Time and frequency transfer with a microwave link in the ACES/PHARAO mission

The Atomic Clocks Ensemble in Space (ACES/PHARAO mission), which will be installed on board the International Space Station (ISS), uses a dedicated two-way Micro-Wave Link (MWL) in order to compare the timescale generated on board with those provided by many ground stations disseminated on the Earth. Phase accuracy and stability of this long range link will have a key role in the success of the ACES/PHARAO experiment. SYRTE laboratory is heavily involved in the design and development of the data processing software : from theoretical modelling and numerical simulations to the development of a software prototype. Our team is working on a wide range of problems that need to be solved in order to achieve high accuracy in (almost) real time. In this article we present some key aspects of the measurement, as well as current status of the software's development.Comment: Proceedings of the European Frequency and Time Forum (EFTF) 2012 held in Gothenburg, Sweden, April 201

Charactérisation à haute fréquence d'un jet balayant

International audienceSweeping jets are an emerging type of actuators that have gained interest due to their potential use in flow control applications. The working principle of these devices is based on the bi-stable attachment of a jet to adjacent walls. They are able to produce unsteady blowing within a wide range of operating frequencies. Nevertheless, the state of art shows a lack of space-time characterization of these actuators for high sweeping frequencies. This paper resents a conditional approach that reconstructs the spatial dynamic response of sweeping jets for sweeping frequencies above 500 Hz. The time-dependent velocity is measured with two single-hot-wire sensors: a reference one placed at the edge of the exit nozzle, and a flying one. The method is then tested to characterize the flow at the exit nozzle of an in-house sweeping jet actuator with 1mm space resolution, and 50 µs time resolution. These measurements are performed with a sweeping frequency of 639 Hz. Overall this paper demonstrates that the conditional approach is very useful for understanding the physics of flow control actuators.Les jets balayants sont des actionneurs fluidiques en pleine extension dans le domaine du contrôle actif des écoulements de par leur large gamme de fréquences et de vitesses. Ils se basent sur le phénomène de bi-stabilité de détachement de l'écoulement sur les parois interne de l'actionneur. Cependant la littérature montre une faiblesse pour la caractérisation expérimentale à haute fréquence de l'écoulement en sortie d'actionneur. Ce papier présente une méthode de reconstruction résolue en espace et en temps, basée sur une approche conditionnelle permettant de reconstruire l'écoulement pour des fréquence de balayage supérieures à 500Hz. Les signaux de vitesse résolus en temps sont mesurés à l'aide de deux fils chauds : un fixe pour le signal de synchronisation et un mobile, se déplaçant sur un maillage de finesse 1mm. Cette méthode est ensuite appliquée à un actionneur de jet balayant fonctionnant a une fréquence de 639Hz, avec un signal de vitesse de résolution temporelle de 50 micro secondes. Ce papier démontre ainsi que l'approche conditionnelle peut être utilisable pour comprendre la physique des écoulements en sortie d'actionneurs fluidiques

Interstitial Lung Abnormalities Detected by CT in Asbestos-Exposed Subjects Are More Likely Associated to Age

OBJECTIVE: the aim of this study was to evaluate the association between interstitial lung abnormalities, asbestos exposure and age in a population of retired workers previously occupationally exposed to asbestos. METHODS: previously occupationally exposed former workers to asbestos eligible for a survey conducted between 2003 and 2005 in four regions of France, underwent chest CT examinations and pulmonary function testing. Industrial hygienists evaluated asbestos exposure and calculated for each subject a cumulative exposure index (CEI) to asbestos. Smoking status information was also collected in this second round of screening. Expert radiologists performed blinded independent double reading of chest CT-scans and classified interstitial lung abnormalities into: no abnormality, minor interstitial findings, interstitial findings inconsistent with UIP, possible or definite UIP. In addition, emphysema was assessed visually (none, minor: emphysema 50% of the lung). Logistic regression models adjusted for age and smoking were used to assess the relationship between interstitial lung abnormalities and occupational asbestos exposure. RESULTS: the study population consisted of 2157 male subjects. Interstitial lung abnormalities were present in 365 (16.7%) and emphysema in 444 (20.4%). Significant positive association was found between definite or possible UIP pattern and age (OR adjusted =1.08 (95% CI: 1.02-1.13)). No association was found between interstitial abnormalities and CEI or the level of asbestos exposure. CONCLUSION: presence of interstitial abnormalities at HRCT was associated to aging but not to cumulative exposure index in this cohort of former workers previously occupationally exposed to asbestos

Deep Learning for the Automatic Quantification of Pleural Plaques in Asbestos-Exposed Subjects

