Sample records for design-based stereological methods
-
A review of state-of-the-art stereology for better quantitative 3D morphology in cardiac research.
Mühlfeld, Christian; Nyengaard, Jens Randel; Mayhew, Terry M
2010-01-01
The aim of stereological methods in biomedical research is to obtain quantitative information about three-dimensional (3D) features of tissues, cells, or organelles from two-dimensional physical or optical sections. With immunogold labeling, stereology can even be used for the quantitative analysis of the distribution of molecules within tissues and cells. Nowadays, a large number of design-based stereological methods offer an efficient quantitative approach to intriguing questions in cardiac research, such as "Is there a significant loss of cardiomyocytes during progression from ventricular hypertrophy to heart failure?" or "Does a specific treatment reduce the degree of fibrosis in the heart?" Nevertheless, the use of stereological methods in cardiac research is rare. The present review article demonstrates how some of the potential pitfalls in quantitative microscopy may be avoided. To this end, we outline the concepts of design-based stereology and illustrate their practical applications to a wide range of biological questions in cardiac research. We hope that the present article will stimulate researchers in cardiac research to incorporate design-based stereology into their study designs, thus promoting an unbiased quantitative 3D microscopy.
-
Ochs, Matthias; Mühlfeld, Christian
2013-07-01
The growing awareness of the importance of accurate morphometry in lung research has recently motivated the publication of guidelines set forth by a combined task force of the American Thoracic Society and the European Respiratory Society (20). This official ATS/ERS Research Policy Statement provides general recommendations on which stereological methods are to be used in quantitative microscopy of the lung. However, to integrate stereology into a particular experimental study design, investigators are left with the problem of how to implement this in practice. Specifically, different animal models of human lung disease require the use of different stereological techniques and may determine the mode of lung fixation, tissue processing, preparation of sections, and other things. Therefore, the present companion articles were designed to allow a short practically oriented introduction into the concepts of design-based stereology (Part 1) and to provide recommendations for choosing the most appropriate methods to investigate a number of important disease models (Part 2). Worked examples with illustrative images will facilitate the practical performance of equivalent analyses. Study algorithms provide comprehensive surveys to ensure that no essential step gets lost during the multistage workflow. Thus, with this review, we hope to close the gap between theory and practice and enhance the use of stereological techniques in pulmonary research.
-
Melvin, Neal R; Poda, Daniel; Sutherland, Robert J
2007-10-01
When properly applied, stereology is a very robust and efficient method to quantify a variety of parameters from biological material. A common sampling strategy in stereology is systematic random sampling, which involves choosing a random sampling [corrected] start point outside the structure of interest, and sampling relevant objects at [corrected] sites that are placed at pre-determined, equidistant intervals. This has proven to be a very efficient sampling strategy, and is used widely in stereological designs. At the microscopic level, this is most often achieved through the use of a motorized stage that facilitates the systematic random stepping across the structure of interest. Here, we report a simple, precise and cost-effective software-based alternative to accomplishing systematic random sampling under the microscope. We believe that this approach will facilitate the use of stereological designs that employ systematic random sampling in laboratories that lack the resources to acquire costly, fully automated systems.
-
Design-based stereology: Planning, volumetry and sampling are crucial steps for a successful study.
Tschanz, Stefan; Schneider, Jan Philipp; Knudsen, Lars
2014-01-01
Quantitative data obtained by means of design-based stereology can add valuable information to studies performed on a diversity of organs, in particular when correlated to functional/physiological and biochemical data. Design-based stereology is based on a sound statistical background and can be used to generate accurate data which are in line with principles of good laboratory practice. In addition, by adjusting the study design an appropriate precision can be achieved to find relevant differences between groups. For the success of the stereological assessment detailed planning is necessary. In this review we focus on common pitfalls encountered during stereological assessment. An exemplary workflow is included, and based on authentic examples, we illustrate a number of sampling principles which can be implemented to obtain properly sampled tissue blocks for various purposes. Copyright © 2013 Elsevier GmbH. All rights reserved.
-
Yurt, Kıymet Kübra; Kivrak, Elfide Gizem; Altun, Gamze; Mohamed, Hamza; Ali, Fathelrahman; Gasmalla, Hosam Eldeen; Kaplan, Suleyman
2018-02-26
A quantitative description of a three-dimensional (3D) object based on two-dimensional images can be made using stereological methods These methods involve unbiased approaches and provide reliable results with quantitative data. The quantitative morphology of the nervous system has been thoroughly researched in this context. In particular, various novel methods such as design-based stereological approaches have been applied in neuoromorphological studies. The main foundations of these methods are systematic random sampling and a 3D approach to structures such as tissues and organs. One key point in these methods is that selected samples should represent the entire structure. Quantification of neurons, i.e. particles, is important for revealing degrees of neurodegeneration and regeneration in an organ or system. One of the most crucial morphometric parameters in biological studies is thus the "number". The disector counting method introduced by Sterio in 1984 is an efficient and reliable solution for particle number estimation. In order to obtain precise results by means of stereological analysis, counting items should be seen clearly in the tissue. If an item in the tissue cannot be seen, these cannot be analyzed even using unbiased stereological techniques. Staining and sectioning processes therefore play a critical role in stereological analysis. The purpose of this review is to evaluate current neuroscientific studies using optical and physical disector counting methods and to discuss their definitions and methodological characteristics. Although the efficiency of the optical disector method in light microscopic studies has been revealed in recent years, the physical disector method is more easily performed in electron microscopic studies. Also, we offered to readers summaries of some common basic staining and sectioning methods, which can be used for stereological techniques in this review. Copyright © 2018 Elsevier B.V. All rights reserved.
-
Mühlfeld, Christian
2014-01-01
The vasculature of the heart is able to adapt to various physiological and pathological stimuli and its failure to do so is well-reflected by the great impact of ischaemic heart disease on personal morbidity and mortality and on the health care systems of industrial countries. Studies on physiological or genetic interventions as well as therapeutic angiogenesis rely on quantitative data to characterize the effects in a statistically robust way. The gold standard for obtaining quantitative morphological data is design-based stereology which allows the estimation of volume, surface area, length and number of blood vessels as well as their thickness, diameter or wall composition. Unfortunately, the use of stereological methods for this purpose is still rare. One of the reasons for this is the fact that the transfer of the theoretical foundations into laboratory practice requires a remarkable amount of considerations before touching the first piece of tissue. These considerations, however, are often based on already acquired experience and are usually not dealt with in stereological review articles. The present article therefore delineates the procedures for estimating the most important characteristics of the cardiac vasculature and highlights potential problems and their practical solutions. Worked examples are used to illustrate the methods and provide examples of the calculations. Hopefully, the considerations and examples contained herein will provide researchers in this field with the necessary equipment to add stereological methods to their study designs. Copyright © 2012 Elsevier GmbH. All rights reserved.
-
Practical Stereology Applications for the Pathologist.
Brown, Danielle L
2017-05-01
Qualitative histopathology is the gold standard for routine examination of morphological tissue changes in the regulatory or academic environment. The human eye is exceptional for pattern recognition but often cannot detect small changes in quantity. In cases where detection of subtle quantitative changes is critical, more sensitive methods are required. Two-dimensional histomorphometry can provide additional quantitative information and is quite useful in many cases. However, the provided data may not be referent to the entire tissue and, as such, it makes several assumptions, which are sources of bias. In contrast, stereology is design based rather than assumption based and uses stringent sampling methods to obtain accurate and precise 3-dimensional information using geometrical and statistical principles. Recent advances in technology have made stereology more approachable and practical for the pathologist in both regulatory and academic environments. This review introduces pathologists to the basic principles of stereology and walks the reader through some real-world examples for the application of these principles in the workplace.
-
Mühlfeld, Christian; Ochs, Matthias
2013-08-01
Design-based stereology provides efficient methods to obtain valuable quantitative information of the respiratory tract in various diseases. However, the choice of the most relevant parameters in a specific disease setting has to be deduced from the present pathobiological knowledge. Often it is difficult to express the pathological alterations by interpretable parameters in terms of volume, surface area, length, or number. In the second part of this companion review article, we analyze the present pathophysiological knowledge about acute lung injury, diffuse parenchymal lung diseases, emphysema, pulmonary hypertension, and asthma to come up with recommendations for the disease-specific application of stereological principles for obtaining relevant parameters. Worked examples with illustrative images are used to demonstrate the work flow, estimation procedure, and calculation and to facilitate the practical performance of equivalent analyses.
-
[Simulation and data analysis of stereological modeling based on virtual slices].
Wang, Hao; Shen, Hong; Bai, Xiao-yan
2008-05-01
To establish a computer-assisted stereological model for simulating the process of slice section and evaluate the relationship between section surface and estimated three-dimensional structure. The model was designed by mathematic method as a win32 software based on the MFC using Microsoft visual studio as IDE for simulating the infinite process of sections and analysis of the data derived from the model. The linearity of the fitting of the model was evaluated by comparison with the traditional formula. The win32 software based on this algorithm allowed random sectioning of the particles distributed randomly in an ideal virtual cube. The stereological parameters showed very high throughput (>94.5% and 92%) in homogeneity and independence tests. The data of density, shape and size of the section were tested to conform to normal distribution. The output of the model and that from the image analysis system showed statistical correlation and consistency. The algorithm we described can be used for evaluating the stereologic parameters of the structure of tissue slices.
-
Vasilescu, Dragoş M.; Klinge, Christine; Knudsen, Lars; Yin, Leilei; Wang, Ge; Weibel, Ewald R.; Ochs, Matthias
2013-01-01
Quantitative assessment of the lung microstructure using standard stereological methods such as volume fractions of tissue, alveolar surface area, or number of alveoli, are essential for understanding the state of normal and diseased lung. These measures are traditionally obtained from histological sections of the lung tissue, a process that ultimately destroys the three-dimensional (3-D) anatomy of the tissue. In comparison, a novel X-ray-based imaging method that allows nondestructive sectioning and imaging of fixed lungs at multiple resolutions can overcome this limitation. Scanning of the whole lung at high resolution and subsequent regional sampling at ultrahigh resolution without physically dissecting the organ allows the application of design-based stereology for assessment of the whole lung structure. Here we validate multiple stereological estimates performed on micro–computed tomography (μCT) images by comparing them with those obtained via conventional histology on the same mouse lungs. We explore and discuss the potentials and limitations of the two approaches. Histological examination offers higher resolution and the qualitative differentiation of tissues by staining, but ultimately loses 3-D tissue relationships, whereas μCT allows for the integration of morphometric data with the spatial complexity of lung structure. However, μCT has limited resolution satisfactory for the sterological estimates presented in this study but not for differentiation of tissues. We conclude that introducing stereological methods in μCT studies adds value by providing quantitative information on internal structures while not curtailing more complex approaches to the study of lung architecture in the context of physiological or pathological studies. PMID:23264542
-
Abdominal fat volume estimation by stereology on CT: a comparison with manual planimetry.
Manios, G E; Mazonakis, M; Voulgaris, C; Karantanas, A; Damilakis, J
2016-03-01
To deploy and evaluate a stereological point-counting technique on abdominal CT for the estimation of visceral (VAF) and subcutaneous abdominal fat (SAF) volumes. Stereological volume estimations based on point counting and systematic sampling were performed on images from 14 consecutive patients who had undergone abdominal CT. For the optimization of the method, five sampling intensities in combination with 100 and 200 points were tested. The optimum stereological measurements were compared with VAF and SAF volumes derived by the standard technique of manual planimetry on the same scans. Optimization analysis showed that the selection of 200 points along with the sampling intensity 1/8 provided efficient volume estimations in less than 4 min for VAF and SAF together. The optimized stereology showed strong correlation with planimetry (VAF: r = 0.98; SAF: r = 0.98). No statistical differences were found between the two methods (VAF: P = 0.81; SAF: P = 0.83). The 95% limits of agreement were also acceptable (VAF: -16.5%, 16.1%; SAF: -10.8%, 10.7%) and the repeatability of stereology was good (VAF: CV = 4.5%, SAF: CV = 3.2%). Stereology may be successfully applied to CT images for the efficient estimation of abdominal fat volume and may constitute a good alternative to the conventional planimetric technique. Abdominal obesity is associated with increased risk of disease and mortality. Stereology may quantify visceral and subcutaneous abdominal fat accurately and consistently. The application of stereology to estimating abdominal volume fat reduces processing time. Stereology is an efficient alternative method for estimating abdominal fat volume.
-
[The application of stereology in radiology imaging and cell biology fields].
Hu, Na; Wang, Yan; Feng, Yuanming; Lin, Wang
2012-08-01
Stereology is an interdisciplinary method for 3D morphological study developed from mathematics and morphology. It is widely used in medical image analysis and cell biology studies. Because of its unbiased, simple, fast, reliable and non-invasive characteristics, stereology has been widely used in biomedical areas for quantitative analysis and statistics, such as histology, pathology and medical imaging. Because the stereological parameters show distinct differences in different pathology, many scholars use stereological methods to do quantitative analysis in their studies in recent years, for example, in the areas of the condition of cancer cells, tumor grade, disease development and the patient's prognosis, etc. This paper describes the stereological concept and estimation methods, also illustrates the applications of stereology in the fields of CT images, MRI images and cell biology, and finally reflects the universality, the superiority and reliability of stereology.
-
A Stereological Method for the Quantitative Evaluation of Cartilage Repair Tissue
Nyengaard, Jens Randel; Lind, Martin; Spector, Myron
2015-01-01
Objective To implement stereological principles to develop an easy applicable algorithm for unbiased and quantitative evaluation of cartilage repair. Design Design-unbiased sampling was performed by systematically sectioning the defect perpendicular to the joint surface in parallel planes providing 7 to 10 hematoxylin–eosin stained histological sections. Counting windows were systematically selected and converted into image files (40-50 per defect). The quantification was performed by two-step point counting: (1) calculation of defect volume and (2) quantitative analysis of tissue composition. Step 2 was performed by assigning each point to one of the following categories based on validated and easy distinguishable morphological characteristics: (1) hyaline cartilage (rounded cells in lacunae in hyaline matrix), (2) fibrocartilage (rounded cells in lacunae in fibrous matrix), (3) fibrous tissue (elongated cells in fibrous tissue), (4) bone, (5) scaffold material, and (6) others. The ability to discriminate between the tissue types was determined using conventional or polarized light microscopy, and the interobserver variability was evaluated. Results We describe the application of the stereological method. In the example, we assessed the defect repair tissue volume to be 4.4 mm3 (CE = 0.01). The tissue fractions were subsequently evaluated. Polarized light illumination of the slides improved discrimination between hyaline cartilage and fibrocartilage and increased the interobserver agreement compared with conventional transmitted light. Conclusion We have applied a design-unbiased method for quantitative evaluation of cartilage repair, and we propose this algorithm as a natural supplement to existing descriptive semiquantitative scoring systems. We also propose that polarized light is effective for discrimination between hyaline cartilage and fibrocartilage. PMID:26069715
-
Wakasaki, Rumie; Eiwaz, Mahaba; McClellan, Nicholas; Matsushita, Katsuyuki; Golgotiu, Kirsti; Hutchens, Michael P
2018-06-14
A technical challenge in translational models of kidney injury is determination of the extent of cell death. Histologic sections are commonly analyzed by area morphometry or unbiased stereology, but stereology requires specialized equipment. Therefore, a challenge to rigorous quantification would be addressed by an unbiased stereology tool with reduced equipment dependence. We hypothesized that it would be feasible to build a novel software component which would facilitate unbiased stereologic quantification on scanned slides, and that unbiased stereology would demonstrate greater precision and decreased bias compared with 2D morphometry. We developed a macro for the widely used image analysis program, Image J, and performed cardiac arrest with cardiopulmonary resuscitation (CA/CPR, a model of acute cardiorenal syndrome) in mice. Fluorojade-B stained kidney sections were analyzed using three methods to quantify cell death: gold standard stereology using a controlled stage and commercially-available software, unbiased stereology using the novel ImageJ macro, and quantitative 2D morphometry also using the novel macro. There was strong agreement between both methods of unbiased stereology (bias -0.004±0.006 with 95% limits of agreement -0.015 to 0.007). 2D morphometry demonstrated poor agreement and significant bias compared to either method of unbiased stereology. Unbiased stereology is facilitated by a novel macro for ImageJ and results agree with those obtained using gold-standard methods. Automated 2D morphometry overestimated tubular epithelial cell death and correlated modestly with values obtained from unbiased stereology. These results support widespread use of unbiased stereology for analysis of histologic outcomes of injury models.
-
Brain Volume Estimation Enhancement by Morphological Image Processing Tools.
Zeinali, R; Keshtkar, A; Zamani, A; Gharehaghaji, N
2017-12-01
Volume estimation of brain is important for many neurological applications. It is necessary in measuring brain growth and changes in brain in normal/abnormal patients. Thus, accurate brain volume measurement is very important. Magnetic resonance imaging (MRI) is the method of choice for volume quantification due to excellent levels of image resolution and between-tissue contrast. Stereology method is a good method for estimating volume but it requires to segment enough MRI slices and have a good resolution. In this study, it is desired to enhance stereology method for volume estimation of brain using less MRI slices with less resolution. In this study, a program for calculating volume using stereology method has been introduced. After morphologic method, dilation was applied and the stereology method enhanced. For the evaluation of this method, we used T1-wighted MR images from digital phantom in BrainWeb which had ground truth. The volume of 20 normal brain extracted from BrainWeb, was calculated. The volumes of white matter, gray matter and cerebrospinal fluid with given dimension were estimated correctly. Volume calculation from Stereology method in different cases was made. In three cases, Root Mean Square Error (RMSE) was measured. Case I with T=5, d=5, Case II with T=10, D=10 and Case III with T=20, d=20 (T=slice thickness, d=resolution as stereology parameters). By comparing these results of two methods, it is obvious that RMSE values for our proposed method are smaller than Stereology method. Using morphological operation, dilation allows to enhance the estimation volume method, Stereology. In the case with less MRI slices and less test points, this method works much better compared to Stereology method.
-
A Stereological Method for the Quantitative Evaluation of Cartilage Repair Tissue.
Foldager, Casper Bindzus; Nyengaard, Jens Randel; Lind, Martin; Spector, Myron
2015-04-01
To implement stereological principles to develop an easy applicable algorithm for unbiased and quantitative evaluation of cartilage repair. Design-unbiased sampling was performed by systematically sectioning the defect perpendicular to the joint surface in parallel planes providing 7 to 10 hematoxylin-eosin stained histological sections. Counting windows were systematically selected and converted into image files (40-50 per defect). The quantification was performed by two-step point counting: (1) calculation of defect volume and (2) quantitative analysis of tissue composition. Step 2 was performed by assigning each point to one of the following categories based on validated and easy distinguishable morphological characteristics: (1) hyaline cartilage (rounded cells in lacunae in hyaline matrix), (2) fibrocartilage (rounded cells in lacunae in fibrous matrix), (3) fibrous tissue (elongated cells in fibrous tissue), (4) bone, (5) scaffold material, and (6) others. The ability to discriminate between the tissue types was determined using conventional or polarized light microscopy, and the interobserver variability was evaluated. We describe the application of the stereological method. In the example, we assessed the defect repair tissue volume to be 4.4 mm(3) (CE = 0.01). The tissue fractions were subsequently evaluated. Polarized light illumination of the slides improved discrimination between hyaline cartilage and fibrocartilage and increased the interobserver agreement compared with conventional transmitted light. We have applied a design-unbiased method for quantitative evaluation of cartilage repair, and we propose this algorithm as a natural supplement to existing descriptive semiquantitative scoring systems. We also propose that polarized light is effective for discrimination between hyaline cartilage and fibrocartilage.
-
First and second order stereology of hyaline cartilage: Application on mice femoral cartilage.
Noorafshan, Ali; Niazi, Behnam; Mohamadpour, Masoomeh; Hoseini, Leila; Hoseini, Najmeh; Owji, Ali Akbar; Rafati, Ali; Sadeghi, Yasaman; Karbalay-Doust, Saied
2016-11-01
Stereological techniques could be considered in research on cartilage to obtain quantitative data. The present study aimed to explain application of the first- and second-order stereological methods on articular cartilage of mice and the methods applied on the mice exposed to cadmium (Cd). The distal femoral articular cartilage of BALB/c mice (control and Cd-treated) was removed. Then, volume and surface area of the cartilage and number of chondrocytes were estimated using Cavalieri and optical dissector techniques on isotropic uniform random sections. Pair-correlation function [g(r)] and cross-correlation function were calculated to express the spatial arrangement of chondrocytes-chondrocytes and chondrocytes-matrix (chondrocyte clustering/dispersing), respectively. The mean±standard deviation of the cartilage volume, surface area, and thickness were 1.4±0.1mm 3 , 26.2±5.4mm 2 , and 52.8±6.7μm, respectively. Besides, the mean number of chondrocytes was 680±200 (×10 3 ). The cartilage volume, cartilage surface area, and number of chondrocytes were respectively reduced by 25%, 27%, and 27% in the Cd-treated mice in comparison to the control animals (p<0.03). Estimates of g(r) for the cells and matrix against the dipole distances, r, have been plotted. This plot showed that the chondrocytes and the matrix were neither dispersed nor clustered in the two study groups. Application of design-based stereological methods and also evaluation of spatial arrangement of the cartilage components carried potential advantages for investigating the cartilage in different joint conditions. Chondrocyte clustering/dispersing and cellularity can be evaluated in cartilage assessment in normal or abnormal situations. Copyright © 2016 Elsevier GmbH. All rights reserved.
-
Mazonakis, Michalis; Sahin, Bunyamin; Pagonidis, Konstantin; Damilakis, John
2011-06-01
The aim of this study was to combine the stereological technique with magnetic resonance (MR) imaging data for the volumetric and functional analysis of the left ventricle (LV). Cardiac MR examinations were performed in 13 consecutive subjects with known or suspected coronary artery disease. The end-diastolic volume (EDV), end-systolic volume, ejection fraction (EF), and mass were estimated by stereology using the entire slice set depicting LV and systematic sampling intensities of 1/2 and 1/3 that provided samples with every second and third slice, respectively. The repeatability of stereology was evaluated. Stereological assessments were compared with the reference values derived by manually tracing the endocardial and epicardial contours on MR images. Stereological EDV and EF estimations obtained by the 1/3 systematic sampling scheme were significantly different from those by manual delineation (P < .05). No difference was observed between the reference values and the LV parameters estimated by the entire slice set or a sampling intensity of 1/2 (P > .05). For these stereological approaches, a high correlation (r(2) = 0.80-0.93) and clinically acceptable limits of agreement were found with the reference method. Stereological estimations obtained by both sample sizes presented comparable coefficient of variation values of 2.9-5.8%. The mean time for stereological measurements on the entire slice set was 3.4 ± 0.6 minutes and it was reduced to 2.5 ± 0.5 minutes with the 1/2 systematic sampling scheme. Stereological analysis on systematic samples of MR slices generated by the 1/2 sampling intensity provided efficient and quick assessment of LV volumes, function, and mass. Copyright © 2011 AUR. Published by Elsevier Inc. All rights reserved.
-
Assessment of cardiac fibrosis: a morphometric method comparison for collagen quantification.
Schipke, Julia; Brandenberger, Christina; Rajces, Alexandra; Manninger, Martin; Alogna, Alessio; Post, Heiner; Mühlfeld, Christian
2017-04-01
Fibrotic remodeling of the heart is a frequent condition linked to various diseases and cardiac dysfunction. Collagen quantification is an important objective in cardiac fibrosis research; however, a variety of different histological methods are currently used that may differ in accuracy. Here, frequently applied collagen quantification techniques were compared. A porcine model of early stage heart failure with preserved ejection fraction was used as an example. Semiautomated threshold analyses were imprecise, mainly due to inclusion of noncollagen structures or failure to detect certain collagen deposits. In contrast, collagen assessment by automated image analysis and light microscopy (LM)-stereology was more sensitive. Depending on the quantification method, the amount of estimated collagen varied and influenced intergroup comparisons. PicroSirius Red, Masson's trichrome, and Azan staining protocols yielded similar results, whereas the measured collagen area increased with increasing section thickness. Whereas none of the LM-based methods showed significant differences between the groups, electron microscopy (EM)-stereology revealed a significant collagen increase between cardiomyocytes in the experimental group, but not at other localizations. In conclusion, in contrast to the staining protocol, section thickness and the quantification method being used directly influence the estimated collagen content and thus, possibly, intergroup comparisons. EM in combination with stereology is a precise and sensitive method for collagen quantification if certain prerequisites are considered. For subtle fibrotic alterations, consideration of collagen localization may be necessary. Among LM methods, LM-stereology and automated image analysis are appropriate to quantify fibrotic changes, the latter depending on careful control of algorithm and comparable section staining. NEW & NOTEWORTHY Direct comparison of frequently applied histological fibrosis assessment techniques revealed a distinct relation of measured collagen and utilized quantification method as well as section thickness. Besides electron microscopy-stereology, which was precise and sensitive, light microscopy-stereology and automated image analysis proved to be appropriate for collagen quantification. Moreover, consideration of collagen localization might be important in revealing minor fibrotic changes. Copyright © 2017 the American Physiological Society.
-
Stereology techniques in radiation biology
NASA Technical Reports Server (NTRS)
Kubinova, Lucie; Mao, XiaoWen; Janacek, Jiri; Archambeau, John O.; Nelson, G. A. (Principal Investigator)
2003-01-01
Clinicians involved in conventional radiation therapy are very concerned about the dose-response relationships of normal tissues. Before proceeding to new clinical protocols, radiation biologists involved with conformal proton therapy believe it is necessary to quantify the dose response and tolerance of the organs and tissues that will be irradiated. An important focus is on the vasculature. This presentation reviews the methodology and format of using confocal microscopy and stereological methods to quantify tissue parameters, cell number, tissue volume and surface area, and vessel length using the microvasculature as a model tissue. Stereological methods and their concepts are illustrated using an ongoing study of the dose response of the microvessels in proton-irradiated hemibrain. Methods for estimating the volume of the brain and the brain cortex, the total number of endothelial cells in cortical microvessels, the length of cortical microvessels, and the total surface area of cortical microvessel walls are presented step by step in a way understandable for readers with little mathematical background. It is shown that stereological techniques, based on a sound theoretical basis, are powerful and reliable and have been used successfully.
-
Extending unbiased stereology of brain ultrastructure to three-dimensional volumes
NASA Technical Reports Server (NTRS)
Fiala, J. C.; Harris, K. M.; Koslow, S. H. (Principal Investigator)
2001-01-01
OBJECTIVE: Analysis of brain ultrastructure is needed to reveal how neurons communicate with one another via synapses and how disease processes alter this communication. In the past, such analyses have usually been based on single or paired sections obtained by electron microscopy. Reconstruction from multiple serial sections provides a much needed, richer representation of the three-dimensional organization of the brain. This paper introduces a new reconstruction system and new methods for analyzing in three dimensions the location and ultrastructure of neuronal components, such as synapses, which are distributed non-randomly throughout the brain. DESIGN AND MEASUREMENTS: Volumes are reconstructed by defining transformations that align the entire area of adjacent sections. Whole-field alignment requires rotation, translation, skew, scaling, and second-order nonlinear deformations. Such transformations are implemented by a linear combination of bivariate polynomials. Computer software for generating transformations based on user input is described. Stereological techniques for assessing structural distributions in reconstructed volumes are the unbiased bricking, disector, unbiased ratio, and per-length counting techniques. A new general method, the fractional counter, is also described. This unbiased technique relies on the counting of fractions of objects contained in a test volume. A volume of brain tissue from stratum radiatum of hippocampal area CA1 is reconstructed and analyzed for synaptic density to demonstrate and compare the techniques. RESULTS AND CONCLUSIONS: Reconstruction makes practicable volume-oriented analysis of ultrastructure using such techniques as the unbiased bricking and fractional counter methods. These analysis methods are less sensitive to the section-to-section variations in counts and section thickness, factors that contribute to the inaccuracy of other stereological methods. In addition, volume reconstruction facilitates visualization and modeling of structures and analysis of three-dimensional relationships such as synaptic connectivity.
-
Schmitz, Christoph; Eastwood, Brian S.; Tappan, Susan J.; Glaser, Jack R.; Peterson, Daniel A.; Hof, Patrick R.
2014-01-01
Stereologic cell counting has had a major impact on the field of neuroscience. A major bottleneck in stereologic cell counting is that the user must manually decide whether or not each cell is counted according to three-dimensional (3D) stereologic counting rules by visual inspection within hundreds of microscopic fields-of-view per investigated brain or brain region. Reliance on visual inspection forces stereologic cell counting to be very labor-intensive and time-consuming, and is the main reason why biased, non-stereologic two-dimensional (2D) “cell counting” approaches have remained in widespread use. We present an evaluation of the performance of modern automated cell detection and segmentation algorithms as a potential alternative to the manual approach in stereologic cell counting. The image data used in this study were 3D microscopic images of thick brain tissue sections prepared with a variety of commonly used nuclear and cytoplasmic stains. The evaluation compared the numbers and locations of cells identified unambiguously and counted exhaustively by an expert observer with those found by three automated 3D cell detection algorithms: nuclei segmentation from the FARSIGHT toolkit, nuclei segmentation by 3D multiple level set methods, and the 3D object counter plug-in for ImageJ. Of these methods, FARSIGHT performed best, with true-positive detection rates between 38 and 99% and false-positive rates from 3.6 to 82%. The results demonstrate that the current automated methods suffer from lower detection rates and higher false-positive rates than are acceptable for obtaining valid estimates of cell numbers. Thus, at present, stereologic cell counting with manual decision for object inclusion according to unbiased stereologic counting rules remains the only adequate method for unbiased cell quantification in histologic tissue sections. PMID:24847213
-
NASA Astrophysics Data System (ADS)
Haller, John W.; Botteron, K.; Brunsden, Barry S.; Sheline, Yvette I.; Walkup, Ronald K.; Black, Kevin J.; Gado, Mokhtar; Vannier, Michael W.
1994-09-01
Goal: To estimate hippocampal volumes from in vivo 3D magnetic resonance (MR) brain images and determine inter-rater and intra- rater repeatability. Objective: The precision and repeatability of hippocampal volume estimates using stereologic measurement methods is sought. Design: Five normal control and five schizophrenic subjects were MR scanned using a MPRAGE protocol. Fixed grid stereologic methods were used to estimate hippocampal volumes on a graphics workstation. The images were preprocessed using histogram analysis to standardize 3D MR image scaling from 16 to 8 bits and image volumes were interpolated to 0.5 mm3 isotropic voxels. The following variables were constant for the repeated stereologic measures: grid size, inter-slice distance (1.5 mm), voxel dimensions (0.5 mm3), number of hippocampi measured (10), total number of measurements per rater (40), and number of raters (5). Two grid sizes were tested to determine the coefficient of error associated with the number of sampled 'hits' (approximately 140 and 280) on the hippocampus. Starting slice and grid position were randomly varied to assure unbiased volume estimates. Raters were blind to subject identity, diagnosis, and side of the brain from which the image volumes were extracted and the order of subject presentation was randomized for each of the raters. Inter- and intra-rater intraclass correlation coefficients (ICC) were determined. Results: The data indicate excellent repeatability of fixed grid stereologic hippocampal volume measures when using an inter-slice distance of 1.5 mm and a 6.25 mm2 grid (inter-rater ICCs equals 0.86 - 0.97, intra- rater ICCs equals 0.85 - 0.97). One major advantage of the current study was the use of 3D MR data which significantly improved visualization of hippocampal boundaries by providing the ability to access simultaneous orthogonal views while counting stereological marks within the hippocampus. Conclusion: Stereological estimates of 3D volumes from 2D MR sections provide an inexpensive, unbiased and efficient way of determining brain structural volumes. The high precision and repeatability demonstrated with stereological MR volumetry suggest that these methods may be efficiently used to measure small volume reductions associated with schizophrenia and other brain disorders.
-
St. Pierre, Tim G.; House, Michael J.; Bangma, Sander J.; Pang, Wenjie; Bathgate, Andrew; Gan, Eng K.; Ayonrinde, Oyekoya T.; Bhathal, Prithi S.; Clouston, Andrew; Olynyk, John K.; Adams, Leon A.
2016-01-01
Background and Aims Validation of non-invasive methods of liver fat quantification requires a reference standard. However, using standard histopathology assessment of liver biopsies is problematical because of poor repeatability. We aimed to assess a stereological method of measuring volumetric liver fat fraction (VLFF) in liver biopsies and to use the method to validate a magnetic resonance imaging method for measurement of VLFF. Methods VLFFs were measured in 59 subjects (1) by three independent analysts using a stereological point counting technique combined with the Delesse principle on liver biopsy histological sections and (2) by three independent analysts using the HepaFat-Scan® technique on magnetic resonance images of the liver. Bland Altman statistics and intraclass correlation (IC) were used to assess the repeatability of each method and the bias between the methods of liver fat fraction measurement. Results Inter-analyst repeatability coefficients for the stereology and HepaFat-Scan® methods were 8.2 (95% CI 7.7–8.8)% and 2.4 (95% CI 2.2–2.5)% VLFF respectively. IC coefficients were 0.86 (95% CI 0.69–0.93) and 0.990 (95% CI 0.985–0.994) respectively. Small biases (≤3.4%) were observable between two pairs of analysts using stereology while no significant biases were observable between any of the three pairs of analysts using HepaFat-Scan®. A bias of 1.4±0.5% VLFF was observed between the HepaFat-Scan® method and the stereological method. Conclusions Repeatability of the stereological method is superior to the previously reported performance of assessment of hepatic steatosis by histopathologists and is a suitable reference standard for validating non-invasive methods of measurement of VLFF. PMID:27501242
-
Romppanen, T; Huttunen, E; Helminen, H J
1980-07-01
An improved light microscopical histoquantitative method for the analysis of the stereologic structure of the ventral lobe of the rat prostate is introduced. From paraffin-embedded tissue sections, volumetric fractions of the acinar parenchyma, the glandular epithelium, the glandular lumen, and the interacinar tissue were determined. The surface density of the glandular epithelium and the length density of the glandular tubules per cubic millimeter of tissue were also calculated. The corresponding total amount/quantity of each tissue compartment was computed for the whole ventral lobe based on the weight of the lobe. Using established stereologic laws, the height of the epithelium, the diameter of the glandular tubules, the free distance between the glandular tubules, and the distance between the glandular centers (means) were determined. The fitness of the method was tested by analyzing, in addition to normal prostates, ventral prostates of rats castrated 30 days before sacrifice.
-
SU-E-J-12: A New Stereological Method for Tumor Volume Evaluation for Esophageal Cancer
DOE Office of Scientific and Technical Information (OSTI.GOV)
Feng, Y; Tianjin Medical University Cancer Institute and Hospital; East Carolina University
2014-06-01
Purpose: Stereological method used to obtain three dimensional quantitative information from two dimensional images is a widely used tool in the study of cells and pathology. But the feasibility of the method for quantitative evaluation of volumes with 3D image data sets for radiotherapy clinical application has not been explored. On the other hand, a quick, easy-to-use and reliable method is highly desired in image-guided-radiotherapy(IGRT) for tumor volume measurement for the assessment of response to treatment. To meet this need, a stereological method for evaluating tumor volumes for esophageal cancer is presented in this abstract. Methods: The stereology method wasmore » optimized by selecting the appropriate grid point distances and sample types. 7 patients with esophageal cancer were selected retrospectively for this study, each having pre and post treatment computed tomography (CT) scans. Stereological measurements were performed for evaluating the gross tumor volume (GTV) changes after radiotherapy and the results was compared with the ones by planimetric measurements. Two independent observers evaluated the reproducibility for volume measurement using the new stereological technique. Results: The intraobserver variation in the GTV volume estimation was 3.42±1.68cm3 (the Wilcoxon matched-pairs test Resultwas Z=−1.726,P=0.084>0.05); the interobserver variation in the GTV volume estimation was 22.40±7.23 cm3 (Z=−3.296,P=0.083>0.05), which showed the consistency in GTV volume calculation with the new method for the same and different users. The agreement level between the results from the two techniques was also evaluated. Difference between the measured GTVs was 20.10±5.35 cm3 (Z=−3.101,P=0.089>0.05). Variation of the measurement results using the two techniques was low and clinically acceptable. Conclusion: The good agreement between stereological and planimetric techniques proves the reliability of the stereological tumor volume estimations. The optimized stereological technique described in this abstract may provide a quick, unbiased and reproducible tool for tumor volume estimation for treatment response assessment. Supported by NSFC (#81041107, #81171342 and #31000784)« less
-
A simple tool for stereological assessment of digital images: the STEPanizer.
Tschanz, S A; Burri, P H; Weibel, E R
2011-07-01
STEPanizer is an easy-to-use computer-based software tool for the stereological assessment of digitally captured images from all kinds of microscopical (LM, TEM, LSM) and macroscopical (radiology, tomography) imaging modalities. The program design focuses on providing the user a defined workflow adapted to most basic stereological tasks. The software is compact, that is user friendly without being bulky. STEPanizer comprises the creation of test systems, the appropriate display of digital images with superimposed test systems, a scaling facility, a counting module and an export function for the transfer of results to spreadsheet programs. Here we describe the major workflow of the tool illustrating the application on two examples from transmission electron microscopy and light microscopy, respectively. © 2011 The Authors Journal of Microscopy © 2011 Royal Microscopical Society.
-
Geuna, S
2000-11-20
Quantitative morphology of the nervous system has undergone great developments over recent years, and several new technical procedures have been devised and applied successfully to neuromorphological research. However, a lively debate has arisen on some issues, and a great deal of confusion appears to exist that is definitely responsible for the slow spread of the new techniques among scientists. One such element of confusion is related to uncertainty about the meaning, implications, and advantages of the design-based sampling strategy that characterize the new techniques. In this article, to help remove this uncertainty, morphoquantitative methods are described and contrasted on the basis of the inferential paradigm of the sampling strategy: design-based vs model-based. Moreover, some recommendations are made to help scientists judge the appropriateness of a method used for a given study in relation to its specific goals. Finally, the use of the term stereology to label, more or less expressly, only some methods is critically discussed. Copyright 2000 Wiley-Liss, Inc.
-
2014-01-01
Background Digital image analysis (DIA) enables better reproducibility of immunohistochemistry (IHC) studies. Nevertheless, accuracy of the DIA methods needs to be ensured, demanding production of reference data sets. We have reported on methodology to calibrate DIA for Ki67 IHC in breast cancer tissue based on reference data obtained by stereology grid count. To produce the reference data more efficiently, we propose digital IHC wizard generating initial cell marks to be verified by experts. Methods Digital images of proliferation marker Ki67 IHC from 158 patients (one tissue microarray spot per patient) with an invasive ductal carcinoma of the breast were used. Manual data (mD) were obtained by marking Ki67-positive and negative tumour cells, using a stereological method for 2D object enumeration. DIA was used as an initial step in stereology grid count to generate the digital data (dD) marks by Aperio Genie and Nuclear algorithms. The dD were collected into XML files from the DIA markup images and overlaid on the original spots along with the stereology grid. The expert correction of the dD marks resulted in corrected data (cD). The percentages of Ki67 positive tumour cells per spot in the mD, dD, and cD sets were compared by single linear regression analysis. Efficiency of cD production was estimated based on manual editing effort. Results The percentage of Ki67-positive tumor cells was in very good agreement in the mD, dD, and cD sets: regression of cD from dD (R2=0.92) reflects the impact of the expert editing the dD as well as accuracy of the DIA used; regression of the cD from the mD (R2=0.94) represents the consistency of the DIA-assisted ground truth (cD) with the manual procedure. Nevertheless, the accuracy of detection of individual tumour cells was much lower: in average, 18 and 219 marks per spot were edited due to the Genie and Nuclear algorithm errors, respectively. The DIA-assisted cD production in our experiment saved approximately 2/3 of manual marking. Conclusions Digital IHC wizard enabled DIA-assisted stereology to produce reference data in a consistent and efficient way. It can provide quality control measure for appraising accuracy of the DIA steps. PMID:25565221
-
Eriksen, Ann C; Andersen, Johnnie B; Kristensson, Martin; dePont Christensen, René; Hansen, Torben F; Kjær-Frifeldt, Sanne; Sørensen, Flemming B
2017-08-29
Precise prognostic and predictive variables allowing improved post-operative treatment stratification are missing in patients treated for stage II colon cancer (CC). Investigation of tumor infiltrating lymphocytes (TILs) may be rewarding, but the lack of a standardized analytic technique is a major concern. Manual stereological counting is considered the gold standard, but digital pathology with image analysis is preferred due to time efficiency. The purpose of this study was to compare manual stereological estimates of TILs with automatic counts obtained by image analysis, and at the same time investigate the heterogeneity of TILs. From 43 patients treated for stage II CC in 2002 three paraffin embedded, tumor containing tissue blocks were selected one of them representing the deepest invasive tumor front. Serial sections from each of the 129 blocks were immunohistochemically stained for CD3 and CD8, and the slides were scanned. Stereological estimates of the numerical density and area fraction of TILs were obtained using the computer-assisted newCAST stereology system. For the image analysis approach an app-based algorithm was developed using Visiopharm Integrator System software. For both methods the tumor areas of interest (invasive front and central area) were manually delineated by the observer. Based on all sections, the Spearman's correlation coefficients for density estimates varied from 0.9457 to 0.9638 (p < 0.0001), whereas the coefficients for area fraction estimates ranged from 0.9400 to 0.9603 (P < 0.0001). Regarding heterogeneity, intra-class correlation coefficients (ICC) for CD3+ TILs varied from 0.615 to 0.746 in the central area, and from 0.686 to 0.746 in the invasive area. ICC for CD8+ TILs varied from 0.724 to 0.775 in the central area, and from 0.746 to 0.765 in the invasive area. Exact objective and time efficient estimates of numerical densities and area fractions of CD3+ and CD8+ TILs in stage II colon cancer can be obtained by image analysis and are highly correlated to the corresponding estimates obtained by the gold standard based on stereology. Since the intra-tumoral heterogeneity was low, this method may be recommended for quantifying TILs in only one histological section representing the deepest invasive tumor front.
-
Practical application of stereological methods in experimental kidney animal models.
Fernández García, María Teresa; Núñez Martínez, Paula; García de la Fuente, Vanessa; Sánchez Pitiot, Marta; Muñiz Salgueiro, María Del Carmen; Perillán Méndez, Carmen; Argüelles Luis, Juan; Astudillo González, Aurora
The kidneys are vital organs responsible for excretion, fluid and electrolyte balance and hormone production. The nephrons are the kidney's functional and structural units. The number, size and distribution of the nephron components contain relevant information on renal function. Stereology is a branch of morphometry that applies mathematical principles to obtain three-dimensional information from serial, parallel and equidistant two-dimensional microscopic sections. Because of the complexity of stereological studies and the lack of scientific literature on the subject, the aim of this paper is to clearly explain, through animal models, the basic concepts of stereology and how to calculate the main kidney stereological parameters that can be applied in future experimental studies. Copyright © 2016 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.
-
TAIWO, OLUWADAMILOLA O.; FINEGAN, DONAL P.; EASTWOOD, DAVID S.; FIFE, JULIE L.; BROWN, LEON D.; DARR, JAWWAD A.; LEE, PETER D.; BRETT, DANIEL J.L.
2016-01-01
Summary Lithium‐ion battery performance is intrinsically linked to electrode microstructure. Quantitative measurement of key structural parameters of lithium‐ion battery electrode microstructures will enable optimization as well as motivate systematic numerical studies for the improvement of battery performance. With the rapid development of 3‐D imaging techniques, quantitative assessment of 3‐D microstructures from 2‐D image sections by stereological methods appears outmoded; however, in spite of the proliferation of tomographic imaging techniques, it remains significantly easier to obtain two‐dimensional (2‐D) data sets. In this study, stereological prediction and three‐dimensional (3‐D) analysis techniques for quantitative assessment of key geometric parameters for characterizing battery electrode microstructures are examined and compared. Lithium‐ion battery electrodes were imaged using synchrotron‐based X‐ray tomographic microscopy. For each electrode sample investigated, stereological analysis was performed on reconstructed 2‐D image sections generated from tomographic imaging, whereas direct 3‐D analysis was performed on reconstructed image volumes. The analysis showed that geometric parameter estimation using 2‐D image sections is bound to be associated with ambiguity and that volume‐based 3‐D characterization of nonconvex, irregular and interconnected particles can be used to more accurately quantify spatially‐dependent parameters, such as tortuosity and pore‐phase connectivity. PMID:26999804
-
Taiwo, Oluwadamilola O; Finegan, Donal P; Eastwood, David S; Fife, Julie L; Brown, Leon D; Darr, Jawwad A; Lee, Peter D; Brett, Daniel J L; Shearing, Paul R
2016-09-01
Lithium-ion battery performance is intrinsically linked to electrode microstructure. Quantitative measurement of key structural parameters of lithium-ion battery electrode microstructures will enable optimization as well as motivate systematic numerical studies for the improvement of battery performance. With the rapid development of 3-D imaging techniques, quantitative assessment of 3-D microstructures from 2-D image sections by stereological methods appears outmoded; however, in spite of the proliferation of tomographic imaging techniques, it remains significantly easier to obtain two-dimensional (2-D) data sets. In this study, stereological prediction and three-dimensional (3-D) analysis techniques for quantitative assessment of key geometric parameters for characterizing battery electrode microstructures are examined and compared. Lithium-ion battery electrodes were imaged using synchrotron-based X-ray tomographic microscopy. For each electrode sample investigated, stereological analysis was performed on reconstructed 2-D image sections generated from tomographic imaging, whereas direct 3-D analysis was performed on reconstructed image volumes. The analysis showed that geometric parameter estimation using 2-D image sections is bound to be associated with ambiguity and that volume-based 3-D characterization of nonconvex, irregular and interconnected particles can be used to more accurately quantify spatially-dependent parameters, such as tortuosity and pore-phase connectivity. © 2016 The Authors. Journal of Microscopy published by John Wiley & Sons Ltd on behalf of Royal Microscopical Society.
-
Plancoulaine, Benoît; Laurinaviciene, Aida; Meskauskas, Raimundas; Baltrusaityte, Indra; Besusparis, Justinas; Herlin, Paulette; Laurinavicius, Arvydas
2014-01-01
Digital image analysis (DIA) enables better reproducibility of immunohistochemistry (IHC) studies. Nevertheless, accuracy of the DIA methods needs to be ensured, demanding production of reference data sets. We have reported on methodology to calibrate DIA for Ki67 IHC in breast cancer tissue based on reference data obtained by stereology grid count. To produce the reference data more efficiently, we propose digital IHC wizard generating initial cell marks to be verified by experts. Digital images of proliferation marker Ki67 IHC from 158 patients (one tissue microarray spot per patient) with an invasive ductal carcinoma of the breast were used. Manual data (mD) were obtained by marking Ki67-positive and negative tumour cells, using a stereological method for 2D object enumeration. DIA was used as an initial step in stereology grid count to generate the digital data (dD) marks by Aperio Genie and Nuclear algorithms. The dD were collected into XML files from the DIA markup images and overlaid on the original spots along with the stereology grid. The expert correction of the dD marks resulted in corrected data (cD). The percentages of Ki67 positive tumour cells per spot in the mD, dD, and cD sets were compared by single linear regression analysis. Efficiency of cD production was estimated based on manual editing effort. The percentage of Ki67-positive tumor cells was in very good agreement in the mD, dD, and cD sets: regression of cD from dD (R2=0.92) reflects the impact of the expert editing the dD as well as accuracy of the DIA used; regression of the cD from the mD (R2=0.94) represents the consistency of the DIA-assisted ground truth (cD) with the manual procedure. Nevertheless, the accuracy of detection of individual tumour cells was much lower: in average, 18 and 219 marks per spot were edited due to the Genie and Nuclear algorithm errors, respectively. The DIA-assisted cD production in our experiment saved approximately 2/3 of manual marking. Digital IHC wizard enabled DIA-assisted stereology to produce reference data in a consistent and efficient way. It can provide quality control measure for appraising accuracy of the DIA steps.
-
MRI volumetry of prefrontal cortex
NASA Astrophysics Data System (ADS)
Sheline, Yvette I.; Black, Kevin J.; Lin, Daniel Y.; Pimmel, Joseph; Wang, Po; Haller, John W.; Csernansky, John G.; Gado, Mokhtar; Walkup, Ronald K.; Brunsden, Barry S.; Vannier, Michael W.
1995-05-01
Prefrontal cortex volumetry by brain magnetic resonance (MR) is required to estimate changes postulated to occur in certain psychiatric and neurologic disorders. A semiautomated method with quantitative characterization of its performance is sought to reliably distinguish small prefrontal cortex volume changes within individuals and between groups. Stereological methods were tested by a blinded comparison of measurements applied to 3D MR scans obtained using an MPRAGE protocol. Fixed grid stereologic methods were used to estimate prefrontal cortex volumes on a graphic workstation, after the images are scaled from 16 to 8 bits using a histogram method. In addition images were resliced into coronal sections perpendicular to the bicommissural plane. Prefrontal cortex volumes were defined as all sections of the frontal lobe anterior to the anterior commissure. Ventricular volumes were excluded. Stereological measurement yielded high repeatability and precision, and was time efficient for the raters. The coefficient of error was
-
Stereological study of developing glomerular forms during human fetal kidney development.
Dakovic Bjelakovic, Marija; Vlajkovic, Slobodan; Petrovic, Aleksandar; Bjelakovic, Marko; Antic, Milorad
2018-05-01
Human fetal kidney development is a complex and stepwise process. The number, shape, size and distribution of glomeruli provide important information on kidney organization. The aim of this study was to quantify glomerular developing forms during human fetal kidney development using stereological methods. Kidney tissue specimens of 40 human fetuses with gestational ages ranging from 9 to 40 weeks were analyzed. Specimens were divided into eight groups based on gestational age, each corresponding to 1 lunar month. Stereological methods were used at the light microscopy level to estimate volume, surface and numerical density of the glomerular developing forms. During gestation, nephrogenesis continually advanced, and the number of nephrons increased. Volume, surface and numerical densities of vesicular forms and S-shaped bodies decreased gradually in parallel with gradual increases in estimated stereological parameters for vascularized glomeruli. Volume density and surface density of vascularized glomeruli increased gradually during fetal kidney development, and numerical density increased until the seventh lunar month. A relative decrease in vascularized glomeruli per unit volume of cortex occurred during the last 3 lunar months. Nephrogenesis began to taper off by 32 weeks and was completed by 36 weeks of gestation. The last sample in which we observed vesicles was from a fetus aged 32 weeks, and the last sample with S-shaped bodies was from a fetus aged 36 weeks. The present study is one of few quantitative studies conducted on human kidney development. Knowledge of normal human kidney morphogenesis during development could be important for future medical practice. Events occurring during fetal life may have significant consequences later in life.
-
LHOTÁKOVÁ, Z; ALBRECHTOVÁ, J; JANÁČEK, J; KUBÍNOVÁ, L
2008-01-01
The anatomical structure of mesophyll tissue in the leaf is tightly connected with many physiological processes in plants. One of the most important mesophyll parameters related to photosynthesis is the internal leaf surface area, i.e. the surface area of mesophyll cell walls exposed to intercellular spaces. An efficient design-based stereological method can be applied for estimation of this parameter, using software-randomized virtual fakir test probes in stacks of optical sections acquired by a confocal microscope within thick physical free-hand sections (i.e. acquired using a hand microtome), as we have shown in the case of fresh Norway spruce needles recently. However, for wider practical use in plant ecophysiology, a suitable form of sample storage and other possible technical constraints of this methodology need to be checked. We tested the effect of freezing conifer needles on their anatomical structure as well as the effect of possible deformations due to the cutting of unembedded material by a hand microtome, which can result in distortions of cutting surfaces. In the present study we found a higher proportion of intercellular spaces in mesophyll in regions near to the surface of a physical section, which means that the measurements should be restricted only to the middle region of the optical section series. On the other hand, the proportion of intercellular spaces in mesophyll as well as the internal needle surface density in mesophyll did not show significant difference between fresh and frozen needles; therefore, we conclude that freezing represents a suitable form of storage of sampled material for proposed stereological evaluation. PMID:19017201
-
Lhotáková, Z; Albrechtová, J; Janácek, J; Kubínová, L
2008-10-01
The anatomical structure of mesophyll tissue in the leaf is tightly connected with many physiological processes in plants. One of the most important mesophyll parameters related to photosynthesis is the internal leaf surface area, i.e. the surface area of mesophyll cell walls exposed to intercellular spaces. An efficient design-based stereological method can be applied for estimation of this parameter, using software-randomized virtual fakir test probes in stacks of optical sections acquired by a confocal microscope within thick physical free-hand sections (i.e. acquired using a hand microtome), as we have shown in the case of fresh Norway spruce needles recently. However, for wider practical use in plant ecophysiology, a suitable form of sample storage and other possible technical constraints of this methodology need to be checked. We tested the effect of freezing conifer needles on their anatomical structure as well as the effect of possible deformations due to the cutting of unembedded material by a hand microtome, which can result in distortions of cutting surfaces. In the present study we found a higher proportion of intercellular spaces in mesophyll in regions near to the surface of a physical section, which means that the measurements should be restricted only to the middle region of the optical section series. On the other hand, the proportion of intercellular spaces in mesophyll as well as the internal needle surface density in mesophyll did not show significant difference between fresh and frozen needles; therefore, we conclude that freezing represents a suitable form of storage of sampled material for proposed stereological evaluation.
-
Stereological assessment of normal Persian squirrels (Sciurus anomalus) kidney.
Akbari, Mohsen; Goodarzi, Nader; Tavafi, Majid
2017-03-01
The functions of the mammalian kidney are closely related to its structure. This suggests that renal function can be completely characterized by accurate knowledge of its quantitative morphological features. The aim of this study was to investigate the histomorphometric features of the kidney using design-based and unbiased stereological methods in the Persian squirrel (Sciurus anomalus), which is the only representative of the Sciuridae family in the Middle East. The left kidneys of five animals were examined. Total volume of the kidney, cortex, and medulla were determined to be 960.75 ± 87.4, 754.31 ± 77.09 and 206.1 ± 16.89 mm 3 , respectively. The glomerular number was 32844.03 ± 1069.19, and the total glomerular volume was estimated to be 36.7 ± 1.45 mm 3 . The volume and length of the proximal convoluted tubule were estimated at 585.67 ± 60.7 mm 3 and 328.8 ± 14.8 m, respectively, with both values being greater than those reported in the rat kidney. The volume and length of the distal convoluted tubule were calculated at 122.34 ± 7.38 mm 3 and 234.4 ± 17.45 m, respectively, which are also greater than those reported in the rat kidney. Despite the comparable body weight, the total number and mean individual volume of glomeruli in the Persian squirrel kidney were greater than those in the rat kidney. Overall, the stereological variables of the kidneys elucidated in this study are exclusive to the Persian squirrel. Our findings, together with future renal physiological data, will contribute to a better understanding of the renal structure-function relationship in the Persian squirrel.
-
Barger, Nicole; Stefanacci, Lisa; Schumann, Cynthia M.; Sherwood, Chet C.; Annese, Jacopo; Allman, John M.; Buckwalter, Joseph A.; Hof, Patrick R.; Semendeferi, Katerina
2016-01-01
In human and nonhuman primates, the amygdala is known to play critical roles in emotional and social behavior. Anatomically, individual amygdaloid nuclei are connected with many neural systems that are either differentially expanded or conserved over the course of primate evolution. To address amygdala evolution in humans and our closest living relatives, the apes, we used design-based stereological methods to obtain neuron counts for the amygdala and each of four major amygdaloid nuclei (the lateral, basal, accessory basal, and central nuclei) in humans, all great ape species, lesser apes, and one monkey species. Our goal was to determine whether there were significant differences in the number or percent of neurons distributed to individual nuclei among species. Additionally, regression analyses were performed on independent contrast data to determine whether any individual species deviated from allometric trends. There were two major findings. In humans, the lateral nucleus contained the highest number of neurons in the amygdala, whereas in apes the basal nucleus contained the highest number of neurons. Additionally, the human lateral nucleus contained 59% more neurons than predicted by allometric regressions on nonhuman primate data. Based on the largest sample ever analyzed in a comparative study of the hominoid amygdala, our findings suggest that an emphasis on the lateral nucleus is the main characteristic of amygdala specialization over the course of human evolution. PMID:22473387
-
Acer, N; Bayar, B; Basaloglu, H; Oner, E; Bayar, K; Sankur, S
2008-11-20
The size and shape of tarsal bones are especially relevant when considering some orthopedic diseases such as clubfoot. For this reason, the measurements of the tarsal bones have been the subject of many studies, none of which has used stereological methods to estimate the volume. In the present stereological study, we estimated the volume of calcaneal bone of normal feet and dry bones. We used a combination of the Cavalieri principle and computer tomographic scans taken from eight males and nine dry calcanei to estimate the volumes of calcaneal bones. The mean volume of dry calcaneal bones was estimated, producing mean results using the point-counting method and Archimedes principle being 49.11+/-10.7 or 48.22+/-11.92 cm(3), respectively. A positive correlation was found between anthropometric measurements and the volume of calcaneal bones. The findings of the present study using the stereological methods could provide data for the evaluation of normal and pathological volumes of calcaneal bones.
-
Marner, Lisbeth
2012-04-01
The communication among neurons is the prerequisite for the working brain. To understand the cellular, neurochemical, and structural basis of this communication, and the impacts of aging and disease on brain function, quantitative measures are necessary. This thesis evaluates several quantitative neurobiological methods with respect to possible bias and methodological issues. Stereological methods are suited for the unbiased estimation of number, length, and volumes of components of the nervous system. Stereological estimates of the total length of myelinated nerve fibers were made in white matter of post mortem brains, and the impact of aging and diseases as Schizophrenia and Alzheimer's disease were evaluated. Although stereological methods are in principle unbiased, shrinkage artifacts are difficult to account for. Positron emission tomography (PET) recordings, in conjunction with kinetic modeling, permit the quantitation of radioligand binding in brain. The novel serotonin 5-HT4 antagonist [11C]SB207145 was used as an example of the validation process for quantitative PET receptor imaging. Methods based on reference tissue as well as methods based on an arterial plasma input function were evaluated with respect to precision and accuracy. It was shown that [11C]SB207145 binding had high sensitivity to occupancy by unlabeled ligand, necessitating high specific activity in the radiosynthesis to avoid bias. The established serotonin 5-HT2A ligand [18F]altanersin was evaluated in a two-year follow-up study in elderly subjects. Application of partial volume correction of the PET data diminished the reliability of the measures, but allowed for the correct distinction between changes due to brain atrophy and receptor availability. Furthermore, a PET study of patients with Alzheimer's disease with the serotonin transporter ligand [11C]DASB showed relatively preserved serotonergic projections, despite a marked decrease in 5-HT2A receptor binding. Possible confounders are considered and the relation to the prevailing beta-amyloid hypothesis is discussed.
-
Acer, Niyazi; Sahin, Bunyamin; Ucar, Tolga; Usanmaz, Mustafa
2009-01-01
The size of the eyeball has been the subject of a few studies. None of them used stereological methods to estimate the volume. In the current study, we estimated the volume of eyeball in normal men and women using the stereological methods. Eyeball volume (EV) was estimated using the Cavalieri principle as a combination of point-counting and planimetry techniques. We used computed tomography scans taken from 36 participants (15 men and 21 women) to estimate the EV. The mean (SD) EV values obtained by planimetry method were 7.49 (0.79) and 7.06 (0.85) cm in men and women, respectively. By using point-counting method, the mean (SD) values were 7.48 (0.85) and 7.21 (0.84) cm in men and women, respectively. There was no statistically significant difference between the findings from the 2 methods (P > 0.05). A weak correlation was found between the axial length of eyeball and the EV estimated by point counting and planimetry (P < 0.05, r = 0.494 and r = 0.523, respectively). The findings of the current study using the stereological methods could provide data for the evaluation of normal and pathologic volumes of the eyeball.
-
The expression of MCM-2 in invasive breast carcinoma: a stereologic approach.
Cobanoglu, Umit; Mungan, Sevdegul; Gundogdu, Cemal; Ersoz, Safak; Ozoran, Yavuz; Aydin, Fazil
2010-01-01
The aim of this study is to examine the expression of MCM-2 and conventional proliferation marker Ki-67 in breast carcinoma by stereologic technique and to compare it with various clinicopathologic parameters. The expression of MCM-2 and Ki-67 on paraffin-embedded tumor tissue sections of patients with invasive breast carcinoma was analyzed immunohistochemically. Stereologic method was used for evaluation of the percentage of positively stained tumor cells. Significant positive correlation was found between the expression of MCM-2 and that of Ki-67 (r = 0.74, p < 0.001). MCM-2 and Ki-67 expression was significantly associated with histologic grade (p < 0.05), and negative correlation was observed between MCM-2 or Ki-67 expression and estrogen status (p < 0.05). No significant association was observed between MCM-2 or Ki-67 expression and patient age, tumor size, lymph node status, clinical stage and menopausal status. Our results suggest that MCM-2 expression is significantly associated with histologic grade of breast carcinoma and with cell proliferation capacity (Ki-67 labelling index). Additional studies are required using the stereologic method to compare and understand the utility of Ki-67 and MCM-2 expression in invasive breast carcinoma (Tab. 1, Fig. 4, Ref. 34). Full Text (Free, PDF) www.bmj.sk.
-
Acar, Nihat; Karakasli, Ahmet; Karaarslan, Ahmet; Mas, Nermin Ng; Hapa, Onur
2017-01-01
Volumetric measurements of benign tumors enable surgeons to trace volume changes during follow-up periods. For a volumetric measurement technique to be applicable, it should be easy, rapid, and inexpensive and should carry a high interobserver reliability. We aimed to assess the interobserver reliability of a volumetric measurement technique using the Cavalier's principle of stereological methods. The computerized tomography (CT) of 15 patients with a histopathologically confirmed diagnosis of enchondroma with variant tumor sizes and localizations was retrospectively reviewed for interobserver reliability evaluation of the volumetric stereological measurement with the Cavalier's principle, V = t × [((SU) × d) /SL]2 × Σ P. The volumes of the 15 tumors collected by the observers are demonstrated in Table 1. There was no statistical significance between the first and second observers ( p = 0.000 and intraclass correlation coefficient = 0.970) and between the first and third observers ( p = 0.000 and intraclass correlation coefficient = 0.981). No statistical significance was detected between the second and third observers ( p = 0.000 and intraclass correlation coefficient = 0.976). The Cavalier's principle with the stereological technique using the CT scans is an easy, rapid, and inexpensive technique in volumetric evaluation of enchondromas with a trustable interobserver reliability.
-
Ashkani-Esfahani, Soheil; Hosseinabadi, Omid Koohi; Moezzi, Parinaz; Moafpourian, Yalda; Kardeh, Sina; Rafiee, Shima; Fatheazam, Reza; Noorafshan, Ali; Nadimi, Elham; Mehrvarz, Shayan; Khoshneviszadeh, Mehdi; Khoshneviszadeh, Mahsima
2016-08-01
Calcium can play noticeable roles in the wound-healing process, such as its effects on organization of F-actinin collagen bundles by fibroblasts at the injury site. In addition, calcium-channel blockers such as verapamil have antioxidant activity by increasing nitric oxide production that promotes angiogenesis, proliferation of fibroblasts, and endothelial cells in the skin-regeneration process. Therefore, in this study, the authors' objective was to investigate the effects of verapamil on the process of wound healing in rat models according to stereological parameters. In this experimental study, 36 male Wistar rats were randomly divided into 3 groups (n = 12): the control group that received no treatment, gel-base-treated group, and the 5% verapamil gel-treated group. Treatments were done every 24 hours for 15 days. Wound closure rate, volume densities of the collagen bundles and the vessels, vessel's length density and mean diameter, and fibroblast populations were estimated using stereological methods and were analyzed by the Kruskal-Wallis and Mann-Whitney U tests; P < .05 was considered statistically significant. The verapamil-treated group showed a faster wound closure rate in comparison with control and gel-base groups (P = .007 and P = .011). The numerical density of fibroblasts, volume density of collagen bundles, mean diameter, and volume densities of the vessels in the verapamil group were significantly higher than those in the control and the base groups (P < .005). The authors showed that verapamil has the ability to improve wound healing by enhancing fibroblast proliferation, collagen bundle synthesis, and revascularization in skin injuries.
-
Barger, Nicole; Stefanacci, Lisa; Schumann, Cynthia M; Sherwood, Chet C; Annese, Jacopo; Allman, John M; Buckwalter, Joseph A; Hof, Patrick R; Semendeferi, Katerina
2012-09-01
In human and nonhuman primates, the amygdala is known to play critical roles in emotional and social behavior. Anatomically, individual amygdaloid nuclei are connected with many neural systems that are either differentially expanded or conserved over the course of primate evolution. To address amygdala evolution in humans and our closest living relatives, the apes, we used design-based stereological methods to obtain neuron counts for the amygdala and each of four major amygdaloid nuclei (the lateral, basal, accessory basal, and central nuclei) in humans, all great ape species, lesser apes, and one monkey species. Our goal was to determine whether there were significant differences in the number or percent of neurons distributed to individual nuclei among species. Additionally, regression analyses were performed on independent contrast data to determine whether any individual species deviated from allometric trends. There were two major findings. In humans, the lateral nucleus contained the highest number of neurons in the amygdala, whereas in apes the basal nucleus contained the highest number of neurons. Additionally, the human lateral nucleus contained 59% more neurons than predicted by allometric regressions on nonhuman primate data. Based on the largest sample ever analyzed in a comparative study of the hominoid amygdala, our findings suggest that an emphasis on the lateral nucleus is the main characteristic of amygdala specialization over the course of human evolution. Copyright © 2012 Wiley Periodicals, Inc.
-
Classification of polycystic ovary based on ultrasound images using competitive neural network
NASA Astrophysics Data System (ADS)
Dewi, R. M.; Adiwijaya; Wisesty, U. N.; Jondri
2018-03-01
Infertility in the women reproduction system due to inhibition of follicles maturation process causing the number of follicles which is called polycystic ovaries (PCO). PCO detection is still operated manually by a gynecologist by counting the number and size of follicles in the ovaries, so it takes a long time and needs high accuracy. In general, PCO can be detected by calculating stereology or feature extraction and classification. In this paper, we designed a system to classify PCO by using the feature extraction (Gabor Wavelet method) and Competitive Neural Network (CNN). CNN was selected because this method is the combination between Hemming Net and The Max Net so that the data classification can be performed based on the specific characteristics of ultrasound data. Based on the result of system testing, Competitive Neural Network obtained the highest accuracy is 80.84% and the time process is 60.64 seconds (when using 32 feature vectors as well as weight and bias values respectively of 0.03 and 0.002).
-
Herculano-Houzel, Suzana; von Bartheld, Christopher S; Miller, Daniel J; Kaas, Jon H
2015-04-01
The number of cells comprising biological structures represents fundamental information in basic anatomy, development, aging, drug tests, pathology and genetic manipulations. Obtaining unbiased estimates of cell numbers, however, was until recently possible only through stereological techniques, which require specific training, equipment, histological processing and appropriate sampling strategies applied to structures with a homogeneous distribution of cell bodies. An alternative, the isotropic fractionator (IF), became available in 2005 as a fast and inexpensive method that requires little training, no specific software and only a few materials before it can be used to quantify total numbers of neuronal and non-neuronal cells in a whole organ such as the brain or any dissectible regions thereof. This method entails transforming a highly anisotropic tissue into a homogeneous suspension of free-floating nuclei that can then be counted under the microscope or by flow cytometry and identified morphologically and immunocytochemically as neuronal or non-neuronal. We compare the advantages and disadvantages of each method and provide researchers with guidelines for choosing the best method for their particular needs. IF is as accurate as unbiased stereology and faster than stereological techniques, as it requires no elaborate histological processing or sampling paradigms, providing reliable estimates in a few days rather than many weeks. Tissue shrinkage is also not an issue, since the estimates provided are independent of tissue volume. The main disadvantage of IF, however, is that it necessarily destroys the tissue analyzed and thus provides no spatial information on the cellular composition of biological regions of interest.
-
Huang, Rui; Zhu, Wei-Jie; Li, Jing; Gu, Yi-Qun
2014-12-01
To evaluate the changes of stage distribution of seminiferous epithelium cycle and its correlations with Leydig cell stereological parameters in aging men. Point counting method was used to analyze the stereological parameters of Leydig cells. The stage number of seminiferous epithelium cycle was calculated in the same testicular tissue samples which were used for Leydig cell stereological analysis. The aging group had shown more severe pathological changes as well as higher pathologic scores than the young group. Compared with the control group, the volume density (VV) and surface density (NA) of Leydig cells in the aging group were increased significantly. The stage number of seminiferous epithelium cycle in the aging group was decreased coincidently compared to the young group. Leydig cell Vv in the young group has a positive relationship with stages I, II, III, V and VI of seminiferous epithelium cycle, and Leydig cell NA and numerical density (NV) were positively related to stage IV. However, only the correlation between NV and stage II was found in the aging group. The stage number of seminiferous epithelium cycle was decreased in aging testes. Changes in the stage distribution in aging testes were related to the Leydig cell stereological parameters which presented as a sign of morphological changes. Copyright © 2014 Elsevier GmbH. All rights reserved.
-
An extension of the Saltykov method to quantify 3D grain size distributions in mylonites
NASA Astrophysics Data System (ADS)
Lopez-Sanchez, Marco A.; Llana-Fúnez, Sergio
2016-12-01
The estimation of 3D grain size distributions (GSDs) in mylonites is key to understanding the rheological properties of crystalline aggregates and to constraining dynamic recrystallization models. This paper investigates whether a common stereological method, the Saltykov method, is appropriate for the study of GSDs in mylonites. In addition, we present a new stereological method, named the two-step method, which estimates a lognormal probability density function describing the 3D GSD. Both methods are tested for reproducibility and accuracy using natural and synthetic data sets. The main conclusion is that both methods are accurate and simple enough to be systematically used in recrystallized aggregates with near-equant grains. The Saltykov method is particularly suitable for estimating the volume percentage of particular grain-size fractions with an absolute uncertainty of ±5 in the estimates. The two-step method is suitable for quantifying the shape of the actual 3D GSD in recrystallized rocks using a single value, the multiplicative standard deviation (MSD) parameter, and providing a precision in the estimate typically better than 5%. The novel method provides a MSD value in recrystallized quartz that differs from previous estimates based on apparent 2D GSDs, highlighting the inconvenience of using apparent GSDs for such tasks.
-
Quantification of myocardial fibrosis by digital image analysis and interactive stereology
2014-01-01
Background Cardiac fibrosis disrupts the normal myocardial structure and has a direct impact on heart function and survival. Despite already available digital methods, the pathologist’s visual score is still widely considered as ground truth and used as a primary method in histomorphometric evaluations. The aim of this study was to compare the accuracy of digital image analysis tools and the pathologist’s visual scoring for evaluating fibrosis in human myocardial biopsies, based on reference data obtained by point counting performed on the same images. Methods Endomyocardial biopsy material from 38 patients diagnosed with inflammatory dilated cardiomyopathy was used. The extent of total cardiac fibrosis was assessed by image analysis on Masson’s trichrome-stained tissue specimens using automated Colocalization and Genie software, by Stereology grid count and manually by Pathologist’s visual score. Results A total of 116 slides were analyzed. The mean results obtained by the Colocalization software (13.72 ± 12.24%) were closest to the reference value of stereology (RVS), while the Genie software and Pathologist score gave a slight underestimation. RVS values correlated strongly with values obtained using the Colocalization and Genie (r > 0.9, p < 0.001) software as well as the pathologist visual score. Differences in fibrosis quantification by Colocalization and RVS were statistically insignificant. However, significant bias was found in the results obtained by using Genie versus RVS and pathologist score versus RVS with mean difference values of: -1.61% and 2.24%. Bland-Altman plots showed a bidirectional bias dependent on the magnitude of the measurement: Colocalization software overestimated the area fraction of fibrosis in the lower end, and underestimated in the higher end of the RVS values. Meanwhile, Genie software as well as the pathologist score showed more uniform results throughout the values, with a slight underestimation in the mid-range for both. Conclusion Both applied digital image analysis methods revealed almost perfect correlation with the criterion standard obtained by stereology grid count and, in terms of accuracy, outperformed the pathologist’s visual score. Genie algorithm proved to be the method of choice with the only drawback of a slight underestimation bias, which is considered acceptable for both clinical and research evaluations. Virtual slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/9857909611227193 PMID:24912374
-
Quantifying Golgi structure using EM: combining volume-SEM and stereology for higher throughput.
Ferguson, Sophie; Steyer, Anna M; Mayhew, Terry M; Schwab, Yannick; Lucocq, John Milton
2017-06-01
Investigating organelles such as the Golgi complex depends increasingly on high-throughput quantitative morphological analyses from multiple experimental or genetic conditions. Light microscopy (LM) has been an effective tool for screening but fails to reveal fine details of Golgi structures such as vesicles, tubules and cisternae. Electron microscopy (EM) has sufficient resolution but traditional transmission EM (TEM) methods are slow and inefficient. Newer volume scanning EM (volume-SEM) methods now have the potential to speed up 3D analysis by automated sectioning and imaging. However, they produce large arrays of sections and/or images, which require labour-intensive 3D reconstruction for quantitation on limited cell numbers. Here, we show that the information storage, digital waste and workload involved in using volume-SEM can be reduced substantially using sampling-based stereology. Using the Golgi as an example, we describe how Golgi populations can be sensed quantitatively using single random slices and how accurate quantitative structural data on Golgi organelles of individual cells can be obtained using only 5-10 sections/images taken from a volume-SEM series (thereby sensing population parameters and cell-cell variability). The approach will be useful in techniques such as correlative LM and EM (CLEM) where small samples of cells are treated and where there may be variable responses. For Golgi study, we outline a series of stereological estimators that are suited to these analyses and suggest workflows, which have the potential to enhance the speed and relevance of data acquisition in volume-SEM.
-
Nisari, Mehtap; Ertekin, Tolga; Ozçelik, Ozlem; Cınar, Serife; Doğanay, Selim; Acer, Niyazi
2012-11-01
Brain development in early life is thought to be critical period in neurodevelopmental disorder. Knowledge relating to this period is currently quite limited. This study aimed to evaluate the volume relation of total brain (TB), cerebrum, cerebellum and bulbus+pons by the use of Archimedes' principle and stereological (point-counting) method and after that to compare these approaches with each other in newborns. This study was carried out on five newborn cadavers mean weighing 2.220 ± 1.056 g with no signs of neuropathology. The mean (±SD) age of the subjects was 39.7 (±1.5) weeks. The volume and volume fraction of the total brain, cerebrum, cerebellum and bulbus+pons were determined on magnetic resonance (MR) images using the point-counting approach of stereological methods and by the use of fluid displacement technique. The mean (±SD) TB, cerebrum, cerebellum and bulbus+pons volumes by fluid displacement were 271.48 ± 78.3, 256.6 ± 71.8, 12.16 ± 6.1 and 2.72 ± 1.6 cm3, respectively. By the Cavalieri principle (point-counting) using sagittal MRIs, they were 262.01 ± 74.9, 248.11 ± 68.03, 11.68 ± 6.1 and 2.21 ± 1.13 cm3, respectively. The mean (± SD) volumes by point-counting technique using axial MR images were 288.06 ± 88.5, 275.2 ± 83.1, 19.75 ± 5.3 and 2.11 ± 0.7 cm3, respectively. There were no differences between the fluid displacement and point-counting (using axial and sagittal images) for all structures (p > 0.05). This study presents the basic data for studies relative to newborn's brain volume fractions according to two methods. Stereological (point-counting) estimation may be accepted a beneficial and new tool for neurological evaluation in vivo research of the brain. Based on these techniques we introduce here, the clinician may evaluate the growth of the brain in a more efficient and precise manner.
-
Karlsen, Anna Schou; Pakkenberg, Bente
2011-11-01
The total numbers of neurons and glial cells in the neocortex and basal ganglia in adults with Down syndrome (DS) were estimated with design-based stereological methods, providing quantitative data on brains affected by delayed development and accelerated aging. Cell numbers, volume of regions, and densities of neurons and glial cell subtypes were estimated in brains from 4 female DS subjects (mean age 66 years) and 6 female controls (mean age 70 years). The DS subjects were estimated to have about 40% fewer neocortical neurons in total (11.1 × 10(9) vs. 17.8 × 10(9), 2p ≤ 0.001) and almost 30% fewer neocortical glial cells with no overlap to controls (12.8 × 10(9) vs. 18.2 × 10(9), 2p = 0.004). In contrast, the total number of neurons in the basal ganglia was the same in the 2 groups, whereas the number of oligodendrocytes in the basal ganglia was reduced by almost 50% in DS (405 × 10(6) vs. 816 × 10(6), 2p = 0.01). We conclude that trisomy 21 affects cortical structures more than central gray matter emphasizing the differential impairment of brain development. Despite concomitant Alzheimer-like pathology, the neurodegenerative outcome in a DS brain deviates from common Alzheimer disease.
-
Mayhew, Terry M; Mühlfeld, Christian; Vanhecke, Dimitri; Ochs, Matthias
2009-04-01
Detecting, localising and counting ultrasmall particles and nanoparticles in sub- and supra-cellular compartments are of considerable current interest in basic and applied research in biomedicine, bioscience and environmental science. For particles with sufficient contrast (e.g. colloidal gold, ferritin, heavy metal-based nanoparticles), visualization requires the high resolutions achievable by transmission electron microscopy (TEM). Moreover, if particles can be counted, their spatial distributions can be subjected to statistical evaluation. Whatever the level of structural organisation, particle distributions can be compared between different compartments within a given structure (cell, tissue and organ) or between different sets of structures (in, say, control and experimental groups). Here, a portfolio of stereology-based methods for drawing such comparisons is presented. We recognise two main scenarios: (1) section surface localisation, in which particles, exemplified by antibody-conjugated colloidal gold particles or quantum dots, are distributed at the section surface during post-embedding immunolabelling, and (2) section volume localisation (or full section penetration), in which particles are contained within the cell or tissue prior to TEM fixation and embedding procedures. Whatever the study aim or hypothesis, the methods for quantifying particles rely on the same basic principles: (i) unbiased selection of specimens by multistage random sampling, (ii) unbiased estimation of particle number and compartment size using stereological test probes (points, lines, areas and volumes), and (iii) statistical testing of an appropriate null hypothesis. To compare different groups of cells or organs, a simple and efficient approach is to compare the observed distributions of raw particle counts by a combined contingency table and chi-squared analysis. Compartmental chi-squared values making substantial contributions to total chi-squared values help identify where the main differences between distributions reside. Distributions between compartments in, say, a given cell type, can be compared using a relative labelling index (RLI) or relative deposition index (RDI) combined with a chi-squared analysis to test whether or not particles preferentially locate in certain compartments. This approach is ideally suited to analysing particles located in volume-occupying compartments (organelles or tissue spaces) or surface-occupying compartments (membranes) and expected distributions can be generated by the stereological devices of point, intersection and particle counting. Labelling efficiencies (number of gold particles per antigen molecule) in immunocytochemical studies can be determined if suitable calibration methods (e.g. biochemical assays of golds per membrane surface or per cell) are available. In addition to relative quantification for between-group and between-compartment comparisons, stereological methods also permit absolute quantification, e.g. total volumes, surfaces and numbers of structures per cell. Here, the utility, limitations and recent applications of these methods are reviewed.
-
Quantification of myocardial fibrosis by digital image analysis and interactive stereology.
