1,151 research outputs found

    Citizen Science Time Domain Astronomy with Astro-COLIBRI

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    Astro-COLIBRI is an innovative tool designed for professional astronomers to facilitate the study of transient astronomical events. Transient events - such as supernovae, gamma-ray bursts and stellar mergers - are fleeting cataclysmic phenomena that can offer profound insights into the most violent processes in the universe. Revealing their secrets requires rapid and precise observations: Astro-COLIBRI alerts its users of new transient discoveries from observatories all over the world in real-time. The platform also provides observers the details they need to make follow-up observations. Some of the transient phenomena available through Astro-COLIBRI are accessible by amateur astronomers and citizen scientists. A subset of the features dedicated to this growing group of users are highlighted here. They include the possibility of receiving only alerts on very bright events, the possibility of defining custom observer locations, as well as the calculation of optimized observation plans for searches for optical counterparts to gravitational wave events.Comment: Proceedings Atelier Pro-AM Gemini, Journ\'ees SF2A 2023. arXiv admin note: text overlap with arXiv:2308.0704

    Drug hypersensitivity caused by alteration of the MHC-presented self-peptide repertoire

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    Idiosyncratic adverse drug reactions are unpredictable, dose independent and potentially life threatening; this makes them a major factor contributing to the cost and uncertainty of drug development. Clinical data suggest that many such reactions involve immune mechanisms, and genetic association studies have identified strong linkage between drug hypersensitivity reactions to several drugs and specific HLA alleles. One of the strongest such genetic associations found has been for the antiviral drug abacavir, which causes severe adverse reactions exclusively in patients expressing the HLA molecular variant B*57:01. Abacavir adverse reactions were recently shown to be driven by drug-specific activation of cytokine-producing, cytotoxic CD8+ T cells that required HLA-B*57:01 molecules for their function. However, the mechanism by which abacavir induces this pathologic T cell response remains unclear. Here we show that abacavir can bind within the F-pocket of the peptide-binding groove of HLA-B*57:01 thereby altering its specificity. This supports a novel explanation for HLA-linked idiosyncratic adverse drug reactions; namely that drugs can alter the repertoire of self-peptides presented to T cells thus causing the equivalent of an alloreactive T cell response. Indeed, we identified specific self-peptides that are presented only in the presence of abacavir, and that were recognized by T cells of hypersensitive patients. The assays we have established can be applied to test additional compounds with suspected HLA linked hypersensitivities in vitro. Where successful, these assays could speed up the discovery and mechanistic understanding of HLA linked hypersensitivities as well as guide the development of safer drugs

    Barents-2.5km v2.0: An operational data-assimilative coupled ocean and sea ice ensemble prediction model for the Barents Sea and Svalbard

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    An operational ocean and sea ice forecast model, Barents-2.5, is implemented at MET Norway for short-term forecasting at the coast off Northern Norway, the Barents Sea, and waters around Svalbard. Primary forecast parameters are the sea ice concentration (SIC), sea surface temperature (SST), and ocean currents. The model is also a substantial input for drift modeling of pollutants, ice berg, and in search-and-rescue pertinent applications in the Arctic domain. Barents-2.5 has recently been upgraded to include an Ensemble Prediction System with 24 daily realizations of the model state. SIC, SST and in-situ hydrography are constrained through the Ensemble Kalman Filter (EnKF) data assimilation scheme executed in daily forecast cycles with lead time up to 66 hours. While the ocean circulation is not directly constrained by assimilation of ocean currents, the model ensemble represents the given uncertainty in the short-term current field by retaining the current state for each member throughout forecast cycles. Here we present the model setup and a validation in terms of SIC, SST and in-situ hydrography. The performance of the ensemble to represent the models uncertainty, and the performance of the EnKF to constrain the model state are discussed, in addition to the model&rsquo;s forecast capabilities for SIC and SST.</p

    Decision process in large-scale crisis management

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    International audienceThis paper deals with the decision-aiding process in large-scale crisis such as natural disasters. It consists in four phases: decision context characterization, system modelling, aggregation and integration. The elements of the context, such as crisis level, risk situation, decision-maker problem issue are defined through the characterization phase. At the feared event occurrence, these elements will interact on a target system. Through the model on this system, the consequences to stakes could be assessed or estimated. The presented aggregation approaches will allow taking the right decisions. The architecture of a Decision Support System is presented in the integration phase

