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Heterogeneity of chronic obstructive pulmonary disease: from phenotype to genotype

null

《医学前沿（英文）》 2013年第7卷第4期页码 425-432 doi: 10.1007/s11684-013-0295-x

摘要：

Chronic obstructive pulmonary disease (COPD) is one of the leading causes of morbidity and mortality throughout the world and is mainly characterized by persistent airflow limitation. Given that multiple systems other than the lung can be impaired in COPD patients, the traditional FEV₁/FVC ratio shows many limitations in COPD diagnosis and assessment. Certain heterogeneities are found in terms of clinical manifestations, physiology, imaging findings, and inflammatory reactions in COPD patients; thus, phenotyping can provide effective information for the prognosis and treatment. However, phenotypes are often based on symptoms or pathophysiological impairments in late-stage COPD, and the role of phenotypes in COPD prevention and early diagnosis remains unclear. This shortcoming may be overcome by the potential genotypes defined by the heterogeneities in certain genes. This review briefly describes the heterogeneity of COPD, with focus on recent advances in the correlations between genotypes and phenotypes. The potential roles of these genotypes and phenotypes in the molecular mechanisms and management of COPD are also elucidated.

关键词： chronic obstructive pulmonary disease heterogeneity phenotype genotype prediction

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Intratumor heterogeneity, microenvironment, and mechanisms of drug resistance in glioma recurrence and

Zhaoshi Bao, Yongzhi Wang, Qiangwei Wang, Shengyu Fang, Xia Shan, Jiguang Wang, Tao Jiang

《医学前沿（英文）》 2021年第15卷第4期页码 551-561 doi: 10.1007/s11684-020-0760-2

摘要： Glioma is the most common lethal tumor of the human brain. The median survival of patients with primary World Health Organization grade IV glioma is only 14.6 months. The World Health Organization classification of tumors of the central nervous system categorized gliomas into lower-grade gliomas and glioblastomas. Unlike primary glioblastoma that usually develop in the elderly, secondary glioblastoma enriched with an isocitrate dehydrogenase mutant typically progresses from lower-grade glioma within 5–10 years from the time of diagnosis. Based on various evolutional trajectories brought on by clonal and subclonal alterations, the evolution patterns of glioma vary according to different theories. Some important features distinguish the normal brain from other tissues, e.g., the composition of the microenvironment around the tumor cells, the presence of the blood-brain barrier, and others. The underlying mechanism of glioma recurrence and evolution patterns of glioma are different from those of other types of cancer. Several studies correlated tumor recurrence with tumor heterogeneity and the immune microenvironment. However, the detailed reasons for the progression and recurrence of glioma remain controversial. In this review, we introduce the different mechanisms involved in glioma progression, including tumor heterogeneity, the tumor microenvironment and drug resistance, and their pre-clinical implements in clinical trials. This review aimed to provide new insights into further clinical strategies for the treatment of patients with recurrent and secondary glioma.

关键词： glioma evolution mechanism strategies tumor heterogeneity secondary glioma

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Heterogeneity of the tumor immune microenvironment and clinical interventions

《医学前沿（英文）》页码 617-648 doi: 10.1007/s11684-023-1015-9

摘要： Heterogeneity of the tumor immune microenvironment and clinical interventions

关键词： Heterogeneity tumor immune

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Computational modeling of fracture in concrete: A review

Luthﬁ Muhammad Mauludin, Chahmi Oucif

《结构与土木工程前沿（英文）》 2020年第14卷第3期页码 586-598 doi: 10.1007/s11709-020-0573-z

摘要： This paper presents a review of fracture modeling of concrete. The complex material, such as concrete, has been widely used in construction industries and become trending issue in the last decades. Based on comprehensive literature review, there are two main approaches considered to-date of concrete fracture modeling, such as macroscopic and micromechanical models. The purpose of this review is to provide insight comparison from different techniques in modeling of fracture in concrete which are available. In the first section, an overview of fracture modeling in general is highlighted. Two different approaches both of macroscopic and micromechanical models will be reviewed. As heterogeneity of concrete material is major concern in micromechanical-based concrete modeling, one section will discuss this approach. Finally, the summary from all of reviewed techniques will be pointed out before the future perspective is given.