Daunoravicius, Dainius; Besusparis, Justinas; Zurauskas, Edvardas; Laurinaviciene, Aida; Bironaite, Daiva; Pankuweit, Sabine; Plancoulaine, Benoit; Herlin, Paulette; Bogomolovas, Julius; Grabauskiene, Virginija; Laurinavicius, Arvydas
2014-06-09
Cardiac fibrosis disrupts the normal myocardial structure and has a direct impact on heart function and survival. Despite already available digital methods, the pathologist's visual score is still widely considered as ground truth and used as a primary method in histomorphometric evaluations. The aim of this study was to compare the accuracy of digital image analysis tools and the pathologist's visual scoring for evaluating fibrosis in human myocardial biopsies, based on reference data obtained by point counting performed on the same images. Endomyocardial biopsy material from 38 patients diagnosed with inflammatory dilated cardiomyopathy was used. The extent of total cardiac fibrosis was assessed by image analysis on Masson's trichrome-stained tissue specimens using automated Colocalization and Genie software, by Stereology grid count and manually by Pathologist's visual score. A total of 116 slides were analyzed. The mean results obtained by the Colocalization software (13.72 ± 12.24%) were closest to the reference value of stereology (RVS), while the Genie software and Pathologist score gave a slight underestimation. RVS values correlated strongly with values obtained using the Colocalization and Genie (r>0.9, p<0.001) software as well as the pathologist visual score. Differences in fibrosis quantification by Colocalization and RVS were statistically insignificant. However, significant bias was found in the results obtained by using Genie versus RVS and pathologist score versus RVS with mean difference values of: -1.61% and 2.24%. Bland-Altman plots showed a bidirectional bias dependent on the magnitude of the measurement: Colocalization software overestimated the area fraction of fibrosis in the lower end, and underestimated in the higher end of the RVS values. Meanwhile, Genie software as well as the pathologist score showed more uniform results throughout the values, with a slight underestimation in the mid-range for both. Both applied digital image analysis methods revealed almost perfect correlation with the criterion standard obtained by stereology grid count and, in terms of accuracy, outperformed the pathologist's visual score. Genie algorithm proved to be the method of choice with the only drawback of a slight underestimation bias, which is considered acceptable for both clinical and research evaluations. The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/9857909611227193.
-
Xiao, Xia; Feng, Ya-Ping; Du, Bin; Sun, Han-Ru; Ding, You-Quan; Qi, Jian-Guo
2017-03-01
Fluorescent immunolabeling and imaging in free-floating thick (50-60 μm) tissue sections is relatively simple in practice and enables design-based non-biased stereology, or 3-D reconstruction and analysis. This method is widely used for 3-D in situ quantitative biology in many areas of biological research. However, the labeling quality and efficiency of standard protocols for fluorescent immunolabeling of these tissue sections are not always satisfactory. Here, we systematically evaluate the effects of raising the conventional antibody incubation temperatures (4°C or 21°C) to mammalian body temperature (37°C) in these protocols. Our modification significantly enhances the quality (labeling sensitivity, specificity, and homogeneity) and efficiency (antibody concentration and antibody incubation duration) of fluorescent immunolabeling of free-floating thick tissue sections.
-
Pérez Plasencia, D; Flores Corral, T; Urrutia Avisrror, M; Santa Cruz Ruiz, S; Benito González, J; Mateos Pérez, M M; Gómez González, J L
2002-01-01
Computer nuclear morphometry and stereology are attractive methods because its objectivity and cheapness allowing histologic diagnosis when identifying minimal variations respectively the normality and also detect negligible disparities between anormal cells which could escape to the assessment of the pathologist. We present the data gained from several morphogenic and stereologic parameters resulting of measurements of tumoral cells procured from 40 patients with nasopharyngeal carcinomata. Middle values have been: nuclear area 27.70 microns 2; nuclear perimeter 20.80 microns; nuclear factor of form 0.81 microns; nuclear outline index 4.01; nuclear orientation angle 87.29 degrees; nuclear ellipsiticity 704.14; nuclear regularity 61.83; middle lineal length 4.30, middle linear distance 107.94; and nuclear volume 118.80 microns 3. Our series is the largest studied till now of all found in the literature. Comparison our data with those of previous publications.
-
The neuroprotective role of boric acid on aluminum chloride-induced neurotoxicity.
Colak, Suat; Geyikoglu, Fatime; Keles, Osman Nuri; Türkez, Hasan; Topal, Ahmet; Unal, Bünyami
2011-09-01
This study was designed to investigate the qualitative and quantitative changes in brain tissue following aluminum chloride (AlCl(3)) administration and to determine whether boric acid (BA) has a protective effect against brain damage induced by AlCl( 3). For this aim, Sprague-Dawley rats were randomly separated into eight groups: (1) control, (2) AlCl(3) (5 mg/kg/day), (3, 4 and 5) BA (3.25, 36 and 58.5 mg/kg/day), (6, 7 and 8) AlCl(3) (5 mg/kg/day) plus BA (3.25, 36 and 58.5 mg/kg/day). After the animals were killed, the total numbers of neuron in the brain of all groups were determined using an unbiased stereological analysis. In addition to the stereological analysis, all brains were examined histopathologically by using light and electron microscopy. The stereological and histopathological results indicated a high damage of the rat brain tissues in the AlCl(3) and AlCl(3) + high dose BA (36 and 58.5) treatment groups. However, protective effects on neuron were observed in the AlCl(3) + low dose BA (3.25) group when compared other AlCl(3) groups. Our stereological and histopathological findings show that low-dose BA, as a proteasome inhibitor, can decrease the adverse effects of AlCl(3) on the cerebral cortex.
-
Agashiwala, Rajiv M; Louis, Elan D; Hof, Patrick R; Perl, Daniel P
2008-10-21
Non-biased systematic sampling using the principles of stereology provides accurate quantitative estimates of objects within neuroanatomic structures. However, the basic principles of stereology are not optimally suited for counting objects that selectively exist within a limited but complex and convoluted portion of the sample, such as occurs when counting cerebellar Purkinje cells. In an effort to quantify Purkinje cells in association with certain neurodegenerative disorders, we developed a new method for stereologic sampling of the cerebellar cortex, involving calculating the volume of the cerebellar tissues, identifying and isolating the Purkinje cell layer and using this information to extrapolate non-biased systematic sampling data to estimate the total number of Purkinje cells in the tissues. Using this approach, we counted Purkinje cells in the right cerebella of four human male control specimens, aged 41, 67, 70 and 84 years, and estimated the total Purkinje cell number for the four entire cerebella to be 27.03, 19.74, 20.44 and 22.03 million cells, respectively. The precision of the method is seen when comparing the density of the cells within the tissue: 266,274, 173,166, 167,603 and 183,575 cells/cm3, respectively. Prior literature documents Purkinje cell counts ranging from 14.8 to 30.5 million cells. These data demonstrate the accuracy of our approach. Our novel approach, which offers an improvement over previous methodologies, is of value for quantitative work of this nature. This approach could be applied to morphometric studies of other similarly complex tissues as well.
-
Agashiwala, Rajiv M.; Louis, Elan D.; Hof, Patrick R.; Perl, Daniel P.
2010-01-01
Non-biased systematic sampling using the principles of stereology provides accurate quantitative estimates of objects within neuroanatomic structures. However, the basic principles of stereology are not optimally suited for counting objects that selectively exist within a limited but complex and convoluted portion of the sample, such as occurs when counting cerebellar Purkinje cells. In an effort to quantify Purkinje cells in association with certain neurodegenerative disorders, we developed a new method for stereologic sampling of the cerebellar cortex, involving calculating the volume of the cerebellar tissues, identifying and isolating the Purkinje cell layer and using this information to extrapolate non-biased systematic sampling data to estimate the total number of Purkinje cells in the tissues. Using this approach, we counted Purkinje cells in the right cerebella of four human male control specimens, aged 41, 67, 70 and 84 years, and estimated the total Purkinje cell number for the four entire cerebella to be 27.03, 19.74, 20.44 and 22.03 million cells, respectively. The precision of the method is seen when comparing the density of the cells within the tissue: 266,274, 173,166, 167,603 and 183,575 cells/cm3, respectively. Prior literature documents Purkinje cell counts ranging from 14.8 to 30.5 million cells. These data demonstrate the accuracy of our approach. Our novel approach, which offers an improvement over previous methodologies, is of value for quantitative work of this nature. This approach could be applied to morphometric studies of other similarly complex tissues as well. PMID:18725208
-
The Effect of Estrogen Usage on Eccentric Exercise-Induced Damage in Rat Testes
Can, Serpil; Selli, Jale; Buyuk, Basak; Aydin, Sergulen; Kocaaslan, Ramazan; Guvendi, Gulname Findik
2015-01-01
Background: Recent years, lots of scientific studies are focused on the possible mechanism of inflammatory response and oxidative stress which are the mechanism related with tissue damage and exercise fatigue. It is well-known that free oxygen radicals may be induced under invitro conditions as well as oxidative stress by exhaustive physical exercise. Objectives: The aim of this study was to investigate the effects of anabolic steroids in conjunction with exercise in the process of spermatogenesis in the testes, using histological and stereological methods. Materials and Methods: Thirty-six male Sprague Dawley rats were divided to six groups, including the control group, the eccentric exercise administered group, the estrogen applied group, the estrogen applied and dissected one hour after eccentric exercise group, the no estrogen applied and dissected 48 hours after eccentric exercise group and the estrogen applied and dissected 48 hours after eccentric exercise group. Eccentric exercise was performed on a motorized rodent treadmill and the estrogen applied groups received daily physiological doses by subcutaneous injections. Testicular tissues were examined using specific histopathological, immunohistochemical and stereological methods. Sections of the testes tissue were stained using the TUNEL method to identify apoptotic cells. Apoptosis was calculated as the percentage of positive cells, using stereological analysis. A statistical analysis of the data was carried out with one-way analysis of variance (ANOVA) for the data obtained from stereological analysis. Results: Conventional light microscopic results revealed that testes tissues of the eccentric exercise administered group and the estrogen supplemented group exhibited slight impairment. In groups that were both eccentrically exercised and estrogen supplemented, more deterioration was detected in testes tissues. Likewise, immunohistochemistry findings were also more prominent in the eccentrically exercised and estrogen supplemented groups. Conclusions: The findings suggest that estrogen supplementation increases damage in testicular tissue due to eccentric exercise. PMID:26023337
-
A stereological analysis of ductile fracture by microvoid coalescence
DOE Office of Scientific and Technical Information (OSTI.GOV)
Steele, J.H., Jr.
A stereological analysis for ductile fracture by microvoid coalescence is presented based upon the model of Widgery and Knott which postulates that microvoids link with a propagating crack if they lie within a certain interaction distance of its plane. A 3- dimensional analytical expression for dimple density and shape is developed from this model using projected image relationships for a thin slab. Void nucleation and growth are incorporated into the analysis using numerical integration of the Rice-Tracey growth equation over the appropriate strain range. An evaluation of the stereological approach is given using tensile data from a spheroidized 1045 steelmore » to predict the effect of hydrostatic pressure upon the dimple density. The analysis, which is consistent with observed correlations between dimple density and second phase particle density, is shown to provide an estimate of dimple size and microroughness parameter used in local stain models for microvoid coalescence. 24 refs., 10 figs.« less
-
Røge, Rasmus; Riber-Hansen, Rikke; Nielsen, Søren; Vyberg, Mogens
2016-07-01
Manual estimation of Ki67 Proliferation Index (PI) in breast carcinoma classification is labor intensive and prone to intra- and interobserver variation. Standard Digital Image Analysis (DIA) has limitations due to issues with tumor cell identification. Recently, a computer algorithm, DIA based on Virtual Double Staining (VDS), segmenting Ki67-positive and -negative tumor cells using digitally fused parallel cytokeratin (CK) and Ki67-stained slides has been introduced. In this study, we compare VDS with manual stereological counting of Ki67-positive and -negative cells and examine the impact of the physical distance of the parallel slides on the alignment of slides. TMAs, containing 140 cores of consecutively obtained breast carcinomas, were stained for CK and Ki67 using optimized staining protocols. By means of stereological principles, Ki67-positive and -negative cell profiles were counted in sampled areas and used for the estimation of PIs of the whole tissue core. The VDS principle was applied to both the same sampled areas and the whole tissue core. Additionally, five neighboring slides were stained for CK in order to examine the alignment algorithm. Correlation between manual counting and VDS in both sampled areas and whole core was almost perfect (correlation coefficients above 0.97). Bland-Altman plots did not reveal any skewness in any data ranges. There was a good agreement in alignment (>85 %) in neighboring slides, whereas agreement decreased in non-neighboring slides. VDS gave similar results compared with manual counting using stereological principles. Introduction of this method in clinical and research practice may improve accuracy and reproducibility of Ki67 PI.
-
Mayhew, Terry M; Lucocq, John M
2015-01-01
The terms morphome and morphomics are not new but, recently, a group of morphologists and cell biologists has given them clear definitions and emphasised their integral importance in systems biology. By analogy to other ‘-omes’, the morphome refers to the distribution of matter within 3-dimensional (3D) space. It equates to the totality of morphological features within a biological system (virus, single cell, multicellular organism or populations thereof) and morphomics is the systematic study of those structures. Morphomics research has the potential to generate ‘big data’ because it includes all imaging techniques at all levels of achievable resolution and all structural scales from gross anatomy and medical imaging, via optical and electron microscopy, to molecular characterisation. As with other ‘-omics’, quantification is an important part of morphomics and, because biological systems exist and operate in 3D space, precise descriptions of form, content and spatial relationships require the quantification of structure in 3D. Revealing and quantifying structural detail inside the specimen is achieved currently in two main ways: (i) by some form of reconstruction from serial physical or tomographic slices or (ii) by using randomly-sampled sections and simple test probes (points, lines, areas, volumes) to derive stereological estimates of global and/or individual quantities. The latter include volumes, surfaces, lengths and numbers of interesting features and spatial relationships between them. This article emphasises the value of stereological design, sampling principles and estimation tools as a template for combining with alternative imaging techniques to tackle the ‘big data’ issue and advance knowledge and understanding of the morphome. The combination of stereology, TEM and immunogold cytochemistry provides a practical illustration of how this has been achieved in the sub-field of nanomorphomics. Applying these quantitative tools/techniques in a carefully managed study design offers us a deeper appreciation of the spatiotemporal relationships between the genome, metabolome and morphome which are integral to systems biology. PMID:25753334
-
Merchán-Pérez, Angel; Rodriguez, José-Rodrigo; Alonso-Nanclares, Lidia; Schertel, Andreas; Defelipe, Javier
2009-01-01
The advent of transmission electron microscopy (TEM) in the 1950s represented a fundamental step in the study of neuronal circuits. The application of this technique soon led to the realization that the number of synapses changes during the course of normal life, as well as under certain pathological or experimental circumstances. Since then, one of the main goals in neurosciences has been to define simple and accurate methods to estimate the magnitude of these changes. Contrary to analysing single sections, TEM reconstructions are extremely time-consuming and difficult. Therefore, most quantitative studies use stereological methods to define the three-dimensional characteristics of synaptic junctions that are studied in two dimensions. Here, to count the exact number of synapses per unit of volume we have applied a new three-dimensional reconstruction method that involves the combination of focused ion beam milling and scanning electron microscopy (FIB/SEM). We show that the images obtained with FIB/SEM are similar to those obtained with TEM, but with the advantage that FIB/SEM permits serial reconstructions of large volumes of tissue to be generated rapidly and automatically. Furthermore, we compared the estimates of the number of synapses obtained with stereological methods with the values obtained by FIB/SEM reconstructions. We concluded that FIB/SEM not only provides the actual number of synapses per volume but it is also much easier and faster to use than other currently available TEM methods. More importantly, it also avoids most of the errors introduced by stereological methods and overcomes the difficulties associated with these techniques.
-
Sengul, Aysen Taslak; Sahin, Bunyamin; Celenk, Cetin; Basoglu, Ahmet; Sengul, Bilal
2014-04-01
To assess the increase in lung volume after Nuss surgery in patients with pectus excavatum (PE) by using stereological methods and to evaluate the correlation between the lung volume and spirometry findings. Twenty patients, treated for PE between 2008 and 2010, were evaluated prospectively. They underwent preoperative chest radiography, computed thorax tomography (CTT), and spirometry. Thereafter, the Haller index was calculated for each patient. In the third postoperative month, CTT and spirometry were repeated.Lung volumes and volume fractions were evaluated using CTT images, applying the Cavalieri principle for stereological methods. Then the correlation between the pre- and postoperative values of the lung volumes with spirometry findings was determined. Volumes of the right and left lungs were calculated stereologically, using CTT images. Postoperative volume increase of ∼417.6 ± 747.6 mL was detected. The maximum volume increase was observed in the left lung. In the postoperative period, the total volume increase and the volume increase detected in the left lung were found to be statistically significant (p < 0.05).The preoperative correlation coefficients (r) for forced vital capacity, forced expiratory volume in 1 second, and forced expiratory flow 25 to 75% were 0.67, 0.68, and 0.61, respectively; the postoperative r figures were 0.43, 0.42, and 0.35, respectively. Although there was a strong correlation between the preoperative lung volume and spirometry findings (p < 0.05), no correlation was observed between the postoperative lung volume and spirometry findings (p > 0.05). Postoperative pulmonary volume increase occurs in patients with PE after Nuss surgery. However, postoperative spirometry findings may not reflect morphological improvement because pain restricts thoracic movements. Therefore, in patients with PE, quantitative evaluation of the results of surgical repair is possible using the CTT images through a combination of stereological methods. Georg Thieme Verlag KG Stuttgart · New York.
-
Counting glomeruli and podocytes: rationale and methodologies
Puelles, Victor G.; Bertram, John F.
2015-01-01
Purpose of review There is currently much interest in the numbers of both glomeruli and podocytes. This interest stems from greater understanding of the effects of suboptimal fetal events on nephron endowment, the associations between low nephron number and chronic cardiovascular and kidney disease in adults, and the emergence of the podocyte depletion hypothesis. Recent findings Obtaining accurate and precise estimates of glomerular and podocyte number has proven surprisingly difficult. When whole kidneys or large tissue samples are available, design-based stereological methods are considered gold-standard because they are based on principles that negate systematic bias. However, these methods are often tedious and time-consuming, and oftentimes inapplicable when dealing with small samples such as biopsies. Therefore, novel methods suitable for small tissue samples, and innovative approaches to facilitate high through put measurements, such as magnetic resonance imaging (MRI) to estimate glomerular number and flow cytometry to estimate podocyte number, have recently been described. Summary This review describes current gold-standard methods for estimating glomerular and podocyte number, as well as methods developed in the past 3 years. We are now better placed than ever before to accurately and precisely estimate glomerular and podocyte number, and to examine relationships between these measurements and kidney health and disease. PMID:25887899
-
Sharma, Kanishka; Caroli, Anna; Quach, Le Van; Petzold, Katja; Bozzetto, Michela; Serra, Andreas L.; Remuzzi, Giuseppe; Remuzzi, Andrea
2017-01-01
Background In autosomal dominant polycystic kidney disease (ADPKD), total kidney volume (TKV) is regarded as an important biomarker of disease progression and different methods are available to assess kidney volume. The purpose of this study was to identify the most efficient kidney volume computation method to be used in clinical studies evaluating the effectiveness of treatments on ADPKD progression. Methods and findings We measured single kidney volume (SKV) on two series of MR and CT images from clinical studies on ADPKD (experimental dataset) by two independent operators (expert and beginner), twice, using all of the available methods: polyline manual tracing (reference method), free-hand manual tracing, semi-automatic tracing, Stereology, Mid-slice and Ellipsoid method. Additionally, the expert operator also measured the kidney length. We compared different methods for reproducibility, accuracy, precision, and time required. In addition, we performed a validation study to evaluate the sensitivity of these methods to detect the between-treatment group difference in TKV change over one year, using MR images from a previous clinical study. Reproducibility was higher on CT than MR for all methods, being highest for manual and semiautomatic contouring methods (planimetry). On MR, planimetry showed highest accuracy and precision, while on CT accuracy and precision of both planimetry and Stereology methods were comparable. Mid-slice and Ellipsoid method, as well as kidney length were fast but provided only a rough estimate of kidney volume. The results of the validation study indicated that planimetry and Stereology allow using an importantly lower number of patients to detect changes in kidney volume induced by drug treatment as compared to other methods. Conclusions Planimetry should be preferred over fast and simplified methods for accurately monitoring ADPKD progression and assessing drug treatment effects. Expert operators, especially on MR images, are required for performing reliable estimation of kidney volume. The use of efficient TKV quantification methods considerably reduces the number of patients to enrol in clinical investigations, making them more feasible and significant. PMID:28558028
-
Vurdem, Ümit Erkan; Acer, Niyazi; Ertekin, Tolga; Savranlar, Ahmet; İnci, Mehmet Fatih
2012-01-01
Objective. The aim of this study was to determine the posterior cranial fossa volume, cerebellar volume, and herniated tonsillar volume in patients with chiari type I malformation and control subjects using stereological methods. Material and Methods. These volumes were estimated retrospectively using the Cavalieri principle as a point-counting technique. We used magnetic resonance images taken from 25 control subjects and 30 patients with chiari type I malformation. Results. The posterior cranial fossa volume in patients with chiari type I malformation was significantly smaller than the volume in the control subjects (P < 0.05). In the chiari type I malformation group, the cerebellar volume was smaller than the control group, but this difference was not statistically significant (P > 0.05). In the chiari type I malformation group, the ratio of cerebellar volume to posterior cranial fossa volume was higher than in the control group. We also found a positive correlation between the posterior cranial fossa volume and cerebellar volume for each of the groups (r = 0.865, P < 0.001). The mean (±SD) herniated tonsillar volume and length were 0.89 ± 0.50 cm3 and 9.63 ± 3.37 mm in the chiari type I malformation group, respectively. Conclusion. This study has shown that posterior cranial fossa and cerebellum volumes can be measured by stereological methods, and the ratio of these measurements can contribute to the evaluation of chiari type I malformation cases. PMID:22629166
-
Rickmann, M; Siklós, L; Joó, F; Wolff, J R
1990-09-01
An interface for IBM XT/AT-compatible computers is described which has been designed to read the actual specimen stage position of electron microscopes. The complete system consists of (i) optical incremental encoders attached to the x- and y-stage drivers of the microscope, (ii) two keypads for operator input, (iii) an interface card fitted to the bus of the personal computer, (iv) a standard configuration IBM XT (or compatible) personal computer optionally equipped with a (v) HP Graphic Language controllable colour plotter. The small size of the encoders and their connection to the stage drivers by simple ribbed belts allows an easy adaptation of the system to most electron microscopes. Operation of the interface card itself is supported by any high-level language available for personal computers. By the modular concept of these languages, the system can be customized to various applications, and no computer expertise is needed for actual operation. The present configuration offers an inexpensive attachment, which covers a wide range of applications from a simple notebook to high-resolution (200-nm) mapping of tissue. Since section coordinates can be processed in real-time, stereological estimations can be derived directly "on microscope". This is exemplified by an application in which particle numbers were determined by the disector method.
-
Knopf, Julian P; Hof, Patrick R; Oelschläger, Helmut H A
2016-01-01
We investigated the morphology of four primary neocortical projection areas (somatomotor, somatosensory, auditory, visual) qualitatively and quantitatively in the Indian river dolphins (Platanista gangetica gangetica, P. gangetica minor) with histological and stereological methods. For comparison, we included brains of other toothed whale species. Design-based stereology was applied to the primary neocortical areas (M1, S1, A1, V1) of the Indian river dolphins and compared to those of the bottlenose dolphin with respect to layers III and V. These neocortical fields were identified using existing electrophysiological and morphological data from marine dolphins as to their topography and histological structure, including the characteristics of the neuron populations concerned. In contrast to other toothed whales, the visual area (V1) of the 'blind' river dolphins seems to be rather small. M1 is displaced laterally and the auditory area (A1) is larger than in marine species with respect to total brain size. The layering is similar in the cortices of all the toothed whale brains investigated; a layer IV could not be identified. Cell density in layer III is always higher than in layer V. The maximal neuron density in P. gangetica gangetica is found in layer III of A1, followed by layers III in V1, S1, and M1. The cell density in layer V is at a similar level in all primary areas. There are, however, some differences in neuron density between the two subspecies of Indian river dolphins. Taken as a whole, it appears that the neocortex of platanistids exhibits a considerable expansion of the auditory field. Even more than other toothed whales, they seem to depend on their biosonar abilities for navigation, hunting, and communication in their riverine habitat. © 2016 S. Karger AG, Basel.
-
A Quantitative Technique for Beginning Microscopists.
ERIC Educational Resources Information Center
Sundberg, Marshall D.
1984-01-01
Stereology is the study of three-dimensional objects through the interpretation of two-dimensional images. Stereological techniques used in introductory botany to quantitatively examine changes in leaf anatomy in response to different environments are discussed. (JN)
-
Ertekin, T; Değermenci, M; Nisari, M; Unur, E; Coşkun, A
2016-01-01
The anatomy of the human nasal cavity (NC) is complex and its structures are closely related to the functions of the NC. Studies which assessing the mean volumes of NC and conchae are very infrequent. The purpose of current study is to investigate development of NC and conchae according to age and sex by using stereological method. This retrospective volumetric study was carried out on 342 individuals (166 females and 176 males) between 0 and 18 years old with no pathological conditions or medical procedures that affected the skeletal morphology of the NC. Volumetric estimations were determined on computed tomography (CT) images using point-counting approach of stereological methods. NC, inferior nasal conchae (INC) and middle nasal conchae (MNC) volume measurements that obtained using point-counting method were increased with age in both sexes until 15 years old. Regardless of gender; no significant difference was determined between the left and right values for NC, conchae volumes and choanae measurements. Generally, significant differences were determined in NC and INC volumes according to gender after they reached maximum growth period. According to age the volume ratios of INC to NC and MNC to NC were ranged from 18% to 32% and 9% to15%, respectively. The current study demonstrated that the point-counting method is effective in determining volume estimation of NC and is well suited for CT studies. Our results could provide volumetric indexes for the NC and conchae, which could help the physician for both patient selections for surgery, and for the assessment of any surgical technique used to treatment of nasal obstruction. (.
-
Morphological respiratory diffusion capacity of the lungs of ball pythons (Python regius).
Starck, J Matthias; Aupperle, Heike; Kiefer, Ingmar; Weimer, Isabel; Krautwald-Junghanns, Maria-Elisabeth; Pees, Michael
2012-08-01
This study aims at a functional and morphological characterization of the lung of a boid snake. In particular, we were interested to see if the python's lungs are designed with excess capacity as compared to resting and working oxygen demands. Therefore, the morphological respiratory diffusion capacity of ball pythons (Python regius) was examined following a stereological, hierarchically nested approach. The volume of the respiratory exchange tissue was determined using computed tomography. Tissue compartments were quantified using stereological methods on light microscopic images. The tissue diffusion barrier for oxygen transport was characterized and measured using transmission electron micrographs. We found a significant negative correlation between body mass and the volume of respiratory tissue; the lungs of larger snakes had relatively less respiratory tissue. Therefore, mass-specific respiratory tissue was calculated to exclude effects of body mass. The volume of the lung that contains parenchyma was 11.9±5.0mm(3)g(-1). The volume fraction, i.e., the actual pulmonary exchange tissue per lung parenchyma, was 63.22±7.3%; the total respiratory surface was, on average, 0.214±0.129m(2); it was significantly negatively correlated to body mass, with larger snakes having proportionally smaller respiratory surfaces. For the air-blood barrier, a harmonic mean of 0.78±0.05μm was found, with the epithelial layer representing the thickest part of the barrier. Based on these findings, a median diffusion capacity of the tissue barrier ( [Formula: see text] ) of 0.69±0.38ml O(2)min(-1)mmHg(-1) was calculated. Based on published values for blood oxygen concentration, a total oxygen uptake capacity of 61.16mlO(2)min(-1)kg(-1) can be assumed. This value exceeds the maximum demand for oxygen in ball pythons by a factor of 12. We conclude that healthy individuals of P. regius possess a considerable spare capacity for tissue oxygen exchange. Copyright © 2012 Elsevier GmbH. All rights reserved.
-
NASA Technical Reports Server (NTRS)
Mao, Xiao W.; Archambeau, John O.; Kubinova, Lucie; Boyle, Soames; Petersen, Georgia; Grove, Roger; Nelson, G. A. (Principal Investigator)
2003-01-01
This study quantified architectural and population changes in the rat retinal vasculature after proton irradiation using stereology. A 100 MeV conformal proton beam delivered 8, 14, 20 and 28 Gy as single and split doses to the whole eye. The vascular networks were prepared from retinal digests. Stereological methods were used to obtain the area of the retina and unbiased estimates of microvessel/artery/vein endothelial, pericyte and smooth muscle population, and vessel length. The retinal area increased progressively in the unirradiated, age-matched controls and in the retinas irradiated with 8 and 14 Gy, indicating uniform progressive retinal growth. No growth occurred after 20 and 28 Gy. Regression analysis of total endothelial cell number in all vessels (arteries, veins and capillaries) after irradiation documented a progressive time- and dose-dependent cell loss occurring over 15 to 24 months. The difference from controls was significant (P<0.01) after 28 Gy given in single and split doses and after 20 Gy given as a split dose (P<0.05). Total vessel length in microvessel was significantly shortened at 20 and 28 Gy compared to that of controls (P<0.05). No evident dose recovery was observed in the endothelial populations after split doses. At 10 Gy, the rate of endothelial cell loss, a dose parameter used to characterize the time- and dose-dependent loss of the endothelial population, was doubled.
-
In search for a gold-standard procedure to count motor neurons in the spinal cord.
Ferrucci, Michela; Lazzeri, Gloria; Flaibani, Marina; Biagioni, Francesca; Cantini, Federica; Madonna, Michele; Bucci, Domenico; Limanaqi, Fiona; Soldani, Paola; Fornai, Francesco
2018-03-14
Counting motor neurons within the spinal cord and brainstem represents a seminal step to comprehend the anatomy and physiology of the final common pathway sourcing from the CNS. Motor neuron loss allows to assess the severity of motor neuron disorders while providing a tool to assess disease modifying effects. Counting motor neurons at first implies gold standard identification methods. In fact, motor neurons may occur within mixed nuclei housing a considerable amount of neurons other than motor neurons. In the present review, we analyse various approaches to count motor neurons emphasizing both the benefits and bias of each protocol. A special emphasis is placed on discussing automated stereology. When automated stereology does not take into account site-specificity and does not distinguish between heterogeneous neuronal populations, it may confound data making such a procedure a sort of "guide for the perplex". Thus, if on the one hand automated stereology improves our ability to quantify neuronal populations, it may also hide false positives/negatives in neuronal counts. For instance, classic staining for antigens such as SMI-32, SMN and ChAT, which are routinely considered to be specific for motor neurons, may also occur in other neuronal types of the spinal cord. Even site specificity within Lamina IX may be misleading due to neuronal populations having a size and shape typical of motor neurons. This is the case of spinal border cells, which often surpass the border of Lamina VII and intermingle with motor neurons of Lamina IX. The present article discusses the need to join automated stereology with a dedicated knowledge of each specific neuroanatomical setting.
-
Systematic versus random sampling in stereological studies.
West, Mark J
2012-12-01
The sampling that takes place at all levels of an experimental design must be random if the estimate is to be unbiased in a statistical sense. There are two fundamental ways by which one can make a random sample of the sections and positions to be probed on the sections. Using a card-sampling analogy, one can pick any card at all out of a deck of cards. This is referred to as independent random sampling because the sampling of any one card is made without reference to the position of the other cards. The other approach to obtaining a random sample would be to pick a card within a set number of cards and others at equal intervals within the deck. Systematic sampling along one axis of many biological structures is more efficient than random sampling, because most biological structures are not randomly organized. This article discusses the merits of systematic versus random sampling in stereological studies.
-
Schmitz, C; Dafotakis, M; Heinsen, H; Mugrauer, K; Niesel, A; Popken, G J; Stephan, M; Van de Berg, W D; von Hörsten, S; Korr, H
2000-10-01
Adequate tissue preparation is essential for both modern stereological and immunohistochemical investigations. However, combining these methodologies in a single study presents a number of obstacles pertaining to optimal histological preparation. Tissue shrinkage and loss of nuclei/nucleoli from the unprotected section surfaces of unembedded tissue used for immunohistochemistry may be problematic with regard to adequate stereological design. In this study, frozen cryostat sections from hippocampal and cerebellar regions of two rat strains and cerebellar and cerebral regions from a human brain were analyzed to determine the potential impact of these factors on estimates of neuron number obtained using the optical disector. Neuronal nuclei and nucleoli were clearly present in thin sections of snap-frozen rat (3 microm) and human (6 microm) tissue, indicating that neuronal nuclei/nucleoli are not unavoidably lost from unprotected section surfaces of unembedded tissue. In order to quantify the potential impact of any nuclear loss, optical fractionator estimates of rat hippocampal pyramidal cells in areas CA1-3 and cerebellar granule and Purkinje cells were made using minimal (1 microm) upper guard zones. Estimates did not differ from data reported previously in the literature. This data indicates that cryostat sections of snap-frozen nervous tissue may successfully be used for estimating total neuronal numbers using optical disectors.
-
Luciw, Paul A; Oslund, Karen L; Yang, Xiao-Wei; Adamson, Lourdes; Ravindran, Resmi; Canfield, Don R; Tarara, Ross; Hirst, Linda; Christensen, Miles; Lerche, Nicholas W; Offenstein, Heather; Lewinsohn, David; Ventimiglia, Frank; Brignolo, Laurie; Wisner, Erik R; Hyde, Dallas M
2011-11-01
Infection with Mycobacterium tuberculosis primarily produces a multifocal distribution of pulmonary granulomas in which the pathogen resides. Accordingly, quantitative assessment of the bacterial load and pathology is a substantial challenge in tuberculosis. Such assessments are critical for studies of the pathogenesis and for the development of vaccines and drugs in animal models of experimental M. tuberculosis infection. Stereology enables unbiased quantitation of three-dimensional objects from two-dimensional sections and thus is suited to quantify histological lesions. We have developed a protocol for stereological analysis of the lung in rhesus macaques inoculated with a pathogenic clinical strain of M. tuberculosis (Erdman strain). These animals exhibit a pattern of infection and tuberculosis similar to that of naturally infected humans. Conditions were optimized for collecting lung samples in a nonbiased, random manner. Bacterial load in these samples was assessed by a standard plating assay, and granulomas were graded and enumerated microscopically. Stereological analysis provided quantitative data that supported a significant correlation between bacterial load and lung granulomas. Thus this stereological approach enables a quantitative, statistically valid analysis of the impact of M. tuberculosis infection in the lung and will serve as an essential tool for objectively comparing the efficacy of drugs and vaccines.
-
Chen, Linmu; Zhou, Chunni; Tan, Chuanxue; Wang, Feifei; Gao, Yuan; Huang, Chunxia; Zhang, Yi; Jiang, Lin; Tang, Yong
2017-01-01
Running exercise is an effective method to improve depressive symptoms when combined with drugs. However, the underlying mechanisms are not fully clear. Cerebral blood flow perfusion in depressed patients is significantly lower in the hippocampus. Physical activity can achieve cerebrovascular benefits. The purpose of this study was to evaluate the impacts of running exercise on capillaries in the hippocampal CA1 and dentate gyrus (DG) regions. The chronic unpredictable stress (CUS) depression model was used in this study. CUS rats were given 4 weeks of running exercise from the fifth week to the eighth week (20 min every day from Monday to Friday each week). The sucrose consumption test was used to measure anhedonia. Furthermore, stereological methods were used to investigate the capillary changes among the control group, CUS/Standard group and CUS/Running group. Sucrose consumption significantly increased in the CUS/Running group. Running exercise has positive effects on the capillaries parameters in the hippocampal CA1 and DG regions, such as the total volume, total length and total surface area. These results demonstrated that capillaries are protected by running exercise in the hippocampal CA1 and DG might be one of the structural bases for the exercise-induced treatment of depression-like behavior. These results suggest that drugs and behavior influence capillaries and may be considered as a new means for depression treatment in the future.
-
Postmortem structural studies of the thalamus in schizophrenia
Dorph-Petersen, Karl-Anton; Lewis, David A.
2017-01-01
In this review, we seek to answer the following question: Do findings in the current literature support the idea that thalamo-cortical dysfunction in schizophrenia is due to structural abnormalities in the thalamus? We base our review on the existing literature of design-unbiased stereological studies of the postmortem thalamus from subjects with schizophrenia. Thus, all reported results are based upon the use of unbiased principles of sampling to determine volume and/or total cell numbers of thalamus or its constituent nuclei. We found 28 such papers covering 26 studies. In a series of tables we list all positive and negative findings from the total thalamus, the mediodorsal, pulvinar and anterior nuclei, as well as less frequently studied thalamic regions. Only four studies examined the entire thalamus and the results were inconsistent. We found largely consistent evidence for structural changes (reduced volume and cell numbers) in the pulvinar located in the posterior thalamus. In contrast, findings in the mediodorsal thalamic nucleus are inconsistent, with the largest and most recent studies generally failing to support earlier reports of a lower number of neurons in schizophrenia. Thus, the current findings of stereological studies of the thalamus in schizophrenia support the idea that thalamo-cortical dysfunction in schizophrenia might be attributable, at least in part, to structural alterations in the pulvinar that could impair thalamic inputs to higher order cortical association areas in the frontal and parietal lobes. However, more studies are needed before robust conclusions can be drawn. PMID:27567291
-
Noorafshan, Ali; Asadi-Golshan, Reza; Abdollahifar, Mohammad-Amin; Karbalay-Doust, Saied
2015-08-01
Sodium metabisulfite as a food preservative can affect the central nervous system. Curcumin, the main ingredient of turmeric has neuroprotective activity. This study was designed to evaluate the effects of sulfite and curcumin on the medial prefrontal cortex (mPFC) using stereological methods. Thirty rats were randomly divided into five groups. The rats in groups I-V received distilled water, olive oil, curcumin (100 mg/kg/day), sodium metabisulfite (25 mg/kg/day), and sulfite + curcumin, respectively, for 8 weeks. The brains were subjected to the stereological methods. Cavalieri and optical disector techniques were used to estimate the total volume of mPFC and the number of neurons and glial cells. Intersections counting were applied on the thick vertical uniform random sections to estimate the dendrites length, and classify the spines. Non-parametric tests were used to analyze the data. The mean mPFC volume, neurons number, glia number, dendritic length, and total spines per neuron were 3.7 mm(3), 365,000, 180,000, 1820 µm, and 1700 in distilled water group, respectively. A reduction was observed in the volume of mPFC (∼8%), number of neurons (∼15%), and number of glia (∼14%) in mPFC of the sulfite group compared to the control groups (P < 0.005). Beside, dendritic length per neuron (∼10%) and the total spines per neuron (mainly mushroom spines) (∼25%) were reduced in the sulfite group (P < 0.005). The sulfite-induced structural changes in mPFC and curcumin had a protective role against the changes in the rats.
-
Growth of alveoli during postnatal development in humans based on stereological estimation.
Herring, Matt J; Putney, Lei F; Wyatt, Gregory; Finkbeiner, Walter E; Hyde, Dallas M
2014-08-15
Alveolarization in humans and nonhuman primates begins during prenatal development. Advances in stereological counting techniques allow accurate assessment of alveolar number; however, these techniques have not been applied to the developing human lung. Based on the recent American Thoracic Society guidelines for stereology, lungs from human autopsies, ages 2 mo to 15 yr, were fractionated and isometric uniform randomly sampled to count the number of alveoli. The number of alveoli was compared with age, weight, and height as well as growth between right and left lungs. The number of alveoli in the human lung increased exponentially during the first 2 yr of life but continued to increase albeit at a reduced rate through adolescence. Alveolar numbers also correlated with the indirect radial alveolar count technique. Growth curves for human alveolarization were compared using historical data of nonhuman primates and rats. The alveolar growth rate in nonhuman primates was nearly identical to the human growth curve. Rats were significantly different, showing a more pronounced exponential growth during the first 20 days of life. This evidence indicates that the human lung may be more plastic than originally thought, with alveolarization occurring well into adolescence. The first 20 days of life in rats implies a growth curve that may relate more to prenatal growth in humans. The data suggest that nonhuman primates are a better laboratory model for studies of human postnatal lung growth than rats. Copyright © 2014 the American Physiological Society.
-
Matenaers, Cyrill; Popper, Bastian; Rieger, Alexandra; Wanke, Rüdiger; Blutke, Andreas
2018-01-01
The accuracy of quantitative stereological analysis tools such as the (physical) disector method substantially depends on the precise determination of the thickness of the analyzed histological sections. One conventional method for measurement of histological section thickness is to re-embed the section of interest vertically to its original section plane. The section thickness is then measured in a subsequently prepared histological section of this orthogonally re-embedded sample. However, the orthogonal re-embedding (ORE) technique is quite work- and time-intensive and may produce inaccurate section thickness measurement values due to unintentional slightly oblique (non-orthogonal) positioning of the re-embedded sample-section. Here, an improved ORE method is presented, allowing for determination of the factual section plane angle of the re-embedded section, and correction of measured section thickness values for oblique (non-orthogonal) sectioning. For this, the analyzed section is mounted flat on a foil of known thickness (calibration foil) and both the section and the calibration foil are then vertically (re-)embedded. The section angle of the re-embedded section is then calculated from the deviation of the measured section thickness of the calibration foil and its factual thickness, using basic geometry. To find a practicable, fast, and accurate alternative to ORE, the suitability of spectral reflectance (SR) measurement for determination of plastic section thicknesses was evaluated. Using a commercially available optical reflectometer (F20, Filmetrics®, USA), the thicknesses of 0.5 μm thick semi-thin Epon (glycid ether)-sections and of 1-3 μm thick plastic sections (glycolmethacrylate/ methylmethacrylate, GMA/MMA), as regularly used in physical disector analyses, could precisely be measured within few seconds. Compared to the measured section thicknesses determined by ORE, SR measures displayed less than 1% deviation. Our results prove the applicability of SR to efficiently provide accurate section thickness measurements as a prerequisite for reliable estimates of dependent quantitative stereological parameters.
-
Matenaers, Cyrill; Popper, Bastian; Rieger, Alexandra; Wanke, Rüdiger
2018-01-01
The accuracy of quantitative stereological analysis tools such as the (physical) disector method substantially depends on the precise determination of the thickness of the analyzed histological sections. One conventional method for measurement of histological section thickness is to re-embed the section of interest vertically to its original section plane. The section thickness is then measured in a subsequently prepared histological section of this orthogonally re-embedded sample. However, the orthogonal re-embedding (ORE) technique is quite work- and time-intensive and may produce inaccurate section thickness measurement values due to unintentional slightly oblique (non-orthogonal) positioning of the re-embedded sample-section. Here, an improved ORE method is presented, allowing for determination of the factual section plane angle of the re-embedded section, and correction of measured section thickness values for oblique (non-orthogonal) sectioning. For this, the analyzed section is mounted flat on a foil of known thickness (calibration foil) and both the section and the calibration foil are then vertically (re-)embedded. The section angle of the re-embedded section is then calculated from the deviation of the measured section thickness of the calibration foil and its factual thickness, using basic geometry. To find a practicable, fast, and accurate alternative to ORE, the suitability of spectral reflectance (SR) measurement for determination of plastic section thicknesses was evaluated. Using a commercially available optical reflectometer (F20, Filmetrics®, USA), the thicknesses of 0.5 μm thick semi-thin Epon (glycid ether)-sections and of 1–3 μm thick plastic sections (glycolmethacrylate/ methylmethacrylate, GMA/MMA), as regularly used in physical disector analyses, could precisely be measured within few seconds. Compared to the measured section thicknesses determined by ORE, SR measures displayed less than 1% deviation. Our results prove the applicability of SR to efficiently provide accurate section thickness measurements as a prerequisite for reliable estimates of dependent quantitative stereological parameters. PMID:29444158
-
Sharma, Gulshan B; Robertson, Douglas D; Laney, Dawn A; Gambello, Michael J; Terk, Michael
2016-06-14
Type 1 Gaucher disease (GD) is an autosomal recessive lysosomal storage disease, affecting bone metabolism, structure and strength. Current bone assessment methods are not ideal. Semi-quantitative MRI scoring is unreliable, not standardized, and only evaluates bone marrow. DXA BMD is also used but is a limited predictor of bone fragility/fracture risk. Our purpose was to measure trabecular bone microarchitecture, as a biomarker of bone disease severity, in type 1 GD individuals with different GD genotypes and to apply machine learning based analytics to discriminate between GD patients and healthy individuals. Micro-MR imaging of the distal radius was performed on 20 type 1 GD patients and 10 healthy controls (HC). Fifteen stereological and textural measures (STM) were calculated from the MR images. General linear models demonstrated significant differences between GD and HC, and GD genotypes. Stereological measures, main contributors to the first two principal components (PCs), explained ~50% of data variation and were significantly different between males and females. Subsequent PCs textural measures were significantly different between GD patients and HC individuals. Textural measures also significantly differed between GD genotypes, and distinguished between GD patients with normal and pathologic DXA scores. PCA and SVM predictive analyses discriminated between GD and HC with maximum accuracy of 73% and area under ROC curve of 0.79. Trabecular STM differences can be quantified between GD patients and HC, and GD sub-types using micro-MRI and machine learning based analytics. Work is underway to expand this approach to evaluate GD disease burden and treatment efficacy. Copyright © 2016 Elsevier Ltd. All rights reserved.
-
Karbalay-Doust, Saied; Noorafshan, Ali
2012-07-05
Changes in the number and size of oocytes can lead to fertilization problems. The present study aimed to evaluate the number, volume, and surface area of oocytes in healthy as well as nandrolone decanoate-treated (ND) mice using stereological methods. Five control mice received vehicle, and five ND-treated mice received ND. Using the 'isotropic Cavalieri' design', the ovary was sectioned. The volume of the ovary (cortex and medulla) was estimated. The oocytes' volume and surface area were estimated using the invariator. The number of the oocytes was estimated using an optical disector. The volumes of the ovary, cortex, and medulla decreased ~50% in the ND-treated mice. The mean number (coefficient of variation) of preantral, antral, and atretic oocytes in the control ovary were 1,690 (0.29), 2,100 (0.52), and 3,900 (0.2), respectively, which decreased ~54%, ~87%, and ~91%, respectively in the ND-treated animals. The mean volume (coefficient of variation) of the preantral, antral, and atretic oocytes were 86,000 (0.27), 110,000 (0.48), and 27,000 (0.33) μm³, respectively. The mean surface area (coefficient of variation) of the three types of oocytes were 9,000 (0.24), 9,900 (0.28), and 4,700 (0.21) μm², respectively. These parameters remained unchanged in the ND-treated mice. ND induces reduction in the number of oocytes, but not in the volume or the surface area.
-
Yin, T T; Loughna, P; Ong, S S; Padfield, J; Mayhew, T M
2009-08-01
We test the experimental hypothesis that early changes in the ultrasound appearance of the placenta reflect poor or reduced placental function. The sonographic (Grannum) grade of placental maturity was compared to placental function as expressed by the morphometric oxygen diffusive conductance of the villous membrane. Ultrasonography was used to assess the Grannum grade of 32 placentas at 31-34 weeks of gestation. Indications for the scans included a history of previous fetal abnormalities, previous fetal growth problems or suspicion of IUGR. Placentas were classified from grade 0 (most immature) to grade III (most mature). We did not exclude smokers or complicated pregnancies as we aimed to correlate the early appearance of mature placentas with placental function. After delivery, microscopical fields on formalin-fixed, trichrome-stained histological sections of each placenta were obtained by multistage systematic uniform random sampling. Using design-based stereological methods, the exchange surface areas of peripheral (terminal and intermediate) villi and their fetal capillaries and the arithmetic and harmonic mean thicknesses of the villous membrane (maternal surface of villous trophoblast to adluminal surface of vascular endothelium) were estimated. An index of the variability in thickness of this membrane, and an estimate of its oxygen diffusive conductance, were derived secondarily as were estimates of the mean diameters and total lengths of villi and fetal capillaries. Group comparisons were drawn using analysis of variance. We found no significant differences in placental volume or composition or in the dimensions or diffusive conductances of the villous membrane. Subsequent exclusion of smokers did not alter these main findings. Grannum grades at 31-34 weeks of gestation appear not to provide reliable predictors of the functional capacity of the term placenta as expressed by the surrogate measure, morphometric diffusive conductance.
-
Guthrie, O'neil W
2015-10-01
Xeroderma pigmentosum-A (XPA) is a C4-type zinc-finger scaffolding protein that regulates the removal of bulky-helix distorting DNA damage products from the genome. Phosphorylation of serine residues within the XPA protein is associated with improved protection of genomic DNA and cell death resistance. Therefore, kinase signaling is one important mechanism for regulating the protective function of XPA. Previous experiments have shown that spiral ganglion neurons (SGNs) may mobilize XPA as a general stress response to chemical and physical ototoxicants. Therapeutic optimization of XPA via kinase signaling could serve as a means to improve DNA repair capacity within neurons following injury. The kinase signaling activity of the epidermal growth factor receptor (EGFR) has been shown in tumor cell lines to increase the repair of DNA damage products that are primarily repaired by XPA. Such observations suggest that EGFR may regulate the protective function of XPA. However, it is not known whether SGNs in particular or neurons in general could co-express XPA and EGFR. In the current study gene and protein expression of XPA and EGFR were determined from cochlear homogenates. Immunofluorescence assays were then employed to localize neurons expressing both EGFR and XPA within the ganglion. This work was then confirmed with double-immunohistochemistry. Rosenthal's canal served as the reference space in these experiments and design-based stereology was employed in first-order stereology quantification of immunoreactive neurons. The results confirmed that a population of SGNs that constitutively express XPA may also express the EGFR. These results provide the basis for future experiments designed to therapeutically manipulate the EGFR in order to regulate XPA activity and restore gene function in neurons following DNA damage. Copyright © 2015 Elsevier GmbH. All rights reserved.
-
Microstructure characterization via stereological relations — A shortcut for beginners
DOE Office of Scientific and Technical Information (OSTI.GOV)
Pabst, Willi, E-mail: pabstw@vscht.cz; Gregorová, Eva; Uhlířová, Tereza
Stereological relations that can be routinely applied for the quantitative characterization of microstructures of heterogeneous single- and two-phase materials via global microstructural descriptors are reviewed. It is shown that in the case of dense, single-phase polycrystalline materials (e.g., transparent yttrium aluminum garnet ceramics) two quantities have to be determined, the interface density (or, equivalently, the mean chord length of the grains) and the mean curvature integral density (or, equivalently, the Jeffries grain size), while for two-phase materials (e.g., highly porous, cellular alumina ceramics), one additional quantity, the volume fraction (porosity), is required. The Delesse–Rosiwal law is recalled and size measuresmore » are discussed. It is shown that the Jeffries grain size is based on the triple junction line length density, while the mean chord length of grains is based on the interface density (grain boundary area density). In contrast to widespread belief, however, these two size measures are not alternative, but independent (and thus complementary), measures of grain size. Concomitant with this fact, a clear distinction between linear and planar grain size numbers is proposed. Finally, based on our concept of phase-specific quantities, it is shown that under certain conditions it is possible to define a Jeffries size also for two-phase materials and that the ratio of the mean chord length and the Jeffries size has to be considered as an invariant number for a certain type of microstructure, i.e., a characteristic value that is independent of the absolute size of the microstructural features (e.g., grains, inclusions or pores). - Highlights: • Stereology-based image analysis is reviewed, including error considerations. • Recipes are provided for measuring global metric microstructural descriptors. • Size measures are based on interface density and mean curvature integral density. • Phase-specific quantities and a generalized Jeffries size are introduced. • Linear and planar grain size numbers are clearly distinguished and explained.« less
-
Acer, Niyazi; Ilıca, Ahmet Turan; Turgut, Ahmet Tuncay; Ozçelik, Ozlem; Yıldırım, Birdal; Turgut, Mehmet
2012-01-01
Pineal gland is a very important neuroendocrine organ with many physiological functions such as regulating circadian rhythm. Radiologically, the pineal gland volume is clinically important because it is usually difficult to distinguish small pineal tumors via magnetic resonance imaging (MRI). Although many studies have estimated the pineal gland volume using different techniques, to the best of our knowledge, there has so far been no stereological work done on this subject. The objective of the current paper was to determine the pineal gland volume using stereological methods and by the region of interest (ROI) on MRI. In this paper, the pineal gland volumes were calculated in a total of 62 subjects (36 females, 26 males) who were free of any pineal lesions or tumors. The mean ± SD pineal gland volumes of the point-counting, planimetry, and ROI groups were 99.55 ± 51.34, 102.69 ± 40.39, and 104.33 ± 40.45 mm(3), respectively. No significant difference was found among the methods of calculating pineal gland volume (P > 0.05). From these results, it can be concluded that each technique is an unbiased, efficient, and reliable method, ideally suitable for in vivo examination of MRI data for pineal gland volume estimation.
-
Acer, Niyazi; Ilıca, Ahmet Turan; Turgut, Ahmet Tuncay; Özçelik, Özlem; Yıldırım, Birdal; Turgut, Mehmet
2012-01-01
Pineal gland is a very important neuroendocrine organ with many physiological functions such as regulating circadian rhythm. Radiologically, the pineal gland volume is clinically important because it is usually difficult to distinguish small pineal tumors via magnetic resonance imaging (MRI). Although many studies have estimated the pineal gland volume using different techniques, to the best of our knowledge, there has so far been no stereological work done on this subject. The objective of the current paper was to determine the pineal gland volume using stereological methods and by the region of interest (ROI) on MRI. In this paper, the pineal gland volumes were calculated in a total of 62 subjects (36 females, 26 males) who were free of any pineal lesions or tumors. The mean ± SD pineal gland volumes of the point-counting, planimetry, and ROI groups were 99.55 ± 51.34, 102.69 ± 40.39, and 104.33 ± 40.45 mm3, respectively. No significant difference was found among the methods of calculating pineal gland volume (P > 0.05). From these results, it can be concluded that each technique is an unbiased, efficient, and reliable method, ideally suitable for in vivo examination of MRI data for pineal gland volume estimation. PMID:22619577
-
A Novel Application for the Cavalieri Principle: A Stereological and Methodological Study
Altunkaynak, Berrin Zuhal; Altunkaynak, Eyup; Unal, Deniz; Unal, Bunyamin
2009-01-01
Objective The Cavalieri principle was applied to consecutive pathology sections that were photographed at the same magnification and used to estimate tissue volumes via superimposing a point counting grid on these images. The goal of this study was to perform the Cavalieri method quickly and practically. Materials and Methods In this study, 10 adult female Sprague Dawley rats were used. Brain tissue was removed and sampled both systematically and randomly. Brain volumes were estimated using two different methods. First, all brain slices were scanned with an HP ScanJet 3400C scanner, and their images were shown on a PC monitor. Brain volume was then calculated based on these images. Second, all brain slices were photographed in 10× magnification with a microscope camera, and brain volumes were estimated based on these micrographs. Results There was no statistically significant difference between the volume measurements of the two techniques (P>0.05; Paired Samples t Test). Conclusion This study demonstrates that personal computer scanning of serial tissue sections allows for easy and reliable volume determination based on the Cavalieri method. PMID:25610077
-
Stereology shows that damaged liver recovers after protein refeeding.
Gomes, Silvio Pires; da Silva, Andréa Almeida Pinto; Crisma, Amanda Rabello; Borelli, Primavera; Hernandez-Blazquez, Francisco Javier; de Melo, Mariana P; Bacci, Barbara; Loesch, Andrzej; Coppi, A Augusto
2017-06-01
The aim of the present study was to investigate the putative effects of a low-protein diet on the three-dimensional structure of hepatocytes and determine whether this scenario could be reversed by restoring the adequate levels of protein to the diet. Using design-based stereology, the total number and volume of hepatocytes were estimated in the liver of mice in healthy and altered (by protein malnutrition) conditions and after protein renutrition. This study demonstrated a 65% decrease in the liver volume (3302 mm 3 for the control for undernourished versus 1141 mm 3 for the undernourished group) accompanied by a 46% reduction in the hepatocyte volume (8223 μm 3 for the control for undernourished versus 4475 μm 3 for the undernourished group) and a 90% increase in the total number of binucleate hepatocytes (1 549 393 for the control for undernourished versus 2 941 353 for the undernourished group). Reinstating a normoproteinic diet (12% casein) proved to be effective in restoring the size of hepatocytes, leading to an 85% increase in the total number of uninucleate hepatocytes (15 988 560 for the undernourished versus 29 600 520 for the renourished group), and partially reversed the liver atrophy. Awareness of these data will add to a better morphologic understanding of malnutrition-induced hepatopathies and will help clinicians improve the diagnosis and treatment of this condition in humans and in veterinary practice. Copyright © 2017 Elsevier Inc. All rights reserved.
-
Ekinci, Nihat; Acer, Niyazi; Akkaya, Akcan; Sankur, Seref; Kabadayi, Taner; Sahin, Bünyamin
2008-08-01
The Cavalieri estimator using a point grid is used to estimate the volume of three-dimensional structures based on two-dimensional slices of the object. The size of the components of intracranial neural structures should have proportional relations among them. The volume fraction approach of stereological methods provides information about volumetric relations of the components of structures. The purpose of our study is to estimate the volume and volume fraction data related to the cerebrum, cerebellum and brain stem. In this study, volume of the total brain, cerebrum, cerebellum and brain stem were estimated in 24 young Turkish volunteers (12 males and 12 females) who are free of any neurological symptoms and signs. The volume and volume fraction of the total brain, cerebrum, cerebellum and brain stem were determined on magnetic resonance (MR) images using the point-counting approach of stereological methods. The mean (+/-SD) total brain, cerebrum and cerebellum volumes were 1,202.05 +/- 103.51, 1,143.65 +/- 106.25 cm3 in males and females, 1,060.0 +/- 94.6, 1,008.9 +/- 104.3 cm3 in males and females, 117.75 +/- 10.7, 111.83 +/- 8.0 cm3 in males and females, respectively. The mean brain stem volumes were 24.3 +/- 2.89, 22.9 +/- 4.49 cm3 in males and females, respectively. Our results revealed that female subjects have less cerebral, cerebellar and brain stem volumes compared to males, although there was no statistically significant difference between genders (P > 0.05). The volume ratio of the cerebrum to total brain volume (TBV), cerebellum to TBV and brain stem to TBV were 88.16 and 88.13% in males and females, 9.8 and 9.8% in males and females, 2.03 and 2.03% in males and females, respectively. The volume ratio of the cerebellum to cerebrum, brain stem to cerebrum and brain stem to cerebellum were 11.12 and 11.16% in males and females, 2.30 and 2.31% in males and females, 20.7 and 20.6% in males and females, respectively. The difference between the genders was not statistically significant (P > 0.05). Our results revealed that the volumetric composition of the cerebrum, cerebellum and brain stem does not show sexual dimorphism.
-
Quantitative analysis of the renal aging in rats. Stereological study.
Melchioretto, Eduardo Felippe; Zeni, Marcelo; Veronez, Djanira Aparecida da Luz; Martins, Eduardo Lopes; Fraga, Rogério de
2016-05-01
To evaluate the renal function and the renal histological alterations through the stereology and morphometrics in rats submitted to the natural process of aging. Seventy two Wistar rats, divided in six groups. Each group was sacrificed in a different age: 3, 6, 9, 12, 18 and 24 months. It was performed right nephrectomy, stereological and morphometric analysis of the renal tissue (renal volume and weight, density of volume (Vv[glom]) and numerical density (Nv[glom]) of the renal glomeruli and average glomerular volume (Vol[glom])) and also it was evaluated the renal function for the dosage of serum creatinine and urea. There was significant decrease of the renal function in the oldest rats. The renal volume presented gradual increase during the development of the rats with the biggest values registered in the group of animals at 12 months of age and significant progressive decrease in older animals. Vv[glom] presented statistically significant gradual reduction between the groups and the Nv[glom] also decreased significantly. The renal function proved to be inferior in senile rats when compared to the young rats. The morphometric and stereological analysis evidenced renal atrophy, gradual reduction of the volume density and numerical density of the renal glomeruli associated to the aging process.
-
Post-natal growth in the rat pineal gland: a stereological study.
Erbagci, H; Kizilkan, N; Ozbag, D; Erkilic, S; Kervancioglu, P; Canan, S; Gumusburun, E
2012-10-01
The purpose was to observe the changes in a rat pineal gland using stereological techniques during lactation and post-weaning periods. Thirty Wistar albino rats were studied during different post-natal periods using light microscopy. Pineal gland volume was estimated using the Cavalieri Method. Additionally, the total number of pinealocytes was estimated using the optical fractionator technique. Pineal gland volume displayed statistically significant changes between lactation and after weaning periods. A significant increase in pineal gland volume was observed from post-natal day 10 to post-natal day 90. The numerical density of pinealocytes became stabilized during lactation and decreased rapidly after weaning. However, the total number of pinealocytes continuously increased during post-natal life of all rats in the study. However, this increment was not statistically significant when comparing the lactation and after weaning periods. The increase in post-natal pineal gland volume may depend on increment of immunoreactive fibres, capsule thickness or new synaptic bodies. © 2012 Blackwell Verlag GmbH.
-
A novel application for the cavalieri principle: a stereological and methodological study.
Altunkaynak, Berrin Zuhal; Altunkaynak, Eyup; Unal, Deniz; Unal, Bunyamin
2009-08-01
The Cavalieri principle was applied to consecutive pathology sections that were photographed at the same magnification and used to estimate tissue volumes via superimposing a point counting grid on these images. The goal of this study was to perform the Cavalieri method quickly and practically. In this study, 10 adult female Sprague Dawley rats were used. Brain tissue was removed and sampled both systematically and randomly. Brain volumes were estimated using two different methods. First, all brain slices were scanned with an HP ScanJet 3400C scanner, and their images were shown on a PC monitor. Brain volume was then calculated based on these images. Second, all brain slices were photographed in 10× magnification with a microscope camera, and brain volumes were estimated based on these micrographs. There was no statistically significant difference between the volume measurements of the two techniques (P>0.05; Paired Samples t Test). This study demonstrates that personal computer scanning of serial tissue sections allows for easy and reliable volume determination based on the Cavalieri method.
-
Nuñez, P; Fernandez, T; García-Arévalo, M; Alonso-Magdalena, P; Nadal, A; Perillan, C; Arguelles, J
2018-04-01
Bisphenol A (BPA) is a chemical found in plastics that resembles oestrogen in organisms. Developmental exposure to endocrine-disrupting chemicals, such as BPA, increases the susceptibility to type 2 diabetes (T2DM) and cardiovascular diseases. Animal studies have reported a nephron deficit in offspring exposed to maternal diabetes. The aim of this study was to investigate the prenatal BPA exposure effects on nephrogenesis in a mouse model that was predisposed to T2DM. This study quantitatively evaluated the renal structural changes using stereology and histomorphometry methods. The OF1 pregnant mice were treated with a vehicle or BPA (10 or 100 μg/kg/day) during days 9-16 of gestation (early nephrogenesis). The 30-day-old offspring were sacrificed, and tissue samples were collected and prepared for histopathological and stereology studies. Glomerular abnormalities and reduced glomerular formation were observed in the BPA offspring. The kidneys of the BPA10 and BPA100 female offspring had a significantly lower glomerular number and density than those of the CONTROL female offspring. The glomerular histomorphometry revealed a significant difference between the female and male CONTROL offspring for the analysed glomerular parameters that disappeared in the BPA10 and BPA100 offspring. In addition, the kidney histopathological examination showed typical male cuboidal epithelial cells of the Bowman capsule in the female BPA offspring. Exposure to environmentally relevant doses of BPA during embryonic development altered nephrogenesis. These structural changes could be associated with an increased risk of developing cardiometabolic diseases later in life.
-
Development of the Cell Population in the Brain White Matter of Young Children.
Sigaard, Rasmus Krarup; Kjær, Majken; Pakkenberg, Bente
2016-01-01
While brain gray matter is primarily associated with sensorimotor processing and cognition, white matter modulates the distribution of action potentials, coordinates communication between different brain regions, and acts as a relay for input/output signals. Previous studies have described morphological changes in gray and white matter during childhood and adolescence, which are consistent with cellular genesis and maturation, but corresponding events in infants are poorly documented. In the present study, we estimated the total number of cells (neurons, oligodendrocytes, astrocytes, and microglia) in the cerebral white matter of 9 infants aged 0-33 months, using design-based stereological methods to obtain quantitative data about brain development. There were linear increases with age in the numbers of oligodendrocytes (7-28 billion) and astrocytes (1.5-6.7 billion) during the first 3 years of life, thus attaining two-thirds of the corresponding numbers in adults. The numbers of neurons (0.7 billion) and microglia (0.2 billion) in the white matter did not increase during the first 3 years of life, but showed large biological variation. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
-
[Stereological analysis of rat bone tissue after a flight on the Kosmos-1129 biosatellite].
Prokhonchukov, A A; Peschanskiĭ, V S
1982-01-01
Stereological measurements of volume fractions of 53 samples of compact and spongy structures of bones of 15 rats were carried out. The measurements were performed on cortical lamellae, trabecules and lacunae, channels of osteons and matrices of femoral, tibial and fibular bones of rats. Postflight no significant changes were seen in the above parameters as compared to the vivarium controls. During readaptation to I g a slight increase in the volume fraction of spongy bones was noted.
-
Smeyne, Richard Jay; Breckenridge, Charles B.; Beck, Melissa; Jiao, Yun; Butt, Mark T.; Wolf, Jeffrey C.; Zadory, Dan; Minnema, Daniel J.; Sturgess, Nicholas C.; Travis, Kim Z.; Cook, Andrew R.; Smith, Lewis L.; Botham, Philip A.
2016-01-01
The neurotoxicity of paraquat dichloride (PQ) was assessed in two inbred strains of 9- or 16-week old male C57BL/6 mice housed in two different laboratories and compared to the effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). PQ was administered by intraperitoneal injections; either once (20 mg/kg) or twice (10 mg/kg) weekly for 3 weeks, while MPTP-HCl was injected 4 times on a single day (20 mg/kg/dose). Brains were collected 8, 16, 24, 48, 96 or 168 hours after the last PQ treatment, and 48 or 168 hours after MPTP treatment. Dopamine neurons in the substantia nigra pars compacta (SNpc) were identified by antibodies to tyrosine hydroxylase (TH+) and microglia were identified using Iba-1 immunoreactivity. The total number of TH+ neurons and the number of resting and activated microglia in the SNpc at 168 hours after the last dose were estimated using model- or design-based stereology, with investigators blinded to treatment. In a further analysis, a pathologist, also blinded to treatment, evaluated the SNpc and/or striatum for loss of TH+ neurons (SNpc) or terminals (striatum), cell death (as indicated by amino cupric silver uptake, TUNEL and/or caspase 3 staining) and neuroinflammation (as indicated by Iba-1 and/or GFAP staining). PQ, administered either once or twice weekly to 9- or 16-week old mice from two suppliers, had no effect on the number of TH+ neurons or microglia in the SNpc, as assessed by two groups, each blinded to treatment, using different stereological methods. PQ did not induce neuronal cell loss or degeneration in the SNpc or striatum. Additionally, there was no evidence of apoptosis, microgliosis or astrogliosis. In MPTP-treated mice, the number of TH+ neurons in the SNpc was significantly decreased and the number of activated microglia increased. Histopathological assessment found degenerating neurons/terminals in the SNpc and striatum but no evidence of apoptotic cell death. MPTP activated microglia in the SNpc and increased the number of astrocytes in the SNpc and striatum. PMID:27788145
-
Smeyne, Richard Jay; Breckenridge, Charles B; Beck, Melissa; Jiao, Yun; Butt, Mark T; Wolf, Jeffrey C; Zadory, Dan; Minnema, Daniel J; Sturgess, Nicholas C; Travis, Kim Z; Cook, Andrew R; Smith, Lewis L; Botham, Philip A
2016-01-01
The neurotoxicity of paraquat dichloride (PQ) was assessed in two inbred strains of 9- or 16-week old male C57BL/6 mice housed in two different laboratories and compared to the effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). PQ was administered by intraperitoneal injections; either once (20 mg/kg) or twice (10 mg/kg) weekly for 3 weeks, while MPTP-HCl was injected 4 times on a single day (20 mg/kg/dose). Brains were collected 8, 16, 24, 48, 96 or 168 hours after the last PQ treatment, and 48 or 168 hours after MPTP treatment. Dopamine neurons in the substantia nigra pars compacta (SNpc) were identified by antibodies to tyrosine hydroxylase (TH+) and microglia were identified using Iba-1 immunoreactivity. The total number of TH+ neurons and the number of resting and activated microglia in the SNpc at 168 hours after the last dose were estimated using model- or design-based stereology, with investigators blinded to treatment. In a further analysis, a pathologist, also blinded to treatment, evaluated the SNpc and/or striatum for loss of TH+ neurons (SNpc) or terminals (striatum), cell death (as indicated by amino cupric silver uptake, TUNEL and/or caspase 3 staining) and neuroinflammation (as indicated by Iba-1 and/or GFAP staining). PQ, administered either once or twice weekly to 9- or 16-week old mice from two suppliers, had no effect on the number of TH+ neurons or microglia in the SNpc, as assessed by two groups, each blinded to treatment, using different stereological methods. PQ did not induce neuronal cell loss or degeneration in the SNpc or striatum. Additionally, there was no evidence of apoptosis, microgliosis or astrogliosis. In MPTP-treated mice, the number of TH+ neurons in the SNpc was significantly decreased and the number of activated microglia increased. Histopathological assessment found degenerating neurons/terminals in the SNpc and striatum but no evidence of apoptotic cell death. MPTP activated microglia in the SNpc and increased the number of astrocytes in the SNpc and striatum.
-
NASA Astrophysics Data System (ADS)
Saber, Sámar; Macías, David; Ortiz de Urbina, Josetxu; Kjesbu, Olav Sigurd
2015-01-01
Traditional histological protocols in marine fish reproductive laboratories using paraffin as the embedding medium are now increasingly being replaced with protocols using resin instead. These procedures entail different degrees of tissue shrinkage complicating direct comparisons of measurement results across laboratories or articles. In this work we selected ovaries of spawning Mediterranean albacore (Thunnus alalunga) as the subject of our study to address the issue of structural changes, by contrasting values on oocyte recruitment and final batch fecundity given from the same tissue samples in both paraffin and resin. A modern stereological method, the oocyte packing density (OPD) theory, was used supported by initial studies on ovarian tissue sampling and measurement design. Examples of differences in the volume fraction of oocyte stages, free space and connective tissue were found between the embedding media. Mean oocyte diameters were smaller in paraffin than in resin with differences ranging between 0.5% in primary growth and 24.3% in hydration (HYD) stage oocytes. Fresh oocyte measurements showed that oocytes shrank as a consequence of the embedding process, reaching the maximal degree of shrinkage for oocytes in the HYD stage (45.8% in paraffin and 26.5% in resin). In order to assess the effect of oocyte shrinkage on the OPD result, and thereby on relative batch fecundity (Fr), oocyte diameters corrected and uncorrected for shrinkage, were used for estimations. Statistical significant differences were found (P < 0.05) between these two approaches in both embedding media. The average Fr was numerically smaller in paraffin compared to resin (86 ± 61 vs. 106 ± 54 oocytes per gram of body mass (mean ± SD)). For both embedding media statistical significant differences (P < 0.05) were seen between Fr results based on either oocytes in the germinal vesicle migration stage or HYD stage. As a valuable adjunct, the present use of the OPD theory made it possible to document that the oocyte recruitment of spawning ovaries of Mediterranean albacore followed the typical pattern of an asynchronous oocyte development and indeterminate fecundity.
-
Stereological Cell Morphometry In Right Atrium Myocardium Of Primates
NASA Astrophysics Data System (ADS)
Mandarim-De-Lacerda, Carlos A...; Hureau, Jacques
1986-07-01
The mechanism by which the cardiac impulse is propagated in normal hearts from its origin in the sinus node to the atrio-ventricular node has not been agreed on fully. We studied the "internodal posterior tract" through the crista terminalis by light microscopy and stereological morphometry. The hearts of 12 Papio cynocephalus were perfused , after sacrifice,with phosphate-buffered formol saline. The regions of the crista terminalis (CT), interatrial septum (IAS), atrioventricular bundle (AVB) and interventricular septum (IVS) were cut off and embedded in paraplast and sectioned (10 4m). The multipurpose test system M 42 was superimposed over the photomicrographs (1,890 points test, ESR = 2%) to the stereological computing. The quantitative results show that the cells from CT were more closely relationed with IAS cells than others cells (IVS and AVB cells). This results are not a morphological evidence to establish the specificity of the "internodal posterior tract". The cellular arrangement and anatomical variation in CT myocardium is very important.
-
Xu, Y H; Dragan, Y P; Campbell, H A; Pitot, H C
1998-04-01
The most common organ site of neoplasms induced by carcinogenic chemicals in the rodent bioassay is the liver. The development of cancer in rodent liver is a multistage process involving sequentially the stages of initiation, promotion, and progression. During the stages of promotion and progression, numerous lesions termed altered hepatic foci (AHF) develop. STEREO was developed for the purpose of efficient and accurate quantitation of AHF and related lesions in experimental and test rodents. The system utilized is equipped with a microcomputer (IBM-compatible PC running Windows 95) and a Summagraphics MICROGRID or SummaSketch tablet digitizer. The program records information from digitization of single or serial sections obtained randomly from rat liver tissue. With this information and the methods of quantitative stereology, both the number and volume percentage fraction of AHF in liver are calculated in three dimensions. The recorded data files can be printed graphically or in the format of tabular numerical data. The results of stereologic calculations are stored on floppy disks and can be sorted into different categories and analyzed or displayed with the use of statistics and graphic functions built into the overall program. Results may also be exported into Microsoft Excel for use at a later time. Any IBM-compatible PC capable of utilizing Windows 95 and MS Office can be used with STEREO, which offers inexpensive, easily operated software to obtain three-dimensional information from sections of two dimensions for the identification and relative potency of initiators, promoters, and progressors, and for the establishment of information potentially useful in developing estimations of risk for human cancer.
-
Rakesh Minocha; Carolyn McQuattie; Wayne Fagerberg; Stephanie Long; Eun Woon Noh
2001-01-01
The effects of Al on red spruce (Picea rubens Sarg.) cell suspension cultures were examined using biochemical, stereo-logical and microscopic methods. Exposure to Al for 24-48 h resulted in a loss of cell viability, inhibition of growth and a significant decrease in mitochondrial activity. Soluble protein content increased in cells treated with Al....
-
A Stereological Study of Synapse Number in the Epileptic Human Hippocampus
Alonso-Nanclares, Lidia; Kastanauskaite, Asta; Rodriguez, Jose-Rodrigo; Gonzalez-Soriano, Juncal; DeFelipe, Javier
2011-01-01
Hippocampal sclerosis is the most frequent pathology encountered in resected mesial temporal structures from patients with intractable temporal lobe epilepsy (TLE). Here, we have used stereological methods to compare the overall density of synapses and neurons between non-sclerotic and sclerotic hippocampal tissue obtained by surgical resection from patients with TLE. Specifically, we examined the possible changes in the subiculum and CA1, regions that seem to be critical for the development and/or maintenance of seizures in these patients. We found a remarkable decrease in synaptic and neuronal density in the sclerotic CA1, and while the subiculum from the sclerotic hippocampus did not display changes in synaptic density, the neuronal density was higher. Since the subiculum from the sclerotic hippocampus displays a significant increase in neuronal density, as well as a various other neurochemical changes, we propose that the apparently normal subiculum from the sclerotic hippocampus suffers profound alterations in neuronal circuits at both the molecular and synaptic level that are likely to be critical for the development or maintenance of seizure activity. PMID:21390290
-
Microstructural Effects on Initiation Behavior in HMX
NASA Astrophysics Data System (ADS)
Molek, Christopher; Welle, Eric; Hardin, Barrett; Vitarelli, Jim; Wixom, Ryan; Samuels, Philip
Understanding the role microstructure plays on ignition and growth behavior has been the subject of a significant body of research within the detonation physics community. The pursuit of this understanding is important because safety and performance characteristics have been shown to strongly correlate to particle morphology. Historical studies have often correlated bulk powder characteristics to the performance or safety characteristics of pressed materials. We believe that a clearer and more relevant correlation is made between the pressed microstructure and the observed detonation behavior. This type of assessment is possible, as techniques now exist for the quantification of the pressed microstructures. Our talk will report on experimental efforts that correlate directly measured microstructural characteristics to initiation threshold behavior of HMX based materials. The internal microstructures were revealed using an argon ion cross-sectioning technique. This technique enabled the quantification of density and interface area of the pores within the pressed bed using methods of stereology. These bed characteristics are compared to the initiation threshold behavior of three HMX based materials using an electric gun based test method. Finally, a comparison of experimental threshold data to supporting theoretical efforts will be made.
-
Examining cerebral angiogenesis in response to physical exercise.
Berggren, Kiersten L; Kay, Jacob J M; Swain, Rodney A
2014-01-01
Capillary growth and expansion (angiogenesis) is a prerequisite for many forms of neural and behavioral plasticity. It is commonly observed in both brain and muscle of aerobically exercising animals. As such, several histological methods have been used to quantify capillary density, including perfusion with India ink, various Nissl stains, and immunohistochemistry. In this chapter, we will describe these histological procedures and describe the stereological analysis used to quantify vessel growth in response to aerobic exercise.
-
Mattfeldt, Torsten
2011-04-01
Computer-intensive methods may be defined as data analytical procedures involving a huge number of highly repetitive computations. We mention resampling methods with replacement (bootstrap methods), resampling methods without replacement (randomization tests) and simulation methods. The resampling methods are based on simple and robust principles and are largely free from distributional assumptions. Bootstrap methods may be used to compute confidence intervals for a scalar model parameter and for summary statistics from replicated planar point patterns, and for significance tests. For some simple models of planar point processes, point patterns can be simulated by elementary Monte Carlo methods. The simulation of models with more complex interaction properties usually requires more advanced computing methods. In this context, we mention simulation of Gibbs processes with Markov chain Monte Carlo methods using the Metropolis-Hastings algorithm. An alternative to simulations on the basis of a parametric model consists of stochastic reconstruction methods. The basic ideas behind the methods are briefly reviewed and illustrated by simple worked examples in order to encourage novices in the field to use computer-intensive methods. © 2010 The Authors Journal of Microscopy © 2010 Royal Microscopical Society.
-
Borner, Roseane; Bento-Torres, João; Souza, Diego RV; Sadala, Danyelle B; Trevia, Nonata; Farias, José Augusto; Lins, Nara; Passos, Aline; Quintairos, Amanda; Diniz, José Antônio; Perry, Victor Hugh; Vasconcelos, Pedro Fernando; Cunningham, Colm
2011-01-01
Behavioral and neuropathological changes have been widely investigated in murine prion disease but stereological based unbiased estimates of key neuropathological features have not been carried out. After injections of ME7 infected (ME7) or normal brain homogenates (NBH) into dorsal CA1 of albino Swiss mice and C57BL6, we assessed behavioral changes on hippocampal-dependent tasks. We also estimated by optical fractionator at 15 and 18 weeks post-injections (w.p.i.) the total number of neurons, reactive astrocytes, activated microglia and perineuronal nets (PN) in the polymorphic layer of dentate gyrus (PolDG), CA1 and septum in albino Swiss mice. On average, early behavioral changes in albino Swiss mice start four weeks later than in C57BL6. Cluster and discriminant analysis of behavioral data in albino Swiss mice revealed that four of nine subjects start to change their behavior at 12 w.p.i. and reach terminal stage at 22 w.p.i and the remaining subjects start at 22 w.p.i. and reach terminal stage at 26 w.p.i. Biotinylated dextran-amine BDA-tracer experiments in mossy fiber pathway confirmed axonal degeneration and stereological data showed that early astrocytosis, microgliosis and reduction in the perineuronal nets are independent of a change in the number of neuronal cell bodies. Statistical analysis revealed that the septal region had greater levels of neuroinflammation and extracellular matrix damage than CA1. This stereological and multivariate analysis at early stages of disease in an outbred model of prion disease provided new insights connecting behavioral changes and neuroinflammation and seems to be important to understand the mechanisms of prion disease progression. PMID:21862877
-
Yurttas, Canan; Schmitz, Christoph; Turgut, Mehmet; Strekalova, Tatyana; Steinbusch, Harry W M
2017-09-01
Bilateral olfactory bulbectomy (OBX) has been used as an animal model for major depression that results in behavioral, neurochemical, and neuroendocrinological changes were reversed by chronic treatment with antidepressants, including fluoxetine. However, both etiological and construct validities are lacking in OBX for rats. In the present study, we investigated the morphological changes in the hippocampi of rats undergoing OBX that were treated with fluoxetine (10mg/kg, p.o. once daily for 4 and 12 weeks) using stereological techniques. Our results revealed that OBX caused a reduction in the volumes of the CA1/2, CA3, and dentate gyrus regions 4 weeks after OBX without fluoxetine treatment. With fluoxetine treatment, these reductions were achieved 12 weeks after OBX and the volumes were comparable to normal control rats. Nevertheless, fluoxetine treatment did not reverse neuron loss in all hippocampal regions 12 weeks after OBX. Therefore, we suggest that the OBX rat model should not be used to detect the antidepressant activity of various pharmacological agents such as fluoxetine. Copyright © 2017 Elsevier Inc. All rights reserved.
