Atherosclerotic plaque destabilization in Mice: A comparative study

Atherosclerosis-Associated diseases are the main cause ofmortality and morbidity in western societies. The progression of atherosclerosis is a dynamic process evolving from early to advanced lesions thatmay 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 animalmodelsmimicking 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

Evolution of Reproductive Morphology in Leaf Endophytes

The endophytic lifestyle has played an important role in the evolution of the morphology of reproductive structures (body) in one of the most problematic groups in fungal classification, the Leotiomycetes (Ascomycota). Mapping fungal morphologies to two groups in the Leiotiomycetes, the Rhytismatales and Hemiphacidiaceae reveals significant divergence in body size, shape and complexity. Mapping ecological roles to these taxa reveals that the groups include endophytic fungi living on leaves and saprobic fungi living on duff or dead wood. Finally, mapping of the morphologies to ecological roles reveals that leaf endophytes produce small, highly reduced fruiting bodies covered with fungal tissue or dead host tissue, while saprobic species produce large and intricate fruiting bodies. Intriguingly, resemblance between asexual conidiomata and sexual ascomata in some leotiomycetes implicates some common developmental pathways for sexual and asexual development in these fungi

Mobile Asteroid Surface Scout (MASCOT) - Design, Development and Delivery of a Small Asteroid Lander Aboard Hayabusa2

MASCOT is a small asteroid lander launched on December 3rd, 2014, aboard the Japanese HAYABUSA2 asteroid sample-return mission towards the 980 m diameter C-type near-Earth asteroid (162173) 1999 JU3. MASCOT carries four full-scale asteroid science instruments and an uprighting and relocation device within a shoebox-sized 10 kg spacecraft; a complete lander comparable in mass and volume to a medium-sized science instrument on interplanetary missions. Asteroid surface science will be obtained by: MicrOmega, a hyperspectral near- to mid-infrared soil microscope provided by IAS; MASCAM, a wide-angle Si CMOS camera with multicolour LED illumination unit; MARA, a multichannel thermal infrared surface radiometer; the magnetometer, MASMAG, provided by the Technical University of Braunschweig. Further information on the conditions at or near the lander‘s surfaces is generated as a byproduct of attitude sensors and other system sensors. MASCOT uses a highly integrated, ultra-lightweight truss-frame structure made from a CFRP-foam sandwich. It has three internal mechanisms: a preload release mechanism, to release the structural preload applied for launch across the separation mechanism interface; a separation mechanism, to realize the ejection of MASCOT from the semi-recessed stowed position within HAYABUSA2; and the mobility mechanism, for uprighting and hopping. MASCOT uses semi-passive thermal control with Multi-Layer Insulation, two heatpipes and a radiator for heat rejection during operational phases, and heaters for thermal control of the battery and the main electronics during cruise. MASCOT is powered by a primary battery during its on-asteroid operational phase, but supplied by HAYABUSA2 during cruise for check-out and calibration operations as well as thermal control. All housekeeping and scientific data is transmitted to Earth via a relay link with the HAYABUSA2 main-spacecraft, also during cruise operations. The link uses redundant omnidirectional UHF-Band transceivers and patch antennae on the lander. The MASCOT On-Board Computer is a redundant system providing data storage, instrument interfacing, command and data handling, as well as autonomous surface operation functions. Knowledge of the lander’s attitude on the asteroid is key to the success of its uprighting and hopping function. The attitude is determined by a threefold set of sensors: optical distance sensors, photo electric cells and thermal sensors. A range of experimental sensors is also carried. MASCOT was build by the German Aerospace Center, DLR, with contributions from the French space agency, CNES. The system design, science instruments, and operational concept of MASCOT will be presented, with sidenotes on the development of the mission and its integration with HAYABUSA2

More Bucks for the Bang: New Space Solutions, Impact Tourism and one Unique Science & Engineering Opportunity at T-6 Months and Counting

