47 research outputs found
Ketogenic diet enhances human T-cell immunity and reprograms the immunometabolism of Th17 and regulatory T cells
Untersuchung des molekularen Wirkmechanismus der Photodynamischen Therapie bei der Behandlung von Glioblastomen
The IL-1 antagonist anakinra attenuates glioblastoma aggressiveness by dampening tumor-associated inflammation
Intronic miR-744 inhibits glioblastoma migration by functionally antagonizing its host gene MAP2K4
Software-Enabled Smallsat Autonomy: Discussion with Examples
Smallsat missions using cooperating constellations offer significant benefits compared to traditional space missions. These benefits include lower unit costs, better robustness to failures, and the ability to collect data in a distributed fashion. Significant commercial smallsat missions are active in low Earth orbit, and spacecraft operators have expressed interest in smallsat constellations operating both at higher altitudes and in proximity operations missions. Autonomy plays a significant role in extending smallsat missions to these more challenging domains. Autonomy in a broad sense refers to a spacecraft\u27s or constellation\u27s ability to operate independently of ground systems, and affects every part of a typical mission. For example, onboard processing of data can significantly reduce the frequency and expense of communications to a terrestrial ground station link. Onboard safety and health management is critical in proximity operations with fast dynamics, or in remote operations where offboard monitoring is available infrequently. Onboard monitoring of mission objectives enables remote operations and reduces the required operator workload.
Emergent Space Technologies has developed flight software products to enable future missions with greater autonomy. Navigator is a standalone application for cooperative absolute and relative navigation within a cluster of space vehicles. The Autopilot software suite enables routine orbit maintenance and satellite maneuvers to be monitored and executed onboard, increasing safety and reducing reliance on ground systems. Guardian is a suite of applications thatenable fault detection, isolation, and recovery on modules within a distributed mission. The Cirrus cloud computing framework enables distributed computing tasks within a fleet of cooperating platforms, allowing complex data processing algorithms to be executed onboard and distributed among vehicles according to their computational availability. Finally, Commander is a set of applications for autonomous execution of a planned mission on a distributed group of platforms. Critically, Commander enables autonomous coordination of the actions of Navigator, Autopilot, Guardian, and Cirrus, providing a significantly greater level of autonomy than the suites provide individually. In this paper, we describe the capabilities of the flight software and demonstrate how coordination using Commander enables desired operator missions. The following missions are considered: (1) autonomous lunar injection; (2) rendezvous and proximity operations; (3) constellation intelligence, surveillance, and reconnaissance. Discussion is informed by use case diagrams and simulation results using Emergent\u27s Ascent simulation environment
Identification of suitable controls for miRNA quantification in T-cells and whole blood cells in sepsis
Complex immune dysregulation is a hallmark of sepsis. The occurring phases of immunosuppression and hyperinflammation require rapid detection and close monitoring. Reliable tools to monitor patient's immune status are yet missing. Currently, microRNAs are being discussed as promising new biomarkers in sepsis. However, no suitable internal control for normalization of miRNA expression by qPCR has been validated so far, thus hampering their potential benefit. We here present the first evaluation of endogenous controls for miRNA analysis in human sepsis. Novel candidate reference miRNAs were identified via miRNA microArray. TaqMan qPCR assays were performed to evaluate these microRNAs in T-cells and whole blood cells of sepsis patients and healthy controls in two independent cohorts. In T-cells, U48 and miR-320 proved suitable as endogenous controls, while in whole blood cells, U44 and miR-942 provided best stability values for normalization of miRNA quantification. Commonly used snRNA U6 exhibited worst stability in all sample groups. The identified internal controls have been prospectively validated in independent cohorts. The critical importance of housekeeping gene selection is emphasized by exemplary quantification of imuno-miR-150 in sepsis patients. Use of appropriate internal controls could facilitate research on miRNA-based biomarker-use and might even improve treatment strategies in the future
