Paris Sciences and Letters (PSL) University

Existing fault diagnosis methods for brushless dc motors (BLDCMs) encounter problems of limited adaptability in terms ofmultiple faults, multiple motor types, and cross-operating conditions. Therefore, we propose an operating condition generalization network (OCGN) based on the recently proposed domain-invariant feature exploration (DIFEX) method to address it. First, a tacholess order tracking method is constructed to alleviate the influence of rotating speed variation on the line current. Second, order harmonic features are extracted from the angular line current and inputted into a fully connected neural network to create an order neural network (ONN). Finally, ONN is used as the teacher network in the knowledge distillation framework of DIFEX, and the student network is improved with a Gaussian random projection layer. Based on extensive fault data of BLDCMs, OCGN is compared with other state-of-the-art methods and confirmed to have superior performance.

The influence of solvent vapor on the dielectric properties of films of polystyrene, poly(2-vinylpyridine), and poly(4-vinylpyridine) has been investigated. A procedure for the measurement of dielectric permittivity via the capacitor method under conditions of strong swelling of the films has been elaborated. It has been found that the swelling in chloroform vapor is the most prominent and leads to noticeable increase in the real part of the dielectric permittivity of the samples. This effect can be used to enhance the dielectric contrast between the domains of a block copolymer. It has been demonstrated that the observed decrease in the polymer glass transition temperature under condition of swelling can be approximated by the group contributions method.

This paper introduces an approach to transform academic North-South collaborations. Critiquing entrenched dynamics in inter-university collaborations, we propose a methodology for unlearning colonial modes of thinking and relating. The trans-formative dialogues proposed in this paper illustrate how researchers can jointly engage in generating collective reflexivity and mutual accountability to challenge established norms in academia. Using autoethnographic vignettes, we demonstrate how these dialogues bring to the fore our complicities in reproducing North-South imbalances as well as the difficulty of unsettling power dynamics and fostering collective coexistence across differences. By nurturing a safe space for tuning in with each other, transformative dialogues turn self-reflexivity into a relational and dia-logical process. They help (1) to reflect on our past and present experiences, (2) to perceive failure as a learning stimulus rather than deficiency or shame, (3) to confront us with our complicity in reproducing neocolonial power dynamics in academic collaborations, and (4) to transform interpersonal dynamics within academic collaborations.

Background The prognosis for patients with relapse of localized rhabdomyosarcoma (RMS) remains poor, with limited evidence for optimal second‐line therapy. This study describes the management and outcomes of relapsed RMS patients in France. Methods We retrospectively reviewed all nonmetastatic RMS patients enrolled in France in the RMS 2005 study who relapsed between 2006 and 2019 after achieving complete local control, defined as complete remission or stable residue ≥ 6 months after treatment completion. Data were extracted from the RMS 2005 database and medical records. Results Ninety‐five patients relapsed at a median age of 6.0 years (range: 1.0–27.0). The median time from diagnosis to relapse was 17.5 months (range: 7.4–82.0). Most patients had embryonal RMS (65.3%) and local/locoregional relapses (71.6%). The first relapse treatment included chemotherapy (all except two patients), radiotherapy (52.6%), and surgery (48.4%). Second‐line chemotherapy yielded a 58.5% objective response rate after 3 ± 1 cycles. Fifty‐five patients achieved second complete remission. With a median follow‐up of 7.2 years from the first relapse (range: 0.3–11.3), 5‐year progression‐free survival was 26% (95% CI: 18–36), and 5‐year overall survival was 35% (95% CI: 25–45). Importantly, no patient survived relapse without receiving locoregional treatment (surgery and/or radiotherapy). Conclusion This study confirmed the inconsistencies in therapy and the poor prognosis for relapsed RMS but highlighted the potential for long‐term survival in patients who received surgery and/or radiotherapy, emphasizing the crucial role of achieving local control in improving outcomes at relapse.

Prognostics and health management (PHM) has garnered significant attention in industrial fields, particularly due to its successful application in managing battery degradation. However, current approaches are inadequate in addressing multiple thresholds, including both theoretical formulation and practical computational complexity. These limitations hinder the development and implementation of threshold-varying assessments, thereby impeding the advancement of PHM application. This article investigates prognostic applications with different failure thresholds and highlights the importance of failure threshold selection. In addition, theoretical evaluation and analysis are provided for multiple threshold settings, encompassing both discrete and continuous series. This introduces a novel technical domain for prognostic applications. The effectiveness of threshold-varying assessment is verified with several different approaches on real battery degradation experiments. Furthermore, we demonstrate the practical significance of threshold-varying assessments in enabling on-demand scheduling for maintenance or replacement of spare parts. Most importantly, to meet the real-time requirements of practical prognostic applications, this article also discusses the computational complexity of threshold-varying assessment and finds an applicable solution for this common difficulty.