For now, the Planetary Defense Conference Exercise 2021's incoming fictitious(!) asteroid, 2021 PDC, seems headed for impact on October 20th, 2021, exactly 6 months after its discovery. Today (April 26th, 2021), the impact probability is 5%, in a steep rise from 1 in 2500 upon discovery six days ago. We all know how these things end. Or do we? Unless somebody kicked off another headline-grabbing media scare or wants to keep civil defense very idle very soon, chances are that it will hit (note: this is an exercise!). Taking stock, it is barely 6 months to impact, a steadily rising likelihood that it will actually happen, and a huge uncertainty of possible impact energies: First estimates range from 1.2 MtTNT to 13 GtTNT, and this is not even the worst-worst case: a 700 m diameter massive NiFe asteroid (covered by a thin veneer of Ryugu-black rubble to match size and brightness) would come in at 70 GtTNT. In down to Earth terms, this could be all between smashing fireworks over some remote area of the globe and a 7.5 km crater downtown somewhere. Considering the deliberate and sedate ways of development of interplanetary missions it seems we can only stand and stare until we know well enough where to tell people to pack up all that can be moved at all and save themselves. But then, it could just as well be a smaller bright rock. The best estimate is 120 m diameter from optical observation alone, by 13% standard albedo. NASA's upcoming DART mission to binary asteroid (65803) Didymos is designed to hit such a small target, its moonlet Dimorphos. The Deep Impact mission's impactor in 2005 successfully guided itself to the brightest spot on comet 9P/Tempel 1, a relatively small feature on the 6 km nucleus. And 'space' has changed: By the end of this decade, one satellite communication network plans to have launched over 11000 satellites at a pace of 60 per launch every other week. This level of series production is comparable in numbers to the most prolific commercial airliners. Launch vehicle production has not simply increased correspondingly - they can be reused, although in a trade for performance. Optical and radio astronomy as well as planetary radar have made great strides in the past decade, and so has the design and production capability for everyday 'high-tech' products. 60 years ago, spaceflight was invented from scratch within two years, and there are recent examples of fastpaced space projects as well as a drive towards 'responsive space'. It seems it is not quite yet time to abandon all hope. We present what could be done and what is too close to call once thinking is shoved out of the box by a clear and present danger, to show where a little more preparedness or routine would come in handy - or become decisive. And if we fail, let's stand and stare safely and well instrumented anywhere on Earth together in the greatest adventure of science

Planetary Defense Ground Zero: MASCOT's View on the Rocks - an Update between First Images and Sample Return

At 01:57:20 UTC on October 3rd, 2018, after 3½ years of cruise aboard the JAXA spacecraft HAYABUSA2 and about 3 months in the vicinity of its target, the MASCOT lander was separated successfully by from an altitude of 41 m. After a free-fall of only ~5m51s MASCOT made first contact with C-type near-Earth and potentially hazardous asteroid (162173) Ryugu, by hitting a big boulder. MASCOT then bounced for ~11m3s, in the process already gathering valuable information on mechanical properties of the surface before it came to rest. It was able to perform science measurements at 3 different locations on the surface of Ryugu and took many images of its spectacular pitch-black landscape. MASCOT’s payload suite was designed to investigate the fine-scale structure, multispectral reflectance, thermal characteristics and magnetic properties of the surface. Somewhat unexpectedly, MASCOT encountered very rugged terrain littered with large surface boulders. Observing in-situ, it confirmed the absence of fine particles and dust as already implied by the remote sensing instruments aboard the HAYABUSA2 spacecraft. After some 17h of operations, MASCOT‘s mission ended with the last communication contact as it followed Ryugu’s rotation beyond the horizon as seen from HAYABUSA2. Soon after, its primary battery was depleted. We present a broad overview of the recent scientific results of the MASCOT mission from separation through descent, landing and in-situ investigations on Ryugu until the end of its operation and relate them to the needs of planetary defense interactions with asteroids. We also recall the agile, responsive and sometimes serendipitous creation of MASCOT, the two-year rush of building and delivering it to JAXA’s HAYABUSA2 spacecraft in time for launch, and the four years of in-flight operations and on-ground testing to make the most of the brief on-surface mission

Failure of human rhombic lip differentiation underlies medulloblastoma formation

Medulloblastoma (MB) comprises a group of heterogeneous paediatric embryonal neoplasms of the hindbrain with strong links to early development of the hindbrain 1–4. Mutations that activate Sonic hedgehog signalling lead to Sonic hedgehog MB in the upper rhombic lip (RL) granule cell lineage 5–8. By contrast, mutations that activate WNT signalling lead to WNT MB in the lower RL 9,10. However, little is known about the more commonly occurring group 4 (G4) MB, which is thought to arise in the unipolar brush cell lineage 3,4. Here we demonstrate that somatic mutations that cause G4 MB converge on the core binding factor alpha (CBFA) complex and mutually exclusive alterations that affect CBFA2T2, CBFA2T3, PRDM6, UTX and OTX2. CBFA2T2 is expressed early in the progenitor cells of the cerebellar RL subventricular zone in Homo sapiens, and G4 MB transcriptionally resembles these progenitors but are stalled in developmental time. Knockdown of OTX2 in model systems relieves this differentiation blockade, which allows MB cells to spontaneously proceed along normal developmental differentiation trajectories. The specific nature of the split human RL, which is destined to generate most of the neurons in the human brain, and its high level of susceptible EOMES +KI67 + unipolar brush cell progenitor cells probably predisposes our species to the development of G4 MB

