F-theory, GUTs, and the Weak Scale

In this paper we study a deformation of gauge mediated supersymmetry breaking in a class of local F-theory GUT models where the scale of supersymmetry breaking determines the value of the mu term. Geometrically correlating these two scales constrains the soft SUSY breaking parameters of the MSSM. In this scenario, the hidden SUSY breaking sector involves an anomalous U(1) Peccei-Quinn symmetry which forbids bare mu and B mu terms. This sector typically breaks supersymmetry at the desired range of energy scales through a simple stringy hybrid of a Fayet and Polonyi model. A variant of the Giudice-Masiero mechanism generates the value mu ~ 10^2 - 10^3 GeV when the hidden sector scale of supersymmetry breaking is F^(1/2) ~ 10^(8.5) GeV. Further, the B mu problem is solved due to the mild hierarchy between the GUT scale and Planck scale. These models relate SUSY breaking with the QCD axion, and solve the strong CP problem through an axion with decay constant f_a ~ M_(GUT) * mu / L, where L ~ 10^5 GeV is the characteristic scale of gaugino mass unification in gauge mediated models, and the ratio \mu / L ~ M_(GUT)/M_(pl) ~ 10^(-3). We find f_a ~ 10^12 GeV, which is near the high end of the phenomenologically viable window. Here, the axino is the goldstino mode which is eaten by the gravitino. The gravitino is the LSP with a mass of about 10^1 - 10^2 MeV, and a bino-like neutralino is (typically) the NLSP with mass of about 10^2 - 10^3 GeV. Compatibility with electroweak symmetry breaking also determines the value of tan(beta) ~ 30 +/- 7.Comment: v3: 94 pages, 9 figures, clarification of Fayet-Polonyi model and instanton corrections to axion potentia

Particle interactions with single or multiple 3D solar reconnecting current sheets

The acceleration of charged particles (electrons and protons) in flaring solar active regions is analyzed by numerical experiments. The acceleration is modelled as a stochastic process taking place by the interaction of the particles with local magnetic reconnection sites via multiple steps. Two types of local reconnecting topologies are studied: the Harris-type and the X-point. A formula for the maximum kinetic energy gain in a Harris-type current sheet, found in a previous work of ours, fits well the numerical data for a single step of the process. A generalization is then given approximating the kinetic energy gain through an X-point. In the case of the multiple step process, in both topologies the particles' kinetic energy distribution is found to acquire a practically invariant form after a small number of steps. This tendency is interpreted theoretically. Other characteristics of the acceleration process are given, such as the mean acceleration time and the pitch angle distributions of the particles.Comment: 18 pages, 9 figures, Solar Physics, in pres

Improving Genetic Prediction by Leveraging Genetic Correlations Among Human Diseases and Traits

Genomic prediction has the potential to contribute to precision medicine. However, to date, the utility of such predictors is limited due to low accuracy for most traits. Here theory and simulation study are used to demonstrate that widespread pleiotropy among phenotypes can be utilised to improve genomic risk prediction. We show how a genetic predictor can be created as a weighted index that combines published genome-wide association study (GWAS) summary statistics across many different traits. We apply this framework to predict risk of schizophrenia and bipolar disorder in the Psychiatric Genomics consortium data, finding substantial heterogeneity in prediction accuracy increases across cohorts. For six additional phenotypes in the UK Biobank data, we find increases in prediction accuracy ranging from 0.7 for height to 47 for type 2 diabetes, when using a multi-trait predictor that combines published summary statistics from multiple traits, as compared to a predictor based only on one trait. © 2018 The Author(s)

Genome-wide association study identifies 30 Loci Associated with Bipolar Disorder

