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Determination of Statistical Properties of Microtubule Populations. 微管种群统计特性的测定。
Pub Date : 2016-08-01 Epub Date: 2016-08-15 DOI: 10.4236/am.2016.713125
Tyson DiLorenzo, Lee Ligon, Donald Drew

Microtubules are structures within the cell that form a transportation network along which motor proteins tow cargo to destinations. To establish and maintain a structure capable of serving the cell's tasks, microtubules undergo deconstruction and reconstruction regularly. This change in structure is critical to tasks like wound repair and cell motility. Images of fluorescing microtubule networks are captured in grayscale at different wavelengths, displaying different tagged proteins. The analysis of these polymeric structures involves identifying the presence of the protein and the direction of the structure in which it resides. This study considers the problem of finding statistical properties of sections of microtubules. We consider the research done on directional filters and utilize a basic solution to find the center of a ridge. The method processes the captured image by centering a circle around pre-determined pixel locations so that the highest possible average pixel intensity is found within the circle, thus marking the center of the microtubule. The location of these centers allows us to estimate angular direction and curvature of the microtubules, statistically estimate the direction of microtubules in a region of the cell, and compare properties of different types of microtubule networks in the same region. To verify accuracy, we study the results of the method on a test image.

微管是细胞内形成运输网络的结构,运动蛋白沿着这个运输网络将货物拖到目的地。为了建立和维持一个能够服务于细胞任务的结构,微管经常经历解构和重建。这种结构的改变对伤口修复和细胞运动等任务至关重要。荧光微管网络的图像以不同波长的灰度捕获,显示不同的标记蛋白质。对这些聚合物结构的分析包括确定蛋白质的存在及其所在结构的方向。本研究考虑了寻找微管截面统计特性的问题。我们考虑了方向滤波器的研究,并利用一个基本的解决方案来寻找脊的中心。该方法通过围绕预先确定的像素位置使圆居中来处理捕获的图像,以便在圆内找到可能的最高平均像素强度,从而标记微管的中心。这些中心的位置使我们能够估计微管的角方向和曲率,统计估计细胞某个区域内微管的方向,并比较同一区域内不同类型微管网络的性质。为了验证该方法的准确性,我们研究了该方法在测试图像上的结果。
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引用次数: 0
Fraction of Missing Information (γ) at Different Missing Data Fractions in the 2012 NAMCS Physician Workflow Mail Survey. 2012年NAMCS医师工作流程邮件调查中不同缺失数据部分的缺失信息比例(γ)
Pub Date : 2016-06-01 Epub Date: 2016-06-15 DOI: 10.4236/am.2016.710093
Qiyuan Pan, Rong Wei

In his 1987 classic book on multiple imputation (MI), Rubin used the fraction of missing information, γ, to define the relative efficiency (RE) of MI as RE = (1 + γ/m)-1/2, where m is the number of imputations, leading to the conclusion that a small m (≤5) would be sufficient for MI. However, evidence has been accumulating that many more imputations are needed. Why would the apparently sufficient m deduced from the RE be actually too small? The answer may lie with γ. In this research, γ was determined at the fractions of missing data (δ) of 4%, 10%, 20%, and 29% using the 2012 Physician Workflow Mail Survey of the National Ambulatory Medical Care Survey (NAMCS). The γ values were strikingly small, ranging in the order of 10-6 to 0.01. As δ increased, γ usually increased but sometimes decreased. How the data were analysed had the dominating effects on γ, overshadowing the effect of δ. The results suggest that it is impossible to predict γ using δ and that it may not be appropriate to use the γ-based RE to determine sufficient m.

在1987年的经典著作《多重归算》(MI)中,Rubin使用缺失信息的分数γ将MI的相对效率(RE)定义为RE = (1 + γ/m)-1/2,其中m是归算的数量,从而得出结论,对于MI来说,一个小m(≤5)就足够了。然而,越来越多的证据表明需要更多的归算。为什么从RE推导出的明显足够的m实际上太小了?答案可能与γ有关。在本研究中,利用2012年全国门诊医疗调查(NAMCS)的医生工作流程邮件调查,在缺失数据(δ)的4%、10%、20%和29%的分数处确定γ。γ值非常小,范围在10-6到0.01之间。随着δ的增大,γ通常增大,但有时减小。数据的分析方式对γ的影响占主导地位,掩盖了δ的影响。结果表明,用δ来预测γ是不可能的,用γ基RE来确定足够的m可能是不合适的。
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引用次数: 9
Determining Sufficient Number of Imputations Using Variance of Imputation Variances: Data from 2012 NAMCS Physician Workflow Mail Survey. 利用方差的方差确定足够数量的Imputation:来自2012年NAMCS医师工作流程邮件调查的数据。
Pub Date : 2014-12-01 DOI: 10.4236/am.2014.521319
Qiyuan Pan, Rong Wei, Iris Shimizu, Eric Jamoom

How many imputations are sufficient in multiple imputations? The answer given by different researchers varies from as few as 2 - 3 to as many as hundreds. Perhaps no single number of imputations would fit all situations. In this study, η, the minimally sufficient number of imputations, was determined based on the relationship between m, the number of imputations, and ω, the standard error of imputation variances using the 2012 National Ambulatory Medical Care Survey (NAMCS) Physician Workflow mail survey. Five variables of various value ranges, variances, and missing data percentages were tested. For all variables tested, ω decreased as m increased. The m value above which the cost of further increase in m would outweigh the benefit of reducing ω was recognized as the η. This method has a potential to be used by anyone to determine η that fits his or her own data situation.