-
Rubinow, Marisa J; Mahajan, Gouri; May, Warren; Overholser, James C; Jurjus, George J; Dieter, Lesa; Herbst, Nicole; Steffens, David C; Miguel-Hidalgo, Jose J; Rajkowska, Grazyna; Stockmeier, Craig A
2016-01-01
Functional imaging studies consistently report abnormal amygdala activity in major depressive disorder (MDD). Neuroanatomical correlates are less clear: imaging studies have produced mixed results on amygdala volume, and postmortem neuroanatomic studies have only examined cell densities in portions of the amygdala or its subregions in MDD. Here, we present a stereological analysis of the volume of, and the total number of, neurons, glia, and neurovascular (pericyte and endothelial) cells in the basolateral amygdala in MDD. Postmortem tissues from 13 subjects with MDD and 10 controls were examined. Sections (~15/subject) taken throughout the rostral-caudal extent of the basolateral amygdala (BLA) were stained for Nissl substance and utilized for stereological estimation of volume and cell numbers. Results indicate that depressed subjects had a larger lateral nucleus than controls and a greater number of total BLA neurovascular cells than controls. There were no differences in the number or density of neurons or glia between depressed and control subjects. These findings present a more detailed picture of BLA cellular anatomy in depression than has previously been available. Further studies are needed to determine whether the greater number of neurovascular cells in depressed subjects may be related to increased amygdala activity in depression.
-
Pamuk, F; Cetinkaya, B O; Ayas, B; Keles, G C; Gacar, A
2015-10-01
It has previously been shown that both cyclosporine A and tacrolimus cause gingival overgrowth in the rat. We proposed that sirolimus may play an important role in decreasing the severity of gingival overgrowth. Therefore, the aim of this study was to evaluate the gingival changes induced by immunosuppressants, in the presence and absence of sirolimus, using histopathology and stereological methods. Thirty-six male Sprague-Dawley rats were distributed into six treatment groups, each containing six rats, as follows: (i) cyclosporine A for 8 wk; (ii) tacrolimus for 8 wk; (iii) sirolimus for 8 wk; (iv) cyclosporine A + sirolimus for 8 wk; (v) tacrolimus + sirolimus for 8 wk; and (vi) distilled water for 8 wk. Histomorphometric analyses included measurements of epithelial thickness and connective tissue width and height. Stereological analyses included measurements of volumetric densities of fibroblasts (Vf ), collagen fibers (Vcf ) and blood vessels (Vbv ). Connective tissue width and height were significantly increased in cyclosporine A, tacrolimus and cyclosporine A + sirolimus groups compared with the control group (p < 0.05), and epithelial thickness was significantly increased in the cyclosporine A group and tacrolimus group compared with the control group (p < 0.05). Vf was significantly increased in the cyclosporine A group and the tacrolimus group compared with the control group (p < 0.05), whereas Vcf and Vbv were significantly increased in the cyclosporine A, tacrolimus and cyclosporine A + sirolimus groups compared with the control group (p < 0.05). The results of the study suggest that sirolimus seems not to be associated with gingival overgrowth, and combined usage of sirolimus and immunosuppressants decreases the severity of gingival overgrowth. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
-
Wong, M; Wuethrich, P; Eggli, P; Hunziker, E
1996-05-01
A new methodology was developed to measure spatial variations in chondrocyte/matrix structural parameters and chondrocyte biosynthetic activity in articular cartilage. This technique is based on the use of a laser scanning confocal microscope that can "optically" section chemically fixed, unembedded tissue. The confocal images are used for morphometric measurement of stereologic parameters such as cell density (cells/mm3), cell volume fraction (%), surface density (l/cm), mean cell volume (micron3), and mean cell surface area (micron2). Adjacent pieces of tissue are simultaneously processed for conventional liquid emulsion autoradiography, and a semiautomated grain counting program is used to measure the silver grain density at regions corresponding to the same sites used for structural measurements. An estimate of chondrocyte biosynthetic activity in terms of grains per cell is obtained by dividing the value for grain density by that for cell density. In this paper, the newly developed methodology was applied to characterize the zone-specific behavior of adult articular cartilage in the free-swelling state. Cylinders of young adult bovine articular cartilage were labelled with either [3H]proline or [35S]sulfate, and chondrocyte biosynthesis and structural parameters were measured from the articular surface to the tidemark. The results showed that chondrocytes of the radial zone occupied twice the volume and surface area of the chondrocytes of the superficial zone but were 10 times more synthetically active. This efficient and unbiased technique may prove useful in studying the correlation between mechanically induced changes in cell form and biosynthetic activity within inhomogeneous tissue as well as metabolic changes in cartilage due to ageing and disease.
-
King, Michael A; Scotty, Nicole; Klein, Ronald L; Meyer, Edwin M
2002-10-01
Assessing the efficacy of in vivo gene transfer often requires a quantitative determination of the number, size, shape, or histological visualization characteristics of biological objects. The optical fractionator has become a choice stereological method for estimating the number of objects, such as neurons, in a structure, such as a brain subregion. Digital image processing and analytic methods can increase detection sensitivity and quantify structural and/or spectral features located in histological specimens. We describe a hardware and software system that we have developed for conducting the optical fractionator process. A microscope equipped with a video camera and motorized stage and focus controls is interfaced with a desktop computer. The computer contains a combination live video/computer graphics adapter with a video frame grabber and controls the stage, focus, and video via a commercial imaging software package. Specialized macro programs have been constructed with this software to execute command sequences requisite to the optical fractionator method: defining regions of interest, positioning specimens in a systematic uniform random manner, and stepping through known volumes of tissue for interactive object identification (optical dissectors). The system affords the flexibility to work with count regions that exceed the microscope image field size at low magnifications and to adjust the parameters of the fractionator sampling to best match the demands of particular specimens and object types. Digital image processing can be used to facilitate object detection and identification, and objects that meet criteria for counting can be analyzed for a variety of morphometric and optical properties. Copyright 2002 Elsevier Science (USA)
-
PREFACE: Anti-counterfeit Image Analysis Methods (A Special Session of ICSXII)
NASA Astrophysics Data System (ADS)
Javidi, B.; Fournel, T.
2007-06-01
The International Congress for Stereology is dedicated to theoretical and applied aspects of stochastic tools, image analysis and mathematical morphology. A special emphasis on `anti-counterfeit image analysis methods' has been given this year for the XIIth edition (ICSXII). Facing the economic and social threat of counterfeiting, this devoted session presents recent advances and original solutions in the field. A first group of methods are related to marks located either on the product (physical marks) or on the data (hidden information) to be protected. These methods concern laser fs 3D encoding and source separation for machine-readable identification, moiré and `guilloche' engraving for visual verification and watermarking. Machine-readable travel documents are well-suited examples introducing the second group of methods which are related to cryptography. Used in passports for data authentication and identification (of people), cryptography provides some powerful tools. Opto-digital processing allows some efficient implementations described in the papers and promising applications. We would like to thank the reviewers who have contributed to a session of high quality, and the authors for their fine and hard work. We would like to address some special thanks to the invited lecturers, namely Professor Roger Hersch and Dr Isaac Amidror for their survey of moiré methods, Prof. Serge Vaudenay for his survey of existing protocols concerning machine-readable travel documents, and Dr Elisabet Pérez-Cabré for her presentation on optical encryption for multifactor authentication. We also thank Professor Dominique Jeulin, President of the International Society for Stereology, Professor Michel Jourlin, President of the organizing committee of ICSXII, for their help and advice, and Mr Graham Douglas, the Publisher of Journal of Physics: Conference Series at IOP Publishing, for his efficiency. We hope that this collection of papers will be useful as a tool to further develop a very important field. Bahram Javidi University of Connecticut (USA) Thierry Fournel University of Saint-Etienne (France) Chairs of the special session on `Anti-counterfeit image analysis methods', July 2007
-
[Morphometry of pulmonary tissue: From manual to high throughput automation].
Sallon, C; Soulet, D; Tremblay, Y
2017-12-01
Weibel's research has shown that any alteration of the pulmonary structure has effects on function. This demonstration required a quantitative analysis of lung structures called morphometry. This is possible thanks to stereology, a set of methods based on principles of geometry and statistics. His work has helped to better understand the morphological harmony of the lung, which is essential for its proper functioning. An imbalance leads to pathophysiology such as chronic obstructive pulmonary disease in adults and bronchopulmonary dysplasia in neonates. It is by studying this imbalance that new therapeutic approaches can be developed. These advances are achievable only through morphometric analytical methods, which are increasingly precise and focused, in particular thanks to the high-throughput automation of these methods. This review makes a comparison between an automated method that we developed in the laboratory and semi-manual methods of morphometric analyzes. The automation of morphometric measurements is a fundamental asset in the study of pulmonary pathophysiology because it is an assurance of robustness, reproducibility and speed. This tool will thus contribute significantly to the acceleration of the race for the development of new drugs. Copyright © 2017 SPLF. Published by Elsevier Masson SAS. All rights reserved.
-
Buyuk, Basak; Parlak, Secil Nazife; Keles, Osman Nuri; Can, Ismail; Yetim, Zeliha; Toktay, Erdem; Selli, Jale; Unal, Bunyami
2015-01-01
Objective: The menopause in elderly women is a physiological process where ovarian and uterine cycles end. Diabetes means higher blood glucose level that is a metabolic disease and has an increased incidence. The aim of the study was to examine the single or combined effects of menopause and diabetes that causes pathophysiological processes on submandibular gland on ovariectomy and diabetes induced rat models. Materials and Methods: Sprague Dawley twelve weeks old female (n=24) rats were divided randomly into four groups; Healthy control group (n=6), diabetic group (DM, n=6), ovariectomized group (OVX, n=6), post ovariectomy diabetes induced group (DM+OVX, n=6) individually. Histopathological, histochemical and stereological analyses were done in these groups. Results: Significant neutrophil cell infiltrations and myoepithelial cell proliferations, granular duct and seromucous acini damages and changes in the content of especially seromucous acini secretion in DM and/or OVX groups and distinctive interstitial and striated duct damages in post ovariectomy diabetes induced group were detected. Alterations ingranular ducts hypertrophic and in seromucous acini atrophic were determined in DM and/or OVX groups. Conclusion: The results revealed the pathophysiological processes that lead to morphological and functional alterations on the cellular level in submandibular glands. The molecular mechanisms related with pathogenesis of diabetes and menopause need further investigation. PMID:26644770
-
Noorafshan, Ali; Karbalay-Doust, Saied; Ardekani, Fakhrodin Mesbah
2005-02-01
Anabolic-androgenic steroid (AAS) compounds rank among the drugs most widely abused with the goal of improving athletic ability, appearance, or muscle mass. It has been shown that these compounds have adverse effects on human and animal physiology and sperm quality, but quantitative structural changes of the testis have received less attention. The present study was conducted to evaluate the effects of nandrolone decanoate, which is one of the AAS compounds, on testis weight and volume, diameter and length of seminiferous tubules in rats by unbiased stereological methods. Adult rats were divided into three groups. The first comprised control rats; the second and third groups received low and high doses of nandrolone decanoate for 14 weeks. The rats were then left untreated for 14 weeks. After removal of the testis, stereological study of these tissues showed that the mean volume of testis and length of the seminiferous tubules in the animals that received high doses of nandrolone decanoate were reduced approximately 32% (p<0.01) and approximately 31% (p<0.04), respectively, in comparison with the control group. It can be concluded that the high doses of nandrolone decanoate produce structural changes in the rat testis that remain 14 weeks after stopping injection of the drug.
-
Follicle Detection on the USG Images to Support Determination of Polycystic Ovary Syndrome
NASA Astrophysics Data System (ADS)
Adiwijaya; Purnama, B.; Hasyim, A.; Septiani, M. D.; Wisesty, U. N.; Astuti, W.
2015-06-01
Polycystic Ovary Syndrome(PCOS) is the most common endocrine disorders affected to female in their reproductive cycle. This has gained the attention from married couple which affected by infertility. One of the diagnostic criteria considereded by the doctor is analysing manually the ovary USG image to detect the number and size of ovary's follicle. This analysis may affect low varibilites, reproducibility, and efficiency. To overcome this problems. automatic scheme is suggested to detect the follicle on USG image in supporting PCOS diagnosis. The first scheme is determining the initial homogeneous region which will be segmented into real follicle form The next scheme is selecting the appropriate regions to follicle criteria. then measuring the segmented region attribute as the follicle. The measurement remains the number and size that aimed at categorizing the image into the PCOS or non-PCOS. The method used is region growing which includes region-based and seed-based. To measure the follicle diameter. there will be the different method including stereology and euclidean distance. The most optimum system plan to detect PCO is by using region growing and by using euclidean distance on quantification of follicle.
-
Gutierre, R C; Vannucci Campos, D; Mortara, R A; Coppi, A A; Arida, R M
2017-04-01
Confocal laser-scanning microscopy is a useful tool for visualizing neurons and glia in transparent preparations of brain tissue from laboratory animals. Currently, imaging capillaries and venules in transparent brain tissues requires the use of fluorescent proteins. Here, we show that vessels can be imaged by confocal laser-scanning microscopy in transparent cortical, hippocampal and cerebellar preparations after clarification of China ink-injected specimens by the Spalteholz method. This method may be suitable for global, three-dimensional, quantitative analyses of vessels, including stereological estimations of total volume and length and of surface area of vessels, which constitute indirect approaches to investigate angiogenesis. © 2017 Anatomical Society.
-
Validation of a Three-Dimensional Method for Counting and Sizing Podocytes in Whole Glomeruli
van der Wolde, James W.; Schulze, Keith E.; Short, Kieran M.; Wong, Milagros N.; Bensley, Jonathan G.; Cullen-McEwen, Luise A.; Caruana, Georgina; Hokke, Stacey N.; Li, Jinhua; Firth, Stephen D.; Harper, Ian S.; Nikolic-Paterson, David J.; Bertram, John F.
2016-01-01
Podocyte depletion is sufficient for the development of numerous glomerular diseases and can be absolute (loss of podocytes) or relative (reduced number of podocytes per volume of glomerulus). Commonly used methods to quantify podocyte depletion introduce bias, whereas gold standard stereologic methodologies are time consuming and impractical. We developed a novel approach for assessing podocyte depletion in whole glomeruli that combines immunofluorescence, optical clearing, confocal microscopy, and three-dimensional analysis. We validated this method in a transgenic mouse model of selective podocyte depletion, in which we determined dose-dependent alterations in several quantitative indices of podocyte depletion. This new approach provides a quantitative tool for the comprehensive and time-efficient analysis of podocyte depletion in whole glomeruli. PMID:26975438
-
2010-01-01
Background Although the injury to the peripheral nervous system is a common clinical problem, understanding of the role of melatonin in nerve degeneration and regeneration is incomplete. Methods The current study investigated the effects of neonatal pinealectomy on the sciatic nerve microarchitecture in the chicken. The chickens were divided into two equal groups: unpinealectomized controls and pinealectomized chickens. At the end of the study, biochemical examination of 10 sciatic nerve samples from both groups was performed and a quantitative stereological evaluation of 10 animals in each group was performed. The results were compared using Mann-Whitney test. Results In this study, the results of axon number and thickness of the myelin sheath of a nerve fiber in newly hatched pinealectomy group were higher than those in control group. Similarly, surgical pinealectomy group had significantly larger axonal cross-sectional area than the control group (p < 0.05). In addition, the average hydroxyproline content of the nerve tissue in neonatal pinealectomy group was higher than those found in control group. Our results suggest that melatonin may play a role on the morphologic features of the peripheral nerve tissue and that melatonin deficiency might be a pathophysiological mechanism in some degenerative diseases of peripheral nerves. The changes demonstrated by quantitative morphometric methods and biochemical analysis has been interpreted as a reflection of the effects of melatonin upon nerve tissue. Conclusion In the light of these results from present animal study, changes in sciatic nerve morphometry may be indicative of neuroprotective feature of melatonin, but this suggestion need to be validated in the human setting. PMID:20409336
-
Noorafshan, A; Asadi-Golshan, R; Monjezi, S; Karbalay-Doust, S
2014-01-01
Sodium metabisulphite is used as an antioxidant agent in many pharmaceutical formulations. It is extensively used as a food preservative and disinfectant. It has been demonstrated that sulphite exposure can affect some organs. Curcumin, the main element of Curcuma longa, has been identified to have multiple protective properties. The present study extends the earlier works to quantitative evaluation of the effects of sulphite and curcumin on the heart structure using stereological methods. In this study, 28 rats were randomly divided into four experimental groups. The rats in groups I to IV received distilled water (group I), sodium metabisulphite (25 mg/ kg/day) (group II), curcumin (100 mg/kg/day) (group III), and sodium metabisulphite+curcumin (group IV), respectively, for 8 weeks. The left ventricle was subjected to stereological methods to estimate the quantitative parameters of the myocardium. A 20 % decrease was observed in the total volume of ventricular tissue in the sulphite-treated animals compared to the distilled water treatment (P < 0.02). Also, the volume and length of the capillaries were reduced by 43 % on average in the sulphite-treated rats in comparison to the distilled water-treated animals (P < 0.02). However, no significant change was seen in the mean and total volume of the myocardium and the cavity and diameter of the capillaries after sulphite ingestion. Treatment with curcumin did not protect the animals against the structural changes of the ventricle. Sulphite, as a preservative food agent, reduced the length and volume of the ventricular capillaries and curcumin could not protect them.
-
Haass-Koffler, Carolina L; Naeemuddin, Mohammad; Bartlett, Selena E
2012-08-31
The most common software analysis tools available for measuring fluorescence images are for two-dimensional (2D) data that rely on manual settings for inclusion and exclusion of data points, and computer-aided pattern recognition to support the interpretation and findings of the analysis. It has become increasingly important to be able to measure fluorescence images constructed from three-dimensional (3D) datasets in order to be able to capture the complexity of cellular dynamics and understand the basis of cellular plasticity within biological systems. Sophisticated microscopy instruments have permitted the visualization of 3D fluorescence images through the acquisition of multispectral fluorescence images and powerful analytical software that reconstructs the images from confocal stacks that then provide a 3D representation of the collected 2D images. Advanced design-based stereology methods have progressed from the approximation and assumptions of the original model-based stereology even in complex tissue sections. Despite these scientific advances in microscopy, a need remains for an automated analytic method that fully exploits the intrinsic 3D data to allow for the analysis and quantification of the complex changes in cell morphology, protein localization and receptor trafficking. Current techniques available to quantify fluorescence images include Meta-Morph (Molecular Devices, Sunnyvale, CA) and Image J (NIH) which provide manual analysis. Imaris (Andor Technology, Belfast, Northern Ireland) software provides the feature MeasurementPro, which allows the manual creation of measurement points that can be placed in a volume image or drawn on a series of 2D slices to create a 3D object. This method is useful for single-click point measurements to measure a line distance between two objects or to create a polygon that encloses a region of interest, but it is difficult to apply to complex cellular network structures. Filament Tracer (Andor) allows automatic detection of the 3D neuronal filament-like however, this module has been developed to measure defined structures such as neurons, which are comprised of dendrites, axons and spines (tree-like structure). This module has been ingeniously utilized to make morphological measurements to non-neuronal cells, however, the output data provide information of an extended cellular network by using a software that depends on a defined cell shape rather than being an amorphous-shaped cellular model. To overcome the issue of analyzing amorphous-shaped cells and making the software more suitable to a biological application, Imaris developed Imaris Cell. This was a scientific project with the Eidgenössische Technische Hochschule, which has been developed to calculate the relationship between cells and organelles. While the software enables the detection of biological constraints, by forcing one nucleus per cell and using cell membranes to segment cells, it cannot be utilized to analyze fluorescence data that are not continuous because ideally it builds cell surface without void spaces. To our knowledge, at present no user-modifiable automated approach that provides morphometric information from 3D fluorescence images has been developed that achieves cellular spatial information of an undefined shape (Figure 1). We have developed an analytical platform using the Imaris core software module and Imaris XT interfaced to MATLAB (Mat Works, Inc.). These tools allow the 3D measurement of cells without a pre-defined shape and with inconsistent fluorescence network components. Furthermore, this method will allow researchers who have extended expertise in biological systems, but not familiarity to computer applications, to perform quantification of morphological changes in cell dynamics.
-
The acute effect of ethanol on adrenal cortex in female rats--possible role of nitric oxide.
Dikić, Dragoslava; Budeč, Mirela; Vranješ-Durić, Sanja; Koko, Vesna; Vignjević, Sanja; Mitrović, Olivera
2011-01-01
The present study was designed to investigate a possible role of endogenous nitric oxide (NO) in the adrenal response to an acute alcohol administration in female rats. To this end, N(ω)-nitro-L-arginine-methyl ester (L-NAME), a competitive inhibitor of all isoforms of NO synthase, was used. Adult female Wistar rats showing diestrus Day 1 were treated with: (a) ethanol (2 or 4 g/kg, intraperitoneally); (b) L-NAME (30 or 50 mg/kg, subcutaneously) followed by either ethanol or saline 3 h later. Untreated and saline-injected rats were used as controls. The animals were killed 30 min after last injection. Adrenal cortex was analyzed morphometrically, and plasma levels of adrenocorticotropic hormone (ACTH) and serum concentrations of corticosterone were determined. Acute ethanol treatment enhanced the levels of ACTH and corticosterone in a dose-dependent manner. Stereological analysis revealed that acute alcohol administration induced a significant increase in absolute volume of the cortex and the zona fasciculata (ZF). In addition, ethanol at a dose of 4 g/kg increased volume density and length of the capillaries in the ZF. However, other stereological parameters were unaffected by alcohol exposure. Pretreatment with both doses of L-NAME had no effect on ethanol-induced changes. Obtained findings indicate that acute ethanol treatment stimulates the activity of the adrenal cortex and that this effect is not mediated by endogenous NO in female rats under these experimental conditions.
-
Clérin, Emmanuelle; Wicker, Nicolas; Mohand-Saïd, Saddek; Poch, Olivier; Sahel, José-Alain; Léveillard, Thierry
2011-12-20
Retinitis pigmentosa is characterized by the sequential loss of rod and cone photoreceptors. The preservation of cones would prevent blindness due to their essential role in human vision. Rod-derived Cone Viability Factor is a thioredoxin-like protein that is secreted by rods and is involved in cone survival. To validate the activity of Rod-derived Cone Viability Factors (RdCVFs) as therapeutic agents for treating retinitis Pigmentosa, we have developed e-conome, an automated cell counting platform for retinal flat mounts of rodent models of cone degeneration. This automated quantification method allows for faster data analysis thereby accelerating translational research. An inverted fluorescent microscope, motorized and coupled to a CCD camera records images of cones labeled with fluorescent peanut agglutinin lectin on flat-mounted retinas. In an average of 300 fields per retina, nine Z-planes at magnification X40 are acquired after two-stage autofocus individually for each field. The projection of the stack of 9 images is subject to a threshold, filtered to exclude aberrant images based on preset variables. The cones are identified by treating the resulting image using 13 variables empirically determined. The cone density is calculated over the 300 fields. The method was validated by comparison to the conventional stereological counting. The decrease in cone density in rd1 mouse was found to be equivalent to the decrease determined by stereological counting. We also studied the spatiotemporal pattern of the degeneration of cones in the rd1 mouse and show that while the reduction in cone density starts in the central part of the retina, cone degeneration progresses at the same speed over the whole retinal surface. We finally show that for mice with an inactivation of the Nucleoredoxin-like genes Nxnl1 or Nxnl2 encoding RdCVFs, the loss of cones is more pronounced in the ventral retina. The automated platform ℮-conome used here for retinal disease is a tool that can broadly accelerate translational research for neurodegenerative diseases.
-
Stereological analysis of gravitropism in protonemata of the moss Ceratodon
NASA Technical Reports Server (NTRS)
Walker, L. M.; Sack, F. D.
1997-01-01
Apical cells of dark-grown protonemata of the moss Cerotodon purpureus are negatively gravitropic. Previous light microscopy has shown that reorientation to the horizontal induces amyloplast sedimentation and redistribution of microtubules. To determine whether other components become redistributed laterally or axially, the apical 35 micrometers of both vertical and horizontal apical cells were compared stereologically using transmission electron microscopy. Reorientation to the horizontal changed the longitudinal distributions of tubular ER, Golgi stacks, and vesicles but not cisternal ER, mitochondria, and plastids. Only plastids showed a statistically significant lateral redistribution after horizontal placement. Qualitative examination of the sedimentation zone showed plastids sedimented close to peripherally located ER with vacuoles displaced above plastids. These results argue against a model where differential tip growth results from a redistribution of Golgi stacks or exocytic vesicles.
-
Tourtellotte, W G; Lawrence, D T; Getting, P A; Van Hoesen, G W
1989-07-01
This report describes a computerized microscope charting system based on the IBM personal computer or compatible. Stepping motors are used to control the movement of the microscope stage and to encode its position by hand manipulation of a joystick. Tissue section contours and the location of cells labeled with various compounds are stored by the computer, plotted at any magnification and manipulated into composites created from several charted sections. The system has many advantages: (1) it is based on an industry standardized computer that is affordable and familiar; (2) compact and commercially available stepping motor microprocessors control the stage movement. These controllers increase reliability, simplify implementation, and increase efficiency by relieving the computer of time consuming control tasks; (3) the system has an interactive graphics interface allowing the operator to view the image during data collection. Regions of the graphics display can be enlarged during the charting process to provide higher resolution and increased accuracy; (4) finally, the digitized data are stored at 0.5 micron resolution and can be routed directly to a multi-pen plotter or exported to a computer-aided design (CAD) program to generate a publication-quality montage composed of several computerized chartings. The system provides a useful tool for the acquisition and qualitative analysis of data representing stained cells or chemical markers in tissue. The modular design, together with data storage at high resolution, allows for potential analytical enhancements involving planimetric, stereologic and 3-D serial section reconstruction.
-
Effects of local vibration and pulsed electromagnetic field on bone fracture: A comparative study.
Bilgin, Hakkı Murat; Çelik, Ferhat; Gem, Mehmet; Akpolat, Veysi; Yıldız, İsmail; Ekinci, Aysun; Özerdem, Mehmet Siraç; Tunik, Selçuk
2017-07-01
The effectiveness of various therapeutic methods on bone fracture has been demonstrated in several studies. In the present study, we tried to evaluate the effect of local low-magnitude, high-frequency vibration (LMHFV) on rat tibia fracture in comparison with pulsed electromagnetic fields (PEMF) during the healing process. Mid-diaphysis tibiae fractures were induced in 30 Sprague-Dawley rats. The rats were assigned into groups such as control (CONT), LMHFV (15 min/day, 7 days/week), and PEMF (3.5 h/day, 7 days/week) for a three-week treatment. Nothing was applied to control group. Radiographs, serum osteocalcin levels, and stereological bone analyses of the three groups were compared. The X-rays of tibiae were taken 21 days after the end of the healing process. PEMF and LMHFV groups had more callus formation when compared to CONT group; however, the difference was not statistically significant (P = 0.375). Serum osteocalcin levels were elevated in the experimental groups compared to CONT (P ≤ 0.001). Stereological tests also showed higher osteogenic results in experimental groups, especially in LMHFV group. The results of the present study suggest that application of direct local LMHFV on fracture has promoted bone formation, showing great potential in improving fracture outcome. Bioelectromagnetics. 38:339-348, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.
-
Noorafshan, Ali; Karimi, Fatemeh; Kamali, Ali-Mohammad; Karbalay-Doust, Saied; Nami, Mohammad
2017-11-15
The present study examined the consequences of rapid eye-movement sleep-deprivation (REM-SD) with or without curcumin treatment. The outcome measures comprised quantitative features in the three-dimensional reconstruction (3DR) CA1 and dentate gyrus in experimental and control animals using stereological procedures. Male rats were arbitrarily assigned to nine groups based on the intervention and treatment administered including: 1-cage control+distilled water, 2-cage control+curcumin (100mg/kg/day), 3-cage control+olive oil, 4-REM-SD+distilled water, 5-REM-SD+curcumin, 6-REM-SD+olive oil, 7-grid-floor control+distilled water, 8-grid-floor control+curcumin, and 9-grid-floor control+olive oil. Animals in the latter three groups were placed on wire-mesh grids in the sleep-deprivation box. REM-SD was induced by an apparatus comprising a water tank and multiple platforms. After a period of 21days, rats were submitted to the novel object-recognition task. Later, their brains were excised and evaluated using stereological methods. Our results indicated a respective 29% and 31% reduction in the total volume of CA1, and dentate gyrus in REM-SD+distilled water group as compared to the grid-floor control+distilled water group (p<0.05). Other than the above, the overall number of the pyramidal cells of CA1 and granular cells of dentate gyrus in the sleep-deprived group were found to be reduced by 48% and 25%, respectively. The REM-SD+distilled water group also exhibited impaired object recognition memory and deformed three-dimensional reconstructions of these regions. The volume, cell number, reconstruction, object recognition time, and body weight were however recovered in the REM-SD+curcumin compared to the REM-SD+distilled water group. This suggests the potential neuro-restorative effects of curcumin in our model. Copyright © 2017 Elsevier Inc. All rights reserved.
-
Psychiatric Brain Banking: Three Perspectives on Current Trends and Future Directions
Deep-Soboslay, Amy; Benes, Francine M.; Haroutunian, Vahram; Ellis, Justin K.; Kleinman, Joel E.; Hyde, Thomas M.
2011-01-01
Introduction The study of postmortem human brain tissue is central to the advancement of the neurobiological studies of psychiatric illness, particularly for the study of brain-specific isoforms and molecules. Methods The state-of-the-art methods and recommendations for maintaining a successful brain bank for psychiatric disorders are discussed, using the convergence of viewpoints from three brain collections, the National Institute of Mental Health Brain Collection (NIMH), the Harvard Brain Tissue Resource Center (HBTRC), and the Mt. Sinai School of Medicine Brain Bank (MSSM-BB), with diverse research interests and divergent approaches to tissue acquisition. Results While the NIMH obtains donations from medical examiners for its collection, and places particular emphasis on clinical diagnosis, toxicology, and building lifespan control cohorts, the HBTRC is uniquely designed as a repository whose sole purpose is to collect large-volume, high quality brain tissue from community-based donors based on relationships across an expansive nationwide network, and places emphasis on the accessibility of its bank in disseminating tissue and related data to research groups worldwide. The MSSM-BB collection has shown that, with dedication, prospective recruitment is a successful approach to tissue donation, and places particular emphasis on rigorous clinical diagnosis through antemortem contact with donors. The MSSM-BB places great importance on stereological tissue sampling methods for neuroanatomical studies, and frozen tissue sampling approaches that enable multiple assessments (RNA, DNA, protein, enzyme activity, binding, etc.) of the same tissue block. Promising scientific approaches for elucidating the molecular and cellular pathways in brain that may contribute to schizophrenia and/or bipolar disorder, such as cell culture techniques and microarray-based gene expression and genotyping studies are briefly discussed. Conclusions Despite unique perspectives from three established brain collections, there is a consensus that (1) diverse strategies for tissue acquisition, (2) rigor in tissue and diagnostic characterization, (3) the importance of sample accessibility, and (4) continual application of innovative scientific approaches to the study of brain tissue are all integral to the success and future of psychiatric brain banking. The future of neuropsychiatric research depends upon in the availability of high quality brain specimens from large numbers of subjects, including non-psychiatric controls. PMID:20673875
-
Effect of acute heat stress on rat adrenal glands: a morphological and stereological study.
Koko, Vesna; Djordjeviae, Jelena; Cvijiae, Gordana; Davidoviae, Vukosava
2004-11-01
The morphological and stereological structure of rat adrenal gland was analysed by light microscopy after an acute (60 min) exposure to high ambient temperature (38 degrees C). A significant increase in plasma corticotrophin (ACTH) and serum corticosterone (CORT) concentrations was observed, confirming that acute heat exposure has a strong stressful effect. Under these conditions the adrenal gland mass and volume were decreased, probably as the consequence of adrenal cortex reduction, especially that of the zona fasciculata (ZF). Histological examination revealed that many ZF cells were deprived of lipid droplets. Fibrosis was observed in all parts of the adrenal gland, both cortex and medulla, of heat stressed animals. Mitotic figures were absent in cortical cells after heat exposure, but there were no differences in ZF and zona reticularis (ZR) small blood vessels compared to nonstressed controls.
-
García-Amado, María; Prensa, Lucía
2012-01-01
Cell number alterations in the amygdaloid complex (AC) might coincide with neurological and psychiatric pathologies with anxiety imbalances as well as with changes in brain functionality during aging. This stereological study focused on estimating, in samples from 7 control individuals aged 20 to 75 years old, the number and density of neurons, glia and endothelial cells in the entire AC and in its 5 nuclear groups (including the basolateral (BL), corticomedial and central groups), 5 nuclei and 13 nuclear subdivisions. The volume and total cell number in these territories were determined on Nissl-stained sections with the Cavalieri principle and the optical fractionator. The AC mean volume was 956 mm(3) and mean cell numbers (x10(6)) were: 15.3 neurons, 60 glial cells and 16.8 endothelial cells. The numbers of endothelial cells and neurons were similar in each AC region and were one fourth the number of glial cells. Analysis of the influence of the individuals' age at death on volume, cell number and density in each of these 24 AC regions suggested that aging does not affect regional size or the amount of glial cells, but that neuron and endothelial cell numbers respectively tended to decrease and increase in territories such as AC or BL. These accurate stereological measures of volume and total cell numbers and densities in the AC of control individuals could serve as appropriate reference values to evaluate subtle alterations in this structure in pathological conditions.
-
Stereological Analysis of Neuron, Glial and Endothelial Cell Numbers in the Human Amygdaloid Complex
García-Amado, María; Prensa, Lucía
2012-01-01
Cell number alterations in the amygdaloid complex (AC) might coincide with neurological and psychiatric pathologies with anxiety imbalances as well as with changes in brain functionality during aging. This stereological study focused on estimating, in samples from 7 control individuals aged 20 to 75 years old, the number and density of neurons, glia and endothelial cells in the entire AC and in its 5 nuclear groups (including the basolateral (BL), corticomedial and central groups), 5 nuclei and 13 nuclear subdivisions. The volume and total cell number in these territories were determined on Nissl-stained sections with the Cavalieri principle and the optical fractionator. The AC mean volume was 956 mm3 and mean cell numbers (x106) were: 15.3 neurons, 60 glial cells and 16.8 endothelial cells. The numbers of endothelial cells and neurons were similar in each AC region and were one fourth the number of glial cells. Analysis of the influence of the individuals’ age at death on volume, cell number and density in each of these 24 AC regions suggested that aging does not affect regional size or the amount of glial cells, but that neuron and endothelial cell numbers respectively tended to decrease and increase in territories such as AC or BL. These accurate stereological measures of volume and total cell numbers and densities in the AC of control individuals could serve as appropriate reference values to evaluate subtle alterations in this structure in pathological conditions. PMID:22719923
-
Stereological study of rat spleen following acute ethanol treatment.
Budec, M; Milićević, Z; Koko, V
2000-05-01
To investigate the acute effect of ethanol (4 g/kg, i.p.) on spleen adult female Wistar rats were treated intraperitoneally with: a) ethanol (4 g/kg body wt), b) naltrexone (5 mg/kg body wt) followed 45 minutes later by ethanol (4 g/kg body wt) and c) naltrexone (5 mg/kg body wt) alone. Untreated and saline-treated rats were used as controls. Twenty hours after the ethanol treatment the animals were sacrificed and the spleens were removed. A piece of tissue from the central part of each organ was fixed in Bouin's solution. Paraffin sections were stained with hematoxylin-eosin and analysed using stereological measurements. The volume densities of the following tissue compartments: red pulp, white pulp (divided in follicles, periarterioral lymphatic sheath and marginal zone) and the connective tissue were determined. Stereological analysis also included parameters of follicles: the areal numerical density (the number of follicles per 1 mm2 of tissue section), the numerical density (the number of follicles per mm3 of tissue) and the mean follicle diameter. The immunoarchitecture of the spleen was preserved following acute ethanol treatment. Unlike other parameters that were unaffected, ethanol evoked a decrease in both volume density of follicle and the mean follicle diameter. Naltrexone pretreatment had no influence on ethanol-induced changes. The data obtained indicate that a single dose of ethanol has a profound effect on rat spleen affecting the follicles, but the mechanism of its action remains to be elucidated.
-
Xiao, Qian; Luo, Yanmin; Lv, Fulin; He, Qi; Wu, Hong; Chao, Fenglei; Qiu, Xuan; Zhang, Lei; Gao, Yuan; Huang, Chunxia; Wang, Sanrong; Zhou, Chunni; Zhang, Yi; Jiang, Lin; Tang, Yong
2018-06-14
Estrogen replacement therapy (ERT) improves hippocampus-dependent cognition. This study investigated the impact of estrogen on hippocampal volume, CA1 subfield volume and myelinated fibers in the CA1 subfield of middle-aged ovariectomized rats. Ten-month-old bilaterally ovariectomized (OVX) female rats were randomly divided into OVX + E2 and OVX + Veh groups. After four weeks of subcutaneous injection with 17β-estradiol or a placebo, the OVX + E2 rats exhibited significantly short mean escape latency in a spatial learning task than that in the OVX + Veh rats. Using stereological methods, we did not observe significant differences in the volumes of the hippocampus and CA1 subfields between the two groups. However, using stereological methods and electron microscopy techniques, the total length of myelinated fibers and the total volumes of myelinated fibers, myelin sheaths and myelinated axons in the CA1 subfields of OVX + E2 rats were significantly 38.1%, 34.2%, 36.1% and 32.5%, respectively, higher than those in the OVX + Veh rats. After the parameters were calculated according to different diameter ranges, the estrogen replacement-induced remodeling of myelinated fibers in CA1 was mainly manifested in the myelinated fibers with a diameter of <1.0 μm. Therefore, four weeks of continuous E2 replacement improved the spatial learning capabilities of middle-aged ovariectomized rats. The E2 replacement-induced protection of spatial learning abilities might be associated with the beneficial effects of estrogen on myelinated fibers, particularly those with the diameters less than 1.0 μm, in the hippocampal CA1 region of middle-aged ovariectomized rats. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.
-
Bolat, D; Bahar, S; Tipirdamaz, S; Selcuk, M L
2013-12-01
The aims of this study were to determine the total volume of the horse kidney and volume fractions of its functional subcomponents (cortex, medulla, renal pelvis) using stereological methods and investigate any possible difference in the functional subcomponents of the right and left kidneys that may arise from differences in shape. The study was carried out on the kidneys of 5 horses of different breed and sex. The weight of the kidneys was measured by a digital scale, and kidney volume was calculated by Archimedes' principle. Total kidney volume and volume fractions of subcomponents of the right and left kidneys were estimated by the Cavalieri's principle. The weights of the right and left kidneys were 550 ± 25 g and 585 ± 23 g, respectively. The volumes of the right and left kidneys estimated using the Cavalieri method were 542 ± 46 ml and 581 ± 29 ml. The relative organ weight of the kidneys was calculated as 1:330. The densities of the right and left kidneys were determined to be 1.01 and 1.00, respectively. The mean volume fractions of the cortex, medulla and renal pelvis were determined as 55.6, 42.7 and 1.7 in both kidneys. No statistically significant difference existed between morphometric data pertaining to the right and left kidneys (P > 0.05). To determine precisely whether differences in shape cause any difference in the functional subcomponents of the right and left kidneys requires further investigation of differences in the number of microscopically functional unit of the kidney such as renal glomeruli and nephrons. © 2013 Blackwell Verlag GmbH.
-
RandomSpot: A web-based tool for systematic random sampling of virtual slides.
Wright, Alexander I; Grabsch, Heike I; Treanor, Darren E
2015-01-01
This paper describes work presented at the Nordic Symposium on Digital Pathology 2014, Linköping, Sweden. Systematic random sampling (SRS) is a stereological tool, which provides a framework to quickly build an accurate estimation of the distribution of objects or classes within an image, whilst minimizing the number of observations required. RandomSpot is a web-based tool for SRS in stereology, which systematically places equidistant points within a given region of interest on a virtual slide. Each point can then be visually inspected by a pathologist in order to generate an unbiased sample of the distribution of classes within the tissue. Further measurements can then be derived from the distribution, such as the ratio of tumor to stroma. RandomSpot replicates the fundamental principle of traditional light microscope grid-shaped graticules, with the added benefits associated with virtual slides, such as facilitated collaboration and automated navigation between points. Once the sample points have been added to the region(s) of interest, users can download the annotations and view them locally using their virtual slide viewing software. Since its introduction, RandomSpot has been used extensively for international collaborative projects, clinical trials and independent research projects. So far, the system has been used to generate over 21,000 sample sets, and has been used to generate data for use in multiple publications, identifying significant new prognostic markers in colorectal, upper gastro-intestinal and breast cancer. Data generated using RandomSpot also has significant value for training image analysis algorithms using sample point coordinates and pathologist classifications.
-
Geraci, Stefania; Chacon-Caldera, Jorge; Cullen-McEwen, Luise; Schad, Lothar R; Sticht, Carsten; Puelles, Victor G; Bertram, John F; Gretz, Norbert
2017-09-01
Recently, new methods for assessing renal function in conscious mice (transcutaneous assessment) and for counting and sizing all glomeruli in whole kidneys (MRI) have been described. In the present study, these methods were used to assess renal structure and function in aging mice, and in mice born with a congenital low-nephron endowment. Age-related nephron loss was analyzed in adult C57BL/6 mice (10-50 wk of age), and congenital nephron deficit was assessed in glial cell line-derived neurotrophic factor heterozygous (GDNF HET)-null mutant mice. Renal function was measured through the transcutaneous quantitation of fluorescein isothiocyanate-sinistrin half-life ( t 1/2 ) in conscious mice. MRI was used to image, count, and size cationic-ferritin labeled glomeruli in whole kidneys ex vivo. Design-based stereology was used to validate the MRI measurements of glomerular number and mean volume. In adult C57BL/6 mice, older age was associated with fewer and larger glomeruli, and a rightward shift in the glomerular size distribution. These changes coincided with a decrease in renal function. GNDF HET mice had a congenital nephron deficit that was associated with glomerular hypertrophy and exacerbated by aging. These findings suggest that glomerular hypertrophy and hyperfiltration are compensatory processes that can occur in conjunction with both age-related nephron loss and congenital nephron deficiency. The combination of measurement of renal function in conscious animals and quantitation of glomerular number, volume, and volume distribution provides a powerful new tool for investigating aspects of renal aging and functional changes. Copyright © 2017 the American Physiological Society.
-
Xu, Yihua; Pitot, Henry C
2006-03-01
In the studies of quantitative stereology of rat hepatocarcinogenesis, we have used image analysis technology (automatic particle analysis) to obtain data such as liver tissue area, size and location of altered hepatic focal lesions (AHF), and nuclei counts. These data are then used for three-dimensional estimation of AHF occurrence and nuclear labeling index analysis. These are important parameters for quantitative studies of carcinogenesis, for screening and classifying carcinogens, and for risk estimation. To take such measurements, structures or cells of interest should be separated from the other components based on the difference of color and density. Common background problems seen on the captured sample image such as uneven light illumination or color shading can cause severe problems in the measurement. Two application programs (BK_Correction and Pixel_Separator) have been developed to solve these problems. With BK_Correction, common background problems such as incorrect color temperature setting, color shading, and uneven light illumination background, can be corrected. With Pixel_Separator different types of objects can be separated from each other in relation to their color, such as seen with different colors in immunohistochemically stained slides. The resultant images of such objects separated from other components are then ready for particle analysis. Objects that have the same darkness but different colors can be accurately differentiated in a grayscale image analysis system after application of these programs.
-
Wikström, B; Hjerpe, A; Hultenby, K; Reinholt, F P; Engfeldt, B
1984-01-01
The brachymorphic (bm/bm) mutation in the mouse leads to disproportional dwarfism due to a disturbance of endochondral bone formation. The morphological characteristics of bm/bm epiphyseal growth cartilage are signs of cellular degeneration and disintegration and alteration of the composition of the extracellular matrix, with an abnormal mineralization pattern. The present stereological study of the bm/bm growth plate revealed a clearly altered distribution of matrix vesicles as compared with the controls. It was also demonstrated that the bm/bm matrix vesicles have an abnormal size distribution, with an increased mean caliper diameter. The biological significance of these findings is discussed in relation to the different hypotheses on the origin of matrix vesicles and their possible role in the mineralization process. The results support the opinion that extracellular matrix vesicles, at least partly, constitute cellular debris.
-
Immediate versus delayed primary nerve repair in the rabbit sciatic nerve
Piskin, Ahmet; Altunkaynak, Berrin Zühal; Çιtlak, Atilla; Sezgin, Hicabi; Yazιcι, Ozgür; Kaplan, Süleyman
2013-01-01
It is well known that peripheral nerve injury should be treated immediately in the clinic, but in some instances, repair can be delayed. This study investigated the effects of immediate versus delayed (3 days after injury) neurorrhaphy on repair of transected sciatic nerve in New Zealand rabbits using stereological, histomorphological and biomechanical methods. At 8 weeks after immediate and delayed neurorrhaphy, axon number and area in the sciatic nerve, myelin sheath and epineurium thickness, Schwann cell morphology, and the mechanical property of nerve fibers did not differ obviously. These results indicate that delayed neurorrhaphy do not produce any deleterious effect on sciatic nerve repair. PMID:25206663
-
Keller, Simon S.; Das, Kumar; Vidyasagar, Rishma; Parkes, Laura M.; Burnside, Girvan; Griffiths, Michael; Kopelman, Michael; Roberts, Neil; Solomon, Tom
2017-01-01
Objectives To assess whether it is feasible to quantify acute change in temporal lobe volume and total oedema volumes in herpes simplex virus (HSV) encephalitis as a preliminary to a trial of corticosteroid therapy. Methods The study analysed serially acquired magnetic resonance images (MRI), of patients with acute HSV encephalitis who had neuroimaging repeated within four weeks of the first scan. We performed volumetric measurements of the left and right temporal lobes and of cerebral oedema visible on T2 weighted Fluid Attenuated Inversion Recovery (FLAIR) images using stereology in conjunction with point counting. Results Temporal lobe volumes increased on average by 1.6% (standard deviation (SD 11%) in five patients who had not received corticosteroid therapy and decreased in two patients who had received corticosteroids by 8.5%. FLAIR hyperintensity volumes increased by 9% in patients not receiving treatment with corticosteroids and decreased by 29% in the two patients that had received corticosteroids. Conclusions This study has shown it is feasible to quantify acute change in temporal lobe and total oedema volumes in HSV encephalitis and suggests a potential resolution of swelling in response to corticosteroid therapy. These techniques could be used as part of a randomized control trial to investigate the efficacy of corticosteroids for treating HSV encephalitis in conjunction with assessing clinical outcomes and could be of potential value in helping to predict the clinical outcomes of patients with HSV encephalitis. PMID:28125598
-
Eggers, R; Haug, H; Fischer, D
1984-01-01
The studies here reported were performed on the prosencephalons of 12 human brains between 37 and 86 years of age having no signs of neuropathological alteration. The evaluation was carried out on serial frontal sections with a mean thickness of 5 mm with stereological point counting procedures for volume and surface area. The results were mainly given in relative values since the range of variation is very high and the sample small. The aging process was evaluated with the aid of a linear regression function. The stereological investigation regarding the absolute values of volume and surface area (border face) of the macroscopical brain parts show a high interindividual variability. However, the relative volume of brain parts shows only small variations. Changes during aging could consequently only be revealed with the help of the relative values. The relative volumes and surface areas of the frontal lobe and the prosencephalic ganglia decrease with aging, while the parieto-occipital lobe and the striate cortex increase. However, if we refer these relative increases to the absolute decrease of brain volume, corresponding changes cannot be found in the parieto-occipital lobe until old age. The shrinkage of the frontal lobe, of the centrum semiovale and of the prosencephalic ganglia exceeds 10%. In the grays it is probably accompanied by a loss of neurons. The relative sizes of the surface area do not change significantly during aging with exception of the frontal cortex. The thickness of the cortex remains probably constant. The size of lateral ventricles increases with aging.
-
Marcos, Ricardo; Correia-Gomes, Carla
2016-12-01
Male/female differences in enzyme activity and gene expression in the liver are known to be attenuated with ageing. Nevertheless, the effect of ageing on liver structure and quantitative cell morphology remains unknown. Male and female Wistar rats aged 2, 6, 12 and 18 months were examined by means of stereological techniques and immunohistochemical tagging of hepatocytes (HEP), liver sinusoidal endothelial cells (LSEC), Kupffer cells (KC) and hepatic stellate cells (HSC) in order to assess the total number and number per gram of these cells throughout life. The mean cell volume of HEP and HSC, the lobular position and the collagen content of the liver were also evaluated with stereological techniques. The number per gram of HSC was similar for both genders and was maintained throughout ageing. The mean volume of HSC was also conserved but differences in the cell body and lobular location were observed. Statistically significant gender differences in HEP were noted in young rats (females had smaller and more binucleated HEP) but were attenuated with ageing. The same occurred for KC and LSEC, since the higher number per gram in young females disappeared in older animals. Liver collagen increased with ageing but only in males. Thus, the numbers of these four cell types are related throughout ageing, with well-defined cell ratios. The shape and lobular position of HSC change with ageing in both males and females. Gender dimorphism in HEP, KC and LSEC of young rat liver disappears with ageing.
-
Comparison of volume estimation methods for pancreatic islet cells
NASA Astrophysics Data System (ADS)
Dvořák, JiřÃ.; Å vihlík, Jan; Habart, David; Kybic, Jan
2016-03-01
In this contribution we study different methods of automatic volume estimation for pancreatic islets which can be used in the quality control step prior to the islet transplantation. The total islet volume is an important criterion in the quality control. Also, the individual islet volume distribution is interesting -- it has been indicated that smaller islets can be more effective. A 2D image of a microscopy slice containing the islets is acquired. The input of the volume estimation methods are segmented images of individual islets. The segmentation step is not discussed here. We consider simple methods of volume estimation assuming that the islets have spherical or ellipsoidal shape. We also consider a local stereological method, namely the nucleator. The nucleator does not rely on any shape assumptions and provides unbiased estimates if isotropic sections through the islets are observed. We present a simulation study comparing the performance of the volume estimation methods in different scenarios and an experimental study comparing the methods on a real dataset.
-
Sampling theory and automated simulations for vertical sections, applied to human brain.
Cruz-Orive, L M; Gelšvartas, J; Roberts, N
2014-02-01
In recent years, there have been substantial developments in both magnetic resonance imaging techniques and automatic image analysis software. The purpose of this paper is to develop stereological image sampling theory (i.e. unbiased sampling rules) that can be used by image analysts for estimating geometric quantities such as surface area and volume, and to illustrate its implementation. The methods will ideally be applied automatically on segmented, properly sampled 2D images - although convenient manual application is always an option - and they are of wide applicability in many disciplines. In particular, the vertical sections design to estimate surface area is described in detail and applied to estimate the area of the pial surface and of the boundary between cortex and underlying white matter (i.e. subcortical surface area). For completeness, cortical volume and mean cortical thickness are also estimated. The aforementioned surfaces were triangulated in 3D with the aid of FreeSurfer software, which provided accurate surface area measures that served as gold standards. Furthermore, a software was developed to produce digitized trace curves of the triangulated target surfaces automatically from virtual sections. From such traces, a new method (called the 'lambda method') is presented to estimate surface area automatically. In addition, with the new software, intersections could be counted automatically between the relevant surface traces and a cycloid test grid for the classical design. This capability, together with the aforementioned gold standard, enabled us to thoroughly check the performance and the variability of the different estimators by Monte Carlo simulations for studying the human brain. In particular, new methods are offered to split the total error variance into the orientations, sectioning and cycloid components. The latter prediction was hitherto unavailable--one is proposed here and checked by way of simulations on a given set of digitized vertical sections with automatically superimposed cycloid grids of three different sizes. Concrete and detailed recommendations are given to implement the methods. © 2013 The Authors Journal of Microscopy © 2013 Royal Microscopical Society.
-
Ladd, Fernando V L; Ladd, Aliny A B L; Ribeiro, Antônio Augusto C M; Costa, Samuel B C; Coutinho, Bruna P; Feitosa, George André S; de Andrade, Geanne M; de Castro-Costa, Carlos Maurício; Magalhães, Carlos Emanuel C; Castro, Ibraim C; Oliveira, Bruna B; Guerrant, Richard L; Lima, Aldo Angelo M; Oriá, Reinaldo B
2010-06-01
The effect of zinc and glutamine on brain development was investigated during the lactation period in Swiss mice. Malnutrition was induced by clustering the litter size from 6-7 pups/dam (nourished control) to 12-14 pups/dam (undernourished control) following birth. Undernourished groups received daily supplementation with glutamine by subcutaneous injections starting at day 2 and continuing until day 14. Glutamine (100 mM, 40-80 microL) was used for morphological and behavioral studies. Zinc acetate was added in the drinking water (500 mg/L) to the lactating dams. Synaptophysin and myelin basic protein brain expressions were evaluated by immunoblot. Zinc serum and brain levels and hippocampal neurotransmitters were also evaluated. Zinc with or without glutamine improved weight gain as compared to untreated, undernourished controls. In addition, zinc supplementation improved cliff avoidance and head position during swim behaviors especially on days 9 and 10. Using design-based stereological methods, we found a significant increase in the volume of CA1 neuronal cells in undernourished control mice, which was not seen in mice receiving zinc or glutamine alone or in combination. Undernourished mice given glutamine showed increased CA1 layer volume as compared with the other groups, consistent with the trend toward increased number of neurons. Brain zinc levels were increased in the nourished and undernourished-glutamine treated mice as compared to the undernourished controls on day 7. Undernourished glutamine-treated mice showed increased hippocampal gamma-aminobutyric acid and synaptophysin levels on day 14. We conclude that glutamine or zinc protects against malnutrition-induced brain developmental impairments. Copyright 2010 Elsevier Inc. All rights reserved.
-
Glomerular hypertrophy in subjects with low nephron number: contributions of sex, body size and race
Puelles, Victor G.; Douglas-Denton, Rebecca N.; Zimanyi, Monika A.; Armitage, James A.; Hughson, Michael D.; Kerr, Peter G.; Bertram, John F.
2014-01-01
Background We have shown that low nephron number (Nglom) is a strong determinant of individual glomerular volume (IGV) in male Americans. However, whether the same pattern is present in female Americans remains unclear. The contributions of body surface area (BSA) and race to IGV in the context of Nglom also require further evaluation. Methods Kidneys without overt renal disease were collected at autopsy in Mississippi, USA. The extremes of female Nglom were used to define high and low Nglom for both sexes. Nglom and IGV were estimated by design-based stereology. A total of 24 African and Caucasian American females (n = 12 per race; 6 per Nglom extreme) were included. These subjects were subsequently matched to 24 comparable males by age and Nglom and to 18 additional males by age, Nglom and BSA. Results IGV average and variance were very similar in female African and Caucasian Americans with high and low Nglom. Males with low Nglom from both races showed greater IGV average and variance than comparable females matched by age and Nglom. These differences in IGV between sexes were not observed in Caucasian Americans with low Nglom that were matched by age, Nglom and BSA. In contrast, glomeruli from African Americans were larger than those from Caucasian Americans, especially in subjects with high Nglom. Conclusions While female Americans with low Nglom did not show glomerular hypertrophy, comparable males with low Nglom showed marked glomerular hypertrophy that was closely associated with high BSA. Glomerular size in African Americans may be confounded by multiple additional factors. PMID:24792374
-
Lengths of nephron tubule segments and collecting ducts in the CD-1 mouse kidney: an ontogeny study.
Walton, Sarah L; Moritz, Karen M; Bertram, John F; Singh, Reetu R
2016-11-01
The kidney continues to mature postnatally, with significant elongation of nephron tubules and collecting ducts to maintain fluid/electrolyte homeostasis. The aim of this project was to develop methodology to estimate lengths of specific segments of nephron tubules and collecting ducts in the CD-1 mouse kidney using a combination of immunohistochemistry and design-based stereology (vertical uniform random sections with cycloid arc test system). Lengths of tubules were determined at postnatal day 21 (P21) and 2 and 12 mo of age and also in mice fed a high-salt diet throughout adulthood. Immunohistochemistry was performed to identify individual tubule segments [aquaporin-1, proximal tubules (PT) and thin descending limbs of Henle (TDLH); uromodulin, distal tubules (DT); aquaporin-2, collecting ducts (CD)]. All tubular segments increased significantly in length between P21 and 2 mo of age (PT, 602% increase; DT, 200% increase; TDLH, 35% increase; CD, 53% increase). However, between 2 and 12 mo, a significant increase in length was only observed for PT (76% increase in length). At 12 mo of age, kidneys of mice on a high-salt diet demonstrated a 27% greater length of the TDLH, but no significant change in length was detected for PT, DT, and CD compared with the normal-salt group. Our study demonstrates an efficient method of estimating lengths of specific segments of the renal tubular system. This technique can be applied to examine structure of the renal tubules in combination with the number of glomeruli in the kidney in models of altered renal phenotype. Copyright © 2016 the American Physiological Society.
-
Influence of grazing management on the seasonal change in testicular morphology in Corriedale rams.
Bielli, A; Pedrana, G; Gastel, M T; Castrillejo, A; Moraña, A; Lundeheim, N; Forsberg, M; Rodriguez-Martinez, H
1999-06-28
The present study was conducted: (a) to determine the degree of seasonal variation in testis stereology in Corriedale rams between autumn and winter; (b) to test the hypothesis that testis stereology of Corriedale rams grazing native pastures during autumn and winter would differ from those of Corriedale rams grazing sown pastures and supplemented with grain during the same period; and (c) to determine whether Sertoli cell numbers differ in adult rams between the breeding season (autumn) and the following non-breeding season (winter). Twenty experimental animals were studied. Six rams (autumn control group, C-A) that had been grazing on native pasture (stocking rate = 2-3 animals ha(-1)) were castrated at the beginning of the experiment (March, early autumn). Seven rams (winter control group, C-W) continued to graze on native pasture at the same stocking rate until the end of the experiment (August, late winter). Another seven rams (treated group, T) grazed on improved pasture (stocking rate = 1-2 animals ha(-1)) and were supplemented with 1 kg grain ram(-1) day(-1) until the end of the experiment. Live weight, scrotal circumference, serum testosterone concentration and selected testicular stereological parameters were measured. The treatment did not impede the winter reduction in testicular activity and reduced its magnitude slightly (group T) compared with controls (group C-W). Sertoli cell numbers were higher in autumn (group C-A) than in winter, both on native (group C-W) and sown pastures (group T). Diminishing Sertoli cell numbers between autumn and the following winter suggest the occurrence of that Sertoli cell death during this period. The results indicate that, although the reproductive activity of Corriedale rams is moderately seasonal, a restricted change in grazing and grain supplementation can only modify it to a limited extent.
-
Microstructural analysis of aluminum high pressure die castings
NASA Astrophysics Data System (ADS)
David, Maria Diana
Microstructural analysis of aluminum high pressure die castings (HPDC) is challenging and time consuming. Automating the stereology method is an efficient way in obtaining quantitative data; however, validating the accuracy of this technique can also pose some challenges. In this research, a semi-automated algorithm to quantify microstructural features in aluminum HPDC was developed. Analysis was done near the casting surface where it exhibited fine microstructure. Optical and Secondary electron (SE) and backscatter electron (BSE) SEM images were taken to characterize the features in the casting. Image processing steps applied on SEM and optical micrographs included median and range filters, dilation, erosion, and a hole-closing function. Measurements were done on different image pixel resolutions that ranged from 3 to 35 pixel/μm. Pixel resolutions below 6 px/μm were too low for the algorithm to distinguish the phases from each other. At resolutions higher than 6 px/μm, the volume fraction of primary α-Al and the line intercept count curves plateaued. Within this range, comparable results were obtained validating the assumption that there is a range of image pixel resolution relative to the size of the casting features at which stereology measurements become independent of the image resolution. Volume fraction within this curve plateau was consistent with the manual measurements while the line intercept count was significantly higher using the computerized technique for all resolutions. This was attributed to the ragged edges of some primary α-Al; hence, the algorithm still needs some improvements. Further validation of the code using other castings or alloys with known phase amount and size may also be beneficial.
-
GROWTH AND DIFFERENTIATION OF MITOCHONDRIA IN THE REGENERATING RAT ADRENAL CORTEX
Yago, Nagasumi; Seki, Masatoshi; Sekiyama, Shigetaka; Kobayashi, Shigeru; Kurokawa, Hiromi; Iwai, Yuko; Sato, Fumiaki; Shiragai, Akihiro
1972-01-01
Diameters of the circular profiles of spherical mitochondria in parenchymal cells of the zona fasciculata in rat adrenal cortex were measured for intact controls and for the regenerating adrenal cortex on electron micrographs recorded at random. The diameter data were then processed by Bach's method which deals with the sphere size distribution. The structural parameters of the mitochondria were computed with the aid of an electronic computer. The total number of mitochondria in all the parenchymal cells of the zona fasciculata were calculated. The surface area of the inner mitochondrial membrane was then determined stereologically. Biochemical parameters were obtained for the protein, the phospholipid, and the cytochrome P-450 content, per averaged mitochondrion. The number of cytochrome P-450 molecules contained in the inner membrane was determined in terms of the unit surface area and of the unit amount of phospholipid. These correlated biochemical and stereological parameters have led to the following conclusions. (a) The genesis of the mitochondria after the adrenal enucleation is almost completed within 10 days. (b) During the period of mitochondrial proliferation, the mitochondria are small in size and also immature both in the structure and in the function of their inner membrane, (c) These small and immature mitochondria grow through an increase of the phospholipid and protein, and this increase is accompanied by expansion of the area of the membrane surface, (d) An enrichment of the inner membrane with cytochrome P-450 molecules occurs, thus indicating the differentiation of adrenocortical mitochondria. The process of membrane differentiation is not tightly coupled with that of membrane growth. PMID:5009515
-
White matter atrophy and myelinated fiber disruption in a rat model of depression.
Gao, Yuan; Ma, Jing; Tang, Jing; Liang, Xin; Huang, Chun-Xia; Wang, San-Rong; Chen, Lin-Mu; Wang, Fei-Fei; Tan, Chuan-Xue; Chao, Feng-Lei; Zhang, Lei; Qiu, Xuan; Luo, Yan-Min; Xiao, Qian; Du, Lian; Xiao, Qian; Tang, Yong
2017-06-01
Brain imaging and postmortem studies have indicated that white matter abnormalities may contribute to the pathology and pathogenesis of depression. However, until now, no study has quantitatively investigated white matter changes in depression in rats. The current study used the chronic unpredictable stress (CUS) model of depression. Body weight and sucrose preference test (SPT) scores were assessed weekly. Upon successfully establishing the CUS animal model, all animals were tested using the SPT and the open field test (OFT). Then, transmission electron microscopy and unbiased stereological methods were used to investigate white matter changes in the rats. Compared with the control group, the body weight and sucrose preference of the CUS rats were significantly decreased (p < .001, p < .001, respectively). In the OFT, the total time spent and the total distance traveled in the inner area by the CUS rats were significantly lower than those of the control group (p = .002, p = .001, respectively). The stereological results revealed that white matter volume, the total volume, and the total length and mean diameter of myelinated fibers in the white matter of the CUS rats were significantly decreased compared to the control rats (p = .042, p = .038, p = .035, p = .019, respectively). The results of this study suggested that white matter atrophy and disruption of myelinated fibers in the white matter may contribute to the pathophysiology underlying depression, which might provide new targets for the development of novel therapeutic interventions for depression. © 2017 Wiley Periodicals, Inc.
-
2014-01-01
Introduction Immunohistochemical Ki67 labelling index (Ki67 LI) reflects proliferative activity and is a potential prognostic/predictive marker of breast cancer. However, its clinical utility is hindered by the lack of standardized measurement methodologies. Besides tissue heterogeneity aspects, the key element of methodology remains accurate estimation of Ki67-stained/counterstained tumour cell profiles. We aimed to develop a methodology to ensure and improve accuracy of the digital image analysis (DIA) approach. Methods Tissue microarrays (one 1-mm spot per patient, n = 164) from invasive ductal breast carcinoma were stained for Ki67 and scanned. Criterion standard (Ki67-Count) was obtained by counting positive and negative tumour cell profiles using a stereology grid overlaid on a spot image. DIA was performed with Aperio Genie/Nuclear algorithms. A bias was estimated by ANOVA, correlation and regression analyses. Calibration steps of the DIA by adjusting the algorithm settings were performed: first, by subjective DIA quality assessment (DIA-1), and second, to compensate the bias established (DIA-2). Visual estimate (Ki67-VE) on the same images was performed by five pathologists independently. Results ANOVA revealed significant underestimation bias (P < 0.05) for DIA-0, DIA-1 and two pathologists’ VE, while DIA-2, VE-median and three other VEs were within the same range. Regression analyses revealed best accuracy for the DIA-2 (R-square = 0.90) exceeding that of VE-median, individual VEs and other DIA settings. Bidirectional bias for the DIA-2 with overestimation at low, and underestimation at high ends of the scale was detected. Measurement error correction by inverse regression was applied to improve DIA-2-based prediction of the Ki67-Count, in particular for the clinically relevant interval of Ki67-Count < 40%. Potential clinical impact of the prediction was tested by dichotomising the cases at the cut-off values of 10, 15, and 20%. Misclassification rate of 5-7% was achieved, compared to that of 11-18% for the VE-median-based prediction. Conclusions Our experiments provide methodology to achieve accurate Ki67-LI estimation by DIA, based on proper validation, calibration, and measurement error correction procedures, guided by quantified bias from reference values obtained by stereology grid count. This basic validation step is an important prerequisite for high-throughput automated DIA applications to investigate tissue heterogeneity and clinical utility aspects of Ki67 and other immunohistochemistry (IHC) biomarkers. PMID:24708745
-
A new computerized moving stage for optical microscopes
NASA Astrophysics Data System (ADS)
Hatiboglu, Can Ulas; Akin, Serhat
2004-06-01
Measurements of microscope stage movements in the x and y directions are of importance for some stereological methods. Traditionally, the length of stage movements is measured with differing precision and accuracy using a suitable motorized stage, a microscope and software. Such equipment is generally expensive and not readily available in many laboratories. One other challenging problem is the adaptability to available microscope systems which weakens the possibility of the equipment to be used with any kind of light microscope. This paper describes a simple and cheap programmable moving stage that can be used with the available microscopes in the market. The movements of the stage are controlled by two servo-motors and a controller chip via a Java-based image processing software. With the developed motorized stage and a microscope equipped with a CCD camera, the software allows complete coverage of the specimens with minimum overlap, eliminating the optical strain associated with counting hundreds of images through an eyepiece, in a quick and precise fashion. The uses and the accuracy of the developed stage are demonstrated using thin sections obtained from a limestone core plug.
-
Microglia in the Cerebral Cortex in Autism
ERIC Educational Resources Information Center
Tetreault, Nicole A.; Hakeem, Atiya Y.; Jiang, Sue; Williams, Brian A.; Allman, Elizabeth; Wold, Barbara J.; Allman, John M.
2012-01-01
We immunocytochemically identified microglia in fronto-insular (FI) and visual cortex (VC) in autopsy brains of well-phenotyped subjects with autism and matched controls, and stereologically quantified the microglial densities. Densities were determined blind to phenotype using an optical fractionator probe. In FI, individuals with autism had…
-
Robertson, George N; Lindsey, Benjamin W; Dumbarton, Tristan C; Croll, Roger P; Smith, Frank M
2008-06-01
Many teleost fishes use a swimbladder, a gas-filled organ in the coelomic cavity, to reduce body density toward neutral buoyancy, thus minimizing the locomotory cost of maintaining a constant depth in the water column. However, for most swimbladder-bearing teleosts, the contribution of this organ to the attainment of neutral buoyancy has not been quantified. Here, we examined the quantitative contribution of the swimbladder to buoyancy and three-dimensional stability in a small cyprinid, the zebrafish (Danio rerio). In aquaria during daylight hours, adult animals were observed at mean depths from 10.1 +/- 6.0 to 14.2 +/- 5.6 cm below the surface. Fish mass and whole-body volume were linearly correlated (r(2) = 0.96) over a wide range of body size (0.16-0.73 g); mean whole-body density was 1.01 +/- 0.09 g cm(-3). Stereological estimations of swimbladder volume from linear dimensions of lateral X-ray images and direct measurements of gas volumes recovered by puncture from the same swimbladders showed that results from these two methods were highly correlated (r(2) = 0.85). The geometric regularity of the swimbladder thus permitted its volume to be accurately estimated from a single lateral image. Mean body density in the absence of the swimbladder was 1.05 +/- 0.04 g cm(-3). The swimbladder occupied 5.1 +/- 1.4% of total body volume, thus reducing whole-body density significantly. The location of the centers of mass and buoyancy along rostro-caudal and dorso-ventral axes overlapped near the ductus communicans, a constriction between the anterior and posterior swimbladder chambers. Our work demonstrates that the swimbladder of the adult zebrafish contributes significantly to buoyancy and attitude stability. Furthermore, we describe and verify a stereological method for estimating swimbladder volume that will aid future studies of the functions of this organ. 2008 Wiley-Liss, Inc
-
Species of Perkinsus are responsible for high mortalities of bivalve molluscs world-wide. Techniques to accurately estimate parasites in tissues are required to improve understanding of perkinsosis. This study quantifies the number and tissue distribution of Perkinsus marinus in ...
-
2013-01-01
Background Stereology is an established method to extrapolate three-dimensional quantities from two-dimensional images. It was applied to placentation in the mouse, but not yet for other rodents. Herein, we provide the first study on quantitative placental development in a sigmodontine rodent species with relatively similar gestational time. Placental structure was also compared to the mouse, in order to evaluate similarities and differences in developmental patterns at the end of gestation. Methods Fetal and placental tissues of Necromys lasiurus were collected and weighed at 3 different stages of gestation (early, mid and late gestation) for placental stereology. The total and relative volumes of placenta and of its main layers were investigated. Volume fractions of labyrinth components were quantified by the One Stop method in 31 placentae collected from different individuals, using the Mercator® software. Data generated at the end of gestation from N. lasiurus placentae were compared to those of Mus musculus domesticus obtained at the same stage. Results A significant increase in the total absolute volumes of the placenta and its main layers occurred from early to mid-gestation, followed by a reduction near term, with the labyrinth layer becoming the most prominent area. Moreover, at the end of gestation, the total volume of the mouse placenta was significantly increased compared to that of N. lasiurus although the proportions of the labyrinth layer and junctional zones were similar. Analysis of the volume fractions of the components in the labyrinth indicated a significant increase in fetal vessels and sinusoidal giant cells, a decrease in labyrinthine trophoblast whereas the proportion of maternal blood space remained stable in the course of gestation. On the other hand, in the mouse, volume fractions of fetal vessels and sinusoidal giant cells decreased whereas the volume fraction of labyrinthine trophoblast increased compared to N. lasiurus placenta. Conclusions Placental development differed between N. lasiurus and M. musculus domesticus. In particular, the low placental efficiency in N. lasiurus seemed to induce morphological optimization of fetomaternal exchanges. In conclusion, despite similar structural aspects of placentation in these species, the quantitative dynamics showed important differences. PMID:23433040
-
Improved In vivo Assessment of Pulmonary Fibrosis in Mice using X-Ray Dark-Field Radiography
NASA Astrophysics Data System (ADS)
Yaroshenko, Andre; Hellbach, Katharina; Yildirim, Ali Önder; Conlon, Thomas M.; Fernandez, Isis Enlil; Bech, Martin; Velroyen, Astrid; Meinel, Felix G.; Auweter, Sigrid; Reiser, Maximilian; Eickelberg, Oliver; Pfeiffer, Franz
2015-12-01
Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive lung disease with a median life expectancy of 4-5 years after initial diagnosis. Early diagnosis and accurate monitoring of IPF are limited by a lack of sensitive imaging techniques that are able to visualize early fibrotic changes at the epithelial-mesenchymal interface. Here, we report a new x-ray imaging approach that directly visualizes the air-tissue interfaces in mice in vivo. This imaging method is based on the detection of small-angle x-ray scattering that occurs at the air-tissue interfaces in the lung. Small-angle scattering is detected with a Talbot-Lau interferometer, which provides the so-called x-ray dark-field signal. Using this imaging modality, we demonstrate-for the first time-the quantification of early pathogenic changes and their correlation with histological changes, as assessed by stereological morphometry. The presented radiography method is significantly more sensitive in detecting morphological changes compared with conventional x-ray imaging, and exhibits a significantly lower radiation dose than conventional x-ray CT. As a result of the improved imaging sensitivity, this new imaging modality could be used in future to reduce the number of animals required for pulmonary research studies.
-
Decreased frontal white-matter volume in chronic substance abuse.
Schlaepfer, Thomas E; Lancaster, Eric; Heidbreder, Rebecca; Strain, Eric C; Kosel, Markus; Fisch, Hans-Ulrich; Pearlson, Godfrey D
2006-04-01
There is quite a body of work assessing functional brain changes in chronic substance abuse, much less is known about structural brain abnormalities in this patient population. In this study we used magnetic resonance imaging (MRI) to determine if structural brain differences exist in patients abusing illicit drugs compared to healthy controls. Sixteen substance abusers who abused heroin, cocaine and cannabis but not alcohol and 16 age-, sex- and race-matched controls were imaged on a MRI scanner. Contiguous, 5-mm-thick axial slices were acquired with simultaneous T2 and proton density sequences. Volumes were estimated for total grey and white matter, frontal grey and white matter, ventricles, and CSF using two different methods: a conventional segmentation and a stereological method based on the Cavalieri principle. Overall brain volume differences were corrected for by expressing the volumes of interest as a percentage of total brain volume. Volume measures obtained with the two methods were highly correlated (r=0.65, p<0.001). Substance abusers had significantly less frontal white-matter volume percentage than controls. There were no significant differences in any of the other brain volumes measured. This difference in frontal lobe white matter might be explained by a direct neurotoxic effect of drug use on white matter, a pre-existing abnormality in the development of the frontal lobe or a combination of both effects. This last explanation might be compelling based on the fact that newer concepts on shared aspects of some neuropsychiatric disorders focus on the promotion and inhibition of the process of myelination throughout brain development and subsequent degeneration.
-
Wound Healing Effect of Arnebia euchroma gel on Excisional Wounds in Rats
Mohsenikia, Maryam; Khakpour, Shahrzad; Azizian, Zahra; Ashkani-Esfahani, Soheil; Razavipour, Seyyede Tahereh; Toghiani, Pooya
2017-01-01
Background: Wound healing is a complex process leading to regeneration of damaged skin tissue. Arnebia euchroma (AE) have many effective activities such as anti-inflammatory, antimicrobial, antioxidative, and anti-tumoral effects. The extract of AE has positive effects on burn wounds. This study is designed to investigate the healing effects of AE on excisional wounds in rats. Materials and Methods: Thirty six rats with the age of 8 weeks divided into three groups. One group (E1) was treated with AE gel at a concentration of 10%. Control group (C1) received normal saline and the vehicle group (C2) was treated with carboxymethyl cellulose gel as the vehicle for 14 days. Stereological analysis was done to investigate the collagen bundle and hair follicale synthesis, vascularization, fibroblast proliferation. Pathological evaluation was also conducted. Results: In this study, pathological evaluation showed severe acute inflammation in C2 group, chronic and acute inflammation in C1 and also more wound contraction in E1 in comparison with other groups. There was a meaningful difference between E1 and C1 regarding fibroblast proliferation (P < 0.05). Conclusion: Results of this study revealed the healing effect of AE on excisional wounds and recommend its administration after further clinical investigations. PMID:28217647
-
Brain Aging and AD-Like Pathology in Streptozotocin-Induced Diabetic Rats
Wang, Jian-Qin; Yin, Jie; Song, Yan-Feng; Zhang, Lang; Ren, Ying-Xiang; Wang, De-Gui; Gao, Li-Ping; Jing, Yu-Hong
2014-01-01
Objective. Numerous epidemiological studies have linked diabetes mellitus (DM) with an increased risk of developing Alzheimer's disease (AD). However, whether or not diabetic encephalopathy shows AD-like pathology remains unclear. Research Design and Methods. Forebrain and hippocampal volumes were measured using stereology in serial coronal sections of the brain in streptozotocin- (STZ-) induced rats. Neurodegeneration in the frontal cortex, hypothalamus, and hippocampus was evaluated using Fluoro-Jade C (FJC). Aβ aggregation in the frontal cortex and hippocampus was tested using immunohistochemistry and ELISA. Dendritic spine density in the frontal cortex and hippocampus was measured using Golgi staining, and western blot was conducted to detect the levels of synaptophysin. Cognitive ability was evaluated through the Morris water maze and inhibitory avoidant box. Results. Rats are characterized by insulin deficiency accompanied with polydipsia, polyphagia, polyuria, and weight loss after STZ injection. The number of FJC-positive cells significantly increased in discrete brain regions of the diabetic rats compared with the age-matched control rats. Hippocampal atrophy, Aβ aggregation, and synapse loss were observed in the diabetic rats compared with the control rats. The learning and memory of the diabetic rats decreased compared with those of the age-matched control rats. Conclusions. Our results suggested that aberrant metabolism induced brain aging as characterized by AD-like pathologies. PMID:25197672
-
Digital image analysis in pathology: benefits and obligation.
Laurinavicius, Arvydas; Laurinaviciene, Aida; Dasevicius, Darius; Elie, Nicolas; Plancoulaine, Benoît; Bor, Catherine; Herlin, Paulette
2012-01-01
Pathology has recently entered the era of personalized medicine. This brings new expectations for the accuracy and precision of tissue-based diagnosis, in particular, when quantification of histologic features and biomarker expression is required. While for many years traditional pathologic diagnosis has been regarded as ground truth, this concept is no longer sufficient in contemporary tissue-based biomarker research and clinical use. Another major change in pathology is brought by the advancement of virtual microscopy technology enabling digitization of microscopy slides and presenting new opportunities for digital image analysis. Computerized vision provides an immediate benefit of increased capacity (automation) and precision (reproducibility), but not necessarily the accuracy of the analysis. To achieve the benefit of accuracy, pathologists will have to assume an obligation of validation and quality assurance of the image analysis algorithms. Reference values are needed to measure and control the accuracy. Although pathologists' consensus values are commonly used to validate these tools, we argue that the ground truth can be best achieved by stereology methods, estimating the same variable as an algorithm is intended to do. Proper adoption of the new technology will require a new quantitative mentality in pathology. In order to see a complete and sharp picture of a disease, pathologists will need to learn to use both their analogue and digital eyes.
