Quiver Structure of Heterotic Moduli

We analyse the vector bundle moduli arising from generic heterotic compactifications from the point of view of quiver representations. Phenomena such as stability walls, crossing between chambers of supersymmetry, splitting of non-Abelian bundles and dynamic generation of D-terms are succinctly encoded into finite quivers. By studying the Poincar\'e polynomial of the quiver moduli space using the Reineke formula, we can learn about such useful concepts as Donaldson-Thomas invariants, instanton transitions and supersymmetry breaking.Comment: 38 pages, 5 figures, 1 tabl

Heterotic Models from Vector Bundles on Toric Calabi-Yau Manifolds

We systematically approach the construction of heterotic E_8 X E_8 Calabi-Yau models, based on compact Calabi-Yau three-folds arising from toric geometry and vector bundles on these manifolds. We focus on a simple class of 101 such three-folds with smooth ambient spaces, on which we perform an exhaustive scan and find all positive monad bundles with SU(N), N=3,4,5 structure groups, subject to the heterotic anomaly cancellation constraint. We find that anomaly-free positive monads exist on only 11 of these toric three-folds with a total number of bundles of about 2000. Only 21 of these models, all of them on three-folds realizable as hypersurfaces in products of projective spaces, allow for three families of quarks and leptons. We also perform a preliminary scan over the much larger class of semi-positive monads which leads to about 44000 bundles with 280 of them satisfying the three-family constraint. These 280 models provide a starting point for heterotic model building based on toric three-folds.Comment: 41 pages, 5 figures. A table modified and a table adde

Heterotic Model Building: 16 Special Manifolds

We study heterotic model building on 16 specific Calabi-Yau manifolds constructed as hypersurfaces in toric four-folds. These 16 manifolds are the only ones among the more than half a billion manifolds in the Kreuzer-Skarke list with a non-trivial first fundamental group. We classify the line bundle models on these manifolds, both for SU(5) and SO(10) GUTs, which lead to consistent supersymmetric string vacua and have three chiral families. A total of about 29000 models is found, most of them corresponding to SO(10) GUTs. These models constitute a starting point for detailed heterotic model building on Calabi-Yau manifolds in the Kreuzer-Skarke list

Heterotic Bundles on Calabi-Yau Manifolds with Small Picard Number

We undertake a systematic scan of vector bundles over spaces from the largest database of known Calabi-Yau three-folds, in the context of heterotic string compactification. Specifically, we construct positive rank five monad bundles over Calabi-Yau hypersurfaces in toric varieties, with the number of Kahler moduli equal to one, two, and three and extract physically interesting models. We select models which can lead to three families of matter after dividing by a freely-acting discrete symmetry and including Wilson lines. About 2000 such models on two manifolds are found.Comment: 26 pages, 1 figur

Presymptomatic risk assessment for chronic non-communicable diseases

The prevalence of common chronic non-communicable diseases (CNCDs) far overshadows the prevalence of both monogenic and infectious diseases combined. All CNCDs, also called complex genetic diseases, have a heritable genetic component that can be used for pre-symptomatic risk assessment. Common single nucleotide polymorphisms (SNPs) that tag risk haplotypes across the genome currently account for a non-trivial portion of the germ-line genetic risk and we will likely continue to identify the remaining missing heritability in the form of rare variants, copy number variants and epigenetic modifications. Here, we describe a novel measure for calculating the lifetime risk of a disease, called the genetic composite index (GCI), and demonstrate its predictive value as a clinical classifier. The GCI only considers summary statistics of the effects of genetic variation and hence does not require the results of large-scale studies simultaneously assessing multiple risk factors. Combining GCI scores with environmental risk information provides an additional tool for clinical decision-making. The GCI can be populated with heritable risk information of any type, and thus represents a framework for CNCD pre-symptomatic risk assessment that can be populated as additional risk information is identified through next-generation technologies.Comment: Plos ONE paper. Previous version was withdrawn to be updated by the journal's pdf versio

Combined acoustic radiation force impulse, aminotransferase to platelet ratio index and Forns index assessment for hepatic fibrosis grading in hepatitis B

published_or_final_versio

A cross-national study on the antecedents of work–life balance from the fit and balance perspective

