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

《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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A novel variant in the gene in a large Chinese family with a unique phenotype of Clouston syndrome

《医学前沿（英文）》 2023年 第17卷 第2期   页码 330-338 doi: 10.1007/s11684-022-0933-2

摘要： Clouston syndrome (OMIM #129500), also known as hidrotic ectodermal dysplasia type 2, is a rare autosomal dominant skin disorder. To date, four mutations in the GJB6 gene, G11R, V37E, A88V, and D50N, have been confirmed to cause this condition. In previous studies, the focus has been mainly on gene sequencing, and there has been a lack of research on clinical manifestations and pathogenesis. To confirm the diagnosis of this pedigree at the molecular level and summarize and analyse the clinical phenotype of patients and to provide a basis for further study of the pathogenesis of the disease, we performed whole-exome and Sanger sequencing on a large Chinese Clouston syndrome pedigree. Detailed clinical examination included histopathology, hair microscopy, and scanning electron microscopy. We found a novel heterozygous missense variant (c.134G>C:p.G45A) for Clouston syndrome. We identified a new clinical phenotype involving all nail needling pain in all patients and found a special honeycomb hole structure in the patients’ hair under scanning electron microscopy. Our data reveal that a novel variant (c.134G>C:p.G45A) plays a likely pathogenic role in this pedigree and highlight that genetic testing is necessary for the diagnosis of Clouston syndrome.

关键词： Clouston syndrome     whole exome sequencing     GJB6 gene     novel variant     unique phenotype    

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不同类型意大利蜜蜂MDH Ⅱ同工酶的研究

陈盛禄,鲍秀良,苏松坤,刘艳荷

《中国工程科学》 2000年 第2卷 第1期   页码 57-61

摘要：

运用聚丙烯酰胺凝胶等电聚焦技术（IEF-PAGE），对有代表性的王浆蜂蜜双高产的"浙农大1号"意蜂品种（浙意，Ea）和中国本地意蜂（本意，Eb）、美国意蜂（美意，Em）、澳大利亚意蜂（澳意Eo）、意大利意蜂（原意，Ee）等5个意大利蜂（Apis mellifera Ligustica）品种试飞前的幼龄工蜂进行了苹果酸脱氢酶（MDH）同工酶的基因型、基因型频率、基因频率、杂合度和纯合度的研究。由a、b、c 3个等位基因编码的MDH图谱第二区带应有的a/a、a/b、a/c、b/b、b/c和c/c 6种基因型，在Ea、Eb、Ee 3种意蜂中全部出现；在Eo中出现a/b，a/c，b/c，c/c 4种，在Em中出现a/c，b/c，c/c 3种。联列表独立性检验结果，5个意蜂品种间的基因型频率、基因频率、杂合度、纯合度存在显著差异。

关键词： 意蜂品种     苹果酸脱氢酶     基因型     基因频率     杂合度    

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Effectiveness of inactivated COVID-19 vaccine against the severity of Omicron variant

《医学前沿（英文）》 2023年 第17卷 第3期   页码 576-580 doi: 10.1007/s11684-023-0991-0

摘要： Effectiveness of inactivated COVID-19 vaccine against the severity of Omicron variant

关键词： variant    

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BULKED SEGREGANT RNA SEQUENCING (BSR-SEQ) IDENTIFIES A NOVEL ALLELE ASSOCIATED WITH WEEPING TRAITS IN

《农业科学与工程前沿（英文）》 2021年 第8卷 第2期

摘要：

Weeping species are used both as ornamental plants and for breeding dwarf plant types. However, exploration of casual genes controlling weeping traits is rather limited. Here, we identified individuals with contrasting phenotypes from an F1 bi-parental mapping population of Prunus mume which was developed from a cross between the upright cultivar ‘Liuban’ and the weeping cultivar ‘Fentai Chuizhi’. Bulked segregant RNA sequencing was used and five QTLs on Chromosome 7 were identified. The Pm024074(PmUGT72B3) allele, belonging to the UDP-glycosyltransferase superfamily containing the coniferyl-alcohol glucosyltransferase domain, was identified in a genomic region overlapping with a previously identified QTL, and had a synonymous transition of T66(upright) to C (weeping) in the coding sequence and a 470-bp deletion in the promoter region. Pm024074 had exceptionally high expression in buds and stems of weeping P. mume. Weighted correlation network analysis indicates that genes neighboring Pm024074 were significantly associated with plant architecture. In addition, a reliable single nucleotide polymorphism marker was developed based on the variation in the Pm024074 gene, providing precise marker-assisted breeding for weeping traits. This study provides insights into the genetic mechanism governing the weeping trait in P. mume, and indicates potential applications for the manipulation of tree architecture.

