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BackgroundThe airway epithelium of chronic obstructive pulmonary disease (COPD) patients undergoes aberrant repair and remodeling after repetitive injury following exposure to environmental factors. Abnormal airway regeneration observed in COPD is thought to originate in the stem/progenitor cells of the airway epithelium, the basal cells (BCs). However, the molecular mechanisms underlying these changes remain unknown. Here, trophoblast cell surface antigen 2 (TROP2), a protein implicated in the regulation of stem cell activity, was examined in lung tissue samples from COPD patients.MethodsThe expression of TROP2 and hyperplasia index Ki67 was assessed in lung epithelium specimens from non-smokers (n = 24), smokers (n = 24) and smokers with COPD (n = 24). Primary airway BCs were isolated by bronchoscopy from healthy individuals and COPD patients and subsequently transfected with pcDNA3.1-TROP2 or siRNA sequence in vitro. The functional consequences of TROP2 overexpression in BCs were explored.ResultsImmunohistochemistry and immunofluorescence revealed increased TROP2 expression in airway BCs in smokers with COPD compared to nonsmokers and smokers without COPD, and staining was highly localized to hyperplastic regions containing Ki67 positive cells. TROP2 expression was also inversely correlated with airflow limitation in patients with COPD (r = −0.53, P < 0.01). pcDNA3.1-TROP2-BCs in vitro exhibited improved proliferation with activation of ERK1/2 phosphorylation signaling pathway. In parallel, changes in vimentin and E-cadherin in pcDNA3.1-TROP2-BCs were consistent with an epithelial-mesenchymal transition (EMT)-like change, and secretion of inflammatory factors IL-1β, IL-8 and IL-6 was increased. Moreover, down-regulation of TROP2 by siRNA significantly attenuated the proliferation of BCs derived from COPD patients. EMT-like features and cytokine levels of COPD basal cells were also weakened following the down-regulation of TROP2.ConclusionThe results indicate that TROP2 may play a crucial role in COPD by affecting BC function and thus airway remodeling through increased BC hyperplasia, EMT-like change, and introduction of inflammatory molecules into the microenvironment.

Accurately determining the energy consumed by each task in a system will become of prominent importance in future multicore-based systems because it offers several benefits, including (i) better application energy/performance optimizations, (ii) improved energy-aware task scheduling, and (iii) energy-aware billing in data centers. Unfortunately, existing methods for energy metering in multicores fail to provide accurate energy estimates for each task when several tasks run simultaneously. This article makes a case for accurate Per-Task Energy Metering (PTEM) based on tracking the resource utilization and occupancy of each task. Different hardware implementations with different trade-offs between energy prediction accuracy and hardware-implementation complexity are proposed. Our evaluation shows that the energy consumed in a multicore by each task can be accurately measured. For a 32-core, 2-way, simultaneous multithreaded core setup, PTEM reduces the average accuracy error from more than 12% when our hardware support is not used to less than 4% when it is used. The maximum observed error for any task in the workload we used reduces from 58% down to 9% when our hardware support is used. ACM Reference Format:Liu, Q., Moreto, M., Jimenez, V., Abella, J., Cazorla, F. J., and Valero M. 2013. Hardware support for accurate per-task energy metering in multicore systems. ACM Trans.

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