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Multi-Objective Optimal Regulation of Glucose Concentration in Type I Diabetes Mellitus 1型糖尿病血糖浓度的多目标优化调控
Pub Date : 2022-11-08 DOI: 10.1115/1.4056176
Raya Abushaker, Y. Sardahi, Ahmad M. Alshorman
Type I diabetes is a chronic disease in which insulin is not adequately produced by the pancreatic β-cells, which leads to a high glucose concentration. In practice, external Insulin delivery is the only method to deal with this disease. To this end, a multi-objective optimal control for insulin delivery is introduced in this paper. Three conflicting objectives are considered: minimizing the risk of hypoglycemia and hyperglycemia, and reducing the amount of injected insulin. These objectives are simultaneously minimized while tuning the closed-loop system parameters that include the design details of the linear-quadratic regulator(LQR) and estimator speed of convergence. The lower and upper bounds of the LQR setup parameters are determined by Bryson's rule taking into account the nominal glucose range (70 – 160 mg/dL) and maximum and minimum pump infusion rates (0.0024 –15 mU/min). The lower and upper bounds of the estimator convergence speed are chosen such that the estimator is faster than the fastest mode of the closed-loop system. For computer simulations, Bergman's minimal model, which is one of the commonly used models, is employed to simulate glucose-insulin dynamics in Type-I diabetic patients. The non-dominated sorting genetic algorithm (NSGA-II) solves the optimization problem, one of the widely used algorithms in solving multi-objective optimization problems (MOPs). The optimal solutions in terms of the Pareto set and its image, the Pareto front, are obtained and analyzed. The results show that the MOP solution introduces many optimal options from which the decision-maker can choose to implement. Furthermore, under high initial glucose levels, parametric variations of Bergman's model, and external disturbance; the optimal control performance is tested to show that the system can bring glucose levels quickly to the desired value regardless of high initial glucose concentrations, can efficiently work for different patients, and is robust against irregular snacks or meals.
1型糖尿病是一种慢性疾病,其中胰腺β细胞不能充分产生胰岛素,从而导致葡萄糖浓度升高。在实践中,外部胰岛素输送是治疗这种疾病的唯一方法。为此,本文提出了胰岛素输送的多目标优化控制方法。考虑到三个相互冲突的目标:最小化低血糖和高血糖的风险,减少注射胰岛素的量。在调整闭环系统参数(包括线性二次型调节器(LQR)和估计器收敛速度的设计细节)时,这些目标同时最小化。LQR设置参数的下界和上界由Bryson规则确定,考虑标称葡萄糖范围(70 - 160 mg/dL)和最大和最小泵注速率(0.0024 - 15 mU/min)。选取估计器收敛速度的下界和上界,使估计器收敛速度快于闭环系统的最快模式。在计算机模拟方面,采用常用的模型之一Bergman最小模型来模拟i型糖尿病患者的葡萄糖-胰岛素动力学。非支配排序遗传算法(non- dominant sorting genetic algorithm, NSGA-II)是求解多目标优化问题中应用最广泛的算法之一。得到并分析了Pareto集合及其图像Pareto front的最优解。结果表明,MOP解决方案引入了许多最优选项,决策者可以从中选择实施。此外,在高初始血糖水平下,Bergman模型的参数变化和外部干扰;优化控制性能测试表明,无论初始葡萄糖浓度高,该系统都能快速将葡萄糖水平降至所需值,可以有效地为不同的患者工作,并且对不规则的零食或膳食具有鲁棒性。
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引用次数: 0
Gender Differences in Cervical Spine Motions and Loads With Head Supported Mass Using Finite Element Models. 基于有限元模型的颈椎运动和头部承重的性别差异。
Pub Date : 2022-11-01 Epub Date: 2022-07-07 DOI: 10.1115/1.4054856
Yuvaraj Purushothaman, Narayan Yoganandan

While many studies have been conducted to delineate the role of gender in rear impact via experiments, clinical investigations, modeling, and epidemiological research, the effect of the added head mass on segmental motions has received less attention. The objective of the study is to determine the role of the head supported mass on the segmental motions and loads on the cervical spinal column from rear impact loading. The study used finite element modeling. The model was subjected to mesh convergence studies. It was validated with human cadaver experimental data by applying the rear impact acceleration pulse to the base of the spine. At all levels of the subaxial spinal column, a comparison was made between male and female spines and with and without the use of an army combat helmet. For this purpose, segmental motions, forces, and bending moments were used as biomechanical parameters. Results showed that female spines responded with increased motions than males, and the presence of a helmet increased motions and loads in males and female spines at all levels. Numerical data are given. Head supported mass affects spine responses at all levels. The present computational modeling study, from one geometry for the male spine and one geometry for the female spine (limitations are addressed in the paper), provided insights into the mechanisms of the internal load transfer with the presence of head supported mass, prevalent in certain civilian occupations and active-duty Service members in the military.

