Chronic Mucocutaneous Candidiasis in Autoimmune Polyendocrine Syndrome Type 1

Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) is an autosomal recessive disease caused by mutations in the autoimmune regulator (AIRE) gene, characterized by the clinical triad of chronic mucocutaneous candidiasis (CMC), hypoparathyroidism, and adrenal insufficiency. CMC can be complicated by systemic candidiasis or oral squamous cell carcinoma (SCC), and may lead to death. The role of chronic Candida infection in the etiopathogenesis of oral SCC is unclear. Long-term use of fluconazole has led to the emergence of Candida albicans strains with decreased susceptibility to azoles. CMC is associated with an impaired Th17 cell response; however, it remains unclear whether decreased serum IL-17 and IL-22 levels are related to a defect in cytokine production or to neutralizing autoantibodies resulting from mutations in the AIRE gene

Identification of novel genes potentially involved in somatic embryogenesis in chicory (Cichorium intybus L.)

<p>Abstract</p> <p>Background</p> <p>In our laboratory we use cultured chicory (<it>Cichorium intybus</it>) explants as a model to investigate cell reactivation and somatic embryogenesis and have produced 2 chicory genotypes (K59, C15) sharing a similar genetic background. K59 is a responsive genotype (embryogenic) capable of undergoing complete cell reactivation <it>i.e</it>. cell de- and re-differentiation leading to somatic embryogenesis (SE), whereas C15 is a non-responsive genotype (non-embryogenic) and is unable to undergo SE. Previous studies <abbrgrp><abbr bid="B1">1</abbr></abbrgrp> showed that the use of the β-D-glucosyl Yariv reagent (β-GlcY) that specifically binds arabinogalactan-proteins (AGPs) blocked somatic embryo production in chicory root explants. This observation indicates that β-GlcY is a useful tool for investigating somatic embryogenesis (SE) in chicory. In addition, a putative AGP (DT212818) encoding gene was previously found to be significantly up-regulated in the embryogenic K59 chicory genotype as compared to the non-embryogenic C15 genotype suggesting that this AGP could be involved in chicory re-differentiation <abbrgrp><abbr bid="B2">2</abbr></abbrgrp>. In order to improve our understanding of the molecular and cellular regulation underlying SE in chicory, we undertook a detailed cytological study of cell reactivation events in K59 and C15 genotypes, and used microarray profiling to compare gene expression in these 2 genotypes. In addition we also used β-GlcY to block SE in order to identify genes potentially involved in this process.</p> <p>Results</p> <p>Microscopy confirmed that only the K59, but not the C15 genotype underwent complete cell reactivation leading to SE formation. β-GlcY-treatment of explants blocked <it>in vitro </it>SE induction, but not cell reactivation, and induced cell wall modifications. Microarray analyses revealed that 78 genes were differentially expressed between induced K59 and C15 genotypes. The expression profiles of 19 genes were modified by β-GlcY-treatment. Eight genes were both differentially expressed between K59 and C15 genotypes during SE induction and transcriptionally affected by β-GlcY-treatment: <it>AGP </it>(DT212818), <it>26 S proteasome AAA ATPase subunit 6 </it>(<it>RPT6</it>), <it>remorin </it>(<it>REM</it>), <it>metallothionein-1 </it>(<it>MT1</it>), two non-specific lipid transfer proteins genes (<it>SDI-9 and DEA1</it>), <it>3-hydroxy-3-methylglutaryl-CoA reductase </it>(<it>HMG-CoA reductase</it>), and <it>snakin 2 </it>(<it>SN2</it>). These results suggest that the 8 genes, including the previously-identified <it>AGP </it>gene (DT212818), could be involved in cell fate determination events leading to SE commitment in chicory.</p> <p>Conclusion</p> <p>The use of two different chicory genotypes differing in their responsiveness to SE induction, together with β-GlcY-treatment represented an efficient tool to discriminate cell reactivation from the SE morphogenetic pathway. Such an approach, together with microarray analyses, permitted us to identify several putative key genes related to the SE morphogenetic pathway in chicory.</p

Gamma-ray and radio properties of six pulsars detected by the fermi large area telescope

