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Computer acquisition, analysis and presentation of results from a Cobas Bio analyser.

Two computer programs for Macintosh computers have been developed in the LabVIEW programming language to perform data acquisition, analyses and presentation of results originating from a Cobas Bio analysing machine. One program is very flexible in its human interface, and is intended for research use. The program allows the results to be combined in a variety of ways, and allows the user to generate graphs to highlight the results. The other program is intended for routinely follow-up of analyses of proteases. It only allows the user to follow strict instructions, and only limited flexibility is built-in.

Autoanalysis↗

A graph conceptual model for developing Human Genome Center databases.

We have developed a representation of genome data which has proven itself useful for describing data at a Human Genome Center. Genomic data have a graph-like structure and representing the concepts and relationships of genetics as a graph simplifies the development of databases for genome laboratories. Graphs are a comfortable communication medium for biologists and computer scientists and graph diagrams assist in the development of databases by facilitating the exchange of expertise. We have tailored a graph language for modeling genomic data and describe our process of using graphs to develop genome databases.

Computer Graphics↗

Changes in intercellular junctions. II. Modulation in embryonic chick liver in vitro by cytosine arabinoside and dexamethasone.

We have used an in vitro model to investigate the relationship between cell proliferation, cell maturation, and intercellular junctional changes that are seen during normal liver development. Chick liver fragments of embryonic stages 21, 28, and 39 were grown in organ culture in Medium 199 with 10% bovine serum albumin for 24 hr. Concurrent cultures were treated with cytosine arabinoside (ara-c, 20 micrograms/ml) to inhibit cell proliferation or with dexamethasone (2 microns/ml) to promote cell maturation. Control and treated liver cultures were analyzed using autoradiography to determine labeling index and quantitative computer graphic analysis of freeze-fracture micrographs to evaluate junctional changes. Explants treated with ara-c had a near zero labeling index. Those from embryonic stage 21 showed a 4-fold increase in tight junctional area, while those from embryonic stage 28 showed a 2.5-fold increase in tight junctional area and a 5-fold increase in gap junctional area. In liver of embryonic stage 39, junctional area increased, and conformation of junctions took on the typical form seen in the liver of the hatched chick. Thus high mitotic activity appears to disrupt cell junctions, reducing the amount of junctions present and causing pleomorphic configurations. Junctional area could also be modified with no change in mitotic activity by treatment with dexamethasone. Stage 28 embryo livers in culture with dexamethasone showed a 4-fold increase in the amount of tight junctions with no change in the amount of gap junctions. Some major findings based on these age-dependent responses are (1) if mitosis is blocked in young embryonic stages when proliferation is high, intercellular junctions tend to increase in amount, and to be more mature in configuration; (2) if maturation is stimulated with no change in proliferation, those junctions which normally increase with differentiation will increase in amount; and (3) it is possible to produce a change in the amount of one junctional type without affecting the other. Therefore the amount of cell surface occupied by junctions at any given time seems to depend on both the pattern of synthetic activity in the cell and the degree to which cell to cell contacts are stable and undisrupted by mitotic activity.

Animals↗

Modelling the ATP-binding site of oncogene products, the epidermal growth factor receptor and related proteins.

A three-dimensional model for the ATP-binding site of the oncogene product v-src is proposed by the use of interactive computer graphics. A similar model would apply to sequence related proteins such as other oncogene products, the epidermal growth factor receptor, cAMP-dependent protein kinase and the cell division control protein CDC28. The model was proposed on the basis of the conservation of certain key residues between the oncogene product family of proteins and several nucleotide binding proteins of known structures.

Adenosine Triphosphate↗

The three-dimensional similarity between a dimeric antiparallel extended structure and a beta-turn folded form of enkephalin.

The three-dimensional similarity between two fundamental conformations, a dimeric antiparallel extended structure and a type I' beta-turn folded form, of enkephalin was examined by computer graphic and empirical energy calculation methods. By the rotation of Tyr and Phe side chains, one half of the former structure could mimic the three-dimensional form of the latter without a large loss of conformational energy. This result provides a new idea for considering the conformation of enkephalin suitable for the multiple opioid receptors. The active conformation of enkephalin for mu- and delta-opioid receptors is discussed in the light of the present study.

Enkephalins↗

Three-dimensional structure of catalase from Micrococcus lysodeikticus at 1.5 A resolution.

The three-dimensional crystal structure of catalase from Micrococcus lysodeikticus has been solved by multiple isomorphous replacement and refined at 1.5 A resolution. The subunit of the tetrameric molecule of 222 symmetry consists of a single polypeptide chain of about 500 amino acid residues and one haem group. The crystals belong to space group P4(2)2(1)2 with unit cell parameters a = b = 106.7 A, c = 106.3 A, and there is one subunit of the tetramer per asymmetric unit. The amino acid sequence has been tentatively determined by computer graphics model building and comparison with the known three-dimensional structure of beef liver catalase and sequences of several other catalases. The atomic model has been refined by Hendrickson and Konnert's least-squares minimisation against 94,315 reflections between 8 A and 1.5 A. The final model consists of 3,977 non-hydrogen atoms of the protein and haem group, 426 water molecules and one sulphate ion. The secondary and tertiary structures of the bacterial catalase have been analyzed and a comparison with the structure of beef liver catalase has been made.

