The Incidence of X-ray selected AGN in Nearby Galaxies

We present the identification and analysis of an unbiased sample of AGN that lie within the local galaxy population. Using the MPA-JHU catalogue (based on SDSS DR8) and 3XMM DR7 we define a parent sample of 25,949 local galaxies ($z \leq 0.33$). After confirming that there was strictly no AGN light contaminating stellar mass and star-formation rate calculations, we identified 917 galaxies with central, excess X-ray emission likely originating from an AGN. We analysed their optical emission lines using the BPT diagnostic and confirmed that such techniques are more effective at reliably identifying sources as AGN in higher mass galaxies: rising from 30% agreement in the lowest mass bin to 93% in the highest. We then calculated the growth rates of the black holes powering these AGN in terms of their specific accretion rates ($\propto L_X/M_*$). Our sample exhibits a wide range of accretion rates, with the majority accreting at rates $\leq 0.5\%$ of their Eddington luminosity. Finally, we used our sample to calculate the incidence of AGN as a function of stellar mass and redshift. After correcting for the varying sensitivity of 3XMM, we split the galaxy sample by stellar mass and redshift and investigated the AGN fraction as a function of X-ray luminosity and specific black hole accretion rate. From this we found the fraction of galaxies hosting AGN above a fixed specific accretion rate limit of $10^{-3.5}$ is constant (at $\approx 1\%$) over stellar masses of $8 < \log \mathrm{M_*/M_\odot} < 12$ and increases (from $\approx 1\%$ to $10\%$) with redshift.Comment: 18 pages, 10 figures, 2 appendices. Accepted for publication in MNRA

Random-matrix theory of amplifying and absorbing resonators with PT or PTT' symmetry

We formulate gaussian and circular random-matrix models representing a coupled system consisting of an absorbing and an amplifying resonator, which are mutually related by a generalized time-reversal symmetry. Motivated by optical realizations of such systems we consider a PT or a PTT' time-reversal symmetry, which impose different constraints on magneto-optical effects, and then focus on five common settings. For each of these, we determine the eigenvalue distribution in the complex plane in the short-wavelength limit, which reveals that the fraction of real eigenvalues among all eigenvalues in the spectrum vanishes if all classical scales are kept fixed. Numerically, we find that the transition from real to complex eigenvalues in the various ensembles display a different dependence on the coupling strength between the two resonators. These differences can be linked to the level spacing statistics in the hermitian limit of the considered models.Comment: 19 pages, 9 figure

Formulation of hydrophobic peptides for skin delivery via coated microneedles

Microneedles (MNs) have been investigated as a minimally-invasive delivery technology for a range of active pharmaceutical ingredients (APIs). Various formulations and methods for coating the surface of MNs with therapeutics have been proposed and exemplified, predominantly for hydrophilic drugs and particulates. The development of effective MN delivery formulations for hydrophobic drugs is more challenging with dosing restrictions and the use of organic solvents impacting on both the bioactivity and the kinetics of drug release. In this study we propose a novel formulation that is suitable for MN coating of hydrophobic auto-antigen peptides currently being investigated for antigen specific immunotherapy (ASI) of type 1 diabetes. The formulation, comprising three co-solvents (water, 2-methyl-2-butanol and acetic acid) and polyvinylalcohol 2000 (PVA2000) can dissolve both hydrophilic and hydrophobic peptide auto-antigens at relatively high, and clinically relevant, concentrations (25 mg/ml or 12.5 mg/ml). The drug:excipient ratio is restricted to 10:1 w/w to maximise dose whilst ensuring that the dry-coated payload does not significantly impact on MN skin penetration performance. The coating formulation and process does not adversely affect the biological activity of the peptide. The delivery efficiency of the coated peptide into skin is influenced by a number of parameters. Electropolishing the metal MN surface increases delivery efficiency from 2.0 ± 1.0% to 59.9 ± 6.7%. An increased mass of peptide formulation per needle, from 0.37 μg to 2 μg peptide dose, resulted in a thicker coating and a 20% reduction in the efficiency of skin delivery. Other important performance parameters for coated MNs include the role of excipients in assisting dissolution from the MNs, the intrinsic hydrophobicity of the peptide and the species of skin model used in laboratory studies. This study therefore both exemplifies the potential of a novel formulation for coating hydrophobic and hydrophilic peptides onto MN devices and provides new insight into the factors that influence delivery efficiency from coated MNs. Importantly, the results provide guidance for identifying critical attributes of the formulation, coating process and delivery device, that confer reproducible and effective delivery from coated MNs, and thus contribute to the requirements of the regulators appraising these devices

High-resolution survey for planetary companions to young stars in the Taurus Molecular Cloud

Direct imaging in the infrared at the diffraction limit of large telescopes is a unique probe of the properties of young planetary systems. We survey 55 single class I and class II stars in Taurus in the L' filter using natural and laser guide star adaptive optics and the near-infrared camera (NIRC2) of the Keck II telescope, in order to search for planetary mass companions. We use both reference star differential imaging and kernel phase techniques, achieving typical 5-sigma contrasts of ~6 magnitudes at separations of 0.2" and ~8 magnitudes beyond 0.5". Although we do not detect any new faint companions, we constrain the frequency of wide separation massive planets, such as HR 8799 analogues. We find that, assuming hot-start models and a planet distribution with power-law mass and semi-major axis indices of -0.5 and -1, respectively, less than 20% of our target stars host planets with masses >2 MJ at separations >10 AU.Comment: 16 pages, 14 figures, accepted for publication in MNRA