On Time, On Target – How the Small Asteroid Lander MASCOT Caught a Ride Aboard HAYABUSA-2 in 3 Years, 1 Week and 48 Hours

Delayed only 3 days by weather, the small asteroid lander MASCOT was launched aboard the Japanese HAYABUSA2 asteroid sample-return mission on December 3 rd , 2014, 04:22 UT, within the first interplanetary launch window. Their target is the near-Earth asteroid (162173) 1999 JU 3. The fully autonomous MASCOT carries four asteroid science instruments, orientation sensors, and an uprighting/relocation mechanism within a shoebox-sized 10 kg spacecraft. Though only an instrument-sized lander, its complexity is comparable to a similarly equipped standalone spacecraft. MASCOT is a fast paced high performance project, developed under strict constraints of volume, mass, available personnel, budget, and accessible infrastructures, to a timely deadline of a celestially fixed launch date. With a model philosophy tailored 'live' at system level, it integrates a unique mix of conventional and tailored model philosophies at units level. A dynamically adapted test programme using Concurrent Assembly Integration and Verification (Concurrent-AIV) kept project risks within acceptable bounds and shortened the system-level AIV phase from the typical 4 to 5 year to 2½ years within a project timeline of 3 years focused on the specific launch opportunity. Here, MASCOT benefited from a preceding phase of a range of lander concept studies at the DLR Bremen Concurrent Engineering Facility since 2008. Within the 3 years project timeline, from the first integrated breadboard model (½ year after first unit-level hardware breadboarding) the MASCOT team has successfully completed approx. 30 MASCOT system level tests, more than 50 additional subunit tests (excluding payloads) as well as approx. 10 test campaigns on its carrier satellite HAYABUSA2. This culminates in almost 100 different test campaigns performed in roughly half the time allocated for such a prototype project which would have followed a standardized way. MASCOT provided useful lessons in assembly, integration, testing and its related management that could be applied to increase the efficiency and decrease the lead time of future interplanetary projects from concept to launch. These lessons may become vital when the first sizeable Earth-impacting asteroid is discovered before its terminal dive. Currently, the MASCOT Flight Spare is planned to be used as Ground Reference Model and to continue functional and environmental testing on system level

Concurrent AIV and Dynamic Model Strategy in Response to the New Normal of so called Death March Projects: The Engineering Venture as Experienced in the DLR MASCOT and Hayabusa-2 Project

As today’s projects increase quickly in complexity and development times are shortened to save budgets, the term “Death March Project” has been recently used to describe projects which schedules are so compressed that current and well established processes cannot be followed in order to finalize the project in the given time. MASCOT, a small 11 kg Asteroid Landing Package on-board JAXA’s Hayabusa-2 space probe is currently being finalized at DLR. Its last stages during the Assembly, Integration and Verification (AIV) process show that by applying a unique mix of conventional and tailored Model Philosophies it is possible to dynamical adapt the test program, limited by a fixed launch date, to accomplish for the shortest planning and a suitable weighing of costs and risks. Introducing “Concurrent AIV” to identify and mitigate design and manufacturing issues shortened the MASCOT project timeline further from a general 4 year AIV phase to less than 2 years

Concurrent AIV as a Method to hard tailor Test- and Model Philosophies in Times of Need

MASCOT, a small 11 kg Asteroid Lander on-board JAXA's Hayabusa2 space probe, was launched on December 3rd, 2014. To catch this particular launch opportunity its development timeline needed to be heavily compressed so that current and well established verification processes could not be followed in order to finalize the project in the given time. 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

Going Beyond the Possible, Going Beyond the “Standard” of Spacecraft Integration and Testing!

MASCOT, a small 10kg Asteroid landing package on-board Hayabusa-2 is currently finalizing Phase-C of its development and after official go-ahead during the Critical Design Review it will undergo a final verification program at DLR before send to JAXA to be integrated into the mother spacecraft. Its last stages during the Assembly, Integration and Verification (AIV) process show that by applying a unique mix of conventional and tailored Model Philosophies it is possible to dynamical adapt the test program, limited by a fixed launch date, to accomplish for the shortest planning and a suitable weighing of costs and risks. In addition, this paper introduces the term Concurrent AIV to express the many simultaneous running test and verification activities