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Growth suppression of colorectal cancer expressing S492R EGFR by monoclonal antibody CH12

Qiongna Dong, Bizhi Shi, Min Zhou, Huiping Gao, Xiaoying Luo, Zonghai Li, Hua Jiang

《医学前沿（英文）》 2019年 第13卷 第1期   页码 83-93 doi: 10.1007/s11684-019-0682-z

摘要：

Colorectal cancer (CRC) is a common malignant tumor in the digestive tract, and 30%–85% of CRCs express epidermal growth factor receptors (EGFRs). Recently, treatments using cetuximab, also named C225, an anti-EGFR monoclonal antibody, for CRC have been demonstrated to cause an S492R mutation in EGFR. However, little is known about the biological function of S492R EGFR. Therefore, we attempted to elucidate its biological function in CRC cells and explore new treatment strategies for this mutant form. Our study indicated that EGFR and S492R EGFR accelerate the growth of CRC cells in vitro and in vivo and monoclonal antibody CH12, which specifically recognizes an EGFR tumor-specific epitope, can bind efficiently to S492R EGFR. Furthermore, mAb CH12 showed significantly stronger growth suppression activities and induced a more potent antibody-dependent cellular cytotoxicity effect on CRC cells bearing S492R EGFR than mAb C225. mAb CH12 obviously suppressed the growth of CRC xenografts with S492R EGFR mutations in vivo. Thus, mAb CH12 may be a promising therapeutic agent in treating patients with CRC bearing an S492R EGFR mutation.

关键词： S492R EGFR ectodomain mutation     colorectal cancer     mAb CH12     immunnotherapy    

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Targeting apoptosis to manage acquired resistance to third generation EGFR inhibitors

《医学前沿（英文）》 2022年 第16卷 第5期   页码 701-713 doi: 10.1007/s11684-022-0951-0

摘要： A significant clinical challenge in lung cancer treatment is management of the inevitable acquired resistance to third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (EGFR-TKIs), such as osimertinib, which have shown remarkable success in the treatment of advanced NSCLC with EGFR activating mutations, in order to achieve maximal response duration or treatment remission. Apoptosis is a major type of programmed cell death tightly associated with cancer development and treatment. Evasion of apoptosis is considered a key hallmark of cancer and acquisition of apoptosis resistance is accordingly a key mechanism of drug acquired resistance in cancer therapy. It has been clearly shown that effective induction of apoptosis is a key mechanism for third generation EGFR-TKIs, particularly osimertinib, to exert their therapeutic efficacies and the development of resistance to apoptosis is tightly associated with the emergence of acquired resistance. Hence, restoration of cell sensitivity to undergo apoptosis using various means promises an effective strategy for the management of acquired resistance to third generation EGFR-TKIs.

关键词： acquired resistance     EGFR inhibitor     apoptosis     lung cancer    

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Mechanisms of resistance to third-generation EGFR tyrosine kinase inhibitors

null

《医学前沿（英文）》 2016年 第10卷 第4期   页码 383-388 doi: 10.1007/s11684-016-0488-1

摘要：

The tyrosine kinase inhibitors (TKI) of the epidermal growth factor receptor (EGFR) are becoming the first line of therapy for advanced non-small cell lung cancer (NSCLC). Acquired mutations in EGFR account for one of the major mechanisms of resistance to the TKIs. Three generations of EGFR TKIs have been used in clinical applications. AZD9291 (osimertinib; Tagrisso) is the first and only FDA approved third-generation EGFR TKI for T790M-positive advanced NSCLC patients. However, resistance to AZD9291 arises after 9–13 months of therapy. The mechanisms of resistance to third-generation inhibitors reported to date include the EGFR C797S mutation, EGFR L718Q mutation, and amplifications of HER-2, MET, or ERBB2. To overcome the acquired resistance to AZD9291, EAI045 was discovered and recently reported to be an allosteric EGFR inhibitor that overcomes T790M- and C797S-mediated resistance. This review summarizes recent investigations on the mechanisms of resistance to the EGFR TKIs, as well as the latest development of EAI045 as a fourth-generation EGFR inhibitor.

