A robust collagen scoring method for human liver fibrosis by second harmonic microscopy.

International audienceSecond Harmonic Generation (SHG) microscopy offers the opportunity to image collagen of type I without staining. We recently showed that a simple scoring method, based on SHG images of histological human liver biopsies, correlates well with the Metavir assessment of fibrosis level (Gailhouste et al., J. Hepatol., 2010). In this article, we present a detailed study of this new scoring method with two different objective lenses. By using measurements of the objectives point spread functions and of the photomultiplier gain, and a simple model of the SHG intensity, we show that our scoring method, applied to human liver biopsies, is robust to the objective's numerical aperture (NA) for low NA, the choice of the reference sample and laser power, and the spatial sampling rate. The simplicity and robustness of our collagen scoring method may open new opportunities in the quantification of collagen content in different organs, which is of main importance in providing diagnostic information and evaluation of therapeutic efficiency

Hydrogen contribution to the thermal expansion of hydrided Zircaloy-4 cladding tubes

International audienceThis study is focused on the hydrogen-induced dimensional change or "growth" of zirconium alloys. Dilatometric experiments were performed on samples taken from a unirradiated Zircaloy-4 (Zy-4) fuel cladding loaded up to 940 wppm hydrogen. Samples were taken in the axial direction of the tube or at 45° to the axial and transverse directions. The results indicate that hydrogen-induced expansion is anisotropic. Theoretical expansion calculations were carried out considering the partition of hydrogen in solid solution and hydrides together with the material crystallographic texture. Hydride-induced expansion was calculated using two different assumptions reported in the literature, namely "Pure Lattice Transformation Strains" (PLTS) and "Pure Shear Transformation Strains" (PSTS). Calculations based on the PSTS hypothesis satisfactorily predicted the anisotropy observed in the dilatometric curve. Under this assumption, the contribution of hydrides to the axial growth of high-burnup Zy-4 cladding is limited to 12%. This study shows it is important to consider the respective contribution of hydrogen in both states, together with the material crystallographic texture, to understand the dilatometric behavior of hydrided zirconium alloys

Build Your Own Hercules : une interface tangible de choix de parcours de visites personnalisées au musée

National audienceIn this demonstration we present “Build your own Hercules”. This tangible token+constraint system allows museum visitors to indicate their characteristics and desires in order to choose a personalized visit. We designed this system in collaboration with Musée Saint-Raymond in Toulouse, which hosted a pilot study of the prototype in-situ.Dans cette démonstration, nous présentons « Build your own Hercules ». Ce système tangible de type token+constraint permet aux visiteurs d’un musée d’indiquer leurs caractéristiques et leurs envies afin de choisir une visite personnalisée. Nous avons conçu ce système en collaboration avec le musée Saint-Raymond de Toulouse, qui a accueilli une étude pilote du prototype

Structural Characterization of CYP51 from Trypanosoma cruzi and Trypanosoma brucei Bound to the Antifungal Drugs Posaconazole and Fluconazole

Chagas Disease is caused by kinetoplastid protozoa Trypanosoma cruzi, whose sterols resemble those of fungi, in both composition and biosynthetic pathway. Azole inhibitors of sterol 14α-demethylase (CYP51), such as fluconazole, itraconazole, voriconazole, and posaconazole, successfully treat fungal infections in humans. Efforts have been made to translate anti-fungal azoles into a second-use application for Chagas Disease. Ravuconazole and posaconazole have been recently proposed as candidates for clinical trials with Chagas Disease patients. However, the widespread use of posaconazole for long-term treatment of chronic infections may be limited by hepatic and renal toxicity, a requirement for simultaneous intake of a fatty meal or nutritional supplement to enhance absorption, and cost. To aid our search for structurally and synthetically simple CYP51 inhibitors, we have determined the crystal structures of the CYP51 targets in T. cruzi and T. brucei, both bound to the anti-fungal drugs fluconazole or posaconazole. The structures provide a basis for a design of new drugs targeting Chagas Disease, and also make it possible to model the active site characteristics of the highly homologous Leishmania CYP51. This work provides a foundation for rational synthesis of new therapeutic agents targeting the three kinetoplastid parasites

The Comet Interceptor Mission

Here we describe the novel, multi-point Comet Interceptor mission. It is dedicated to the exploration of a little-processed long-period comet, possibly entering the inner Solar System for the first time, or to encounter an interstellar object originating at another star. The objectives of the mission are to address the following questions: What are the surface composition, shape, morphology, and structure of the target object? What is the composition of the gas and dust in the coma, its connection to the nucleus, and the nature of its interaction with the solar wind? The mission was proposed to the European Space Agency in 2018, and formally adopted by the agency in June 2022, for launch in 2029 together with the Ariel mission. Comet Interceptor will take advantage of the opportunity presented by ESA's F-Class call for fast, flexible, low-cost missions to which it was proposed. The call required a launch to a halo orbit around the Sun-Earth L2 point. The mission can take advantage of this placement to wait for the discovery of a suitable comet reachable with its minimum ΔV capability of 600 ms-1. Comet Interceptor will be unique in encountering and studying, at a nominal closest approach distance of 1000 km, a comet that represents a near-pristine sample of material from the formation of the Solar System. It will also add a capability that no previous cometary mission has had, which is to deploy two sub-probes - B1, provided by the Japanese space agency, JAXA, and B2 - that will follow different trajectories through the coma. While the main probe passes at a nominal 1000 km distance, probes B1 and B2 will follow different chords through the coma at distances of 850 km and 400 km, respectively. The result will be unique, simultaneous, spatially resolved information of the 3-dimensional properties of the target comet and its interaction with the space environment. We present the mission's science background leading to these objectives, as well as an overview of the scientific instruments, mission design, and schedule

