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

Familiarity and strangeness: seeing everyday practices of punishment and resistance in Holloway Prison

London’s Holloway Prison, the largest women’s prison in western Europe, closed in 2016. The impact of the closure on the women incarcerated in Holloway, and the prison’s place in the local community, is the focus of a project led by Islington Museum. Here, we develop an innovation, emotion-led methodology to explore photographs of the decommissioned Holloway, asking what they communicate about experiences of imprisonment and practices of punishment. The images illustrate the strategies of control, mechanisms of punishment and tactics of resistance that operate through the carceral space. From a feminist, anti-carceral perspective, we emphasise the importance of seeing prison spaces and attending to the emotional responses generated. We offer a creative intervention into dominant government and media narratives of Holloway’s closure and suggest that considering what it is that feels familiar and strange about carceral spaces has the potential to operate as a form of anti-carceral work

Robust point correspondence applied to two and three-dimensional image registration

Accurate and robust correspondence calculations are very important in many medical and biological applications. Often, the correspondence calculation forms part of a rigid registration algorithm, but accurate correspondences are especially important for elastic registration algorithms and for quantifying changes over time. In this paper, a new correspondence calculation algorithm, CSM (correspondence by sensitivity to movement), is described. A robust corresponding point is calculated by determining the sensitivity of a correspondence to movement of the point being matched. If the correspondence is reliable, a perturbation in the position of this point should not result in a large movement of the correspondence. A measure of reliability is also calculated. This correspondence calculation method is independent of the registration transformation and has been incorporated into both a 2D elastic registration algorithm for warping serial sections and a 3D rigid registration algorithm for registering pre and postoperative facial range scans. These applications use different methods for calculating the registration transformation and accurate rigid and elastic alignment of images has been achieved with the CSM method. It is expected that this method will be applicable to many different applications and that good results would be achieved if it were to be inserted into other methods for calculating a registration transformation from correspondence