This paper is dedicated to the memory of Psychiatric Genomics Consortium (PGC) founding member and Bipolar disorder working group co-chair Pamela Sklar. We thank the participants who donated their time, experiences and DNA to this research, and to the clinical and scientific teams that worked with them. We are deeply indebted to the investigators who comprise the PGC. The views expressed are those of the authors and not necessarily those of any funding or regulatory body. Analyses were carried out on the NL Genetic Cluster Computer (http://www.geneticcluster.org ) hosted by SURFsara, and the Mount Sinai high performance computing cluster (http://hpc.mssm.edu).Bipolar disorder is a highly heritable psychiatric disorder. We performed a genome-wide association study including 20,352 cases and 31,358 controls of European descent, with follow-up analysis of 822 variants with P<1x10-4 in an additional 9,412 cases and 137,760 controls. Eight of the 19 variants that were genome-wide significant (GWS, p < 5x10-8) in the discovery GWAS were not GWS in the combined analysis, consistent with small effect sizes and limited power but also with genetic heterogeneity. In the combined analysis 30 loci were GWS including 20 novel loci. The significant loci contain genes encoding ion channels, neurotransmitter transporters and synaptic components. Pathway analysis revealed nine significantly enriched gene-sets including regulation of insulin secretion and endocannabinoid signaling. BDI is strongly genetically correlated with schizophrenia, driven by psychosis, whereas BDII is more strongly correlated with major depressive disorder. These findings address key clinical questions and provide potential new biological mechanisms for BD.This work was funded in part by the Brain and Behavior Research Foundation, Stanley Medical Research Institute, University of Michigan, Pritzker Neuropsychiatric Disorders Research Fund L.L.C., Marriot Foundation and the Mayo Clinic Center for Individualized Medicine, the NIMH Intramural Research Program; Canadian Institutes of Health Research; the UK Maudsley NHS Foundation Trust, NIHR, NRS, MRC, Wellcome Trust; European Research Council; German Ministry for Education and Research, German Research Foundation IZKF of Münster, Deutsche Forschungsgemeinschaft, ImmunoSensation, the Dr. Lisa-Oehler Foundation, University of Bonn; the Swiss National Science Foundation; French Foundation FondaMental and ANR; Spanish Ministerio de Economía, CIBERSAM, Industria y Competitividad, European Regional Development Fund (ERDF), Generalitat de Catalunya, EU Horizon 2020 Research and Innovation Programme; BBMRI-NL; South-East Norway Regional Health Authority and Mrs. Throne-Holst; Swedish Research Council, Stockholm County Council, Söderström Foundation; Lundbeck Foundation, Aarhus University; Australia NHMRC, NSW Ministry of Health, Janette M O'Neil and Betty C Lynch

Fine-Scale Mapping of the 4q24 Locus Identifies Two Independent Loci Associated with Breast Cancer Risk

Background: A recent association study identified a common variant (rs9790517) at 4q24 to be associated with breast cancer risk. Independent association signals and potential functional variants in this locus have not been explored. Methods: We conducted a fine-mapping analysis in 55,540 breast cancer cases and 51,168 controls from the Breast Cancer Association Consortium. Results: Conditional analyses identified two independent association signals among women of European ancestry, represented by rs9790517 [conditional P = 2.51 × 10−4; OR, 1.04; 95% confidence interval (CI), 1.02–1.07] and rs77928427 (P = 1.86 × 10−4; OR, 1.04; 95% CI, 1.02–1.07). Functional annotation using data from the Encyclopedia of DNA Elements (ENCODE) project revealed two putative functional variants, rs62331150 and rs73838678 in linkage disequilibrium (LD) with rs9790517 (r2 ≥ 0.90) residing in the active promoter or enhancer, respectively, of the nearest gene, TET2. Both variants are located in DNase I hypersensitivity and transcription factor–binding sites. Using data from both The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC), we showed that rs62331150 was associated with level of expression of TET2 in breast normal and tumor tissue. Conclusion: Our study identified two independent association signals at 4q24 in relation to breast cancer risk and suggested that observed association in this locus may be mediated through the regulation of TET2. Impact: Fine-mapping study with large sample size warranted for identification of independent loci for breast cancer risk

Search for high-mass diphoton resonances in proton-proton collisions at 13 TeV and combination with 8 TeV search

Peer reviewe

Search for a pseudoscalar boson decaying into a Z boson and the 125 GeV Higgs boson in ℓ+ℓ-bb final states

Results are reported on a search for decays of a pseudoscalar A boson into a Z boson and a light scalar h boson, where the Z boson decays into a pair of oppositely-charged electrons or muons, and the h boson decays into bb- The search is based on data from proton-proton collisions at a center-of-mass energy s=8 TeV collected with the CMS detector, corresponding to an integrated luminosity of 19.7 fb-1. The h boson is assumed to be the standard model-like Higgs boson with a mass of 125 GeV. With no evidence for signal, upper limits are obtained on the product of the production cross section and the branching fraction of the A boson in the Zh channel. Results are also interpreted in the context of two Higgs doublet models. © 2015