The goal of the current experiments was to assess the role of estrogen receptor alpha (ERë±) in the ability of a prior, short-term exposure to estradiol in mid-life to enhance cognition and affect the hippocampus in aging, ovariectomized rats, as well as to investigate a possible mechanism involving the insulin-like growth factor-1 system by which ERë± may exert these effects. In Experiment 1, rats were trained on the radial maze, ovariectomized, and implanted with estradiol or cholesterol vehicle capsules for 40 days. Rats then continuously received JB1 or aCSF vehicle i.c.v. and were tested on delay trials on the radial maze. Using Western blotting, I determined effects of treatment on protein levels of ERë±, ChAT, IGF-1R, IGF-1BP2, and phosphorylated and total p42/p44 MAPK and Akt in the hippocampus. Antagonism of IGF-1 receptors blocked the ability of prior estradiol exposure to enhance cognition and increase ERë±, phosphorylated ERK/MAPK, and ChAT in the hippocampus. The second experiment was divided into two parts. In Experiment 2A, rats were trained on the radial maze and ovariectomized. After 40 days, rats underwent stereotaxic surgery to receive lentiviral delivery of the gene encoding for ERë± or control virus to the hippocampus, and were then tested on delay trials. Using Western blotting, I determined if proteins of interest previously found to be affected by a prior exposure to estradiol in Experiment 1 would be affected by treatments for all subsequent experiments. Lentiviral delivery of ERë± to the hippocampus was sufficient to enhance cognition and increase phosphorylation of ERK/MAPK in the hippocampus. In Experiment 2B, rats were trained on the radial maze, ovariectomized, and implanted with estradiol or cholesterol vehicle capsules for 40 days. Rats then continuously received an ER antagonist or aCSF vehicle i.c.v. and were tested on delay trials. Antagonism of ERë± blocked the ability of prior estradiol exposure to enhance cognition. In the third experiment, rats were trained on the radial maze, ovariectomized, and implanted with estradiol or cholesterol vehicle capsules for 40 days. Rats then underwent stereotaxic surgery to receive i.c.v. cannula. Infusion of an ERK/MAPK inhibitor or aCSF vehicle was administered every 12 hours during delay trials. Inhibition of ERK/MAPK did not block the ability of prior estradiol exposure to enhance cognition, although it did block an increase in levels of ERë± in the hippocampus. Altogether, these results indicate that ERë± plays an important role in the ability of prior estradiol exposure to enhance cognition and affect the hippocampus in aging, ovariectomized rats, and likely interacts with the IGF-1 system and its associated ERK/MAPK signaling pathway. / acase@tulane.edu

This work is motivated by two non-intuitive predictions of Quantum Mechanics: non-locality and contextuality. Non-locality is a phenomenon whereby interactions between spatially separated objects appear to be occurring faster than the speed of light. Contextuality is a phenomenon whereby the outcome of a measurement cannot be interpreted as the revelation of an intrinsic fixed property of the system being measured, but instead necessarily depends on the configuration of the measurement apparatus. Quantum Mechanics predicts non-local behavior in certain types of experiments collectively known as Bell tests. However, ruling out all possible alternative local theories is a subtle and demanding task. In this work, we lay out a mathematically-rigorous framework for analyzing Bell experiments. Using this framework, we derive the famous Clauser-Horne-Shimony-Holt (CHSH) inequality, an important constraint that is obeyed by all local theories and violated by Quantum Mechanics. We further demonstrate how to analyze the data of a CHSH experiment without assuming that successive experimental trials are independent and/or identically distributed. We also derive the Clauser-Horne (CH74) inequality, an inequality that is more well-suited for realistic Bell experiments using photons. We demonstrate a robust method for statistically analyzing the data of a CH74 experiment, and show how to calculate exact p-values for this analysis, improving on the previously-best-known (loose) upper bounds obtained from Hoeffding-style inequalities. The work concludes with an exploration of contextuality. The Kochen-Specker theorem -- a result demonstrating the contextual nature of Quantum Mechanics -- is applied to resolve a conjecture in Domain Theory regarding the spectral order on quantum states. / acase@tulane.edu