关键词： BSR-seq / PmUGT72B3 / Prunus mume / UDP-glycosyltransferase / weeping shoots / WGCNA    

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Novel variants in LAMA3 and COL7A1 and recurrent variant in KRT5 underlying epidermolysis bullosa in

《医学前沿（英文）》 2022年 第16卷 第5期   页码 808-814 doi: 10.1007/s11684-021-0878-x

摘要： Epidermolysis bullosa (EB) is a group of clinically and genetically heterogeneous diseases characterized by trauma-induced mucocutaneous fragility and blister formation. Here, we investigated five Chinese families with EB, and eight variants including a novel nonsense variant (c.47G>A, p.W16*) in LAMA3, a known recurrent variant (c.74C>T, p.P25L) in KRT5, 2 novel (c.2531T>A, p.V844E; c.6811_6814del, p.R2271fs) and 4 known (c.6187C>T, p.R2063W; c.7097G>A, p.G2366D; c.8569G>T, p.E2857*; c.3625_3635del, p.S1209fs) variants in COL7A1 were detected. Notably, this study identified a nonsense variant in LAMA3 that causes EB within the Chinese population and revealed that this variant resulted in a reduction in LAMA3 mRNA and protein expression levels by nonsense-mediated mRNA decay. Our study expands the mutation spectra of Chinese patients with EB.

关键词： epidermolysis bullosa     LAMA3     COL7A1     KRT5     Chinese families    

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Antithrombin deficiency and decreased protein C activity in a young man with venous thromboembolism: a case report

null

《医学前沿（英文）》 2018年 第12卷 第3期   页码 319-323 doi: 10.1007/s11684-017-0553-4

摘要：

Antithrombin and protein C are two crucial members in the anticoagulant system and play important roles in hemostasis. Mutations in and lead to deficiency or dysfunction of the two proteins, which could result in venous thromboembolism (VTE). Here, we report a Chinese 22-year-old young man who developed recurrent and serious VTE in cerebral veins, visceral veins, and deep veins of the lower extremity. Laboratory tests and direct sequencing of and were conducted for the patient and his family members. Coagulation tests revealed that the patient presented type I antithrombin deficiency combined with decreased protein C activity resulting from a small insertion mutation c.848_849insGATGT in and a short deletion variant c.572_574delAGA in . This combination of the two mutations was absent in 400 healthy subjects each from southern and northern China. Then, we summarized all the mutations of the and gene reported in the Chinese Han population. This study demonstrates that the combination of antithrombin deficiency and decreased protein C activity can result in severe VTE and that the coexistence of different genetic factors may increase the risk of VTE.

关键词： antithrombin deficiency     protein C activity     mutation     variant     venous thromboembolism     anticoagulants    

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Exergy and exergoeconomic analyses for integration of aromatics separation with aromatics upgrading

《化学科学与工程前沿（英文）》 2023年 第17卷 第2期   页码 183-193 doi: 10.1007/s11705-022-2192-9

摘要： Methanol to aromatics produces multiple products, resulting in a limited selectivity of xylene. Aromatics upgrading is an effective way to produce more valuable xylene product, and different feed ratios generate discrepant product distributions. This work integrates the aromatics separation with toluene disproportionation, transalkylation of toluene and trimethylbenzene, and isomerization of xylene and trimethylbenzene. Exergy and exergoeconomic analyses are conducted to give insights in the splitting ratios of benzene, toluene and heavy aromatics for aromatics upgrading. First, a detailed simulation model is developed in Aspen HYSYS. Then, 300 splitting ratio sets of benzene and toluene for conversion are studied to investigate the process performances. The results indicate that there are different preferences for the splitting ratios of benzene and toluene in terms of exergy and exergoeconomic performances. The process generates lower total exergy destruction when the splitting ratio of toluene varies between 0.07 and 0.18, and that of benzene fluctuates between 0.55 and 0.6. Nevertheless, the process presents lower total product unit cost with the splitting ratio of toluene less than 0.18 and that of benzene fluctuating between 0.44 and 0.89. Besides, it is found that distillation is the biggest contributor to the total exergy destruction, accounting for 94.97%.

