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Prediction models in the design of neural network based ECG classifiers: a neural network and genetic programming approach.

BACKGROUND: Classification of the electrocardiogram using Neural Networks has become a widely used method in recent years. The efficiency of these classifiers depends upon a number of factors including network training. Unfortunately, there is a shortage of evidence available to enable specific design choices to be made and as a consequence, many designs are made on the basis of trial and error. In this study we develop prediction models to indicate the point at which training should stop for Neural Network based Electrocardiogram classifiers in order to ensure maximum generalisation. METHODS: Two prediction models have been presented; one based on Neural Networks and the other on Genetic Programming. The inputs to the models were 5 variable training parameters and the output indicated the point at which training should stop. Training and testing of the models was based on the results from 44 previously developed bi-group Neural Network classifiers, discriminating between Anterior Myocardial Infarction and normal patients. RESULTS: Our results show that both approaches provide close fits to the training data; p = 0.627 and p = 0.304 for the Neural Network and Genetic Programming methods respectively. For unseen data, the Neural Network exhibited no significant differences between actual and predicted outputs (p = 0.306) while the Genetic Programming method showed a marginally significant difference (p = 0.047). CONCLUSIONS: The approaches provide reverse engineering solutions to the development of Neural Network based Electrocardiogram classifiers. That is given the network design and architecture, an indication can be given as to when training should stop to obtain maximum network generalisation.

Electrocardiography↗

A simplified method for power-law modelling of metabolic pathways from time-course data and steady-state flux profiles.

BACKGROUND: In order to improve understanding of metabolic systems there have been attempts to construct S-system models from time courses. Conventionally, non-linear curve-fitting algorithms have been used for modelling, because of the non-linear properties of parameter estimation from time series. However, the huge iterative calculations required have hindered the development of large-scale metabolic pathway models. To solve this problem we propose a novel method involving power-law modelling of metabolic pathways from the Jacobian of the targeted system and the steady-state flux profiles by linearization of S-systems. RESULTS: The results of two case studies modelling a straight and a branched pathway, respectively, showed that our method reduced the number of unknown parameters needing to be estimated. The time-courses simulated by conventional kinetic models and those described by our method behaved similarly under a wide range of perturbations of metabolite concentrations. CONCLUSION: The proposed method reduces calculation complexity and facilitates the construction of large-scale S-system models of metabolic pathways, realizing a practical application of reverse engineering of dynamic simulation models from the Jacobian of the targeted system and steady-state flux profiles.

Kinetics↗

Sparse graphical Gaussian modeling of the isoprenoid gene network in Arabidopsis thaliana.

We present a novel graphical Gaussian modeling approach for reverse engineering of genetic regulatory networks with many genes and few observations. When applying our approach to infer a gene network for isoprenoid biosynthesis in Arabidopsis thaliana, we detect modules of closely connected genes and candidate genes for possible cross-talk between the isoprenoid pathways. Genes of downstream pathways also fit well into the network. We evaluate our approach in a simulation study and using the yeast galactose network.

Arabidopsis↗

Leaflet geometry extraction and parametric representation of a pericardial artificial heart valve.

Reverse engineering technology was used to reconstruct the complex leaflet geometry of a commercial pericardial valve in our study. Results show that the three-dimensional computer-aided design model of the leaflet surface can be rendered by fitting the surface either to cloud points or by a group of B-splines fitted to a set of cloud points that had been obtained by the process of laser-scanning digitizing. However, an acceptable smooth surface is usually not guaranteed and additional manipulation is required. An alternative method is introduced in this paper, which involves the fitting of an equation to the leaflet geometry to create a smooth surface. The geometrical profile of a pericardial artificial heart valve was scanned using a laser digitizing system. The leaflet profile is represented as a set of cloud points. A quadric surface is fitted to a set of unique points, which were located on the set of cloud points. A mathematical equation is obtained by solving a least-squares fit. The geometry of the fitted leaflet surface has been proven to be closely represented by an elliptical hyperboloid. The quadratic equations of the leaflet curvatures, calculated along both the circumferential and the radial directions, resulted in simple hyperbolic curvatures. The advantages of using elliptical hyperboloid geometry for the leaflet surface are discussed and compared with other types of conicoid geometries. The concepts of parametric representation of the leaflet geometry and parametric design for leaflets are discussed. A smooth surface without inflection points and with an adjustable surface area suitable for a series of stent sizes with incremented diameters is created by this method of a single parametric design. Finally, a generic method to apply the geometry extraction and parametric representation to most pericardial heart valve prostheses was discussed. The application to valves with natural shape was introduced, challenges were identified, and a technical solution was proposed.

Algorithms↗

Parametric modelling of a knee joint prosthesis.

