Molecular pathogenesis of sporadic prion diseases in man

The yeast, fungal and mammalian prions determine heritable and infectious traits that are encoded in alternative conformations of proteins. They cause lethal sporadic, familial and infectious neurodegenerative conditions in man, including Creutzfeldt-Jakob disease (CJD), Gerstmann-Sträussler-Scheinker syndrome (GSS), kuru, sporadic fatal insomnia (SFI) and likely variable protease-sensitive prionopathy (VPSPr). The most prevalent of human prion diseases is sporadic (s)CJD. Recent advances in amplification and detection of prions led to considerable optimism that early and possibly preclinical diagnosis and therapy might become a reality. Although several drugs have already been tested in small numbers of sCJD patients, there is no clear evidence of any agent’s efficacy. Therefore, it remains crucial to determine the full spectrum of sCJD prion strains and the conformational features in the pathogenic human prion protein governing replication of sCJD prions. Research in this direction is essential for the rational development of diagnostic as well as therapeutic strategies. Moreover, there is growing recognition that fundamental processes involved in human prion propagation – intercellular induction of protein misfolding and seeded aggregation of misfolded host proteins – are of far wider significance. This insight leads to new avenues of research in the ever-widening spectrum of age-related human neurodegenerative diseases that are caused by protein misfolding and that pose a major challenge for healthcare

First-Order Melting of a Moving Vortex Lattice: Effects of Disorder

We study the melting of a moving vortex lattice through numerical simulations with the current driven 3D XY model with disorder. We find that there is a first-order phase transition even for large disorder when the corresponding equilibrium transition is continuous. The low temperature phase is an anisotropic moving glass.Comment: Important changes from original version. Finite size analysis of results has been added. Figure 2 has been changed. There is a new additional Figure. To be published in Physical Review Letter

First-Order Vortex Lattice Melting and Magnetization of YBa2_2Cu3_3O$_{7-\delta}

We present the first non-mean-field calculation of the magnetization $M(T)$ of YBa$_2$Cu$_3$O$_{7-\delta}$ both above and below the flux-lattice melting temperature $T_m(H)$. The results are in good agreement with experiment as a function of transverse applied field $H$. The effects of fluctuations in both order parameter $\psi({\bf r})$ and magnetic induction $B$ are included in the Ginzburg-Landau free energy functional: $\psi({\bf r})$ fluctuates within the lowest Landau level in each layer, while $B$ fluctuates uniformly according to the appropriate Boltzmann factor. The second derivative $(\partial^2 M/\partial T^2)_H$ is predicted to be negative throughout the vortex liquid state and positive in the solid state. The discontinuities in entropy and magnetization at melting are calculated to be $\sim 0.034\, k_B$ per flux line per layer and $\sim 0.0014$~emu~cm$^{-3}$ at a field of 50 kOe.Comment: 11 pages, 4 PostScript figures in one uuencoded fil

Energy cost associated with vortex crossing in superconductors

Starting from the Ginzburg-Landau free energy of a type II superconductor in a magnetic field we estimate the energy associated with two vortices crossing. The calculations are performed by assuming that we are in a part of the phase diagram where the lowest Landau level approximation is valid. We consider only two vortices but with two markedly different sets of boundary conditions: on a sphere and on a plane with quasi-periodic boundary conditions. We find that the answers are very similar suggesting that the energy is localised to the crossing point. The crossing energy is found to be field and temperature dependent -- with a value at the experimentally measured melting line of $U_\times \simeq 7.5 k T_m \simeq 1.16/c_L^2$, where $c_L$ is the Lindemann melting criterion parameter. The crossing energy is then used with an extension of the Marchetti, Nelson and Cates hydrodynamic theory to suggest an explanation of the recent transport experiments of Safar {{\em et al.}\ }.Comment: 15 pages, RevTex v3.0, followed by 5 postscript figure

First order phase transition of the vortex lattice in twinned YBa2Cu3O7 single crystals in tilted magnetic fields

We present an exhaustive analysis of transport measurements performed in twinned YBa2Cu3O7 single crystals which stablishes that the vortex solid-liquid transition is first order when the magnetic field H is applied at an angle theta away from the direction of the twin planes. We show that the resistive transitions are hysteretic and the V-I curves are non-linear, displaying a characteristic s-shape at the melting line Hm(T), which scales as epsilon(theta)Hm(T,theta). These features are gradually lost when the critical point H*(theta) is approached. Above H*(theta) the V-I characteristics show a linear response in the experimentally accessible V-I window, and the transition becomes reversible. Finally we show that the first order phase transition takes place between a highly correlated vortex liquid in the field direction and a solid state of unknown symmetry. As a consequence, the available data support the scenario for a vortex-line melting rather than a vortex sublimation as recently suggested [T.Sasagawa et al. PRL 80, 4297 (1998)].Comment: 10 pages, 8 figures, submitted to PR

Dynamics of Flux Creep in Underdoped Single Crystals of Y_1-xPr_xBa_2Cu_3O_7-d

Transport as well as magnetic relaxation properties of the mixed state were studied on strongly underdoped Y_1-xPr_xBa_2Cu_3O_7-d crystals. We observed two correlated phenomena - a coupling transition and a transition to quantum creep. The distribution of transport current below the coupling transition is highly nonuniform, which facilitates quantum creep. We speculate that in the mixed state below the coupling transition, where dissipation is nonohmic, the current distribution may be unstable with respect to self-channeling resulting in the formation of very thin current-carrying layers.Comment: 11 pages, 9 figures, Submitted to Phys. Rev.

Density-functional theory of freezing of vortex-liquid in quasi two-dimensional superconductors

We present a theory of vortex liquid-to-solid transition in homogeneous quasi 2D superconductors. The free energy is written as a functional l of density of zeroes of the fluctuating order parameter. The transition is weakly first-order and well below the Hc2(T) line. Transition temperature, discontinuities of the average Abrikosov ratio and of the average superfluid density, the Debay-Waller factor and the latent heat are in good agreement with Monte Carlo simulations. The density is only weakly modulated in the "vortex-solid" phase, consistent with the density-wave behavior.Comment: 12 pages and 1 figure available upon request, LaTex Version 2.09, submitted to Phys. Rev. Let

Vortex pinning by natural defects in thin films of YBa2Cu3O7−δ

Although vortex pinning in laser-ablated YBa2Cu3O7−δ films on (100) SrTiO3 is dominated by threading dislocations, many other natural pinning sites are present. To identify the contribution from twin planes, surface corrugations and point defects, we manipulate the relative densities of all defects by post-annealing films with various as-grown dislocation densities, ndisl. While a universal magnetic field B dependence of the transport current density js(B, T) is observed (independently of ndisl, temperature T and the annealing treatment), the defect structure changes considerably. Correlating the microstructure to js(B, T), it becomes clear that surface roughness, twins and point defects are not important at low magnetic fields compared to linear defect pinning. Transmission electron microscopy indicates that threading dislocations are not part of grain boundaries nor are they related to the twin domain structure. We conclude that js(B, T) is essentially determined by pinning along threading dislocations, naturally induced during the growth process. Even in high magnetic fields, where the vortex density outnumbers ndisl, it appears that linear defects stabilize the vortex lattice by means of the vortex–vortex interaction.