Electrospun pH-sensitive core-shell polymer nanocomposites fabricated using a tri-axial process

A modified tri-axial electrospinning process was developed for the generation of a new type of pH-sensitive polymer/lipid nanocomposite. The systems produced are able to promote both dissolution and permeation of a model poorly water-soluble drug. First, we show that it is possible to run a tri-axial procress with only one of the three fluids being electrospinnable. Using an electrospinnable middle fluid of Eudragit S100 (ES100) with pure ethanol as the outer solvent and an unspinnable lecithin-diclofenac sodium (PL-DS) core solution, nanofibers with linear morphology and clear core/shell structures can be fabricated continuously and smoothly. X-ray diffraction proved that these nanofibers are structural nanocomposites with the drug present in an amorphous state. In vitro dissolution tests demonstrated that the formulations could preclude release in acidic conditions, and that the drug was released from the fibers in two successive steps at neutral pH. The first step is the dissolution of the shell ES100 and the conversion of the core PL-DS into sub-micron sized particles. This frees some DS into solution, and later the remaining DS is gradually released from the PL-DS particles through diffusion. Ex vivo permeation results showed that the composite nanofibers give a more than two-fold uplift in the amount of DS passing through the colonic membrane as compared to pure DS; 74% of the transmitted drug was in the form of PL-DS particles. The new tri-axial electrospinning process developed in this work provides a platform to fabricate structural nanomaterials, and the core-shell polymer-PL nanocomposites we have produced have significant potential applications for oral colon-targeted drug delivery. STATEMENT OF SIGNIFICANCE: A modified tri-axial electrospinning is demonstrated to create a new type of core-shell pH-sensitive polymer/lipid nanocomposites, in which an electrospinnable middle fluid is exploited to support the un-spinnable outer and inner fluids. The structural nanocomposites are able to provide a colon-targeted sustained release and an enhanced permeation performance of diclofenac sodium. The developed tri-axial process can provide a platform for fabricating new structural nanomaterials with high quality. The strategy of a combined usage of polymeric excipients and phosphilipid in a core-shell format should provide new possibilities of developing novel drug delivery systems for efficacious oral administration of poorly-water soluble drugs

An investigation of minimisation criteria

Minimisation can be used within treatment trials to ensure that prognostic factors are evenly distributed between treatment groups. The technique is relatively straightforward to apply but does require running tallies of patient recruitments to be made and some simple calculations to be performed prior to each allocation. As computing facilities have become more widely available, minimisation has become a more feasible option for many. Although the technique has increased in popularity, the mode of application is often poorly reported and the choice of input parameters not justified in any logical way

Evidence for genetic association of TBX21 and IFNG with systemic lupus erythematosus in a Chinese Han population

TBX21 recode T-bet which is an important transcription factor that drives the Th1 immune response primarily by promoting expression of the interferon-gamma (IFNG) gene. Recent studies have shown that genetic variants in TBX21 and IFNG are connected with risk of systemic lupus erythematosus (SLE). The aim of the present study was to replicate these genetic associations with SLE in Anhui Chinese population. Genotyping of 3 variants (rs4794067 in TBX21, rs2069705 and rs2069718 in IFNG) was performed. A total of 3732 subjects were included in the final analysis. The study only identified the association of rs2069705 with SLE susceptibility (T vs. C: odds ratio [OR] = 1.12, 95% confidence interval [CI] = 1.00-1.26, P = 0.046). Combined analysis with Hong Kong GWAS showed that the OR for rs2069705 was 1.10 (95% CI: 1.01-1.21, P = 0.027). Further pooled analysis with Korean populations involving 10498 subjects showed a more significant association between rs2069705 and SLE (T vs. C: OR = 1.11, 95%CI = 1.04-1.19, P = 0.002; TT + TC vs. CC: OR = 1.11, 95%CI = 1.02-1.21, P = 0.012; TT vs. TC + CC: OR = 1.28, 95%CI = 1.07-1.54, P = 0.008; TT vs. CC: OR = 1.33, 95%CI = 1.10-1.60, P = 0.003). In addition, we also identified a significant genetic interaction between rs2069705 and rs4794067 in Anhui Chinese population. Our study suggests that IFNG and IFNG-TBX21 interaction are involved in SLE susceptibility.published_or_final_versio

