline, patients reported a mean score for GHS of 57.6 (SD=22.7), for PF of 75.8 (23.2), for EF of 62.2 (25.8), for FA of 42.2 (29.60) and for PA of 38.1 (31.5). The Median TUDDs for the 5 targeted dimensions was 10.1 months [7.5-16.9] for GHS, 6.1 months [4.1-8.9] for PF, 21.6 [18.7-31.2] for EF, 10.8 [6.2-16.6] for FA and 13.6[10.1-22.5] months for PA. CTC counts were available in 261 patients at base line and in 229 patients after 4 weeks of treatment, before second cycle of chemotherapy. CTC high count was independent of main clinical and biological characteristics except lobular subtype. We confirmed the poor outcome of patients with high CTC count at base line and after one cycle of treatment with the threshold of > 4CTC/7.5 ml of blood. Out of the 5 dimensions of HRQOL, TUDD of EF was significantly correlated with a high CTC level at base line (p=0.0262) and even more with still an elevated count of CTC after one cycle of chemotherapy(p=0.0137). There was no association of CTC with the other dimensions of HRQOL. Conclusion: This is the first study ever reporting an analysis of QoL and CTC. We observed an association of high CTC count with one component of HRQOL scale. This suggests that CTC could be complementary to clinical factors that could influence HRQOL in HER2 negative metastatic BC treated with first line chemotherapy. Citation Format: Jean-Yves Pierga, Oumar Billa, Sandrine Dabakuyo, Jérôme Lemonnier, Frédérique Berger, Olivier Trédan, William Jacot, Anthony Gonçalves, Marc Debled, Christelle Levy, Christelle Jouannaud, Marie-Ange Mouret-Reynier, Jean-Marc Ferrero, Florence Dalenc, Fatima-Zohra Toumi, Franck Bonnetain, Francois-Clement Bidard, Shufang Renault. Circulating tumor cells enumeration and Health Related Quality of Life of patients treated with first-line chemotherapy for HER2 negative metastatic breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-07-24.

Le maintien ou le retour à l’emploi pour les personnes atteintes d’un cancer est un enjeu majeur. Une personne sur cinq est en perte d’emploi à cinq ans du diagnostic. La problématique est complexe, en lien avec les conséquences de la maladie, des traitements, des connaissances partielles des dispositifs d’aide et des particularités socioprofessionnelles. Tout d’abord, une mise au point sur l’état des lieux en France est faite, pour comprendre la situation sur le plan démographique, les conséquences matérielles et psychologiques. Ensuite, l’article retrace l’expérience d’un centre de lutte contre le cancer dans la mise en place d’un dispositif d’accompagnement de la vie professionnelle des personnes suivies en cancérologie. Ce projet s’appuie sur plusieurs travaux d’enquêtes préalables et fait l’objet d’une aide à la mise en place grâce à une subvention de l’Institut national du cancer. Il s’articule autour de trois axes : ceux des professionnels, des patients et de l’entreprise. Enfin, la synthèse des travaux entrepris tente de dresser des recommandations transférables aux établissements accueillant des personnes atteintes de cancer.

Micropillar compression is a method of choice to understand mechanics at small scale. It is mainly studied with electron microscopy or white-beam micro-Laue X-ray diffraction. The aim of the present article is to show the possibilities of the use of diffraction with a coherent X-ray beam. InSb micropillars in epitaxy with their pedestals (i.e. their support) are studied in situ during compression. Firstly, an experiment using a collimated beam matching the pillar size allows determination of when the sample enters the plastic regime, independently of small defects induced by experimental artefacts. A second experiment deals with scanning X-ray diffraction maps with a nano-focused beam; despite the coherence of the beam, the contributions from the pedestal and from the micropillar in the diffraction patterns can be separated, making possible a spatially resolved study of the plastic strain fields. A quantitative measurement of the elastic strain field is nevertheless hampered by the fact that the pillar diffracts at the same angles as the pedestal. Finally, no image reconstructions were possible in these experiments, either in situ due to a blurring of the fringes during loading or post-mortem because the defect density after yielding was too high. However, it is shown how to determine the elastic bending of the pillar in the elastic regime. Bending angles of around 0.3° are found, and a method to estimate the sample's radius of curvature is suggested.

