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Epitope prediction algorithms for peptide-based vaccine design.

Peptide-based vaccines, in which small peptides derived from target proteins (eptiopes) are used to provoke an immune reaction, have attracted considerable attention recently as a potential means both of treating infectious diseases and promoting the destruction of cancerous cells by a patient's own immune system. With the availability of large sequence databases and computers fast enough for rapid processing of large numbers of peptides, computer aided design of peptide-based vaccines has emerged as a promising approach to screening among billions of possible immune-active peptides to find those likely to provoke an immune response to a particular cell type. In this paper, we describe the development of three novel classes of methods for the prediction problem. We present a quadratic programming approach that can be trained on quantitative as well as qualitative data. The second method uses linear programming to counteract the fact that our training data contains mostly positive examples. The third class of methods uses sequence profiles obtained by clustering known epitopes to score candidate peptides. By integrating these methods, using a simple voting heuristic, we achieve improved accuracy over the state of the art.

Algorithms↗

Combined effects of errors in frontal-view asymmetry diagnosis.

The aim of the present investigation was to determine the relative extent of geometric error and errors in point identification in postero-anterior roentgenography. In one series of tests a group of dry human skulls was used, and the same cephalometric landmarks were identified twice by two orthodontists, using postero-anterior roentgenographs, first using the dry skulls as such, and then the same skulls with metal markers inserted to show the exact locations of the cephalometric points. Consistency and normal variation in the reproducibility of head position in the cephalostat between repeated roentgenographs were studied by a photographic technique in a group of young healthy adults, measuring the extent of minor head movements. Geometric error was calculated using a computer-aided design program (CAD) by rotating the three-dimensional co-ordinates of the cephalometric landmarks and thus obtaining projection error in the frontal view. Accuracy in cephalometric point identification was best in dental landmarks and vertical orientation of superior orbital margins. Geometric error was least when landmarks near the anterior midsagittal plane, such as upper and lower dental midlines or point gonion were compared with each other. Width measurements from frontal-view cephalograms are most sensitive to minor movements in head posture. Due to combined errors, the use of width measurements in facial asymmetry diagnosis should not be used since variance in errors in landmark identification can be larger than that in actual landmark location.

Adult↗

Ten-year in vivo wear measurement of a fully congruent mobile bearing unicompartmental knee arthroplasty.

Polyethylene particulate wear debris continues to be implicated in the aetiology of aseptic loosening following knee arthroplasty. The Oxford unicompartmental knee arthroplasty employs a spherical femoral component and a fully congruous meniscal bearing to increase contact area and theoretically reduce the potential for polyethylene wear. This study measures the in vivo ten-year linear wear of the device, using a roentgenstereophotogrammetric technique. In this in vivo study, seven medial Oxford unicompartmental prostheses, which had been implanted ten years previously were studied. Stereo pairs of radiographs were acquired for each patient and the films were analysed using a roentgen stereophotogrammetric analysis calibration and a computer-aided design model silhouette-fitting technique. Penetration of the femoral component into the original volume of the bearing was our estimate of linear wear. In addition, eight control patients were examined less than three weeks post-insertion of an Oxford prosthesis, where no wear would be expected. The control group showed no measured wear and suggested a system accuracy of 0.1 mm. At ten years, the mean linear wear rate was 0.02 mm/year. The results from this in vivo study confirm that the device has low ten-year linear wear in clinical practice. This may offer the device a survival advantage in the long term.

Adult↗

Accuracy of machine milling and spark erosion with a CAD/CAM system.

A method for manufacturing crowns and fixed partial dentures based on CAD/CAM has been developed as an alternative to the lost wax technique and the casting of an alloy. In this process two steps are included: milling and spark erosion. The computer-assisted design (CAD) relies heavily on the accuracy of the milling and spark erosion processes to achieve a clinically acceptable restoration. These two processes must be able to produce the crown data generated in the CAD files. This study evaluated the accuracy of the Procera CAD/CAM system in creating specific geometric bodies that were compared with the known dimensions in the CAD files for these bodies. The manufacturing errors of milling (ellipse +/- 6.5 microm, square +/- 3.4 microm, and cylinder +/- 5.8 microm) and spark erosion (ellipse +/- 8.6 microm and square +/- 10.4 microm) were determined. The accuracy of this manufacturing process demonstrated that this system was capable of producing a crown with a clinically accepted range for marginal opening gap dimension of less than 100 microm.