This paper presents an approach for the establishment of a parametric model of knee joint prosthesis. Four different sizes of a commercial prosthesis are used as an example in the study. A reverse engineering technique was employed to reconstruct the prosthesis on CATIA, a CAD (computer aided design) system. Parametric models were established as a result of the analysis. Using the parametric model established and the knee data obtained from a clinical study on 21 pairs of cadaveric Asian knees, the development of a prototype prosthesis that suits a patient with a very small knee joint is presented. However, it was found that modification to certain parameters may be inevitable due to the uniqueness of the Asian knee. An avenue for rapid modelling and eventually economical production of a customized knee joint prosthesis for patients is proposed and discussed.

Asian People↗

The Decim system for the production of dental restorations.

The general background to the development of CAD/CAM is presented in short. Specific problems when using this technique for the manufacturing of dental restorations are emphasized, and then the reverse engineering and CAD/CAM process that have been implemented in the Decim (Dentronic AB, Skellefteå, Sweden) system are presented. The system is organized in the following way: 1. The measurement process is encapsulated in a product called Decim Reader. 2. The design functionality is provided by software running on a conventional personal computer. This unit is called Decim Designer. 3. The CAM calculation is done by a dedicated personal computer, the Decim Calculator, that does not require any user interaction. 4. The actual manufacturing of the restorations is performed in the Decim Producer that works with a grinding technique. These components communicate via a local computer network or, when a distributed solution is desired, via internet. The Decim System is presently used for the production of dental ceramic restorations, and it is the only system which can be used for manufacturing inlays of yttria-stabilized zirconia. This ceramic material is CE-approved under the brand name Denzir (Dentronic AB, Skellefteå, Sweden). Due to its favorable mechanical properties, it may be an alternative to dental amalgam, and is therefore of topical interest in dentistry. The use of computer-based techniques for manufacturing dental restorations is briefly outlined and commented on.

Ceramics↗

Building local research and development capacity for the prevention and cure of neglected diseases: the case of India.

This paper examines the proposal to build research and development (R&D) capabilities for dealing with neglected infectious and tropical diseases in countries where they are endemic, as a potentially cost- and time-effective way to fill the gap between the supply of and need for new medicines. With reference to the situation in India, we consider the competencies and incentives needed by companies so that their strategy can be shifted from reverse engineering of existing products to investment in R&D for new products. This requires complex reforms, of which the intellectual property rights agreement is only one. We also consider whether Indian companies capable of conducting research and development are likely to target neglected diseases. Patterns of patenting and of R&D, together with evidence from interviews we have conducted, suggest that Indian companies, like multinational corporations, are likely to target global diseases because of the prospect of much greater returns. Further studies are required on how Indian companies would respond to push and pull incentives originally designed to persuade multinational corporations to do more R&D on neglected diseases.

Communicable Diseases↗

Design and production of dental prosthetic restorations: basic research on dental CAD/CAM technology.

Dental prosthetic restorations (crowns and FPDs) are currently produced mainly by conventional dental technology methods. The automation of the production process can be achieved by the use of CAD/CAM techniques. In addition, it has become possible to use materials that previously could not be processed for technical reasons or could not be processed economically, especially high-performance ceramics. Although CAD/CAM methods for producing fixed restorations are of increasing interest, little information has been published about their mode of operation and functionality. To date, studies have focused mostly on special systems. However, basic studies are lacking. Basic research on the most important aspects of CAD/CAM fixed dental restorations from the viewpoint of production, information technology, and dentistry/dental technology are the subject of a current research project. The aim of this study is the presentation of preliminary results. The CAD/CAM process for fixed restorations was analyzed and broken down into single steps. In order to examine the influence of the single steps in the process chain, a computer test model with the teeth of the maxilla and mandible in static occlusion was developed and reverse engineered. While producing the test model, fundamental knowledge regarding the manufacturing of dental restorations with functional occlusal surfaces was gained. The intersection of the maxillary and mandibulary occlusal surfaces allows the qualitative analysis of occlusal contacts analogous to the conventional technique. Furthermore, a quantitative assessment of the size of the occlusal contacts and the measurement of intersection is possible.

Analog-Digital Conversion↗

[Morphologic features of the acetabulum bone joint area].

