Microphysics of SO(10) Cosmic Strings

We uncover a rich microphysical structure for SO(10) cosmic strings. For the abelian string the electroweak symmetry is restored around it in a region depending on the electroweak scale. A rich structure of nonabelian strings is found. Some of these also restore the electroweak symmetry. We investigate the zero mode structure of our strings. Whilst there are right handed neutrino zero modes for the abelian string, they do not survive the electroweak phase transition. In general the nonabelian strings do not have fermion zero modes. We consider the generalisation of our results to other theories and consider cosmological consequences of them.Comment: 34 pages, LATEX. Replaced version is restructured, and has small correction to fermion zero mode analysis. To be published in Physical Review

Quantum-Hall Quantum-Bits

Bilayer quantum Hall systems can form collective states in which electrons exhibit spontaneous interlayer phase coherence. We discuss the possibility of using bilayer quantum dot many-electron states with this property to create two-level systems that have potential advantages as quantum bits.Comment: 4 pages, 4 figures included, version to appear in Phys. Rev. B (Rapid Communications

Quasars and their host galaxies

This review attempts to describe developments in the fields of quasar and quasar host galaxies in the past five. In this time period, the Sloan and 2dF quasar surveys have added several tens of thousands of quasars, with Sloan quasars being found to z>6. Obscured, or partially obscured quasars have begun to be found in significant numbers. Black hole mass estimates for quasars, and our confidence in them, have improved significantly, allowing a start on relating quasar properties such as radio jet power to fundamental parameters of the quasar such as black hole mass and accretion rate. Quasar host galaxy studies have allowed us to find and characterize the host galaxies of quasars to z>2. Despite these developments, many questions remain unresolved, in particular the origin of the close relationship between black hole mass and galaxy bulge mass/velocity dispersion seen in local galaxies.Comment: Review article, to appear in Astrophysics Update

Nucleation of a sodium droplet on C60

We investigate theoretically the progressive coating of C60 by several sodium atoms. Density functional calculations using a nonlocal functional are performed for NaC60 and Na2C60 in various configurations. These data are used to construct an empirical atomistic model in order to treat larger sizes in a statistical and dynamical context. Fluctuating charges are incorporated to account for charge transfer between sodium and carbon atoms. By performing systematic global optimization in the size range 1<=n<=30, we find that Na_nC60 is homogeneously coated at small sizes, and that a growing droplet is formed above n=>8. The separate effects of single ionization and thermalization are also considered, as well as the changes due to a strong external electric field. The present results are discussed in the light of various experimental data.Comment: 17 pages, 10 figure

Light propagation in statistically homogeneous and isotropic universes with general matter content

We derive the relationship of the redshift and the angular diameter distance to the average expansion rate for universes which are statistically homogeneous and isotropic and where the distribution evolves slowly, but which have otherwise arbitrary geometry and matter content. The relevant average expansion rate is selected by the observable redshift and the assumed symmetry properties of the spacetime. We show why light deflection and shear remain small. We write down the evolution equations for the average expansion rate and discuss the validity of the dust approximation.Comment: 42 pages, no figures. v2: Corrected one detail about the angular diameter distance and two typos. No change in result

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

Limits on νμ(νˉμ)→ντ(νˉτ)\nu_\mu(\bar{\nu}_\mu)\to\nu_\tau(\bar{\nu}_\tau) and νμ(νˉμ)→νe(νˉe)\nu_\mu(\bar{\nu}_\mu)\to\nu_e(\bar{\nu}_e) Oscillations from a Precision Measurement of Neutrino-Nucleon Neutral Current Interactions

