La pollution par les composés fluorés et ses effets sur les arbres fruitiers du Valais

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Multi-criteria Performance Assessment of Adaptive Radar Resources Management: Application to Naval Scenario

International audienceMultifunction radars (MFR) must achieve their capability requirements in an increasingly complex environment, populated with diverse and hostile targets (e.g. low Radar Cross-Section, low speed targets in clutter or high speed, ballistic targets) in saturating scenarios (due to e.g. RF interference or threats). These radar systems are increasingly exploiting active electronically scanned array (AESA) technology to dynamically schedule the use of multiple functions in a short duration. However, the increasing complexity and adaptive nature of MFR radar makes it very difficult to specify their performance in a way which can both deliver the required capability and which can be verified in a cost-effective manner. Due to their multi-function feature, the operational scenarios have a strong impact on MFR radars; their performances should be specified accordingly. Addressing the challenges in this area will benefit via better understood requirements which can be more easily interpreted. After definition of FoM (Figures of Merit) for phased array radar operation and performance, we have computed them on benchmark test scenarios of varying complexity. We describe a new methodology to aggregate these metrics to provide a global notation of MFR radar performances

The Mitotic Protein Kinase Haspin and Its Inhibitors

Haspin is an atypical serine/threonine protein kinase essential to mitosis. Unlike other protein kinases, its kinase domain does not require phosphorylation in order to be activated and bears very high substrate specificity and selectivity. Few substrates have been identified so far. Haspin phosphorylation on threonine 3 of Histone H3 from prophase to anaphase participates to centromeric Aurora B localization and ensures proper kinetochore-microtubule attachment. Haspin is also involved in the maintenance of centromeric cohesion and the mitotic spindle. Inhibitors have been developed and provided tools to dissect Haspin function. The kinase is now considered as a potential therapeutic target against cancer. We discuss here the latest findings on this essential mitotic protein

Prodromal neuroinflammatory, cholinergic and metabolite dysfunction detected by PET and MRS in the TgF344-AD transgenic rat model of AD: a collaborative multi-modal study

Mouse models of Alzheimer's disease (AD) are valuable but do not fully recapitulate human AD pathology, such as spontaneous Tau fibril accumulation and neuronal loss, necessitating the development of new AD models. The transgenic (TG) TgF344-AD rat has been reported to develop age-dependent AD features including neuronal loss and neurofibrillary tangles, despite only expressing APP and PSEN1 mutations, suggesting an improved modelling of AD hallmarks. Alterations in neuronal networks as well as learning performance and cognition tasks have been reported in this model, but none have combined a longitudinal, multimodal approach across multiple centres, which mimics the approaches commonly taken in clinical studies. We therefore aimed to further characterise the progression of AD-like pathology and cognition in the TgF344-AD rat from young-adults (6 months (m)) to mid- (12 m) and advanced-stage (18 m, 25 m) of the disease. Methods: TgF344-AD rats and wild-type (WT) littermates were imaged at 6 m, 12 m and 18 m with [18F]DPA-714 (TSPO, neuroinflammation), [18F]Florbetaben (Aβ) and [18F]ASEM (α7-nicotinic acetylcholine receptor) and with magnetic resonance spectroscopy (MRS) and with (S)-[18F]THK5117 (Tau) at 15 and 25 m. Behaviour tests were also performed at 6 m, 12 m and 18 m. Immunohistochemistry (CD11b, GFAP, Aβ, NeuN, NeuroChrom) and Tau (S)-[18F]THK5117 autoradiography, immunohistochemistry and Western blot were also performed. Results: [18F]DPA-714 positron emission tomography (PET) showed an increase in neuroinflammation in TG vs wildtype animals from 12 m in the hippocampus (+11%), and at the advanced-stage AD in the hippocampus (+12%), the thalamus (+11%) and frontal cortex (+14%). This finding coincided with strong increases in brain microgliosis (CD11b) and astrogliosis (GFAP) at these time-points as assessed by immunohistochemistry. In vivo [18F]ASEM PET revealed an age-dependent increase uptake in the striatum and pallidum/nucleus basalis of Meynert in WT only, similar to that observed with this tracer in humans, resulting in TG being significantly lower than WT by 18 m. In vivo [18F]Florbetaben PET scanning detected Aβ accumulation at 18 m, and (S)-[18F]THK5117 PET revealed subsequent Tau accumulation at 25m in hippocampal and cortical regions. Aβ plaques were low but detectable by immunohistochemistry from 6 m, increasing further at 12 and 18 m with Tau-positive neurons adjacent to Aβ plaques at 18 m. NeuroChrom (a pan neuronal marker) immunohistochemistry revealed a loss of neuronal staining at the Aβ plaques locations, while NeuN labelling revealed an age-dependent decrease in hippocampal neuron number in both genotypes. Behavioural assessment using the novel object recognition task revealed that both WT & TgF344-AD animals discriminated the novel from familiar object at 3 m and 6 m of age. However, low levels of exploration observed in both genotypes at later time-points resulted in neither genotype successfully completing the task. Deficits in social interaction were only observed at 3 m in the TgF344-AD animals. By in vivo MRS, we showed a decrease in neuronal marker N-acetyl-aspartate in the hippocampus at 18 m (-18% vs age-matched WT, and -31% vs 6 m TG) and increased Taurine in the cortex of TG (+35% vs age-matched WT, and +55% vs 6 m TG). Conclusions: This multi-centre multi-modal study demonstrates, for the first time, alterations in brain metabolites, cholinergic receptors and neuroinflammation in vivo in this model, validated by robust ex vivo approaches. Our data confirm that, unlike mouse models, the TgF344-AD express Tau pathology that can be detected via PET, albeit later than by ex vivo techniques, and is a useful model to assess and longitudinally monitor early neurotransmission dysfunction and neuroinflammation in AD