虽然许多研究通过实验、临床调查、建模和流行病学研究来描述性别在后部碰撞中的作用,但增加的头部质量对节段运动的影响却很少受到关注。本研究的目的是确定头部支撑物对颈椎节段运动和后部冲击载荷的作用。本研究采用有限元模型。对模型进行了网格收敛研究。将后冲击加速度脉冲作用于脊柱基部,用人体尸体实验数据进行了验证。在脊柱下轴的所有水平上,对男性和女性的脊柱以及是否使用军队战斗头盔进行了比较。为此,采用节段运动、力和弯矩作为生物力学参数。结果表明,女性脊柱的运动响应比男性增加,并且在所有水平上,头盔的存在增加了男性和女性脊柱的运动和负荷。给出了数值数据。头部支撑的肿块影响脊柱各层次的反应。目前的计算建模研究,从男性脊柱的一种几何形状和女性脊柱的一种几何形状(局限性在文中得到了解决),提供了对头部支撑质量存在的内部载荷传递机制的见解,这种机制普遍存在于某些平民职业和现役军人中。
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引用次数: 4
Assessment of Heterogeneity in Lung Structure and Function During Mechanical Ventilation: A Review of Methodologies. 机械通气过程中肺结构和功能异质性的评估:方法综述。
Pub Date : 2022-11-01 Epub Date: 2022-05-11 DOI: 10.1115/1.4054386
Jacob Herrmann, Michaela Kollisch-Singule, Joshua Satalin, Gary F Nieman, David W Kaczka

The mammalian lung is characterized by heterogeneity in both its structure and function, by incorporating an asymmetric branching airway tree optimized for maintenance of efficient ventilation, perfusion, and gas exchange. Despite potential benefits of naturally occurring heterogeneity in the lungs, there may also be detrimental effects arising from pathologic processes, which may result in deficiencies in gas transport and exchange. Regardless of etiology, pathologic heterogeneity results in the maldistribution of regional ventilation and perfusion, impairments in gas exchange, and increased work of breathing. In extreme situations, heterogeneity may result in respiratory failure, necessitating support with a mechanical ventilator. This review will present a summary of measurement techniques for assessing and quantifying heterogeneity in respiratory system structure and function during mechanical ventilation. These methods have been grouped according to four broad categories: (1) inverse modeling of heterogeneous mechanical function; (2) capnography and washout techniques to measure heterogeneity of gas transport; (3) measurements of heterogeneous deformation on the surface of the lung; and finally (4) imaging techniques used to observe spatially-distributed ventilation or regional deformation. Each technique varies with regard to spatial and temporal resolution, degrees of invasiveness, risks posed to patients, as well as suitability for clinical implementation. Nonetheless, each technique provides a unique perspective on the manifestations and consequences of mechanical heterogeneity in the diseased lung.

