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A 3D-Printed Biomaterials-Based Platform to Advance Established Therapy Avenues Against Primary Bone Cancers 基于3d打印生物材料的平台推进针对原发性骨癌的既定治疗途径
Pub Date : 2020-10-08 DOI: 10.2139/ssrn.3632518
C. A. Lahr, Marietta Landgraf, Alvaro Sanchez-Herrero, Hoang Phuc Dang, F. Wagner, Onur Bas, L. Bray, P. Tran, B. Holzapfel, A. Shafiee, J. McGovern, D. Hutmacher
In this study we developed and validated a 3D-printed drug delivery system (3DPDDS) to 1) improve local treatment efficacy of commonly applied chemotherapeutic agents in bone cancers to ultimately decrease their systemic side effects and 2) explore its concomitant diagnostic potential. Thus, we locally applied 3D-printed medical-grade polycaprolactone (mPCL) scaffolds loaded with Doxorubicin (DOX) and measured its effect in a humanized primary bone cancer model. A bioengineered species-sensitive orthotopic humanized bone niche was established at the femur of NOD-SCID IL2Rγnull (NSG) mice. After 6 weeks of in vivo maturation into a humanized ossicle, Luc-SAOS-2 cells were injected orthotopically to induce local growth of osteosarcoma (OS). After 16 weeks of OS development, a biopsy-like defect was created within the tumor tissue to locally implant the 3DPDDS with 3 different DOX loading doses into the defect zone. Histo- and morphological analysis demonstrated a typical invasive OS growth pattern inside a functionally intact humanized ossicle as well as metastatic spread to the murine lung parenchyma. Analysis of the 3DPDDS revealed the implants' ability to inhibit tumor infiltration and showed local tumor cell death adjacent to the scaffolds without any systemic side effects. Together these results indicate a therapeutic and diagnostic capacity of 3DPDDS in an orthotopic humanized OS tumor model.
在这项研究中,我们开发并验证了一种3d打印药物传递系统(3DPDDS),以1)提高骨癌常用化疗药物的局部治疗效果,最终减少其全身副作用;2)探索其伴随的诊断潜力。因此,我们局部应用装载阿霉素(DOX)的3d打印医用级聚己内酯(mPCL)支架,并测量其在人源原发性骨癌模型中的效果。在NOD-SCID il - 2r - γ缺失(NSG)小鼠股骨上建立了生物工程物种敏感的原位人源化骨生态位。在体内成熟成人源小骨6周后,原位注射Luc-SAOS-2细胞诱导骨肉瘤(OS)局部生长。术后16周,在肿瘤组织内形成活检样缺损,将3种不同DOX负荷剂量的3DPDDS局部植入缺损区。组织和形态学分析表明,在功能完整的人源小骨内,典型的侵袭性骨肉瘤生长模式以及转移扩散到小鼠肺实质。对3DPDDS的分析显示,植入物具有抑制肿瘤浸润的能力,并显示支架附近的局部肿瘤细胞死亡,无任何全身副作用。总之,这些结果表明3DPDDS在原位人源化OS肿瘤模型中的治疗和诊断能力。
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引用次数: 9
Native Mass Spectrometry-Based Screening for Optimal Sample Preparation in Single Particle Cryo-EM 基于原生质谱的单颗粒低温电镜样品制备筛选
Pub Date : 2020-10-07 DOI: 10.2139/ssrn.3689208
P. D. Olinares, J. Kang, E. Llewellyn, C. Chiu, James Chen, B. Malone, R. Saecker, E. Campbell, S. Darst, B. Chait
Recent advances in single-particle cryogenic electron microscopy (cryo-EM) have enabled the structural determination of numerous protein assemblies at high resolution, yielding unprecedented insights into their function. However, despite its extraordinary capabilities, cryo-EM remains time-consuming and resource-intensive. It is therefore beneficial to have a means for rapidly assessing and optimizing the quality of samples prior to lengthy cryo-EM analyses. To do this, we have developed a native mass spectrometry (nMS) platform that provides rapid feedback on sample quality and highly streamlined biochemical screening. Because nMS enables accurate mass analysis of protein complexes, it is well suited to routine evaluation of the composition, integrity, and homogeneity of samples prior to their plunge-freezing on EM grids. We demonstrate the utility of our nMS-based platform for facilitating cryo-EM studies using structural characterizations of exemplar bacterial transcription complexes as well as the replication-transcription assembly from the SARS-CoV-2 virus that is responsible for the COVID-19 pandemic.
