60 research outputs found

    Improving sample efficiency and multi-agent communication in RL-based train rescheduling

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    We present preliminary results from our sixth placed entry to the Flatland international competition for train rescheduling, including two improvements for optimized reinforcement learning (RL) training efficiency, and two hypotheses with respect to the prospect of deep RL for complex real-world control tasks: first, that current state of the art policy gradient methods seem inappropriate in the domain of high-consequence environments; second, that learning explicit communication actions (an emerging machine-to-machine language, so to speak) might offer a remedy. These hypotheses need to be confirmed by future work. If confirmed, they hold promises with respect to optimizing highly efficient logistics ecosystems like the Swiss Federal Railways railway network

    Self-associated molecular patterns mediate cancer immune evasion by engaging Siglecs on T cells

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    © 2018, American Society for Clinical Investigation. This article has been published in final form at https://doi.org/10.1172/JCI120612First-generation immune checkpoint inhibitors, including anti-CTLA-4 and anti-programmed death 1 (anti-PD-1) antibodies, have led to major clinical progress, yet resistance frequently leads to treatment failure. Thus, new targets acting on T cells are needed. CD33-related sialic acid-binding immunoglobulin-like lectins (Siglecs) are pattern-recognition immune receptors binding to a range of sialoglycan ligands, which appear to function as self-associated molecular patterns (SAMPs) that suppress autoimmune responses. Siglecs are expressed at very low levels on normal T cells, and these receptors were not until recently considered as interesting targets on T cells for cancer immunotherapy. Here, we show an upregulation of Siglecs, including Siglec-9, on tumor-infiltrating T cells from non-small cell lung cancer (NSCLC), colorectal, and ovarian cancer patients. Siglec-9-expressing T cells coexpressed several inhibitory receptors, including PD-1. Targeting of the sialoglycan-SAMP/Siglec pathway in vitro and in vivo resulted in increased anticancer immunity. T cell expression of Siglec-9 in NSCLC patients correlated with reduced survival, and Siglec-9 polymorphisms showed association with the risk of developing lung and colorectal cancer. Our data identify the sialoglycan-SAMP/Siglec pathway as a potential target for improving T cell activation for immunotherapy.Peer reviewe

    Isotopic evidence (<sup>87</sup>Sr/<sup>86</sup>Sr, δ<sup>7</sup>Li) for alteration of the oceanic crust at deep-rooted mud volcanoes in the Gulf of Cadiz, NE Atlantic Ocean [(Sr-87/Sr-86, delta Li-7) ]

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    The chemical and isotopic composition of pore fluids is presented for five deep-rooted mud volcanoes aligned on a transect across the Gulf of Cadiz continental margin at water depths between 350 and 3860 m. Generally decreasing interstitial Li concentrations and Sr-87/Sr-86 ratios with increasing distance from shore are attributed to systematically changing fluid sources across the continental margin. Although highest Li concentrations at the near-shore mud volcanoes coincide with high salinities derived from dissolution of halite and late-stage evaporites, clayey, terrigenous sediments are identified as the ultimate Li source to all pore fluids investigated. Light delta Li-7 values, partly close to those of hydrothermal vent fluids (delta Li-7: +11.9 parts per thousand), indicate that Li has been mobilized during high-temperature fluid/sediment or fluid/rock interactions in the deep sub-surface. Intense leaching of terrigenous clay has led to radiogenic Sr-87/Sr-86 ratios (similar to 0.7106) in pore fluids of the near-shore mud volcanoes. In contrast, non-radiogenic Sr-87/Sr-86 ratios (similar to 0.7075) at the distal locations are attributed to admixing of a basement-derived fluid component, carrying an isotopic signature from interaction with the basaltic crust. This inference is substantiated by temperature constraints from Li isotope equilibrium calculations suggesting exchange processes at particularly high temperatures (&gt;200 degrees C) for the least radiogenic pore fluids of the most distal location.Advective pore fluids in the off-shore reaches of the Gulf of Cadiz are influenced by successive exchange processes with both oceanic crust and terrigenous, fine-grained sediments, resulting in a chemical and isotopic signature similar to that of fluids in near-shore ridge flank hydrothermal systems. This suggests that deep-rooted mud volcanoes in the Gulf of Cadiz represent a fluid pathway intermediate between mid-ocean ridge hydrothermal vent and shallow, marginal cold seep. Due to the thicker sediment coverage and slower fluid advection rates, the overall geochemical signature is shifted towards the sediment-diagenetic signal compared to ridge flank hydrothermal environments. (C) 2009 Elsevier Ltd. All rights reserved

