Myeloid-Specific Rictor Deletion Induces M1 Macrophage Polarization and Potentiates In Vivo Pro-Inflammatory Response to Lipopolysaccharide

The phosphoinositide-3-kinase (PI3K)/protein kinase B (Akt) axis plays a central role in attenuating inflammation upon macrophage stimulation with toll-like receptor (TLR) ligands. The mechanistic target of rapamycin complex 2 (mTORC2) relays signal from PI3K to Akt but its role in modulating inflammation in vivo has never been investigated. To evaluate the role of mTORC2 in the regulation of inflammation in vivo, we have generated a mouse model lacking Rictor, an essential mTORC2 component, in myeloid cells. Primary macrophages isolated from myeloid-specific Rictor null mice exhibited an exaggerated response to TLRs ligands, and expressed high levels of M1 genes and lower levels of M2 markers. To determine whether the loss of Rictor similarly affected inflammation in vivo, mice were either fed a high fat diet, a situation promoting chronic but low-grade inflammation, or were injected with lipopolysaccharide (LPS), which mimics an acute, severe septic inflammatory condition. Although high fat feeding contributed to promote obesity, inflammation, macrophage infiltration in adipose tissue and systemic insulin resistance, we did not observe a significant impact of Rictor loss on these parameters. However, mice lacking Rictor exhibited a higher sensitivity to sceptic shock when injected with LPS. Altogether, these results indicate that mTORC2 is a key negative regulator of macrophages TLR signalling and that its role in modulating inflammation is particularly important in the context of severe inflammatory challenges. These observations suggest that approaches aimed at modulating mTORC2 activity may represent a possible therapeutic approach for diseases linked to excessive inflammation.Howard Hughes Medical Institute (Investigator)National Institutes of Health (U.S.) (NIH grant CA103866)National Institutes of Health (U.S.) (NIH grant CA129105)National Institutes of Health (U.S.) (NIH grant AI47389)Canadian Institutes of Health ResearchNatural Sciences and Engineering Research Council of CanadaFonds de la recherche en santé du Québe

Exploiting wind to optimize flight paths for greener commercial flight operations

Trajectory Based Operations (TBO) has been identified by ICAO as a key aviation evolution with significant developments in Next Gen Flight Management Systems (FMS) to communicate with ground based 4DT Air Traffic Management (ATM) system of the future. The Next generation ATM and FMS systems will include the capability of generating 4D trajectories to increase aircraft efficiency and reduce emissions. Natural resources, such as the wind, can be exploited to reduce the aircraft's fuel usage and travel time while improving its operational efficiency. These benefits are realized if trajectories are formulated to maximise the time in tailwind scenarios. The results presented here quantify the fuel and time savings of a typical Australasian route using a simulated wind field as an input to the optimization problem. Minimum fuel burn and emissions are achieved by minimising flight time at constant cruise speed. The attainable savings appeal to aircraft operators as they reduce operational cost. Optimization algorithms to formulate efficient flight trajectories are hence an essential tool in reducing aviation's carbon footprint. Future research will focus on the implementation of 4DT operations and associated logistics. Simulations of common commercial and international flight routes from departure to destination using 4DT intent negotiation and validation routines will allow for an accurate evaluation of the potential savings in fuel and reduction in emissions

Automated ATM system enabling 4DT-based operations

As part of the current initiatives aimed at enhancing safety, efficiency and environmental sustainability of aviation, a significant improvement in the efficiency of aircraft operations is currently pursued. Innovative Communication, Navigation, Surveillance and Air Traffic Management (CNS/ATM) technologies and operational concepts are being developed to achieve the ambitious goals for efficiency and environmental sustainability set by national and international aviation organizations. These technological and operational innovations will be ultimately enabled by the introduction of novel CNS/ATM and Avionics (CNS+A) systems, featuring higher levels of automation. A core feature of such systems consists in the real-time multi-objective optimization of flight trajectories, incorporating all the operational, economic and environmental aspects of the aircraft mission. This article describes the conceptual design of an innovative ground-based Air Traffic Management (ATM) system featuring automated 4-Dimensional Trajectory (4DT) functionalities. The 4DT planning capability is based on the multi-objective optimization of 4DT intents. After summarizing the concept of operations, the top-level system architecture and the key 4DT optimization modules, we discuss the segmentation algorithm to obtain flyable and concisely described 4DT. Simulation case studies in representative scenarios show that the adopted algorithms generate solutions consistently within the timeframe of online tactical rerouting tasks, meeting the set design requirements

A low-cost vision based navigation system for small size unmanned aerial vehicle applications

