Christopher Nguyen

© 2016 ACM.While tremendously useful, automated techniques for tuning the precision of floating-point programs face important scalability challenges. We present Blame Analysis, a novel dynamic approach that speeds up precision tuning. Blame Analysis performs floating-point instructions using different levels of accuracy for their operands. The analysis determines the precision of all operands such that a given precision is achieved in the final result of the program. Our evaluation on ten scientific programs shows that Blame Analysis is successful in lowering operand precision. As it executes the program only once, the analysis is particularly useful when targeting reductions in execution time. In such case, the analysis needs to be combined with search-based tools such as Precimonious. Our experiments show that combining Blame Analysis with Precimonious leads to obtaining better results with significant reduction in analysis time: the optimized programs execute faster and the combined analysis time is 9× faster on average, and up to 38× faster than Precimonious alone.

Introduction: Mutations in the valosin-containing protein gene cause hereditary inclusion body myopathy associated with Paget disease of bone, and frontotemporal dementia. More recently, these mutations have been linked to 2% of familial amyotrophic lateral sclerosis cases. A knock-in mouse model offers the opportunity to study VCP-associated pathogenesis. Methods: The VCPR155H/+ knock-in mouse model was assessed for muscle strength and immunohistochemical, Western blot, apoptosis, autophagy, and microPET/CT imaging analyses. Results: VCPR155H/+ mice developed significant progressive muscle weakness, and the quadriceps and brain developed progressive cytoplasmic accumulation of TDP-43, ubiquitin-positive inclusion bodies, and increased LC3-II staining. MicroCT analyses revealed Paget-like lesions at the ends of long bones. Spinal cord demonstrated neurodegenerative changes, ubiquitin, and TDP-43 pathology of motor neurons. Conclusions: VCPR155H/+ knock-in mice represent an excellent preclinical model for understanding VCP-associated disease mechanisms and future treatments. © 2012 Wiley Periodicals, Inc.