39 research outputs found
Ultra-filtration of human serum for improved quantitative analysis of low molecular weight biomarkers using ATR-IR spectroscopy
The Athena X-ray Integral Field Unit: a consolidated design for the system requirement review of the preliminary definition phase
The Athena X-ray Integral Unit (X-IFU) is the high resolution X-ray
spectrometer, studied since 2015 for flying in the mid-30s on the Athena space
X-ray Observatory, a versatile observatory designed to address the Hot and
Energetic Universe science theme, selected in November 2013 by the Survey
Science Committee. Based on a large format array of Transition Edge Sensors
(TES), it aims to provide spatially resolved X-ray spectroscopy, with a
spectral resolution of 2.5 eV (up to 7 keV) over an hexagonal field of view of
5 arc minutes (equivalent diameter). The X-IFU entered its System Requirement
Review (SRR) in June 2022, at about the same time when ESA called for an
overall X-IFU redesign (including the X-IFU cryostat and the cooling chain),
due to an unanticipated cost overrun of Athena. In this paper, after
illustrating the breakthrough capabilities of the X-IFU, we describe the
instrument as presented at its SRR, browsing through all the subsystems and
associated requirements. We then show the instrument budgets, with a particular
emphasis on the anticipated budgets of some of its key performance parameters.
Finally we briefly discuss on the ongoing key technology demonstration
activities, the calibration and the activities foreseen in the X-IFU Instrument
Science Center, and touch on communication and outreach activities, the
consortium organisation, and finally on the life cycle assessment of X-IFU
aiming at minimising the environmental footprint, associated with the
development of the instrument. Thanks to the studies conducted so far on X-IFU,
it is expected that along the design-to-cost exercise requested by ESA, the
X-IFU will maintain flagship capabilities in spatially resolved high resolution
X-ray spectroscopy, enabling most of the original X-IFU related scientific
objectives of the Athena mission to be retained. (abridged).Comment: 48 pages, 29 figures, Accepted for publication in Experimental
Astronomy with minor editin
The Athena X-ray Integral Field Unit: a consolidated design for the system requirement review of the preliminary definition phase
The Athena X-ray Integral Unit (X-IFU) is the high resolution X-ray spectrometer studied since 2015 for flying in the mid-30s on the Athena space X-ray Observatory. Athena is a versatile observatory designed to address the Hot and Energetic Universe science theme, as selected in November 2013 by the Survey Science Committee. Based on a large format array of Transition Edge Sensors (TES), X-IFU aims to provide spatially resolved X-ray spectroscopy, with a spectral resolution of 2.5 eV (up to 7 keV) over a hexagonal field of view of 5 arc minutes (equivalent diameter). The X-IFU entered its System Requirement Review (SRR) in June 2022, at about the same time when ESA called for an overall X-IFU redesign (including the X-IFU cryostat and the cooling chain), due to an unanticipated cost overrun of Athena. In this paper, after illustrating the breakthrough capabilities of the X-IFU, we describe the instrument as presented at its SRR (i.e. in the course of its preliminary definition phase, so-called B1), browsing through all the subsystems and associated requirements. We then show the instrument budgets, with a particular emphasis on the anticipated budgets of some of its key performance parameters, such as the instrument efficiency, spectral resolution, energy scale knowledge, count rate capability, non X-ray background and target of opportunity efficiency. Finally, we briefly discuss the ongoing key technology demonstration activities, the calibration and the activities foreseen in the X-IFU Instrument Science Center, touch on communication and outreach activities, the consortium organisation and the life cycle assessment of X-IFU aiming at minimising the environmental footprint, associated with the development of the instrument. Thanks to the studies conducted so far on X-IFU, it is expected that along the design-to-cost exercise requested by ESA, the X-IFU will maintain flagship capabilities in spatially resolved high resolution X-ray spectroscopy, enabling most of the original X-IFU related scientific objectives of the Athena mission to be retained. The X-IFU will be provided by an international consortium led by France, The Netherlands and Italy, with ESA member state contributions from Belgium, Czech Republic, Finland, Germany, Poland, Spain, Switzerland, with additional contributions from the United States and Japan.The French contribution to X-IFU is funded by CNES, CNRS and CEA. This work has been also supported by ASI (Italian Space Agency) through the Contract 2019-27-HH.0, and by the ESA (European Space Agency) Core Technology Program (CTP) Contract No. 4000114932/15/NL/BW and the AREMBES - ESA CTP No.4000116655/16/NL/BW. This publication is part of grant RTI2018-096686-B-C21 funded by MCIN/AEI/10.13039/501100011033 and by âERDF A way of making Europeâ. This publication is part of grant RTI2018-096686-B-C21 and PID2020-115325GB-C31 funded by MCIN/AEI/10.13039/501100011033