单粒子低温电子显微镜(cryo-EM)的最新进展已经能够以高分辨率确定许多蛋白质组件的结构,从而对其功能产生前所未有的见解。然而,尽管具有非凡的能力,冷冻电镜仍然是耗时和资源密集的。因此,在冗长的冷冻电镜分析之前,有一种快速评估和优化样品质量的方法是有益的。为此,我们开发了一种原生质谱(nMS)平台,可提供样品质量的快速反馈和高度精简的生化筛选。由于nMS能够对蛋白质复合物进行精确的质量分析,因此它非常适合于样品在EM网格上冷冻前的组成、完整性和均匀性的常规评估。我们展示了基于nms的平台的实用性,该平台利用样本细菌转录复合物的结构特征以及导致COVID-19大流行的SARS-CoV-2病毒的复制转录组装来促进冷冻电镜研究。
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引用次数: 19
New Insights on Recovery and Early Recrystallization of Ferrite-Pearlite Banded Cold Rolled High Strength Steels by High Speed Nanoindentation Mapping 高速纳米压痕成像对铁素体-珠光体带状冷轧高强钢恢复和早期再结晶的新认识
Pub Date : 2020-10-05 DOI: 10.2139/ssrn.3692027
S. Janakiram, P. S. Phani, G. Ummethala, S. Malladi, J. Gautam, L. Kestens
Abstract This work unravels structure-property correlations at the micrometer length scale during recovery and early recrystallization of a cold rolled high strength steel comprised of ferrite and pearlite. High resolution nano-indention mapping is used to measure the hardness of ferrite, pearlite and the transition zone between them, which correlates well with the local microstructure obtained from scanning and transmission electron microscopy. A clustering algorithm is used to determine the properties of the constituent microstructural features. The variation in the hardness of the phases with annealing temperature agrees well with the dislocation activity observed using Transmission Electron Microscopy (TEM) and a simple mechanism to reconcile the observations is presented.
本文在微米长度尺度上揭示了由铁素体和珠光体组成的冷轧高强度钢在恢复和早期再结晶过程中的组织-性能相关性。采用高分辨率纳米压痕图测量了铁素体、珠光体及其过渡区的硬度,其硬度与扫描电镜和透射电镜观察到的局部显微组织吻合良好。使用聚类算法确定组成微观结构特征的性质。相变相硬度随退火温度的变化与透射电镜观察到的位错活度吻合较好,并提出了一种简单的协调机制。
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引用次数: 11
Comparison of Rendering Processes on 3D Model 三维模型渲染过程的比较
Pub Date : 2020-10-05 DOI: 10.5121/ijcsit.2020.12502
Filip Popovski, Nikola Spasov, Svetlana Mijakovska, G. Nalevska
Creating 3D vehicle model is complex process that requires basic knowledge of polygonal modeling. In this research, environment map is used as lighting with HDRI image. The final process of converting 3D scene to 2D image is called rendering. Image data will be obtained in four ways with various toolsets used in 3ds Max. They are: Scaneline, V-Ray, Mental Ray and Corona Renderer. At final step was made critical analysis on all of these techniques on the same computer system and excellent results were obtained.