We report the detection of pulsed γ-rays for PSRs J0631+1036, J0659+1414, J0742-2822, J1420-6048, J1509-5850, and J1718-3825 using the Large Area Telescope on board the Fermi Gamma-ray Space Telescope (formerly known as GLAST). Although these six pulsars are diverse in terms of their spin parameters, they share an important feature: their γ-ray light curves are (at least given the current count statistics) single peaked. For two pulsars, there are hints for a double-peaked structure in the light curves. The shapes of the observed light curves of this group of pulsars are discussed in the light of models for which the emission originates from high up in the magnetosphere. The observed phases of the γ-ray light curves are, in general, consistent with those predicted by high-altitude models, although we speculate that the γ-ray emission of PSR J0659+1414, possibly featuring the softest spectrum of all Fermi pulsars coupled with a very low efficiency, arises from relatively low down in the magnetosphere. High-quality radio polarization data are available showing that all but one have a high degree of linear polarization. This allows us to place some constraints on the viewing geometry and aids the comparison of the γ-ray light curves with high-energy beam models

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 ‘‘Green” 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. Instruments’ development and satellite missions’ 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

Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis.

RATIONALE: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. OBJECTIVES: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 <80 or PaCO2 ≥60 mmHg). We controlled for confounding using a multivariable Cox model based on predefined variables. MAIN RESULTS: 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability at Day-7 from the onset of eligibility criteria (87% vs 83%, risk difference: 4%, 95% CI 0;9%) which decreased during follow-up (survival at Day-90: 63% vs 65%, risk difference: -2%, 95% CI -10;5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand, and when initiated within the first 4 days of MV and in profoundly hypoxemic patients. CONCLUSIONS: In an emulated trial based on a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and in regions with ECMO capacities specifically organized to handle high demand. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)

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 “Green” 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. Instruments’ development and satellite missions’ 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

Évaluation des impacts environnementaux des pratiques agricoles à l’échelle de la parcelle et de l’exploitation en vue de l’élaboration d’un plan d’actions : une méthode de diagnostic spatialisé fondée sur des indicateurs, le DAE-G1

National audienceEn Picardie, dès le début des années deux mille, les chambres d’agriculture ont initié un projet de recherche-développement dont l’objectif était de concevoir une démarche innovante de gestion de la qualité et de l’environnement inspirée des normes ISO 14001 dans les exploitations agricoles, qui permette l’amélioration des pratiques. Ce projet a conduit à la construction d’une méthode de diagnostic agri-environnemental : le DAE-G, diagnostic agri-environnemental géographique, conçu par Agro-Transfert en collaboration avec l’INRA, les chambres d’agriculture de Picardie, l’Institut LaSalle Beauvais et avec le soutien financier de la région Picardie et de l’Ademe. Associé à un système d’information géographique, cet outil de diagnostic agrienvironnemental fondé sur des indicateurs permet, à partir de la connaissance des caractéristiques du milieu physique et des pratiques de l’agriculteur, de qualifier un niveau de risque environnemental à l’échelle parcellaire. L’agriculteur dispose ainsi d’une photographie de son exploitation qui met en évidence les parcelles les plus à risque pour un enjeu environnemental donné. Les données d’entrée nécessaires au calcul des indicateurs sont récupérées auprès de l’agriculteur avec d’éventuels documents existants sur les caractéristiques de sol du département ou de la petite région naturelle dans laquelle s’insère l’exploitation. La méthode DAE-G aborde des thématiques environnementales à l’échelle parcellaire (pollution de l’eau par les nitrates) mais aussi à l’échelle de l’exploitation agricole (biodiversité, gestion des déchets…). Chacune de ces thématiques ont fait l’objet d’une constitution d’un groupe d’experts, (chercheurs et conseillers), pour déterminer les indicateurs, l’agrégation des données d’entrée, les méthodes de calcul et surtout, la détermination des seuils de référence. Après sa deuxième année d’utilisation, le DAE-G fait état d’environ deux cent exploitations enquêtées qui peuvent donc bénéficier d’un rapport de diagnostic et de l’appui d’un conseiller agricole pour améliorer leurs pratiques. Parmi toutes ces enquêtes, l’objectif de réalisation d’un diagnostic environnemental n’est pas le même. En effet, le DAE-G est utilisé dans le cadre du management environnemental auprès d’agriculteurs volontaires, mais aussi dans le cadre de mise en place d’actions dans des bassins versants. Ces dernières, conduites par les agences de l’eau en partenariat avec les chambres d’agriculture, visent à améliorer la qualité des eaux souterraines en réduisant les pollutions diffuses dues aux nitrates et aux produits phytosanitaires. C’est ce cas d’usage du DAE-G qui sera étudié avec la présentation des résultats sur l’ensemble des parcelles du bassin versant. Un zoom sur une parcelle en culture de blé tendre d’hiver sera fait pour présenter et interpréter les résultats du DAE-G à l’échelle parcellaire. Cependant, l’utilisation d’une méthode de diagnostic environnemental pour plusieurs usages pose la question du paramétrage (quelles données d’entrée, quels seuils…). En effet, l’outil DAE-G est utilisé sur une échelle autre que celle de la parcelle : celle du bassin versant. Comme pour le DAE-G, pour toute méthode de diagnostic se pose la question de sa pertinence pour un cas d’usage donné lorsque celle-ci n’a pas été conçue pour cet usage précis

