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Computer-aided pattern representation of microscope pictures with the mosaic grid.

The conventional study of larger areas with the necessary low lens magnification may affect cytoarchitectonical investigations since the material is insufficiently magnified. Faroff lying structures cannot be seen with the requested high magnification, i.e. they are only visible in the microscope with low magnification. The present work aims at providing the morphologist with a computer-assisted solution of this technical problem. The software developed by our scientists permits a hardcopy representation of a standardized model of a theoretically unlimited investigational area with free-choice magnification. Furthermore, this paper tackles, problems of the increase of the resolution level of modelling.

Animals↗

A new approach to evaluate toxicity of gases on mobile cells in culture.

A novel technique is described that measures the degree of toxicity of short-term exposure to gaseous pollutants or other chemical compounds on cultured cells, in 30 min. This technique, based on the study of the mobility properties of activated macrophages, consists of an image analysis procedure incorporating a specific exposure chamber (EC). The EC, which is developed from commercial culture flasks (50 ml, 25 cm(2) of culture surface), was first used to maintain cells in culture conditions, overnight, prior to the assay. In order to measure toxicity, it was then connected to the gaseous pollutant or chemical source. After exposing the culture medium and cells to the gas stream for 10 min, fMLP, a chemotactic factor, was added and the mobility of the macrophages measured by superimposing sequential analogue images captured by a CCD camera that were digitised and analysed using a software developed for this purpose. For example, the effect of ozone on macrophage-like cell (THP-1) was investigated. After exposure to 0.1 and 0.5 ppm, cells lost, respectively 79% and 90% of their mobility, compared to the control sample.

Atmosphere Exposure Chambers↗

Prediction of quaternary structure from primary structure.

MOTIVATION: The 'sequence implies conformation' principle has been the motivation for the construction of numerous systems of secondary and tertiary structure prediction. Computational experiments have shown that this principle can now be extended to quaternary structure prediction. This work appears to be the first effort to predict quaternary structure properties from sequence. RESULTS: The software developed to conduct these experiments was the Quaternary Structure Explorer (QSE). Successful rule-based classifiers have been found that can discriminate between the primary sequences of homodimers and non-homodimers.

Algorithms↗

[PC-based computer monitoring in an intensive care unit].

The lack of direct communication with the intensive care patient means the medical staff have to try to achieve a realistic picture of the condition of the patient from numerous pieces of detailed information fitted together something like a jigsaw. The immense amount of data thus gained means an overall interpretation of the many individual data would be hardly imaginable without the use of a computer. PC networks in conjunction with a high-level language provide an ideal basis for building up a background monitoring system that can be used at the bedside. Simple PC-ATs and software developed in house in Turbo-Pascal have enabled us to realize a useful and very economical computer-aided background monitoring system. Any online and offline data important for an operative critical care unit can be collected, documented, displayed and processed in secondary parameters.

Austria↗

A simple method for hardware and software evaluation.

Subjective data are often the only data available for making decisions and choices in both hardware and software development. These data are therefore both important and valuable. Their importance is such that it is necessary to elicit subjective data from a variety of sources and in a manner that is relatively unbiased. A method which requires participants to compare all criteria and all proposed concepts by pairs provides a non-statistical mechanism for collecting data from a broad base of expertise, for giving appropriate weight to all input, and for reducing personal bias. These characteristics make a comparison of all pairs a useful tool for hardware and software evaluation when decisions and choices must be made. The efficacy of the method was recently demonstrated in the selection of a restraint-attachment device for Space Station Freedom.

Journal Article↗

A multi-user networked database for analysis of clinical and temperature data from patients treated with simultaneous radiation and ultrasound hyperthermia.

A database was developed using commercially available development software that allows the entry of clinical data and automatically analyses temperature and power data from a commercial ultrasound hyperthermia system. The database can be accessed via network connections by more than one authorized user, thus facilitating the entry, management, and analysis of clinical data. The software automatically estimates ultrasound induced temperature artifacts and calculates thermal dose parameters such as T90s, equivalent minutes at 43 degrees, and time at or above index temperatures using the corrected temperatures. These parameters also become part of the database. Digital photographs of treatment setup, probe placement, and tumour or normal tissue response can be included in the database for documentation and reference. Ultrasound diagnostic images that document the depth and reproducibility of probe placement can be scanned into the PC and included in the database as well. This short communication documents experiences developing this tool that may be useful to other investigators.

Combined Modality Therapy↗

G-language Genome Analysis Environment: a workbench for nucleotide sequence data mining.

