A large number of compiler optimizations are nowadays available to users. These optimizations interact with each other and with the input code in several and complex ways. The sequence of application of optimization passes can have a significant impact on the performance achieved. The effect of the optimizations is both platform and application dependent. The exhaustive exploration of all viable sequences of compiler optimizations for a given code fragment is not feasible. As this exploration is a complex and time-consuming task, several researchers have focused on Design Space Exploration (DSE) strategies both to select optimization sequences to improve the performance of each function of the application and to reduce the exploration time. In this article, we present a DSE scheme based on a clustering approach for grouping functions with similarities and exploration of a reduced search space resulting from the combination of optimizations previously suggested for the functions in each group. The identification of similarities between functions uses a data mining method that is applied to a symbolic code representation. The data mining process combines three algorithms to generate clusters: the Normalized Compression Distance, the Neighbor Joining, and a new ambiguity-based clustering algorithm. Our experiments for evaluating the effectiveness of the proposed approach address the exploration of optimization sequences in the context of the ReflectC compiler, considering 49 compilation passes while targeting a Xilinx MicroBlaze processor, and aiming at performance improvements for 51 functions and four applications. Experimental results reveal that the use of our clustering-based DSE approach achieves a significant reduction in the total exploration time of the search space (20× over a Genetic Algorithm approach) at the same time that considerable performance speedups (41% over the baseline) were obtained using the optimized codes. Additional experiments were performed considering the LLVM compiler, considering 124 compilation passes, and targeting a LEON3 processor. The results show that our approach achieved geometric mean speedups of 1.49×, 1.32×, and 1.24× for the best 10, 20, and 30 functions, respectively, and a global improvement of 7% over the performance obtained when compiling with-O2. CCS Concepts: r Software and its engineering → Compilers; r Mathematics of computing → Combinatorial optimization; r Computing methodologies → Discrete space search This work has been partially supported by the FCT (Portuguese Science Foundation) under research grants SFRH/BD/82606/2011 and FEDER/ON2 and FCT project NORTE-07-124-FEDER-000062. LGAM had a scholarship granted by CAPES (process: 0352/13-6). The FEUP authors acknowledge the CoSy license and technical support provided by ACE Associated Compiler Experts bv, The Netherlands.

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This study analyzed the genotype distribution and frequency of lamivudine (LAM) and tenofovir (TDF) resistance mutations in a group of patients co-infected with HIV and hepatitis B virus (HBV). A cross-sectional study of 847 patients with HIV was conducted. Patients provided blood samples for HBsAg detection. The load of HBV was determined using an "in-house" real-time polymerase chain reaction. HBV genotypes/subgenotypes, antiviral resistance, basal core promoter (BCP), and precore mutations were detected by DNA sequencing. Twenty-eight patients with co-infection were identified. The distribution of HBV genotypes among these patients was A (n = 9; 50%), D (n = 4; 22.2%), G (n = 3; 16.7%), and F (n = 2; 11.1%). Eighteen patients were treated with LAM and six patients were treated with LAM plus TDF. The length of exposure to LAM and TDF varied from 4 to 216 months. LAM resistance substitutions (rtL180M + rtM204V) were detected in 10 (50%) of the 20 patients with viremia. This pattern and an accompanying rtV173L mutation was found in four patients. Three patients with the triple polymerase substitution pattern (rtV173L + rtL180M + rtM204V) had associated changes in the envelope gene (sE164D + sI195M). Mutations in the BCP region (A1762T, G1764A) and in the precore region (G1896A, G1899A) were also found. No putative TDF resistance substitution was detected. The data suggest that prolonged LAM use is associated with the emergence of particular changes in the HBV genome, including substitutions that may elicit a vaccine escape phenotype. No putative TDF resistance change was detected after prolonged use of TDF.