Altimetry for the future: Building on 25 years of progress
In 2018 we celebrated 25 years of development of radar altimetry, and the progress achieved by this methodology in the fields of global and coastal oceanography, hydrology, geodesy and cryospheric sciences. Many symbolic major events have celebrated these developments, e.g., in Venice, Italy, the 15th (2006) and 20th (2012) years of progress and more recently, in 2018, in Ponta Delgada, Portugal, 25 Years of Progress in Radar Altimetry. On this latter occasion it was decided to collect contributions of scientists, engineers and managers involved in the worldwide altimetry community to depict the state of altimetry and propose recommendations for the altimetry of the future. This paper summarizes contributions and recommendations that were collected and provides guidance for future mission design, research activities, and sustainable operational radar altimetry data exploitation. Recommendations provided are fundamental for optimizing further scientific and operational advances of oceanographic observations by altimetry, including requirements for spatial and temporal resolution of altimetric measurements, their accuracy and continuity. There are also new challenges and new openings mentioned in the paper that are particularly crucial for observations at higher latitudes, for coastal oceanography, for cryospheric studies and for hydrology. The paper starts with a general introduction followed by a section on Earth System Science including Ocean Dynamics, Sea Level, the Coastal Ocean, Hydrology, the Cryosphere and Polar Oceans and the ââGreenâ Ocean, extending the frontier from biogeochemistry to marine ecology. Applications are described in a subsequent section, which covers Operational Oceanography, Weather, Hurricane Wave and Wind Forecasting, Climate projection. Instrumentsâ development and satellite missionsâ evolutions are described in a fourth section. A fifth section covers the key observations that altimeters provide and their potential complements, from other Earth observation measurements to in situ data. Section 6 identifies the data and methods and provides some accuracy and resolution requirements for the wet tropospheric correction, the orbit and other geodetic requirements, the Mean Sea Surface, Geoid and Mean Dynamic Topography, Calibration and Validation, data accuracy, data access and handling (including the DUACS system). Section 7 brings a transversal view on scales, integration, artificial intelligence, and capacity building (education and training). Section 8 reviews the programmatic issues followed by a conclusion
Altimetry for the future: building on 25 years of progress
In 2018 we celebrated 25âŻyears of development of radar altimetry, and the progress achieved by this methodology in the fields of global and coastal oceanography, hydrology, geodesy and cryospheric sciences. Many symbolic major events have celebrated these developments, e.g., in Venice, Italy, the 15th (2006) and 20th (2012) years of progress and more recently, in 2018, in Ponta Delgada, Portugal, 25 Years of Progress in Radar Altimetry. On this latter occasion it was decided to collect contributions of scientists, engineers and managers involved in the worldwide altimetry community to depict the state of altimetry and propose recommendations for the altimetry of the future. This paper summarizes contributions and recommendations that were collected and provides guidance for future mission design, research activities, and sustainable operational radar altimetry data exploitation. Recommendations provided are fundamental for optimizing further scientific and operational advances of oceanographic observations by altimetry, including requirements for spatial and temporal resolution of altimetric measurements, their accuracy and continuity. There are also new challenges and new openings mentioned in the paper that are particularly crucial for observations at higher latitudes, for coastal oceanography, for cryospheric studies and for hydrology.
The paper starts with a general introduction followed by a section on Earth System Science including Ocean Dynamics, Sea Level, the Coastal Ocean, Hydrology, the Cryosphere and Polar Oceans and the âGreenâ Ocean, extending the frontier from biogeochemistry to marine ecology. Applications are described in a subsequent section, which covers Operational Oceanography, Weather, Hurricane Wave and Wind Forecasting, Climate projection. Instrumentsâ development and satellite missionsâ evolutions are described in a fourth section. A fifth section covers the key observations that altimeters provide and their potential complements, from other Earth observation measurements to in situ data. Section 6 identifies the data and methods and provides some accuracy and resolution requirements for the wet tropospheric correction, the orbit and other geodetic requirements, the Mean Sea Surface, Geoid and Mean Dynamic Topography, Calibration and Validation, data accuracy, data access and handling (including the DUACS system). Section 7 brings a transversal view on scales, integration, artificial intelligence, and capacity building (education and training). Section 8 reviews the programmatic issues followed by a conclusion
