Integrated transcriptional profiling and linkage analysis for disease gene identification in a rat model of metabolic syndrome

Development of the metabolic syndrome is detennined by a complex interaction of environmental and genetic factors and as with other complex human traits, disease gene identification is problematic due to a lack of statistical power and genetic heterogeneity in patients. Identifying genes' that underlie metabolic syndrome risk factors will allow better understanding and development of treatments which would decrease disease health burden. The spontaneously hypertensive rat (SHR) is a widely studied model of insulin resistance and hypertension and, as in humans, the hypertensive phenotype clusters with metabolic traits. SHR was crossed with nonnotensive Brown Norway rats to develop the BXHIHXB recombinant inbred (RI) strain panel. . In these studies this RI panel is being used to identify genomic regions influencing gene expression, tenned expression quantitative trait loci- (eQTL). Affymetrix microarray expression profiles from two tissues (fat and kidney) in the RI and parental strains were generated. Transcript abundance for each gene on the microarray was treated as a quantitative trait and these eQTL were defined as: cis-acting, and trans-acting. This work examines a subset of cis-acting eQTL (P<lO-4) to look for polymorphisms in the putative promoters of these genes. These polymorphisms may cause the differential expression detected in these strains and underlie the phenotypic variation seen. In silico comparative mapping was carried out to investigate the applicability of the detected rat cis-acting eQTL genes to human disease. This used human QTL for metabolic and cardiovascular phenotypes to identify rat cis-acting eQTL and their human orthologs as potential candidate genes. This analysis detected several genes with known involvement in human metabolic syndrome phenotypes and a large number of novel candidate genes that merit testing in human populations. The results demonstrate an integrated genome-wide expression profiling with linkage analysis approach and its use in identification of candidate genes which may underlie complex traits.Imperial Users onl

Excavations at Iona Abbey 2017: Data Structure Report

Initial summary of 2017 excavations at Iona Abbey

Feedback Synthesis for Controllable Underactuated Systems using Sequential Second Order Actions

This paper derives nonlinear feedback control synthesis for general control affine systems using second-order actions---the needle variations of optimal control---as the basis for choosing each control response to the current state. A second result of the paper is that the method provably exploits the nonlinear controllability of a system by virtue of an explicit dependence of the second-order needle variation on the Lie bracket between vector fields. As a result, each control decision necessarily decreases the objective when the system is nonlinearly controllable using first-order Lie brackets. Simulation results using a differential drive cart, an underactuated kinematic vehicle in three dimensions, and an underactuated dynamic model of an underwater vehicle demonstrate that the method finds control solutions when the first-order analysis is singular. Moreover, the simulated examples demonstrate superior convergence when compared to synthesis based on first-order needle variations. Lastly, the underactuated dynamic underwater vehicle model demonstrates the convergence even in the presence of a velocity field.Comment: 9 page

Omnidirectional Sensory and Motor Volumes in Electric Fish

Active sensing organisms, such as bats, dolphins, and weakly electric fish, generate a 3-D space for active sensation by emitting self-generated energy into the environment. For a weakly electric fish, we demonstrate that the electrosensory space for prey detection has an unusual, omnidirectional shape. We compare this sensory volume with the animal's motor volume—the volume swept out by the body over selected time intervals and over the time it takes to come to a stop from typical hunting velocities. We find that the motor volume has a similar omnidirectional shape, which can be attributed to the fish's backward-swimming capabilities and body dynamics. We assessed the electrosensory space for prey detection by analyzing simulated changes in spiking activity of primary electrosensory afferents during empirically measured and synthetic prey capture trials. The animal's motor volume was reconstructed from video recordings of body motion during prey capture behavior. Our results suggest that in weakly electric fish, there is a close connection between the shape of the sensory and motor volumes. We consider three general spatial relationships between 3-D sensory and motor volumes in active and passive-sensing animals, and we examine hypotheses about these relationships in the context of the volumes we quantify for weakly electric fish. We propose that the ratio of the sensory volume to the motor volume provides insight into behavioral control strategies across all animals