Electrostatics in the Stability and Misfolding of the Prion Protein: Salt Bridges, Self-Energy, and Solvation

Using a recently developed mesoscopic theory of protein dielectrics, we have calculated the salt bridge energies, total residue electrostatic potential energies, and transfer energies into a low dielectric amyloid-like phase for 12 species and mutants of the prion protein. Salt bridges and self energies play key roles in stabilizing secondary and tertiary structural elements of the prion protein. The total electrostatic potential energy of each residue was found to be invariably stabilizing. Residues frequently found to be mutated in familial prion disease were among those with the largest electrostatic energies. The large barrier to charged group desolvation imposes regional constraints on involvement of the prion protein in an amyloid aggregate, resulting in an electrostatic amyloid recruitment profile that favours regions of sequence between alpha helix 1 and beta strand 2, the middles of helices 2 and 3, and the region N-terminal to alpha helix 1. We found that the stabilization due to salt bridges is minimal among the proteins studied for disease-susceptible human mutants of prion protein

DScent Final Report

DScent was a joint project between five UK universities combining research theories in the disciplines of computational inference, forensic psychology and expert decision-making in the area of counter-terrorism. This document discusses the work carried out by Leeds Metropolitan University which covers the research, design and development work of an investigator support system in the area of deception using artificial intelligence. For the purposes of data generation along with system and hypothesis testing the project team devised two closed world games, the Cutting Corners Board Game and the Location Based Game. DScentTrail presents the investigator with a ‘scent trail’ of a suspect’s behaviour over time, allowing the investigator to present multiple challenges to a suspect from which they may prove the suspect guilty outright or receive cognitive or emotional clues of deception (Ekman 2002; Ekman & Frank 1993; Ekman & Yuille 1989; Hocking & Leathers 1980; Knapp & Comadena 1979). A scent trail is a collection of ordered, relevant behavioural information over time for a suspect. There are links into a neural network, which attempts to identify deceptive behavioural patterns of individuals. Preliminary work was carried out on a behavioural based AI module which would work separately alongside the neural network, with both identifying deception before integrating their results to update DScentTrail. Unfortunately the data that was necessary to design such a system was not provided and therefore, this section of research only reached its preliminary stages. To date research has shown that there are no specific patterns of deceptive behaviour that are consistent in all people, across all situations (Zuckerman 1981). DScentTrail is a decision support system, incorporating artificial intelligence (AI), which is intended to be used by investigators and attempts to find ways around the problem stated by Zuckerman above

Sustainable Design of Wastewater Treatment Systems: Evaluations of Operational Flexibility and Phototrophs for Resource Recovery.

The overarching goal of this dissertation is to advance the sustainability of wastewater systems. Although concepts surrounding sustainable wastewater infrastructure have advanced in recent years, a defined methodology to develop designs and elucidate trade-offs across dimensions of sustainability (social, economic, environmental, functional), space (local, regional, global), and time (present, future) does not exist. In particular, social barriers have not been sufficiently addressed and there is a lack of integration in quantitative assessments of economic, environmental, and functional sustainability. This limitation not only impacts the industry’s ability to develop more sustainable designs and evaluate configuration alternatives, but it also inhibits the comparative evaluation of traditional with emerging technologies in wastewater management (e.g., the use of phototrophic microorganisms for energy recovery). In order to address social factors, we have developed a planning and design process for wastewater treatment systems that is centered on a process of continuous stakeholder participation and that is enhanced through communication tools and lessons learned from the social sciences literature. To provide stakeholders with the a broader set of information in the context of WWTP design, we have also integrated state of the art tools to assess the performance, cost, and life cycle environmental impacts of WWTP designs. Although these tools have been developed independent of one another in the literature, their integration creates opportunities to elucidate tensions and synergistic relationships among goals for sustainability. Ultimately, this methodology and the case study used for its demonstration offer insight into broader themes of WWTP sustainability, improve designs in multiple dimensions, and provide a framework to evaluate emerging technologies in wastewater management. Finally, we have developed a phototrophic process model to predict the performance of phototrophic microorganisms as an energy recovery technology. Through these efforts, this dissertation advances the sustainability of wastewater treatment systems by facilitating sustainable design and decision-making in the context of WWTP design and operation.Ph.D.Environmental EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/91603/1/jsguest_1.pd

Geodesic Flow on the Normal Congruence of a Minimal Surface

We study the geodesic flow on the normal line congruence of a minimal surface in ${\Bbb{R}}^3$ induced by the neutral K\"ahler metric on the space of oriented lines. The metric is lorentz with isolated degenerate points and the flow is shown to be completely integrable. In addition, we give a new holomorphic description of minimal surfaces in ${\Bbb{R}}^3$ and relate it to the classical Weierstrass representation.Comment: AMS-LATEX 8 pages 2, figure

Propulsion system ignition overpressure for the Space Shuttle

Liquid and solid rocket motor propulsion systems create an overpressure wave during ignition, caused by the accelerating gas particles pushing against or displacing the air contained in the launch pad or launch facility and by the afterburning of the fuel-rich gases. This wave behaves as a blast or shock wave characterized by a positive triangular-shaped first pulse and a negative half-sine wave second pulse. The pulse travels up the space vehicle and has the potential of either overloading individual elements or exciting overall vehicle dynamics. The latter effect results from the phasing difference of the wave from one side of the vehicle to the other. This overpressure phasing, or delta P environment, because of its frequency content as well as amplitude, becomes a design driver for certain panels (e.g., thermal shields) and payloads for the Space Shuttle. The history of overpressure effects on the Space Shuttle, the basic overpressure phenomenon, Space Shuttle overpressure environment, scale model overpressure testing, and techniques for suppressing the overpressure environments are considered

Inextensional Packaging of Thin Shell Slit Reflectors

Carbon-fibre-reinforced-plastic reflector antennas based on a thin shell that is folded elastically have been recently developed; this paper presents a new concept for packaging reflectors of this type. The idea is to cut the surface into 6-8 petals along curved lines, whose shape is such that in the packaged configuration the petals wrap around a central part. During deployment, they open out and unwrap, driven by the energy stored during folding. Analytical expressions are derived for the stresses induced by inextensional elastic folding of a doubly-curved shell. A simple, approximate method for analysing the packaging scheme is introduced, and its predictions are used to set up an optimization scheme that determines the cutting pattern required to achieve optimal packaging of the reflector, for a given yield stress and elastic modulus of the material. For a dish with diameter of 0.9 m an optimised cutting pattern is determined, and then a detailed finite-element analysis and an experimental verification of the curvatures induced by packaging are carried out. These results confirm that these predictions from the approximate analysis are accurate and conservative. A reduction in diameter of 3 is achieved for this particular dish

Conduction of topologically-protected charged ferroelectric domain walls

We report on the observation of nanoscale conduction at ferroelectric domain walls in hexagonal HoMnO3 protected by the topology of multiferroic vortices using in situ conductive atomic force microscopy, piezoresponse force microscopy, and kelvin-probe force microscopy at low temperatures. In addition to previously observed Schottky-like rectification at low bias [Phys. Rev. Lett., 104, 217601 (2010)], conductance spectra reveal that negatively charged tail-to-tail walls exhibit enhanced conduction at high forward bias, while positively charged head-to-head walls exhibit suppressed conduction at high reverse bias. Our results pave the way for understanding the semiconducting properties of the domains and domain walls in small-gap ferroelectrics.Comment: 8 pages, 4 figure