SUMMARY: G-language Genome Analysis Environment (G-language GAE) is an open source generic software package aimed for higher efficiency in bioinformatics analysis. G-language GAE has an interface as a set of Perl libraries for software development, and a graphical user interface for easy manipulation. Both Windows and Linux versions are available. AVAILABILITY: From http://www.g-language.org/ under GNU General Public License. CD-ROMs are distributed freely in major conferences.

Database Management Systems↗

A case study in pathway knowledgebase verification.

BACKGROUND: Biological databases and pathway knowledge-bases are proliferating rapidly. We are developing software tools for computer-aided hypothesis design and evaluation, and we would like our tools to take advantage of the information stored in these repositories. But before we can reliably use a pathway knowledge-base as a data source, we need to proofread it to ensure that it can fully support computer-aided information integration and inference. RESULTS: We design a series of logical tests to detect potential problems we might encounter using a particular knowledge-base, the Reactome database, with a particular computer-aided hypothesis evaluation tool, HyBrow. We develop an explicit formal language from the language implicit in the Reactome data format and specify a logic to evaluate models expressed using this language. We use the formalism of finite model theory in this work. We then use this logic to formulate tests for desirable properties (such as completeness, consistency, and well-formedness) for pathways stored in Reactome. We apply these tests to the publicly available Reactome releases (releases 10 through 14) and compare the results, which highlight Reactome's steady improvement in terms of decreasing inconsistencies. We also investigate and discuss Reactome's potential for supporting computer-aided inference tools. CONCLUSION: The case study described in this work demonstrates that it is possible to use our model theory based approach to identify problems one might encounter using a knowledge-base to support hypothesis evaluation tools. The methodology we use is general and is in no way restricted to the specific knowledge-base employed in this case study. Future application of this methodology will enable us to compare pathway resources with respect to the generic properties such resources will need to possess if they are to support automated reasoning.

Algorithms↗

Decreased precision for BMD measurements in the prosthetic knee using a non-knee-specific software.

Non-knee-specific software has been widely used for bone mineral density (BMD) measurement at the knee, which coincide with a higher measurement error. This study was conducted to test whether software developed for BMD measurement at the hip could be used in the knee by using dual-energy X-ray absorptiometry (DXA) and whether knee rotational alignment or differences in soft tissue substitutes would influence the precision of the BMD measurement. Twelve knees operated with total knee arthroplasty were included. The knees were scanned four to six times each in four rotational positions using DXA with either a Plexiglas rod or rice bags as a soft tissue substitute. The BMD was measured in one manually defined region at the proximal tibia by using the software of Orthopedic. The precision (coefficient of variation) at the knee was 5.1-9.0% when using the Plexiglas rod and 7.3% when using rice bags. The poor precision was mainly explained by inconsistency in tissue baseline establishment and/or by low baseline bone density (Adj R2 = 0.78-0.90, p < 0.000). Neither intentional rotation of the knee nor using different soft tissue substitutes significantly altered the precision. The results suggest that the use of a non-knee-specific software in the prosthetic knee is not appropriate.

Absorptiometry, Photon↗

Parametric images of antibody pharmacokinetics in Bi213-HuM195 therapy of leukemia.

UNLABELLED: Kinetic analysis of gamma camera patient images can provide time-dependent information about antibody behavior. Current region-of-interest-based techniques for the kinetic analysis of these images rely on user selection and drawing of regions to be analyzed. Such analyses do not reveal unexpected kinetic activity outside of the selected regions of interest and do not provide a whole-image assessment regarding the pharmacokinetics of an agent. At Memorial Sloan-Kettering Cancer Center, a method for generating images in which the pixel value represents a kinetic parameter has been developed. This work extends the method into a new application in which whole-body parametric images are used to examine the kinetics of Bi213-HuM195 in patients with leukemia. METHODS: Bi213-HuM195 is typically administered in multiple injections over 2-4 d, yielding a progressive increase in the amount of antibody administered. Patients are injected with individual doses while positioned in a gamma camera, and imaging is initiated at the start of the injection. The acquisition is performed in dynamic mode with images collected at several time intervals over 1 h. Using software developed in-house, images are corrected for patient movement through iterative alignments, decay corrected, and summed to yield a series of images over regular time intervals. Parametric rate images are obtained by fitting a linear expression to the counts in each pixel. In this study, rate images from a patient's first injection were compared with rate images from the last injection. RESULTS: The conventional planar images of antibody distribution showed significant uptake in liver, spleen, and marrow, whereas the generated rate images displayed different patterns, sometimes with negative values in liver and spleen and positive values in marrow, reflecting clearance and uptake rates rather than total accumulation. The impact of the progressive increase in antibody administration was observed by comparing the first with the last rate images. Interpatient comparisons were also made and showed that rate image patterns varied depending on patient-specific conditions such as the amount of disease and previous therapies undergone by the patient. CONCLUSION: Rate images make it possible to succinctly display kinetic information about an agent's behavior over the entire acquired image.

