Visuohaptic Simulation of a Borescope for Aircraft Engine Inspection

Consisting of a long, fiber optic probe containing a small CCD camera controlled by hand-held articulation interface, a video borescope is used for remote visual inspection of hard to reach components in an aircraft. The knowledge and psychomotor skills, specifically the hand-eye coordination, required for effective inspection are hard to acquire through limited exposure to the borescope in aviation maintenance schools. Inexperienced aircraft maintenance technicians gain proficiency through repeated hands-on learning in the workplace along a steep learning curve while transitioning from the classroom to the workforce. Using an iterative process combined with focused user evaluations, this dissertation details the design, implementation and evaluation of a novel visuohaptic simulator for training novice aircraft maintenance technicians in the task of engine inspection using a borescope. First, we describe the development of the visual components of the simulator, along with the acquisition and modeling of a representative model of a {PT-6} aircraft engine. Subjective assessments with both expert and novice aircraft maintenance engineers evaluated the visual realism and the control interfaces of the simulator. In addition to visual feedback, probe contact feedback is provided through a specially designed custom haptic interface that simulates tip contact forces as the virtual probe intersects with the {3D} model surfaces of the engine. Compared to other haptic interfaces, the custom design is unique in that it is inexpensive and uses a real borescope probe to simulate camera insertion and withdrawal. User evaluation of this simulator with probe tip feedback suggested a trend of improved performance with haptic feedback. Next, we describe the development of a physically-based camera model for improved behavioral realism of the simulator. Unlike a point-based camera, the enhanced camera model simulates the interaction of the borescope probe, including multiple points of contact along the length of the probe. We present visual comparisons of a real probe\u27s motion with the simulated probe model and develop a simple algorithm for computing the resultant contact forces. User evaluation comparing our custom haptic device with two commonly available haptic devices, the Phantom Omni and the Novint Falcon, suggests that the improved camera model as well as probe contact feedback with the 3D engine model plays a significant role in the overall engine inspection process. Finally, we present results from a skill transfer study comparing classroom-only instruction with both simulator and hands-on training. Students trained using the simulator and the video borescope completed engine inspection using the real video borescope significantly faster than students who received classroom-only training. The speed improvements can be attributed to reduced borescope probe maneuvering time within the engine and improved psychomotor skills due to training. Given the usual constraints of limited time and resources, simulator training may provide beneficial skills needed by novice aircraft maintenance technicians to augment classroom instruction, resulting in a faster transition into the aviation maintenance workforce

Evaluation of Motion Artifact Metrics for Coronary CT Angiography

Purpose This study quantified the performance of coronary artery motion artifact metrics relative to human observer ratings. Motion artifact metrics have been used as part of motion correction and best‐phase selection algorithms for Coronary Computed Tomography Angiography (CCTA). However, the lack of ground truth makes it difficult to validate how well the metrics quantify the level of motion artifact. This study investigated five motion artifact metrics, including two novel metrics, using a dynamic phantom, clinical CCTA images, and an observer study that provided ground‐truth motion artifact scores from a series of pairwise comparisons. Method Five motion artifact metrics were calculated for the coronary artery regions on both phantom and clinical CCTA images: positivity, entropy, normalized circularity, Fold Overlap Ratio (FOR), and Low‐Intensity Region Score (LIRS). CT images were acquired of a dynamic cardiac phantom that simulated cardiac motion and contained six iodine‐filled vessels of varying diameter and with regions of soft plaque and calcifications. Scans were repeated with different gantry start angles. Images were reconstructed at five phases of the motion cycle. Clinical images were acquired from 14 CCTA exams with patient heart rates ranging from 52 to 82 bpm. The vessel and shading artifacts were manually segmented by three readers and combined to create ground‐truth artifact regions. Motion artifact levels were also assessed by readers using a pairwise comparison method to establish a ground‐truth reader score. The Kendall\u27s Tau coefficients were calculated to evaluate the statistical agreement in ranking between the motion artifacts metrics and reader scores. Linear regression between the reader scores and the metrics was also performed. Results On phantom images, the Kendall\u27s Tau coefficients of the five motion artifact metrics were 0.50 (normalized circularity), 0.35 (entropy), 0.82 (positivity), 0.77 (FOR), 0.77(LIRS), where higher Kendall\u27s Tau signifies higher agreement. The FOR, LIRS, and transformed positivity (the fourth root of the positivity) were further evaluated in the study of clinical images. The Kendall\u27s Tau coefficients of the selected metrics were 0.59 (FOR), 0.53 (LIRS), and 0.21 (Transformed positivity). In the study of clinical data, a Motion Artifact Score, defined as the product of FOR and LIRS metrics, further improved agreement with reader scores, with a Kendall\u27s Tau coefficient of 0.65. Conclusion The metrics of FOR, LIRS, and the product of the two metrics provided the highest agreement in motion artifact ranking when compared to the readers, and the highest linear correlation to the reader scores. The validated motion artifact metrics may be useful for developing and evaluating methods to reduce motion in Coronary Computed Tomography Angiography (CCTA) images