Deciphering the structure of pectic oligosaccharides by a new tandem mass spectrometry method based on photo-activation in the Vacuum UltraViolet range

Deciphering the structure of pectic oligosaccharides by a new tandem mass spectrometry method based on photo-activation in the Vacuum UltraViolet range. Pacifichem 201

Designing human–system cooperation in industry 4.0 with cognitive work analysis: a first evaluation

International audienceOne objective of Industry 4.0 is to reach a better system performance as well as to have a better consideration of humans. This would be done by benefiting from knowledge and experience of humans, and balancing in a reactive way some complex or complicated tasks with intelligent systems. Several studies already dealt with such an objective, but few are done at a methodological level, which forbids, for example, the correct evaluation of design choices in terms of human awareness of the situation or mental workload when designing intelligent manufacturing systems integrating the human. Indeed, increasing the intelligence and autonomy of industrial systems and their composing entities (resources, products, robots…), as fostered by Industry 4.0, increases their overall complexity. This modification reduces the ability to understand the behaviors of these systems, and leads to the difficulty for humans not only to elaborate alternative decisions when required, but also to make effective decisions and understand their consequences. This paper evaluates such a design methodology, the Cognitive Work Analysis (CWA), and its applicability when designing an assistance system to support Human in the control of Intelligent Manufacturing System in Industry 4.0. Among several functions identified through the application of CWA, the assistant system might have to integrate a digital twin of the intelligent manufacturing system. The evaluation of the methodology through the one of the designed assistant systems is done using a micro-world, which is an intelligent manufacturing cell composed of intelligent mobile ground robots, products, and static production robots interacting together and with a human supervisor in charge of the reaching of several time-based and energy-based performances indicators. The assistant system embeds a digital twin of the intelligent manufacturing system. Twenty-three participants took part in experiments to evaluate the designed assistance system. First results show that the assistance system enables participants to have a correct awareness of the situation and a correct evaluation of their alternative decisions, while their mental workload is managed and expected production performances are reached. This paper contains an analysis of these experiments and points out some limits of the CWA method in the context of Industry 4.0, especially the lack of tool enabling to specify clearly the cooperation processes between the supervisor and the intelligent manufacturing system. This paper concludes with potential research avenues, the main one being the potential benefits of coupling CWA with human–machine cooperation principles to fine tune and adapt the cooperation between the human and the intelligent manufacturing system

Deciphering the structure of isomeric oligosaccharides in a complex mixture by tandem mass spectrometry: photon activation with vacuum ultra-violet brings unique information and enables definitive structure assignment.

International audienceCarbohydrates have a wide variety of structures whose complexity and heterogeneity challenge the field of analytical chemistry. Tandem mass spectrometry, with its remarkable sensitivity and high information content, provides key advantages to addressing the structural elucidation of polysaccharides. Yet, classical fragmentation by collision-activated dissociation (CAD) in many cases fails to reach a comprehensive structural determination, especially when isomers have to be differentiated. In this work, for the first time, vacuum ultra-violet (VUV) synchrotron radiation is used as the activation process in tandem mass spectrometry of large oligosaccharides. Compared to low energy CAD (LE-CAD), photon activated dissociation brought more straightforward and valuable structural information. The outstanding feature was that complete series of informative ions were produced, with only minor neutral losses. Moreover, systematic fragmentation rules could be drawn thus facilitating the definitive assignments of fragment identities. As a result, most of the structures present in a complex mixture of oligogalacturonans could be comprehensively resolved, including many isomers differing in the position of methyl groups along the galacturonic acid backbone