Analysis of Variance↗

The precision of computer-generated surgical splints.

PURPOSE: The purpose of this study was to assess the precision of stereolithographic surgical splints generated by the authors' computer-aided design and manufacturing (CAD/CAM) technique by comparing them with the conventional acrylic splints. MATERIALS AND METHODS: Seven volunteers were used. A pair of surgical splints, stereolithographic and conventional acrylic splints, was fabricated for each subject. A novel method was developed to quantify the airspace between the teeth and the splint. Conventional acrylic surgical splints served as a control group. The airspaces were recorded by impression materials and sliced cross-sectionally. Corresponding areas of the cross-sectional airspaces between stereolithographic and acrylic splints were measured and compared. Pearson's correlation coefficient and linear regression tests were performed. RESULTS: Seven pairs of surgical splints were created. The areas of 98 pairs of cross-sectional airspaces were measured. The average difference between the conventional and the STL splints was 0.24 +/- 0.23 mm(2). The correlation coefficient (r) of the airspace areas between the stereolithographic and conventional acrylic splints was 1.00, and the regression coefficient (beta) was 1.03 (P <.01). CONCLUSIONS: The results indicated that the stereolithographic splints, generated by the authors' CAD/CAM technique, had a high degree of accuracy. The fit of the STL splints was the same as the conventional surgical splints. In the future, traditional plaster dental model surgery will be replaced by computer-assisted surgical planning. The surgical splints will be made in the computer and the treatment plan will be directly transferred to the patient.

Acrylic Resins↗

[Construction of inlay axial surface using B-Spline curve network].

OBJECTIVE: To realize the requirement of adjacent area accuracy, axial surface physical contour and smoothness in the process of inlay computer-aided design (CAD). METHODS: A compromised method was brought forward that some assistant 3-D constraint lines from occlusion to gingiva were used to lead the inlay contour on axial corner and other characterized areas, and two perpendicular 3-D constructing lines at adjacent area were used to construct accurate 3-D configuration of this area. The axial surface was completely defined by the network of specified curves which were two constructing lines and four borders. RESULTS: Inlay axial surface was smooth, the contour was consistent with the residual tooth body and the 3-D configuration in adjacent area was accurate. CONCLUSION: It is feasible to realize the inlay axial surface accuracy, smoothness, and consistency using the method of special distributed 3-D B-Spline curve network.

Computer-Aided Design↗

An in vitro evaluation of titanium, zirconia, and alumina procera abutments with hexagonal connection.

PURPOSE: The purpose of this study was to assess the precision at the implant interface of titanium, zirconia, and alumina Procera abutments with a hexagonal connection for single-tooth restorations. MATERIALS AND METHODS: Twenty Procera abutments were produced with commercially pure titanium, 20 with zirconia, and 20 with alumina using computer-assisted design and manufacture (CAD/CAM). The rotational freedom of the abutments was assessed to detect the precision of fit of each abutment on the top of the implant hexagon. RESULTS: Significant differences relative to rotational freedom were found between groups: the titanium group and the zirconia group did not differ significantly, but both demonstrated significantly smaller mean rotational freedoms than the alumina group (P < .05). Rotational freedom was less than 3 degrees for all abutments. CONCLUSIONS: The hexagonal misfit of the Procera abutment on the implant hexagon may be implicated in screw joint loosening. In the present study, all types of CAD/CAM Procera abutments consistently showed less than 3 degrees of rotational freedom in a situation where the abutment was connected to an implant by a hexagonal external connection.

Aluminum Oxide↗

Spatial domain wavelet design for feature preservation in computational data sets.