-
Machado-Santos, Clarice; Aquino, Júlio Cesar Fraulob; da Rocha, Patrício Adriano; Abidu-Figueiredo, Marcelo; de Brito-Gitirana, Lycia; Sales, Armando
2017-02-01
Pteronotus personatus as an insectivore bat and has a diet that consists of a high protein diet, whereas the diet of Anoura geoffroyi, a predominantly nectarivore bat, is rich in simple sugars like sucrose, glucose and fructose. Considering that diet influences the activation of different pathways, which may influence morphological adaptations in the gastrointestinal system, the aim of this study was to compare the morphology of the endocrine pancreas in P. personatus and A. geoffroyi. For this, histological, stereological and immunohistochemical methods were used. In P. personatus, the average diameter of the pancreatic islet was 40.47μm±13.94, while in A. geoffroyi was 88.16μm±36.40. The total number of pancreatic islets in P. personatus was 26150±2346 and in A. geoffroyi was 15970±1666. In P. personatus, the volume density of the pancreatic islets was 3.4%± 2.6, whereas in A. geoffroyi the volume density was 6.1%±3.7. In addition, the immunodensity of the α, β and δ cells, in P. personatus was 25.8%±11.9, 35.5%±13.5, 3.9%±0.7, respectively, and in A. geoffroyi was 33.10%±12.7, 55.08%±7.4, 6.2%±4.6, respectively. In conclusion, the results of this study indicate differences in the pancreatic weight/body, weight ratio, diameter and volume density of pancreatic islets and in immunodensity of the β and α cells between both species, which have different dietary habits. Copyright © 2017 Elsevier Ltd. All rights reserved.
-
Gevrek, Fikret
2018-05-01
Cellular phones are major sources of electromagnetic radiation (EMR) that can penetrate the human body and pose serious health hazards. The increasingly widespread use of mobile communication systems has raised concerns about the effects of cellphone radiofrequency (RF) on the hippocampus because of its close proximity to radiation during cellphone use. The effects of cellphone EMR exposure on the hippocampus of rats and the possible counteractive effects of Ginkgo biloba (Egb761) were aimed to investigate. Rats were divided into three groups: Control, EMR, and EMR+Egb761. The EMR and EMR+Egb761 groups were exposed to cellphone EMR for one month. Egb761 was also administered to the EMR+Egb761 group. Specifically, we evaluated the effect of RF exposure on rat hippocampi at harmful EMR levels (0.96 W/kg specific absorption rate [SAR]) for one month and also investigated the possible impact of Ginkgo biloba (Egb761) using stereological, TUNEL-staining, and immunohistochemical methods. An increase in apoptotic proteins (Bax, Acas-3) and a decrease in anti-apoptotic protein (Bcl-2) immunoreactivity along with a decrease in the total granule and pyramidal cell count were noted in the EMR group. A decrease in Bax and Acas-3 and an increase in Bcl-2 immunoreactivity were observed in rats treated with Egb761 in addition to a decrease in TUNEL-stained apoptotic cells and a higher total viable cell number. In conclusion, chronic cellphone EMR exposure may affect hippocampal cell viability, and Egb761 may be used to mitigate some of the deleterious effects.
-
Xu, Yi-Hua; Pitot, Henry C
2003-09-01
Single enzyme-altered hepatocytes; altered hepatic foci (AHF); and nodular lesions have been implicated, respectively in the processes of initiation, promotion, and progression in rodent hepatocarcinogenesis. Qualitative and quantitative analyses of such lesions have been utilized both to identify and to determine the potency of initiating, promoting, and progressor agents in rodent liver. Of a number of possible parameters determined in the study of such lesions, estimation of the number of foci or nodules in the liver is very important. The method of Saltykov has been used for estimating the number of AHF in rat liver. However, in practice, the Saltykov calculation has at least two weak points: (a) the size class range is limited to 12, which in many instances is too narrow to cover the range of AHF data obtained; and (b) under some conditions, the Saltykov equation generates negative values in several size classes, an obvious impossibility in the real world. In order to overcome these limitations in the Saltykov calculations, a study of the particle size distribution in a wide-range, polydispersed sphere system was performed. A stereologic method, termed the 25F Association method, was developed from this study. This method offers 25 association factors that are derived from the frequency of different-sized transections obtained from transecting a spherical particle, thus expanding the size class range to be analyzed up to 25, which is sufficiently wide to encompass all rat AHF found in most cases. This method exhibits greater flexibility, which allows adjustments to be made within the calculation process when NA((k,k)), the net number of transections from the same size spheres, was found to be a negative value, which is not possible in real situations. The reliability of the 25F Association method was tested thoroughly by computer simulation in both monodispersed and polydispersed sphere systems. The test results were compared with the original Saltykov method. We found that the 25F Association method yielded a better estimate of the total number of spheres in the three-dimensional tissue sample as well as the detailed size distribution information. Although the 25F Association method was derived from the study of a polydispersed sphere system, it can be used for continuous size distribution sphere systems. Application of this method to the estimation of parameters of preneoplastic foci in rodent liver is presented as an example of its utility. An application software program, 3D_estimation.exe, which uses the 25F Association method to estimate the number of AHF in rodent liver, has been developed and is now available at the website of this laboratory.
-
Quantification of lung microstructure with hyperpolarized 3He diffusion MRI
Sukstanskii, Alexander L.; Woods, Jason C.; Gierada, David S.; Quirk, James D.; Hogg, James C.; Cooper, Joel D.; Conradi, Mark S.
2009-01-01
The structure and integrity of pulmonary acinar airways and their changes in different diseases are of great importance and interest to a broad range of physiologists and clinicians. The introduction of hyperpolarized gases has opened a door to in vivo studies of lungs with MRI. In this study we demonstrate that MRI-based measurements of hyperpolarized 3He diffusivity in human lungs yield quantitative information on the value and spatial distribution of lung parenchyma surface-to-volume ratio, number of alveoli per unit lung volume, mean linear intercept, and acinar airway radii—parameters that have been used by lung physiologists for decades and are accepted as gold standards for quantifying emphysema. We validated our MRI-based method in six human lung specimens with different levels of emphysema against direct unbiased stereological measurements. We demonstrate for the first time MRI images of these lung microgeometric parameters in healthy lungs and lungs with different levels of emphysema (mild, moderate, and severe). Our data suggest that decreases in lung surface area per volume at the initial stages of emphysema are due to dramatic decreases in the depth of the alveolar sleeves covering the alveolar ducts and sacs, implying dramatic decreases in the lung's gas exchange capacity. Our novel methods are sufficiently sensitive to allow early detection and diagnosis of emphysema, providing an opportunity to improve patient treatment outcomes, and have the potential to provide safe and noninvasive in vivo biomarkers for monitoring drug efficacy in clinical trials. PMID:19661452
-
Orientational analysis of planar fibre systems observed as a Poisson shot-noise process.
Kärkkäinen, Salme; Lantuéjoul, Christian
2007-10-01
We consider two-dimensional fibrous materials observed as a digital greyscale image. The problem addressed is to estimate the orientation distribution of unobservable thin fibres from a greyscale image modelled by a planar Poisson shot-noise process. The classical stereological approach is not straightforward, because the point intensities of thin fibres along sampling lines may not be observable. For such cases, Kärkkäinen et al. (2001) suggested the use of scaled variograms determined from grey values along sampling lines in several directions. Their method is based on the assumption that the proportion between the scaled variograms and point intensities in all directions of sampling lines is constant. This assumption is proved to be valid asymptotically for Boolean models and dead leaves models, under some regularity conditions. In this work, we derive the scaled variogram and its approximations for a planar Poisson shot-noise process using the modified Bessel function. In the case of reasonable high resolution of the observed image, the scaled variogram has an approximate functional relation to the point intensity, and in the case of high resolution the relation is proportional. As the obtained relations are approximative, they are tested on simulations. The existing orientation analysis method based on the proportional relation is further experimented on images with different resolutions. The new result, the asymptotic proportionality between the scaled variograms and the point intensities for a Poisson shot-noise process, completes the earlier results for the Boolean models and for the dead leaves models.
-
The myelinated fiber loss in the corpus callosum of mouse model of schizophrenia induced by MK-801.
Xiu, Yun; Kong, Xiang-ru; Zhang, Lei; Qiu, Xuan; Gao, Yuan; Huang, Chun-xia; Chao, Feng-lei; Wang, San-rong; Tang, Yong
2015-04-01
Previous magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) investigations have shown that the white matter volume and fractional anisotropy (FA) were decreased in schizophrenia (SZ), which indicated impaired white matter integrity in SZ. However, the mechanism underlying these abnormalities has been less studied. The current study was designed to investigate the possible reasons for white matter abnormalities in the mouse model of SZ induced by NMDA receptor antagonist using the unbiased stereological methods and transmission electron microscope technique. We found that the mice treated with MK-801 demonstrated a series of schizophrenia-like behaviors including hyperlocomotor activity and more anxiety. The myelinated fibers in the corpus callosum (CC) of the mice treated with MK-801 were impaired with splitting lamellae of myelin sheaths and segmental demyelination. The CC volume and the total length of the myelinated fibers in the CC of the mice treated with MK-801 were significantly decreased by 9.4% and 16.8% when compared to those of the mice treated with saline. We further found that the loss of the myelinated fibers length was mainly due to the marked loss of the myelinated nerve fibers with the diameter of 0.4-0.5 μm. These results indicated that the splitting myelin sheaths, demyelination and the loss of myelinated fibers with small diameter might provide one of the structural bases for impaired white matter integrity of CC in the mouse model of SZ. These results might also provide a baseline for further studies searching for the treatment of SZ through targeting white matter. Copyright © 2015 Elsevier Ltd. All rights reserved.
-
Salehi, Mohammad Saied; Mirzaii-Dizgah, Iraj; Vasaghi-Gharamaleki, Behnoosh; Zamiri, Mohammad Javad
2016-11-09
Hindlimb unloading (HU) can cause motion and cognition dysfunction, although its cellular and molecular mechanisms are not well understood. The aim of the present study was to determine the stereological parameters of the brain areas involved in motion (motor cortex) and spatial learning - memory (hippocampus) under an HU condition. Sixteen adult male rats, kept under a 12 : 12 h light-dark cycle, were divided into two groups of freely moving (n=8) and HU (n=8) rats. The volume of motor cortex and hippocampus, the numerical cell density of neurons in layers I, II-III, V, and VI of the motor cortex, the entire motor cortex as well as the primary motor cortex, and the numerical density of the CA1, CA3, and dentate gyrus subregions of the hippocampus were estimated. No significant differences were observed in the evaluated parameters. Our results thus indicated that motor cortical and hippocampal atrophy and cell loss may not necessarily be involved in the motion and spatial learning memory impairment in the rat.
-
Characterization of glass-infiltrated alumina-based ceramics
Bona, Alvaro Della; Mecholsky, John J; Barrett, Allyson A; Griggs, Jason A
2010-01-01
Objective characterize the microstructure, composition, and important properties of glass-infiltrated alumina-based ceramics similar to the In-Ceram system. Methods Materials used were: IA- In-Ceram Alumina (Vita); IAE- IA electrophoretically deposited (Vita); AEM- IA using a vacuum driven method (Vita); VC- Vitro-Ceram (Angelus); TC- Turkom-Cera (Turkom-Ceramic); CC- Ceramcap (Foto-Ceram); and AG- Alglass (EDG). Ceramic specimens were fabricated following manufacturers’ instructions and ISO6872 standard and polished successively through 1μm alumina abrasive. Semi-quantitative and qualitative analyses were performed using scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), and stereology (Vv). The elastic modulus (E) and Poisson’s ratio (ν) were determined using time-of-flight data measured in an ultrasonic pulser/receiver and the density (ρ) was determined using a helium pycnometer. Vicker’s indentation was used to calculate hardness (H). Bar specimens (25×4×1.2mm3) were loaded in three-point bending to fracture using a universal testing machine with cross-head speed of 1mm/min. Flexural strength (σ3P) was calculated and statistically analyzed using ANOVA, Tukey (α=0.05) and Weibull (m= modulus, σ0= characteristic strength). Results SEM and EDS analyses revealed similar microstructure for all ceramics, except for a lead-based matrix in CC and a zirconia phase in VC. TC, AG and CC showed significantly lower mean σ3P values than the other ceramics (p 0.05). AEM showed the greatest m (16). Conclusion Despite few differences in microstructure and composition, the IA, IAE, AEM and VC ceramics have similar properties. Significance The glass-infiltrated alumina-based ceramics from different manufacturers presented distinct characteristics. It is necessary to characterize new commercially available materials to understand their properties. PMID:18692231
-
Mostafavinia, Ataroalsadat; Masteri Farahani, Reza; Abdollahifar, Mohammad-Amin; Ghatrehsamani, Mahdi; Ghoreishi, Seyed Kamran; Hajihossainlou, Behnam; Chien, Sufan; Dadras, Sara; Rezaei, Fatemehalsadat; Bayat, Mohammad
2018-05-31
We examined the effects of photobiomodulation (PBM) on stereological parameters, and gene expression of Runt-related transcription factor 2 (RUNX2), osteocalcin, and receptor activator of nuclear factor kappa-B ligand (RANKL) in repairing tissue of tibial bone defect in streptozotocin (STZ)-induced type 1 diabetes mellitus (TIDM) in rats during catabolic response of fracture healing. There were conflicting results regarding the efficacy of PBM on bone healing process in healthy and diabetic animals. Forty-eight rats have been distributed into four groups: group 1 (healthy control, no TIDM and no PBM), group 2 (healthy test, no TIDM and PBM), group 3 (diabetic control, TIDM and no PBM), and group 4 (diabetic test, no TIDM and PBM). TIDM was induced in the groups 3 and 4. A partial bone defect in tibia was made in all groups. The bone defects of groups second and fourth were irradiated by a laser (890 nm, 80 Hz, 1.5 J/cm 2 ). Thirty days after the surgery, all bone defects were extracted and were submitted to stereological examination and real-time polymerase chain reaction (RT-PCR). PBM significantly increased volumes of total callus, total bone, bone marrow, trabecular bone, and cortical bone, and the numbers of osteocytes and osteoblasts of callus in TIDM rats compared to those of callus in diabetic control. In addition, TIDM increased RUNX2, and osteocalcin in callus of tibial bone defect compared to healthy group. PBM significantly decreased osteocalcin gene expression in TIDM rats. PBM significantly increased many stereological parameters of bone repair in an STZ-induced TIDM during catabolic response of fracture healing. Further RT-PCR test demonstrated that bone repair was modulated in diabetic rats during catabolic response of fracture healing by significant increase in mRNA expression of RUNX2, and osteocalcin compared to healthy control rats. PBM also decreased osteocalcin mRNA expression in TIDM rats.
-
Kubínová, Zuzana
2014-01-01
Chloroplast number per cell is a frequently examined quantitative anatomical parameter, often estimated by counting chloroplast profiles in two-dimensional (2D) sections of mesophyll cells. However, a mesophyll cell is a three-dimensional (3D) structure and this has to be taken into account when quantifying its internal structure. We compared 2D and 3D approaches to chloroplast counting from different points of view: (i) in practical measurements of mesophyll cells of Norway spruce needles, (ii) in a 3D model of a mesophyll cell with chloroplasts, and (iii) using a theoretical analysis. We applied, for the first time, the stereological method of an optical disector based on counting chloroplasts in stacks of spruce needle optical cross-sections acquired by confocal laser-scanning microscopy. This estimate was compared with counting chloroplast profiles in 2D sections from the same stacks of sections. Comparing practical measurements of mesophyll cells, calculations performed in a 3D model of a cell with chloroplasts as well as a theoretical analysis showed that the 2D approach yielded biased results, while the underestimation could be up to 10-fold. We proved that the frequently used method for counting chloroplasts in a mesophyll cell by counting their profiles in 2D sections did not give correct results. We concluded that the present disector method can be efficiently used for unbiased estimation of chloroplast number per mesophyll cell. This should be the method of choice, especially in coniferous needles and leaves with mesophyll cells with lignified cell walls where maceration methods are difficult or impossible to use. PMID:24336344
-
Measuring glomerular number from kidney MRI images
NASA Astrophysics Data System (ADS)
Thiagarajan, Jayaraman J.; Natesan Ramamurthy, Karthikeyan; Kanberoglu, Berkay; Frakes, David; Bennett, Kevin; Spanias, Andreas
2016-03-01
Measuring the glomerular number in the entire, intact kidney using non-destructive techniques is of immense importance in studying several renal and systemic diseases. Commonly used approaches either require destruction of the entire kidney or perform extrapolation from measurements obtained from a few isolated sections. A recent magnetic resonance imaging (MRI) method, based on the injection of a contrast agent (cationic ferritin), has been used to effectively identify glomerular regions in the kidney. In this work, we propose a robust, accurate, and low-complexity method for estimating the number of glomeruli from such kidney MRI images. The proposed technique has a training phase and a low-complexity testing phase. In the training phase, organ segmentation is performed on a few expert-marked training images, and glomerular and non-glomerular image patches are extracted. Using non-local sparse coding to compute similarity and dissimilarity graphs between the patches, the subspace in which the glomerular regions can be discriminated from the rest are estimated. For novel test images, the image patches extracted after pre-processing are embedded using the discriminative subspace projections. The testing phase is of low computational complexity since it involves only matrix multiplications, clustering, and simple morphological operations. Preliminary results with MRI data obtained from five kidneys of rats show that the proposed non-invasive, low-complexity approach performs comparably to conventional approaches such as acid maceration and stereology.
-
On representation of mechanical behavior and stereological measures of microstructure
NASA Technical Reports Server (NTRS)
Onat, E. T.; Wright, S. I.
1991-01-01
Macroscopic homogeneity of a heterogeneous body is defined from various points of view. The applicability of the principle of Delesse to a single macroscopically homogeneous body is discussed. It is then seen that a function derived from a consideration of the area fraction of a phase can serve as a measure of clustering of particles of that phase.
-
Buckmaster, Paul S.; Wen, Xiling; Toyoda, Izumi; Gulland, Frances M. D.; Van Bonn, William
2014-01-01
California sea lions (Zalophus californianus) are abundant human-sized carnivores with large gyrencephalic brains. They develop epilepsy after experiencing status epilepticus when naturally exposed to domoic acid. We tested whether sea lions previously exposed to DA (chronic DA sea lions) display hippocampal neuropathology similar to that of human patients with temporal lobe epilepsy. Hippocampi were obtained from control and chronic DA sea lions. Stereology was used to estimate numbers of Nissl-stained neurons per hippocampus in the granule cell layer, hilus, and the pyramidal cell layer of CA3, CA2, and CA1 subfields. Adjacent sections were processed for somatostatin-immunoreactivity or Timm-stained, and the extent of mossy fiber sprouting was measured stereologically. Chronic DA sea lions displayed hippocampal neuron loss in patterns and extents similar but not identical to those reported previously for human patients with temporal lobe epilepsy. Similar to human patients, hippocampal sclerosis in sea lions was unilateral in 79% of cases, mossy fiber sprouting was a common neuropathological abnormality, and somatostatin-immunoreactive axons were exuberant in the dentate gyrus despite loss of immunopositive hilar neurons. Thus, hippocampal neuropathology of chronic DA sea lions is similar to that of human patients with temporal lobe epilepsy. PMID:24638960
-
Wright, David A; Nam, Diane; Whyne, Cari M
2012-08-31
In attempting to develop non-invasive image based measures for the determination of the biomechanical integrity of healing fractures, traditional μCT based measurements have been limited. This study presents the development and evaluation of a tool for assessment of fracture callus mechanical properties through determination of the geometric characteristics of the fracture callus, specifically along the surface of failure identified during destructive mechanical testing. Fractures were created in tibias of ten male mice and subjected to μCT imaging and biomechanical torsion testing. Failure surface analysis, along with previously described image based measures was calculated using the μCT image data, and correlated with mechanical strength and stiffness. Three-dimensional measures along the surface of failure, specifically the surface area and torsional rigidity of bone, were shown to be significantly correlating with mechanical strength and stiffness. It was also shown that surface area of bone along the failure surface exhibits stronger correlations with both strength and stiffness than measures of average and minimum torsional rigidity of the entire callus. Failure surfaces observed in this study were generally oriented at 45° to the long axis of the bone, and were not contained exclusively within the callus. This work represents a proof of concept study, and shows the potential utility of failure surface analysis in the assessment of fracture callus stability. Copyright © 2012 Elsevier Ltd. All rights reserved.
-
Microwave energy fixation for electron microscopy.
Login, G. R.; Dvorak, A. M.
1985-01-01
We have demonstrated that microwave energy (MW) can be used in conjunction with chemical cross-linking agents in order to rapidly fix cell suspensions and tissue blocks for electron microscopy in 7-9 seconds. The optimal MW fixation method involved immersing tissues up to 1 cu cm in dilute aldehyde fixation and immediately irradiating the specimens in a conventional microwave oven for 9 seconds to 50 C. Ultrastructural preservation of samples irradiated by MW energy was comparable to that of the control samples immersed in aldehyde fixative for 2 hours at 25 C. Stereologic analysis showed that tissue blocks fixed by the MW fixation method did not cause organelles such as liver mitochondria and salivary gland granules to shrink or to swell. Potential applications for this new fixation technology include the investigation of rapid intracellular processes (eg, vesicular transport) and preservation of proteins that are difficult to demonstrate with routine fixation methods (eg, antigens and enzymes). Images Figure 4 Figure 5 Figure 2 Figure 3 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Figure 11 PMID:3927740
-
Kerimoğlu, Gökçen; Hancı, Hatice; Baş, Orhan; Aslan, Ali; Erol, Hüseyin Serkan; Turgut, Alpgiray; Kaya, Haydar; Çankaya, Soner; Sönmez, Osman Fikret; Odacı, Ersan
2016-11-01
The central nervous system (CNS) begins developing in the intrauterine period, a process that continues until adulthood. Contact with chemical substances, drugs or environmental agents such as electromagnetic field (EMF) during adolescence therefore has the potential to disturb the development of the morphological architecture of components of the CNS (such as the hippocampus). The hippocampus is essential to such diverse functions as memory acquisition and integration and spatial maneuvering. EMF can result in severe damage to both the morphology of the hippocampus and its principal functions during adolescence. Although children and adolescents undergo greater exposure to EMF than adults, the information currently available regarding the effects of exposure to EMF during this period is as yet insufficient. This study investigated the 60-day-old male rat hippocampus following exposure to 900 megahertz (MHz) EMF throughout the adolescent period using stereological, histopathological and biochemical analysis techniques. Eighteen male Sprague Dawley rats aged 21days were assigned into control, sham and EMF groups on a random basis. No procedure was performed on the control group rats. The EMF group (EMFGr) was exposed to a 900-MHz EMF for 1h daily from beginning to end of adolescence. The sham group rats were held in the EMF cage but were not exposed to EMF. All rats were sacrificed at 60days of age. Their brains were extracted and halved. The left hemispheres were set aside for biochemical analyses and the right hemispheres were subjected to stereological and histopathological evaluation. Histopathological examination revealed increased numbers of pyknotic neurons with black or dark blue cytoplasm on EMFGr slides stained with cresyl violet. Stereological analyses revealed fewer pyramidal neurons in EMFGr than in the other two groups. Biochemical analyses showed an increase in malondialdehyde and glutathione levels, but a decrease in catalase levels in EMFGr. Our results indicate that oxidative stress-related morphological damage and pyramidal neuron loss may be observed in the rat hippocampus following exposure to 900-MHz EMF throughout the adolescent period. Copyright © 2016 Elsevier B.V. All rights reserved.
-
Evaluation of biodegradable electric conductive tube-guides and mesenchymal stem cells
Ribeiro, Jorge; Pereira, Tiago; Caseiro, Ana Rita; Armada-da-Silva, Paulo; Pires, Isabel; Prada, Justina; Amorim, Irina; Amado, Sandra; França, Miguel; Gonçalves, Carolina; Lopes, Maria Ascensão; Santos, José Domingos; Silva, Dina Morais; Geuna, Stefano; Luís, Ana Lúcia; Maurício, Ana Colette
2015-01-01
AIM: To study the therapeutic effect of three tube-guides with electrical conductivity associated to mesenchymal stem cells (MSCs) on neuro-muscular regeneration after neurotmesis. METHODS: Rats with 10-mm gap nerve injury were tested using polyvinyl alcohol (PVA), PVA-carbon nanotubes (CNTs) and MSCs, and PVA-polypyrrole (PPy). The regenerated nerves and tibialis anterior muscles were processed for stereological studies after 20 wk. The functional recovery was assessed serially for gait biomechanical analysis, by extensor postural thrust, sciatic functional index and static sciatic functional index (SSI), and by withdrawal reflex latency (WRL). In vitro studies included cytocompatibility, flow cytometry, reverse transcriptase polymerase chain reaction and karyotype analysis of the MSCs. Histopathology of lung, liver, kidneys, and regional lymph nodes ensured the biomaterials biocompatibility. RESULTS: SSI remained negative throughout and independently from treatment. Differences between treted groups in the severity of changes in WRL existed, showing a faster regeneration for PVA-CNTs-MSCs (P < 0.05). At toe-off, less acute ankle joint angles were seen for PVA-CNTs-MSCs group (P = 0.051) suggesting improved ankle muscles function during the push off phase of the gait cycle. In PVA-PPy and PVA-CNTs groups, there was a 25% and 42% increase of average fiber area and a 13% and 21% increase of the “minimal Feret’s diameter” respectively. Stereological analysis disclosed a significantly (P < 0.05) increased myelin thickness (M), ratio myelin thickness/axon diameter (M/d) and ratio axon diameter/fiber diameter (d/D; g-ratio) in PVA-CNT-MSCs group (P < 0.05). CONCLUSION: Results revealed that treatment with MSCs and PVA-CNTs tube-guides induced better nerve fiber regeneration. Functional and kinematics analysis revealed positive synergistic effects brought by MSCs and PVA-CNTs. The PVA-CNTs and PVA-PPy are promising scaffolds with electric conductive properties, bio- and cytocompatible that might prevent the secondary neurogenic muscular atrophy by improving the reestablishment of the neuro-muscular junction. PMID:26240682
-
Burke, Mark W; Inyatkin, Alexey; Ptito, Maurice; Ervin, Frank R; Palmour, Roberta M
2016-10-27
Fetal alcohol exposure (FAE) alters hippocampal cell numbers in rodents and primates, and this may be due, in part, to a reduction in the number or migration of neuronal progenitor cells. The olfactory bulb exhibits substantial postnatal cellular proliferation and a rapid turnover of newly formed cells in the rostral migratory pathway, while production and migration of postnatal neurons into the dentate gyrus may be more complex. The relatively small size of the olfactory bulb, compared to the hippocampus, potentially makes this structure ideal for a rapid analysis. This study used the St. Kitts vervet monkey ( Chlorocebus sabeus ) to (1) investigate the normal developmental sequence of post-natal proliferation in the olfactory bulb and dentate gyrus and (2) determine the effects of naturalistic prenatal ethanol exposure on proliferation at three different ages (neonate, five months and two years). Using design-based stereology, we found an age-related decrease of actively proliferating cells in the olfactory bulb and dentate gyrus for both control and FAE groups. Furthermore, at the neonatal time point, the FAE group had fewer actively proliferating cells as compared to the control group. These data are unique with respect to fetal ethanol effects on progenitor proliferation in the primate brain and suggest that the olfactory bulb may be a useful structure for studies of cellular proliferation.
-
Guthrie, O'neil W
2017-03-01
In response to toxic stressors, cancer cells defend themselves by mobilizing one or more epidermal growth factor receptor (EGFR) cascades that employ xeroderma pigmentosum-A (XPA) to repair damaged genes. Recent experiments discovered that neurons within the auditory nerve exhibit basal levels of EGFR+XPA co-expression. This finding implied that auditory neurons in particular or neurons in general have the capacity to mobilize an EGFR+XPA defense. Therefore, the current study tested the hypothesis that noise stress would alter the expression pattern of EGFR/XPA within the auditory nerve. Design-based stereology was used to quantify the proportion of neurons that expressed EGFR, XPA, and EGFR+XPA with and without noise stress. The results revealed an intricate neuronal response that is suggestive of alterations to both co-expression and individual expression of EGFR and XPA. In both the apical and middle cochlear coils, the noise stress depleted EGFR+XPA expression. Furthermore, there was a reduction in the proportion of neurons that expressed XPA-alone in the middle coils. However, the noise stress caused a significant increase in the proportion of neurons that expressed EGFR-alone in the middle coils. The basal cochlear coils failed to mobilize a significant response to the noise stress. These results suggest that EGFR and XPA might be part of the molecular defense repertoire of the auditory nerve.
-
Guthrie, O’neil W.
2017-01-01
In response to toxic stressors, cancer cells defend themselves by mobilizing one or more epidermal growth factor receptor (EGFR) cascades that employ xeroderma pigmentosum–A (XPA) to repair damaged genes. Recent experiments discovered that neurons within the auditory nerve exhibit basal levels of EGFR+XPA co-expression. This finding implied that auditory neurons in particular or neurons in general have the capacity to mobilize an EGFR+XPA defense. Therefore, the current study tested the hypothesis that noise stress would alter the expression pattern of EGFR/XPA within the auditory nerve. Design-based stereology was used to quantify the proportion of neurons that expressed EGFR, XPA, and EGFR+XPA with and without noise stress. The results revealed an intricate neuronal response that is suggestive of alterations to both co-expression and individual expression of EGFR and XPA. In both the apical and middle cochlear coils, the noise stress depleted EGFR+XPA expression. Furthermore, there was a reduction in the proportion of neurons that expressed XPA-alone in the middle coils. However, the noise stress caused a significant increase in the proportion of neurons that expressed EGFR-alone in the middle coils. The basal cochlear coils failed to mobilize a significant response to the noise stress. These results suggest that EGFR and XPA might be part of the molecular defense repertoire of the auditory nerve. PMID:28056182
-
Mayhew, Terry M
2014-01-01
For many organisms, respiratory gas exchange is a vital activity and different types of gas-exchange apparatus have evolved to meet individual needs. They include not only skin, gills, tracheal systems and lungs but also transient structures such as the chorioallantois of avian eggs and the placenta of eutherian mammals. The ability of these structures to allow passage of oxygen by passive diffusion can be expressed as a diffusive conductance (units: cm(3) O2 min(-1) kPa(-1)). Occasionally, the ability to estimate diffusive conductance by physiological techniques is compromised by the difficulty of obtaining O2 partial pressures on opposite sides of the tissue interface between the delivery medium (air, water, blood) and uptake medium (usually blood). An alternative strategy is to estimate a morphometric diffusive conductance by combining stereological estimates of key structural quantities (volumes, surface areas, membrane thicknesses) with complementary physicochemical data (O2-haemoglobin chemical reaction rates and Krogh's permeability coefficients). This approach has proved valuable in a variety of comparative studies on respiratory organs from diverse species. The underlying principles were formulated in pioneering studies on the pulmonary lung but are illustrated here by taking the human placenta as the gas exchanger. Copyright © 2012 Elsevier GmbH. All rights reserved.
-
Buckmaster, Paul S; Wen, Xiling; Toyoda, Izumi; Gulland, Frances M D; Van Bonn, William
2014-05-01
California sea lions (Zalophus californianus) are abundant human-sized carnivores with large gyrencephalic brains. They develop epilepsy after experiencing status epilepticus when naturally exposed to domoic acid. We tested whether sea lions previously exposed to DA (chronic DA sea lions) display hippocampal neuropathology similar to that of human patients with temporal lobe epilepsy. Hippocampi were obtained from control and chronic DA sea lions. Stereology was used to estimate numbers of Nissl-stained neurons per hippocampus in the granule cell layer, hilus, and pyramidal cell layer of CA3, CA2, and CA1 subfields. Adjacent sections were processed for somatostatin immunoreactivity or Timm-stained, and the extent of mossy fiber sprouting was measured stereologically. Chronic DA sea lions displayed hippocampal neuron loss in patterns and extents similar but not identical to those reported previously for human patients with temporal lobe epilepsy. Similar to human patients, hippocampal sclerosis in sea lions was unilateral in 79% of cases, mossy fiber sprouting was a common neuropathological abnormality, and somatostatin-immunoreactive axons were exuberant in the dentate gyrus despite loss of immunopositive hilar neurons. Thus, hippocampal neuropathology of chronic DA sea lions is similar to that of human patients with temporal lobe epilepsy. Copyright © 2013 Wiley Periodicals, Inc.
-
Systematic, Cross-Cortex Variation in Neuron Numbers in Rodents and Primates
Charvet, Christine J.; Cahalane, Diarmuid J.; Finlay, Barbara L.
2015-01-01
Uniformity, local variability, and systematic variation in neuron numbers per unit of cortical surface area across species and cortical areas have been claimed to characterize the isocortex. Resolving these claims has been difficult, because species, techniques, and cortical areas vary across studies. We present a stereological assessment of neuron numbers in layers II–IV and V–VI per unit of cortical surface area across the isocortex in rodents (hamster, Mesocricetus auratus; agouti, Dasyprocta azarae; paca, Cuniculus paca) and primates (owl monkey, Aotus trivigratus; tamarin, Saguinus midas; capuchin, Cebus apella); these chosen to vary systematically in cortical size. The contributions of species, cortical areas, and techniques (stereology, “isotropic fractionator”) to neuron estimates were assessed. Neurons per unit of cortical surface area increase across the rostro-caudal (RC) axis in primates (varying by a factor of 1.64–2.13 across the rostral and caudal poles) but less in rodents (varying by a factor of 1.15–1.54). Layer II–IV neurons account for most of this variation. When integrated into the context of species variation, and this RC gradient in neuron numbers, conflicts between studies can be accounted for. The RC variation in isocortical neurons in adulthood mirrors the gradients in neurogenesis duration in development. PMID:23960207
-
Smith, Andrew M; Pappalardo, Dana; Chen, Wei-Jung A
2008-01-01
In this study, the effects of amphetamine exposure during a portion of the brain growth spurt on the total number of hippocampal pyramidal cells (CA1/CA3 subregions) and the granule cells (dentate gyrus) were examined in both neonatal and adult rats. Intragastric intubation was used to administer 5, 15 or 25 mg/kg/day of amphetamine to Sprague-Dawley rat pups from PDs 4-9. Unbiased stereology was used to estimate the total number of cells present within each hippocampal subregion at both PD 9 and PD 68. The results indicated that neonatal amphetamine exposure did not alter the cell number, the reference volume or the density in any of the hippocampal subregions assessed, regardless of age. However, amphetamine significantly altered the rate of neuronal incorporation in both the hippocampal CA3 subregion and the dentate gyrus, and this effect appeared to be dose-related with the most robust effect observed in the highest amphetamine dose. While these findings did not demonstrate significant injurious effects of neonatal amphetamine treatment on the number of hippocampal neurons, these data suggest that amphetamine may interfere with proper hippocampal development. Future studies employing more sensitive measurements or exposing amphetamine during an alternate period of development may provide more information regarding amphetamine-mediated developmental neurotoxicity.
-
Instillation and Fixation Methods Useful in Mouse Lung Cancer Research.
Limjunyawong, Nathachit; Mock, Jason; Mitzner, Wayne
2015-08-31
The ability to instill live agents, cells, or chemicals directly into the lung without injuring or killing the mice is an important tool in lung cancer research. Although there are a number of methods that have been published showing how to intubate mice for pulmonary function measurements, none are without potential problems for rapid tracheal instillation in large cohorts of mice. In the present paper, a simple and quick method is described that enables an investigator to carry out such instillations in an efficient manner. The method does not require any special tools or lighting and can be learned with very little practice. It involves anesthetizing a mouse, making a small incision in the neck to visualize the trachea, and then inserting an intravenous catheter directly. The small incision is quickly closed with tissue adhesive, and the mice are allowed to recover. A skilled student or technician can do instillations at an average rate of 2 min/mouse. Once the cancer is established, there is frequently a need for quantitative histologic analysis of the lungs. Traditionally pathologists usually do not bother to standardize lung inflation during fixation, and analyses are often based on a scoring system that can be quite subjective. While this may sometime be sufficiently adequate for gross estimates of the size of a lung tumor, any proper stereological quantification of lung structure or cells requires a reproducible fixation procedure and subsequent lung volume measurement. Here we describe simple reliable procedures for both fixing the lungs under pressure and then accurately measuring the fixed lung volume. The only requirement is a laboratory balance that is accurate over a range of 1 mg-300 g. The procedures presented here thus could greatly improve the ability to create, treat, and analyze lung cancers in mice.
-
Martínez-Martínez, Eduardo; Galván-Hernández, Claudio I.; Toscano-Márquez, Brenda; Gutiérrez-Ospina, Gabriel
2012-01-01
Background The bulge region of the hair follicle contains resident epithelial stem cells (SCs) that are activated and mobilized during hair growth and after epidermal wounding. However, little is known about the signals that modulate these processes. Clinical and experimental observations show that a reduced supply of sensory innervation is associated with delayed wound healing. Since axon terminals of sensory neurons are among the components of the bulge SC niche, we investigated whether these neurons are involved in the activation and mobilization of the hair stem cells during wound healing. Methodology/Principal Findings We used neonatal capsaicin treatment to reduce sensory terminals in the rat skin and performed morphometric analyses using design-based stereological methods. Epithelial proliferation was analyzed by quantifying the number of bromodeoxyuridine-labeled (BrdU+) nuclei in the epidermis and hair follicles. After wounding, the epidermis of capsaicin-treated rats presented fewer BrdU+ nuclei than in control rats. To assess SC progeny migration, we employed a double labeling protocol with iododeoxyuridine and chlorodeoxyuridine (IdU+/CldU+). The proportion of double-labeled cells was similar in the hair follicles of both groups at 32 h postwounding. IdU+/CldU+ cell proportion increased in the epidermis of control rats and decreased in treated rats at 61 h postwounding. The epidermal volume immunostained for keratin 6 was greater in treated rats at 61 h. Confocal microscopy analysis revealed that substance P (SP) and calcitonin gene-related peptide (CGRP) receptor immunoreactivity were both present in CD34+ and BrdU-retaining cells of the hair follicles. Conclusions/Significance Our results suggest that capsaicin denervation impairs SC progeny egress from the hair follicles, a circumstance associated with a greater epidermal activation. Altogether, these phenomena would explain the longer times for healing in denervated skin. Thus, sensory innervation may play a functional role in the modulation of hair SC physiology during wound healing. PMID:22574159
-
Martínez-Martínez, Eduardo; Galván-Hernández, Claudio I; Toscano-Márquez, Brenda; Gutiérrez-Ospina, Gabriel
2012-01-01
The bulge region of the hair follicle contains resident epithelial stem cells (SCs) that are activated and mobilized during hair growth and after epidermal wounding. However, little is known about the signals that modulate these processes. Clinical and experimental observations show that a reduced supply of sensory innervation is associated with delayed wound healing. Since axon terminals of sensory neurons are among the components of the bulge SC niche, we investigated whether these neurons are involved in the activation and mobilization of the hair stem cells during wound healing. We used neonatal capsaicin treatment to reduce sensory terminals in the rat skin and performed morphometric analyses using design-based stereological methods. Epithelial proliferation was analyzed by quantifying the number of bromodeoxyuridine-labeled (BrdU(+)) nuclei in the epidermis and hair follicles. After wounding, the epidermis of capsaicin-treated rats presented fewer BrdU(+) nuclei than in control rats. To assess SC progeny migration, we employed a double labeling protocol with iododeoxyuridine and chlorodeoxyuridine (IdU(+)/CldU(+)). The proportion of double-labeled cells was similar in the hair follicles of both groups at 32 h postwounding. IdU(+)/CldU(+) cell proportion increased in the epidermis of control rats and decreased in treated rats at 61 h postwounding. The epidermal volume immunostained for keratin 6 was greater in treated rats at 61 h. Confocal microscopy analysis revealed that substance P (SP) and calcitonin gene-related peptide (CGRP) receptor immunoreactivity were both present in CD34(+) and BrdU-retaining cells of the hair follicles. Our results suggest that capsaicin denervation impairs SC progeny egress from the hair follicles, a circumstance associated with a greater epidermal activation. Altogether, these phenomena would explain the longer times for healing in denervated skin. Thus, sensory innervation may play a functional role in the modulation of hair SC physiology during wound healing.
-
Analysis of tomographic mineralogical data using YaDiV—Overview and practical case study
NASA Astrophysics Data System (ADS)
Friese, Karl-Ingo; Cichy, Sarah B.; Wolter, Franz-Erich; Botcharnikov, Roman E.
2013-07-01
We introduce the 3D-segmentation and -visualization software YaDiV to the mineralogical application of rock texture analysis. YaDiV has been originally designed to process medical DICOM datasets. But due to software advancements and additional plugins, this open-source software can now be easily used for the fast quantitative morphological characterization of geological objects from tomographic datasets. In this paper, we give a summary of YaDiV's features and demonstrate the advantages of 3D-stereographic visualization and the accuracy of 3D-segmentation for the analysis of geological samples. For this purpose, we present a virtual and a real use case (here: experimentally crystallized and vesiculated magmatic rocks, corresponding to the composition of the 1991-1995 Unzen eruption, Japan). Especially the spacial representation of structures in YaDiV allows an immediate, intuitive understanding of the 3D-structures, which may not become clear by only looking on 2D-images. We compare our results of object number density calculations with the established classical stereological 3D-correction methods for 2D-images and show that it was possible to achieve a seriously higher quality and accuracy. The methods described in this paper are not dependent on the nature of the object. The fact, that YaDiV is open-source and users with programming skills can create new plugins themselves, may allow this platform to become applicable to a variety of geological scenarios from the analysis of textures in tiny rock samples to the interpretation of global geophysical data, as long as the data are provided in tomographic form.
-
Urtica Dioica Distillate Regenerates Pancreatic Beta Cells in Streptozotocin-Induced Diabetic Rats
Gohari, Ali; Noorafshan, Ali; Akmali, Masoumeh; Zamani-Garmsiri, Fahimeh; Seghatoleslam, Atefeh
2018-01-01
Background Urtica dioica is known as an anti-hyperglycemic plant. Urtica dioica distillate (UD) is a traditional Iranian drink, locally known as “aragh gazaneh”. In spite of its widespread consumption in Iran, according to traditional Iranian medicine, there is no scientific report on the usefulness of UD for diabetic patients. This survey was designed to evaluate its protective effects for the recovery from diabetes by determining the serum insulin, blood glucose, volume of pancreatic islets, and the number and volume of β-cells in diabetic rats. Methods A total of 48 Sprague-Dawley male rats (200-250 g) were randomly distributed into 6 groups (n=8), including non-diabetic plus distilled water (DW), non-diabetic plus UD, diabetic plus DW, diabetic plus UD, diabetic plus insulin, and diabetic plus glibenclamide. DW, UD, and glibenclamide were administered via intragastric gavage and insulin was injected subcutaneously. After four weeks of experiments, blood samples were collected for serum insulin and blood glucose assay. Pancreas was also evaluated using stereological method. The SPSS software was used for statistical analysis. Kruskal-Wallis, repeated measurements, and Mann-Whitney U test were applied for comparisons between the groups. Results The treatment of diabetic rats with UD reduced the blood glucose dramatically (P<0.001) and increased serum insulin levels significantly (P=0.03) in comparison to the diabetic plus DW rats. Treatment with UD did not affect the mean β-cell volumes in the diabetic rats when compared to the diabetic plus DW rats, but the islet volumes and β-cell numbers were significantly recovered. Conclusion UD treatment in diabetic rats improves hyperglycemia by partially restoring plasma insulin levels. The data suggest that UD prevents islet atrophy and/or regenerate pancreatic β-cells. PMID:29749986
-
Boron Carbide Aluminum Cermets for External Pressure Housing Applications
1992-09-01
CHEMISTRY AND MICROSTRUCTURES OF THE B4C/Al SYSTEM ......................................... 4 3.2 MECHANICAL PROPERTIES OF B4C/AI COMPOSITES ....... 10...TABLES 1. Phase chemistry of B4C/A1 composites as a function of baking temperature (by stereology) .................. ...... 10 2. Summary of the...diffractometer using CuKo radiation and a scan rate of 2° per minute. The chemistry of all phases was determined from electron microprobe analysis of
-
Larsen, Karen B
2017-01-01
Human fetal brain development is a complex process which is vulnerable to disruption at many stages. Although histogenesis is well-documented, only a few studies have quantified cell numbers across normal human fetal brain growth. Due to the present lack of normative data it is difficult to gauge abnormal development. Furthermore, many studies of brain cell numbers have employed biased counting methods, whereas innovations in stereology during the past 20-30 years enable reliable and efficient estimates of cell numbers. However, estimates of cell volumes and densities in fetal brain samples are unreliable due to unpredictable shrinking artifacts, and the fragility of the fetal brain requires particular care in handling and processing. The optical fractionator design offers a direct and robust estimate of total cell numbers in the fetal brain with a minimum of handling of the tissue. Bearing this in mind, we have used the optical fractionator to quantify the growth of total cell numbers as a function of fetal age. We discovered a two-phased development in total cell numbers in the human fetal forebrain consisting of an initial steep rise in total cell numbers between 13 and 20 weeks of gestation, followed by a slower linear phase extending from mid-gestation to 40 weeks of gestation. Furthermore, we have demonstrated a reduced total cell number in the forebrain in fetuses with Down syndome at midgestation and in intrauterine growth-restricted fetuses during the third trimester.
-
The density of apical cells of dark-grown protonemata of the moss Ceratodon purpureus
NASA Technical Reports Server (NTRS)
Schwuchow, J. M.; Kern, V. D.; Wagner, T.; Sack, F. D.
2000-01-01
Determinations of plant or algal cell density (cell mass divided by volume) have rarely accounted for the extracellular matrix or shrinkage during isolation. Three techniques were used to indirectly estimate the density of intact apical cells from protonemata of the moss Ceratodon purpureus. First, the volume fraction of each cell component was determined by stereology, and published values for component density were used to extrapolate to the entire cell. Second, protonemal tips were immersed in bovine serum albumin solutions of different densities, and then the equilibrium density was corrected for the mass of the cell wall. Third, apical cell protoplasts were centrifuged in low-osmolarity gradients, and values were corrected for shrinkage during protoplast isolation. Values from centrifugation (1.004 to 1.015 g/cm3) were considerably lower than from other methods (1.046 to 1.085 g/cm3). This work appears to provide the first corrected estimates of the density of any plant cell. It also documents a method for the isolation of protoplasts specifically from apical cells of protonemal filaments.
-
X-ray Computed Tomography Assessment of Air Void Distribution in Concrete
NASA Astrophysics Data System (ADS)
Lu, Haizhu
Air void size and spatial distribution have long been regarded as critical parameters in the frost resistance of concrete. In cement-based materials, entrained air void systems play an important role in performance as related to durability, permeability, and heat transfer. Many efforts have been made to measure air void parameters in a more efficient and reliable manner in the past several decades. Standardized measurement techniques based on optical microscopy and stereology on flat cut and polished surfaces are widely used in research as well as in quality assurance and quality control applications. Other more automated methods using image processing have also been utilized, but still starting from flat cut and polished surfaces. The emergence of X-ray computed tomography (CT) techniques provides the capability of capturing the inner microstructure of materials at the micrometer and nanometer scale. X-ray CT's less demanding sample preparation and capability to measure 3D distributions of air voids directly provide ample prospects for its wider use in air void characterization in cement-based materials. However, due to the huge number of air voids that can exist within a limited volume, errors can easily arise in the absence of a formalized data processing procedure. In this study, air void parameters in selected types of cement-based materials (lightweight concrete, structural concrete elements, pavements, and laboratory mortars) have been measured using micro X-ray CT. The focus of this study is to propose a unified procedure for processing the data and to provide solutions to deal with common problems that arise when measuring air void parameters: primarily the reliable segmentation of objects of interest, uncertainty estimation of measured parameters, and the comparison of competing segmentation parameters.
-
Antequera, Desiree; Portero, Aitziber; Bolos, Marta; Orive, Gorka; Hernández, Rosa M Rm A; Pedraz, José Luis; Carro, Eva
2012-01-01
Vascular endothelial growth factor (VEGF) promotes neurogenesis in the adult hippocampus, but the way in which this process occurs in the Alzheimer's disease (AD) brain is still unknown. We examined the proliferation of neuronal precursors with an ex vivo approach, using encapsulated VEGF secreting cells, in AβPP/PS1 mice, a mouse model of AD. Overexpression of VEGF and VEGF receptor flk-1 was observed in the cerebral cortex from VEGF microcapsules-treated AβPP/PS1 mice at 1, 3 and 6 months after VEGF-microcapsule implantation. Stereological counting of 5-bromodeoxyuridine positive cells revealed that encapsulated VEGF secreting cells significantly enhanced cellular proliferation in the hippocampal dentate gyrus (DG). The number of neuronal precursors in VEGF microcapsules-treated AβPP/PS1 mice was also greater, and this effect remains after 6 months. We also confirmed that encapsulated VEGF secreting cells also stimulated angiogenesis in the cerebral cortex and hippocampal dentate gyrus. In addition, we found that VEGF-microcapsule treatment was associated with a depressed expression and activity of acetylcholinesterase in the hippocampus of AβPP/PS1 mice, a similar pattern as first-line medications for the treatment of AD. We conclude that stereologically-implanted VEGF-microcapsules exert an acute and long-standing neurotrophic effects, and could be utilized to improve potential therapies to control the progression of AD.
-
Comparative stereology of the mouse and finch left ventricle.
Bossen, E H; Sommer, J R; Waugh, R A
1978-01-01
The volume fractions and surface per unit cell volume of some subcellular components of the left ventricles of the finch and mouse were quantitated by stereologic techniques. These species were chosen for study because they have similar heart rates but differ morphologically in some respects: fiber diameter is larger in the mouse; the mouse has transverse tubules while the finch does not; and the finch has a form of junctional sarcoplasmic reticulum (JSR), extended JSR (EJSR), located in the cell interior with no direct plasmalemmal contact, while the mouse interior JSR (IJSR) abuts on transverse tubules. Our data show that the volume fraction (Vv) and surface area per unit cell volume (Sv) of total SR, and free SR (FSR) are similar. The volume fractions of mitochondria, myofibrils, and total junctional SR were also similar. The Sv of the cell surface of the finch was similar to the Sv of the cell surface of the mouse (Sv-plasmalemma plus Sv of the transverse tubules). The principal difference was in the distribution of JSR; the mouse peripheral JSR (PJSR) represents only 9% of the total JSR, while the finch PJSR accounts for 24% of the bird's JSR. The similar volume fractions of total junctional SR (PJSR + EJSR in the finch; PJSR + IJSR in the mouse) suggest that the EJSR is not an embryologic remnant, and raises the possibility that some function of JSR is independent of plasmalemmal contact.
-
Jalali, Ali Shalizar; Hasanzadeh, Shapour; Malekinejad, Hassan
2012-01-01
Cyclophosphamide (CP) is extensively used as an antineoplastic agent for the treatment of various cancers, as well as an immunosuppressive agent. However, despite its wide spectrum of clinical uses, CP is known to cause several adverse effects including reproductive toxicity. Crataegus monogyna is one of the oldest pharmaceutical plants that have been shown to be cytoprotective by scavenging free radicals. The present study was conducted to assess whether Crataegus monogyna fruits aqueous extract with anti-oxidant properties, could serve as a protective agent against reproductive toxicity during CP treatment in a rat model. Male Wistar rats were categorized into four groups. Two groups of rats were administered CP at a dose of 5 mg in 5 ml saline/kg/day for 28 days by oral gavages. One of these groups received Crataegus monogyna aqueous extract at a dose of 20 mg/kg/day orally four hours after cyclophosphamide administration. A vehicle treated control group and a Crataegus monogyna control group were also included. The CP-treated group showed significant decreases in the body, testes and epididymides weights as well as many histological alterations. Stereological parameters and spermatogenic activities (Sertoli cell, repopulation and miotic indices) were also significantly decreased by CP treatment. Notably, Crataegus coadministration caused a partial recovery in above-mentined parameters. These findings indicate that Crataegus monogyna may be partially protective against CP-induced testicular toxicity.
-
Barghash, Z; Larsen, J O; Al-Bishri, A; Kahnberg, K-E
2013-12-01
The aim of this study was to evaluate the degeneration and regeneration of a sensory nerve and a motor nerve at the histological level after a crush injury. Twenty-five female Wistar rats had their mental nerve and the buccal branch of their facial nerve compressed unilaterally against a glass rod for 30s. Specimens of the compressed nerves and the corresponding control nerves were dissected at 3, 7, and 19 days after surgery. Nerve cross-sections were stained with osmium tetroxide and toluidine blue and analysed using two-dimensional stereology. We found differences between the two nerves both in the normal anatomy and in the regenerative pattern. The mental nerve had a larger cross-sectional area including all tissue components. The mental nerve had a larger volume fraction of myelinated axons and a correspondingly smaller volume fraction of endoneurium. No differences were observed in the degenerative pattern; however, at day 19 the buccal branch had regenerated to the normal number of axons, whereas the mental nerve had only regained 50% of the normal number of axons. We conclude that the regenerative process is faster and/or more complete in the facial nerve (motor function) than it is in the mental nerve (somatosensory function). Copyright © 2013 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.
-
Systematic, cross-cortex variation in neuron numbers in rodents and primates.
Charvet, Christine J; Cahalane, Diarmuid J; Finlay, Barbara L
2015-01-01
Uniformity, local variability, and systematic variation in neuron numbers per unit of cortical surface area across species and cortical areas have been claimed to characterize the isocortex. Resolving these claims has been difficult, because species, techniques, and cortical areas vary across studies. We present a stereological assessment of neuron numbers in layers II-IV and V-VI per unit of cortical surface area across the isocortex in rodents (hamster, Mesocricetus auratus; agouti, Dasyprocta azarae; paca, Cuniculus paca) and primates (owl monkey, Aotus trivigratus; tamarin, Saguinus midas; capuchin, Cebus apella); these chosen to vary systematically in cortical size. The contributions of species, cortical areas, and techniques (stereology, "isotropic fractionator") to neuron estimates were assessed. Neurons per unit of cortical surface area increase across the rostro-caudal (RC) axis in primates (varying by a factor of 1.64-2.13 across the rostral and caudal poles) but less in rodents (varying by a factor of 1.15-1.54). Layer II-IV neurons account for most of this variation. When integrated into the context of species variation, and this RC gradient in neuron numbers, conflicts between studies can be accounted for. The RC variation in isocortical neurons in adulthood mirrors the gradients in neurogenesis duration in development. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
-
de Fraga, Rogerio; Dambros, Miriam; Miyaoka, Ricardo; Riccetto, Cássio Luís Zanettini; Palma, Paulo César Rodrigues
2007-10-01
The authors quantified the type IV collagen fibers volumetric density in the basement membrane of bladder wall of ovariectomized rats with and without estradiol replacement. This study was conducted on 40 Wistar rats (3 months old) randomly divided in 4 groups: group 1, remained intact (control); group 2, submitted to bilateral oophorectomy and daily replacement 4 weeks later of 17 beta-estradiol for 12 weeks; group 3, sham operated and daily replacement 4 weeks later of sesame oil for 12 weeks; and group 4, submitted to bilateral oophorectomy and killed after 12 weeks. It was used in immunohistochemistry evaluation using type IV collagen polyclonal antibody to stain the fibers on paraffin rat bladder sections. The M-42 stereological grid system was used to analyze the fibers. Ovariectomy had an increase effect on the volumetric density of the type IV collagen fibers in the basement membrane of rat bladder wall. Estradiol replacement in castrated animals demonstrated a significative difference in the stereological parameters when compared to the castrated group without hormonal replacement. Surgical castration performed on rats induced an increasing volumetric density of type IV collagen fibers in the basement membrane of rats bladder wall and the estradiol treatment had a significant effect in keeping a low volumetric density of type IV collagen fibers in the basement membrane of rats bladder wall.
-
The Nun study: clinically silent AD, neuronal hypertrophy, and linguistic skills in early life.
Iacono, D; Markesbery, W R; Gross, M; Pletnikova, O; Rudow, G; Zandi, P; Troncoso, J C
2009-09-01
It is common to find substantial Alzheimer disease (AD) lesions, i.e., neuritic beta-amyloid plaques and neurofibrillary tangles, in the autopsied brains of elderly subjects with normal cognition assessed shortly before death. We have termed this status asymptomatic AD (ASYMAD). We assessed the morphologic substrate of ASYMAD compared to mild cognitive impairment (MCI) in subjects from the Nun Study. In addition, possible correlations between linguistic abilities in early life and the presence of AD pathology with and without clinical manifestations in late life were considered. Design-based stereology was used to measure the volumes of neuronal cell bodies, nuclei, and nucleoli in the CA1 region of hippocampus (CA1). Four groups of subjects were compared: ASYMAD (n = 10), MCI (n = 5), AD (n = 10), and age-matched controls (n = 13). Linguistic ability assessed in early life was compared among all groups. A significant hypertrophy of the cell bodies (+44.9%), nuclei (+59.7%), and nucleoli (+80.2%) in the CA1 neurons was found in ASYMAD compared with MCI. Similar differences were observed with controls. Furthermore, significant higher idea density scores in early life were observed in controls and ASYMAD group compared to MCI and AD groups. 1) Neuronal hypertrophy may constitute an early cellular response to Alzheimer disease (AD) pathology or reflect compensatory mechanisms that prevent cognitive impairment despite substantial AD lesions; 2) higher idea density scores in early life are associated with intact cognition in late life despite the presence of AD lesions.
-
Running exercise protects the capillaries in white matter in a rat model of depression.
Chen, Lin-Mu; Zhang, Ai-Pin; Wang, Fei-Fei; Tan, Chuan-Xue; Gao, Yuan; Huang, Chun-Xia; Zhang, Yi; Jiang, Lin; Zhou, Chun-Ni; Chao, Feng-Lei; Zhang, Lei; Tang, Yong
2016-12-01
Running has been shown to improve depressive symptoms when used as an adjunct to medication. However, the mechanisms underlying the antidepressant effects of running are not fully understood. Changes of capillaries in white matter have been discovered in clinical patients and depression model rats. Considering the important part of white matter in depression, running may cause capillary structural changes in white matter. Chronic unpredictable stress (CUS) rats were provided with a 4-week running exercise (from the fifth week to the eighth week) for 20 minutes each day for 5 consecutive days each week. Anhedonia was measured by a behavior test. Furthermore, capillary changes were investigated in the control group, the CUS/Standard group, and the CUS/Running group using stereological methods. The 4-week running increased sucrose consumption significantly in the CUS/Running group and had significant effects on the total volume, total length, and total surface area of the capillaries in the white matter of depression rats. These results demonstrated that exercise-induced protection of the capillaries in white matter might be one of the structural bases for the exercise-induced treatment of depression. It might provide important parameters for further study of the vascular mechanisms of depression and a new research direction for the development of clinical antidepressant means. J. Comp. Neurol. 524:3577-3586, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.
-
The development and plasticity of alveolar type 1 cells
Yang, Jun; Hernandez, Belinda J.; Martinez Alanis, Denise; Narvaez del Pilar, Odemaris; Vila-Ellis, Lisandra; Akiyama, Haruhiko; Evans, Scott E.; Ostrin, Edwin J.; Chen, Jichao
2016-01-01
Alveolar type 1 (AT1) cells cover >95% of the gas exchange surface and are extremely thin to facilitate passive gas diffusion. The development of these highly specialized cells and its coordination with the formation of the honeycomb-like alveolar structure are poorly understood. Using new marker-based stereology and single-cell imaging methods, we show that AT1 cells in the mouse lung form expansive thin cellular extensions via a non-proliferative two-step process while retaining cellular plasticity. In the flattening step, AT1 cells undergo molecular specification and remodel cell junctions while remaining connected to their epithelial neighbors. In the folding step, AT1 cells increase in size by more than 10-fold and undergo cellular morphogenesis that matches capillary and secondary septa formation, resulting in a single AT1 cell spanning multiple alveoli. Furthermore, AT1 cells are an unexpected source of VEGFA and their normal development is required for alveolar angiogenesis. Notably, a majority of AT1 cells proliferate upon ectopic SOX2 expression and undergo stage-dependent cell fate reprogramming. These results provide evidence that AT1 cells have both structural and signaling roles in alveolar maturation and can exit their terminally differentiated non-proliferative state. Our findings suggest that AT1 cells might be a new target in the pathogenesis and treatment of lung diseases associated with premature birth. PMID:26586225
-
Constraining pre-eruptive volatile contents and degassing histories in submarine lavas
NASA Astrophysics Data System (ADS)
Jones, M.; Soule, S. A.; Liao, Y.; Le Roux, V.; Brodsky, H.; Kurz, M. D.
2017-12-01
Vesicle textures in submarine lavas have been used to calculate total (pre-eruption) volatile concentrations in mid-ocean ridge basalts (MORB), which provide constraints on upper mantle volatile contents and CO2 fluxes along the global MOR. In this study, we evaluate vesicle size distributions and volatile contents in a suite of 20 MORB samples, which span the range of typical vesicularities and bubble number densities observed in global MORB. We demonstrate that 2D imaging coupled with traditional stereological methods closely reproduces vesicle size distributions and vesicularities measured using 3D x-ray micro-computed tomography (μ-CT). We further demonstrate that x-ray μ-CT provides additional information about bubble deformation and clustering that are linked to bubble nucleation and lava emplacement dynamics. The validation of vesicularity measurements allows us to evaluate the methods for calculating total CO2 concentrations in MORB using dissolved volatile content (SIMS), vesicularity, vesicle gas density, and equations of state. We model bubble and melt contraction during lava quenching and show that the melt viscosity prevents bubbles from reaching equilibrium at the glass transition temperature. Thus, we suggest that higher temperatures should be used to calculate exsolved volatile concentrations based on observed vesicularities. Our revised method reconciles discrepancies between exsolved volatile contents measured by gas manometry and calculated from vesicularity. In addition, our revised method suggests that some previous studies may have overestimated MORB volatile concentrations by up to a factor of two, with the greatest differences in samples with the highest vesicularities (e.g., `popping rock' 2πD43). These new results have important implications for CO2/Nb of `undegassed' MORB and global ridge CO2 fluxes. Lastly, our revised method yields constant total CO2 concentrations in sample suites from individual MOR eruptions that experienced syn-eruptive degassing. These results imply closed-system degassing during magma ascent and emplacement following equilibration at the depth of melt storage in the crust.
-
Ebrahimian, Zeinab; Karimi, Zeinab; Khoshnoud, Mohammad Javad; Namavar, Mohammad Reza; Daraei, Bahram; Haidari, Mohsen Raza
2017-01-01
Background: 3,4-methylenedioxy-methamphetamine or MDMA (also known as "ecstasy" or "molly") is a commonly abused drug that affects behavior and can lead to neuronal damage. Intermittent feeding is an effective dietary protocol that promotes neuroprotection and improves behavioral outcomes in animal models of neurotoxicity and neurodegenerative diseases. In this study, we investigated the behavioral and histological outcomes of the effect of intermittent feeding on the orally administered MDMA in mice. Methods: The animals (male albino mice) were divided into four groups: ad libitum (AL), intermittent feeding (IF) (food given every other day), and AL and IF control groups. After five weeks, AL and IF groups were given a single oral dose of 20 or 60mg/kg MDMA. Behavior was assessed with the elevated plus-maze and the open field tests. Each of the treatment groups were then divided in to two groups: AL-AL (AL diet throughout), AL-IF (IF after MDMA administration), IF-IF (IF diet throughout), IF-AL (AL after MDMA administration). The second behavioral assessment was performed on ninth and 12th day after MDMA administration. The brains were then prepared with cresyl fast violet stain for stereology of the CA1 area of hippocampus. Results: The AL groups showed enhanced locomotion and anxiety compared to the IF ( p <0.001); however, IF groups showed significantly ( p <0.05) more locomotor activity and less anxiety recovery at ninth and 12th days compared to the AL animals. The neuronal numerical density was significantly ( p <0.05) higher in the hippocampus in the AL-IF groups compared to the AL-AL. Conclusion: IF regimen can significantly modify various behavioral characteristics induced by MDMA and promotes faster recovery from MDMA's anxiogenic effects. Additionally, IF regimen had neuroprotective effects on the neurons of the CA1 area of the hippocampus after a single oral dose of MDMA. We believe the results of our study support the need for further research examining the behavior modifying and neuroprotective potential of the IF regminen for the treatment of drug addiction in humans.
-
Bu, Wei; Ren, Huiling; Deng, Yunping; Del Mar, Nobel; Guley, Natalie M.; Moore, Bob M.; Honig, Marcia G.; Reiner, Anton
2016-01-01
We have previously reported that mild TBI created by focal left-side cranial blast in mice produces widespread axonal injury, microglial activation, and a variety of functional deficits. We have also shown that these functional deficits are reduced by targeting microglia through their cannabinoid type-2 (CB2) receptors using 2-week daily administration of the CB2 inverse agonist SMM-189. CB2 inverse agonists stabilize the G-protein coupled CB2 receptor in an inactive conformation, leading to increased phosphorylation and nuclear translocation of the cAMP response element binding protein (CREB), and thus bias activated microglia from a pro-inflammatory M1 to a pro-healing M2 state. In the present study, we showed that SMM-189 boosts nuclear pCREB levels in microglia in several brain regions by 3 days after TBI, by using pCREB/CD68 double immunofluorescent labeling. Next, to better understand the basis of motor deficits and increased fearfulness after TBI, we used unbiased stereological methods to characterize neuronal loss in cortex, striatum, and basolateral amygdala (BLA) and assessed how neuronal loss was affected by SMM-189 treatment. Our stereological neuron counts revealed a 20% reduction in cortical and 30% reduction in striatal neurons bilaterally at 2–3 months post blast, with SMM-189 yielding about 50% rescue. Loss of BLA neurons was restricted to the blast side, with 33% of Thy1+ fear-suppressing pyramidal neurons and 47% of fear-suppressing parvalbuminergic (PARV) interneurons lost, and Thy1-negative fear-promoting pyramidal neurons not significantly affected. SMM-189 yielded 50–60% rescue of Thy1+ and PARV neuron loss in BLA. Thus, fearfulness after mild TBI may result from the loss of fear-suppressing neuron types in BLA, and SMM-189 may reduce fearfulness by their rescue. Overall, our findings indicate that SMM-189 rescues damaged neurons and thereby alleviates functional deficits resulting from TBI, apparently by selectively modulating microglia to the beneficial M2 state. CB2 inverse agonists thus represent a promising therapeutic approach for mitigating neuroinflammation and neurodegeneration. PMID:27766068
-
Laurinavicius, Arvydas; Plancoulaine, Benoit; Laurinaviciene, Aida; Herlin, Paulette; Meskauskas, Raimundas; Baltrusaityte, Indra; Besusparis, Justinas; Dasevicius, Darius; Elie, Nicolas; Iqbal, Yasir; Bor, Catherine
2014-01-01
Immunohistochemical Ki67 labelling index (Ki67 LI) reflects proliferative activity and is a potential prognostic/predictive marker of breast cancer. However, its clinical utility is hindered by the lack of standardized measurement methodologies. Besides tissue heterogeneity aspects, the key element of methodology remains accurate estimation of Ki67-stained/counterstained tumour cell profiles. We aimed to develop a methodology to ensure and improve accuracy of the digital image analysis (DIA) approach. Tissue microarrays (one 1-mm spot per patient, n = 164) from invasive ductal breast carcinoma were stained for Ki67 and scanned. Criterion standard (Ki67-Count) was obtained by counting positive and negative tumour cell profiles using a stereology grid overlaid on a spot image. DIA was performed with Aperio Genie/Nuclear algorithms. A bias was estimated by ANOVA, correlation and regression analyses. Calibration steps of the DIA by adjusting the algorithm settings were performed: first, by subjective DIA quality assessment (DIA-1), and second, to compensate the bias established (DIA-2). Visual estimate (Ki67-VE) on the same images was performed by five pathologists independently. ANOVA revealed significant underestimation bias (P < 0.05) for DIA-0, DIA-1 and two pathologists' VE, while DIA-2, VE-median and three other VEs were within the same range. Regression analyses revealed best accuracy for the DIA-2 (R-square = 0.90) exceeding that of VE-median, individual VEs and other DIA settings. Bidirectional bias for the DIA-2 with overestimation at low, and underestimation at high ends of the scale was detected. Measurement error correction by inverse regression was applied to improve DIA-2-based prediction of the Ki67-Count, in particularfor the clinically relevant interval of Ki67-Count < 40%. Potential clinical impact of the prediction was tested by dichotomising the cases at the cut-off values of 10, 15, and 20%. Misclassification rate of 5-7% was achieved, compared to that of 11-18% for the VE-median-based prediction. Our experiments provide methodology to achieve accurate Ki67-LI estimation by DIA, based on proper validation, calibration, and measurement error correction procedures, guided by quantified bias from reference values obtained by stereology grid count. This basic validation step is an important prerequisite for high-throughput automated DIA applications to investigate tissue heterogeneity and clinical utility aspects of Ki67 and other immunohistochemistry (IHC) biomarkers.
-
DOE Office of Scientific and Technical Information (OSTI.GOV)
Garcia-Mateo, Carlos, E-mail: cgm@cenim.csic.es
Since the major strengthening mechanisms in nanocrystalline bainitic steels arise from the exceptionally small size of the bainitc ferrite plate, accurate determination of this parameter is fundamental for quantitative relating the microstructure to the mechanical properties. In this work, the thickness of the bainitic ferrite subunits obtained by different bainitic heat treatments was determined in two steels, with carbon contents of 0.3 and 0.7 wt.%, from SEM and TEM micrographs. As these measurements were made on 2D images taken from random sections, the method includes some stereological correction factors to obtain accurate information. Finally, the determined thicknesses of bainitic ferritemore » plates were compared with the crystallite size calculated from the analysis of X-ray diffraction peak broadening. Although in some case the values obtained for crystallite size and plate thickness can be similar, this study confirms that indeed they are two different parameters. - Highlights: •Bainitic microstructure in a nanostructured and sub-micron steel •Bainitic ferrite plate thickness measured by SEM and TEM •Crystallite size determined by X-ray analysis.« less
-
Jespersen, Sune N.; Bjarkam, Carsten R.; Nyengaard, Jens R.; Chakravarty, M. Mallar; Hansen, Brian; Vosegaard, Thomas; Østergaard, Leif; Yablonskiy, Dmitriy; Nielsen, Niels Chr.; Vestergaard-Poulsen, Peter
2010-01-01
Due to its unique sensitivity to tissue microstructure, diffusion-weighted magnetic resonance imaging (MRI) has found many applications in clinical and fundamental science. With few exceptions, a more precise correspondence between physiological or biophysical properties and the obtained diffusion parameters remain uncertain due to lack of specificity. In this work, we address this problem by comparing diffusion parameters of a recently introduced model for water diffusion in brain matter to light microscopy and quantitative electron microscopy. Specifically, we compare diffusion model predictions of neurite density in rats to optical myelin staining intensity and stereological estimation of neurite volume fraction using electron microscopy. We find that the diffusion model describes data better and that its parameters show stronger correlation with optical and electron microscopy, and thus reflect myelinated neurite density better than the more frequently used diffusion tensor imaging (DTI) and cumulant expansion methods. Furthermore, the estimated neurite orientations capture dendritic architecture more faithfully than DTI diffusion ellipsoids. PMID:19732836
-
Exercise protects myelinated fibers of white matter in a rat model of depression.
Xiao, Qian; Wang, Feifei; Luo, Yanmin; Chen, Linmu; Chao, Fenglei; Tan, Chuanxue; Gao, Yuan; Huang, Chunxia; Zhang, Lei; Liang, Xin; Tang, Jing; Qi, Yingqing; Jiang, Lin; Zhang, Yi; Zhou, Chunni; Tang, Yong
2018-02-15
The antidepressive effects of exercise have been a focus of research and are hypothesized to remodel the brain networks constructed by myelinated fibers. However, whether the antidepressant effects of exercise are dependent on changes in white matter myelination are unknown. Therefore, we chose chronic unpredictable stress (CUS) as a model of depression and designed an experiment. After a 4-week CUS period, 40 animals were tested using the sucrose preference test (SPT) and the open field test (OFT). The depressed rats then underwent 4-week running exercise. Next, electron microscopy and unbiased stereological methods were used to investigate white matter changes in the rats. After the 4-week CUS stimulation, body weight, sucrose preference and scores on the OFT were significantly lower in the depression rats than in the unstressed rats (p < .05). After undergoing a 4-week running exercise, the depression rats showed a significantly greater sucrose preference than the depression control rats without running exercise (p < .05). Furthermore, the white matter parameters of the depression rats (including the white matter volumes, the length and volumes of myelinated fibers, and the volumes and thickness of the myelin sheaths) were significantly reduced after the CUS period (p < .05). However, these white matter parameters were significantly increased after running exercise (p < .05). The present study is the first to provide evidence that running exercise has positive effects on white matter and the myelinated fibers of white matter in depressed rats, and this evidence might provide an important theoretical basis for the exercise-mediated treatment of depression. © 2017 Wiley Periodicals, Inc.
-
Campos, Mônica S; Ribeiro, Naiara C S; de Lima, Rodrigo F; Santos, Mariana B; Vilamaior, Patrícia S L; Regasini, Luis O; Biancardi, Manoel F; Taboga, Sebastião R; Santos, Fernanda C A
2018-03-07
Chrysin is a bioflavonoid found in fruits, flowers, tea, honey and wine, which has antioxidant, anti-inflammatory, antiallergic and anticarcinogenic properties. This flavone has also been considered as beneficial for reproduction due its testosterone-boosting potential. Thus, the aim of this study was to evaluate the effects of chrysin on the prostate and gonads of male and female adult gerbils. In addition, a comparative analysis of the effects of testosterone on these same organs was conducted. Ninety-day-old male and female gerbils were treated with chrysin (50mgkg-1day-1) or testosterone cypionate (1mgkg-1week-1) for 21 days. The ventral male prostate and female prostate were dissected out for morphological, morphometric-stereological and ultrastructural assays. Testes and ovaries were submitted to morphological and morphometric---stereological analyses. Chrysin treatment caused epithelial hyperplasia and stromal remodelling of the ventral male and female prostate. Ultrastructurally, male and female prostatic epithelial cells in the chrysin group presented marked development of the organelles involved in the biosynthetic-secretory pathway, whereas cellular toxicity was observed only in female glands. Chrysin preserved normal testicular morphology and increased the number of growing ovarian follicles. Comparatively, testosterone treatment was detrimental to the prostate and gonads, since foci of prostatic intraepithelial neoplasia and gonadal degeneration were observed in both sexes. Thus, under the experimental conditions of this study, chrysin was better tolerated than testosterone in the prostate and gonads.
-
Defres, Sylviane; Keller, Simon S; Das, Kumar; Vidyasagar, Rishma; Parkes, Laura M; Burnside, Girvan; Griffiths, Michael; Kopelman, Michael; Roberts, Neil; Solomon, Tom
2017-01-01
To assess whether it is feasible to quantify acute change in temporal lobe volume and total oedema volumes in herpes simplex virus (HSV) encephalitis as a preliminary to a trial of corticosteroid therapy. The study analysed serially acquired magnetic resonance images (MRI), of patients with acute HSV encephalitis who had neuroimaging repeated within four weeks of the first scan. We performed volumetric measurements of the left and right temporal lobes and of cerebral oedema visible on T2 weighted Fluid Attenuated Inversion Recovery (FLAIR) images using stereology in conjunction with point counting. Temporal lobe volumes increased on average by 1.6% (standard deviation (SD 11%) in five patients who had not received corticosteroid therapy and decreased in two patients who had received corticosteroids by 8.5%. FLAIR hyperintensity volumes increased by 9% in patients not receiving treatment with corticosteroids and decreased by 29% in the two patients that had received corticosteroids. This study has shown it is feasible to quantify acute change in temporal lobe and total oedema volumes in HSV encephalitis and suggests a potential resolution of swelling in response to corticosteroid therapy. These techniques could be used as part of a randomized control trial to investigate the efficacy of corticosteroids for treating HSV encephalitis in conjunction with assessing clinical outcomes and could be of potential value in helping to predict the clinical outcomes of patients with HSV encephalitis.
-
Sherwood, Chet C; Holloway, Ralph L; Erwin, Joseph M; Hof, Patrick R
2004-01-01
This study presents a comparative stereologic investigation of neurofilament protein- and calcium-binding protein-immunoreactive neurons within the region of orofacial representation of primary motor cortex (Brodmann's area 4) in several catarrhine primate species (Macaca fascicularis, Papio anubis, Pongo pygmaeus, Gorilla gorilla, Pan troglodytes, and Homo sapiens). Results showed that the density of interneurons involved in vertical interlaminar processing (i.e., calbindin- and calretinin-immunoreactive neurons) as well pyramidal neurons that supply heavily-myelinated projections (i.e., neurofilament protein-immunoreactive neurons) are correlated with overall neuronal density, whereas interneurons making transcolumnar connections (i.e., parvalbumin-immunoreactive neurons) do not exhibit such a relationship. These results suggest that differential scaling rules apply to different neuronal subtypes depending on their functional role in cortical circuitry. For example, cortical columns across catarrhine species appear to involve a similar conserved network of intracolumnar inhibitory interconnections, as represented by the distribution of calbindin- and calretinin-immunoreactive neurons. The subpopulation of horizontally-oriented wide-arbor interneurons, on the other hand, increases in density relative to other interneuron subpopulations in large brains. Due to these scaling trends, the region of orofacial representation of primary motor cortex in great apes and humans is characterized by a greater proportion of neurons enriched in neurofilament protein and parvalbumin compared to the Old World monkeys examined. These modifications might contribute to the voluntary dexterous control of orofacial muscles in great ape and human communication. Copyright 2004 S. Karger AG, Basel
-
Chang, Joshua C; Leung, Mark; Gokozan, Hamza Numan; Gygli, Patrick Edwin; Catacutan, Fay Patsy; Czeisler, Catherine; Otero, José Javier
2015-03-01
Late embryonic and postnatal cerebellar folial surface area expansion promotes cerebellar cortical cytoarchitectural lamination. We developed a streamlined sampling scheme to generate unbiased estimates of murine cerebellar surface area and volume using stereologic principles. We demonstrate that, during the proliferative phase of the external granular layer (EGL) and folial surface area expansion, EGL thickness does not change and thus is a topological proxy for progenitor self-renewal. The topological constraints indicate that, during proliferative phases, migration out of the EGL is balanced by self-renewal. Progenitor self-renewal must, therefore, include mitotic events yielding 2 cells in the same layer to increase surface area (β events) and mitotic events yielding 2 cells, with 1 cell in a superficial layer and 1 cell in a deeper layer (α events). As the cerebellum grows, therefore, β events lie upstream of α events. Using a mathematical model constrained by the measurements of volume and surface area, we could quantify intermitotic times for β events on a per-cell basis in postnatal mouse cerebellum. Furthermore, we found that loss of CCNA2, which decreases EGL proliferation and secondarily induces cerebellar cortical dyslamination, shows preserved α-type events. Thus, CCNA2-null cerebellar granule progenitor cells are capable of self-renewal of the EGL stem cell niche; this is concordant with prior findings of extensive apoptosis in CCNA2-null mice. Similar methodologies may provide another layer of depth to the interpretation of results from stereologic studies.
-
Effect of chronic antipsychotic exposure on astrocyte and oligodendrocyte numbers in macaque monkeys
Konopaske, Glenn T.; Dorph-Petersen, Karl-Anton; Sweet, Robert A.; Pierri, Joseph N.; Zhang, Wei; Sampson, Allan R.; Lewis, David A.