Current therapeutic options for ischemic stroke are limited to tissue plasminogen activator and mechanical clot removal therapies. Diazoxide (DZ) is a mitochondrial ATP-sensitive potassium channel opener and is protective in models of brain ischemia, but the signaling pathways involved are unknown. The mammalian target of rapamycin (mTOR) is a master regulator of protein synthesis and is involved in protection against cerebral ischemia. The neuronal nitric oxide synthase (nNOS) pathway has also been shown to provide protection from ischemic insults. Additionally, mitochondrial respiratory status has not been investigated. I examined the role of the mTOR pathway, the nNOS pathway, and mitochondrial respiration in delayed DZ-induced preconditioning of neurons. I cultured rat primary cortical neurons and simulated ischemic stroke using oxygen-glucose deprivation (OGD) for 3 h followed by re-oxygenation. Viability, mitochondrial membrane potential, reactive oxygen species (ROS) measurements, and western blots were performed. The mTOR pathway was inhibited by rapamycin, Torin-1, and S6K targeted silencing RNA. The NOS pathway was inhibited by L-NAME. NO-donors SNP and DEANONOate (DEANO) were applied to rescue the effects of L-NAME. Mitochondrial oxygen consumption rate (OCR) was measured in intact neurons by serial injections of oligomycin, FCCP, and antimycin/rotenone. OGD decreased viability by 50 percent, depolarized mitochondria, and reduced mitochondrial respiration whereas DZ improved viability to 75 percent and suppressed reactive oxygen species production, but did not restore mitochondrial membrane potential after OGD. Diazoxide also increased phosphorylation of protein kinase B, mTOR, and S6K. Rapamycin, Torin-1, and S6K targeted siRNA abolished the protective effects of DZ. Co-application of L-NAME with DZ prevented preconditioning whereas adding SNP or DEANO along with L-NAME and DZ restored protection. Diazoxide increased phosphorylated nNOS. Interestingly, co-application of LNAME with DZ blocked the phosphorylation of nNOS as well as S6K. The ratio of phosphorylated/total Akt and mTOR were not significantly altered with L-NAME co-application. Diazoxide altered OCR 24 and 48 h after the ischemic period. Diazoxide had no acute effect on OCR but increased ECAR significantly. Activation of the mTOR and nNOS pathways is critical for DZ preconditioning in neurons. Furthermore, OCR is modified by the DZ-induced preconditioning of neurons. / acase@tulane.edu

Nanowires and nanotubes are central elements in nanoscience and nanotechnology for applications such as nanoelectronic devices, chemical sensors, and high-density data storage. Among various synthesis methods, the template assisted electrodeposition is particularly attractive because it provides an efficient route to fabricate arrays of nanomatenals of desired composition, size, and aspect ratio. Advanced applications need morphological control. Mesoporous materials with uniform and arranged pores with pore diameters between 2 and 50 nm have attracted much attention due to their unique structures and applications. This dissertation presents the fabrication, structure, and property investigation of magnetic, superconducting metal, and semiconductor nanostructures We will report three-dimensional (3D) macroporous magnetic and superconducting metal films using opal templates, 2D hexagonal and 3D cubic metal nanowire thin films with tunable 3-10 nm wire diameters using mesoporous silica as templates, mesoporous cobalt and nickel films with hexagonal and lamellar structures direct templated by lyotropic liquid crystal phases. Compared with bulk and dense films, the porous magnetic films show higher coercivities. The cobalt nanowire thin films exhibit enhanced coercivities and controllable magnetic anisotropy through tuning the mesostructure and dimension of the nanowires We will present a novel method, confined-assembly-template assisted (CATA) electrodeposition, by combination of nanoconfinement, supramolecular templating and electrodeposition technique to prepare mesoporous metal and semiconductor nanowires and nanotubes. Mesoporous palladium and cobalt nanowires are obtained by electrodeposition of hexagonal liquid crystal in porous membranes, mesoporous platinum and nickel nanotubes with controlled length are obtained by electrodeposition of lamellar liquid crystal, mesoporous zinc oxide nanowires are obtained by electrodeposition of interfacial SDS surfactant self-assembly. As compared to the solid nanowires and nanotubes, those porous wires and tubes show higher coercivities. Such novel nanowires may provide a new platform for high-density information storage applications We have studied the electrodeposition and magnetic properties of manganese doped zinc oxide films - diluted magnetic semiconductors, and found the materials show both of paramagnetism and ferromagnetism with Curie temperature of 39 K, after calcinations, the samples show paramagnetism and ferromagnetism with high coercivity of above 1 T and Curie temperature of 44 K / acase@tulane.edu