创建三维车辆模型是一个复杂的过程,需要多边形建模的基本知识。在本研究中,使用环境地图作为HDRI图像的照明。将3D场景转换为2D图像的最后过程称为渲染。图像数据将在3ds Max中使用各种工具集以四种方式获得。它们是:Scaneline, V-Ray, Mental Ray和Corona Renderer。最后,在同一计算机系统上对所有这些技术进行了批判性分析,并获得了良好的结果。
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引用次数: 1
Microstructure Evolution of Thin Nickel Films with Embedded Chromium Oxide Nanoparticles 纳米氧化铬包埋镍薄膜的微观结构演变
Pub Date : 2020-09-30 DOI: 10.2139/ssrn.3680388
Hagit Barda, L. Klinger, E. Rabkin
Abstract We developed a fabrication method of thin metal matrix composite films reinforced with ceramic nanoparticles. To this end, we deposited a 20 nm Ni / ultrathin Cr-oxide layer / 20 nm Ni tri-layer on a sapphire substrate, and annealed the sample at the temperature of 700°C. We found that after annealing for 10 min the Cr-oxide layer agglomerates into single- or bi-crystalline faceted Cr2O3 nanoparticles, with the orientation relationship of ( 11 1 ¯ ) N i ∥ ( 0006 ) C r 2 O 3 and [ 112 ] N i ∥ [ 1 2 ¯ 10 ] C r 2 O 3 to the Ni matrix. We encountered a surprising vertical spread of the centers of mass of the Cr-oxide particles with respect to the initial position of the Cr-oxide layer. We developed a kinetic model of the evolution of particles shape and of their vertical drift, which enabled an estimate of the effective diffusion coefficient of the Ni-Cr2O3 interface ( D i = 7.4 · 10 − 19 m 2 s ). Though much slower than grain boundary diffusion in Ni, this interface diffusion enables fast transformation of ultra-thin Cr-oxide layer into an array of isolated Cr2O3nanoparticles embedded in the Ni film. The insight into the kinetics of the system obtained in the present work paves the way for the design of particle reinforcement of thin metal films with a precise control over the spatial positions of the particles.
研究了一种陶瓷纳米颗粒增强金属基复合薄膜的制备方法。为此,我们在蓝宝石衬底上沉积了20nm Ni /超薄cr -氧化物层/ 20nm Ni三层,并在700℃的温度下退火样品。研究发现,退火10 min后,cr -氧化物层团聚成单晶或双晶切面Cr2O3纳米颗粒,其取向关系为(11¯)Ni∥(0006)Cr2O3和[112]Ni∥[12¯10]Cr2O3与Ni基体的取向关系为(11¯)Ni∥(0006)Cr2O3。我们发现,相对于氧化铬层的初始位置,氧化铬颗粒的质心出现了令人惊讶的垂直扩散。我们建立了颗粒形状演变及其垂直漂移的动力学模型,从而可以估计Ni-Cr2O3界面的有效扩散系数(d1 = 7.4·10−19 m 2 s)。虽然比Ni中的晶界扩散慢得多,但这种界面扩散使超薄cr -氧化物层快速转变为嵌入Ni膜中的孤立的cr2o3纳米颗粒阵列。在本工作中获得的对系统动力学的深入了解为金属薄膜的颗粒增强设计铺平了道路,并精确控制了颗粒的空间位置。
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引用次数: 1
About Darsy's Law During Fluids Motion in the Micro-Cracked Channels 流体在微裂纹通道中的运动达西定律研究
Pub Date : 2020-09-30 DOI: 10.21303/2461-4262.2020.001386
M. Mammadova
Firstly it has been experimentally revealed that during fluid motion in the micro-cracked channel and in the equivalent porous medium an unknown additional resistance arises in the scientific technical literature that is the “microcrack-fluid” effect. It has been demonstrated that the determined “microcrack-fluid” effect is the cause of linear Darcy’s law violation in the micro-cracked channels.It has been revealed in the work that during fluids moving in the microcracked channel there is a critical size of crack for the homogeneous fluid (water, viscous and anomalous fluids) and a hydrodynamic effect as so-called “microcrack-fluid” is manifested.So for the first time we determined the critical value of opening − hcr on the basis of experimental investigations in cracks. It was found that at h
首先,实验揭示了流体在微裂纹通道和等效多孔介质中的运动过程中,在科学技术文献中会产生一种未知的附加阻力,即“微裂纹-流体”效应。结果表明,确定的“微裂纹-流体”效应是微裂纹通道中线性达西定律违反的原因。研究表明,流体在微裂纹通道中运动时,均匀流体(水、粘性流体和异常流体)存在临界裂纹尺寸,并表现出所谓“微裂纹-流体”的水动力效应。因此,我们首次在裂纹试验研究的基础上确定了打开- hcr的临界值。结果表明,当h
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引用次数: 0
The Mechanism of Dynamic Strain Aging for Type a Serrations in Tensile Curves of a Medium-Mn Steel 中锰钢拉伸曲线a型锯齿动态应变时效机理研究