OBJECTIVE: This study aimed to develop and validate an automated artificial intelligence (AI)-driven quantification of pleural plaques in a population of retired workers previously occupationally exposed to asbestos. METHODS: CT scans of former workers previously occupationally exposed to asbestos who participated in the multicenter APEXS (Asbestos PostExposure Survey) study were collected retrospectively between 2010 and 2017 during the second and the third rounds of the survey. A hundred and forty-one participants with pleural plaques identified by expert radiologists at the 2nd and the 3rd CT screenings were included. Maximum Intensity Projection (MIP) with 5 mm thickness was used to reduce the number of CT slices for manual delineation. A Deep Learning AI algorithm using 2D-convolutional neural networks was trained with 8280 images from 138 CT scans of 69 participants for the semantic labeling of Pleural Plaques (PP). In all, 2160 CT images from 36 CT scans of 18 participants were used for AI testing versus ground-truth labels (GT). The clinical validity of the method was evaluated longitudinally in 54 participants with pleural plaques. RESULTS: The concordance correlation coefficient (CCC) between AI-driven and GT was almost perfect (>0.98) for the volume extent of both PP and calcified PP. The 2D pixel similarity overlap of AI versus GT was good (DICE = 0.63) for PP, whether they were calcified or not, and very good (DICE = 0.82) for calcified PP. A longitudinal comparison of the volumetric extent of PP showed a significant increase in PP volumes (p < 0.001) between the 2nd and the 3rd CT screenings with an average delay of 5 years. CONCLUSIONS: AI allows a fully automated volumetric quantification of pleural plaques showing volumetric progression of PP over a five-year period. The reproducible PP volume evaluation may enable further investigations for the comprehension of the unclear relationships between pleural plaques and both respiratory function and occurrence of thoracic malignancy

BMJ Open

INTRODUCTION: Guidelines concerning the follow-up of subjects occupationally exposed to lung carcinogens, published in France in 2015, recommended the setting up of a trial of low-dose chest CT lung cancer screening in subjects at high risk of lung cancer. OBJECTIVE: To evaluate the organisation of low-dose chest CT lung cancer screening in subjects occupationally exposed to lung carcinogens and at high risk of lung cancer. METHODS AND ANALYSIS: This trial will be conducted in eight French departments by six specialised reference centres (SRCs) in occupational health. In view of the exploratory nature of this trial, it is proposed to test initially the feasibility and acceptability over the first 2 years in only two SRCs then in four other SRCs to evaluate the organisation. The target population is current or former smokers with more than 30 pack-years (who have quit smoking for less than 15 years), currently or previously exposed to International Agency for Research on Cancer group 1 lung carcinogens, and between the ages of 55 and 74 years. The trial will be conducted in the following steps: (1) identification of subjects by a screening invitation letter; (2) evaluation of occupational exposure to lung carcinogens; (3) evaluation of the lung cancer risk level and verification of eligibility; (4) screening procedure: annual chest CT scans performed by specialised centres and (5) follow-up of CT scan abnormalities. ETHICS AND DISSEMINATION: This protocol study has been approved by the French Committee for the Protection of Persons. The results from this study will be submitted to peer-reviewed journals and reported at suitable national and international meetings. TRIAL REGISTRATION NUMBER: NCT03562052; Pre-results

GENESIS: Co-location of Geodetic Techniques in Space

Improving and homogenizing time and space reference systems on Earth and, more directly, realizing the Terrestrial Reference Frame (TRF) with an accuracy of 1mm and a long-term stability of 0.1mm/year are relevant for many scientific and societal endeavors. The knowledge of the TRF is fundamental for Earth and navigation sciences. For instance, quantifying sea level change strongly depends on an accurate determination of the geocenter motion but also of the positions of continental and island reference stations, as well as the ground stations of tracking networks. Also, numerous applications in geophysics require absolute millimeter precision from the reference frame, as for example monitoring tectonic motion or crustal deformation for predicting natural hazards. The TRF accuracy to be achieved represents the consensus of various authorities which has enunciated geodesy requirements for Earth sciences. Today we are still far from these ambitious accuracy and stability goals for the realization of the TRF. However, a combination and co-location of all four space geodetic techniques on one satellite platform can significantly contribute to achieving these goals. This is the purpose of the GENESIS mission, proposed as a component of the FutureNAV program of the European Space Agency. The GENESIS platform will be a dynamic space geodetic observatory carrying all the geodetic instruments referenced to one another through carefully calibrated space ties. The co-location of the techniques in space will solve the inconsistencies and biases between the different geodetic techniques in order to reach the TRF accuracy and stability goals endorsed by the various international authorities and the scientific community. The purpose of this white paper is to review the state-of-the-art and explain the benefits of the GENESIS mission in Earth sciences, navigation sciences and metrology.Comment: 31 pages, 9 figures, submitted to Earth, Planets and Space (EPS

