Computer-generated Models Research Articles

Rapid Enzyme-Linked Immunosorbent Assay and Colloidal Gold Immunoassay for Kanamycin and Tobramycin in Swine Tissues

A monoclonal antibody (Mab) was produced by using the kanamycin-glutaraldehyde-bovine serum albumin (Kan-GDA-BSA) conjugate as the immunogen. The anti-Kan Mab exhibited high cross-reactivity with tobramycin (Tob) and slight or negligible cross-reactivity with other aminoglycosides. The specificity and cross-reactivity of this Mab are discussed regarding the three-dimensional, computer-generated molecular models of the aminoglycosides. Using this Mab, a rapid enzyme-linked immunosorbent assay (ELISA) and a colloidal gold-based strip test for Kan and Tob were developed. The rapid ELISA showed a 50% inhibition value (IC 50) of 0.83 ng/mL for Kan and 0.89 ng/mL for Tob with the analysis time less than 40 min, and the recoveries from spiked swine tissues at levels of 25-200 microg/kg ranged from 52% to 96% for Kan and 61% to 86% for Tob. In contrast, the strip test for Kan or Tob had a visual detection limit of 5 ng/mL in PBS, 50 microg/kg in meat or liver, and 100 microg/kg in kidney, and the results can be judged within 5-10 min. Observed positive samples judged by the strip test can be further quantitated by ELISA, hence the two assays can complement each other for rapid detection of residual Kan and Tob in swine tissues. Moreover, physical-chemical factors that affected the ELISA and strip test performance were also investigated. The effect of pH and antibody amount for gold-antibody conjugation on the strip test sensitivity was determined followed by a theoretical explanation of the effects.

Extended-Release Tramadol (ULTRAM®ER): A Pharmacotherapeutic, Pharmacokinetic, and Pharmacodynamic Focus on Effectiveness and Safety in Patients with Chronic/Persistent Pain

Tramadol is a centrally acting synthetic opioid analgesic that has a dual mechanism of action, binding to mu-opioid receptors and weakly inhibiting the neuronal reuptake of norepinephrine and serotonin. Extended-release (ER) tramadol tablets (ULTRAM ER) are indicated for the management of moderate to moderately severe chronic (also referred to as persistent) pain in adults who require around-the-clock treatment of pain for an extended period of time. Because once-daily tramadol ER results in less frequent fluctuations in plasma concentrations than equivalent daily doses of short-acting tramadol, it may benefit patients experiencing pain throughout the dosing interval. On the basis of computer-generated pharmacokinetic models, one can easily transition patients who are receiving short-acting tramadol for chronic/persistent pain to tramadol ER, by calculating the current total daily dose of short-acting tramadol and starting tramadol ER at the nearest lower 100-mg-dose increment. In clinical studies, tramadol ER significantly reduced pain in patients with chronic pain from osteoarthritis and improved pain-related sleep parameters, joint stiffness, and physical function. Tramadol ER has been shown to be safe and well-tolerated and may be a suitable alternative for patients with inadequate analgesic response or contraindications (eg, cardiovascular disease, gastrointestinal ulcer) to use of nonsteroidal anti-inflammatory drugs (NSAIDs) or cyclooxygenase-2 (COX-2) inhibitors. The proven efficacy and safety profile--and the low potential for abuse--make tramadol ER a viable therapeutic option for the management of chronic/persistent nonmalignant pain in some patients. This article reviews the pharmacology, pharmacokinetics, pharmacodynamics, dosage, delivery system, administration, analgesic efficacy, and safety and tolerability profile of tramadol ER.

Correction of a mandibular asymmetry using a custom-made titanium onlay

The diagnosis and treatment of facial deformities, including mandibular asymmetries, can pose a significant clinical problem. The limitations, accuracy and predictability of treatment options available and the expectations of the patient can further compound this. In this article we present a case of facial asymmetry secondary to mandibular angle deficiency corrected by the manufacture and placement of a custom-made titanium onlay. Although alternative methods were potentially available to correct this deformity, patient factors including occlusion, dental/skeletal relationship and chin position limited our options. Furthermore, construction of the custom-made titanium onlay involved the development of a computer-generated 3D virtual model and computer-aided design and computer-aided manufacture (CAD-CAM) of the inlay. This report demonstrates that this technique can be used successfully to address certain cases of facial asymmetry.