关键词： concrete fracture macroscopic micromechanical heterogeneity

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Analysis of stress and failure in rock specimens with closed and open flaws on the surface

《结构与土木工程前沿（英文）》 2021年第15卷第5期页码 1222-1237 doi: 10.1007/s11709-021-0773-1

摘要： The influence of closed and open surface flaws on the stress distribution and failure in rock specimens is investigated. Heterogeneous finite element models are developed to simulate the compression tests on flawed rock specimens. The simulated specimens include those with closed flaws and those with open flaws on the surface. Systematic analyses are conducted to investigate the influences of the flaw inclination, friction coefficient and the confining stress on failure behavior. Numerical results show significant differences in the stress, displacement, and failure behavior of the closed and open flaws when they are subjected to pure compression; however, their behaviors under shear and tensile loads are similar. According to the results, when compression is the dominant mode of stress applied to the flaw surface, an open flaw may play a destressing role in the rock and relocate the stress concentration and failure zones. The presented results in this article suggest that failure at the rock surface may be managed in a favorable manner by fabricating open flaws on the rock surface. The insights gained from this research can be helpful in managing failure at the boundaries of rock structures.

关键词： surface flaw heterogeneity circular hole numerical modeling relative displacement

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A multiscale material model for heterogeneous liquid droplets in solid soft composites

《结构与土木工程前沿（英文）》 2021年第15卷第5期页码 1292-1299 doi: 10.1007/s11709-021-0771-3

摘要： Liquid droplets in solid soft composites have been attracting increasing attention in biological applications. In contrary with conventional composites, which are made of solid elastic inclusions, available material models for composites including liquid droplets are for highly idealized configurations and do not include all material real parameters. They are also all deterministic and do not address the uncertainties arising from droplet radius, volume fraction, dispersion and agglomeration. This research revisits the available models for liquid droplets in solid soft composites and presents a multiscale computational material model to determine their elastic moduli, considering nearly all relevant uncertainties and heterogeneities at different length scales. The effects of surface tension at droplets interface, their volume fraction, size, size polydispersity and agglomeration on elastic modulus, are considered. Different micromechanical material models are incorporated into the presented computational framework. The results clearly indicate both softening and stiffening effects of liquid droplets and show that the model can precisely predict the effective properties of liquid droplets in solid soft composites.

关键词： liquid in solid soft composite computational modeling multiscale model heterogeneity

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Heterogeneous influence of individuals’ behavior on mask efficacy in gathering environments

《工程管理前沿（英文）》页码 550-562 doi: 10.1007/s42524-022-0193-5

摘要： Wearing masks is an easy way to operate and popular measure for preventing epidemics. Although masks can slow down the spread of viruses, their efficacy in gathering environments involving heterogeneous person-to-person contacts remains unknown. Therefore, we aim to investigate the epidemic prevention effect of masks in different real-life gathering environments. This study uses four real interpersonal contact datasets to construct four empirical networks to represent four gathering environments. The transmission of COVID-19 is simulated using the Monte Carlo simulation method. The heterogeneity of individuals can cause mask efficacy in a specific gathering environment to be different from the baseline efficacy in general society. Furthermore, the heterogeneity of gathering environments causes the epidemic prevention effect of masks to differ. Wearing masks can greatly reduce the probability of clustered epidemics and the infection scale in primary schools, high schools, and hospitals. However, the use of masks alone in primary schools and hospitals cannot control outbreaks. In high schools with social distancing between classes and in workplaces where the interpersonal contact is relatively sparse, masks can meet the need for prevention. Given the heterogeneity of individual behavior, if individuals who are more active in terms of interpersonal contact are prioritized for mask-wearing, the epidemic prevention effect of masks can be improved. Finally, asymptomatic infection has varying effects on the prevention effect of masks in different environments. The effect can be weakened or eliminated by increasing the usage rate of masks in high schools and workplaces. However, the effect on primary schools and hospitals cannot be weakened. This study contributes to the accurate evaluation of mask efficacy in various gathering environments to provide scientific guidance for epidemic prevention.