2008-01-01
Background Both in vivo and post-mortem studies suggest that oligodendrocyte and myelination alterations are present in individuals with schizophrenia. However, it is unclear whether prolonged treatment with antipsychotic medications contributes to these disturbances. We recently reported that chronic exposure of macaque monkeys to haloperidol or olanzapine was associated with a 10−18% lower glial cell number in the parietal grey matter. Consequently, in this study we sought to determine whether the lower glial cell number was due to fewer oligodendrocytes as opposed to lower numbers of astrocytes. Methods Using fluorescent immunocytochemical techniques, we optimized the visualization of each cell type throughout the entire thickness of tissue sections, while minimizing final tissue shrinkage. As a result, we were able to obtain robust stereological estimates of total oligodendrocyte and astrocyte numbers in the parietal grey matter using the optical fractionator method. Results We found a significant 20.5% lower astrocyte number with a non-significant 12.9% lower oligodendrocyte number in the antipsychotic-exposed monkeys. Similar effects were seen in both the haloperidol and olanzapine groups. Conclusion These findings suggest that studies investigating glial cell alterations in schizophrenia must take into account the effect of antipsychotic treatment. PMID:17945195
-
Effect of Early Neonatal Exposure to Deltamethrin on the Purkinje Cell Number in Rat Cerebellum
Asari, Mohd Asnizam; Abdullah, Mohammad Shukri; Abdullah, Suryati
2008-01-01
Deltamethrin is a widely used insecticide belonging to the class of pyrethroid. Although the neurotoxicity of pyrethroids including deltamethrin is well established, it is still unclear whether exposure to deltamethrin during neonatal period has any deleterious effect on the survival of the Purkinje cells in the cerebellum. In the study, we investigated the total number of Purkinje cells in experimental rats exposed to deltamethrin using a stereological method, the fractionator. Deltamethrin in a dose of 1 mg/kg/day (corresponds to 20% of LD50 ) was administered through oral gavage to male pups from 2nd to 5th postnatal day (PND). At PND 21 the animals were sacrificed and their cerebelli were removed. The cerebelli were systematically sampled using the fractionator method and stained with cresyl fast violet. The number of the Purkinje cells was counted for each cerebellum. The results showed that there was no significant difference in the total number of Purkinje cells in the deltamethrin-treated group as compared to the control animals. This suggests that deltamethrin exposure at the current dosage during the neonatal period do not have any significant effect on the survival of the Purkinje cells in the cerebellum. PMID:22570585
-
The Evolution of 3D Microimaging Techniques in Geosciences
NASA Astrophysics Data System (ADS)
Sahagian, D.; Proussevitch, A.
2009-05-01
In the analysis of geomaterials, it is essential to be able to analyze internal structures on a quantitative basis. Techniques have evolved from rough qualitative methods to highly accurate quantitative methods coupled with 3-D numerical analysis. The earliest primitive method for "seeing'" what was inside a rock was multiple sectioning to produce a series of image slices. This technique typically completely destroyed the sample being analyzed. Another destructive method was developed to give more detailed quantitative information by forming plastic casts of internal voids in sedimentary and volcanic rocks. For this, void were filled with plastic and the rock dissolved away with HF to reveal plastic casts of internal vesicles. Later, new approaches to stereology were developed to extract 3D information from 2D cross-sectional images. This has long been possible for spheres because the probability distribution for cutting a sphere along any small circle is known analytically (greatest probability is near the equator). However, large numbers of objects are required for statistical validity, and geomaterials are seldom spherical, so crystals, vesicles, and other inclusions would need a more sophisticated approach. Consequently, probability distributions were developed using numerical techniques for rectangular solids and various ellipsoids so that stereological techniques could be applied to these. The "holy grail" has always been to obtain 3D quantitative images non-destructively. A key method is Computed X-ray Tomography (CXT), in which attenuation of X-rays is recorded as a function of angular position in a cylindrical sample, providing a 2D "slice" of the interior. When a series of these "slices" is stacked (in increments equivalent with the resolution of the X-ray to make cubic voxels), a 3D image results with quantitative information regarding internal structure, particle/void volumes, nearest neighbors, coordination numbers, preferred orientations, etc. CXT can be done at three basic levels of resolution, with "normal" x-rays providing tens of microns resolution, synchrotron sources providing single to few microns, and emerging XuM techniques providing a practical 300 nm and theoretical 60 nm. The main challenges in CXT imaging have been in segmentation, which delineates material boundaries, and object recognition (registration), in which the individual objects within a material are identified. The former is critical in quantifying object volume, while the latter is essential for preventing the false appearance of individual objects as a continuous structure. Additional, new techniques are now being developed to enhance resolution and provide more detailed analysis without the complex infrastructure needed for CXT. One such method is Laser Scanning Confocal Microscopy, in which a laser is reflected from individual interior surfaces of a fluorescing material, providing a series of sharp images of internal slices with quantitative information available, just as in x-ray tomography, after "z-stacking" of planes of pixels. Another novel approach is the use of Stereo Scanning Electron Microscopy to create digital elevation models of 3D surficial features such as partial bubble margins on the surfaces of fine volcanic ash particles. As other novel techniques emerge, new opportunities will be presented to the geological research community to obtain ever more detailed and accurate information regarding the interior structure of geomaterials.
-
Human podocyte depletion in association with older age and hypertension.
Puelles, Victor G; Cullen-McEwen, Luise A; Taylor, Georgina E; Li, Jinhua; Hughson, Michael D; Kerr, Peter G; Hoy, Wendy E; Bertram, John F
2016-04-01
Podocyte depletion plays a major role in the development and progression of glomerulosclerosis. Many kidney diseases are more common in older age and often coexist with hypertension. We hypothesized that podocyte depletion develops in association with older age and is exacerbated by hypertension. Kidneys from 19 adult Caucasian American males without overt renal disease were collected at autopsy in Mississippi. Demographic data were obtained from medical and autopsy records. Subjects were categorized by age and hypertension as potential independent and additive contributors to podocyte depletion. Design-based stereology was used to estimate individual glomerular volume and total podocyte number per glomerulus, which allowed the calculation of podocyte density (number per volume). Podocyte depletion was defined as a reduction in podocyte number (absolute depletion) or podocyte density (relative depletion). The cortical location of glomeruli (outer or inner cortex) and presence of parietal podocytes were also recorded. Older age was an independent contributor to both absolute and relative podocyte depletion, featuring glomerular hypertrophy, podocyte loss, and thus reduced podocyte density. Hypertension was an independent contributor to relative podocyte depletion by exacerbating glomerular hypertrophy, mostly in glomeruli from the inner cortex. However, hypertension was not associated with podocyte loss. Absolute and relative podocyte depletion were exacerbated by the combination of older age and hypertension. The proportion of glomeruli with parietal podocytes increased with age but not with hypertension alone. These findings demonstrate that older age and hypertension are independent and additive contributors to podocyte depletion in white American men without kidney disease. Copyright © 2016 the American Physiological Society.
-
Alveolar derecruitment and collapse induration as crucial mechanisms in lung injury and fibrosis.
Lutz, Dennis; Gazdhar, Amiq; Lopez-Rodriguez, Elena; Ruppert, Clemens; Mahavadi, Poornima; Günther, Andreas; Klepetko, Walter; Bates, Jason H; Smith, Bradford; Geiser, Thomas; Ochs, Matthias; Knudsen, Lars
2015-02-01
Idiopathic pulmonary fibrosis (IPF) and bleomycin-induced pulmonary fibrosis are associated with surfactant system dysfunction, alveolar collapse (derecruitment), and collapse induration (irreversible collapse). These events play undefined roles in the loss of lung function. The purpose of this study was to quantify how surfactant inactivation, alveolar collapse, and collapse induration lead to degradation of lung function. Design-based stereology and invasive pulmonary function tests were performed 1, 3, 7, and 14 days after intratracheal bleomycin-instillation in rats. The number and size of open alveoli was correlated to mechanical properties. Active surfactant subtypes declined by Day 1, associated with a progressive alveolar derecruitment and a decrease in compliance. Alveolar epithelial damage was more pronounced in closed alveoli compared with ventilated alveoli. Collapse induration occurred on Day 7 and Day 14 as indicated by collapsed alveoli overgrown by a hyperplastic alveolar epithelium. This pathophysiology was also observed for the first time in human IPF lung explants. Before the onset of collapse induration, distal airspaces were easily recruited, and lung elastance could be kept low after recruitment by positive end-expiratory pressure (PEEP). At later time points, the recruitable fraction of the lung was reduced by collapse induration, causing elastance to be elevated at high levels of PEEP. Surfactant inactivation leading to alveolar collapse and subsequent collapse induration might be the primary pathway for the loss of alveoli in this animal model. Loss of alveoli is highly correlated with the degradation of lung function. Our ultrastructural observations suggest that collapse induration is important in human IPF.
-
Hypertrophy and neuron loss: structural changes in sheep SCG induced by unilateral sympathectomy.
Fioretto, Emerson T; Rahal, Sheila C; Borges, Alexandre S; Mayhew, Terry M; Nyengaard, Jens R; Marcondes, Julio S; Balieiro, Júlio C de Carvalho; Teixeira, Carlos R; de Melo, Mariana P; Ladd, Fernando V Lobo; Ladd, Aliny A B Lobo; de Lima, Ana R; da Silva, Andrea A P; Coppi, Antonio A
2011-06-01
Recently, superior cervical ganglionectomy has been performed to investigate a variety of scientific topics from regulation of intraocular pressure to suppression of lingual tumour growth. Despite these recent advances in our understanding of the functional mechanisms underlying superior cervical ganglion (SCG) growth and development after surgical ablation, there still exists a need for information concerning the quantitative nature of the relationships between the removed SCG and its remaining contralateral ganglion and between the remaining SCG and its modified innervation territory. To this end, using design-based stereological methods, we have investigated the structural changes induced by unilateral ganglionectomy in sheep at three distinct timepoints (2, 7 and 12 weeks) after surgery. The effects of time, and lateral (left-right) differences, were examined by two-way analyses of variance and paired t-tests. Following removal of the left SCG, the main findings were: (i) the remaining right SCG was bigger at shorter survival times, i.e. 74% at 2 weeks, 55% at 7 weeks and no increase by 12 weeks, (ii) by 7 weeks after surgery, the right SCG contained fewer neurons (no decrease at 2 weeks, 6% fewer by 7 weeks and 17% fewer by 12 weeks) and (iii) by 7 weeks, right SCG neurons were also larger and the magnitude of this increase grew substantially with time (no rise at 2 weeks, 77% by 7 weeks and 215% by 12 weeks). Interaction effects between time and ganglionectomy-induced changes were significant for SCG volume and mean perikaryal volume. These findings show that unilateral superior cervical ganglionectomy has profound effects on the contralateral ganglion. For future investigations, it would be interesting to examine the interaction between SCGs and their innervation targets after ganglionectomy. Is the ganglionectomy-induced imbalance between the sizes of innervation territories the milieu in which morphoquantitative changes, particularly changes in perikaryal volume and neuron number, occur? Mechanistically, how would those changes arise? Are there any grounds for believing in a ganglionectomy-triggered SCG cross-innervation and neuroplasticity? Copyright © 2011 ISDN. Published by Elsevier Ltd. All rights reserved.
-
Knudsen, Lars; Ochs, Matthias; MacKay, Rosemarie; Townsend, Paul; Deb, Roona; Mühlfeld, Christian; Richter, Joachim; Gilbert, Fabian; Hawgood, Samuel; Reid, Kenneth; Clark, Howard
2007-01-01
Background Surfactant protein D (SP-D) deficient mice develop emphysema-like pathology associated with focal accumulations of foamy alveolar macrophages, an excess of surfactant phospholipids in the alveolar space and both hypertrophy and hyperplasia of alveolar type II cells. These findings are associated with a chronic inflammatory state. Treatment of SP-D deficient mice with a truncated recombinant fragment of human SP-D (rfhSP-D) has been shown to decrease the lipidosis and alveolar macrophage accumulation as well as production of proinflammatory chemokines. The aim of this study was to investigate if rfhSP-D treatment reduces the structural abnormalities in parenchymal architecture and type II cells characteristic of SP-D deficiency. Methods SP-D knock-out mice, aged 3 weeks, 6 weeks and 9 weeks were treated with rfhSP-D for 9, 6 and 3 weeks, respectively. All mice were sacrificed at age 12 weeks and compared to both PBS treated SP-D deficient and wild-type groups. Lung structure was quantified by design-based stereology at the light and electron microscopic level. Emphasis was put on quantification of emphysema, type II cell changes and intracellular surfactant. Data were analysed with two sided non-parametric Mann-Whitney U-test. Main Results After 3 weeks of treatment, alveolar number was higher and mean alveolar size was smaller compared to saline-treated SP-D knock-out controls. There was no significant difference concerning these indices of pulmonary emphysema within rfhSP-D treated groups. Type II cell number and size were smaller as a consequence of treatment. The total volume of lamellar bodies per type II cell and per lung was smaller after 6 weeks of treatment. Conclusion Treatment of SP-D deficient mice with rfhSP-D leads to a reduction in the degree of emphysema and a correction of type II cell hyperplasia and hypertrophy. This supports the concept that rfhSP-D might become a therapeutic option in diseases that are characterized by decreased SP-D levels in the lung. PMID:17915009
-
Ehrenberg, A J; Nguy, A K; Theofilas, P; Dunlop, S; Suemoto, C K; Di Lorenzo Alho, A T; Leite, R P; Diehl Rodriguez, R; Mejia, M B; Rüb, U; Farfel, J M; de Lucena Ferretti-Rebustini, R E; Nascimento, C F; Nitrini, R; Pasquallucci, C A; Jacob-Filho, W; Miller, B; Seeley, W W; Heinsen, H; Grinberg, L T
2017-08-01
Hyperphosphorylated tau neuronal cytoplasmic inclusions (ht-NCI) are the best protein correlate of clinical decline in Alzheimer's disease (AD). Qualitative evidence identifies ht-NCI accumulating in the isodendritic core before the entorhinal cortex. Here, we used unbiased stereology to quantify ht-NCI burden in the locus coeruleus (LC) and dorsal raphe nucleus (DRN), aiming to characterize the impact of AD pathology in these nuclei with a focus on early stages. We utilized unbiased stereology in a sample of 48 well-characterized subjects enriched for controls and early AD stages. ht-NCI counts were estimated in 60-μm-thick sections immunostained for p-tau throughout LC and DRN. Data were integrated with unbiased estimates of LC and DRN neuronal population for a subset of cases. In Braak stage 0, 7.9% and 2.6% of neurons in LC and DRN, respectively, harbour ht-NCIs. Although the number of ht-NCI+ neurons significantly increased by about 1.9× between Braak stages 0 to I in LC (P = 0.02), we failed to detect any significant difference between Braak stage I and II. Also, the number of ht-NCI+ neurons remained stable in DRN between all stages 0 and II. Finally, the differential susceptibility to tau inclusions among nuclear subdivisions was more notable in LC than in DRN. LC and DRN neurons exhibited ht-NCI during AD precortical stages. The ht-NCI increases along AD progression on both nuclei, but quantitative changes in LC precede DRN changes. © 2017 British Neuropathological Society.
-
Trifunović, Svetlana; Manojlović-Stojanoski, Milica; Ristić, Nataša; Nestorović, Nataša; Medigović, Ivana; Živanović, Jasmina; Milošević, Verica
2016-12-01
Genistein is a plant-derived estrogenic isoflavone commonly found in dietary and therapeutic supplements, due to its potential health benefits. Growth hormone-releasing hormone (GHRH) and somatostatin (SS) are neurosecretory peptides synthesized in neurons of the hypothalamus and regulate the growth hormone secretion. Early reports indicate that estrogens have highly involved in the regulation of GHRH and SS secretions. Since little is known about the potential effects of genistein on GHRH and SS neurons, we exposed rats to genistein. Genistein were administered to adult rats in dose of 30 mg/kg, for 3 weeks. The estradiol-dipropionate treatment was used as the adequate controls to genistein. Using applied stereology on histological sections of hypothalamus, we obtained the quantitative information on arcuate (Arc) and periventricular (Pe) nucleus volume and volume density of GHRH neurons and SS neurons. Image analyses were used to obtain GHRH and SS contents in the median eminence (ME). Administration of estradiol-dipropionate caused the increase of Arc and Pe nucleus volume, SS neuron volume density, GHRH and SS staining intensity in the ME, when compared with control. Genistein treatment increased: Arc nucleus volume and the volume density of GHRH neurons (by 26%) and SS neurons (1.5 fold), accompanied by higher GHRH and SS staining intensity in the ME, when compared to the orhidectomized group. These results suggest that genistein has a significant effect on hypothalamic region, involved in the regulation of somatotropic system function, and could contribute to the understanding of genistein as substance that alter the hormonal balance.
-
L-arginine and glycine supplementation in the repair of the irradiated colonic wall of rats.
de Aguiar Picanço, Etiene; Lopes-Paulo, Francisco; Marques, Ruy G; Diestel, Cristina F; Caetano, Carlos Eduardo R; de Souza, Mônica Vieira Mano; Moscoso, Gabriela Mendes; Pazos, Helena Maria F
2011-05-01
Radiotherapy is widely used for cancer treatment but has harmful effects. This study aimed to assess the effects of L-arginine and glycine supplementation on the colon wall of rats submitted to abdominal irradiation. Forty male Wistar rats were randomly divided into four groups: I-healthy, II-irradiated with no amino acid supplementation, III-irradiated and supplemented with L-arginine, and IV-irradiated and supplemented with glycine. The animals received supplementation for 14 days, with irradiation being applied on the eighth day of the experiment. All animals underwent laparotomy on the 15th day for resection of a colonic segment for stereologic analysis. Parametric and nonparametric tests were used for statistical analysis, with the level of significance set at p ≤0.05. Stereologic analysis showed that irradiation induced a reduction of the total volume of the colon wall of group II and III animals compared to healthy controls, but not of group IV animals supplemented with glycine. The mucosal layer of the irradiated animals of all groups was reduced compared to healthy group I animals, but supplementation with L-arginine and glycine was effective in maintaining the epithelial surface of the mucosal layer. The present results suggest that glycine supplementation had a superior effect on the irradiated colon wall compared to L-arginine supplementation since it was able to maintain the thickness of the wall and the epithelial surface of the mucosa, whereas L-arginine maintained the partial volume of the epithelium and the epithelial surface, but not the total volume of the intestinal wall.
-
Do neural tube defects lead to structural alterations in the human bladder?
Pazos, Helena M F; Lobo, Márcio Luiz de P; Costa, Waldemar S; Sampaio, Francisco J B; Cardoso, Luis Eduardo M; Favorito, Luciano Alves
2011-05-01
Anencephaly is the most severe neural tube defect in human fetuses. The objective of this paper is to analyze the structure of the bladder in anencephalic human fetuses. We studied 40 bladders of normal human fetuses (20 male and 20 female, aged 14 to 23 WPC) and 12 bladders of anencephalic fetuses (5 male and 7 female, aged 18 to 22 WPC). The bladders were removed and processed by routine histological techniques. Stereological analysis of collagen, elastic system fibers and smooth muscle was performed in sections. Data were expressed as volumetric density (Vv-%). The images were captured with Olympus BX51 microscopy and Olympus DP70 camera. The stereological analysis was done using the software Image Pro and Image J. For biochemical analysis, samples were fixed in acetone, and collagen concentrations were expressed as micrograms of hydroxyproline per mg of dry tissue. Means were statistically compared using the unpaired t-test (p<0.05). We observed a significant increase (p<0.0001) in the Vv of collagen in the bladders of anencephalic fetuses (69.71%) when compared to normal fetuses (52.74%), and a significant decrease (p<0.0001) in the Vv of smooth muscle cells in the bladders of anencephalic fetuses (23.96%) when compared to normal fetuses (38.35%). The biochemical analyses showed a higher concentration of total collagen in the bladders of anencephalic fetuses (37354 µg/mg) when compared to normal fetuses (48117 µg/mg, p<0.02). The structural alterations of the bladder found in this study may suggest the existence of functional alterations in the bladder of anencephalic human fetuses.
-
Chao, Fenglei; Jiang, Lin; Zhang, Yi; Zhou, Chunni; Zhang, Lei; Tang, Jing; Liang, Xin; Qi, Yingqiang; Zhu, Yanqing; Ma, Jing; Tang, Yong
2018-01-01
The risk of cognitive decline during Alzheimer's disease (AD) can be reduced if physical activity is maintained; however, the specific neural events underlying this beneficial effect are still uncertain. To quantitatively investigate the neural events underlying the effect of running exercise on middle-aged AD subjects, 12-month-old male APP/PS1 mice were randomly assigned to a control group or running group, and age-matched non-transgenic littermates were used as a wild-type group. AD running group mice were subjected to a treadmill running protocol (regular and moderate intensity) for four months. Spatial learning and memory abilities were assessed using the Morris water maze. Hippocampal amyloid plaques were observed using Thioflavin S staining and immunohistochemistry. Hippocampal volume, number of neurons, and number of newborn cells (BrdU+ cells) in the hippocampus were estimated using stereological techniques, and newborn neurons were observed using double-labelling immunofluorescence. Marked neuronal loss in both the CA1 field and dentate gyrus (DG) and deficits in both the neurogenesis and survival of new neurons in the DG of middle-aged APP/PS1 mice were observed. Running exercise could improve the spatial learning and memory abilities, reduce amyloid plaques in the hippocampi, delay neuronal loss, induce neurogenesis, and promote the survival of newborn neurons in the DG of middle-aged APP/PS1 mice. Exercise-induced protection of neurons and adult neurogenesis within the DG might be part of the important structural basis of the improved spatial learning and memory abilities observed in AD mice.
-
Efficacy of monopolar radiofrequency on skin collagen remodeling: a veterinary study.
Fritz, Klaus; Bernardy, Jan; Tiplica, George Sonn; Machovcova, Alena
2015-01-01
The aesthetic market offers various radiofrequency treatments for the reduction of wrinkles and rhytids. Even though this not an uncommon aesthetic therapy, there is considerable lack of clinical evidence on the various energy delivery systems available (unipolar, bipolar, tripolar, multipolar, etc.). The purpose of this study was to demonstrate the efficacy of a monopolar radiofrequency device (Exilis Elite, BTL Industries Inc., Boston, MA, USA) on the skin collagen in an animal model. The study treatment was done on the abdominal area of the potbellied Vietnamese mini pigs in the Veterinary Research Institute facility. All pigs were treated once per week for 4 weeks. The treatment area was sized 20 × 10 cm. The surface temperature was kept in the therapeutic interval from 39 °C to 43 °C and the therapy lasted for 10 minutes after reaching the therapeutic temperature. Biopsy samples were taken before the therapy and at the 3-month follow-up. The histology samples were stained and magnified (×400) before computer processing. The collagen volume was calculated using the stereological analysis and the data were statistically processed (using the nonparametric two-sample t-test). The collagen content tissue increased from average of 9.0% before the therapy up to 25.9% after the 3-month follow-up period. The statistical comparison of 54 samples taken before and after the treatment acknowledged the significant difference (p = 0.018). The stereological analysis proved large-scale improvement of collagen in the treated area. We have observed that the monopolar radiofrequency therapy significantly increases collagen remodeling. © 2015 Wiley Periodicals, Inc.
-
DOE Office of Scientific and Technical Information (OSTI.GOV)
Bassuk, James; Lendvay, Thomas S.; Sweet, Robert
Diseases and conditions affecting the lower urinary tract are a leading cause of dysfunctional sexual health, incontinence, infection, and kidney failure. The growth, differentiation, and repair of the bladder's epithelial lining are regulated, in part, by fibroblast growth factor (FGF)-7 and -10 via a paracrine cascade originating in the mesenchyme (lamina propria) and targeting the receptor for FGF-7 and -10 within the transitional epithelium (urothelium). The FGF-7 gene is located at the 15q15-q21.1 locus on chromosome 15 and four exons generate a 3.852-kb mRNA. Five duplicated FGF-7 gene sequences that localized to chromosome 9 were predicted not to generate functionalmore » protein products, thus validating the use of FGF-7-null mice as an experimental model. Recombinant FGF-7 and -10 induced proliferation of human urothelial cells in vitro and transitional epithelium of wild-type and FGF-7-null mice in vivo.To determine the extent that induction of urothelial cell proliferation during the bladder response to injury is dependent on FGF-7, an animal model of partial bladder outlet obstruction was developed. Unbiased stereology was used to measure the percentage of proliferating urothelial cells between obstructed groups of wild-type and FGF-7-null mice. The stereological analysis indicated that a statistical significant difference did not exist between the two groups, suggesting that FGF-7 is not essential for urothelial cell proliferation in response to partial outlet obstruction. In contrast, a significant increase in FGF-10 expression was observed in the obstructed FGF-7-null group, indicating that the compensatory pathway that functions in this model results in urothelial repair.« less
-
Montalvo-Javé, Eduardo Esteban; Mendoza-Barrera, German Eduardo; García-Pineda, Manuel Alejandro; Jaime Limón, Álvaro Rodrigo; Montalvo-Arenas, César; Castell Rodríguez, Andrés Eliú; Tapia Jurado, Jesús
2016-01-01
To evaluate macro and microscopically the adhesions developed after using the anti-adherence compound sodium hyaluronate and carboxymethylcellulose (SH-CBMC) gel and to determine the volume of the adhesions using a stereological estimation. The study was experimental, random, comparative, and prospective. The subjects of the study were male Wistar rats divided in three groups (n = 10). Group I (control) included rats with no peritoneal injury. Group II rats had a 2 cm diameter injury created bilaterally in the parietal peritoneum at 3 cm from the abdominal midline with electrocautery coated with physiological solution. Group III rats were given the same injuries and coated with SH-CBMC gel. All groups were followed up postoperatively for 30 days, after which a laparotomy was performed to macroscopically determine the presence and type of adhesions. Experimental models were euthanized with anesthetic overdose and biopsies were taken for histopathological examination and stereological estimate of the volume of adhesions. Macroscopic adhesions were 20% less prevalent in Group III compared to Group II, which presented 40% more multiple and firm adhesions, unlike in Group III, in which they were unique and lax. There was a statistically significant decrease in the presence and number of adhesions in rats treated with SH-CBMC gel. Inflammatory infiltrate was significantly lower in rats treated with SH-CBMC gel, but there were no differences in connective tissue, fibrosis, and angiogenesis among groups. There was no statistical difference in the overall volume of adhesions among the treatment groups. SH-CBMC gel reduces macroscopic presence and number of adhesions and the severity of the inflammatory infiltrate.
-
Resistance training controls arterial blood pressure in rats with L-NAME- induced hypertension.
Araujo, Ayslan Jorge Santos de; Santos, Anne Carolline Veríssimo dos; Souza, Karine dos Santos; Aires, Marlúcia Bastos; Santana-Filho, Valter Joviniano; Fioretto, Emerson Ticona; Mota, Marcelo Mendonça; Santos, Márcio Roberto Viana
2013-04-01
Arterial hypertension is a multifactorial chronic condition caused by either congenital or acquired factors. To evaluate the effects of Resistance Training (RT) on arterial pressure, and on vascular reactivity and morphology, of L-NAME-treated hypertensive rats. Male Wistar rats (200 - 250 g) were allocated into Sedentary Normotensive (SN), Sedentary Hypertensive (SH) and Trained Hypertensive (TH) groups. Hypertension was induced by adding L-NAME (40 mg/Kg) to the drinking water for four weeks. Arterial pressure was evaluated before and after RT. RT was performed using 50% of 1RM, 3 sets of 10 repetitions, 3 times per week for four weeks. Vascular reactivity was measured in rat mesenteric artery rings by concentration-response curves to sodium nitroprusside (SNP); phenylephrine (PHE) was also used for histological and stereological analysis. Resistance training inhibited the increase in mean and diastolic arterial pressures. Significant reduction was observed in Rmax (maximal response) and pD2 (potency) of PHE between SH and TH groups. Arteries demonstrated normal intima, media and adventitia layers in all groups. Stereological analysis demonstrated no significant difference in luminal, tunica media, and total areas of arteries in the SH and TH groups when compared to the SN group. Wall-to-lumen ratio of SH arteries was significantly different compared to SN arteries (p<0.05) but there was no difference when compared to TH arteries. RT was able to prevent an increase in blood pressure under the conditions in this study. This appears to involve a vasoconstrictor regulation mechanism and maintenance of luminal diameter in L-NAME induced hypertensive rats.
-
Chen, Wei-Jung A; King, Karen A; Lee, Ruby E; Sedtal, Christopher S; Smith, Andrew M
2006-11-02
Smoking during pregnancy poses a potential risk to unborn children. The present study examined the long-term effects of early nicotine exposure on the number of pyramidal and granule cells in the hippocampus, and Purkinje cells in the cerebellar vermis. The loss of neurons is the most severe form of brain injury with significant functional implications. In this study, rats were exposed to nicotine during either the prenatal (PRE) period or both the prenatal and early postnatal (PERI) period. It was hypothesized that nicotine treatment would result in long-term decreases in neuronal numbers, and that PERI treatment would be more detrimental to these cell populations than the PRE treatment. The results showed that neither PRE nor PERI nicotine exposure reduces the numbers of pyramidal, granule or Purkinje cells. Neither the regions where these cells reside, nor the cell densities were affected by nicotine. Although no significant cell loss was observed, the current nicotine exposure regimens may lead to alterations in cellular functions or cytoarchitectures. The present results in conjunction with previous reports showing significant cell loss from nicotine exposure during the brain growth spurt suggest that "patch-like" nicotine exposure during prenatal period may alter the sensitivity or the responsiveness of the developing brain to the injurious effects of nicotine during the most vulnerable stage of brain development - the brain growth spurt. Furthermore, the current stereology cell counting results are not in agreement with some reports in the literature, and this discrepancy may simply be a function of different cell counting techniques used.
-
McBride, E L; Rao, A; Zhang, G; Hoyne, J D; Calco, G N; Kuo, B C; He, Q; Prince, A A; Pokrovskaya, I D; Storrie, B; Sousa, A A; Aronova, M A; Leapman, R D
2018-06-01
Microscopies based on focused electron probes allow the cell biologist to image the 3D ultrastructure of eukaryotic cells and tissues extending over large volumes, thus providing new insight into the relationship between cellular architecture and function of organelles. Here we compare two such techniques: electron tomography in conjunction with axial bright-field scanning transmission electron microscopy (BF-STEM), and serial block face scanning electron microscopy (SBF-SEM). The advantages and limitations of each technique are illustrated by their application to determining the 3D ultrastructure of human blood platelets, by considering specimen geometry, specimen preparation, beam damage and image processing methods. Many features of the complex membranes composing the platelet organelles can be determined from both approaches, although STEM tomography offers a higher ∼3 nm isotropic pixel size, compared with ∼5 nm for SBF-SEM in the plane of the block face and ∼30 nm in the perpendicular direction. In this regard, we demonstrate that STEM tomography is advantageous for visualizing the platelet canalicular system, which consists of an interconnected network of narrow (∼50-100 nm) membranous cisternae. In contrast, SBF-SEM enables visualization of complete platelets, each of which extends ∼2 µm in minimum dimension, whereas BF-STEM tomography can typically only visualize approximately half of the platelet volume due to a rapid non-linear loss of signal in specimens of thickness greater than ∼1.5 µm. We also show that the limitations of each approach can be ameliorated by combining 3D and 2D measurements using a stereological approach. Copyright © 2018. Published by Elsevier Inc.
-
N-terminal region of myelin basic protein reduces fibrillar amyloid-β deposition in Tg-5xFAD mice.
Ou-Yang, Ming-Hsuan; Xu, Feng; Liao, Mei-Chen; Davis, Judianne; Robinson, John K; Van Nostrand, William E
2015-02-01
Alzheimer's disease is a progressive neurodegenerative disorder that is characterized by extensive deposition of fibrillar amyloid-β (Aβ) in the brain. Previously, myelin basic protein (MBP) was identified to be a potent inhibitor to Aβ fibril formation, and this inhibitory activity was localized to the N-terminal residues 1-64, a fragment designated MBP1. Here, we show that the modest neuronal expression of a fusion protein of the biologically active MBP1 fragment and the enhanced green fluorescent protein (MBP1-EGFP) significantly improved the performance of spatial learning memory in Tg-5xFAD mice, a model of pathologic Aβ accumulation in brain. The levels of insoluble Aβ and fibrillar amyloid were significantly reduced in bigenic Tg-5xFAD/Tg-MBP1-EGFP mice. Quantitative stereological analysis revealed that the reduction in amyloid was because of a reduction in the size of fibrillar plaques rather than a decrease in plaque numbers. The current findings support previous studies showing that MBP1 inhibits Aβ fibril formation in vitro and demonstrate the ability of MBP1 to reduce Aβ pathology and improve behavioral performance. Copyright © 2015 Elsevier Inc. All rights reserved.
-
Legland, David; Guillon, Fabienne; Kiêu, Kiên; Bouchet, Brigitte; Devaux, Marie-Françoise
2010-01-01
Background and Aims The cellular structure of fleshy fruits is of interest to study fruit shape, size, mechanical behaviour or sensory texture. The cellular structure is usually not observed in the whole fruit but, instead, in a sample of limited size and volume. It is therefore difficult to extend measurements to the whole fruit and/or to a specific genotype, or to describe the cellular structure heterogeneity within the fruit. Methods An integrated method is presented to describe the cellular structure of the whole fruit from partial three-dimensional (3D) observations, involving the following steps: (1) fruit sampling, (2) 3D image acquisition and processing and (3) measurement and estimation of relevant 3D morphological parameters. This method was applied to characterize DR12 mutant and wild-type tomatoes (Solanum lycopersicum). Key Results The cellular structure was described using the total volume of the pericarp, the surface area of the cell walls and the ratio of cell-wall surface area to pericarp volume, referred to as the cell-wall surface density. The heterogeneity of cellular structure within the fruit was investigated by estimating variations in the cell-wall surface density with distance to the epidermis. Conclusions The DR12 mutant presents a greater pericarp volume and an increase of cell-wall surface density under the epidermis. PMID:19952012
-
Urtica Dioica Distillate Regenerates Pancreatic Beta Cells in Streptozotocin-Induced Diabetic Rats.
Gohari, Ali; Noorafshan, Ali; Akmali, Masoumeh; Zamani-Garmsiri, Fahimeh; Seghatoleslam, Atefeh
2018-03-01
Urtica dioica is known as an anti-hyperglycemic plant. Urtica dioica distillate (UD) is a traditional Iranian drink, locally known as "aragh gazaneh". In spite of its widespread consumption in Iran, according to traditional Iranian medicine, there is no scientific report on the usefulness of UD for diabetic patients. This survey was designed to evaluate its protective effects for the recovery from diabetes by determining the serum insulin, blood glucose, volume of pancreatic islets, and the number and volume of β-cells in diabetic rats. A total of 48 Sprague-Dawley male rats (200-250 g) were randomly distributed into 6 groups (n=8), including non-diabetic plus distilled water (DW), non-diabetic plus UD, diabetic plus DW, diabetic plus UD, diabetic plus insulin, and diabetic plus glibenclamide. DW, UD, and glibenclamide were administered via intragastric gavage and insulin was injected subcutaneously. After four weeks of experiments, blood samples were collected for serum insulin and blood glucose assay. Pancreas was also evaluated using stereological method. The SPSS software was used for statistical analysis. Kruskal-Wallis, repeated measurements, and Mann-Whitney U test were applied for comparisons between the groups. The treatment of diabetic rats with UD reduced the blood glucose dramatically (P<0.001) and increased serum insulin levels significantly (P=0.03) in comparison to the diabetic plus DW rats. Treatment with UD did not affect the mean β-cell volumes in the diabetic rats when compared to the diabetic plus DW rats, but the islet volumes and β-cell numbers were significantly recovered. UD treatment in diabetic rats improves hyperglycemia by partially restoring plasma insulin levels. The data suggest that UD prevents islet atrophy and/or regenerate pancreatic β-cells.
-
Kazdal, Hizir; Kanat, Ayhan; Aydin, Mehmet Dumlu; Yazar, Ugur; Guvercin, Ali Riza; Calik, Muhammet; Gundogdu, Betul
2017-01-01
Context: Sudden death from subarachnoid hemorrhage (SAH) is not uncommon. Aims: The goal of this study is to elucidate the effect of the cervical spinal roots and the related dorsal root ganglions (DRGs) on cardiorespiratory arrest following SAH. Settings and Design: This was an experimental study conducted on rabbits. Materials and Methods: This study was conducted on 22 rabbits which were randomly divided into three groups: control (n = 5), physiologic serum saline (SS; n = 6), SAH groups (n = 11). Experimental SAH was performed. Seven of 11 rabbits with SAH died within the first 2 weeks. After 20 days, other animals were sacrificed. The anterior spinal arteries, arteriae nervorum of cervical nerve roots (C6–C8), DRGs, and lungs were histopathologically examined and estimated stereologically. Statistical Analysis Used: Statistical analysis was performed using the PASW Statistics 18.0 for Windows (SPSS Inc., Chicago, Illinois, USA). Intergroup differences were assessed using a one-way ANOVA. The statistical significance was set at P < 0.05. Results: In the SAH group, histopathologically, severe anterior spinal artery (ASA) and arteriae nervorum vasospasm, axonal and neuronal degeneration, and neuronal apoptosis were observed. Vasospasm of ASA did not occur in the SS and control groups. There was a statistically significant increase in the degenerated neuron density in the SAH group as compared to the control and SS groups (P < 0.05). Cardiorespiratory disturbances, arrest, and lung edema more commonly developed in animals in the SAH group. Conclusion: We noticed interestingly that C6–C8 DRG degenerations were secondary to the vasospasm of ASA, following SAH. Cardiorespiratory disturbances or arrest can be explained with these mechanisms. PMID:28250634
-
Grothausmann, Roman; Knudsen, Lars; Ochs, Matthias; Mühlfeld, Christian
2017-02-01
Grothausmann R, Knudsen L, Ochs M, Mühlfeld C. Digital 3D reconstructions using histological serial sections of lung tissue including the alveolar capillary network. Am J Physiol Lung Cell Mol Physiol 312: L243-L257, 2017. First published December 2, 2016; doi:10.1152/ajplung.00326.2016-The alveolar capillary network (ACN) provides an enormously large surface area that is necessary for pulmonary gas exchange. Changes of the ACN during normal or pathological development or in pulmonary diseases are of great functional impact and warrant further analysis. Due to the complexity of the three-dimensional (3D) architecture of the ACN, 2D approaches are limited in providing a comprehensive impression of the characteristics of the normal ACN or the nature of its alterations. Stereological methods offer a quantitative way to assess the ACN in 3D in terms of capillary volume, surface area, or number but lack a 3D visualization to interpret the data. Hence, the necessity to visualize the ACN in 3D and to correlate this with data from the same set of data arises. Such an approach requires a large sample volume combined with a high resolution. Here, we present a technically simple and cost-efficient approach to create 3D representations of lung tissue ranging from bronchioles over alveolar ducts and alveoli up to the ACN from more than 1 mm sample extent to a resolution of less than 1 μm. The method is based on automated image acquisition of serially sectioned epoxy resin-embedded lung tissue fixed by vascular perfusion and subsequent automated digital reconstruction and analysis of the 3D data. This efficient method may help to better understand mechanisms of vascular development and pathology of the lung. Copyright © 2017 the American Physiological Society.
-
Fabric dependence of wave propagation in anisotropic porous media
Cowin, Stephen C.; Cardoso, Luis
2012-01-01
Current diagnosis of bone loss and osteoporosis is based on the measurement of the Bone Mineral Density (BMD) or the apparent mass density. Unfortunately, in most clinical ultrasound densitometers: 1) measurements are often performed in a single anatomical direction, 2) only the first wave arriving to the ultrasound probe is characterized, and 3) the analysis of bone status is based on empirical relationships between measurable quantities such as Speed of Sound (SOS) and Broadband Ultrasound Attenuation (BUA) and the density of the porous medium. However, the existence of a second wave in cancellous bone has been reported, which is an unequivocal signature of poroelastic media, as predicted by Biot’s poroelastic wave propagation theory. In this paper the governing equations for wave motion in the linear theory of anisotropic poroelastic materials are developed and extended to include the dependence of the constitutive relations upon fabric - a quantitative stereological measure of the degree of structural anisotropy in the pore architecture of a porous medium. This fabric-dependent anisotropic poroelastic approach is a theoretical framework to describe the microarchitectural-dependent relationship between measurable wave properties and the elastic constants of trabecular bone, and thus represents an alternative for bone quality assessment beyond BMD alone. PMID:20461539
-
Aguirre, Jose A; Kehr, Jan; Yoshitake, Takashi; Liu, Fang-Ling; Rivera, Alicia; Fernandez-Espinola, Sergio; Andbjer, Beth; Leo, Giuseppina; Medhurst, Andrew D; Agnati, Luigi F; Fuxe, Kjell
2005-02-08
The mGluR5 antagonist MPEP was used to study the role of mGluR5 in MPTP-induced injury of the nigrostriatal DA neurons. The findings indicate that acute blockade of mGluR5 may result in neuroprotective actions against MPTP neurotoxicity on nigral DA cell bodies and striatal DA terminals using stereological analysis of TH immunoreactivity and microdensitometry. Biochemical analysis showed no restoration of DA levels and metabolism indicating a maintained reduction of DA transmission.
-
Preserved number of entorhinal cortex layer II neurons in aged macaque monkeys
NASA Technical Reports Server (NTRS)
Gazzaley, A. H.; Thakker, M. M.; Hof, P. R.; Morrison, J. H.; Bloom, F. E. (Principal Investigator)
1997-01-01
The perforant path, which consists of the projection from the layer II neurons of the entorhinal cortex to the outer molecular layer of the dentate gyrus, is a critical circuit involved in learning and memory formation. Accordingly, disturbances in this circuit may contribute to age-related cognitive deficits. In a previous study, we demonstrated a decrease in N-methyl-D-aspartate receptor subunit 1 immunofluorescence intensity in the outer molecular layer of aged macaque monkeys. In this study, we used the optical fractionator, a stereological method, to determine if a loss of layer II neurons occurred in the same animals in which the N-methyl-D-aspartate receptor subunit 1 alteration was observed. Our results revealed no significant differences in the number of layer II neurons between juvenile, young adult, and aged macaque monkeys. These results suggest that the circuit-specific decrease in N-methyl-D-aspartate receptor subunit 1 reported previously occurs in the absence of structural compromise of the perforant path, and thus may be linked to an age-related change in the physiological properties of this circuit.
-
Somer, Ljiljana; Dusan, Lalosević; Dolai, Matilda
2007-01-01
The theoretical and practical aspects of teaching are generally defined by the curriculum, but professional experience plays an important role as well. The teaching experience of the faculty members is developed through health services, education and research. THE DEPARTMENT OFHISTOLOGY AND EMBRIOLOGY: This paper reviews the activities of the teaching staff of the Department of Histology and Embryology, pointing to the importance of pathologic diagnostics and research. It underlines the necessity of using some non-standard histologic staining methods on some tissues, organs and pathogens, as well as the results of experimental studies of the endocrine system. The experimental tumor models are used to demonstrate the interdependence of the endocrine and immune systems. Modalities and possibilities of regeneration of the digestive tract and connective tissue mucosa are explained This paper also deals with histologic criteria used for assessment of fetal age and in the diagnosis of developmental malformations. Linear and stereologic methods, used in quantification of normal morphology, the degree of pathologic changes, and regeneration of normal structures in the courses of and after therapy, are given. The authors particularly emphasized the importance of above-mentioned activities in the teaching of Histology and Embryology to undergraduate students.
-
Stereological determination of the volume of the rat hemimandible tissues.
Silva, M A; Merzel, J
2001-07-01
Rodent incisors are useful models to study the development and behavior of dental and periodontal tissues. Some studies require three-dimensional reconstructions of the tooth but none of the described methods yield actual volumetric data. Unlike the rat lower incisors the hemimandible can be easily isolated and its volume was determined by Cavalieri's geometrical principle. This method associated with point-counting volumetry was used to calculate the volume of the structures found in that bone mainly those related to the lower incisor. For 172 g male rats the mean volume of the hemimandible was 182.7 mm(3), statistically not different from 184.9 mm(3) the mean volume of the same hemimandibles determined by Archimedes' principle. The coefficients of error (CE) of Cavalieri's estimates for the hemimandible, incisor as a whole (the tooth itself, odontogenic region and periodontium) and bone tissue were less than 0.04. For the incisor individual tissues the CEs were usually above 0.05, however their calculated volumes are probably not different from the actual ones. The data for incisors and their periodontal tissues and for bone, because of continuous growth of these structures, are meaningful only for rats of the same gender, strain and weight range. Copyright 2001 Wiley-Liss, Inc.
-
Shao, Jing-Yuan; Qu, Hai-Bin; Gong, Xing-Chu
2018-05-01
In this work, two algorithms (overlapping method and the probability-based method) for design space calculation were compared by using the data collected from extraction process of Codonopsis Radix as an example. In the probability-based method, experimental error was simulated to calculate the probability of reaching the standard. The effects of several parameters on the calculated design space were studied, including simulation number, step length, and the acceptable probability threshold. For the extraction process of Codonopsis Radix, 10 000 times of simulation and 0.02 for the calculation step length can lead to a satisfactory design space. In general, the overlapping method is easy to understand, and can be realized by several kinds of commercial software without coding programs, but the reliability of the process evaluation indexes when operating in the design space is not indicated. Probability-based method is complex in calculation, but can provide the reliability to ensure that the process indexes can reach the standard within the acceptable probability threshold. In addition, there is no probability mutation in the edge of design space by probability-based method. Therefore, probability-based method is recommended for design space calculation. Copyright© by the Chinese Pharmaceutical Association.
-
Fritsch, Roland; Collin, Shaun P.; Michiels, Nico K.
2017-01-01
The environment and lifestyle of a species are known to exert selective pressure on the visual system, often demonstrating a tight link between visual morphology and ecology. Many studies have predicted the visual requirements of a species by examining the anatomical features of the eye. However, among the vast number of studies on visual specializations in aquatic animals, only a few have focused on small benthic fishes that occupy a heterogeneous and spatially complex visual environment. This study investigates the general retinal anatomy including the topography of both the photoreceptor and ganglion cell populations and estimates the spatial resolving power (SRP) of the eye of the Mediterranean triplefin Tripterygion delaisi. Retinal wholemounts were prepared to systematically and quantitatively analyze photoreceptor and retinal ganglion cell (RGC) densities using design-based stereology. To further examine the retinal structure, we also used magnetic resonance imaging (MRI) and histological examination of retinal cross sections. Observations of the triplefin’s eyes revealed them to be highly mobile, allowing them to view the surroundings without body movements. A rostral aphakic gap and the elliptical shape of the eye extend its visual field rostrally and allow for a rostro-caudal accommodatory axis, enabling this species to focus on prey at close range. Single and twin cones dominate the retina and are consistently arranged in one of two regular patterns, which may enhance motion detection and color vision. The retina features a prominent, dorso-temporal, convexiclivate fovea with an average density of 104,400 double and 30,800 single cones per mm2, and 81,000 RGCs per mm2. Based on photoreceptor spacing, SRP was calculated to be between 6.7 and 9.0 cycles per degree. Location and resolving power of the fovea would benefit the detection and identification of small prey in the lower frontal region of the visual field. PMID:29311852
-
Fritsch, Roland; Collin, Shaun P; Michiels, Nico K
2017-01-01
The environment and lifestyle of a species are known to exert selective pressure on the visual system, often demonstrating a tight link between visual morphology and ecology. Many studies have predicted the visual requirements of a species by examining the anatomical features of the eye. However, among the vast number of studies on visual specializations in aquatic animals, only a few have focused on small benthic fishes that occupy a heterogeneous and spatially complex visual environment. This study investigates the general retinal anatomy including the topography of both the photoreceptor and ganglion cell populations and estimates the spatial resolving power (SRP) of the eye of the Mediterranean triplefin Tripterygion delaisi . Retinal wholemounts were prepared to systematically and quantitatively analyze photoreceptor and retinal ganglion cell (RGC) densities using design-based stereology. To further examine the retinal structure, we also used magnetic resonance imaging (MRI) and histological examination of retinal cross sections. Observations of the triplefin's eyes revealed them to be highly mobile, allowing them to view the surroundings without body movements. A rostral aphakic gap and the elliptical shape of the eye extend its visual field rostrally and allow for a rostro-caudal accommodatory axis, enabling this species to focus on prey at close range. Single and twin cones dominate the retina and are consistently arranged in one of two regular patterns, which may enhance motion detection and color vision. The retina features a prominent, dorso-temporal, convexiclivate fovea with an average density of 104,400 double and 30,800 single cones per mm 2 , and 81,000 RGCs per mm 2 . Based on photoreceptor spacing, SRP was calculated to be between 6.7 and 9.0 cycles per degree. Location and resolving power of the fovea would benefit the detection and identification of small prey in the lower frontal region of the visual field.
-
Långsjö, Teemu K; Vasara, Anna I; Hyttinen, Mika M; Lammi, Mikko J; Kaukinen, Antti; Helminen, Heikki J; Kiviranta, Ilkka
2010-01-01
The aim of this study was to undertake a stereological analysis to quantify the dimensions of the collagen network in the repair tissue of porcine joints after they had been subjected to autologous chondrocyte transplantation (ACT). ACT was used to repair cartilage lesions in knee joints of pigs. Electron-microscopic stereology, immunostaining for type II collagen, and quantitative polarized-light microscopy were utilized to study the collagen fibrils in the repair tissue 3 and 12 months after the operation. The collagen volume density (V(V)) was lower in the repair tissue than in normal cartilage at 3 months (20.4 vs. 23.7%) after the operation. The collagen surface density (S(V), 1.5·10(-2) vs. 3.1·10(-2) nm(2)/nm(3)) and V(V) increased with time in the repair tissue (20.4 vs. 44.7%). Quantitative polarized-light microscopy detected a higher degree of collagen parallelism in the repair tissue at 3 months after the operation (55.7 vs. 49.7%). In contrast, 1 year after the operation, fibril parallelism was lower in the repair tissue than in the control cartilage (47.5 vs. 69.8%). Following ACT, V(V) and S(V) increased in the repair tissue with time, reflecting maturation of the tissue. One year after the operation, there was a lower level of fibril organization in the repair tissue than in the control cartilage. Thus, the newly synthesized collagen fibrils in the repair tissue appeared to form a denser network than in the control cartilage, but the fibrils remained more randomly oriented. Copyright © 2010 S. Karger AG, Basel.
-
Amado, Sandra; Rodrigues, Jorge M; Luís, Ana L; Armada-da-Silva, Paulo A S; Vieira, Márcia; Gartner, Andrea; Simões, Maria J; Veloso, António P; Fornaro, Michele; Raimondo, Stefania; Varejão, Artur S P; Geuna, Stefano; Maurício, Ana C
2010-02-11
Peripheral nerves possess the capacity of self-regeneration after traumatic injury but the extent of regeneration is often poor and may benefit from exogenous factors that enhance growth. The use of cellular systems is a rational approach for delivering neurotrophic factors at the nerve lesion site, and in the present study we investigated the effects of enwrapping the site of end-to-end rat sciatic nerve repair with an equine type III collagen membrane enriched or not with N1E-115 pre-differentiated neural cells. After neurotmesis, the sciatic nerve was repaired by end-to-end suture (End-to-End group), end-to-end suture enwrapped with an equine collagen type III membrane (End-to-EndMemb group); and end-to-end suture enwrapped with an equine collagen type III membrane previously covered with neural cells pre-differentiated in vitro from N1E-115 cells (End-to-EndMembCell group). Along the postoperative, motor and sensory functional recovery was evaluated using extensor postural thrust (EPT), withdrawal reflex latency (WRL) and ankle kinematics. After 20 weeks animals were sacrificed and the repaired sciatic nerves were processed for histological and stereological analysis. Results showed that enwrapment of the rapair site with a collagen membrane, with or without neural cell enrichment, did not lead to any significant improvement in most of functional and stereological predictors of nerve regeneration that we have assessed, with the exception of EPT which recovered significantly better after neural cell enriched membrane employment. It can thus be concluded that this particular type of nerve tissue engineering approach has very limited effects on nerve regeneration after sciatic end-to-end nerve reconstruction in the rat.
-
2010-01-01
Peripheral nerves possess the capacity of self-regeneration after traumatic injury but the extent of regeneration is often poor and may benefit from exogenous factors that enhance growth. The use of cellular systems is a rational approach for delivering neurotrophic factors at the nerve lesion site, and in the present study we investigated the effects of enwrapping the site of end-to-end rat sciatic nerve repair with an equine type III collagen membrane enriched or not with N1E-115 pre-differentiated neural cells. After neurotmesis, the sciatic nerve was repaired by end-to-end suture (End-to-End group), end-to-end suture enwrapped with an equine collagen type III membrane (End-to-EndMemb group); and end-to-end suture enwrapped with an equine collagen type III membrane previously covered with neural cells pre-differentiated in vitro from N1E-115 cells (End-to-EndMembCell group). Along the postoperative, motor and sensory functional recovery was evaluated using extensor postural thrust (EPT), withdrawal reflex latency (WRL) and ankle kinematics. After 20 weeks animals were sacrificed and the repaired sciatic nerves were processed for histological and stereological analysis. Results showed that enwrapment of the rapair site with a collagen membrane, with or without neural cell enrichment, did not lead to any significant improvement in most of functional and stereological predictors of nerve regeneration that we have assessed, with the exception of EPT which recovered significantly better after neural cell enriched membrane employment. It can thus be concluded that this particular type of nerve tissue engineering approach has very limited effects on nerve regeneration after sciatic end-to-end nerve reconstruction in the rat. PMID:20149260
-
Marcek, John; Okerberg, Carlin; Liu, Chang-Ning; Potter, David; Butler, Paul; Boucher, Magalie; Zorbas, Mark; Mouton, Peter; Nyengaard, Jens R; Somps, Chris
2016-10-01
Nerve growth factor (NGF) blocking therapies are an emerging and effective approach to pain management. However, concerns about the potential for adverse effects on the structure and function of the peripheral nervous system have slowed their development. Early studies using NGF antisera in adult rats reported effects on the size and number of neurons in the sympathetic chain ganglia. In the work described here, both young adult (6-8 week) and fully mature (7-8 month) rats were treated with muMab 911, a selective, murine, anti-NGF monoclonal antibody, to determine if systemic exposures to pharmacologically active levels of antibody for 1 month cause loss of neurons in the sympathetic superior cervical ganglia (SCG). State-of-the-art, unbiased stereology performed by two independent laboratories was used to determine the effects of muMab 911 on SCG neuronal number and size, as well as ganglion size. Following muMab 911 treatment, non-statistically significant trends toward smaller ganglia, and smaller and fewer neurons, were seen when routine, nonspecific stains were used in stereologic assessments. However, when noradrenergic neurons were identified using tyrosine hydroxylase (TH) immunoreactivity, trends toward fewer neurons observed with routine stains were not apparent. The only statistically significant effects detected were lower SCG weights in muMab 911-treated rats, and a smaller volume of TH immunoreactivity in neurons from younger rats treated with muMab 911. These results indicate that therapeutically relevant exposures to the anti-NGF monoclonal antibody muMab 911 for 1 month have no effect on neuron numbers within the SCG from young or old adult rats. Copyright © 2016 Elsevier B.V. All rights reserved.
-
Karbalay-Doust, S; Noorafshan, A
2011-01-01
Metronidazole (MTZ) is used as an antiparasitic drug. Curcumin is considered as anti-oxidant and anti-inflammatory agent. The ameliorative effects of curcumin on MTZ induced toxicity on mice spermatozoon tail length, count, motility and testosterone level were investigated. MTZ was administered in 500 and 165 (high and therapeutic doses) mg/kg/day, with and without curcumin (100 mg/kg/day). After 16 days the above parameters were assessed. Spermatozoon count and motility and serum testosterone level MTZ-treated (500 and 165) mice were reduced. In the mice treated with MTZ+curcumin these parameters decreased but in a lesser extent than the MTZ-treated animals. Mid-piece and total lengths of the spermatozoon tail in control animals were 31.6 ± 9.0 μm and 100.3 ± 15.0 μm and in the mice treated with high doses (500) of MTZ were reduced. The mid-piece and total spermatozoon tail length has been decreased in a lesser extent in the mice treated with high dose MTZ+curcumin than the mice treated with high dose MTZ (p<0.01). But the length was not changed in animals treated with therapeutic dose of MTZ. It means curcumin treated animals had ~52% and ~39% average increase in mid-piece and total lengths in comparison with the MTZ-treated (500) animals. Stereological estimation of the sperm tail length, including sampling of spermatozoa and also counting of the intersections of their tails with the stereological grids was a rapid technique and took only 5-10 minutes. It can be concluded that curcumin has an ameliorative effect on the spermatozoon, testosterone level and tail length in MTZ-treated mice.
-
Miladpour, B; Rasti, M; Owji, A A; Mostafavipour, Z; Khoshdel, Z; Noorafshan, A; Zal, F
2017-05-01
Type 1 diabetes is an autoimmune disease caused by the destruction of β-cells in the pancreas. Bone marrow mesenchymal stem cells are multipotent and easy accessible adult stem cells that may provide options in the treatment of type 1 diabetes. Injured pancreatic extract can promote the differentiation of rat bone marrow mesenchymal stem cells into β-cells. We aimed to observe the effect of quercetin in differentiation and insulin secretion in β-cells. Bone marrow mesenchymal stem cells were obtained from the tibiae of rats. Cell surface markers were analyzed by flow cytometry. The cells were treated with rat injured pancreatic extract and quercetin for 2 weeks. Insulin secretion was measured by ELISA. Insulin expression and some islet factors were evaluated by RT-PCR. PDX1, a marker for β-cell function and differentiation, was evaluated by both immunocytochemistry and Western blot. β-cell count was determined by stereology and cell count assay. ELISA showed significant differences in insulin secretion in the cells treated with RIPE + 20 μM quercetin (0.55 ± 0.01 µg/L) compared with the cells treated with RIPE alone (0.48 ± 0.01 µg/L) (P = 0.026). RT-PCR results confirmed insulin expression in both groups. PDX1 protein was detected in both groups by Western blot and immunocytochemistry. Stereology results showed a significant increase in β-cell number in the RIPE + quercetin-treated cells (47 ± 2.0) when compared with RIPE treatment alone (44 ± 2.5) (P = 0.015). Quercetin has a strengthening effect on the differentiation of rat bone marrow mesenchymal stem cells into β-cells and increases insulin secretion from the differentiated β-cells in vitro.
-
Wittwer, Thorsten; Franke, Ulrich F W; Ochs, Matthias; Sandhaus, Tim; Schuette, Alex; Richter, Stefan; Dreyer, Niels; Knudsen, Lars; Müller, Thomas; Schubert, Harald; Richter, Joachim; Wahlers, Thorsten
2005-10-01
Lung transplantation is effective for end-stage pulmonary disease, but its successful application is still limited by organ shortage and sub-optimal preservation techniques. Therefore, optimal allograft protection is essential to reduce organ dysfunction, especially in the early post-operative period. Intravenous prostanoids are routinely used to ameliorate reperfusion injury. However, the latest evidence suggests similar efficacy using inhaled prostacyclin. Thus, we evaluated the impact of donor pre-treatment using the prostacyclin analog, iloprost, on post-ischemic function of Perfadex-protected allografts. In Group 1, 5 pig lungs were preserved with Perfadex (PER group) solution and stored for 27 hours. In Group 2, 100 microg of iloprost was aerosolized over 30 minutes using a novel mobile ultrasonic nebulizer (Optineb) before identical organ harvest (PER-ILO group). After left lung transplantation and contralateral lung exclusion, hemodynamic variables, Po2/Fio2 and dynamic compliance were monitored for 6 hours and compared with sham-operated controls. Pulmonary edema was determined stereologically and by wet-to-dry (W/D) weight ratio. Statistical assessment included analysis of variance (ANOVA) with repeated measures. Dynamic compliance and pulmonary vascular resistance (PVR) were superior in iloprost-treated compared with untreated organs (p < 0.05), whereas oxygenation was comparable between groups. W/D ratio revealed a significantly smaller amount of lung water in PER-ILO organs (p = 0.048), whereas stereologic data showed a trend toward less intra-alveolar edema. Endobronchial application of iloprost in donor lungs before Perfadex preservation decreases post-ischemic edema and significantly improves lung compliance and vascular resistance. This innovative approach is easily applicable in the clinical setting and offers a new strategy for improvement of pulmonary allograft preservation.
-
Excitatory and inhibitory innervation of the mouse orofacial motor nuclei: A stereological study.
Faunes, Macarena; Oñate-Ponce, Alejandro; Fernández-Collemann, Sara; Henny, Pablo
2016-03-01
Neurons in the trigeminal (Mo5), facial (Mo7), ambiguus (Amb), and hypoglossal (Mo12) motor nuclei innervate jaw, facial, pharynx/larynx/esophagus, and tongue muscles, respectively. They are essential for movements subserving feeding, exploration of the environment, and social communication. These neurons are largely controlled by sensory afferents and premotor neurons of the reticular formation, where central pattern generator circuits controlling orofacial movements are located. To provide a description of the orofacial nuclei of the adult mouse and to ascertain the influence of excitatory and inhibitory afferents upon them, we used stereology to estimate the number of motoneurons as well as of varicosities immunopositive for glutamate (VGluT1+, VGluT2+) and GABA/glycine (known as VIAAT+ or VGAT+) vesicular transporters in the Mo5, Mo7, Amb, and Mo12. Mo5, Mo7, Amb, and Mo12 contain ∼1,000, ∼3,000, ∼600, and ∼1,700 cells, respectively. VGluT1+, VGluT2+, and VIAAT+ varicosities respectively represent: 28%, 41%, and 31% in Mo5; 2%, 49%, and 49% in Mo7; 12%, 42%, and 46% in Amb; and 4%, 54%, and 42% in Mo12. The Mo5 jaw-closing subdivision shows the highest VGluT1+ innervation. Noticeably, the VGluT2+ and VIAAT+ varicosity density in Mo7 is 5-fold higher than in Mo5 and 10-fold higher than in Amb and Mo12. The high density of terminals in Mo7 likely reflects the convergence and integration of numerous inputs to motoneurons subserving the wide range of complex behaviors to which this nucleus contributes. Also, somatic versus neuropil location of varicosities suggests that most of these afferents are integrated in the dendritic trees of Mo7 neurons. © 2015 Wiley Periodicals, Inc.
-
Puelles, Victor G; Douglas-Denton, Rebecca N; Zimanyi, Monika A; Armitage, James A; Hughson, Michael D; Kerr, Peter G; Bertram, John F
2014-09-01
We have shown that low nephron number (Nglom) is a strong determinant of individual glomerular volume (IGV) in male Americans. However, whether the same pattern is present in female Americans remains unclear. The contributions of body surface area (BSA) and race to IGV in the context of Nglom also require further evaluation. Kidneys without overt renal disease were collected at autopsy in Mississippi, USA. The extremes of female Nglom were used to define high and low Nglom for both sexes. Nglom and IGV were estimated by design-based stereology. A total of 24 African and Caucasian American females (n = 12 per race; 6 per Nglom extreme) were included. These subjects were subsequently matched to 24 comparable males by age and Nglom and to 18 additional males by age, Nglom and BSA. IGV average and variance were very similar in female African and Caucasian Americans with high and low Nglom. Males with low Nglom from both races showed greater IGV average and variance than comparable females matched by age and Nglom. These differences in IGV between sexes were not observed in Caucasian Americans with low Nglom that were matched by age, Nglom and BSA. In contrast, glomeruli from African Americans were larger than those from Caucasian Americans, especially in subjects with high Nglom. While female Americans with low Nglom did not show glomerular hypertrophy, comparable males with low Nglom showed marked glomerular hypertrophy that was closely associated with high BSA. Glomerular size in African Americans may be confounded by multiple additional factors. © The Author 2014. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.
-
DOE Office of Scientific and Technical Information (OSTI.GOV)
Herring, M.J.; Putney, L.F.; St George, J.A.
In rhesus macaques, previous studies have shown that episodic exposure to allergen alone or combined with ozone inhalation during the first 6 months of life results in a condition with many of the hallmarks of asthma. This exposure regimen results in altered development of the distal airways and parenchyma (Avdalovic et al., 2012). We hypothesized that the observed alterations in the lung parenchyma would be permanent following a long-term recovery in filtered air (FA) housing. Forty-eight infant rhesus macaques (30 days old) sensitized to house dust mite (HDM) were treated with two week cycles of FA, house dust mite allergenmore » (HDMA), ozone (O{sub 3}) or HDMA/ozone (HDMA + O{sub 3}) for five months. At the end of the five months, six animals from each group were necropsied. The other six animals in each group were allowed to recover in FA for 30 more months at which time they were necropsied. Design-based stereology was used to estimate volumes of lung components, number of alveoli, size of alveoli, distribution of alveolar volumes, interalveolar capillary density. After 30 months of recovery, monkeys exposed to HDMA, in either group, had significantly more alveoli than filtered air. These alveoli also had higher capillary densities as compared with FA controls. These results indicate that early life exposure to HDMA alone or HDMA + O{sub 3} alters the development process in the lung alveoli. - Highlights: • Abnormal lung development after postnatal exposure to ozone and allergen • This remodeling is shown as smaller, more numerous alveoli and narrower airways. • Allergen appears to have more of an effect than ozone during recovery. • These animals also have continued airway hyperresponsiveness (Moore et al. 2014)« less
-
Strackx, E; Van den Hove, D L A; Steinbusch, H P; Steinbusch, H W M; Vles, J S H; Blanco, C E; Gavilanes, A W D
2008-06-01
Fetal asphyxic insults in the brain are known to be associated with developmental neurological problems like neuromotor disorders. However, little is known about the long-term consequences of fetal asphyxia (FA). For that reason, the present study investigated the long-term effects of FA on motor behavior and dopaminergic circuitry. FA was induced at embryonic day 17 by 75-minute clamping of the uterine circulation. SHAM animals underwent the same procedure except for the clamping. This was followed by full-term vaginal delivery of animals in all groups (FA, SHAM and untreated controls). At 6 months, basal and amphetamine-induced locomotor activity was measured during open field testing. Brain sections were stained for tyrosine hydroxylase (TH) and glial fibrillary acidic protein (GFAP). TH-positive cells and GFAP-positive cells in substantia nigra pars compacta (SN(C)) and striatum were counted using design-based stereology. Moreover, TH-immunoreactivity in the striatum was assessed by grey value measurements. Behavioral analysis demonstrated that SHAM and FA showed less basal and amphetamine-induced activity than controls. Histochemically, FA decreased the number of TH-positive neurons in the SN(C) and lowered TH-positive in the striatum. Furthermore, more GFAP-positive cells were found in the SN(C) and striatum in FA than in either control and SHAM groups. Additionally, FA animals showed ventriculomegaly associated with smaller white matter as well as grey matter volumes. The data show that FA was associated with deficits in both dopamine-related motor behavior and biochemistry. These alterations were associated with nigrostriatal astrogliosis. The present study demonstrates the sensitivity of the dopaminergic system towards FA.
-
Puelles, Victor G.; Douglas-Denton, Rebecca N.; Cullen-McEwen, Luise A.; Li, Jinhua; Hughson, Michael D.; Hoy, Wendy E.; Kerr, Peter G.
2015-01-01
Increases in glomerular size occur with normal body growth and in many pathologic conditions. In this study, we determined associations between glomerular size and numbers of glomerular resident cells, with a particular focus on podocytes. Kidneys from 16 male Caucasian-Americans without overt renal disease, including 4 children (≤3 years old) to define baseline values of early life and 12 adults (≥18 years old), were collected at autopsy in Jackson, Mississippi. We used a combination of immunohistochemistry, confocal microscopy, and design-based stereology to estimate individual glomerular volume (IGV) and numbers of podocytes, nonepithelial cells (NECs; tuft cells other than podocytes), and parietal epithelial cells (PECs). Podocyte density was calculated. Data are reported as medians and interquartile ranges (IQRs). Glomeruli from children were small and contained 452 podocytes (IQR=335–502), 389 NECs (IQR=265–498), and 146 PECs (IQR=111–206). Adult glomeruli contained significantly more cells than glomeruli from children, including 558 podocytes (IQR=431–746; P<0.01), 1383 NECs (IQR=998–2042; P<0.001), and 367 PECs (IQR=309–673; P<0.001). However, large adult glomeruli showed markedly lower podocyte density (183 podocytes per 106 µm3) than small glomeruli from adults and children (932 podocytes per 106 µm3; P<0.001). In conclusion, large adult glomeruli contained more podocytes than small glomeruli from children and adults, raising questions about the origin of these podocytes. The increased number of podocytes in large glomeruli does not match the increase in glomerular size observed in adults, resulting in relative podocyte depletion. This may render hypertrophic glomeruli susceptible to pathology. PMID:25568174
-
Atochina-Vasserman, Elena N.; Massa, Christopher B.; Birkelbach, Bastian; Guo, Chang-Jiang; Scott, Pamela; Haenni, Beat; Beers, Michael F.; Ochs, Matthias; Gow, Andrew J.
2015-01-01
Surfactant protein D (SP-D) modulates the lung's immune system. Its absence leads to NOS2-independent alveolar lipoproteinosis and NOS2-dependent chronic inflammation, which is critical for early emphysematous remodeling. With aging, SP-D knockout mice develop an additional interstitial fibrotic component. We hypothesize that this age-related interstitial septal wall remodeling is mediated by NOS2. Using invasive pulmonary function testing such as the forced oscillation technique and quasistatic pressure-volume perturbation and design-based stereology, we compared 29-wk-old SP-D knockout (Sftpd−/−) mice, SP-D/NOS2 double-knockout (DiNOS) mice, and wild-type mice (WT). Structural changes, including alveolar epithelial surface area, distribution of septal wall thickness, and volumes of septal wall components (alveolar epithelium, interstitial tissue, and endothelium) were quantified. Twenty-nine-week-old Sftpd−/− mice had preserved lung mechanics at the organ level, whereas elastance was increased in DiNOS. Airspace enlargement and loss of surface area of alveolar epithelium coexist with increased septal wall thickness in Sftpd−/− mice. These changes were reduced in DiNOS, and compared with Sftpd−/− mice a decrease in volumes of interstitial tissue and alveolar epithelium was found. To understand the effects of lung pathology on measured lung mechanics, structural data were used to inform a computational model, simulating lung mechanics as a function of airspace derecruitment, septal wall destruction (loss of surface area), and septal wall thickening. In conclusion, NOS2 mediates remodeling of septal walls, resulting in deposition of interstitial tissue in Sftpd−/−. Forward modeling linking structure and lung mechanics describes the complex mechanical properties by parenchymatous destruction (emphysema), interstitial remodeling (septal wall thickening), and altered recruitability of acinar airspaces. PMID:26320150
-
Ladd, Aliny A B Lobo; Ladd, Fernando V Lobo; da Silva, Andrea A P; Oliveira, Moacir F; de Souza, Romeu R; Coppi, Antonio A
2012-04-01
Whilst a fall in neuron numbers seems a common pattern during postnatal development, several authors have nonetheless reported an increase in neuron number, which may be associated with any one of a number of possible processes encapsulating either neurogenesis or late maturation and incomplete differentiation. Recent publications have thus added further fuel to the notion that a postnatal neurogenesis may indeed exist in sympathetic ganglia. In the light of these uncertainties surrounding the effects exerted by postnatal development on the number of superior cervical ganglion (SCG) neurons, we have used state-of-the-art design-based stereology to investigate the quantitative structure of SCG at four distinct timepoints after birth, viz., 1-3 days, 1 month, 12 months and 36 months. The main effects exerted by ageing on the SCG structure were: (i) a 77% increase in ganglion volume; (ii) stability in the total number of the whole population of SCG nerve cells (no change--either increase or decrease) during post-natal development; (iii) a higher proportion of uninucleate neurons to binucleate neurons only in newborn animals; (iv) a 130% increase in the volume of uninucleate cell bodies; and (v) the presence of BrdU positive neurons in animals at all ages. At the time of writing our results support the idea that neurogenesis takes place in the SCG of preás, albeit it warrants confirmation by further markers. We also hypothesise that a portfolio of other mechanisms: cell repair, maturation, differentiation and death may be equally intertwined and implicated in the numerical stability of SCG neurons during postnatal development. Copyright © 2011 ISDN. Published by Elsevier Ltd. All rights reserved.
-
NASA Technical Reports Server (NTRS)
Olds, John Robert; Walberg, Gerald D.
1993-01-01
Multidisciplinary design optimization (MDO) is an emerging discipline within aerospace engineering. Its goal is to bring structure and efficiency to the complex design process associated with advanced aerospace launch vehicles. Aerospace vehicles generally require input from a variety of traditional aerospace disciplines - aerodynamics, structures, performance, etc. As such, traditional optimization methods cannot always be applied. Several multidisciplinary techniques and methods were proposed as potentially applicable to this class of design problem. Among the candidate options are calculus-based (or gradient-based) optimization schemes and parametric schemes based on design of experiments theory. A brief overview of several applicable multidisciplinary design optimization methods is included. Methods from the calculus-based class and the parametric class are reviewed, but the research application reported focuses on methods from the parametric class. A vehicle of current interest was chosen as a test application for this research. The rocket-based combined-cycle (RBCC) single-stage-to-orbit (SSTO) launch vehicle combines elements of rocket and airbreathing propulsion in an attempt to produce an attractive option for launching medium sized payloads into low earth orbit. The RBCC SSTO presents a particularly difficult problem for traditional one-variable-at-a-time optimization methods because of the lack of an adequate experience base and the highly coupled nature of the design variables. MDO, however, with it's structured approach to design, is well suited to this problem. The result of the application of Taguchi methods, central composite designs, and response surface methods to the design optimization of the RBCC SSTO are presented. Attention is given to the aspect of Taguchi methods that attempts to locate a 'robust' design - that is, a design that is least sensitive to uncontrollable influences on the design. Near-optimum minimum dry weight solutions are determined for the vehicle. A summary and evaluation of the various parametric MDO methods employed in the research are included. Recommendations for additional research are provided.
-
NASA Technical Reports Server (NTRS)
Zang, Thomas A.; Hemsch, Michael J.; Hilburger, Mark W.; Kenny, Sean P; Luckring, James M.; Maghami, Peiman; Padula, Sharon L.; Stroud, W. Jefferson
2002-01-01
This report consists of a survey of the state of the art in uncertainty-based design together with recommendations for a Base research activity in this area for the NASA Langley Research Center. This report identifies the needs and opportunities for computational and experimental methods that provide accurate, efficient solutions to nondeterministic multidisciplinary aerospace vehicle design problems. Barriers to the adoption of uncertainty-based design methods are identified. and the benefits of the use of such methods are explained. Particular research needs are listed.
-
NASA Astrophysics Data System (ADS)
Sun, Li; Wang, Deyu
2011-09-01
A new multi-level analysis method of introducing the super-element modeling method, derived from the multi-level analysis method first proposed by O. F. Hughes, has been proposed in this paper to solve the problem of high time cost in adopting a rational-based optimal design method for ship structural design. Furthermore, the method was verified by its effective application in optimization of the mid-ship section of a container ship. A full 3-D FEM model of a ship, suffering static and quasi-static loads, was used as the analyzing object for evaluating the structural performance of the mid-ship module, including static strength and buckling performance. Research results reveal that this new method could substantially reduce the computational cost of the rational-based optimization problem without decreasing its accuracy, which increases the feasibility and economic efficiency of using a rational-based optimal design method in ship structural design.
-
Sperm Flagellum Volume Determines Freezability in Red Deer Spermatozoa
Ros-Santaella, José Luis; Domínguez-Rebolledo, Álvaro Efrén; Garde, José Julián
2014-01-01
The factors affecting the inter-individual differences in sperm freezability is a major line of research in spermatology. Poor sperm freezability is mainly characterised by a low sperm velocity, which in turn is associated with low fertility rates in most animal species. Studies concerning the implications of sperm morphometry on freezability are quite limited, and most of them are based on sperm head size regardless of the structural parts of the flagellum, which provides sperm motility. Here, for the first time, we determined the volumes of the flagellum structures in fresh epididymal red deer spermatozoa using a stereological method under phase contrast microscopy. Sperm samples from thirty-three stags were frozen and classified as good freezers (GF) or bad freezers (BF) at two hours post-thawing using three sperm kinetic parameters which are strongly correlated with fertility in this species. Fourteen stags were clearly identified as GF, whereas nineteen were BF. No significant difference in sperm head size between the two groups was found. On the contrary, the GF exhibited a lower principal piece volume than the BF (6.13 µm3 vs 6.61 µm3, respectively, p = 0.006). The volume of the flagellum structures showed a strong negative relationship with post-thawing sperm velocity. For instance, the volume of the sperm principal piece was negatively correlated with sperm velocity at two hours post-thawing (r = −0.60; p<0.001). Our results clearly show that a higher volume of the sperm principal piece results in poor freezability, and highlights the key role of flagellum size in sperm cryopreservation success. PMID:25380133
-
Stiffness Parameter Design of Suspension Element of Under-Chassis-Equipment for A Rail Vehicle
NASA Astrophysics Data System (ADS)
Ma, Menglin; Wang, Chengqiang; Deng, Hai
2017-06-01
According to the frequency configuration requirements of the vibration of railway under-chassis-equipment, the three- dimension stiffness of the suspension elements of under-chassis-equipment is designed based on the static principle and dynamics principle. The design results of the concrete engineering case show that, compared with the design method based on the static principle, the three- dimension stiffness of the suspension elements designed by the dynamic principle design method is more uniform. The frequency and decoupling degree analysis show that the calculation frequency of under-chassis-equipment under the two design methods is basically the same as the predetermined frequency. Compared with the design method based on the static principle, the design method based on the dynamic principle is adopted. The decoupling degree can be kept high, and the coupling vibration of the corresponding vibration mode can be reduced effectively, which can effectively reduce the fatigue damage of the key parts of the hanging element.
-
Integrating structure-based and ligand-based approaches for computational drug design.
Wilson, Gregory L; Lill, Markus A
2011-04-01
Methods utilized in computer-aided drug design can be classified into two major categories: structure based and ligand based, using information on the structure of the protein or on the biological and physicochemical properties of bound ligands, respectively. In recent years there has been a trend towards integrating these two methods in order to enhance the reliability and efficiency of computer-aided drug-design approaches by combining information from both the ligand and the protein. This trend resulted in a variety of methods that include: pseudoreceptor methods, pharmacophore methods, fingerprint methods and approaches integrating docking with similarity-based methods. In this article, we will describe the concepts behind each method and selected applications.
-
NASA Technical Reports Server (NTRS)
Butler, J. P.; Mair, R. W.; Hoffmann, D.; Hrovat, M. I.; Rogers, R. A.; Topulos, G. P.; Walsworth, R. L.; Patz, S.
2002-01-01
We demonstrate a minimally invasive nuclear magnetic resonance (NMR) technique that enables determination of the surface-area-to-volume ratio (S/V) of soft porous materials from measurements of the diffusive exchange of laser-polarized 129Xe between gas in the pore space and 129Xe dissolved in the solid phase. We apply this NMR technique to porous polymer samples and find approximate agreement with destructive stereological measurements of S/V obtained with optical confocal microscopy. Potential applications of laser-polarized xenon interphase exchange NMR include measurements of in vivo lung function in humans and characterization of gas chromatography columns.
-
Stereo imaging with spaceborne radars
NASA Technical Reports Server (NTRS)
Leberl, F.; Kobrick, M.
1983-01-01
Stereo viewing is a valuable tool in photointerpretation and is used for the quantitative reconstruction of the three dimensional shape of a topographical surface. Stereo viewing refers to a visual perception of space by presenting an overlapping image pair to an observer so that a three dimensional model is formed in the brain. Some of the observer's function is performed by machine correlation of the overlapping images - so called automated stereo correlation. The direct perception of space with two eyes is often called natural binocular vision; techniques of generating three dimensional models of the surface from two sets of monocular image measurements is the topic of stereology.
