Abstract-This paper studies real-time scheduling of mixedcriticality systems where low-criticality tasks are still guaranteed some service in the high-criticality mode, with reduced execution budgets. First, we present a utilization-based schedulability test for such systems under EDF-VD scheduling. Second, we quantify the suboptimality of EDF-VD (with our test condition) in terms of speedup factors. In general, the speedup factor is a function with respect to the ratio between the amount of resource required by different types of tasks in different criticality modes, and reaches 4/3 in the worst case. Furthermore, we show that the proposed utilization-based schedulability test and speedup factor results apply to the elastic mixed-criticality model as well. Experiments show effectiveness of our proposed method and confirm the theoretical suboptimality results.
In this paper, we study the scheduling problem of the imprecise mixed-criticality model (IMC) under earliest deadline first with virtual deadline (EDF-VD) scheduling upon uniprocessor systems. Two schedulability tests are presented. The first test is a concise utilizationbased test which can be applied to the implicit deadline IMC task set. The suboptimality of the proposed utilization-based test is evaluated via a widely-used scheduling metric, speedup factors. The second test is a more effective test but with higher complexity which is based on the concept of demand bound function (DBF). The proposed DBF-based test is more generic and can apply to constrained deadline IMC task set. Moreover, in order to address the high time cost of the existing deadline tuning algorithm, we propose a novel algorithm which significantly improve the efficiency of the deadline tuning procedure. Experimental results show the effectiveness of our proposed schedulability tests, confirm the theoretical suboptimality results with respect to speedup factor, and demonstrate the efficiency of our proposed algorithm over the existing deadline tunning algorithm. In addition, issues related to the implementation of the IMC model under EDF-VD are discussed.
This study aimed to investigate the impact of indoleamine 2,3-dioxygenase 1 (IDO1) expression, programmed cell death-ligand 1 (PD-L1) expression, CD8+ tumor-infiltrating lymphocyte (TIL) status, and their combination on pathologic complete response (pCR) and recurrence in esophageal squamous cell carcinoma (ESCC) treated with neoadjuvant chemoradiotherapy (CRT). Indoleamine 2,3-dioxygenase 1, PD-L1, and CD8+ TIL statuses were evaluated by immunohistochemical analysis on pre-CRT biopsies of 158 patients. Sixty-eight patients (43.0%) achieved pCR after neoadjuvant CRT and 48 patients (30.4%) developed recurrences after surgery. IDO1 and PD-L1 proteins were co-expressed in 28 patients (17.7%). Indoleamine 2,3-dioxygenase 1 positive patients showed a significantly lower pCR rate than IDO1 negative patients (28.6% vs. 51.0%, P = 0.007). Similarly, PD-L1 high expression was significantly negatively correlated with pCR rate (27.3% vs. 51.5%, P = 0.004). On multivariate analysis, IDO1 expression was an independent prognostic factor for developing recurrences. Stratification analysis revealed that patients with co-expression of IDO1 and PD-L1 were significantly associated with a lower pCR rate and worse recurrence-free survival than those with one or none positive protein. In conclusion, IDO1 and PD-L1 co-expression could predict poor pathologic response and high risk of recurrence in ESCC after neoadjuvant CRT, indicating a subset of patients who may benefit from CRT combined with immunotherapy.
Radioresistance‐induced residual and recurrent tumours are the main cause of treatment failure in nasopharyngeal carcinoma (NPC). Thus, the mechanisms of NPC radioresistance and predictive markers of NPC prognosis and radioresistance need to be investigated and identified. In this study, we identified RPA3 as a candidate radioresistance marker using RNA‐seq of NPC samples. In vitro studies further confirmed that RPA3 affected the radiosensitivity of NPC cells. Specifically, the overexpression of RPA3 enhanced radioresistance and the capacity for DNA repair of NPC cells, whereas inhibiting RPA3 expression sensitized NPC cells to irradiation and decreased the DNA repair capacity. Furthermore, the overexpression of RPA3 enhanced RAD51 foci formation in NPC cells after irradiation. Immunohistochemical assays in 104 NPC specimens and 21 normal epithelium specimens indicated that RPA3 was significantly up‐regulated in NPC tissues, and a log‐rank test suggested that in patients with NPC, high RPA3 expression was associated with shorter overall survival (OS) and a higher recurrence rate compared with low expression (5‐year OS rates: 67.2% versus 86.2%; 5‐year recurrence rates: 14.8% versus 2.3%). Moreover, TCGA data also indicated that high RPA3 expression correlated with poor OS and a high recurrence rate in patients with head and neck squamous cell carcinoma (HNSC) after radiotherapy. Taken together, the results of our study demonstrated that RPA3 regulated the radiosensitivity and DNA repair capacity of NPC cells. Thus, RPA3 may serve as a new predictive biomarker for NPC prognosis and radioresistance to help guide the diagnosis and individualized treatment of patients with NPC.
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