Characterisation of protein stability in rod-insert vaginal rings

A major goal in vaccine development is elimination of the ‘cold chain’, the transport and storage system for maintenance and distribution of the vaccine product. This is particularly pertinent to liquid formulation of vaccines. We have previously described the rod-insert vaginal ring (RiR) device, comprising an elastomeric body into which are inserted lyophilised, rod-shaped, solid drug dosage forms, and having potential for sustained mucosal delivery of biomacromolecules, such as HIV envelope protein-based vaccine candidates. Given the solid, lyophilised nature of these insert dosage forms, we hypothesised that antigen stability may be significantly increased compared with more conventional solubilised vaginal gel format. In this study, we prepared and tested vaginal ring devices fitted with lyophilised rod inserts containing the model antigen bovine serum albumin (BSA). Both the RiRs and the gels that were freeze-dried to prepare the inserts were evaluated for BSA stability using PAGE, turbidimetry, microbial load, MALDI-TOF and qualitative precipitate solubility measurements. When stored at 4 oC, but not when stored at 40 oC / 75% RH, the RiR formulation offered protection against structural and conformational changes to BSA. The insert also retained matrix integrity and release characteristics. The results demonstrate that lypophilised gels can provide relative protection against degradation at lower temperatures compared to semi-solid gels. The major mechanism of degradation at 40 oC / 75% RH was shown to be protein aggregation. Finally, in a preliminary study, we found that addition of trehalose to the formulation significantly reduces the rate of BSA degradation as compared to the original formulation when stored at 40 oC /75% RH. Establishing the mechanism of degradation, and finding that degradation is decelerated in the presence of trehalose, will help inform further development of RiRs specifically and polymer based freeze-dried systems in general.

Kinship, parentage and temporal stability in nursery colonies of Leisler’s bat (Nyctalus leisleri)

Levels of genetic relatedness within bat colonies are often unknown, and consequently the reasons for group formation and social organization are unclear. The Leisler's bat (Nyctalus leisleri), like most temperate bat species, forms nursery colonies in summer. We used microsatellite markers to examine identity and to attempt to estimate relatedness among females within a nursery colony, over 2 consecutive years, to ascertain whether females show kinship and natal philopatry, testing the hypothesis that this is the basis of colony formation. Parentage and relatedness of young born within a colony was assessed to investigate mating patterns via male reproductive skew and whether males achieve mating success within their natal colony. While there was evidence for female philopatry, levels of genetic relatedness within colonies were low. This suggests that kinship is not a major determinant in group formation, as roosts also comprise a large number of distant relatives or non-kin. Roost switching and gene flow are likely to be high. Both sexes reproduced in their first year, whereas males appear to be the more dispersive sex. We argue that the physical environment as well as information sharing provided by communal roosting are likely to be important factors for the formation of these large natal colonies in N. leisleri and possibly other lineages of bats. © 2012 The Author.

ON THE PROGENITOR AND EARLY EVOLUTION OF THE TYPE II SUPERNOVA 2009kr

We identify a source coincident with SN 2009kr in Hubble Space Telescope pre-explosion images. The object appears to be a single point source with an intrinsic color V - I = 1.1 +/- 0.25 and M-V = -7.6 +/- 0.6. If this is a single star, it would be a yellow supergiant of log L/L-circle dot similar to 5.1 and a mass of 15(-4)(+5) M-circle dot. The spatial resolution does not allow us yet to definitively determine if the progenitor object is a single star, a binary system, or a compact cluster. We show that the early light curve is similar to a Type IIL SN, but the prominent H alpha P-Cygni profiles and the signature of the end of a recombination phase are reminiscent of a Type IIP. The evolution of the expanding ejecta will play an important role in understanding the progenitor object.

Massive stars exploding in a He-rich circumstellar medium - II. The transitional case of SN 2005la

We present photometric and spectroscopic data of the peculiar SN 2005la, an object which shows an optical light curve with some luminosity fluctuations and spectra with comparably strong narrow hydrogen and helium lines, probably of circumstellar nature. The increasing full width at half-maximum velocity of these lines is indicative of an acceleration of the circumstellar material. SN 2005la exhibits hybrid properties, sharing some similarities with both Type IIn supernovae and 2006jc-like (Type Ibn) events. We propose that the progenitor of SN 2005la was a very young Wolf-Rayet (WN-type) star which experienced mass ejection episodes shortly before core collapse.

