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An Empirical Muscle Intracellular Action Potential Model with Multiple Erlang Probability Density Functions based on a Modified Newton Method. 基于改进牛顿法的多Erlang概率密度肌肉细胞内动作电位经验模型。
IF 2.8 Q3 ENGINEERING, BIOMEDICAL Pub Date : 2013-04-14 eCollection Date: 2013-01-01 DOI: 10.4137/BECB.S11646
Gyutae Kim, Mohammed M Ferdjallah, Frederic D McKenzie

The convolution of the transmembrane current of an excitable cell and a weighting function generates a single fiber action potential (SFAP) model by using the volume conductor theory. Here, we propose an empirical muscle IAP model with multiple Erlang probability density functions (PDFs) based on a modified Newton method. In addition, we generate SFAPs based on our IAP model and referent sources, and use the peak-to-peak ratios (PPRs) of SFAPs for model verification. Through this verification, we find that the relation between an IAP profile and the PPR of its SFAP is consistent with some previous studies, and our IAP model shows close profiles to the referent sources. Moreover, we simulate and discuss some possible ionic activities by using the Erlang PDFs in our IAP model, which might present the underlying activities of ions or their channels during an IAP.

利用体积导体理论,将可兴奋细胞的跨膜电流与加权函数进行卷积,得到单纤维动作电位模型。在这里,我们提出了一个基于改进牛顿方法的具有多个Erlang概率密度函数(pdf)的经验肌肉IAP模型。此外,我们基于我们的IAP模型和参考源生成SFAPs,并使用SFAPs的峰峰比(ppr)进行模型验证。通过验证,我们发现一个IAP profile与其SFAP的PPR之间的关系与之前的一些研究是一致的,我们的IAP模型与参考来源表现出接近的profile。此外,我们通过在IAP模型中使用Erlang pdf来模拟和讨论一些可能的离子活动,这些活动可能会呈现IAP期间离子或其通道的潜在活动。
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引用次数: 2
Current status of endovascular devices to treat abdominal aortic aneurysms. 血管内装置治疗腹主动脉瘤的现状。
IF 2.8 Q3 ENGINEERING, BIOMEDICAL Pub Date : 2013-04-10 eCollection Date: 2013-01-01 DOI: 10.4137/BECB.S10970
Kamell Eckroth-Bernard, Robert Garvin, Evan Ryer

The introduction of endovascular abdominal aortic aneurysm (AAA) repair has revolutionized the therapeutic approach to patients with AAA. Due to an on-going and prolific collaboration between vascular interventionalists and biomedical engineers, the devices used to perform endovascular AAA repair have also changed dramatically. The purpose of this publication is to provide an overview of the currently available and upcoming options for endovascular AAA repair.

血管内腹主动脉瘤(AAA)修复的引入彻底改变了AAA患者的治疗方法。由于血管介入学家和生物医学工程师之间持续而丰富的合作,用于进行血管内AAA修复的设备也发生了巨大变化。本出版物的目的是概述当前可用的和即将到来的血管内AAA修复选择。
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引用次数: 24
Some perspectives on network modeling in therapeutic target prediction. 治疗目标预测中网络建模的一些观点。
IF 2.8 Q3 ENGINEERING, BIOMEDICAL Pub Date : 2013-02-21 eCollection Date: 2013-01-01 DOI: 10.4137/BECB.S10793
Reka Albert, Bhaskar DasGupta, Nasim Mobasheri

Drug target identification is of significant commercial interest to pharmaceutical companies, and there is a vast amount of research done related to the topic of therapeutic target identification. Interdisciplinary research in this area involves both the biological network community and the graph algorithms community. Key steps of a typical therapeutic target identification problem include synthesizing or inferring the complex network of interactions relevant to the disease, connecting this network to the disease-specific behavior, and predicting which components are key mediators of the behavior. All of these steps involve graph theoretical or graph algorithmic aspects. In this perspective, we provide modelling and algorithmic perspectives for therapeutic target identification and highlight a number of algorithmic advances, which have gotten relatively little attention so far, with the hope of strengthening the ties between these two research communities.

