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Potential for improvement in radiation therapy.

A successful strategy for improving the efficacy of radiation therapy has been to improve dose distribution, that is, reduce treatment volume toward target volume. This is so as the smaller treatment volume has permitted a higher dose to the target (hence a high tumor control probability) and a lesser volume of non-target tissues being irradiated (consequently a reduced frequency and severity of treatment related morbidity). There are in place several important means for further improvements in dose distributions. These include: (a) 3D graphic reconstruction of the affected part with definition of the position of the tumor vis-a-vis the adjacent normal structures; (b) explicit inclusion in the treatment plan of the uncertainty band around each isodose contour; (c) on-line contrast enhanced visual monitoring of the target tissue during the individual treatment session; (d) gating of treatment so as to reduce the impact of patient motion on the needed treatment volume; (e) use of computer control systems to execute the treatment; and (f) use of treatment methods which achieve a reduced treatment volume. In an examination for sites for which treatment volumes might be decreased by a substantial factor we have compared treatment volumes for radical surgical and radiation therapy. Results are presented for carcinomas of the cervix (Stage IB), breast (Stage II), floor of mouth (Stage II). We describe a system developed here for on-line visual monitoring of the tissues covered by the treatment field. Brief descriptions are given of results of low LET charged particle radiation therapy and of intraoperative electron beam therapy. Also, the program developed here to use computer graphic techniques to display tumor and normal structures and isodose countours with uncertainty bands around each contour is mentioned.

Combined Modality Therapy↗

Dense photometric stereo: a Markov random field approach.

We address the problem of robust normal reconstruction by dense photometric stereo, in the presence of complex geometry, shadows, highlight, transparencies, variable attenuation in light intensities, and inaccurate estimation in light directions. The input is a dense set of noisy photometric images, conveniently captured by using a very simple set-up consisting of a digital video camera, a reflective mirror sphere, and a handheld spotlight. We formulate the dense photometric stereo problem as a Markov network and investigate two important inference algorithms for Markov Random Fields (MRFs)--graph cuts and belief propagation--to optimize for the most likely setting for each node in the network. In the graph cut algorithm, the MRF formulation is translated into one of energy minimization. A discontinuity-preserving metric is introduced as the compatibility function, which allows alpha-expansion to efficiently perform the maximum a posteriori (MAP) estimation. Using the identical dense input and the same MRF formulation, our tensor belief propagation algorithm recovers faithful normal directions, preserves underlying discontinuities, improves the normal estimation from one of discrete to continuous, and drastically reduces the storage requirement and running time. Both algorithms produce comparable and very faithful normals for complex scenes. Although the discontinuity-preserving metric in graph cuts permits efficient inference of optimal discrete labels with a theoretical guarantee, our estimation algorithm using tensor belief propagation converges to comparable results, but runs faster because very compact messages are passed and combined. We present very encouraging results on normal reconstruction. A simple algorithm is proposed to reconstruct a surface from a normal map recovered by our method. With the reconstructed surface, an inverse process, known as relighting in computer graphics, is proposed to synthesize novel images of the given scene under user-specified light source and direction. The synthesis is made to run in real time by exploiting the state-of-the-art graphics processing unit (GPU). Our method offers many unique advantages over previous relighting methods and can handle a wide range of novel light sources and directions.

Algorithms↗

Dynamics for communications data.

To create a complex dynamical model for a complex system, it is normally necessary to have a directed graph of the network, a dynamical model for each node, and a coupling function for each directed edge. But in many applications, the only observable data consists of communications from one node to another. In this situation, the modeler may infer a complex dynamical model for the network without any explicit knowledge of the independent dynamical behavior of the component systems (nodes). Here we present one procedure for this type of modeling problem, inspired by the attractor reconstruction procedure of chaos theory. Part of this proposal consists of a strategy for computer graphic presentation of the interactive dynamics of the complex system (or social network of dynamical schemes) called a netscope. We can imagine applications to diverse situations, such as decision groups, management, forecasting, international relations, classroom monitoring, therapy (personal, family, group, etc.) and distributed processors, to name a few.