High-fidelity wavelet transforms can facilitate visualization and analysis of large scientific data sets. However, it is important that salient characteristics of the original features be preserved under the transformation. We present a set of filter design axioms in the spatial domain which ensure that certain feature characteristics are preserved from scale to scale and that the resulting filters correspond to wavelet transforms admitting in-place implementation. We demonstrate how the axioms can be used to design linear feature-preserving filters that are optimal in the sense that they are closest in L2 to the ideal low pass filter. We are particularly interested in linear wavelet transforms for large data sets generated by computational fluid dynamics simulations. Our effort is different from classical filter design approaches which focus solely on performance in the frequency domain. Results are included that demonstrate the feature-preservation characteristics of our filters.

Algorithms↗

Flow input waveform effects on the temporal and spatial wall shear stress gradients in a femoral graft-artery connector.

Employing a validated finite volume code, a computer-aided design of the distal end of a femoral graft-artery junction has been considered to simulate transient three-dimensional blood flow for various flow input waveforms. The study relies on the hypothesis that large sustained wall shear stress gradients play a major role in the rapid recurrence of intimal hyperplasia plus atheroma after bypass surgery, leading to early graft failure. Two new dimensionless parameters have been introduced to correlate flow waveform characteristics with the severity of nonuniform hemodynamics and hence the potential risk for restenosis. The transient and, more importantly, the time-averaged wall shear stress gradient distributions shown, map out the junction areas which are still susceptible to restenosis, especially the toe region. Future geometric modifications will further reduce disturbed flow patterns and hence the probability of graft failure.

Anastomosis, Surgical↗

A structural model for molded thermoplastic ankle-foot orthoses.

The structural response of a posterior leaf spring, ankle-foot orthosis (AFO) was studied both experimentally and with a simple theoretical model. The theoretical model, which was compared with other analytical solutions and experimental data, predicted the bending and twisting of the AFO due to unit loads. The simple theoretical model utilized beam equations and small deflection theory. Excellent agreement between test and predicted values was achieved, indicating that the simple theoretical model, which was relatively easy to implement computationally, could serve as the major component of a computer-aided design program.

Ankle↗

Job demands, muscle activity and musculoskeletal symptoms in relation to work with the computer mouse.

OBJECTIVES: This study assessed work postures, movements, psychosocial job demands, and shoulder and wrist extensor muscle activity and registered the prevalence of musculoskeletal symptoms of computer-aided design (CAD) operators. METHODS: A questionnaire survey was used to study the use of the computer mouse, psychosocial work factors, and musculoskeletal symptoms among 149 CAD operators. A workplace study was performed using observations, electrogoniometers on the wrists, and electromyography to measure exposures and physiological responses during CAD work among a subgroup of the CAD operators. RESULTS: Musculoskeletal symptoms were far more prevalent for the arm or hand operating the mouse than for the other arm or hand, and women were more affected than men. The symptoms may be related to such risk factors as repetitive movements, static postures (eg, ulnar-deviated and extended wrist on the mouse side), and static muscular activation patterns. The risk factors were present due to continuous mouse use and possibly also due to high demands for mental attentiveness, precision, and information processing. CONCLUSIONS: Exposure during work with a computer mouse may present a risk for developing musculoskeletal symptoms. Improvements should focus on introducing more variation.

Adult↗

[Evaluation of individual ceramic implants made of Bioverit with CAD/CAM technology to reconstruct multidimensional craniofacial defects of the human skull].