关键词： aromatics separation and upgrading     variant splitting ratios     total exergy destruction     total product unit cost    

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BULKED SEGREGANT RNA SEQUENCING (BSR-SEQ) IDENTIFIES A NOVEL ALLELE ASSOCIATED WITH WEEPING TRAITS IN

Xiaokang ZHUO, Tangchun ZHENG, Zhiyong ZHANG, Suzhen LI, Yichi ZHANG, Lidan SUN, Weiru YANG, Jia WANG, Tangren CHENG, Qixiang ZHANG

《农业科学与工程前沿（英文）》   页码 196-214 doi: 10.15302/J-FASE-2020379

摘要： Weeping species are used both as ornamental plants and for breeding dwarf plant types. However, exploration of casual genes controlling weeping traits is rather limited. Here, we identified individuals with contrasting phenotypes from an F bi-parental mapping population of which was developed from a cross between the upright cultivar ‘Liuban’ and the weeping cultivar ‘Fentai Chuizhi’. Bulked segregant RNA sequencing was used and five QTLs on Chromosome 7 were identified. The ( ) allele, belonging to the UDP-glycosyltransferase superfamily containing the coniferyl-alcohol glucosyltransferase domain, was identified in a genomic region overlapping with a previously identified QTL, and had a synonymous transition of T (upright) to C (weeping) in the coding sequence and a 470-bp deletion in the promoter region. had exceptionally high expression in buds and stems of weeping . Weighted correlation network analysis indicates that genes neighboring were significantly associated with plant architecture. In addition, a reliable single nucleotide polymorphism marker was developed based on the variation in the gene, providing precise marker-assisted breeding for weeping traits. This study provides insights into the genetic mechanism governing the weeping trait in , and indicates potential applications for the manipulation of tree architecture.

关键词： BSR-seq     PmUGT72B3     Prunus mume     UDP-glycosyltransferase     weeping shoots     WGCNA    

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Research and development of a novel subunit vaccine for the currently circulating pseudorabies virus variant

Yuzhou WANG,Tongyan WANG,He YAN,Fanli YANG,Linghua GUO,Qingyuan YANG,Xule HU,Feifei TAN,Yan XIAO,Xiangdong LI,Kegong TIAN

《农业科学与工程前沿（英文）》 2015年 第2卷 第3期   页码 216-222 doi: 10.15302/J-FASE-2015072

摘要： Pseudorabies (PR) is a devastating viral disease which leads to fatal encephalitis and respiratory disorders in pigs. Commercial gE-deleted live pseudorabies virus (PRV) vaccine has been widely used to control this disease in China. However, the new-emerging variants of PRV compromises the protection provided by current vaccines and lead to the outbreak of PR in vaccinated pig herds. Several killed and live vaccine candidates based on current PRV variants have been reported to be effective to control the disease. A subunit vaccine based on gB protein, one major PRV glycoprotein which elicits strong humoral and cellular immune responses, however, was never evaluated for protection against the current circulating PRV variants. In this study, full-length PRV gB protein was successfully expressed in baculovirus/insect cells in the soluble format and was tested on 3-week-old piglets as a subunit vaccine. Compared with unvaccinated pigs, the gB-vaccinated pigs developed specific antibody-mediated responses and were protected from the virulent PRV HN1201 challenge. All vaccinated pigs survived without showing any PRV-specific respiratory and neurological signs, but all unvaccinated pigs died within 7 days after HN1201 challenge. Hence, this novel gB-based vaccine could be applied as an effective subunit vaccine to control PRV variant in China.

