Superconductor-to-Normal Phase Transition in a Vortex Glass Model: Numerical Evidence for a New Percolation Universality Class

The three-dimensional strongly screened vortex-glass model is studied numerically using methods from combinatorial optimization. We focus on the effect of disorder strength on the ground state and found the existence of a disorder-driven normal-to-superconducting phase transition. The transition turns out to be a geometrical phase transition with percolating vortex loops in the ground state configuration. We determine the critical exponents and provide evidence for a new universality class of correlated percolation.Comment: 11 pages LaTeX using IOPART.cls, 11 eps-figures include

Many Many Leagues at Sea

At eve I pace the whiten\u27d sandsI wipe my hair with nervous handsSo thick with dew the shining bands,I sigh I moan oh wearilyFor many, many leagues of seaNow lie between my love and me!For many many leagues of seaNow lie between my love and me. His lips rain\u27d kisses on my hair,He left me standing tumbling there;He said in words, so soft so fair, I will come back, come back to theeThough many, many leagues of seaMay lie between my love and me!Though many, many leagues of seaMay lie between my love and me. Oh say not that I wait in vain!That others watch\u27d with throbbing brainFor truant ones who never came,So false to me, he could bot beThough many, many leagues of seaDo lie between my love and me!Though many, many leagues of seaDo lie between my love and me

Renormalized field theory of collapsing directed randomly branched polymers

We present a dynamical field theory for directed randomly branched polymers and in particular their collapse transition. We develop a phenomenological model in the form of a stochastic response functional that allows us to address several interesting problems such as the scaling behavior of the swollen phase and the collapse transition. For the swollen phase, we find that by choosing model parameters appropriately, our stochastic functional reduces to the one describing the relaxation dynamics near the Yang-Lee singularity edge. This corroborates that the scaling behavior of swollen branched polymers is governed by the Yang-Lee universality class as has been known for a long time. The main focus of our paper lies on the collapse transition of directed branched polymers. We show to arbitrary order in renormalized perturbation theory with $\varepsilon$-expansion that this transition belongs to the same universality class as directed percolation.Comment: 18 pages, 7 figure

Percolation with excluded small clusters and Coulomb blockade in a granular system

We consider dc-conductivity $\sigma$ of a mixture of small conducting and insulating grains slightly below the percolation threshold, where finite clusters of conducting grains are characterized by a wide spectrum of sizes. The charge transport is controlled by tunneling of carriers between neighboring conducting clusters via short ``links'' consisting of one insulating grain. Upon lowering temperature small clusters (up to some $T$-dependent size) become Coulomb blockaded, and are avoided, if possible, by relevant hopping paths. We introduce a relevant percolational problem of next-nearest-neighbors (NNN) conductivity with excluded small clusters and demonstrate (both numerically and analytically) that $\sigma$ decreases as power law of the size of excluded clusters. As a physical consequence, the conductivity is a power-law function of temperature in a wide intermediate temperature range. We express the corresponding index through known critical indices of the percolation theory and confirm this relation numerically.Comment: 7 pages, 6 figure

Towards complete integrability of two dimensional Poincar\'e gauge gravity

It is shown that gravity on the line can be described by the two dimensional (2D) Hilbert-Einstein Lagrangian supplemented by a kinetic term for the coframe and a translational {\it boundary} term. The resulting model is equivalent to a Yang-Mills theory of local {\it translations} and frozen Lorentz gauge degrees. We will show that this restricted Poincar\'e gauge model in 2 dimensions is completely integrable. {\it Exact} wave, charged black hole, and `dilaton' solutions are then readily found. In vacuum, the integrability of the {\it general} 2D Poincar\'e gauge theory is formally proved along the same line of reasoning.Comment: 35 pages, report Cologne-thp-1993-H

Negative Staining and Image Classification – Powerful Tools in Modern Electron Microscopy

Vitrification is the state-of-the-art specimen preparation technique for molecular electron microscopy (EM) and therefore negative staining may appear to be an outdated approach. In this paper we illustrate the specific advantages of negative staining, ensuring that this technique will remain an important tool for the study of biological macromolecules. Due to the higher image contrast, much smaller molecules can be visualized by negative staining. Also, while molecules prepared by vitrification usually adopt random orientations in the amorphous ice layer, negative staining tends to induce preferred orientations of the molecules on the carbon support film. Combining negative staining with image classification techniques makes it possible to work with very heterogeneous molecule populations, which are difficult or even impossible to analyze using vitrified specimens

Population dynamics of an RNA virus and its defective interfering particles in passage cultures

<p>Abstract</p> <p>Background</p> <p>Viruses can fall prey to their defective interfering (DI) particles. When viruses are cultured by serial passage on susceptible host cells, the presence of virus-like DI particles can cause virus populations to rise and fall, reflecting predator-prey interactions between DI and virus particles. The levels of virus and DI particles in each population passage can be determined experimentally by plaque and yield-reduction assays, respectively.</p> <p>Results</p> <p>To better understand DI and virus particle interactions we measured vesicular stomatitis virus and DI particle production during serial-passage culture on BHK cells. When the multiplicity of infection (MOI, or ratio of infectious virus particles to cells) was fixed, virus yields followed a pattern of progressive decline, with higher MOI driving earlier and faster drops in virus level. These patterns of virus decline were consistent with predictions from a mathematical model based on single-passage behavior of cells co-infected with virus and DI particles. By contrast, the production of virus during fixed-volume passages exhibited irregular fluctuations that could not be described by either the steady-state or regular oscillatory dynamics of the model. However, these irregularities were, to a significant degree, reproduced when measured host-cell levels were incorporated into the model, revealing a high sensitivity of virus and DI particle populations to fluctuations in available cell resources.</p> <p>Conclusions</p> <p>This study shows how the development of mathematical models, when guided by quantitative experiments, can provide new insight into the dynamic behavior of virus populations.</p