SN 1999ga: a low-luminosity linear type II supernova?

Context. Type II-linear supernovae are thought to arise from progenitors that have lost most of their H envelope by the time of the explosion, and they are poorly understood because they are only occasionally discovered. It is possible that they are intrinsically rare, but selection effects due to their rapid luminosity evolution may also play an important role in limiting the number of detections. In this context, the discovery of a subluminous type II-linear event is even more interesting.

VLT DETECTION OF A RED SUPERGIANT PROGENITOR OF THE TYPE II-P SUPERNOVA 2008bk

We report the identification of a source coincident with the position of the nearby Type II-P supernova (SN) 2008bk in high-quality optical and near-infrared preexplosion images from the ESO Very Large Telescope (VLT). The SN position in the optical and near-infrared preexplosion images is identified to within about +/- 70 and +/- 40 mas, respectively, using postexplosion-band images obtained with the NAOS CONICA adaptive optics system K-s on the VLT. The preexplosion source detected in four different bands is precisely coincident with SN 2008bk and is consistent with being dominated by a single point source. We determine the nature of the point source using the STARS stellar evolutionary models and find that its colors and luminosity are consistent with the source being a red supergiant progenitor of SN 2008bk with an initial mass of 8.5 +/- 1.0 M-circle dot.

The type IIb SN 2008ax: the nature of the progenitor

A source coincident with the position of the type IIb supernova (SN) 2008ax is identified in pre-explosion Hubble Space Telescope (HST) Wide Field Planetary Camera 2 observations in three optical filters. We identify and constrain two possible progenitor systems: (i) a single massive star that lost most of its hydrogen envelope through radiatively driven mass-loss processes, prior to exploding as a helium-rich Wolf-Rayet star with a residual hydrogen envelope, and (ii) an interacting binary in a low-mass cluster producing a stripped progenitor. Late time, high-resolution observations along with detailed modelling of the SN will be required to reveal the true nature of this progenitor star.

The Type IIb SN 2008ax: spectral and light curve evolution

We present spectroscopy and photometry of the He-rich supernova (SN) 2008ax. The early-time spectra show prominent P-Cygni H lines, which decrease with time and disappear completely about 2 months after the explosion. In the same period He I lines become the most prominent spectral features. SN 2008ax displays the ordinary spectral evolution of a Type IIb supernova. A stringent pre-discovery limit constrains the time of the shock breakout of SN 2008ax to within only a few hours. Its light curve, which peaks in the B band about 20 d after the explosion, strongly resembles that of other He-rich core-collapse supernovae. The observed evolution of SN 2008ax is consistent with the explosion of a young Wolf-Rayet (of WNL type) star, which had retained a thin, low-mass shell of its original H envelope. The overall characteristics of SN 2008ax are reminiscent of those of SN 1993J, except for a likely smaller H mass. This may account for the findings that the progenitor of SN 2008ax was a WNL star and not a K supergiant as in the case of SN 1993J, that a prominent early-time peak is missing in the light curve of SN 2008ax, and that H alpha is observed at higher velocities in SN 2008ax than in SN 1993J.

The birth place of the type Ic supernova 2007gr

We report our attempts to locate the progenitor of the peculiar Type Ic SN 2007gr in Hubble Space Telescope (HST) preexplosion images of the host galaxy, NGC 1058. Aligning adaptive optics Altair/NIRI imaging of SN 2007gr from the Gemini ( North) Telescope with the preexplosion HST WFPC2 images, we identify the supernova (SN) position on the HST frames with an accuracy of 20 mas. Although nothing is detected at the SN position, we show that it lies on the edge of a bright source 134 +/- 23 mas (6.9 pc) from its nominal center. On the basis of its luminosity, we suggest that this object is possibly an unresolved, compact, and coeval cluster and that the SN progenitor was a cluster member, although we note that model profile fitting favors a single bright star. We find two solutions for the age of this assumed cluster: 7 -/+ 0.5 Myr and 20 - 30 Myr, with turnoff masses of 28 +/- M-circle dot and 12 - 9 M-circle dot, respectively. Preexplosion ground-based K- band images marginally favor the younger cluster 4 age/higher turnoff mass. Assuming the SN progenitor was a cluster member, the turnoff mass provides the best estimate for its initial mass. More detailed observations, after the SN has faded, should determine whether the progenitor was indeed part of a cluster and, if so, allow an age estimate to within similar to 2 Myr, thereby favoring either a high-mass single star or lower-mass interacting binary progenitor.