Cost-effectiveness of recombinant follicle-stimulating hormone (FSH) versus human FSH in intrauterine insemination cycles: A statistical model-derived analysis

Objective. Recently we proposed a randomized trial specifically designed to evaluate the cost-effectiveness of two different protocols of stimulation in intrauterine insemination (IUI) cycles. Computer-simulated clinical models have been developed to perform pharmacoeconomic studies, creating a decision tree in which the complex procedure is performed and repeated. The present study was designed to compare the cost-effectiveness of recombinant follicle-stimulating hormone (rFSH) and human-derived FSH (hFSH) in ovarian stimulation and to indicate which protocol should be used in IUI cycles.Study design. Two computer-generated decision tree models were constructed to compare the clinical effects and costs of rFSH versus hFSH in IUI cycles. A first decision tree model was built according to the trial previously published. In a second model, 10 000 hypothetical infertile patients were entered in a computer-generated simulation and were stimulated with two different protocols for IUI. IUI was hypothetically performed in both groups of patients with a known pregnancy, cancellation, miscarriage and abandonment rate. The two protocols were compared using a cost-effective analysis: cost-effectiveness ratios (CE) and incremental cost-effectiveness ratios (ICER) were calculated. The cost-effectiveness acceptability curve (CEAC) was constructed.Results. The overall estimated costs with each ovarian stimulation strategy in the first model demonstrated that rFSH was a less cost-effective strategy, with an ICER of [euro]13 727. The CEAC showed that at a level of [euro]0 of willingness to pay, hFSH was cost-effective in 73% of the samples while rFSH was cost-effective in 27% only. Recombinant FSH would be more cost-effective than hFSH at an effectiveness threshold of 0.170 and at a cost per cycle of [euro]235. This finding was also confirmed by the acceptability curve obtained with 10 000 Monte Carlo simulations, in which hFSH was cost-effective in about 96–98% of samples at any threshold of willingness to pay.Conclusions. This study represents the first statistical model developed with a computer-generated clinical simulation with the intent to elaborate a pharmacoeconomic comparison between rFSH and hFSH in ovarian stimulation for IUI cycles. Results demonstrated that hFSH is more cost-effective than rFSH.

Dynamics and Vibration Damping Behavior of Advanced Meso/Nanoparticle-Reinforced Composites

Nanoparticles and carbon nanotubes have wide potential applications and some of them are vibration damping and noise adsorbing composite materials. The focus in this paper is directed toward the development of the next generation of vibration damping composites, providing a manufacturing route and design concepts. The research work concentrates on an investigation related to nanoparticle-reinforced materials dynamic characterization and modelling of relationships between structure and mechanical properties of the materials across the length scales. The scope is to understand the damping mechanisms in the materials due to nanoparticles/tubes. In this paper the equilibrium equation of damping structure is described with FEM-based models and is solved with the help of a numerical code integrated in computer-based virtual-reality environment. Computational simulation and modelling tools could help to understand many physical effects and predict the behavior of materials and engineering components by computer-generated models.

Adjustment of Virtual Mannequins Through Anthropometric Measurements, Cluster Analysis, and Content-Based Retrieval of 3-D Body Scans

Computer-generated models of the human body generally do not adequately model the complex human morphology. These models, therefore, do not reflect the anthropometric realities and are not specific enough for commercial use. This paper presents an approach to adjust virtual models through the use of body measurements, as obtained from an anthropometric data set. In this approach, the measurements are used in grouping 3D body scans, which are obtained using precise optoelectronic measurement devices, into clusters. The virtual mannequins are then adjusted by using the measurements of the nearest cluster member. In this way, realistic accurate virtual mannequins are created.

