Добірка наукової літератури з теми "INSA Lyon"

In this study, we discussed the sound sources localization and characterization for a spur gear transmission, which deals with a vibro-acoustic surveillance for predictive maintenance. The technique uses is based on the near-field Beam forming using Bartlett and Capon estimators. The measurements done on the gear transmission with a rectangular phased array of microphones were performed in acoustics and vibration laboratory (LVA) of the INSA of Lyon, in a semi-anechoic room. The gear transmission was considered sometimes open and sometimes closed. The results are presented as an image showing the acoustic field distribution radiated by the gear transmission at the most energetic frequencies. Both estimators have satisfactory results, but even better for the method with high resolution capon.

Objective To study of the microcirculatory effects of elastic compression stockings. Materials and methods In phlebology, laser Doppler techniques (flux or imaging) are widely used to investigate cutaneous microcirculation. It is a method used to explore microcirculation by detecting blood flow in skin capillaries. Flux and imaging instruments evaluate, non-invasively in real-time, the perfusion of cutaneous micro vessels. Such tools, well known by the vascular community, are not really suitable to our protocol which requires evaluation through the elastic compression stockings fabric. Therefore, we involve another instrument, called the Hematron (developed by Insa-Lyon, Biomedical Sensor Group, Nanotechnologies Institute of Lyon), to investigate the relationship between skin microcirculatory activities and external compression provided by elastic compression stockings. The Hematron measurement principle is based on the monitoring of the skin’s thermal conductivity. This clinical study examined a group of 30 female subjects, aged 42 years ±2 years, who suffer from minor symptoms of chronic venous disease, classified as C0s, and C1s (CEAP). Results The resulting figures show, subsequent to the pressure exerted by elastic compression stockings, an improvement of microcirculatory activities observed in 83% of the subjects, and a decreased effect was detected in the remaining 17%. Among the total population, the global average increase of the skin’s microcirculatory activities is evaluated at 7.63% ± 1.80% ( p < 0.0001). Conclusion The results from this study show that the pressure effects of elastic compression stockings has a direct influence on the skin’s microcirculation within this female sample group having minor chronic venous insufficiency signs. Further investigations are required for a deeper understanding of the elastic compression stockings effects on the microcirculatory activity in venous diseases at other stages of pathology.

Quy hoạch giao thông bền vững đã được đề cập nhiều trong thời gian gần đây, tuy nhiên để triển khai trong thực tiễn, còn gặp nhiều vấn đề bất cập. Câu hỏi đặt ra là phương pháp tiếp cận nào phù hợp cho phép lồng ghép các mục tiêu phát triển bền vững trong triển khai quy hoạch giao thông. Bài viết đưa ra những đánh giá sơ bộ về phương pháp triển khai quy hoạch giao thông truyền thống theo cách tiếp cận dự báo. Phương pháp này dựa trên hiện trạng, phân tích các xu hướng đã và đang xảy ra để dự báo mô hình phát triển cho tương lai. Tuy nhiên, trong nhiều trường hợp, các xu hướng lại không cho thấy mô hình phát triển bền vững trong tương lai. Phương pháp dự báo theo kịch bản là một cách tiếp cận mới, được áp dụng gần đây tại các thành phố phát triển, cho phép lồng ghép các mục tiêu phát triển bền vững vào quy hoạch giao thông. Phương pháp quy định những nhiệm vụ, hành động cần phải triển khai tại thời điểm hiện tại để lấp đi sự thiếu hụt giữa hiện tại và tương lai mong muốn (kịch bản). Báo cáo giới thiệu phần mềm Vensim, như một công cụ dự báo theo kịch bản, hiện đang sử dụng trong nghiên cứu cải thiện giao thông tại khuôn viên INSA Lyon hướng đến môi trường học tập bền vững. Nhận ngày 20/12/2017; sửa xong 31/01/2018; chấp nhận đăng 28/02/2018

The estimation of the Instantaneous Angular Speed (IAS) has in recent years attracted a growing interest in the diagnostics of rotating machines. Measurement of the IAS can be used as a source of information of the machine condition per se, or for performing angular resampling through Computed Order Tracking, a practice which is essential to highlight the machine spectral signature in case of non-stationary operational conditions. In these regards, the SURVISHNO 2019 international conference held at INSA Lyon on 8–10 July 2019 proposed a challenge about the estimation of the instantaneous non-stationary speed of a fan from a video taken by a smartphone, a pocket, low-cost device which can nowadays be found in everyone’s pocket. This work originated by the author to produce an offline motion-tracking of the fan (actually, of the head of its locking-screw) and obtaining then a reliable estimate of the IAS. The here proposed algorithm is an update of the established Template Matching (TM) technique (i.e., in the Signal Processing community, a two-dimensional matched filter), which is here integrated into a Genetic Algorithm (GA) search. Using a template reconstructed from a simplified parametric mathematical model of the features of interest (i.e., the known geometry of the edges of the screw head), the GA can be used to adapt the template to match the search image, leading to a hybridization of template-based and feature-based approaches which allows to overcome the well-known issues of the traditional TM related to scaling and rotations of the search image with respect to the template. Furthermore, it is able to resolve the position of the center of the screw head at a resolution that goes beyond the limit of the pixel grid. By repeating the analysis frame after frame and focusing on the angular position of the screw head over time, the proposed algorithm can be used as an effective offline video-tachometer able to estimate the IAS from the video, avoiding the need for expensive high-resolution encoders or tachometers.