A deeper search for the progenitor of the Type Ic supernova 2002ap

Images of the site of the Type Ic supernova (SN) 2002ap taken before explosion were analysed previously by Smartt et al. We have uncovered new unpublished, archival pre-explosion images from the Canada-France-Hawaii Telescope (CFHT) that are vastly superior in depth and image quality. In this paper we present a further search for the progenitor star of this unusual Type Ic SN. Aligning high-resolution Hubble Space Telescope observations of the SN itself with the archival CFHT images allowed us to pinpoint the location of the progenitor site on the groundbased observations. We find that a source visible in the B- and R-band pre-explosion images close to the position of the SN is (1) not coincident with the SN position within the uncertainties of our relative astrometry and (2) is still visible similar to 4.7-yr post-explosion in late-time observations taken with the William Herschel Telescope. We therefore conclude that it is not the progenitor of SN 2002ap. We derived absolute limiting magnitudes for the progenitor of M-B >= -4.2 +/- 0.5 and M-R >= -5.1 +/- 0.5. These are the deepest limits yet placed on a Type Ic SN progenitor. We rule out all massive stars with initial masses greater than 7-8 M-circle dot (the lower mass limit for stars to undergo core collapse) that have not evolved to become Wolf-Rayet stars. This is consistent with the prediction that Type Ic SNe should result from the explosions of Wolf-Rayet stars. Comparing our luminosity limits with stellar models of single stars at appropriate metallicity (Z = 0.008) and with standard mass-loss rates, we find no model that produces a Wolf-Rayet star of low enough mass and luminosity to be classed as a viable progenitor. Models with twice the standard mass-loss rates provide possible single star progenitors but all are initially more massive than 30-40 M-circle dot. We conclude that any single star progenitor must have experienced at least twice the standard mass-loss rates, been initially more massive than 30-40 M-circle dot and exploded as a Wolf-Rayet star of final mass 10-12 M-circle dot. Alternatively a progenitor star of lower initial mass may have evolved in an interacting binary system. Mazzali et al. propose such a binary scenario for the progenitor of SN 2002ap in which a star of initial mass 15-20 M-circle dot is stripped by its binary companion, becoming a 5 M-circle dot Wolf-Rayet star prior to explosion. We constrain any possible binary companion to a main-sequence star of

SN 2004A: another type II-P supernova with a red supergiant progenitor

We present a monitoring study of SN 2004A and probable discovery of a progenitor star in pre-explosion Hubble Space Telescope (HST) images. The photometric and spectroscopic monitoring of SN 2004A show that it was a normal Type II-P which was discovered in NGC 6207 about two weeks after explosion. We compare SN 2004A to the similar Type II-P SN 1999em and estimate an explosion epoch of 2004 January 6. We also calculate three new distances to NGC 6207 of 21.0 +/- 4.3, 21.4 +/- 3.5 and 25.1 +/- 1.7 Mpc. The former was calculated using the Standard Candle Method (SCM) for SNe II-P, and the latter two from the brightest supergiants method (BSM). We combine these three distances with existing kinematic distances, to derive a mean value of 20.3 +/- 3.4 Mpc. Using this distance, we estimate that the ejected nickel mass in the explosion is 0.046(-0.017)(+0.031) M-circle dot. The progenitor of SN 2004A is identified in pre-explosion WFPC2 F814W images with a magnitude of m(F814W) = 24.3 +/- 0.3, but is below the detection limit of the F606W images. We show that this was likely a red supergiant (RSG) with a mass of 9(-2)(+3) M-circle dot. The object is detected at 4.7 sigma above the background noise. Even if this detection is spurious, the 5 sigma upper limit would give a robust upper mass limit of 12M(circle dot) for a RSG progenitor. These initial masses are very similar to those of two previously identified RSG progenitors of the Type II-P SNe 2004gd (8(-2)(+4) M circle dot) and 2005cs (9(-2)(+3) M-circle dot).