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Novel ATM and avionic systems for environmentally sustainable aviation

Large-scale air transport modernisation initiatives including the Single European Sky Air Traffic Management Research (SESAR), Next Generation Air Transportation System (NextGen) and Clean Sky Joint Technology Initiative for Aeronautics and Air Transport aim to improve the operational efficiency, safety and environmental sustainability of aviation. Scientific advances in Air Transport Management (ATM) and avionic systems are required to achieve the ambitious goals set by national and international aviation organisations. This paper presents the recent advances in ATM and avionic system concepts, integrated architectures and trajectory generation algorithms, to be adopted in Next Generation Avionics Flight Management Systems (NG-FMS) and ground-based 4-Dimensional Trajectory Planning, Negotiation and Validation (4-PNV) systems. Current research efforts are focussed on the development of NG-FMS and 4-PNV systems for Four Dimensional (4D) Trajectory/Intent Based Operations (TBO/IBO), enabling automated negotiation and validation of aircraft intents and thus alleviating the workload of operators. After describing the NG-FMS/4PNV concept of operations, the overall system architecture and the key mathematical models describing the 4DT optimisation algorithms are introduced. Simulation case studies utilising realistic operational scenarios highlight the generation and optimisation of a family of 4DT intents by the NG-FMS corresponding to a set of performance weightings agreed between Air Navigation Service Providers (ANSP) and Airline Operation Centres (AOC). The savings on time, fuel burn and gaseous emissions (CO2 and NOx) associated with the globally optimal 4DT intents are presented. The developed optimisation and negotiation/validation loops meet the timeframe requirements of typical online tactical routing/rerouting tasks

Changing patterns of conflict between humans, carnivores and crop-raiding prey as large carnivores recolonize human-dominated landscapes

Large carnivores are making remarkable comebacks in Europe, but how this affects human-wildlife conflict remains unclear. Rebounding carnivore populations lead to increasing livestock depredation, which in turn leads to greater economic losses for farmers. However, returning carnivores could also influence the behavior of wild ungulates, which are themselves responsible for major crop damage and associated economic losses. Here, we exploit the natural experiment of a rebounding wolf population in the Italian Apennines to study how this affected both types of human-wildlife conflic. We used large datasets of wolf occurrences (n = 351), livestock depredation events (n = 165), and crop damage events by wild boar (n = 3442) to independently model the determinants of livestock depredation and crop damage distribution in relation to wolf habitat suitability over a ten-year period of increasing wolf numbers. These analyses yielded two major insights. First, livestock depredations were mainly related to insufficient prevention measures (e.g. lacking fencing) rather than landscape context, providing a clear pathway to conflict mitigation. Second, crop damage decreased in areas of higher wolf habitat suitability and became more likely in areas of lower wolf habitat suitability, closer to settlements. This suggests increasing predation pressure forces wild boars to avoid the most suitable wolf habitat, leading to a redistribution of crop damage in the landscape. More generally, our study highlights complex human-wildlife interactions as large carnivores recover in human-dominated landscapes, suggesting that multiple, cooccurring conflicts need to be assessed jointly and adaptively in order to foster coexistence between humans and wildlife

Analysis of the accuracy of ten algorithms for orientation estimation using inertial and magnetic sensing under optimal conditions: One size does not fit all

The orientation of a magneto and inertial measurement unit (MIMU) is estimated by means of sensor fusion algorithms (SFAs) thus enabling human motion tracking. However, despite several SFAs implementations proposed over the last decades, there is still a lack of consensus about the best performing SFAs and their accuracy. As suggested by recent literature, the filter parameters play a central role in determining the orientation errors. The aim of this work is to analyze the accuracy of ten SFAs while running under the best possible conditions (i.e., their parameter values are set using the orientation reference) in nine experimental scenarios including three rotation rates and three commercial products. The main finding is that parameter values must be specific for each SFA according to the experimental scenario to avoid errors comparable to those obtained when the de-fault parameter values are used. Overall, when optimally tuned, no statistically significant differ-ences are observed among the different SFAs in all tested experimental scenarios and the absolute errors are included between 3.8 deg and 7.1 deg. Increasing the rotation rate generally leads to a significant performance worsening. Errors are also influenced by the MIMU commercial model. SFA MATLAB implementations have been made available online

The Lithium Salts of Bis(azolyl)borates as Strontium‐ and Chlorine‐free Red Pyrotechnic Colorants