La synthèse proposée ci-dessus provient d’un exercice visant à produire librement un point de vue collégial sur les recherches avicoles à venir. Elle a été élaborée à partir du travail d’un groupe pluridisciplinaire de chercheurs et de représentants des interprofessions et syndicats avicoles français. Elle est issue de deux réunions de la Commission Spécialisée Avicole de l’INRA (8/06/10 et 1/10/10) auxquelles ont participé&nbsp;: E. Blesbois (INRA PHASE), J. Champagne (ITAVI, CIP, SNAA), B. Coudurier (INRA, APA), J.B. Coulon (INRA PHASE), M. Duclos (INRA PHASE), N. Eterradossi (ANSES), X. Fernandez (INRA PHASE), C. Guérin-Dubiard (UMR Agrocampus-INRA CEPIA), H. Juin (INRA PHASE), E. Le Bihan (INRA GA), A.C. Lalmanach (INRA SA), F. Le Hazif (COOP de France), S. Letue (SYNALAF), P. Magdelaine (ITAVI), G. Martel (INRA SAD), G. Le Pottier (CIDEF), F. Pitel (INRA GA), P. Rault (SYSAAF), J.F. Vautherot (INRA SA), L. Zenner (ENV lyon), E. Zundel (INRA, SA). Des experts extérieurs à la commission ont également été sollicités : B. Dedieu (INRA SAD), A. Torre (INRA SAD).

BackgroundOral squamous cell carcinomas (OSCC) prognosis remains poor. While AJCC TNM 8th edition has slightly improved patients‘ stratification with regard to prognostic, innovative approaches to are still needed. As in other tumor types, tumor immune microenvironment (TiME) might represent an opportunity to improve prognostic assessment.MethodsTiME landscape of 47 HPV-negative OSCC was analyzed using multiplex immunofluorescence (mIF). Markers for tumor cells (PanCK), tumor infiltrating lymphocytes (CD3, CD8), macrophages (CD68), inhibitory (PD-1, PD-L1, TIM3, LAG3, VISTA) or stimulatory (OX40, ICOS) immune checkpoints (ICP) were studied. Regions of interest (ROI), 5 in the tumor core and 5 at the invasion front, were subjected to cell markers identification and quantification (scoring) as well as tissue compartmentalization to divide them in tumor-epithelial and tumor-stroma compartments, respectively. A total of 20 cell phenotypes were defined based on previous work (CK+, CK+PD-L1+, CD3+, CD3+CD8+, CD3+PD-1+, CD3+CD8+PD-1+, CD3+PD-L1+, CD3+CD8+PD-L1+, CD3+PD-L1+PD-1+, CD3+CD8+PD-L1+PD-1+, CD68+, CD68+PD-L1+, CK+OX40+, CD3+VISTA+, CD3+ICOS+, CD3+LAG3+, CD3+OX-40+, CD3+TIM3+). Results were correlated with clinical features including disease-specific survival (DSS) using the Kaplan-Meier method and a multivariate Cox model. A multivariate general linear model (GLM) was built to test the specific association of each variable with a given cell density by correcting the possible confusion due to other variables.ResultsImmune cells densities were significantly higher overall in the stroma. The intra-tumor stroma showed a significant enrichment of in CD3+PD-1+ T cells compared to peri-tumor stroma. None of the clinical or pathological (resection margin, tumor stage, lymph node invasion, perineural invasion) was significantly associated with DSS. In contrast, the following cell phenotypes in the tumor invasion front were strongly associated with a poor DSS, including CD3+PD-L1+ (P-value= 0.004), CD3+PD1+PD-L1+ (P-value= 0.02) and CD3+OX40+ (P-value= 0.02) T cells as well as CD3+CD8+PD-1+ (P-value= 0.048), CD3+CD8+PD-L1+ (P-value= 0.008) and CD3+CD8+PD1+PD-L1+ (P-value= 0.01) cytotoxic T cells. In the tumor core, CD68+PD-L1- macrophages (P-value= 0.06) were marginally associated with better DSS. Using a GLM, we found that tumor from smoker-drinker patients