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Mapping the human brain: past, present, and future.

The ability to map functional activity in the living human brain has rekindled interest in the organization of human neural circuitry specifically and in animal neural circuitry generally. Faced with incredible complexity, researchers are turning to the power of computer graphics for two- and three-dimensional interactive mapping, to the mathematical modeling of dynamics in proposed circuits, and to databases with powerful discovery engines.

Animals↗

New nomenclature and computerized programme of graphics for the description and recording of aortocoronary bypasses.

In the process of drawing up a computerized operation reporting system, a nomenclature for the precise description of recently fitted or existing aortocoronary bypasses has been developed. This is based on a sequence of letters showing in one line which type of bypass has been fitted, the graft material used, the central anastomosis (source) as well as the peripheral anastomoses on the coronary arteries (objective). For this purpose, abbreviations of the customary terms in use in cardiac surgery have been used. A computer graphics programme has been created in parallel, enabling all bypasses (existing and/or new) to be sketched into the diagram of a heart with the aid of a mouse. The bypass nomenclature is automatically generated from the diagram, which can also be printed out as a sketch of the operation. The complete diagram of the heart plus data input forms enable the operation report to be compiled automatically. The nomenclature and the graphics programme are easily learnt, simplify work, can readily be incorporated into a computerized hospital organization and enhance documentation quality.

Abbreviations as Topic↗

A new method for analysing the geometry and timecourse of epicardial potential spreading.

A 256 unipolar electrode matrix fixed at the surface of an isolated rabbit heart was connected to a PC system via an amplifying and analog/digital converting frontend computer. This system allows measurement of 256 electrodes within 100 microseconds with a sampling rate of 0.25 ms. The data are displayed on a PC system either on-line as common ECG-recordings or off-line in projection on a two-dimensional model of the heart surface. Thereby, it is possible to visualize the epicardial potential spreading in a slow-motion presentation on a high resolution computer graphic. The samples are displayed sequentially and can be delayed by choice. This method allows the determination of the origin ("break-through-points") of the epicardial excitation and an analysis of the potential spreading. The electrodes are arranged in four grids with 64 electrodes each at an interelectrode distance of 1 mm. Thereby, it is possible to evaluate the direction of the epicardial excitation wave and the local state of epicardial activation. Furthermore, it is possible to demonstrate irregular pacemakers or re-entry circuits. The method seems to be helpful in analysis of cardiac arrhythmogenesis and mode of action of anti-arrhythmic agents.

Analog-Digital Conversion↗

Drug design with a new type of molecular modeling based on stereochemical complementarity to gene structure.

Why certain chemical structures and not others are present in nature has been a recurring question raised by scientists since the first organic natural products were characterized. Of equal interest has been elucidating what structural features within any given class of organic molecules are responsible for biological activity. Historically, the lack of satisfactory answers to both questions has relegated the development of biologically active molecules either to serendipity or to exhaustive synthesis and biological testing of large numbers of compounds. This frustration is particularly evident in the pharmaceutical industry where the development of drug agonists and antagonists is often time consuming, tedious and expensive. Fortunately, this picture is beginning to change as more information is derived from modern molecular modeling techniques including characterization of the active sites in enzymes and the ligand binding sites in receptors. Over the past 15 years another approach has emerged based upon a series of discoveries made in our laboratories with molecular models. Namely, many biologically active small molecules have been found to possess complementary stereochemical relationships with gene structure. These relationships have proven useful in understanding constraints imposed by nature on the structures of small molecules and in correlating structure with activity among certain classes of compounds. Recently, computer graphics and energy calculations have confirmed salient observations lending credence to what promises to be a powerful and rapidly evolving technology for designing new safe and effective drugs.

Animals↗

Three-dimensional quantification of color-marked occlusal paths on anatomically oriented casts.

STATEMENT OF PROBLEM: The analysis of occlusal contacts on mounted diagnostic casts is an important task in prosthetic diagnostics. However, it is still restricted mainly to qualitative aspects because existing measuring techniques fail to provide 3-dimensional data for more than a few single points in acceptable time. PURPOSE: The aim of this study was to develop a method for quantifying occlusal contacts and paths by using anatomically oriented diagnostic casts and to design the method to allow fast acquisition of digital 3-dimensional coordinates. MATERIAL AND METHODS: Plaster casts with color-marked contacts were digitized optically with a profilometric system based on the fringe projection technique. Digital camera images taken simultaneously were used to define the contact areas by marking them either manually or automatically with the help of image-processing routines. Three-dimensional coordinates were determined by finding the corresponding points within the profilometric data set. RESULTS: Color-marked contact areas on diagnostic casts were successfully digitized with a computer-controlled, automatic setup in approximately 30 seconds. The accuracy of the acquired 3-dimensional data was estimated to be better than 60 microm in lateral and 30 microm in height resolution. The data set was visualized and evaluated in a skull related coordinate system. SUMMARY: This study verified the use of a new tool to quantify color-marked occlusal contacts on diagnostic casts in terms of spatial coordinates. The resulting digital data may be stored easily and analyzed numerically as well as visualized 3-dimensionally with computer graphic equipment. Because the anatomic orientation of the casts is maintained throughout the measurement process, it is possible to compare the data with electronically registered condyle paths and therefore to investigate, for example, their relation to the corresponding guidance paths of the frontal teeth and the canines in dynamic occlusion.