The Rich Structure of Gauss-Bonnet Holographic Superconductors

We study fully backreacting, Gauss-Bonnet (GB) holographic superconductors in 5 bulk spacetime dimensions. We explore the system's dependence on the scalar mass for both positive and negative GB coupling, $\alpha$. We find that when the mass approaches the Breitenlohner-Freedman (BF) bound and $\alpha\rightarrow L^2/4$ the effect of backreaction is to increase the critical temperature, $T_c$, of the system: the opposite of its effect in the rest of parameter space. We also find that reducing $\alpha$ below zero increases $T_c$ and that the effect of backreaction is diminished. We study the zero temperature limit, proving that this system does not permit regular solutions for a non-trivial, tachyonic scalar field and constrain possible solutions for fields with positive masses. We investigate singular, zero temperature solutions in the Einstein limit but find them to be incompatible with the concept of GB gravity being a perturbative expansion of Einstein gravity. We study the conductivity of the system, finding that the inclusion of backreaction hinders the development of poles in the conductivity that are associated with quasi-normal modes approaching the real axis from elsewhere in the complex plane.Comment: 26 pages, 11 figures, V3, Added discussion of non-tachyonic scalars, alterations to figures and tex

Holographic fermions in charged Gauss-Bonnet black hole

We study the properties of the Green's functions of the fermions in charged Gauss-Bonnet black hole. What we want to do is to investigate how the presence of Gauss-Bonnet coupling constant $\alpha$ affects the dispersion relation, which is a characteristic of Fermi or non-Fermi liquid, as well as what properties such a system has, for instance, the Particle-hole (a)symmetry. One important result of this research is that we find for $q=1$, the behavior of this system is different from that of the Landau Fermi liquid and so the system can be candidates for holographic dual of generalized non-Fermi liquids. More importantly, the behavior of this system increasingly similar to that of the Landau Fermi liquid when $\alpha$ is approaching its lower bound. Also we find that this system possesses the Particle-hole asymmetry when $q\neq 0$, another important characteristic of this system. In addition, we also investigate briefly the cases of the charge dependence.Comment: 22 pages, 6 figures; version published in JHE

Dipole Coupling Effect of Holographic Fermion in the Background of Charged Gauss-Bonnet AdS Black Hole

We investigate the holographic fermions in the charged Gauss-Bonnet $AdS_{d}$ black hole background with the dipole coupling between fermion and gauge field in the bulk. We show that in addition to the strength of the dipole coupling, the spacetime dimension and the higher curvature correction in the gravity background also influence the onset of the Fermi gap and the gap distance. We find that the higher curvature effect modifies the fermion spectral density and influences the value of the Fermi momentum for the appearance of the Fermi surface. There are richer physics in the boundary fermion system due to the modification in the bulk gravity.Comment: 16 pages, accepted for publication in JHE

A single sub-km Kuiper Belt object from a stellar Occultation in archival data

The Kuiper belt is a remnant of the primordial Solar System. Measurements of its size distribution constrain its accretion and collisional history, and the importance of material strength of Kuiper belt objects (KBOs). Small, sub-km sized, KBOs elude direct detection, but the signature of their occultations of background stars should be detectable. Observations at both optical and X-ray wavelengths claim to have detected such occultations, but their implied KBO abundances are inconsistent with each other and far exceed theoretical expectations. Here, we report an analysis of archival data that reveals an occultation by a body with a 500 m radius at a distance of 45 AU. The probability of this event to occur due to random statistical fluctuations within our data set is about 2%. Our survey yields a surface density of KBOs with radii larger than 250 m of 2.1^{+4.8}_{-1.7} x 10^7 deg^{-2}, ruling out inferred surface densities from previous claimed detections by more than 5 sigma. The fact that we detected only one event, firmly shows a deficit of sub-km sized KBOs compared to a population extrapolated from objects with r>50 km. This implies that sub-km sized KBOs are undergoing collisional erosion, just like debris disks observed around other stars.Comment: To appear in Nature on December 17, 2009. Under press embargo until 1800 hours London time on 16 December. 19 pages; 7 figure