and/or with pN+, were significantly more infiltrated by PD-1- and/or PD-L1-positive immune cells. On the other hand, floor of mouth and gingiva-mandibular OSCC were significantly less infiltrated than others.ConclusionsThe prognostic value of PD-1+ and/or PD-L1+ cells in the invasion front of resected OSCC was remarkable, underlying the importance of this area when studying the TiME. Incorporating TiME analysis in the invasion front may improve prognostic evaluation of patients treated for OSCC, especially in the context of immunotherapy.AcknowledgementsThis study was supported by a strategic alliance between the Translational Molecular Pathology-Immunoprofiling las (TMP-IL) at the Department Translational Molecular Pathology, the University of Texas MD Anderson Cancer Center and the Université Claude Bernard Lyon, Centre de Recherche en Cancérologie de Lyon and the Department of Translational Medicine, Centre Léon Bérard, Lyon, France. The authors would acknowledge ITMO Cancer 2020, ”Formation à la Recherche Fondamentale et Translationnelle en Cancérologie” (JB); CLARA 2020 ”Soutien à la mobilité des jeunes chercheurs en oncologie, N° CVPPRCAN000198” (JB); Fondation de France 2020 ”Aide à la mobilité international de médecins et pharmaciens, N° 00112162” (JB); Ligue contre le cancer 2021, comité de Saône-et-Loire (PS); 2017-INCa-DGOS-Inserm_12563: INCa SIRIC-LYriCAN INCa-DGOS-Inserm_12563 (PS)Ethics ApprovalThe study was conducted in accordance with all applicable laws, rules, and requests of French and European government authorities. Written informed consent was obtained from all patients and the study was approved by the Centre Leon Bérard institutional review board (Lyon, France). Samples were obtained from the CRB Centre Léon Bérard (n°BB-0033-00050) which is quality certified according NFS96-900 French standard and ISO 9001 for clinical trials.ConsentWritten informed consent was obtained from all patients and the study was approved by the Centre Leon Bérard institutional review board (Lyon, France)

BackgroundHead and Neck Squamous Cell Carcinoma is the 8th leading cancer worldwide and it is associated with significant morbidity and mortality.1 2 Tumor microenvironment (TME) is dynamic and it plays an important role in head and neck carcinogenesis.3 4 Cytotoxic T-cells, immune checkpoint molecules such as programmed cell death 1 (PD-1), its ligand (PD-L1), and other checkpoints molecules have been described in these tumors.1 3 This study aimed to characterize the TME of oral squamous cell carcinoma (OSCC) and compare with their pathology features.MethodsFour microns thickness consecutives slides from representative OSCC (N=46) cases were stained and analyzed using 11 biomarkers (CK, CD3, CD8, CD68, PD1, PDL1, LAG3, TIM3, ICOS, VISTA, OX40) placed in two multiplex immunofluorescence panels to characterize the TME. For image analysis, the samples were divided in tumor, stroma and peritumoral compartment. Co-expression of markers (cell phenotypes) where analyzed as densities by mm2 in each compartment. For PD-L1 expression by malignant cells (CK+PD-L1+) we set up a cutoff of positive case as ≥ than 1%. Cell phenotypes were correlated with anatomopathological information retrieved from records such as tumor size, margin status, stage and perineural, lymphovascular, and bone invasion among others. Statistical analyses and plots were performed using SPSS and Graphpad prism8 software packages.ResultsWe found