International audience; The syntheses of several alkaloids and nitrogen-containing compounds including N-Boc-coniine (14b), pyrrolizidine (1), δ-coniceine (2), and pyrrolo[1,2a]azepine (3) are described. New C-C bonds in the α position relative to the nitrogen atom were formed by the alkylation of metalated α-aminonitriles 4 and 6a-c with alkyl iodides possessing the requisite size and functionality. In all of the reported cases, the pyrrolidine ring was formed in the aqueous medium through a favorable 5-exo-tet process involving a primary or a secondary amino group and a terminal δ-leaving group. Conversely, the azepane ring was efficiently formed in N,N-dimethylformamide (DMF), as the preferred aprotic solvent, through an unreported 7-exo-tet cyclization process involving a more nucleophilic sodium amide and a terminal mesylate borne by a saturated six carbon chain unit. In this way, we successfully synthesized pyrrolo[1,2a]azepane 3 and 2-propyl-azepane 14c in good yields from inexpensive and readily available materials without tedious separation methods.

The Microchannel X-ray Telescope (MXT) will be the first focusing X-ray telescope based on a "Lobster-Eye" optical design to be flown on Sino-French mission SVOM. SVOM will be dedicated to the study of Gamma-Ray Bursts and more generally time-domain astrophysics. The MXT telescope is a compact (focal length ~ 1.15 m) and light (< 42 kg) instrument, sensitive in the 0.2--10 keV energy range. It is composed of an optical system, based on micro-pore optics (MPOs) of 40 micron pore size, coupled to a low-noise pnCDD X-ray detector. In this paper we describe the expected scientific performance of the MXT telescope, based on the End-to-End calibration campaign performed in fall 2021, before the integration of the SVOM payload on the satellite., 22 pages, 12 figures, accepted for publication in Experimental Astronomy

Cancer has one of the highest mortality rates globally. The traditional therapies used to treat cancer have harmful adverse effects. Considering these facts, researchers have explored new therapeutic possibilities with enhanced benefits. Nanoparticle development for cancer detection, in addition to therapy, has shown substantial progress over the past few years.Herein, the latest research regarding cancer treatment employing magnetic nanoparticles (MNPs) in chemo-, immuno-, gene-, and radiotherapy along with hyperthermia is summarized, in addition to their physio-chemical features, advantages, and limitations for clinical translation have also been discussed.MNPs are being extensively investigated and developed into effective modules for cancer therapy. They are highly functional tools aimed at cancer therapy owing to their excellent superparamagnetic, chemical, biocompatible, physical, and biodegradable properties.

International audience; Protactinium (Z = 91) is a very rare actinide with peculiar physico-chemical properties. Indeed, although one may naively think that it behaves similarly to either thorium or uranium by its position in the periodic table, it may in fact follow its own rules. Because of the quite small energy gap between its valence shells (in particular the 5f and 6d ones) and also the strong influence of relativistic effects on its properties, it is actually a challenging element for theoretical chemists. In this article, we combine experimental information, chemical arguments and standard first-principle calculations, complemented by implicit and explicit solvation, to revisit the stepwise complexation of aqueous protactinium(V) with sulfate and oxalate dianionic ligands (SO42- and C2O42-, respectively). From a methodological viewpoint, we notably conclude that it is necessary to at least saturate the coordination sphere of protactinium(V) to reach converged equilibrium constant values. Furthermore, in the case of single complexations (i.e. with one sulfate or oxalate ligand bound in the bidentate fashion), we show that it is necessary to maintain the coordination of one hydroxyl group, thought of in the [PaO(OH)]^3+ precursor, to obtain coherent complexation constants. Therefore, we predict that this hydroxyl group is maintained in the formation of 1:1 complexes while we confirm that it is withdrawn when coordinating three sulfate or oxalate ligands. Finally, we stress that this work is a first step toward the future use of theoretical predictions to elucidate the enigmatic chemistry of protactinium in solution.

