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中国地球物理学会年刊最新文献

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Regulation of cardiac repolarization by adenoviral gene transfer rationalized by computational modeling 计算模型证明了腺病毒基因转移对心脏复极化的调节作用
Pub Date : 2002-12-01 DOI: 10.1109/IEMBS.2002.1053257
R. Mazhari, E. Marbán, R. Winslow
Regulatory subunit KCNE3 (E3) interacts with KCNQ1 (Q1) in epithelia, regulating its activation kinetics and augmenting current density. Since E3 is expressed weakly in the heart, we hypothesized that ectopic expression of E3 in cardiac myocytes might abbreviate action potential duration by interacting with Q1 and augmenting the delayed rectifier current (I/sub K/). We constructed an adenoviral vector co-expressing GFP and E3, and injected it Into the left ventricular cavity of guinea pigs. After 72 hrs, the electrocardiographic QT interval was reduced by /spl sim/10% compared to baseline. E3-transduced cells had an APD/sub 90/ of 87 /spl plusmn/ 8 vs. 298 /spl plusmn/ 19 ms in control cells, while E-4031-insensitive I/sub K/ and activation kinetics were significantly augmented. Quantitative modeling of a transmural cardiac segment rationalized the degree of QT-interval abbreviation as a consequence of electrotonic interactions in the face of limited transduction efficiency and showed that heterogeneous transduction of E3 may actually potentiate arrhythmias. The results provide proof of the principle that ectopic expression of regulatory subunits can be exploited to enhance repolarization, a principle that may be useful in treating long QT syndrome (but only if fairly homogeneous ventricular expression can be achieved).
调控亚基KCNE3 (E3)与上皮细胞中的KCNQ1 (Q1)相互作用,调节其激活动力学并增加电流密度。由于E3在心脏中的表达较弱,我们假设E3在心肌细胞中的异位表达可能通过与Q1相互作用并增加延迟整流电流(I/sub K/)而缩短动作电位持续时间。构建了GFP与E3共表达的腺病毒载体,并将其注入豚鼠左心室。72小时后,心电图QT间期与基线相比减少了10%。e3转导细胞的APD/sub 90/为87 /spl plusmn/ 8,而对照组细胞的APD/sub 90/为298 /spl plusmn/ 19 ms,而e -4031不敏感细胞的I/sub K/和活化动力学显著增强。跨壁心脏段的定量建模合理化了面对有限转导效率的电紧张相互作用导致的qt间期缩短的程度,并表明E3的异质性转导实际上可能加剧心律失常。结果证明了调控亚基的异位表达可以增强复极,这一原理可能对治疗长QT综合征有用(但前提是能够实现相当均匀的心室表达)。
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引用次数: 0
Cell tracking velocimetry for monocyte/endothelial cell interactions 单核细胞/内皮细胞相互作用的细胞跟踪测速仪
Pub Date : 2002-12-01 DOI: 10.1109/IEMBS.2002.1134526
P. Wong, C. H. Kwong, T. Hsiai, C. Ho
This paper reports the study of the trajectory patterns that exist when monocyte and endothelial cells interact within the oscillatory flow known to be present in arterial bifurcations. The rolling and tumbling of monocytes, followed by the tethering and firm attachment to endothelial cells were observed. A cell tracking velocimetry algorithm was developed to characterize the real time cell-cell interactions. The algorithm allows tracking of large amounts of cell trajectories automatically, which is essential for statistical analysis of cell interaction events.
本文报道了当单核细胞和内皮细胞在已知存在于动脉分叉的振荡流动中相互作用时存在的轨迹模式的研究。观察到单核细胞的滚动和翻滚,随后与内皮细胞的系缚和牢固附着。开发了一种细胞跟踪测速算法来描述细胞与细胞之间的实时相互作用。该算法允许自动跟踪大量细胞轨迹,这对于细胞相互作用事件的统计分析至关重要。
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引用次数: 0
Model-based image processing and analysis for fracture classification 基于模型的裂缝分类图像处理与分析
Pub Date : 2002-12-01 DOI: 10.1109/IEMBS.2002.1053408
A. Adami, K. Yang, X. Song, M. Pavel, D. Dirschl
We describe an approach toward improved classification of fractures in the vicinity of ankle joints using image-specific image enhancement and 3D modeling. The enhancement approach is based on the development of a set of linear features from X-ray images. The 3D models of fractures are used to determine the X-ray image representation from a fractured surface. These models are then used in reverse to find surface parameters that are most consistent with the 2D fracture representations.