significant higher cell density for CK+PDL1+ (P= 0.038), CD3+PDL1+ (P= 0.027), CD3+CD8+PDL1+ (P=0.040) in female patients compared with the male population. Interestingly, smaller tumor size (≤ median, 25mm) showed higher densities of CD3+ (P= 0.006), CD3+CD8+ (P= 0.007), CD3+PDL1+ (P= 0.037), CD3+CD8+PDL1+ (P= 0.016), CD3+ICOS+ (P= 0.036), CD3+VISTA+ (P= 0.001), CD68+ (P= 0.001) and CD68+PD-L1+ (P= 0.008) than large tumors. Additionally, high cell density CD3+OX40+ (P= 0.011) was observed in tumors without margin invasion and high cell density for macrophages CD68+ (p= 0.005) in tumors without bone invasion. In ulcerative and infiltrative tumor pattern we observed higher cell density of CD3+PDL1+ (P= 0.020), CD3+CD8+PDL1+ (P=0.006) and CD3+OX40+ (P= 0.022) than non-ulcerate and no infiltrative pattern. Lastly, 58.7% of cases were PDL1+.ConclusionsOur findings of a diminished immune response in larger tumors might be correlated to their potential role in tumor aggressiveness and progression. Furthermore, high cell density of macrophages on tumor bone invasion may suggest an immune suppressive M2 response supported by the presence of PDL1+ expression. All these results can be the first approach for the development of a treatment based of immune interception.AcknowledgementsThis study was supported by a strategic alliance between the Translational Molecular Pathology-Immunoprofiling las (TMP-IL) at the Department Translational Molecular Pathology, the University of Texas MD Anderson Cancer Center and the Université Claude Bernard Lyon, Centre de Recherche en Cancérologie de Lyon and the Department of Translational Medicine, Centre Léon Bérard, Lyon, France. The authors would acknowledge ITMO Cancer 2020, ”Formation à la Recherche Fondamentale et Translationnelle en Cancérologie” (JB); CLARA 2020 ”Soutien à la mobilité des jeunes chercheurs en oncologie, N° CVPPRCAN000198” (JB); Fondation de France 2020 ”Aide à la mobilité international de médecins et pharmaciens, N° 00112162” (JB); Ligue contre le cancer 2021, comité de Saône-et-Loire (PS); 2017-INCa-DGOS-Inserm_12563: INCa SIRIC-LYriCAN INCa-DGOS-Inserm_12563 (PS)ReferencesCohen EEW, Bell RB, Bifulco CB, Burtness B, Gillison ML, Harrington KJ, et al. The society for immunotherapy of cancer consensus statement on immunotherapy for the treatment of squamous cell carcinoma of the head and neck (HNSCC). J Immunother Cancer 2019;7(1):184. Bouaoud J, Foy JP, Tortereau A, Michon L, Lavergne V, Gadot N, et al. Early changes in the immune microenvironment of oral potentially malignant disorders reveal an unexpected association of M2 macrophages with oral cancer free survival. Oncoimmunology 2021;10(1):1944554.Mei Z, Huang J, Qiao B, Lam AK. Immune checkpoint pathways in immunotherapy for head and neck squamous cell carcinoma. Int J Oral Sci 2020;12(1):16.Yokota T, Homma A, Kiyota N, Tahara M, Hanai N, Asakage T, et al. Immunotherapy for squamous cell carcinoma of the head and neck. Jpn J Clin Oncol 2020;50(10):1089–96.Ethics ApprovalThe study was conducted in accordance with all applicable laws, rules, and requests of French and European government authorities. Written informed consent was obtained from all patients and the study was approved by the Centre Leon Bérard institutional review board (Lyon, France). Samples were obtained from the CRB Centre Léon Bérard (n°BB-0033-00050) which is quality certified according NFS96-900 French standard and ISO 9001 for clinical trials.