在多重推算中,多少次推算是足够的?不同研究人员给出的答案少则2 - 3,多则数百。也许没有单一数量的归咎能适用于所有情况。本研究采用2012年全国门诊医疗调查(NAMCS)医师工作流程邮件调查,根据插补数量m与插补方差标准误差ω之间的关系确定最小足够插补数η。测试了5个不同值范围、方差和缺失数据百分比的变量。对于所有测试的变量,ω随着m的增加而减小。在m值以上,进一步增加m的代价大于减小ω的好处,这一值被认为是η。任何人都有可能使用这种方法来确定适合自己数据情况的η值。
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引用次数: 3
Automated Cell Detection and Morphometry on Growth Plate Images of Mouse Bone. 小鼠骨生长板图像的自动细胞检测和形态测定。
Pub Date : 2014-10-01 DOI: 10.4236/am.2014.518273
Maria-Grazia Ascenzi, Xia Du, James I Harding, Emily N Beylerian, Brian M de Silva, Ben J Gross, Hannah K Kastein, Weiguang Wang, Karen M Lyons, Hayden Schaeffer

Microscopy imaging of mouse growth plates is extensively used in biology to understand the effect of specific molecules on various stages of normal bone development and on bone disease. Until now, such image analysis has been conducted by manual detection. In fact, when existing automated detection techniques were applied, morphological variations across the growth plate and heterogeneity of image background color, including the faint presence of cells (chondrocytes) located deeper in tissue away from the image's plane of focus, and lack of cell-specific features, interfered with identification of cell. We propose the first method of automated detection and morphometry applicable to images of cells in the growth plate of long bone. Through ad hoc sequential application of the Retinex method, anisotropic diffusion and thresholding, our new cell detection algorithm (CDA) addresses these challenges on bright-field microscopy images of mouse growth plates. Five parameters, chosen by the user in respect of image characteristics, regulate our CDA. Our results demonstrate effectiveness of the proposed numerical method relative to manual methods. Our CDA confirms previously established results regarding chondrocytes' number, area, orientation, height and shape of normal growth plates. Our CDA also confirms differences previously found between the genetic mutated mouse Smad1/5CKO and its control mouse on fluorescence images. The CDA aims to aid biomedical research by increasing efficiency and consistency of data collection regarding arrangement and characteristics of chondrocytes. Our results suggest that automated extraction of data from microscopy imaging of growth plates can assist in unlocking information on normal and pathological development, key to the underlying biological mechanisms of bone growth.

小鼠生长板的显微镜成像在生物学中被广泛用于了解特定分子对正常骨发育各个阶段和骨病的影响。到目前为止,这种图像分析一直是通过人工检测进行的。事实上,当应用现有的自动检测技术时,生长板上的形态学变化和图像背景颜色的异质性,包括位于远离图像聚焦平面的组织中较深的细胞(软骨细胞)的微弱存在,以及缺乏细胞特异性特征,都会干扰细胞的识别。我们提出了第一种适用于长骨生长板细胞图像的自动检测和形态测量方法。通过对Retinex方法、各向异性扩散和阈值的特殊顺序应用,我们的新细胞检测算法(CDA)在小鼠生长板的明场显微镜图像上解决了这些挑战。用户根据图像特性选择5个参数来调节CDA。结果表明,数值方法相对于手工方法是有效的。我们的CDA证实了之前关于正常生长板的软骨细胞数量、面积、方向、高度和形状的结果。我们的CDA还证实了先前在荧光图像上发现的基因突变小鼠Smad1/5CKO与对照小鼠之间的差异。CDA旨在通过提高有关软骨细胞排列和特征的数据收集的效率和一致性来帮助生物医学研究。我们的研究结果表明,从生长板的显微镜成像中自动提取数据可以帮助解锁正常和病理发育的信息,这是骨生长潜在生物学机制的关键。
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引用次数: 2
The Effect of Ligament Modeling Technique on Knee Joint Kinematics: A Finite Element Study. 韧带建模技术对膝关节运动学影响的有限元研究。
Pub Date : 2014-05-01 DOI: 10.4236/am.2013.45A011
Ata M Kiapour, Vikas Kaul, Ali Kiapour, Carmen E Quatman, Samuel C Wordeman, Timothy E Hewett, Constantine K Demetropoulos, Vijay K Goel

