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Your search keyword '"Emmanuel Grolleau"' showing total 152 results
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152 results on '"Emmanuel Grolleau"'

1. Resource constraint scheduling on two dedicated machines: Application to avionics

Author

Ouissem Mesli-Kesraoui, Loic Ledreck, Emmanuel Grolleau, Soraya Kesraoui, Pascal Berruet, Yassine Ouhammou, and Patrick Girard

Subjects
Resource scheduling, Parallel machines, Dedicated parallel machines, Hydraulic circuits, Linear programming, Applied mathematics. Quantitative methods, T57-57.97, Electronic computers. Computer science, QA75.5-76.95
Abstract

In civil aircraft, two partially redundant hydraulic circuits typically power various systems. During assembly, a critical phase involves simultaneously rinsing and purging these hydraulic circuits using loops. Precedence constraints are necessary to prevent the recontamination of already rinsed loops, leading to increased rinsing time. This paper presents this problem as a unique instance of the Resource Constrained Parallel Machine Scheduling Problem, where each circuit represents a machine, pipe loops to be rinsed represent jobs, and machines share a hydraulic power source. For two dedicated processors and a single resource, an optimal schedule minimizing the makespan can be generated in polynomial time. However, due to the requirement of rinsing certain pipe loops on a circuit before others, there are precedence constraints between some jobs within the same circuit. By employing a reduction of the 3-partition problem, we demonstrate that this situation results in a problem that is NP-hard in the strong sense. We evaluate several Mixed-Integer Linear Programming and Constraint Programming formulations of the problem, using Cplex, CPO, Gurobi, and Z3, against several proposed heuristics. Given that the size of the instances we need to solve exceeds what can be solved in acceptable time by solvers, we propose a heuristic and compare its performance with the optimum. more...

Published
2024
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2. Circulating H3K27 Methylated Nucleosome Plasma Concentration: Synergistic Information with Circulating Tumor DNA Molecular Profiling

Author

Emmanuel Grolleau, Julie Candiracci, Gaelle Lescuyer, David Barthelemy, Nazim Benzerdjeb, Christine Haon, Florence Geiguer, Margaux Raffin, Nathalie Hardat, Julie Balandier, Rémi Rabeuf, Lara Chalabreysse, Anne-Sophie Wozny, Guillaume Rommelaere, Claire Rodriguez-Lafrasse, Fabien Subtil, Sébastien Couraud, Marielle Herzog, and Lea Payen-Gay more...

Subjects
NSCLC, epigenetics, histone PTM, H3K27Me3 nucleosome, ctDNA, liquid biopsy, Microbiology, QR1-502
Abstract

The molecular profiling of circulating tumor DNA (ctDNA) is a helpful tool not only in cancer treatment, but also in the early detection of relapse. However, the clinical interpretation of a ctDNA negative result remains challenging. The characterization of circulating nucleosomes (carrying cell-free DNA) and associated epigenetic modifications (playing a key role in the tumorigenesis of different cancers) may provide useful information for patient management, by supporting the contributive value of ctDNA molecular profiling. Significantly elevated concentrations of H3K27Me3 nucleosomes were found in plasmas at the diagnosis, and during the follow-up, of NSCLC patients, compared to healthy donors (p-value < 0.0001). By combining the H3K27Me3 level and the ctDNA molecular profile, we found that 25.5% of the patients had H3K27Me3 levels above the cut off, and no somatic alteration was detected at diagnosis. This strongly supports the presence of non-mutated ctDNA in the corresponding plasma. During the patient follow-up, a high H3K27Me3-nucleosome level was found in 15.1% of the sample, despite no somatic mutations being detected, allowing the identification of disease progression from 43.1% to 58.2% over molecular profiling alone. Measuring H3K27Me3-nucleosome levels in combination with ctDNA molecular profiling may improve confidence in the negative molecular result for cfDNA in lung cancer at diagnosis, and may also be a promising biomarker for molecular residual disease (MRD) monitoring, during and/or after treatment. more...

Published
2023
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47. Paired Comparison of Routine Molecular Screening of Patient Samples with Advanced Non-Small Cell Lung Cancer in Circulating Cell-Free DNA Using Three Targeted Assays

Author

David Barthelemy, Gaelle Lescuyer, Florence Geiguer, Emmanuel Grolleau, Arnaud Gauthier, Julie Balandier, Margaux Raffin, Claire Bardel, Bruno Bouyssounouse, Claire Rodriguez-Lafrasse, Sébastien Couraud, Anne-Sophie Wozny, and Léa Payen more...

Subjects
Cancer Research, lung cancer, MRD, Oncology, digital PCR, cfDNA, NSCLC, early stages, comparison of methods, custom validated NGS assay, performance
Abstract

Introduction: Progressive advanced non-small cell lung cancer (NSCLC) accounts for about 80–85% of all lung cancers. Approximately 10–50% of patients with NSCLC harbor targetable activating mutations, such as in-frame deletions in Exon 19 (Ex19del) of EGFR. Currently, for patients with advanced NSCLC, testing for sensitizing mutations in EGFR is mandatory prior to the administration of tyrosine kinase inhibitors. Patients and Methods: Plasma was collected from patients with NSCLC. We carried out targeted NGS using the Plasma-SeqSensei™ SOLID CANCER IVD kit on cfDNA (circulating free DNA). Clinical concordance for plasma detection of known oncogenic drivers was reported. In a subset of cases, validation was carried out using an orthogonal OncoBEAMTM EGFR V2 assay, as well as with our custom validated NGS assay. Somatic alterations were filtered, removing somatic mutations attributable to clonal hematopoiesis for our custom validated NGS assay. Results: In the plasma samples, driver targetable mutations were studied, with a mutant allele frequency (MAF) ranging from 0.00% (negative detection) to 82.25%, using the targeted next-generation sequencing Plasma-SeqSensei™ SOLID CANCER IVD Kit. In comparison with the OncoBEAMTM EGFR V2 kit, the EGFR concordance is 89.16% (based on the common genomic regions). The sensitivity and specificity rates based on the genomic regions (EGFR exons 18, 19, 20, and 21) were 84.62% and 94.67%. Furthermore, the observed clinical genomic discordances were present in 25% of the samples: 5% in those linked to the lower of coverage of the OncoBEAMTM EGFR V2 kit, 7% in those induced by the sensitivity limit on the EGFR with the Plasma-SeqSensei™ SOLID CANCER IVD Kit, and 13% in the samples linked to the larger KRAS, PIK3CA, BRAF coverage of the Plasma-SeqSensei™ SOLID CANCER IVD kit. Most of these somatic alterations were cross validated in our orthogonal custom validated NGS assay, used in the routine management of patients. The concordance is 82.19% in the common genomic regions (EGFR exons 18, 19, 20, 21; KRAS exons 2, 3, 4; BRAF exons 11, 15; and PIK3CA exons 10, 21). The sensitivity and specificity rates were 89.38% and 76.12%, respectively. The 32% of genomic discordances were composed of 5% caused by the limit of coverage of the Plasma-SeqSensei™ SOLID CANCER IVD kit, 11% induced by the sensitivity limit of our custom validated NGS assay, and 16% linked to the additional oncodriver analysis, which is only covered by our custom validated NGS assay. Conclusions: The Plasma-SeqSensei™ SOLID CANCER IVD kit resulted in de novo detection of targetable oncogenic drivers and resistance alterations, with a high sensitivity and accuracy for low and high cfDNA inputs. Thus, this assay is a sensitive, robust, and accurate test. more...

Published
2023
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