Thermostability profile of Newcastle disease virus (strain I-2) following serial passages without heat selection

I-2 is an avirulent strain of Newcastle disease virus. During establishment of the I-2 strain master vaccine seed, a series of selection procedures was carried out at 56 degrees C in order to enhance heat resistance. This master seed is used to produce a working seed, which is then employed to produce the vaccine. These two passages are done without further heat selection; however, it is not known how rapidly and to what extent thermostable variants would be lost during further passage. The study was therefore conducted to determine the effect of passage on thermostability of strain I-2. The virus was serially passaged and at various passage levels samples were subjected to heat treatment at 56 degrees C for 120 min. The inactivation rates for infectivity and haemagglutinin (HA) titres were assayed by use of chicken embryonated eggs and HA test, respectively. Thermostability of HA and infectivity of I-2 virus were reduced after 10 and 5 passages, respectively, without heat selection at 56 degrees C. These results suggest that 5 more passages could be carried out between the working seed and vaccine levels without excessive loss of thermostability. This would result in increased vaccine production from a single batch of a working seed.

Optimum switching point assessment of parallel braking resistor and serial current limiter for power system stability enhancement

A new control algorithm using parallel braking resistor (BR) and serial fault current limiter (FCL) for power system transient stability enhancement is presented in this paper. The proposed control algorithm can prevent transient instability during first swing by immediately taking away the transient energy gained in faulted period. It can also reduce generator oscillation time and efficiently make system back to the post-fault equilibrium. The algorithm is based on a new system energy function based method to choose optimal switching point. The parallel BR and serial FCL resistor can be switched at the calculated optimal point to get the best control result. This method allows optimum dissipation of the transient energy caused by disturbance so to make system back to equilibrium in minimum time. Case studies are given to verify the efficiency and effectiveness of this new control algorithm.

Magnetic properties and Spin dynamics in magnetic Molecular Rings

Molecular nanomagnets are spin clusters whose topology and magnetic interactions can be modulated at the level of the chemical synthesis. They are formed by a small number of transition metal ions coupled by the Heisenberg's exchange interactions. Each cluster is magnetically isolated from its neighbors by organic ligands, making each unit not interacting with the others. Therefore, we can investigate the magnetic properties of an isolated molecular nanomagnet by bulk measurements. The present thesis has been mostly devoted to the experimental investigation of the magnetic properties and spin dynamics of different classes of antiferromagnetic (AF) molecular rings. This study has been exploiting various techniques of investigations, such as Nuclear Magnetic Resonance (NMR), muon spin relaxation (muSR) and SQUiD magnetometry. We investigate the magnetic properties and the phonon-induced relaxation dynamics of the first regular Cr9 antiferromagnetic (AF) ring, which represents a prototype frustrated AF ring. The magnetically-open AF rings like Cr8Cd are model systems for the study of the microscopic magnetic behaviour of finite AF Heisenberg chains. In this type of system the different magnetic behaviour depends length and on the parity of the chain (odd or even). In order to study the local spin densities on the Cr sites, the Cr-NMR spectra was collected at low temperature. The experimental result confirm the theoretical predictions for the spin configuration. Finally, the study of Dy6, the first rare-earth based ring that has been ever synthesized, has been performed by AC-SQuID and muSR measurements. We found that the dynamics is characterized by more than one characteristic correlation time, whose values depend strongly on the applied field.

From marine ecology to crime analysis: improving the detection of serial sexual offences using a taxonomic similarity measure

Jaccard has been the choice similarity metric in ecology and forensic psychology for comparison of sites or offences, by species or behaviour. This paper applies a more powerful hierarchical measure - taxonomic similarity (s), recently developed in marine ecology - to the task of behaviourally linking serial crime. Forensic case linkage attempts to identify behaviourally similar offences committed by the same unknown perpetrator (called linked offences). s considers progressively higher-level taxa, such that two sites show some similarity even without shared species. We apply this index by analysing 55 specific offence behaviours classified hierarchically. The behaviours are taken from 16 sexual offences by seven juveniles where each offender committed two or more offences. We demonstrate that both Jaccard and s show linked offences to be significantly more similar than unlinked offences. With up to 20% of the specific behaviours removed in simulations, s is equally or more effective at distinguishing linked offences than where Jaccard uses a full data set. Moreover, s retains significant difference between linked and unlinked pairs, with up to 50% of the specific behaviours removed. As police decision-making often depends upon incomplete data, s has clear advantages and its application may extend to other crime types. Copyright © 2007 John Wiley & Sons, Ltd.