Sandwich immunoassays such as the enzyme-linked immunosorbent assay (ELISA) have been miniaturized and performed in a lab-on-a-chip format, but the execution of the multiple assay steps typically requires a computer or complex peripherals. Recently, an ELISA for detecting antibodies was encoded structurally in a chip thanks to the microfluidic chain reaction but the need for precise pipetting and intolerance to commonly used surfactant concentrations limited the potential for broader adoption. Here, we introduce the ELISA-on-a-chip with aliquoting functionality that obviates the need for precise pipetting, accommodates higher surfactant concentrations, includes barrier channels that delay the contact between solutions and prevent undesired mixing, and that executed a quantitative, high sensitivity assay for the SARS-CoV-2 nucleocapsid protein in 4×-diluted saliva. Upon loading the chip using disposable pipettes, capillary flow draws each reagent and the sample into a separate volumetric measuring reservoir for detection antibody (70 µL), enzyme conjugate (50 µL), substrate (80 µL), and sample (210 µL), and splits washing buffer into 4 different reservoirs of 40, 40, 60, and 20 µL. The excess volume is autonomously drained via a structurally encoded capillaric aliquoting circuit, creating aliquots with an accuracy of >93%. Next, the user click-connects the assay module, comprising a nitrocellulose membrane with immobilized capture antibodies and a capillary pump, to the chip which triggers the step-by-step, timed flow of all aliquoted solutions. A colored precipitate forming a line on a nitrocellulose strip serves as an assay readout, and upon digitization, yielded a binding curve with a limit of detection of 54 and 91 pg/mL for buffer and diluted saliva respectively, vastly outperforming rapid tests. The ELISA chip is 3D-printed, modular, adaptable to other targets and assays, and could be used to automate ELISA in the lab; or as a diagnostic test at the point of care with the convenience and form factor of rapid tests while preserving the protocol and performance of central laboratory ELISA.

Inherited myopathies are a group of disease, which, although distinct from a genetic and prognostic point of view, can lead to non-specific clinical pictures due to phenotypic overlap. Acquired immuno-mediated myopathies may also pose the problem of clinically accurate etiological orientation. The assessment of fatty infiltration and pathological increase in water volume of the muscle contingent on whole-body muscle MRI is becoming increasingly important in aiding the initial diagnosis of inherited and acquired myopathies. MRI helps orientating the clinical diagnostic hypotheses thanks to the patterns of muscle involved (more or less specific according to the entities), which led to the development of decision-making algorithms proposed in the literature. The aim of this article is to specify the proper MRI protocol for the evaluation of myopathies and the basis of the interpretation and to provide a summary of the most frequently inherited and acquired myopathies described in the literature.

Extraordinary progress has been made over the past decade in the chemical synthesis of many stilbene oligomers (>2) as well as in biotechnological methods for the production of these compounds.

Understanding the mechanisms of X-ray radiation damage in biological systems is of prime interest in medicine (radioprotection, X-ray therapy…). Study of low-energy rays, such as soft-X rays and light ions, points to attribute their lethal effect to clusters of energy deposition by low-energy electrons. The first step, at the atomic or molecular level, is often the ionization of inner-shell electrons followed by Auger decay in an aqueous environment. We have developed an experimental set-up to perform electron coincidence spectroscopy on molecules in a water micro-jet. We present here the first results obtained on sodium benzoate solutions, irradiated at the oxygen and carbon K-edges.

Purpose - The purpose of this paper is to describe five business incubators in Brazil through the Triple Helix model, their realities and challenges. Theoretical framework – A discussion of Business incubators, Triple Helix and the use of Information and Communication Technologies in incubators are the main lenses used to support the research. Design/methodology/approach – For this purpose, five case studies of incubators in the Northern and Southern Regions of Brazil were used. The paper uses a qualitative approach and collects data through semi-structured interviews. To analyze the results, the theory was compared to the findings from the field research. Findings - The results showed that most incubators are in public universities, the majority focus on technology, and some are diverse (social and cultural). Some internal and external partners help them with financial support. One of the challenges (maybe the most important) is a set of constraints because some lecturers cannot understand how to use academic knowledge in consultancy. Research, Practical & Social implications – The differences found between incubator categories are in the results that lead to this business model being more complex than it is in reality. The presentation of different incubator realities and challenges focusing on the discussion of ‘selling’ knowledge, the use of public resources by private enterprises, are the practical and social implications. Originality/value - The main contribution is to show the reality of these incubators, the empirical results, adding a new perspective to the discussion. Keywords - Business incubators; Challenges; Triple Helix; Information and Communication Technology.

