Pathogenic mutations in the hydrophobic core of the human prion protein can promote structural instability and misfolding

Transmissible spongiform encephalopathies, or prion diseases, are caused by misfolding and aggregation of the prion protein PrP. These diseases can be hereditary in humans and four of the many disease-associated missense mutants of PrP are in the hydrophobic core: V180I, F198S, V203I and V210I. The T183A mutation is related to the hydrophobic core mutants as it is close to the hydrophobic core and known to cause instability. We have performed extensive molecular dynamics simulations of these five PrP mutants and compared their dynamics and conformations to wild-type PrP. The simulations highlight the changes that occur upon introduction of mutations and help to rationalize experimental findings. Changes can occur around the mutation site, but they can also be propagated over long distances. In particular, the F198S and T183A mutations lead to increased flexibility in parts of the structure that are normally stable, and the short β-sheet moves away from the rest of the protein. Mutations V180I, V210I and, to a lesser extent, V203I cause changes similar to those observed upon lowering the pH, which has been linked to misfolding. Early misfolding is observed in one V180I simulation. Overall, mutations in the hydrophobic core have a significant effect on the dynamics and stability of PrP, including the propensity to misfold, which helps to explain their role in the development of familial prion diseases

Constraints on the thermal and tectonic evolution of Greymouth coalfield

The southern end of the Paparoa Range in Westland, South Island, New Zealand, comprises an asymmetrical, southward plunging, faulted (Brunner-Mt Davy) anticline, the eastern limb of which is common with the western limb of an asymmetrical (Grey Valley) syncline forming a Neogene foreland basin (Grey Valley Trough). The faulted anticline is a classic inversion structure: compression during the Neogene, associated with the development of the modern Australia-Pacific plate boundary, caused a pre-existing normal fault zone, about which a late Cretaceous-Oligocene extensional half graben had formed (Paparoa Trough), to change its sense of displacement. The resulting basement loading formed the foreland basin, containing up to 3 km of mainly marine sedimentary section. Fission track results for apatite concentrates from 41 shallow drillhole and outcrop samples from the Greymouth Coalfield part of the Brunner-Mt Davy Anticline are reported and interpreted, to better establish the timing and amount of inversion, and hence the mechanism of inversion. The fission track results integrated with modelling of vitrinite reflectance data, show that the maximum paleotemperatures experienced during burial of the Late Cretaceous and mid-Eocene coal-bearing succession everywhere exceeded 85deg.C, and reached a peak of 180deg.C along the axis of the former basin. Cooling from maximum temperatures occurred during three discrete phases: 20-15 Ma, 12-7 Ma, and c. 2 Ma to the present. The amount of denudation has been variable across the inverted basin, decreasing westward from a maximum of c. 2.5 km during the first deformation phase, c. 1.2 km during the second phase, and 1.4 km during the third phase. It appears that exhumation over the coalfield continued for about 2 m.y. beyond the biostratigraphically determined time ranges of each of two synorogenic unconformities along the western limb of the Grey Valley Syncline. Stick-slip behaviour on the range front fault that localised the inversion is inferred. The tectonic evolution of the anticline-syncline pair at the southern end of the Paparoa Range, is therefore identical in style, and similar in timing, to the development of the Papahaua Range-Westport Trough across the Kongahu Fault Zone, in the vicinity of Buller Coalfield

Ponderomotive manipulation of cold subwavelength plasmas

Ponderomotive forces (PFs) induced in cold subwavelength plasmas by an externally applied electromagnetic wave are studied analytically. To this end, the plasma is modeled as a sphere with a radially varying permittivity, and the internal electric fields are calculated by solving the macroscopic Maxwell equations using an expansion in Debye potentials. It is found that the PF is directed opposite to the plasma density gradient, similarly to large-scale plasmas. In case of a uniform density profile, a residual spherically symmetric compressive PF is found, suggesting possibilities for contactless ponderomotive manipulation of homogeneous subwavelength objects. The presence of a surface PF on discontinuous plasma boundaries is derived. This force is essential for a microscopic description of the radiation-plasma interaction consistent with momentum conservation. It is shown that the PF integrated over the plasma volume is equivalent to the radiation pressure exerted on the plasma by the incident wave. The concept of radiative acceleration of subwavelength plasmas, proposed earlier, is applied to ultracold plasmas. It is estimated that these plasmas may be accelerated to keV ion energies, resulting in a neutralized beam with a brightness comparable to that of current high-performance ion sources.Comment: 16 pages, 6 figure

Two-dimensional anisotropic Heisenberg antiferromagnet in a field

The classical, square lattice, uniaxially anisotropic Heisenberg antiferromagnet in a magnetic field parallel to the easy axis is studied using Monte Carlo techniques. The model displays a long-range ordered antiferromagnetic, an algebraically ordered spin-flop, and a paramagnetic phase. The simulations indicate that a narrow disordered phase intervenes between the ordered phases down to quite low temperatures. Results are compared to previous, partially conflicting findings on related classical models as well as the quantum variant with spin S=1/2.Comment: 8 pages, 9 figure

Classical formulations of the electromagnetic self-force of extended charged bodies

Several noncovariant formulations of the electromagnetic self-force of extended charged bodies, as have been developed in the context of classical models of charged particles, are compared. The mathematical equivalence of the various dissimilar self-force expressions is demonstrated explicitly by deriving these expressions directly from one another. The applicability of the self-force formulations and their significance in the wider context of classical charged particle models are discussed.Comment: 21 pages, 1 figur

The staircase method: integrals for periodic reductions of integrable lattice equations

We show, in full generality, that the staircase method provides integrals for mappings, and correspondences, obtained as traveling wave reductions of (systems of) integrable partial difference equations. We apply the staircase method to a variety of equations, including the Korteweg-De Vries equation, the five-point Bruschi-Calogero-Droghei equation, the QD-algorithm, and the Boussinesq system. We show that, in all these cases, if the staircase method provides r integrals for an n-dimensional mapping, with 2r<n, then one can introduce q<= 2r variables, which reduce the dimension of the mapping from n to q. These dimension-reducing variables are obtained as joint invariants of k-symmetries of the mappings. Our results support the idea that often the staircase method provides sufficiently many integrals for the periodic reductions of integrable lattice equations to be completely integrable. We also study reductions on other quad-graphs than the regular 2D lattice, and we prove linear growth of the multi-valuedness of iterates of high-dimensional correspondences obtained as reductions of the QD-algorithm.Comment: 40 pages, 23 Figure

Involutivity of integrals for sine-Gordon, modified KdV and potential KdV maps

Closed form expressions in terms of multi-sums of products have been given in \cite{Tranclosedform, KRQ} of integrals of sine-Gordon, modified Korteweg-de Vries and potential Korteweg-de Vries maps obtained as so-called $(p,-1)$-traveling wave reductions of the corresponding partial difference equations. We prove the involutivity of these integrals with respect to recently found symplectic structures for those maps. The proof is based on explicit formulae for the Poisson brackets between multi-sums of products.Comment: 24 page