关键词： EGFR     tyrosine kinase inhibitor     AZD9291     EAI045    

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Evaluating R&D efficiency of China’s listed lithium battery enterprises

《工程管理前沿（英文）》   页码 473-485 doi: 10.1007/s42524-022-0213-5

摘要： Promoting the growth of the lithium battery sector has been a critical aspect of China’s energy policy in terms of achieving carbon neutrality. However, despite significant support on research and development (R&D) investments that have resulted in increasing size, the sector seems to be falling behind in technological areas. To guide future policies and understand proper ways of promoting R&D efficiency, we looked into the lithium battery industry of China. Specifically, data envelopment analysis (DEA) was used as the primary approach based on evidence from 22 listed lithium battery enterprises. The performance of the five leading players was compared with that of the industry as a whole. Results revealed little indication of a meaningful improvement in R&D efficiency throughout our sample from 2010 to 2019. However, during this period, a significant increase in R&D expenditure was witnessed. This finding was supported, as the results showed that the average technical efficiency of the 22 enterprises was 0.442, whereas the average pure technical efficiency was at 0.503, thus suggesting that they were suffering from decreasing returns to scale (DRS). In contrast, the performance of the five leading players seemed superior because their average efficiency scores were higher than the industry’s average. Moreover, they were experiencing increasing scale efficiency (IRS). We draw on these findings to suggest to policymakers that supporting technologically intensive sectors should be more than simply increasing investment scale; rather, it should also encompass assisting businesses in developing efficient managerial processes for R&D.

关键词： Data Envelopment Analysis     R&D investment efficiency     China’s listed lithium battery enterprises     technical efficiency     pure technical efficiency     scale efficiency    

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改进的R/S方法与中国火灾数据的分析预测

付昱华,付安捷

《中国工程科学》 2004年 第6卷 第5期   页码 39-44

摘要：

讨论工程和经济学领域中的R/S分析方法（重标极差方法）的若干改进及应用。对于全国火灾起数的分析，计算赫斯特指数H时应用2种新的数据分组方法；引入赫斯特指数的差值ΔH以利于判断下一年的火灾起数是否会激增；对于已计算出的赫斯特指数H进行R/S分析，得到一组新的赫斯特指数依此类推可以得到高阶赫斯特指数及其差值H2，ΔH2，H3，ΔH3等；根据1950—1999年全国火灾起数，用R/S方法预测2000年全国火灾起数。

关键词： R/S分析     重标极差方法     高阶赫斯特指数     全国火灾起数     预测    

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Improvement potential of today’s WEEE recycling performance: The case of LCD TVs in Belgium

Paul Vanegas, Jef R. Peeters, Dirk Cattrysse, Wim Dewulf, Joost R. Duflou

《环境科学与工程前沿（英文）》 2017年 第11卷 第5期 doi: 10.1007/s11783-017-1000-0

摘要： Waste of electrical and electronic equipment (WEEE) constitutes one of the most relevant waste streams because of the quantity and presence of valuable materials. However, there is limited knowledge on the resource potential of urban mining WEEE, as data on material composition, and the efficiency of current recycling treatments are still scarce. In this article, an evaluation of the recycling performance at a national level for one of the fastest growing e-waste streams: LCD TVs is carried out through the following four steps. Firstly, material characterisation is performed by means of sampling of the waste stream. Secondly, a material flow analysis is conducted by evaluating the separation performance of a recycling plant in Belgium. Thirdly, the recovered economic value and avoided environmental impact (EI) of the analysed recycling system is assessed. Finally, the potential of urban mining for Belgium is forecasted. The analysis shows that while recycling performance for ferrous metals and aluminium are relatively high; there is substantial room to better close the material loops for precious metals (PM) and plastics. PMs and plastics account for 66 % of the economic value in LCD TVs and 57% of the EI. With the current, commonly applied recycling technology only one-third of the PM and housing plastics are recycled; meaning that for these materials, at a national level for Belgium, there is a potential for improvement that represents 3.3 million euros in 2016 and 6.8 million euros in 2025.