Quantum Physics Exploring Gravity in the Outer Solar System: The Sagas Project

We summarise the scientific and technological aspects of the SAGAS (Search for Anomalous Gravitation using Atomic Sensors) project, submitted to ESA in June 2007 in response to the Cosmic Vision 2015-2025 call for proposals. The proposed mission aims at flying highly sensitive atomic sensors (optical clock, cold atom accelerometer, optical link) on a Solar System escape trajectory in the 2020 to 2030 time-frame. SAGAS has numerous science objectives in fundamental physics and Solar System science, for example numerous tests of general relativity and the exploration of the Kuiper belt. The combination of highly sensitive atomic sensors and of the laser link well adapted for large distances will allow measurements with unprecedented accuracy and on scales never reached before. We present the proposed mission in some detail, with particular emphasis on the science goals and associated measurements.Comment: 39 pages. Submitted in abridged version to Experimental Astronom

Rôle de miR-142-3p dans la régulation de la différenciation macrophagique

L hématopoïèse est un processus actif, ordonné, et hautement régulé faisant intervenir des étapes de prolifération, de différenciation et d apoptose et permettant la production de toutes les cellules sanguines matures à partir d un nombre restreint de cellules souches hématopoïétiques. La dérégulation des mécanismes intervenant dans l hématopoïèse induit le développement d hémopathies, notamment de leucémies. De nombreux facteurs de transcription et microARN (miARN) ont été identifiés en tant que des régulateurs essentiels à l établissement des différents lignages hématopoïétiques. Mon travail de thèse a porté sur l étude du rôle des miARN dans la régulation de la différenciation macrophagique humaine. Nous avons reproduit le processus de différenciation macrophagique in vitro à partir de monocytes issus du sang périphérique traités avec du CSF-1 (colony stimulating factor-1). Suite à l analyse du profil d expression des miARN au cours du processus de différenciation, notre projet s est orienté sur l étude de miR-142-3p dont le taux d expression diminue le plus fortement au cours de cette différenciation. Nous avons montré que miR-142-3p forme une boucle d auto-régulation négative avec EGR2 (early growth response 2), un facteur de transcription connu pour réguler positivement la différenciation macrophagique. Cette boucle est essentielle au bon déroulement de la différenciation. Par ailleurs, nous avons observé une altération de cette boucle de régulation dans les monocytes de patients atteints d une LMMC (leucémie myélomonocytaire chronique) suggérant que ce mécanisme puisse être impliqué dans la leucémogenèse. Au cours de ce projet, nous avons également initié une étude in vivo via l utilisation du modèle que représente le Poisson-Zèbre. L hématopoïèse du Poisson-Zèbre est très similaire à celle des mammifères que ce soit au niveau des populations hématopoïétiques ou des mécanismes de régulation impliqués. L inhibition de l expression du miR-142a-3p, homologue du miR-142-3p humain, se traduit par une absence de monocytes et de macrophages au niveau de l ICM (intermediate cell mass), organe primaire de l hématopoïèse, ainsi que par une diminution de l expression de la myéloperoxydase, marqueur des granulocytes chez le Poisson-Zèbre. Ainsi, miR-142-3p semble être un inducteur de la formation des granulocytes et monocytes.Hematopoiesis is an active process, orderly and highly regulated, involving proliferation, differentiation and apoptosis steps, and allowing the production of mature blood cells from a restricted number of hematopoietic stem cells. Deregulation of mechanisms involved in hematopoiesis leads to the development of leukemias. Many transcription factors and microRNAs (miRNAs) have been identified as essential regulators in the establishment of different hematopoietic lineages. My thesis investigated the role of miRNAs in the regulation of human macrophage differentiation. We examined macrophage differentiation in vitro, from peripheral blood monocytes treated with CSF-1 (colony stimulating factor-1). After the analysis of miRNAs expression profile, our project has focused on the study of miR-142-3p whose expression levels decreased most strongly during macrophage differentiation. We showed that miR-142-3p involved in a negative feedback loop with EGR2 (early growth response 2), a transcription factor known to favor macrophage differentiation. This molecular circuitry is necessary for the normal processus of differentiation. Furthermore, we observed an alteration of this regulation circuitry in monocytes of CMML (chronic myelomonocytic leukemia) patients, suggesting that this mechanism may be involved in leukemogenesis. During this project, we also initiated a study in vivo through the use of the zebrafish model. Zebrafish hematopoiesis is very similar to that in mammals both at the level of hematopoietic populations or regulatory mechanisms involved. The inhibition of miR-142a-3p expression, homolog of the human miR-142-3p, gave rise to an absence of monocytes and macrophages in ICM (intermediate cell mass), the primary organ of hematopoiesis and a decreased expression of myeloperoxidase, a marker of granulocytes in the zebrafish. Thus, miR-142-3p appears to be an inducer of granulocytes and monocytes formation.DIJON-BU Doc.électronique (212319901) / SudocSudocFranceF

