Lack of in vitro-in vivo correlation for a UC781-releasing vaginal ring in macaques

This study describes the preclinical development of a matrix-type silicone elastomer vaginal ring device designed to provide controlled release of UC781, a non-nucleoside re- verse transcriptase inhibitor. Testing of both human- and macaque-sized rings in a sink condition in vitro release model demonstrated continuous UC781 release in quantities consid- ered sufficient to maintain vaginal fluid concentrations at levels 82–860-fold higher than the in vitro IC50 (2.0 to 10.4 nM) and therefore potentially protect against mucosal trans- mission of HIV. The 100-mg UC781 rings were well tolerated in pig-tailed macaques, did not induce local inflammation as determined by cytokine analysis and maintained median con- centrations in vaginal fluids of UC781 in the range of 0.27 to 5.18 mM during the course of the 28-day study. Analysis of residual UC781 content in rings after completion of both the in vitro release and macaque pharmacokinetic studies revealed that 57 and 5 mg of UC781 was released, respectively. The pharmacokinetic analysis of a 100-mg UC781 vaginal ring in pig-tailed macaques showed poor in vivo–in vitro correlation, attributed to the very poor solubility of UC781 in vaginal fluid and resulting in a dissolution-controlled drug release mecha- nism rather than the expected diffusion-controlled mechanism.

The effect of pH on the photonic efficiency of the destruction of methyl orange under controlled periodic illumination with UV-LED sources

The nature of photon interaction and reaction pH can have significant impacts on semiconductor photocatalysis. This paper describes the effect of pH on the photonic efficiency of photocatalytic reactions in the aqueous phase using TiO2 catalysts. The reactor was irradiated using periodic illumination with UV-LEDs through control of the illumination duty cycle (γ) through a series of light and dark times (Ton/Toff). Photonic efficiencies for methyl orange degradation were found to be comparable at high γ irrespective of pH. At lower γ, pH effects on photonic efficiency were very distinct across acidic, neutral and alkaline pH indicating an effect of complementary parameters. The results suggest photonic efficiency is greatest as illumination time, Ton approaches interfacial electron-transfer characteristic time which is within the range of this study or charge-carrier lifetimes upon extrapolation and also when electrostatic attraction between surface-trapped holes, {TiIVOH}ads+ and substrate molecules is strongest.

Mathematical modelling of quantum yield enhancements of methyl orange photooxidation in aqueous TiO2 suspensions under controlled periodic UV LED illumination

Quantum yields of the photocatalytic degradation of methyl orange under controlled periodic illumination (CPI) have been modelled using existing models. A modified Langmuir-Hinshelwood (L-H) rate equation was used to predict the degradation reaction rates of methyl orange at various duty cycles and a simple photocatalytic model was applied in modelling quantum yield enhancement of the photocatalytic process due to the CPI effect. A good agreement between the modelled and experimental data was observed for quantum yield modelling. The modified L-H model, however, did not accurately predict the photocatalytic decomposition of the dye under periodic illumination.

Lack of genetic structure and evidence for long-distance dispersal in ash (Fraxinus excelsior) populations under threat from an emergent fungal pathogen: implications for restorative planting

Genetic analysis on populations of European ash (Fraxinus excelsior) throughout Ireland was carried out to determine the levels and patterns of genetic diversity in naturally seeded trees in ash woodlands and hedgerows, with the aim of informing conservation and replanting strategies in the face of potential loss of trees as a result of ash dieback. Samples from 33 sites across Northern Ireland and three sites in the Republic of Ireland were genotyped for eight nuclear and ten chloroplast microsatellites. Levels of diversity were high (mean A R = 10.53; mean H O = 0.709; mean H E = 0.765) and were similar to those in Great Britain and continental Europe, whilst levels of population genetic differentiation based on nuclear microsatellites were extremely low (Φ ST = 0.0131). Levels of inbreeding (mean F IS = 0.067) were significantly lower than those reported for populations from Great Britain. Fine-scale analysis of seed dispersal indicated potential for dispersal over hundreds of metres. Our results suggest that ash woodlands across Ireland could be treated as a single management unit, and thus native material from anywhere in Ireland could be used as a source for replanting. In addition, high potential for dispersal has implications for recolonization processes post-ash dieback (Chalara fraxinea) infection, and could aid in our assessment of the capacity of ash to shift its range in response to global climate change.

UV dosimetry for solar water disinfection (SODIS) carried out in different plastic bottles and bags

Solar water disinfection (SODIS) is a well-established inexpensive means of water disinfection in developing countries, but lacks an indicator to illustrate its end-point. A study of the solar UV dosage required for SODIS, in order to achieve a bacteria concentration below the detection limit for: Escherichia coli, Enterococcus spp. and Clostridium perfringens, in water in PET bottles, PE and PE/EVA bags showed disinfection to be most efficient in PE bags, with a solar UV (290–385 nm) dose of 389 kJ m−2 required. In parallel to the disinfection experiments, a range of polyoxometalate, semiconductor photocatalysis and photodegradable dye-based solar UV dosimeter indicators were tested under the same solar UV irradiation conditions. All three types of dosimeter produced indicators that largely and significantly change colour upon exposure to 389 kJ m−2 solar UV; further indicators are reported which change colour at higher doses and hence would be suitable for the less efficient SODIS containers tested. All indicators tested were robust, easy to use and inexpensive so as not to add significantly to the attractive low cost of SODIS. Furthermore, whilst semiconductor photocatalyst and photodegradable dye based indicators are disposable, one-use systems, the polyoxometalate based indicators recover colour in the dark overnight, allowing them to be reused, and hence further decreasing the cost of using indicators during the implementation of the SODIS method.