关键词： pseudorabies virus     glycoprotein B protein     subunit vaccine    

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A frequency error estimation for isogeometric analysis of Kirchhoff–Love cylindrical shells

《结构与土木工程前沿（英文）》 doi: 10.1007/s11709-023-0006-x

摘要： A frequency error estimation is presented for the isogeometric free vibration analysis of Kirchhoff–Love cylindrical shells using both quadratic and cubic basis functions. By analyzing the discrete isogeometric equations with the aid of harmonic wave assumption, the frequency error measures are rationally derived for the quadratic and cubic formulations for Kirchhoff–Love cylindrical shells. In particular, the governing relationship of the continuum frequency for Kirchhoff–Love cylindrical shells is naturally embedded into the frequency error measures without the need of explicit frequency expressions, which usually are not trivial for the shell problems. In accordance with these theoretical findings, the 2nd and 4th orders of frequency accuracy are attained for the isogeometric schemes using quadratic and cubic basis functions, respectively. Numerical results not only thoroughly verify the theoretical convergence rates of frequency solutions, but also manifest an excellent magnitude match between numerical and theoretical frequency errors for the isogeometric free vibration analysis of Kirchhoff–Love cylindrical shells.

关键词： isogeometric analysis     Kirchhoff–Love cylindrical shell     free vibration     frequency error     convergence    

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Calculation of collision frequency function for aerosol particles in free molecule regime in presence

Xiaowei LUO, Yannick BENICHOU, Suyuan YU

《能源前沿（英文）》 2013年 第7卷 第4期   页码 506-510 doi: 10.1007/s11708-013-0275-5

摘要： The collision frequency function for aerosol particles has already been calculated for the free molecule regime and for the continuum range. The present work, taking into account the influence of internal force fields such as magnetic force, electric force and molecular forces, created by particles themselves, recalculated the collision frequency in the case of particles much smaller than the mean free path of the gas (free molecule regime). Attractive forces increase naturally the collision frequency, while repulsive forces decrease it. The calculation was performed for all types of central forces deriving from a potential, including Coulomb forces and Van der Waals forces.

关键词： aerosol particles     collision frequency function     coagulation    

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Fuel variability effect on flickering frequency of diffusion flames

Jizhao LI, Yang ZHANG

《能源前沿（英文）》 2009年 第3卷 第2期   页码 134-140 doi: 10.1007/s11708-009-0034-9

摘要： It is known that fuel variability of different gas suppliers may cause combustion instability in a gas turbine combustor. Mechanisms that control the time scale of the heat release oscillations and acoustic pressure perturbations are both physical and chemical in nature, and thus can be influenced by changes in fuel composition. The intent of this study is to investigate the fuel variability on the flickering frequency of diffusion flames in the hope of understanding some of the fundamental aspects of fuel variability effect on the dynamics of combustion. Experiments were conducted at atmospheric pressure with a matrix of methane and propane blends. An optical fibre system was applied to capture simultaneously the flame flickering at two different light frequencies (430 nm and 516 nm), which provided a means of comparing the chemistry change. It was found that the low frequency oscillation of flow and flame structures depended only weakly on the exit velocities of the fuel, while ambient conditions had a significant effect on flickering frequencies and spectrum. The results of using CH and C H as test fuels at different flow rates showed very little variations, with peak frequencies at 11-13 Hz. When the jet flame was not disturbed, harmonics to at least the third mode were obtained in most of these cases. However, the cases which included CH /C H splits of 90/10, 85/15 and 80/20 by volume showed that unstable flickering frequencies and flame harmonics were not observed. When a mixture of methane/propane at a ratio of 1:1 was used the peak flickering frequency was around 6 Hz, and slight disturbance in the environment would cause the harmonics to disappear. Mechanisms thought to produce changes in the dynamic response and frequency harmonics were discussed.