哺乳动物肺的结构和功能都具有异质性,包括一个不对称的分支气道树,优化了维持有效的通气、灌注和气体交换。尽管肺部自然存在的异质性有潜在的好处,但病理过程也可能产生有害的影响,这可能导致气体输送和交换的不足。无论病因如何,病理异质性导致局部通气和灌注分布不均匀,气体交换受损,呼吸功增加。在极端情况下,异质性可能导致呼吸衰竭,需要机械呼吸机的支持。本文综述了机械通气过程中用于评估和量化呼吸系统结构和功能异质性的测量技术。这些方法可分为四大类:(1)非均质力学函数的逆建模;(2)测量气体输运非均质性的毛细管造影和冲洗技术;(3)肺表面非均匀变形测量;(4)观测空间分布通风或区域变形的成像技术。每种技术在空间和时间分辨率、侵入程度、对患者构成的风险以及临床实施的适用性方面各不相同。尽管如此,每种技术都为病变肺的力学异质性的表现和后果提供了独特的视角。
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引用次数: 2
Gesture Recognition and Master-slave Control of a Manipulator Based On Semg and CNN-GRU 基于Semg和CNN-GRU的机械手手势识别与主从控制
Pub Date : 2022-10-30 DOI: 10.1115/1.4056325
Zhaojie Ge, Zhile Wu, Xu Han, Ping Zhao
Surface electromyography signal (sEMG) is the bioelectric signal accompanied by muscle contraction. For masterslave manipulation scenario such as patients with prosthetic hands, their upper limb sEMG signals can be collected and corresponded to the patient' s gesture intention. Therefore, using a slave manipulator that integrated with the sEMG signal recognition module, the master side could control it to make gestures and meet their needs of daily life. In this paper, gesture recognition is carried out based on sEMG and deep learning, and the master-slave control of manipulator is realized. According to the results of training, the network model with the highest accuracy of gesture classification and recognition can be obtained. Then, combined with the integrated manipulator, the control signal of the manipulator corresponding to the gesture is sent to the control module of the manipulator. In the end, a prototype system is built and the master-slave control of the manipulator using the sEMG signal is realized.
肌表电信号是伴随肌肉收缩的生物电信号。对于主从操作场景,如假手患者,可以收集其上肢肌电信号,并与患者的手势意图相对应。因此,使用与表面肌电信号识别模块集成的从机械手,主方可以控制其做出手势,满足其日常生活的需要。本文基于表面肌电信号和深度学习进行了手势识别,实现了机械手的主从控制。根据训练结果,可以得到具有最高准确率的手势分类识别网络模型。然后结合集成机械手,将手势所对应的机械手的控制信号发送到机械手的控制模块。最后搭建了一个原型系统,利用表面肌电信号实现了机械手的主从控制。
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引用次数: 3
Matrix-Patterned Micromarkers for Tracking Local Contractile Movements of Myotubes Cultured on Thin-Film Scaffold 基质模式微标记跟踪薄膜支架上肌管局部收缩运动
Pub Date : 2022-10-30 DOI: 10.1115/1.4056779
S. Hashimoto
To measure the distribution of local contractile movements in the layer of the myotubes, the movement of the matrix pattern of micro-markers placed on the back surface of the myotube-attached thin film has been tracked in vitro. A matrix pattern of micromarkers (diameter: 4 μm, height: 2 μm, interval: 30 μm) was fabricated on the back of a polydimethylsiloxane thin film (thickness: 6 μm) using photolithography. Mouse myoblasts were seeded on the front of the thin film and cultured for 10 days to differentiate into myotubes. Periodic electrical pulses (amplitude 2 V, pulse period 0.5 s, pulse width 1 ms) were applied between the electrodes of titanium wires immersed in the medium. Movements of both myotubes and markers were observed simultaneously with an optical microscope. Experimental results indicate that the motion distribution of each marker is related to the local periodic motion of the myotube layer. Thin films with matrix-patterned micromarkers fabricated on the back side allow in vitro analysis of the distribution of local repetitive contractile movements in the myotube layer.