The CbiB Protein of Salmonella enterica Is an Integral Membrane Protein Involved in the Last Step of the De Novo Corrin Ring Biosynthetic Pathway

We report results of studies of the conversion of adenosylcobyric acid (AdoCby) to adenosylcobinamide-phosphate, the last step of the de novo corrin ring biosynthetic branch of the adenosylcobalamin (coenzyme B12) pathway of Salmonella enterica serovar Typhimurium LT2. Previous reports have implicated the CbiB protein in this step of the pathway. Hydropathy analysis predicted that CbiB would be an integral membrane protein. We used a computer-generated topology model of the primary sequence of CbiB to guide the construction of CbiB-LacZ and CbiB-PhoA protein fusions, which were used to explore the general topology of CbiB in the cell membrane. A refined model of CbiB as an integral membrane protein is presented. In vivo analyses of the effect of single-amino-acid changes showed that periplasm- and cytosol-exposed residues are critical for CbiB function. Results of in vivo studies also show that ethanolamine-phosphate (EA-P) is a substrate of CbiB, but l-Thr-P is not, and that CbiB likely activates AdoCby by phosphorylation. The latter observation leads us to suggest that CbiB is a synthetase not a synthase enzyme. Results from mass spectrometry and bioassay experiments indicate that serovar Typhimurium synthesizes norcobalamin (cobalamin lacking the methyl group at C176) when EA-P is the substrate of CbiB.

Linear and angular measurements of computer-generated models: Are they accurate, valid, and reliable?

Traditional advanced imaging modalities such as CT and MRI are limited in their ability to perform accurate linear distance and angular measurements regardless of anatomical orientation. The construction of 3D models has been used to perform anthropometric analyses as well as in the reconstruction of rapid prototypes. We hypothesized that such measurements would be precise to within 2 mm or 2 degrees of measurements performed with a coordinate measurement machine (CMM). We also hypothesized that there would be a high degree of interobserver reliability with these measurements.Multiple aluminum screws were implanted in various positions in three foam pelvises which were subsequently scanned by CT and rendered as 3D models using a commercially available software package (Mimics). Linear and angular measurements were performed using a CMM machine, the software package, and a dial caliper or goniometer. The deviation of the measurements from the CMM data was compared using ANOVA. The interobserver reliability of both the manual and computer-generated measurements was calculated.The mean difference between the CMM distances and those measured manually and with the software was 2.12 +/- 1.20 mm and 1.57 +/- 1.05 mm, respectively. The mean difference between the CMM angular measurements and the angular measurements performed manually and with the software was 4.07 +/- 4.70 degrees and 1.62 +/- 1.32 degrees, respectively. In all cases, the manual measurements were significantly less accurate (p < 0.0001) and there was a high degree of interobserver reliability.Computer-generated measurements taken from three-dimensionally reconstructed models are more accurate than manual measurements and are within 2 mm and 2 degrees of measurements performed with a CMM. These measurements have high interobserver reliability.

Computer-Generated Animal Model Stimuli

Communication between animals is diverse and complex. Animals may communicate using auditory, seismic, chemosensory, electrical, or visual signals. In particular, understanding the constraints on visual signal design for communication has been of great interest. Traditional methods for investigating animal interactions have used basic observational techniques, staged encounters, or physical manipulation of morphology. Less intrusive methods have tried to simulate conspecifics using crude playback tools, such as mirrors, still images, or models. As technology has become more advanced, video playback has emerged as another tool in which to examine visual communication (Rosenthal, 2000). However, to move one step further, the application of computer-animation now allows researchers to specifically isolate critical components necessary to elicit social responses from conspecifics, and manipulate these features to control interactions. Here, I provide detail on how to create an animation using the Jacky dragon as a model, but this process may be adaptable for other species. In building the animation, I elected to use Lightwave 3D to alter object morphology, add texture, install bones, and provide comparable weight shading that prevents exaggerated movement. The animation is then matched to select motor patterns to replicate critical movement features. Finally, the sequence must rendered into an individual clip for presentation. Although there are other adaptable techniques, this particular method had been demonstrated to be effective in eliciting both conspicuous and social responses in staged interactions.