Finite element (FE) analysis has become an increasingly popular technique in the study of human joint biomechanics, as it allows for detailed analysis of the joint/tissue behavior under complex, clinically relevant loading conditions. A wide variety of modeling techniques have been utilized to model knee joint ligaments. However, the effect of a selected constitutive model to simulate the ligaments on knee kinematics remains unclear. The purpose of the current study was to determine the effect of two most common techniques utilized to model knee ligaments on joint kinematics under functional loading conditions. We hypothesized that anatomic representations of the knee ligaments with anisotropic hyperelastic properties will result in more realistic kinematics. A previously developed, extensively validated anatomic FE model of the knee developed from a healthy, young female athlete was used. FE models with 3D anatomic and simplified uniaxial representations of main knee ligaments were used to simulate four functional loading conditions. Model predictions of tibiofemoral joint kinematics were compared to experimental measures. Results demonstrated the ability of the anatomic representation of the knee ligaments (3D geometry along with anisotropic hyperelastic material) in more physiologic prediction of the human knee motion with strong correlation (r ≥ 0.9 for all comparisons) and minimum deviation (0.9º ≤ RMSE ≤ 2.29°) from experimental findings. In contrast, non-physiologic uniaxial elastic representation of the ligaments resulted in lower correlations (r ≤ 0.6 for all comparisons) and substantially higher deviation (2.6° ≤ RMSE ≤ 4.2°) from experimental results. Findings of the current study support our hypothesis and highlight the critical role of soft tissue modeling technique on the resultant FE predicted joint kinematics.

有限元(FE)分析已经成为人类关节生物力学研究中越来越流行的技术,因为它可以详细分析关节/组织在复杂的临床相关载荷条件下的行为。各种各样的建模技术已经被用来模拟膝关节韧带。然而,选择本构模型来模拟韧带对膝关节运动学的影响仍不清楚。本研究的目的是确定在功能负荷条件下,两种最常用的膝关节韧带建模技术对关节运动学的影响。我们假设具有各向异性超弹性特性的膝关节韧带的解剖表征将导致更真实的运动学。使用了先前开发的,广泛验证的健康年轻女运动员膝关节解剖FE模型。采用具有三维解剖和简化的膝关节主要韧带单轴表示的有限元模型来模拟四种功能加载条件。胫骨股骨关节运动学的模型预测与实验测量进行了比较。结果表明,膝关节韧带的解剖表征(三维几何形状以及各向异性超弹性材料)能够对人体膝关节运动进行更多的生理预测,与实验结果具有很强的相关性(所有比较的r≥0.9)和最小偏差(0.9º≤RMSE≤2.29°)。相反,韧带的非生理性单轴弹性表示导致较低的相关性(所有比较的r≤0.6)和与实验结果的较大偏差(2.6°≤RMSE≤4.2°)。目前的研究结果支持了我们的假设,并强调了软组织建模技术在所得的有限元预测关节运动学中的关键作用。
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引用次数: 50
A High-Performance Cellular Automaton Model of Tumor Growth with Dynamically Growing Domains. 具有动态生长域的高性能肿瘤生长细胞自动机模型
Pub Date : 2014-01-01 DOI: 10.4236/am.2014.51017
Jan Poleszczuk, Heiko Enderling

Tumor growth from a single transformed cancer cell up to a clinically apparent mass spans many spatial and temporal orders of magnitude. Implementation of cellular automata simulations of such tumor growth can be straightforward but computing performance often counterbalances simplicity. Computationally convenient simulation times can be achieved by choosing appropriate data structures, memory and cell handling as well as domain setup. We propose a cellular automaton model of tumor growth with a domain that expands dynamically as the tumor population increases. We discuss memory access, data structures and implementation techniques that yield high-performance multi-scale Monte Carlo simulations of tumor growth. We discuss tumor properties that favor the proposed high-performance design and present simulation results of the tumor growth model. We estimate to which parameters the model is the most sensitive, and show that tumor volume depends on a number of parameters in a non-monotonic manner.

肿瘤从单个转化癌细胞生长到临床上明显的肿块,跨越了许多空间和时间数量级。对这种肿瘤生长进行细胞自动机模拟可以很简单,但计算性能往往与简单性不相称。通过选择适当的数据结构、内存和细胞处理以及领域设置,可以实现计算方便的模拟时间。我们提出了一种肿瘤生长的细胞自动机模型,其域会随着肿瘤数量的增加而动态扩展。我们讨论了内存访问、数据结构和实现技术,这些技术可产生高性能的肿瘤生长多尺度蒙特卡罗模拟。我们讨论了有利于拟议高性能设计的肿瘤特性,并展示了肿瘤生长模型的仿真结果。我们估计了该模型对哪些参数最为敏感,并表明肿瘤体积以非单调的方式取决于多个参数。
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应用数学(英文)
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