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Identification of novel mutations in and in a family with craniofacial microsomia: evidence of digenic

《医学前沿（英文）》   页码 1006-1009 doi: 10.1007/s11684-023-1000-3

摘要： Identification of novel mutations in and in a family with craniofacial microsomia: evidence of digenic inheritance

关键词： family craniofacial microsomia     Identification novel mutations    

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Mechanical design, modeling, and identification for a novel antagonistic variable stiffness dexterous

《机械工程前沿（英文）》 2022年 第17卷 第3期 doi: 10.1007/s11465-022-0691-5

摘要： This study traces the development of dexterous hand research and proposes a novel antagonistic variable stiffness dexterous finger mechanism to improve the safety of dexterous hand in unpredictable environments, such as unstructured or man-made operational errors through comprehensive consideration of cost, accuracy, manufacturing, and application. Based on the concept of mechanical passive compliance, which is widely implemented in robots for interactions, a finger is dedicated to improving mechanical robustness. The finger mechanism not only achieves passive compliance against physical impacts, but also implements the variable stiffness actuator principle in a compact finger without adding supererogatory actuators. It achieves finger stiffness adjustability according to the biologically inspired stiffness variation principle of discarding some mobilities to adjust stiffness. The mechanical design of the finger and its stiffness adjusting methods are elaborated. The stiffness characteristics of the finger joint and the actuation unit are analyzed. Experimental results of the finger joint stiffness identification and finger impact tests under different finger stiffness presets are provided to verify the validity of the model. Fingers have been experimentally proven to be robust against physical impacts. Moreover, the experimental part verifies that fingers have good power, grasping, and manipulation performance.

关键词： multifingered hand     mechanism design     robot safety     variable stiffness actuator    

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Association of novel mutations and heplotypes in the preS region of hepatitis B virus with hepatocellular

Jia-Xin XIE, Jian-Hua YIN, Qi ZHANG, Rui PU, Wen-Ying LU, Hong-Wei ZHANG, Guang-Wen CAO, Jun ZHAO, Hong-Yang WANG,

《医学前沿（英文）》 2010年 第4卷 第4期   页码 419-429 doi: 10.1007/s11684-010-0160-0

摘要： The association of viral mutations and haplotypic carriages with mutations in the preS region of hepatitis B virus (HBV) genotypes B and C with hepatocellular carcinoma (HCC) is of great significance for the prediction of this malignancy, but it remains obscure. We analyzed the preS sequences of HBV genotypes B and C from 1172 HBV-infected subjects including 231 patients with HCC. As compared with the HBV-infected subjects without HCC, C2875T, G2946C, A3054C, C3060A, T3066C, C3116T, A3120C, G3191A, A1C, C7A, C10A, A31C, C76T, G105C, and G147C in both genotypes were significantly associated with increased risks of HCC. C2875A, G2950A, G2951A, A3054T, C3060T, T3066A, T3069G, A3120T, and G3191C were significantly associated with increased risks of HCC in genotype C, whereas these mutations were inversely associated with HCC in genotype B. Multivariate regression analyses showed that C76A/T was a novel factor independently associated with an increased risk of HCC, as compared with those without HCC. The frequencies of haplotypes 2964A-3116T-preS2 start codon wild-type-7C, 2964C-3116T-7A-76C, and 2964A-3116T-7C-76A/T were significantly higher in the patients with HCC (<0.001), whereas a haplotypic carriage with a single mutation and another three wild-types were inversely associated with HCC. Conclusively, the association of HBV mutations in the preS region with HCC depends on HBV genotype and haplotypic carriage with two or more mutations that are each associated with an increased risk of HCC independently.

关键词： hepatitis B virus     hepatocellular carcinoma     mutation     genotype     haplotype    

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Treatment of advanced non-small cell lung cancer with driver mutations: current applications and future

《医学前沿（英文）》 2023年 第17卷 第1期   页码 18-42 doi: 10.1007/s11684-022-0976-4

摘要： With the improved understanding of driver mutations in non-small cell lung cancer (NSCLC), expanding the targeted therapeutic options improved the survival and safety. However, responses to these agents are commonly temporary and incomplete. Moreover, even patients with the same oncogenic driver gene can respond diversely to the same agent. Furthermore, the therapeutic role of immune-checkpoint inhibitors (ICIs) in oncogene-driven NSCLC remains unclear. Therefore, this review aimed to classify the management of NSCLC with driver mutations based on the gene subtype, concomitant mutation, and dynamic alternation. Then, we provide an overview of the resistant mechanism of target therapy occurring in targeted alternations (“target-dependent resistance”) and in the parallel and downstream pathways (“target-independent resistance”). Thirdly, we discuss the effectiveness of ICIs for NSCLC with driver mutations and the combined therapeutic approaches that might reverse the immunosuppressive tumor immune microenvironment. Finally, we listed the emerging treatment strategies for the new oncogenic alternations, and proposed the perspective of NSCLC with driver mutations. This review will guide clinicians to design tailored treatments for NSCLC with driver mutations.