Pub Date : 2020-09-25 DOI: 10.2139/ssrn.3680373
J. Nam, Seon-Keun Oh, Myeong-heom Park, Young‐kook Lee
Abstract The objective of the present study is to clarify the mechanism of dynamic strain aging (DSA) causing serrations in tensile flow curves of Fe-5.15Mn-0.15C-0.37Si-0.0039N (wt%) medium-Mn steel specimens with triple phases of retained austenite (γR), ferrite (α) and tempered martensite (α'T). For the purpose, tensile tests were performed at various conditions of deformation temperature (Td = 273 - 333 K) and initial strain rate (έini = 5 × 10−4 - 1 × 10−2 s−1). The medium-Mn steel specimens revealed type A serrations after the propagation of the Luders band in their tensile curves. The serrations were not related to both α and α'T; they were not caused by strain-induced martensitic transformation, but by DSA in γR. The DSA was not explained by the short-range diffusion model based on the interaction between partial dislocations and C-Mn complexes due to the absence of intersection between staying time and reorientation time. In a viewpoint of the dislocation arrest model involving long-range diffusion, critical strains of γR for serrations (ecγ) were measured. They showed the normal Portevine-Le Châtelier behavior that the ecγ value decreases with increasing Td and with decreasing έini. The activation energy measured using the ecγ values was similar to the activation energy for the dislocation pipe diffusion of C atoms. This result indicates that the DSA occurring in the present medium-Mn steel is explained by the dislocation arrest model involving the long-range pipe diffusion of C atoms, not by the short-range diffusion model involving the reorientation of C-Mn complexes.
摘要本研究的目的是阐明动态应变时效(DSA)导致Fe-5.15Mn-0.15C-0.37Si-0.0039N (wt%)中锰钢试样拉伸流动曲线出现锯齿状的机理,该试样具有残余奥氏体(γR)、铁素体(α)和回火马氏体(α′T)三相。为此,在变形温度(Td = 273 - 333 K)和初始应变速率(ini = 5 × 10−4 - 1 × 10−2 s−1)的不同条件下进行了拉伸试验。中锰钢试样在拉伸曲线中吕德带扩展后呈现A型锯齿形。锯齿形与α′T和α′T均无相关性;它们不是由应变诱导的马氏体相变引起的,而是由γR中的DSA引起的。由于停留时间和重定向时间没有交集,因此不能用基于部分位错与C-Mn配合物相互作用的短程扩散模型来解释DSA。从位错阻滞模型的观点出发,测量了γ γ γ的临界应变(ecγ)。它们表现出正常的Portevine-Le chtelier行为,即ecγ值随Td的增加和ini的减小而减小。利用ecγ值测量的活化能与C原子位错管扩散的活化能相似。这一结果表明,当前中锰钢中发生的DSA是由位错阻滞模型解释的,该模型涉及C原子的长距离管扩散,而不是由C- mn配合物的重取向的短程扩散模型解释的。
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引用次数: 31
Effects of Annealing on Hardness, Yield Strength and Dislocation Structure in Single Crystals of the Equiatomic Cr-Mn-Fe-Co-Ni High Entropy Alloy 退火对等原子Cr-Mn-Fe-Co-Ni高熵合金硬度、屈服强度和单晶位错结构的影响
Pub Date : 2020-09-25 DOI: 10.2139/ssrn.3680282
Dengshan Zhou, Zhenghao Chen, Kazuki Ehara, Kodai Nitsu, Katsushi Tanaka, H. Inui
Abstract We report that in contrast to the anticipation, the macroscopic mechanical strength of single crystals of the face-centered-cubic single-phase equiatomic Cr-Mn-Fe-Co-Ni high entropy alloy is not influenced by thermal annealing during which short-range ordering is expected to develop. Experimental evidence shows that hardness at room temperature, critical resolved shear stress at room temperature and at 77 K and activation volume values of the alloys do not significantly vary with the annealing temperature in the range from 900 to 1200°C. The stacking fault energies in the specimens deformed at 77 K following annealing at 1000 and 1200°C respectively are essentially identical to each other. These results clearly indicate that the impact of the formation of chemical short-range order on the macroscopic yield strength of the equiatomic Cr-Mn-Fe-Co-Ni high entropy alloy is insignificant, even if it exists.