SACHA‐France (NCT04477681) is a prospective real‐world study that collects clinical safety and efficacy data of novel anticancer therapies prescribed off‐label or on compassionate use to patients <25 years. From March 2020 until February 2024, 640 patients with solid tumors or lymphomas were included, with 176 (28%) reported objective tumor responses. Centralized medical monitoring of local radiological/functional imaging reports by the SACHA coordinating investigator led to response modification in 45 out of 176 cases (26%), highlighting the relevance of the medical review of study data. We suggest this pragmatic approach for improving clinical trial data when centralized radiological review is not performed.

In the current data-rich environment, valorizing of data has become a common task in data science and requires the design of a statistical model to transform input data into a desirable output. The literature in data science regarding the design of new models is abundant, while in parallel, other streams of literature such as epistemology of science, has shown the relevance of anomalies in model design processes. Anomalies are to be understood as unexpected observations in data, an historical example being the discovery of Mercury based on its famous anomalous precession perihelion. Therefore, this paper addresses the various design processes in data science and their relationships to anomalies. To do so, we conceptualize what designing a data science model means, and we derive three design processes based on the latest theories in engineering design. This allows us to formulate assumptions regarding the relationships between each design process and anomalies, which we test with several case studies. Notably, three processes for the design of models in data science are identified and, for each of them, the following information is provided: (1) the various knowledge leveraged and generated and (2) the specific relations with anomalies. From a theoretical standpoint, this work is one of the first applications of design methods in data science. This work paves the way for more research at the intersection of engineering design and data science, which could enrich both fields.

Background Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancers, highly resistant to standard chemotherapy and immunotherapy. Regulatory T cells (Tregs) expressing tumor necrosis factor α receptor 2 (TNFR2) contribute to immunosuppression in PDAC. Treg infiltration correlates with poor survival and tumor progression in patients with PDAC. We hypothesized that TNFR2 inhibition using a blocking monoclonal antibody (mAb) could shift the Treg-effector T cell balance in PDAC, thus enhancing antitumoral responses. Method To support this hypothesis, we first described TNFR2 expression in a cohort of 24 patients with PDAC from publicly available single-cell analysis data. In orthotopic and immunocompetent mouse models of PDAC, we also described the immune environment of PDAC after immune cell sorting and single-cell analysis. The modifications of the immune environment before and after anti-TNFR2 mAb treatment were evaluated as well as the effect on tumor progression. Results Patients with PDAC exhibited elevated TNFR2 expression in Treg, myeloid cells and endothelial cells and lower level in tumor cells. By flow cytometry and single-cell RNA-seq analysis, we identified two Treg populations in orthotopic mouse models: Resting and activated Tregs. The anti-TNFR2 mAb selectively targeted activated tumor-infiltrating Tregs, reducing T cell exhaustion markers in CD8 ⁺ T cells. However, anti-TNFR2 treatment alone had limited efficacy in activating CD8 ⁺ T cells and only slightly reduced the tumor growth. The combination of the anti-TNFR2 mAb with agonistic anti-CD40 mAb promoted stronger T cell activation, tumor growth inhibition, and improved survival and immunological memory in PDAC-bearing mice. Conclusion Our data suggest that combining a CD40 agonist with a TNFR2 antagonist represents a promising therapeutic strategy for patients with PDAC.

Allogeneic chimaeric antigen receptor T cells (allo-CAR T cells) derived from healthy donors could provide rapid access to standardized and affordable batches of therapeutic cells if their rejection by the host’s immune system is avoided. Here, by means of an in vivo genome-wide CRISPR knockout screen, we show that the deletion of Fas or B2m in allo- T cells increases their survival in immunocompetent mice. Human B2M– allo-CAR T cells become highly sensitive to rejection mediated by natural killer (NK) cells, whereas FAS– CAR T cells expressing normal levels of human leukocyte antigen I remain resistant to NK cells. CD3–FAS– CAR T cells outperformed CD3–B2M– CAR T cells in the control of leukaemia growth in mice under allogeneic pressure by T cells and NK cells. The partial protection of CD3–FAS– allo-CAR T cells from cellular rejection may improve the efficacy of allogeneic cellular therapies in patients with cancer.