关键词： Recycling     Waste of electrical and electronic equipment (WEEE)     Material flow analysis     LCD TVs     Precious metals     Plastics    

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Response in piled raft foundation of tall chimneys under along-wind load incorporating flexibility of soil

R. JAYALEKSHMI,S.V. JISHA,R. SHIVASHANKAR

《结构与土木工程前沿（英文）》 2015年 第9卷 第3期   页码 307-322 doi: 10.1007/s11709-015-0288-8

摘要： The present paper deals with the numerical analysis of tall reinforced concrete chimneys with piled raft foundation subjected to along-wind loads considering the flexibility of soil. The analysis was carried out using finite element method on the basis of direct method of soil-structure interaction (SSI). The linear elastic material behavior was assumed for chimney, piled raft and soil. Four different material properties of soil stratum were selected in order to study the effect of SSI. The chimney elevation and the thickness of raft of piled raft foundation were also varied for the parametric study. The chimneys were assumed to be located in terrain category 2 and subjected to a maximum wind speed of 50 m/s as per IS:875 (Part 3)-1987. The along-wind loads were computed according to IS:4998 (Part 1)-1992. The base moments of chimney evaluated from the SSI analysis were compared with those obtained as per IS:4998 (Part 1)-1992. The tangential and radial bending moments of raft of piled raft foundation were evaluated through SSI analysis and compared with those obtained from conventional analysis as per IS:11089-1984, assuming rigidity at the base of the raft foundation. The settlements of raft of piled raft foundation, deflection of pile and moments of the pile due to interaction with different soil stratum were also evaluated. From the analysis, considerable reduction in the base moment of chimney due to the effect of SSI is observed. Higher radial moments and lower tangential moments were obtained for lower elevation chimneys with piled raft resting on loose sand when compared with conventional analysis results. The effect of SSI in the response of the pile is more significant when the structure-foundation system interacts with loose sand.

关键词： finite element method     piled raft     tall chimney     soil-structure interaction     along-wind load    

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Techno-economic evaluation of wind energy in southwest Nigeria

Muyiwa S. ADARAMOLA, Olarenwaju M. OYEWOLA, Olayinka S. OHUNAKIN, Rufus R. DINRIFO

《能源前沿（英文）》 2012年 第6卷 第4期   页码 366-378 doi: 10.1007/s11708-012-0205-y

摘要： In this study, an analysis of the wind energy potential in the southwest geo-political region of Nigeria was conducted. A 37-year (1971–2007) wind speed data set measured at 10 m height, obtained from eight meteorological stations within the region was analyzed using a 2-parameter Weibull function. Besides, a techno-economic evaluation of large wind energy conversion systems with power ratings ranging from 0.6 to 2 MW at different hub heights based on the levelized unit cost of electricity was made for the different sites considered. The result showed that electricity cost varied from 0.06997 and 0.11195 $/(kW·h) to 2.86611 and 4.58578 $/(kW·h) at limit values of turbine specific cost band intervals of 1000 and 1600 $/kW. It was further shown that Lagos, having the highest accumulated power outputs of 430.10 kW/a from DeWind D7 at 70 m hub height, is the most preferred for economically usable power generation in terms of the levelized unit cost.