与预期相反,面心立方单相等原子Cr-Mn-Fe-Co-Ni高熵合金的单晶宏观力学强度不受热退火的影响,在此过程中有望发展出短时有序。实验结果表明,在900 ~ 1200℃的退火温度范围内,合金的室温硬度、室温和77 K临界分解剪应力以及活化体积值没有显著变化。在1000℃和1200℃退火后,77 K变形试样的层错能基本相同。这些结果清楚地表明,化学短程有序的形成即使存在,对等原子Cr-Mn-Fe-Co-Ni高熵合金宏观屈服强度的影响也不显著。
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引用次数: 26
High Compressibility of Synthetic Analogous of Binary Iridium–Ruthenium and Ternaryiridium–Osmium–Ruthenium Minerals 高压缩性合成二元铱-钌和三元铱-锇-钌矿物的类似物
Pub Date : 2020-09-03 DOI: 10.2139/ssrn.3685881
K. Yusenko, S. Martynova, S. Khandarkhaeva, T. Fedotenko, K. Glazyrin, E. Koemets, M. Bykov, M. Hanfland, K. Siemensmeyer, A. Smekhova, S. Gromilov, L. Dubrovinsky
Hcp–Ir0.24Ru0.36Os0.40 and fcc–Ir0.84Ru0.06Os0.10 ternary alloys as well as binary hcp–Ir0.33Ru0.67 and fcc–Ir0.75Ru0.25 alloys were prepared using thermal decomposition of [IrxRu1-x(NH3)5Cl][OsyIr(1-y)Cl6] single-source precursors in hydrogen flow below 1070 K. These single-phase alloys correspond to ternary and binary peritectic phase diagrams and can be used as synthetic models for rare iridosmine minerals. Thermal decomposition of parent bimetallic precursor [Ir(NH3)5Cl][OsСl6] has been investigated using in situ powder X-ray diffraction in inert and reductive atmospheres. In reductive atmosphere, [Ir(NH3)5Cl][OsСl6] forms (NH4)2[OsСl6<] as crystalline intermediate; Ir from its cationic part is reduced by hydrogen with a formation of defect fcc -structured metallic particles; the final product is a metastable hcp I.0.5Os0.5 alloy. In inert atmosphere, the salt decomposes at higher temperature without a formation of any detectable crystalline intermediates; two-phase fcc+hcp mixture forms directly above 800 K. Room temperature compressibility up to 50 GPa has been studied for all prepared alloys in diamond anvil cells. Hcp–Ir0.24Ru0.36Os0.40 (B0 = 362(4) GPa, B0' = 4.8(2)) and fcc–Ir0.84Ru0.06Os0.10 (B0 = 302(7) GPa, B0' = 6.4(5)) ternary alloys as well as hcp–Ir0.33Ru0.67 (B0 = 332(2) GPa, B0' = 5.4(1)) and fcc–Ir0.75Ru0.25 (B0 = 316(1) GPa, B0' = 5.1(1)) binary alloys do not show any phase transitions upon compression at room temperature. In contrast with other investigated ultra incompressible refractory alloys with osmium and iridium, hcp–Ir0.33Ru
用[IrxRu1-x(NH3)5Cl][OsyIr(1-y)Cl6]单源前驱体在1070 K以下氢气流中热分解制备了Hcp-Ir0.24Ru0.36Os0.40和fcc - ir0.84 ru0.060 os0.10三元合金以及hcp-Ir0.33Ru0.67和fcc-Ir0.75Ru0.25二元合金。这些单相合金对应三元和二元包晶相图,可作为稀有铱胺矿物的合成模型。用原位粉末x射线衍射研究了母体双金属前驱体[Ir(NH3)5Cl][OsСl6]在惰性和还原气氛下的热分解。在还原气氛中,[Ir(NH3)5Cl][OsСl6]形成(NH4)2[OsСl6<]其阳离子部分的Ir被氢还原,形成缺陷fcc结构的金属颗粒;最终产物是亚稳的hcp I.0.5Os0.5合金。在惰性气氛中,盐在较高的温度下分解而不形成任何可检测的结晶中间体;两相fcc+hcp混合物直接在800k以上形成。研究了所有合金在金刚石砧细胞中的室温压缩性高达50 GPa。Hcp-Ir0.24Ru0.36Os0.40 (B0 = 362(4) GPa, B0′= 4.8(2))和fcc - ir0.84 ru0.060 os0.10 (B0 = 302(7) GPa, B0′= 6.4(5))三元合金以及hcp-Ir0.33Ru0.67 (B0 = 332(2) GPa, B0′= 5.4(1))和fcc-Ir0.75Ru0.25 (B0 = 316(1) GPa, B0′= 5.1(1))二元合金在室温压缩时均未表现出任何相变。与其他已研究的锇铱超不可压缩耐火合金相比,hcp-Ir0.33Ru