药物靶点识别对制药公司来说具有重大的商业利益,与治疗靶点识别相关的研究成果也不胜枚举。这一领域的跨学科研究涉及生物网络社区和图算法社区。典型的治疗目标识别问题的关键步骤包括综合或推断与疾病相关的复杂相互作用网络,将该网络与疾病的特定行为联系起来,并预测哪些成分是该行为的关键媒介。所有这些步骤都涉及图论或图算法方面。在这一视角中,我们将从建模和算法的角度来探讨治疗目标的识别,并重点介绍迄今为止关注较少的一些算法进展,希望能加强这两个研究领域之间的联系。
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引用次数: 0
Application of a Bioinformatics-Based Approach to Identify Novel Putative in vivo BACE1 Substrates. 应用基于生物信息学的方法鉴定新的假定体内BACE1底物。
IF 2.8 Q3 ENGINEERING, BIOMEDICAL Pub Date : 2013-02-03 eCollection Date: 2013-01-01 DOI: 10.4137/BECB.S8383
Joseph L Johnson, Emily Chambers, Keerthi Jayasundera

BACE1, a membrane-bound aspartyl protease that is implicated in Alzheimer's disease, is the first protease to cut the amyloid precursor protein resulting in the generation of amyloid-β and its aggregation to form senile plaques, a hallmark feature of the disease. Few other native BACE1 substrates have been identified despite its relatively loose substrate specificity. We report a bioinformatics approach identifying several putative BACE1 substrates. Using our algorithm, we successfully predicted the cleavage sites for 70% of known BACE1 substrates and further validated our algorithm output against substrates identified in a recent BACE1 proteomics study that also showed a 70% success rate. Having validated our approach with known substrates, we report putative cleavage recognition sequences within 962 proteins, which can be explored using in vivo methods. Approximately 900 of these proteins have not been identified or implicated as BACE1 substrates. Gene ontology cluster analysis of the putative substrates identified enrichment in proteins involved in immune system processes and in cell surface protein-protein interactions.

BACE1是一种与阿尔茨海默病有关的膜结合的天冬氨酸蛋白酶,是第一个切断淀粉样蛋白前体蛋白的蛋白酶,导致淀粉样蛋白-β的产生及其聚集形成老年斑,这是该疾病的一个标志性特征。很少有其他天然BACE1底物被鉴定,尽管它的底物特异性相对松散。我们报告了一种生物信息学方法,鉴定了几种假定的BACE1底物。使用我们的算法,我们成功地预测了70%已知BACE1底物的切割位点,并进一步验证了我们的算法输出与最近BACE1蛋白质组学研究中鉴定的底物的对比,该研究也显示了70%的成功率。在用已知底物验证了我们的方法后,我们报告了962种蛋白质的切割识别序列,可以使用体内方法进行探索。这些蛋白中约有900种尚未被鉴定或与BACE1底物有关。基因本体聚类分析的假设底物鉴定富集的蛋白质参与免疫系统过程和细胞表面蛋白蛋白相互作用。
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引用次数: 11
A Comparative Approach to Hand Force Estimation using Artificial Neural Networks. 一种基于人工神经网络的手部力估计比较方法。
IF 2.8 Q3 ENGINEERING, BIOMEDICAL Pub Date : 2012-07-30 eCollection Date: 2012-01-01 DOI: 10.4137/BECB.S9335
Farid Mobasser, Keyvan Hashtrudi-Zaad

In many applications that include direct human involvement such as control of prosthetic arms, athletic training, and studying muscle physiology, hand force is needed for control, modeling and monitoring purposes. The use of inexpensive and easily portable active electromyography (EMG) electrodes and position sensors would be advantageous in these applications compared to the use of force sensors which are often very expensive and require bulky frames. Among non-model-based estimation methods, Multilayer Perceptron Artificial Neural Networks (MLPANN) has widely been used to estimate muscle force or joint torque from different anatomical features in humans or animals. This paper investigates the use of Radial Basis Function (RBF) ANN and MLPANN for force estimation and experimentally compares the performance of the two methodologies for the same human anatomy, ie, hand force estimation, under an ensemble of operational conditions. In this unified study, the EMG signal readings from upper-arm muscles involved in elbow joint movement and elbow angular position and velocity are utilized as inputs to the ANNs. In addition, the use of the elbow angular acceleration signal as an input for the ANNs is also investigated.