The present investigations are designed to create components of an integrated system for delivery of angiogenic protein using tissue culture engineered cells. Mesenchymal stromal cells (MSCs) are genetically engineered to produce angiogenic proteins for delivery into heart. Bicistronic cellular vectors are engineered including the HIV-1 Lentivirus vector NL-VEGF-EGFP as well as the as well as the mammalian expression vector pbetaa-VEGF-IRES2-EGFP to produce the protein vascular endothelial cell growth factor (VEGF) and the fluorescent marker enhanced green fluorescent protein (EGFP). Quantitative levels of VEGF are measured using a novel biological assay to quantify endothelial response to protein. Vascular endothelial cells also provide a means to measure NL-VEGF-EGFP based lentiviral production of material. Experimental production of VEGF by co-culture shows that production of VEGF is limited by cellular proliferation and angiogenic tubule formation during angiogenic sprouting. The final components of an angiogenic assay shows limited biological response to feeder layers of cells producing increasing quantities of angiogenic protein. Angiogenic cellular proliferation provides a means to semi-quantitatively analyze the effects of tissue engineered protein production in vitro. Bicistronic protein production provides a means to precisely quantify EGFP and therefore the level of VEGF mRNA by flow cytometry for EGFP. This analysis shows that VEGF measured by enzyme linked immunosobant assay (ELISA) for the 164 murine isoform produce comparable levels of EGFP Therapeutic delivery of engineered tissue into pathogenic myocardial tissue is performed by cardiomyoplasty in a large animal model. Development of a vascular based infusion system indicates selective occlusion and delivery into pathogenic myocardial tissue. This system has the capacity to monitor real time events and prevents damage to myocardium. Basic fluid flow and pressure analysis of the delivery system is tested for both antegrade and retrograde delivery of microspheres and engineered cells into heart. These experiments show that during time course delivery there is an increase in the pressure required to drive dispersions into distal tissues. As microcapillary beds are progressively occluded there is an increase in the resistance required to drive fluid through tissue beds / acase@tulane.edu

Silicon nanoparticles can display properties that are very different from bulk silicon, and as such have potential applications in optoelectronic devices and as fluorescent biomarkers. However, silicon nanoparticles can experience significant degradation to luminescence upon ambient air oxidation. As most real-world applications for luminescent silicon nanoparticles would of course result in exposure to air, it becomes necessary to protect the particle surface in an effort to prevent ambient air oxidation A mechanochemical method for the production of passivated silicon nanoparticles has been developed. This process presents a simple, straightforward, and robust route for the simultaneous production of silicon nanoparticles and the passivation of the nanoparticle surface with covalently bound organic molecules. This procedure has shown to be effective for organic liquids of a wide range of functionalities. Alkynes, alkenes, aldehydes, carboxylic acids, and alcohols have all shown success in passivation of the nanoparticle surface. For example, passivated silicon nanoparticles produced in 1-octyne emit at 435 nm when excited with 360 nm light, and display a quantum yield of 0.60 As they are produced, the smaller nanoparticles become solubilized in the organic liquid medium. Chain length variations in the passivating molecule have shown to affect the size of the silicon nanoparticles that become solubilized in the liquid medium after milling. Process yields increase from 4.1% to 5.2% when the functionalizing chain length is increased from 6 to 12. This allows for a degree of nanoparticle size selection by simple alteration of reactive organic selection Initial investigations into process optimization were performed. Increasing the number of milling balls to three was found to increase process yield. Additionally, silicon was found to be an excess reactant, and thus decreasing the initial charge of silicon was shown to reduce process waste The developed process has shown to be a successful route for the production of passivated silicon nanoparticles, the main advantage of which is the inherent simplicity. The presented method offers a one-step, direct-reaction approach for the simultaneous production and passivation of silicon nanoparticles, without the need for hazardous chemicals or large amounts of waste / acase@tulane.edu

Polymeric liners are widely used in rehabilitation of sewer and potable water lines and containment of solid waste and water (polymeric membranes). Studies conducted to date on the performance of polymeric liners considered the effect of mechanical stress, chemicals, moisture, and temperature. However, no study provided a measure of and tools for a practical method to determine the combined effects of in-situ stresses and exposure to chemicals on the long-term performance of liners. This research work aims at quantifying the simultaneous effects of chemical exposure and stress on material properties of polyethylene typically used in liners for pipeline rehabilitation and waste/water containment. An experimental method with a custom designed soaking apparatus was developed for exposing polymeric specimens to water treatment residuals and other abrasive chemicals under an applied stress. High and low density polyethylene specimens (63.5 x 12.7 x 3.2 mm) were mounted on the apparatuses and tested under different levels of deformation, temperature, and time while being exposed to chlorine and trichloroethylene solutions. Following the soaking under each of the foregoing conditions, the specimens were tested for their flexural strength in accordance with ASTM D 790. A computational analysis using the finite element method was performed to verify the results of the flexure tests and determine the stress and strain distribution over a bent specimen during exposure. The results did not indicate a significant effect of chlorine or TCE on degradation of HDPE and LDPE. The developed method with the chosen variables and their levels allows for an analytical interpretation for the effect of moisture and deformation on the long-term flexural modulus of elasticity, which is indicated by the degradation coefficient zeta. The effect of temperature on the degradation of the two tested materials was evident by the observed early failure in addition to the decreased flexural modulus of elasticity noted in the HDPE specimens. The equation proposed for zeta accounts for the effects of temperature and molecular weight distribution. However, analytical interpretation of the effects of these parameters is subject to a future study / acase@tulane.edu