我们描述了一种使用图像特定图像增强和3D建模来改进踝关节附近骨折分类的方法。增强方法是基于x射线图像的一组线性特征的发展。裂缝的三维模型用于确定裂缝表面的x射线图像表示。然后,反过来使用这些模型来找到与2D裂缝表示最一致的表面参数。
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引用次数: 2
Elucidation of simple optic stimuli based on detected nerve activity 基于检测到的神经活动来解释简单的视觉刺激
Pub Date : 2002-12-01 DOI: 10.1109/IEMBS.2002.1134377
T.D. Coates, S. Wolpert
In this study, a minimally invasive interface to an intact peripheral nerve was developed. The interface was based on a cylindrical cuff installed around the nerve, and fitted with circumferentially dispersed surface electrodes. Differential measurements of bulk potentials were filtered, amplified, and subsequently processed with the objective of identifying unique patterns of electrical activity within the ensheathed nerve bundle. The system was implemented using an in vivo preparation of lateral eye and optic nerve from Limulus polyphemus. Recorded signals were filtered using the discrete wavelet transform and the Daubechies 4 wavelet basis to isolate signal components regarded as significant to the optical pattern. The entropies of the filtered signals were computed and used to build training and testing patterns for a cascade correlation neural network. The values on the eight outputs of the neural network represented the probability of one or more of the eight locations on the lateral eye having been illuminated by the stimulus. From these outputs, an image of the optical stimulus pattern was rendered. In tests, the system displayed an accuracy of 100% in distinguishing stimulus from nonstimulus conditions, and up to 91% in identifying the location(s) illuminated by a given pattern of optical stimulation.
在这项研究中,开发了一种与完整周围神经连接的微创界面。该界面是基于安装在神经周围的圆柱形袖带,并配有沿周分散的表面电极。体积电位的不同测量值经过过滤、放大,并随后进行处理,目的是识别包裹神经束内独特的电活动模式。该系统采用多足limus的侧眼和视神经在体制备。采用离散小波变换和Daubechies 4小波基对记录的信号进行滤波,分离出对光学图形有重要意义的信号分量。计算滤波后信号的熵,并用于建立级联相关神经网络的训练和测试模式。神经网络的8个输出值代表了侧眼上8个位置中一个或多个位置被刺激照亮的概率。从这些输出中,呈现出光学刺激图案的图像。在测试中,该系统在区分刺激和非刺激条件方面的准确率为100%,在识别给定光刺激模式照亮的位置方面的准确率高达91%。
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引用次数: 0
Optimization of PEI/VEGF DNA polyplexes for potenital delivery from tissue engineering scaffolds PEI/VEGF DNA复合物的优化,用于组织工程支架的潜在递送
Pub Date : 2002-12-01 DOI: 10.1109/IEMBS.2002.1136951
J. H. van Zanten, Y. Har-el, J. Hanes
Non-viral vector formation by DNA complexation with cationic condensing agents is a self-assembly process driven primarily by electrostatic interactions and counterion release. DNA complexation kinetics influence three physical parameters that have a direct effect on gene delivery and expression efficiency: DNA complex geometric size, surface charge and density. We demonstrate the utility of time resolved multiangle laser light scattering (TR-MALLS) for probing polyethylenimine (PEI) based polyplex formation kinetics with plasmid DNA. Our studies utilize plasmid DNA coding for VEGF, which may be used to enhance blood vessel in-growth into cell seeded polymeric scaffolds used in tissue engineering applications. We determined PEI/DNA complex size and density in real time and monitored vector stability in various liquid formulations. Parameters such as PEI molecular weight, N/P ratio and solution pH and ionic strength were investigated systematically. The ability to accurately measure polyplex size and density may lead to improvements in the design and control of non-viral gene delivery vectors and facilitate the determination of optimal formulations.
DNA与阳离子凝聚剂络合形成的非病毒载体是一个主要由静电相互作用和反离子释放驱动的自组装过程。DNA络合动力学影响三个对基因传递和表达效率有直接影响的物理参数:DNA复合物的几何尺寸、表面电荷和密度。我们展示了时间分辨多角度激光散射(tr - mall)用于探测基于聚乙烯亚胺(PEI)的多聚体形成动力学与质粒DNA的效用。我们的研究利用质粒DNA编码VEGF,可用于促进血管生长成细胞种子聚合物支架,用于组织工程应用。我们实时测定了PEI/DNA复合物的大小和密度,并监测了载体在各种液体配方中的稳定性。系统地考察了PEI的分子量、N/P比、溶液pH和离子强度等参数。精确测量多聚体大小和密度的能力可能导致非病毒基因传递载体的设计和控制的改进,并有助于确定最佳配方。
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引用次数: 0
Integration of the "How people learn" framework into educational module development and implementation in biotechnology 将“人如何学习”框架整合到生物技术教育模块的开发和实施中
Pub Date : 2002-12-01 DOI: 10.1109/IEMBS.2002.1053468
G. Birol, A. McKenna, H. Smith, T. Giorgio, S. Brophy
A team of domain experts, learning scientists, learning technologists, assessment experts and students are currently working on developing and refining educational tools for biotechnology as well as for other domains within the "How People Learn" framework in the NSF funded VaNTH ERC in Bioengineering Educational Technologies. Educational modules In biotechnology cover a collection of challenges designed around bioreactors, mass and momentum transfer issues, and microbial kinetics, which are among core biotechnology topics. The activities form the core of the STAR Legacy Cycle method that was adopted as the template for module development. These modules have been tested in classrooms both at Vanderbilt and Northwestern and detailed assessment data have also been collected. The focus of this contribution is on development and implementation of these educational modules at two universities (VU and NJU).
