A software system to record and analyze digitized cell images

This paper describes basic software for digitization and processing of microscopic cell images used at the Department of Clinical Cytology at Uppsala University Hospital. A family of programs running on a PDP-8 minicomputer which is connected to a Leitz Orthoplan microscope with two image scanners, one diode-array scanner and a moving-stage photometer, is used for data collection. The digitized image data is converted by converted by conversion program to IBM compatible format. The data structures for image processing and statistical evaluation on the IBM system are also described. Finally, some experiences from the use of the software in cytology automation are discussed.     

Prediction of cervical neoplasia diagnosis groups. Discriminant analysis on digitized cell images

The purpose of this study was to develop discriminant analysis models for predicting cervical dysplasia/neoplasia case diagnoses using cytometric features derived from the digital image analysis of cell monolayers. The data base consisted of 925 cells from 27 cases diagnosed either as moderate dysplasia (n = 10), severe dysplasia (n = 5), carcinoma in situ (n = 8) or invasive carcinoma (n = 4) on both tissue biopsy and monolayer preparations. Cell features examined were cell diameter, nuclear diameter, nuclear mean optical density (OD), nuclear integrated OD (IOD), nuclear OD standard deviation, normalized IOD, nuclear texture and nuclear-cytoplasmic ratio. Features derived from cells visually classified as moderate dysplasia correctly predicted the case diagnosis of moderate dysplasia versus more severe disease for 85% of the cells. Prediction models using summary measures (mean and variance) derived from all visually classified abnormal cells within each case correctly separated all cases into their respective diagnostic categories. These findings suggest that dysplastic cells in a cytologic sample have features that collectively reflect the tissue diagnosis, regardless of the visual differences among the cells. Such information has potential use for diagnosis and possibly for prognosis.     

An interactive computer system for the analysis of cell lineages.

We have developed an interactive computer system for analysing cell lineage data. It can be utilized in studies of cell motility, cell division, cell differentiation, and cell aging. It has enabled us to document the heterogeneity of human foreskin fibroblasts in culture and to propose that loss of proliferative potential may mean that cells enter a state of differentiation which makes them unable to respond to mitotic stimulation. Our method, which enables us to apply immunological and cytochemical probes after recording the history of a cell lineage, should allow us to define precisely features which uniquely distinguish cycling from noncycling cells on an individual cell basis.     

A deep learning-based approach for detecting plant organs from digitized herbarium specimen images

Herbarium specimens are excellent sources of botanical information to facilitate understanding and monitoring the evolution of plants and their effects on global climate change. Globally, many herbaria have undertaken digitization projects of herbarium specimens to preserve them and make them accessible in online repositories to botanists and ecologists. Automated detection of plant organs such as plant leaves, buds, flowers, and fruits on the digitized herbarium specimen images provides valuable information in various scientific contexts. We developed a deep learning approach based on the refined YOLO-V3 approach to detect plant organs within the digitized herbarium specimen images effectively. The proposed approach combines ResNet and DenseNet architectures to improve feature extraction capabilities. Also, a new scale of feature map is added to the existing scales to address the problem of YOLO-V3's low performance in detecting small plant organs. The experimental results demonstrate that our proposed approach can detect organs of different sizes within different specimens, where the precision and recall reached 94.2% and 95.5%, respectively.     

Microscopy images as interactive tools in cell modeling and cell biology education

The advent of genomics, proteomics, and microarray technology has brought much excitement to science, both in teaching and in learning. The public is eager to know about the processes of life. In the present context of the explosive growth of scientific information, a major challenge of modern cell biology is to popularize basic concepts of structures and functions of living cells, to introduce people to the scientific method, to stimulate inquiry, and to analyze and synthesize concepts and paradigms. In this essay we present our experience in mixing science and education in Brazil. For two decades we have developed activities for the science education of teachers and undergraduate students, using microscopy images generated by our work as cell biologists. We describe open-air outreach education activities, games, cell modeling, and other practical and innovative activities presented in public squares and favelas. Especially in developing countries, science education is important, since it may lead to an improvement in quality of life while advancing understanding of traditional scientific ideas. We show that teaching and research can be mutually beneficial rather than competing pursuits in advancing these goals.     

An interactive modeling program for DNA

An interactive program for modeling A-, B- and Z-DNA in a schematic and nonatomic representation has been developed for the Evans and Sutherland PS300. The program lets users display several molecules for which parameters determining the three-dimensional structure can be calculated either on the basis of theoretical models or inferred from experimental data. The calculation of the curvature and torsion of the helical axis, by a method based on Frenet's equations, makes it possible to quantify the effects of the parameters on the helical axis.     