    Uncertainty information in climate data records from Earth observation

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    Climate data records (CDRs) derived from Earth observation (EO) should include rigorous uncertainty information, to support application of the data in policy, climate modelling and numerical weather prediction reanalysis. Uncertainty, error and quality are distinct concepts, and CDR products should follow international norms for presenting quantified uncertainty. Ideally, uncertainty should be quantified per datum in a CDR, and the uncertainty estimates should be able to discriminate more and less certain data with confidence. In this case, flags for data quality should not duplicate uncertainty information, but instead describe complementary information (such as the confidence held in the uncertainty estimate provided, or indicators of conditions violating retrieval assumptions). Errors have many sources and some are correlated across a wide range of time and space scales. Error effects that contribute negligibly to the total uncertainty in a single satellite measurement can be the dominant sources of uncertainty in a CDR on large space and long time scales that are highly relevant for some climate applications. For this reason, identifying and characterizing the relevant sources of uncertainty for CDRs is particularly challenging. Characterisation of uncertainty caused by a given error effect involves assessing the magnitude of the effect, the shape of the error distribution, and the propagation of the uncertainty to the geophysical variable in the CDR accounting for its error correlation properties. Uncertainty estimates can and should be validated as part of CDR validation, where possible. These principles are quite general, but the form of uncertainty information appropriate to different essential climate variables (ECVs) is highly variable, as confirmed by a quick review of the different approaches to uncertainty taken across different ECVs in the European Space Agency’s Climate Change Initiative. User requirements for uncertainty information can conflict with each other, and again a variety of solutions and compromises are possible. The concept of an ensemble CDR as a simple means of communicating rigorous uncertainty information to users is discussed. Our review concludes by providing eight recommendations for good practice in providing and communicating uncertainty in EO-based climate data records

    Cord blood-circulating endothelial progenitors for treatment of vascular diseases

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    Abstract Adult peripheral blood (PB) endothelial progenitor cells (EPC) are produced in the bone marrow and are able to integrate vascular structures in sites of neoangiogenesis. EPCs thus represent a potential therapeutic tool for ischaemic diseases. However, use of autologous EPCs in cell therapy is limited by their rarity in adult PB. Cord blood (CB) contains more EPCs than PB, and they are functional after expansion. They form primary colonies that give rise to secondary colonies, each yielding more than 10 7 cells after few passages. The number of endothelial cells obtained from one unit of CB is compatible with potential clinical application. EPC colonies can be securely produced, expanded and cryopreserved in close culture devices and endothelial cells produced in these conditions are functional as shown in different in vitro and in vivo assays. As CB EPCderived endothelial cells would be allogeneic to patients, it would be of interest to prepare them from ready-existing CB banks. We show that not all frozen CB units from a CB bank are able to generate EPC colonies in culture, and when they do so, number of colonies is lower than that obtained with fresh CB units. However, endothelial cells derived from frozen CB have the same phenotypical and functional properties than those derived from fresh CB. This indicates that CB cryopreservation should be improved to preserve integrity of stem cells other than haematopoietic ones. Feasibility of using CB for clinical applications will be validated in porcine models of ischaemia. Origin and role of EP

    Very-high-energy Îł -Ray Emission from Young Massive Star Clusters in the Large Magellanic Cloud

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    The Tarantula Nebula in the Large Magellanic Cloud is known for its high star formation activity. At its center lies the young massive star cluster R136, providing a significant amount of the energy that makes the nebula shine so brightly at many wavelengths. Recently, young massive star clusters have been suggested to also efficiently produce very high-energy cosmic rays, potentially beyond PeV energies. Here, we report the detection of very-high-energy Îł-ray emission from the direction of R136 with the High Energy Stereoscopic System, achieved through a multicomponent, likelihood-based modeling of the data. This supports the hypothesis that R136 is indeed a very powerful cosmic-ray accelerator. Moreover, from the same analysis, we provide an updated measurement of the Îł-ray emission from 30 Dor C, the only superbubble detected at TeV energies presently. The Îł-ray luminosity above 0.5 TeV of both sources is (2–3) × 1035 erg s−1. This exceeds by more than a factor of 2 the luminosity of HESS J1646−458, which is associated with the most massive young star cluster in the Milky Way, Westerlund 1. Furthermore, the Îł-ray emission from each source is extended with a significance of >3σ and a Gaussian width of about 30 pc. For 30 Dor C, a connection between the Îł-ray emission and the nonthermal X-ray emission appears likely. Different interpretations of the Îł-ray signal from R136 are discussed
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