Molecular determinants of monoclonal antibody pharmacokinetics
La pharmacocinĂ©tique (PK) des anticorps monoclonaux (mAbs) est sujette Ă dâimportantes variations interindividuelles. Le rĂ©cepteur nĂ©onatal au Fc des IgG (FcRn) et le statut immun Ă lâencontre de ces mAbs sont des dĂ©terminants de cette PK. La bioconjugaison des mAbs Ă des cytotoxiques entraĂźne une altĂ©ration de leur PK. Nous montrons que le taux de couplage modifie lâaffinitĂ© de ces espĂšces pour le FcRn Ă pH6. La proportion dâagrĂ©gats au sein des solutions dâanticorps armĂ©s augmente avec le taux de couplage et pourrait entraĂźner une altĂ©ration de leur PK. Par ailleurs, cette agrĂ©gation est impliquĂ©e dans lâimmunogĂ©nicitĂ© des mAbs, et nous avons donc cherchĂ© Ă identifier des acides aminĂ©s impliquĂ©s dans lâagrĂ©gation de mAbs indiquĂ©s en clinique. Il apparait que la nature biochimique de rĂ©sidus des paratopes pourrait augmenter cette agrĂ©gation. Les anti-TNF- prĂ©sentent trĂšs peu d'agrĂ©gats et figurent pourtant parmi les plus immunogĂšnes chez lâHomme. Nous avons donc explorĂ© le rĂŽle des complexes immuns dans leur immunogĂ©nicitĂ© chez la souris. Il apparait que la prĂ©sence du FcRn nâest pas Ă lâorigine de lâimmunisation contre ces mAbs, contrairement Ă celle des complexes immuns. Ces rĂ©sultats donnent des pistes pour la production de mAbs plus efficients et mieux tolĂ©rĂ©s.The pharmacokinetic (PK) profile of monoclonal antibodies (mAbs) shows interindividudal variability. The neonatal Fc receptor (FcRn) and the immounogenicity of these mAbs are determinative factors of mAb PK. Generation of antibody-drug-conjugates alters their PK profile. We show that the the affinity for FcRn at pH6 increases with the drug-to-mAb ratio, as does the amount of aggregates inside the mAb-drug-conjugate. The amount of aggregates could be responsible for an avidity effect towards FcRn. These aggregates are known to cause immunogenicity, so we studied biochemical determinants inside the aminoacid sequence of marketed mAbs. We show that the biochemical nature of some aminoacids inside the paratope has an impact on the amount of aggregation. Anti-TNF- mAbs show very little aggregation but are very immunogenic in humans. We studied the role of the formation of immune complexes in the immunization against anti-TNF- mAbs in mice, and showed that immune complexes, but not FcRn are essential in the immunization process against anti- TNF- mAbs. These results give leads towards the generation of more efficient, better tolerated mAbs
Comparison of prednisolone and dexamethasone effects in the presence of environmental control in heaves-affected horses
This study was designed to compare the efficacy of oral prednisolone and intramuscular (IM) dexamethasone in heaves-affected horses with environmental control. A total of 16 horses, aged 8-20years, with heaves were included in the study. Complete examinations were performed on Day 0 (before treatment), Day 13 (after treatment) and Day 30. Clinical variables, arterial blood gases, mucus scoring and carina evaluation (during endoscopy), and bronchoalveolar lavage (BAL) cytological analysis were all assessed. The horses were randomly assigned to receive either oral prednisolone (1mg/kg) or IM dexamethasone (0.1mg/kg). The animals were clinically scored and mucus accumulation evaluated. Results were analysed by repeated measures ANOVA with time (days of treatment) and treatment as the main effects. When combined with environmental control, prednisolone and dexamethasone treatments had similar effects on heaves score, blood gases and endoscopic scores. However, dexamethasone had a more beneficial effect on BAL cytology
Open check dams: field inventory overview and feedback from the French experience
International audienceWithin a torrential watershed, several complementary facilities can protect people, housing, networks and facilities generally located on alluvial fans. Amongst them, open check dams have an effect on solid transport, i.e. boulders, gravel and wood, before it reaches elements-at-risk. They are generally associated with complementary components: deposit area for the dredged material, access path, and downstream scouring protection. Almost 320 open check dams were inventoried in 2017. About one-quarter are located in French public forests and are managed by the department of Restoration of Mountainous Areas of the National Forestry Office (ONF-RTM). Although the three other quarters are managed by municipalities, the ONF-RTM officers were involved in the design of the majority of them. In France, pioneer structures were implemented just after World War II. However, most of open check dams were built