Groundwater level (GWL) can vary over a wide range of timescales. Previous studies highlighted that interannual (2-8 years) to decadal (>10 years) variability, originating from large-scale climate variability, represents a significant part of GWL variance. How GWL may respond to changes in large-scale climate forcing, affecting precipitation variability, however, remains an open question. Focusing on the Seine River basin, this study therefore aims to assess how GWL respond to changes in interannual to decadal climate variability. We implemented an empirical numerical approach, which enables us to assess the sensitivity of GWL to changes in precipitation variability over a range of timescales, using the whole Seine hydrological system as a case study. The approach consists of: i) identifying and modifying the spectral content of precipitation in the low-frequency range; ii) using such perturbed precipitation fields as input in the physically-based hydrological/hydrogeological CaWaQS model for the Seine River basin for simulating the corresponding GWL response; iii) comparing the spectral content, mean, variance and extremes of perturbed GWL with reference GWL. Two interannual (2-4yr and 5-8yr) and one decadal (15yr) timescales were modified individually by either increasing or decreasing their amplitude by 50%. This led to six scenarios of perturbed lowfrequency precipitation variability, which are subsequently used as input in the CaWaQS model to assess the GWL response. Results indicated increased (decreased) GWL up to 5 meters when low-frequency precipitation variability is increased (decreased) by 50%. This led to an increased occurrence of groundwater floods (droughts) with increased severity and decreased occurrence of groundwater droughts (floods) with decreased severity, respectively. These results indicate: i) how using biased climate data, in terms of low-frequency variability, leads to large deviation in the GWL simulation, ii) how much potential changes in low-frequency climate variability may affect future GWL, and particularly drought and flood occurrence and severity.

Background Quality of life (QoL) in patients undergoing surveillance for uveal melanoma (UM) can be affected by psychological sequelae. Fear of cancer recurrence (FCR) may be acute especially when prognostication indicates an increased risk of metastatic recurrence. Communication with an ophthalmologist or oncologist can then play a key role in impacting QoL. Methods In this prospective study co-designed with patient’s partners and using a mixed-method approach, 250 patients at high versus low risk of metastatic recurrence are recruited in a national UM reference centre in France. At T1, after the 6-months post-treatment surveillance visit, dyads of clinicians and eligible patients complete a questionnaire to assess their respective experience of the communication during that consultation. Patients also complete questionnaires assessing their health literacy, information preference, and satisfaction with the information received (EORTC QLQ-INFO25), genomic testing knowledge, genomic test result receipt, satisfaction with medical care (EORTC PATSAT-C33), perceived recurrence risk, anxiety and depression (HADS), fear of cancer recurrence (FCRI) and quality of life (EORTC QLQ-C30 and QLQ-OPT30). At 12-months post-treatment (T2), patients complete again the HADS, FCRI, EORTC QLQ-C30 and QLQ-OPT30. Multilevel analyses will assess the effect of satisfaction with the information received on FCR and QoL accounting for the clinicians’ and patients’ characteristics. In-depth interviews planned sequentially with ≈25 patients will deepen understanding of patients’ care experience. Discussion As information on prognosis based on medical parameters becomes widely integrated into oncology practice, this study will highlight UM survivors’ information expectations and satisfaction with communication, and its effect on FCR and QoL. Culturally adapted recommendations for doctor-patient communication will be provided for contexts of oncology surveillance involving poor prognosis in cases of recurrence. Trial registration NCT06073548 (October 4, 2023).

Background Parameningeal (PM) site is an unfavorable characteristic in rhabdomyosarcoma (RMS). We described the treatment and outcome for patients with PM RMS and investigated the prognostic value of risk factors. We scored PM site by originating site and by highest risk extension. Methods Patients with PM RMS were treated within the European pediatric Soft tissue sarcoma Study Group (EpSSG) RMS 2005 study with risk‐adapted, multi‐modal treatment. Results Three‐hundred‐eighty‐one patients with PM RMS were included. Radiotherapy was administered in 359 patients (77 with surgery). After a median follow‐up of 75 months, 5‐year event‐free survival was 60% (95% confidence interval (CI) 55%–65%), 5‐year overall survival was 65% (95% CI 60%–70%). Conclusions The outcome for patients with PM RMS has not improved in comparison to previous historical studies, despite the more rigorous application of radiotherapy (94% of patients). Signs of meningeal involvement, PM site, and age at diagnosis remained prognostic risk factors. Trial Registration EudraCT number 2005‐000217‐35