The research on the morphology features of the acetabulum bone joint surface area would be helpful to establishing the acetabulum 3D model for the purpose of the biomechanical analysis of hip joint, and therefore might have its important clinical significance. However, in former studies, the acetabulum was simply considered as a semi sphere. In this study, based on the acetabulum 3D-point data acquired by the 3D laser surface scanner and the reverse engineering technology together with the optimal fit algorithm, two kinds of best-fit model were achieved by a sphere surface and a rotating elliptical surface respectively approaching to the acetabulum bone joint surface. Both fitting errors were then compared and analyzed. The results showed that the fitting error of the rotating elliptical surface was significantly less than that of the sphere surface (P < 0.001). The average radius of fitting sphere was 24.37 +/- 2.22 mm and the average long axis of fitting rotating elliptical surface was 26.02 +/- 2.76 mm while its short axis was 24.17 +/- 2.16 mm. These findings would be helpful to our new recognition of the acetabulum since they were results of the first quantitative analyses for the acetabulum bone surface and also might serve as an important reference base in its further studies and application.

Acetabulum↗

A cheap technical solution for cranioplasty treatments.

Skull defects are treated by cranioplasty techniques, which are required to protect underlying brain, correct major aesthetic deformities, or both. This research is a part of our research project in ASEAN countries to investigate (i) the methods for design and manufacturing of cranioplasty implants, and (ii) the feasible technical solutions of minimizing the implant cost based on available production and biomaterial technologies in the region. In this paper, solutions for design and manufacturing of standardized implant templates (SDT) are presented. SDT are made based on the reverse engineering and rapid tooling techniques. With the use of SDT, surgeons have flexible options in preparing the implant both pre and intra operatively, and the operation time is minimized. In addition, the skills required to prepare an implant from SDT are not highly required. The cost for cranioplasty treatments by using SDT is acceptable for ASEAN region.

Computer-Aided Design↗

[Morphological analysis of acetabulum bony curved surface].

By using the reverse engineering (RE) technology, the mesh surface model of acetabulum was reconstructed by triangulation. Based on this kind of model, the local morphological analysis (LMA) and global morphological analysis (GMA) could be processed. The fitting minimal quadric surface method was applied to calculate the curvature of any point on the acetabulum bony surface, the local morphological character of its surface could be acquired, and its global surface character could be determined by GMA. The results showed that the acetabulum bony surface is elliptical surface, and its three eigenvalues (lambda1, lambda2, lambda3) relations on the three axes (x, y, z) are as follows: lambda1 is short than lambda2 and lambda3, lambda2 is close to lambda3.

Acetabulum↗

[A study on new computer-aided modeling method of hip joint].

The main reason of invalidation of prosthetic hip joint is the prostheses flexibility and shift, dislocation and disjunction. Promoting the long time stability of the prostheses is the key of improving the long term hip joint replacement effect. Former research work was focused on the upper segment of femur, and assumed the acetabulum cup to be a spheric concave, and the external form of acetabulum prostheses was basically semi spheric. This paper presents a method of acquiring the point data on the surface of the hip bone using the reverse engineering technology. By analyzing the acetabulum surface fitting error we use rotating elliptical surface to fit the acetabulum surface, together with the optimal technique to build up the CAD model of acetabulum surface. We compare the fitting error between the sphere fitting and rotating elliptical surface fitting and get the result that the rotating elliptical surface fitting error is smaller than the sphere fitting error, and the rotating elliptical surface can describe the shape of the acetabulum better.

Acetabulum↗

Using prior knowledge to improve genetic network reconstruction from microarray data.

The use of Bayesian Network methods to recover transcriptional regulatory networks from static microarray data is an active area of bioinformatics research. However, early work in this area lacked realistic analysis of the effects of data set size on learning performance and ignored the potentially immense benefits of using prior biological knowledge. More recent work which has utilized such information has tended to focus on qualitative descriptions of the results. In this paper, we construct a detailed, realistic model for glucose homeostasis and use this model to generate static, synthetic gene expression data. We then use a Bayesian Network method to reconstruct this genetic network from the synthetic microarray data utilizing various amounts and types of prior knowledge. By quantitatively analyzing the effects of data set size and the incorporation of different types of prior biological knowledge on our ability to reconstruct the original network, we show that characteristic portions of genetic networks can be reconstructed from microarray data. Incorporating prior knowledge into the learning scheme greatly reduces the data required, allowing these reverse engineering techniques to be used to learn regulatory interactions from microarray data sets of realistic size.

Bayes Theorem↗

Next generation autonomous wheelchair control.

Often times the physically challenged, limited to a wheelchair, also have difficulty with vision. In order to help, something must "see" for them. Therefore there must be some way for a wheelchair to know its environment, sense where it is, and where it must go. It also must be able to avoid any obstacles which are not normally part of the environment. An autonomous wheelchair will serve an important role by allowing users more freedom and independence. This design challenge is broken into four major steps: wheelchair control, environment recognition, route planning, and obstacle avoidance. The first step is to reverse engineer a wheelchair and rebuild the controls, which will be the main topic of discussion for this paper. Two big challenges with this step are high power motor control and joystick control. An H-bridge motor interface, controlled by a microprocessor, was designed for the motors. The joystick control is handled with the same microprocessor.