Genetic and biochemical analyses of Hsp70-Hsp40 interactions in Saccharomyces cerevisiae provide insights into specificity and mechanisms of regulation

Heat shock proteins of 70kDa (Hsp70s) and their J domain-containing Hsp40 cofactors are conserved chaperone pairs that facilitate diverse cellular processes. One essential Hsp70 in the endoplasmic reticulum (ER) lumen, BiP (Kar2p in yeast), participates in polypeptide translocation into the ER, protein folding, and ER-associated degradation (ERAD). Like other Hsp70s, BiP contains an N-terminal ATPase domain, followed by a substrate binding domain and a C-terminal lid domain. To better define how substrate affinity and Hsp40 interaction affect BiP function, I constructed and characterized a mutation, R217A, in the putative J domain-interacting surface of yeast BiP. The mutation compromises ATPase stimulation by Sec63p, an Hsp40 required for translocation, but stimulation by Jem1p, an Hsp40 required for ERAD, is robust. In accordance with these data, yeast expressing R217A BiP exhibit translocation defects, but no ERAD defects, and a genetic interaction study using this mutant yielded data consistent with defects in translocation. In contrast, mutations in the substrate binding domain that either disrupt an ionic contact with the lid or remove this domain are deficient for peptide-stimulated ATPase activity. Expression of these mutants in yeast results in varying translocation and ERAD defects. Taken together, these data indicate that BiP can distinguish between its ER-resident cochaperones, and that optimal substrate binding is a key determinant of BiP function.Next, I tested the hypothesis that the functional specificity of Hsp70s is regulated by cognate Hsp40s. If this is true, one might expect divergent Hsp70-Hsp40 pairs to be unable to function in vivo. However, I discovered that a mammalian ER-lumenal Hsp40, ERdj3, when directed to the yeast cytosol, was able to rescue the temperature-sensitive growth phenotype of yeast containing mutant alleles in two cytosolic Hsp40s, HLJ1 and YDJ1. Moreover, ERdj3 activated the ATPase activity of Ssa1p, the yeast cytosolic Hsp70 that partners with Hlj1p and Ydj1p. Intriguingly, ERdj3 mutants that were compromised for substrate binding were unable to rescue the hlj1ydj1 growth defect, even though they stimulated Ssa1p ATPase activity. These data suggest that the substrate binding properties of certain Hsp40s—not simply the formation of unique Hsp70-Hsp40 pairs—is critical to specify in vivo function

Team Blueberries - Chicago Farmers Market Collective Market Research

In order to answer our business question: How might the Chicago Farmers Market Collective create a Unified Digital Marketing Strategy? Our team has conducted qualitative and quantitative research as well as end-user focus groups for the Chicago Farmers Market Collective. CFMC wants to determine their target market and attain a platform for connecting their customers to their vendors, while making the experience welcoming and equitable for all