BACKGROUND: Restrictions in the bone structure of the craniomandibular region caused by malformation, traumata or malignant tumours are currently of interest in reconstructive oral and maxillofacial surgery. Methods of autologous bone transplantation are well established for reconstruction of those defects. The reconstruction and remodeling of contour-shaping defects is more difficult due to atrophy and resorption of free-transplantable tissues. Artificially induced harmful effects have been reported on harvesting in the donor area. Further available methods of alloplastic reconstruction are computer-assisted design and manufacturing systems (CAD/CAM). The advantages of individual design and fabrication are obvious in the manufacturing of defect-specific implants. MATERIAL AND METHODS: In the present study the application of individual CAD-based reconstructed bioceramic implants made of Bioverit II was evaluated in the region of the facial skull. Clinical results, patient acceptance and the analysis of the postoperative observation period of 30 months are reviewed. RESULTS: Altogether 25 individual Bioverit ceramics were implanted in the facial region. All patients were satisfied with the aesthetic results of the implantations after primary surgery. Three patients developed a need for further correction during the observation period; one implant fracture was observed. CONCLUSION: Finally, it can be stated that the preoperative expenditures in time, experts, technology and fabrication of individual CAD/CAM planned and manufactured implants are justified by the following advantages: fixed volume, reduced operating time, lack of donor morbidity, easy subsequent treatment of the material and the aesthetic results achieved.

Adult↗

Development of an integrated CAD-FEA process for below-knee prosthetic sockets.

BACKGROUND: Computer-aided design and manufacturing has been successfully used in prosthetic applications since 1980s. It simplifies the socket rectification process and improves reproducibility but does not introduce any new principle into socket design. Integrating finite element analysis to CAD will provide a more objective assessment of socket fit and improve the chance of a successful first fitting. METHODS: Current study aims to establish a finite element model generation technique directly from geometrical information of commercial prosthetic CAD workstation. A program developed in-house automatically performs meshing of the stump geometry and assigns suitable material properties, load and boundary conditions to the model. The model was validated by comparing predicted pressure with experimentally measured values for one amputee subject. FINDINGS: The predicted pressure distribution has an root-mean-square error of 8.8 kPa compared to experimental values at 10%, 25% and 50% of the gait cycle. INTERPRETATION: Current method was able to develop a finite element model to predict interface pressure reasonably well and can be integrated with prosthetic CAD system to provide quantitative feedback to the prosthetist in an automated process.

Artificial Limbs↗

Computational fluid dynamics and stent design.

Stents are small, usually metallic tubes that are intended to prop open arteries blocked with atherosclerotic plaques. While stents have been used successfully in recent years, they still suffer from failure due to development of new tissue in stented segment (restenosis). Variations in the failure rates associated with different stent designs have led researchers to investigate the role of near-wall flow patterns. While there is no direct evidence yet, the patterns of flow stagnation as the blood flows past the stent struts may affect the restenosis process. Computational fluid dynamics (CFD) approaches are well suited for obtaining detailed information on stent flow patterns. Many CFD simulations make use of a two-dimensional model. The strong dependence of flow stagnation on stent strut spacing has been clearly demonstrated. These results have been employed to interpret the results of in vitro experiments designed to elucidate the mechanisms of restenosis.

Arteriosclerosis↗

Geometric optimization of a tissue pattern for semilunar valve reconstruction.

BACKGROUND AND AIM OF THE STUDY: A novel geometric trefoil pattern has been suggested for semilunar valve reconstruction. Optimization of the geometry must rely on an appreciation of normal anatomy and knowledge of the mechanical properties of the tissue used for the reconstruction. METHODS: Computer-assisted design (CAD) was used to create an optimized leaflet geometry based on published dimensions for normal human aortic valves. The optimized leaflet geometry was subjected to finite element analysis (FEA) to study stress distribution with pressure loading of the leaflet. In vitro function of the optimized trefoil tissue pattern is being studied by static testing initially, with physiological saline. RESULTS: An optimized leaflet geometry has been developed by CAD, and further refined by FEA. Static testing of the optimized trefoil tissue pattern shows near-normal anatomy, with no prolapse or pin wheeling, and full valve competence to 90 mmHg pressure. CONCLUSIONS: An initial optimized geometry has been developed for a two-dimensional tissue pattern that can be used to reconstruct diseased semilunar heart valves with human pericardium. Optimization studies are based on the mechanical properties of the tissue, CAD to mimic normal anatomy, FEA to study stress distribution, and static load testing to confirm function.

Animals↗

Mathematical three-dimensional solid modeling of biventricular geometry.

