关键词： alternative splicing   carcinogenesis   papillary thyroid cancer   prognosis   The Cancer Genome Atlas  

摘要： As a key mechanism, alternative splicing (AS) plays a role in the cancer initiation and development. However, in papillary thyroid cancer (PTC), data for the comprehensive AS event profile and its clinical implications are lacking. Herein, a genome-wide AS event profiling using RNA-Seq data and its correlation with matched clinical information was performed using a 389 PTC patient cohort from the project of The Cancer Genome Atlas (TCGA). We identified 1,925 cancer-associated AS events (CASEs) by comparing paired tumors and neighboring healthy tissues. Parent genes with CASEs remarkably enriched in the pathways were linked with carcinogenesis, such as P53, KRAS, IL6-JAK-STAT3, apoptosis, and MYC signaling. The regulatory networks of AS implied an obvious correlation between the expression of splicing factor and CASE. We identified eight CASEs as predictors for overall survival (OS) and disease-free survival (DFS). The established risk score model based on DFS-associated CASEs successfully predicted the prognosis of PTC patients. From the unsupervised clustering analysis results, it is found that different clusters based on AS correlated with prognosis, molecular features, and immune characteristics. Taken together, the comprehensive genome-wide AS landscape analysis in PTC showed new AS events linked with tumorigenesis and prognosis, which provide new insights for clinical monitoring and therapy for PTC. © 2021 Zheng et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

关键词： Conformal prediction   data augmentation   electronic nose   herbal medicine   semi-supervised learning  

摘要： Electronic nose has been proven effective in alternative herbal medicine classification, but due to the nature of supervised learning, previous research heavily relies on the labelled training data, which are time-costly and labor-intensive to collect. To alleviate the critical dependency on the training data in real-world applications, this study aims to improve classification accuracy via data augmentation strategies. The effectiveness of five data augmentation strategies under different training data inadequacy are investigated in two scenarios: the noise-free scenario where different availabilitiesof unlabelleddatawere considered, and the noisy scenario where different levels of Gaussian noises and translational shift were added to represent sensor drift. The five augmentation strategies, namely noise-adding data augmentation, semi-supervised learning, classifier-based online learning, Inductive Conformal Prediction (ICP) online learning and our novel ensemble ICP online learning (EICP) proposed in this study, are compared against supervised learning baselines, with Linear Discriminant Analysis (LDA) and Support Vector Machine (SVM) as the classifiers. This study provides a systematic analysis of different augmentation strategies. Our novel strategy, EICP, outperforms the others by showing non-decreasing classification accuracy on all tasks and a significant improvement on most simulated tasks (25 out of 36 tasks, p <= 0.05), which demonstrated both effectiveness and robustness in boosting the classificationmodel generalizability. This strategy can be employed in other machine learning applications.

摘要： Nokes discusses the study by S. A. Joosten et al on oxygen therapy for patients who do not respond to upper airway surgery for obstructive sleep apnea (OSA). The future of OSA treatment will likely be tailored on the basis of underlying patient traits. The gold standard therapy for OSA is continuous positive airway pressure, but adherence remains variable. A group and others have defined multiple OSA endophenolypes with these ideas in mind. It is unclear which patients may have the greatest benefit from upper airway surgery. Furthermore, upper airway surgical procedures are not standardized, and many individuals have residual sleep apnea despite surgical intervention. One OSA endotype of note includes patients with elevated loop.

关键词： Technical jet fuels   Synthetic fuels   Speciation   Soot precursor   Laminar flow reactor   Combustion kinetics  

