Ground state properties of fluxlines in a disordered environment

A new numerical method to calculate exact ground states of multi-fluxline systems with quenched disorder is presented, which is based on the minimum cost flow algorithm from combinatorial optimization. We discuss several models that can be studied with this method including their specific implementations, physically relevant observables and results: 1) the N-line model with N fluxlines (or directed polymers) in a d-dimensional environment with point and/or columnar disorder and hard or soft core repulsion; 2) the vortex glass model for a disordered superconductor in the strong screening limit and 3) the Sine-Gordon model with random pase shifts in the strong coupling limit.Comment: 4 pages RevTeX, 3 eps-figures include

Alpha-l-Locked nucleic acid-modified antisense oligonucleotides induce efficient splice modulation in vitro

Alpha-l-Locked nucleic acid (α-l-LNA) is a stereoisomeric analogue of locked nucleic acid (LNA), which possesses excellent biophysical properties and also exhibits high target binding affinity to complementary oligonucleotide sequences and resistance to nuclease degradations. Therefore, α-l-LNA nucleotides could be utilised to develop stable antisense oligonucleotides (AO), which can be truncated without compromising the integrity and efficacy of the AO. In this study, we explored the potential of α-l-LNA nucleotides-modified antisense oligonucleotides to modulate splicing by inducing Dmd exon-23 skipping in mdx mouse myoblasts in vitro. For this purpose, we have synthesised and systematically evaluated the efficacy of α-l-LNA-modified 2′-O-methyl phosphorothioate (2′-OMePS) AOs of three different sizes including 20mer, 18mer and 16mer AOs in parallel to fully-modified 2′-OMePS control AOs. Our results demonstrated that the 18mer and 16mer truncated AO variants showed slightly better exon-skipping efficacy when compared with the fully-23 modified 2′-OMePS control AOs, in addition to showing low cytotoxicity. As there was no previous report on using α-l-LNA-modified AOs in splice modulation, we firmly believe that this initial study could be beneficial to further explore and expand the scope of α-l-LNA-modified AO therapeutic molecules

Nature of the vortex-glass order in strongly type-II superconductors

The stability and the critical properties of the three-dimensional vortex-glass order in random type-II superconductors with point disorder is investigated in the unscreened limit based on a lattice {\it XY} model with a uniform field. By performing equilibrium Monte Carlo simulations for the system with periodic boundary conditions, the existence of a stable vortex-glass order is established in the unscreened limit. Estimated critical exponents are compared with those of the gauge-glass model.Comment: Error in the reported value of the exponent eta is correcte

Long Range Order at Low Temperature in Dipolar Spin Ice

Recently it has been suggested that long range magnetic dipolar interactions are responsible for spin ice behavior in the Ising pyrochlore magnets ${\rm Dy_{2}Ti_{2}O_{7}}$ and ${\rm Ho_{2}Ti_{2}O_{7}}$. We report here numerical results on the low temperature properties of the dipolar spin ice model, obtained via a new loop algorithm which greatly improves the dynamics at low temperature. We recover the previously reported missing entropy in this model, and find a first order transition to a long range ordered phase with zero total magnetization at very low temperature. We discuss the relevance of these results to ${\rm Dy_{2}Ti_{2}O_{7}}$ and ${\rm Ho_{2}Ti_{2}O_{7}}$.Comment: New version of the manuscript. Now contains 3 POSTSCRIPT figures as opposed to 2 figures. Manuscript contains a more detailed discussion of the (i) nature of long-range ordered ground state, (ii) finite-size scaling results of the 1st order transition into the ground state. Order of authors has been changed. Resubmitted to Physical Review Letters Contact: [email protected]

Investigation of growth responses in saprophytic fungi to charred biomass

We present the results of a study testing the response of two saprophytic white-rot fungi species, Pleurotus pulmonarius and Coriolus versicolor, to charred biomass (charcoal) as a growth substrate. We used a combination of optical microscopy, scanning electron microscopy, elemental abundance measurements, and isotope ratio mass spectrometry (<sup>13</sup>C and <sup>15</sup>N) to investigate fungal colonisation of control and incubated samples of Scots Pine (Pinus sylvestris) wood, and charcoal from the same species produced at 300 °C and 400 °C. Both species of fungi colonise the surface and interior of wood and charcoals over time periods of less than 70 days; however, distinctly different growth forms are evident between the exterior and interior of the charcoal substrate, with hyphal penetration concentrated along lines of structural weakness. Although the fungi were able to degrade and metabolise the pine wood, charcoal does not form a readily available source of fungal nutrients at least for these species under the conditions used in this study