关键词： mean wind speed     Weibull distributions     wind turbine     techno-economic analysis     southwest geopolitical region     Nigeria    

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Estimation of relations among hysteretic response measures and design parameters for RC rectangular shear walls

R. BANAN, Mo. R. BANAN, S. FARHADI

《结构与土木工程前沿（英文）》 2018年 第12卷 第1期   页码 3-15 doi: 10.1007/s11709-017-0418-6

摘要： Seismic design of RC structures requires estimation of structural member behavioral measures as functions of design parameters. In this study, the relations among cyclic behavioral measures and design parameters have been investigated for rectangular RC shear walls using numerical simulations calibrated based on the published laboratory tests. The OpenSEES numerical simulations modeling of plastic hinge hysteretic behavior of RC shear walls and estimation of empirical relations among wall hysteretic indices and design parameters are presented. The principal design parameters considered were wall dimensions, axial force, reinforcement ratios, and end-element design parameters. The estimated hysteretic response measures are wall effective stiffness, yield and ultimate curvatures, plastic moment capacity, yield and ultimate displacements, flexural shear capacity, and dissipated energy. Using results of numerous analyses, the empirical relations among wall cyclic behavioral measures and design parameters are developed and their accuracy is investigated.

关键词： RC wall hysteretic measures     RC wall design parameters     empirical relations     numerical simulations     RC rectangular wall plastic hinge    

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Design concepts of an aircraft wing: composite and morphing airfoil with auxetic structures

P R BUDARAPU,Sudhir Sastry Y B,R NATARAJAN

《结构与土木工程前沿（英文）》 2016年 第10卷 第4期   页码 394-408 doi: 10.1007/s11709-016-0352-z

摘要： This paper is categorized into two parts. (1) A frame work to design the aircraft wing structure and (2) analysis of a morphing airfoil with auxetic structure. The developed design frame work in the first part is used to arrive at the sizes of the various components of an aircraft wing structure. The strength based design is adopted, where the design loads are extracted from the aerodynamic loads. The aerodynamic loads acting on a wing structure are converted to equivalent distributed loads, which are further converted point loads to arrive at the shear forces, bending and twisting moments along the wing span. Based on the estimated shear forces, bending and twisting moments, the strength based design is employed to estimate the sizes of various sections of a composite wing structure. A three dimensional numerical model of the composite wing structure has been developed and analyzed for the extreme load conditions. Glass fiber reinforced plastic material is used in the numerical analysis. The estimated natural frequencies are observed to be in the acceptable limits. Furthermore, the discussed design principles in the first part are extended to the design of a morphing airfoil with auxetic structure. The advantages of the morphing airfoil with auxetic structure are (i) larger displacement with limited straining of the components and (ii) unique deformation characteristics, which produce a theoretical in-plane Poisson’s ratio of −1. Aluminum Alloy AL6061-T651 is considered in the design of all the structural elements. The compliance characteristics of the airfoil are investigated through a numerical model. The numerical results are observed to be in close agreement with the experimental results in the literature.

关键词： wing design     aerodynamic loads     morphing airfoil     auxetic structures     negative Poisson’s ratio    

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Novel mutation c.1210-3C>G in with a poly-T tract of 5T affects mRNA splicing in a Chinese patient

《医学前沿（英文）》 2022年 第16卷 第1期   页码 150-155 doi: 10.1007/s11684-021-0846-5

摘要： Cystic fibrosis (CF) is a rare autosomal recessive disease with only one pathogenic gene cystic fibrosis transmembrane conductance regulator (CFTR). To identify the potential pathogenic mutations in a Chinese patient with CF, we conducted Sanger sequencing on the genomic DNA of the patient and his parents and detected all 27 coding exons of CFTR and their flanking intronic regions. The patient is a compound heterozygote of c.2909G>A, p.Gly970Asp in exon 18 and c.1210-3C>G in cis with a poly-T of 5T (T5) sequence, 3 bp upstream in intron 9. The splicing effect of c.1210-3C>G was verified via minigene assay in vitro, indicating that wild-type plasmid containing c.1210-3C together with T7 sequence produced a normal transcript and partial exon 10-skipping-transcript, whereas mutant plasmid containing c.1210-3G in cis with T5 sequence caused almost all mRNA to skip exon 10. Overall, c.1210-3C>G, the newly identified pathogenic mutation in our patient, in combination with T5 sequence in cis, affects the CFTR gene splicing and produces nearly no normal transcript in vitro. Moreover, this patient carries a p.Gly970Asp mutation, thus confirming the high-frequency of this mutation in Chinese patients with CF.