Communication↗

Characterization of phospholipase A2 (PLA2) from Taiwan Cobra: isoenzymes and their site-directed mutants.

Extracellular and secretory phospholipase A2 (PLA2), a class of phospholipid digesting enzyme, is widely distributed in animal venoms of reptiles and insects. Two cDNAs encoding PLA2 isoenzymes from Taiwan Cobra (Naja naja atra) were cloned into pQE-30 plasmid vector and expressed in Escherichia coli. The recombinant products were subjected to refolding using sulfonation under reduction/oxidation conditions with glutathione and enterokinase removal of His-tag, resulting in the active recombinant PLA2 with the same molecular masses of native enzymes as determined by mass spectrometry. The recombinant PLA2 was also shown by circular dichroism to possess a secondary structure similar to native PLA2. The enzymatic activity of the major isoenzyme (PLA2-1) is higher than the other minor isoenzyme (PLA2-2), which shows two amino acid difference from PLA2-1. Site-directed mutagenesis was used to probe the structure/function relationship of two highly conserved residues among all reported PLA2, i.e., His-47 and Asp-93. Replacement of His-47 residue by either Ala or Arg resulted in the complete loss of activity. Similarly, the mutant Asp-93 --> Asn (D93N) also retained little activity. These results suggest that both His-47 and Asp-93 are essential for the catalytic activity of PLA2. Computer graphic study, based on homology modelling, highlights the differences between native PLA2 isoenzymes and their site-directed mutants, which may account for the differences in the observed biological activity.

Base Sequence↗

A comparative computational study of blood flow through prosthetic heart valves using the finite element method.

The steady flow of blood through three common types of prosthetic heart valves was simulated numerically using the finite element method. The velocity, pressure and stress fields were obtained for the disk-type, tilting-disk and ball-type prosthetic heart valves in aortic position, for increasing Reynolds numbers up to 900, 1500 and 2000 respectively. Computer graphics of calculated velocities are presented, showing in detail the accelerated flow, recirculation and stagnation areas developed in the prosthesis. Maximum wall shear stresses were found at 0.5, 1.4, and 1.2 diameters from the sewing ring downstream for the disk, tilting-disk and ball valves being the values of 55, 18 and 33 dyn cm-2 respectively. In the vicinity of the occluder, maximum shear stresses of 38, 30 and 47 dyn cm-2 respectively were computed. The flow characteristics and performance for each valve are compared, the results are presented in terms of energy loss and maximum shear stress. The velocity and stress fields are compared with in vitro evaluations found in the literature.

Aortic Valve↗

Grafting of discontinuous sites: a protein modeling strategy.

A strategy for modeling continuous as well as discontinuous sites in protein structures has been developed. Central to this modeling strategy is the search algorithm of FITSITE, a program to search a given target structure for suitable combinations of backbone positions mirroring as closely as possible the geometric relationships of a source structural motif of interest. All target sites detected by FITSITE are further refined to mimic the source geometry. The sidechain rotamer library concept fails to precisely describe side chains involved in coordinative bonding (e.g, metal binding sites). Therefore an algorithm using detailed data-base bonding parameter information was applied for the side-chain construction. The FITSITE program and the subsequent processing of the program output are presented in a test case. The Rop protein, a four-helix bundle structure, served as the target protein. It was searched for candidate sites to model a variety of metal binding sites, with structures extracted from Brookhaven Protein Database entries. The preliminary protein models were investigated for structural overlaps with neighboring residues by interactive computer graphics; if required, additional changes were performed. A set of parameters for energy minimization with AMBER (including metal ions) was developed, and the completed Rop variants were energy minimized. Finally, 12 potentially metal binding Rop variants were selected for production via genetic engineering.

Algorithms↗

Starting research in interaction design with visuals for low-functioning children in the autistic spectrum: a protocol.