between 1980 and 2000. We aimed at understanding why their implementation has decreased in France since 2000? First hypothesis is that maintenance experience puts on light several problems such as downstream incision, excessive dredging costs, etc. Second hypothesis is that design is not so easy in practice. A field inventory and feedback was thus undertaken to cluster and formalize main problems. This contribution to EGU aims at presenting its method and main results. The used methodology involved four main steps. (1) A bibliography analysis specified potential functions of open check dams, physical mechanisms involved and existing design processes. (2) A GIS general inventory of French open check dams sorted them according to their storage capacity but also achieved functions. (3) A more detailed inventory was implemented by field ONF-RTM officers for 'large' open check dams, i.e. with more than 1000 m3 retention capacity. They described design context, involved solid transport processes, elements-at-risk, structural components, history of maintenance interventions, and malfunctions. (4) In-depth feedbacks on a dozen of specific facilities involved a watershed analysis, description of local peculiarities, definition of structure objectives, and functional and structural analysis. It was performed by gathering several specialists on site. As a result of step 3, no malfunctions were reported for 60 % of registered large open check dams. For the other 40%, main identified functional malfunctions were (i) deposit areas too frequently filled (46 %), (ii) lateral bypasses of the structure (27 %), (iii) structures located too upstream along the channel (21 %), and (ic) a lack of regular dredging. For step 4, a feedback methodology with standardized forms was developed and tested allowing clustering and disentangling several failure modes of open check dams. Thanks to this feedback, the global design process has been improved on three main points: (i) analysis for a minimum of three scenarios (frequent, project, danger), (ii) clarification of potential functions of open check dams, (iii) design of their opening sizes. Finally, this feedback approach helps to exchange between specialists and field practitioners, to cluster information according to a similar knowledge, and to improve design and maintenance processes. As it is based on a formalized methodology and reporting tools, it can be easily implemented in other sites and countries
Formation du Jugement Politique. Rapport pour la PrĂ©fecture de l'IsĂšre (1): Election PrĂ©sidentielle 2007. RĂ©sultats de la 1Ăšre vague d'enquĂȘte rĂ©alisĂ©e en fĂ©vrier.
Pour Ă©tudier le choix Ă©lectoral, le programme « Formation du Jugement Politique » du laboratoire PACTE (UMR : Iep, CNRS, UPMF, UJF) a mis au point un dispositif d'observation qui articule l'analyse de la campagne Ă©lectorale, Ă la TV, dans la presse et sur Internet et l'analyse des Ă©lecteurs grĂące Ă 60 entretiens qualitatifs et trois enquĂȘtes tĂ©lĂ©phoniques par sondage. L'objectif est de comprendre comment les Ă©lecteurs dĂ©cident de voter pour un candidat et quelles sont les influences sur leur choix de leurs appartenances sociales et politiques, leur lieu de vie, leurs prĂ©occupations prioritaires, leur perception des programmes et des candidats.Ce rapport prĂ©sente les rĂ©sultats de la premiĂšre enquĂȘte rĂ©alisĂ©e en fĂ©vrier 2007 et notamment :- problĂ©matique, hypothĂšses et mĂ©thode- prĂ©sentation des territoires- politisation et suivi de la campagne- inquiĂ©tudes et demandes de dĂ©bats- comportements Ă©lectoraux et intentions de vote.Le programme FJP n'aurait pu ĂȘtre rĂ©alisĂ© sans l'aide financiĂšre de la RĂ©gion RhĂŽne Alpes et du MinistĂšre de l'IntĂ©rieur
Formation du Jugement Politique. Rapport pour la PrĂ©fecture de l'IsĂšre (2): Election PrĂ©sidentielle 2007. RĂ©sultats de la 2Ăšme vague d'enquĂȘte rĂ©alisĂ©e en avril.
Pour Ă©tudier le choix Ă©lectoral, le programme « Formation du Jugement Politique » du laboratoire PACTE (UMR : IEP, CNRS, UPMF, UJF) a mis au point un dispositif d'observation qui articule l'analyse de la campagne Ă©lectorale, Ă la TV, dans la presse et sur Internet et l'analyse des Ă©lecteurs grĂące Ă 60 entretiens qualitatifs et trois enquĂȘtes tĂ©lĂ©phoniques par sondage. L'objectif est de comprendre comment les Ă©lecteurs dĂ©cident de voter pour un candidat et quelles sont les influences sur leur choix de leurs appartenances sociales et politiques, leur lieu de vie, leurs prĂ©occupations prioritaires, leur perception des programmes et des candidats.Ce 2Ăšme rapport prĂ©sente les rĂ©sultats de la seconde enquĂȘte rĂ©alisĂ©e en avril 2007 auprĂšs d'un millier d'Ă©lecteurs de trois cantons et une commune du dĂ©partement de l'IsĂšre. Il aborde notamment :- le contexte du scrutin et les rĂ©sultats dans les quatre territoires- les perspectives pour le 2Ăšme tour de l'Ă©lection prĂ©sidentielle.Cf. pour la premiĂšre vague, rapport en date de mars 2007.Le programme FJP n'aurait pu ĂȘtre rĂ©alisĂ© sans l'aide financiĂšre de la RĂ©gion RhĂŽne Alpes et du MinistĂšre de l'IntĂ©rieur