-
Kosiba, Graham D.; Wixom, Ryan R.; Oehlschlaeger, Matthew A.
2017-10-27
Image processing and stereological techniques were used to characterize the heterogeneity of composite propellant and inform a predictive burn rate model. Composite propellant samples made up of ammonium perchlorate (AP), hydroxyl-terminated polybutadiene (HTPB), and aluminum (Al) were faced with an ion mill and imaged with a scanning electron microscope (SEM) and x-ray tomography (micro-CT). Properties of both the bulk and individual components of the composite propellant were determined from a variety of image processing tools. An algebraic model, based on the improved Beckstead-Derr-Price model developed by Cohen and Strand, was used to predict the steady-state burning of the aluminized compositemore » propellant. In the presented model the presence of aluminum particles within the propellant was introduced. The thermal effects of aluminum particles are accounted for at the solid-gas propellant surface interface and aluminum combustion is considered in the gas phase using a single global reaction. In conclusion, properties derived from image processing were used directly as model inputs, leading to a sample-specific predictive combustion model.« less
-
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kosiba, Graham D.; Wixom, Ryan R.; Oehlschlaeger, Matthew A.
Image processing and stereological techniques were used to characterize the heterogeneity of composite propellant and inform a predictive burn rate model. Composite propellant samples made up of ammonium perchlorate (AP), hydroxyl-terminated polybutadiene (HTPB), and aluminum (Al) were faced with an ion mill and imaged with a scanning electron microscope (SEM) and x-ray tomography (micro-CT). Properties of both the bulk and individual components of the composite propellant were determined from a variety of image processing tools. An algebraic model, based on the improved Beckstead-Derr-Price model developed by Cohen and Strand, was used to predict the steady-state burning of the aluminized compositemore » propellant. In the presented model the presence of aluminum particles within the propellant was introduced. The thermal effects of aluminum particles are accounted for at the solid-gas propellant surface interface and aluminum combustion is considered in the gas phase using a single global reaction. In conclusion, properties derived from image processing were used directly as model inputs, leading to a sample-specific predictive combustion model.« less
-
Computational Methods in Drug Discovery
Sliwoski, Gregory; Kothiwale, Sandeepkumar; Meiler, Jens
2014-01-01
Computer-aided drug discovery/design methods have played a major role in the development of therapeutically important small molecules for over three decades. These methods are broadly classified as either structure-based or ligand-based methods. Structure-based methods are in principle analogous to high-throughput screening in that both target and ligand structure information is imperative. Structure-based approaches include ligand docking, pharmacophore, and ligand design methods. The article discusses theory behind the most important methods and recent successful applications. Ligand-based methods use only ligand information for predicting activity depending on its similarity/dissimilarity to previously known active ligands. We review widely used ligand-based methods such as ligand-based pharmacophores, molecular descriptors, and quantitative structure-activity relationships. In addition, important tools such as target/ligand data bases, homology modeling, ligand fingerprint methods, etc., necessary for successful implementation of various computer-aided drug discovery/design methods in a drug discovery campaign are discussed. Finally, computational methods for toxicity prediction and optimization for favorable physiologic properties are discussed with successful examples from literature. PMID:24381236
-
Bae, Kyongtae T; Tao, Cheng; Wang, Jinhong; Kaya, Diana; Wu, Zhiyuan; Bae, Junu T; Chapman, Arlene B; Torres, Vicente E; Grantham, Jared J; Mrug, Michal; Bennett, William M; Flessner, Michael F; Landsittel, Doug P
2013-01-01
Objective To evaluate whether kidney and cyst volumes can be accurately estimated based on limited area measurements from MR images of patients with autosomal dominant polycystic kidney disease (ADPKD). Materials and Methods MR coronal images of 178 ADPKD participants from the Consortium for Radiologic Imaging Studies of ADPKD (CRISP) were analyzed. For each MR image slice, we measured kidney and renal cyst areas using stereology and region-based thresholding methods, respectively. The kidney and cyst ‘observed’ volumes were calculated by summing up the area measurements of all the slices covering the kidney. To estimate the volume, we selected a coronal mid-slice in each kidney and multiplied its area by the total number of slices (‘PANK2’ for kidney and ‘PANC2’ for cyst). We then compared the kidney and cyst volumes predicted from PANK2 and PANC2, respectively, to the corresponding observed volumes, using a linear regression analysis. Results The kidney volume predicted from PANK2 correlated extremely well with the observed kidney volume: R2=0.994 for right and 0.991 for left kidney. The linear regression coefficient multiplier to PANK2 that best fit the kidney volume was 0.637 (95%CI: 0.629–0.644) for right and 0.624 (95%CI: 0.616–0.633) for left kidney. The correlation between the cyst volume predicted from PANC2 and the observed cyst volume was also very high: R2=0.984 for right and 0.967 for left kidney. The least squares linear regression coefficient for PANC2 was 0.637 (95%CI: 0.624–0.649) for right and 0.608 (95%CI: 0.591–0.625) for left kidney. Conclusion Kidney and cyst volumes can be closely approximated by multiplying the product of the mid-slice area measurement and the total number of slices in the coronal MR images of ADPKD kidneys by 0.61–0.64. This information will help save processing time needed to estimate total kidney and cyst volumes of ADPKD kidneys. PMID:24107679
-
Green design assessment of electromechanical products based on group weighted-AHP
NASA Astrophysics Data System (ADS)
Guo, Jinwei; Zhou, MengChu; Li, Zhiwu; Xie, Huiguang
2015-11-01
Manufacturing industry is the backbone of a country's economy while environmental pollution is a serious problem that human beings must face today. The green design of electromechanical products based on enterprise information systems is an important method to solve the environmental problem. The question on how to design green products must be answered by excellent designers via both advanced design methods and effective assessment methods of electromechanical products. Making an objective and precise assessment of green design is one of the problems that must be solved when green design is conducted. An assessment method of green design on electromechanical products based on Group Weighted-AHP (Analytic Hierarchy Process) is proposed in this paper, together with the characteristics of green products. The assessment steps of green design are also established. The results are illustrated via the assessment of a refrigerator design.
-
An XML-based method for astronomy software designing
NASA Astrophysics Data System (ADS)
Liao, Mingxue; Aili, Yusupu; Zhang, Jin
XML-based method for standardization of software designing is introduced and analyzed and successfully applied to renovating the hardware and software of the digital clock at Urumqi Astronomical Station. Basic strategy for eliciting time information from the new digital clock of FT206 in the antenna control program is introduced. By FT206, the need to compute how many centuries passed since a certain day with sophisticated formulas is eliminated and it is no longer necessary to set right UT time for the computer holding control over antenna because the information about year, month, day are all deduced from Julian day dwelling in FT206, rather than from computer time. With XML-based method and standard for software designing, various existing designing methods are unified, communications and collaborations between developers are facilitated, and thus Internet-based mode of developing software becomes possible. The trend of development of XML-based designing method is predicted.
-
Intelligent design of permanent magnet synchronous motor based on CBR
NASA Astrophysics Data System (ADS)
Li, Cong; Fan, Beibei
2018-05-01
Aiming at many problems in the design process of Permanent magnet synchronous motor (PMSM), such as the complexity of design process, the over reliance on designers' experience and the lack of accumulation and inheritance of design knowledge, a design method of PMSM Based on CBR is proposed in order to solve those problems. In this paper, case-based reasoning (CBR) methods of cases similarity calculation is proposed for reasoning suitable initial scheme. This method could help designers, by referencing previous design cases, to make a conceptual PMSM solution quickly. The case retain process gives the system self-enrich function which will improve the design ability of the system with the continuous use of the system.
-
Estimation of the brain stem volume by stereological method on magnetic resonance imaging.
Erbagci, Hulya; Keser, Munevver; Kervancioglu, Selim; Kizilkan, Nese
2012-11-01
Neuron loss that occurs in some neurodegenerative diseases can lead to volume alterations by causing atrophy in the brain stem. The aim of this study was to determine the brain stem volume and the volume ratio of the brain stem to total brain volume related to gender and age using new Stereo Investigator system in normal subjects. For this purpose, MR images of 72 individuals who have no pathologic condition were evaluated. The total brain volumes of female and male were calculated as 966.81 ± 77.44 and 1,074.06 ± 111.75 cm3, respectively. Brain stem volumes of female and male were determined as 18.99 ± 2.36 and 22.05 ± 4.01 cm3, respectively. The ratios of brain stem volume to total brain volume were 1.96 ± 0.17 in female and 2.05 ± 0.29 in male. The total brain and brain stem volumes were observed smaller in female and it is statistically significant. Among the individuals whose ages are between 20 and 40, total brain and brain stem volume measurements with aging were not statistically significant. As a result, we believe that the measurement of brain stem volume with an objective and efficient calculation method will contribute to the early diagnosis of neurodegenerative diseases, as well as to determine the rate of disease progression, and the outcomes of treatment.
-
Systematic random sampling of the comet assay.
McArt, Darragh G; Wasson, Gillian R; McKerr, George; Saetzler, Kurt; Reed, Matt; Howard, C Vyvyan
2009-07-01
The comet assay is a technique used to quantify DNA damage and repair at a cellular level. In the assay, cells are embedded in agarose and the cellular content is stripped away leaving only the DNA trapped in an agarose cavity which can then be electrophoresed. The damaged DNA can enter the agarose and migrate while the undamaged DNA cannot and is retained. DNA damage is measured as the proportion of the migratory 'tail' DNA compared to the total DNA in the cell. The fundamental basis of these arbitrary values is obtained in the comet acquisition phase using fluorescence microscopy with a stoichiometric stain in tandem with image analysis software. Current methods deployed in such an acquisition are expected to be both objectively and randomly obtained. In this paper we examine the 'randomness' of the acquisition phase and suggest an alternative method that offers both objective and unbiased comet selection. In order to achieve this, we have adopted a survey sampling approach widely used in stereology, which offers a method of systematic random sampling (SRS). This is desirable as it offers an impartial and reproducible method of comet analysis that can be used both manually or automated. By making use of an unbiased sampling frame and using microscope verniers, we are able to increase the precision of estimates of DNA damage. Results obtained from a multiple-user pooled variation experiment showed that the SRS technique attained a lower variability than that of the traditional approach. The analysis of a single user with repetition experiment showed greater individual variances while not being detrimental to overall averages. This would suggest that the SRS method offers a better reflection of DNA damage for a given slide and also offers better user reproducibility.
-
A new design approach to MMI-based (de)multiplexers
NASA Astrophysics Data System (ADS)
Yueyu, Xiao; Sailing, He
2004-09-01
A novel design method of the wavelength (de)multiplexer is presented. The output spectral response of a (de)multiplexer is designed from the view of FIR filters. Avoiding laborious mathematic analysis, the (de)multiplexer is analyzed and designed in this explicit and simple method. A four channel (de)multiplexer based on multimode interference (MMI) is designed as an example. The result obtained agrees with that of the commonly used method, and is verified by a finite difference beam propagation method (FDBPM) simulation.
-
NASA Astrophysics Data System (ADS)
Mooney, Robin P.; McFadden, Shaun
2017-12-01
In-situ observation of crystal growth in transparent media allows us to observe solidification phase change in real-time. These systems are analogous to opaque systems such as metals. The interpretation of transient 2-dimensional area projections from 3-dimensional phase change phenomena occurring in a bulky sample is problematic due to uncertainty of impingement and hidden nucleation events; in stereology this problem is known as over-projection. This manuscript describes and demonstrates a continuous model for nucleation and growth using the well-established Johnson-Mehl-Avrami-Kolmogorov model, and provides a method to relate 3-dimensional volumetric data (nucleation events, volume fraction) to observed data in a 2-dimensional projection (nucleation count, area fraction). A parametric analysis is performed; the projection phenomenon is shown to be significant in cases where nucleation is occurring continuously with a relatively large variance. In general, area fraction on a projection plane will overestimate the volume fraction within the sample and the nuclei count recorded on the projection plane will underestimate the number of real nucleation events. The statistical framework given in this manuscript provides a methodology to deal with the differences between the observed (projected) data and the real (volumetric) measures.
-
Mueller matrix polarimetry on plasma sprayed thermal barrier coatings for porosity measurement.
Luo, David A; Barraza, Enrique T; Kudenov, Michael W
2017-12-10
Yttria-stabilized zirconia (YSZ) is the most widely used material for thermal plasma sprayed thermal barrier coatings (TBCs) used to protect gas turbine engine parts in demanding operation environments. The superior material properties of YSZ coatings are related to their internal porosity level. By quantifying the porosity level, tighter control on the spraying process can be achieved to produce reliable coatings. Currently, destructive measurement methods are widely used to measure the porosity level. In this paper, we describe a novel nondestructive approach that is applicable to classify the porosity level of plasma sprayed YSZ TBCs via Mueller matrix polarimetry. A rotating retarder Mueller matrix polarimeter was used to measure the polarization properties of the plasma sprayed YSZ coatings with different porosity levels. From these measurements, it was determined that a sample's measured depolarization ratio is dependent on the sample's surface roughness and porosity level. To this end, we correlate the depolarization ratio with the samples' surface roughness, as measured by a contact profilometer, as well as the total porosity level, in percentage measured using a micrograph and stereological analysis. With the use of this technique, a full-field and rapid measurement of porosity level can be achieved.
-
Raghanti, Mary Ann; Edler, Melissa K; Meindl, Richard S; Sudduth, Jessica; Bohush, Tatiana; Erwin, Joseph M; Stimpson, Cheryl D; Hof, Patrick R; Sherwood, Chet C
2014-01-01
Neuropeptide Y (NPY) plays a role in a variety of basic physiological functions and has also been implicated in regulating cognition, including learning and memory. A decrease in neocortical NPY has been reported for Alzheimer's disease, schizophrenia, bipolar disorder, and depression, potentially contributing to associated cognitive deficits. The goal of the present analysis was to examine variation in neocortical NPY-immunoreactive axon and varicosity density among haplorhine primates (monkeys, apes, and humans). Stereologic methods were used to measure the ratios of NPY-expressing axon length density to total neuron density (ALv/Nv) and NPY-immunoreactive varicosity density to neuron density (Vv/Nv), as well as the mean varicosity spacing in neocortical areas 10, 24, 44, and 22 (Tpt) of humans, African great apes, New World monkeys, and Old World monkeys. Humans and great apes showed increased cortical NPY innervation relative to monkey species for ALv/Nv and Vv/Nv. Furthermore, humans and great apes displayed a conserved pattern of varicosity spacing across cortical areas and layers, with no differences between cortical layers or among cortical areas. These phylogenetic differences may be related to shared life history variables and may reflect specific cognitive abilities.
-
Quantification of idiopathic pulmonary fibrosis using computed tomography and histology.
Coxson, H O; Hogg, J C; Mayo, J R; Behzad, H; Whittall, K P; Schwartz, D A; Hartley, P G; Galvin, J R; Wilson, J S; Hunninghake, G W
1997-05-01
We used computed tomography (CT) and histologic analysis to quantify lung structure in idiopathic pulmonary fibrosis (IPF). CT scans were obtained from IPF and control patients and lung volumes were estimated from measurements of voxel size, and X-ray attenuation values of each voxel. Quantitative estimates of lung structure were obtained from biopsies obtained from diseased and normal CT regions using stereologic methods. CT density was used to calculate the proportion of tissue and air, and this value was used to correct the biopsy specimens to the level of inflation during the CT scan. The data show that IPF is associated with a reduction in airspace volume with no change in tissue volume or weight compared with control lungs. Lung surface area decreased two-thirds (p < 0.001) and mean parenchymal thickness increased tenfold (p < 0.001). An exudate of fluid and cells was present in the airspace of the diseased lung regions and the number of inflammatory cells, collagen, and proteoglycans was increased per 100 g of tissue in IPF. We conclude that IPF reorganized lung tissue content causing a loss of airspace and surface area without increasing the total lung tissue.
-
Population control of resident and immigrant microglia by mitosis and apoptosis.
Wirenfeldt, Martin; Dissing-Olesen, Lasse; Anne Babcock, Alicia; Nielsen, Marianne; Meldgaard, Michael; Zimmer, Jens; Azcoitia, Iñigo; Leslie, Robert Graham Quinton; Dagnaes-Hansen, Frederik; Finsen, Bente
2007-08-01
Microglial population expansion occurs in response to neural damage via processes that involve mitosis and immigration of bone marrow-derived cells. However, little is known of the mechanisms that regulate clearance of reactive microglia, when microgliosis diminishes days to weeks later. We have investigated the mechanisms of microglial population control in a well-defined model of reactive microgliosis in the mouse dentate gyrus after perforant pathway axonal lesion. Unbiased stereological methods and flow cytometry demonstrate significant lesion-induced increases in microglial numbers. Reactive microglia often occurred in clusters, some having recently incorporated bromodeoxyuridine, showing that proliferation had occurred. Annexin V labeling and staining for activated caspase-3 and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling showed that apoptotic mechanisms participate in dissolution of the microglial response. Using bone marrow chimeric mice, we found that the lesion-induced proliferative capacity of resident microglia superseded that of immigrant microglia, whereas lesion-induced kinetics of apoptosis were comparable. Microglial numbers and responses were severely reduced in bone marrow chimeric mice. These results broaden our understanding of the microglial response to neural damage by demonstrating that simultaneously occurring mitosis and apoptosis regulate expansion and reduction of both resident and immigrant microglial cell populations.
-
Effects of Aging on Hippocampal Neurogenesis After Irradiation
DOE Office of Scientific and Technical Information (OSTI.GOV)
Cheng, Zoey; Institute of Medical Science, University of Toronto, Toronto, Ontario; Li, Yu-Qing
Purpose: To assess the influence of aging on hippocampal neuronal development after irradiation (IR). Methods and Materials: Male mice, 2, 4, 6, 12, and 18 months of age, were given a single dose of 0 or 5 Gy of IR. A bromodeoxyuridine (BrdU) incorporation study was used to label newborn cells. Neural progenitors, newborn neurons, and microglia in dentate gyrus (DG) were identified by phenotypic markers, and their numbers were quantified by nonbiased stereology 9 weeks after IR. Results: BrdU-positive or newborn cells in DG decreased with aging and after IR. The number of neuroblasts and newborn neurons decreased with aging, and amore » further significant reduction was observed after IR. Total type 1 cells (the putative neural stem cells), and newborn type 1 cells decreased with aging, and further reduction in total type 1 cells was observed after IR. Aging-associated activation of microglia in hippocampus was enhanced after IR. Conclusions: The aging-associated decline in hippocampal neurogenesis was further inhibited after IR. Ablation of neural progenitors and activation of microglia may contribute to the inhibition of neuronal development after IR across all ages.« less
-
Fernandes, Marisa Narciso; da Cruz, André Luis; da Costa, Oscar Tadeu Ferreira; Perry, Steven Franklin
2012-09-01
The gills and the respiratory swim bladders of juvenile specimens (mean body mass 100g) of the basal teleost Arapaima gigas (Cuvier 1829) were evaluated using stereological methods in vertical sections. The surface areas, harmonic mean barrier thicknesses and morphometric diffusing capacities for oxygen and carbon dioxide were estimated. The average respiratory surface area of the swim bladder (2173 cm² kg⁻¹) exceeded that of the gills (780 cm² kg⁻¹) by a factor of 2.79. Due to the extremely thin air-blood barrier in the swim bladder (harmonic mean 0.22 μm) and the much thicker water-blood barrier of the gills (9.61 μm), the morphometric diffusing capacity for oxygen and carbon dioxide was 88 times greater in the swim bladder than in the gills. These data clearly indicate the importance of the swim bladder, even in juvenile A. gigas that still engage in aquatic respiration. Because of the much greater diffusion constant of CO₂ than O₂ in water, the gills also remain important for CO₂ release. Copyright © 2012 Elsevier Ltd. All rights reserved.
-
da Cruz, André Luis; Fernandes, Marisa Narciso
2016-12-01
The purpose of the present study was to evaluate the morphometric respiratory potential of gills compared to the stomach in obtaining oxygen for aerobic metabolism in Pterygoplichthys anisitsi, a facultative air-breathing fish. The measurements were done using stereological methods. The gills showed greater total volume, volume-to-body mass ratio, potential surface area, and surface-to-volume ratio than the stomach. The water-blood diffusion barrier of the gills is thicker than the air-blood diffusion barrier of the stomach. Taken together, the surface area, the surface-to-volume ratio and the diffusion distance for O 2 transfer from the respiratory medium to blood yield a greater diffusing capacity for gills than for the stomach, suggesting greater importance of aquatic respiration in this species. On the other hand, water breathing is energetically more expensive than breathing air. Under severe hypoxic conditions, O 2 uptake by the stomach is more efficient than by the gills, although the stomach has a much lower diffusing capacity. Thus, P. anisitsi uses gills under normoxic conditions but the stomach may also support aerobic metabolism depending on environmental conditions. Copyright © 2016 Elsevier GmbH. All rights reserved.
-
Innovating Method of Existing Mechanical Product Based on TRIZ Theory
NASA Astrophysics Data System (ADS)
Zhao, Cunyou; Shi, Dongyan; Wu, Han
Main way of product development is adaptive design and variant design based on existing product. In this paper, conceptual design frame and its flow model of innovating products is put forward through combining the methods of conceptual design and TRIZ theory. Process system model of innovating design that includes requirement analysis, total function analysis and decomposing, engineering problem analysis, finding solution of engineering problem and primarily design is constructed and this establishes the base for innovating design of existing product.
-
A New Automated Design Method Based on Machine Learning for CMOS Analog Circuits
NASA Astrophysics Data System (ADS)
Moradi, Behzad; Mirzaei, Abdolreza
2016-11-01
A new simulation based automated CMOS analog circuit design method which applies a multi-objective non-Darwinian-type evolutionary algorithm based on Learnable Evolution Model (LEM) is proposed in this article. The multi-objective property of this automated design of CMOS analog circuits is governed by a modified Strength Pareto Evolutionary Algorithm (SPEA) incorporated in the LEM algorithm presented here. LEM includes a machine learning method such as the decision trees that makes a distinction between high- and low-fitness areas in the design space. The learning process can detect the right directions of the evolution and lead to high steps in the evolution of the individuals. The learning phase shortens the evolution process and makes remarkable reduction in the number of individual evaluations. The expert designer's knowledge on circuit is applied in the design process in order to reduce the design space as well as the design time. The circuit evaluation is made by HSPICE simulator. In order to improve the design accuracy, bsim3v3 CMOS transistor model is adopted in this proposed design method. This proposed design method is tested on three different operational amplifier circuits. The performance of this proposed design method is verified by comparing it with the evolutionary strategy algorithm and other similar methods.
-
Enhanced learning through design problems - teaching a components-based course through design
NASA Astrophysics Data System (ADS)
Jensen, Bogi Bech; Högberg, Stig; Fløtum Jensen, Frida av; Mijatovic, Nenad
2012-08-01
This paper describes a teaching method used in an electrical machines course, where the students learn about electrical machines by designing them. The aim of the course is not to teach design, albeit this is a side product, but rather to teach the fundamentals and the function of electrical machines through design. The teaching method is evaluated by a student questionnaire, designed to measure the quality and effectiveness of the teaching method. The results of the questionnaire conclusively show that this method labelled 'learning through design' is a very effective way of teaching a components-based course. This teaching method can easily be generalised and used in other courses.
-
An overview of very high level software design methods
NASA Technical Reports Server (NTRS)
Asdjodi, Maryam; Hooper, James W.
1988-01-01
Very High Level design methods emphasize automatic transfer of requirements to formal design specifications, and/or may concentrate on automatic transformation of formal design specifications that include some semantic information of the system into machine executable form. Very high level design methods range from general domain independent methods to approaches implementable for specific applications or domains. Applying AI techniques, abstract programming methods, domain heuristics, software engineering tools, library-based programming and other methods different approaches for higher level software design are being developed. Though one finds that a given approach does not always fall exactly in any specific class, this paper provides a classification for very high level design methods including examples for each class. These methods are analyzed and compared based on their basic approaches, strengths and feasibility for future expansion toward automatic development of software systems.
-
ERIC Educational Resources Information Center
Kautz, Tim; Schochet, Peter Z.; Tilley, Charles
2017-01-01
A new design-based theory has recently been developed to estimate impacts for randomized controlled trials (RCTs) and basic quasi-experimental designs (QEDs) for a wide range of designs used in social policy research (Imbens & Rubin, 2015; Schochet, 2016). These methods use the potential outcomes framework and known features of study designs…
-
Educating Instructional Designers: Different Methods for Different Outcomes.
ERIC Educational Resources Information Center
Rowland, Gordon; And Others
1994-01-01
Suggests new methods of teaching instructional design based on literature reviews of other design fields including engineering, architecture, interior design, media design, and medicine. Methods discussed include public presentations, visiting experts, competitions, artifacts, case studies, design studios, and internships and apprenticeships.…
-
A decision-based perspective for the design of methods for systems design
NASA Technical Reports Server (NTRS)
Mistree, Farrokh; Muster, Douglas; Shupe, Jon A.; Allen, Janet K.
1989-01-01
Organization of material, a definition of decision based design, a hierarchy of decision based design, the decision support problem technique, a conceptual model design that can be manufactured and maintained, meta-design, computer-based design, action learning, and the characteristics of decisions are among the topics covered.
-
A Rapid Aerodynamic Design Procedure Based on Artificial Neural Networks
NASA Technical Reports Server (NTRS)
Rai, Man Mohan
2001-01-01
An aerodynamic design procedure that uses neural networks to model the functional behavior of the objective function in design space has been developed. This method incorporates several improvements to an earlier method that employed a strategy called parameter-based partitioning of the design space in order to reduce the computational costs associated with design optimization. As with the earlier method, the current method uses a sequence of response surfaces to traverse the design space in search of the optimal solution. The new method yields significant reductions in computational costs by using composite response surfaces with better generalization capabilities and by exploiting synergies between the optimization method and the simulation codes used to generate the training data. These reductions in design optimization costs are demonstrated for a turbine airfoil design study where a generic shape is evolved into an optimal airfoil.
-
Design Tool Using a New Optimization Method Based on a Stochastic Process
NASA Astrophysics Data System (ADS)
Yoshida, Hiroaki; Yamaguchi, Katsuhito; Ishikawa, Yoshio
Conventional optimization methods are based on a deterministic approach since their purpose is to find out an exact solution. However, such methods have initial condition dependence and the risk of falling into local solution. In this paper, we propose a new optimization method based on the concept of path integrals used in quantum mechanics. The method obtains a solution as an expected value (stochastic average) using a stochastic process. The advantages of this method are that it is not affected by initial conditions and does not require techniques based on experiences. We applied the new optimization method to a hang glider design. In this problem, both the hang glider design and its flight trajectory were optimized. The numerical calculation results prove that performance of the method is sufficient for practical use.
-
NASA Astrophysics Data System (ADS)
Wang, Nianfeng; Guo, Hao; Chen, Bicheng; Cui, Chaoyu; Zhang, Xianmin
2018-05-01
Dielectric elastomers (DE), known as electromechanical transducers, have been widely used in the field of sensors, generators, actuators and energy harvesting for decades. A large number of DE actuators including bending actuators, linear actuators and rotational actuators have been designed utilizing an experience design method. This paper proposes a new method for the design of DE actuators by using a topology optimization method based on pairs of curves. First, theoretical modeling and optimization design are discussed, after which a rotary dielectric elastomer actuator has been designed using this optimization method. Finally, experiments and comparisons between several DE actuators have been made to verify the optimized result.
-
A global parallel model based design of experiments method to minimize model output uncertainty.
Bazil, Jason N; Buzzard, Gregory T; Rundell, Ann E
2012-03-01
Model-based experiment design specifies the data to be collected that will most effectively characterize the biological system under study. Existing model-based design of experiment algorithms have primarily relied on Fisher Information Matrix-based methods to choose the best experiment in a sequential manner. However, these are largely local methods that require an initial estimate of the parameter values, which are often highly uncertain, particularly when data is limited. In this paper, we provide an approach to specify an informative sequence of multiple design points (parallel design) that will constrain the dynamical uncertainty of the biological system responses to within experimentally detectable limits as specified by the estimated experimental noise. The method is based upon computationally efficient sparse grids and requires only a bounded uncertain parameter space; it does not rely upon initial parameter estimates. The design sequence emerges through the use of scenario trees with experimental design points chosen to minimize the uncertainty in the predicted dynamics of the measurable responses of the system. The algorithm was illustrated herein using a T cell activation model for three problems that ranged in dimension from 2D to 19D. The results demonstrate that it is possible to extract useful information from a mathematical model where traditional model-based design of experiments approaches most certainly fail. The experiments designed via this method fully constrain the model output dynamics to within experimentally resolvable limits. The method is effective for highly uncertain biological systems characterized by deterministic mathematical models with limited data sets. Also, it is highly modular and can be modified to include a variety of methodologies such as input design and model discrimination.
-
NASA Astrophysics Data System (ADS)
Sizov, Gennadi Y.
In this dissertation, a model-based multi-objective optimal design of permanent magnet ac machines, supplied by sine-wave current regulated drives, is developed and implemented. The design procedure uses an efficient electromagnetic finite element-based solver to accurately model nonlinear material properties and complex geometric shapes associated with magnetic circuit design. Application of an electromagnetic finite element-based solver allows for accurate computation of intricate performance parameters and characteristics. The first contribution of this dissertation is the development of a rapid computational method that allows accurate and efficient exploration of large multi-dimensional design spaces in search of optimum design(s). The computationally efficient finite element-based approach developed in this work provides a framework of tools that allow rapid analysis of synchronous electric machines operating under steady-state conditions. In the developed modeling approach, major steady-state performance parameters such as, winding flux linkages and voltages, average, cogging and ripple torques, stator core flux densities, core losses, efficiencies and saturated machine winding inductances, are calculated with minimum computational effort. In addition, the method includes means for rapid estimation of distributed stator forces and three-dimensional effects of stator and/or rotor skew on the performance of the machine. The second contribution of this dissertation is the development of the design synthesis and optimization method based on a differential evolution algorithm. The approach relies on the developed finite element-based modeling method for electromagnetic analysis and is able to tackle large-scale multi-objective design problems using modest computational resources. Overall, computational time savings of up to two orders of magnitude are achievable, when compared to current and prevalent state-of-the-art methods. These computational savings allow one to expand the optimization problem to achieve more complex and comprehensive design objectives. The method is used in the design process of several interior permanent magnet industrial motors. The presented case studies demonstrate that the developed finite element-based approach practically eliminates the need for using less accurate analytical and lumped parameter equivalent circuit models for electric machine design optimization. The design process and experimental validation of the case-study machines are detailed in the dissertation.
-
Computer Aided Drug Design: Success and Limitations.
Baig, Mohammad Hassan; Ahmad, Khurshid; Roy, Sudeep; Ashraf, Jalaluddin Mohammad; Adil, Mohd; Siddiqui, Mohammad Haris; Khan, Saif; Kamal, Mohammad Amjad; Provazník, Ivo; Choi, Inho
2016-01-01
Over the last few decades, computer-aided drug design has emerged as a powerful technique playing a crucial role in the development of new drug molecules. Structure-based drug design and ligand-based drug design are two methods commonly used in computer-aided drug design. In this article, we discuss the theory behind both methods, as well as their successful applications and limitations. To accomplish this, we reviewed structure based and ligand based virtual screening processes. Molecular dynamics simulation, which has become one of the most influential tool for prediction of the conformation of small molecules and changes in their conformation within the biological target, has also been taken into account. Finally, we discuss the principles and concepts of molecular docking, pharmacophores and other methods used in computer-aided drug design.
-
Diffusion of nitrogen oxides and oxygenated volatile organic compounds through snow
NASA Astrophysics Data System (ADS)
Bartels-Rausch, T.; Ammann, M.; Schneebeli, M.; Riche, F.; Wren, S. N.
2013-12-01
Release of trace gases from surface snow on Earth drives atmospheric chemistry, especially in the Polar Regions. The exchange of atmospheric trace gases between snow or firn and atmosphere can also determine how these species are incorporated into glacial ice, which serves as archive. At low wind conditions, such fluxes between the porous surface snow and the overlaying atmosphere are driven by diffusion through the interstitial air. Here we present results from two laboratory studies where we looked at how the structure of the snowpack, the interaction of the trace gases with the snow surface, and the grain boundaries influence the diffusion of NO, NO2, HONO, methanol, and acetone on time scales up to 1 h. The diffusion through a snow sample was the direct observable of the experiments. Results for different snow types are presented, the structures of which were analysed by means of X-ray computed micro-tomography. Grain boundary content was quantified in one sample using a stereological method. The observed diffusion profiles were very well reproduced in simulations based on gas-phase diffusion and the known structure of the snow sample at temperatures above 253 K. At colder temperatures surface interactions start to dominate the diffusion. Parameterizing these in terms of adsorption to the solid ice surface gave much better agreement to the observations than the use of air - liquid partitioning coefficients. This is a central result as field and modelling studies have indicated that the partitioning to liquid water might describe the diffusion through snow much better even at cold temperatures. This will be discussed using our recent results from surface sensitive spectroscopy experiments. No changes in the diffusion was observed by increasing the number of grain boundaries in the snow sample by a factor of 7.
-
NASA Astrophysics Data System (ADS)
Yoshida, Hiroaki; Yamaguchi, Katsuhito; Ishikawa, Yoshio
The conventional optimization methods were based on a deterministic approach, since their purpose is to find out an exact solution. However, these methods have initial condition dependence and risk of falling into local solution. In this paper, we propose a new optimization method based on a concept of path integral method used in quantum mechanics. The method obtains a solutions as an expected value (stochastic average) using a stochastic process. The advantages of this method are not to be affected by initial conditions and not to need techniques based on experiences. We applied the new optimization method to a design of the hang glider. In this problem, not only the hang glider design but also its flight trajectory were optimized. The numerical calculation results showed that the method has a sufficient performance.
-
[Optimum design of imaging spectrometer based on toroidal uniform-line-spaced (TULS) spectrometer].
Xue, Qing-Sheng; Wang, Shu-Rong
2013-05-01
Based on the geometrical aberration theory, a optimum-design method for designing an imaging spectrometer based on toroidal uniform grating spectrometer is proposed. To obtain the best optical parameters, twice optimization is carried out using genetic algorithm(GA) and optical design software ZEMAX A far-ultraviolet(FUV) imaging spectrometer is designed using this method. The working waveband is 110-180 nm, the slit size is 50 microm x 5 mm, and the numerical aperture is 0.1. Using ZEMAX software, the design result is analyzed and evaluated. The results indicate that the MTF for different wavelengths is higher than 0.7 at Nyquist frequency 10 lp x mm(-1), and the RMS spot radius is less than 14 microm. The good imaging quality is achieved over the whole working waveband, the design requirements of spatial resolution 0.5 mrad and spectral resolution 0.6 nm are satisfied. It is certificated that the optimum-design method proposed in this paper is feasible. This method can be applied in other waveband, and is an instruction method for designing grating-dispersion imaging spectrometers.
-
Garza-Gisholt, Eduardo; Hemmi, Jan M; Hart, Nathan S; Collin, Shaun P
2014-01-01
Topographic maps that illustrate variations in the density of different neuronal sub-types across the retina are valuable tools for understanding the adaptive significance of retinal specialisations in different species of vertebrates. To date, such maps have been created from raw count data that have been subjected to only limited analysis (linear interpolation) and, in many cases, have been presented as iso-density contour maps with contour lines that have been smoothed 'by eye'. With the use of stereological approach to count neuronal distribution, a more rigorous approach to analysing the count data is warranted and potentially provides a more accurate representation of the neuron distribution pattern. Moreover, a formal spatial analysis of retinal topography permits a more robust comparison of topographic maps within and between species. In this paper, we present a new R-script for analysing the topography of retinal neurons and compare methods of interpolating and smoothing count data for the construction of topographic maps. We compare four methods for spatial analysis of cell count data: Akima interpolation, thin plate spline interpolation, thin plate spline smoothing and Gaussian kernel smoothing. The use of interpolation 'respects' the observed data and simply calculates the intermediate values required to create iso-density contour maps. Interpolation preserves more of the data but, consequently includes outliers, sampling errors and/or other experimental artefacts. In contrast, smoothing the data reduces the 'noise' caused by artefacts and permits a clearer representation of the dominant, 'real' distribution. This is particularly useful where cell density gradients are shallow and small variations in local density may dramatically influence the perceived spatial pattern of neuronal topography. The thin plate spline and the Gaussian kernel methods both produce similar retinal topography maps but the smoothing parameters used may affect the outcome.
-
Dai, Sheng-Yun; Xu, Bing; Shi, Xin-Yuan; Xu, Xiang; Sun, Ying-Qiang; Qiao, Yan-Jiang
2017-03-01
This study is aimed to propose a continual improvement strategy based on quality by design (QbD). An ultra high performance liquid chromatography (UPLC) method was developed to accomplish the method transformation from HPLC to UPLC of Panax notogineng saponins (PNS) and achieve the continual improvement of PNS based on QbD, for example. Plackett-Burman screening design and Box-Behnken optimization design were employed to further understand the relationship between the critical method parameters (CMPs) and critical method attributes (CMAs). And then the Bayesian design space was built. The separation degree of the critical peaks (ginsenoside Rg₁ and ginsenoside Re) was over 2.0 and the analysis time was less than 17 min by a method chosen from the design space with 20% of the initial concentration of the acetonitrile, 10 min of the isocratic time and 6%•min⁻¹ of the gradient slope. At last, the optimum method was validated by accuracy profile. Based on the same analytical target profile (ATP), the comparison of HPLC and UPLC including chromatograph method, CMA identification, CMP-CMA model and system suitability test (SST) indicated that the UPLC method could shorten the analysis time, improve the critical separation and satisfy the requirement of the SST. In all, HPLC method could be replaced by UPLC for the quantity analysis of PNS. Copyright© by the Chinese Pharmaceutical Association.
-
Knudsen, Anders R; Andersen, Kasper J; Hamilton-Dutoit, Stephen; Nyengaard, Jens R; Mortensen, Frank V
2016-04-01
Circulating liver enzymes such as alanine transaminase are often used as markers of hepatocellular damage. Ischaemia/reperfusion (I/R) injury is an inevitable consequence of prolonged liver ischaemia. The aim of this study was to examine the correlation between liver enzymes and volume of liver cell necrosis after ischaemia/reperfusion injuries, using design-unbiased stereological methods. Forty-seven male Wistar rats were subjected to 1 h of partial liver ischaemia, followed by either 4 or 24 h of reperfusion. Within each group, one-third of animals were subjected to ischaemic preconditioning and one-third to ischaemic postconditioning. At the end of reperfusion, blood and liver samples were collected for analysis. The volume of necrotic liver tissue was subsequently correlated to circulating markers of I/R injury. Correlation between histological findings and circulating markers was performed using Pearson's correlation coefficient. Alanine transferase peaked after 4 h of reperfusion; however, at this time-point, only mild necrosis was observed, with a Pearson's correlation coefficient of 0.663 (P = 0.001). After 24 h of reperfusion, alanine aminotransferase was found to be highly correlated to the degree of hepatocellular necrosis R = 0.836 (P = 0.000). Furthermore, alkaline phosphatase (R = 0.806) and α-2-macroglobulin (R = 0.655) levels were also correlated with the degree of necrosis. We show for the first time that there is a close correlation between the volume of hepatocellular necrosis and alanine aminotransferase levels in a model of I/R injury. This is especially apparent after 24 h of reperfusion. Similarly, increased levels of alkaline phosphatase and α-2-macroglobulin are correlated to the volume of liver necrosis. © 2016 The Authors. International Journal of Experimental Pathology © 2016 International Journal of Experimental Pathology.
-
Swept-sine noise-induced damage as a hearing loss model for preclinical assays
Sanz, Lorena; Murillo-Cuesta, Silvia; Cobo, Pedro; Cediel-Algovia, Rafael; Contreras, Julio; Rivera, Teresa; Varela-Nieto, Isabel; Avendaño, Carlos
2015-01-01
Mouse models are key tools for studying cochlear alterations in noise-induced hearing loss (NIHL) and for evaluating new therapies. Stimuli used to induce deafness in mice are usually white and octave band noises that include very low frequencies, considering the large mouse auditory range. We designed different sound stimuli, enriched in frequencies up to 20 kHz (“violet” noises) to examine their impact on hearing thresholds and cochlear cytoarchitecture after short exposure. In addition, we developed a cytocochleogram to quantitatively assess the ensuing structural degeneration and its functional correlation. Finally, we used this mouse model and cochleogram procedure to evaluate the potential therapeutic effect of transforming growth factor β1 (TGF-β1) inhibitors P17 and P144 on NIHL. CBA mice were exposed to violet swept-sine noise (VS) with different frequency ranges (2–20 or 9–13 kHz) and levels (105 or 120 dB SPL) for 30 min. Mice were evaluated by auditory brainstem response (ABR) and otoacoustic emission tests prior to and 2, 14 and 28 days after noise exposure. Cochlear pathology was assessed with gross histology; hair cell number was estimated by a stereological counting method. Our results indicate that functional and morphological changes induced by VS depend on the sound level and frequency composition. Partial hearing recovery followed the exposure to 105 dB SPL, whereas permanent cochlear damage resulted from the exposure to 120 dB SPL. Exposure to 9–13 kHz noise caused an auditory threshold shift (TS) in those frequencies that correlated with hair cell loss in the corresponding areas of the cochlea that were spotted on the cytocochleogram. In summary, we present mouse models of NIHL, which depending on the sound properties of the noise, cause different degrees of cochlear damage, and could therefore be used to study molecules which are potential players in hearing loss protection and repair. PMID:25762930
-
Design Optimization Method for Composite Components Based on Moment Reliability-Sensitivity Criteria
NASA Astrophysics Data System (ADS)
Sun, Zhigang; Wang, Changxi; Niu, Xuming; Song, Yingdong
2017-08-01
In this paper, a Reliability-Sensitivity Based Design Optimization (RSBDO) methodology for the design of the ceramic matrix composites (CMCs) components has been proposed. A practical and efficient method for reliability analysis and sensitivity analysis of complex components with arbitrary distribution parameters are investigated by using the perturbation method, the respond surface method, the Edgeworth series and the sensitivity analysis approach. The RSBDO methodology is then established by incorporating sensitivity calculation model into RBDO methodology. Finally, the proposed RSBDO methodology is applied to the design of the CMCs components. By comparing with Monte Carlo simulation, the numerical results demonstrate that the proposed methodology provides an accurate, convergent and computationally efficient method for reliability-analysis based finite element modeling engineering practice.
-
Innovative design method of automobile profile based on Fourier descriptor
NASA Astrophysics Data System (ADS)
Gao, Shuyong; Fu, Chaoxing; Xia, Fan; Shen, Wei
2017-10-01
Aiming at the innovation of the contours of automobile side, this paper presents an innovative design method of vehicle side profile based on Fourier descriptor. The design flow of this design method is: pre-processing, coordinate extraction, standardization, discrete Fourier transform, simplified Fourier descriptor, exchange descriptor innovation, inverse Fourier transform to get the outline of innovative design. Innovative concepts of the innovative methods of gene exchange among species and the innovative methods of gene exchange among different species are presented, and the contours of the innovative design are obtained separately. A three-dimensional model of a car is obtained by referring to the profile curve which is obtained by exchanging xenogeneic genes. The feasibility of the method proposed in this paper is verified by various aspects.
-
Pollano, Antonella; Zalosnik, María I; Durando, Patricia E; Suárez, Marta M
2016-11-01
Early maternal separation (MS) may produce lasting effects in the dorsal hippocampus (DH) that can change its response to chronic stress in adulthood. Chronic stress affects DH morphology and function, but tianeptine (an anti-depressant) can reverse the stress-induced morphological impairments. Morphologic alterations of hippocampus can affect contextual memory. Therefore, we evaluated the effect of tianeptine in MS and chronically stressed rats on: 1) volume of the DH and its areas using stereology and 2) hippocampal-dependent memory using a fear conditioning test. Male Wistar rats were subjected to daily MS for 4.5 h between postnatal days (PND) 1-21, or to animal facility rearing (AFR). Between (PND) days 50 and 74, rats were exposed to chronic unpredictable stress and were treated daily with tianeptine (10 mg/kg) or vehicle, providing eight groups: AFR-unstressed/vehicle (n = 5 for stereology, n = 18 for fear conditioning test); AFR unstressed/tianeptine (n = 6 and n = 10); AFR-chronic stress/vehicle (n = 6 and n = 14); AFR-chronic stress/tianeptine (n = 6 and n = 10), MS-unstressed/vehicle (n = 5 and n = 19), MS-unstressed/tianeptine (n = 6 and n = 10), MS-chronic stress/vehicle (n = 6 and n = 18), and MS-chronic stress/tianeptine (n = 6 and n = 10). MS-chronic stress/tianeptine rats showed a diminished CA1 area than the corresponding MS-unstressed/tianeptine rats. The combination of stressors produced a freezing response similar to those of the control group during postconditioning. During retrieval, MS led to a diminished freezing response compared to the AFR-unstressed groups. Tianeptine had no effect on freezing behavior. Our results show that tianeptine can affect the CA1 area volume differently depending on the nature and quantity of stressors but cannot alter freezing to context.
-
de Barros Mendes Lopes, Thais; Groth, Espen E; Veras, Mariana; Furuya, Tatiane K; de Souza Xavier Costa, Natalia; Ribeiro Júnior, Gabriel; Lopes, Fernanda Degobbi; de Almeida, Francine M; Cardoso, Wellington V; Saldiva, Paulo Hilario Nascimento; Chammas, Roger; Mauad, Thais
2018-06-04
Gestational exposure to air pollution is associated with negative outcomes in newborns and children. In a previous study, we demonstrated a synergistic negative effect of pre- and postnatal exposure to PM 2.5 on lung development in mice. However, the means by which air pollution affects development of the lung have not yet been identified. In this study, we exposed pregnant BALB/c mice and their offspring to concentrated urban PM 2.5 (from São Paulo, Brazil; target dose 600 μg/m 3 for 1 h daily). Exposure was started on embryonic day 5.5 (E5.5, time of placental implantation). Lung tissue of fetuses and offspring was submitted to stereological and transcriptomic analyses at E14.5 (pseudoglandular stage of lung development), E18.5 (saccular stage) and P40 (postnatal day 40, alveolarized lung). Additionally, lung function and cellularity of bronchoalveolar lavage (BAL) fluid were studied in offspring animals at P40. Compared to control animals that were exposed to filtered air throughout gestation and postnatal life, PM-exposed mice exhibited higher lung elastance and a lower alveolar number at P40 whilst the total lung volume and cellularity of BAL fluid were not affected. Glandular and saccular structures of fetal lungs were not altered upon gestational exposure; transcriptomic signatures, however, showed changes related to DNA damage and its regulation, inflammation and regulation of cell proliferation. A differential expression was validated at E14.5 for the candidates Sox8, Angptl4 and Gas1. Our data substantiate the in utero biomolecular effect of gestational exposure to air pollution and provide first-time stereological evidence that pre- and early life-postnatal exposure compromise lung development, leading to a reduced number of alveoli and an impairment of lung function in the adult mouse. Copyright © 2018 Elsevier Ltd. All rights reserved.
-
Torul, Damla; Bereket, Mehmet Cihan; Onger, Mehmet Emin; Altun, Gamze
2018-04-20
The aim of this study was to investigate the effects of platelet-rich fibrin (PRF) and plasma rich in growth factors (PRGF) on peripheral nerve injury in the early period of healing. Thirty Wistar albino rats were used in this study. Rats were divided into control (C), damaged (D), PRF, and PRGF groups. The left sciatic nerves of each group were identified as group C. Crush-type injury was performed on the right sciatic nerves of the D, PRF, and PRGF groups. In the PRF and PRGF groups, blood 2 mL was obtained to prepare the PRF and PRGF and the biomaterials were applied to the injured nerve area. After 8 weeks, functional, electrophysiologic, and stereological evaluations were performed. For the electrophysiologic evaluation, the latency and amplitude values in the D, PRF, and PRGF groups were significantly lower than those in the C group (P > .05). According to the sciatic functional index result, there were significant differences between groups D and PRF and between groups D and PRGF (P = .000). For the stereological evaluations, although no significant difference was observed between the PRGF and C groups (P > .05), a significant difference was observed among the D, PRF, and PRGF groups for myelinated axon number. There were significant differences between groups D and PRF and between groups D and PRGF for axon area (P = .021 and .001, respectively). No significant difference was observed among the D, PRF, and PRGF groups for myelin sheath thickness and ratio of axon area to myelin sheath thickness (P > .05). The results of this study suggest that PRGF increases nerve regeneration in the early period of healing and that the limited early action of PRF should be re-evaluated in the late period. Copyright © 2018 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.
-
Minnema, Daniel J; Travis, Kim Z; Breckenridge, Charles B; Sturgess, Nicholas C; Butt, Mark; Wolf, Jeffrey C; Zadory, Dan; Beck, Melissa J; Mathews, James M; Tisdel, Merrill O; Cook, Andrew R; Botham, Philip A; Smith, Lewis L
2014-03-01
Several investigations have reported that mice administered paraquat dichloride (PQ·Cl2) by intraperitoneal injection exhibit a loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). In this study, male and female C57BL/6J mice were administered PQ·Cl2 in the diet at concentrations of 0 (control), 10, and 50ppm for a duration of 13weeks. A separate group of mice were administered 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) during week 12 as positive controls to produce a loss of dopaminergic neurons in the SNpc. The comparative effects of PQ and MPTP on the SNpc and/or striatum were assessed using neurochemical, neuropathological, and stereological endpoints. Morphological and stereological assessments were performed by investigators 'blinded' to the origin of the tissue. Neither dose of PQ·Cl2 (10 or 50 ppm in the diet) caused a loss of striatal dopamine or dopamine metabolite concentrations in the brains of mice. Pathological assessments of the SNpc and striatum showed no evidence of neuronal degeneration or astrocytic/microglial activation. Furthermore, the number of tyrosine hydroxylase-positive (TH(+)) neurons in the SNpc was not reduced in PQ-treated mice. In contrast, MPTP caused a decrease in striatal dopamine concentration, a reduction in TH(+) neurons in the SNpc, and significant pathological changes including astrocytic and microglial activation in the striatum and SNpc. The MPTP-induced effects were greater in males than in females. It is concluded that 13weeks of continuous dietary exposure of C57BL/6J mice to 50ppm PQ·Cl2 (equivalent to 10.2 and 15.6mg PQ ion/kg body weight/day for males and females, respectively) does not result in the loss of, or damage to, dopaminergic neurons in the SNpc. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.
-
Optimal fractional order PID design via Tabu Search based algorithm.
Ateş, Abdullah; Yeroglu, Celaleddin
2016-01-01
This paper presents an optimization method based on the Tabu Search Algorithm (TSA) to design a Fractional-Order Proportional-Integral-Derivative (FOPID) controller. All parameter computations of the FOPID employ random initial conditions, using the proposed optimization method. Illustrative examples demonstrate the performance of the proposed FOPID controller design method. Copyright © 2015 ISA. Published by Elsevier Ltd. All rights reserved.
-
DOE Office of Scientific and Technical Information (OSTI.GOV)
Wang, Weiguo, E-mail: wang_weiguo@vip.163.com
High purity (99.99%) iron samples were cold rolled with a thickness reduction of 87% followed by a annealing at 620 °C for 15 and 45 min, then the grain boundary plane distributions were characterized by electron backscatter diffraction and a stereology and statistics based five parameter analysis. The results showed that the grain boundary planes were mainly distributed on (1 0 0) and such distribution was enhanced obviously when the holding time of annealing increased from 15 to 45 min during which an extensive grain growth and a dramatic texture evolution took place. Further analysis indicated such distribution was largelymore » due to the rotation of grain boundary planes of the [1 0 0] misoriented grains. Additionally, it was also observed that some random boundaries of [1 0 0] misoriented grains were changing from asymmetrical tilt into (1 0 0)/(− 1 0 0) twist when annealing proceeded from 15 to 45 min. Based on the present work and the results reported by other investigators, it was suggested that the chemistry appeared to be critical in determining the grain boundary plane distribution in iron based materials. - Highlights: •Grain boundary (GB) plane distribution (GBPD) in a high purity (99.99%) was studied. •GB planes are mainly distributed on (1 0 0) in the cold rolled and annealed samples. •Such distribution is largely due to the rotation of GB planes of [100] misoriented grains. •Some [1 0 0] asymmetrical tilt boundaries are evolving into twist ones during annealing.« less
-
Design for a Manufacturing Method for Memristor-Based Neuromorphic Computing Processors
2013-03-01
DESIGN FOR A MANUFACTURING METHOD FOR MEMRISTOR- BASED NEUROMORPHIC COMPUTING PROCESSORS UNIVERSITY OF PITTSBURGH MARCH 2013...BASED NEUROMORPHIC COMPUTING PROCESSORS 5a. CONTRACT NUMBER FA8750-11-1-0271 5b. GRANT NUMBER N/A 5c. PROGRAM ELEMENT NUMBER 62788F 6. AUTHOR(S...synapses and implemented a neuromorphic computing system based on our proposed synapse designs. The robustness of our system is also evaluated by
-
NASA Astrophysics Data System (ADS)
Fan, Xiao-Ning; Zhi, Bo
2017-07-01
Uncertainties in parameters such as materials, loading, and geometry are inevitable in designing metallic structures for cranes. When considering these uncertainty factors, reliability-based design optimization (RBDO) offers a more reasonable design approach. However, existing RBDO methods for crane metallic structures are prone to low convergence speed and high computational cost. A unilevel RBDO method, combining a discrete imperialist competitive algorithm with an inverse reliability strategy based on the performance measure approach, is developed. Application of the imperialist competitive algorithm at the optimization level significantly improves the convergence speed of this RBDO method. At the reliability analysis level, the inverse reliability strategy is used to determine the feasibility of each probabilistic constraint at each design point by calculating its α-percentile performance, thereby avoiding convergence failure, calculation error, and disproportionate computational effort encountered using conventional moment and simulation methods. Application of the RBDO method to an actual crane structure shows that the developed RBDO realizes a design with the best tradeoff between economy and safety together with about one-third of the convergence speed and the computational cost of the existing method. This paper provides a scientific and effective design approach for the design of metallic structures of cranes.
-
Fabric dependence of quasi-waves in anisotropic porous media
Cardoso, Luis; Cowin, Stephen C.
2011-01-01
Assessment of bone loss and osteoporosis by ultrasound systems is based on the speed of sound and broadband ultrasound attenuation of a single wave. However, the existence of a second wave in cancellous bone has been reported and its existence is an unequivocal signature of poroelastic media. To account for the fact that ultrasound is sensitive to microarchitecture as well as bone mineral density (BMD), a fabric-dependent anisotropic poroelastic wave propagation theory was recently developed for pure wave modes propagating along a plane of symmetry in an anisotropic medium. Key to this development was the inclusion of the fabric tensor—a quantitative stereological measure of the degree of structural anisotropy of bone—into the linear poroelasticity theory. In the present study, this framework is extended to the propagation of mixed wave modes along an arbitrary direction in anisotropic porous media called quasi-waves. It was found that differences between phase and group velocities are due to the anisotropy of the bone microarchitecture, and that the experimental wave velocities are more accurately predicted by the poroelastic model when the fabric tensor variable is taken into account. This poroelastic wave propagation theory represents an alternative for bone quality assessment beyond BMD. PMID:21568431
-
Ultrastructural analysis of cell component distribution in the apical cell of Ceratodon protonemata
NASA Technical Reports Server (NTRS)
Walker, L. M.; Sack, F. D.
1995-01-01
A distinctive feature of tip-growing plant cells is that cell components are distributed differentially along the length of the cell, although most ultrastructural analyses have been qualitative. The longtitudinal distribution of cell components was studied both qualitatively and quantitatively in the apical cell of dark-grown protonemata of the moss Ceratodon. The first 35 micrometers of the apical cell was analyzed stereologically using transmission electron microscopy. There were four types of distributions along the cell's axis, three of them differential: (1) tubular endoplasmic reticulum was evenly distributed, (2) cisternal endoplasmic reticulum and Golgi vesicles were distributed in a tip-to-base gradient, (3) plastids, vacuoles, and Golgi stacks were enriched in specific areas, although the locations of the enrichments varied, and (4) mitochondria were excluded in the tip-most 5 micrometers and evenly distributed throughout the remaining 30 micrometers. This study provides one of the most comprehensive quantitative, ultrastructural analyses of the distribution of cell components in the apex of any tip-growing plant cell. The finding that almost every component had its own spatial arrangement demonstrates the complexity of the organization and regulation of the distribution of components in tip-growing cells.
-
Influence of a magnetic field during directional solidification of MAR-M 246 + Hf superalloy
NASA Technical Reports Server (NTRS)
Andrews, J. Barry; Alter, Wendy; Schmidt, Dianne
1991-01-01
An area that has been almost totally overlooked in the optimization of properties in directionally solidified superalloys is the control of microstructural features through the application of a magnetic field during solidification. The influence of a magnetic field on the microstructural features of a nickel-base superalloys is investigated. Studies were performed on the dendritic MAR-M 246+Hf alloy, which was solidified under both a 5 K gauss magnetic field and under no-applied-field conditions. The possible influences of the magnetic field on the solidification process were observed by studying variations in microstructural features including volume fraction, surface area, number, and shape of the carbide particles. Stereological factors analyzed also included primary and secondary dendrite arm spacing and the volume fraction of the interdendritic eutectic constituent. Microprobe analysis was performed to determine the chemistry of the carbides, dendrites, and interdendritic constituents, and how it varied between field and no-field solidification samples. Experiments involving periodic application and removal of the magnetic field were also performed in order to permit a comparison with structural variations observed in a MAR-M 246+Hf alloy solidified during KC-135 high-g, low-g maneuvers.
-
Morphometric analysis of epidermal differentiation in primary roots of Zea mays
NASA Technical Reports Server (NTRS)
Moore, R.; Smith, H. S.
1990-01-01
Epidermal differentiation in primary roots of Zea mays was divided into six cell types based on cellular shape and cytoplasmic appearance. These six cell types are: 1) apical protoderm, located at the tip of the root pole and characterized by periclinally flattened cells; 2) cuboidal protoderm, located approximately 230 microns from the root pole and characterized by cuboidal cells; 3) tabular epidermis, located approximately 450 microns from the root pole and characterized by anticlinally flattened cells; 4) cuboidal epidermis, located approximately 900 microns from the root pole and characterized by cuboidal cells having numerous small vacuoles; 5) vacuolate cuboidal epidermis, located approximately 1,500 microns from the root pole and characterized by cuboidal cells containing several large vacuoles; and 6) columnar epidermis, located approximately 2,200 microns from the root pole (i.e., at the beginning of the zone of elongation) and characterized by elongated cells. We also used stereology to quantify the cellular changes associated with epidermal differentiation. The quiescent center and the apical protoderm have significantly different ultrastructures. The relative volume of dictyosomes increases dramatically during the early stages of epidermal differentiation. This increase correlates inversely with the amount of coverage provided by the root cap and mucilage.
-
Meeting Report: Tissue-based Image Analysis.
Saravanan, Chandra; Schumacher, Vanessa; Brown, Danielle; Dunstan, Robert; Galarneau, Jean-Rene; Odin, Marielle; Mishra, Sasmita
2017-10-01
Quantitative image analysis (IA) is a rapidly evolving area of digital pathology. Although not a new concept, the quantification of histological features on photomicrographs used to be cumbersome, resource-intensive, and limited to specialists and specialized laboratories. Recent technological advances like highly efficient automated whole slide digitizer (scanner) systems, innovative IA platforms, and the emergence of pathologist-friendly image annotation and analysis systems mean that quantification of features on histological digital images will become increasingly prominent in pathologists' daily professional lives. The added value of quantitative IA in pathology includes confirmation of equivocal findings noted by a pathologist, increasing the sensitivity of feature detection, quantification of signal intensity, and improving efficiency. There is no denying that quantitative IA is part of the future of pathology; however, there are also several potential pitfalls when trying to estimate volumetric features from limited 2-dimensional sections. This continuing education session on quantitative IA offered a broad overview of the field; a hands-on toxicologic pathologist experience with IA principles, tools, and workflows; a discussion on how to apply basic stereology principles in order to minimize bias in IA; and finally, a reflection on the future of IA in the toxicologic pathology field.
-
Charvet, Christine J; Hof, Patrick R; Raghanti, Mary Ann; Van Der Kouwe, Andre J; Sherwood, Chet C; Takahashi, Emi
2017-04-01
The isocortex of primates is disproportionately expanded relative to many other mammals, yet little is known about what the expansion of the isocortex entails for differences in cellular composition and connectivity patterns in primates. Across the depth of the isocortex, neurons exhibit stereotypical patterns of projections. Upper-layer neurons (i.e., layers II-IV) project within and across cortical areas, whereas many lower-layer pyramidal neurons (i.e., layers V-VI) favor connections to subcortical regions. To identify evolutionary changes in connectivity patterns, we quantified upper (i.e., layers II-IV)- and lower (i.e., layers V-VI)-layer neuron numbers in primates and other mammals such as rodents and carnivores. We also used MR tractography based on high-angular resolution diffusion imaging and diffusion spectrum imaging to compare anterior-to-posterior corticocortical tracts between primates and other mammals. We found that primates possess disproportionately more upper-layer neurons as well as an expansion of anterior-to-posterior corticocortical tracts compared with other mammals. Taken together, these findings demonstrate that primates deviate from other mammals in exhibiting increased cross-cortical connectivity. J. Comp. Neurol. 525:1075-1093, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.
-
Fabric dependence of quasi-waves in anisotropic porous media.
Cardoso, Luis; Cowin, Stephen C
2011-05-01
Assessment of bone loss and osteoporosis by ultrasound systems is based on the speed of sound and broadband ultrasound attenuation of a single wave. However, the existence of a second wave in cancellous bone has been reported and its existence is an unequivocal signature of poroelastic media. To account for the fact that ultrasound is sensitive to microarchitecture as well as bone mineral density (BMD), a fabric-dependent anisotropic poroelastic wave propagation theory was recently developed for pure wave modes propagating along a plane of symmetry in an anisotropic medium. Key to this development was the inclusion of the fabric tensor--a quantitative stereological measure of the degree of structural anisotropy of bone--into the linear poroelasticity theory. In the present study, this framework is extended to the propagation of mixed wave modes along an arbitrary direction in anisotropic porous media called quasi-waves. It was found that differences between phase and group velocities are due to the anisotropy of the bone microarchitecture, and that the experimental wave velocities are more accurately predicted by the poroelastic model when the fabric tensor variable is taken into account. This poroelastic wave propagation theory represents an alternative for bone quality assessment beyond BMD.
-
Point Analysis in Java applied to histological images of the perforant pathway: a user's account.
Scorcioni, Ruggero; Wright, Susan N; Patrick Card, J; Ascoli, Giorgio A; Barrionuevo, Germán
2008-01-01
The freeware Java tool Point Analysis in Java (PAJ), created to perform 3D point analysis, was tested in an independent laboratory setting. The input data consisted of images of the hippocampal perforant pathway from serial immunocytochemical localizations of the rat brain in multiple views at different resolutions. The low magnification set (x2 objective) comprised the entire perforant pathway, while the high magnification set (x100 objective) allowed the identification of individual fibers. A preliminary stereological study revealed a striking linear relationship between the fiber count at high magnification and the optical density at low magnification. PAJ enabled fast analysis for down-sampled data sets and a friendly interface with automated plot drawings. Noted strengths included the multi-platform support as well as the free availability of the source code, conducive to a broad user base and maximum flexibility for ad hoc requirements. PAJ has great potential to extend its usability by (a) improving its graphical user interface, (b) increasing its input size limit, (c) improving response time for large data sets, and (d) potentially being integrated with other Java graphical tools such as ImageJ.
-
Multiobjective Optimization of Rocket Engine Pumps Using Evolutionary Algorithm
NASA Technical Reports Server (NTRS)
Oyama, Akira; Liou, Meng-Sing
2001-01-01
A design optimization method for turbopumps of cryogenic rocket engines has been developed. Multiobjective Evolutionary Algorithm (MOEA) is used for multiobjective pump design optimizations. Performances of design candidates are evaluated by using the meanline pump flow modeling method based on the Euler turbine equation coupled with empirical correlations for rotor efficiency. To demonstrate the feasibility of the present approach, a single stage centrifugal pump design and multistage pump design optimizations are presented. In both cases, the present method obtains very reasonable Pareto-optimal solutions that include some designs outperforming the original design in total head while reducing input power by one percent. Detailed observation of the design results also reveals some important design criteria for turbopumps in cryogenic rocket engines. These results demonstrate the feasibility of the EA-based design optimization method in this field.
-
ERIC Educational Resources Information Center
Cha, H. J.; Ahn, M. L.
2014-01-01
The purpose of this study was to elicit design guidelines for a teacher tool to support students' diverse needs by facilitating differentiated instructions (DIs). The study used a framework based on activity theory and principles from universal design for learning. As for the research methods, design-based research methods were adopted, and as the…
-
Grid Based Technologies for in silico Screening and Drug Design.
Potemkin, Vladimir; Grishina, Maria
2018-03-08
Various techniques for rational drug design are presented in the paper. The methods are based on a substitution of antipharmacophore atoms of the molecules of training dataset by new atoms and/or group of atoms increasing the atomic bioactivity increments obtained at a SAR study. Furthermore, a design methodology based on the genetic algorithm DesPot for discrete optimization and generation of new drug candidate structures is described. Additionally, wide spectra of SAR approaches (3D/4D QSAR interior and exterior-based methods - BiS, CiS, ConGO, CoMIn, high-quality docking method - ReDock) using MERA force field and/or AlteQ quantum chemical method for correct prognosis of bioactivity and bioactive probability is described. The design methods are implemented now at www.chemosophia.com web-site for online computational services. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.
-
Research on the Bionics Design of Automobile Styling Based on the Form Gene
NASA Astrophysics Data System (ADS)
Aili, Zhao; Long, Jiang
2017-09-01
From the heritage of form gene point of view, this thesis has analyzed the gene make-up, cultural inheritance and aesthetic features in the evolution and development of forms of brand automobiles and proposed the bionic design concept and methods in the automobile styling design. And this innovative method must be based on the form gene, and the consistency and combination of form element must be maintained during the design. Taking the design of Maserati as an example, the thesis will show you the design method and philosophy in the aspects of form gene expression and bionic design innovation for the future automobile styling.
-
Pang, Y; Lin, S; Wright, C; Shen, J; Carter, K; Bhatt, A; Fan, L-W
2016-03-24
Protection of substantia nigra (SN) dopaminergic (DA) neurons by neurotrophic factors (NTFs) is one of the promising strategies in Parkinson's disease (PD) therapy. A major clinical challenge for NTF-based therapy is that NTFs need to be delivered into the brain via invasive means, which often shows limited delivery efficiency. The nose to brain pathway is a non-invasive brain drug delivery approach developed in recent years. Of particular interest is the finding that intranasal insulin improves cognitive functions in Alzheimer's patients. In vitro, insulin has been shown to protect neurons against various insults. Therefore, the current study was designed to test whether intranasal insulin could afford neuroprotection in the 6-hydroxydopamine (6-OHDA)-based rat PD model. 6-OHDA was injected into the right side of striatum to induce a progressive DA neuronal lesion in the ipsilateral SN pars compact (SNc). Recombinant human insulin was applied intranasally to rats starting from 24h post lesion, once per day, for 2 weeks. A battery of motor behavioral tests was conducted on day 8 and 15. The number of DA neurons in the SNc was estimated by stereological counting. Our results showed that 6-OHDA injection led to significant motor deficits and 53% of DA neuron loss in the ipsilateral side of injection. Treatment with insulin significantly ameliorated 6-OHDA-induced motor impairments, as shown by improved locomotor activity, tapered/ledged beam-walking performance, vibrissa-elicited forelimb-placing, initial steps, as well as methamphetamine-induced rotational behavior. Consistent with behavioral improvements, insulin treatment provided a potent protection of DA neurons in the SNc against 6-OHDA neurotoxicity, as shown by a 74.8% increase in tyrosine hydroxylase (TH)-positive neurons compared to the vehicle group. Intranasal insulin treatment did not affect body weight and blood glucose levels. In conclusion, our study showed that intranasal insulin provided strong neuroprotection in the 6-OHDA rat PD model, suggesting that insulin signaling may be a novel therapeutic target in broad neurodegenerative disorders. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.
-
Clinicopathologic correlations in Alibert-type mycosis fungoides.
Eng, A M; Blekys, I; Worobec, S M
1981-06-01
Five cases of mycosis fungoides of the Alibert type were studied by taking multiple biopsy specimens at different stages of the disease. Large hyperchromatic, slightly irregular mononuclear cells are the most frequent cells. Ultrastructurally, the cells were only slightly convoluted, had prominent heterochromatin banding at the nuclear membrane, and unremarkable cytoplasmic organelles. Highly convoluted cerebriform nucleated cells were few. Large regular vesicular histiocytes were prominent in the early stages. Ultrastructurally, the cells showed evenly distributed euchromatin. Epidermotrophism was equally as important as Pautrier's abscess as a hallmark of the disease. Stereologic techniques comparing the infiltrate with regard to size and convolution of cells in all stages of mycosis fungoides with infiltrates seen in a variety of benign dermatoses showed no statistically significant differences.
-
A Government/Industry Summary of the Design Analysis Methods for Vibrations (DAMVIBS) Program
NASA Technical Reports Server (NTRS)
Kvaternik, Raymond G. (Compiler)
1993-01-01
The NASA Langley Research Center in 1984 initiated a rotorcraft structural dynamics program, designated DAMVIBS (Design Analysis Methods for VIBrationS), with the objective of establishing the technology base needed by the rotorcraft industry for developing an advanced finite-element-based dynamics design analysis capability for vibrations. An assessment of the program showed that the DAMVIBS Program has resulted in notable technical achievements and major changes in industrial design practice, all of which have significantly advanced the industry's capability to use and rely on finite-element-based dynamics analyses during the design process.
-
Biomimetic design processes in architecture: morphogenetic and evolutionary computational design.
Menges, Achim
2012-03-01
Design computation has profound impact on architectural design methods. This paper explains how computational design enables the development of biomimetic design processes specific to architecture, and how they need to be significantly different from established biomimetic processes in engineering disciplines. The paper first explains the fundamental difference between computer-aided and computational design in architecture, as the understanding of this distinction is of critical importance for the research presented. Thereafter, the conceptual relation and possible transfer of principles from natural morphogenesis to design computation are introduced and the related developments of generative, feature-based, constraint-based, process-based and feedback-based computational design methods are presented. This morphogenetic design research is then related to exploratory evolutionary computation, followed by the presentation of two case studies focusing on the exemplary development of spatial envelope morphologies and urban block morphologies.
-
NASA Astrophysics Data System (ADS)
Villanueva Perez, Carlos Hernan
Computational design optimization provides designers with automated techniques to develop novel and non-intuitive optimal designs. Topology optimization is a design optimization technique that allows for the evolution of a broad variety of geometries in the optimization process. Traditional density-based topology optimization methods often lack a sufficient resolution of the geometry and physical response, which prevents direct use of the optimized design in manufacturing and the accurate modeling of the physical response of boundary conditions. The goal of this thesis is to introduce a unified topology optimization framework that uses the Level Set Method (LSM) to describe the design geometry and the eXtended Finite Element Method (XFEM) to solve the governing equations and measure the performance of the design. The methodology is presented as an alternative to density-based optimization approaches, and is able to accommodate a broad range of engineering design problems. The framework presents state-of-the-art methods for immersed boundary techniques to stabilize the systems of equations and enforce the boundary conditions, and is studied with applications in 2D and 3D linear elastic structures, incompressible flow, and energy and species transport problems to test the robustness and the characteristics of the method. A comparison of the framework against density-based topology optimization approaches is studied with regards to convergence, performance, and the capability to manufacture the designs. Furthermore, the ability to control the shape of the design to operate within manufacturing constraints is developed and studied. The analysis capability of the framework is validated quantitatively through comparison against previous benchmark studies, and qualitatively through its application to topology optimization problems. The design optimization problems converge to intuitive designs and resembled well the results from previous 2D or density-based studies.
-
Design method of ARM based embedded iris recognition system
NASA Astrophysics Data System (ADS)
Wang, Yuanbo; He, Yuqing; Hou, Yushi; Liu, Ting
2008-03-01
With the advantages of non-invasiveness, uniqueness, stability and low false recognition rate, iris recognition has been successfully applied in many fields. Up to now, most of the iris recognition systems are based on PC. However, a PC is not portable and it needs more power. In this paper, we proposed an embedded iris recognition system based on ARM. Considering the requirements of iris image acquisition and recognition algorithm, we analyzed the design method of the iris image acquisition module, designed the ARM processing module and its peripherals, studied the Linux platform and the recognition algorithm based on this platform, finally actualized the design method of ARM-based iris imaging and recognition system. Experimental results show that the ARM platform we used is fast enough to run the iris recognition algorithm, and the data stream can flow smoothly between the camera and the ARM chip based on the embedded Linux system. It's an effective method of using ARM to actualize portable embedded iris recognition system.
-
Optimization Design of Minimum Total Resistance Hull Form Based on CFD Method
NASA Astrophysics Data System (ADS)
Zhang, Bao-ji; Zhang, Sheng-long; Zhang, Hui
2018-06-01
In order to reduce the resistance and improve the hydrodynamic performance of a ship, two hull form design methods are proposed based on the potential flow theory and viscous flow theory. The flow fields are meshed using body-fitted mesh and structured grids. The parameters of the hull modification function are the design variables. A three-dimensional modeling method is used to alter the geometry. The Non-Linear Programming (NLP) method is utilized to optimize a David Taylor Model Basin (DTMB) model 5415 ship under the constraints, including the displacement constraint. The optimization results show an effective reduction of the resistance. The two hull form design methods developed in this study can provide technical support and theoretical basis for designing green ships.
-
NASA Astrophysics Data System (ADS)
Dukes, Michael Dickey
The objective of this research is to compare problem-based learning and lecture as methods to teach whole-systems design to engineering students. A case study, Appendix A, exemplifying successful whole-systems design was developed and written by the author in partnership with the Rocky Mountain Institute. Concepts to be tested were then determined, and a questionnaire was developed to test students' preconceptions. A control group of students was taught using traditional lecture methods, and a sample group of students was taught using problem-based learning methods. After several weeks, the students were given the same questionnaire as prior to the instruction, and the data was analyzed to determine if the teaching methods were effective in correcting misconceptions. A statistically significant change in the students' preconceptions was observed in both groups on the topic of cost related to the design process. There was no statistically significant change in the students' preconceptions concerning the design process, technical ability within five years, and the possibility of drastic efficiency gains with current technologies. However, the results were inconclusive in determining that problem-based learning is more effective than lecture as a method for teaching the concept of whole-systems design, or vice versa.
-
Reeder, Blaine; Turner, Anne M
2011-01-01
Responding to public health emergencies requires rapid and accurate assessment of workforce availability under adverse and changing circumstances. However, public health information systems to support resource management during both routine and emergency operations are currently lacking. We applied scenario-based design as an approach to engage public health practitioners in the creation and validation of an information design to support routine and emergency public health activities. Methods: Using semi-structured interviews we identified the information needs and activities of senior public health managers of a large municipal health department during routine and emergency operations. Results: Interview analysis identified twenty-five information needs for public health operations management. The identified information needs were used in conjunction with scenario-based design to create twenty-five scenarios of use and a public health manager persona. Scenarios of use and persona were validated and modified based on follow-up surveys with study participants. Scenarios were used to test and gain feedback on a pilot information system. Conclusion: The method of scenario-based design was applied to represent the resource management needs of senior-level public health managers under routine and disaster settings. Scenario-based design can be a useful tool for engaging public health practitioners in the design process and to validate an information system design. PMID:21807120
-
A Comparison of Functional Models for Use in the Function-Failure Design Method
NASA Technical Reports Server (NTRS)
Stock, Michael E.; Stone, Robert B.; Tumer, Irem Y.
2006-01-01
When failure analysis and prevention, guided by historical design knowledge, are coupled with product design at its conception, shorter design cycles are possible. By decreasing the design time of a product in this manner, design costs are reduced and the product will better suit the customer s needs. Prior work indicates that similar failure modes occur with products (or components) with similar functionality. To capitalize on this finding, a knowledge base of historical failure information linked to functionality is assembled for use by designers. One possible use for this knowledge base is within the Elemental Function-Failure Design Method (EFDM). This design methodology and failure analysis tool begins at conceptual design and keeps the designer cognizant of failures that are likely to occur based on the product s functionality. The EFDM offers potential improvement over current failure analysis methods, such as FMEA, FMECA, and Fault Tree Analysis, because it can be implemented hand in hand with other conceptual design steps and carried throughout a product s design cycle. These other failure analysis methods can only truly be effective after a physical design has been completed. The EFDM however is only as good as the knowledge base that it draws from, and therefore it is of utmost importance to develop a knowledge base that will be suitable for use across a wide spectrum of products. One fundamental question that arises in using the EFDM is: At what level of detail should functional descriptions of components be encoded? This paper explores two approaches to populating a knowledge base with actual failure occurrence information from Bell 206 helicopters. Functional models expressed at various levels of detail are investigated to determine the necessary detail for an applicable knowledge base that can be used by designers in both new designs as well as redesigns. High level and more detailed functional descriptions are derived for each failed component based on NTSB accident reports. To best record this data, standardized functional and failure mode vocabularies are used. Two separate function-failure knowledge bases are then created aid compared. Results indicate that encoding failure data using more detailed functional models allows for a more robust knowledge base. Interestingly however, when applying the EFDM, high level descriptions continue to produce useful results when using the knowledge base generated from the detailed functional models.
-
Novotová, Marta; Tarabová, Bohumila; Tylková, Lucia; Ventura-Clapier, Renée; Zahradník, Ivan
2016-10-01
Creatine kinase content, isoform distribution, and participation in energy transfer are muscle type specific. We analysed ultrastructural changes in slow muscle fibres of soleus due to invalidation of creatine kinase (CK) to reveal a difference in the remodelling strategy in comparison with fast muscle fibres of gastrocnemius published previously. We have employed the stereological method of vertical sections and electron microscopy of soleus muscles of wild type (WT) and CK-/- mice. The mitochondrial volume density was 1.4× higher but that of sarcoplasmic reticulum (SR) was almost 5× lower in slow CK-/- muscles fibres than in WT fibres. The volume density of terminal cisterns and of t-tubules was also lower in CK-/- than in WT fibres. The analysis of organelle environment revealed increased neighbourhood of mitochondria and A-bands that resulted from the decreased volume density of SR, from relocation of mitochondria along myofibrils, and from intrusion of mitochondria to myofibrils. These processes direct ATP supply closer to the contractile machinery. The decreased interaction between mitochondria and SR suggests reduced dependence of calcium uptake on oxidative ATP production. In conclusion, the architecture of skeletal muscle cells is under control of a cellular program that optimizes energy utilization specifically for a given muscle type.
-
Li, Fang; Yan, Chao-Qun; Lin, Li-Ting; Li, Hui; Zeng, Xiang-Hong; Liu, Yi; Du, Si-Qi; Zhu, Wen; Liu, Cun-Zhi
2015-04-28
Decreased cognition is recognized as one of the most severe and consistent behavioral impairments in dementia. Experimental studies have reported that acupuncture may improve cognitive deficits, relieve vascular dementia (VD) symptoms, and increase cerebral perfusion and electrical activity. Multi-infarction dementia was modeled in rats with 3% microemboli saline suspension. Two weeks after acupuncture at Zusanli (ST36), all rats were subjected to a hidden platform trial to test their 3-day spatial memory using the Morris water maze test. To estimate the numbers of pyramidal neuron, astrocytes, and synaptic boutons in hippocampal CA1 area, we adopted an unbiased stereology method to accurately sample and measure the size of cells. We found that acupuncture at ST36 significantly decreased the escape latency of VD rats. In addition, acupuncture significantly increased the pyramidal neuron number in hippocampal CA1 area (P < 0.05) and tended to decrease the number of astrocytes (P = 0.063). However, there was no significant change in the synaptic bouton number of hippocampal CA1 area in any of the groups (P > 0.05). These findings suggest that acupuncture may improve cognitive deficits and increase pyramidal neuron number of hippocampal CA1 area in VD rats.
