518 research outputs found

    Predicting pilot behavior in medium-scale scenarios using game theory and reinforcement learning

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    Cataloged from PDF version of article.A key element to meet the continuing growth in air traffic is the increased use of automation. Decision support systems, computer-based information acquisition, trajectory planning systems, high-level graphic display systems, and all advisory systems are considered to be automation components related to next generation (NextGen) air space. Given a set of goals represented as reward functions, the actions of the players may be predicted. However, several challenges need to be overcome. First, determining how a player can attempt to maximize their reward function can be a difficult inverse problem. Second, players may not be able to perfectly maximize their reward functions. ADS-B technology can provide pilots the information, position, velocity, etc. of other aircraft. However, a pilot has limited ability to use all this information for his/her decision making. For this scenario, the authors model these pilot limitations by assuming that pilots can observe a limited section of the grid in front of them

    The unusual 2006 dwarf nova outburst of GK Perseii

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    The 2006 outburst of GK Perseii differed significantly at optical and ultraviolet wavelengths from typical outbursts of this object. We present multi-wavelength (X-ray, UV and optical) Swift and AAVSO data, giving unprecedented broad-band coverage of the outburst, allowing us to follow the evolution of the longer-than-normal 2006 outburst across these wavelengths. In the optical and UV we see a triple-peaked morphology with maximum brightness ~1.5 magnitudes lower than in previous years. In contrast, the peak hard X-ray flux is the same as in previous outbursts. We resolve this dichotomy by demonstrating that the hard X-ray flux only accounts for a small fraction of the total energy liberated during accretion, and interpret the optical/UV outburst profile as arising from a series of heating and cooling waves traversing the disc, caused by its variable density profile.Comment: 9 pages, 7 figures, accepted for publication in MNRA

    Effects of Oxygen During Long-term Hypothermic Machine Perfusion in a Porcine Model of Kidney Donation After Circulatory Death

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    International audienceBackground:Hypothermic machine perfusion (HMP) has become standard care in many center’s to preserve kidneys donated after circulatory death (DCD). Despite a significant reduction in metabolism at low temperatures, remaining cellular activity requires oxygen. Since the role and safety of oxygen during HMP has not been fully clarified, its supply during HMP is not standard yet. This study investigates the effect of administering oxygen during HMP on renal function in a porcine DCD model.Methods: After 30 minutes of warm ischemia, porcine slaughterhouse kidneys were preserved for 24 hours by means of cold storage (CS), or HMP with Belzer Machine Perfusion Solution (UW- MPS) supplemented with no oxygen, 21% or 100% oxygen. Next, kidneys were reperfused for 4 hours in a normothermic machine perfusion (NMP) setup.Results:HMP resulted in significantly better kidney function during NMP. Thiobarbituric acid-reactive substances (TBARS), markers of oxidative stress, were significantly lower in HMP preserved kidneys. HMP preserved kidneys showed significantly lower ASAT and LDH levels compared to kidneys preserved by CS. No differences were found between the HMP groups subjected to different oxygen concentrations. ATP levels significantly improved during HMP when active oxygenation was applied.Conclusion:This study showed that preservation of DCD kidneys with HMP is superior to CS. Although the addition of oxygen to HMP did not result in significantly improved renal function, beneficial effects were found in terms of reduced oxidative stress and energy status. Oxygen addition proofed to be safe and did not show detrimental effects

    Proteomic analysis of machine perfusion solution from brain dead donor kidneys reveals that elevated complement, cytoskeleton and lipid metabolism proteins are associated with 1-year outcome

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    Assessment of donor kidney quality is based on clinical scores or requires biopsies for histological assessment. Noninvasive strategies to identify and predict graft outcome at an early stage are, therefore, needed. We evaluated the perfusate of donation after brain death (DBD) kidneys during nonoxygenated hypothermic machine perfusion (HMP). In particular, we compared perfusate protein profiles of good outcome (GO) and suboptimal outcome (SO) 1-year post-transplantation. Samples taken 15 min after the start HMP (T1) and before the termination of HMP (T2) were analysed using quantitative liquid chromatography-tandem mass spectrometry (LC-MS/MS). Hierarchical clustering of the 100 most abundant proteins showed discrimination between grafts with a GO and SO at T1. Elevated levels of proteins involved in classical complement cascades at both T1 and T2 and a reduced abundance of lipid metabolism at T1 and of cytoskeletal proteins at T2 in GO versus SO was observed. ATP-citrate synthase and fatty acid-binding protein 5 (T1) and immunoglobulin heavy variable 2-26 and desmoplakin (T2) showed 91% and 86% predictive values, respectively, for transplant outcome. Taken together, DBD kidney HMP perfusate profiles can distinguish between outcome 1-year post-transplantation. Furthermore, it provides insights into mechanisms that could play a role in post-transplant outcomes.</p

    Clinical Laboratory Testing Practices in Diffuse Gliomas Prior to Publication of 2021 World Health Organization Classification of Central Nervous System Tumors