Generation of Three-Qubit Entangled States using Superconducting Phase Qubits

Entanglement is one of the key resources required for quantum computation, so experimentally creating and measuring entangled states is of crucial importance in the various physical implementations of a quantum computer. In superconducting qubits, two-qubit entangled states have been demonstrated and used to show violations of Bell's Inequality and to implement simple quantum algorithms. Unlike the two-qubit case, however, where all maximally-entangled two-qubit states are equivalent up to local changes of basis, three qubits can be entangled in two fundamentally different ways, typified by the states $|\mathrm{GHZ}> = (|000> + |111>)/\sqrt{2}$ and $|\mathrm{W}> = (|001> + |010> + |100>)/\sqrt{3}$. Here we demonstrate the operation of three coupled superconducting phase qubits and use them to create and measure $|\mathrm{GHZ}>$ and $|\mathrm{W}>$ states. The states are fully characterized using quantum state tomography and are shown to satisfy entanglement witnesses, confirming that they are indeed examples of three-qubit entanglement and are not separable into mixtures of two-qubit entanglement.Comment: 9 pages, 5 figures. Version 2: added supplementary information and fixed image distortion in Figure 2

TGF-beta 1 induces human alveolar epithelial to mesenchymal cell transition (EMT)

Background: Fibroblastic foci are characteristic features in lung parenchyma of patients with idiopathic pulmonary fibrosis (IPF). They comprise aggregates of mesenchymal cells which underlie sites of unresolved epithelial injury and are associated with progression of fibrosis. However, the cellular origins of these mesenchymal phenotypes remain unclear. We examined whether the potent fibrogenic cytokine TGF-β1 could induce epithelial mesenchymal transition (EMT) in the human alveolar epithelial cell line, A549, and investigated the signaling pathway of TGF-β1-mediated EMT. Methods: A549 cells were examined for evidence of EMT after treatment with TGF-β1. EMT was assessed by: morphology under phase-contrast microscopy; Western analysis of cell lysates for expression of mesenchymal phenotypic markers including fibronectin EDA (Fn-EDA), and expression of epithelial phenotypic markers including E-cadherin (E-cad). Markers of fibrogenesis, including collagens and connective tissue growth factor (CTGF) were also evaluated by measuring mRNA level using RT-PCR, and protein by immunofluorescence or Western blotting. Signaling pathways for EMT were characterized by Western analysis of cell lysates using monoclonal antibodies to detect phosphorylated Erk1/2 and Smad2 after TGF-β1 treatment in the presence or absence of MEK inhibitors. The role of Smad2 in TGF-β1-mediated EMT was investigated using siRNA. Results: The data showed that TGF-β1, but not TNF-α or IL-1β, induced A549 cells with an alveolar epithelial type II cell phenotype to undergo EMT in a time-and concentration-dependent manner. The process of EMT was accompanied by morphological alteration and expression of the fibroblast phenotypic markers Fn-EDA and vimentin, concomitant with a downregulation of the epithelial phenotype marker E-cad. Furthermore, cells that had undergone EMT showed enhanced expression of markers of fibrogenesis including collagens type I and III and CTGF. MMP-2 expression was also evidenced. TGF-β1-induced EMT occurred through phosphorylation of Smad2 and was inhibited by Smad2 gene silencing; MEK inhibitors failed to attenuate either EMT-associated Smad2 phosphorylation or the observed phenotypic changes. Conclusion: Our study shows that TGF-β1 induces A549 alveolar epithelial cells to undergo EMT via Smad2 activation. Our data support the concept of EMT in lung epithelial cells, and suggest the need for further studies to investigate the phenomenon