The MSW Effect in Quantum Field Theory

We show in detail the general relationship between the Schr\"{o}dinger equation approach to calculating the MSW effect and the quantum field theoretical S-matrix approach. We show the precise form a generic neutrino propagator must have to allow a physically meaningful ``oscillation probability'' to be decoupled from neutrino production fluxes and detection cross-sections, and explicitly list the conditions---not realized in cases of current experimental interest---in which the field theory approach would be useful.Comment: 20 page REVTeX file, submitted to Phys. Rev.

Second-order corrections to neutrino two-flavor oscillation parameters in the wave packet approach

We report about an analytic study involving the {\em intermediate} wave packet formalism for quantifying the physically relevant information which appear in the neutrino two-flavor conversion formula and help us to obtain more precise limits and ranges for neutrino flavor oscillation. By following the sequence of analytic approximations where we assume a strictly peaked momentum distribution and consider the second-order corrections in a power series expansion of the energy, we point out a {\em residual} time-dependent phase which, coupled with the {\em spreading/slippage} effects, can subtly modify the neutrino oscillation parameters and limits. Such second-order effects are usually ignored in the relativistic wave packet treatment, but they present an evident dependence on the propagation regime so that some small modifications to the oscillation pattern, even in the ultra-relativistic limit, can be quantified. These modifications are implemented in the confront with the neutrino oscillation parameter range (mass-squared difference \Delta m^{\2} and the mixing-angle $\theta$) where we assume the same wave packet parameters previously noticed in the literature in a kind of {\em toy model} for some reactor experiments. Generically speaking, our analysis parallels the recent experimental purposes which concern with higher precision parameter measurements. To summarize, we show that the effectiveness of a more accurate determination of \Delta m^{\2} and $\theta$ depends on the wave packet width $a$ and on the averaged propagating energy flux $\bar{E}$ which still correspond to open variables for some classes of experiments. \Comment: 25 pages, 5 figure

Multiethnic meta-analysis identifies ancestry-specific and cross-ancestry loci for pulmonary function

Nearly 100 loci have been identified for pulmonary function, almost exclusively in studies of European ancestry populations. We extend previous research by meta-analyzing genome-wide association studies of 1000 Genomes imputed variants in relation to pulmonary function in a multiethnic population of 90,715 individuals of European (N = 60,552), African (N = 8429), Asian (N = 9959), and Hispanic/Latino (N = 11,775) ethnicities. We identify over 50 additional loci at genome-wide significance in ancestry-specific or multiethnic meta-analyses. Using recent fine-mapping methods incorporating functional annotation, gene expression, and differences in linkage disequilibrium between ethnicities, we further shed light on potential causal variants and genes at known and newly identified loci. Several of the novel genes encode proteins with predicted or established drug targets, including KCNK2 and CDK12. Our study highlights the utility of multiethnic and integrative genomics approaches to extend existing knowledge of the genetics of l

Pulmonary Function and Blood DNA Methylation A Multiancestry Epigenome-Wide Association Meta-analysis

Rationale: Methylation integrates factors present at birth and modifiable across the lifespan that can influence pulmonary function. Studies are limited in scope and replication. Objectives: To conduct large-scale epigenome-wide meta-analyses of blood DNA methylation and pulmonary function. Methods: Twelve cohorts analyzed associations of methylation at cytosine-phosphate-guanine probes (CpGs), using Illumina 450K or EPIC/850K arrays, with FEV1, FVC, and FEV1/FVC. We performed multiancestry epigenome-wide meta-analyses (total of 17,503 individuals; 14,761 European, 2,549 African, and 193 Hispanic/Latino ancestries) and interpreted results using integrative epigenomics. Measurements and Main Results: We identified 1,267 CpGs (1,042 genes) differentially methylated (false discovery rate,,0.025) in relation to FEV1, FVC, or FEV1/FVC, including 1,240 novel and 73 also related to chronic obstructive pulmonary disease (1,787 cases). We found 294 CpGs unique to European or African ancestry and 395 CpGs unique to never or ever smokers. The majority of significant CpGs correlated with nearby gene expression in blood. Findings were enriched in key regulatory elements for gene function, including accessible chromatin elements, in both blood and lung. Sixty-nine implicated genes are targets of investigational or approved drugs. One example novel gene highlighted by integrative epigenomic and druggable target analysis is TNFRSF4. Mendelian randomization and colocalization analyses suggest that epigenome-wide association study signals capture causal regulatory genomic loci. Conclusions: We identified numerous novel loci differentially methylated in relation to pulmonary function; few were detected in large genome-wide association studies. Integrative analyses highlight functional relevance and potential therapeutic targets. This comprehensive discovery of potentially modifiable, novel lung function loci expands knowledge gained from genetic studies, providing insights into lung pathogenesis

FBXO44 promotes DNA replication-coupled repetitive element silencing in cancer cells

Repetitive elements (REs) compose ∼50% of the human genome and are normally transcriptionally silenced, although the mechanism has remained elusive. Through an RNAi screen, we identified FBXO44 as an essential repressor of REs in cancer cells. FBXO44 bound H3K9me3-modified nucleosomes at the replication fork and recruited SUV39H1, CRL4, and Mi-2/NuRD to transcriptionally silence REs post-DNA replication. FBXO44/SUV39H1 inhibition reactivated REs, leading to DNA replication stress and stimulation of MAVS/STING antiviral pathways and interferon (IFN) signaling in cancer cells to promote decreased tumorigenicity, increased immunogenicity, and enhanced immunotherapy response. FBXO44 expression inversely correlated with replication stress, antiviral pathways, IFN signaling, and cytotoxic T cell infiltration in human cancers, while a FBXO44-immune gene signature correlated with improved immunotherapy response in cancer patients. FBXO44/SUV39H1 were dispensable in normal cells. Collectively, FBXO44/SUV39H1 are crucial repressors of RE transcription, and their inhibition selectively induces DNA replication stress and viral mimicry in cancer cells