Color↗

A molecular model for the retinol binding protein-transthyretin complex.

A three-dimensional model for the complex between human serum retinol binding protein and transthyretin (formerly named prealbumin) is presented. The model was obtained by interactive rigid-body computer graphics docking and the characterization of the molecular surfaces in terms of fractal dimension. Available experimental data, as well as results from molecular dynamics calculations, support the proposed model.

Computer Graphics↗

Three-dimensional magnetic resonance imaging of the heart.

Three-dimensional surface images of the human heart may be produced from magnetic resonance imaging. These examinations are used in the evaluation of congenital heart disease for preoperative planning and postoperative evaluation. Computer graphics software has been adapted to produce three-dimensional images of the beating heart from contiguous two-dimensional serial EKG-triggered magnetic resonance image data sets. The natural boundary between flowing blood and cardiac tissue serves to outline cardiac structures. The techniques for producing these images and pitfalls in the operation of the system as well as examples of their application to the study of patients with congenital heart disease are outlined in this article.

Adolescent↗

Preparing camera-ready figures.

Today, authors can develop figures to illustrate their articles or books because of new computer graphics programs. However, some publication standards must be met in order for publishers to use the illustrations. This article describes current standards that will help authors develop high-quality figures.

Art↗

Use and misuse of multiple comparisons in animal experiments.

The objective of many animal experiments is to detect meaningful relationships among treatments and associated responses. Types of comparisons of means include pairwise multiple comparisons, planned orthogonal or nonorthogonal contrasts, and orthogonal polynomials. Some procedures are appropriate only for specific types of treatment designs and specific types of objectives. Pairwise, multiple comparisons are appropriate only for comparing unstructured, qualitative treatments. Planned comparisons partition the overall set of treatment effects into independent or nonindependent subsets, with special application to factorials. Orthogonal polynomial (regression) procedures assess relationships between quantitative treatments and response when a full range of responses or an optimal dose is of interest. Recommendations for appropriate use of each mean comparison procedure are illustrated using data from three Journal of Animal Science articles. Also mentioned are a number of computer graphics packages that provide creative ways to display biological relationships and can be linked to statistical packages for input and to word processors or 35-mm cameras for output.

Analysis of Variance↗

Computer-generated three-dimensional reconstructions of serially sectioned mouse embryos.

We have been involved with a group of computer scientists and anatomists in the development of computer-based methodologies that not only combine the advantages of scanning electron microscopy and conventional histology, but provide the additional dimension of tissue recognition. The latter is achieved by the appropriate labelling of tissues and structures by delineation or 'painting'. Individually segmented anatomically defined tissues can be highlighted in a particular colour and viewed either in isolation or in combination with other appropriately labelled tissues and organs. Tissues can be shown in any orientation either as a transparent overlay on computer-generated histological sections or as 3-D images without the histological background. An additional feature of the system is that computer graphics technology combined with 3-D glasses now also allows the viewer to see the object under analysis in stereo. This facility has been found to be particularly helpful in drawing attention to topological relationships that had not previously been readily noted. As the mouse is now the mammalian model of choice in many areas of developmental research, it is of critical importance that a basic level of skill is available in the research community in the interpretation of serially sectioned material, for example, for the rapidly expanding field in which gene expression studies play a significant role. It is equally important that there is an understanding of the dynamic changes that occur in relation to the differentiation of the various organ systems seen in these early stages of development. What we emphasise here is the additional information that it is possible to gain from the use of this tool which, in our view, could not readily have been gained from the analysis of scanning electron micrographs or by studying conventional serial histological sections of similar stages of mouse embryonic development. The methodology has been developed as part of a large project to prepare a database of mouse developmental anatomy covering all stages from fertilisation to birth in order to allow the accurate spatial mapping of gene expression and cell lineage data onto the digital Atlas of normal mouse development. In this paper we show how this digital anatomical Atlas also represents a valuable teaching aid and research tool in anatomy.

Anatomy, Cross-Sectional↗

A large screen digitizer system for radiation therapy treatment planning.