Hollow silicon microneedle fabrication using advanced plasma etch technologies for applications in transdermal drug delivery

A novel production process flow is presented here for the manufacture of hollow silicon microneedles using deep reactive-ion etching (DRIE) technology. The patent-pending three-step process flow has been developed to produce multiple arrays of sharp-tipped, hollow microneedles, which facilitate easy insertion and controlled fluid injection into excised skin samples. A bevelled tip and vertical sidewalls for the microneedle have been achieved with good uniformity, despite >45% open etch area. Processing steps and etch challenges are discussed, and preliminary skin testing results are presented, showing effective needle insertion and delivery of fluorescent dye into ex vivo skin from human breast tissue

Hydrodynamic gene delivery in human skin using a hollow microneedle device

Microneedle devices have been proposed as a minimally invasive delivery system for the intradermal administration of nucleic acids, both plasmid DNA (pDNA) and siRNA, to treat localised disease or provide vaccination. Different microneedle types and application methods have been investigated in the laboratory, but limited and irreproducible levels of gene expression have proven to be significant challenges to pre-clinical to clinical progression. This study is the first to explore the potential of a hollow microneedle device for the delivery and subsequent expression of pDNA in human skin. The regulatory approved MicronJet600® (MicronJet hereafter) device was used to deliver reporter plasmids (pCMVβ and pEGFP-N1) into viable excised human skin. Exogenous gene expression was subsequently detected at multiple locations that were distant from the injection site but within the confines of the bleb created by the intradermal bolus. The observed levels of gene expression in the tissue are at least comparable to that achieved by the most invasive microneedle application methods e.g. lateral application of a microneedle. Gene expression was predominantly located in the epidermis, although also evident in the papillary dermis. Optical coherence tomography permitted real time visualisation of the sub-surface skin architecture and, unlike a conventional intradermal injection, MicronJet administration of a 50 μL bolus appears to create multiple superficial microdisruptions in the papillary dermis and epidermis. These were co-localised with expression of the pCMVβ reporter plasmid. We have therefore shown, for the first time, that a hollow microneedle device can facilitate efficient and reproducible gene expression of exogenous naked pDNA in human skin using volumes that are considered to be standard for intradermal administration, and postulate a hydrodynamic effect as the mechanism of gene delivery

Supramolecular Behaviour and Fluorescence of Rhodamine-Functionalised ROMP Polymers

Inherently fluorescent polymers are of interest in materials and medicine. We report a ring-opening metathesis polymerisation (ROMP) platform for creation of amphiphilic block copolymers in which one block is formed from rhodamine B-containing monomers. The polymers self-assemble into well-defined micelles which are able to sequester molecular dyes and further interact with them by energy transfer. Despite incorporating a cationic dye known to bind DNA, the polymer micelles do not interact with DNA, indicating that they are potentially safe for use in bioanalytical applications

In vitro susceptibility of Clostridium difficile to SMT19969 and comparators, as well as the killing kinetics and post-antibiotic effects of SMT19969 and comparators against C. difficile

© The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/ 4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.OBJECTIVES: SMT19969 is a novel antimicrobial under clinical development for the treatment of Clostridium difficile infection (CDI). The objective was to determine the comparative susceptibility of 82 C. difficile clinical isolates (which included ribotype 027 isolates and isolates with reduced metronidazole susceptibility) to SMT19969, fidaxomicin, vancomycin and metronidazole and to determine the killing kinetics and post-antibiotic effects of SMT19969, fidaxomicin and vancomycin against C. difficile. METHODS: MICs were determined by agar incorporation. Killing kinetics and post-antibiotic effects were determined against C. difficile BI1, 630 and 5325 (ribotypes 027, 012 and 078, respectively). RESULTS: SMT19969 showed potent inhibition of C. difficile (MIC90=0.125 mg/L) and was markedly more active than either metronidazole (MIC90 = 8 mg/L) or vancomycin (MIC90 = 2 mg/L). There were no differences in susceptibility to SMT19969 between different ribotypes. Fidaxomicin was typically one doubling dilution more active than SMT19969 and both agents maintained activity against isolates with reduced susceptibility to metronidazole. In addition, SMT19969 was bactericidal against the C. difficile strains tested, with reductions in viable counts to below the limit of detection by 24 h post-inoculation. Vancomycin was bacteriostatic against all three strains. Fidaxomicin was bactericidal although reduced killing was observed at concentrations <20 × MIC against C. difficile BI1 (ribotype 027) compared with other strains tested. CONCLUSIONS: These data demonstrate that SMT19969 is associated with potent and bactericidal activity against the strains tested and support further investigation of SMT19969 as potential therapy for CDI.Peer reviewedFinal Published versio