Multiple star systems in the Orion nebula

This is the author accepted manuscript. The final fersion is available from EDP Sciences via the DOI in this record.This work presents an interferometric study of the massive-binary fraction in the Orion Trapezium cluster with the recently comissioned GRAVITY instrument. We observed a total of 16 stars of mainly OB spectral type. We find three previously unknown companions for θ1 Ori B, θ2 Ori B, and θ2 Ori C. We determined a separation for the previously suspected companion of NU Ori. We confirm four companions for θ1 Ori A, θ1 Ori C, θ1 Ori D, and θ2 Ori A, all with substantially improved astrometry and photometric mass estimates. We refined the orbit of the eccentric high-mass binary θ1 Ori C and we are able to derive a new orbit for θ1 Ori D. We find a system mass of 21.7 M⊙ and a period of 53 days. Together with other previously detected companions seen in spectroscopy or direct imaging, eleven of the 16 high-mass stars are multiple systems. We obtain a total number of 22 companions with separations up to 600 AU. The companion fraction of the early B and O stars in our sample is about two, significantly higher than in earlier studies of mostly OB associations. The separation distribution hints toward a bimodality. Such a bimodality has been previously found in A stars, but rarely in OB binaries, which up to this point have been assumed to be mostly compact with a tail of wider companions. We also do not find a substantial population of equal-mass binaries. The observed distribution of mass ratios declines steeply with mass, and like the direct star counts, indicates that our companions follow a standard power law initial mass function. Again, this is in contrast to earlier findings of flat mass ratio distributions in OB associations. We excluded collision as a dominant formation mechanism but find no clear preference for core accretion or competitive accretion.Marie Skłodowska-Curie Grant AgreementFCT-PortugalERC Starting Gran

Design, Synthesis and SAR in 2,4,7-Trisubstituted Pyrido[3,2-d]Pyrimidine Series as Novel PI3K/mTOR Inhibitors

This work describes the synthesis, enzymatic activities on PI3K and mTOR, in silico docking and cellular activities of various uncommon 2,4,7 trisubstituted pyrido[3,2-d]pyrimidines. The series synthesized offers a chemical diversity in C-7 whereas C-2 (3-hydroxyphenyl) and C-4 groups (morpholine) remain unchanged, in order to provide a better understanding of the molecular determinants of PI3K selectivity or dual activity on PI3K and mTOR. Some C-7 substituents were shown to improve the efficiency on kinases compared to the 2,4-di-substituted pyrimidopyrimidine derivatives used as references. Six novel derivatives possess IC50 values on PI3Kα between 3 and 10 nM. The compounds with the best efficiencies on PI3K and mTOR induced micromolar cytotoxicity on cancer cell lines possessing an overactivated PI3K pathway

Etude de complexes ates en série diazinique (Synthèse de molécules biologiquement actives à cœur pyrazinique)