The characterization of regional myocardial stress distribution has been limited by the use of idealized mathematical representations of biventricular geometry. State-of-the-art computer-aided design and engineering (CAD/CAE) techniques can be used to create complete, unambiguous mathematical representations (solid models) of complex object geometry that are suitable for a variety of applications, including stress-strain analyses. We have used advanced CAD/CAE software to create a 3-D solid model of the biventricular unit using planar geometric data extracted from an ex vivo canine heart. Volumetric analysis revealed global volume errors of 4.7%, -1.3%, -1.6%, and -1.1% for the left ventricular cavity, right ventricular cavity, myocardial wall, and total enclosed volumes, respectively. Model errors for 34 in-plane area and circumference determinations (mean +/- SD) were 5.3 +/- 6.7% and 3.8 +/- 2.7%. Error analysis suggested that model volume errors may be due to operator variability. These results demonstrate that solid modeling of the ex vivo biventricular unit yields an accurate mathematical representation of myocardial geometry which is suitable for meshing and subsequent finite element analysis. The use of CAD/CAE solid modeling in the representation of biventricular geometry may thereby facilitate the characterization of regional myocardial stress distribution.

Animals↗

Measurements of tooth movements in relation to single-implant restorations during 16 years: a case report.

BACKGROUND: Osseointegrated implants behave as ankylotic abutments, and their positions are not affected by dentofacial changes. PURPOSE: To measure changes in occlusion in relation to single implants in one patient after more than 15 years in function. MATERIALS AND METHODS: One 25-year-old female was treated with two single implants in the upper central incisor and bicuspid area after trauma. Study casts made prior to treatment (1987) and after 16 years in function (2004) were scanned by means of an optical scanner. Using the palate as the reference, the models were placed in the same coordinate system and analyzed and compared in a computer-aided design (CAD) program. The results of the measurements of the casts were also compared with clinical photographs taken at the time of treatment (1988), after 9 years (1997), and after 16 years (2004) in function. RESULTS: The clinical photographs showed obvious signs of implant infraposition after 9 years. New crowns were made in the incisor region after 15 years (2002), but signs of infraposition were again present at the final examination (2004). Measurements of the casts indicated small tooth movements with a pattern of slight eruption of upper teeth combined with a palatal inclination, mesial drift, and lingual inclination and crowding of the lower anterior teeth. The small measured vertical eruption of the teeth was less than the observed clinical infraposition of the implant crowns, indicating that the vertical position of the palatal may have changed in relation to the implants as well. CONCLUSION: Obvious dentofacial changes may take place in adult patients. Teeth may adjust for this, and no major problems may arise in the dentate patient. However, because the positions of implants are not affected by dentofacial changes, other patterns of clinical problems can be seen when implant patients present with these changes. The character and frequency of these dentofacial changes that may compromise implant treatment in the long term are not yet known.

Adult↗

The muscle standardized femur: a step forward in the replication of numerical studies in biomechanics.

The standardized femur is the computer aided design (CAD) solid model of a synthetic human femur, commonly used in experiments in vitro, available in the public domain through the International Society of Biomechanics Finite Element Mesh Repository. Currently used by hundreds of researchers, it was made available to simplify the experimental cross-validation of numerical studies as well as their replication by other researchers. One aspect that the standardized femur left uncovered is the definition of muscles and ligaments. In particular, for a variety of simulations it would be extremely useful to map on to the femoral surface the insertion of the principal muscles. The aim of the present study was to create a new solid model, called the muscle standardized femur, where the femoral insertion of each muscle is mapped on to the surface of the femur. Published data on muscle insertion morphometry were registered to the model by applying an affine scaling defined on bone landmarks. Good agreement was found with another similar study in which only the insertion centres were defined. The new model will be made available in the public domain for no-profit uses. When combined with published data on the direction and intensity of muscular forces this model is expected to make a useful contribution to the steadily growing library of models and data sets made available to the biomechanical community.

Anatomy, Cross-Sectional↗