Artificial Intelligence↗

[Individual digital design and functional reconstruction of large mandibular defect with computer-aided design/computer aided manufacture technique].

OBJECTIVE: To build up a new contour and functional reconstruction technique of mandibular defects with rapid prototyping and reverse engineering technique. METHODS: From April 2002 to August 2004, 4 cases of mandibular defects due to resection of large mandible lesion were treated. Of 4 patients, there were 3 females and 1 male, with an age range of 21-42 years, which underwent secondary operation and presented a deviation as mandibular movement. The opening-mouth extent was 1.8-2.5 cm (2.2 cm on average). The data of defects area were renewed with Mimics and Geomagic Studio software; and the titanium reconstructive frame was designed and manufactured with rapid prototyping technique. Defect were reconstructed by using CT digital data of patients. RESULTS: The CT data could be used by image software directly. The implant design could be completed by computer-aimed design (CAD) / computer-aided manufacture (CAM). The resin model and titanium frame were manufactured accurately by RP technique. Four patients achieved one stage healing. After a follow-up of 3 months to 2 years, large mandibular defect was reconstructed satisfactorily and the opening-mouth extent was 3.0-3.4 cm (3.2 cm on average). The occluding relation was normal. The implant denture was put on and the mastication function was good in 1 case. CONCLUSION: Individual design and repair of large mandibular defect with CAD/CAM techniques is worth extending application clinically. It is a simple and accurate method.

Adult↗

Fractal genomics modeling: a new approach to genomic analysis and biomarker discovery.

Reverse engineering of genetics networks generally requires establishing correlative behavior within and between a very large number of genes. This becomes a difficult analytical problem for even a few hundred genes and the difficulty tends to grow exponentially as more genes are examined. Using a hybrid data analysis method known as Fractal Genomics Modeling (FGM), this problem is reduced to examining correlative behavior within small gene groups that can then be compared and integrated to produce a picture of larger networks using a type pf shotgun approach. We have applied FGM toward examining genetic networks involved in HIV infection in the brain. These networks have relevance both to processes related to HIV infection and neurodegenerative disorders. Our preliminary findings have produced conjectures of related pathways and networks as well new candidates for genetic markers in HIV brain infection. Evidence has also been produced which appears to show the presence of a hierarchical network structure within the genes studied. We will discuss the background and methodology of FGM as well as our recent findings.

AIDS Dementia Complex↗

Reconstruction of gene regulatory networks under the finite state linear model.

We study the Finite State Linear Model (FSLM) for modelling gene regulatory networks proposed by A. Brazma and T. Schlitt in [4]. The model incorporates biologically intuitive gene regulatory mechanism similar to that in Boolean networks, and can describe also the continuous changes in protein levels. We consider several theoretical properties of this model; in particular we show that the problem whether a particular gene will reach an active state is algorithmically unsolvable. This imposes some practical difficulties in simulation and reverse engineering of FSLM networks. Nevertheless, our simulation experiments show that sufficiently many of FSLM networks exhibit a regular behaviour and that the model is still quite adequate to describe biological reality. We also propose a comparatively efficient O(2(K)n(K+1)M(2K)m log m) time algorithm for reconstruction of FSLM networks from experimental data. Experiments on reconstruction of random networks are performed to estimate the running time of the algorithm in practice, as well as the number of measurements needed for successful network reconstruction.

Algorithms↗

Improving computational predictions of cis-regulatory binding sites.

The location of cis-regulatory binding sites determine the connectivity of genetic regulatory networks and therefore constitute a natural focal point for research into the many biological systems controlled by such regulatory networks. Accurate computational prediction of these binding sites would facilitate research into a multitude of key areas, including embryonic development, evolution, pharmacogenemics, cancer and many other transcriptional diseases, and is likely to be an important precursor for the reverse engineering of genome wide, genetic regulatory networks. Many algorithmic strategies have been developed for the computational prediction of cis-regulatory binding sites but currently all approaches are prone to high rates of false positive predictions, and many are highly dependent on additional information, limiting their usefulness as research tools. In this paper we present an approach for improving the accuracy of a selection of established prediction algorithms. Firstly, it is shown that species specific optimization of algorithmic parameters can, in some cases, significantly improve the accuracy of algorithmic predictions. Secondly, it is demonstrated that the use of non-linear classification algorithms to integrate predictions from multiple sources can result in more accurate predictions. Finally, it is shown that further improvements in prediction accuracy can be gained with the use of biologically inspired post-processing of predictions.

Algorithms↗