摘要： A comprehensive collection of technical aviation fuels enabled an experimental and numerical study on detailed combustion chemistry and pollutant formation presented in a series of 3 interlinking parts. Part-I: Experimental Flow Reactor Study focuses on the characterization of 42 technical jet fuels and provides experimental speciation data for model development presented in Part-II: Model and Surrogate Strategy. Model validation based on the presented technical fuels here is presented in Part-III: Model Application on Technical Jet Fuels. The fuels investigated in this study cover a broad range of approved SAFs (Sustainable Aviation Fuels), candidates for approval, and technical products outside the present ASTM-D7566 specification and is completed by reference fuels (ASTM-D1655). This includes SAF components such as HEFA (Hydroprocessed Esters and Fatty Acids), ATJ (Alcohol-To-Jet), SIP (Synthesized Iso-Paraffins), and Fischer-Tropsch-products as well as their blends. A systematic investigation of the soot precursor chemistry by analyzing the influence of the complex chemical fuel composition on the intermediate species pool is presented. The experimental set-up consists of an atmospheric flow reactor with coupled molecular-beam mass spectrometer (MBMS). Quantitative evolution of combustion reaction intermediates is recorded for fuel-rich (phi = 1.2) and fuel-lean (phi = 0.8) conditions at intermediate temperatures up to 1200 K including small intermediate species (e.g. ethylene, butene) and soot precursor species (e.g. benzene, naphthalene, phenanthrene). A general systematic dependency of the soot precursor concentration on the degree of unsaturation (Index of Hydrogen Deficiency) or the hydrogen content, respectively, is demonstrated. Furthermore, larger soot precursor concentrations depend on the naphthalene content of the fuel.

关键词： Boundary arbitrary Lagrangian-Eulerian   Deformable domains   Mesh deformation   Lagrangian   Eulerian  

摘要： Many physical problems can be modelled by partial differential equations (PDEs) on unknown domains. Several examples can be easily found in the dynamics of free interfaces in fluid dynamics, solid mechanics or in fluid-solid interactions. To solve these equations in an arbitrary domain with nonlinear deformations, the Arbitrary Lagrangian-Eulerian (ALE) method is in widespread use. For this method, a change of spatial variables is used, which should fulfil a given partial differential equation in the domain together with boundary conditions at the boundary. In the normal direction, the boundary should follow the material point, thus using a Lagrangian approach, whereas in the tangential direction, there are infinite possibilities. In this direction, whereas in solid mechanics a Lagrangian approach is common, in fluid mechanics an Eulerian approach is usually more convenient. Alternative approaches are also usually taken which are problem (physics and geometry) dependent, not always valid and may eventually lead to large mesh deformations. We propose a method to determine the tangential displacement of the boundary based on the boundary displacement fulfilling a boundary partial differential equation, which does not depend on the problem and leads to an uniform deformation of the mesh. Due to the analogy with the ALE method, we refer to this as Differential Boundary Arbitrary Lagrangian-Eulerian (DBALE) method. We illustrate the advantages of the method concerning problem independency and capabilities to control the mesh distortion by means of reference and real problems. (C) 2021 Elsevier Inc. All rights reserved.

关键词： Reaction mechanism   Aviation fuels   Validation   Hydrocarbons   Oxygenates   Soot precursors  

摘要： Conventional transportation fuels used in aviation (jet fuel) or in ground transportation (gasoline, diesel) contain multitude of hydrocarbon components and are difficult to be modeled, if one has to consider each of the component present. A typical approach is the definition of a fuel surrogate with a limited number of fuel components. In this context, a single semi-detailed high temperature reaction kinetic mechanism is presented in this work, which contains all the important molecular classes required for the detailed surrogate modeling of a hydrocarbon fuel. The appeal of the mechanism is the suitability for a broad range of technical fuels covering gasoline, diesel and jet fuels. The reaction mechanism for hydrocarbon combustion is consisted of 238 species and 1814 reactions and is rigorously validated for 70 neat hydrocarbon components over a wide range of experimental conditions including combustion setups such as shock-tubes, laminar flames, jet-stirred and flow reactors. The purpose of this study is to provide a single reaction model that (1) includes variety of hydrocarbon molecules of varying degree of complexity and carbon numbers, (2) has capability to model a spectrum of different fuels, initially aviation fuels, and (3) is compact to apply both in simple (fundamental kinetic investigations) and complex geometries (CFD studies) of combustion system enabled through customized mechanism reductions. The ultimate goal is to resolve the fuel differences using the model predictions obtained from the reaction mechanism that will supply parameters for fuel design and optimization of fuels. Extensive supporting information is available in this work.