关键词： non-small cell lung cancer     driver mutations     treatment strategy     resistant mechanism     immune-checkpoint inhibitors    

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Identification of cancer stem cells provides novel tumor models for drug discovery

null

《医学前沿（英文）》 2012年 第6卷 第2期   页码 112-121 doi: 10.1007/s11684-012-0199-1

摘要：

Cancer stem cells (CSCs) have received considerable attention from the research community since they were first reported in human acute myeloid leukemia 15 years ago. Accumulating evidence suggests that CSCs are responsible for tumor initiation and progression, drug resistance, and metastasis in both liquid and solid tumors. These findings lead to the development of novel compounds targeting CSC populations that is becoming increasingly important for eradicating CSCs in heterogeneous tumor masses and to cure the cancer. Since 2003, we have participated in CSC studies and encountered crucial early events in the field. This article reviews the history of CSC biology, clarifies the term and its definition, and further addresses the issue of how to utilize CSCs in therapeutic target discovery and drug development based on our substantial experience.

关键词： cancer stem cell     tumor model     drug discovery    

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Characteristics of compensatory mutations in the

Shengfen Wang, Yang Zhou, Bing Zhao, Xichao Ou, Hui Xia, Yang Zheng, Yuanyuan Song, Qian Cheng, Xinyang Wang, Yanlin Zhao

《医学前沿（英文）》 2020年 第14卷 第1期   页码 51-59 doi: 10.1007/s11684-019-0720-x

摘要： The aim of this study was to characterize gene mutations in (MTB) and investigate the factors associated with mutations and the relation between mutations and tuberculosis (TB) transmission. A total of 245 MTB clinical isolates from patients with TB in six provinces and two municipalities in China were characterized based on gene mutations through DNA sequencing of and genes, phenotyping via standard drug susceptibility testing, and genotypic profiling by mycobacterial interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR) typing. Approximately 36.4% of the rifampin-resistant isolates harbored nonsynonymous mutations in the gene. Twenty-nine nonsynonymous single mutations and three double mutations were identified. The mutations at locus 483 (11.3%) were predominant, and the mutations at V483G, W484G, I491V, L516P, L566R, N698K, and A788E accounted for 54.5% of the total detected mutations. Fifteen new mutations in the gene were identified. Rifampin resistance and mutations at locus 531 were significantly associated with mutations. MIRU-VNTR genotype results indicated that 18.4% of the studied isolates were clustered, and the mutations were not significantly associated with MIRU-VNTR clusters. A large proportion of mutation was observed in the rifampicin-resistant MTB isolates. However, the findings of this study do not support the association of mutation with compensated transmissibility.

关键词： tuberculosis     drug resistance     compensatory mutations     transmission    

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122-binding site polymorphism at the interleukin-1 α gene and its interaction with hepatitis B virus mutations

null

《医学前沿（英文）》 2014年 第8卷 第2期   页码 217-226 doi: 10.1007/s11684-014-0326-2

摘要：

This study was designed to investigate the contribution of miRNA-122-binding site polymorphism at the IL-1A gene and its multiplicative interactions with hepatitis B virus (HBV) mutations in the risk of hepatocellular carcinoma (HCC). A total of 1021 healthy controls, 302 HBV surface antigen (HBsAg) seroclearance subjects, and 2011 HBsAg-positive subjects (including 1021 HCC patients) were enrolled in this study. Quantitative PCR was used to genotype rs3783553. HBV mutations were determined by direct sequencing. Multivariate logistic regression analyses were performed to test the associations of rs3783553, mutations, and their interactions with the risk of HCC. No significant association was found between rs3783553 and the risk of HCC among healthy controls, HBsAg seroclearance subjects, HBsAg-positive subjects without HCC, and all controls. Additionally, rs3783553 was not significantly associated with chronic HBV infection, liver cirrhosis, HBV e antigen seroconversion, abnormal alanine aminotransferase, and high viral load (>104 copies/ml). However, the TTCA insertion allele of rs3783553 was significantly associated with an increased frequency of HBV C7A mutation compared with homozygous TTCA deletion carriers [(del/ins+ ins/ins) vs. del/del, adjusted odds ratio (OR)=1.48, 95% confidence interval (CI)=1.09-2.02, P=0.013]. Multiplicative interaction of rs3783553 with HBV preS deletion significantly reduced the risk of HCC in males, with an adjusted OR of 0.64 (95% CI=0.42-0.98; P=0.041) after age and HBV genotype were adjusted. Although rs3783553 did not significantly affect genetic susceptibility to HBV-related HCC, its variant allele may predispose the host to selecting HBV C7A mutation during evolution and significantly reduce the risk of HCC caused by HBV preS deletion. This study provides an insight into the complex host-virus interaction in HBV-induced hepatocarcinogenesis and is helpful in determining HBsAg-positive subjects who are likely to develop HCC.