-
Synaptic Changes in the Dentate Gyrus of APP/PS1 Transgenic Mice Revealed by Electron Microscopy
Merino-Serrais, Paula; Gonzalez, Santiago; DeFelipe, Javier
2013-01-01
Abstract Numerous studies have reported widespread synaptic dysfunction or loss in early stages of both Alzheimer disease (AD) patients and animal models; it is widely accepted that synapse loss is the major structural correlate of cognitive dysfunction. Elucidation of the changes that may affect synapses is crucial for understanding the pathogenic mechanisms underlying AD, but ultrastructural preservation of human postmortem brain tissue is often poor, and classical methods for quantification of synapses have significant technical limitations. We previously observed changes in dendritic spines in plaque-free regions of the neuropil of the dentate gyrus of double-transgenic APP/PS1 (amyloid precursor protein/presenilin 1) model mice by light microscopy. Here, we used electron microscopy to examine possible synaptic alterations in this region. We used standard stereologic techniques to determine numbers of synapses per volume. We were able to reconstruct and analyze thousands of synapses and their 3-dimensional characteristics using a focused ion beam/scanning electron microscope and 3-dimensional reconstruction software (EspINA), which performs semiautomated segmentation of synapses. Our results show that both numbers of synapses per volume and synaptic morphology are affected in plaque-free regions of APP/PS1 mice. Therefore, changes in the number and morphology of synapses seem to be widespread alterations in this animal model. PMID:23584198
-
Hajszan, Tibor; Szigeti-Buck, Klara; Sallam, Nermin L; Bober, Jeremy; Parducz, Arpad; MacLusky, Neil J; Leranth, Csaba; Duman, Ronald S
2009-01-01
Background Despite the fact that women are twice as likely to develop depression as men, our understanding of depression neurobiology in females is limited. We have recently reported in male rats that development of helpless behavior is associated with a severe loss of hippocampal spine synapses, which is reversed by treatment with the antidepressant, desipramine. Considering the fact that estradiol has a hippocampal synaptogenic effect similar to those of antidepressants, the presence of estradiol during the female reproductive life may influence behavioral and synaptic responses to stress and depression. Methods Using electron microscopic stereology, we analyzed hippocampal spine synapses in association with helpless behavior in ovariectomized female rats (n=70), under different conditions of estradiol exposure. Results Stress induced an acute and persistent loss of hippocampal spine synapses, while subchronic treatment with desipramine reversed the stress-induced synaptic loss. Estradiol supplementation given either prior to stress or prior to escape testing of nonstressed animals both increased the number of hippocampal spine synapses. Correlation analysis demonstrated a statistically significant negative correlation between the severity of helpless behavior and hippocampal spine synapse numbers. Conclusions These findings suggest that hippocampal spine synapse remodeling may be a critical factor underlying learned helplessness and, possibly, the neurobiology of depression. PMID:19811775
-
Carvalho, Andrezza Sossai Rodrigues; Torres, Laila Brito; Persike, Daniele Suzete; Fernandes, Maria José Silva; Amado, Debora; Naffah-Mazzacoratti, Maria da Graça; Cavalheiro, Esper Abrão; da Silva, Alexandre Valotta
2011-02-01
Recent research data have shown that systemic administration of pyruvate and oxaloacetate causes an increased brain-to-blood glutamate efflux. Since increased release of glutamate during epileptic seizures can lead to excitotoxicity and neuronal cell death, we tested the hypothesis that glutamate scavenging mediated by pyruvate and oxaloacetate systemic administration could have a neuroprotective effect in rats subjected to status epilepticus (SE). SE was induced by a single dose of pilocarpine (350mg/kgi.p.). Thirty minutes after SE onset, a single dose of pyruvate (250mg/kgi.p.), oxaloacetate (1.4mg/kgi.p.), or both substances was administrated. Acute neuronal loss in hippocampal regions CA1 and hilus was quantitatively determined five hours after SE onset, using the optical fractionator method for stereological cell counting. Apoptotic cascade in the hippocampus was also investigated seven days after SE using caspase-1 and -3 activity assays. SE-induced neuronal loss in CA1 was completely prevented in rats treated with pyruvate plus oxaloacetate. The SE-induced caspase-1 activation was significantly reduced when rats were treated with oxaloacetate or pyruvate plus oxaloacetate. The treatment with pyruvate and oxaloacetate caused a neuroprotective effect in rats subjected to pilocarpine-induced SE. Copyright © 2010 Elsevier Ltd. All rights reserved.
-
Design-based and model-based inference in surveys of freshwater mollusks
Dorazio, R.M.
1999-01-01
Well-known concepts in statistical inference and sampling theory are used to develop recommendations for planning and analyzing the results of quantitative surveys of freshwater mollusks. Two methods of inference commonly used in survey sampling (design-based and model-based) are described and illustrated using examples relevant in surveys of freshwater mollusks. The particular objectives of a survey and the type of information observed in each unit of sampling can be used to help select the sampling design and the method of inference. For example, the mean density of a sparsely distributed population of mollusks can be estimated with higher precision by using model-based inference or by using design-based inference with adaptive cluster sampling than by using design-based inference with conventional sampling. More experience with quantitative surveys of natural assemblages of freshwater mollusks is needed to determine the actual benefits of different sampling designs and inferential procedures.
-
Prevalence of Mixed-Methods Sampling Designs in Social Science Research
ERIC Educational Resources Information Center
Collins, Kathleen M. T.
2006-01-01
The purpose of this mixed-methods study was to document the prevalence of sampling designs utilised in mixed-methods research and to examine the interpretive consistency between interpretations made in mixed-methods studies and the sampling design used. Classification of studies was based on a two-dimensional mixed-methods sampling model. This…
-
Prenatal growth of the interorbital septum in Macaca mulatta.
Lozanoff, Scott; Doll, Sara; Hallgrimsson, Benedikt; Neufeld, Eric
2004-12-01
The interorbital septum is the portion of the anterior cranial base directly contiguous with the eyes. It is considered to be a primitive trait that has evolved independently in various primate groups as a result of ocular and olfactory convergence with concomitant encephalization. This process is hypothesized to have reduced the size of the lateral nasal capsule exposing the anterior cranial base to the ocular apparatus and thus creating an interorbital septum. The purpose of this study was to determine whether differential growth trajectories occur among the chondrocranial elements corresponding to this hypothesis. Macaca mulatta embryos from the Zingeser Collection were selected for this analysis since this primate shows a well-developed interorbital septum throughout ontogeny. Embryos between 40 and 90 days of gestation were selected from the collection and coronal sections including the eye, anterior cranial base and lateral nasal capsule were subjected to video microscopy and computerized reconstruction using SURFdriver Software. Tissue volumes were computed for these tissues while chondrocytic growth attributes were measured utilizing stereological techniques. Results showed a strong correlation between the volume of the lateral nasal capsule and anterior cranial base and these two structures showed a consistent correlation with an increasing eye volume. Chondrocytic volume density and average diameter were larger in the lateral nasal capsule while shape, numerical density and average volume did not differ between the two tissues. These data suggest if differential growth does account for a reduction of the nasal capsule compared to the central cranial base stem, it does not appear to result from differential tissue size change. However, certain cellular growth activities leading to premature chondrocytic hypertrophy may be involved.
-
Project Lifespan-based Nonstationary Hydrologic Design Methods for Changing Environment
NASA Astrophysics Data System (ADS)
Xiong, L.
2017-12-01
Under changing environment, we must associate design floods with the design life period of projects to ensure the hydrologic design is really relevant to the operation of the hydrologic projects, because the design value for a given exceedance probability over the project life period would be significantly different from that over other time periods of the same length due to the nonstationarity of probability distributions. Several hydrologic design methods that take the design life period of projects into account have been proposed in recent years, i.e. the expected number of exceedances (ENE), design life level (DLL), equivalent reliability (ER), and average design life level (ADLL). Among the four methods to be compared, both the ENE and ER methods are return period-based methods, while DLL and ADLL are risk/reliability- based methods which estimate design values for given probability values of risk or reliability. However, the four methods can be unified together under a general framework through a relationship transforming the so-called representative reliability (RRE) into the return period, i.e. m=1/1(1-RRE), in which we compute the return period m using the representative reliability RRE.The results of nonstationary design quantiles and associated confidence intervals calculated by ENE, ER and ADLL were very similar, since ENE or ER was a special case or had a similar expression form with respect to ADLL. In particular, the design quantiles calculated by ENE and ADLL were the same when return period was equal to the length of the design life. In addition, DLL can yield similar design values if the relationship between DLL and ER/ADLL return periods is considered. Furthermore, ENE, ER and ADLL had good adaptability to either an increasing or decreasing situation, yielding not too large or too small design quantiles. This is important for applications of nonstationary hydrologic design methods in actual practice because of the concern of choosing the emerging nonstationary methods versus the traditional stationary methods. There is still a long way to go for the conceptual transition from stationarity to nonstationarity in hydrologic design.
-
He, Jianbo; Li, Jijie; Huang, Zhongwen; Zhao, Tuanjie; Xing, Guangnan; Gai, Junyi; Guan, Rongzhan
2015-01-01
Experimental error control is very important in quantitative trait locus (QTL) mapping. Although numerous statistical methods have been developed for QTL mapping, a QTL detection model based on an appropriate experimental design that emphasizes error control has not been developed. Lattice design is very suitable for experiments with large sample sizes, which is usually required for accurate mapping of quantitative traits. However, the lack of a QTL mapping method based on lattice design dictates that the arithmetic mean or adjusted mean of each line of observations in the lattice design had to be used as a response variable, resulting in low QTL detection power. As an improvement, we developed a QTL mapping method termed composite interval mapping based on lattice design (CIMLD). In the lattice design, experimental errors are decomposed into random errors and block-within-replication errors. Four levels of block-within-replication errors were simulated to show the power of QTL detection under different error controls. The simulation results showed that the arithmetic mean method, which is equivalent to a method under random complete block design (RCBD), was very sensitive to the size of the block variance and with the increase of block variance, the power of QTL detection decreased from 51.3% to 9.4%. In contrast to the RCBD method, the power of CIMLD and the adjusted mean method did not change for different block variances. The CIMLD method showed 1.2- to 7.6-fold higher power of QTL detection than the arithmetic or adjusted mean methods. Our proposed method was applied to real soybean (Glycine max) data as an example and 10 QTLs for biomass were identified that explained 65.87% of the phenotypic variation, while only three and two QTLs were identified by arithmetic and adjusted mean methods, respectively.
-
NASA Astrophysics Data System (ADS)
Kobayashi, Takashi; Komoda, Norihisa
The traditional business process design methods, in which the usecase is the most typical, have no useful framework to design the activity sequence with. Therefore, the design efficiency and quality vary widely according to the designer’s experience and skill. In this paper, to solve this problem, we propose the business events and their state transition model (a basic business event model) based on the language/action perspective, which is the result in the cognitive science domain. In the business process design, using this model, we decide event occurrence conditions so that every event synchronizes with each other. We also propose the design pattern to decide the event occurrence condition (a business event improvement strategy). Lastly, we apply the business process design method based on the business event model and the business event improvement strategy to the credit card issue process and estimate its effect.
-
An Engineering Method of Civil Jet Requirements Validation Based on Requirements Project Principle
NASA Astrophysics Data System (ADS)
Wang, Yue; Gao, Dan; Mao, Xuming
2018-03-01
A method of requirements validation is developed and defined to meet the needs of civil jet requirements validation in product development. Based on requirements project principle, this method will not affect the conventional design elements, and can effectively connect the requirements with design. It realizes the modern civil jet development concept, which is “requirement is the origin, design is the basis”. So far, the method has been successfully applied in civil jet aircraft development in China. Taking takeoff field length as an example, the validation process and the validation method of the requirements are detailed introduced in the study, with the hope of providing the experiences to other civil jet product design.
-
Research on conceptual/innovative design for the life cycle
NASA Technical Reports Server (NTRS)
Cagan, Jonathan; Agogino, Alice M.
1990-01-01
The goal of this research is developing and integrating qualitative and quantitative methods for life cycle design. The definition of the problem includes formal computer-based methods limited to final detailing stages of design; CAD data bases do not capture design intent or design history; and life cycle issues were ignored during early stages of design. Viewgraphs outline research in conceptual design; the SYMON (SYmbolic MONotonicity analyzer) algorithm; multistart vector quantization optimization algorithm; intelligent manufacturing: IDES - Influence Diagram Architecture; and 1st PRINCE (FIRST PRINciple Computational Evaluator).
-
Creating A Data Base For Design Of An Impeller
NASA Technical Reports Server (NTRS)
Prueger, George H.; Chen, Wei-Chung
1993-01-01
Report describes use of Taguchi method of parametric design to create data base facilitating optimization of design of impeller in centrifugal pump. Data base enables systematic design analysis covering all significant design parameters. Reduces time and cost of parametric optimization of design: for particular impeller considered, one can cover 4,374 designs by computational simulations of performance for only 18 cases.
-
Li, Zhifei; Qin, Dongliang
2014-01-01
In defense related programs, the use of capability-based analysis, design, and acquisition has been significant. In order to confront one of the most challenging features of a huge design space in capability based analysis (CBA), a literature review of design space exploration was first examined. Then, in the process of an aerospace system of systems design space exploration, a bilayer mapping method was put forward, based on the existing experimental and operating data. Finally, the feasibility of the foregoing approach was demonstrated with an illustrative example. With the data mining RST (rough sets theory) and SOM (self-organized mapping) techniques, the alternative to the aerospace system of systems architecture was mapping from P-space (performance space) to C-space (configuration space), and then from C-space to D-space (design space), respectively. Ultimately, the performance space was mapped to the design space, which completed the exploration and preliminary reduction of the entire design space. This method provides a computational analysis and implementation scheme for large-scale simulation. PMID:24790572
-
Li, Zhifei; Qin, Dongliang; Yang, Feng
2014-01-01
In defense related programs, the use of capability-based analysis, design, and acquisition has been significant. In order to confront one of the most challenging features of a huge design space in capability based analysis (CBA), a literature review of design space exploration was first examined. Then, in the process of an aerospace system of systems design space exploration, a bilayer mapping method was put forward, based on the existing experimental and operating data. Finally, the feasibility of the foregoing approach was demonstrated with an illustrative example. With the data mining RST (rough sets theory) and SOM (self-organized mapping) techniques, the alternative to the aerospace system of systems architecture was mapping from P-space (performance space) to C-space (configuration space), and then from C-space to D-space (design space), respectively. Ultimately, the performance space was mapped to the design space, which completed the exploration and preliminary reduction of the entire design space. This method provides a computational analysis and implementation scheme for large-scale simulation.
-
Radiofrequency pulse design using nonlinear gradient magnetic fields.
Kopanoglu, Emre; Constable, R Todd
2015-09-01
An iterative k-space trajectory and radiofrequency (RF) pulse design method is proposed for excitation using nonlinear gradient magnetic fields. The spatial encoding functions (SEFs) generated by nonlinear gradient fields are linearly dependent in Cartesian coordinates. Left uncorrected, this may lead to flip angle variations in excitation profiles. In the proposed method, SEFs (k-space samples) are selected using a matching pursuit algorithm, and the RF pulse is designed using a conjugate gradient algorithm. Three variants of the proposed approach are given: the full algorithm, a computationally cheaper version, and a third version for designing spoke-based trajectories. The method is demonstrated for various target excitation profiles using simulations and phantom experiments. The method is compared with other iterative (matching pursuit and conjugate gradient) and noniterative (coordinate-transformation and Jacobian-based) pulse design methods as well as uniform density spiral and EPI trajectories. The results show that the proposed method can increase excitation fidelity. An iterative method for designing k-space trajectories and RF pulses using nonlinear gradient fields is proposed. The method can either be used for selecting the SEFs individually to guide trajectory design, or can be adapted to design and optimize specific trajectories of interest. © 2014 Wiley Periodicals, Inc.
-
NASA Astrophysics Data System (ADS)
Alfadhlani; Samadhi, T. M. A. Ari; Ma’ruf, Anas; Setiasyah Toha, Isa
2018-03-01
Assembly is a part of manufacturing processes that must be considered at the product design stage. Design for Assembly (DFA) is a method to evaluate product design in order to make it simpler, easier and quicker to assemble, so that assembly cost is reduced. This article discusses a framework for developing a computer-based DFA method. The method is expected to aid product designer to extract data, evaluate assembly process, and provide recommendation for the product design improvement. These three things are desirable to be performed without interactive process or user intervention, so product design evaluation process could be done automatically. Input for the proposed framework is a 3D solid engineering drawing. Product design evaluation is performed by: minimizing the number of components; generating assembly sequence alternatives; selecting the best assembly sequence based on the minimum number of assembly reorientations; and providing suggestion for design improvement.
-
Why does Japan use the probability method to set design flood?
NASA Astrophysics Data System (ADS)
Nakamura, S.; Oki, T.
2015-12-01
Design flood is hypothetical flood to make flood prevention plan. In Japan, a probability method based on precipitation data is used to define the scale of design flood: Tone River, the biggest river in Japan, is 1 in 200 years, Shinano River is 1 in 150 years, and so on. It is one of important socio-hydrological issue how to set reasonable and acceptable design flood in a changing world. The method to set design flood vary among countries. Although the probability method is also used in Netherland, but the base data is water level or discharge data and the probability is 1 in 1250 years (in fresh water section). On the other side, USA and China apply the maximum flood method which set the design flood based on the historical or probable maximum flood. This cases can leads a question: "what is the reason why the method vary among countries?" or "why does Japan use the probability method?" The purpose of this study is to clarify the historical process which the probability method was developed in Japan based on the literature. In the late 19the century, the concept of "discharge" and modern river engineering were imported by Dutch engineers, and modern flood prevention plans were developed in Japan. In these plans, the design floods were set based on the historical maximum method. Although the historical maximum method had been used until World War 2, however, the method was changed to the probability method after the war because of limitations of historical maximum method under the specific socio-economic situations: (1) the budget limitation due to the war and the GHQ occupation, (2) the historical floods: Makurazaki typhoon in 1945, Kathleen typhoon in 1947, Ione typhoon in 1948, and so on, attacked Japan and broke the record of historical maximum discharge in main rivers and the flood disasters made the flood prevention projects difficult to complete. Then, Japanese hydrologists imported the hydrological probability statistics from the West to take account of socio-economic situation in design flood, and they applied to Japanese rivers in 1958. The probability method was applied Japan to adapt the specific socio-economic and natural situation during the confusion after the war.
-
General design method of ultra-broadband perfect absorbers based on magnetic polaritons.
Liu, Yuanbin; Qiu, Jun; Zhao, Junming; Liu, Linhua
2017-10-02
Starting from one-dimensional gratings and the theory of magnetic polaritons (MPs), we propose a general design method of ultra-broadband perfect absorbers. Based on the proposed design method, the obtained absorber can keep the spectrum-average absorptance over 99% at normal incidence in a wide range of wavelengths; this work simultaneously reveals the robustness of the absorber to incident angles and polarization angles of incident light. Furthermore, this work shows that the spectral band of perfect absorption can be flexibly extended to near the infrared regime by adjusting the structure dimension. The findings of this work may facilitate the active design of ultra-broadband absorbers based on plasmonic nanostructures.
-
A method of designing smartphone interface based on the extended user's mental model
NASA Astrophysics Data System (ADS)
Zhao, Wei; Li, Fengmin; Bian, Jiali; Pan, Juchen; Song, Song
2017-01-01
The user's mental model is the core guiding theory of product design, especially practical products. The essence of practical product is a tool which is used by users to meet their needs. Then, the most important feature of a tool is usability. The design method based on the user's mental model provides a series of practical and feasible theoretical guidance for improving the usability of the product according to the user's awareness of things. In this paper, we propose a method of designing smartphone interface based on the extended user's mental model according to further research on user groups. This approach achieves personalized customization of smartphone application interface and enhance application using efficiency.
-
Applying Case-Based Method in Designing Self-Directed Online Instruction: A Formative Research Study
ERIC Educational Resources Information Center
Luo, Heng; Koszalka, Tiffany A.; Arnone, Marilyn P.; Choi, Ikseon
2018-01-01
This study investigated the case-based method (CBM) instructional-design theory and its application in designing self-directed online instruction. The purpose of this study was to validate and refine the theory for a self-directed online instruction context. Guided by formative research methodology, this study first developed an online tutorial…
-
What Is Design-Based Causal Inference for RCTs and Why Should I Use It? NCEE 2017-4025
ERIC Educational Resources Information Center
Schochet, Peter Z.
2017-01-01
Design-based methods have recently been developed as a way to analyze data from impact evaluations of interventions, programs, and policies. The impact estimators are derived using the building blocks of experimental designs with minimal assumptions, and have good statistical properties. The methods apply to randomized controlled trials (RCTs) and…
-
Sampling Strategies and Processing of Biobank Tissue Samples from Porcine Biomedical Models.
Blutke, Andreas; Wanke, Rüdiger
2018-03-06
In translational medical research, porcine models have steadily become more popular. Considering the high value of individual animals, particularly of genetically modified pig models, and the often-limited number of available animals of these models, establishment of (biobank) collections of adequately processed tissue samples suited for a broad spectrum of subsequent analyses methods, including analyses not specified at the time point of sampling, represent meaningful approaches to take full advantage of the translational value of the model. With respect to the peculiarities of porcine anatomy, comprehensive guidelines have recently been established for standardized generation of representative, high-quality samples from different porcine organs and tissues. These guidelines are essential prerequisites for the reproducibility of results and their comparability between different studies and investigators. The recording of basic data, such as organ weights and volumes, the determination of the sampling locations and of the numbers of tissue samples to be generated, as well as their orientation, size, processing and trimming directions, are relevant factors determining the generalizability and usability of the specimen for molecular, qualitative, and quantitative morphological analyses. Here, an illustrative, practical, step-by-step demonstration of the most important techniques for generation of representative, multi-purpose biobank specimen from porcine tissues is presented. The methods described here include determination of organ/tissue volumes and densities, the application of a volume-weighted systematic random sampling procedure for parenchymal organs by point-counting, determination of the extent of tissue shrinkage related to histological embedding of samples, and generation of randomly oriented samples for quantitative stereological analyses, such as isotropic uniform random (IUR) sections generated by the "Orientator" and "Isector" methods, and vertical uniform random (VUR) sections.
-
Design of Composite Structures Using Knowledge-Based and Case Based Reasoning
NASA Technical Reports Server (NTRS)
Lambright, Jonathan Paul
1996-01-01
A method of using knowledge based and case based reasoning to assist designers during conceptual design tasks of composite structures was proposed. The cooperative use of heuristics, procedural knowledge, and previous similar design cases suggests a potential reduction in design cycle time and ultimately product lead time. The hypothesis of this work is that the design process of composite structures can be improved by using Case-Based Reasoning (CBR) and Knowledge-Based (KB) reasoning in the early design stages. The technique of using knowledge-based and case-based reasoning facilitates the gathering of disparate information into one location that is easily and readily available. The method suggests that the inclusion of downstream life-cycle issues into the conceptual design phase reduces potential of defective, and sub-optimal composite structures. Three industry experts were interviewed extensively. The experts provided design rules, previous design cases, and test problems. A Knowledge Based Reasoning system was developed using the CLIPS (C Language Interpretive Procedural System) environment and a Case Based Reasoning System was developed using the Design Memory Utility For Sharing Experiences (MUSE) xviii environment. A Design Characteristic State (DCS) was used to document the design specifications, constraints, and problem areas using attribute-value pair relationships. The DCS provided consistent design information between the knowledge base and case base. Results indicated that the use of knowledge based and case based reasoning provided a robust design environment for composite structures. The knowledge base provided design guidance from well defined rules and procedural knowledge. The case base provided suggestions on design and manufacturing techniques based on previous similar designs and warnings of potential problems and pitfalls. The case base complemented the knowledge base and extended the problem solving capability beyond the existence of limited well defined rules. The findings indicated that the technique is most effective when used as a design aid and not as a tool to totally automate the composites design process. Other areas of application and implications for future research are discussed.
-
The Development of a Robot-Based Learning Companion: A User-Centered Design Approach
ERIC Educational Resources Information Center
Hsieh, Yi-Zeng; Su, Mu-Chun; Chen, Sherry Y.; Chen, Gow-Dong
2015-01-01
A computer-vision-based method is widely employed to support the development of a variety of applications. In this vein, this study uses a computer-vision-based method to develop a playful learning system, which is a robot-based learning companion named RobotTell. Unlike existing playful learning systems, a user-centered design (UCD) approach is…
-
Trends in study design and the statistical methods employed in a leading general medicine journal.
Gosho, M; Sato, Y; Nagashima, K; Takahashi, S
2018-02-01
Study design and statistical methods have become core components of medical research, and the methodology has become more multifaceted and complicated over time. The study of the comprehensive details and current trends of study design and statistical methods is required to support the future implementation of well-planned clinical studies providing information about evidence-based medicine. Our purpose was to illustrate study design and statistical methods employed in recent medical literature. This was an extension study of Sato et al. (N Engl J Med 2017; 376: 1086-1087), which reviewed 238 articles published in 2015 in the New England Journal of Medicine (NEJM) and briefly summarized the statistical methods employed in NEJM. Using the same database, we performed a new investigation of the detailed trends in study design and individual statistical methods that were not reported in the Sato study. Due to the CONSORT statement, prespecification and justification of sample size are obligatory in planning intervention studies. Although standard survival methods (eg Kaplan-Meier estimator and Cox regression model) were most frequently applied, the Gray test and Fine-Gray proportional hazard model for considering competing risks were sometimes used for a more valid statistical inference. With respect to handling missing data, model-based methods, which are valid for missing-at-random data, were more frequently used than single imputation methods. These methods are not recommended as a primary analysis, but they have been applied in many clinical trials. Group sequential design with interim analyses was one of the standard designs, and novel design, such as adaptive dose selection and sample size re-estimation, was sometimes employed in NEJM. Model-based approaches for handling missing data should replace single imputation methods for primary analysis in the light of the information found in some publications. Use of adaptive design with interim analyses is increasing after the presentation of the FDA guidance for adaptive design. © 2017 John Wiley & Sons Ltd.
-
RF Pulse Design using Nonlinear Gradient Magnetic Fields
Kopanoglu, Emre; Constable, R. Todd
2014-01-01
Purpose An iterative k-space trajectory and radio-frequency (RF) pulse design method is proposed for Excitation using Nonlinear Gradient Magnetic fields (ENiGMa). Theory and Methods The spatial encoding functions (SEFs) generated by nonlinear gradient fields (NLGFs) are linearly dependent in Cartesian-coordinates. Left uncorrected, this may lead to flip-angle variations in excitation profiles. In the proposed method, SEFs (k-space samples) are selected using a Matching-Pursuit algorithm, and the RF pulse is designed using a Conjugate-Gradient algorithm. Three variants of the proposed approach are given: the full-algorithm, a computationally-cheaper version, and a third version for designing spoke-based trajectories. The method is demonstrated for various target excitation profiles using simulations and phantom experiments. Results The method is compared to other iterative (Matching-Pursuit and Conjugate Gradient) and non-iterative (coordinate-transformation and Jacobian-based) pulse design methods as well as uniform density spiral and EPI trajectories. The results show that the proposed method can increase excitation fidelity significantly. Conclusion An iterative method for designing k-space trajectories and RF pulses using nonlinear gradient fields is proposed. The method can either be used for selecting the SEFs individually to guide trajectory design, or can be adapted to design and optimize specific trajectories of interest. PMID:25203286
-
Design Oriented Structural Modeling for Airplane Conceptual Design Optimization
NASA Technical Reports Server (NTRS)
Livne, Eli
1999-01-01
The main goal for research conducted with the support of this grant was to develop design oriented structural optimization methods for the conceptual design of airplanes. Traditionally in conceptual design airframe weight is estimated based on statistical equations developed over years of fitting airplane weight data in data bases of similar existing air- planes. Utilization of such regression equations for the design of new airplanes can be justified only if the new air-planes use structural technology similar to the technology on the airplanes in those weight data bases. If any new structural technology is to be pursued or any new unconventional configurations designed the statistical weight equations cannot be used. In such cases any structural weight estimation must be based on rigorous "physics based" structural analysis and optimization of the airframes under consideration. Work under this grant progressed to explore airframe design-oriented structural optimization techniques along two lines of research: methods based on "fast" design oriented finite element technology and methods based on equivalent plate / equivalent shell models of airframes, in which the vehicle is modelled as an assembly of plate and shell components, each simulating a lifting surface or nacelle / fuselage pieces. Since response to changes in geometry are essential in conceptual design of airplanes, as well as the capability to optimize the shape itself, research supported by this grant sought to develop efficient techniques for parametrization of airplane shape and sensitivity analysis with respect to shape design variables. Towards the end of the grant period a prototype automated structural analysis code designed to work with the NASA Aircraft Synthesis conceptual design code ACS= was delivered to NASA Ames.
-
Patel, Prinesh N; Karakam, Vijaya Saradhi; Samanthula, Gananadhamu; Ragampeta, Srinivas
2015-10-01
Quality-by-design-based methods hold greater level of confidence for variations and greater success in method transfer. A quality-by-design-based ultra high performance liquid chromatography method was developed for the simultaneous assay of sumatriptan and naproxen along with their related substances. The first screening was performed by fractional factorial design comprising 44 experiments for reversed-phase stationary phases, pH, and organic modifiers. The results of screening design experiments suggested phenyl hexyl column and acetonitrile were the best combination. The method was further optimized for flow rate, temperature, and gradient time by experimental design of 20 experiments and the knowledge space was generated for effect of variable on response (number of peaks ≥ 1.50 - resolution). Proficient design space was generated from knowledge space by applying Monte Carlo simulation to successfully integrate quantitative robustness metrics during optimization stage itself. The final method provided the robust performance which was verified and validated. Final conditions comprised Waters® Acquity phenyl hexyl column with gradient elution using ammonium acetate (pH 4.12, 0.02 M) buffer and acetonitrile at 0.355 mL/min flow rate and 30°C. The developed method separates all 13 analytes within a 15 min run time with fewer experiments compared to the traditional quality-by-testing approach. ©2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
-
Design of crusher liner based on time - varying uncertainty theory
NASA Astrophysics Data System (ADS)
Tang, J. C.; Shi, B. Q.; Yu, H. J.; Wang, R. J.; Zhang, W. Y.
2017-09-01
This article puts forward the time-dependent design method considering the load fluctuation factors for the liner based on the time-varying uncertainty theory. In this method, the time-varying uncertainty design model of liner is constructed by introducing the parameters that affect the wear rate, the volatility and the drift rate. Based on the design example, the timevarying design outline of the moving cone liner is obtained. Based on the theory of minimum wear, the gap curve of wear resistant cavity is designed, and the optimized cavity is obtained by the combination of the thickness of the cone and the cavity gap. Taking the PYGB1821 multi cylinder hydraulic cone crusher as an example, it is proved that the service life of the new liner is improved by more than 14.3%.
-
Fabricating biomedical origami: a state-of-the-art review
Johnson, Meredith; Chen, Yue; Hovet, Sierra; Xu, Sheng; Wood, Bradford; Ren, Hongliang; Tokuda, Junichi; Tse, Zion Tsz Ho
2018-01-01
Purpose Origami-based biomedical device design is an emerging technology due to its ability to be deployed from a minimal foldable pattern to a larger volume. This paper aims to review state-of-the-art origami structures applied in the medical device field. Methods Publications and reports of origami structure related to medical device design from the past 10 years are reviewed and categorized according to engineering specifications, including the application field, fabrication material, size/volume, deployment method, manufacturability, and advantages. Results This paper presents an overview of the biomedical applications of devices based on origami structures, including disposable sterilization covers, cardiac catheterization, stent grafts, encapsulation and microsurgery, gastrointestinal microsurgery, laparoscopic surgical grippers, microgrippers, microfluidic devices, and drug delivery. Challenges in terms of materials and fabrication, assembly, modeling and computation design, and clinical adoptability are discussed at the end of this paper to provide guidance for future origami-based design in the medical device field. Conclusion Concepts from origami can be used to design and develop novel medical devices. Origami-based medical device design is currently progressing, with researchers improving design methods, materials, fabrication techniques, and folding efficiency. PMID:28260164
-
ERIC Educational Resources Information Center
Daghan, Gökhan; Akkoyunlu, Buket
2014-01-01
In this study, Information Technologies teachers' views and usage cases on performance based assesment methods (PBAMs) are examined. It is aimed to find out which of the PBAMs are used frequently or not used, preference reasons of these methods and opinions about the applicability of them. Study is designed with the phenomenological design which…
-
Aircraft digital control design methods
NASA Technical Reports Server (NTRS)
Powell, J. D.; Parsons, E.; Tashker, M. G.
1976-01-01
Variations in design methods for aircraft digital flight control are evaluated and compared. The methods fall into two categories; those where the design is done in the continuous domain (or s plane) and those where the design is done in the discrete domain (or z plane). Design method fidelity is evaluated by examining closed loop root movement and the frequency response of the discretely controlled continuous aircraft. It was found that all methods provided acceptable performance for sample rates greater than 10 cps except the uncompensated s plane design method which was acceptable above 20 cps. A design procedure based on optimal control methods was proposed that provided the best fidelity at very slow sample rates and required no design iterations for changing sample rates.
-
Performance-Based Seismic Design of Steel Frames Utilizing Colliding Bodies Algorithm
Veladi, H.
2014-01-01
A pushover analysis method based on semirigid connection concept is developed and the colliding bodies optimization algorithm is employed to find optimum seismic design of frame structures. Two numerical examples from the literature are studied. The results of the new algorithm are compared to the conventional design methods to show the power or weakness of the algorithm. PMID:25202717
-
Performance-based seismic design of steel frames utilizing colliding bodies algorithm.
Veladi, H
2014-01-01
A pushover analysis method based on semirigid connection concept is developed and the colliding bodies optimization algorithm is employed to find optimum seismic design of frame structures. Two numerical examples from the literature are studied. The results of the new algorithm are compared to the conventional design methods to show the power or weakness of the algorithm.
-
NASA Astrophysics Data System (ADS)
Adrich, Przemysław
2016-05-01
In Part I of this work existing methods and problems in dual foil electron beam forming system design are presented. On this basis, a new method of designing these systems is introduced. The motivation behind this work is to eliminate the shortcomings of the existing design methods and improve overall efficiency of the dual foil design process. The existing methods are based on approximate analytical models applied in an unrealistically simplified geometry. Designing a dual foil system with these methods is a rather labor intensive task as corrections to account for the effects not included in the analytical models have to be calculated separately and accounted for in an iterative procedure. To eliminate these drawbacks, the new design method is based entirely on Monte Carlo modeling in a realistic geometry and using physics models that include all relevant processes. In our approach, an optimal configuration of the dual foil system is found by means of a systematic, automatized scan of the system performance in function of parameters of the foils. The new method, while being computationally intensive, minimizes the involvement of the designer and considerably shortens the overall design time. The results are of high quality as all the relevant physics and geometry details are naturally accounted for. To demonstrate the feasibility of practical implementation of the new method, specialized software tools were developed and applied to solve a real life design problem, as described in Part II of this work.
-
NASA Technical Reports Server (NTRS)
Yang, Y. L.; Tan, C. S.; Hawthorne, W. R.
1992-01-01
A computational method, based on a theory for turbomachinery blading design in three-dimensional inviscid flow, is applied to a parametric design study of a radial inflow turbine wheel. As the method requires the specification of swirl distribution, a technique for its smooth generation within the blade region is proposed. Excellent agreements have been obtained between the computed results from this design method and those from direct Euler computations, demonstrating the correspondence and consistency between the two. The computed results indicate the sensitivity of the pressure distribution to a lean in the stacking axis and a minor alteration in the hub/shroud profiles. Analysis based on Navier-Stokes solver shows no breakdown of flow within the designed blade passage and agreement with that from design calculation; thus the flow in the designed turbine rotor closely approximates that of an inviscid one. These calculations illustrate the use of a design method coupled to an analysis tool for establishing guidelines and criteria for designing turbomachinery blading.
-
Design of transonic airfoil sections using a similarity theory
NASA Technical Reports Server (NTRS)
Nixon, D.
1978-01-01
A study of the available methods for transonic airfoil and wing design indicates that the most powerful technique is the numerical optimization procedure. However, the computer time for this method is relatively large because of the amount of computation required in the searches during optimization. The optimization method requires that base and calibration solutions be computed to determine a minimum drag direction. The design space is then computationally searched in this direction; it is these searches that dominate the computation time. A recent similarity theory allows certain transonic flows to be calculated rapidly from the base and calibration solutions. In this paper the application of the similarity theory to design problems is examined with the object of at least partially eliminating the costly searches of the design optimization method. An example of an airfoil design is presented.
-
NASA Astrophysics Data System (ADS)
Kajiwara, Itsuro; Furuya, Keiichiro; Ishizuka, Shinichi
2018-07-01
Model-based controllers with adaptive design variables are often used to control an object with time-dependent characteristics. However, the controller's performance is influenced by many factors such as modeling accuracy and fluctuations in the object's characteristics. One method to overcome these negative factors is to tune model-based controllers. Herein we propose an online tuning method to maintain control performance for an object that exhibits time-dependent variations. The proposed method employs the poles of the controller as design variables because the poles significantly impact performance. Specifically, we use the simultaneous perturbation stochastic approximation (SPSA) to optimize a model-based controller with multiple design variables. Moreover, a vibration control experiment of an object with time-dependent characteristics as the temperature is varied demonstrates that the proposed method allows adaptive control and stably maintains the closed-loop characteristics.
-
Case-based reasoning in design: An apologia
NASA Technical Reports Server (NTRS)
Pulaski, Kirt
1990-01-01
Three positions are presented and defended: the process of generating solutions in problem solving is viewable as a design task; case-based reasoning is a strong method of problem solving; and a synergism exists between case-based reasoning and design problem solving.
-
A knowledge-based design framework for airplane conceptual and preliminary design
NASA Astrophysics Data System (ADS)
Anemaat, Wilhelmus A. J.
The goal of work described herein is to develop the second generation of Advanced Aircraft Analysis (AAA) into an object-oriented structure which can be used in different environments. One such environment is the third generation of AAA with its own user interface, the other environment with the same AAA methods (i.e. the knowledge) is the AAA-AML program. AAA-AML automates the initial airplane design process using current AAA methods in combination with AMRaven methodologies for dependency tracking and knowledge management, using the TechnoSoft Adaptive Modeling Language (AML). This will lead to the following benefits: (1) Reduced design time: computer aided design methods can reduce design and development time and replace tedious hand calculations. (2) Better product through improved design: more alternative designs can be evaluated in the same time span, which can lead to improved quality. (3) Reduced design cost: due to less training and less calculation errors substantial savings in design time and related cost can be obtained. (4) Improved Efficiency: the design engineer can avoid technically correct but irrelevant calculations on incomplete or out of sync information, particularly if the process enables robust geometry earlier. Although numerous advancements in knowledge based design have been developed for detailed design, currently no such integrated knowledge based conceptual and preliminary airplane design system exists. The third generation AAA methods are tested over a ten year period on many different airplane designs. Using AAA methods will demonstrate significant time savings. The AAA-AML system will be exercised and tested using 27 existing airplanes ranging from single engine propeller, business jets, airliners, UAV's to fighters. Data for the varied sizing methods will be compared with AAA results, to validate these methods. One new design, a Light Sport Aircraft (LSA), will be developed as an exercise to use the tool for designing a new airplane. Using these tools will show an improvement in efficiency over using separate programs due to the automatic recalculation with any change of input data. The direct visual feedback of 3D geometry in the AAA-AML, will lead to quicker resolving of problems as opposed to conventional methods.
-
Problem Solving Techniques for the Design of Algorithms.
ERIC Educational Resources Information Center
Kant, Elaine; Newell, Allen
1984-01-01
Presents model of algorithm design (activity in software development) based on analysis of protocols of two subjects designing three convex hull algorithms. Automation methods, methods for studying algorithm design, role of discovery in problem solving, and comparison of different designs of case study according to model are highlighted.…
-
Small-Tip-Angle Spokes Pulse Design Using Interleaved Greedy and Local Optimization Methods
Grissom, William A.; Khalighi, Mohammad-Mehdi; Sacolick, Laura I.; Rutt, Brian K.; Vogel, Mika W.
2013-01-01
Current spokes pulse design methods can be grouped into methods based either on sparse approximation or on iterative local (gradient descent-based) optimization of the transverse-plane spatial frequency locations visited by the spokes. These two classes of methods have complementary strengths and weaknesses: sparse approximation-based methods perform an efficient search over a large swath of candidate spatial frequency locations but most are incompatible with off-resonance compensation, multifrequency designs, and target phase relaxation, while local methods can accommodate off-resonance and target phase relaxation but are sensitive to initialization and suboptimal local cost function minima. This article introduces a method that interleaves local iterations, which optimize the radiofrequency pulses, target phase patterns, and spatial frequency locations, with a greedy method to choose new locations. Simulations and experiments at 3 and 7 T show that the method consistently produces single- and multifrequency spokes pulses with lower flip angle inhomogeneity compared to current methods. PMID:22392822
-
Ward, Logan; Steel, James; Le Compte, Aaron; Evans, Alicia; Tan, Chia-Siong; Penning, Sophie; Shaw, Geoffrey M; Desaive, Thomas; Chase, J Geoffrey
2012-01-01
Introduction Tight glycemic control (TGC) has shown benefits but has been difficult to implement. Model-based methods and computerized protocols offer the opportunity to improve TGC quality and compliance. This research presents an interface design to maximize compliance, minimize real and perceived clinical effort, and minimize error based on simple human factors and end user input. Method The graphical user interface (GUI) design is presented by construction based on a series of simple, short design criteria based on fundamental human factors engineering and includes the use of user feedback and focus groups comprising nursing staff at Christchurch Hospital. The overall design maximizes ease of use and minimizes (unnecessary) interaction and use. It is coupled to a protocol that allows nurse staff to select measurement intervals and thus self-manage workload. Results The overall GUI design is presented and requires only one data entry point per intervention cycle. The design and main interface are heavily focused on the nurse end users who are the predominant users, while additional detailed and longitudinal data, which are of interest to doctors guiding overall patient care, are available via tabs. This dichotomy of needs and interests based on the end user's immediate focus and goals shows how interfaces must adapt to offer different information to multiple types of users. Conclusions The interface is designed to minimize real and perceived clinical effort, and ongoing pilot trials have reported high levels of acceptance. The overall design principles, approach, and testing methods are based on fundamental human factors principles designed to reduce user effort and error and are readily generalizable. PMID:22401330
-
Applying Item Response Theory Methods to Design a Learning Progression-Based Science Assessment
ERIC Educational Resources Information Center
Chen, Jing
2012-01-01
Learning progressions are used to describe how students' understanding of a topic progresses over time and to classify the progress of students into steps or levels. This study applies Item Response Theory (IRT) based methods to investigate how to design learning progression-based science assessments. The research questions of this study are: (1)…
-
ERIC Educational Resources Information Center
Said, Asnah; Syarif, Edy
2016-01-01
This research aimed to evaluate of online tutorial program design by applying problem-based learning Research Methods currently implemented in the system of Open Distance Learning (ODL). The students must take a Research Methods course to prepare themselves for academic writing projects. Problem-based learning basically emphasizes the process of…
-
An Evolution-Based Approach to De Novo Protein Design and Case Study on Mycobacterium tuberculosis
Brender, Jeffrey R.; Czajka, Jeff; Marsh, David; Gray, Felicia; Cierpicki, Tomasz; Zhang, Yang
2013-01-01
Computational protein design is a reverse procedure of protein folding and structure prediction, where constructing structures from evolutionarily related proteins has been demonstrated to be the most reliable method for protein 3-dimensional structure prediction. Following this spirit, we developed a novel method to design new protein sequences based on evolutionarily related protein families. For a given target structure, a set of proteins having similar fold are identified from the PDB library by structural alignments. A structural profile is then constructed from the protein templates and used to guide the conformational search of amino acid sequence space, where physicochemical packing is accommodated by single-sequence based solvation, torsion angle, and secondary structure predictions. The method was tested on a computational folding experiment based on a large set of 87 protein structures covering different fold classes, which showed that the evolution-based design significantly enhances the foldability and biological functionality of the designed sequences compared to the traditional physics-based force field methods. Without using homologous proteins, the designed sequences can be folded with an average root-mean-square-deviation of 2.1 Å to the target. As a case study, the method is extended to redesign all 243 structurally resolved proteins in the pathogenic bacteria Mycobacterium tuberculosis, which is the second leading cause of death from infectious disease. On a smaller scale, five sequences were randomly selected from the design pool and subjected to experimental validation. The results showed that all the designed proteins are soluble with distinct secondary structure and three have well ordered tertiary structure, as demonstrated by circular dichroism and NMR spectroscopy. Together, these results demonstrate a new avenue in computational protein design that uses knowledge of evolutionary conservation from protein structural families to engineer new protein molecules of improved fold stability and biological functionality. PMID:24204234
-
NASA Astrophysics Data System (ADS)
Gulliver, Eric A.
The objective of this thesis to identify and develop techniques providing direct comparison between simulated and real packed particle mixture microstructures containing submicron-sized particles. This entailed devising techniques for simulating powder mixtures, producing real mixtures with known powder characteristics, sectioning real mixtures, interrogating mixture cross-sections, evaluating and quantifying the mixture interrogation process and for comparing interrogation results between mixtures. A drop and roll-type particle-packing model was used to generate simulations of random mixtures. The simulated mixtures were then evaluated to establish that they were not segregated and free from gross defects. A powder processing protocol was established to provide real mixtures for direct comparison and for use in evaluating the simulation. The powder processing protocol was designed to minimize differences between measured particle size distributions and the particle size distributions in the mixture. A sectioning technique was developed that was capable of producing distortion free cross-sections of fine scale particulate mixtures. Tessellation analysis was used to interrogate mixture cross sections and statistical quality control charts were used to evaluate different types of tessellation analysis and to establish the importance of differences between simulated and real mixtures. The particle-packing program generated crescent shaped pores below large particles but realistic looking mixture microstructures otherwise. Focused ion beam milling was the only technique capable of sectioning particle compacts in a manner suitable for stereological analysis. Johnson-Mehl and Voronoi tessellation of the same cross-sections produced tessellation tiles with different the-area populations. Control charts analysis showed Johnson-Mehl tessellation measurements are superior to Voronoi tessellation measurements for detecting variations in mixture microstructure, such as altered particle-size distributions or mixture composition. Control charts based on tessellation measurements were used for direct, quantitative comparisons between real and simulated mixtures. Four sets of simulated and real mixtures were examined. Data from real mixture was matched with simulated data when the samples were well mixed and the particle size distributions and volume fractions of the components were identical. Analysis of mixture components that occupied less than approximately 10 vol% of the mixture was not practical unless the particle size of the component was extremely small and excellent quality high-resolution compositional micrographs of the real sample are available. These methods of analysis should allow future researchers to systematically evaluate and predict the impact and importance of variables such as component volume fraction and component particle size distribution as they pertain to the uniformity of powder mixture microstructures.
-
Mass-based design and optimization of wave rotors for gas turbine engine enhancement
NASA Astrophysics Data System (ADS)
Chan, S.; Liu, H.
2017-03-01
An analytic method aiming at mass properties was developed for the preliminary design and optimization of wave rotors. In the present method, we introduce the mass balance principle into the design and thus can predict and optimize the mass qualities as well as the performance of wave rotors. A dedicated least-square method with artificial weighting coefficients was developed to solve the over-constrained system in the mass-based design. This method and the adoption of the coefficients were validated by numerical simulation. Moreover, the problem of fresh air exhaustion (FAE) was put forward and analyzed, and exhaust gas recirculation (EGR) was investigated. Parameter analyses and optimization elucidated which designs would not only achieve the best performance, but also operate with minimum EGR and no FAE.
-
A rapid method for soil cement design : Louisiana slope value method.
DOT National Transportation Integrated Search
1964-03-01
The current procedure used by the Louisiana Department of Highways for laboratory design of cement stabilized soil base and subbase courses is taken from standard AASHO test methods, patterned after Portland Cement Association criteria. These methods...
-
Investigation of model-based physical design restrictions (Invited Paper)
NASA Astrophysics Data System (ADS)
Lucas, Kevin; Baron, Stanislas; Belledent, Jerome; Boone, Robert; Borjon, Amandine; Couderc, Christophe; Patterson, Kyle; Riviere-Cazaux, Lionel; Rody, Yves; Sundermann, Frank; Toublan, Olivier; Trouiller, Yorick; Urbani, Jean-Christophe; Wimmer, Karl
2005-05-01
As lithography and other patterning processes become more complex and more non-linear with each generation, the task of physical design rules necessarily increases in complexity also. The goal of the physical design rules is to define the boundary between the physical layout structures which will yield well from those which will not. This is essentially a rule-based pre-silicon guarantee of layout correctness. However the rapid increase in design rule requirement complexity has created logistical problems for both the design and process functions. Therefore, similar to the semiconductor industry's transition from rule-based to model-based optical proximity correction (OPC) due to increased patterning complexity, opportunities for improving physical design restrictions by implementing model-based physical design methods are evident. In this paper we analyze the possible need and applications for model-based physical design restrictions (MBPDR). We first analyze the traditional design rule evolution, development and usage methodologies for semiconductor manufacturers. Next we discuss examples of specific design rule challenges requiring new solution methods in the patterning regime of low K1 lithography and highly complex RET. We then evaluate possible working strategies for MBPDR in the process development and product design flows, including examples of recent model-based pre-silicon verification techniques. Finally we summarize with a proposed flow and key considerations for MBPDR implementation.
-
NASA Astrophysics Data System (ADS)
Li, Leihong
A modular structural design methodology for composite blades is developed. This design method can be used to design composite rotor blades with sophisticate geometric cross-sections. This design method hierarchically decomposed the highly-coupled interdisciplinary rotor analysis into global and local levels. In the global level, aeroelastic response analysis and rotor trim are conduced based on multi-body dynamic models. In the local level, variational asymptotic beam sectional analysis methods are used for the equivalent one-dimensional beam properties. Compared with traditional design methodology, the proposed method is more efficient and accurate. Then, the proposed method is used to study three different design problems that have not been investigated before. The first is to add manufacturing constraints into design optimization. The introduction of manufacturing constraints complicates the optimization process. However, the design with manufacturing constraints benefits the manufacturing process and reduces the risk of violating major performance constraints. Next, a new design procedure for structural design against fatigue failure is proposed. This procedure combines the fatigue analysis with the optimization process. The durability or fatigue analysis employs a strength-based model. The design is subject to stiffness, frequency, and durability constraints. Finally, the manufacturing uncertainty impacts on rotor blade aeroelastic behavior are investigated, and a probabilistic design method is proposed to control the impacts of uncertainty on blade structural performance. The uncertainty factors include dimensions, shapes, material properties, and service loads.
-
NASA Astrophysics Data System (ADS)
Ghasem, Nayef
2016-07-01
This paper illustrates a teaching technique used in computer applications in chemical engineering employed for designing various unit operation processes, where the students learn about unit operations by designing them. The aim of the course is not to teach design, but rather to teach the fundamentals and the function of unit operation processes through simulators. A case study presenting the teaching method was evaluated using student surveys and faculty assessments, which were designed to measure the quality and effectiveness of the teaching method. The results of the questionnaire conclusively demonstrate that this method is an extremely efficient way of teaching a simulator-based course. In addition to that, this teaching method can easily be generalised and used in other courses. A student's final mark is determined by a combination of in-class assessments conducted based on cooperative and peer learning, progress tests and a final exam. Results revealed that peer learning can improve the overall quality of student learning and enhance student understanding.
-
Design method of LED rear fog lamp based on freeform micro-surface reflectors
NASA Astrophysics Data System (ADS)
Yu, Jindong; Wu, Heng
2017-11-01
We propose a practical method for the design of a light-emitting diode (LED) rear fog lamp based on freeform micro-surface reflectors. The lamp consists of nine LEDs and each of them has a freeform micro-surface reflector correspondingly. The micro-surface reflector design includes three steps. An initial freeform reflector is first built based on the light energy maps. The micro-surface reflector is then constructed on the bias of the initial one. Finally, a two-step method is designed to optimize the micro-surface reflector. With the proposed method, a module is designed and LCW DURIS E5 LED source whose emitting surface is 5.7 mm × 3.0 mm is adopted for simulation. A prototype is also assembled and fabricated to verify the real performance. Both the simulation and experimental results demonstrate that the luminous intensity distribution can well fulfill the requirements of ECE No.38 regulation. Furthermore, more than 79% energy can be saved when compared with the rear fog lamps using conventional sources.
-
Design and fabrication of multimode interference couplers based on digital micro-mirror system
NASA Astrophysics Data System (ADS)
Wu, Sumei; He, Xingdao; Shen, Chenbo
2008-03-01
Multimode interference (MMI) couplers, based on the self-imaging effect (SIE), are accepted popularly in integrated optics. According to the importance of MMI devices, in this paper, we present a novel method to design and fabricate MMI couplers. A technology of maskless lithography to make MMI couplers based on a smart digital micro-mirror device (DMD) system is proposed. A 1×4 MMI device is designed as an example, which shows the present method is efficient and cost-effective.
-
NASA Astrophysics Data System (ADS)
Ma, Yuan-Zhuo; Li, Hong-Shuang; Yao, Wei-Xing
2018-05-01
The evaluation of the probabilistic constraints in reliability-based design optimization (RBDO) problems has always been significant and challenging work, which strongly affects the performance of RBDO methods. This article deals with RBDO problems using a recently developed generalized subset simulation (GSS) method and a posterior approximation approach. The posterior approximation approach is used to transform all the probabilistic constraints into ordinary constraints as in deterministic optimization. The assessment of multiple failure probabilities required by the posterior approximation approach is achieved by GSS in a single run at all supporting points, which are selected by a proper experimental design scheme combining Sobol' sequences and Bucher's design. Sequentially, the transformed deterministic design optimization problem can be solved by optimization algorithms, for example, the sequential quadratic programming method. Three optimization problems are used to demonstrate the efficiency and accuracy of the proposed method.
-
Distribution of Particles in the Z-axis of Tissue Sections: Relevance for Counting Methods.
von Bartheld, Christopher S
2012-01-01
The distribution of particles in the z-axis of thick tissue sections has gained considerable attention, primarily because of implications for the accuracy of modern stereological counting methods. Three major types of artifacts can affect these sections: loss of particles from the surfaces of tissue sections (lost caps), homogeneous collapse in the z-axis, and differential deformation in the z-axis. Initially it was assumed that thick sections were not compromised by differential shrinkage or compression (differential uniform deformation). Studies in the last decade showed that such artifacts are common and that they depend on embedding media and sectioning devices. Paraffin, glycolmethacrylate and vibratome sections are affected by this artifact, but not celloidin sections or cryostat-derived cryosections. Differential distribution of particles in the z-axis is likely due to compression of the surface areas (margins) during sectioning, resulting in differential particle densities in the core and margin of tissue sections. This deformation of tissue sections can be rapidly assessed by measuring the position of particles in the z-axis. The analysis is complicated by potential secondary effects on section surfaces through loss of particles, the so-called "lost caps" phenomenon. Secondary effects necessitate the use of guard spaces, while their use in case of primary effects (compression due to sectioning) would enhance the artifact's impact on bias. Symmetric versus asymmetric patterns of z-axis distortion can give clues to distinguish primary and secondary effects. Studies that use the optical disector need to take these parameters into account to minimize biases.
-
Stereological and Morphometric Analysis of MRI Chiari Malformation Type-1
Alkoç, Ozan Alper; Songur, Ahmet; Eser, Olcay; Toktas, Muhsin; Esi, Ertap; Haktanir, Alpay
2015-01-01
Objective In this study, we aimed to investigate the underlying ethiological factors in chiari malformation (CM) type-I (CMI) via performing volumetric and morphometric length-angle measurements. Methods A total of 66 individuals [33 patients (20-65 years) with CMI and 33 control subjects] were included in this study. In sagittal MR images, tonsillar herniation length and concurrent anomalies were evaluated. Supratentorial, infratentorial, and total intracranial volumes were measured using Cavalieri method. Various cranial distances and angles were used to evaluate the platybasia and posterior cranial fossa (PCF) development. Results Tonsillar herniation length was measured 9.09±3.39 mm below foramen magnum in CM group. Tonsillar herniation/concurrent syringomyelia, concavity/defect of clivus, herniation of bulbus and fourth ventricle, basilar invagination and craniovertebral junction abnormality rates were 30.3, 27, 18, 2, 3, and 3 percent, respectively. Absence of cisterna magna was encountered in 87.9% of the patients. Total, IT and ST volumes and distance between Chamberlain line and tip of dens axis, Klaus index, clivus length, distance between internal occipital protuberance and opisthion were significantly decreased in patient group. Also in patient group, it was found that Welcher basal angle/Boogard angle increased and tentorial slope angle decreased. Conclusion Mean cranial volume and length-angle measurement values significantly decreased and there was a congenital abnormality association in nearly 81.5 percent of the CM cases. As a result, it was concluded that CM ethiology can be attributed to multifactorial causes. Moreover, congenital defects can also give rise to this condition. PMID:26713146
-
DOE Office of Scientific and Technical Information (OSTI.GOV)
Man, Jun; Zhang, Jiangjiang; Li, Weixuan
2016-10-01
The ensemble Kalman filter (EnKF) has been widely used in parameter estimation for hydrological models. The focus of most previous studies was to develop more efficient analysis (estimation) algorithms. On the other hand, it is intuitively understandable that a well-designed sampling (data-collection) strategy should provide more informative measurements and subsequently improve the parameter estimation. In this work, a Sequential Ensemble-based Optimal Design (SEOD) method, coupled with EnKF, information theory and sequential optimal design, is proposed to improve the performance of parameter estimation. Based on the first-order and second-order statistics, different information metrics including the Shannon entropy difference (SD), degrees ofmore » freedom for signal (DFS) and relative entropy (RE) are used to design the optimal sampling strategy, respectively. The effectiveness of the proposed method is illustrated by synthetic one-dimensional and two-dimensional unsaturated flow case studies. It is shown that the designed sampling strategies can provide more accurate parameter estimation and state prediction compared with conventional sampling strategies. Optimal sampling designs based on various information metrics perform similarly in our cases. The effect of ensemble size on the optimal design is also investigated. Overall, larger ensemble size improves the parameter estimation and convergence of optimal sampling strategy. Although the proposed method is applied to unsaturated flow problems in this study, it can be equally applied in any other hydrological problems.« less
-
Wang, Xun; Sun, Beibei; Liu, Boyang; Fu, Yaping; Zheng, Pan
2017-01-01
Experimental design focuses on describing or explaining the multifactorial interactions that are hypothesized to reflect the variation. The design introduces conditions that may directly affect the variation, where particular conditions are purposely selected for observation. Combinatorial design theory deals with the existence, construction and properties of systems of finite sets whose arrangements satisfy generalized concepts of balance and/or symmetry. In this work, borrowing the concept of "balance" in combinatorial design theory, a novel method for multifactorial bio-chemical experiments design is proposed, where balanced templates in combinational design are used to select the conditions for observation. Balanced experimental data that covers all the influencing factors of experiments can be obtianed for further processing, such as training set for machine learning models. Finally, a software based on the proposed method is developed for designing experiments with covering influencing factors a certain number of times.
-
On Some Methods in Safety Evaluation in Geotechnics
NASA Astrophysics Data System (ADS)
Puła, Wojciech; Zaskórski, Łukasz
2015-06-01
The paper demonstrates how the reliability methods can be utilised in order to evaluate safety in geotechnics. Special attention is paid to the so-called reliability based design that can play a useful and complementary role to Eurocode 7. In the first part, a brief review of first- and second-order reliability methods is given. Next, two examples of reliability-based design are demonstrated. The first one is focussed on bearing capacity calculation and is dedicated to comparison with EC7 requirements. The second one analyses a rigid pile subjected to lateral load and is oriented towards working stress design method. In the second part, applications of random field to safety evaluations in geotechnics are addressed. After a short review of the theory a Random Finite Element algorithm to reliability based design of shallow strip foundation is given. Finally, two illustrative examples for cohesive and cohesionless soils are demonstrated.
-
Diffraction-based study of fatigue crack initiation and propagation in aerospace aluminum alloys
NASA Astrophysics Data System (ADS)
Gupta, Vipul K.
The crack initiation sites and microstructure-sensitive growth of small fatigue cracks are experimentally characterized in two precipitation-hardened aluminum alloys, 7075-T651 and 7050-T7451, stressed in ambient temperature moist-air (warm-humid) and -50°C dry N2 (cold-dry) environmental conditions. Backscattered electron imaging (BSE) and energy dispersive spectroscopy (EDS) of the fracture surfaces showed that Fe-Cu rich constituent particle clusters are the most common initiation sites within both alloys stressed in either environment. The crack growth within each alloy, on average, was observed to be slowed in the cold-dry environment than in the warm-humid environment, but only at longer crack lengths. Although no overwhelming effects of grain boundaries and grain orientations on small-crack growth were observed, crack growth data showed local fluctuations within individual grains. These observations are understood as crack propagation through the underlying substructure at the crack surface and frequent interaction with low/high-angle grain and subgrain boundaries, during cyclic loading, and, are further attributed to periodic changes in crack propagation path and multiple occurrences of crack-branching observed in the current study. SEM-based stereology in combination with electron backscattered diffraction (EBSD) established fatigue crack surface crystallography within the region from ˜1 to 50 mum of crack initiating particle clusters. Fatigue crack facets were parallel to a wide variety of crystallographic planes, with pole orientations distributed broadly across the irreducible stereographic triangle between the {001} and {101}-poles within both warm-humid and cold-dry environments. The results indicate environmentally affected fatigue cracking in both cases, given the similarity between the observed morphology and crystallography with that of a variety of aerospace aluminum alloys cracked in the presence of moist-air. There was no evidence of crystallographic {111} slip-plane cracking typical of the Stage I crack growth mode observed in single crystals and high purity polycrystals of face centered cubic metals, and which has presently been assumed for the present materials within fatigue crack initiation models. Rather, the facets tend to have near-Mode I spatial orientation, which is another indicator of the importance of environmentally affected fatigue damage. The results provide a physical basis to develop microstructurally-based next generation multi-stage fatigue (MSF) models that should include a new crack decohesion criteria based upon environmental fatigue cracking mechanisms. EBSD study of small-cracks in alloy 7050-T7451, stressed in warm-humid environment, showed that crack-path orientation changes and crack-branching occurred at both low/high-angle grain and subgrain boundaries. Single surface trace analysis suggests that the crack-path differs substantially from crystallographic slip-planes. EBSD-based observations of small-crack propagation through subgrain structure, either formed by cyclic plastic strain accumulation or pre-existing (typical of unrecrystallized grain structure in the present materials), suggest that subgrain structure plays a crucial role in small fatigue crack propagation. As mentioned earlier, local fluctuations in small-crack growth rates appear to be caused by frequent interaction with subgrain boundaries, and multiple occurrences of crack-branching and crack-path orientation changes at low/high-angle grain and subgrain boundaries. The aforementioned deviation from low-index {001}/{101}-planes and the occurrence of high-index cracking planes observed by EBSD/Stereology, in this study and others, are interpreted as trans-subgranular decohesion or inter-subgranular cracking, due to trapped hydrogen. In summary, the results provide a firmer experimental foundation for, and clearer understanding of, the mechanisms of environmental fatigue cracking of aluminum alloys, especially the role of inter-subgranular cracking, which had previously been advanced based upon fracture surface observations alone.
-
On the Use of Parmetric-CAD Systems and Cartesian Methods for Aerodynamic Design
NASA Technical Reports Server (NTRS)
Nemec, Marian; Aftosmis, Michael J.; Pulliam, Thomas H.
2004-01-01
Automated, high-fidelity tools for aerodynamic design face critical issues in attempting to optimize real-life geometry arid in permitting radical design changes. Success in these areas promises not only significantly shorter design- cycle times, but also superior and unconventional designs. To address these issues, we investigate the use of a parmetric-CAD system in conjunction with an embedded-boundary Cartesian method. Our goal is to combine the modeling capabilities of feature-based CAD with the robustness and flexibility of component-based Cartesian volume-mesh generation for complex geometry problems. We present the development of an automated optimization frame-work with a focus on the deployment of such a CAD-based design approach in a heterogeneous parallel computing environment.
-
NASA Astrophysics Data System (ADS)
Hong, Haibo; Yin, Yuehong; Chen, Xing
2016-11-01
Despite the rapid development of computer science and information technology, an efficient human-machine integrated enterprise information system for designing complex mechatronic products is still not fully accomplished, partly because of the inharmonious communication among collaborators. Therefore, one challenge in human-machine integration is how to establish an appropriate knowledge management (KM) model to support integration and sharing of heterogeneous product knowledge. Aiming at the diversity of design knowledge, this article proposes an ontology-based model to reach an unambiguous and normative representation of knowledge. First, an ontology-based human-machine integrated design framework is described, then corresponding ontologies and sub-ontologies are established according to different purposes and scopes. Second, a similarity calculation-based ontology integration method composed of ontology mapping and ontology merging is introduced. The ontology searching-based knowledge sharing method is then developed. Finally, a case of human-machine integrated design of a large ultra-precision grinding machine is used to demonstrate the effectiveness of the method.
-
Analysis of pre-service physics teacher skills designing simple physics experiments based technology
NASA Astrophysics Data System (ADS)
Susilawati; Huda, C.; Kurniawan, W.; Masturi; Khoiri, N.
2018-03-01
Pre-service physics teacher skill in designing simple experiment set is very important in adding understanding of student concept and practicing scientific skill in laboratory. This study describes the skills of physics students in designing simple experiments based technologicall. The experimental design stages include simple tool design and sensor modification. The research method used is descriptive method with the number of research samples 25 students and 5 variations of simple physics experimental design. Based on the results of interviews and observations obtained the results of pre-service physics teacher skill analysis in designing simple experimental physics charged technology is good. Based on observation result, pre-service physics teacher skill in designing simple experiment is good while modification and sensor application are still not good. This suggests that pre-service physics teacher still need a lot of practice and do experiments in designing physics experiments using sensor modifications. Based on the interview result, it is found that students have high enough motivation to perform laboratory activities actively and students have high curiosity to be skilled at making simple practicum tool for physics experiment.
-
Yashchenko, Varvara V; Gavrilova, Olga V; Rautian, Maria S; Jakobsen, Kjetill S
2012-05-01
Paramecium bursaria Chlorella viruses were observed by applying transmission electron microscopy in the native symbiotic system Paramecium bursaria (Ciliophora, Oligohymenophorea) and the green algae Chlorella (Chlorellaceae, Trebouxiophyceae). Virus particles were abundant and localized in the ciliary pits of the cortex and in the buccal cavity of P. bursaria. This was shown for two types of the symbiotic systems associated with two types of Chlorella viruses - Pbi or NC64A. A novel quantitative stereological approach was applied to test whether virus particles were distributed randomly on the Paramecium surface or preferentially occupied certain zones. The ability of the virus to form an association with the ciliate was investigated experimentally; virus particles were mixed with P. bursaria or with symbiont-free species P. caudatum. Our results confirmed that in the freshwater ecosystems two types of P. bursaria -Chlorella symbiotic systems exist, those without Chlorella viruses and those associated with a large amount of the viruses. The fate of Chlorella virus particles at the Paramecium surface was determined based on obtained statistical data and taking into account ciliate feeding currents and cortical reorganization during cell division. A life cycle of the viruses in the complete symbiotic system is proposed. Copyright © 2011 Elsevier GmbH. All rights reserved.
-
Cellular morphometry of the bronchi of human and dog lungs
DOE Office of Scientific and Technical Information (OSTI.GOV)
Robbins, E.S.
1991-03-01
One hundred and thirty-one bronchial samples from 62 patients have been dissected by generation from fixed surgical lung specimens obtained after the removal of pathological lesions. Complete patient records including occupational and smoking histories, as well as possible exposure to radon, are obtained. In addition, one hundred and sixty-two mongol dog bronchi dissected from different lobes of 23 dog lungs have also been similarly prepared. Ninety-four human samples have been completely processed for electron microscopy and have yielded 994 electron micrographs of which 532 have been entered into the Computerized Stereological Analysis System (COSAS) and been used for the measurementmore » of the distances of basal and mucous cell nuclei to the epithelial free surface. Similarly 240 micrographs of dog epithelium from 31 bronchial samples have been entered into COSAS. We have, using the COSAS planimetry program, established data bases which describe the volume density and nuclear numbers per electron micrograph for 5 cell types of the human bronchial epithelial lining of men and women, as well as smokers, non-smokers and ex-smokers and similar parameters for the epithelial cell types of dog bronchi. The data are being used to develop weighting factors for dosimetry and radon risk analysis. 26 refs., 7 figs., 4 tabs.« less
-
Topology optimization based design of unilateral NMR for generating a remote homogeneous field.
Wang, Qi; Gao, Renjing; Liu, Shutian
2017-06-01
This paper presents a topology optimization based design method for the design of unilateral nuclear magnetic resonance (NMR), with which a remote homogeneous field can be obtained. The topology optimization is actualized by seeking out the optimal layout of ferromagnetic materials within a given design domain. The design objective is defined as generating a sensitive magnetic field with optimal homogeneity and maximal field strength within a required region of interest (ROI). The sensitivity of the objective function with respect to the design variables is derived and the method for solving the optimization problem is presented. A design example is provided to illustrate the utility of the design method, specifically the ability to improve the quality of the magnetic field over the required ROI by determining the optimal structural topology for the ferromagnetic poles. Both in simulations and experiments, the sensitive region of the magnetic field achieves about 2 times larger than that of the reference design, validating validates the feasibility of the design method. Copyright © 2017. Published by Elsevier Inc.
-
Ligand design by a combinatorial approach based on modeling and experiment: application to HLA-DR4
NASA Astrophysics Data System (ADS)
Evensen, Erik; Joseph-McCarthy, Diane; Weiss, Gregory A.; Schreiber, Stuart L.; Karplus, Martin
2007-07-01
Combinatorial synthesis and large scale screening methods are being used increasingly in drug discovery, particularly for finding novel lead compounds. Although these "random" methods sample larger areas of chemical space than traditional synthetic approaches, only a relatively small percentage of all possible compounds are practically accessible. It is therefore helpful to select regions of chemical space that have greater likelihood of yielding useful leads. When three-dimensional structural data are available for the target molecule this can be achieved by applying structure-based computational design methods to focus the combinatorial library. This is advantageous over the standard usage of computational methods to design a small number of specific novel ligands, because here computation is employed as part of the combinatorial design process and so is required only to determine a propensity for binding of certain chemical moieties in regions of the target molecule. This paper describes the application of the Multiple Copy Simultaneous Search (MCSS) method, an active site mapping and de novo structure-based design tool, to design a focused combinatorial library for the class II MHC protein HLA-DR4. Methods for the synthesizing and screening the computationally designed library are presented; evidence is provided to show that binding was achieved. Although the structure of the protein-ligand complex could not be determined, experimental results including cross-exclusion of a known HLA-DR4 peptide ligand (HA) by a compound from the library. Computational model building suggest that at least one of the ligands designed and identified by the methods described binds in a mode similar to that of native peptides.
-
John C. Byrne
1993-01-01
Methods for solving some recurring problems of maintaining a permanent plot data base for growth and yield reseuch are described. These methods include documenting data from diverse sampling designs, changing sampling designs, changing field procedures, and coordinating activities in the plots with the land management agency. Managing a permanent plot data base (...
-
ERIC Educational Resources Information Center
Hung, Yen-Chu
2012-01-01
The instructional value of web-based education systems has been an important area of research in information systems education. This study investigates the effect of various teaching methods on program design learning for students with specific learning styles in web-based education systems. The study takes first-year Computer Science and…
-
Embracing model-based designs for dose-finding trials
Love, Sharon B; Brown, Sarah; Weir, Christopher J; Harbron, Chris; Yap, Christina; Gaschler-Markefski, Birgit; Matcham, James; Caffrey, Louise; McKevitt, Christopher; Clive, Sally; Craddock, Charlie; Spicer, James; Cornelius, Victoria
2017-01-01
Background: Dose-finding trials are essential to drug development as they establish recommended doses for later-phase testing. We aim to motivate wider use of model-based designs for dose finding, such as the continual reassessment method (CRM). Methods: We carried out a literature review of dose-finding designs and conducted a survey to identify perceived barriers to their implementation. Results: We describe the benefits of model-based designs (flexibility, superior operating characteristics, extended scope), their current uptake, and existing resources. The most prominent barriers to implementation of a model-based design were lack of suitable training, chief investigators’ preference for algorithm-based designs (e.g., 3+3), and limited resources for study design before funding. We use a real-world example to illustrate how these barriers can be overcome. Conclusions: There is overwhelming evidence for the benefits of CRM. Many leading pharmaceutical companies routinely implement model-based designs. Our analysis identified barriers for academic statisticians and clinical academics in mirroring the progress industry has made in trial design. Unified support from funders, regulators, and journal editors could result in more accurate doses for later-phase testing, and increase the efficiency and success of clinical drug development. We give recommendations for increasing the uptake of model-based designs for dose-finding trials in academia. PMID:28664918
-
Reeder, Blaine; Hills, Rebecca A.; Turner, Anne M.; Demiris, George
2014-01-01
Objectives The objectives of the study were to use persona-driven and scenario-based design methods to create a conceptual information system design to support public health nursing. Design and Sample We enrolled 19 participants from two local health departments to conduct an information needs assessment, create a conceptual design, and conduct a preliminary design validation. Measures Interviews and thematic analysis were used to characterize information needs and solicit design recommendations from participants. Personas were constructed from participant background information, and scenario-based design was used to create a conceptual information system design. Two focus groups were conducted as a first iteration validation of information needs, personas, and scenarios. Results Eighty-nine information needs were identified. Two personas and 89 scenarios were created. Public health nurses and nurse managers confirmed the accuracy of information needs, personas, scenarios, and the perceived usefulness of proposed features of the conceptual design. Design artifacts were modified based on focus group results. Conclusion Persona-driven design and scenario-based design are feasible methods to design for common work activities in different local health departments. Public health nurses and nurse managers should be engaged in the design of systems that support their work. PMID:24117760
-
Bueters, Ruud Rg; van de Kar, Nicole Caj; Schreuder, Michiel F
2013-01-01
Renal size is often used as a marker for nephron numbers as estimation of glomerular numbers is not yet possible in vivo. However, the validity of an association between the two is questionable. As a proper marker for nephron number in an individual is needed in clinical practice, this study was designed to assess the association between renal size and nephron numbers. An individual patient data meta-analysis was performed on data retrieved with a PubMed and Embase search. Only studies were included that described individual human data on kidney size and nephron numbers determined by stereology, the gold standard methodology to estimate nephron numbers. As renal size increases until the end of puberty, and nephron numbers decline after the age of 60 years, only data from individuals aged 18-60 years without renal disease were included. Six papers were identified that provided data on renal weight and nephron numbers from 114 individuals. Backward linear regression identified kidney weight and race as the only 2 significant factors explaining nephron numbers (R square 0.085, p=0.007). Controlling for race, there was a significant correlation between nephron number and kidney weight (r=0.231, r square=0.053, p=0.01). These data indicate that only ∼5% of the variation in nephron numbers is explained by differences in renal size. Renal size in adulthood should not be used as a marker for nephron numbers in an individual. © 2013 S. Karger AG, Basel.
-
A streamline curvature method for design of supercritical and subcritical airfoils
NASA Technical Reports Server (NTRS)
Barger, R. L.; Brooks, C. W., Jr.
1974-01-01
An airfoil design procedure, applicable to both subcritical and supercritical airfoils, is described. The method is based on the streamline curvature velocity equation. Several examples illustrating this method are presented and discussed.
-
Şahin, Arzu; Aslan, Ali; Baş, Orhan; İkinci, Ayşe; Özyılmaz, Cansu; Fikret Sönmez, Osman; Çolakoğlu, Serdar; Odacı, Ersan
2015-10-22
Children are at potential risk due to their intense use of mobile phones. We examined 8-week-old rats because this age of the rats is comparable with the preadolescent period in humans. The number of pyramidal neurons in the cornu ammonis of the Sprague Dawley male rat (8-weeks old, weighing 180-250 g) hippocampus following exposure to a 900 MHz (MHz) electromagnetic field (EMF) were examined. The study consisted of control (CN-G), sham exposed (SHM-EG) and EMF exposed (EMF-EG) groups with 6 rats in each. The EMF-EG rats were exposed to 900 MHz EMF (1h/day for 30 days) in an EMF jar. The SHM-EG rats were placed in the EMF jar but not exposed to the EMF (1h/day for 30 days). The CN-G rats were not placed into the exposure jar and were not exposed to the EMF during the study period. All animals were sacrificed at the end of the experiment, and their brains were removed for histopathological and stereological analysis. The number of pyramidal neurons in the cornu ammonis of the hippocampus was estimated on Cresyl violet stained sections of the brain using the optical dissector counting technique. Histopathological evaluations were also performed on these sections. Histopathological observation showed abundant cells with abnormal, black or dark blue cytoplasm and shrunken morphology among the normal pyramidal neurons. The largest lateral ventricles were observed in the EMF-EG sections compared to those from the other groups. Stereological analyses showed that the total number of pyramidal neurons in the cornu ammonis of the EMF-EG rats was significantly lower than those in the CN-G (p<0.05) and the SHM-EG (p<0.05). In conclusion, our results suggest that pyramidal neuron loss and histopathological changes in the cornu ammonis of 8-week-old male rats may be due to the 900-MHz EMF exposure. Copyright © 2015 Elsevier B.V. All rights reserved.
-
Percolation of fracture networks and stereology
NASA Astrophysics Data System (ADS)
Thovert, Jean-Francois; Mourzenko, Valeri; Adler, Pierre
2017-04-01
The overall properties of fractured porous media depend on the percolative character of the fracture network in a crucial way. The most important examples are permeability and transport. In a recent systematic study, a very wide range of regular, irregular and random fracture shapes is considered, in monodisperse or polydisperse networks containing fractures with different shapes and/or sizes. A simple and new model involving a dimensionless density and a new shape factor is proposed for the percolation threshold, which accounts very efficiently for the influence of the fracture shape. It applies with very good accuracy to monodisperse or moderately polydisperse networks, and provides a good first estimation in other situations. A polydispersity index is shown to control the need for a correction, and the corrective term is modelled for the investigated size distributions. Moreover, and this is crucial for practical applications, the relevant quantities which are present in the expression of the percolation threshold can all be determined from trace maps. An exact and complete set of relations can be derived when the fractures are assumed to be Identical, Isotropically Oriented and Uniformly Distributed (I2OUD). Therefore, the dimensionless density of such networks can be derived directly from the trace maps and its percolating character can be a priori predicted. These relations involve the first five moments of the trace lengths. It is clear that the higher order moments are sensitive to truncation due to the boundaries of the sampling domain. However, it can be shown that the truncation effect can be fully taken into account and corrected, for any fracture shape, size and orientation distributions, if the fractures are spatially uniformly distributed. Systematic applications of these results are made to real fracture networks that we previously analyzed by other means and to numerically simulated networks. It is important to know if the stereological results and their applications can be extended to networks which are not I2OUD. In other words, for a given trace map, an equivalent I2OUD network is defined whose percolating character and permeability are readily deduced. The conditions under which these predicted properties are not too far from the real properties are under investigation.