关键词： COVID-19 masks behavioral heterogeneity asymptomatic infection

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Temporal and spatial stability of the EM/PM molecular subtypes in adult diffuse glioma

《医学前沿（英文）》 2023年第17卷第2期页码 240-262 doi: 10.1007/s11684-022-0936-z

摘要： Detailed characterizations of genomic alterations have not identified subtype-specific vulnerabilities in adult gliomas. Mapping gliomas into developmental programs may uncover new vulnerabilities that are not strictly related to genomic alterations. After identifying conserved gene modules co-expressed with EGFR or PDGFRA (EM or PM), we recently proposed an EM/PM classification scheme for adult gliomas in a histological subtype- and grade-independent manner. By using cohorts of bulk samples, paired primary and recurrent samples, multi-region samples from the same glioma, single-cell RNA-seq samples, and clinical samples, we here demonstrate the temporal and spatial stability of the EM and PM subtypes. The EM and PM subtypes, which progress in a subtype-specific mode, are robustly maintained in paired longitudinal samples. Elevated activities of cell proliferation, genomic instability and microenvironment, rather than subtype switching, mark recurrent gliomas. Within individual gliomas, the EM/PM subtype was preserved across regions and single cells. Malignant cells in the EM and PM gliomas were correlated to neural stem cell and oligodendrocyte progenitor cell compartment, respectively. Thus, while genetic makeup may change during progression and/or within different tumor areas, adult gliomas evolve within a neurodevelopmental framework of the EM and PM molecular subtypes. The dysregulated developmental pathways embedded in these molecular subtypes may contain subtype-specific vulnerabilities.

关键词： glioma progression molecular classification EM/PM subtyping intratumor heterogeneity

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Numerical simulation of damage in high arch dam due to earthquake

Hong ZHONG , Gao LIN , Hongjun LI

《结构与土木工程前沿（英文）》 2009年第3卷第3期页码 316-322 doi: 10.1007/s11709-009-0039-9

摘要： Based on the assumption that concrete is macroscopic homogeneous, the cracking evolution process and damage mode of high arch dams are studied in consideration of the heterogeneity of concrete in mesoscale. The bilinear damage evolution model and the damage evolution model expressed in power function with descending section are adopted to combine with the Mohr-Coulomb criterion to investigate the crack development and fracture mode of high arch dams under the action of an earthquake. The analysis result of a high arch dam in China under design shows that cracks that take place in concrete are caused by excessive tensile stress. The cracks initiate at the middle of the dam top and distribute at the upper half of the dam while the rest of the parts remain intact. This conclusion agrees with the model test result.

关键词： mesoscopic heterogeneity damage simulation in earthquakes arch dam

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Changes in lncRNAs and related genes in β-thalassemia minor and β-thalassemia major

null

《医学前沿（英文）》 2017年第11卷第1期页码 74-86 doi: 10.1007/s11684-017-0503-1

摘要：

β-thalassemia is caused by β-globin gene mutations. However, heterogeneous phenotypes were found in individuals with same genotype, and still undescribed mechanism underlies such variation. We collected blood samples from 30 β-thalassemia major, 30 β-thalassemia minor patients, and 30 matched normal controls. Human lncRNA Array v2.0 (8 × 60 K, Arraystar) was used to detect changes in long non-coding RNAs (lncRNAs) and mRNAs in three samples each from β-thalassemia major, β-thalassemia minor, and control groups. Compared with normal controls, 1424 and 2045 lncRNAs were up- and downregulated, respectively, in β-thalassemia major patients, whereas 623 and 349 lncRNAs were up- and downregulated, respectively, in β-thalassemia minor patients. Compared with β-thalassemia minor group, 1367 and 2356 lncRNAs were up- and downregulated, respectively, in β-thalassemia major group. We selected five lncRNAs that displayed altered expressions (DQ583499, X-inactive specific transcript (Xist), lincRNA-TPM1, MRFS16P, and lincRNA-RUNX2-2) and confirmed their expression levels in all samples using real-time polymerase chain reaction. Based on coding-non-coding gene co-expression network and gene ontology biological process analyses, several signaling pathways were associated with three common organ systems exhibiting β-thalassemia phenotypes: hematologic, skeletal, and hepatic systems. This study implicates that abnormal expression levels of lncRNAs and mRNA in β-thalassemia cases may be correlated with its various clinical phenotypes.

