Spectral Functions in Holographic Renormalization Group Flows

The spectrum of two-point functions in a holographic renormalization group flow from an ultraviolet (UV) to an infrared (IR) conformal fixed point is necessarily continuous. For a toy model, the spectral function does not only show the expected UV and IR behaviours, but other interesting features such as sharp peaks and oscillations in the UV. The spectral functions for the SU(3)xU(1) flow in AdS_4/CFT_3 and the SU(2)xU(1) flow in AdS_5/CFT_4 are calculated numerically. They exhibit a simple cross-over behaviour and reproduce the conformal dimensions of the dual operators in the UV and IR conformal phases.Comment: 20 pages, 6 figures v2: added referene

Dyons in N=4 Gauged Supergravity

We study monopole and dyon solutions to the equations of motion of the bosonic sector of N = 4 gauged supergravity in four dimensional space-time. A static, spherically symmetric ansatz for the metric, gauge fields, dilaton and axion leads to soliton solutions which, in the electrically charged case, have compact spatial sections. Both analytical and numerical results for the solutions are presented.Comment: 12 pages, 7 figures. Minor changes, references adde

Role of lepton flavor violating (LFV) muon decay in Seesaw model and LSND

The aim of the work is to study LFV in a newly proposed Seesaw model of neutrino mass and to see whether it could explain LSND excess. The motivation of this Seesaw model was that there was no new physics beyond the TeV scale. By studying \mu \to 3e in this model, it is shown that the upper bound on the branching ratio requires Higgs mass m_{h} of a new scalar doublet with lepton number L=-1 needed in the model has to be about 9 TeV. The predicted branching ratio for \mu \to e\nu_{l}\bar{\nu}_{l} is too small to explain the LSND. PACS: 11.30.Hv, 14.60.PqComment: 05 pages, three figures, the version to appear in PR

Relic Neutralino Densities and Detection Rates with Nonuniversal Gaugino Masses

We extend previous analyses on the interplay between nonuniversalities in the gaugino mass sector and the thermal relic densities of LSP neutralinos, in particular to the case of moderate to large tan beta. We introduce a set of parameters that generalizes the standard unified scenario to cover the complete allowed parameter space in the gaugino mass sector. We discuss the physical significance of the cosmologically preferred degree of degeneracy between charginos and the LSP and study the effect this degree of degeneracy has on the prospects for direct detection of relic neutralinos in the next round of dark matter detection experiments. Lastly, we compare the fine tuning required to achieve a satisfactory relic density with the case of universal gaugino masses, as in minimal supergravity, and find it to be of a similar magnitude. The sensitivity of quantifiable measures of fine-tuning on such factors as the gluino mass and top and bottom masses is also examined.Comment: Uses RevTeX; 14 pages, 16 figure

Solvable Models of Domain Walls in N=1 Supergravity

A class of exactly solvable models of domain walls are worked out in D=4 ${\cal N}=1$ supergravity. We develop a method to embed globally supersymmetric theories with exact BPS domain wall solutions into supergravity, by introducing a gravitationally deformed superpotential. The gravitational deformation is natural in the spirit of maintaining the K\"ahler invariance. The solutions of the warp factor and the Killing spinor are also obtained. We find that three distinct behaviors of warp factors arise depending on the value of a constant term in the superpotential : exponentially decreasing in both sides of the wall, flat in one side and decreasing in the other, and increasing in one side and decreasing in the other. Only the first possibility gives the localized massless graviton zero mode. Models with multi-walls and models with runaway vacua are also discussed.Comment: 10 pages, 3 figures; Misprints in three formulas are correcte

Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease

Next-generation sequencing (NGS) is quickly revolutionizing how research into the genetic determinants of constitutional disease is performed. The technique is highly efficient with millions of sequencing reads being produced in a short time span and at relatively low cost. Specifically, targeted NGS is able to focus investigations to genomic regions of particular interest based on the disease of study. Not only does this further reduce costs and increase the speed of the process, but it lessens the computational burden that often accompanies NGS. Although targeted NGS is restricted to certain regions of the genome, preventing identification of potential novel loci of interest, it can be an excellent technique when faced with a phenotypically and genetically heterogeneous disease, for which there are previously known genetic associations. Because of the complex nature of the sequencing technique, it is important to closely adhere to protocols and methodologies in order to achieve sequencing reads of high coverage and quality. Further, once sequencing reads are obtained, a sophisticated bioinformatics workflow is utilized to accurately map reads to a reference genome, to call variants, and to ensure the variants pass quality metrics. Variants must also be annotated and curated based on their clinical significance, which can be standardized by applying the American College of Medical Genetics and Genomics Pathogenicity Guidelines. The methods presented herein will display the steps involved in generating and analyzing NGS data from a targeted sequencing panel, using the ONDRISeq neurodegenerative disease panel as a model, to identify variants that may be of clinical significance

Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus

A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk

Meta-analysis of type 2 Diabetes in African Americans Consortium

Type 2 diabetes (T2D) is more prevalent in African Americans than in Europeans. However, little is known about the genetic risk in African Americans despite the recent identification of more than 70 T2D loci primarily by genome-wide association studies (GWAS) in individuals of European ancestry. In order to investigate the genetic architecture of T2D in African Americans, the MEta-analysis of type 2 DIabetes in African Americans (MEDIA) Consortium examined 17 GWAS on T2D comprising 8,284 cases and 15,543 controls in African Americans in stage 1 analysis. Single nucleotide polymorphisms (SNPs) association analysis was conducted in each study under the additive model after adjustment for age, sex, study site, and principal components. Meta-analysis of approximately 2.6 million genotyped and imputed SNPs in all studies was conducted using an inverse variance-weighted fixed effect model. Replications were performed to follow up 21 loci in up to 6,061 cases and 5,483 controls in African Americans, and 8,130 cases and 38,987 controls of European ancestry. We identified three known loci (TCF7L2, HMGA2 and KCNQ1) and two novel loci (HLA-B and INS-IGF2) at genome-wide significance (4.15 × 10(-94)<P<5 × 10(-8), odds ratio (OR)  = 1.09 to 1.36). Fine-mapping revealed that 88 of 158 previously identified T2D or glucose homeostasis loci demonstrated nominal to highly significant association (2.2 × 10(-23) < locus-wide P<0.05). These novel and previously identified loci yielded a sibling relative risk of 1.19, explaining 17.5% of the phenotypic variance of T2D on the liability scale in African Americans. Overall, this study identified two novel susceptibility loci for T2D in African Americans. A substantial number of previously reported loci are transferable to African Americans after accounting for linkage disequilibrium, enabling fine mapping of causal variants in trans-ethnic meta-analysis studies.Peer reviewe

Associations of autozygosity with a broad range of human phenotypes

In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (F-ROH) for >1.4 million individuals, we show that F-ROH is significantly associated (p <0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: F-ROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44-66%] in the odds of having children. Finally, the effects of F-ROH are confirmed within full-sibling pairs, where the variation in F-ROH is independent of all environmental confounding.Peer reviewe