Translational Retinal Research and Therapies.

The following review summarizes the state of the art in representative aspects of gene therapy/translational medicine and evolves from a symposium held at the School of Veterinary Medicine, University of Pennsylvania on November 16, 2017 honoring Dr. Gustavo Aguirre, recipient of ARVO's 2017 Proctor Medal. Focusing on the retina, speakers highlighted current work on moving therapies for inherited retinal degenerative diseases from the laboratory bench to the clinic

Homage to Rushikesh M. Maru

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68443/2/10.1177_097206349900100102.pd

Development and Demonstration of Control Strategies for a Common Rail Direct Injection Armoured Fighting Vehicle Engine

The development of a controller which can be used for engines used in armoured fighting vehicles is discussed. This involved choosing a state of the art reference common rail automotive Diesel engine and setting-up of a transient engine testing facility. The dynamometer through special real-time software was controlled to vary the engine speed and throttle position. The reference engine was first tested with its stock ECU and its bounds of operation were identified. Several software modules were developed in-house in stages and evaluated on special test benches before being integrated and tested on the reference engine. Complete engine control software was thus developed in Simulink and flashed on to an open engine controller which was then interfaced with the engine. The developed control software includes strategies for closed loop control of fuel rail pressure, boost pressure, idle speed, coolant temperature based engine de-rating, control of fuel injection timing, duration and number of injections per cycle based on engine speed and driver input. The developed control algorithms also facilitated online calibration of engine maps and manual over-ride and control of engine parameters whenever required. The software was further tuned under transient conditions on the actual engine for close control of various parameters including rail pressure, idling speed and boost pressure. Finally, the developed control strategies were successfully demonstrated and validated on the reference engine being loaded on customised transient cycles on the transient engine testing facility with inputs based on military driving conditions. The developed controller can be scaled up for armoured fighting vehicle engines

Panoramic optical and near-infrared SETI instrument: prototype design and testing

The Pulsed All-sky Near-infrared Optical Search for ExtraTerrestrial Intelligence (PANOSETI) is an instrument program that aims to search for fast transient signals (nano-second to seconds) of artificial or astrophysical origin. The PANOSETI instrument objective is to sample the entire observable sky during all observable time at optical and near-infrared wavelengths over 300 - 1650 nm$^1$. The PANOSETI instrument is designed with a number of modular telescope units using Fresnel lenses ($\sim$0.5m) arranged on two geodesic domes in order to maximize sky coverage$^2$. We present the prototype design and tests of these modular Fresnel telescope units. This consists of the design of mechanical components such as the lens mounting and module frame. One of the most important goals of the modules is to maintain the characteristics of the Fresnel lens under a variety of operating conditions. We discuss how we account for a range of operating temperatures, humidity, and module orientations in our design in order to minimize undesirable changes to our focal length or angular resolution.Comment: 12 pages, 8 figures, 1 tabl

Green Tea Extract and (−)-Epigallocatechin-3-Gallate Inhibit Mast Cell-Stimulated Type I Collagen Expression in Keloid Fibroblasts via Blocking PI-3K/Akt Signaling Pathways

Keloid, a chronic fibro-proliferative disease, exhibits distinctive histological features characterized by an abundant extracellular matrix stroma, a local infiltration of inflammatory cells including mast cells (MCs), and a milieu of enriched cytokines. Previous studies have demonstrated that co-culture with MCs stimulate type I collagen synthesis in fibroblasts, but the signaling mechanisms remain largely unknown. In this study, we investigated the signaling pathways involved in MC-stimulated type I collagen synthesis and the effects of green tea extract (GTE) and its major catechin, (-)-epigallocatechin-3-gallate (EGCG), on collagen homeostasis in keloid fibroblasts. Our results showed that MCs significantly stimulated type I collagen expression in keloid fibroblasts, and the upregulation of type I collagen was significantly attenuated by blockade of phosphatidylinositol-3-kinase (PI-3K), mammalian target of rapamycin (mTOR), and p38 MAPK signaling pathways, but not by blockade of ERK1/2 pathway. Furthermore, GTE and EGCG dramatically inhibited type I collagen production possibly by interfering with the PI-3K/Akt/mTOR signaling pathway. Our findings suggest that interaction between MCs and keloid fibroblasts may contribute to excessive collagen accumulation in keloids and imply a therapeutic potential of green tea for the intervention and prevention of keloids and other fibrotic diseases. © 2006 The Society for Investigative Dermatology

Green Tea Extract and (−)-Epigallocatechin-3-Gallate Inhibit Mast Cell-Stimulated Type I Collagen Expression in Keloid Fibroblasts via Blocking PI-3K/Akt Signaling Pathways

Keloid, a chronic fibro-proliferative disease, exhibits distinctive histological features characterized by an abundant extracellular matrix stroma, a local infiltration of inflammatory cells including mast cells (MCs), and a milieu of enriched cytokines. Previous studies have demonstrated that co-culture with MCs stimulate type I collagen synthesis in fibroblasts, but the signaling mechanisms remain largely unknown. In this study, we investigated the signaling pathways involved in MC-stimulated type I collagen synthesis and the effects of green tea extract (GTE) and its major catechin, (-)-epigallocatechin-3-gallate (EGCG), on collagen homeostasis in keloid fibroblasts. Our results showed that MCs significantly stimulated type I collagen expression in keloid fibroblasts, and the upregulation of type I collagen was significantly attenuated by blockade of phosphatidylinositol-3-kinase (PI-3K), mammalian target of rapamycin (mTOR), and p38 MAPK signaling pathways, but not by blockade of ERK1/2 pathway. Furthermore, GTE and EGCG dramatically inhibited type I collagen production possibly by interfering with the PI-3K/Akt/mTOR signaling pathway. Our findings suggest that interaction between MCs and keloid fibroblasts may contribute to excessive collagen accumulation in keloids and imply a therapeutic potential of green tea for the intervention and prevention of keloids and other fibrotic diseases. © 2006 The Society for Investigative Dermatology

7T multi-shell hybrid diffusion imaging (HYDI) for mapping brain connectivity in mice

Diffusion weighted imaging (DWI) is widely used to study microstructural characteristics of the brain. High angular resolution diffusion imaging (HARDI) samples diffusivity at a large number of spherical angles, to better resolve neural fibers that mix or cross. Here, we implemented a framework for advanced mathematical analysis of mouse 5-shell HARDI (b=1000, 3000, 4000, 8000, 12000 s/mm^2), also known as hybrid diffusion imaging (HYDI). Using q-ball imaging (QBI) at ultra-high field strength (7 Tesla), we computed diffusion and fiber orientation distribution functions (dODF, fODF) to better detect crossing fibers. We also computed a quantitative anisotropy (QA) index, and deterministic tractography, from the peak orientation of the fODFs. We found that the signal to noise ratio (SNR) of the QA was significantly higher in single and multi-shell reconstructed data at the lower b-values (b=1000, 3000, 4000 s/mm^2) than at higher b-values (b=8000, 12000 s/mm2); the b=1000 s/mm^2 shell increased the SNR of the QA in all multi-shell reconstructions, but when used alone or in <5-shell reconstruction, it led to higher angular error for the major fibers, compared to 5-shell HYDI. Multi-shell data reconstructed major fibers with less error than single-shell data, and was most successful at reducing the angular error when the lowest shell was excluded (b=1000 s/mm2). Overall, high-resolution connectivity mapping with 7T HYDI offers great potential for understanding unresolved changes in mouse models of brain disease