Dans une première partie, nous avons mis au point une nouvelle méthodologie de synthèse en série diazinique, en effectuant la réaction d échange halogène métal par l utilisation du tri-n-butylmagnésiate de lithium. Dans une seconde partie, nous nous sommes proposé de réaliser une synthèse énantiosélective des Barrenazines par formation du cycle pyrazinique à partir de l acide (L)-aspartique. Nous avons pu synthétiser un précurseur de la Barrenazine A. Nous avons effectué la synthèse de produits naturels extraits des ascidies : les Botryllazines A et B qui présentent des propriétés cytotoxiques. Notre stratégie de synthèse est basée sur la fonctionnalisation du cycle pyrazinique en utilisant des réactions de métallation et de couplage croisé. Nous avons aussi synthétisé un isomère de la Botryllazine A.In a first part, we developed a new methodology of synthesis in the diazine series by carrying out the Metal Halogene Exchange by the use of n-Butyl Lithium Magnesate. In the second part, we proposed to synthesize Barrenazines by pyrazinic ring formation from the (L)-aspartic acid and we could synthesize a precursor of Barrenazine A. We synthesized natural products extracted from ascidies : Botryllazines A and B which present cytotoxic properties. Our synthetic strategy is based on the pyrazinic ring fonctionnalisation by using metalation and cross coupling reactions. We have synthesized Botryllazine A and B as well as an isomer of Botryllazine A.ROUEN-BU Sciences (764512102) / SudocROUEN-BU Sciences Madrillet (765752101) / SudocSudocFranceF

Collaborative Multi-Radars Tracking by Distributed Auctions

International audienceIn this paper, we present an algorithm which lies in the domain of task allocation for a set of static autonomous radars with rotating antennas. It allows a set of radars to allocate in a fully decentralized way a set of active tracking tasks according to their location, considering that a target can be tracked by several radars, in order to improve accuracy with which the target is tracked. The allocation algorithm proceeds through a collaborative and fully decentralized auction protocol, using a collaborative auction protocol (Consensus Based Bundle Auction algorithm). Our algorithm is based on a double use of our allocation protocol among the radars. The latter begin by allocating targets, then launch a second round of allocation if theyhave resources left, in order to improve accuracy on targets already tracked. Our algorithm is also able to adapt to dynamism, i.e. to take into account the fact that the targets are moving and that the radar(s) most suitable for Tracking them changes as the mission progresses. To do this, the algorithm is restarted on a regular basis, to ensure that a bid made by a radar can decrease when the target moves away from it. Since our algorithm is based on collaborative auctions, it does not plan the following rounds, assuming that the targets are not predictable enough for this. Our algorithm is however based on radars capable of anticipating the positions of short-term targets, thanks to a Kalman filter. The algorithm will be illustrated based on a multi-radar tracking scenario where the radars, autonomous, must follow a set of targets in order to reduce the position uncertainty of the targets. Standby aspects will not be considered in this scenario. It is assumed that the radars can pick up targets in active pursuit, with an area ofuncertainty corresponding to their distance

Collaborative Multi-Radars Tracking by Distributed Auctions

In this paper, we present an algorithm which lies in the domain of task allocation for a set of static autonomous radars with rotating antennas. It allows a set of radars to allocate in a fully decentralized way a set of active tracking tasks according to their location, considering that a target can be tracked by several radars, in order to improve accuracy with which the target is tracked. The allocation algorithm proceeds through a collaborative and fully decentralized auction protocol, using a collaborative auction protocol (Consensus Based Bundle Auction algorithm). Our algorithm is based on a double use of our allocation protocol among the radars. The latter begin by allocating targets, then launch a second round of allocation if theyhave resources left, in order to improve accuracy on targets already tracked. Our algorithm is also able to adapt to dynamism, i.e. to take into account the fact that the targets are moving and that the radar(s) most suitable for Tracking them changes as the mission progresses. To do this, the algorithm is restarted on a regular basis, to ensure that a bid made by a radar can decrease when the target moves away from it. Since our algorithm is based on collaborative auctions, it does not plan the following rounds, assuming that the targets are not predictable enough for this. Our algorithm is however based on radars capable of anticipating the positions of short-term targets, thanks to a Kalman filter. The algorithm will be illustrated based on a multi-radar tracking scenario where the radars, autonomous, must follow a set of targets in order to reduce the position uncertainty of the targets. Standby aspects will not be considered in this scenario. It is assumed that the radars can pick up targets in active pursuit, with an area ofuncertainty corresponding to their distance