Amino Acid Sequence↗

Structural characterization of extracellular ribonuclease of Bacillus polymyxa: amino acid sequence determination and spatial structure prediction.

The primary structure of extracellular Bacillus polymyxa ribonuclease (RNase Bpo) was established by mass spectroscopy analysis and automatic Edman degradation of the individual peptides obtained from protein digestion with Glu-specific protease V8. RNase Bpo consists of 111 amino acid residues, with a relative molecular weight of 12 607. RNase Bpo is a close structural homolog of RNases of B. amyloliquefaciens (RNase Ba) and B. intermedius (RNase Bi), the similarity of their primary structures being 68%. Molecular modelling of the structure of the complex of RNase Bpo with substrate analog d(CGAC) was performed and a spatial model based on the known crystal structure of RNase Ba complex with the corresponding nucleotide was constructed using the methods of interactive computer graphics and energy minimization. The differences in the primary and tertiary structures of the enzymes were analyzed in order to understand the substrate specificity of Bacillus RNases.

Amino Acid Sequence↗

Criteria for the design of fetal heart rate analysis systems.

Criteria are described for the automated analysis of fetal pulse intervals, fetal movements and of uterine contractions measured externally, antenatally and interactively on-line, for implementation on a personal computer interfaced to an appropriate fetal monitor, and tested on 10,000 records. Measurements of short and longer term fetal heart rate variation are compared; both are required to identify sinister records. Recall and display of records acquired on the same patient over several weeks has proved a useful diagnostic aid.

Computer Graphics↗

The health care professional multimedia workstation: development and integration issues.

Workstations for health care professionals provide access to distributed healthcare information systems. They are complex systems that have to manage, in a unified framework, the distributed and multimedia information needed for optimal patient care. The objective is to provide the end-user with a virtual and unified device that conceals the complexity of the underlying information system. Integration and reuse of modular software components are important in the development of such a workstation. A reference set of evaluation criteria is proposed that includes functional, technical, organizational, medical, cultural and ethical, economic and industrial components.

Computer Communication Networks↗

A method for analysis of back shape in scoliosis.

The shape of the back is an important factor in the clinical assessment of various spinal disorders, in particular scoliosis. A method of analysis of back surface shape is described which was designed to present most of the numerical parameters needed to assess the progress of the disease as it affects body shape. Measurements of back surface shape and manually marked anatomical landmarks were taken from a television/computer surface measurement system in which a plane of light was scanned over the back and from moiré topographs. The anatomical landmarks were used to define reference planes from which successive analyses were matched. Asymmetry in the transverse plane was illustrated by horizontal cross-sections and skin surface angles. The lateral deformity was shown by an estimate of the line of the vertebral bodies beneath the skin, derived by adding an extra lateral displacement to the palpated positions of the spinous processes, proportional to the rotation of the skin in the transverse plane. This model was used to estimate vertebral end-plate angles and Cobb angles. Lateral sections showed kyphosis and lordosis. Correlations of Lateral Asymmetry from the surface shape analysis with Cobb angle from X-ray measurements in three groups of patients (totalling 119 subjects) were in the range r = 0.77 to r = 0.94, p less than 0.0001. The analysis has reduced follow-up X-ray examinations at the Nuffield Orthopaedic Centre because it indicates quantitatively and with complete safety both lateral asymmetry and deformity in the transverse plane.

Adolescent↗

A television/computer three-dimensional surface shape measurement system.

An optical scanner is described which has been designed primarily for the measurement of human back shape. A projector and television camera were mounted together in a box which could rotate about a horizontal axis. The projector shone a horizontal plane of light, which was viewed at an angle from below by the television camera, linked directly to a minicomputer. The shape of the line of light formed by the plane as it fell on an object, together with a knowledge of the geometry of the system, enabled three-dimensional coordinates of points on the line to be calculated. A record of a surface shape was built up by scanning the object in about 2 s. Calibration of the system was achieved by scanning an object of known dimensions. Sets of algorithms are described which derive geometric parameters from the calibration scan and which sort surface shape coordinates, outline them and detect special markers from the surface shape scan. The accuracy of measurement exceeded the design aim of +/- 3 mm in each axis within a volume of 400 mm x 500 mm x 300 mm.

Back↗

The simulation of aerial movement--I. The determination of orientation angles from film data.

Quantitative mechanical analyses of human movement require the time histories of the angles which specify body configuration and orientation. When these angles are obtained from a filmed performance they may be used to evaluate the accuracy of a simulation model. This paper presents a method of determining orientation angles and their rates of change from film data. The stages used comprise the synchronization of data obtained from two camera views, the determination of three-dimensional coordinates of joint centres, the calculation of an angle from a sequence of sine and cosine values and the curve fitting of angles using quintic splines. For each stage, other possible approaches are discussed. Original procedures are presented for obtaining individual error estimates of both the film data and the calculated angles to permit the automatic fitting of quintic splines for interpolation and differentiation and for deriving the time history of an angle as a continuous function from a sequence of sine and cosine values. The method is applied to a forward somersault with 1 1/2 twists and the average error estimate of 17 orientation angles is obtained as 2.1 degrees.