Dix années après la publication du rapport de la FAO « Livestock’s long shadow », qui fait toujours référence dans les débats sur les impacts de l’élevage et la part des produits animaux dans notre alimentation, quels sont les nouveaux résultats de recherche qui affinent ce panorama mondial ? Pour répondre à cette question, les ministères français en charge de l’Environnement et de l’Agriculture ainsi que l’ADEME ont sollicité l’INRA pour synthétiser les connaissances scientifiques disponibles sur les rôles, impacts et services issus des élevages en Europe. L’exercice, qui a pris la forme d’une Expertise scientifique collective (ESCo), s’est donc intéressé aux différentes fonctions et conséquences de la production et de la consommation de produits animaux sur l’environnement et le climat, l’utilisation des ressources, les marchés, le travail et l’emploi, et les enjeux sociaux et culturels. L’expertise s’est centrée sur les services et impacts des principaux animaux d’élevage « terrestres », bovins laitiers ou allaitants, petits ruminants, porcs et volailles, et de leurs filières à l’échelle européenne. Le terme « services » renvoie à la fourniture d’un avantage marchand ou non marchand issu des activités d’élevage et/ou de l’usage de produits d’origine animale, soit une acceptation plus large que celle des services écosystémiques fournis par les agroécosystèmes. Nous utilisons l’expression « services et impacts » car les deux termes sont spontanément complémentaires, les services étant en général connotés de manière positive tandis que les impacts le sont négativement. Associer ces deux termes conduit à considérer les différents effets de l’élevage conjointement, et à souligner les complémentarités et antagonismes qui résultent des interactions entre les processus écologiques, biotechniques et économiques mis en jeu. La notion de « bouquets de services » constitue aujourd’hui un front de science dynamique dont nous avons cherché à extraire ce qui est spécifique à l’élevage. L’analyse a mis l’accent sur la variabilité des bouquets de services fournis par l’élevage selon les territoires. Une expertise scientifique consiste en un état des lieux critique des connaissances disponibles à partir d’une analyse exhaustive de la littérature scientifique. L’objectif est de dégager les acquis sur lesquels peut s’appuyer la décision publique, et de pointer les controverses, incertitudes ou lacunes du savoir scientifique. Placée sous la responsabilité scientifique de Bertrand Dumont, zootechnicien et écologue (INRA), et de Pierre Dupraz, économiste (INRA) celle-ci a réuni, pendant deux ans, vingt-six experts1 issus de différentes disciplines et institutions, et travaillant dans différents contextes afin que la diversité des résultats et des arguments scientifiques soit prise en compte. Le collectif d’experts a bénéficié de l’encadrement méthodologique de la Délégation à l’expertise, à la prospective et aux études (Depe) qui a assuré la coordination du projet, l’appui documentaire (avec la contribution des départements Phase et SAE2) et l’analyse cartographique. Le travail a abouti à la rédaction d’un rapport principal de plus de mille pages présenté publiquement en novembre 2016, d’une synthèse de 126 pages et d’un résumé en français et en anglais de huit pages. Le tout est disponible sur le site de l’INRA : http://institut.inra.fr/Missions/Eclairer-les-decisions/Expertises/Toutes-les-actualites/Roles-impacts-et-services-issus-des-elevages-europeens. Ce numéro spécial s’appuie principalement sur les éléments développés dans les chapitres 2, 6 et 7 du rapport. Le regard critique des relecteurs et le travail de réécriture des auteurs y apportent une réelle plus-value. Le premier article, coordonné par Michel Duru, présente le cadre conceptuel que nous avons proposé à partir de la littérature sur les systèmes socio-écologiques, afin de