Les documents scientifiques informels: un patrimoine peu exploré, témoin de la construction des savoirs

L'objectif du projet ECRITO était de contribuer à préserver et à valoriser les documents scientifiques produits quotidiennement par les chercheurs de Midi-Pyrénées, en amont des publications formelles : non seulement les articles, communications ou monographies, qui constituent la partie visible de la recherche, mais aussi tous les matériaux et informations accumulés par les chercheurs, et sur la base desquels se construit leur travail. Ces matériaux sont de types très divers : littérature " grise " (rapports, mémoires, documentation techniques...), documents textuels " informels " (carnets, notes, brouillons, correspondances, cahiers de laboratoires), corpus visuels, sonores ou multimédia (campagnes photographiques, campagnes d'enquêtes, enregistrements audio ou vidéo), données électroniques (bases de données, fichiers informatiques), etc. Le projet visait également à prolonger, de manière exploratoire, le questionnement sur le patrimoine scientifique à partir des traces matérielles produites quotidiennement par les chercheurs dans leurs activités de recherche. Ces traces représentent en effet une fenêtre irremplaçable sur la science en train de se construire : elles permettent de rendre visible et compréhensible le processus habituellement dissimulé de production de la science, ce qui constitue un enjeu scientifique et pédagogique fondamental

Photometric stereo data for the validation of a structural health monitoring test rig

Photometric stereo uses images of objects illuminated from various directions to calculate surface normals which can be used to generate 3D meshes of the object. Such meshes can be used by engineers to estimate damage of a concrete surface, or track damage progression over time to inform maintenance decisions. This dataset [1] was collected to quantify the uncertainty in a photometric stereo test rig through both the comparison with a well characterised method (coordinate measurement machine) and experiment virtualisation. Data was collected for 9 real objects using both the test rig and the coordinate measurement machine. These objects range from clay statues to damaged concrete slabs. Furthermore, synthetic data for 12 objects was created via virtual renders generated using Blender (3D software) [2]. The two methods of data generation allowed the decoupling of the physical rig (used to light and photograph objects) and the photometric stereo algorithm (used to convert images and lighting information into 3D meshes). This data can allow users to: test their own photometric stereo algorithms, with specialised data created for structural health monitoring applications; provide an industrially relevant case study to develop and test uncertainty quantification methods on test rigs for structural health monitoring of concrete; or develop data processing methodologies for the alignment of scaled, translated, and rotated data

In Vivo Determination of Fluctuating Forces during Endosome Trafficking Using a Combination of Active and Passive Microrheology

BACKGROUND: Regulation of intracellular trafficking is a central issue in cell biology. The forces acting on intracellular vesicles (endosomes) can be assessed in living cells by using a combination of active and passive microrheology. METHODOLOGY/PRINCIPAL FINDINGS: This dual approach is based on endosome labeling with magnetic nanoparticles. The resulting magnetic endosomes act both as probes that can be manipulated with external magnetic fields to infer the viscoelastic modulus of their surrounding microenvironment, and as biological vehicles that are trafficked along the microtubule network by means of forces generated by molecular motors. The intracellular viscoelastic modulus exhibits power law dependence with frequency, which is microtubule and actin-dependent. The mean square displacements of endosomes do not follow the predictions of the fluctuation-dissipation theorem, which offers evidence for active force generation. Microtubule disruption brings the intracellular medium closer to thermal equilibrium: active forces acting on the endosomes depend on microtubule-associated motors. The power spectra of these active forces, deduced through the use of a generalized Langevin equation, show a power law decrease with frequency and reveal an actin-dependent persistence of the force with time. Experimental spectra have been reproduced by a simple model consisting in a series of force steps power-law distributed in time. This model enlightens the role of the cytoskeleton dependent force exerted on endosomes to perform intracellular trafficking. CONCLUSIONS/SIGNIFICANCE: In this work, the influence of cytoskeleton components and molecular motors on intracellular viscoelasticity and transport is addressed. The use of an original probe, the magnetic endosome, allows retrieving the power spectrum of active forces on these organelles thanks to interrelated active and passive measures. Finally a computational model gives estimates of the force itself and hence of the number of the motors pulling on endosomes

Ploidy of Cell-Sorted Trophic and Cystic Forms of Pneumocystis carinii

Once regarded as an AIDS-defining illness, Pneumocystis pneumonia (PcP) is nowadays prevailing in immunocompromised HIV-negative individuals such as patients receiving immunosuppressive therapies or affected by primary immunodeficiency. Moreover, Pneumocystis clinical spectrum is broadening to non-severely-immunocompromised subjects who could be colonized by the fungus while remaining asymptomatic for PcP, thus being able to transmit the infection by airborne route to susceptible hosts. Although the taxonomical position of the Pneumocystis genus has been clarified, several aspects of its life cycle remain elusive such as its mode of proliferation within the alveolus or its ploidy level. As no long-term culture model exists to grow Pneumocystis organisms in vitro, an option was to use a model of immunosuppressed rat infected with Pneumocystis carinii and sort life cycle stage fractions using a high-through-put cytometer. Subsequently, ploidy levels of the P. carinii trophic and cystic form fractions were measured by flow cytometry. In the cystic form, eight contents of DNA were measured thus strengthening the fact that each mature cyst contains eight haploid spores. Following release, each spore evolves into a trophic form. The majority of the trophic form fraction was haploid in our study. Some less abundant trophic forms displayed two contents of DNA indicating that they could undergo (i) mating/fusion leading to a diploid status or (ii) asexual mitotic division or (iii) both. Even less abundant trophic forms with four contents of DNA were suggestive of mitotic divisions occurring following mating in diploid trophic forms. Of interest, was the presence of trophic forms with three contents of DNA, an unusual finding that could be related to asymmetrical mitotic divisions occurring in other fungal species to create genetic diversity at lower energetic expenses than mating. Overall, ploidy data of P. carinii life cycle stages shed new light on the complexity of its modes of proliferation