Safety of nintedanib added to pirfenidone treatment for idiopathic pulmonary fibrosis

We assessed safety and tolerability of treatment with pirfenidone (1602-2403 mg day-1) and nintedanib (200-300 mg day-1) in patients with idiopathic pulmonary fibrosis (IPF). This 24-week, single-arm, open-label, phase IV study (ClinicalTrials.gov identifier NCT02598193) enrolled patients with IPF with forced vital capacity % pred ≫50% and diffusing capacity of the lung for carbon monoxide % pred ≫30%. Before initiating nintedanib, patients had received pirfenidone for ≫16 weeks and tolerated a stable dose of ≫1602 mg day-1 for ≫28 days. The primary end-point was the proportion of patients who completed 24 weeks of combination treatment on pirfenidone (1602- 2403 mg day-1) and nintedanib (200-300 mg day-1). Investigators recorded treatment-emergent adverse events (TEAEs), attributing them to pirfenidone, nintedanib, both or neither. 89 patients were enrolled; 73 completed 24 weeks of treatment (69 meeting the primary end-point) and 16 discontinued treatment prematurely (13 due to TEAEs). 74 patients had 418 treatment-related TEAEs, of which diarrhoea, nausea and vomiting were the most common. Two patients had serious treatmentrelated TEAEs. Combined pirfenidone and nintedanib use for 24 weeks was tolerated by the majority of patients with IPF and associated with a similar pattern of TEAEs expected for either treatment alone. These results encourage further study of combination treatment with pirfenidone and nintedanib in patients with IPF

Expression of a protein involved in bone resorption, Dkk1, is activated by HTLV-1 bZIP factor through its activation domain

<p>Abstract</p> <p>Background</p> <p>Human T-cell leukemia virus type 1 (HTLV-1) is the etiologic agent of adult T-cell leukemia, a malignancy characterized by uncontrolled proliferation of virally-infected CD4+ T-cells. Hypercalcemia and bone lesions due to osteoclast-mediated bone resorption are frequently associated with more aggressive forms of the disease. The HTLV-1 provirus contains a unique antisense gene that expresses HTLV-1 basic leucine zipper (bZIP) factor (HBZ). HBZ is localized to the nucleus where it regulates levels of transcription by binding to certain cellular transcriptional regulators. Among its protein targets, HBZ forms a stable complex with the homologous cellular coactivators, p300 and CBP, which is modulated through two N-terminal LXXLL motifs in the viral protein and the conserved KIX domain in the coactivators.</p> <p>Results</p> <p>To determine the effects of these interactions on transcription, we performed a preliminary microarray analysis, comparing levels of gene expression in cells with wild-type HBZ versus cells with HBZ mutated in its LXXLL motifs. <it>DKK1</it>, which encodes the secreted Wnt signaling inhibitor, Dickkopf-1 (Dkk1), was confirmed to be transcriptionally activated by HBZ, but not its mutant. Dkk1 plays a major role in the development of bone lesions caused by multiple myeloma. In parallel with the initial findings, activation of Dkk1 expression by HBZ was abrogated by siRNA-mediated knockdown of p300/CBP or by a truncated form of p300 containing the KIX domain. Among HTLV-1-infected T-cell lines tested, the detection of Dkk1 mRNA partially correlated with a threshold level of HBZ mRNA. In addition, an uninfected and an HTLV-1-infected T-cell line transfected with an HBZ expression vector exhibited <it>de novo </it>and increased DKK1 transcription, respectively. In contrast to HBZ, The HTLV-1 Tax protein repressed Dkk1 expression.</p> <p>Conclusions</p> <p>These data indicate that HBZ activates Dkk1 expression through its interaction with p300/CBP. However, this effect is limited in HTLV-1-infected T-cell lines, which in part, may be due to suppression of Dkk1 expression by Tax. Consequently, the ability of HBZ to regulate expression of Dkk1 and possibly other cellular genes may only be significant during late stages of ATL, when Tax expression is repressed.</p

The Biochemistry, Ultrastructure, and Subunit Assembly Mechanism of AMPA Receptors

The AMPA-type ionotropic glutamate receptors (AMPA-Rs) are tetrameric ligand-gated ion channels that play crucial roles in synaptic transmission and plasticity. Our knowledge about the ultrastructure and subunit assembly mechanisms of intact AMPA-Rs was very limited. However, the new studies using single particle EM and X-ray crystallography are revealing important insights. For example, the tetrameric crystal structure of the GluA2cryst construct provided the atomic view of the intact receptor. In addition, the single particle EM structures of the subunit assembly intermediates revealed the conformational requirement for the dimer-to-tetramer transition during the maturation of AMPA-Rs. These new data in the field provide new models and interpretations. In the brain, the native AMPA-R complexes contain auxiliary subunits that influence subunit assembly, gating, and trafficking of the AMPA-Rs. Understanding the mechanisms of the auxiliary subunits will become increasingly important to precisely describe the function of AMPA-Rs in the brain. The AMPA-R proteomics studies continuously reveal a previously unexpected degree of molecular heterogeneity of the complex. Because the AMPA-Rs are important drug targets for treating various neurological and psychiatric diseases, it is likely that these new native complexes will require detailed mechanistic analysis in the future. The current ultrastructural data on the receptors and the receptor-expressing stable cell lines that were developed during the course of these studies are useful resources for high throughput drug screening and further drug designing. Moreover, we are getting closer to understanding the precise mechanisms of AMPA-R-mediated synaptic plasticity