Rosiglitazone, a Peroxisome Proliferator-Activated Receptor-γ Agonist, Prevents Microparticle-Induced Vascular Hyporeactivity through the Regulation of Proinflammatory Proteins

Microparticles are plasma membrane vesicles with procoagulant and proinflammatory properties. We recently demonstrated that microparticles induce vascular hyporeactivity and evoke up-regulation of proinflammatory protein expression. This study dissected the effect of either in vitro treatment or short-term oral administration of the peroxisome proliferator-activated receptor-γ (PPARγ) agonist, rosiglitazone, on microparticle-induced vascular hyporeactivity of mouse vessels. Microparticles were produced from T cells by actinomycin D treatment. The effects of rosiglitazone on mouse aortic rings incubated with microparticles were investigated. Aortae treated in vitro with rosiglitazone or aortae taken from mice treated by oral administration of the same agonist completely prevented microparticle-induced vascular hyporeactivity in response to U46619 [9,11-dideoxy-11α, 9α-epoxymethanoprostaglandin F2α). These effects of rosiglitazone occurred independently of the presence of endothelium without modifications in blood parameters. The mechanisms involved abrogation of nitric oxide (NO) and prostacyclin overproduction linked to up-regulation of inducible NO-synthase and cyclooxygenase 2 elicited by microparticles. In addition, rosiglitazone treatment reduced the ability of microparticles to evoke increases in interleukin (IL)-6, IL-8, and nuclear factor (NF)-κB transcription, and NF-κB expression and activation. These results suggest that rosiglitazone, via PPARγ activation, counteracts vascular dysfunction associated with increased release of proinflammatory proteins elicited by microparticles. They underscore therapeutic perspective for rosiglitazone in vascular diseases involving enhanced participation of microparticles

Collaborative Aircraft Engine Preliminary Design using a Virtual Engine Platform, Part A: Architecture and Methodology

As in many other industries, the sector of aircraft engines and gas turbines is also undergoing a change towards digitalization. The intention is to make digital technologies applicable over the entire life cycle of the product and thus improve planning, design, construction, assembly, operation, and maintenance. Intelligent digitalization technologies like the digital thread or digital twin will drastically change engineering and construction processes. Consequently, the preliminary aircraft engine design must also be embedded into the context of digitalization. As part of the projects PEGASUS and PERFECT, the German Aerospace Center (DLR) has started the development of the virtual engine platform GTlab (Gas Turbine Laboratory). Its modular architecture ensures a high degree of usability, expandability, and flexibility for the design and assessment of innovative next generation engine and gas turbine concepts. The purpose of this paper is to present the most important aspects of the GTlab framework and how they contribute to meet the requirements of preliminary aircraft engine design in the context of digitalization. A central topic is the digital representation of the engine system, which is realized by a central data model approach. This includes the geometric description of all engine components, as well as additional data such as thermodynamics, aerodynamics, structural characteristics and mass breakdown. In addition, the central data model enables an efficient management of the intricate data flow and the extensive amount of data transferred between the different disciplines and fidelity levels during the aircraft engine design. Further functionalities of the GTlab framework include the automated generation of 3-D geometries by means of a CAD kernel interface, the acquisition of material data via a material database and a standardized gas model interface. Besides the core functionalities, GTlab includes three major modules for the preliminary aircraft engine design from 0-D-performance up to 3-D. The detailed collaborative predesign proces by means of the framework is presented in part B, exemplary for a ultra high bypass turbofan suited to a middle of the market aircraft configuration

Gender differences and game-based learning in secondary education

In the Netherlands, differences in school motivation and performance between boys and girls are a major issue in political debates. In the first years of secondary education in the Netherlands, boys tend to underachieve and to be disengaged from school. Game-based learning might improve the school motivation and performance of both boys and girls. In two studies with game-based learning, gender differences were examined in students' school motivation and learning outcomes. Both boys and girls showed an increase in motivation and learning outcomes. Only in the second study about a digital role-play citizenship game, boys additionally showed a larger increase in media literacy than girls. This means that game-based learning showed potential to solve the so-called boys problem in Dutch secondary education

Sensitivity-based Multifidelity Multidisciplinary Optimization of a Powered Aircraft Subject to a Comprehensive Set of Loads

Over the past decade, profound attention was given to exploring the benefits of engaging numerical multidisciplinary design optimization in aircraft design. Due to its importance, aerostructural wing design optimization is the most visited multidisciplinary problem in research institutes. To deal with this problem efficiently, gradient-based algorithms are popularly used. The complexity of the gradient-based aerostructural optimization, however, forced researchers to apply several simplifications to the problem formulation, such as neglecting engine effects or oversimplifying the loads process into few predefined load cases. The authors of this paper aim at running a gradients-based multidisciplinary design optimization of a commercial aircraft while including a powered engine and engaging a comprehensive, multi-fidelity loads process, subject to flutter as well as overall aircraft design constraints. The work, done by experts in the mentioned fields, is performed on a commercial aircraft provided by Airbus with many industry-relevant constraints. The results, showed the necessity to include a comprehensive loads process during the optimization. Additionally, it was concluded that engaging powered engines during the optimization is inevitable to come up with realistic designs; significantly different design geometries resulted when engaging a powered engine than when running the optimization with a flow-through nacelle