一个由领域专家、学习科学家、学习技术专家、评估专家和学生组成的团队目前正致力于开发和完善生物技术的教育工具,以及在美国国家科学基金会资助的VaNTH生物工程教育技术ERC的“人们如何学习”框架下的其他领域。生物技术的教育模块涵盖了围绕生物反应器、质量和动量转移问题以及微生物动力学设计的一系列挑战,这些都是生物技术的核心主题。这些活动构成了STAR遗留周期方法的核心,该方法被用作模块开发的模板。这些模块已经在范德比尔特大学和西北大学的课堂上进行了测试,并收集了详细的评估数据。这项贡献的重点是在两所大学(VU和NJU)开发和实施这些教育模块。
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引用次数: 9
Shear stress distributions on the membrane of endothelial cells using 3-D computational modeling with fluid-structure interactions 基于流固耦合的内皮细胞膜剪切应力三维计算模型研究
Pub Date : 2002-12-01 DOI: 10.1109/IEMBS.2002.1136852
D. Tang, Chun Yang, S.Q. Liu
Fluid shear stress may play an important role in regulating cell activities and motility of growth factors in artery remodeling, atherosclerosis and re-stenosis process. 3-D computational models based on a multi-cell experimental model are introduced and solved to quantify shear stress distributions on cell surfaces under physiological setting. Combined with experimental data, relationship between fluid shear stress and endothelial cell activities can be established. Cell geometry and membrane mechanical properties affect micro flow environment leading to considerable changes in shear stress distributions and various cell activities such as cell migration and activation of cell migration signaling mechanisms.
流体剪切应力可能在动脉重构、动脉粥样硬化和再狭窄过程中调节细胞活性和生长因子的运动中起重要作用。引入并求解了基于多细胞实验模型的三维计算模型,以量化生理条件下细胞表面的剪应力分布。结合实验数据,建立了流体剪切应力与内皮细胞活性之间的关系。细胞几何和膜力学特性影响微流环境,导致剪切应力分布和各种细胞活动的显著变化,如细胞迁移和激活细胞迁移信号机制。
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引用次数: 0
Microarray analysis of the chondrocytic cell line T/C-28a2 under dynamic fluid shear 动态流体剪切作用下T/C-28a2软骨细胞微阵列分析
Pub Date : 2002-12-01 DOI: 10.1109/IEMBS.2002.1137001
J. Abulencia, R. Gaspard, John Quackenbush, K. Konstantopoulos
The behavior of the chondrocytic cell line T/C-28a2 under shear flow was examined using a 32,448 element microarray. A parallel plate flow chamber was used to generate a shear stress level of 20 dyn/cm/sup 2/ for 1.5 or 24 hours (h), after which gene regulation was measured. Microarray analysis revealed differentially regulated genes affecting proliferation/differentiation, extracellular matrix/cytoskeleton, and inflammation at both time points. A ribonuclease protection assay was performed on a subset of genes to confirm the data obtained from the microarray. However, the cyclooxygenase-2 (COX-2) gene, which plays a role in the prostaglandin production in inflamed tissues and the synovium of rheumatoid arthritis (RA) patients, was studied further. Western hybridization revealed that COX-2 protein is present at 24 h, but not at 6 or 12 h. Also, immunofluorescence microscopy shows that COX-2 protein localizes in the cytosol after 24 h of shear, and is not present after 1.5 h. By examining the overall gene expression profiles of chondrocytes under different conditions of dynamic fluid shear, new insights on the pathogenesis of cartilage related diseases such as rheumatoid arthritis might be generated.