Evolution of Corrections Processing for MC/MF Ground Based Augmentations System (GBAS)

International audienceThe Ground Based Augmentation System (GBAS) is currently standardized at the International Civil Aviation organization (ICAO) level to provide precision approach navigation services up to Category I using the GPS or LONASS constellations. Current investigations into he use of GBAS for a Category II/III service type known as GAST D are ongoing. However, some gaps in performance have been identified and open issues remain Multi-frequency and multi-constellation solutions are being explored within the European SESAR program (WP 15.3.7) to address these issues. The addition of a secondary constellation provides many advantages such as better geometry, robustness against signal outages, relaxing of demanding constraints. Furthermore, new signals offer the potential to combine measurements on multiple frequencies to mitigate the effects of the ionosphere including during disturbances and helps the stringent continuity and availability requirements to be met.However, whilst the advantages of using many more signals is clear, there exists a major constraint with respect to the available space for message transmission from the GBAS VHF Data Broadcast (VDB) unit [5]. Currently, corrections and their integrity are provided in combined messages broadcast every half second (2Hz). However, extending this approach to multiple correction types, based on the different signals and observables for two or more constellations will not be possible. Furthermore, if the need arises to include future signals from the modernized constellations or expand further than two constellations then no additional transmission space would be available. It is for these reasons that the authors have investigated the possibility of providing corrections at a lower rate than the current 2Hz, with a separate message type dedicated to providing the integrity status of each correction in a manner akin to the Satellite Based Augmentation System (SBAS) [6].In order to justify this approach and to select the ideal correction message rate, a number of items must be addressed

Troposphere Reassessment in the scope of MC/MF Ground Based Augmentation System (GBAS)

International audienceIn civil aviation, there is currently a demand for greater airspace capacity and efficiency. In order to meet these long term goals, services must be expanded to provide more reliable and robust approach and landing operations in all weather conditions, globally. One potential application would be to use the Ground Based Augmentation System (GBAS) to enable Cat II /III precision approaches, the most stringent operation currently defined and with the lowest separation minima. Whilst a GBAS solution using a single frequency of the Global Positioning System (GPS) is under the late stages of development and standardization to meet CAT II/III performance requirements, some open questions remain and availability will not be assured for installations worldwide and all of the time. This paper details the activities related to the measurement processing techniques under investigation for the Multi-Constellation (MC) and Multi-Frequency (MF) Ground Based Augmentation System (GBAS) within the SESAR (Single European Sky ATM Research) Framework Work Package 15.3.7. In this scope several research threads are being undertaken to improve the performance of Ground Based Augmentation System (GBAS) to support CAT II/III precision approaches. Several challenges and key issues must be solved including those related to atmospheric modelling. Previous work principally undertaken at Ohio University [1] [2] [3] highlighted the need to consider the troposphere as a possible source of positioning failure. GBAS activities in Europe have followed the approach of validating the values of the protection levels, which include a component relating to ionospheric gradients. Therefore the position error induced by tropospheric failure should be safely bounded by validating that the combination of atmospheric errors does not exceed the assumed models. However, there are a number of arguments for revisiting this topic and specifically addressing the tropospheric threat. Firstly, recent observations [4], reported at last ICAO NSP (International Civil Aviation Organization – Navigation System Panel) meeting, showed unexpected atmospheric behaviour. These observations have been confirmed by the FAA (Federal Aviation Administration) and Boeing and have shown that significant spatial gradients with no link to ionosphere activity are likely to appear mainly during warm and sunny days. The root could be related to a non-modelled behaviour of the troposphere. Even if the range errors induced by this phenomenon are around 9 cm and are not significant compared to those due to ionospheric gradients, the combination of these “troposphere” gradients with ionospheric gradients could lead to missed detection or false detection of the ground subsystem’s ionospheric monitor, thus impacting integrity and continuity. Secondly, in the advent of dual-frequency GBAS, the ionosphere may feasibly be removed through the ionosphere-free smoothing technique. In this case, the main contributor to the atmospheric error will come from the tropospheric delay. Under such a scenario, the troposphere threat model must be defined and a means for bounding the potential errors derived. This paper presents an initial analysis with the aim of evaluating the impact of non-nominal troposphere on Vertical Protection Level (VPL) for different scenarios. The goal of this comparison is to ascertain the extent to which the proposed tropospheric bounding methodology increases the VPLs used at the aircraft. Finally, this paper has initiated the process of assessing the impact of modelling the non-nominal troposphere on GBAS VPLs. Indeed a new methodology is proposed and seems to improve performance in terms of availability while respecting some constraints on a low data requirements for the VDB transmission

Development of processing models for Multi-Constellation/Multi-Frequency GBAS

National audience The primary aim of this thesis is to determine an optimum processing methodology for Dual Constellation (GPS and Galileo) and Dual Frequency GBAS, thus resolving the challenges this presents. The thesis is performed within the scope of SESAR WP 15.3.7 and more precisely sub-task 3.6 of this work package on the subject of measurement processing. SESAR WP 15.3.7 is a SESAR Joint Undertaking funded project consisting of major European industry and research institutes.</p