représenter de manière structurée la diversité des services et impacts rendus par les systèmes d’élevage (et de polyculture-élevage) dans les territoires. Le deuxième article coordonné par Jonathan Hercule et Vincent Chatellier établit une typologie des territoires d’élevage européens qui repose sur deux critères simples et disponibles dans les bases de données : la part des prairies permanentes dans la Surface Agricole Utile (SAU) et la densité animale par hectare de SAU. En croisant ces deux variables, nous distinguons six types de territoires que nous avons cartographiés à l’échelle européenne. Dans les cinq articles qui suivent, nous décrivons les bouquets de services rendus par l’élevage dans les territoires où il est bien représenté, le sixième type correspondant aux zones de grandes cultures. Nous analysons la variabilité qui existe autour du bouquet de services propre à chaque type, et la dynamique d’évolution de l’élevage selon les territoires. Nous traitons ainsi des territoires à haute densité animale qui concentrent 29% du cheptel européen sur seulement 10% du territoire (Dourmad et al), des territoires herbagers à haute (Delaby et al), moyenne (Vollet et al) ou faible densité animale (Lemauviel-Lavenant et Sabatier), et des territoires de polyculture-élevage (Ryschawy et al). Les deux articles qui suivent s’attachent à des configurations qui ne sont pas représentées sur la carte européenne, mais sont potentiellement présentes dans chaque catégorie de notre typologie. Nous analysons comment certaines filières s’adaptent à des attentes sociétales accrues en matière d’alimentation (produits de qualité, circuits courts) et de qualité de la vie. Marc Benoit et Bertrand Méda abordent cette question à partir d’une analyse croisée des systèmes ovins en Agriculture Biologique et poulets Label Rouge, Claire Delfosse et al en synthétisant la littérature encore fragmentaire sur l’élevage urbain et périurbain. L’article conclusif, coordonné par Bertrand Dumont, porte au débat les enseignements tirés des cartographies de services, et des modélisations et scénarios prospectifs globaux. Il propose différentes pistes pour mieux valoriser la diversité des services fournis par l’élevage. Les différents articles de ce numéro illustrent ainsi le large panorama des services et impacts de l’élevage européen. Nous espérons qu’ils donnent à voir non seulement le rôle de l’élevage vis-à-vis de la production de denrées alimentaires, de l’emploi, des dynamiques territoriales et de la construction des paysages, mais aussi comment l’élevage pourrait mieux répondre aux attentes légitimes de nos concitoyens en matière de préservation de l’environnement, de bien-être animal et de traçabilité des circuits alimentaires. Notre ambition est d’aider à sortir d’un débat qui ne considère trop souvent qu’une partie de ces effets. L’intérêt pédagogique de la grange et de la typologie des territoires d’élevage européens a déjà été largement souligné. Gageons qu’il confère à ce numéro spécial un intérêt particulier pour l’enseignement agronomique et le développement agricole. Bertrand Dumont (Inra Phase), Pierre Dupraz (Inra SAE2), Julie Ryschawy (Inra SAD, INPT) et Catherine Donnars (Inra Depe) -------1 Composition du collectif d’experts : B Dumont et P Dupraz (coord.), J. Aubin (INRA), M. Benoit (INRA), Z. Bouamra-Mechemache (INRA), V. Chatellier (INRA), L. Delaby (INRA), C. Delfosse (Univ. Lyon II), J.-Y. Dourmad (INRA), M. Duru (INRA), M. Friant-Perrot (CNRS, Univ. Nantes), C. Gaigné (INRA), J.-L. Guichet (Univ. Beauvais), P. Havlik (IIASA, Autriche), N. Hostiou (INRA), O. Huguenin-Elie (Agroscope, Suisse), K. Klumpp (INRA), A. Langlais (CNRS, Univ. Rennes), S. Lemauviel-Lavenant (Univ. Caen), O. Lepiller (CNRS, Univ. Toulouse), B. Méda (INRA), J. Ryschawy (INRA, INPT), R. Sabatier (INRA), I. Veissier (INRA), E. Verrier (Agroparistech), D. Vollet (Irstea).