为了测量肌管层局部收缩运动的分布,我们在体外跟踪了放置在肌管附着薄膜背面的微标记物基质图案的运动。采用光刻技术在厚度为6 μm的聚二甲基硅氧烷薄膜背面制备了直径为4 μm、高度为2 μm、间距为30 μm的微标记基质图案。将小鼠成肌细胞播种于薄膜前部,培养10天分化成肌管。在浸泡在介质中的钛丝电极之间施加周期电脉冲(振幅2 V,脉冲周期0.5 s,脉冲宽度1 ms)。用光学显微镜同时观察肌管和标记物的运动。实验结果表明,各标记物的运动分布与肌管层的局部周期性运动有关。在背面制造的带有基质图案微标记的薄膜允许在体外分析肌管层局部重复收缩运动的分布。
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引用次数: 1
Molecular Mechanisms Underlying the Effect of Paeoniae Radix Rubra On Sepsis-Induced Coagulopathy: A Network Pharmacology and Molecular Docking Approach 赤芍抗脓毒症凝血功能的分子机制:网络药理学和分子对接方法
Pub Date : 2022-10-28 DOI: 10.1115/1.4056104
Shan Gao, Dongsheng Wang
To investigate the effective components and underlying mechanism of Paeoniae radix rubra (PRR) in treating sepsis-induced coagulopathy (SIC) on the basis of network pharmacology and molecular docking approaches. At present, no therapeutic agent has been approved for the treatment of SIC. Identifying drugs for SIC from Chinese medicine is an encouraging research direction. The predicted targets and effective components of PRR were identified by analysis of the TCMSP database. Bioinformatics databases were employed to identify the disease targets of SIC. These key targets were then uploaded to the STRING database to generate protein-protein interaction networks. The ORG package in R v4.1.2 software was applied for functional and pathway enrichment analyses of the key targets. Finally, discovery studio software was used to perform docking analyses of key targets and effective components. Nine chemically active components and eighty-four common targets associated with drugs and SIC were identified. PPI network analysis identified several key targets. Further analysis identified enrichment in several signaling pathways; these changes could exert influence on a number of biological processes, including responses to xenobiotic stimuli, oxidative stress, molecules of bacterial origin, thus playing an anti-SIC pharmacological role. According to molecular docking results, these key targets had strong binding affinity to the active components. PRR can contribute to SIC by medicating core target genes (e.g., CASP3, PTGS2, TP53, AKT1, MMP9, TNF, JUN, IL6, and CXCL8), and regulating multiple key pathways (e.g., the Lipid and atherosclerosis pathway).
基于网络药理学和分子对接方法,探讨丹芍治疗脓毒症致凝血病(SIC)的有效成分及其作用机制。目前,还没有药物被批准用于治疗SIC。从中药中鉴别SIC药物是一个令人鼓舞的研究方向。通过对TCMSP数据库的分析,确定了PRR的预测靶点和有效成分。利用生物信息学数据库确定SIC的疾病靶点。然后将这些关键靶点上传到STRING数据库,以生成蛋白质-蛋白质相互作用网络。使用R v4.1.2软件中的ORG包对关键靶点进行功能和途径富集分析。最后,利用discovery studio软件对关键目标和有效成分进行对接分析。鉴定出9种化学活性成分和84种与药物和SIC相关的共同靶点。PPI网络分析确定了几个关键目标。进一步分析发现了几个信号通路的富集;这些变化可能对许多生物过程产生影响,包括对外源刺激、氧化应激、细菌源分子的反应,从而发挥抗sic的药理作用。根据分子对接结果,这些关键靶点与活性成分具有较强的结合亲和力。PRR可通过给药核心靶基因(如CASP3、PTGS2、TP53、AKT1、MMP9、TNF、JUN、IL6、CXCL8)和调节多个关键通路(如脂质和动脉粥样硬化通路)来促进SIC。
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引用次数: 0
Obstacle Avoidance for Omnidirectional Mobile Robot Using SLAM 基于SLAM的全向移动机器人避障研究
Pub Date : 2022-09-21 DOI: 10.1115/1.4055689
V. Nandikolla, Bryan Ghoslin
In the field of mobile robotics, Simultaneous Localization and Mapping (SLAM) is an algorithmic approach to the computational problem of creating and updating a map of an environment while simultaneously keeping track of where the robot is within the environment. Applications of a SLAM algorithm are important for autonomous mobile systems to traverse an environment while avoiding obstacles and accurately achieving designated goal destinations. This paper presents the design of a SLAM-driven controller for a semi-autonomous omnidirectional mobile robot. Input to the system comes from a Brain Computer Interface in the form of simple driving commands or a goal destination as decided by the user. Due to latency issues of reacting and responding in real time, the system must safely navigate following the last given commands until it runs out of free space, reaches a goal designation, or receives a new command. The robotic system utilizes a three-wheeled robot kit with an upgraded sensor system. The Intel RealSense Depth Camera D435 and two lidar sensors are utilized to construct a full 360° field of view. The SLAM algorithm and system controllers are developed using the Robot Operating System (ROS). The controllers are developed and tested within Gazebo, which is a physics simulation engine utilized for rapid prototyping. Testing was performed to validate controller performance when given varying commands as well as performing long distance path planning and obstacle avoidance. The system was often capable of achieving its goal destinations with a small error of around 3% or less though the error was found to increase with the more commands the system processed.