在许多包括人类直接参与的应用中,例如假肢手臂的控制、运动训练和肌肉生理学的研究,都需要手的力量来进行控制、建模和监测。与使用通常非常昂贵且需要笨重框架的力传感器相比,使用廉价且易于携带的主动肌电图(EMG)电极和位置传感器在这些应用中是有利的。在非基于模型的估计方法中,多层感知器人工神经网络(Multilayer Perceptron Artificial Neural Networks, MLPANN)被广泛用于从人类或动物的不同解剖特征中估计肌肉力或关节扭矩。本文研究了径向基函数(RBF)神经网络和MLPANN用于力估计的使用,并在实验中比较了两种方法在相同人体解剖结构(即手的力估计)下在操作条件集合下的性能。在这个统一的研究中,上臂肌肉参与肘关节运动的肌电图信号读数和肘关节的角位置和速度被用作人工神经网络的输入。此外,还研究了肘关节角加速度信号作为人工神经网络输入的方法。
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引用次数: 23
Support Vector Machine Based Classification Model for Screening Plasmodium falciparum Proliferation Inhibitors and Non-Inhibitors 基于支持向量机的恶性疟原虫增殖抑制剂和非抑制剂筛选分类模型
IF 2.8 Q3 ENGINEERING, BIOMEDICAL Pub Date : 2011-01-01 DOI: 10.4137/BECB.S7503
S. Subramaniam, Monica Mehrotra, D. Gupta
There is an urgent need to develop novel anti-malarials in view of the increasing disease burden and growing resistance of the currently used drugs against the malarial parasites. Proliferation inhibitors targeting P. falciparum intraerythrocytic cycle are one of the important classes of compounds being explored for its potential to be novel antimalarials. Support Vector Machine (SVM) based model developed by us can facilitate rapid screening of large and diverse chemical libraries by reducing false hits and prioritising compounds before setting up expensive High Throughput Screening experiment. The SVM model, trained with molecular descriptors of proliferation inhibitors and non-inhibitors, displayed a satisfactory performance on cross validations and independent data set, with an average accuracy of 83% and AUC of 0.88. Intriguingly, the method displayed remarkable accuracy for the recently submitted P. falciparum whole cell screening datasets. The method also predicted several inhibitors in the National Cancer Institute diversity set, mostly similar to the known inhibitors.
鉴于疾病负担的增加和目前使用的抗疟疾药物的耐药性日益增强,迫切需要开发新的抗疟疾药物。针对恶性疟原虫红细胞内周期的增殖抑制剂是一类重要的化合物,因其潜在的新型抗疟药物而被探索。我们开发的基于支持向量机(SVM)的模型可以在建立昂贵的高通量筛选实验之前,通过减少错误命中和对化合物进行优先排序,促进大型和多样化化学文库的快速筛选。使用增殖抑制剂和非抑制剂分子描述符训练的SVM模型在交叉验证和独立数据集上表现出令人满意的性能,平均准确率为83%,AUC为0.88。有趣的是,该方法对最近提交的恶性疟原虫全细胞筛选数据集显示出显著的准确性。该方法还预测了国家癌症研究所多样性集中的几种抑制剂,大多数与已知抑制剂相似。
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引用次数: 7
Automated Cardiac Drug Infusion System Using Adaptive Fuzzy Neural Networks Controller 基于自适应模糊神经网络控制器的心脏药物自动输注系统
IF 2.8 Q3 ENGINEERING, BIOMEDICAL Pub Date : 2011-01-01 DOI: 10.4137/BECB.S6495
M. E. Karar, M. El-Brawany
This paper presents a fuzzy neural network (FNN) control system to automatically manage the hemodynamic variables of patients with hypertension and congestive heart failure (CHF) via simultaneous infusion of cardiac drugs such as vasodilators and inotropic agents. The developed system includes two FNN sub-controllers for regulating cardiac output (CO) and mean arterial pressure (MAP) by cardiac drugs, considering interactive pharmacological effects. The adaptive FNN controller was tested and evaluated on a cardiovascular model. Six short-term therapy conditions of hypertension and CHF are presented under different sensitivities of a vasodilator drug. The results of the automated system showed that root mean square errors were ≤ 5.56 mmHg and ≤ 0.22 L min-1 for regulating MAP and CO, respectively, providing short settling time responses of MAP (≤ 10.9 min) and CO (≤ 8.22 min) in all therapy conditions. The proposed FNN control scheme can significantly improve the performance of cardiac drug infusion System.