On starting to think about interaction design for low-functioning persons in the autistic spectrum (PAS), especially children, one finds a number of questions that are difficult to answer: Can we typify the PAS user? Can we engage the user in interactive communication without generating frustrating or obsessive situations? What sort of visual stimuli can we provide? Will they prefer representational or abstract visual stimuli? Will they understand three-dimensional (3D) graphic representation? What sort of interfaces will they accept? Can we set ambitious goals such as education or therapy? Unfortunately, most of these questions have no answer yet. Hence, we decided to set an apparently simple goal: to design a "fun application," with no intention to reach the level of education or therapy. The goal was to be attained by giving the users a sense of agency--by providing first a sense of control in the interaction dialogue. Our approach to visual stimuli design has been based on the use of geometric, abstract, two-dimensional (2D), real-time computer graphics in a full-body, non-invasive, interactive space. The results obtained within the European-funded project MultiSensory Environment Design for an Interface between Autistic and Typical Expressiveness (MEDIATE) have been extremely encouraging.

Autistic Disorder↗

The in vivo wear resistance of 12 composite resins.

PURPOSE: The in vivo wear resistance of 12 composite resins were compared with an amalgam control using the Latin Square experimental design. Sixteen edentulous patients wearing specially designed complete dentures formed the experimental population. MATERIALS AND METHODS: The Michigan Computer Graphics Measurement System was used to digitize the surface of the control and composite resin samples before and after 3-month test periods to obtain wear data. The 12 composite resins selected for this investigation based on their published composite classification types were seven fine particle composites, three blends, and two microfilled composite resins. The Latin Square experimental design was found to be valid with the factor of material being statistically different at the 5% level of significance. Wear was computed as volume loss (mm3/mm2), and all of the composites studied had more wear than the amalgam control (P = .001). RESULTS: After 3 months, the mean (error) of wear of the amalgam was 0.028 (0.006). Means (error) of wear for the 12 composites were ranked from most to least wear by mean wear volume loss. CONCLUSION: The absence of any relationship between mean wear volume loss and the volume percentage filler was confirmed by the correlation coefficient r = -0.158.

Analysis of Variance↗

1995 Joseph E. Whitley, MD, Award. A World Wide Web gateway to the radiologic learning file.

RATIONALE AND OBJECTIVES: Computer networks in general, and the Internet specifically, are changing the way information is manipulated in the world at large and in radiology. The goal of this project was to develop a computer system in which images from the Radiologic Learning File, available previously only via a single-user laser disc, are made available over a generic, high-availability computer network to many potential users simultaneously. METHODS: Using a networked workstation in our laboratory and freely available distributed hypertext software, we established a World Wide Web (WWW) information server for radiology. Images from the Radiologic Learning File are requested through the WWW client software, digitized from a single laser disc containing the entire teaching file and then transmitted over the network to the client. The text accompanying each image is incorporated into the transmitted document. RESULTS: The Radiologic Learning File is now on-line, and requests to view the cases result in the delivery of the text and images. Image digitization via a frame grabber takes 1/30th of a second. Conversion of the image to a standard computer graphic format takes 45-60 sec. Text and image transmission speed on a local area network varies between 200 and 400 kilobytes (KB) per second depending on the network load. CONCLUSION: We have made images from a laser disc of the Radiologic Learning File available through an Internet-based hypertext server. The images previously available through a single-user system located in a remote section of our department are now ubiquitously available throughout our department via the department's computer network. We have thus converted a single-user, limited functionality system into a multiuser, widely available resource.

CD-ROM↗

A robust and efficient automated docking algorithm for molecular recognition.