After concerns regarding the use of chlorinated material for pyrotechnic items had reinforced, the action of the U.S. Environmental Protection Agency on health concerns about strontium ushered in a new era in the production of red light. Lithium was shown to impart red color to a pyrotechnic flame, however only a very narrow selection of such formulations can be found in the literature. Dihydrobis(azolyl)borates are a well investigated, easily accessible class of materials which have been proven to be suitable as pyrotechnic coloring agents. With their high nitrogen contents such moieties should also meet the requirements of a low combustion temperature and a reducing flame atmosphere for a lithium‐based red‐burning composition. This work evaluates the capability of the lithium salts of dihydrobis(pyrazol‐1‐yl)borate, dihydrobis(1,2,4‐triazol‐1‐yl)borate, and dihydrobis(tetrazol‐1‐yl)borate to serve as red color imparters. The latter compounds were characterized by multinuclear NMR experiments, IR spectroscopy, elemental analysis, and single‐crystal X‐ray diffraction and were investigated with respect to their thermal stabilities as well as sensitivities toward various ignition stimuli

Survey of ortho-H2D+in high-mass star-forming regions

Context. Deuteration has been suggested to be a reliable chemical clock of star-forming regions due to its strong dependence on density and temperature changes during cloud contraction. In particular, the H3+ isotopologues (e.g. ortho-H2D+) seem to act as good proxies of the evolutionary stages of the star formation process. While this has been widely explored in low-mass star-forming regions, in the high-mass counterparts only a few studies have been pursued, and the reliability of deuteration as a chemical clock remains inconclusive. Aims. We present a large sample of o-H2D+ observations in high-mass star-forming regions and discuss possible empirical correlations with relevant physical quantities to assess its role as a chronometer of star-forming regions through different evolutionary stages. Methods. APEX observations of the ground-state transition of o-H2D+ were analysed in a large sample of high-mass clumps selected from the ATLASGAL survey at different evolutionary stages. Column densities and beam-Averaged abundances of o-H2D+ with respect to H2, X(o-H2D+), were obtained by modelling the spectra under the assumption of local thermodynamic equilibrium. Results. We detect 16 sources in o-H2D+ and find clear correlations between X(o-H2D+) and the clump bolometric luminosity and the dust temperature, while only a mild correlation is found with the CO-depletion factor. In addition, we see a clear correlation with the luminosity-To-mass ratio, which is known to trace the evolution of the star formation process. This would indicate that the deuterated forms of H3+ are more abundant in the very early stages of the star formation process and that deuteration is influenced by the time evolution of the clumps. In this respect, our findings would suggest that the X(o-H2D+) abundance is mainly affected by the thermal changes rather than density changes in the gas. We have employed these findings together with observations of H13CO+, DCO+, and C17O to provide an estimate of the cosmic-ray ionisation rate in a sub-sample of eight clumps based on recent analytical work. Conclusions. Our study presents the largest sample of o-H2D+ in star-forming regions to date. The results confirm that the deuteration process is strongly affected by temperature and suggests that o-H2D+ can be considered a reliable chemical clock during the star formation processes, as proved by its strong temporal dependence

Incoherent transient radio emission from stellar-mass compact objects in the SKA era

The universal link between the processes of accretion and ejection leads to the formation of jets and outflows around accreting compact objects. Incoherent synchrotron emission from these outflows can be observed from a wide range of accreting binaries, including black holes, neutron stars, and white dwarfs. Monitoring the evolution of the radio emission during their sporadic outbursts provides important insights into the launching of jets, and, when coupled with the behaviour of the source at shorter wavelengths, probes the underlying connection with the accretion process. Radio observations can also probe the impact of jets/outflows (including other explosive events such as magnetar giant flares) on the ambient medium, quantifying their kinetic feedback. The high sensitivity of the SKA will open up new parameter space, enabling the monitoring of accreting stellar-mass compact objects from their bright, Eddington-limited outburst states down to the lowest-luminosity quiescent levels, whose intrinsic faintness has to date precluded detailed studies. A census of quiescently accreting black holes will also constrain binary evolution processes. By enabling us to extend our existing investigations of black hole jets to the fainter jets from neutron star and white dwarf systems, the SKA will permit comparative studies to determine the role of the compact object in jet formation. The high sensitivity, wide field of view and multi-beaming capability of the SKA will enable the detection and monitoring of all bright flaring transients in the observable local Universe, including the ULXs, ... [Abridged] This chapter reviews the science goals outlined above, demonstrating the progress that will be made by the SKA. We also discuss the potential of the astrometric and imaging observations that would be possible should a significant VLBI component be included in the SKA.Comment: To be published in: "Advancing Astrophysics with the Square Kilometre Array", Proceedings of Science, PoS(AASKA14