PURPOSE: This paper describes a new technique for manually drawing contours of anatomy over image data for the purposes of radiation therapy treatment planning. METHODS AND MATERIALS: A large area rear-projectible digitizer tablet is used together with a projection TV system to display computer graphics and image data. Large images of computed tomography or magnetic resonance cross-sections are displayed and the digitizer is used to directly trace outlines of important organs. Digitizer menus allow multiple functions for selecting images and structures, for changing the grayscale level and window, and for zooming and roaming the image. RESULTS: This device has been in clinical operation for many years and has proven to greatly increase the speed of entering cross-sectional outlines defined for serial computed tomography images sets. A small timing study of clinical usage demonstrates up to a factor of ten improvement in the speed of contour entry. CONCLUSION: For 3-dimensional radiation therapy, tumor, and target volumes, as well as important critical organs, must be delineated from serial sets of computed tomography or magnetic resonance images. Often 30 or more slices must be considered and the process of outlining structures on this number of slices can represent a significant fraction of the total treatment planning time. The device described in this paper greatly improve the ease and speed of manual contour entry for 3-dimensional radiation therapy planning.

Humans↗

Chymotrypsin hydrolysis of X-phenyl hippurates. A quantitative structure-activity relationship and molecular graphics analysis.

The hydrolysis of a set of 28 X-phenyl hippurates by chymotrypsin was investigated. From the derived Km and kcat values a quantitative structure-activity relationship was developed. This equation shows that para substituents correlated by sigma- display only an electronic effect on the formation of the ES complex whereas meta hydrophobic substituents show a hydrophobic interaction correlated by pi in addition to their electronic effect. Meta polar substituents avoid contact with the enzyme and show only electronic effects on Km. Using the x-ray crystallographic coordinates for chymotrypsin and computer graphics, a model was constructed which is used to interpret the quantitative structure-activity relationship. As with a number of previously reported examples, we have found that when polar substituents have the option of binding to hydrophobic space or remaining in the aqueous phase they follow the latter possibility.

Binding Sites↗

The visible animal project: a three-dimensional, digital database for high quality three-dimensional reconstructions.

The "Visible Animal Project" (VAP) is comprised of axial anatomic cryosections and corresponding CT and MR images of a mature dog. The digital database is used for the creation of three-dimensional computer graphics of canine anatomy. The technique of cryodissection is described in detail. The combining of the corresponding CT and MR images, and cryosections as well as the data processing for the creation of three-dimensional reconstructions is presented and examples are shown. For the first time a complete high-resolution three-dimensional database of a dog is available, which can be used as the base for further high quality three-dimensional reconstructions, similar to the "Visible Human Project" (VHP).

Anatomy, Cross-Sectional↗

New representations of otolithic primary afferent spatial tuning--a re-processing of the Fernández & Goldberg (1976) data.

In 1976 Fernández & Goldberg published detailed results of the polarization vectors for squirrel monkey primary otolithic afferents (1). Each vector represented the direction in three-dimensional space of the linear acceleration which caused maximum facilitation of the otolith afferent. The published plots were separate views of the projections of the polarization vectors of all the individual neurons in the superior (mainly utricular) and inferior (mainly saccular) divisions of the vestibular nerve. There were distinctly different clusters of vectors for each division. We have used new computer graphic procedures to re-process these data and show the data three-dimensionally in relation to the major planes of the head.

Afferent Pathways↗

Actin-actin contact: chemical cross-linking between actin and the 2.6-kDa peptide from subdomain 4 of actin.

Previously, we demonstrated that the 2.6-kDa peptide extending from Arg177 to Tyr198 in subdomain 4 of rabbit skeletal actin bound to actin itself, inhibited the elongation of actin filament, and severed F-actin. The corresponding segment in actin, therefore, is thought to contain the most critical actin-actin contact [Hori, K. and Morita, F. (1992) J. Biochem. 112, 401-408; Hori, K., Itoh, T., Takahashi, K., and Morita, F. (1994) Biochim. Biophys. Acta 1186, 35-42]. In this paper, we report on the binding site in actin for the 2.6-kDa peptide studied by using a zero-length cross-linker, 1-ethyl-3(3-dimethylaminopropyl)carbodiimide (EDC). We conducted limited digestion of actin cross-linked with the 125I-labeled 2.6-kDa peptide with various proteases, and developed peptide maps. The cross-linked region of the 2.6-kDa peptide was found to be within the region of Ala114 to Glu167 in actin by identifying the radioactive peptide fragments. The region was further restricted by isolation of radioactive peptide from alpha-chymotryptic digest of the cross-linked actin. The binding site of the 2.6-kDa peptide was finally assigned to be within the 24 amino acid segment from Ala144 to Glu167, which lies in subdomain 3 of actin. Using computer graphics, actin-actin contact provided by the two segments was suggested to be along the left-handed genetic helix of actin filament.

Actins↗