Introduction In the last decade, intensive multi-agent combination treatment has boosted survival and cure to approximately 80% of pediatric T-cell acute lymphoblastic leukemia (T-ALL) patients. Nevertheless, patients that relapse have a very poor prognosis due to acquired therapy resistance. The current highly intensive chemotherapy is accompanied by severe toxicity, resulting in either death or frequent detrimental long-term side effects for survivors, with a relevant impairment of their quality of life. Therefore, there is an urgent need for new targeted therapies as well as reliable biomarkers that can predict treatment outcome and therapy resistance. Protein kinase inhibitors are amongst the most successful small-molecule drugs used for cancer treatment. However, for T-ALL patients the use of protein kinase inhibitors is still limited to clinical trials. Furthermore, targetable kinases activated by gene fusions are rare in T-ALL in contrast to other types of leukemia, and are often present at the subclonal level (e.g. episomal amplification of the NUP214-ABL1 fusion in 6% of patients at diagnosis). Nevertheless, leukemic blasts rely on enhanced kinase signaling to sustain dysregulated proliferation. Therefore, protein kinases can be activated even in the absence of genetic mutations in their coding sequences. In addition to screening for disease-associated genomic alterations in patient biopsies, profiling of aberrant protein kinase activity may offer opportunities for targeted therapeutic approaches. Aim High-throughput phospho-proteomics can provide direct information on pathway activation, kinase signaling networks and may therefore be used to identify novel therapy targets. Here, we aimed to identify kinase activation patterns in established T-ALL cell lines and to test their differential sensitivity to targeted kinase inhibitors in order to develop a strategy to predict leukemia dependencies. Methods We performed unbiased, mass spectrometry-based phospho-proteomic profiling of 11 established T-ALL cell lines. By combining titanium dioxide-based enrichment with selective phospho-tyrosine immunoprecipitation, we identified about 3700 tyrosine phospho-sites and more than 13300 serine/threonine phosphorylation sites. Multiple approaches have been developed to infer kinase activity from phospho-proteomic data. We applied the Inferred Kinase Activity (INKA) scoring to rank kinase activation in our cell lines. This ranking is not only based on the phosphorylation of kinases but also integrates information on phosphorylated substrates (Beekhof et al, Mol Syst Biol. 2019). Results We found SRC-family members as most activated kinases in T-ALL cell lines, with a major role for LCK, SRC, FYN, and YES1. Certain cell lines also revealed high activity of ABL1, ZAP70, LYN, and FGR. Additionally, other active kinases identified include INSR, CLK1, CDK1/2/7 and PAK1/2. To test the dependency of the cell lines to the predicted SRC-family kinases activation, cellular response levels were measured towards dasatinib, a SRC/ABL multi-kinase inhibitor. Surprisingly, only the cell lines with known genetic kinases aberrations-e.g. HSB-2 (TCRB-LCK translocated) and ALL-SIL (NUP214-ABL1 rearranged)-showed strong sensitivity to dasatinib. The remaining 9 lines were resistant to dasatinib treatment and seemed not to be solely dependent on the predicted kinase activities for their survival, indicating the need for therapeutic combinations that target additional parallel kinase activities. To unravel actual kinase dependencies rather than kinase activities, analysis of the overall phosphorylation profiles yielded specific 'phospho'-signatures that associate with dasatinib responsiveness. Therefore, individual T-ALL cell lines can be used as calibrator to predict and quantify signaling dependencies that associate with response to targeted kinase inhibitors in primary T-ALL biopsies. Conclusion The identification of oncogenic dependencies by ranking kinases activities and their signaling networks from phospho-proteomic profiling data can guide the assignment of T-ALL patients to specific kinase inhibitors treatment. Furthermore, these phospho-signatures may provide important drug response biomarkers as well as explain possible compensatory mechanisms for therapy resistance. Disclosures No relevant conflicts of interest to declare.

Les évolutions du paysage informationnel suggèrent qu’il est nécessaire d’acquérir une culture informationnelle c’est-à-dire des connaissances techniques et pratiques d’outils numériques et la conscience des enjeux et impacts des informations à retenir, diffuser ou éviter. Pourtant, l’université n’intègre pas systématiquement de cursus de formation prenant cet aspect en compte. Notre travail de recherche est situé dans le contexte d’une grande école, l’INSA Lyon, qui se propose de former des ‘Ingénieurs Humanistes’. Il interroge la possibilité pour une bibliothèque universitaire, sur l’exemple de la bibliothèque Marie Curie, de mobiliser les ressources nécessaires pour impulser la mise en place d’un cursus de formation pour la compétence informationnelle. En croisant le concept de ‘compétence’, ses implications théoriques et pratiques pour la construction de la compétence chez l’apprenant, avec les concepts de ‘compétence informationnelle’ et de ‘culture informationnelle’, nous proposons un modèle pour la conception de l’enseignement-apprentissage visant la construction de la compétence informationnelle. Ce modèle devient notre grille de lecture et d’analyse des documents et propos recueillis. Tous nos recueils de données, analyse qualitative de documents, d’interviews d’enseignants et responsables de département, puis d’étudiants après l’analyse quantitative d’une enquête par questionnaire, participent à notre compréhension de notre objet de recherche, restituée dans cette thèse. Malgré les