关键词： hepatocellular carcinoma (HCC)     interaction     miRNA-122-binding site     IL-1A     rs3783553     hepatitis B virus (HBV) mutations    

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Conceptual design and kinematic analysis of a novel parallel robot for high-speed pick-and-place operations

Qizhi MENG, Fugui XIE, Xin-Jun LIU

《机械工程前沿（英文）》 2018年 第13卷 第2期   页码 211-224 doi: 10.1007/s11465-018-0471-4

摘要：

This paper deals with the conceptual design, kinematic analysis and workspace identification of a novel four degrees-of-freedom (DOFs) high-speed spatial parallel robot for pick-and-place operations. The proposed spatial parallel robot consists of a base, four arms and a 1½ mobile platform. The mobile platform is a major innovation that avoids output singularity and offers the advantages of both single and double platforms. To investigate the characteristics of the robot’s DOFs, a line graph method based on Grassmann line geometry is adopted in mobility analysis. In addition, the inverse kinematics is derived, and the constraint conditions to identify the correct solution are also provided. On the basis of the proposed concept, the workspace of the robot is identified using a set of presupposed parameters by taking input and output transmission index as the performance evaluation criteria.

关键词： spatial parallel robot     pick-and-place operations     mobility analysis     kinematic modeling     workspace identification    

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Distinct gene expression pattern of mutations coordinated by target repression and promoter hypermethylation

《医学前沿（英文）》 2022年 第16卷 第4期   页码 627-636 doi: 10.1007/s11684-020-0815-4

摘要： Runt-related transcription factor 1 (RUNX1) is an essential regulator of normal hematopoiesis. Its dysfunction, caused by either fusions or mutations, is frequently reported in acute myeloid leukemia (AML). However, RUNX1 mutations have been largely under-explored compared with RUNX1 fusions mainly due to their elusive genetic characteristics. Here, based on 1741 patients with AML, we report a unique expression pattern associated with RUNX1 mutations in AML. This expression pattern was coordinated by target repression and promoter hypermethylation. We first reanalyzed a joint AML cohort that consisted of three public cohorts and found that RUNX1 mutations were mainly distributed in the Runt domain and almost mutually exclusive with NPM1 mutations. Then, based on RNA-seq data from The Cancer Genome Atlas AML cohort, we developed a 300-gene signature that significantly distinguished the patients with RUNX1 mutations from those with other AML subtypes. Furthermore, we explored the mechanisms underlying this signature from the transcriptional and epigenetic levels. Using chromatin immunoprecipitation sequencing data, we found that RUNX1 target genes tended to be repressed in patients with RUNX1 mutations. Through the integration of DNA methylation array data, we illustrated that hypermethylation on the promoter regions of RUNX1-regulated genes also contributed to dysregulation in RUNX1-mutated AML. This study revealed the distinct gene expression pattern of RUNX1 mutations and the underlying mechanisms in AML development.

关键词： RUNX1     gene mutation     acute myeloid leukemia     transcriptional repression     DNA methylation    

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Variational mode decomposition based modal parameter identification in civil engineering

Mingjie ZHANG, Fuyou XU

《结构与土木工程前沿（英文）》 2019年 第13卷 第5期   页码 1082-1094 doi: 10.1007/s11709-019-0537-3

摘要： An out-put only modal parameter identification method based on variational mode decomposition (VMD) is developed for civil structure identifications. The recently developed VMD technique is utilized to decompose the free decay response (FDR) of a structure into to modal responses. A novel procedure is developed to calculate the instantaneous modal frequencies and instantaneous modal damping ratios. The proposed identification method can straightforwardly extract the mode shape vectors using the modal responses extracted from the FDRs at all available sensors on the structure. A series of numerical and experimental case studies are conducted to demonstrate the efficiency and highlight the superiority of the proposed method in modal parameter identification using both free vibration and ambient vibration data. The results of the present method are compared with those of the empirical mode decomposition-based method, and the superiorities of the present method are verified. The proposed method is proved to be efficient and accurate in modal parameter identification for both linear and nonlinear civil structures, including structures with closely spaced modes, sudden modal parameter variation, and amplitude-dependent modal parameters, etc.