关键词： fuel variability     flickering frequency     diffusion flames     dynamics of combustion    

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Capacity limitation of nuclear units in grid based on analysis of frequency regulation

Yiping DAI, Pan JIANG, Lin GAO, Weimin KAN, Xiaoqing XIAO, Ge JIN

《能源前沿（英文）》 2012年 第6卷 第2期   页码 148-154 doi: 10.1007/s11708-012-0174-1

摘要： The increasing capacity of nuclear units in power grid poses threat to system stability and security. Load disturbance may cause overspeed of the units and trigger the overspeed protection controller (OPC). Repeating actions of valves have a strong impact on the security of the equipment and may result in a collapse of the power system. Based on the analysis of frequency regulation, mathematic models for nuclear units in the grid are established in this paper to simulate the dynamic process when load disturbance occurs. The critical action of the OPC is proposed as the constraint of safe operation for the units. The relationship between different styles of frequency regulation and the allowable capacity of the nuclear units in the grid is discussed. This research can help to estimate the capacity limitation of nuclear units in the grid.

关键词： nuclear units capacity     overspeed     primary frequency control (PFC)     second frequency control (SFC)    

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Oscillation frequency of simplified arterial tubes

Hui AN, Fan HE, Lingxia XING, Xiaoyang LI

《机械工程前沿（英文）》 2009年 第4卷 第3期   页码 300-304 doi: 10.1007/s11465-009-0038-5

摘要： To construct the spatial kinetic equation of an arterial tube and obtain its radial natural frequency, a linear-elastic and small deformation condition is assumed. The theoretical analysis is first presented and the finite element method is then used to numerically simulate the spatial kinematics. The results show that the first-order frequency is 15.8 Hz and the obtained exact analytical solutions agree well with numerical solutions, which proves that the theoretical analysis and numerical simulation are both correct.

关键词： spatial kinematics     natural frequency     finite element method    

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标题 作者 时间 类型 操作

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

期刊论文

A novel variant in the gene in a large Chinese family with a unique phenotype of Clouston syndrome

期刊论文

不同类型意大利蜜蜂MDH Ⅱ同工酶的研究

陈盛禄,鲍秀良,苏松坤,刘艳荷

期刊论文

Effectiveness of inactivated COVID-19 vaccine against the severity of Omicron variant

期刊论文

BULKED SEGREGANT RNA SEQUENCING (BSR-SEQ) IDENTIFIES A NOVEL ALLELE ASSOCIATED WITH WEEPING TRAITS IN

期刊论文

Novel variants in LAMA3 and COL7A1 and recurrent variant in KRT5 underlying epidermolysis bullosa in

期刊论文

Antithrombin deficiency and decreased protein C activity in a young man with venous thromboembolism: a case report

null

期刊论文

Exergy and exergoeconomic analyses for integration of aromatics separation with aromatics upgrading

期刊论文

BULKED SEGREGANT RNA SEQUENCING (BSR-SEQ) IDENTIFIES A NOVEL ALLELE ASSOCIATED WITH WEEPING TRAITS IN

Xiaokang ZHUO, Tangchun ZHENG, Zhiyong ZHANG, Suzhen LI, Yichi ZHANG, Lidan SUN, Weiru YANG, Jia WANG, Tangren CHENG, Qixiang ZHANG

期刊论文

Research and development of a novel subunit vaccine for the currently circulating pseudorabies virus variant

Yuzhou WANG,Tongyan WANG,He YAN,Fanli YANG,Linghua GUO,Qingyuan YANG,Xule HU,Feifei TAN,Yan XIAO,Xiangdong LI,Kegong TIAN

期刊论文

A frequency error estimation for isogeometric analysis of Kirchhoff–Love cylindrical shells

期刊论文

Calculation of collision frequency function for aerosol particles in free molecule regime in presence

Xiaowei LUO, Yannick BENICHOU, Suyuan YU

期刊论文

Fuel variability effect on flickering frequency of diffusion flames

Jizhao LI, Yang ZHANG

期刊论文

Capacity limitation of nuclear units in grid based on analysis of frequency regulation

Yiping DAI, Pan JIANG, Lin GAO, Weimin KAN, Xiaoqing XIAO, Ge JIN

期刊论文

Oscillation frequency of simplified arterial tubes

Hui AN, Fan HE, Lingxia XING, Xiaoyang LI

期刊论文