使用32,448个元件的微阵列检测了软骨细胞系T/C-28a2在剪切流下的行为。平行板流室产生20 dyn/cm/sup 2/的剪切应力水平,持续1.5或24小时(h),之后测量基因调控。微阵列分析显示,在两个时间点,影响增殖/分化、细胞外基质/细胞骨架和炎症的基因受到差异调节。核糖核酸酶保护试验对基因子集进行,以确认从微阵列获得的数据。然而,对类风湿性关节炎(RA)患者炎症组织和滑膜中前列腺素生成的环氧化酶-2 (COX-2)基因进行了进一步的研究。Western杂交显示COX-2蛋白在24 h时存在,但在6或12 h时不存在。免疫荧光显微镜显示COX-2蛋白在剪切24 h后定位于细胞质中,在1.5 h后不存在。通过检测不同动态流体剪切条件下软骨细胞的整体基因表达谱,可能对类风湿性关节炎等软骨相关疾病的发病机制产生新的见解。
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引用次数: 0
New degradable cationic polyesters for nonviral gene delivery 用于非病毒基因传递的新型可降解阳离子聚酯
Pub Date : 2002-12-01 DOI: 10.1109/IEMBS.2002.1136945
Jie Fu, E. Krauland, Y. Har-el, J. Hanes
A new family of biodegradable cationic polyesters consisting of aspartic acid and aliphatic diols of various lengths has been synthesized. Since the polymers formed are strictly alternating, the cationic charge density can be controlled by simply changing the size of the spacer aliphatic monomer. One such polymer, poly(aspartic anhydride-co-ethylene glycol) (PAE), was found to be capable of self-assembly (/spl sim/100 nm) into polymeric micelles and complexation with DNA. Kinetic studies reveal PAE initially complexes DNA into sub-100 nm complexes and subsequently releases it after 3-6 days at room temperature. With the ability to degrade and unpack its genetic material, this new family of biodegradable cationic polymers shows promise as versatile gene carriers for in vitro and in vivo applications.
合成了一个由天冬氨酸和不同长度的脂肪二醇组成的可生物降解阳离子聚酯新家族。由于形成的聚合物是严格交替的,阳离子电荷密度可以通过简单地改变间隔脂肪族单体的大小来控制。其中一种聚合物,聚天冬氨酸酸酐-共乙二醇(PAE),被发现能够自组装(/spl sim/100 nm)成聚合物胶束并与DNA络合。动力学研究表明,PAE最初将DNA配合成亚100 nm的复合物,随后在室温下3-6天后释放DNA。由于具有降解和拆封其遗传物质的能力,这种新的可生物降解阳离子聚合物家族有望成为体外和体内应用的多功能基因载体。
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引用次数: 0
Assembly and characterization of biofunctional GABA-immobilized surfaces 生物功能氨基丁酸固定表面的组装和表征
Pub Date : 2002-12-01 DOI: 10.1109/IEMBS.2002.1053050
T. Vu, U. Saifuddin, M. Řezáč, H. Qian, D. R. Pepperberg, T. Desai
Here we report progress toward the development of bioactive surfaces based on GABA, a major neurotransmitter in the nervous system. While immobilization techniques have focused largely on antibodies, enzymes, and receptors, to our knowledge, this is the first report of a prototype neurotransmitter-immobilized surface. Biosurfaces were assembled onto either mica or glass using passive adsorption of avidin and subsequent attachment of a derivatized form of GABA via a biotin-avidin affinity bond. Surface characterization was carried out using atomic force microscopy to visualize surface topology. The data reveal 1) passive adsorption of avidin is uniformly dispersed and cluster densities can be controlled through the concentration of the avidin incubation solution; and 2) GABA tethered via biotin to these avidin surfaces showed a homogenous distribution of the tethered neurotransmitter molecule onto glass and two different population distributions onto mica. Functional assays performed to test the biological activity or the synthesized GABA, direct sandwich ELISA, as well as comparison of AFM images of anti-GABA antibody incubation of these prepared GABA surfaces to control studies using anti-IgG antibody, together support the idea that these synthesized surfaces are biofunctional.
在这里,我们报告了基于GABA(神经系统中的一种主要神经递质)的生物活性表面的发展进展。虽然固定化技术主要集中在抗体、酶和受体上,但据我们所知,这是第一次报道神经递质固定化表面的原型。生物表面通过生物素-亲和素亲和键被动吸附在云母或玻璃上,然后通过生物素-亲和素亲和键连接衍生形式的GABA。使用原子力显微镜进行表面表征以可视化表面拓扑结构。结果表明:1)亲和素的被动吸附是均匀分散的,通过亲和素培养液的浓度可以控制簇密度;2) GABA通过生物素拴在亲和素表面上,显示出拴在玻璃上的神经递质分子均匀分布,而在云母上则有两种不同的种群分布。用于测试合成GABA生物活性的功能分析,直接夹心ELISA,以及对这些制备的GABA表面的抗GABA抗体孵育的AFM图像进行比较,以使用抗igg抗体进行对照研究,共同支持这些合成表面具有生物功能的观点。
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引用次数: 0
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中国地球物理学会年刊
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