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  • 1
    Online Resource
    Online Resource
    Association for Computing Machinery (ACM) ; 2020
    In:  Proceedings of the VLDB Endowment Vol. 13, No. 8 ( 2020-04), p. 1176-1189
    In: Proceedings of the VLDB Endowment, Association for Computing Machinery (ACM), Vol. 13, No. 8 ( 2020-04), p. 1176-1189
    Abstract: With the growing market of cloud databases, careful detection and elimination of slow queries are of great importance to service stability. Previous studies focus on optimizing the slow queries that result from internal reasons (e.g., poorly-written SQLs). In this work, we discover a different set of slow queries which might be more hazardous to database users than other slow queries. We name such queries Intermittent Slow Queries (iSQs), because they usually result from intermittent performance issues that are external (e.g., at database or machine levels). Diagnosing root causes of iSQs is a tough but very valuable task. This paper presents iSQUAD, Intermittent Slow QUery Anomaly Diagnoser, a framework that can diagnose the root causes of iSQs with a loose requirement for human intervention. Due to the complexity of this issue, a machine learning approach comes to light naturally to draw the interconnection between iSQs and root causes, but it faces challenges in terms of versatility, labeling overhead and interpretability. To tackle these challenges, we design four components, i.e., Anomaly Extraction, Dependency Cleansing, Type-Oriented Pattern Integration Clustering (TOPIC) and Bayesian Case Model. iSQUAD consists of an offline clustering & explanation stage and an online root cause diagnosis & update stage. DBAs need to label each iSQ cluster only once at the offline stage unless a new type of iSQs emerges at the online stage. Our evaluations on real-world datasets from Alibaba OLTP Database show that iSQUAD achieves an iSQ root cause diagnosis average F1-score of 80.4%, and outperforms existing diagnostic tools in terms of accuracy and efficiency.
    Type of Medium: Online Resource
    ISSN: 2150-8097
    Language: English
    Publisher: Association for Computing Machinery (ACM)
    Publication Date: 2020
    detail.hit.zdb_id: 2478691-3
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  • 2
    Online Resource
    Online Resource
    American Association for Cancer Research (AACR) ; 2019
    In:  Clinical Cancer Research Vol. 25, No. 6 ( 2019-03-15), p. 1923-1935
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 25, No. 6 ( 2019-03-15), p. 1923-1935
    Abstract: How exosomal RNAs released within the bone marrow microenvironment affect proteasome inhibitors' (PI) sensitivity of multiple myeloma is currently unknown. This study aims to evaluate which exosomal RNAs are involved and by which molecular mechanisms they exert this function. Experimental Design: Exosomes were characterized by dynamic light scattering, transmission electron microscopy, and Western blot analysis. Coculture experiments were performed to assess exosomal RNAs transferring from mesenchymal stem cells (MSC) to multiple myeloma cells. The role of PSMA3-AS1 in PI sensitivity was further evaluated in vivo. To determine the prognostic significance of circulating exosomal PSMA3 and PSMA3-AS1, a cohort of patients with newly diagnosed multiple myeloma was enrolled to study. Cox regression models and Kaplan–Meier curves were used to analyze progression-free survival (PFS) and overall survival (OS). Results: We identified that PSMA3 and PSMA3-AS1 in MSCs could be packaged into exosomes and transferred to myeloma cells, thus promoting PI resistance. PSMA3-AS1 could form an RNA duplex with pre-PSMA3, which transcriptionally promoted PSMA3 expression by increasing its stability. In xenograft models, intravenously administered siPSMA3-AS1 was found to be effective in increasing carfilzomib sensitivity. Moreover, plasma circulating exosomal PSMA3 and PSMA3-AS1 derived from patients with multiple myeloma were significantly associated with PFS and OS. Conclusions: This study suggested a unique role of exosomal PSMA3 and PSMA3-AS1 in transmitting PI resistance from MSCs to multiple myeloma cells, through a novel exosomal PSMA3-AS1/PSMA3 signaling pathway. Exosomal PSMA3 and PSMA3-AS1 might act as promising therapeutic targets for PI resistance and prognostic predictors for clinical response.
    Type of Medium: Online Resource
    ISSN: 1078-0432 , 1557-3265
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2019
    detail.hit.zdb_id: 1225457-5
    detail.hit.zdb_id: 2036787-9
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