关键词： Fuel cells   Polymer electrolyte membrane   Direct methanol fuel cell   SANS   Monte Carlo simulation  

摘要： The use of fuel cells is strategic in the global energy system;their inclusion in eco-cars, avoiding CO2 emission, represents a crucial enhancement for the environment. For this reason, any improvement in their use and optimization is fundamental for our society. Since one of the main components in these cells is their polymeric proton exchange membrane, in this work, the commercial Fumapem F-14100 and F-1850 membranes have been studied, both representing a cheap and effective alternative in direct methanol fuel cell (DMFC) applications. Their characterization will provide a new insight about them, in order to optimize and improve future fuel cell operation conditions. Small angle neutron scattering (SANS) has been used in this work to achieve a nanometric structural characterization of these membranes, which is key for understanding their physicochemical properties. Starting from SANS measurements, empirical fitting models were applied in order to obtain global sample features, which allowed to propose a lamellar water channel structure. Then, 2D scattering length density maps generated by Monte Carlo simulations were optimized to match the experimental SANS intensity profiles by using the inverse Fourier transform method. In addition, the crystalline contribution from the sample ordered domains was also studied by using X-ray diffraction.

关键词： Aviation fuels   Fuel surrogate   Modeling   Flow reactor   Hydrogen deficiency  

摘要： In Part III of our study on alternative aviation fuels, we present a comprehensive database of modeled speciation data consisting of seven hydrocarbons of varying molecular structure and 26 alternative and conventional aviation fuels. The speciation data is obtained from the DLR atmospheric high temperature flow reactor with a coupled molecular beam mass spectrometry (MBMS) detection system (Part-I). The chemical reactivity of these real liquid fuels is investigated both experimentally and numerically. For modeling, detailed fuel surrogates (up to 14 components) are employed for characterizing the fuels. The surrogate formulation strategy is defined based on the fuels' compositional analysis. This work employs high temperature reaction kinetic mechanism for the combustion of wide variety of hydrocarbons of varying molecular classes from n-, iso-, cy-paraffins, to five-ring aromatics presented in Part-II. The reaction mechanism is applied to model 26 aviation fuels using 21 different validated fuel surrogate components to predict the fuel intermediates and soot precursors measured in the reactor. This work aims to identify the effect of fuel surrogate components on the intermediates' formation and its influence on the emissions. Through compilation of many fuels with composition of wide range of chemical classes, we provide a systematic evaluation of how the fuel composition can be used to extract information of specific fuel intermediates and emissions formed.

关键词： Throughput  

摘要： We present a review of the field of high-throughput virtual screening for organic electronics materials focusing on the sequence of methodological choices that determine each virtual screening protocol. These choices are present in all high-throughput virtual screenings and addressing them systematically will lead to optimised workflows and improve their applicability. We consider the range of properties that can be computed and illustrate how their accuracy can be determined depending on the quality and size of the experimental datasets. The approaches to generate candidates for virtual screening are also extremely varied and their relative strengths and weaknesses are discussed. The analysis of high-throughput virtual screening is almost never limited to the identification of top candidates and often new patterns and structure-property relations are the most interesting findings of such searches. The review reveals a very dynamic field constantly adapting to match an evolving landscape of applications, methodologies and datasets.

关键词： RNA processing   alternative polyadenylation   DNA damage   apoptosis   MSL   PCF11   cisplatin   cancer   chemotherapy   p53  

摘要： DNA damage reshapes the cellular transcriptome by modulating RNA transcription and processing. In cancer cells, these changes can alter the expression of genes in the immune surveillance and cell death pathways. Here, we investigate how DNA damage impacts alternative polyadenylation (APA) using the PAPERCLIP technique. We find that APA shifts are a coordinated response for hundreds of genes to DNA damage, and we identify PCF11 as an important contributor of DNA damage-induced APA shifts. One of these APA shifts results in upregulation of the full-length MSL1 mRNA isoform, which protects cells from DNA damage-induced apoptosis and promotes cell survival from DNA-damaging agents. Importantly, blocking MSL1 upregulation enhances cytotoxicity of chemotherapeutic agents even in the absence of p53 and overcomes chemoresistance. Our study demonstrates that characterizing adaptive APA shifts to DNA damage has therapeutic implications and reveals a link between PCF11, the MSL complex, and DNA damage-induced apoptosis.