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

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

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

Nanometer-scale striped surface terminations on fractured SrTiO3_{3} surfaces

Using cross-sectional scanning tunneling microscopy on in situ fractured SrTiO$_{3}$, one of the most commonly used substrates for the growth of complex oxide thin films and superlattices, atomically smooth terraces have been observed on (001) surfaces. Furthermore, it was discovered that fracturing this material at room temperature results in the formation of stripe patterned domains having characteristic widths (~10 nm to ~20 nm) of alternating surface terminations that extend over a long-range. Spatial characterization utilizing spectroscopy techniques revealed a strong contrast in the electronic structure of the two domains. Combining these results with topographic data, we are able to assign both TiO$_{2}$ and SrO terminations to their respective domains. The results of this proof-of-principle experiment reveal that fracturing this material leads to reproducibly flat surfaces that can be characterized at the atomic-scale and suggests that this technique can be utilized for the study of technologically relevant complex oxide interfaces.Comment: 15 pages, 4 figure

Calculation of energy levels and transition amplitudes for barium and radium

The radium atom is a promising system for studying parity and time invariance violating weak interactions. However, available experimental spectroscopic data for radium is insufficient for designing an optimal experimental setup. We calculate the energy levels and transition amplitudes for radium states of significant interest. Forty states corresponding to all possible configurations consisting of the $7s$, $7p$ and $6d$ single-electron states as well as the states of the $7s8s$, $7s8p$ and $7s7d$ configurations have been calculated. The energies of ten of these states corresponding to the $6d^2$, $7s8s$, $7p^2$, and $6d7p$ configurations are not known from experiment. Calculations for barium are used to control the accuracy.Comment: 12 pages, 4 table