We present limits on $\nu_\mu(\bar{\nu}_\mu)\to\nu_\tau(\bar{\nu}_\tau)$ and $\nu_\mu(\bar{\nu}_\mu)\to\nu_e(\bar{\nu}_e)$ oscillations based on a study of inclusive $\nu N$ interactions performed using the CCFR massive coarse grained detector in the FNAL Tevatron Quadrupole Triplet neutrino beam. The sensitivity to oscillations is from the difference in the longitudinal energy deposition pattern of $\nu_\mu N$ versus $\nu_\tau N$ or $\nu_e N$ charged current interactions. The $\nu_\mu$ energies ranged from 30 to 500 GeV with a mean of 140 GeV. The minimum and maximum $\nu_\mu$ flight lengths are 0.9 km and 1.4 km respectively. For $\nu_\mu\to\nu_\tau$ oscillations, the lowest 90% confidence upper limit in $\sin^22\alpha$ of $2.7\times 10^{-3}$ is obtained at $\Delta m^2\sim50$~eV$^2$. This result is the most stringent limit to date for $25<\Delta m^2<90$ eV$^2$. For $\nu_\mu\to\nu_e$ oscillations, the lowest 90% confidence upper limit in $\sin^22\alpha$ of $1.9\times 10^{-3}$ is obtained at $\Delta m^2\sim350$~eV$^2$. This result is the most stringent limit to date for $250<\Delta m^2<450$ eV$^2$, and also excludes at 90% confidence much of the high $\Delta m^2$ region favored by the recent LSND observation.Comment: Revised version contains limit on $\nu_\mu\to\nu_e$ oscillations as well as limit on $\nu_\mu\to\nu_\tau$ oscillations found in original. 15 pages, ReVTeX, 3 figures in uuencoded file, submitted to PR

The Use of Phage-Displayed Peptide Libraries to Develop Tumor-Targeting Drugs

Monoclonal antibodies have been successfully utilized as cancer-targeting therapeutics and diagnostics, but the efficacies of these treatments are limited in part by the size of the molecules and non-specific uptake by the reticuloendothelial system. Peptides are much smaller molecules that can specifically target cancer cells and as such may alleviate complications with antibody therapy. Although many endogenous and exogenous peptides have been developed into clinical therapeutics, only a subset of these consists of cancer-targeting peptides. Combinatorial biological libraries such as bacteriophage-displayed peptide libraries are a resource of potential ligands for various cancer-related molecular targets. Target-binding peptides can be affinity selected from complex mixtures of billions of displayed peptides on phage and further enriched through the biopanning process. Various cancer-specific ligands have been isolated by in vitro, in vivo, and ex vivo screening methods. As several peptides derived from phage-displayed peptide library screenings have been developed into therapeutics in current clinical trials, which validates peptide-targeting potential, the use of phage display to identify cancer-targeting therapeutics should be further exploited

Comprehensive analysis of epigenetic clocks reveals associations between disproportionate biological ageing and hippocampal volume

The concept of age acceleration, the difference between biological age and chronological age, is of growing interest, particularly with respect to age-related disorders, such as Alzheimer’s Disease (AD). Whilst studies have reported associations with AD risk and related phenotypes, there remains a lack of consensus on these associations. Here we aimed to comprehensively investigate the relationship between five recognised measures of age acceleration, based on DNA methylation patterns (DNAm age), and cross-sectional and longitudinal cognition and AD-related neuroimaging phenotypes (volumetric MRI and Amyloid-β PET) in the Australian Imaging, Biomarkers and Lifestyle (AIBL) and the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Significant associations were observed between age acceleration using the Hannum epigenetic clock and cross-sectional hippocampal volume in AIBL and replicated in ADNI. In AIBL, several other findings were observed cross-sectionally, including a significant association between hippocampal volume and the Hannum and Phenoage epigenetic clocks. Further, significant associations were also observed between hippocampal volume and the Zhang and Phenoage epigenetic clocks within Amyloid-β positive individuals. However, these were not validated within the ADNI cohort. No associations between age acceleration and other Alzheimer’s disease-related phenotypes, including measures of cognition or brain Amyloid-β burden, were observed, and there was no association with longitudinal change in any phenotype. This study presents a link between age acceleration, as determined using DNA methylation, and hippocampal volume that was statistically significant across two highly characterised cohorts. The results presented in this study contribute to a growing literature that supports the role of epigenetic modifications in ageing and AD-related phenotypes

Fine-mapping of prostate cancer susceptibility loci in a large meta-analysis identifies candidate causal variants

Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling. © 2018 The Author(s).Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling. © 2018 The Author(s).Peer reviewe