Investigating the Diabetic Brain: The Effects of Pioglitazone and Insulin on the Cellular Processes and Pathology of Alzheimer's Disease

Alzheimer’s disease (AD) is the sixth leading cause of death in the US. Some researchers refer to AD as “Type III Diabetes” because of reported glucose metabolism dysfunction. Preclinical studies suggest increasing insulin decreases AD pathology, although the mechanism remains unclear. To sensitize insulin signaling, this study activated Peroxisome Proliferator-Activated Receptor Gamma using intranasal co-administration of pioglitazone (PGZ) and insulin. This method targeted the site of action to reduce peripheral effects and to maximize impact in transgenic mice expressing AD pathology. Data from GC-MS fluxomics analysis suggested that PGZ+Insulin increased glucose metabolism in the brain. Immunohistochemistry with relevant antibodies was used to identify AD pathological markers in the subiculum, indicating that PGZ+Insulin decreased pathology compared to Insulin and Saline. This suggests that increasing glucose uptake in the brain alleviated AD pathology, further clarifying the role of insulin signaling in AD pathology.Gemstone

Measurement and Simulation of Suppression Effects in a Buoyant Turbulent Line Fire

An experimental and numerical study of turbulent fire suppression is presented. For this work, a novel and canonical facility has been developed, featuring a buoyant, turbulent, methane or propane-fueled diffusion flame suppressed via either nitrogen dilution of the oxidizer or application of a fine water mist. Flames are stabilized on a slot burner surrounded by a co-flowing oxidizer, which allows controlled delivery of either suppressant to achieve a range of conditions from complete combustion through partial and total flame quenching. A minimal supply of pure oxygen is optionally applied along the burner to provide a strengthened flame base that resists liftoff extinction and permits the study of substantially weakened turbulent flames. The carefully designed facility features well-characterized inlet and boundary conditions that are especially amenable to numerical simulation. Non-intrusive diagnostics provide detailed measurements of suppression behavior, yielding insight into the governing suppression processes, and aiding the development and validation of advanced suppression models. Diagnostics include oxidizer composition analysis to determine suppression potential, flame imaging to quantify visible flame structure, luminous and radiative emissions measurements to assess sooting propensity and heat losses, and species-based calorimetry to evaluate global heat release and combustion efficiency. The studied flames experience notable suppression effects, including transition in color from bright yellow to dim blue, expansion in flame height and structural intermittency, and reduction in radiative heat emissions. Still, measurements indicate that the combustion efficiency remains close to unity, and only near the extinction limit do the flames experience an abrupt transition from nearly complete combustion to total extinguishment. Measurements are compared with large eddy simulation results obtained using the Fire Dynamics Simulator, an open-source computational fluid dynamics software package. Comparisons of experimental and simulated results are used to evaluate the performance of available models in predicting fire suppression. Simulations in the present configuration highlight the issue of spurious reignition that is permitted by the classical eddy-dissipation concept for modeling turbulent combustion. To address this issue, simple treatments to prevent spurious reignition are developed and implemented. Simulations incorporating these treatments are shown to produce excellent agreement with the experimentally measured data, including the global combustion efficiency.