Antibodies, Monoclonal↗

ANN-based QRS-complex analysis of ECG.

Reliable detection the QRS complex in either a normal or an abnormal ECG and its analysis is the first and foremost task in almost every ECG signal analysis system aimed at the diagnostic interpretation of ECG. Conventionally, detection of the QRS complex is accomplished using a rule-based/algorithmic approach. This work, uses the learn and generalize approach of an artificial neural network (ANN) for the detection of QRS complexes in either a normal or an abnormal ECG. This is followed by the analysis of the QRS complex to designate and measure the morphological components within the QRS complex in all 12 standard leads. An ANN has been developed to detect the QRS complex in ECG and trained, with the help of back propagation algorithm, on more than a hundred ECGs selected from the CSE Data Set-3. The trained ANN was tested on all the recordings of the CSE Data Set-3 and the sensitivity has been found to be 99.11%. Subsequent to the identification of the QRS complex, an analysis of this complex and measurement of peak amplitudes of the component waves is done. The results are validated using the CSE multilead measurement results. Both the QRS detection and the QRS analysis software developed in C-language have been successfully implemented on a PC-AT. The results are found to be in agreement with visual measurements carried out by medical experts.

Electrocardiography↗

Patient specific quality assurance for the delivery of intensity modulated radiotherapy.

A patient specific quality assurance program has been developed to facilitate the clinical implementation of intensity modulated radiotherapy (IMRT) delivered using a micro-multileaf collimator. The methodology includes several dosimetric tasks that are performed prior to the treatment of each patient. Film dosimetry is performed for each individual field and for the multifield composite plan. Individual field measurements are performed at a depth of 5 cm in a water equivalent slab phantom; export of dose calculations from the treatment planning system is similarly specified. For the composite distribution, parameters from the patient plan are applied to an IMRT phantom, and film is exposed in an axial orientation. Distributions are compared with the aid of software developed for the specific tasks. The measured and calculated dose distributions can be superimposed and positioned graphically using move, rotate, and mirror tools, as well as by specifying isocenter coordinates and using fiducial marks. Horizontal and vertical profiles are available for analysis. Dose difference, distance-to-agreement, and gamma index, the minimum scaled multidimensional distance between a measurement and a calculation point determined in combined dose and physical distance space, are calculated along a specified isodose line and displayed. gamma provides an excellent measure of disagreement between measurement and calculation for complex intensity distributions. We specify 3% dose difference and 3 mm distance as our scaling acceptability criteria. Absolute dosimetry for each composite plan is performed using an ionization chamber. To date, excellent agreement between measurements and calculations has been observed.

Humans↗

An interactive image analysis system for quantitative cytology & to classify cervical cells.

Introduction of computers and image analysis systems are gaining faster momentum in order to quantitate the assessment of cells for diagnosis and prognosis, and this system aims to relieve the operator from the tedium of microscopic observation and reduce operator bias and human error. This paper discusses the design and configuration of an interactive image analysis system built in the laboratory for the purpose of cell analysis and classification. The software developed to compute various textural and morphological parameters of cells on smear are briefly described. The results of the experiments carried out to classify normal and abnormal cells on cervical smear show 94 per cent success rate.

Cytological Techniques↗

Novel instrumentation for multifield time-lapse cinemicrography.

The most significant feature of the system that is described is its ability to image essentially simultaneously the growth of up to 99 single cells into macroscopic colonies, each in its own microscope field. Operationally, fields are first defined and programmed by a trained observer. All subsequent steps are automatic and under computer control. Salient features of the hardware are stepper motor-controlled movement of the stage and fine adjustment of an inverted microscope, a high-quality 16-mm cine camera with light meter and controls, and a miniature incubator in which cells may be grown under defined conditions directly on the microscope stage. This system, termed MUTLAS, necessitates reordering of the primary images by rephotographing them on fresh film. Software developed for the analysis of cell and colony growth requires frame-by-frame examination of the secondary film and the use of a mouse-driven cursor to trace microscopically visible (4X objective magnification) events.

