232 research outputs found

    Sources of variation in false discovery rate estimation include sample size, correlation, and inherent differences between groups

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    BACKGROUND: High-throughtput technologies enable the testing of tens of thousands of measurements simultaneously. Identification of genes that are differentially expressed or associated with clinical outcomes invokes the multiple testing problem. False Discovery Rate (FDR) control is a statistical method used to correct for multiple comparisons for independent or weakly dependent test statistics. Although FDR control is frequently applied to microarray data analysis, gene expression is usually correlated, which might lead to inaccurate estimates. In this paper, we evaluate the accuracy of FDR estimation. METHODS: Using two real data sets, we resampled subgroups of patients and recalculated statistics of interest to illustrate the imprecision of FDR estimation. Next, we generated many simulated data sets with block correlation structures and realistic noise parameters, using the Ultimate Microarray Prediction, Inference, and Reality Engine (UMPIRE) R package. We estimated FDR using a beta-uniform mixture (BUM) model, and examined the variation in FDR estimation. RESULTS: The three major sources of variation in FDR estimation are the sample size, correlations among genes, and the true proportion of differentially expressed genes (DEGs). The sample size and proportion of DEGs affect both magnitude and precision of FDR estimation, while the correlation structure mainly affects the variation of the estimated parameters. CONCLUSIONS: We have decomposed various factors that affect FDR estimation, and illustrated the direction and extent of the impact. We found that the proportion of DEGs has a significant impact on FDR; this factor might have been overlooked in previous studies and deserves more thought when controlling FDR

    Formalizing and verifying software architectures

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    Master'sMASTER OF SCIENC

    Optimization of traffic safety facilities in highway tunnels based on driver’s visual perception

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    This paper delves into the optimization of traffic safety facilities within highway tunnels by leveraging the inherent visual perception characteristics of drivers. Grounded in the context of Zhejiang Province’s highway construction, the study draws from practical insights provided by highway tunnel projects within the region. Through a meticulous blend of on-site investigations and empirical experimentation, the research assesses the effectiveness of existing safety installations in highway tunnels. The analysis extends to the exploration of optimizing the design and placement of traffic safety facilities, informed by the distinct visual perception tendencies exhibited by drivers. By amalgamating the insights derived from driver perception and real-world highway tunnel dynamics, the paper proposes a refined and contextually attuned approach to enhancing traffic safety measures. This study not only contributes to the field of transportation engineering but also holds the potential to significantly enhance the overall safety of highway tunnel environments

    Formalizing and verifying stochastic system architectures using Monterey Phoenix

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    The analysis of software architecture plays an important role in understanding the system structures and facilitate proper implementation of user requirements. Despite its importance in the software engineering practice, the lack of formal description and verification support in this domain hinders the development of quality architectural models. To tackle this problem, in this work, we develop an approach for modeling and verifying software architectures specified using Monterey Phoenix (MP) architecture description language. MP is capable of modeling system and environment behaviors based on event traces, as well as supporting different architecture composition operations and views. First, we formalize the syntax and operational semantics for MP; therefore, formal verification of MP models is feasible. Second, we extend MP to support shared variables and stochastic characteristics, which not only increases the expressiveness of MP, but also widens the properties MP can check, such as quantitative requirements. Third, a dedicated model checker for MP has been implemented, so that automatic verification of MP models is supported. Finally, several experiments are conducted to evaluate the applicability and efficiency of our approachNo Full Tex

    Drug development progress in duchenne muscular dystrophy

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    Duchenne muscular dystrophy (DMD) is a severe, progressive, and incurable X-linked disorder caused by mutations in the dystrophin gene. Patients with DMD have an absence of functional dystrophin protein, which results in chronic damage of muscle fibers during contraction, thus leading to deterioration of muscle quality and loss of muscle mass over time. Although there is currently no cure for DMD, improvements in treatment care and management could delay disease progression and improve quality of life, thereby prolonging life expectancy for these patients. Furthermore, active research efforts are ongoing to develop therapeutic strategies that target dystrophin deficiency, such as gene replacement therapies, exon skipping, and readthrough therapy, as well as strategies that target secondary pathology of DMD, such as novel anti-inflammatory compounds, myostatin inhibitors, and cardioprotective compounds. Furthermore, longitudinal modeling approaches have been used to characterize the progression of MRI and functional endpoints for predictive purposes to inform Go/No Go decisions in drug development. This review showcases approved drugs or drug candidates along their development paths and also provides information on primary endpoints and enrollment size of Ph2/3 and Ph3 trials in the DMD space

    Mechanism, prevention and treatment of cognitive impairment caused by high altitude exposure

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    Hypobaric hypoxia (HH) characteristics induce impaired cognitive function, reduced concentration, and memory. In recent years, an increasing number of people have migrated to high-altitude areas for work and study. Headache, sleep disturbance, and cognitive impairment from HH, severely challenges the physical and mental health and affects their quality of life and work efficiency. This review summarizes the manifestations, mechanisms, and preventive and therapeutic methods of HH environment affecting cognitive function and provides theoretical references for exploring and treating high altitude-induced cognitive impairment
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