4 research outputs found
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Effective Performance Analysis and Debugging
Performance is once again a first-class concern. Developers can no longer wait for the next generation of processors to automatically optimize their software. Unfortunately, existing techniques for performance analysis and debugging cannot cope with complex modern hardware, concurrent software, or latency-sensitive software services.
While processor speeds have remained constant, increasing transistor counts have allowed architects to increase processor complexity. This complexity often improves performance, but the benefits can be brittle; small changes to a program’s code, inputs, or execution environment can dramatically change performance, resulting in unpredictable performance in deployed software and complicating performance evaluation and debugging. Developers seeking to improve performance must resort to manual performance tuning for large performance gains. Software profilers are meant to guide developers to important code, but conventional profilers do not produce actionable information for concurrent applications. These profilers report where a program spends its time, not where optimizations will yield performance improvements. Furthermore, latency is a critical measure of performance for software services and interactive applications, but conventional profilers measure only throughput. Many performance issues appear only when a system is under high load, but generating this load in development is often impossible. Developers need to identify and mitigate scalability issues before deploying software, but existing tools offer developers little or no assistance.
In this dissertation, I introduce an empirically-driven approach to performance analysis and debugging. I present three systems for performance analysis and debugging. Stabilizer mitigates the performance variability that is inherent in modern processors, enabling both predictable performance in deployment and statistically sound performance evaluation. Coz conducts performance experiments using virtual speedups to create the effect of an optimization in a running application. This approach accurately predicts the effect of hypothetical optimizations, guiding developers to code where optimizations will have the largest effect. Amp allows developers to evaluate system scalability using load amplification to create the effect of high load in a testing environment. In combination, Amp and Coz allow developers to pinpoint code where manual optimizations will improve the scalability of their software
Expression quantitative trait locus fine mapping of the 17q12–21 asthma locus in African American children: a genetic association and gene expression study
Background: African ancestry is associated with a higher prevalence and greater severity of asthma than European ancestries, yet genetic studies of the most common locus associated with childhood-onset asthma, 17q12–21, in African Americans have been inconclusive. The aim of this study was to leverage both the phenotyping of the Children's Respiratory and Environmental Workgroup (CREW) birth cohort consortium, and the reduced linkage disequilibrium in African Americans, to fine map the 17q12–21 locus. Methods: We first did a genetic association study and meta-analysis using 17q12–21 tag single-nucleotide polymorphisms (SNPs) for childhood-onset asthma in 1613 European American and 870 African American children from the CREW consortium. Nine tag SNPs were selected based on linkage disequilibrium patterns at 17q12–21 and their association with asthma, considering the effect allele under an additive model (0, 1, or 2 effect alleles). Results were meta-analysed with publicly available summary data from the EVE consortium (on 4303 European American and 3034 African American individuals) for seven of the nine SNPs of interest. Subsequently, we tested for expression quantitative trait loci (eQTLs) among the SNPs associated with childhood-onset asthma and the expression of 17q12–21 genes in resting peripheral blood mononuclear cells (PBMCs) from 85 African American CREW children and in upper airway epithelial cells from 246 African American CREW children; and in lower airway epithelial cells from 44 European American and 72 African American adults from a case-control study of asthma genetic risk in Chicago (IL, USA). Findings: 17q12–21 SNPs were broadly associated with asthma in European Americans. Only two SNPs (rs2305480 in gasdermin-B [GSDMB] and rs8076131 in ORMDL sphingolipid biosynthesis regulator 3 [ORMDL3]) were associated with asthma in African Americans, at a Bonferroni-corrected threshold of p<0·0055 (for rs2305480_G, odds ratio [OR] 1·36 [95% CI 1·12–1·65], p=0·0014; and for rs8076131_A, OR 1·37 [1·13–1·67], p=0·0010). In upper airway epithelial cells from African American children, genotype at rs2305480 was the most significant eQTL for GSDMB (eQTL effect size [β] 1·35 [95% CI 1·25–1·46], p<0·0001), and to a lesser extent showed an eQTL effect for post-GPI attachment to proteins phospholipase 3 (β 1·15 [1·08–1·22], p<0·0001). No SNPs were eQTLs for ORMDL3. By contrast, in PBMCs, the five core SNPs were associated only with expression of GSDMB and ORMDL3. Genotype at rs12936231 (in zona pellucida binding protein 2) showed the strongest associations across both genes (for GSDMB, eQTLβ 1·24 [1·15–1·32], p<0·0001; and for ORMDL3 (β 1·19 [1·12–1·24], p<0·0001). The eQTL effects of rs2305480 on GSDMB expression were replicated in lower airway cells from African American adults (β 1·29 [1·15–1·44], p<0·0001). Interpretation: Our study suggests that SNPs regulating GSDMB expression in airway epithelial cells have a major role in childhood-onset asthma, whereas SNPs regulating the expression levels of 17q12–21 genes in resting blood cells are not central to asthma risk. Our genetic and gene expression data in African Americans and European Americans indicated GSDMB to be the leading candidate gene at this important asthma locus.6 month embargo; published: 01 May 2020This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]