Pub Date : 2016-08-01Epub Date: 2016-08-15DOI: 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.
{"title":"Determination of Statistical Properties of Microtubule Populations.","authors":"Tyson DiLorenzo, Lee Ligon, Donald Drew","doi":"10.4236/am.2016.713125","DOIUrl":"https://doi.org/10.4236/am.2016.713125","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":64940,"journal":{"name":"应用数学(英文)","volume":"7 13","pages":"1456-1475"},"PeriodicalIF":0.0,"publicationDate":"2016-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6528678/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36993236","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2016-06-01Epub Date: 2016-06-15DOI: 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.
{"title":"Fraction of Missing Information (<i>γ</i>) at Different Missing Data Fractions in the 2012 NAMCS Physician Workflow Mail Survey.","authors":"Qiyuan Pan, Rong Wei","doi":"10.4236/am.2016.710093","DOIUrl":"https://doi.org/10.4236/am.2016.710093","url":null,"abstract":"<p><p>In his 1987 classic book on multiple imputation (MI), Rubin used the fraction of missing information, <i>γ</i>, to define the relative efficiency (RE) of MI as RE = (1 + <i>γ</i>/<i>m</i>)<sup>-1/2</sup>, where <i>m</i> is the number of imputations, leading to the conclusion that a small <i>m</i> (≤5) would be sufficient for MI. However, evidence has been accumulating that many more imputations are needed. Why would the apparently sufficient <i>m</i> deduced from the RE be actually too small? The answer may lie with <i>γ</i>. In this research, <i>γ</i> was determined at the fractions of missing data (<i>δ</i>) of 4%, 10%, 20%, and 29% using the 2012 Physician Workflow Mail Survey of the National Ambulatory Medical Care Survey (NAMCS). The <i>γ</i> values were strikingly small, ranging in the order of 10<sup>-6</sup> to 0.01. As <i>δ</i> increased, <i>γ</i> usually increased but sometimes decreased. How the data were analysed had the dominating effects on <i>γ</i>, overshadowing the effect of <i>δ</i>. The results suggest that it is impossible to predict <i>γ</i> using <i>δ</i> and that it may not be appropriate to use the <i>γ</i>-based RE to determine sufficient <i>m</i>.</p>","PeriodicalId":64940,"journal":{"name":"应用数学(英文)","volume":"7 10","pages":"1057-1067"},"PeriodicalIF":0.0,"publicationDate":"2016-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4934387/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34653832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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.
{"title":"Determining Sufficient Number of Imputations Using Variance of Imputation Variances: Data from 2012 NAMCS Physician Workflow Mail Survey.","authors":"Qiyuan Pan, Rong Wei, Iris Shimizu, Eric Jamoom","doi":"10.4236/am.2014.521319","DOIUrl":"https://doi.org/10.4236/am.2014.521319","url":null,"abstract":"<p><p>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, <i>η</i>, the minimally sufficient number of imputations, was determined based on the relationship between <i>m</i>, the number of imputations, and <i>ω</i>, 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, <i>ω</i> decreased as <i>m</i> increased. The <i>m</i> value above which the cost of further increase in <i>m</i> would outweigh the benefit of reducing <i>ω</i> was recognized as the <i>η</i>. This method has a potential to be used by anyone to determine <i>η</i> that fits his or her own data situation.</p>","PeriodicalId":64940,"journal":{"name":"应用数学(英文)","volume":"5 ","pages":"3421-3430"},"PeriodicalIF":0.0,"publicationDate":"2014-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4937882/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34653831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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.
{"title":"Automated Cell Detection and Morphometry on Growth Plate Images of Mouse Bone.","authors":"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","doi":"10.4236/am.2014.518273","DOIUrl":"https://doi.org/10.4236/am.2014.518273","url":null,"abstract":"<p><p>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 <i>Smad1/5<sup>CKO</sup></i> 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.</p>","PeriodicalId":64940,"journal":{"name":"应用数学(英文)","volume":"5 18","pages":"2866-2880"},"PeriodicalIF":0.0,"publicationDate":"2014-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4267696/pdf/nihms617421.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32921143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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.
{"title":"The Effect of Ligament Modeling Technique on Knee Joint Kinematics: A Finite Element Study.","authors":"Ata M Kiapour, Vikas Kaul, Ali Kiapour, Carmen E Quatman, Samuel C Wordeman, Timothy E Hewett, Constantine K Demetropoulos, Vijay K Goel","doi":"10.4236/am.2013.45A011","DOIUrl":"https://doi.org/10.4236/am.2013.45A011","url":null,"abstract":"<p><p>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 (<i>r</i> ≥ 0.9 for all comparisons) and minimum deviation (0.9º ≤ <i>RMSE</i> ≤ 2.29°) from experimental findings. In contrast, non-physiologic uniaxial elastic representation of the ligaments resulted in lower correlations (<i>r</i> ≤ 0.6 for all comparisons) and substantially higher deviation (2.6° ≤ <i>RMSE</i> ≤ 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.</p>","PeriodicalId":64940,"journal":{"name":"应用数学(英文)","volume":"4 5A","pages":"91-97"},"PeriodicalIF":0.0,"publicationDate":"2014-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4236/am.2013.45A011","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32668658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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.
{"title":"A High-Performance Cellular Automaton Model of Tumor Growth with Dynamically Growing Domains.","authors":"Jan Poleszczuk, Heiko Enderling","doi":"10.4236/am.2014.51017","DOIUrl":"10.4236/am.2014.51017","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":64940,"journal":{"name":"应用数学(英文)","volume":"5 1","pages":"144-152"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4208695/pdf/nihms613995.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32772270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}