Computer-Generated Animal Model Stimuli

Communication between animals is diverse and complex. Animals may communicate using auditory, seismic, chemosensory, electrical, or visual signals. In particular, understanding the constraints on visual signal design for communication has been of great interest. Traditional methods for investigating animal interactions have used basic observational techniques, staged encounters, or physical manipulation of morphology. Less intrusive methods have tried to simulate conspecifics using crude playback tools, such as mirrors, still images, or models. As technology has become more advanced, video playback has emerged as another tool in which to examine visual communication (Rosenthal, 2000). However, to move one step further, the application of computer-animation now allows researchers to specifically isolate critical components necessary to elicit social responses from conspecifics, and manipulate these features to control interactions. Here, I provide detail on how to create an animation using the Jacky dragon as a model, but this process may be adaptable for other species. In building the animation, I elected to use Lightwave 3D to alter object morphology, add texture, install bones, and provide comparable weight shading that prevents exaggerated movement. The animation is then matched to select motor patterns to replicate critical movement features. Finally, the sequence must rendered into an individual clip for presentation. Although there are other adaptable techniques, this particular method had been demonstrated to be effective in eliciting both conspicuous and social responses in staged interactions.

Point mutations in the potato leafroll virus major capsid protein alter virion stability and aphid transmission

The coat protein (CP) of potato leafroll virus (PLRV) is the primary component of the capsid, and is a multifunctional protein known to be involved in vector transmission and virus movement within plant hosts, in addition to particle assembly. Thirteen mutations were generated in various regions of the CP and tested for their ability to affect virus-host and virus-vector interactions. Nine of the mutations prevented the assembly of stable virions. These mutants were unable to infect systemically four different host species. Furthermore, although virus replication and translation of the CP were similar for the mutants and wild-type virus in individual plant cells, the translation of the CP readthrough product was affected in several of the mutants. Four of the mutants were able to assemble stable particles and infect host plants systemically, similarly to the wild-type virus; however, two of the mutants were transmitted less efficiently by aphid vectors. Based on a computer-generated model of the PLRV CP, the mutations that prevented virion assembly were associated with subunit interfaces, while the amino acid alterations in the assembly-competent mutants were associated with surface loops. This and previous work indicates that the CP structural model has value in predicting the structural architecture of the virion.

Comparison of Measured and Computer-Modeled Objective Parameters for an Existing Coupled Volume Concert Hall

This paper details the comparison of a built coupled volume concert hall and a computer-generated model of the hall. Coupled volume spaces typically have an auxiliary volume connected to the main volume through an acoustically transparent aperture. In this type of space, architectural parameters such as volume size and surface absorption can be designed to produce a non-linear reverberant decay, known as double-slope decay. Objective reverberation and clarity parameters were calculated for the sound fields measured in the built hall and predicted in the computer modeled hall. These objective parameters were compared between the two modalities for several configurations of the hall to determine the accuracy of the computer modeling prediction scheme for coupled volume spaces. The results showed a high level of computer model accuracy in the high frequency range, with differences in reverberation parameters being less than 1 just noticeable difference (jnd). Lower frequencies proved computer modeling to be less accurate, particularly for the clarity parameter, which had differences up to 8 jnd.

Modeling techniques

Computer graphic artists are constantly trying to emulate the real world. A main canvas that we paint reality on is the computer generated (CG) 3D model. CG models are used in a variety of ways for many disciplines. Although uses can run the gamut from medical visualization, accident recreation and entomology, main uses of this technology lie within the realm of movie visual effects and 3D gaming. The models themselves are not always accomplished the same way, and depend greatly upon which application it is being utilized in. The main difference between the two is that the CG movie model is simply built to be seen, while its video game cousin is built to interact with.

The Immunoglobulin Heavy Chain Constant Region Affects Kinetic and Thermodynamic Parameters of Antibody Variable Region Interactions with Antigen

A central dogma in immunology is that antibody specificity is a function of the variable (V) region. However serological analysis of IgG(1), IgG(2a), and IgG(2b) switch variants of murine monoclonal antibody (mAb) 3E5 IgG(3) with identical V domains revealed apparent specificity differences for Cryptococcus neoformans glucuronoxylomannan (GXM). Kinetic and thermodynamic binding properties of mAbs 3E5 to a 12-mer peptide mimetic of GXM revealed differences in the affinity of these mAbs for a monovalent ligand, a result that implied that the constant (C) region affects the secondary structure of the antigen binding site, thus accounting for variations in specificity. Structural models of mAbs 3E5 suggested that isotype-related differences in binding resulted from amino acid sequence polymorphisms in the C region. This study implies that isotype switching is another mechanism for generating diversity in antigen binding and that isotype restriction of certain antibody responses may reflect structural constraints imposed by C region on V region binding. Furthermore, isotype affected the polyreactivity of V region identical antibodies, implying a role for C region in determining self-reactivity.

