Hautes Études d'Ingénieur

La théorie démocratique du vote imagine des électeurs, suffisamment et identiquement informés, opérant leurs choix individuellement en un for intérieur se prolongeant jusque dans l’intimité de l’isoloir, au terme de calculs coûts/avantages générant un arbitrage supposé rationnel sur la participation électorale (paradoxe de l’électeur) et, si l’option d’aller voter est retenue, sur le choix d’un candidat, censé conduire telle politique

Abstract Idiopathic pulmonary fibrosis (IPF) is an aggressive interstitial lung disease associated with progressive and irreversible deterioration of respiratory functions that lacks curative therapies. Despite IPF being associated with a dysregulated immune response, current antifibrotics aim only at limiting fibroproliferation. We show here that the P2RX7/IL-18/IFNG axis is downregulated in IPF patients and that P2RX7 has immunoregulatory functions. Using our positive modulator of P2RX7, we show that activation of the P2RX7/IL-18 axis in immune cells limits lung fibrosis progression in a mouse model by favoring an anti-fibrotic immune environment, with notably an enhanced IL-18-dependent IFN-γ production by lung T cells leading to a decreased production of IL-17 and TGFβ. Overall, we show the ability of the immune system to limit lung fibrosis progression by targeting the immunomodulator P2RX7. Hence, treatment with a small activator of P2RX7 may represent a promising strategy to help patients with lung fibrosis.

Only a subpopulation of non-small cell lung cancer (NSCLC) patients responds to immunotherapies, highlighting the urgent need to develop therapeutic strategies to improve patient outcome. We develop a chemical positive modulator (HEI3090) of the purinergic P2RX7 receptor that potentiates αPD-1 treatment to effectively control the growth of lung tumors in transplantable and oncogene-induced mouse models and triggers long lasting antitumor immune responses. Mechanistically, the molecule stimulates dendritic P2RX7-expressing cells to generate IL-18 which leads to the production of IFN-γ by Natural Killer and CD4+ T cells within tumors. Combined with immune checkpoint inhibitor, the molecule induces a complete tumor regression in 80% of LLC tumor-bearing mice. Cured mice are also protected against tumor re-challenge due to a CD8-dependent protective response. Hence, combination treatment of small-molecule P2RX7 activator followed by immune checkpoint inhibitor represents a strategy that may be active against NSCLC.

Abstract Dihydro‐1,4‐thiazine skeletons bearing olefin fragment at their α‐position were prepared through a Pd(OAc)2‐catalysed Fujiwara‐Moritani type reaction via C−H alkenylation with olefins. This approach is selective, generalizable to a wide range of olefins and requires only 1 eq. of Ag2CO3 without the need of co‐oxidant. The C−H bond activation proved to be strongly dependent on the olefin's substitution while unfused dihydro‐1,4‐thiazines seemed to be affected by the oxidation state of the sulfur atom. The utility of olefins obtained was demonstrated by their implication in the dipolar cycloaddition reaction with a non‐stabilized azomethine ylide.magnified image

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A common problem in ECG analysis is the removal of unwanted noise that corrupt the signal while recording and can hinder the correct interpretation. To provide high-quality ECG records, many approaches have been developed. This paper introduces a comprehensive survey of filtering methods to cope with the noise artifacts in the ECG signals in order to find the best-suited filter for each type of noise. For this purpose, we used 47 half hour signals coming from adding artifacts to clean ECG records taken from real clinical databases. We calculated the Signal to Noise Ratio (SNR) and the Root Mean Square Error (RMSE) after filtering and then a statistical test was used to select the most efficient method. The noises that were filtered are Power Line Interference (PLI), Baseline Wander (BW), Electrod Motion Artifacts (EM) and Muscle Artifacts (MA). Empirical Mode Decomposition was the best method to filter PLI noise. BW, MA and EM were removed to a large extent using Wavelet+Adaptive filtering method.