Ex vivo profiling of CD8(+)-T-cell responses to human cytomegalovirus reveals broad and multispecific reactivities in healthy virus carriers

Human cytomegalovirus (HCMV) can establish both nonproductive (latent) and productive (lytic) infections. Many of the proteins expressed during these phases of infection could be expected to be targets of the immune response; however, much of our understanding of the CD8(+)-T-cell response to HCMV is mainly based on the pp65 antigen. Very little is known about T-cell control over other antigens expressed during the different stages of virus infection; this imbalance in our understanding undermines the importance of these antigens in several aspects of HCMV disease pathogenesis. In the present study, an efficient and rapid strategy based on predictive bioinformatics and ex vivo functional T-cell assays was adopted to profile CD8(+)-T-cell responses to a large panel of HCMV antigens expressed during different phases of replication. These studies revealed that CD8(+)-T-cell responses to HCMV often contained multiple antigen-specific reactivities, which were not just constrained to the previously identified pp65 or IE-1 antigens. Unexpectedly, a number of viral proteins including structural, early/late antigens and HCMV-encoded immunomodulators (pp28, pp50, gH, gB, US2, US3, US6, and UL18) were also identified as potential targets for HCMV-specific CD8(+)-T-cell immunity. Based on this extensive analysis, numerous novel HCMV peptide epitopes and their HLA-restricting determinants recognized by these T cells have been defined. These observations contrast with previous findings that viral interference with the antigen-processing pathway during lytic infection would render immediate-early and early/late proteins less immunogenic. This work strongly suggests that successful HCMV-specific immune control in healthy virus carriers is dependent on a strong T-cell response towards a broad repertoire of antigens.

The growth of private property vehicles in the UK: causes and conditions

The UK private indirect real estate market has seen a rapid growth in the last seven years. The gross asset value (GAV) of the private property vehicle (PPV) market has about tripled from a GAV of £22.6bn in 1998 to a GAV of £67.1 billion at the end of 2005 (OPC, 2006). Although this trend of growing syndication of real estate is not only a UK phenomenon, the rate of growth has been significantly faster in the UK. For example the German open-ended funds have grown over the same period from €50.4bn to €85.1bn (BVI, 2006). In the US the market capitalization of equity real estate investment trusts (REIT) has grown 155% since 1999 to US$ 301bn (NAREIT, 2006). Each jurisdiction is offering different formats to invest indirectly into real estate but at the core all these vehicles are the same in that they provide a different route for investors to access real estate. In the UK, although the range of ‘products’ is now quite diverse, all structures have in common the ‘wrapping’ of property assets into a multi-investor vehicle. This paper examines the nature, pattern and process of market growth in PPVs and constructs a series of associations between causes and effects to explain this market shift.

Non-normal real estate return distributions by property type in the U.K.

Investment risk models with infinite variance provide a better description of distributions of individual property returns in the IPD database over the period 1981 to 2003 than Normally distributed risk models, which mirrors results in the U.S. and Australia using identical methodology. Real estate investment risk is heteroscedastic, but the Characteristic Exponent of the investment risk function is constant across time yet may vary by property type. Asset diversification is far less effective at reducing the impact of non-systematic investment risk on real estate portfolios than in the case of assets with Normally distributed investment risk. Multi-risk factor portfolio allocation models based on measures of investment codependence from finite-variance statistics are ineffectual in the real estate context.

Appraiser behaviour and appraisal smoothing: some qualitative and quantitative evidence

There is a substantial literature which suggests that appraisals are smoothed and lag the true level of prices. This study combines a qualitative interview survey of the leading fund manager/owners in the UK and their appraisers with a empirical study of the number of appraisals which change each month within the IPD Monthly Index. The paper concentrates on how the appraisal process operates for commercial real estate performance measurement purposes. The survey interviews suggest that periodic appraisal services are consolidating in fewer firms and, within these major firms, appraisers adopt different approaches to changing appraisals on a period by period basis, with some wanting hard transaction evidence while others act on ‘softer’ signals. The survey also indicates a seasonal effect with greater effort and information being applied to annual and quarterly appraisals than monthly. The analysis of the appraisals within the IPD Monthly Index confirms this effect with around 5% more appraisals being moved at each quarter day than the other months. More November appraisals change than expected and this suggests that the increased information flows for the December end year appraisals are flowing through into earlier appraisals, especially as client/appraiser draft appraisal meetings for the December appraisals, a regular occurrence in the UK, can occur in November. January illustrates significantly less activity than other months, a seasonal effect after the exertions of the December appraisals.

Continental shift? An analysis of convergence trends in European real estate equities

European economic and political integration have been recognised as having implications for patterns of performance in national real estate and capital markets and have generated a wide body of research and commentary. In 1999, progress towards monetary integration within the European Union culminated in the introduction of a common currency and monetary policy. This paper investigates the effects of this ‘event’ on the behaviour of stock returns in European real estate companies. A range of statistical tests is applied to the performance of European property companies to test for changes in segmentation, co-movement and causality. The results suggest that, relative to the wider equity markets, the dispersion of performance is higher, correlations are lower, a common contemporaneous factor has much lower explanatory power whilst lead-lag relationships are stronger. Consequently, the evidence of transmission of monetary integration to real estate securities is less noticeable than to general securities. Less and slower integration is attributed to the relatively small size of the real estate securities market and the local and national nature of the majority of the companies’ portfolios.

Detection of anthropogenic climate change using a fingerprint method

A fingerprint method for detecting anthropogenic climate change is applied to new simulations with a coupled ocean-atmosphere general circulation model (CGCM) forced by increasing concentrations of greenhouse gases and aerosols covering the years 1880 to 2050. In addition to the anthropogenic climate change signal, the space-time structure of the natural climate variability for near-surface temperatures is estimated from instrumental data over the last 134 years and two 1000 year simulations with CGCMs. The estimates are compared with paleoclimate data over 570 years. The space-time information on both the signal and the noise is used to maximize the signal-to-noise ratio of a detection variable obtained by applying an optimal filter (fingerprint) to the observed data. The inclusion of aerosols slows the predicted future warming. The probability that the observed increase in near-surface temperatures in recent decades is of natural origin is estimated to be less than 5%. However, this number is dependent on the estimated natural variability level, which is still subject to some uncertainty.

Tegument Protein Subcellular Localization of Human Cytomegalovirus

To determine the subcellular localization of the tegument proteins pp65, pp71, pp150, and pp28 as fusions to one of several fluorescent proteins. Since these tegument proteins play pivotal roles in several stages of the viral life cycle, knowledge of where and the mechanism of how these proteins localize upon release could result in a better understanding of their function during a lytic infection as well as assist in the development of an effective, novel antiviral treatment.