Computer simulations of hard pear-shaped particles

We report results obtained from Monte Carlo simulations investi- gating mesophase formation in two model systems of hard pear-shaped particles. The first model considered is a hard variant of the trun- cated Stone-Expansion model previously shown to form nematic and smectic mesophases when embedded within a 12-6 Gay-Berne-like po- tential [1]. When stripped of its attractive interactions, however, this system is found to lose its liquid crystalline phases. For particles of length to breadth ratio k = 3, glassy behaviour is seen at high pressures, whereas for k = 5 several bi-layer-like domains are seen, with high intradomain order but little interdomain orientational correlation. For the second model, which uses a parametric shape parameter based on the generalised Gay-Berne formalism, results are presented for particles with elongation k = 3; 4 and 5. Here, the systems with k = 3 and 4 fail to display orientationally ordered phases, but that with k = 5 shows isotropic, nematic and, unusually for a hard-particle model, interdigitated smectic A2 phases.</p

Chandra Monitoring of the Candidate Anomalous X-ray Pulsar AX J1845.0-0258

The population of clearly identified anomalous X-ray pulsars has recently grown to seven, however, one candidate anomalous X-ray pulsar (AXP) still eludes re-confirmation. Here, we present a set of seven Chandra ACIS-S observations of the transient pulsar AX J1845.0-0258, obtained during 2003. Our observations reveal a faint X-ray point source within the ASCA error circle of AX J1845.0-0258's discovery, which we designate CXOU J184454.6-025653 and tentatively identify as the quiescent AXP. Its spectrum is well described by an absorbed single-component blackbody (kT~2.0 keV) or power law (Gamma~1.0) that is steady in flux on timescales of at least months, but fainter than AX J1845.0-0258 was during its 1993 period of X-ray enhancement by at least a factor of 13. Compared to the outburst spectrum of AX J1845.0-0258, CXOU J184454.6-025653 is considerably harder: if truly the counterpart, then its spectral behaviour is contrary to that seen in the established transient AXP XTE J1810-197, which softened from kT~0.67 keV to ~0.18 keV in quiescence. This unexpected result prompts us to examine the possibility that we have observed an unrelated source, and we discuss the implications for AXPs, and magnetars in general.Comment: 4 pages, 3 figures. To be published in the proceedings of the conference "Isolated Neutron Stars: from the Interior to the Surface" (April 24-28, 2006, London, UK), eds. D. Page, R. Turolla, & S. Zan

C21orf57 is a human homologue of bacterial YbeY proteins

The product of the human C21orf57 (huYBEY) gene is predicted to be a homologue of the highly conserved YbeY proteins found in nearly all bacteria. We show that, like its bacterial and chloroplast counterparts, the HuYbeY protein is an RNase and that it retains sufficient function in common with bacterial YbeY proteins to partially suppress numerous aspects of the complex phenotype of an Escherichia coli ΔybeY mutant. Expression of HuYbeY in Saccharomyces cerevisiae, which lacks a YbeY homologue, results in a severe growth phenotype. This observation suggests that the function of HuYbeY in human cells is likely regulated through specific interactions with partner proteins similarly to the way YbeY is regulated in bacteria.National Institutes of Health (U.S.) (Grant GM31010)National Institutes of Health (U.S.) (Grant GM17151

Genome-wide meta-analysis identifies novel genes associated with recurrence and progression in non–muscle-invasive bladder cancer

Background Non–muscle-invasive bladder cancer (NMIBC) is characterized by frequent recurrences and a risk of progression in stage and grade. Increased knowledge of underlying biological mechanisms is needed. Objective To identify single nucleotide polymorphisms (SNPs) associated with recurrence-free (RFS) and progression-free (PFS) survival in NMIBC. Design, setting, and participants We analyzed outcome data from 3400 newly diagnosed NMIBC patients from the Netherlands, the UK, Canada, and Spain. We generated genome-wide germline SNP data using Illumina OmniExpress and Infinium Global Screening Array in combination with genotype imputation. Outcome measurements and statistical analysis Cohort-specific genome-wide association studies (GWASs) for RFS and PFS were performed using a Cox proportional hazard model. Results were combined in a fixed-effect inverse-variance weighted meta-analysis. Candidate genes for the identified SNP associations were prioritized using functional annotation, gene-based analysis, expression quantitative trait locus analysis, and transcription factor binding site databases. Tumor expression levels of prioritized genes were tested for association with RFS and PFS in an independent NMIBC cohort. Results and limitations This meta-analysis revealed a genome-wide significant locus for RFS on chromosome 14 (lead SNP rs12885353, hazard ratio [HR] C vs T allele 1.55, 95% confidence interval [CI] 1.33–1.82, p = 4.0 × 10–8), containing genes G2E3 and SCFD1. Higher expression of SCFD1 was associated with increased RFS (HR 0.70, 95% CI 0.59–0.84, pFDR = 0.003). Twelve other loci were suggestively associated with RFS (p < 10–5), pointing toward 18 additional candidate genes. For PFS, ten loci showed suggestive evidence of association, indicating 36 candidate genes. Expression levels of ten of these genes were statistically significantly associated with PFS, of which four (IFT140, UBE2I, FAHD1, and NME3) showed directional consistency with our meta-analysis results and published literature. Conclusions In this first prognostic GWAS in NMIBC, we identified several novel candidate loci and five genes that showed convincing associations with recurrence or progression. Patient summary In this study, we searched for inherited DNA changes that affect the outcome of non–muscle-invasive bladder cancer (NMIBC). We identified several genes that are associated with disease recurrence and progression. The roles and mechanisms of these genes in NMIBC prognosis should be investigated in future studies