Biomechanical Phenomena↗

The simulation of aerial movement--IV. A computer simulation model.

A computer simulation model of human airborne movement is described. The body is modelled as 11 rigid linked segments with 17 degrees of freedom which are chosen with a view to modelling twisting somersaults. The accuracy of the model is evaluated by comparing the simulation values of the angles describing somersault, tilt and twist with the corresponding values obtained from film data of nine twisting somersaults. The maximum deviations between simulation and film are found to be 0.04 revolutions for somersault, seven degrees for tilt and 0.12 revolutions for twist. It is shown that anthropometric measurement errors, from which segmental inertia parameters are calculated, have a small effect on a simulation, whereas film digitization errors can account for a substantial part of the deviation between simulation and film values.

Anthropometry↗

A three-dimensional analysis of a bioprosthetic heart valve.

A three-dimensional finite element model of the leaflets of a bicuspid bioprosthetic heart valve is presented. The model is based on a non-linear elastic representation of the tissue behaviour which closely simulates that found in experiments. The geometry of the model is based on measurements from a real valve. Shell elements which permit bending have been used in the analysis. The results indicate that bending stresses in the leaflets make a significant contribution to their deformation. This confirms earlier two-dimensional work which had suggested that analyses, where only membrane stresses were modelled, were likely to produce significant errors in the stress states. The analysis also predicts peak stresses close to, but not at, the attachment of the leaflet to the stent post.

Biomechanical Phenomena↗

Non-interacting modes for stress, strain and energy in anisotropic hard tissue.

The six non-interacting modes for stress, strain and energy in an orthotropic elastic model of human femoral cortical bone tissue are discussed and illustrated. The stress and strain modes are illustrated using the representation of the stress and strain fields around a circular hole in a flat plate of cortical bone subjected to a uniaxial field of tension as the example. The six modes play a role in the stress analysis of orthotropic elastic materials similar to the roles played by the hydrostatic and deviatoric non-interacting stress, strain and energy modes in isotropic elasticity. The biomechanical significance of the six non-interacting modes for stress, strain and energy in hard tissue is both practical and suggestive. The modes suggest a practical scheme for the representation of stress and strain fields in hard tissue. The existence of the modes suggests physical insights, for example, possible failure mechanisms or adaptation strategies possessed by the hard tissues.

Anisotropy↗

An EMG-assisted model of loads on the lumbar spine during asymmetric trunk extensions.

An EMG-assisted, low-back, lifting model is presented which simulates spinal loading as a function of dynamic, asymmetric, lifting exertions. The purpose of this study has been to develop a model which overcomes the limitations of previous models including static or isokinetic mechanics, inaccurate predictions of muscle coactivity, static interpretation of myoelectric activity, and physiologically unrealistic or variable muscle force per unit area. The present model predicts individual muscle forces from processed EMG data, normalized as a function of trunk angle and asymmetry, and modified to account for muscle length and velocity artifacts. The normalized EMGs are combined with muscle cross-sectional area and intrinsic strength capacity as determined on a per subject basis, to represent tensile force amplitudes. Dynamic internal and external force vectors are employed to predict trunk moments, spinal compression, lateral and anterior shear forces. Data from 20 subjects performing a total of 2160 exertions showed good agreement between predicted and measured values under all trunk angle, asymmetry, velocity, and acceleration conditions. The design represents a significant step toward accurate, fully dynamic modeling of the low-back in multiple dimensions. The benefits of such a model are the insights provided into the effects of motion induced, muscle co-activity on spinal loading in multiple dimensions.

Adult↗

Pressure distribution on mattresses.

Measurements of pressure distribution are usually performed on a hard base, such as those in gait analysis or tire research; measurements on soft surfaces are avoided because of technical problems. A sensor mat was developed which consists of 512 pressure sensors, glued to arbitrary locations of a fabric. The mat can be bent to spherical and saddle shapes so that it can be utilised on soft and flexible surfaces like chairs and beds. Performance of eight hospital mattresses concerning decubitus prophylactics and support in supine and side position was studied in four subjects representing extreme body build. It was found that one particular mattress served well for three subjects, whereas no mattress was suitable for the high and heavy type. It was concluded that measurement of pressure distribution is a valuable tool for designing and selecting.

Beds↗

Interaction of mutant lambda repressors with operator and non-operator DNA.

We have described a set of mutations that alter side-chains on the operator binding surface of lambda repressor. In this paper, we study the interactions of 12 purified mutant repressors with operator and non-operator DNA. The mutant proteins have operator affinities that are reduced from tenfold to greater than 10,000-fold compared to wild-type. Nine of the mutants have affinities for non-operator DNA that are similar to wild-type, two mutants show decreased non-specific binding, and one mutant has increased affinity for non-operator DNA. We discuss these findings in terms of the structural and energetic contributions of side-chain--DNA interactions, and show that certain contacts between the repressor and the operator backbone contribute both energy and specificity to the interaction.

Amino Acid Sequence↗