Vaccinia virus requires heat-shock proteins for genome replication and virion assembly

The large double-stranded DNA virus, vaccinia virus (VACV), is closely related to variola virus, the causative agent of smallpox. While the poxvirus lifecycle has been studied for over 50 years, much is still unknown about the complex multi-step process of genome uncoating. Viral and cellular factors involved in poxvirus uncoating have been identified, including host cell proteasomes, ubiquitin, and heat-shock proteins (HSPs), which play a critical role in protein folding and the prevention of protein aggregation. Although HSPs have been linked to the lifecycle of many viruses including VACV, the role of these proteins in poxvirus infection has not been defined. Using various small compound inhibitors and RNAi, in combination with a battery of virus-specific assays, I show that heat-shock proteins are required for multiple stages of the VACV lifecycle. I demonstrate that Hsp90 is required for two stages of infection: release of the genome from the viral core and assembly of new virions. Following the finding that HSF1, the transcription factor for inducible HSPs, is required for infection, I also identify the Hsp105 as the inducible HSP required for post-replication formation of nascent virions. Given the clinical relevance of HSP inhibitors these results highlight HSPs as potential anti-poxviral drug targets. Collectively, through this work I define new cell factors required for poxvirus infection and demonstrate that subjugation of cellular HSPs during the poxvirus lifecycle is far more complex than previously appreciated

Scaling and trends of hourly precipitation extremes in two different climate zones – Hong Kong and the Netherlands

Hourly precipitation extremes in very long time series from the Hong Kong Observatory and the Netherlands are investigated. Using the 2 m dew point temperature from 4 h before the rainfall event as a measure of near surface absolute humidity, hourly precipitation extremes closely follow a 14% per degree dependency – a scaling twice as large as following from the Clausius-Clapeyron relation. However, for dew point temperatures above 23 °C no significant dependency on humidity was found. Strikingly, in spite of the large difference in climate, results are almost identical in Hong Kong and the Netherlands for the dew point temperature range where both observational sets have sufficient data. Trends in hourly precipitation extremes show substantial increases over the last century for both De Bilt (the Netherlands) and Hong Kong. For De Bilt, not only the long term trend, but also variations in hourly precipitation extremes on an inter-decadal timescale of 30 yr and longer, can be linked very well to the above scaling; there is a very close resemblance between variations in dew point temperature and precipitation intensity with an inferred dependency of hourly precipitation extremes of 10 to 14% per degree. For Hong Kong there is no connection between variations in humidity and those in precipitation intensity in the wet season, May to September. This is consistent with the found zero-dependency of precipitation intensity on humidity for dew points above 23 °C. Yet, outside the wet season humidity changes do appear to explain the positive trend in hourly precipitation extremes, again following a dependency close to twice the Clausius-Clapeyron relation

Decreased expression of the Id3 gene at 1p36.1 in ovarian adenocarcinomas

The molecular events that drive the initiation and progression of ovarian adenocarcinoma are not well defined. We have investigated changes in gene expression in ovarian cancer cell lines compared to an immortalized human ovarian surface epithelial cell line (HOSE) using a cDNA array. We identified 17 genes that were under-expressed and 10 genes that were over-expressed in the cell lines compared to the HOSE cells. One of the genes under-expressed in the ovarian cancer cell lines, Id3, a transcriptional inactivator, was selected for further investigation. Id3 mRNA was expressed at reduced levels in 6 out of 9 ovarian cancer cell lines compared to the HOSE cells while at the protein level, all 7 ovarian cancer cell lines examined expressed the Id3 protein at greatly reduced levels. Expression of Id3 mRNA was also examined in primary ovarian tumours and was found in only 12/38 (32%) cases. A search was conducted for mutations of Id3 in primary ovarian cancers using single stranded conformation polymorphism (SSCP) analysis. Only one nucleotide substitution, present also in the corresponding constitutional DNA, was found in 94 ovarian tumours. Furthermore no association was found between LOH at 1p36 and lack of expression of Id3. These data suggest that Id3 is not the target of LOH at 1p36. © 2001 Cancer Research Campaign http://www.bjcancer.co

N-Body Simulations of Compact Young Clusters near the Galactic Center

We investigate the dynamical evolution of compact young star clusters (CYCs) near the Galactic center (GC) using Aarseth's Nbody6 codes. The relatively small number of stars in the cluster (5,000-20,000) makes real-number N-body simulations for these clusters feasible on current workstations. Using Fokker-Planck (F-P) models, Kim, Morris, & Lee (1999) have made a survey of cluster lifetimes for various initial conditions, and have found that clusters with a mass <~ 2x10^4 Msun evaporate in ~10 Myr. These results were, however, to be confirmed by N-body simulations because some extreme cluster conditions, such as strong tidal forces and a large stellar mass range participating in the dynamical evolution, might violate assumptions made in F-P models. Here we find that, in most cases, the CYC lifetimes of previous F-P calculations are 5-30% shorter than those from the present N-body simulations. The comparison of projected number density profiles and stellar mass functions between N-body simulations and HST/NICMOS observations by Figer et al. (1999) suggests that the current tidal radius of the Arches cluster is ~1.0 pc, and the following parameters for the initial conditions of that cluster: total mass of 2x10^4 Msun and mass function slope for intermediate-to-massive stars of 1.75 (the Salpeter function has 2.35). We also find that the lower stellar mass limit, the presence of primordial binaries, the amount of initial mass segregation, and the choice of initial density profile (King or Plummer models) do not significantly affect the dynamical evolution of CYCs.Comment: 20 pages including 6 figures, To appear in ApJ, Dec 20 issu

The K\"ahler-Ricci flow with positive bisectional curvature

We show that the K\"ahler-Ricci flow on a manifold with positive first Chern class converges to a K\"ahler-Einstein metric assuming positive bisectional curvature and certain stability conditions.Comment: 15 page

Angle-resolved photoemission study of the rare-earth intermetallic compounds: RNi2Ge2(R=Eu,Gd)

Experimental energy bands mapped from normal-emission photoelectron spectra of EuNi2Ge2 and GdNi2Ge2(001)surfaces show four photoemission features that disperse in both materials in good agreement with band calculations. Segments of the Fermi surfaces mapped by angle-resolved photoemission spectroscopy in the ΓXPZ plane of the Brillouin zones for both EuNi2Ge2 and GdNi2Ge2 are in good agreement with band calculations. This Fermi surface segment changes when one electron is added to EuNi2Ge2, corresponding to GdNi2Ge2, based on the rigid-band approximation