- Browse by Subject
Browsing by Subject "Models, Biological"
Now showing 1 - 7 of 7
Results Per Page
Sort Options
Item An analytical approach to 3D orthodontic load systems(The Angle Orthodontist, 2014-09) Katona, Thomas R.; Isikbay, Serkis C.; Chen, Jie; Department of Orthodontics and Oral Facial Genetics, IU School of DentistryOBJECTIVE: To present and demonstrate a pseudo three-dimensional (3D) analytical approach for the characterization of orthodontic load (force and moment) systems. MATERIALS AND METHODS: Previously measured 3D load systems were evaluated and compared using the traditional two-dimensional (2D) plane approach and the newly proposed vector method. RESULTS: Although both methods demonstrated that the loop designs were not ideal for translatory space closure, they did so for entirely different and conflicting reasons. CONCLUSIONS: The traditional 2D approach to the analysis of 3D load systems is flawed, but the established 2D orthodontic concepts can be substantially preserved and adapted to 3D with the use of a modified coordinate system that is aligned with the desired tooth translation.Item A Comparison of Frictional Forces During Simulated Cuspid Retraction on a Continuous Edgewise Archwire(1982) Allai, W. Wesley; Garner, LaForrest D.; Sondhi, Anoop; Shanks, James C.; Swartz, Marjorie L.; Barton, PaulThis investigation was designed to compare the force (grams) required to overcome a simulated cuspid retraction assembly capable of three dimensional control during the retraction process. It was hypothesized that a significant difference in the mean retraction values exists between the newer orthodontic alloys of Nitinol, Beta-Titanium, as well as Stainless Steel. One hundred eighty bracket and archwire combinations were examined as follows: Sample # Wire Cross-section Wire Material 30 .016”x.022” Stainless Steel 30 .017”x.025” ” 30 .016”x.022” Nitinol 30 .017”x.025” ” 30 .016”x.022 Beta-Titanium (TMA) 30 .017”x.025” ” A statistically significant difference was shown to exist between all six groups examined regarding the variables of wire size and wire material. The statistical analysis revealed that increasing rectangular archwire cross-sectional size from .016"x.022" to .017"x.025” rectangular wire when simulating canine retraction using an .018" slotted Lewis bracket will lead to significantly greater functional forces. The analysis of wire materials indicated that a significant difference (p=.01) exists between rectangular Beta-Titanium (TMA), Nitinol, and stainless steel during simulated cuspid retraction utilizing a narrow .018" Lewis bracket ligated with A-lastik ligatures. The least frictional force was observed with the .016"x.022" stainless steel test cells. The largest frictional force was found in the .017”'x.025" Beta-Titanium retraction specimens. Nitinol revealed force data intermediate between stainless steel and Beta-Titanium. The maximum resistance assembly developed 2.3 times the minimum frictional force observed. The mean grams of frictional force within these test cells ranged from 55.03 grams for the .016"x.022" retraction assembly to 132.68 grams for the .017"x.025" Beta-Titanium assembly. A topographical scanning electron microscope survey of the brackets and archwires utilized was included to provide qualitative insights into the quantitative results described.Item Constructal law of vascular trees for facilitation of flow(PLoS, 2014-12-31) Razavi, Mohammad S.; Shirani, Ebrahim; Salimpour, Mohammad Reza; Kassab, Ghassan S.; Department of Biomedical Engineering, School of Engineering and TechnologyDiverse tree structures such as blood vessels, branches of a tree and river basins exist in nature. The constructal law states that the evolution of flow structures in nature has a tendency to facilitate flow. This study suggests a theoretical basis for evaluation of flow facilitation within vascular structure from the perspective of evolution. A novel evolution parameter (Ev) is proposed to quantify the flow capacity of vascular structures. Ev is defined as the ratio of the flow conductance of an evolving structure (configuration with imperfection) to the flow conductance of structure with least imperfection. Attaining higher Ev enables the structure to expedite flow circulation with less energy dissipation. For both Newtonian and non-Newtonian fluids, the evolution parameter was developed as a function of geometrical shape factors in laminar and turbulent fully developed flows. It was found that the non-Newtonian or Newtonian behavior of fluid as well as flow behavior such as laminar or turbulent behavior affects the evolution parameter. Using measured vascular morphometric data of various organs and species, the evolution parameter was calculated. The evolution parameter of the tree structures in biological systems was found to be in the range of 0.95 to 1. The conclusion is that various organs in various species have high capacity to facilitate flow within their respective vascular structures.Item How to Choose In Vitro Systems to Predict In Vivo Drug Clearance: A System Pharmacology Perspective(Hindawi Publishing Corporation, 2015) Wang, Lei; Chiang, ChienWei; Liang, Hong; Wu, Hengyi; Feng, Weixing; Quinney, Sara K.; Li, Jin; Li, Lang; Department of Obstetrics and Gynecology, IU School of MedicineThe use of in vitro metabolism data to predict human clearance has become more significant in the current prediction of large scale drug clearance for all the drugs. The relevant information (in vitro metabolism data and in vivo human clearance values) of thirty-five drugs that satisfied the entry criteria of probe drugs was collated from the literature. Then the performance of different in vitro systems including Escherichia coli system, yeast system, lymphoblastoid system and baculovirus system is compared after in vitro-in vivo extrapolation. Baculovirus system, which can provide most of the data, has almost equal accuracy as the other systems in predicting clearance. And in most cases, baculovirus system has the smaller CV in scaling factors. Therefore, the baculovirus system can be recognized as the suitable system for the large scale drug clearance prediction.Item Model-Based Individualized Treatment of Chemotherapeutics: Bayesian Population Modeling and Dose Optimization(Public Library of Science, 2015) Jayachandran, Devaraj; Laínez-Aguirre, José; Rundell, Ann; Vik, Terry; Hannemann, Robert; Reklaitis, Gintaras; Ramkrishna, Doraiswami; Department of Pediatrics, IU School of Medicine6-Mercaptopurine (6-MP) is one of the key drugs in the treatment of many pediatric cancers, auto immune diseases and inflammatory bowel disease. 