TIF1 gamma est un régulateur essentiel de l'hématopoïèse et agit en tant que suppresseur de tumeur dans la leucémie myélomonocytaire chronique

Mon travail de thèse consistait à caractériser le rôle de la protéine TIF1g (transcriptional intermediary factor 1 gamma) dans l hématopoïèse adulte. L hématopoïèse est un processus actif, ordonné, et hautement régulé faisant intervenir des étapes de prolifération, de différenciation et d apoptose et permettant la production de toutes les cellules sanguines matures à partir d un nombre restreint de cellules souches hématopoïétiques. La dérégulation des mécanismes intervenant dans l hématopoïèse induit le développement d hémopathies, notamment de leucémies. Les souris nullizygotes pour Tif1g meurent au cours de l embryogenèse du fait de graves défauts du développement. Afin d étudier le rôle de Tif1g dans l hématopoïèse murine, et plus particulièrement sa contribution au développement et à la différenciation des cellules souches et des progéniteurs hématopoïétiques, nous avons généré des souris déficientes pour Tif1g uniquement dans les cellules hématopoïétiques. Nous avons observé que Tif1g agit en tant que gène suppresseur de tumeur dans ces cellules. Nous avons aussi démontré que Tif1g est un régulateur clef du devenir des cellules souches hématopoïétiques chez les mammifères. Nous avons mis en évidence que, chez les souris âgées, la délétion de Tif1g provoque l apparition d un syndrome myéloprolifératif dysplasique, ressemblant fortement au phénotype de la leucémie myélomonocytaire chronique (LMMC) humaine. De façon intéressante, nous avons identifiéé que plus de 40% de patients atteints de cette pathologie présentent un faible taux de TIF1g. La décitabine, molécule hypométhylante utilisée en thérapeutique, permet le rétablissememnt d une expression normale de TIF1g. Chez certains patients, nous avons corrélé la diminution de l expression de TIF1 avec l hyperméthylation de l ADN et un patron spécifique de modifications d histones (acétylations et méthylations) sur le promoteur du gène TIF1g. Ces résultats suggèrent une signature épigénétique spécifique de la leucémie myélomonocytaire chronique sur le promoteur de TIF1g. L ensemble de nos données indiquent donc que TIF1g est un gène suppresseur de tumeur régulé épigénétiquement dans les cellules hématopoïétiques.My thesis deals with the characterization of the role of the protein TIF1g (transcriptional intermediary factor 1 gamma) in adult hematopoiesis. Hematopoiesis is an active process, orderly and highly regulated, using proliferation, differentiation and apoptosis steps, and allowing the production of mature blood cells from a restricted number of hematopoietic stem cells. Deregulation of mechanisms involved in hematopooiesis leads to the development of leukemias. Tif1g knockout mice die during embryogenesis with severe development defects. In order to study the role of Tif1g in murine hematopoiesis, and more particularly its contribution to hematopoietic stem and progenitor cells development and differentiation, we generated hematopoietic Tif1g deleted mice. We showed that Tif1g functions as a tumor suppressor gene in hematopoietic cells. Moreover, we identified Tif1g as a key player in the commitment of mammal hematopoietic stem cells. In ageing mice, we demonstrated that the Tif1g deletion leads to a myeloproliferative and myelodysplastic syndrome, phenotypically very close to the human chronic myelomonocytic leukemia (CMML). We also identified a very low level of TIF1g expression in the monocytes of 40% CMML patients. Decitabine, a hypomethylating molecule used in CMML therapy, allows the restoration of a normal TIF1g expression. In some patients, we have highlighted the correlation between the low expression of TIF1g, the DNA hypermethylation and a specific pattern of histone modifications (acetylation and methylation) on TIF1g gene promoter. These results suggest a specific epigenetic signature of the disease on this promoter. Taking together, our data indicate that TIF1g is a tumor suppressor gene, epigenetically regulated in hematopoietic cells.DIJON-BU Doc.électronique (212319901) / SudocSudocFranceF