A completely automated method is described for determining the most likely mode of binding of two (macro)molecules from the knowledge of their three-dimensional structures alone. The method is based on well-known graph theoretical techniques and has been used successfully to determine and rationalize the binding of a number of known macromolecular complexes. In this article we present results for a special case of the general molecular recognition problem--given the information concerning the particular atoms involved in the binding for one of the molecules, the algorithm can correctly identify the corresponding (contacting) atoms of the other molecule. The approach used can be easily extended to the general molecular recognition problem and requires the extraction of maximal common subgraphs. In these studies the docking of the macromolecules was achieved without the aid of computer graphics or other visual aids. The algorithm has been used to determine the correct mode of binding of a protein antigen to an antibody in approximately 100 min on a DEC micro VAX 3600.

Algorithms↗

A simple way to look at DNA.

A method is presented for embedding nucleotide sequence data in a simple metric space. Computer graphical examination of spatially-represented sequences permits rapid searches for canonical patterns or interesting structures. Sequence comparisons are facilitated by plots of distance measures for homologous sequences, and the large-scale structure of the genetic code can be studied by measures such as fractal dimensionality.

Actins↗

Psychophysical foundations of a model of amplified night vision in target detection tasks.

In this article we examine some of the basic psychophysics relevant to amplified night vision devices. These devices produce images that are substantially different from ordinary visual scenes. Distortions in contrast and luminance and the introduction of visual interference and geometrical artifacts contribute to unusual viewing conditions. We carried out experiments to determine the effect of these parameters of the image on a highly controlled visual target detection task simulated on a computer graphics system that closely models a night vision device. Our results indicate that display luminance and geometrical artifacts degrade detection performance only slightly, whereas contrast and visual interference have a substantial degrading effect.

Adult↗

[The numerical simulation of the dynamic stress field from impacting head].

In order to study the mechanism of impact injury to the head, we have simulated the development of the stress field by using the numerical simulation method. The process of the head having been impacted vertically by an impactor can be described as a 2D problem, and the reactions of the head subjected to impacted force can be simulated and analyzed by the method based on the finite difference method (FDM). The model is subjected to applied force by an impactor with the initial velocity of 25 m/s (90 km/h). The pre-processing for the model is done on the microcomputer software. Once imported to the software, the nodes and elements are generated and material characteristics are assigned. The results demonstrate that the high resolution computer graphics can provide the dynamic distribution of the stress field, which can clearly show how the stress is developed, and how many its value is. The results are helpful to understanding the mechanism of impact injury to head.

Craniocerebral Trauma↗

[Extent of microleakage in relation to root canal morphology].

The purpose of this study was to study with standardized methods the length and extent of the microleakage developing around the root canal fillings. The preparational errors were evaluated in twenty straight and curved root canal using computer graphic analysis. The step back technique was used for root canal preparation. The shape of the instrumented root canals were analyzed macroradiographically in order to evaluate unwanted procedural root canal deformities. The root canals were obturated with lateral condensation technique using AH-26 sealer and guttapercha points. After the teeth having been made transparent a silver nitrate penetration test was performed in vacuum and both the linear dye penetration and the extent of dye penetration surface area were measured from four directions with computer assisted digitized method. The linear dye penetration values were higher in straight root canals than in curved ones: 2.22 + 1.17 mm and 1.81 + 1.24 mm respectively. The dye penetration surface area was slightly also larger in straight than in curved root canals: 1.3 +/- 0.71 mm2 vs. 1.06 +/- 0.5 mm2. Nevertheless the differences were statistically non significant. In curved root canals the highest dye penetration values were measured at the inner curvature of the canals. This findings was also corroborated by a coincidence test.

Coloring Agents↗

Prediction of chemical carcinogenicity from molecular and electronic structures: a comparison of MINDO/3 and CNDO/2 molecular orbital methods.