6-MP is a prodrug, converted to an active metabolite 6-thioguanine nucleotide (6-TGN) through enzymatic reaction involving thiopurine methyltransferase (TPMT). Pharmacogenomic variation observed in the TPMT enzyme produces a significant variation in drug response among the patient population. Despite 6-MP's widespread use and observed variation in treatment response, efforts at quantitative optimization of dose regimens for individual patients are limited. In addition, research efforts devoted on pharmacogenomics to predict clinical responses are proving far from ideal. In this work, we present a Bayesian population modeling approach to develop a pharmacological model for 6-MP metabolism in humans. In the face of scarcity of data in clinical settings, a global sensitivity analysis based model reduction approach is used to minimize the parameter space. For accurate estimation of sensitive parameters, robust optimal experimental design based on D-optimality criteria was exploited. With the patient-specific model, a model predictive control algorithm is used to optimize the dose scheduling with the objective of maintaining the 6-TGN concentration within its therapeutic window. More importantly, for the first time, we show how the incorporation of information from different levels of biological chain-of response (i.e. gene expression-enzyme phenotype-drug phenotype) plays a critical role in determining the uncertainty in predicting therapeutic target. The model and the control approach can be utilized in the clinical setting to individualize 6-MP dosing based on the patient's ability to metabolize the drug instead of the traditional standard-dose-for-all approach.Item Modular synthesis of biologically active phosphatidic acid probes using click chemistry(Royal Society of Chemistry, 2009-09) Smith, Matthew D.; Sudhahar, Christopher G.; Gong, Denghuang; Stahelin, Robert V.; Best, Michael D.; Biochemistry and Molecular Biology, School of MedicinePhosphatidic acid (PA) is an important signaling lipid that plays roles in a range of biological processes including both physiological and pathophysiological events. PA is one of a number of signaling lipids that can act as site-specific ligands for protein receptors in binding events that enforce membrane association and generally regulate both receptor function and subcellular localization. However, elucidation of the full scope of PA activities has proven problematic, primarily due to the lack of a consensus sequence among PA-binding receptors. Thus, experimental approaches, such as those employing lipid probes, are necessary for characterizing interactions at the molecular level. Herein, we describe an efficient modular approach to the synthesis of a range of PA probes that employs a late stage introduction of reporter groups. This strategy was exploited in the synthesis of PA probes bearing fluorescent and photoaffinity tags as well as a bifunctional probe containing both a photoaffinity moiety and an azide as a secondary handle for purification purposes. To discern the ability of these PA analogs to mimic the natural lipid in protein-binding properties, each compound was incorporated into vesicles for binding studies using a known PA receptor, the C2 domain of PKCalpha. In these studies, each compound exhibited binding properties that were comparable to those of synthetic PA, indicating their viability as probes for effectively studying the activities of PA in cellular processes.Item Statistical Analysis of Zebrafish Locomotor Response(PLOS, 2015-10-05) Liu, Yiwen; Carmer, Robert; Zhang, Gaonan; Venkatraman, Prahatha; Brown, Skye Ashton; Pang, Chi-Pui; Zhang, Mingzh; Ma, Ping; Leung, Yuk Fai; Biological Sciences, Purdue UniversityZebrafish larvae display rich locomotor behaviour upon external stimulation. The movement can be simultaneously tracked from many larvae arranged in multi-well plates. The resulting time-series locomotor data have been used to reveal new insights into neurobiology and pharmacology. However, the data are of large scale, and the corresponding locomotor behavior is affected by multiple factors. These issues pose a statistical challenge for comparing larval activities. To address this gap, this study has analyzed a visually-driven locomotor behaviour named the visual motor response (VMR) by the Hotelling's T-squared test. This test is congruent with comparing locomotor profiles from a time period. Different wild-type (WT) strains were compared using the test, which shows that they responded differently to light change at different developmental stages. The performance of this test was evaluated by a power analysis, which shows that the test was sensitive for detecting differences between experimental groups with sample numbers that were commonly used in various studies. In addition, this study investigated the effects of various factors that might affect the VMR by multivariate analysis of variance (MANOVA). The results indicate that the larval activity was generally affected by stage, light stimulus, their interaction, and location in the plate. Nonetheless, different factors affected larval activity differently over time, as indicated by a dynamical analysis of the activity at each second. Intriguingly, this analysis also shows that biological and technical repeats had negligible effect on larval activity. This finding is consistent with that from the Hotelling's T-squared test, and suggests that experimental repeats can be combined to enhance statistical power. Together, these investigations have established a statistical framework for analyzing VMR data, a framework that should be generally applicable to other locomotor data with similar structure.