New polycyclic heterocycles were synthesised and evaluated as potential inhibitors of thymidine phosphorylase (TP). Inspired by the pharmacophoric pyrimidinedione core of the natural substrate, four series have been designed in order to interact with large empty pockets of the active site: pyrimidoquinoline-2,4-diones (series A), pyrimidinedione linked to a pyrroloquinoline-1,3-diones (series B and C), the polycyclic heterocycle has been replaced by a pyrimidopyridopyrrolidinetetraone (series D). In each series, the tricyclic nitrogen heterocyclic moiety has been synthesised by a one-pot multicomponent reaction. Compared to 7-DX used as control, 2d, 2l, 2p (series A), 28a (series D), and the open intermediate 30 showed modest to good activities. A kinetic study confirmed that the most active compounds 2d, 2p are competitive inhibitors. Molecular docking analysis confirmed the interaction of these new compounds at the active binding site of TP and highlighted a plausible specific interaction in a pocket that had not yet been explored.

Breast carcinomas (BC) with osteoclast-like giant cells (OGC) are rare. Despite their distinct stromal features, their molecular characteristics remain unknown. Here, we report comprehensive clinico-pathological and molecular findings for 27 patients diagnosed with BC-OGC at Institut Curie between 2000 and 2021. Seventeen (63%) cases were invasive carcinomas of no special type (IC NST) with OGC (OGC-IC NST), four (15%) were mixed or multifocal cases with and without OGC (OGC-Mixed), and six (22%) were metaplastic carcinomas with OGC (OGC-MC). All OGC-IC NST and OGC-Mixed cases were ER+ HER2- tumors (most being luminal A based on transcriptomic subtyping, when available), while all OGC-MC were triple-negative. The median age at diagnosis was 46, 45 and 62 years for OGC-IC NST, OGC-Mixed and OGC-MC, respectively. Three patients developed distant metastases (one OGC-IC NST, two OGC-Mixed), one of whom died of metastatic disease (OGC-Mixed), and one other patient died of locally advanced disease (OGC-MC). Histopathological evaluation comparing 13 OGC-IC NST and 19 control IC NST without OGC confirmed that OGC-IC NST showed significantly higher density of vessels (by CD34 immunohistochemistry (IHC)), iron deposits (Perls stain), and CD68 and CD163-positive cell infiltrates. Genomic findings for nine OGC-IC NST and four OGC-MC were consistent with the underlying histologic subtype, including activating alterations of the PI3K/AKT/mTOR pathway in 7/13 cases. Using RNA-seq data, differential gene expression analysis between OGC-IC NST (n = 7) and control IC NST without OGC (n = 7) revealed significant overexpression of TNFSF11 (RANK-L), TNFRSF11A (RANK), CSF1 (M-CSF), CSF1R, and genes encoding osteoclastic enzymes (MMP9, ACP5, CTSK, CTSB) in OGC-IC NST, while OPG (osteoprotegerin) was underexpressed. We also confirmed for the first time RANK-L expression in BC with OGC by IHC (seen in 15 out of 16 cases, and only in 2 of 16 controls without OGC). These findings could offer a rationale for further investigating RANK-L as a therapeutic target in BC with OGC.

International audience

Cannabinoid receptor 1 (CB1) is a promising drug target involved in many physiological processes. Using atomistic molecular dynamics (MD) simulations, we examined the structural effect of F237L mutation on CB1, a mutation that has qualitatively similar effects to allosteric ligand ORG27569 binding. This mutation showed a global effect on CB1 conformations. Among the observed effects, TM6 outward movement and the conformational change of the NPxxY motif upon receptor activation by CB1 agonist CP55940 were hindered compared to wt CB1. Within the orthosteric binding site, CP55940 interactions with CB1 were altered. Our results revealed that allosteric perturbations introduced by the mutation had a global impact on receptor conformations, suggesting that the mutation site is a key region for allosteric modulation in CB1.