Oligonucleotides Targeting DNA Repeats Downregulate Huntingtin Gene Expression in Huntington's Patient-Derived Neural Model System

Huntington's disease (HD) is one of the most common, dominantly inherited neurodegenerative disorders. It affects the striatum, cerebral cortex, and other subcortical structures leading to involuntary movement abnormalities, emotional disturbances, and cognitive impairments. HD is caused by a CAG•CTG trinucleotide-repeat expansion in exon 1 of the huntingtin (HTT) gene leading to the formation of mutant HTT (mtHTT) protein aggregates. Besides the toxicity of the mutated protein, there is also evidence that mtHTT transcripts contribute to the disease. Thus, the reduction of both mutated mRNA and protein would be most beneficial as a treatment. Previously, we designed a novel anti-gene oligonucleotide (AGO)-based strategy directly targeting the HTT trinucleotide-repeats in DNA and reported downregulation of mRNA and protein in HD patient fibroblasts. In this study, we differentiate HD patient-derived induced pluripotent stem cells to investigate the efficacy of the AGO, a DNA/Locked Nucleic Acid mixmer with phosphorothioate backbone, to modulate HTT transcription during neural in vitro development. For the first time, we demonstrate downregulation of HTT mRNA following both naked and magnetofected delivery into neural stem cells (NSCs) and show that neither emergence of neural rosette structures nor self-renewal of NSCs is compromised. Furthermore, the inhibition potency of both HTT mRNA and protein without off-target effects is confirmed in neurons. These results further validate an anti-gene approach for the treatment of HD

Ground state properties of solid-on-solid models with disordered substrates

We study the glassy super-rough phase of a class of solid-on-solid models with a disordered substrate in the limit of vanishing temperature by means of exact ground states, which we determine with a newly developed minimum cost flow algorithm. Results for the height-height correlation function are compared with analytical and numerical predictions. The domain wall energy of a boundary induced step grows logarithmically with system size, indicating the marginal stability of the ground state, and the fractal dimension of the step is estimated. The sensibility of the ground state with respect to infinitesimal variations of the quenched disorder is analyzed.Comment: 4 pages RevTeX, 3 eps-figures include

Zero Temperature Glass Transition in the Two-Dimensional Gauge Glass Model

We investigate dynamic scaling properties of the two-dimensional gauge glass model for the vortex glass phase in superconductors with quenched disorder. From extensive Monte Carlo simulations we obtain static and dynamic finite size scaling behavior, where the static simulations use a temperature exchange method to ensure convergence at low temperatures. Both static and dynamic scaling of Monte Carlo data is consistent with a glass transition at zero temperature. We study a dynamic correlation function for the superconducting order parameter, as well as the phase slip resistance. From the scaling of these two functions, we find evidence for two distinct diverging correlation times at the zero temperature glass transition. The longer of these time scales is associated with phase slip fluctuations across the system that lead to finite resistance at any finite temperature, while the shorter time scale is associated with local phase fluctuations.Comment: 8 pages, 10 figures; v2: some minor correction

Numerical study of the strongly screened vortex glass model in an external field

The vortex glass model for a disordered high-T_c superconductor in an external magnetic field is studied in the strong screening limit. With exact ground state (i.e. T=0) calculations we show that 1) the ground state of the vortex configuration varies drastically with infinitesimal variations of the strength of the external field, 2) the minimum energy of global excitation loops of length scale L do not depend on the strength of the external field, however 3) the excitation loops themself depend sensibly on the field. From 2) we infer the absence of a true superconducting state at any finite temperature independent of the external field.Comment: 6 pages RevTeX, 5 eps-figures include

The Phase Diagram of Disordered Vortices from London Langevin Simulations

We study the phase diagram of vortex matter in disordered type-II superconductors. We performed numerical simulations in the London Langevin approximation, using a new realistic representation of the disorder. At low magnetic fields we find a disentangled and dislocation free Bragg-glass regime. Increasing the field introduces disorder-driven entanglement in a discontinuous manner, leading to a vortex-glass phase, which subsequently melts into the vortex liquid. The obtained phase boundaries are in quantitative agreement with the experimental data.Comment: 4 pages, revtex, 8 postscript figures include