关键词： cystic fibrosis     CFTR     splicing mutation     minigene    

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Detection of void and metallic inclusion in 2D piezoelectric cantilever beam using impedance measurements

S. SAMANTA, S. S. NANTHAKUMAR, R. K. ANNABATTULA, X. ZHUANG

《结构与土木工程前沿（英文）》 2019年 第13卷 第3期   页码 542-556 doi: 10.1007/s11709-018-0496-0

摘要： The aim of current work is to improve the existing inverse methodology of void-detection based on a target impedance curve, leading to quick-prediction of the parameters of single circular void. In this work, mode-shape dependent shifting phenomenon of peaks of impedance curve with change in void location has been analyzed. A number of initial guesses followed by an iterative optimization algorithm based on univariate method has been used to solve the problem. In each iteration starting from each initial guess, the difference between the computationally obtained impedance curve and the target impedance curve has been reduced. This methodology has been extended to detect single circular metallic inclusion in 2D piezoelectric cantilever beam. A good accuracy level was observed for detection of flaw radius and flaw-location along beam-length, but not the precise location along beam-width.

关键词： piezoelectricity     impedance curve     mode shapes     inverse problem     flaw detection     curve shifting    

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Correlations for estimating solar radiation using sunshine hours and temperature measurement in Osogbo, Osun State, Nigeria

S. OHUNAKIN, M. S. ADARAMOLA, O. M. OYEWOLA, R. O. FAGBENLE

《能源前沿（英文）》 2013年 第7卷 第2期   页码 214-222 doi: 10.1007/s11708-013-0241-2

摘要： In this study, the global solar radiation on horizontal surface in Osogbo, Osun state, Nigeria was analyzed using 11-year data (1997–2007). Correlations using linear and quadratic expressions were developed to relate the global solar radiation on horizontal surface based on relative sunshine hours and temperature measurements for evaluating the monthly average daily global solar radiation. The calculated monthly clearness index values indicate that the prevailing weather condition in Osogbo is heavily overcast. All the developed quadratic correlations gave better correlation coefficients (0.834, 0.872 and 0.823 respectively) than the linear models. However, the Hargreaves and Samani related based quadratic model gave the best among the three developed quadratic expressions and is therefore suggested for estimating the monthly global radiation in this site and its surroundings.

关键词： global solar radiation     Hargreaves model     sunshine hour     ambient temperatures     Osogbo    

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Kinematical synthesis of an inversion of the double linked fourbar for morphing wing applications

AGUIRREBEITIA, R. AVILéS, I. FERNáNDEZ, M. ABASOLO

《机械工程前沿（英文）》 2013年 第8卷 第1期   页码 17-32 doi: 10.1007/s11465-013-0364-5

摘要：

This paper presents the kinematical features of an inversion of the double linked fourbar for morphing wing purposes. The structure of the mechanism is obtained using structural synthesis concepts, from an initial conceptual schematic. Then, kinematic characteristics as instant center of rotation, lock positions, dead point positions and uncertainty positions are derived for this mechanism in order to face the last step, the dimensional synthesis; in this sense, two kinds of dimensional synthesis are arranged to guide the wing along two positions, and to fulfill with the second one some aerodynamic and minimum actuation energy related issues.

