Concurrent AIV as a method to hard tailor test- and model philosophies in times of need.

MASCOT, a small 11 kg prototype Asteroid Lander on-board JAXA's Hayabusa2 space probe, was launched on December 3rd, 2014, and arrived at its destined target asteroid (162173) Ryugu on June 27, 2018. MASCOT was separated from its mother spacecraft and successfully landed on October 3rd, 2018, accomplishing the first ever landing of a European spacecraft on the surface of an asteroid. To catch this particular launch opportunity its development timeline needed to be heavily compressed. In particular, the kick-off for hardware production was released in February 2012, only 2 years before the initially planned delivery of the flight unit. Due to this compact schedule, current and well established verification processes could not be followed in order to finalize the project in the given time. But by applying a unique mix of conventional and tailored model philosophies it was possible to dynamical adapt the test program to accomplish for the shortest planning and a suitable weighing of costs and risks. A strategy of Concurrent Assembly, Integration and Verification (C-AIV) helped to identify and mitigate design and manufacturing issues and shortened the test timeline further from a general 4-5 year C/D-phase down to 2,5 year C/D-phase. This short article outlines the general idea of the applied method which could be used by AIV and System Engineers in a general tailoring process for projects of similar nature which could be run in an alternative and much faster way, if the circumstances would call for it. •Concurrent AIV, a new agile methodology to hard tailor test and model philosophies for space projects is presented,•The methodology is based on parallelization of test activities, creation of independent unique test threads and synergizing their dependencies at key points,•On the baseline of the asteroid lander MASCOT, this methodology has been successfully applied to shorten the overall test and implementation schedule to only 2.5 years.

Human Neutrophil Peptide 1 Limits Hypercholesterolemia-induced Atherosclerosis by Increasing Hepatic LDL Clearance.

Increases in plasma LDL-cholesterol have unequivocally been established as a causal risk factor for atherosclerosis. Hence, strategies for lowering of LDL-cholesterol may have immediate therapeutic relevance. Here we study the role of human neutrophil peptide 1 (HNP1) in a mouse model of atherosclerosis and identify its potent atheroprotective effect both upon transgenic overexpression and therapeutic delivery. The effect was found to be due to a reduction of plasma LDL-cholesterol. Mechanistically, HNP1 binds to apolipoproteins enriched in LDL. This interaction facilitates clearance of LDL particles in the liver via LDL receptor. Thus, we here identify a non-redundant mechanism by which HNP1 allows for reduction of LDL-cholesterol, a process that may be therapeutically instructed to lower cardiovascular risk.

Atherosclerotic Plaque Destabilization in Mice: A Comparative Study.

Atherosclerosis-associated diseases are the main cause of mortality and morbidity in western societies. The progression of atherosclerosis is a dynamic process evolving from early to advanced lesions that may become rupture-prone vulnerable plaques. Acute coronary syndromes are the clinical manifestation of life-threatening thrombotic events associated with high-risk vulnerable plaques. Hyperlipidemic mouse models have been extensively used in studying the mechanisms controlling initiation and progression of atherosclerosis. However, the understanding of mechanisms leading to atherosclerotic plaque destabilization has been hampered by the lack of proper animal models mimicking this process. Although various mouse models generate atherosclerotic plaques with histological features of human advanced lesions, a consensus model to study atherosclerotic plaque destabilization is still lacking. Hence, we studied the degree and features of plaque vulnerability in different mouse models of atherosclerotic plaque destabilization and find that the model based on the placement of a shear stress modifier in combination with hypercholesterolemia represent with high incidence the most human like lesions compared to the other models.