在移动机器人领域,同时定位和映射(SLAM)是一种算法方法,用于创建和更新环境地图,同时跟踪机器人在环境中的位置。SLAM算法的应用对于自主移动系统在穿越环境的同时避开障碍物并准确到达指定的目标目的地非常重要。介绍了一种半自主全向移动机器人slam驱动控制器的设计。系统的输入来自脑机接口,以简单的驾驶命令或用户决定的目标目的地的形式。由于实时反应和响应的延迟问题,系统必须按照最后给定的命令安全地导航,直到耗尽可用空间、达到目标指定或接收到新命令。该机器人系统利用一个带有升级传感器系统的三轮机器人套件。英特尔RealSense深度相机D435和两个激光雷达传感器被用来构建一个完整的360°视野。利用机器人操作系统(ROS)开发了SLAM算法和系统控制器。控制器是在Gazebo中开发和测试的,Gazebo是一个用于快速原型设计的物理模拟引擎。测试是为了验证控制器在给定不同命令时的性能,以及执行长距离路径规划和避障。系统通常能够以大约3%或更小的误差实现其目标目的地,尽管发现错误随着系统处理的命令越多而增加。
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引用次数: 0
Relations of Radial Vibration of the Arterial Wall to Pulsatile Parameters in Blood Flow for Extraction of Arterial Indices 动脉壁径向振动与血流脉动参数的关系,用于提取动脉指标
Pub Date : 2022-08-30 DOI: 10.1115/1.4055390
Z. Hao
Given the wide utility of radial vibration of the arterial wall for clinical values, this paper presents a theoretical study on the relations of radial vibration of the arterial wall to pulsatile parameters in blood flow. Pulse wave propagation in an artery is formulated as a combination of the governing equations of blood flow and the arterial wall and no-slip conditions at the blood-wall interface, and is analyzed to obtain the wave velocity and the theoretical expressions for blood flow rate and radial wall displacement in terms of pulsatile pressure. With the harmonics of a pulse signal, theoretical relations of radial vibration of the arterial wall to pulsatile parameters in blood flow are derived under two conditions: without and with wave reflection. These theoretical relations identify the assumptions for the simplified relations employed in the utility of radial vibration of the arterial wall for clinical values. With the arterial wall treated as a unit-mass vibration system, these simplified relations are utilized for extraction of arterial indices from radial vibration of the arterial wall. Other applications of such relations for clinical values are discussed, and the interaction between the arterial wall and blood flow is further revealed from the perspective of energy and 1D wave equations. With harmonics and wave reflection considered, the derived theoretical expressions for radial wall vibration, pulsatile parameters in blood flow, and the relations between them provide a theoretical guidance for improving their interpretation for clinical values with clearly-defined physiological implications and assumptions.
鉴于动脉壁径向振动在临床上的广泛应用,本文对动脉壁径向振动与血流脉动参数的关系进行了理论研究。将脉搏波在动脉内的传播表述为血流与动脉壁的控制方程和血壁交界面无滑移条件的组合,并对其进行了分析,得到了脉搏波在动脉内的传播速度以及脉搏压力对血流速率和径向壁位移的理论表达式。利用脉冲信号的谐波,导出了无波反射和有波反射两种情况下动脉壁径向振动与血流中脉动参数的理论关系。这些理论关系确定了简化关系的假设,应用于动脉壁径向振动的临床价值。将动脉壁视为一个单位质量振动系统,利用这些简化关系从动脉壁径向振动中提取动脉指标。讨论了该关系在临床价值中的其他应用,并从能量和一维波动方程的角度进一步揭示了动脉壁与血流的相互作用。在考虑了谐波和波反射的情况下,推导出的径向壁振动、血流脉动参数及其相互关系的理论表达式,为提高对临床价值的解释提供了理论指导,具有明确的生理意义和假设。
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引用次数: 1
Numerical Modelling of Conical-Shaped Bone Marrow Biopsy Needle Into Multilayer Iliac Crest Model 锥形骨髓活检针在多层髂骨模型中的数值模拟
Pub Date : 2022-08-12 DOI: 10.1115/1.4055221
R. Nadda, R. Repaka, A. Sahani
Bone marrow biopsy (BMB) is a standard technique used in various therapies, research, diagnosis, and prognosis. The extensive forces during biopsy result in unnecessary stress concentrations that are primarily hazardous to weak end bones. To enhance protection and to better identify the risks of bone biopsy, it is essential to understand and predict the interaction of needles with multiple layers of skin and bone. The present investigation aimed to find out the numerical evaluation of forces involved in the insertion and extraction of the needle into multilayer iliac crest model. The insertion and extraction forces have been studied at different diameters of biopsy needles up to a depth of 15.35 mm and insertion speeds in the range of 1 mm/sec - 10 mm/sec. The results showed that the insertion and extraction forces vary according to the needle diameter and relative velocity among the needle and tissue layers. A linear force vs. depth relationship has been obtained in the preliminary phase, and as the depth of insertion increases, the forces increase non-linearly. At the end phase of penetration, the forces augmented more rapidly at a low insertion rate compared to the high insertion rate.