关键词： modal parameter identification     variational mode decomposition     civil structure     nonlinear system     closely spaced modes    

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宿主微生物组内的基因组突变——适应性进化或净化选择 Review

张家超, Rob Knight

《工程（英文）》 2023年 第20卷 第1期   页码 96-102 doi: 10.1016/j.eng.2021.11.018

摘要：

二代测序技术转变了人们评估宿主相关微生物区系和微生物组的分类组成功能的能力。未来10 年将会开展更多的人类微生物组研究，特别是那些探索微生物组内基因组突变的研究。本文聚焦于微生物组内菌株之间的共同进化，塑造了宿主肠道微生物种内和种间的菌株水平多样性。还探讨了微生物基因组突变与常见代谢疾病之间的关联，以及病原体和益生菌在入侵和定植过程中的适应性进化。最后，讨论了注释和分析微生物基因组突变方法和算法的研究进展。

关键词： 肠道菌群     基因组突变     适应性进化     净化选择     单核苷酸变异    

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Non-convex sparse optimization-based impact force identification with limited vibration measurements

《机械工程前沿（英文）》 2023年 第18卷 第3期 doi: 10.1007/s11465-023-0762-2

摘要： Impact force identification is important for structure health monitoring especially in applications involving composite structures. Different from the traditional direct measurement method, the impact force identification technique is more cost effective and feasible because it only requires a few sensors to capture the system response and infer the information about the applied forces. This technique enables the acquisition of impact locations and time histories of forces, aiding in the rapid assessment of potentially damaged areas and the extent of the damage. As a typical inverse problem, impact force reconstruction and localization is a challenging task, which has led to the development of numerous methods aimed at obtaining stable solutions. The classical ℓ2 regularization method often struggles to generate sparse solutions. When solving the under-determined problem, ℓ2 regularization often identifies false forces in non-loaded regions, interfering with the accurate identification of the true impact locations. The popular ℓ1 sparse regularization, while promoting sparsity, underestimates the amplitude of impact forces, resulting in biased estimations. To alleviate such limitations, a novel non-convex sparse regularization method that uses the non-convex ℓ1−2 penalty, which is the difference of the ℓ1 and ℓ2 norms, as a regularizer, is proposed in this paper. The principle of alternating direction method of multipliers (ADMM) is introduced to tackle the non-convex model by facilitating the decomposition of the complex original problem into easily solvable subproblems. The proposed method named ℓ1−2-ADMM is applied to solve the impact force identification problem with unknown force locations, which can realize simultaneous impact localization and time history reconstruction with an under-determined, sparse sensor configuration. Simulations and experiments are performed on a composite plate to verify the identification accuracy and robustness with respect to the noise of the ℓ1−2-ADMM method. Results indicate that compared with other existing regularization methods, the ℓ1−2-ADMM method can simultaneously reconstruct and localize impact forces more accurately, facilitating sparser solutions, and yielding more accurate results.

关键词： impact force identification     inverse problem     sparse regularization     under-determined condition     alternating direction method of multipliers    

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The research on structural damage identification using rough set and integrated neural network

Juelong LI, Hairui LI, Jianchun XING, Qiliang YANG

《机械工程前沿（英文）》 2013年 第8卷 第3期   页码 305-310 doi: 10.1007/s11465-013-0259-5

摘要：

A huge amount of information and identification accuracy in large civil engineering structural damage identification has not been addressed yet. To efficiently solve this problem, a new damage identification method based on rough set and integrated neural network is first proposed. In brief, rough set was used to reduce attributes so as to decrease spatial dimensions of data and extract effective features. And then the reduced attributes will be put into the sub-neural network. The sub-neural network can give the preliminary diagnosis from different aspects of damage. The decision fusion network will give the final damage identification results. The identification examples show that this method can simplify the redundant information to reduce the neural network model, making full use of the range of information to effectively improve the accuracy of structural damage identification.