Identification, Characterization, Epitope Mapping, and Three-Dimensional Modeling of the α-Subunit of β-Conglycinin of Soybean, a Potential Allergen for Young Pigs

Soybean meal (SBM), the major byproduct of soybean oil extraction, is the main protein source for swine diets globally. In the United States, 8.6 million metric tons of SBM was used in swine rations in 2004. The pathological effect and immunological response of SBM feeding have been demonstrated in swine. In this study, we have utilized plasma collected from piglet feed with SBM in immunoblot analysis to detect proteins that elicited antigenic responses. We have identified soybean beta-conglycinin alpha-subunit as being a potential allergen for young piglets. Characterization of this protein indicated that deglycosylation and pepsin digestion did not eliminate immunoreactivity of this protein. Epitope mapping utilizing planar cellulose supports technology (SPOT) showed that three peptides spanning amino acids S185-R231 were critical for the allergenicity. A computer-generated three-dimensional structure model of the alpha-subunit of beta-conglycinin indicated that the antigenic epitopes were located on the surface of the protein. Information from this study may assist in the construction of recombinant nonallergenic soybean protein useable for both immunotherapy and the potential production of hypoallergenic soybean plants.

Hypoplastic Left Heart Syndrome

See related article, pages 1363–1370 Hypoplastic left heart syndrome (HLHS) is one of the most severe congenital heart defects, accounting for 20% to 25% of mortality in infants born with congenital heart disease. In the United States, ≈2000 infants are born each year with HLHS.1 To date, there is a paucity of studies that define the underlying genetic, molecular and cellular mechanisms of HLHS.2–4 Most cases of HLHS are thought to arise secondarily because of decreased flow into the developing embryonic left ventricle, although in some cases, abnormal left ventricular growth could be the primary defect. There is strong evidence for a genetic etiology for HLHS, although very little is understood about the genetic mechanisms underlying HLHS. Nineteen percent of first degree relatives of infants with HLHS have a congenital heart defect.5 In addition, there are several chromosomal disorders that are associated with HLHS. For example, 10% of all infants born with a terminal 11q deletion (Jacobsen syndrome) have HLHS.6 Mutations in at least one gene, the cardiac transcription factor NKX2.5, have been identified in patients with HLHS.7,8 Similar to many of the most severe congenital heart defects, treatment strategies for HLHS have evolved and are still changing. The two current surgical strategies include the three-stage Norwood/Fontan procedure, or, alternatively, cardiac transplantation. The Norwood procedure, which is performed optimally in the neonatal period to avoid the development of pulmonary vascular disease, entails reconstructing the aortic arch, transecting the pulmonary artery, anastamosing the pulmonary artery root to the reconstructed aorta, and placing a systemic to pulmonary artery shunt (either from aorta or more recently, from the right ventricle). Although there has been significant progress in outcomes, neither surgical approach is curative and long-term outcomes are uncertain. Consequently, there has been an ongoing effort to develop …

The pydA–pydB fusion gene produces an active dioxygenase–hydrolase that degrades 3-hydroxy-4-pyridone, an intermediate of mimosine metabolism

The objective of this research was to construct a pydA-pydB hybrid gene that encodes a functional dioxygenase-hydrolase (PydA-PydB) fusion protein for degradation of 3-hydroxy-4-pyridone (HP). HP is an intermediate in both synthesis and degradation of mimosine, a toxic amino acid produced by the tree legume Leucaena leucocephala. Computer-generated models of the fusion proteins suggested that joining of PydA and PydB with 0, 3, or 7 glycine residues as a linker should produce a functional PydA-PydB fusion protein. Accordingly, three hybrid genes, G0, G3, and G7, were constructed in which pydA and pydB were connected with 0, 9, and 21 nucleotides, respectively, encoding the glycine residues of the linker region. When these hybrid genes were expressed in Rhizobium and Escherichia coli, only one of them, G3, produced a functional PydA-PydB fusion protein, having both the dioxygenase and hydrolase activities. The G3 hybrid gene could complement both pydA and pydB mutants of Rhizobium, and E. coli lysate containing the overexpressed G3 protein was able to degrade HP. This hybrid gene may be useful for developing mimosine-free L. leucocephala plants in the future.