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引用次数: 0
An Analysis of Using the Method of Two-Dimensional Digital Image Correlation in Glass Column Research 二维数字图像相关方法在玻璃柱研究中的应用分析
Pub Date : 2020-08-31 DOI: 10.15587/1729-4061.2020.209761
B. Demchyna, M. Surmai, R. Tkach, Vasylyna Hula, R. Kozak
The study of glass multilayer columns made of ordinary glass using triplexing technology. The main disadvantage of using ordinary glass is the fragile nature of its destruction, it breaks instantly. To avoid this effect, triplexing technology is used: the glass is joined in several layers with an EVASAFE polymer film (Bridgestone, Japan), after which the columns were heated to a temperature of 130 °C and kept for 30 minutes. The film material is an elastomer (a polymer with highly elastic properties in a wide temperature range). This allowed restraining parts of fragments of glass structures, making them plastic inside the bonding plane, increased their reliability, prevented the instantaneous opening of cracks in the depth of the section. A method for studying multilayer glass columns for central-axial compression using the method of two-dimensional digital image correlation is developed. Two series of prototypes were manufactured and tested. The tests were performed on a hydraulic press. The model of the destruction of glass columns of different cross-section is investigated and described. The accuracy of the digital image correlation method using two-dimensional correlation for glass centrally compressed columns is estimated. The results of the digital image correlation method with the results of measurements of absolute deformations by mechanical devices are compared. Based on the analysis of the results, the dependences of relative deformations e on the applied load N were determined using the digital image correlation method. The dependences of relative deformations e on normal stresses σ=N/A and dependences of relative deformations e on the outer glass surfaces on the applied load N are determined
以普通玻璃为原料,采用三工合成技术制备玻璃多层柱。使用普通玻璃的主要缺点是它的易碎性,它会瞬间破碎。为了避免这种影响,使用了三层复合技术:将玻璃与EVASAFE聚合物薄膜(普利司通,日本)连接在几层中,之后将柱加热到130°C并保持30分钟。薄膜材料是一种弹性体(在宽温度范围内具有高弹性的聚合物)。这允许限制玻璃结构碎片的部分,使它们在粘合平面内具有可塑性,增加了它们的可靠性,防止了截面深度裂缝的瞬间打开。提出了一种利用二维数字图像相关方法研究多层玻璃柱中心轴向压缩的方法。制造和测试了两个系列的原型机。试验是在液压机上进行的。对不同截面玻璃柱的破坏模型进行了研究和描述。对玻璃中心压缩柱的二维相关数字图像相关方法的精度进行了估计。将数字图像相关法的测量结果与机械装置的绝对变形测量结果进行了比较。在分析结果的基础上,采用数字图像相关方法确定了相对变形e与外加载荷N的依赖关系。确定了相对变形e对法向应力σ=N/A的依赖关系,以及玻璃外表面相对变形e对外加载荷N的依赖关系
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引用次数: 3
期刊
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