Molecular orbital methods have been used to calculate the electronic structures of a number of chemical carcinogens and non-carcinogens using the MINDO/3 (Modified Intermediate Neglect of Differential Overlap, version 3) and CNDO/2 (Complete Neglect of Differential Overlap) procedures; results from the two methods show good agreement. Spatial conformations of the same series of chemicals have also been determined. High affinity for cytochromes P-448 (P450 I) and high potential for chemical carcinogenicity/toxicity show good correlation with molecular planarity (high values of area/depth2) and low values of the difference between the frontier orbital energies (delta E) of the chemical. This computer graphic procedure identifies substrates of the cytochromes P-448 and is highly suited for the rapid screening of new chemicals for potential mutagenicity, carcinogenicity and certain other forms of toxicity. The implications of these findings to the mechanism of chemical carcinogenicity are discussed.

Carcinogenicity Tests↗

The putidaredoxin reductase-putidaredoxin electron transfer complex: theoretical and experimental studies.

Interaction and electron transfer between putidaredoxin reductase (Pdr) and putidaredoxin (Pdx) from Pseudomonas putida was studied by molecular modeling, mutagenesis, and stopped flow techniques. Based on the crystal structures of Pdr and Pdx, a complex between the proteins was generated using computer graphics methods. In the model, Pdx is docked above the isoalloxazine ring of FAD of Pdr with the distance between the flavin and [2Fe-2S] of 14.6 A. This mode of interaction allows Pdx to easily adjust and optimize orientation of its cofactor relative to Pdr. The key residues of Pdx located at the center, Asp(38) and Trp(106), and at the edge of the protein-protein interface, Tyr(33) and Arg(66), were mutated to test the Pdr-Pdx computer model. The Y33F, Y33A, D38N, D38A, R66A, R66E, W106F, W106A, and Delta106 mutations did not affect assembly of the [2Fe-2S] cluster and resulted in a marginal change in the redox potential of Pdx. The electron-accepting ability of Delta106 Pdx was similar to that of the wild-type protein, whereas electron transfer rates from Pdr to other mutants were diminished to various degrees with the smallest and largest effects on the kinetic parameters of the Pdr-to-Pdx electron transfer reaction caused by the Trp(106) and Tyr(33)/Arg(66) substitutions, respectively. Compared with wild-type Pdx, the binding affinity of all studied mutants to Pdr was significantly higher. Experimental results were in agreement with theoretical predictions and suggest that: (i) Pdr-Pdx complex formation is mainly driven by steric complementarity, (ii) bulky side chains of Tyr(33), Arg(66), and Trp(106) prevent tight binding of oxidized Pdx and facilitate dissociation of the reduced iron-sulfur protein from Pdr, and (iii) transfer of an electron from FAD to [2Fe-2S] can occur with various orientations between the cofactors through multiple electron transfer pathways that do not involve Trp(106) but are likely to include Asp(38) and Cys(39).

Ferredoxins↗

Computer-assisted 3D-reconstruction and statistics of the limbic system. 1. Computer-assisted 3D-reconstruction of the hippocampal formation, the fornix, and the mamillary bodies.

The hippocampal formation of eight perfusion-fixed human brains was examined using new methods according to stereotactic and morphometric principles (macrovibratome and computer-aided 3D reconstruction). The reconstructions form part of a neuroanatomical reference system (NeuRef). This reference system allows for 3D visualisation of the brain and its components on a computer graphic workstation, as well as for the presentation of the union set based on a neuroanatomical structure taken from this sample of brains. This retrievable knowledge of neurofunctional systems is important for the preoperative planning of neurosurgeons and the adjustment of radiotherapy.

Adult↗

One left-handed strand in DNA-oligonucleotide complexes?

A single strand of oligonucleotide can bind to double helical DNA under certain conditions. This must involve some unwinding of the original double helix in a process leading to the formation of a three-stranded region. The free energy for such an entropically unlikely reaction may come from a change in the degree of supercoiling of the original DNA. The conformation of the triple strand is investigated here using computer graphics and molecular mechanics calculations. It is suggested that on binding the oligonucleotide (strand 3) to two paired strands (1 and 2) in a supercoiled DNA molecule, strand 2 might adopt a left-handed conformation whilst strand 1 and strand 3 pair in the normal Watson-Crick B-configuration.

Computer Simulation↗