Automating Spacecraft Analysis: The Era of Ontological Modeling & Simulation

Verification by analysis is a predicted compliance of a design to imposed requirements. The levels of performance specified by performance requirements can be related to Technical Performance Measures (TPM) in a Model-Based Systems Engineering (MBSE) environment, but engineers performing verification by analysis are not commonly versed in professional Systems Engineering (SE) techniques or modeling languages such as SysML. As the formal application of Systems Engineering (SE) results in a diminution of time, effort, and money for large-scale projects, enabling technical engineers performing verification by analysis to contribute to MBSE improvements in the course of their daily work is financially incentivized. Ontologies applied to technical analysis methodologies are shown to improve the quality of verification by analysis activities while adhering to professional organization standards such as the International Council on Systems Engineering (INCOSE) SE Handbook and the National Aeronautics and Space Administration (NASA) standard 7009A: Standard for Models and Simulations

A noncoding variant near PPP1R3B promotes liver glycogen storage and MetS, but protects against myocardial infarction

CONTEXT: Glycogen storage diseases are rare. Increased glycogen in the liver results in increased attenuation. OBJECTIVE: Investigate the association and function of a noncoding region associated with liver attenuation but not histologic nonalcoholic fatty liver disease. DESIGN: Genetics of Obesity-associated Liver Disease Consortium. SETTING: Population-based Main Outcome: Computed tomography measured liver attenuation. RESULTS: Carriers of rs4841132-A (frequency 2-19%) do not show increased hepatic steatosis; they have increased liver attenuation indicative of increased glycogen deposition. rs4841132 falls in a noncoding RNA LOC157273 ~190kb upstream of PPP1R3B. We demonstrate that rs4841132-A increases PPP1R3B through a cis genetic effect. Using CRISPR/Cas9 we engineered a 105bp deletion including rs4841132-A in human hepatocarcinoma cells which increases PPP1R3B, decreases LOC157273 and increases glycogen perfectly mirroring the human disease. Overexpression of PPP1R3B or knockdown of LOC157273 increased glycogen but did not result in decreased LOC157273 or increased PPP1R3B, respectively, suggesting that the effects may not all occur via affecting RNA levels. Based on EHR data, rs4841132-A associates with all components of the metabolic syndrome (MetS). However, rs4841132-A associated with decreased low-density lipoprotein (LDL) cholesterol and risk for myocardial infarction (MI). A metabolic signature for rs4841132-A includes increased glycine, lactate, triglycerides and decreased acetoacetate and beta-hydroxybutyrate. CONCLUSIONS: These results show that rs4841132-A promotes a hepatic glycogen storage disease by increasing PPP1R3B and decreasing LOC157273. rs4841132-A promotes glycogen accumulation and development of MetS but lowers LDL cholesterol and risk for MI. These results suggest that elevated hepatic glycogen is one cause of MetS that does not invariably promote MI