Impact of carbohydrate-reduced nutrition in septic patients on ICU: study protocol for a prospective randomised controlled trial
Introduction: Sepsis is defined as detrimental immune response to an infection. This overwhelming reaction often abolishes a normal reconstitution of the immune cell homeostasis that in turn increases the risk for further complications. Recent studies revealed a favourable impact of ketone bodies on resolution of inflammation. Thus, a ketogenic diet may provide an easy-to-apply and cost-effective treatment option potentially alleviating sepsis-evoked harm. This study is designed to assess the feasibility, efficiency and safety of a ketogenic diet in septic patients. Methods and analysis: This monocentric study is a randomised, controlled and open-label trial, which is conducted on an intensive care unit of a German university hospital. As intervention enteral nutrition with reduced amount of carbohydrates (ketogenic) or standard enteral nutrition (control) is applied. The primary endpoint is the detection of ketone bodies in patients' blood and urine samples. As secondary endpoints, the impact on important safety-relevant issues (eg, glucose metabolism, lactate serum concentration, incidence of metabolic acidosis, thyroid function and 30-day mortality) and the effect on the immune system are analysed. Ethics and dissemination The study has received the following approvals: Ethics Committee of the Medical Faculty of Ruhr-University Bochum (No. 18-6557-BR). Results will be made available to critical care survivors, their caregivers, the funders, the critical care societies and other researchers by publication in a peer-reviewed journal
Cell-crossing functional network driven by microRNA-125a regulates endothelial permeability and monocyte trafficking in acute inflammation
Opening of the endothelial barrier and targeted infiltration of leukocytes into the affected tissue are hallmarks of the inflammatory response. The molecular mechanisms regulating these processes are still widely elusive. In this study, we elucidate a novel regulatory network, in which miR-125a acts as a central hub that regulates and synchronizes both endothelial barrier permeability and monocyte migration. We found that inflammatory stimulation of endothelial cells induces miR-125a expression, which consecutively inhibits a regulatory network consisting of the two adhesion molecules VE-Cadherin (CDH5) and Claudin-5 (CLDN5), two regulatory tyrosine phosphatases (PTPN1, PPP1CA) and the transcription factor ETS1 eventually leading to the opening of the endothelial barrier. Moreover, under the influence of miR-125a, endothelial expression of the chemokine CCL2, the most predominant ligand for the monocytic chemokine receptor CCR2, was strongly enhanced. In monocytes, on the other hand, we detected markedly repressed expression levels of miR-125a upon inflammatory stimulation. This induced a forced expression of its direct target gene CCR2, entailing a strongly enhanced monocyte chemotaxis. Collectively, cell-type-specific differential expression of miR-125a forms a synergistic functional network controlling monocyte trafficking across the endothelial barrier towards the site of inflammation. In addition to the known mechanism of miRNAs being shuttled between cells via extracellular vesicles, our study uncovers a novel dimension of miRNA function: One miRNA, although disparately regulated in the cells involved, directs a biologic process in a synergistic and mutually reinforcing manner. These findings provide important new insights into the regulation of the inflammatory cascade and may be of great use for future clinical applications
WFIRST coronagraph detector trap modeling results and improvements
The WFIRST coronagraph is being designed to detect and characterize mature exoplanets through the starlight reflected from their surfaces and atmospheres. The light incident on the detector from these distant exoplanets is estimated to be on the order of a few photons per pixel per hour. To measure such small signals, the project has baselined the CCD201 detector made by e2v, a low-noise and high-efficiency electron-multiplying charge-coupled device (EMCCD), and has instituted a rigorous test and modeling program to characterize the device prior to flight. An important consideration is detector performance degradation over the proposed mission lifetime due to radiation exposure in space. To quantify this estimated loss in performance, the project has built a detector trap model that takes into account detailed trap interactions at the sub-pixel level, including stochastic trap capture and release, and the deferment of charge into subsequent pixels during parallel and serial clocking of the pseudo-two-phase CCD201 device. This paper describes recent detector trap model improvements and modeling results