关键词： β-thalassemia long non-coding RNA mRNA phenotypic heterogeneity pathway

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Schedule refinement for homogeneousmulti-core processors in the presence of manufacturing-caused heterogeneity

Zhi-xiang CHEN,Zhao-lin LI,Shan CAO,Fang WANG,Jie ZHOU

《信息与电子工程前沿（英文）》 2015年第16卷第12期页码 1018-1033 doi: 10.1631/FITEE.1500035

摘要： Multi-core homogeneous processors have been widely used to deal with computation-intensive embedded applications. However, with the continuous down scaling of CMOS technology, within-die variations in the manufacturing process lead to a significant spread in the operating speeds of cores within homogeneous multi-core processors. Task scheduling approaches, which do not consider such heterogeneity caused by within-die variations, can lead to an overly pessimistic result in terms of performance. To realize an optimal performance according to the actual maximum clock frequencies at which cores can run, we present a heterogeneity-aware schedule refining (HASR) scheme by fully exploiting the heterogeneities of homogeneous multi-core processors in embedded domains. We analyze and show how the actual maximum frequencies of cores are used to guide the scheduling. In the scheme, representative chip operating points are selected and the corresponding optimal schedules are generated as candidate schedules. During the booting of each chip, according to the actual maximum clock frequencies of cores, one of the candidate schedules is bound to the chip to maximize the performance. A set of applications are designed to evaluate the proposed scheme. Experimental results show that the proposed scheme can improve the performance by an average value of 22.2%, compared with the baseline schedule based on the worst case timing analysis. Compared with the conventional task scheduling approach based on the actual maximum clock frequencies, the proposed scheme also improves the performance by up to 12%.

关键词： Schedule refining Multi-core processor Heterogeneity Representative chip operating point

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探索生态水利工程学

董哲仁

《中国工程科学》 2007年第9卷第1期页码 1-7

摘要：

人类社会与生态系统对于河流都具有高度的依赖性，人类应该与生态系统共享水资源。水利工程是对河流生态系统的胁迫因子之一。需要建立新的准则和开发新的技术方法，使水利工程在满足人类社会需求的同时，兼顾河流生态系统健康和可持续性的需求，构建与生态友好的水利工程技术体系。

关键词：生态水利工程学胁迫非连续化异质性反馈式设计

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基于多关系平移图注意力网络的需融中小企业挖掘方法 Research Article

梁倩乔1,卫华2,吴亚熙2,韦峰2,赵登3,何建衫3,郑小林1,马国芳4,韩冰2

《信息与电子工程前沿（英文）》 2023年第24卷第3期页码 388-402 doi: 10.1631/FITEE.2200151

摘要：需融企业挖掘任务指挖掘财务困难、需要融资的中小企业，其有利于金融机构帮助中小企业的发展，在金融领域中发挥着越来越重要的作用。本文首先深入分析中小企业的融资需求在企业社交网络中的传递现象，从而提供了一个利用企业社交网络来提升需融企业挖掘有效性的想法，即学习企业社交网络中企业节点的表征并利用该表征挖掘需融企业。然而，该想法面临两种异构性挑战，即融资需求在不同关系下的传递异构性和中小企业在不同关系类型下的行为模式异构性。为了应对这些挑战，本文提出一种基于多关系平移图注意力网络的需融企业挖掘方法。该方法不仅基于一种新颖的实体-关系组合算子来对不同关系类型下的融资需求传递异构性进行建模，还基于本文所设计的关系超平面平移机制来获得中小企业在不同关系类型下的表征，以区分中小企业在不同关系类型下的异构行为模式。最后，本文在两个大型真实数据集上进行大量实验，实验结果证明了所提方法在需融企业挖掘任务中优于最先进的方法。

关键词：需融企业挖掘；图表征学习；传递异构性；行为模型异构性

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Potential unreliability of ALK variant allele frequency in the efficacy prediction of targeted therapy in NSCLC

