The Effects of Aqueous Atorvastatin on Steroidogenesis of \u3ci\u3eXenopus laevis\u3c/i\u3e at Environmentally Relevant Concentrations

Statin drugs are a class of drug that work to reduce endogenous production of cholesterol by competitively inhibiting 3-hydroxy-3-methyl-glutaryl-CoA reductase (Hmgcr) thus inhibiting production of mevalonic acid in the mevalonate pathway. Atorvastatin (Lipitor) is one of the most widely prescribed statin drugs and contamination of wastewater effluent is a growing environmental concern because of the potential to interfere with steroidogenesis in wildlife. Amphibians may be particularly susceptible to the effects of atorvastatin contamination because of their highly permeable integument. I used an amphibian model, Xenopus laevis to test the hypothesis that chronic exposure to low concentrations of atorvastatin in water has an adverse effect on steroid hormone levels, growth and development. This hypothesis was tested via a series of toxicity assays designed to evaluate potential endocrine disrupting effects of atorvastatin using traditional aquatic toxicology assays combined with modern molecular biology techniques to identify and report regulatory alteration of physiological pathways. Results indicated significant dose-dependent upregulation of steroidogenesis as confirmed by both qPCR and total RNA sequencing and supported by evidence of alteration of testosterone and estradiol concentrations. Such effects have the potential to significantly alter sex ratios in amphibian populations localized around wastewater effluent sites. This research provides insight into the potentially harmful effects of relatively low concentrations of aqueous atorvastatin

Fault propagation timing analysis to aid in the selection of sensors fro health management systems

Sensor data is processed to assess performance and health of complex systems. Proper sensor selection, placement, and implementation are critical to build an effective health management system. For complex systems in which the timely assessment of the health is desired to avoid expensive consequences of failure, sensor placement is vital. The ability to identify a critical failure early is completely dependent on sensor location within the fault propagation path. A strategy for assessing a sensor suite with respect to timely critical failure detection is presented in this thesis. To illustrate the strategy, Fault Propagation Timing Analysis (FPTA) will be performed on the Rocketdyne RS-68 rocket engine --Abstract, page iii

The Shock of Presence Peter Brook & Jerzy Grotowski – The Reinvention of Australian Theatre

Peter Brook and Jerzy Grotowski were seminal influences upon the Australian performance revolution in the 1970s and into the 1980s through the methodologies and concepts of theatre practice outlined in their respective texts: The Empty Space and Towards a Poor Theatre. These manifestos served as a blue print for a theatrical groundswell emerging from Melbourne in the early 1970s in Carlton at both La Mama and Australian Performance Group (APG) at the Pram Factory, and at the same time in Sydney with the Nimrod theatre and Rex Cramphorn’s Performance Syndicate. An examination reveals these Directors shared spiritual and traditional sources from Eastern European backgrounds (Brook being of Russian Jewish heritage and Grotowski Eastern Orthodox Catholic), the approach of Constantin Stanislavski (particularly for Grotowski), and their mutual reverence for the teachings of Armenian mystic, George Ivanovitch Gurdjieff. An analysis of key moments and how Brook and Grotowski were central figures in the initiation of an Australian performance revolution of the 1970s; and the performance renaissance which emerged from women’s theatre as a reaction to the male-centric ‘ocker’ sensibilities at the time during a movement in which Brook and Grotowski figured prominently. How Brook and Grotowski’s methodological ideas uncovering meaning in tradition and deeper levels of performance enquiry were sidelined, and eventually marginalized to all but a few fringe groups as a result of mainstream performance concerns with aesthetic considerations, and the globalization of economic rationalism is observed

Diffusive Migration of Low-Mass Proto-planets in Turbulent Disks

Torque fluctuations due to magnetorotational turbulence in proto-planetary disks may greatly influence the migration patterns and survival probabilities of nascent planets. Provided that the turbulence is a stationary stochastic process with finite amplitude and correlation time, the resulting diffusive migration can be described with a Fokker-Planck equation, which we reduce to an advection-diffusion equation. We calibrate the coefficients with existing turbulent-disk simulations and mean-migration estimates, and solve the equation both analytically and numerically. Diffusion tends to dominate over advection for planets of low-mass and those in the outer regions of proto-planetary disks, whether they are described by the Minimum Mass Solar Nebula (MMSN) or by T-Tauri alpha disks. Diffusion systematically reduces the lifetime of most planets, yet it allows a declining fraction of them to survive for extended periods of time at large radii. Mean planet lifetimes can even be formally infinite (e.g. in an infinite steady MMSN), though median lifetimes are always finite. Surviving planets may linger near specific radii where the combined effects of advection and diffusion are minimized, or at large radii, depending on model specifics. The stochastic nature of migration in turbulent disks challenges deterministic planet formation scenarios and suggests instead that a wide variety of planetary outcomes are possible from similar initial conditions. This would contribute to the diversity of (extrasolar) planetary systems.Comment: 31 pages, 7 figures, accepted for publication in Ap

The Unusual Substrate Specificity of a Virulence Associated Serine Hydrolase from the Highly Toxic Bacterium, \u3cem\u3eFrancisella tularensis\u3c/em\u3e

Francisella tularensis is the causative agent of the highly, infectious disease, tularemia. Amongst the genes identified as essential to the virulence of F. tularensis was the proposed serine hydrolase FTT0941c. Herein, we purified FTT0941c to homogeneity and then characterized the folded stability, enzymatic activity, and substrate specificity of FTT0941c. Based on phylogenetic analysis, FTT0941c was classified within a divergent Francisella subbranch of the bacterial hormone sensitive lipase (HSL) superfamily, but with the conserved sequence motifs of a bacterial serine hydrolase. FTT0941c showed broad hydrolase activity against diverse libraries of ester substrates, including significant hydrolytic activity across alkyl ester substrates from 2 to 8 carbons in length. Among a diverse library of fluorogenic substrates, FTT0941c preferred α-cyclohexyl ester substrates, matching with the substrate specificity of structural homologues and the broad open architecture of its modeled binding pocket. By substitutional analysis, FTT0941c was confirmed to have a classic catalytic triad of Ser115, His278, and Asp248 and to remain thermally stable even after substitution. Its overall substrate specificity profile, divergent phylogenetic homology, and preliminary pathway analysis suggested potential biological functions for FTT0941c in diverse metabolic degradation pathways in F. tularensis

Issues in Evaluating Special Education Teachers: Challenges and Current Perspectives

Educatio