骨髓活检(BMB)是一项标准技术,用于各种治疗、研究、诊断和预后。活组织检查过程中广泛的作用力导致不必要的应力集中,这主要对弱端骨有害。为了加强保护和更好地识别骨活检的风险,了解和预测针与多层皮肤和骨骼的相互作用是至关重要的。本研究旨在对多层髂骨模型中针的插拔力进行数值计算。研究了不同直径的活检针的插入和拔出力,深度为15.35 mm,插入速度为1 mm/秒- 10 mm/秒。结果表明,针的直径和针与组织层之间的相对速度不同,针的插拔力也不同。在初始阶段,力与深度呈线性关系,随着插入深度的增加,力呈非线性增加。在穿透的最后阶段,与高插入率相比,低插入率下的力增强更快。
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引用次数: 3
Optimization of Synthetic Vocal Fold Models for Glottal Closure. 声门闭合合成声带模型的优化。
Pub Date : 2022-08-01 Epub Date: 2022-04-27 DOI: 10.1115/1.4054194
Cassandra J Taylor, Scott L Thomson

Synthetic, self-oscillating models of the human vocal folds are used to study the complex and inter-related flow, structure, and acoustical aspects of voice production. The vocal folds typically collide during each cycle, thereby creating a brief period of glottal closure that has important implications for flow, acoustic, and motion-related outcomes. Many previous synthetic models, however, have been limited by incomplete glottal closure during vibration. In this study, a low-fidelity, two-dimensional, multilayer finite element model of vocal fold flow-induced vibration was coupled with a custom genetic algorithm optimization code to determine geometric and material characteristics that would be expected to yield physiologically-realistic frequency and closed quotient values. The optimization process yielded computational models that vibrated with favorable frequency and closed quotient characteristics. A tradeoff was observed between frequency and closed quotient. A synthetic, self-oscillating vocal fold model with geometric and material properties informed by the simulation outcomes was fabricated and tested for onset pressure, oscillation frequency, and closed quotient. The synthetic model successfully vibrated at a realistic frequency and exhibited a nonzero closed quotient. The methodology described in this study provides potential direction for fabricating synthetic models using isotropic silicone materials that can be designed to vibrate with physiologically-realistic frequencies and closed quotient values. The results also show the potential for a low-fidelity model optimization approach to be used to tune synthetic vocal fold model characteristics for specific vibratory outcomes.

合成的,人类声带的自振荡模型被用来研究复杂的和相互关联的流动,结构,以及声音产生的声学方面。在每个周期中,声带通常会发生碰撞,从而造成短暂的声门关闭,这对流动、声学和运动相关的结果具有重要意义。然而,许多先前的合成模型受到振动时声门关闭不完全的限制。在这项研究中,将低保真度、二维、多层声带流诱发振动的有限元模型与定制的遗传算法优化代码相结合,以确定几何和材料特征,这些特征将产生生理上真实的频率和闭合商值。优化过程得到的计算模型具有良好的频率和闭商特性。在频率和闭商之间观察到一种权衡。根据模拟结果,合成了具有几何和材料特性的自振荡声带模型,并对其启动压力、振荡频率和闭合商进行了测试。该模型成功地在真实频率下振动,并表现出非零闭商。本研究中描述的方法为使用各向同性硅树脂材料制造合成模型提供了潜在的方向,这些材料可以设计成以生理真实的频率和封闭商值振动。结果还显示了一种低保真模型优化方法的潜力,可用于调整合成声带模型的特定振动结果特征。
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引用次数: 2
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Journal of engineering and science in medical diagnostics and therapy
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