《医学前沿（英文）》 2023年第17卷第3期页码 493-502 doi: 10.1007/s11684-022-0946-x

摘要： Anaplastic lymphoma kinase (ALK) is the most common fusion gene involved in non-small cell lung cancer (NSCLC), and remarkable response has been achieved with the use of ALK tyrosine kinase inhibitors (ALK-TKIs). However, the clinical efficacy is highly variable. Pre-existing intratumoral heterogeneity (ITH) has been proven to contribute to the poor treatment response and the resistance to targeted therapies. In this work, we investigated whether the variant allele frequencies (VAFs) of ALK fusions can help assess ITH and predict targeted therapy efficacy. Through the application of next-generation sequencing (NGS), 7.2% (326/4548) of patients were detected to be ALK positive. On the basis of the adjusted VAF (adjVAF, VAF normalization for tumor purity) of four different threshold values (adjVAF < 50%, 40%, 30%, or 20%), the association of ALK subclonality with crizotinib efficacy was assessed. Nonetheless, no statistical association was observed between median progression-free survival (PFS) and ALK subclonality assessed by adjVAF, and a poor correlation of adjVAF with PFS was found among the 85 patients who received first-line crizotinib. Results suggest that the ALK VAF determined by hybrid capture-based NGS is probably unreliable for ITH assessment and targeted therapy efficacy prediction in NSCLC.

关键词： ALK fusion next-generation sequencing fluorescence in situ hybridization immunohistochemistry variant allele frequency intratumoral heterogeneity targeted therapy

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Finite element simulation for elastic dislocation of the North-Tehran fault: The effects of geologic layering and slip distribution for the segment located in Karaj

Pooya ZAKIAN; Hossein ASADI HAYEH

《结构与土木工程前沿（英文）》 2022年第16卷第4期页码 533-549 doi: 10.1007/s11709-022-0802-8

摘要： The present study uses the finite element method for simulating the crustal deformation due to the dislocation of a segment of the North-Tehran fault located in the Karaj metropolis region. In this regard, a geological map of Karaj that includes the fault segment is utilized in order to create the geometry of finite element model. First, finite element analysis of homogeneous counterpart of the fault’s domain with two different sections was performed, and the results were compared to those of Okada’s analytical solutions. The fault was modeled with the existing heterogeneity of the domain having been considered. The influences of both uniform and non-uniform slip distributions were investigated. Furthermore, three levels of simplification for geometric creation of geological layers’ boundaries were defined in order to evaluate the effects of the geometric complexity of the geological layering on the displacement responses obtained with the finite element simulations. In addition to the assessment of slip distribution, layering complexity and heterogeneity, the results demonstrate both the capability and usefulness of the proposed models in the dislocation analysis for the Karaj segment of North-Tehran fault.

关键词： finite element method fault dislocation slip distribution the North-Tehran fault heterogeneity geological layering

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标题作者时间类型操作

Heterogeneity of chronic obstructive pulmonary disease: from phenotype to genotype

null

期刊论文

Intratumor heterogeneity, microenvironment, and mechanisms of drug resistance in glioma recurrence and

Zhaoshi Bao, Yongzhi Wang, Qiangwei Wang, Shengyu Fang, Xia Shan, Jiguang Wang, Tao Jiang

期刊论文

Heterogeneity of the tumor immune microenvironment and clinical interventions

期刊论文

Computational modeling of fracture in concrete: A review

Luthﬁ Muhammad Mauludin, Chahmi Oucif

期刊论文

Analysis of stress and failure in rock specimens with closed and open flaws on the surface

期刊论文

A multiscale material model for heterogeneous liquid droplets in solid soft composites

期刊论文

Heterogeneous influence of individuals’ behavior on mask efficacy in gathering environments

期刊论文

Temporal and spatial stability of the EM/PM molecular subtypes in adult diffuse glioma

期刊论文

Numerical simulation of damage in high arch dam due to earthquake

Hong ZHONG , Gao LIN , Hongjun LI

期刊论文

Changes in lncRNAs and related genes in β-thalassemia minor and β-thalassemia major

null

期刊论文

Schedule refinement for homogeneousmulti-core processors in the presence of manufacturing-caused heterogeneity

Zhi-xiang CHEN,Zhao-lin LI,Shan CAO,Fang WANG,Jie ZHOU

期刊论文

探索生态水利工程学

董哲仁

期刊论文

基于多关系平移图注意力网络的需融中小企业挖掘方法

梁倩乔1,卫华2,吴亚熙2,韦峰2,赵登3,何建衫3,郑小林1,马国芳4,韩冰2

期刊论文

Potential unreliability of ALK variant allele frequency in the efficacy prediction of targeted therapy in NSCLC

期刊论文

Finite element simulation for elastic dislocation of the North-Tehran fault: The effects of geologic layering and slip distribution for the segment located in Karaj

Pooya ZAKIAN; Hossein ASADI HAYEH

期刊论文

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