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Three-dimensional reconstructions from incomplete data: interpretability of density maps at "atomic" resolution.

Three dimensional data collection in electron microscopy is normally limited to a range of tilt angles that is less than +/- 90 degrees. Thus, even under the best conditions, experimental values of the structure factors will be missing within a solid cone in reciprocal space. Previous work has already shown that the missing cone of data can produce serious artifacts in three-dimensional density maps at modest resolution, for example approximately 15A. We now report, however, that a missing cone as large as +/- 30 degrees appears to have no serious effect on the three-dimensional density map of a protein at 3.6 A resolution, and we attribute this result to the fact that the electron density features are quite well separated from one another at that resolution. The map calculated with a +/- 30 degree missing cone is, furthermore, no more sensitive to noise (error) than is the full (isotropic) Fourier map. This result does not seem to be unreasonable in view of the fact that less than 14% of the data (i.e., signal) is lost due to the missing cone. Our numerical simulations therefore indicate that there should be no difficulty in interpreting high-resolution Fourier maps that can be produced with data that fall within realistic estimates of achievable resolution, tilt angles, and experimental error.

Electronic Data Processing↗

Computer system for the acquisition and analysis of vascular contractility. Application to a bioassay of endothelial cell function.

A system for the digital acquisition and subsequent analysis of the tension developed by isolated blood vessels in response to an endothelial cell superfusate is reported. Tension of the isolated rat aortic rings was measured by strain gauge. Strain-gauge output was then amplified, and the analog signal was digitized on a 16-channel A/D board. Lab tech Notebook software was used to display and store the data. The sampling rate was 0.1 Hz, and the data was written concurrently to hard disk and printer. Both disk and printer output were accompanied by a time stamp for subsequent ease of retrieval. The endothelial cell bioassay system allowed measurement of changes in vascular tension after the release of endothelium-dependent relaxing factor, nitric oxide (EDRF-NO) from cultured cells. Cells were cultured on microcarrier beads, formed into columns, and perfused with physiological salt solution. Significant (p < 0.05) relaxant responses occurred after agonist stimulation with bradykinin (10(-8) M; Emax -31.0% +/- 8.2%), acetylcholine (10(-8) M; Emax -33.2% +/- 5.0%), and calcium ionophore A 23187 (10(-6) M; Emax -55.7% +/- 15.4%). These responses were dependent on EDRF-NO, as shown by both the lack of relaxation in the absence of endothelial cells, and that relaxation to A 23187 was overcome by hemoglobin (3 x 10(-6) M). Results were manipulated graphically to allow the superimposition of data and thereby provide a mean and standard error of the mean for the entire time course of each response. Thus, a system was produced where fidelity of data expression was not dependent on measurements made at single points, but on the sampling frequency of the acquisition system.

Animals↗

A software package for the manipulation, display and analysis of electron and light microscope data.

Quantitative light and electron microscopy is an expanding field which has found applications in many biological disciplines. Computer-enhanced data-acquisition has led to increased speed and accuracy, and combined with computational analysis, stereological parameters can be quickly derived and spatial hypotheses can be easily tested. A software package is described, which controls the manipulation, display and analysis of two-dimensional microscope data. Features include alignment of specimens, rotations, translations, deletions, recoding, perimeter and area measurement, point-counts, tests of dispersion and tests of spatial distributions. The programme is graphics-orientated and supports various point-plot modes and histograms. It includes linear and non-linear curve-fitting options and has been specifically designed to encourage new analysis procedures, which automatically benefit from existing graphics options.

Data Collection↗

Electronic processing of cardiac rehabilitation data.

With the incidence of ischaemic heart disease at epidemic levels and rising, techniques for detecting, predicting, and rehabilitating the condition of cardiac dysfunction are constantly under development. One technique, that of exercise stress testing, has been used in recent decades in the prediction, detection, and rehabilitation of cardiopulmonary disease. However, ergometric studies in this regard have been hampered by the tedium of physiologic data collection and analysis. With the advent of automated digital and analogue computation procedures and equipment, such data can be both operated on real-time for immediate display or stored for post-exercise and patient-history studies. Such automated data manipulation provides an systematic and comprehensive testing of each patient and permits a much greater case-load. In addition, special computer programs can compile and index specific parameters from a large sample size to facilitate statistical surveys of selected patient populations. The results of such statistical analyses can, if desired, be automatically printed out in a graphical form.

Computers↗

NERVOUS SYSTEM RESEARCH WITH COMPUTERS.

The experimental system described above has been in full-scale operation now for about one year. It has been possible in this short period only to begin the exploration of the potentialities of the system for aiding nervous system research. The most intensively developed programs have been those on the insect (3) and on human vision and eye movements (5). In both of these programs the facility has permitted new research techniques which have provided answers to important questions, answers which would have been unobtainable without such a data-processing and control system.

Animals↗

Process, structure and context in relation to integrative biology.

This paper seeks to provide some integrative tools of thought regarding biological function related to ideas of process, structure, and context. The incorporation of linguistic and mathematical thinking is discussed within the context of managing thinking about natural systems as described by Robert Rosen. Examples from ecology, protein networks, and liver function are introduced to illustrate key ideas. It is hoped that these tools of thought, and the further work needed to mobilise such ideas, will continue to address a number of issues raised and pursued by Michael Conrad, such as the seed-germination model and vertical information processing.

Animals↗

The WA Hospital Morbidity Data System: an evaluation of its performance and the impact of electronic data transfer.

The paper evaluates the performance of the Hospital Morbidity Data System, maintained by the Health Statistics Branch (HSB) of the Health Department of Western Australia (WA). The time taken to process discharge summaries was compared in the first and second halves of 1995, using the number of weeks taken to process 90% of all discharges and the percentage of records processed within four weeks as indicators of throughput. Both the hospitals and the HSB showed improvements in timeliness during the second half of the year. The paper also examines the impact of a recently introduced electronic data transfer system for WA country public hospitals on the timeliness of morbidity data. The processing time of country hospital records by the HSB was reduced to a similar time as for metropolitan hospitals, but the processing time in the hospitals increased, resulting in little improvement in total processing time.

Databases, Factual↗