limites de ce travail, inhérent à notre posture impliquée dans notre terrain de recherche, notre vision globale de l’enseignement-apprentissage visant la construction de la compétence informationnelle montre l’intérêt d’un référentiel de formation, mais révèle les points de blocages, avec en particulier l’absence d’une vision commune de la compétence informationnelle nécessaire aux ingénieurs. En conséquence, la prise en compte des composantes de la compétence informationnelle par les étudiants reste très hétérogène. Les blocages se situent aussi en dehors de la vision de la compétence informationnelle et concernent la formation pour des compétences : conception de l’enseignement encore imprégnée du modèle épistémique de la connaissance transmise, collaborations souvent sur un mode disciplinaire ou pluridisciplinaire, classements des étudiants qui hiérarchisent les disciplines, projets parfois orientés par les solutions pour un client. La formation pour la compétence informationnelle à l’INSA Lyon, exigerait, avant la définition des situations complexes propices à la mobilisation de compétences, un consensus autour de ‘l’ingénieur humaniste’. Sa culture technique et scientifique serait reconnue ; il pourrait s’affirmer comme un ingénieur particulièrement apte au travail relationnel, ne reniant pas son rôle et sa responsabilité politique dans la société, soucieux de s’appuyer sur l’intelligence collective et le partage d’une information fiable dans l’entreprise. Sa formation nécessiterait un cadre épistémique de la connaissance socio-construite, l’interdisciplinarité, la réflexion sur l’information et la construction des savoirs avec des projets mis en perspective au-delà des besoins actuels de l’entreprise. La vision partagée du profil de sortie de l’ingénieur, à construire selon l’approche programme, permettrait aux enseignantes-bibliothécaires de travailler à de nouvelles propositions, autour des concepts et des outils d’information. Notre étude engage à poursuivre les travaux autour de la transformation pédagogique du supérieur et ouvre des perspectives de recherches collaboratives, entre sciences de l’information et de la communication, sciences de l’éducation et de la formation et d’autres disciplines pour reproblématiser et recontextualiser la compétence informationnelle afin de développer une formation visant une culture informationnelle du 21ème siècle
Changes in the information landscape suggest that it is necessary to acquire an information culture, i.e. technical and practical knowledge of digital tools and awareness of the issues and impacts of information to be retained, disseminated or avoided. However, universities do not systematically integrate training programmes that take this aspect into account. Our research work is situated in the context of a major school, INSA Lyon, which aims to train 'Humanist Engineers'. It questions the possibility for a university library, on the example of the Marie Curie library, to mobilise the necessary resources to encourage the setting up of a training course for information literacy. By crossing the concept of 'competence', its theoretical and practical implications for the construction of competence in the learner, with the concepts of 'information literacy' and 'information culture', we propose a model for the design of teaching-learning aimed at the construction of information literacy. This model becomes our grid for reading and analysing the documents and statements collected. All our data collection, qualitative analysis of documents, interviews with teachers and department heads, and students after the quantitative analysis of a questionnaire survey, contribute to our understanding of our research object, which is presented in this thesis. Despite the limits of this work, inherent to our posture involved in our research field, our global vision of teaching-learning aiming at the construction of information literacy shows the relevance of a training framework, but reveals the blocking points, with in particular the absence of a common vision of the information literacy necessary for engineers. As a result, students' consideration of the components of information literacy remains very heterogeneous. The blockages also lie outside the vision of information literacy and concern training for competences: conception of teaching still impregnated with the epistemic model of transmitted knowledge, collaborations often in a disciplinary or multidisciplinary mode, student rankings that prioritise disciplines, projects sometimes oriented by solutions for a client. Training for informational competence at INSA Lyon would require, before defining complex situations conducive to the mobilisation of skills, a consensus around the 'humanist engineer'. His technical and scientific culture would be recognised; he would be able to assert himself as an engineer particularly suited to relational work, not denying his role and his political responsibility in society, anxious to rely on collective intelligence and the sharing of reliable information within the company. Its training would require an epistemic framework of socio-constructed knowledge, interdisciplinarity, reflection on information and the construction of knowledge with projects put into perspective beyond the current needs of the company. The shared vision of the engineer's output profile, to be constructed according to the programme approach, would allow teacher-librarians to work on new proposals, around information concepts and tools. Our study calls for further work on the pedagogical transformation of higher education and opens up prospects for collaborative research between information and communication sciences, education and training sciences and other disciplines to re-problematise and re-contextualise information literacy in order to develop training for 21st century information literacy