关键词： rough set     integrated neural network     damage identification     decision making fusion    

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Molecular pathogenesis of acute myeloid leukemia: A diverse disease with new perspectives

Felicitas THOL, Arnold GANSER

《医学前沿（英文）》 2010年 第4卷 第4期   页码 356-362 doi: 10.1007/s11684-010-0220-5

摘要： Acute myeloid leukemia (AML) is a very heterogeneous neoplasm of the hematopoietic stem cell. Despite important achievements in the treatment of AML, the long term survival of patients with the disease remains poor. Understanding the pathogenesis of AML better is crucial for finding new treatment approaches. During AML development hematopoietic precursor cells undergo clonal transformation in a multistep process through acquisition of chromosomal rearrangements and/or different gene mutations. Over recent years, novel gene mutations have been found in patients with AML. These mutations can be divided into two important categories, class I mutations that confer a proliferation advantage and class II mutations that inhibit myeloid differentiation. Screening for some of these mutations is now part of the initial diagnostic work-up in newly diagnosed AML patients. Information about the mutation status of specific genes is useful for risk-stratification, minimal residual disease (MRD) monitoring and increasingly also for targeted therapy, especially for patients with cytogenetically normal AML (CN-AML). Besides chromosomal rearrangements and gene mutations, epigenetic regulation of genes – meaning changes in gene expression by mechanisms other than changes in the underlying DNA sequence – also represents an important mechanism of leukemogenesis. This article reviews some of the most common mutations in CN-AML and gives a perspective of the translation of these discoveries from bench to bedside.

关键词： acute myeloid leukemia     mutations     risk stratification    

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Damage identification in connections of moment frames using time domain responses and an optimization

《结构与土木工程前沿（英文）》 2021年 第15卷 第4期   页码 851-866 doi: 10.1007/s11709-021-0739-3

摘要： Damage is defined as changes to the material and/or geometric properties of a structural system, comprising changes to the boundary conditions and system connectivity, adversely affecting the system’s performance. Inspecting the elements of structures, particularly critical components, is vital to evaluate the structural lifespan and safety. In this study, an optimization-based method for joint damage identification of moment frames using the time-domain responses is introduced. The beam-to-column connection in a metallic moment frame structure is modeled by a zero-length rotational spring at both ends of the beam element. For each connection, an end-fixity factor is specified, which changes between 0 and 1. Then, the problem of joint damage identification is converted to a standard optimization problem. An objective function is defined using the nodal point accelerations extracted from the damaged structure and an analytical model of the structure in which the nodal accelerations are obtained using the Newmark procedure. The optimization problem is solved by an improved differential evolution algorithm (IDEA) for identifying the location and severity of the damage. To assess the capability of the proposed method, two numerical examples via different damage scenarios are considered. Then, a comparison between the proposed method and the existing damage identification method is provided. The outcomes reveal the high efficiency of the proposed method for finding the severity and location of joint damage considering noise effects.

关键词： damage identification     beam-to-column connection     time-domain response     optimization    

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标题 作者 时间 类型 操作

Identification of novel mutations in and in a family with craniofacial microsomia: evidence of digenic

期刊论文

Mechanical design, modeling, and identification for a novel antagonistic variable stiffness dexterous

期刊论文

Association of novel mutations and heplotypes in the preS region of hepatitis B virus with hepatocellular

Jia-Xin XIE, Jian-Hua YIN, Qi ZHANG, Rui PU, Wen-Ying LU, Hong-Wei ZHANG, Guang-Wen CAO, Jun ZHAO, Hong-Yang WANG,

期刊论文

Treatment of advanced non-small cell lung cancer with driver mutations: current applications and future

期刊论文

Identification of cancer stem cells provides novel tumor models for drug discovery

null

期刊论文

Characteristics of compensatory mutations in the

Shengfen Wang, Yang Zhou, Bing Zhao, Xichao Ou, Hui Xia, Yang Zheng, Yuanyuan Song, Qian Cheng, Xinyang Wang, Yanlin Zhao

期刊论文

122-binding site polymorphism at the interleukin-1 α gene and its interaction with hepatitis B virus mutations

null

期刊论文

Conceptual design and kinematic analysis of a novel parallel robot for high-speed pick-and-place operations

Qizhi MENG, Fugui XIE, Xin-Jun LIU

期刊论文

Distinct gene expression pattern of mutations coordinated by target repression and promoter hypermethylation

期刊论文

Variational mode decomposition based modal parameter identification in civil engineering

Mingjie ZHANG, Fuyou XU

期刊论文

宿主微生物组内的基因组突变——适应性进化或净化选择

张家超, Rob Knight

期刊论文

Non-convex sparse optimization-based impact force identification with limited vibration measurements

期刊论文

The research on structural damage identification using rough set and integrated neural network

Juelong LI, Hairui LI, Jianchun XING, Qiliang YANG

期刊论文

Molecular pathogenesis of acute myeloid leukemia: A diverse disease with new perspectives

Felicitas THOL, Arnold GANSER

期刊论文

Damage identification in connections of moment frames using time domain responses and an optimization

期刊论文