本文提出了一种模糊神经网络(FNN)控制系统,通过同时输注血管扩张剂和肌力药物等心脏药物,自动管理高血压和充血性心力衰竭(CHF)患者的血流动力学变量。该系统包括两个FNN子控制器,用于通过心脏药物调节心输出量(CO)和平均动脉压(MAP),并考虑了相互作用的药理作用。在心血管模型上对自适应FNN控制器进行了测试和评价。在不同的血管扩张剂药物敏感性下,提出了高血压和CHF的六种短期治疗条件。自动化系统的结果表明,调节MAP和CO的均方根误差分别≤5.56 mmHg和≤0.22 L min-1,在所有治疗条件下MAP和CO的稳定时间响应均较短(≤10.9 min)。所提出的FNN控制方案可以显著提高心脏药物输注系统的性能。
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引用次数: 23
Modelling the Molecular Transportation of Subcutaneously Injected Salubrinal 皮下注射Salubrinal的分子运输模型
IF 2.8 Q3 ENGINEERING, BIOMEDICAL Pub Date : 2011-01-01 DOI: 10.4137/BECB.S7050
Andy B. Chen, Ping Zhang, Z. Duan, Guofeng Wang, H. Yokota
For the subcutaneous administration of a chemical agent (salubrinal), we constructed a mathematical model of molecule transportation and subsequently evaluated the kinetics of diffusion, convection, and molecular turnover. Salubrinal is a potential therapeutic agent that can reduce cellular damage and death. The understanding of its temporal profiles in local tissue as well as in a whole body is important to develop a proper strategy for its administration. Here, the diffusion and convection kinetics was formulated using partial and ordinary differential equations in one- and three-dimensional (semi-spherical) coordinates. Several key parameters including an injection velocity, a diffusion coefficient, thickness of subcutaneous tissue, and a permeability factor at the tissue-blood boundary were estimated from experimental data in rats. With reference to analytical solutions in a simplified model without convection, numerical solutions revealed that the diffusion coefficient and thickness of subcutaneous tissue determined the timing of the peak concentration in the plasma, and its magnitude was dictated by the permeability factor. Furthermore, the initial velocity, induced by needle injection, elevated an immediate transport of salubrinal at t < 1h. The described analysis with a combination of partial and ordinary differential equations contributes to the prediction of local and systemic effects and the understanding of the transportation mechanism of salubrinal and other agents.
对于化学制剂(salubrinal)的皮下给药,我们构建了分子运输的数学模型,并随后评估了扩散、对流和分子周转的动力学。Salubrinal是一种潜在的治疗药物,可以减少细胞损伤和死亡。了解其在局部组织和整个身体中的时间概况对于制定适当的管理策略非常重要。在这里,扩散和对流动力学用偏微分方程和常微分方程在一维和三维(半球面)坐标下表示。根据大鼠的实验数据,估计了注射速度、扩散系数、皮下组织厚度和组织-血液边界的渗透系数等几个关键参数。参考简化模型中无对流的解析解,数值解表明,扩散系数和皮下组织厚度决定了血浆中浓度峰值的时间,其大小由渗透因子决定。此外,针注射诱导的初始速度在t < 1h时增加了钠盐的即时转运。所描述的结合偏微分方程和常微分方程的分析有助于局部和系统效应的预测,以及对盐和其他物质的运输机制的理解。
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引用次数: 1
Computational Methodologies for Analyzing, Modeling and Controlling Gene Regulatory Networks 分析、建模和控制基因调控网络的计算方法
IF 2.8 Q3 ENGINEERING, BIOMEDICAL Pub Date : 2010-01-01 DOI: 10.4137/BECB.S5594
Zahra Zamani, A. Hajihosseini, A. Masoudi-Nejad