A web server for interactive and zoomable Chaos Game Representation images

Chaos Game Representation (CGR) is a generalized scale-independent Markov transition table, which is useful for the visualization and comparative study of genomic signature, or for the study of characteristic sequence motifs. However, in order to fully utilize the scale-independent properties of CGR, it should be accessible through scale-independent user interface instead of static images. Here we describe a web server and Perl library for generating zoomable CGR images utilizing Google Maps API, which is also easily searchable for specific motifs. The web server is freely accessible at , and the Perl library as well as the source code is distributed with the G-language Genome Analysis Environment under GNU General Public License.     

A general interactive model for B cell activation

The general interactive model described in the previous paper was subjected to experimental testing. We examined the high affinity anti-TNP? plaqueforming cell response of cultures of murine lymphocytes exposed to lipopolysaccharide and trinitrophenylated lipopolysaccharide (TNP-LPS). From our model we predicted the effects of the addition of free LPS on the dose response to TNP-LPS, the effect of the addition of Polymyxin B to cultures stimulated with TNP-LPS, and the effect on the response to TNP-LPS preparations with different haptenation ratios. The results obtained were consistent with the predictions of the general interactive model.     

A general interactive model for B cell activation II. Experimental verification

The general interactive model described in the previous paper was subjected to experimental testing. We examined the high affinity anti-TNP plaque-forming cell response of cultures of murine lymphocytes exposed to lipopolysaccharide and trinitrophenylated lipopolysaccharide (TNP--LPS). From our model we predicted the effects of the addition of free LPS on the dose response to TNP--LPS, the effect of the addition of Polymyxin B to cultures stimulated with TNP--LPS, and the effect on the response to TNP--LPS preparations with different haptenation ratios. The results obtained were consistent with the predictions of the general interactive model.     

Motion of mitochondria in cultured cells quantified by analysis of digitized images.

Translational movements of mitochondria in cultured rat liver cells were characterized quantitatively by using a video camera to detect and a video digitizer-computer system to analyze fluorescent images of mitochondria stained with rhodamine 123. The centroids of the images of individual mitochondria were determined at selected time intervals and the paths followed by the mitochondria were defined by the paths of the centroids. The predominant translation motion of the mitochondria satisfied the formal conditions of a Brownian random walk for a free particle, although in several cases there was a slow drift superimposed on the random motion. The apparent diffusion coefficients were approximately 5 X 10(-12) cm2 s-1, and the drift speeds approximately 2 X 10(-3) micron s-1.     

A scene-segmentation method for multispectral cell images

A scene-segmentation method for two-color digitized images acquired from a Papanicolaou-stained cervical smear is proposed. The method first segments a scene into background, red cytoplasm, blue cytoplasm and nuclear regions by a pixel-wise classification and then merges the segmented regions for both types of cytoplasm into a single region. To create the minimum-distance classifier used for the pixel classification, class median vectors are selected from a two-dimensional histogram formed from the optical densities in the red and green images (scanned at 610 nm and 535 nm, respectively). Reference points defined from knowledge about the two-color images played an important role in selecting the vectors for the red and blue cytoplasm. This method was applied to 33 sets of the two-color images. The resulting segmented regions corresponded well with regions apparent to the the human observer. Three different investigations related to the method were carried out; these studies confirmed the suitability of the proposed method.     

A new interactive computerized data base and retrieval system.

A new computerized data base and retrieval system for a minicomputer has been devised for storing and retrieving clinical data. It features interactive terminal input and output using a pagination scheme as well as a subset mapping scheme for interactive retrieval. The pagination system, file structuring and retrieval system are discussed.     

A teaching exercise for the identification of bacteria using an interactive computer program

An interactive computer program written in Fortran is described which provides an exercise in the identification of bacteria. The program, IDEN, provides a novel way of enhancing a student's approach to systematic bacteriology and numerical identification procedures. An unknown bacterium is assigned to a student who is provided with a list of possible species and a list of tests which may be carried out. The student's objective is the correct identification of the unknown in the most economical manner. An indication is given concerning the way in which this program can be used to enhance theoretical instruction and practical investigation.     

A computer program for the morphometric analysis of cell profiles.

A computer program which yields values for the volumes, surface areas, and volume/surface area ratios of cell profiles is described for use on a desktop calculator (minicomputer). This program uses standard morphometric procedures, and incorporates data obtained from electron micrographs at two levels of sampling. The main program yields values for the 'average cell volume' at the tissue level of sampling. Two options at the cellular level of sampling are also included which yield values for the volumes, surface areas and volume/surface area ratios for the organelles. The first option allows an analysis of 'whole cells' containing equatorial profiles through the nucleus, while the second option permits a 'fractional' approach using segments of the cells. Finally, some of the advantages of the two options are discussed.