-
da Rocha, Alisson L; Pereira, Bruno C; Pauli, José R; de Souza, Claudio T; Teixeira, Giovana R; Lira, Fábio S; Cintra, Dennys E; Ropelle, Eduardo R; Júnior, Carlos R B; da Silva, Adelino S R
2016-05-01
The aim of this study was to verify the effects of running overtraining protocols performed in downhill, uphill, and without inclination on the proteins related to hypertrophy signaling pathway in extensor digitorum longus (EDL) and soleus of C57BL/6 mice. We also performed histological and stereological analyses. Rodents were divided into control (CT; sedentary mice), overtrained by downhill running (OTR/down), overtrained by uphill running (OTR/up), and overtrained by running without inclination (OTR). The incremental load, exhaustive, and grip force tests were used as performance evaluation parameters. 36 h after the grip force test, EDL and soleus were removed and immediately used for immunoblotting analysis or stored at -80°C for histological and stereological analyses. For EDL, OTR/down decreased the protein kinase B (Akt) and tuberous sclerosis protein 2 (TSC2) phosphorylation (p), and increased myostatin, receptor-activated Smads (pSMAD2-3), and insulin receptor substrate-1 (pIRS-1; Ser307/636). OTR/down also presented low and high relative proportions of cytoplasm and connective tissue, respectively. OTR/up increased the mammalian target of rapamycin (pmTOR), 70-kDa ribosomal protein S6 kinase 1 (pS6K1) and pSMAD2-3, and decreased pTSC2. OTR decreased pTSC2 and increased pIRS-1 (Ser636). For soleus, OTR/down increased S6 ribosomal protein (pS6RP) and pSMAD2-3, and decreased pIRS-1 (Ser639). OTR/up decreased pS6K1, pS6RP and pIRS-1 (Ser639), and increased pTSC2 (Ser939), and pSMAD2-3. OTR increased pS6RP, 4E-binding protein-1 (p4E-BP1), pTSC2 (Ser939), and pSMAD2-3, and decreased pIRS-1 (Ser639). In summary, OTR/down inhibited the skeletal muscle hypertrophy with concomitant signs of atrophy in EDL. The effects of OTR/up and OTR depended on the analyzed skeletal muscle type. © 2015 Wiley Periodicals, Inc.
-
Mohsenifar, Zhaleh; Fridoni, Mohammadjavad; Ghatrehsamani, Mahdi; Abdollahifar, Mohammad-amin; Abbaszadeh, Hojjatallah; Mostafavinia, Atarodalsadat; Fallahnezhad, Somaye; Asghari, Mohammadali; Bayat, Saba; Bayat, Mohammad
2016-05-01
Osteoporosis (OP) and osteoporotic fracture are major public health issues for society; the burden for the affected individual is also high. Previous studies have shown that pulsed wave low-level laser therapy (PW LLLT) has osteogenic effects. This study intended to evaluate the impacts of PW LLLT on the cortical bone of osteoporotic rats' tibias in two experimental models, ovariectomized and dexamethasone-treated. We divided the rats into four ovariectomized induced OP (OVX-d) and four dexamethasone-treated (glucocorticoid-induced OP, GIOP) groups. A healthy (H) group of rats was considered for baseline evaluations. At 14 weeks following ovariectomy, we subdivided the OVX-d rats into the following groups: (i) control which had OP, (ii) OVX-d rats treated with alendronate (1 mg/kg), (iii) OVX-d rats treated with LLLT, and (iv) OVX-d rats treated with alendronate and PW LLLT. The remaining rats received dexamethasone over a 5-week period and were also subdivided into four groups: (i) control rats treated with intramuscular (i.m.) injections of distilled water (vehicle), (ii) rats treated with subcutaneous alendronate injections (1 mg/kg), (iii) laser-treated rats, and (iv) rats simultaneously treated with laser and alendronate. The rats received alendronate for 30 days and underwent PW LLLT (890 nm, 80 Hz, 0.972 J/cm(2)) three times per week during 8 weeks. Then, the right tibias were extracted and underwent a stereological analysis of histological parameters and real-time polymerase chain reaction (RT-PCR). A significant increase in cortical bone volume (mm(3)) existed in all study groups compared to the healthy rats. There were significant decreases in trabecular bone volume (mm(3)) in all study groups compared to the group of healthy rats. The control rats with OP and rats from the vehicle group showed significantly increased osteoclast numbers compared to most other groups. Alendronate significantly decreased osteoclast numbers in osteoporotic rats. Concurrent treatments (compounded by PW LLLT and alendronate) produce the same effect on osteoporotic bone.
-
Mutual information based feature selection for medical image retrieval
NASA Astrophysics Data System (ADS)
Zhi, Lijia; Zhang, Shaomin; Li, Yan
2018-04-01
In this paper, authors propose a mutual information based method for lung CT image retrieval. This method is designed to adapt to different datasets and different retrieval task. For practical applying consideration, this method avoids using a large amount of training data. Instead, with a well-designed training process and robust fundamental features and measurements, the method in this paper can get promising performance and maintain economic training computation. Experimental results show that the method has potential practical values for clinical routine application.
-
A method to estimate weight and dimensions of large and small gas turbine engines
NASA Technical Reports Server (NTRS)
Onat, E.; Klees, G. W.
1979-01-01
A computerized method was developed to estimate weight and envelope dimensions of large and small gas turbine engines within + or - 5% to 10%. The method is based on correlations of component weight and design features of 29 data base engines. Rotating components were estimated by a preliminary design procedure which is sensitive to blade geometry, operating conditions, material properties, shaft speed, hub tip ratio, etc. The development and justification of the method selected, and the various methods of analysis are discussed.
-
Pandey, Ram Vinay; Pulverer, Walter; Kallmeyer, Rainer; Beikircher, Gabriel; Pabinger, Stephan; Kriegner, Albert; Weinhäusel, Andreas
2016-01-01
Bisulfite (BS) conversion-based and methylation-sensitive restriction enzyme (MSRE)-based PCR methods have been the most commonly used techniques for locus-specific DNA methylation analysis. However, both methods have advantages and limitations. Thus, an integrated approach would be extremely useful to quantify the DNA methylation status successfully with great sensitivity and specificity. Designing specific and optimized primers for target regions is the most critical and challenging step in obtaining the adequate DNA methylation results using PCR-based methods. Currently, no integrated, optimized, and high-throughput methylation-specific primer design software methods are available for both BS- and MSRE-based methods. Therefore an integrated, powerful, and easy-to-use methylation-specific primer design pipeline with great accuracy and success rate will be very useful. We have developed a new web-based pipeline, called MSP-HTPrimer, to design primers pairs for MSP, BSP, pyrosequencing, COBRA, and MSRE assays on both genomic strands. First, our pipeline converts all target sequences into bisulfite-treated templates for both forward and reverse strand and designs all possible primer pairs, followed by filtering for single nucleotide polymorphisms (SNPs) and known repeat regions. Next, each primer pairs are annotated with the upstream and downstream RefSeq genes, CpG island, and cut sites (for COBRA and MSRE). Finally, MSP-HTPrimer selects specific primers from both strands based on custom and user-defined hierarchical selection criteria. MSP-HTPrimer produces a primer pair summary output table in TXT and HTML format for display and UCSC custom tracks for resulting primer pairs in GTF format. MSP-HTPrimer is an integrated, web-based, and high-throughput pipeline and has no limitation on the number and size of target sequences and designs MSP, BSP, pyrosequencing, COBRA, and MSRE assays. It is the only pipeline, which automatically designs primers on both genomic strands to increase the success rate. It is a standalone web-based pipeline, which is fully configured within a virtual machine and thus can be readily used without any configuration. We have experimentally validated primer pairs designed by our pipeline and shown a very high success rate of primer pairs: out of 66 BSP primer pairs, 63 were successfully validated without any further optimization step and using the same qPCR conditions. The MSP-HTPrimer pipeline is freely available from http://sourceforge.net/p/msp-htprimer.
-
Reeder, Blaine; Hills, Rebecca A; Turner, Anne M; Demiris, George
2014-01-01
The objectives of the study were to use persona-driven and scenario-based design methods to create a conceptual information system design to support public health nursing. We enrolled 19 participants from two local health departments to conduct an information needs assessment, create a conceptual design, and conduct a preliminary design validation. Interviews and thematic analysis were used to characterize information needs and solicit design recommendations from participants. Personas were constructed from participant background information, and scenario-based design was used to create a conceptual information system design. Two focus groups were conducted as a first iteration validation of information needs, personas, and scenarios. Eighty-nine information needs were identified. Two personas and 89 scenarios were created. Public health nurses and nurse managers confirmed the accuracy of information needs, personas, scenarios, and the perceived usefulness of proposed features of the conceptual design. Design artifacts were modified based on focus group results. Persona-driven design and scenario-based design are feasible methods to design for common work activities in different local health departments. Public health nurses and nurse managers should be engaged in the design of systems that support their work. © 2013 Wiley Periodicals, Inc.
-
Using Mathematical Modeling and Set-Based Design Principles to Recommend an Existing CVL Design
2017-09-01
designs, it would be worth researching the feasibility of varying the launch method on some of the larger light aircraft carriers, such as the Liaoning...thesis examines the trade space in major design areas such as tonnage, aircraft launch method , propulsion, and performance in order to illustrate...future conflict. This thesis examines the trade space in major design areas such as tonnage, aircraft launch method , propulsion, and performance in
-
Model-based optimal design of experiments - semidefinite and nonlinear programming formulations
Duarte, Belmiro P.M.; Wong, Weng Kee; Oliveira, Nuno M.C.
2015-01-01
We use mathematical programming tools, such as Semidefinite Programming (SDP) and Nonlinear Programming (NLP)-based formulations to find optimal designs for models used in chemistry and chemical engineering. In particular, we employ local design-based setups in linear models and a Bayesian setup in nonlinear models to find optimal designs. In the latter case, Gaussian Quadrature Formulas (GQFs) are used to evaluate the optimality criterion averaged over the prior distribution for the model parameters. Mathematical programming techniques are then applied to solve the optimization problems. Because such methods require the design space be discretized, we also evaluate the impact of the discretization scheme on the generated design. We demonstrate the techniques for finding D–, A– and E–optimal designs using design problems in biochemical engineering and show the method can also be directly applied to tackle additional issues, such as heteroscedasticity in the model. Our results show that the NLP formulation produces highly efficient D–optimal designs but is computationally less efficient than that required for the SDP formulation. The efficiencies of the generated designs from the two methods are generally very close and so we recommend the SDP formulation in practice. PMID:26949279
-
Model-based optimal design of experiments - semidefinite and nonlinear programming formulations.
Duarte, Belmiro P M; Wong, Weng Kee; Oliveira, Nuno M C
2016-02-15
We use mathematical programming tools, such as Semidefinite Programming (SDP) and Nonlinear Programming (NLP)-based formulations to find optimal designs for models used in chemistry and chemical engineering. In particular, we employ local design-based setups in linear models and a Bayesian setup in nonlinear models to find optimal designs. In the latter case, Gaussian Quadrature Formulas (GQFs) are used to evaluate the optimality criterion averaged over the prior distribution for the model parameters. Mathematical programming techniques are then applied to solve the optimization problems. Because such methods require the design space be discretized, we also evaluate the impact of the discretization scheme on the generated design. We demonstrate the techniques for finding D -, A - and E -optimal designs using design problems in biochemical engineering and show the method can also be directly applied to tackle additional issues, such as heteroscedasticity in the model. Our results show that the NLP formulation produces highly efficient D -optimal designs but is computationally less efficient than that required for the SDP formulation. The efficiencies of the generated designs from the two methods are generally very close and so we recommend the SDP formulation in practice.
-
A performance goal-based seismic design philosophy for waste repository facilities
DOE Office of Scientific and Technical Information (OSTI.GOV)
Hossain, Q.A.
1994-12-31
A performance goal-based seismic design philosophy, compatible with DOE`s present natural phenomena hazards mitigation and {open_quotes}graded approach{close_quotes} philosophy, has been proposed for high level nuclear waste repository facilities. The rationale, evolution, and the desirable features of this method have been described. Why and how the method should and can be applied to the design of a repository facility are also discussed.
-
ERIC Educational Resources Information Center
Sahrir, Muhammad Sabri; Alias, Nor Aziah; Ismail, Zawawi; Osman, Nurulhuda
2012-01-01
The design and development research, first proposed by Brown and Collins in the 1990s, is currently among the well-known methods in educational research to test theory and validate its practicality. The method is also known as developmental research, design research, design-based research, formative research and design-cased and possesses…
-
Study of Fuze Structure and Reliability Design Based on the Direct Search Method
NASA Astrophysics Data System (ADS)
Lin, Zhang; Ning, Wang
2017-03-01
Redundant design is one of the important methods to improve the reliability of the system, but mutual coupling of multiple factors is often involved in the design. In my study, Direct Search Method is introduced into the optimum redundancy configuration for design optimization, in which, the reliability, cost, structural weight and other factors can be taken into account simultaneously, and the redundant allocation and reliability design of aircraft critical system are computed. The results show that this method is convenient and workable, and applicable to the redundancy configurations and optimization of various designs upon appropriate modifications. And this method has a good practical value.
-
A Principled Approach to the Specification of System Architectures for Space Missions
NASA Technical Reports Server (NTRS)
McKelvin, Mark L. Jr.; Castillo, Robert; Bonanne, Kevin; Bonnici, Michael; Cox, Brian; Gibson, Corrina; Leon, Juan P.; Gomez-Mustafa, Jose; Jimenez, Alejandro; Madni, Azad
2015-01-01
Modern space systems are increasing in complexity and scale at an unprecedented pace. Consequently, innovative methods, processes, and tools are needed to cope with the increasing complexity of architecting these systems. A key systems challenge in practice is the ability to scale processes, methods, and tools used to architect complex space systems. Traditionally, the process for specifying space system architectures has largely relied on capturing the system architecture in informal descriptions that are often embedded within loosely coupled design documents and domain expertise. Such informal descriptions often lead to misunderstandings between design teams, ambiguous specifications, difficulty in maintaining consistency as the architecture evolves throughout the system development life cycle, and costly design iterations. Therefore, traditional methods are becoming increasingly inefficient to cope with ever-increasing system complexity. We apply the principles of component-based design and platform-based design to the development of the system architecture for a practical space system to demonstrate feasibility of our approach using SysML. Our results show that we are able to apply a systematic design method to manage system complexity, thus enabling effective data management, semantic coherence and traceability across different levels of abstraction in the design chain. Just as important, our approach enables interoperability among heterogeneous tools in a concurrent engineering model based design environment.
-
The application of quadratic optimal cooperative control synthesis to a CH-47 helicopter
NASA Technical Reports Server (NTRS)
Townsend, Barbara K.
1987-01-01
A control-system design method, quadratic optimal cooperative control synthesis (CCS), is applied to the design of a stability and control augmentation system (SCAS). The CCS design method is different from other design methods in that it does not require detailed a priori design criteria, but instead relies on an explicit optimal pilot-model to create desired performance. The design method, which was developed previously for fixed-wing aircraft, is simplified and modified for application to a Boeing CH-47 helicopter. Two SCAS designs are developed using the CCS design methodology. The resulting CCS designs are then compared with designs obtained using classical/frequency-domain methods and linear quadratic regulator (LQR) theory in a piloted fixed-base simulation. Results indicate that the CCS method, with slight modifications, can be used to produce controller designs which compare favorably with the frequency-domain approach.
-
Progress in multirate digital control system design
NASA Technical Reports Server (NTRS)
Berg, Martin C.; Mason, Gregory S.
1991-01-01
A new methodology for multirate sampled-data control design based on a new generalized control law structure, two new parameter-optimization-based control law synthesis methods, and a new singular-value-based robustness analysis method are described. The control law structure can represent multirate sampled-data control laws of arbitrary structure and dynamic order, with arbitrarily prescribed sampling rates for all sensors and update rates for all processor states and actuators. The two control law synthesis methods employ numerical optimization to determine values for the control law parameters. The robustness analysis method is based on the multivariable Nyquist criterion applied to the loop transfer function for the sampling period equal to the period of repetition of the system's complete sampling/update schedule. The complete methodology is demonstrated by application to the design of a combination yaw damper and modal suppression system for a commercial aircraft.
-
interest: mechanical system design sensitivity analysis and optimization of linear and nonlinear structural systems, reliability analysis and reliability-based design optimization, computational methods in committee member, ISSMO; Associate Editor, Mechanics Based Design of Structures and Machines; Associate
-
Boulesteix, Anne-Laure; Wilson, Rory; Hapfelmeier, Alexander
2017-09-09
The goal of medical research is to develop interventions that are in some sense superior, with respect to patient outcome, to interventions currently in use. Similarly, the goal of research in methodological computational statistics is to develop data analysis tools that are themselves superior to the existing tools. The methodology of the evaluation of medical interventions continues to be discussed extensively in the literature and it is now well accepted that medicine should be at least partly "evidence-based". Although we statisticians are convinced of the importance of unbiased, well-thought-out study designs and evidence-based approaches in the context of clinical research, we tend to ignore these principles when designing our own studies for evaluating statistical methods in the context of our methodological research. In this paper, we draw an analogy between clinical trials and real-data-based benchmarking experiments in methodological statistical science, with datasets playing the role of patients and methods playing the role of medical interventions. Through this analogy, we suggest directions for improvement in the design and interpretation of studies which use real data to evaluate statistical methods, in particular with respect to dataset inclusion criteria and the reduction of various forms of bias. More generally, we discuss the concept of "evidence-based" statistical research, its limitations and its impact on the design and interpretation of real-data-based benchmark experiments. We suggest that benchmark studies-a method of assessment of statistical methods using real-world datasets-might benefit from adopting (some) concepts from evidence-based medicine towards the goal of more evidence-based statistical research.
-
A design guide for subdivision pavements in Virginia.
DOT National Transportation Integrated Search
1973-01-01
The design method for secondary roads and that for subdivision roads are based on AASHO Road Test Results and Virginia's design experience. For flexible pavements, the methods are divided into two parts: (1) the evaluation of the soil support value o...
-
NASA Astrophysics Data System (ADS)
Asaithambi, Sasikumar; Rajappa, Muthaiah
2018-05-01
In this paper, an automatic design method based on a swarm intelligence approach for CMOS analog integrated circuit (IC) design is presented. The hybrid meta-heuristics optimization technique, namely, the salp swarm algorithm (SSA), is applied to the optimal sizing of a CMOS differential amplifier and the comparator circuit. SSA is a nature-inspired optimization algorithm which mimics the navigating and hunting behavior of salp. The hybrid SSA is applied to optimize the circuit design parameters and to minimize the MOS transistor sizes. The proposed swarm intelligence approach was successfully implemented for an automatic design and optimization of CMOS analog ICs using Generic Process Design Kit (GPDK) 180 nm technology. The circuit design parameters and design specifications are validated through a simulation program for integrated circuit emphasis simulator. To investigate the efficiency of the proposed approach, comparisons have been carried out with other simulation-based circuit design methods. The performances of hybrid SSA based CMOS analog IC designs are better than the previously reported studies.
-
Asaithambi, Sasikumar; Rajappa, Muthaiah
2018-05-01
In this paper, an automatic design method based on a swarm intelligence approach for CMOS analog integrated circuit (IC) design is presented. The hybrid meta-heuristics optimization technique, namely, the salp swarm algorithm (SSA), is applied to the optimal sizing of a CMOS differential amplifier and the comparator circuit. SSA is a nature-inspired optimization algorithm which mimics the navigating and hunting behavior of salp. The hybrid SSA is applied to optimize the circuit design parameters and to minimize the MOS transistor sizes. The proposed swarm intelligence approach was successfully implemented for an automatic design and optimization of CMOS analog ICs using Generic Process Design Kit (GPDK) 180 nm technology. The circuit design parameters and design specifications are validated through a simulation program for integrated circuit emphasis simulator. To investigate the efficiency of the proposed approach, comparisons have been carried out with other simulation-based circuit design methods. The performances of hybrid SSA based CMOS analog IC designs are better than the previously reported studies.
-
ERIC Educational Resources Information Center
Kurtulus, Aytac
2013-01-01
The aim of this study was to investigate the effects of web-based interactive virtual tours on the development of prospective mathematics teachers' spatial skills. The study was designed based on experimental method. The "one-group pre-test post-test design" of this method was taken as the research model. The study was conducted with 3rd year…
-
Conceptual design of distillation-based hybrid separation processes.
Skiborowski, Mirko; Harwardt, Andreas; Marquardt, Wolfgang
2013-01-01
Hybrid separation processes combine different separation principles and constitute a promising design option for the separation of complex mixtures. Particularly, the integration of distillation with other unit operations can significantly improve the separation of close-boiling or azeotropic mixtures. Although the design of single-unit operations is well understood and supported by computational methods, the optimal design of flowsheets of hybrid separation processes is still a challenging task. The large number of operational and design degrees of freedom requires a systematic and optimization-based design approach. To this end, a structured approach, the so-called process synthesis framework, is proposed. This article reviews available computational methods for the conceptual design of distillation-based hybrid processes for the separation of liquid mixtures. Open problems are identified that must be addressed to finally establish a structured process synthesis framework for such processes.
-
Review of Reliability-Based Design Optimization Approach and Its Integration with Bayesian Method
NASA Astrophysics Data System (ADS)
Zhang, Xiangnan
2018-03-01
A lot of uncertain factors lie in practical engineering, such as external load environment, material property, geometrical shape, initial condition, boundary condition, etc. Reliability method measures the structural safety condition and determine the optimal design parameter combination based on the probabilistic theory. Reliability-based design optimization (RBDO) is the most commonly used approach to minimize the structural cost or other performance under uncertainty variables which combines the reliability theory and optimization. However, it cannot handle the various incomplete information. The Bayesian approach is utilized to incorporate this kind of incomplete information in its uncertainty quantification. In this paper, the RBDO approach and its integration with Bayesian method are introduced.
-
Shape optimization using a NURBS-based interface-enriched generalized FEM
Najafi, Ahmad R.; Safdari, Masoud; Tortorelli, Daniel A.; ...
2016-11-26
This study presents a gradient-based shape optimization over a fixed mesh using a non-uniform rational B-splines-based interface-enriched generalized finite element method, applicable to multi-material structures. In the proposed method, non-uniform rational B-splines are used to parameterize the design geometry precisely and compactly by a small number of design variables. An analytical shape sensitivity analysis is developed to compute derivatives of the objective and constraint functions with respect to the design variables. Subtle but important new terms involve the sensitivity of shape functions and their spatial derivatives. As a result, verification and illustrative problems are solved to demonstrate the precision andmore » capability of the method.« less
-
Permeability enhancement by shock cooling
NASA Astrophysics Data System (ADS)
Griffiths, Luke; Heap, Michael; Reuschlé, Thierry; Baud, Patrick; Schmittbuhl, Jean
2015-04-01
The permeability of an efficient reservoir, e.g. a geothermal reservoir, should be sufficient to permit the circulation of fluids. Generally speaking, permeability decreases over the life cycle of the geothermal system. As a result, is usually necessary to artificially maintain and enhance the natural permeability of these systems. One of the methods of enhancement -- studied here -- is thermal stimulation (injecting cold water at low pressure). This goal of this method is to encourage new thermal cracks within the reservoir host rocks, thereby increasing reservoir permeability. To investigate the development of thermal microcracking in the laboratory we selected two granites: a fine-grained (Garibaldi Grey granite, grain size = 0.5 mm) and a course-grained granite (Lanhelin granite, grain size = 2 mm). Both granites have an initial porosity of about 1%. Our samples were heated to a range of temperatures (100-1000 °C) and were either cooled slowly (1 °C/min) or shock cooled (100 °C/s). A systematic microstructural (2D crack area density, using standard stereological techniques, and 3D BET specific surface area measurements) and rock physical property (porosity, P-wave velocity, uniaxial compressive strength, and permeability) analysis was undertaken to understand the influence of slow and shock cooling on our reservoir granites. Microstructurally, we observe that the 2D crack surface area per unit volume and the specific surface area increase as a result of thermal stressing, and, for the same maximum temperature, crack surface area is higher in the shock cooled samples. This observation is echoed by our rock physical property measurements: we see greater changes for the shock cooled samples. We can conclude that shock cooling is an extremely efficient method of generating thermal microcracks and modifying rock physical properties. Our study highlights that thermal treatments are likely to be an efficient method for the "matrix" permeability enhancement of granitic geothermal reservoirs.
-
Garza-Gisholt, Eduardo; Hemmi, Jan M.; Hart, Nathan S.; Collin, Shaun P.
2014-01-01
Topographic maps that illustrate variations in the density of different neuronal sub-types across the retina are valuable tools for understanding the adaptive significance of retinal specialisations in different species of vertebrates. To date, such maps have been created from raw count data that have been subjected to only limited analysis (linear interpolation) and, in many cases, have been presented as iso-density contour maps with contour lines that have been smoothed ‘by eye’. With the use of stereological approach to count neuronal distribution, a more rigorous approach to analysing the count data is warranted and potentially provides a more accurate representation of the neuron distribution pattern. Moreover, a formal spatial analysis of retinal topography permits a more robust comparison of topographic maps within and between species. In this paper, we present a new R-script for analysing the topography of retinal neurons and compare methods of interpolating and smoothing count data for the construction of topographic maps. We compare four methods for spatial analysis of cell count data: Akima interpolation, thin plate spline interpolation, thin plate spline smoothing and Gaussian kernel smoothing. The use of interpolation ‘respects’ the observed data and simply calculates the intermediate values required to create iso-density contour maps. Interpolation preserves more of the data but, consequently includes outliers, sampling errors and/or other experimental artefacts. In contrast, smoothing the data reduces the ‘noise’ caused by artefacts and permits a clearer representation of the dominant, ‘real’ distribution. This is particularly useful where cell density gradients are shallow and small variations in local density may dramatically influence the perceived spatial pattern of neuronal topography. The thin plate spline and the Gaussian kernel methods both produce similar retinal topography maps but the smoothing parameters used may affect the outcome. PMID:24747568
-
Case-Based Capture and Reuse of Aerospace Design Rationale
NASA Technical Reports Server (NTRS)
Leake, David B.
2001-01-01
The goal of this project was to apply artificial intelligence techniques to facilitate capture and reuse of aerospace design rationale. The project combined case-based reasoning (CBR) and concept maps (CMaps) to develop methods for capturing, organizing, and interactively accessing records of experiences encapsulating the methods and rationale underlying expert aerospace design, in order to bring the captured knowledge to bear to support future reasoning. The project's results contribute both principles and methods for effective design-aiding systems that aid capture and access of useful design knowledge. The project has been guided by the tenets that design-aiding systems must: (1) Leverage a designer's knowledge, rather than attempting to replace it; (2) Be able to reflect different designers' differing conceptualizations of the design task, and to clarify those conceptualizations to others; (3) Include capabilities to capture information both by interactive knowledge modeling and during normal use; and (4) Integrate into normal designer tasks as naturally and unobtrusive as possible.
-
Establishment and validation for the theoretical model of the vehicle airbag
NASA Astrophysics Data System (ADS)
Zhang, Junyuan; Jin, Yang; Xie, Lizhe; Chen, Chao
2015-05-01
The current design and optimization of the occupant restraint system (ORS) are based on numerous actual tests and mathematic simulations. These two methods are overly time-consuming and complex for the concept design phase of the ORS, though they're quite effective and accurate. Therefore, a fast and directive method of the design and optimization is needed in the concept design phase of the ORS. Since the airbag system is a crucial part of the ORS, in this paper, a theoretical model for the vehicle airbag is established in order to clarify the interaction between occupants and airbags, and further a fast design and optimization method of airbags in the concept design phase is made based on the proposed theoretical model. First, the theoretical expression of the simplified mechanical relationship between the airbag's design parameters and the occupant response is developed based on classical mechanics, then the momentum theorem and the ideal gas state equation are adopted to illustrate the relationship between airbag's design parameters and occupant response. By using MATLAB software, the iterative algorithm method and discrete variables are applied to the solution of the proposed theoretical model with a random input in a certain scope. And validations by MADYMO software prove the validity and accuracy of this theoretical model in two principal design parameters, the inflated gas mass and vent diameter, within a regular range. This research contributes to a deeper comprehension of the relation between occupants and airbags, further a fast design and optimization method for airbags' principal parameters in the concept design phase, and provides the range of the airbag's initial design parameters for the subsequent CAE simulations and actual tests.
-
A systematic composite service design modeling method using graph-based theory.
Elhag, Arafat Abdulgader Mohammed; Mohamad, Radziah; Aziz, Muhammad Waqar; Zeshan, Furkh
2015-01-01
The composite service design modeling is an essential process of the service-oriented software development life cycle, where the candidate services, composite services, operations and their dependencies are required to be identified and specified before their design. However, a systematic service-oriented design modeling method for composite services is still in its infancy as most of the existing approaches provide the modeling of atomic services only. For these reasons, a new method (ComSDM) is proposed in this work for modeling the concept of service-oriented design to increase the reusability and decrease the complexity of system while keeping the service composition considerations in mind. Furthermore, the ComSDM method provides the mathematical representation of the components of service-oriented design using the graph-based theoryto facilitate the design quality measurement. To demonstrate that the ComSDM method is also suitable for composite service design modeling of distributed embedded real-time systems along with enterprise software development, it is implemented in the case study of a smart home. The results of the case study not only check the applicability of ComSDM, but can also be used to validate the complexity and reusability of ComSDM. This also guides the future research towards the design quality measurement such as using the ComSDM method to measure the quality of composite service design in service-oriented software system.
-
A Systematic Composite Service Design Modeling Method Using Graph-Based Theory
Elhag, Arafat Abdulgader Mohammed; Mohamad, Radziah; Aziz, Muhammad Waqar; Zeshan, Furkh
2015-01-01
The composite service design modeling is an essential process of the service-oriented software development life cycle, where the candidate services, composite services, operations and their dependencies are required to be identified and specified before their design. However, a systematic service-oriented design modeling method for composite services is still in its infancy as most of the existing approaches provide the modeling of atomic services only. For these reasons, a new method (ComSDM) is proposed in this work for modeling the concept of service-oriented design to increase the reusability and decrease the complexity of system while keeping the service composition considerations in mind. Furthermore, the ComSDM method provides the mathematical representation of the components of service-oriented design using the graph-based theoryto facilitate the design quality measurement. To demonstrate that the ComSDM method is also suitable for composite service design modeling of distributed embedded real-time systems along with enterprise software development, it is implemented in the case study of a smart home. The results of the case study not only check the applicability of ComSDM, but can also be used to validate the complexity and reusability of ComSDM. This also guides the future research towards the design quality measurement such as using the ComSDM method to measure the quality of composite service design in service-oriented software system. PMID:25928358
-
Overlay design method based on visual pavement distress.
DOT National Transportation Integrated Search
1978-01-01
A method for designing the thickness of overlays for bituminous concrete pavements in Virginia is described. In this method the thickness is calculated by rating the amount and severity of observed pavement distress and determining the total accumula...
-
Integration of mask and silicon metrology in DFM
NASA Astrophysics Data System (ADS)
Matsuoka, Ryoichi; Mito, Hiroaki; Sugiyama, Akiyuki; Toyoda, Yasutaka
2009-03-01
We have developed a highly integrated method of mask and silicon metrology. The method adopts a metrology management system based on DBM (Design Based Metrology). This is the high accurate contouring created by an edge detection algorithm used in mask CD-SEM and silicon CD-SEM. We have inspected the high accuracy, stability and reproducibility in the experiments of integration. The accuracy is comparable with that of the mask and silicon CD-SEM metrology. In this report, we introduce the experimental results and the application. As shrinkage of design rule for semiconductor device advances, OPC (Optical Proximity Correction) goes aggressively dense in RET (Resolution Enhancement Technology). However, from the view point of DFM (Design for Manufacturability), the cost of data process for advanced MDP (Mask Data Preparation) and mask producing is a problem. Such trade-off between RET and mask producing is a big issue in semiconductor market especially in mask business. Seeing silicon device production process, information sharing is not completely organized between design section and production section. Design data created with OPC and MDP should be linked to process control on production. But design data and process control data are optimized independently. Thus, we provided a solution of DFM: advanced integration of mask metrology and silicon metrology. The system we propose here is composed of followings. 1) Design based recipe creation: Specify patterns on the design data for metrology. This step is fully automated since they are interfaced with hot spot coordinate information detected by various verification methods. 2) Design based image acquisition: Acquire the images of mask and silicon automatically by a recipe based on the pattern design of CD-SEM.It is a robust automated step because a wide range of design data is used for the image acquisition. 3) Contour profiling and GDS data generation: An image profiling process is applied to the acquired image based on the profiling method of the field proven CD metrology algorithm. The detected edges are then converted to GDSII format, which is a standard format for a design data, and utilized for various DFM systems such as simulation. Namely, by integrating pattern shapes of mask and silicon formed during a manufacturing process into GDSII format, it makes it possible to bridge highly accurate pattern profile information over to the design field of various EDA systems. These are fully integrated into design data and automated. Bi-directional cross probing between mask data and process control data is allowed by linking them. This method is a solution for total optimization that covers Design, MDP, mask production and silicon device producing. This method therefore is regarded as a strategic DFM approach in the semiconductor metrology.
-
Abdi, Nasrin; Sadeghi, Roya; Zamani-alavijeh, Fereshteh; Taghdisi, Mohammad Hossein; Shojaeezadeh, Davoud
2016-01-01
Introduction Health and behavior are closely related subjects because disease is typically rooted in individuals’ unhealthy behaviors and habits. This study aims to identify women’s nutritional habits and behaviors in order to design interventions to promote nutritional literacy. Methods This qualitative research is part of a mixed method (quantitative-qualitative) study, conducted based on content analysis. Data were collected using semistructured interviews, group discussions, and in-depth interviews with married women, aged 18–50 years, who were referred to four health care centers in Sanandaj in 2013–2014. Results Nutritional habits and behaviors of participants were classified into two categories: representation of nutritional behavior based on consumption pattern and representation of nutritional behavior based on consumption method. For the former, eight consumption pattern subcategories were formed: meat, dairy, fast food, local foods, fruits and vegetables, soft drinks, and oils. The latter (representation of nutritional behavior based on consumption method), included two subcategories: consumption method in line with health and consumption method inconsistent with health. Conclusion Results of this qualitative study provide a solid foundation for development and designing interventions to nutritional literacy promotion based on needs. The designed intervention to healthy nutritional behavior should be based on empowering women and providing facilitator factors of a healthy diet. While designing this study, with a holistic perspective, individual and social aspects of a healthy diet should be taken into account. PMID:26955443
-
NASA Astrophysics Data System (ADS)
Zhang, Yunpeng; Ho, Siu-lau; Fu, Weinong
2018-05-01
This paper proposes a dynamic multi-level optimal design method for power transformer design optimization (TDO) problems. A response surface generated by second-order polynomial regression analysis is updated dynamically by adding more design points, which are selected by Shifted Hammersley Method (SHM) and calculated by finite-element method (FEM). The updating stops when the accuracy requirement is satisfied, and optimized solutions of the preliminary design are derived simultaneously. The optimal design level is modulated through changing the level of error tolerance. Based on the response surface of the preliminary design, a refined optimal design is added using multi-objective genetic algorithm (MOGA). The effectiveness of the proposed optimal design method is validated through a classic three-phase power TDO problem.
-
Zhong, Yi; Gross, Herbert
2017-05-01
Freeform surfaces play important roles in improving the imaging performance of off-axis optical systems. However, for some systems with high requirements in specifications, the structure of the freeform surfaces could be very complicated and the number of freeform surfaces could be large. That brings challenges in fabrication and increases the cost. Therefore, to achieve a good initial system with minimum aberrations and reasonable structure before implementing freeform surfaces is essential for optical designers. The already existing initial system design methods are limited to certain types of systems. A universal tool or method to achieve a good initial system efficiently is very important. In this paper, based on the Nodal aberration theory and the system design method using Gaussian Brackets, the initial system design method is extended from rotationally symmetric systems to general non-rotationally symmetric systems. The design steps are introduced and on this basis, two off-axis three-mirror systems are pre-designed using spherical shape surfaces. The primary aberrations are minimized using the nonlinear least-squares solver. This work provides insight and guidance for initial system design of off-axis mirror systems.
-
Abdi, Nasrin; Sadeghi, Roya; Zamani-Alavijeh, Fereshteh; Taghdisi, Mohammad Hossein; Shojaeezadeh, Davoud
2016-01-01
Health and behavior are closely related subjects because disease is typically rooted in individuals' unhealthy behaviors and habits. This study aims to identify women's nutritional habits and behaviors in order to design interventions to promote nutritional literacy. This qualitative research is part of a mixed method (quantitative-qualitative) study, conducted based on content analysis. Data were collected using semistructured interviews, group discussions, and in-depth interviews with married women, aged 18-50 years, who were referred to four health care centers in Sanandaj in 2013-2014. Nutritional habits and behaviors of participants were classified into two categories: representation of nutritional behavior based on consumption pattern and representation of nutritional behavior based on consumption method. For the former, eight consumption pattern subcategories were formed: meat, dairy, fast food, local foods, fruits and vegetables, soft drinks, and oils. The latter (representation of nutritional behavior based on consumption method), included two subcategories: consumption method in line with health and consumption method inconsistent with health. Results of this qualitative study provide a solid foundation for development and designing interventions to nutritional literacy promotion based on needs. The designed intervention to healthy nutritional behavior should be based on empowering women and providing facilitator factors of a healthy diet. While designing this study, with a holistic perspective, individual and social aspects of a healthy diet should be taken into account.
-
The Segmental Morphometric Properties of the Horse Cervical Spinal Cord: A Study of Cadaver
Bahar, Sadullah; Bolat, Durmus; Selcuk, Muhammet Lutfi
2013-01-01
Although the cervical spinal cord (CSC) of the horse has particular importance in diseases of CNS, there is very little information about its segmental morphometry. The objective of the present study was to determine the morphometric features of the CSC segments in the horse and possible relationships among the morphometric features. The segmented CSC from five mature animals was used. Length, weight, diameter, and volume measurements of the segments were performed macroscopically. Lengths and diameters of segments were measured histologically, and area and volume measurements were performed using stereological methods. The length, weight, and volume of the CSC were 61.6 ± 3.2 cm, 107.2 ± 10.4 g, and 95.5 ± 8.3 cm3, respectively. The length of the segments was increased from C 1 to C 3, while it decreased from C 3 to C 8. The gross section (GS), white matter (WM), grey matter (GM), dorsal horn (DH), and ventral horn (VH) had the largest cross-section areas at C 8. The highest volume was found for the total segment and WM at C 4, GM, DH, and VH at C 7, and the central canal (CC) at C 3. The data obtained not only contribute to the knowledge of the normal anatomy of the CSC but may also provide reference data for veterinary pathologists and clinicians. PMID:23476145
-
Partanen, Sanna; Haapanen, Aleksi; Kielar, Catherine; Pontikis, Charles; Alexander, Noreen; Inkinen, Teija; Saftig, Paul; Gillingwater, Thomas H; Cooper, Jonathan D; Tyynelä, Jaana
2008-01-01
Cathepsin D (CTSD; EC 3.4.23.5) is a lysosomal aspartic protease, the deficiency of which causes early-onset and particularly aggressive forms of neuronal ceroid-lipofuscinosis in infants, sheep, and mice. Cathepsin D deficiencies are characterized by severe neurodegeneration, but the molecular mechanisms behind the neuronal death remain poorly understood. In this study, we have systematically mapped the distribution of neuropathologic changes in CTSD-deficient mouse brains by stereologic, immunologic, and electron microscopic methods. We report highly accentuated neuropathologic changes within the ventral posterior nucleus (ventral posteromedial [VPM]/ventral posterolateral [VPL]) of thalamus and in neuronal laminae IV and VI of the somatosensory cortex (S1BF), which receive and send information to the thalamic VPM/VPL. These changes included pronounced astrocytosis and microglial activation that begin in the VPM/VPL thalamic nucleus of CTSD-deficient mice and are associated with reduced neuronal number and redistribution of presynaptic markers. In addition, loss of synapses, axonal pathology, and aggregation of synaptophysin and synaptobrevin were observed in the VPM/VPL. These synaptic alterations are accompanied by changes in the amount of synaptophysin/synaptobrevin heterodimer, which regulates formation of the SNARE complex at the synapse. Taken together, these data reveal the somatosensory thalamocortical circuitry as a particular focus of pathologic changes and provide the first evidence for synaptic alterations at the molecular and ultrastructural levels in CTSD deficiency.
-
Functional Analysis of Dopaminergic Systems in a DYT1 Knock-in Mouse Model of Dystonia
Song, Chang-Hyun; Fan, Xueliang; Exeter, Cicely J.; Hess, Ellen J.; Jinnah, H. A.
2012-01-01
The dystonias are a group of disorders characterized by involuntary twisting movements and abnormal posturing. The most common of the inherited dystonias is DYT1 dystonia, which is due to deletion of a single GAG codon (ΔE) in the TOR1A gene that encodes torsinA. Since some forms of dystonia have been linked with dysfunction of brain dopamine pathways, the integrity of these pathways was explored in a knock-in mouse model of DYT1 dystonia. In DYT1(ΔE) knock-in mice, neurochemical measures revealed only small changes in the content of dopamine or its metabolites in tissue homogenates from caudoputamen or midbrain, but microdialysis studies revealed robust decreases in baseline and amphetamine-stimulated extracellular dopamine in the caudoputamen. Quantitative stereological methods revealed no evidence for striatal or midbrain atrophy, but substantia nigra neurons immunopositive for tyrosine hydroxylase were slightly reduced in numbers and enlarged in size. Behavioral studies revealed subtle abnormalities in gross motor activity and motor coordination without overt dystonia. Neuropharmacological challenges of dopamine systems revealed normal behavioral responses to amphetamine and a minor increase in sensitivity to haloperidol. These results demonstrate that this DYT1(ΔE) knock-in mouse model of dystonia harbors neurochemical and structural changes of the dopamine pathways, as well as motor abnormalities. PMID:22659308
-
Effect of Omegaven on mast cell concentration in diabetic wound healing.
Babaei, Saeid; Ansarihadipour, Hadi; Nakhaei, Mahmoodreza; Darabi, Mohammadreza; Bayat, Parvindokht; Sakhaei, Mohammadhassan; Baazm, Maryam; Mohammadhoseiny, Atefe
2017-05-01
Diabetic wound healing is a complicated process. In all over the world 15% of 200 million diabetic people suffer from diabetic foot problems. Mast cells are known to participate in three phases of wound healing: the inflammatory reaction, angiogenesis and extracellular-matrix reabsorption. The inflammatory reaction is mediated by released histamine and arachidonic acid metabolites. Omega-3 fatty acids alter proinflammatory cytokine production during wound healing which affects the presence of inflammatory cells in wound area as well, but how this events specifically influences the presence of mast cells in wound healing is not clearly understood. This study is conducted to determine the effect of Omegaven, eicosapentaenoic (EPA) and docosahexaenoic (DHA) on pattern of presence of mast cells in diabetic wound area. Diabetic male wistar rats were euthanized at 1, 3, 5, 7 and 15 days after the excision was made. To estimate the number of mast cells histological sections were provided from wound area and stained with toluidine blue. In this relation wound area (8400 microscopic field, 45.69 mm 2 ) were examined by stereological methods by light microscope. We found that comparing experimental and control group, omega-3 fatty acids significantly decreased wound area in day 7 and also the number of grade three mast cells in day 3 and 5. We also found that wound strength has significantly increased in experimental group at day 15. Copyright © 2016. Published by Elsevier Ltd.
-
Tähkä, K M
1988-08-01
Juvenile bank voles (18-22 days of age) born and reared in a stimulatory long photoperiod (18L:6D, lights on 0600-2400 hr) were subjected either to a long photoperiod (18L:6D, Group L) or to a short photoperiod (6L:18D, lights on 0800-1400 hr, Group S) for 6 to 8 weeks whereafter the animals were killed by decapitation. Possible photoperiod-induced changes in Leydig cell ultrastructure were studied by conventional transmission electron microscopy and stereological methods. Striking differences in Leydig cell ultrastructure between the experimental groups were encountered. Light deprivation induced a marked decrease in the cytoplasmic and nuclear volume as well as in the amounts of smooth endoplasmic reticulum (SER), rough endoplasmic reticulum, mitochondria, and lipid inclusions in the Leydig cells. The number of myelin bodies and dense bodies seemed to be somewhat higher in the regressive Group S Leydig cells. These results are in good agreement with our previous histological and biochemical studies on the effects of photoperiod on Leydig cell function and suggest that in the bank vole the volume of mitochondria and SER in particular correlates positively with the steroidogenic capacity (the activity of C20 alpha 22-C27 desmolase, 17 alpha-hydroxylase, and C17-20 lyase in particular) in the Leydig cell.
-
Razga, Zsolt; Talapka, Petra; Nyengaard, Jens Randel
2014-01-01
Introduction. The renin granulation of kidney arterioles is enhanced in diabetes despite the fact that the level of angiotensin II in the diabetic kidney is elevated. Therefore, the number of angiotensin II AT1-A and AT1-B receptors in afferent and efferent arteriole's renin-positive and renin-negative smooth muscle cells (SMC) was estimated. Method. Immunohistochemistry at the electron microscopic level was combined with 3D stereological sampling techniques. Results. In diabetes the enhanced downregulation of AT1-B receptors in the renin-positive than in the renin-negative SMCs in both arterioles was resulted: the significant difference in the number of AT1 (AT1-A + AT1-B) receptors between the two types of SMCs in the normal rats was further increased in diabetes and in contrast with the significant difference observed between the afferent and efferent arterioles in the normal animals, there was no such difference in diabetes. Conclusions. The enhanced downregulation of the AT1-B receptors in the renin-negative SMCs in the efferent arterioles demonstrates that the regulation of the glomerular filtration rate by the pre- and postglomerular arterioles is changed in diabetes. The enhanced downregulation of the AT1-B receptors in the renin-positive SMCs in the arterioles may result in an enhanced level of renin granulation in the arterioles. PMID:24587998
-
Brain organization of gorillas reflects species differences in ecology
Barks, Sarah K.; Calhoun, Michael E.; Hopkins, William D.; Cranfield, Michael R.; Mudakikwa, Antoine; Stoinski, Tara S.; Patterson, Francine G.; Erwin, Joseph M.; Hecht, Erin E.; Hof, Patrick R.; Sherwood, Chet C.
2014-01-01
Gorillas include separate eastern (Gorilla beringei) and western (Gorilla gorilla) African species that diverged from each other approximately 2 million years ago. Although anatomical, genetic, behavioral, and socioecological differences have been noted among gorilla populations, little is known about variation in their brain structure. This study examines neuroanatomical variation between gorilla species using structural neuroimaging. Postmortem magnetic resonance images were obtained of brains from 18 captive western lowland gorillas (Gorilla gorilla gorilla), 15 wild mountain gorillas (Gorilla beringei beringei), and 3 Grauer's gorillas (Gorilla beringei graueri) (both wild and captive). Stereologic methods were used to measure volumes of brain structures, including left and right frontal lobe gray and white matter, temporal lobe gray and white matter, parietal and occipital lobes gray and white matter, insular gray matter, hippocampus, striatum, thalamus, each hemisphere and the vermis of the cerebellum, and the external and extreme capsules together with the claustrum. Among the species differences, the volumes of the hippocampus and cerebellum were significantly larger in G. gorilla than G. beringei. These anatomical differences may relate to divergent ecological adaptations of the two species. Specifically, G. gorilla engage in more arboreal locomotion and thus may rely more on cerebellar circuits. In addition, they tend to eat more fruit and have larger home ranges and consequently might depend more on spatial mapping functions of the hippocampus. PMID:25360547
-
Protective effect of Brewer's yeast on methimazole-induced-adrenal atrophy (a stereological study).
Dehghani, Farzaneh; Zabolizadeh, Jamal; Noorafshan, Ali; Panjehshahin, Mohammad Reza; Karbalay-Doust, Saied
2010-04-20
Induction of hypothyroidism by thioamide drugs will cause adrenal gland atrophy and decrease in its hormones. To prevent side effect on the adrenal gland, brewer's yeast, a natural product rich in vitamins and minerals was used. Serological techniques were applied to measure the volume of adrenal gland. For this purpose, 48 Sprague-Dawley rats were randomly divided into one control and three experimental groups. In group 1, methimazole was administered at the dose of 30 mg/kg/day days, in group 2, 120 mg/kg/day of, brewer's yeast, in group 3, 30 mg/kg/day of methimazole plus 120 mg/kg/day of brewer yeast, and for the control group, an equal volume of saline (0.5 ml/rat/day) was orally given. After 30 days, all the animals were anesthetized and their adrenal glands were removed, fixed, embedded and stained. The volume of different zones of the adrenal glands was estimated by Cavalieri principle and point counting methods. statistical analysis was performed using Mann-Withney test and p < 0.05 was considered as statistically significant. The results indicated that methimazole decreased the volume of fasciculata zone in the cortex of the adrenal gland and also decreased the blood cortisol level. Brewer's yeast reduced the methimazole side effects on this zone. In conclusion, it seems that the use of brewer's yeast could prevent methimazole-induced atrophy of the adrenal gland.
-
Structural and stereological analysis of elastic fibers in the glans penis of young men.
Andrade, F; Cardoso, G P; Bastos, Ana Luiza; Costa, W; Chagas, M; Babinski, M
2012-01-01
The extracellular matrix is an important element in penile function and pathology, although little is known about its components in human glans. This study evaluates the morphological organization and volumetric density of elastic fibers in the glans penis of young men without any evidence of urogenital disease at autopsy or medical history. Penile glans were obtained from five young men who died of causes not related to the urogenital tract, ranging in age from 18 to 30 years (mean 24 years). Samples were fixed in formalin, embedded in paraffin, and histologically processed. Tissue was analyzed by light microscopy using Weigert's resorcin-fuchsin, after previous oxidation with oxone. The point-counting method was used for morphometrical evaluation. Quantities were expressed as volumetric densities (Vv) and were determined on 25 random fields for each individual. Elastic system fibers were easily identified. These fibers had tortuous profile and surrounded sinusoids in the glans penis. An irregular elastic fibers network was identified in the mucosa, while in the corpus spongiosum the elastic fibers were longitudinally distributed. Volumetric density of elastic fibers in the glans penis is 29.4% ± 3.1. These data could provide valuable information in order to draw parallels regarding patients with erectile dysfunction. Further studies regarding extracellular matrix of the penis are necessary to better elucidate the relation between elastic fibers and erectile dysfunction.
-
Rağbetli, Murat Cetin; Aydinlioğlu, Atif; Koyun, Necat; Rağbetli, Cennet; Karayel, Metin
2009-01-01
Because of the possible risk factor for the health, World Health Organization (WHO) recommended the study with animals on the developing nervous system concerning the exposure to radiofrequency (RF) field. A few studies related to hippocampal exposure are available, which indicate the impact of RF field in some parameters. The present study investigated the effect of exposure to mobile phone on developing hippocampus. Male and female Swiss albino mice were housed as control and mobile phone exposed groups. The pregnant animals in tested group were exposed to the effects of mobile phone in a room possessing the exposure system. The left hemispheres of the brains were processed by frozen microtome. The sections obtained were stained with Hematoxylin & Eosin. For cell counting by the optical fractionator method, a pilot study was first performed. Hippocampal areas were analyzed using Axiovision software running on a personal computer. The optical dissector, systematically and randomly spaced, was focused to the widest profile of the pyramidal cell nucleus. No significant difference in pyramidal cell number of total Cornu Ammonis (CA) sectors of hippocampus was found between the control and the mobile phone exposed groups (p > .05). It was concluded that further study is needed in this field due to popular use of mobile telephones and relatively high exposure to the developing brain.
-
Brain organization of gorillas reflects species differences in ecology.
Barks, Sarah K; Calhoun, Michael E; Hopkins, William D; Cranfield, Michael R; Mudakikwa, Antoine; Stoinski, Tara S; Patterson, Francine G; Erwin, Joseph M; Hecht, Erin E; Hof, Patrick R; Sherwood, Chet C
2015-02-01
Gorillas include separate eastern (Gorilla beringei) and western (Gorilla gorilla) African species that diverged from each other approximately 2 million years ago. Although anatomical, genetic, behavioral, and socioecological differences have been noted among gorilla populations, little is known about variation in their brain structure. This study examines neuroanatomical variation between gorilla species using structural neuroimaging. Postmortem magnetic resonance images were obtained of brains from 18 captive western lowland gorillas (Gorilla gorilla gorilla), 15 wild mountain gorillas (Gorilla beringei beringei), and 3 Grauer's gorillas (Gorilla beringei graueri) (both wild and captive). Stereologic methods were used to measure volumes of brain structures, including left and right frontal lobe gray and white matter, temporal lobe gray and white matter, parietal and occipital lobes gray and white matter, insular gray matter, hippocampus, striatum, thalamus, each hemisphere and the vermis of the cerebellum, and the external and extreme capsules together with the claustrum. Among the species differences, the volumes of the hippocampus and cerebellum were significantly larger in G. gorilla than G. beringei. These anatomical differences may relate to divergent ecological adaptations of the two species. Specifically, G. gorilla engages in more arboreal locomotion and thus may rely more on cerebellar circuits. In addition, they tend to eat more fruit and have larger home ranges and consequently might depend more on spatial mapping functions of the hippocampus. © 2015 Wiley Periodicals, Inc.
-
Methods and Design: Measuring Recognition Performance Using Computer- Based and Paper-Based Methods.
1991-01-01
FEDERICO Navy Personnel Research and Development Center, San Diego, California Using a within-subjects design , we administered to 83 naval pilots and...blank. The students were encouraged to go through the the research subjects into two groups according to whether 344 FEDERICO or not their performance...E Dt0WARDS, A L. (1964). Expermental design in psycholo ical research psychological assessment of elernentary-school-age children Contem- New York
-
NASA Technical Reports Server (NTRS)
Hou, Gene J.-W; Newman, Perry A. (Technical Monitor)
2004-01-01
A major step in a most probable point (MPP)-based method for reliability analysis is to determine the MPP. This is usually accomplished by using an optimization search algorithm. The minimum distance associated with the MPP provides a measurement of safety probability, which can be obtained by approximate probability integration methods such as FORM or SORM. The reliability sensitivity equations are derived first in this paper, based on the derivatives of the optimal solution. Examples are provided later to demonstrate the use of these derivatives for better reliability analysis and reliability-based design optimization (RBDO).
-
NASA Astrophysics Data System (ADS)
Huang, C.; Hsu, N.
2013-12-01
This study imports Low-Impact Development (LID) technology of rainwater catchment systems into a Storm-Water runoff Management Model (SWMM) to design the spatial capacity and quantity of rain barrel for urban flood mitigation. This study proposes a simulation-optimization model for effectively searching the optimal design. In simulation method, we design a series of regular spatial distributions of capacity and quantity of rainwater catchment facilities, and thus the reduced flooding circumstances using a variety of design forms could be simulated by SWMM. Moreover, we further calculate the net benefit that is equal to subtract facility cost from decreasing inundation loss and the best solution of simulation method would be the initial searching solution of the optimization model. In optimizing method, first we apply the outcome of simulation method and Back-Propagation Neural Network (BPNN) for developing a water level simulation model of urban drainage system in order to replace SWMM which the operating is based on a graphical user interface and is hard to combine with optimization model and method. After that we embed the BPNN-based simulation model into the developed optimization model which the objective function is minimizing the negative net benefit. Finally, we establish a tabu search-based algorithm to optimize the planning solution. This study applies the developed method in Zhonghe Dist., Taiwan. Results showed that application of tabu search and BPNN-based simulation model into the optimization model not only can find better solutions than simulation method in 12.75%, but also can resolve the limitations of previous studies. Furthermore, the optimized spatial rain barrel design can reduce 72% of inundation loss according to historical flood events.
-
Luan, Xiaoli; Chen, Qiang; Liu, Fei
2014-09-01
This article presents a new scheme to design full matrix controller for high dimensional multivariable processes based on equivalent transfer function (ETF). Differing from existing ETF method, the proposed ETF is derived directly by exploiting the relationship between the equivalent closed-loop transfer function and the inverse of open-loop transfer function. Based on the obtained ETF, the full matrix controller is designed utilizing the existing PI tuning rules. The new proposed ETF model can more accurately represent the original processes. Furthermore, the full matrix centralized controller design method proposed in this paper is applicable to high dimensional multivariable systems with satisfactory performance. Comparison with other multivariable controllers shows that the designed ETF based controller is superior with respect to design-complexity and obtained performance. Copyright © 2014 ISA. Published by Elsevier Ltd. All rights reserved.
-
Doimo, Nayara T S; Zárate-Bladés, Carlos R; Rodrigues, Rodrigo F; Tefé-Silva, Cristiane; Trotte, Marcele N S; Souza, Patrícia R M; Soares, Luana S; Rios, Wendy M; Floriano, Elaine M; Brandão, Izaira T; Masson, Ana P; Coelho, Verônica; Ramos, Simone G; Silva, Celio L
2014-01-01
Despite substantial efforts in recent years toward the development of new vaccines and drugs against tuberculosis (TB), success has remained elusive. Immunotherapy of TB with mycobacterial Hsp65 as a DNA vaccine (DNA-hsp65) results in a reduction of systemic bacterial loads and lung tissue damage, but the high homology of Hsp65 with the mammalian protein raises concern that pathological autoimmune responses may also be triggered. We searched for autoimmune responses elicited by DNA-hsp65 immunotherapy in mice chronically infected with TB by evaluating the humoral immune response and comprehensive histopathology using stereology. Cross-reactive antibodies between mycobacterial and mammalian Hsp60/65 were detected; however, no signs of pathological autoimmunity were found up to 60 days after the end of the therapy.
-
Cardiac morphology after conditions of microgravity during Cosmos 2044
NASA Technical Reports Server (NTRS)
Goldstein, Margaret A.; Edwards, Robert J.; Schroeter, John P.
1992-01-01
Light- and electron-microscopic studies were performed on cardiac muscle from rats flown on Cosmos 2044 and from four control groups. Average cross-sectional area of myofibers was measured by video analysis of the light-microscopic images of papillary and ventricular muscle samples from all animals. This cross-sectional area was significantly decreased in flight rats (P = 0.03) compared with synchronous controls. Additional findings at the electron microscopic level consistent with this atrophy were obtained by stereological analysis and optical diffraction analysis of papillary muscle samples. Slightly higher mitochondrial volume density values and mitochondria-to-myofibril ratios as well as normal A-band spacings (d1,0) and Z-band spacings of myofibrils were observed in the tail-suspension and flight groups. General morphological features similar to those in ventricular samples from the previous Cosmos 1887 flight were observed.
-
A probabilistic approach to aircraft design emphasizing stability and control uncertainties
NASA Astrophysics Data System (ADS)
Delaurentis, Daniel Andrew
In order to address identified deficiencies in current approaches to aerospace systems design, a new method has been developed. This new method for design is based on the premise that design is a decision making activity, and that deterministic analysis and synthesis can lead to poor, or misguided decision making. This is due to a lack of disciplinary knowledge of sufficient fidelity about the product, to the presence of uncertainty at multiple levels of the aircraft design hierarchy, and to a failure to focus on overall affordability metrics as measures of goodness. Design solutions are desired which are robust to uncertainty and are based on the maximum knowledge possible. The new method represents advances in the two following general areas. 1. Design models and uncertainty. The research performed completes a transition from a deterministic design representation to a probabilistic one through a modeling of design uncertainty at multiple levels of the aircraft design hierarchy, including: (1) Consistent, traceable uncertainty classification and representation; (2) Concise mathematical statement of the Probabilistic Robust Design problem; (3) Variants of the Cumulative Distribution Functions (CDFs) as decision functions for Robust Design; (4) Probabilistic Sensitivities which identify the most influential sources of variability. 2. Multidisciplinary analysis and design. Imbedded in the probabilistic methodology is a new approach for multidisciplinary design analysis and optimization (MDA/O), employing disciplinary analysis approximations formed through statistical experimentation and regression. These approximation models are a function of design variables common to the system level as well as other disciplines. For aircraft, it is proposed that synthesis/sizing is the proper avenue for integrating multiple disciplines. Research hypotheses are translated into a structured method, which is subsequently tested for validity. Specifically, the implementation involves the study of the relaxed static stability technology for a supersonic commercial transport aircraft. The probabilistic robust design method is exercised resulting in a series of robust design solutions based on different interpretations of "robustness". Insightful results are obtained and the ability of the method to expose trends in the design space are noted as a key advantage.
-
Kuldeep, B; Singh, V K; Kumar, A; Singh, G K
2015-01-01
In this article, a novel approach for 2-channel linear phase quadrature mirror filter (QMF) bank design based on a hybrid of gradient based optimization and optimization of fractional derivative constraints is introduced. For the purpose of this work, recently proposed nature inspired optimization techniques such as cuckoo search (CS), modified cuckoo search (MCS) and wind driven optimization (WDO) are explored for the design of QMF bank. 2-Channel QMF is also designed with particle swarm optimization (PSO) and artificial bee colony (ABC) nature inspired optimization techniques. The design problem is formulated in frequency domain as sum of L2 norm of error in passband, stopband and transition band at quadrature frequency. The contribution of this work is the novel hybrid combination of gradient based optimization (Lagrange multiplier method) and nature inspired optimization (CS, MCS, WDO, PSO and ABC) and its usage for optimizing the design problem. Performance of the proposed method is evaluated by passband error (ϕp), stopband error (ϕs), transition band error (ϕt), peak reconstruction error (PRE), stopband attenuation (As) and computational time. The design examples illustrate the ingenuity of the proposed method. Results are also compared with the other existing algorithms, and it was found that the proposed method gives best result in terms of peak reconstruction error and transition band error while it is comparable in terms of passband and stopband error. Results show that the proposed method is successful for both lower and higher order 2-channel QMF bank design. A comparative study of various nature inspired optimization techniques is also presented, and the study singles out CS as a best QMF optimization technique. Copyright © 2014 ISA. Published by Elsevier Ltd. All rights reserved.
-
Successive equimarginal approach for optimal design of a pump and treat system
NASA Astrophysics Data System (ADS)
Guo, Xiaoniu; Zhang, Chuan-Mian; Borthwick, John C.
2007-08-01
An economic concept-based optimization method is developed for groundwater remediation design. Design of a pump and treat (P&T) system is viewed as a resource allocation problem constrained by specified cleanup criteria. An optimal allocation of resources requires that the equimarginal principle, a fundamental economic principle, must hold. The proposed method is named successive equimarginal approach (SEA), which continuously shifts a pumping rate from a less effective well to a more effective one until equal marginal productivity for all units is reached. Through the successive process, the solution evenly approaches the multiple inequality constraints that represent the specified cleanup criteria in space and in time. The goal is to design an equal protection system so that the distributed contaminant plumes can be equally contained without bypass and overprotection is minimized. SEA is a hybrid of the gradient-based method and the deterministic heuristics-based method, which allows flexibility in dealing with multiple inequality constraints without using a penalty function and in balancing computational efficiency with robustness. This method was applied to design a large-scale P&T system for containment of multiple plumes at the former Blaine Naval Ammunition Depot (NAD) site, near Hastings, Nebraska. To evaluate this method, the SEA results were also compared with those using genetic algorithms.
-
Wideband dichroic-filter design for LED-phosphor beam-combining
Falicoff, Waqidi
2010-12-28
A general method is disclosed of designing two-component dichroic short-pass filters operable for incidence angle distributions over the 0-30.degree. range, and specific preferred embodiments are listed. The method is based on computer optimization algorithms for an N-layer design, specifically the N-dimensional conjugate-gradient minimization of a merit function based on difference from a target transmission spectrum, as well as subsequent cycles of needle synthesis for increasing N. A key feature of the method is the initial filter design, upon which the algorithm proceeds to iterate successive design candidates with smaller merit functions. This initial design, with high-index material H and low-index L, is (0.75 H, 0.5 L, 0.75 H)^m, denoting m (20-30) repetitions of a three-layer motif, giving rise to a filter with N=2 m+1.
-
Method and apparatus for decoupled thermo-catalytic pollution control
Tabatabaie-Raissi, Ali; Muradov, Nazim Z.; Martin, Eric
2006-07-11
A new method for design and scale-up of thermocatalytic processes is disclosed. The method is based on optimizing process energetics by decoupling of the process energetics from the DRE for target contaminants. The technique is applicable to high temperature thermocatalytic reactor design and scale-up. The method is based on the implementation of polymeric and other low-pressure drop support for thermocatalytic media as well as the multifunctional catalytic media in conjunction with a novel rotating fluidized particle bed reactor.
-
Design of Inkjet-Printed RFID-Based Sensor on Paper: Single- and Dual-Tag Sensor Topologies.
Kim, Sangkil; Georgiadis, Apostolos; Tentzeris, Manos M
2018-06-17
The detailed design considerations for the printed RFID-based sensor system is presented in this paper. Starting from material selection and metallization method, this paper discusses types of RFID-based sensors (single- & dual-tag sensor topologies), design procedures, and performance evaluation methods for the wireless sensor system. The electrical properties of the paper substrates (cellulose-based and synthetic papers) and the silver nano-particle-based conductive film are thoroughly characterized for RF applications up to 8 GHz. The reported technology could potentially set the foundation for truly “green”, low-cost, scalable wireless topologies for autonomous Internet-of-Things (IoT), bio-monitoring, and “smart skin” applications.
-
NASA Astrophysics Data System (ADS)
Chaidee, S.; Pakawanwong, P.; Suppakitpaisarn, V.; Teerasawat, P.
2017-09-01
In this work, we devise an efficient method for the land-use optimization problem based on Laguerre Voronoi diagram. Previous Voronoi diagram-based methods are more efficient and more suitable for interactive design than discrete optimization-based method, but, in many cases, their outputs do not satisfy area constraints. To cope with the problem, we propose a force-directed graph drawing algorithm, which automatically allocates generating points of Voronoi diagram to appropriate positions. Then, we construct a Laguerre Voronoi diagram based on these generating points, use linear programs to adjust each cell, and reconstruct the diagram based on the adjustment. We adopt the proposed method to the practical case study of Chiang Mai University's allocated land for a mixed-use complex. For this case study, compared to other Voronoi diagram-based method, we decrease the land allocation error by 62.557 %. Although our computation time is larger than the previous Voronoi-diagram-based method, it is still suitable for interactive design.
-
New methodology for shaft design based on life expectancy
NASA Technical Reports Server (NTRS)
Loewenthal, S. H.
1986-01-01
The design of power transmission shafting for reliability has not historically received a great deal of attention. However, weight sensitive aerospace and vehicle applications and those where the penalties of shaft failure are great, require greater confidence in shaft design than earlier methods provided. This report summarizes a fatigue strength-based, design method for sizing shafts under variable amplitude loading histories for limited or nonlimited service life. Moreover, applications factors such as press-fitted collars, shaft size, residual stresses from shot peening or plating, corrosive environments can be readily accommodated into the framework of the analysis. Examples are given which illustrate the use of the method, pointing out the large life penalties due to occasional cyclic overloads.
-
A reference Pelton turbine design
NASA Astrophysics Data System (ADS)
Solemslie, B. W.; Dahlhaug, O. G.
2012-09-01
The designs of hydraulic turbines are usually close kept corporation secrets. Therefore, the possibility of innovation and co-operation between different academic institutions regarding a specific turbine geometry is difficult. A Ph.D.-project at the Waterpower Laboratory, NTNU, aim to design several model Pelton turbines where all measurements, simulations, the design strategy, design software in addition to the physical model will be available to the public. In the following paper a short description of the methods and the test rig that are to be utilized in the project are described. The design will be based on empirical data and NURBS will be used as the descriptive method for the turbine geometry. In addition CFX and SPH simulations will be included in the design process. Each turbine designed and produced in connection to this project will be based on the experience and knowledge gained from the previous designs. The first design will be based on the philosophy to keep a near constant relative velocity through the bucket.
-
Multidisciplinary design of a rocket-based combined cycle SSTO launch vehicle using Taguchi methods
NASA Technical Reports Server (NTRS)
Olds, John R.; Walberg, Gerald D.
1993-01-01
Results are presented from the optimization process of a winged-cone configuration SSTO launch vehicle that employs a rocket-based ejector/ramjet/scramjet/rocket operational mode variable-cycle engine. The Taguchi multidisciplinary parametric-design method was used to evaluate the effects of simultaneously changing a total of eight design variables, rather than changing them one at a time as in conventional tradeoff studies. A combination of design variables was in this way identified which yields very attractive vehicle dry and gross weights.
-
Enhanced Learning through Design Problems--Teaching a Components-Based Course through Design
ERIC Educational Resources Information Center
Jensen, Bogi Bech; Hogberg, Stig; Jensen, Frida av Flotum; Mijatovic, Nenad
2012-01-01
This paper describes a teaching method used in an electrical machines course, where the students learn about electrical machines by designing them. The aim of the course is not to teach design, albeit this is a side product, but rather to teach the fundamentals and the function of electrical machines through design. The teaching method is…
-
A flexible layout design method for passive micromixers.
Deng, Yongbo; Liu, Zhenyu; Zhang, Ping; Liu, Yongshun; Gao, Qingyong; Wu, Yihui
2012-10-01
This paper discusses a flexible layout design method of passive micromixers based on the topology optimization of fluidic flows. Being different from the trial and error method, this method obtains the detailed layout of a passive micromixer according to the desired mixing performance by solving a topology optimization problem. Therefore, the dependence on the experience of the designer is weaken, when this method is used to design a passive micromixer with acceptable mixing performance. Several design disciplines for the passive micromixers are considered to demonstrate the flexibility of the layout design method for passive micromixers. These design disciplines include the approximation of the real 3D micromixer, the manufacturing feasibility, the spacial periodic design, and effects of the Péclet number and Reynolds number on the designs obtained by this layout design method. The capability of this design method is validated by several comparisons performed between the obtained layouts and the optimized designs in the recently published literatures, where the values of the mixing measurement is improved up to 40.4% for one cycle of the micromixer.
-
A Method for Generating Reduced Order Linear Models of Supersonic Inlets
NASA Technical Reports Server (NTRS)
Chicatelli, Amy; Hartley, Tom T.
1997-01-01
For the modeling of high speed propulsion systems, there are at least two major categories of models. One is based on computational fluid dynamics (CFD), and the other is based on design and analysis of control systems. CFD is accurate and gives a complete view of the internal flow field, but it typically has many states and runs much slower dm real-time. Models based on control design typically run near real-time but do not always capture the fundamental dynamics. To provide improved control models, methods are needed that are based on CFD techniques but yield models that are small enough for control analysis and design.
-
DOE Office of Scientific and Technical Information (OSTI.GOV)
Adams, Brian M.; Ebeida, Mohamed Salah; Eldred, Michael S.
The Dakota (Design Analysis Kit for Optimization and Terascale Applications) toolkit provides a exible and extensible interface between simulation codes and iterative analysis methods. Dakota contains algorithms for optimization with gradient and nongradient-based methods; uncertainty quanti cation with sampling, reliability, and stochastic expansion methods; parameter estimation with nonlinear least squares methods; and sensitivity/variance analysis with design of experiments and parameter study methods. These capabilities may be used on their own or as components within advanced strategies such as surrogate-based optimization, mixed integer nonlinear programming, or optimization under uncertainty. By employing object-oriented design to implement abstractions of the key components requiredmore » for iterative systems analyses, the Dakota toolkit provides a exible and extensible problem-solving environment for design and performance analysis of computational models on high performance computers. This report serves as a user's manual for the Dakota software and provides capability overviews and procedures for software execution, as well as a variety of example studies.« less
-
Yamada, Akira; Terakawa, Mitsuhiro
2015-04-10
We present a design method of a bull's eye structure with asymmetric grooves for focusing oblique incident light. The design method is capable of designing transmission peaks to a desired oblique angle with capability of collecting light from a wider range of angles. The bull's eye groove geometry for oblique incidence is designed based on the electric field intensity pattern around an isolated subwavelength aperture on a thin gold film at oblique incidence, calculated by the finite difference time domain method. Wide angular transmission efficiency is successfully achieved by overlapping two different bull's eye groove patterns designed with different peak angles. Our novel design method would overcome the angular limitations of the conventional methods.
-
Category's analysis and operational project capacity method of transformation in design
NASA Astrophysics Data System (ADS)
Obednina, S. V.; Bystrova, T. Y.
2015-10-01
The method of transformation is attracting widespread interest in fields such contemporary design. However, in theory of design little attention has been paid to a categorical status of the term "transformation". This paper presents the conceptual analysis of transformation based on the theory of form employed in the influential essays by Aristotle and Thomas Aquinas. In the present work the transformation as a method of shaping design has been explored as well as potential application of this term in design has been demonstrated.
-
Control Theory based Shape Design for the Incompressible Navier-Stokes Equations
NASA Astrophysics Data System (ADS)
Cowles, G.; Martinelli, L.
2003-12-01
A design method for shape optimization in incompressible turbulent viscous flow has been developed and validated for inverse design. The gradient information is determined using a control theory based algorithm. With such an approach, the cost of computing the gradient is negligible. An additional adjoint system must be solved which requires the cost of a single steady state flow solution. Thus, this method has an enormous advantage over traditional finite-difference based algorithms. The method of artificial compressibility is utilized to solve both the flow and adjoint systems. An algebraic turbulence model is used to compute the eddy viscosity. The method is validated using several inverse wing design test cases. In each case, the program must modify the shape of the initial wing such that its pressure distribution matches that of the target wing. Results are shown for the inversion of both finite thickness wings as well as zero thickness wings which can be considered a model of yacht sails.
-
Neuron number and size in prefrontal cortex of children with autism.
Courchesne, Eric; Mouton, Peter R; Calhoun, Michael E; Semendeferi, Katerina; Ahrens-Barbeau, Clelia; Hallet, Melodie J; Barnes, Cynthia Carter; Pierce, Karen
2011-11-09
Autism often involves early brain overgrowth, including the prefrontal cortex (PFC). Although prefrontal abnormality has been theorized to underlie some autistic symptoms, the cellular defects that cause abnormal overgrowth remain unknown. To investigate whether early brain overgrowth in children with autism involves excess neuron numbers in the PFC. DESIGN, SETTING, AND CASES: Postmortem prefrontal tissue from 7 autistic and 6 control male children aged 2 to 16 years was examined by expert anatomists who were blinded to diagnostic status. Number and size of neurons were quantified using stereological methods within the dorsolateral (DL-PFC) and mesial (M-PFC) subdivisions of the PFC. Cases were from the eastern and southeastern United States and died between 2000 and 2006. Mean neuron number and size in the DL-PFC and M-PFC were compared between autistic and control postmortem cases. Correlations of neuron number with deviation in brain weight from normative values for age were also performed. Children with autism had 67% more neurons in the PFC (mean, 1.94 billion; 95% CI, 1.57-2.31) compared with control children (1.16 billion; 95% CI, 0.90-1.42; P = .002), including 79% more in DL-PFC (1.57 billion; 95% CI, 1.20-1.94 in autism cases vs 0.88 billion; 95% CI, 0.66-1.10 in controls; P = .003) and 29% more in M-PFC (0.36 billion; 95% CI, 0.33-0.40 in autism cases vs 0.28 billion; 95% CI, 0.23-0.34 in controls; P = .009). Brain weight in the autistic cases differed from normative mean weight for age by a mean of 17.6% (95% CI, 10.2%-25.0%; P = .001), while brains in controls differed by a mean of 0.2% (95% CI, -8.7% to 9.1%; P = .96). Plots of counts by weight showed autistic children had both greater total prefrontal neuron counts and brain weight for age than control children. In this small preliminary study, brain overgrowth in males with autism involved an abnormal excess number of neurons in the PFC.
-
On the design of henon and logistic map-based random number generator
NASA Astrophysics Data System (ADS)
Magfirawaty; Suryadi, M. T.; Ramli, Kalamullah
2017-10-01
The key sequence is one of the main elements in the cryptosystem. True Random Number Generators (TRNG) method is one of the approaches to generating the key sequence. The randomness source of the TRNG divided into three main groups, i.e. electrical noise based, jitter based and chaos based. The chaos based utilizes a non-linear dynamic system (continuous time or discrete time) as an entropy source. In this study, a new design of TRNG based on discrete time chaotic system is proposed, which is then simulated in LabVIEW. The principle of the design consists of combining 2D and 1D chaotic systems. A mathematical model is implemented for numerical simulations. We used comparator process as a harvester method to obtain the series of random bits. Without any post processing, the proposed design generated random bit sequence with high entropy value and passed all NIST 800.22 statistical tests.
-
Invisibility problem in acoustics, electromagnetism and heat transfer. Inverse design method
NASA Astrophysics Data System (ADS)
Alekseev, G.; Tokhtina, A.; Soboleva, O.
2017-10-01
Two approaches (direct design and inverse design methods) for solving problems of designing devices providing invisibility of material bodies of detection using different physical fields - electromagnetic, acoustic and static are discussed. The second method is applied for solving problems of designing cloaking devices for the 3D stationary thermal scattering model. Based on this method the design problems under study are reduced to respective control problems. The material parameters (radial and tangential heat conductivities) of the inhomogeneous anisotropic medium filling the thermal cloak and the density of auxiliary heat sources play the role of controls. A unique solvability of direct thermal scattering problem in the Sobolev space is proved and the new estimates of solutions are established. Using these results, the solvability of control problem is proved and the optimality system is derived. Based on analysis of optimality system, the stability estimates of optimal solutions are established and numerical algorithms for solving particular thermal cloaking problem are proposed.
-
"Drug" Discovery with the Help of Organic Chemistry.
Itoh, Yukihiro; Suzuki, Takayoshi
2017-01-01
The first step in "drug" discovery is to find compounds binding to a potential drug target. In modern medicinal chemistry, the screening of a chemical library, structure-based drug design, and ligand-based drug design, or a combination of these methods, are generally used for identifying the desired compounds. However, they do not necessarily lead to success and there is no infallible method for drug discovery. Therefore, it is important to explore medicinal chemistry based on not only the conventional methods but also new ideas. So far, we have found various compounds as drug candidates. In these studies, some strategies based on organic chemistry have allowed us to find drug candidates, through 1) construction of a focused library using organic reactions and 2) rational design of enzyme inhibitors based on chemical reactions catalyzed by the target enzyme. Medicinal chemistry based on organic chemical reactions could be expected to supplement the conventional methods. In this review, we present drug discovery with the help of organic chemistry showing examples of our explorative studies on histone deacetylase inhibitors and lysine-specific demethylase 1 inhibitors.
-
NASA Astrophysics Data System (ADS)
Chen, Ming-Chih; Hsiao, Shen-Fu
In this paper, we propose an area-efficient design of Advanced Encryption Standard (AES) processor by applying a new common-expression-elimination (CSE) method to the sub-functions of various transformations required in AES. The proposed method reduces the area cost of realizing the sub-functions by extracting the common factors in the bit-level XOR/AND-based sum-of-product expressions of these sub-functions using a new CSE algorithm. Cell-based implementation results show that the AES processor with our proposed CSE method has significant area improvement compared with previous designs.
-
Modeling startup and shutdown transient of the microlinear piezo drive via ANSYS
NASA Astrophysics Data System (ADS)
Azin, A. V.; Bogdanov, E. P.; Rikkonen, S. V.; Ponomarev, S. V.; Khramtsov, A. M.
2017-02-01
The article describes the construction-design of the micro linear piezo drive intended for a peripheral cord tensioner in the reflecting surface shape regulator system for large-sized transformable spacecraft antenna reflectors. The research target -the development method of modeling startup and shutdown transient of the micro linear piezo drive. This method is based on application software package ANSYS. The method embraces a detailed description of the calculation stages to determine the operating characteristics of the designed piezo drive. Based on the numerical solutions, the time characteristics of the designed piezo drive are determined.