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    CONTEXT.—: Integration of molecular data into glioma classification supports diagnostic, prognostic, and therapeutic decision-making; however, testing practices for these informative biomarkers in clinical laboratories remain unclear. OBJECTIVE.—: To examine the prevalence of molecular testing for clinically relevant biomarkers in adult and pediatric gliomas through review of a College of American Pathologists proficiency testing survey prior to the release of the 2021 World Health Organization Classification of Central Nervous System Tumors. DESIGN.—: College of American Pathologists proficiency testing 2020 survey results from 96 laboratories performing molecular testing for diffuse gliomas were used to determine the use of testing for molecular biomarkers in gliomas. RESULTS.—: The data provide perspective into the testing practices for diffuse gliomas from a broad group of clinical laboratories in 2020. More than 98% of participating laboratories perform testing for glioma biomarkers recognized as diagnostic for specific subtypes, including IDH. More than 60% of laboratories also use molecular markers to differentiate between astrocytic and oligodendroglial lineage tumors, with some laboratories providing more comprehensive analyses, including prognostic biomarkers, such as CDKN2A/B homozygous deletions. Almost all laboratories test for MGMT promoter methylation to identify patients with an increased likelihood of responding to temozolomide. CONCLUSIONS.—: These findings highlight the state of molecular testing in 2020 for the diagnosis and classification of diffuse gliomas at large academic medical centers. The findings show that comprehensive molecular testing is not universal across clinical laboratories and highlight the gaps between laboratory practices in 2020 and the recommendations in the 2021 World Health Organization Classification of Central Nervous System Tumors

    A foundation for runtime monitoring

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    Runtime Verification is a lightweight technique that complements other verification methods in an effort to ensure software correctness. The technique poses novel questions to software engineers: it is not easy to identify which specifications are amenable to runtime monitor-ing, nor is it clear which monitors effect the required runtime analysis correctly. This exposition targets a foundational understanding of these questions. Particularly, it considers an expressive specification logic (a syntactic variant of the modal μ-calculus) that is agnostic of the verification method used, together with an elemental framework providing an operational semantics for the runtime analysis performed by monitors. The correspondence between the property satisfactions in the logic on the one hand, and the verdicts reached by the monitors performing the analysis on the other, is a central theme of the study. Such a correspondence underpins the concept of monitorability, used to identify the subsets of the logic that can be adequately monitored for by RV. Another theme of the study is that of understanding what should be expected of a monitor in order for the verification process to be correct. We show how the monitor framework considered can constitute a basis whereby various notions of monitor correctness may be defined and investigated.peer-reviewe

    A Foundation for Runtime Monitoring

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    Runtime Verification is a lightweight technique that complements other verification methods in an effort to ensure software correctness. The technique poses novel questions to software engineers: it is not easy to identify which specifications are amenable to runtime monitoring, nor is it clear which monitors effect the required runtime analysis correctly. This exposition targets a foundational understanding of these questions. Particularly, it considers an expressive specification logic (a syntactic variant of the mmucalc) that is agnostic of the verification method used, together with an elemental framework providing an operational semantics for the runtime analysis performed by monitors. The correspondence between the property satisfactions in the logic on the one hand, and the verdicts reached by the monitors performing the analysis on the other, is a central theme of the study. Such a correspondence underpins the concept of monitorability, used to identify the subsets of the logic that can be adequately monitored for by RV. Another theme of the study is that of understanding what should be expected of a monitor in order for the verification process to be correct. We show how the monitor framework considered can constitute a basis whereby various notions of monitor correctness may be defined and investigated

    An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

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    For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

    Activating mutations of the GNAQ gene: a frequent event in primary melanocytic neoplasms of the central nervous system

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    Primary melanocytic neoplasms of the central nervous system (CNS) are uncommon neoplasms derived from melanocytes that normally can be found in the leptomeninges. They cover a spectrum of malignancy grades ranging from low-grade melanocytomas to lesions of intermediate malignancy and overtly malignant melanomas. Characteristic genetic alterations in this group of neoplasms have not yet been identified. Using direct sequencing, we investigated 19 primary melanocytic lesions of the CNS (12 melanocytomas, 3 intermediate-grade melanocytomas, and 4 melanomas) for hotspot oncogenic mutations commonly found in melanocytic tumors of the skin (BRAF, NRAS, and HRAS genes) and uvea (GNAQ gene). Somatic mutations in the GNAQ gene at codon 209, resulting in constitutive activation of GNAQ, were detected in 7/19 (37%) tumors, including 6/12 melanocytomas, 0/3 intermediate-grade melanocytomas, and 1/4 melanomas. These GNAQ-mutated tumors were predominantly located around the spinal cord (6/7). One melanoma carried a BRAF point mutation that is frequently found in cutaneous melanomas (c.1799 T>A, p.V600E), raising the question whether this is a metastatic rather than a primary tumor. No HRAS or NRAS mutations were detected. We conclude that somatic mutations in the GNAQ gene at codon 209 are a frequent event in primary melanocytic neoplasms of the CNS. This finding provides new insight in the pathogenesis of these lesions and suggests that GNAQ-dependent mitogen-activated kinase signaling is a promising therapeutic target in these tumors. The prognostic and predictive value of GNAQ mutations in primary melanocytic lesions of the CNS needs to be determined in future studies
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