Sarcoglycanopathies: molecular pathogenesis and therapeutic prospects

Sarcoglycanopathies are a group of autosomal recessive muscle-wasting disorders caused by genetic defects in one of four cell membrane glycoproteins, α-, β-, γ- or δ-sarcoglycan. These four sarcoglycans form a subcomplex that is closely linked to the major dystrophin-associated protein complex, which is essential for membrane integrity during muscle contraction and provides a scaffold for important signalling molecules. Proper assembly, trafficking and targeting of the sarcoglycan complex is of vital importance, and mutations that severely perturb tetramer formation and localisation result in sarcoglycanopathy. Gene defects in one sarcoglycan cause the absence or reduced concentration of the other subunits. Most genetic defects generate mutated proteins that are degraded through the cell's quality control system; however, in many cases, conformational modifications do not affect the function of the protein, yet it is recognised as misfolded and prematurely degraded. Recent evidence shows that misfolded sarcoglycans could be rescued to the cell membrane by assisting their maturation along the ER secretory pathway. This review summarises the etiopathogenesis of sarcoglycanopathies and highlights the quality control machinery as a potential pharmacological target for therapy of these genetic disorders

Discovery of a new predominant cytosine DNA modification that is linked to gene expression in malaria parasites

International audienceDNA cytosine modifications are key epigenetic regulators of cellular processes in mammalian cells, with their misregulation leading to varied disease states. In the human malaria parasite Plasmodium falciparum, a unicellular eukaryotic pathogen, little is known about the predominant cytosine modifications, cytosine methylation (5mC) and hydroxymethylation (5hmC). Here, we report the first identification of a hydroxymethylcytosine-like (5hmC-like) modification in P. falciparum asexual blood stages using a suite of biochemical methods. In contrast to mammalian cells, we report 5hmC-like levels in the P. falciparum genome of 0.2–0.4%, which are significantly higher than the methylated cytosine (mC) levels of 0.01–0.05%. Immunoprecipitation of hydroxymethylated DNA followed by next generation sequencing (hmeDIP-seq) revealed that 5hmC-like modifications are enriched in gene bodies with minimal dynamic changes during asexual development. Moreover, levels of the 5hmC-like base in gene bodies positively correlated to transcript levels, with more than 2000 genes stably marked with this modification throughout asexual development. Our work highlights the existence of a new predominant cytosine DNA modification pathway in P. falciparum and opens up exciting avenues for gene regulation research and the development of antimalarial

Crystallization and preliminary X-ray diffraction analysis of the Sel1-like repeats of SEL1L

Terminally misfolded or unassembled proteins are selectively recognized and cleared by the ER-associated degradation (ERAD) pathway. Suppressor/enhancer of lin-12-like (SEL1L), a component of the dislocation machinery containing the E3 ubiquitin ligase Hrd1, plays an important role in selecting and transporting ERAD substrates for degradation in the endoplasmic reticulum. In this study, the purification, crystallization and preliminary X-ray diffraction analysis of recombinant mouse SEL1L (residues 348-533) are reported. The crystals were obtained by the hanging-drop vapour-diffusion method at pH 8.5 and 277 K using 30% 2-propanol as a precipitant. Optimized crystals diffracted to 3.3 angstrom resolution at a synchrotron-radiation source. Preliminary X-ray diffraction analysis revealed that the crystals belonged to space group P2(1) and contained four molecules per asymmetric unit, with a solvent content of 44%.open0

Environmental Stresses Induce Misfolded Protein Aggregation in Plant Cells in a Microtubule-Dependent Manner

Misfolded protein aggregation in mammalian cells is one of the cellular responses to environmental stresses. However, the aggregation of misfolded proteins in plant cells exposed to environmental stresses is still poorly understood. Here, we report the misfolded protein aggregation in plant cells in response to environmental stresses, including ultraviolet (UV) radiation, heat stress and cold stress. Treatment of grape and tobacco cultured cells with MG-132, a proteasome inhibitor, induced misfolded protein aggregation. All of the environmental stresses examined induced the endoplasmic reticulum (ER) stress response in the cells. The cells under ER stress showed aggregation of misfolded proteins. The misfolded protein aggregation was completely inhibited by treatment of the cells with trichostatin A or colchicine, suggesting that the misfolded proteins might be aggregated in plant cells in a microtubule-dependent manner. Detected aggregates were initially observed immediately after exposure to the environmental stresses (1 min after UV radiation, 5 min after heat stress exposure, and 15 min after cold stress exposure). Based on these findings, we hypothesize that environmental stresses induce misfolded protein aggregation in plant cells in a microtubule-dependent manner