Animals↗

Need for optimal body composition data analysis using air-displacement plethysmography in children and adolescents.

Air-displacement plethysmography (ADP) is now widely used for body composition measurement in pediatric populations. However, the manufacturer's software developed for adults leaves a potential bias for application in children and adolescents, and recent publications do not consistently use child-specific corrections. Therefore we analyzed child-specific ADP corrections with respect to quantity and etiology of bias compared with adult formulas. An optimal correction protocol is provided giving step-by-step instructions for calculations. In this study, 258 children and adolescents (143 girls and 115 boys ranging from 5 to 18 y) with a high prevalence of overweight or obesity (28.0% in girls and 22.6% in boys) were examined by ADP applying the manufacturer's software as well as published equations for child-specific corrections for surface area artifact (SAA), thoracic gas volume (TGV), and density of fat-free mass (FFM). Compared with child-specific equations for SAA, TGV, and density of FFM, the mean overestimation of the percentage of fat mass using the manufacturer's software was 10% in children and adolescents. Half of the bias derived from the use of Siri's equation not corrected for age-dependent differences in FFM density. An additional 3 and 2% of bias resulted from the application of adult equations for prediction of SAA and TGV, respectively. Different child-specific equations used to predict TGV did not differ in the percentage of fat mass. We conclude that there is a need for child-specific equations in ADP raw data analysis considering SAA, TGV, and density of FFM.

Adolescent↗

Whole cell segmentation in solid tissue sections.

BACKGROUND: Understanding the cellular and molecular basis of tissue development and function requires analysis of individual cells while in their tissue context. METHODS: We developed software to find the optimum border around each cell (segmentation) from two-dimensional microscopic images of intact tissue. Samples were labeled with a fluorescent cell surface marker so that cell borders were brighter than elsewhere. The optimum border around each cell was defined as the border with an average intensity per unit length greater that any other possible border around that cell, and was calculated using the gray-weighted distance transform. Algorithm initiation requiring the user to mark two points per cell, one approximately in the center and the other on the border, ensured virtually 100% correct segmentation. Thereafter segmentation was automatic. RESULTS: The method was highly robust, because intermittent labeling of the cell borders, diffuse borders, and spurious signals away from the border do not significantly affect the optimum path. Computer-generated cells with increasing levels of added noise showed that the approach was accurate provided the cell could be detected visually. CONCLUSIONS: We have developed a highly robust algorithm for segmenting images of surface-labeled cells, enabling accurate and quantitative analysis of individual cells in tissue.

Algorithms↗

Distance-based clustering of CGH data.

MOTIVATION: We consider the problem of clustering a population of Comparative Genomic Hybridization (CGH) data samples. The goal is to develop a systematic way of placing patients with similar CGH imbalance profiles into the same cluster. Our expectation is that patients with the same cancer types will generally belong to the same cluster as their underlying CGH profiles will be similar. RESULTS: We focus on distance-based clustering strategies. We do this in two steps. (1) Distances of all pairs of CGH samples are computed. (2) CGH samples are clustered based on this distance. We develop three pairwise distance/similarity measures, namely raw, cosine and sim. Raw measure disregards correlation between contiguous genomic intervals. It compares the aberrations in each genomic interval separately. The remaining measures assume that consecutive genomic intervals may be correlated. Cosine maps pairs of CGH samples into vectors in a high-dimensional space and measures the angle between them. Sim measures the number of independent common aberrations. We test our distance/similarity measures on three well known clustering algorithms, bottom-up, top-down and k-means with and without centroid shrinking. Our results show that sim consistently performs better than the remaining measures. This indicates that the correlation of neighboring genomic intervals should be considered in the structural analysis of CGH datasets. The combination of sim with top-down clustering emerged as the best approach. AVAILABILITY: All software developed in this article and all the datasets are available from the authors upon request. CONTACT: juliu@cise.ufl.edu.

Algorithms↗

ENPDA: an evolutionary structure-based de novo peptide design algorithm.

One of the goals of computational chemists is to automate the de novo design of bioactive molecules. Despite significant advances in computational approaches to ligand design and binding energy evaluation, novel procedures for ligand design are required. Evolutionary computation provides a new approach to this design endeavor. We propose an evolutionary tool for de novo peptide design, based on the evaluation of energies for peptide binding to a user-defined protein surface patch. Special emphasis has been placed on the evaluation of the proposed peptides, leading to two different evaluation heuristics. The software developed was successfully tested on the design of ligands for the proteins prolyl oligopeptidase, p53, and DNA gyrase.

Algorithms↗