In situ ATR-FTIR study of H2O and D2O adsorption on TiO2 under UV irradiation

The adsorption of water and deuterium oxide on TiO2 surfaces was investigated in the dark as well as under UV(A) irradiation using in situ ATR-FTIR spectroscopy under oxygen and oxygen free conditions. Adsorption of H2O-D2O mixtures revealed an isotopic exchange reaction occurring onto the surface of TiO2 in the dark. Under UV(A) irradiation, the amount of both OH and OD groups was found to be increased by the presence of molecular oxygen. Furthermore, the photocatalytic formation of hydroperoxide under oxygenated condition has been recorded utilizing Attenuated Total Reflection Fourier Transformed Infrared (ATR-FTIR) spectroscopy which appeared as new band at 3483 cm-1. Different possible mechanisms are discussed in terms of the source of hydroxyl groups formed and/or hydration water on the TiO2 surface for the photocatalytic reaction and photoinduced hydrophilicity.

Rapidly Evolving and Luminous Transients from Pan-STARRS1

In the past decade, several rapidly evolving transients have been discovered whose timescales and luminosities are not easily explained by traditional supernovae (SNe) models. The sample size of these objects has remained small due, at least in part, to the challenges of detecting short timescale transients with traditional survey cadences. Here we present the results from a search within the Pan-STARRS1 Medium Deep Survey (PS1-MDS) for rapidly evolving and luminous transients. We identify 10 new transients with a time above half-maximum (t_1/2) of less than 12 days and -16.5 > M > -20 mag. This increases the number of known events in this region of SN phase space by roughly a factor of three. The median redshift of the PS1-MDS sample is z = 0.275 and they all exploded in star-forming galaxies. In general, the transients possess faster rise than decline timescale and blue colors at maximum light (g_P1-rP1 ≲ -0.2). Best-fit blackbodies reveal photospheric temperatures/radii that expand/cool with time and explosion spectra taken near maximum light are dominated by a blue continuum, consistent with a hot, optically thick, ejecta. We find it difficult to reconcile the short timescale, high peak luminosity (L > 10⁴³erg s^-1), and lack of UV line blanketing observed in many of these transients with an explosion powered mainly by the radioactive decay of ⁵⁶Ni. Rather, we find that many are consistent with either (1) cooling envelope emission from the explosion of a star with a low-mass extended envelope that ejected very little (<0.03 M) radioactive material, or (2) a shock breakout within a dense, optically thick, wind surrounding the progenitor star. After calculating the detection efficiency for objects with rapid timescales in the PS1-MDS we find a volumetric rate of 4800-8000 events yr^-1Gpc^-3(4%-7% of the core-collapse SN rate at z = 0.2).

The Ultraviolet-Bright, Slowly Declining Transient PS1-11af as a Partial Tidal Disruption Event

We present the Pan-STARRS1 discovery of the long-lived and blue transient PS1-11af, which was also detected by Galaxy Evolution Explorer with coordinated observations in the near-ultraviolet (NUV) band. PS1-11af is associated with the nucleus of an early type galaxy at redshift z = 0.4046 that exhibits no evidence for star formation or active galactic nucleus activity. Four epochs of spectroscopy reveal a pair of transient broad absorption features in the UV on otherwise featureless spectra. Despite the superficial similarity of these features to P-Cygni absorptions of supernovae (SNe), we conclude that PS1-11af is not consistent with the properties of known types of SNe. Blackbody fits to the spectral energy distribution are inconsistent with the cooling, expanding ejecta of a SN, and the velocities of the absorption features are too high to represent material in homologous expansion near a SN photosphere. However, the constant blue colors and slow evolution of the luminosity are similar to previous optically selected tidal disruption events (TDEs). The shape of the optical light curve is consistent with models for TDEs, but the minimum accreted mass necessary to power the observed luminosity is only 0.002 M, which points to a partial disruption model. A full disruption model predicts higher bolometric luminosities, which would require most of the radiation to be emitted in a separate component at high energies where we lack observations. In addition, the observed temperature is lower than that predicted by pure accretion disk models for TDEs and requires reprocessing to a constant, lower temperature. Three deep non-detections in the radio with the Very Large Array over the first two years after the event set strict limits on the production of any relativistic outflow comparable to Swift J1644+57, even if off-axis.

Characterisation of Bioresorbable Composite Performance for Validation of New On-Line Process Monitoring Technology

There is an increasing interest in the biomedical field to create implantable medical devices to provide a temporary mechanical function for use inside the human body. In many of these applications bioresorbable polymer composites using PLLA with β-TCP , are increasingly being used due to their biocompatability, biodegradability and mechanical strength.1,3 These medical devices can be manufactured using conventional plastics processing methods such as injection moulding and extrusion, however there is great need to understand and control the process due to a lack of knowledge on the influence of processing on material properties. With the addition of biocompatible additives there is also a requirement to be able to predict the quality and level of dispersion within the polymer matrix. On-line UV-Vis spectroscopy has been shown to monitor the quality of fillers in polymers. This can eliminate time consuming and costly post-process evaluation of additive dispersion. The aim of this work was to identify process and performance relationships of PLLA/β-TCP composites with respect to melt-extrusion conditions. This is part of a wider study into on-line process monitoring of bioresorbable polymers as used in the medical industry.
These results show that final properties of the PLLA/ β-TCP composite are highly influenced by the particle size and loading. UV-Vis spectroscopy can be used on-line to monitor the final product and this can be utilised as a valuable tool for quality control in an application where consistent performance is of paramount importance.