Proteomic Analysis Identifies NDUFS1 and ATP5O as Novel Markers for Survival Outcome in Prostate Cancer

Simple Summary Due to the heterogeneity of prostate cancer (PCa), it is still difficult to provide risk stratification. Metabolic changes in PCa tissue have been described during tumor progression at genetic and transcriptomic level, but these have not yet clearly contributed to improved diagnosis and therapy. The aim of our study was to identify novel markers for aggressive prostate cancer in a proteomics-derived dataset by immunohistochemical analysis and correlation with transcriptomic data. Here, we provide potential new markers-NDUFS1 and ATP5O-for risk stratification in PCa. Additionally, we reveal for the first time a concordant increase of NDUFS1/ATP5O of mRNA expression in transcriptomic datasets and at protein level. We aimed to identify novel markers for aggressive prostate cancer in a STAT3-low proteomics-derived dataset of mitochondrial proteins by immunohistochemical analysis and correlation with transcriptomic data and biochemical recurrence in a STAT3 independent PCa cohort. Formalin-fixed paraffin-embedded tissue (FFPE) sample selection for proteomic analysis and tissue-microarray (TMA) generation was conducted from a cohort of PCa patients. Retrospective data analysis was performed with the same cohort. 153 proteins differentially expressed between STAT3-low and STAT3-high samples were identified. Out of these, 46 proteins were associated with mitochondrial processes including oxidative phosphorylation (OXPHOS), and 45 proteins were upregulated, including NDUFS1/ATP5O. In a STAT3 independent PCa cohort, high expression of NDUFS1/ATP5O was confirmed by immunocytochemistry (IHC) and was significantly associated with earlier biochemical recurrence (BCR). mRNA expression levels for these two genes were significantly higher in intra-epithelial neoplasia and in PCa compared to benign prostate glands. NDUFS1/ATP5O levels are increased both at the mRNA and protein level in aggressive PCa. Our results provide evidence that NDUFS1/ATP5O could be used to identify high-risk PCa patients

The Impact of Recent European Droughts and Heatwaves on Trace Gas Surface Fluxes: Insights from Land Surface Data Assimilation

Heatwave and drought extremes can have significant impacts on vegetation, which can in turn lead to important effects on reactive trace gas fluxes at the land-atmosphere interface that can ultimately alter atmospheric composition. We present results from the EU-funded Sentinel EObased Emission and Deposition Service (SEEDS) project, which aimed at developing upgrades to the existing Copernicus Atmospheric Monitoring Service (CAMS) component on European air quality. In this work, we used land surface modelling (SURFEX – Surface Externalisée) combined with data assimilation (Extended Kalman Filter - EKF) of satellite leaf area index (LAI) to deliver improved estimation of the land surface state. The land surface model is coupled with an online model for dry deposition and an offline model (MEGANv3.1) for biogenic volatile organic compounds (BVOCs) to estimate trace gas losses and emissions, respectively. This approach exploits methods at the forefront of land surface modelling (dynamic vegetation simulation and data assimilation) and combines them with the latest algorithms to estimate trace gas fluxes at the surface. We present findings from two extreme events in Europe: the 2018 drought and the 2019 June/July heat waves. SURFEX was forced using ECMWF meteorology at 0.1° × 0.1° resolution that captured both events. Both extreme events provoked strong responses in the models for dry deposition velocity and BVOC emissions. The 2018 drought began in spring and endured through summer, during which dry deposition velocities declined steadily beyond seasonal norms due to increased stomatal resistance forced by the vegetation response to drought. Over continental Europe, BVOCs initially increased in the early phase of the drought, but then sharply declined into July in the worst-affected regions in Germany, Denmark, and Poland. Meanwhile, BVOCs increased in Scandinavia relative to seasonal norms due to the warmer-than-average conditions. The first episode of severe heat in 2019 arrived in late June, which initially caused a large increase in BVOC emissions compared to seasonal norms. Then drought set in during July and despite a second large heat wave BVOC emissions were lower overall compared to seasonal norms. In fact, the European-wide BVOC emissions were higher in June compared to July due to the drought effects that commenced later in the heat wave cycle. This reverses the normal seasonal cycle in BVOC emissions, and drought impacts on vegetation were the primary driver behind this. Dry deposition velocities are reduced during both heat waves, but we see a larger decline in the second heat wave in July when drought conditions are more severe. Our findings suggest that these impacts on trace gas surface fluxes would have a strong effect on atmospheric composition, and on photochemical ozone formation. We, therefore, conclude that these effects likely played a contributory role to the ozone pollution episodes that occurred coincidentally in time with the heat wave events in both 2018 and 2019. The project aim within SEEDS is to eventually test the BVOC emissions and dry deposition velocities within a chemical transport model participating within the CAMS regional ensemble (MOCAGE) and to therefore evaluate the impact on ozone

