Measurement and physical interpretation of the mean motion of turbulent density patterns detected by the BES system on MAST

The mean motion of turbulent patterns detected by a two-dimensional (2D) beam emission spectroscopy (BES) diagnostic on the Mega Amp Spherical Tokamak (MAST) is determined using a cross-correlation time delay (CCTD) method. Statistical reliability of the method is studied by means of synthetic data analysis. The experimental measurements on MAST indicate that the apparent mean poloidal motion of the turbulent density patterns in the lab frame arises because the longest correlation direction of the patterns (parallel to the local background magnetic fields) is not parallel to the direction of the fastest mean plasma flows (usually toroidal when strong neutral beam injection is present). The experimental measurements are consistent with the mean motion of plasma being toroidal. The sum of all other contributions (mean poloidal plasma flow, phase velocity of the density patterns in the plasma frame, non-linear effects, etc.) to the apparent mean poloidal velocity of the density patterns is found to be negligible. These results hold in all investigated L-mode, H-mode and internal transport barrier (ITB) discharges. The one exception is a high-poloidal-beta (the ratio of the plasma pressure to the poloidal magnetic field energy density) discharge, where a large magnetic island exists. In this case BES detects very little motion. This effect is currently theoretically unexplained.Comment: 28 pages, 15 figures, submitted to PPC

Centralized Modularity of N-Linked Glycosylation Pathways in Mammalian Cells

Glycosylation is a highly complex process to produce a diverse repertoire of cellular glycans that are attached to proteins and lipids. Glycans are involved in fundamental biological processes, including protein folding and clearance, cell proliferation and apoptosis, development, immune responses, and pathogenesis. One of the major types of glycans, N-linked glycans, is formed by sequential attachments of monosaccharides to proteins by a limited number of enzymes. Many of these enzymes can accept multiple N-linked glycans as substrates, thereby generating a large number of glycan intermediates and their intermingled pathways. Motivated by the quantitative methods developed in complex network research, we investigated the large-scale organization of such N-linked glycosylation pathways in mammalian cells. The N-linked glycosylation pathways are extremely modular, and are composed of cohesive topological modules that directly branch from a common upstream pathway of glycan synthesis. This unique structural property allows the glycan production between modules to be controlled by the upstream region. Although the enzymes act on multiple glycan substrates, indicating cross-talk between modules, the impact of the cross-talk on the module-specific enhancement of glycan synthesis may be confined within a moderate range by transcription-level control. The findings of the present study provide experimentally-testable predictions for glycosylation processes, and may be applicable to therapeutic glycoprotein engineering

Small anisotropy of the lower critical field and s±s_\pm-wave two-gap feature in single crystal LiFeAs

The in- and out-of-plane lower critical fields and magnetic penetration depths for LiFeAs were examined. The anisotropy ratio $\gamma_{H_{c1}}(0)$ is smaller than the expected theoretical value, and increased slightly with increasing temperature from 0.6$T_c$ to $T_c$. This small degree of anisotropy was numerically confirmed by considering electron correlation effect. The temperature dependence of the penetration depths followed a power law($\sim$$T^n$) below 0.3$T_c$, with $n$$>$3.5 for both $\lambda_{ab}$ and $\lambda_c$. Based on theoretical studies of iron-based superconductors, these results suggest that the superconductivity of LiFeAs can be represented by an extended $s_\pm$-wave due to weak impurity scattering effect. And the magnitudes of the two gaps were also evaluted by fitting the superfluid density for both the in- and out-of-plane to the two-gap model. The estimated values for the two gaps are consistent with the results of angle resolved photoemission spectroscopy and specific heat experiments.Comment: 10 pages, 5 figure

Intestinal Epithelial Cell-Specific Deletion of PLD2 Alleviates DSS-Induced Colitis by Regulating Occludin