Characterization of an aluminum-filled polyamide powder for applications in selective laser sintering

Solid free-form fabrication (SFF) techniques use layer-based manufacturing to create physical objects directly from computer-generated models. Using an additive approach to manufacture shapes, SFF systems join liquid, powder or sheet materials. Selective laser sintering (SLS) is a SFF technique by which parts are built layer-by-layer offering the key advantage of the direct manufacturing of functional parts. In SLS, a laser beam is traced over the surface of a tightly compacted powder made of thermoplastic material. In this paper is characterized a new aluminum-filled polyamide powder developed for applications in SLS. This material is promising for many applications that require a metallic look of the part, good finishing properties, high stiffness and higher part quality.

Linear and angular measurements of computer-generated models: Are they accurate, valid, and reliable?

Introduction: Traditional advanced imaging modalities such as CT and MRI are limited in their ability to perform accurate linear distance and angular measurements regardless of anatomical orientation. The construction of 3D models has been used to perform anthropometric analyses as well as in the reconstruction of rapid prototypes. We hypothesized that such measurements would be precise to within 2 mm or 2° of measurements performed with a coordinate measurement machine (CMM). We also hypothesized that there would be a high degree of interobserver reliability with these measurements.Materials and Methods: Multiple aluminum screws were implanted in various positions in three foam pelvises which were subsequently scanned by CT and rendered as 3D models using a commercially available software package (Mimics). Linear and angular measurements were performed using a CMM machine, the software package, and a dial caliper or goniometer. The deviation of the measurements from the CMM data was compared using ANOVA. The interobserver reliability of both the manual and computer-generated measurements was calculated.Results: The mean difference between the CMM distances and those measured manually and with the software was 2.12 ± 1.20 mm and 1.57 ± 1.05 mm, respectively. The mean difference between the CMM angular measurements and the angular measurements performed manually and with the software was 4.07 ± 4.70° and 1.62 ± 1.32°, respectively. In all cases, the manual measurements were significantly less accurate (p < 0.0001) and there was a high degree of interobserver reliability.Conclusions: Computer-generated measurements taken from three-dimensionally reconstructed models are more accurate than manual measurements and are within 2 mm and 2° of measurements performed with a CMM. These measurements have high interobserver reliability.

Can virtual reality improve anatomy education? A randomised controlled study of a computer-generated three-dimensional anatomical ear model

The use of computer-generated 3-dimensional (3-D) anatomical models to teach anatomy has proliferated. However, there is little evidence that these models are educationally effective. The purpose of this study was to test the educational effectiveness of a computer-generated 3-D model of the middle and inner ear. We reconstructed a fully interactive model of the middle and inner ear from a magnetic resonance imaging scan of a human cadaver ear. To test the model's educational usefulness, we conducted a randomised controlled study in which 28 medical students completed a Web-based tutorial on ear anatomy that included the interactive model, while a control group of 29 students took the tutorial without exposure to the model. At the end of the tutorials, both groups were asked a series of 15 quiz questions to evaluate their knowledge of 3-D relationships within the ear. The intervention group's mean score on the quiz was 83%, while that of the control group was 65%. This difference in means was highly significant (P < 0.001). Our findings stand in contrast to the handful of previous randomised controlled trials that evaluated the effects of computer-generated 3-D anatomical models on learning. The equivocal and negative results of these previous studies may be due to the limitations of these studies (such as small sample size) as well as the limitations of the models that were studied (such as a lack of full interactivity). Given our positive results, we believe that further research is warranted concerning the educational effectiveness of computer-generated anatomical models.