Serial correlation in the returns of UK capitalization based portfolios

This article examines whether UK portfolio returns are time varying so that expected returns follow an AR(1) process as proposed by Conrad and Kaul for the USA. It explores this hypothesis for four portfolios that have been formed on the basis of market capitalization. The portfolio returns are modelled using a kalman filter signal extraction model in which the unobservable expected return is the state variable and is allowed to evolve as a stationary first order autoregressive process. It finds that this model is a good representation of returns and can account for most of the autocorrelation present in observed portfolio returns. This study concludes that UK portfolio returns are time varying and the nature of the time variation appears to introduce a substantial amount of autocorrelation to portfolio returns. Like Conrad and Kaul if finds a link between the extent to which portfolio returns are time varying and the size of firms within a portfolio but not the monotonic one found for the USA.

Explaining volatility and serial correlation in opening and closing returns:a study of the FT-30 components

In this paper the performance of opening and closing returns, for the components of the FT-30 will be studied. It will be shown that for these stocks opening returns have higher volatility and a greater tendency towards negative serial correlation than closing returns. Unlike previous studies this contrasting performance cannot solely be attributed to differences in the trading mechanism across the trading day. All the stocks used in our sample trade thought the day using a uniform trading mechanism. In this paper, we suggest that it is differences in the speed that closing and opening returns adjust to new information that causes differences in return performance. By estimating the Amihud and Mendelson (1987) [Amihud, Yakov, & Mendelson, Haim (1987). Trading mechanisms and stock returns: An empirical investigation, Journal of Finance, 62 533-553.] partial adjustment model with noise, we show that opening returns have a tendency towards over-reaction, while closing returns have a tendency towards under-reaction. We suggest that it is these differences that cause a substantial proportion (although not all) of the asymmetric return patterns associated with opening and closing returns. © 2005 Elsevier Inc. All rights reserved.

Technological diversification within UK’s small serial innovators

This paper investigates the determinants of technological diversification among UK’s small serial innovators (SSIs). Using a longitudinal study of 339 UK-based small businesses accounting for almost 7000 patents between 1990 and 2006, this study constitutes the first empirical examination of technological diversification among SMEs in the literature. Results demonstrate that technological diversification is not solely a large firm activity, challenging the dominant view that innovative SMEs are extremely focused and specialised players with little technological diversification. Our findings suggest a nonlinear (i.e. inverse-U-shaped) relationship between the level of technological opportunities in the environment and the SSIs’ degree of technological diversification. This points to a trade-off between processes of exploration and exploitation across increasingly volatile technology regimes. The paper also demonstrates that small firms with impactful innovations focus their innovative activity around similar technological capabilities while firms that have introduced platform technologies in the past are more likely to engage in technological diversification.

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°C, but not when stored at 40°C/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°C/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 compared to the original formulation when stored at 40°C/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.

Sustained release of the CCR5 inhibitors CMPD167 and maraviroc from vaginal rings in rhesus macaques

Antiretroviral entry inhibitors are now being considered as vaginally administered microbicide candidates for the prevention of the sexual transmission of human immunodeficiency virus. Previous studies testing the entry inhibitors maraviroc and CMPD167 in aqueous gel formulations showed efficacy in the macaque challenge model, although protection was highly dependent on the time period between initial gel application and subsequent challenge. In this paper, we describe the sustained release of maraviroc and CMPD167 from matrix-type silicone elastomer vaginal rings both in vitro and in vivo. Both inhibitors were released continuously during 28 days from rings in vitro at rates of 100 to 2,500 µg/day. In 28-day pharmacokinetic studies in rhesus macaques, the compounds were measured in the vaginal fluid and vaginal tissue; steady-state fluid concentrations were ~10(6)-fold greater than the 50% inhibitory concentrations (IC(50)s) for simian human immunodeficiency virus 162P3 inhibition in macaque lymphocytes in vitro. Plasma concentrations for both compounds were very low. The pretreatment of macaques with Depo-Provera (DP), which is commonly used in macaque challenge studies, was shown to significantly modify the biodistribution of the inhibitors but not the overall amount released. Vaginal fluid and tissue concentrations were significantly decreased while plasma levels increased with DP pretreatment. These observations have implications for designing macaque challenge experiments and also for ring performance during the human female menstrual cycle.