Drawing on the perceived work–family fit and balance perspective, this study investigates demands and resources as antecedents of work–life balance (WLB) across four countries (New Zealand, France, Italy and Spain), so as to provide empirical cross-national evidence. Using structural equation modelling analysis on a sample of 870 full time employees, we found that work demands, hours worked and family demands were negatively related to WLB, while job autonomy and supervisor support were positively related to WLB. We also found evidence that resources (job autonomy and supervisor support) moderated the relationships between demands and work–life balance, with high resources consistently buffering any detrimental influence of demands on WLB. Furthermore, our study identified additional predictors of WLB that were unique to some national contexts. For example, in France and Italy, overtime hours worked were negatively associated with WLB, while parental status was positively associated with WLB. Overall, the implications for theory and practice are discussed.Peer ReviewedPostprint (author's final draft

Integrated genomics and proteomics define huntingtin CAG length-dependent networks in mice.

To gain insight into how mutant huntingtin (mHtt) CAG repeat length modifies Huntington's disease (HD) pathogenesis, we profiled mRNA in over 600 brain and peripheral tissue samples from HD knock-in mice with increasing CAG repeat lengths. We found repeat length-dependent transcriptional signatures to be prominent in the striatum, less so in cortex, and minimal in the liver. Coexpression network analyses revealed 13 striatal and 5 cortical modules that correlated highly with CAG length and age, and that were preserved in HD models and sometimes in patients. Top striatal modules implicated mHtt CAG length and age in graded impairment in the expression of identity genes for striatal medium spiny neurons and in dysregulation of cyclic AMP signaling, cell death and protocadherin genes. We used proteomics to confirm 790 genes and 5 striatal modules with CAG length-dependent dysregulation at the protein level, and validated 22 striatal module genes as modifiers of mHtt toxicities in vivo

Epigenetic alterations differ in phenotypically distinct human neuroblastoma cell lines

<p>Abstract</p> <p>Background</p> <p>Epigenetic aberrations and a CpG island methylator phenotype have been shown to be associated with poor outcomes in children with neuroblastoma (NB). Seven cancer related genes (<it>THBS-1, CASP8, HIN-1, TIG-1, BLU, SPARC</it>, and <it>HIC-1</it>) that have been shown to have epigenetic changes in adult cancers and play important roles in the regulation of angiogenesis, tumor growth, and apoptosis were analyzed to investigate the role epigenetic alterations play in determining NB phenotype.</p> <p>Methods</p> <p>Two NB cell lines (tumorigenic LA1-55n and non-tumorigenic LA1-5s) that differ in their ability to form colonies in soft agar and tumors in nude mice were used. Quantitative RNA expression analyses were performed on seven genes in LA1-5s, LA1-55n and 5-Aza-dC treated LA1-55n NB cell lines. The methylation status around <it>THBS-1, HIN-1, TIG-1 </it>and <it>CASP8 </it>promoters was examined using methylation specific PCR. Chromatin immunoprecipitation assay was used to examine histone modifications along the <it>THBS-1 </it>promoter. Luciferase assay was used to determine <it>THBS-1 </it>promoter activity. Cell proliferation assay was used to examine the effect of 5-Aza-dC on NB cell growth. The soft agar assay was used to determine the tumorigenicity.</p> <p>Results</p> <p>Promoter methylation values for <it>THBS-1</it>, <it>HIN-1</it>, <it>TIG-1</it>, and <it>CASP8 </it>were higher in LA1-55n cells compared to LA1-5s cells. Consistent with the promoter methylation status, lower levels of gene expression were detected in the LA1-55n cells. Histone marks associated with repressive chromatin states (H3K9Me3, H3K27Me3, and H3K4Me3) were identified in the <it>THBS-1 </it>promoter region in the LA1-55n cells, but not the LA1-5s cells. In contrast, the three histone codes associated with an active chromatin state (acetyl H3, acetyl H4, and H3K4Me3) were present in the <it>THBS-1 </it>promoter region in LA1-5s cells, but not the LA1-55n cells, suggesting that an accessible chromatin structure is important for <it>THBS-1 </it>expression. We also show that 5-Aza-dC treatment of LA1-55n cells alters the DNA methylation status and the histone code in the <it>THBS-1 </it>promoter modifies cell morphology, and inhibits their ability to form colonies in soft agar.</p> <p>Conclusion</p> <p>Our results suggest that epigenetic aberrations contribute to NB phenotype, and that tumorigenic properties can be inhibited by reversing the epigenetic changes with 5-Aza-dC.</p