Genome-wide analyses as part of the international FTLD-TDP whole-genome sequencing consortium reveals novel disease risk factors and increases support for immune dysfunction in FTLD

Frontotemporal lobar degeneration with neuronal inclusions of the TAR DNA-binding protein 43 (FTLD-TDP) represents the most common pathological subtype of FTLD. We established the international FTLD-TDP whole genome sequencing consortium to thoroughly characterize the known genetic causes of FTLD-TDP and identify novel genetic risk factors. Through the study of 1,131 unrelated Caucasian patients, we estimated that C9orf72 repeat expansions and GRN loss-of-function mutations account for 25.5% and 13.9% of FTLD-TDP patients, respectively. Mutations in TBK1 (1.5%) and other known FTLD genes (1.4%) were rare, and the disease in 57.7% of FTLD-TDP patients was unexplained by the known FTLD genes. To unravel the contribution of common genetic factors to the FTLD-TDP etiology in these patients, we conducted a two-stage association study comprising the analysis of whole-genome sequencing data from 517 FTLD-TDP patients and 838 controls, followed by targeted genotyping of the most associated genomic loci in 119 additional FTLD-TDP patients and 1653 controls. We identified three genome-wide significant FTLD-TDP risk loci: one new locus at chromosome 7q36 within the DPP6 gene led by rs118113626 (pvalue=4.82e-08, OR=2.12), and two known loci: UNC13A, led by rs1297319 (pvalue=1.27e-08, OR=1.50) and HLA-DQA2 led by rs17219281 (pvalue=3.22e-08, OR=1.98). While HLA represents a locus previously implicated in clinical FTLD and related neurodegenerative disorders, the association signal in our study is independent from previously reported associations. Through inspection of our whole genome sequence data for genes with an excess of rare loss-of-function variants in FTLD-TDP patients (n≥3) as compared to controls (n=0), we further discovered a possible role for genes functioning within the TBK1-related immune pathway (e.g. DHX58, TRIM21, IRF7) in the genetic etiology of FTLD-TDP. Together, our study based on the largest cohort of unrelated FTLD-TDP patients assembled to date provides a comprehensive view of the genetic landscape of FTLD-TDP, nominates novel FTLD-TDP risk loci, and strongly implicates the immune pathway in FTLD-TDP pathogenesis

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Combinaison multi-capteurs de données de couleur de l'eau : application en océanographie opérationnelle

Phytoplankton play an important role in the carbon cycle on Earth, via the carbon dioxide absorption during photosynthesis. If scientific cruises provide high frequency data at high space-time resolution, the observation from space allows a synoptic description and on long periods of chlorophyll-a, the ocean phytoplankton's main pigment. Each space mission measuring ocean color is limited in ocean spatial coverage (satellite tracks, clouds, etc.). The daily spatial coverage may increase significantly by merging datasets from several sensors. The objective of this Ph.D. was to design, develop and test different methods which combine ocean color data, from the American sensors SeaWiFS and MODIS/Aqua, for near real time applications for operational oceanography. Three concepts have been studied : error-weighted averaging (keeps the structures accuracy but uses only existing data), objective analysis (increases spatial coverage but, in return, smoothes the field), and a last new approach based on the wavelets transform (keeps the structures accuracy and increases the spatial coverage). The operationality of these three methods has been demonstrated.The relevance of using combined data was studied by highlighting the dominant modes of oceanic variability in physical and biological dynamics in the Southern Ocean, by using SeaWiFS + MODIS/Aqua combined data from the Antarctic circumpolar belt during the 2002-2006 period.Le phytoplancton joue un rôle important dans le cycle du carbone sur Terre, de par l'absorption du dioxyde de carbone au cours de la photosynthèse. Si les campagnes en mer offrent la possibilité d'acquérir des données à haute fréquence et à fine échelle spatio-temporelle, l'observation spatiale procure une description synoptique et sur de longues périodes de la chlorophylle-a, pigment principal du phytoplancton océanique. Chaque mission satellitaire qui mesure la couleur de l'eau est limitée en couverture océanique (traces du satellite, nuages, etc.). La couverture spatiale journalière peut augmenter considérablement en combinant les données issues de plusieurs satellites. L'objectif de cette thèse a été de concevoir, développer et tester des méthodes de combinaison de données couleur de l'eau, provenant des capteurs américains SeaWiFS et MODIS/Aqua, pour des applications en temps réel relevant de l'océanographie opérationnelle. Trois concepts ont été retenus : la moyenne pondérée par l'erreur capteur (conserve la netteté des structures mais n'utilise que les données existantes), l'analyse objective (améliore la couverture spatiale, mais lisse le champ en contrepartie), et une dernière approche innovante basée sur la transformée en ondelettes (conserve la netteté des structures et améliore la couverture du champ). L'opérationnalité de ces trois méthodes a été démontrée.L'intérêt d'utiliser des données combinées a été montré à travers la mise en évidence des modes de variabilité dominants de la dynamique océanographique et biologique dans l'Océan Austral, en utilisant les données combinées SeaWiFS + MODIS/Aqua de la ceinture circumpolaire pour la période 2002-2006