    Plasticity in dendroclimatic response across the distribution range of Aleppo pine (Pinus halepensis)

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    We investigated the variability of the climate-growth relationship of Aleppo pine across its distribution range in the Mediterranean Basin. We constructed a network of tree-ring index chronologies from 63 sites across the region. Correlation function analysis identified the relationships of tree-ring index to climate factors for each site. We also estimated the dominant climatic gradients of the region using principal component analysis of monthly, seasonal, and annual mean temperature and total precipitation from 1,068 climatic gridpoints. Variation in ring width index was primarily related to precipitation and secondarily to temperature. However, we found that the dendroclimatic relationship depended on the position of the site along the climatic gradient. In the southern part of the distribution range, where temperature was generally higher and precipitation lower than the regional average, reduced growth was also associated with warm and dry conditions. In the northern part, where the average temperature was lower and the precipitation more abundant than the regional average, reduced growth was associated with cool conditions. Thus, our study highlights the substantial plasticity of Aleppo pine in response to different climatic conditions. These results do not resolve the source of response variability as being due to either genetic variation in provenance, to phenotypic plasticity, or a combination of factors. However, as current growth responses to inter-annual climate variability vary spatially across existing climate gradients, future climate-growth relationships will also likely be determined by differential adaptation and/or acclimation responses to spatial climatic variation. The contribution of local adaptation and/or phenotypic plasticity across populations to the persistence of species under global warming could be decisive for prediction of climate change impacts across populations. In this sense, a more complex forest dynamics modeling approach that includes the contribution of genetic variation and phenotypic plasticity can improve the reliability of the ecological inferences derived from the climate-growth relationships.This work was partially supported by Spanish Ministry of Education and Science co-funded by FEDER program (CGL2012-31668), the European Union and the National Ministry of Education and Religion of Greece (EPEAEK- Environment – Archimedes), the Slovenian Research Agency (program P4-0015), and the USDA Forest Service. The cooperation among international partners was supported by the COST Action FP1106, STREeSS

    Measurement of charged particle spectra in deep-inelastic ep scattering at HERA

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    Charged particle production in deep-inelastic ep scattering is measured with the H1 detector at HERA. The kinematic range of the analysis covers low photon virtualities, 5 LT Q(2) LT 100 GeV2, and small values of Bjorken-x, 10(-4) LT x LT 10(-2). The analysis is performed in the hadronic centre-of-mass system. The charged particle densities are measured as a function of pseudorapidity (n(*)) and transverse momentum (p(T)(*)) in the range 0 LT n(*) LT 5 and 0 LT p(T)(*) LT 10 GeV in bins of x and Q(2). The data are compared to predictions from different Monte Carlo generators implementing various options for hadronisation and parton evolutions

    On-Screen Navigation for 3D Interaction on Multi-Touch-Displays

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    A usability test with novice users was conducted on an initial and an improved navigation concept. The tested system was a multi-touch-display using infrared technology with a limit of detecting two touch-points. The task for participants was to navigate through a virtual environment using either a widget or gesture-only based navigation concept. The goal of these tests was to assess which aspects influenced intuitiveness of a system for novice users as well as to collect user expectations. The results of these tests indicated that further investigations would be necessary in certain domains as some conclusions were based on assumptions. However, this thesis gives good insights on different aspects and gives further interesting areas to be explored
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