Heterogeneous visible light photocatalysis is a compelling approach to address sustainability in synthetic photochemistry. However, the use of solid‐state photocatalysts remains very unpopular in organic synthesis because of their limited accessibility and the black‐box effect associated to the lack of rational between their molecular structure and their photochemical properties. Herein, we disclose the synthesis, characterization, photocatalytic properties and synthetic applications of a simple and readily available solid‐state conjugated organic polymer, poly‐(para‐phenylene ethynylene) 1, which exhibits a strong oxidative power upon irradiation with visible light (E(1*/1⋅⁻)=+1.67 V vs SCE). Comparisons with structural analogues highlighted the superior photocatalytic activity of this linear semiconductor, on account of its fully conjugated architecture. The associated excited‐state reactivity enabled the transformation of various amines into imines in batch and continuous flow reactors together with straightforward photocatalyst recycling. Mechanistic investigations revealed concomitant photoredox and energy transfer pathways, that led to the formation of the desired products. Ultimately, the inline generation of imines was exploited in telescoped three‐component Ugi reactions (3CR) in batch and flow toward biologically relevant α‐acylaminoamides.

Northern blotting is a common technique in RNA biology, allowing to detect and quantify RNAs of interest following separation by gel electrophoresis, transfer to a membrane, and hybridization of specific anti-complementary labelled probes. In this chapter, we describe our protocol for efficient RNA extraction from yeast, separation on agarose gel, and capillary transfer to a membrane. We provide two different methods for strand-specific detection of several types of RNAs using oligonucleotide probes, the first using radioactive 32P-labelled probes, the second based on nonradioactive digoxigenin-labelled probes.

Eukaryotic mRNAs carry an N7-methylguanosine (m7G) cap structure at their 5′ extremity, which protects them from the degradation by 5′-3′ exoribonucleases and plays a pivotal role in mRNA metabolism, promoting splicing, nuclear export, and translation. Decapping, the enzymatic process that removes this structure, is a key event during cytoplasmic mRNA 5′-3′ decay, leading to the degradation of the transcript body by Xrn1. In this chapter, we describe a procedure to assess the cap status of RNA at the transcriptome level. It is based on a treatment of total RNA extracts with a 5′ monophosphate-dependent exonuclease, which like Xrn1 specifically degrades decapped RNAs harboring 5′ monophosphate extremities, but not RNAs with intact m7G cap. The digested RNAs are then analyzed by RNA sequencing.

RNA degradation in mammalian cells is performed by multiple enzymes and cofactors making it difficult to identify the specific impact of each of them separately. The auxin-inducible degron system enables direct depletion of a protein of interest limiting the time of depletion and thus reducing secondary effects due to cell adaptation. In this chapter, using XRN1 as an example of cytoplasmic RNA decay enzyme, we describe a combination of methods to introduce the auxin-inducible degron by CRISPR-Cas9, together with downstream analyses of RNA levels after protein depletion.

Transcription and RNA decay determine steady-state RNA levels in cells available for translation and RNA-mediated regulatory functions. Both processes can be assessed by various techniques, for majority, based on RNA labelling or chromatin immunoprecipitation, but require a high level of expertise. Here, we describe a cost-effective, fast, and simple protocol that enables the profiling of nascent and mature RNA in the cytoplasm, nucleoplasm, and chromatin through subcellular fractionation. The workflow can include α-amanitin inhibition of RNA Polymerase II to assess nascent RNAs as a proxy of transcriptional activity, or it can be used without this treatment to investigate distribution of partially processed or mature transcripts across distinct subcellular compartments. It is applicable for studying any of RNA biotypes, including small and long noncoding RNAs, mRNAs, and their splice variants, on both transcript-specific and transcriptome-wide scales. Nascent or mature RNAs isolated from each fraction can be further analyzed by any technique of choice (northern blot, reverse transcription, RNA sequencing).

Transition of cytosine to thymine in CpG dinucleotides is the most frequent type of mutation in cancer. This increased mutability is commonly attributed to the spontaneous deamination of 5-methylcytosine (5mC), which is normally repaired by the base-excision repair (BER) pathway. However, the contribution of 5mC deamination in the increasing diversity of cancer mutational signatures remains poorly explored. We integrate mutational signatures analysis in a large series of tumor whole genomes with lineage-specific epigenomic data to draw a detailed view of 5mC deamination in cancer. We uncover tumor type-specific patterns of 5mC deamination signatures in CpG and non-CpG contexts. We demonstrate that the BER glycosylase MBD4 preferentially binds to active chromatin and early replicating DNA, which correlates with lower mutational burden in these domains. We validate our findings by modeling BER deficiencies in isogenic cell models. Here, we establish MBD4 as the main actor responsible for 5mC deamination repair in humans.