Molecular biology focuses on genes and their interactions at the transcription, regulation and protein level. Finding genes that cause certain behaviors can make therapeutic interventions more effective. Although biological tools can extract the genes and perform some analyses, without the help of computational methods, deep insight of the genetic function and its effects will not occur. On the other hand, complex systems can be modeled by networks, introducing the main data as nodes and the links in-between as the transactions occurring within the network. Gene regulatory networks are examples that are modeled and analyzed in order to gain insight of their exact functions. Since a cell's specific functionality is greatly determined by the genes it expresses, translation or the act of converting mRNA to proteins is highly regulated by the control network that directs cellular activities. This paper briefly reviews the most important computational methods for analyzing, modeling and controlling the gene regulatory networks.
分子生物学主要研究基因及其在转录、调控和蛋白质水平上的相互作用。找到导致某些行为的基因可以使治疗干预更有效。虽然生物工具可以提取基因并进行一些分析,但如果没有计算方法的帮助,就无法深入了解遗传功能及其影响。另一方面,复杂的系统可以通过网络建模,将主要数据作为节点引入,将中间的链接作为网络中发生的事务引入。基因调控网络是建模和分析的例子,以便深入了解它们的确切功能。由于细胞的特定功能在很大程度上取决于它所表达的基因,翻译或将mRNA转化为蛋白质的行为受到指导细胞活动的控制网络的高度调节。本文简要介绍了基因调控网络分析、建模和控制的主要计算方法。
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引用次数: 3
Computational Identification of Putative miRNAs from Felis Catus 猫类推测mirna的计算鉴定
IF 2.8 Q3 ENGINEERING, BIOMEDICAL Pub Date : 2010-01-01 DOI: 10.4137/BECB.S5233
G. Sathyamurthy, N. Swamy
microRNAs represent a class of noncoding small RNAs of approximately 20–23 nt length, which are evolutionarily conserved and play a vital role in various biological processes by either degrading or repressing mRNA translation. The Felis catus (cat) genome sequence has been published, and just revealed the number of miRNAs in the genome–-without mention of any further details on these miRNAs. This paper discusses an in silico comparative approach using all known sequences of vertebrate pre-miRNA as query sequence, and report 405 putative miRNAs from cat genome. We determine the identity values of pre-miRNAs and mature miRNAs besides statistical sequence characteristics. Interestingly, among 405 miRNAs–-90, 53 and 50 showed 100% identity to cattle, human and dog, respectively. Further, we have validated 6 miRNAs, whose identity are <85% with the query sequence and validated them using MiPred algorithm. We also identify 25 miRNA clusters in cat based on their homologs in other vertebrates. Most importantly, based on identities among pre-miRNA, mature miRNA, miRNA families and clusters, we observe that miRNAs from cat are more identical to cattle, than humans. Our results, therefore may add a new dimension to the studies related to the evolution of cat.
microRNAs是一类长度约为20 - 23nt的非编码小rna,具有进化保守性,通过降解或抑制mRNA翻译在各种生物过程中发挥重要作用。猫科动物(Felis catus)的基因组序列已被公布,仅揭示了基因组中mirna的数量,而没有提及这些mirna的任何进一步细节。本文讨论了一种利用所有已知的脊椎动物pre-miRNA序列作为查询序列的计算机比较方法,并报道了猫基因组中405个推测的mirna。除了统计序列特征外,我们还确定了pre- mirna和成熟mirna的身份值。有趣的是,在405个mirna中,分别有90个、53个和50个与牛、人和狗100%同源。此外,我们还验证了6个与查询序列同源性<85%的mirna,并使用MiPred算法进行了验证。我们还根据它们在其他脊椎动物中的同源物在猫中鉴定了25个miRNA簇。最重要的是,基于pre-miRNA、成熟miRNA、miRNA家族和miRNA簇的特性,我们观察到猫的miRNA与牛的miRNA比人类的miRNA更相似。因此,我们的研究结果可能会为猫的进化研究增加一个新的维度。
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引用次数: 2
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Biomedical Engineering and Computational Biology
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