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Late-onset Alzheimer’s disease (LOAD) is the most common neurodegenerative disorder in older adults, affecting over 50% of those over age 85. Aging is the most important risk factor for the development of LOAD. Aging is associated with the decrease in the ability of cells to cope with cellular stress, especially protein aggregation. Here we will describe how the process of aging affects pathways that control the processing and degradation of abnormal proteins including amyloid-β (Aβ). Genetic association studies in LOAD have successfully identified a large number of genetic variants involved in the development of the disease. However, there is a gap in understanding the interconnections between these pathomolecular events that prevent us from discovering therapies. We will compile pertinent links to elucidate how the biology of aging affects the sequence of events in the development of LOAD. Specifically, in this review we analyze the molecular-pathologic-clinical correlations of the aging process, the HSF1 and FOXO family pathways, Aβ toxicity, Aβ degradation, and the different clinical stages of LOAD.

An independent twelve degree-of-freedom simulation of the X-43A separation trajectory was created with the Program to Optimize Simulated trajectories (POST II). This simulation modeled the multi-body dynamics of the X-43A and its booster and included the effect of two pyrotechnically actuated pistons used to push the vehicles apart as well as aerodynamic interaction forces and moments between the two vehicles. The simulation was developed to validate trajectory studies conducted with a 14 degree-offreedom simulation created early in the program using the Automatic Dynamic Analysis of Mechanics Systems (ADAMS) simulation software. The POST simulation was less detailed than the official ADAMS-based simulation used by the Project, but was simpler, more concise and ran faster, while providing similar results. The increase in speed provided by the POST simulation provided the Project with an alternate analysis tool. This tool was ideal for performing separation control logic trade studies that required the running of numerous Monte Carlo trajectories.

SummaryThe goal of the Hyper-X program is to demons'trate and validate technology for design and performance predictions of hypersonic aircraft with an airframe-integrated supersonic-combustion ramjet propulsion system. Accomplishing this goal requires flight demonstration of a hydrogen-fueled scramjet powered hypersonic aircraft. A key enabling technology for this flight demonstration is flight controls. Closed-loop flight control is required to enable a successful stage separation, to achieve and maintain the design condition during the engine test, and to provide a controlled descent. Before the contract award, NASA developed preliminary flight control laws for the Hyper-X to evaluate the feasibility of the proposed scramjet test sequence and descent trajectory. After the contract award, a Boeing/NASA partnership worked to develop the current control laws. This paper presents a description of the Hyper-X Research Vehicle control law architectures with performance and robustness analyses. Assessments of simulated flight trajectories and stability margin analyses demonstrate that these control laws meet the flight test requirements.

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The objective of the HIAD Mission Applications Study is to quantify the benefits of HIAD infusion to the concept of operations of high priority exploration missions. Results of the study will identify the range of mission concepts ideally suited to HIADs and provide mission-pull to associated technology development programs while further advancing operational concepts associated with HIAD technology. A summary of Year 1 modeling and analysis results is presented covering missions focusing on Earth and Mars-based applications. Recommended HIAD scales are presented for near term and future mission opportunities and the associated environments (heating and structural loads) are described.

The suite of Inflatable Re-Entry Vehicle Experiments (IRVE) is designed to further our knowledge and understanding of Hypersonic Inflatable Aerodynamic Decelerators (HIADs). Before infusion into a future mission, three challenges need to be addressed: surviving the heat pulse during re-entry, demonstrating system performance at relevant scales, and demonstrating controllability in the atmosphere. IRVE-4 will contribute to a better understanding of controllability by characterizing how a HIAD responds to a set of controlled inputs. The ability to control a HIAD is vital for missions that are g-limited, require precision targeting and guidance for aerocapture or entry, descent, and landing. The IRVE-4 flight test will focus on taking a first look into controlling a HIAD. This paper will give an overview of the IRVE-4 mission including the control response portion of the flight test sequence, and will provide a review of the mission's development.

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