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The DEVS model, designed for general discrete event simulation, explores the event status and time advance of all DEVS atomic models deployed at the time of the simulation, and then performs the scheduled simulation step. Each simulation step is accompanied by a re-exploration the event status and time advance, which is needed for maintaining the casual order of the entire model. It is time consuming to simulate a large-scale DEVS model. In a similar vein, attempts to perform an HDL simulation in a DEVS space increase simulation costs by incurring repeated search costs for model transitions. In this study, we performed a statistical analysis of engine behavior to improve simulation speed and we proposed a DP-based memoization technique for the coupled model. Through our method, we can expect significant performance improvements that range statistically from 7.4 to 11.7 times.

Studies proteins involved in the regulation of cullin-containing E3 ubiquitin ligases by immunopurifying CUL4B-containing complex from HeLa cells and by identifying TIP120A as an associated protein by mass spectrometry. Role of cullin-containing ubiquitin-protein isopeptide ligases in regulating the abundance of key proteins involved in cellular processes such as cell cycle and cytokine signaling; Stability of the interaction of TIP120A with cullin family proteins.

Abstract Background A three-drug regimen (macrolide, ethambutol, and rifampicin) is recommended for the treatment of Mycobacterium avium complex pulmonary disease (MAC-PD). Although macrolide has proven efficacy, the role of ethambutol and rifampicin in patients without acquired immune deficiency syndrome is not proven with clinical studies. We aimed to clarify the roles of ethambutol and rifampicin in the treatment of MAC-PD. Methods Patients treated for MAC-PD between March 1st, 2009 and October 31st, 2018 were reviewed retrospectively. Rates of culture conversion, microbiological cure, treatment failure, and recurrence were compared according to the maintenance (≥6 months) of ethambutol or rifampicin with macrolide. Results Among the 237 patients, 122 (51.5%) maintained ethambutol and rifampicin with macrolide, 58 (24.5%) maintained ethambutol and macrolide, 32 (13.5%) maintained rifampicin and macrolide, and 25 (10.6%) maintained macrolide only. Culture conversion was reached for 190/237 (80.2%) patients and microbiological cure was achieved for 129/177 (72.9%) who completed the treatment. Treatment failure despite ≥12 months of treatment was observed in 66/204 (32.4%), and recurrence was identified in 16/129 (12.4%) who achieved microbiological cure. Compared with maintenance of macrolide only, maintenance of ethambutol, rifampicin or both with macrolide were associated with higher odds of culture conversion [odds ratio (OR), 95% confidence interval (CI): 18.06, 3.67–88.92; 15.82, 2.38–105.33; and 17.12, 3.93–74.60, respectively]. Higher odds of microbiological cure were associated with maintenance of both ethambutol and rifampicin with macrolide (OR, 95% CI: 5.74, 1.54–21.42) and macrolide and ethambutol (OR, 95% CI: 5.12, 1.72–15.24) but not macrolide and rifampicin. Maintenance of both ethambutol and rifampicin with macrolide was associated with lower odds of treatment failure (OR, 95% CI: 0.09, 0.01–0.53) compared with macrolide only, while maintenance of one of these with macrolide was not. Maintenance of both ethambutol and rifampicin or one of these with macrolide did not decrease the probability of recurrence when compared with macrolide only. Conclusions Maintenance (≥6 months) of ethambutol and rifampicin with macrolide was associated with the most favorable treatment outcomes among patients with MAC-PD. Given the association between ongoing ethambutol use and microbiological cure, clinicians should maintain ethambutol unless definite adverse events develop.

Abstract Background EGFR genotyping in pulmonary adenocarcinoma patients who develop pleural effusions is mostly performed using cytology or cell block slides with low sensitivity. Liquid biopsy using the supernatant of pleural effusions may be more effective because they contain many components released by cancer cells. Extracellular vesicles (EVs) are known to carry oncogenic double-stranded DNA that is considered a notable biomarker. Here, we investigate the efficiency of liquid biopsy using cell-free DNA (cfDNA) and extracellular vesicle-derived DNA (EV-derived DNA) from the supernatant of pleural effusions for EGFR genotyping in patients with pulmonary adenocarcinoma. Methods Fifty pleural effusion samples from patients with pulmonary adenocarcinoma were evaluated. The supernatant, after removing the cell pellet by centrifugation, was used for liquid biopsy, and EVs were isolated from the pleural effusion by ultracentrifugation. EV-derived DNA and cfDNA were extracted separately, and EGFR genotyping was performed by the PNA clamping method. Results Among 32 patients who were EGFR-tyrosine kinase inhibitor (TKI) naïve with a known tissue EGFR genotype, liquid biopsy using EV-derived DNA from the pleural effusion supernatant showed 100% matching results with tissue EGFR genotyping in 19 EGFR mutant cases and detected three additional EGFR mutations in patients with wild-type (WT) tissue. Liquid biopsy using cfDNA from pleural effusion supernatants missed two cases of tissue-based EGFR mutations and found two additional EGFR mutation cases. In 18 patients who acquired resistance to EGFR-TKI, EGFR genotyping using EV-derived DNA from the pleural effusion supernatant detected the T790 M mutation in 13 of 18 (72.2%) patients, and this mutation was detected in 11 (61.1%) patients using cfDNA. By contrast, only three patients were found to present the T790 M mutation when using cell block or cytology slides. Conclusions Liquid biopsy using the supernatant of pleural effusions showed significantly improved results for EGFR genotyping compared to those using conventional cell block or cytology samples. Liquid biopsy using EV-derived DNA is promising for EGFR genotyping, including T790 M detection in pulmonary adenocarcinoma patients who develop pleural effusions.

In industrial applications, software related to computational lithography using a DP system method, which refers to how efficiently hardware resources are used, has a significant impact on performance. Because the amount of data to be processed per unit of time is comparatively large in the current semiconductor industry, the efficiency of hardware should be increased through job 12 scheduling by using the most efficient load balancing techniques possible. For efficient scheduling of the load balancer, these are necessary to predict the end time of a given job; this is calculated based on the performance of computing resources and the development of effective traffic distribution algorithms. Due to the high integration of semiconductor chips, the volume of mask exposure data has increased exponentially, the number of slave nodes is increasing, and most EDA tools require one license per DP node to perform a simulation. In this paper, in order to improve efficiency and reduce cost through more efficient load balancing scheduling, a new type of DEVS load balancing method was studied based on the existing industrial E-beam cluster model. The designed DEVS model showed up to four times the throughput of the existing legacy model for medium and large clusters when the BSF policy was applied.