关键词： morphing wing     structural synthesis     dimensional synthesis     geometrical kinematics    

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Design of efficient Pt-based electrocatalysts through characterization by X-ray absorption spectroscopy

Nebojsa S. MARINKOVIC, Kotaro SASAKI, Radoslav R. ADZIC

《能源前沿（英文）》 2017年 第11卷 第3期   页码 236-244 doi: 10.1007/s11708-017-0487-1

摘要： A method is described to determine the internal structure of electrocatalyst nanoparticles by X-ray absorption spectroscopy (XAS). The nondestructive spectroscopic technique typically utilizing synchrotron radiation as the source measures changes in the X-ray absorption coefficient as a function of energy. The bulk technique has found its use for materials characterization in all scientific areas, including nanomaterials. The analysis of the internal structure of nanoparticles reveals interatomic distances and coordination numbers for each element, and their values and mutual relations indicate whether the elements form a homogeneous or heterogeneous mixture. The core-shell heterogeneous structure in which certain elements are predominantly located in the core, and others form the encapsulating shell is of particular importance in catalysis and electrocatalysis because it may reduce the amount of precious metals in nanoparticles by replacing the atoms in the core of nanoparticles with more abundant and cheaper alternatives. The examples of nanoparticle structures designed in the laboratory and the approach to model efficient catalysts through systematic analysis of XAS data in electrochemical systems consisting of two and three metals are also demonstrated.

关键词： X-ray absorption spectroscopy     EXAFS     XANES     nanocatalysts     core shell    

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标题 作者 时间 类型 操作

Growth suppression of colorectal cancer expressing S492R EGFR by monoclonal antibody CH12

Qiongna Dong, Bizhi Shi, Min Zhou, Huiping Gao, Xiaoying Luo, Zonghai Li, Hua Jiang

期刊论文

Targeting apoptosis to manage acquired resistance to third generation EGFR inhibitors

期刊论文

Mechanisms of resistance to third-generation EGFR tyrosine kinase inhibitors

null

期刊论文

Evaluating R&D efficiency of China’s listed lithium battery enterprises

期刊论文

改进的R/S方法与中国火灾数据的分析预测

付昱华,付安捷

期刊论文

Improvement potential of today’s WEEE recycling performance: The case of LCD TVs in Belgium

Paul Vanegas, Jef R. Peeters, Dirk Cattrysse, Wim Dewulf, Joost R. Duflou

期刊论文

Response in piled raft foundation of tall chimneys under along-wind load incorporating flexibility of soil

R. JAYALEKSHMI,S.V. JISHA,R. SHIVASHANKAR

期刊论文

Techno-economic evaluation of wind energy in southwest Nigeria

Muyiwa S. ADARAMOLA, Olarenwaju M. OYEWOLA, Olayinka S. OHUNAKIN, Rufus R. DINRIFO

期刊论文

Estimation of relations among hysteretic response measures and design parameters for RC rectangular shear walls

R. BANAN, Mo. R. BANAN, S. FARHADI

期刊论文

Design concepts of an aircraft wing: composite and morphing airfoil with auxetic structures

P R BUDARAPU,Sudhir Sastry Y B,R NATARAJAN

期刊论文

Novel mutation c.1210-3C>G in with a poly-T tract of 5T affects mRNA splicing in a Chinese patient

期刊论文

Detection of void and metallic inclusion in 2D piezoelectric cantilever beam using impedance measurements

S. SAMANTA, S. S. NANTHAKUMAR, R. K. ANNABATTULA, X. ZHUANG

期刊论文

Correlations for estimating solar radiation using sunshine hours and temperature measurement in Osogbo, Osun State, Nigeria

S. OHUNAKIN, M. S. ADARAMOLA, O. M. OYEWOLA, R. O. FAGBENLE

期刊论文

Kinematical synthesis of an inversion of the double linked fourbar for morphing wing applications

AGUIRREBEITIA, R. AVILéS, I. FERNáNDEZ, M. ABASOLO

期刊论文

Design of efficient Pt-based electrocatalysts through characterization by X-ray absorption spectroscopy

Nebojsa S. MARINKOVIC, Kotaro SASAKI, Radoslav R. ADZIC

期刊论文