Ulcerative colitis is a multi-factorial disease involving a dysregulated immune response. Disruptions to the intestinal epithelial barrier and translocation of bacteria, resulting in inflammation, are common in colitis. The mechanisms underlying epithelial barrier dysfunction or regulation of tight junction proteins during disease progression of colitis have not been clearly elucidated. Increase in phospholipase D (PLD) activity is associated with disease severity in colitis animal models. However, the role of PLD2 in the maintenance of intestinal barrier integrity remains elusive. We have generated intestinal specific Pld2 knockout mice (Pld2 IEC-KO) to investigate the mechanism of intestinal epithelial PLD2 in colitis. We show that the knockout of Pld2 confers protection against dextran sodium sulphate (DSS)-induced colitis in mice. Treatment with DSS induced the expression of PLD2 and downregulated occludin in colon epithelial cells. PLD2 was shown to mediate phosphorylation of occludin and induce its proteasomal degradation in a c-Src kinase-dependent pathway. Additionally, we have shown that treatment with an inhibitor of PLD2 can rescue mice from DSS-induced colitis. To our knowledge, this is the first report showing that PLD2 is pivotal in the regulation of the integrity of epithelial tight junctions and occludin turn over, thereby implicating it in the pathogenesis of colitis

Hypothetical biomolecular probe based on a genetic switch with tunable symmetry and stability

Background: Genetic switches are ubiquitous in nature, frequently associated with the control of cellular functions and developmental programs. In the realm of synthetic biology, it is of great interest to engineer genetic circuits that can change their mode of operation from monostable to bistable, or even to multistable, based on the experimental fine-tuning of readily accessible parameters. In order to successfully design robust, bistable synthetic circuits to be used as biomolecular probes, or understand modes of operation of such naturally occurring circuits, we must identify parameters that are key in determining their characteristics. Results: Here, we analyze the bistability properties of a general, asymmetric genetic toggle switch based on a chemical-reaction kinetic description. By making appropriate approximations, we are able to reduce the system to two coupled differential equations. Their deterministic stability analysis and stochastic numerical simulations are in excellent agreement. Drawing upon this general framework, we develop a model of an experimentally realized asymmetric bistable genetic switch based on the LacI and TetR repressors. By varying the concentrations of two synthetic inducers, doxycycline and isopropyl ??-D-1-thiogalactopyranoside, we predict that it will be possible to repeatedly fine-tune the mode of operation of this genetic switch from monostable to bistable, as well as the switching rates over many orders of magnitude, in an experimental setting. Furthermore, we find that the shape and size of the bistability region is closely connected with plasmid copy number. Conclusions: Based on our numerical calculations of the LacI-TetR asymmetric bistable switch phase diagram, we propose a generic work-flow for developing and applying biomolecular probes: Their initial state of operation should be specified by controlling inducer concentrations, and dilution due to cellular division would turn the probes into memory devices in which information could be preserved over multiple generations. Additionally, insights from our analysis of the LacI-TetR system suggest that this particular system is readily available to be employed in this kind of probe.clos

Skin Vaccination against Cervical Cancer Associated Human Papillomavirus with a Novel Micro-Projection Array in a Mouse Model

Background: Better delivery systems are needed for routinely used vaccines, to improve vaccine uptake. Many vaccines contain alum or alum based adjuvants. Here we investigate a novel dry-coated densely-packed micro-projection array skin patch (Nanopatch (TM)) as an alternate delivery system to intramuscular injection for delivering an alum adjuvanted human papillomavirus (HPV) vaccine (Gardasil (R)) commonly used as a prophylactic vaccine against cervical cancer

Multiplicity of uses of monoclonal antibodies that define papillomavirus linear immunodominant epitopes.

During the last 10 yr, we have derived monoclonal antibodies from animals immunized with denatured bovine papillomaviruses type 1 major capsid (L1) protein, mapped their corresponding immunodominant epitopes to within a single amino acid (aa), and compared the reactivity of authentic L1 proteins to the predicted response by collinear analysis of the aa sequences of the same and other papillomaviruses (PVs). The data obtained from this approach has provided us with new insights into the sensitivity and specificity of the antibody response to viral proteins. We have included here some observations and conclusions that appear to be generic for the immune response, some of which might have applications for working with linear epitopes in other experimental systems