The use of the Airtraq® optical laryngoscope for routine tracheal intubation in high-risk cardio-surgical patients

<p>Abstract</p> <p>Background</p> <p>The Airtraq^®optical laryngoscope (Prodol Ltd., Vizcaya, Spain) is a novel disposable device facilitating tracheal intubation in routine and difficult airway patients. No data investigating routine tracheal intubation using the Airtaq^®in patients at a high cardiac risk are available at present. Purpose of this study was to investigate the feasibility and hemodynamic implications of tracheal intubation with the Aitraq^®optical laryngoscope, in high-risk cardio-surgical patients.</p> <p>Methods</p> <p>123 consecutive ASA III patients undergoing elective coronary artery bypass grafting were routinely intubated with the Airtraq^®laryngoscope. Induction of anesthesia was standardized according to our institutional protocol. All tracheal intubations were performed by six anesthetists trained in the use of the Airtraq^®prior.</p> <p>Results</p> <p>Overall success rate was 100% (n = 123). All but five patients trachea could be intubated in the first attempt (95,9%). 5 patients were intubated in a 2nd (n = 4) or 3rd (n = 1) attempt. Mean intubation time was 24.3 s (range 16-128 s). Heart rate, arterial blood pressure and SpO₂were not significantly altered. Minor complications were observed in 6 patients (4,8%), i.e. two lesions of the lips and four minor superficial mucosal bleedings. Intubation duration (p = 0.62) and number of attempts (p = 0.26) were independent from BMI and Mallampati score.</p> <p>Conclusion</p> <p>Tracheal intubation with the Airtraq^®optical laryngoscope was feasible, save and easy to perform in high-risk patients undergoing cardiac surgery. In all patients, a sufficient view on the vocal cords could be obtained, independent from BMI and preoperative Mallampati score.</p> <p>Trial Registration</p> <p>DRKS 00003230</p

Confidence in uncertainty: Error cost and commitment in early speech hypotheses

© 2018 Loth et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Interactions with artificial agents often lack immediacy because agents respond slower than their users expect. Automatic speech recognisers introduce this delay by analysing a user’s utterance only after it has been completed. Early, uncertain hypotheses of incremental speech recognisers can enable artificial agents to respond more timely. However, these hypotheses may change significantly with each update. Therefore, an already initiated action may turn into an error and invoke error cost. We investigated whether humans would use uncertain hypotheses for planning ahead and/or initiating their response. We designed a Ghost-in-the-Machine study in a bar scenario. A human participant controlled a bartending robot and perceived the scene only through its recognisers. The results showed that participants used uncertain hypotheses for selecting the best matching action. This is comparable to computing the utility of dialogue moves. Participants evaluated the available evidence and the error cost of their actions prior to initiating them. If the error cost was low, the participants initiated their response with only suggestive evidence. Otherwise, they waited for additional, more confident hypotheses if they still had time to do so. If there was time pressure but only little evidence, participants grounded their understanding with echo questions. These findings contribute to a psychologically plausible policy for human-robot interaction that enables artificial agents to respond more timely and socially appropriately under uncertainty

Synthesis and characterization of naphthalimide-functionalized polynorbornenes

ABSTRACT: Highly fluorescent and photostable (2-alkyl)-1H-benzo[de]isoquinoline-1,3(2H)-diones with a polymerizable norbornene scaffold have been synthesized and polymerized using ring-opening metathesis polymerization. The monomers presented herein could be polymerized in a living fashion, using different comonomers and different monomer ratios. All obtained materials showed good film-forming properties and bright fluorescence caused by the incorporated push–pull chromophores. Additionally, one of the monomers containing a methylpiperazine functionality showed protonation-dependent photoinduced electron transfer which opens up interesting applications for logic gates and sensing. GRAPHICAL ABSTRACT: [Image: see text