Segmentation and Strain Mapping of a Beating Heart

Conventional methods of estimating deformation optically often compare image intensities before and after deformation to help estimate the strain fields. However, these current meth ods often introduce undesirable error that propagates through the system, growing larger through each strain calculation. These errors create false, concentrated regions of strain throughout the image. Additionally, gathering and evaluating images in three- and four dimensional space creates even more difficulty for conventional methods. Here, by imple menting new techniques of gathering four-dimensional ultrasound data sets and calculating deformation fields with traditional errors reduced three-fold, four-dimensional images were evaluated to create a novel visualization tool used for representing the strains in a four dimensional modeling world. In general, this computer program has applications across a wide range of disciplines

MEMS 411 Senior Design: Wind Powered Walking Robot

Build a ‘Machine That Walks’ using leg like linkages that is only powered by wind. It must walk a minimum of 4 meters to prove that it is capable of walking and at least half of the materials used must be recyclable or reusable within the greater St. Louis area. The machine must not exceed 10 kg and must fit in the volume of 30 cm x 60 cm x 40 cm and must be unable to be easily knocked over

In Vitro Approach to Assess the Potential for Risk of Idiosyncratic Adverse Reactions Caused by Candidate Drugs

Idiosyncratic adverse drug reactions (IADRs) in humans can result in a broad range of clinically significant toxicities leading to attrition during drug development as well as postlicensing withdrawal or labeling. IADRs arise from both drug and patient related mechanisms and risk factors. Drug related risk factors, resulting from parent compound or metabolites, may involve multiple contributory mechanisms including organelle toxicity, effects related to compound disposition, and/or immune activation. In the current study, we evaluate an <i>in vitro</i> approach, which explored both cellular effects and covalent binding (CVB) to assess IADR risks for drug candidates using 36 drugs which caused different patterns and severities of IADRs in humans. The cellular effects were tested in an <i>in vitro</i> Panel of five assays which quantified (1) toxicity to THLE cells (SV40 T-antigen-immortalized human liver epithelial cells), which do not express P450s, (2) toxicity to a THLE cell line which selectively expresses P450 3A4, (3) cytotoxicity in HepG2 cells in glucose and galactose media, which is indicative of mitochondrial injury, (4) inhibition of the human bile salt export pump, BSEP, and (5) inhibition of the rat multidrug resistance associated protein 2, Mrp2. In addition, the CVB Burden was estimated by determining the CVB of radiolabeled compound to human hepatocytes and factoring in both the maximum prescribed daily dose and the fraction of metabolism leading to CVB. Combining the aggregated results from the <i>in vitro</i> Panel assays with the CVB Burden data discriminated, with high specificity (78%) and sensitivity (100%), between 27 drugs, which had severe or marked IADR concern, and 9 drugs, which had low IADR concern, we propose that this integrated approach has the potential to enable selection of drug candidates with reduced propensity to cause IADRs in humans

Biofilm differentiation and dispersal in mucoid pseudomonas aeruginosa isolates from patients with cystic fibrosis

Intractable biofilm infections with Pseudomonas aeruginosa are the major cause of premature death associated with cystic fibrosis (CF). Few studies have explored the biofilm developmental cycle of P. aeruginosa isolates from chronically infected individuals. This study shows that such clinical isolates exhibit biofilm differentiation and dispersal processes similar to those of the better-studied laboratory P. aeruginosa strain PAO1 in the glass flow-cell (continuous-culture) biofilm model, albeit they are initially less adherent and their microcolonies are slower to develop and show heterogeneous, strain-specific variations in architecture. Confocal scanning laser microscopy combined with LIVE/DEAD viability staining revealed that in all CF biofilms bacterial cell death occurred in maturing biofilms, extending from the substratum to the central regions of mature microcolonies to varying degrees, depending on the strain. Bacteriophage activity was detected in the maturing biofilms of all CF strains examined and the amount of phage produced paralleled the degree of cell death seen in the biofilm. Some CF strains exhibited 'seeding dispersal' associated with the above phenomena, producing 'hollowing' as motile cells evacuated from the microcolony interiors as has been described for strain PAO1. Moreover, morphotypic cell variants were seen in the biofilm effluents of all CF strains. For those CF strains where marked cell death and seeding dispersal occurred in the microcolonies, variants were more diverse (up to five morphotypes) compared to those of strain PAO1 (two morphotypes). Given that variants of strain PAO1 have enhanced colonization traits, it seems likely that the similar biofilm dispersal events described here for CF strains contribute to the variability seen in clinical isolates and the overall persistence of the P. aeruginosa in the CF airwa