Quantized algebras of functions on homogeneous spaces with Poisson stabilizers

Let G be a simply connected semisimple compact Lie group with standard Poisson structure, K a closed Poisson-Lie subgroup, 0<q<1. We study a quantization C(G_q/K_q) of the algebra of continuous functions on G/K. Using results of Soibelman and Dijkhuizen-Stokman we classify the irreducible representations of C(G_q/K_q) and obtain a composition series for C(G_q/K_q). We describe closures of the symplectic leaves of G/K refining the well-known description in the case of flag manifolds in terms of the Bruhat order. We then show that the same rules describe the topology on the spectrum of C(G_q/K_q). Next we show that the family of C*-algebras C(G_q/K_q), 0<q\le1, has a canonical structure of a continuous field of C*-algebras and provides a strict deformation quantization of the Poisson algebra \C[G/K]. Finally, extending a result of Nagy, we show that C(G_q/K_q) is canonically KK-equivalent to C(G/K).Comment: 23 pages; minor changes, typos correcte

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

Multi-ancestry transcriptome-wide association analyses yield insights into tobacco use biology and drug repurposing

Most transcriptome-wide association studies (TWASs) so far focus on European ancestry and lack diversity. To overcome this limitation, we aggregated genome-wide association study (GWAS) summary statistics, whole-genome sequences and expression quantitative trait locus (eQTL) data from diverse ancestries. We developed a new approach, TESLA (multi-ancestry integrative study using an optimal linear combination of association statistics), to integrate an eQTL dataset with a multi-ancestry GWAS. By exploiting shared phenotypic effects between ancestries and accommodating potential effect heterogeneities, TESLA improves power over other TWAS methods. When applied to tobacco use phenotypes, TESLA identified 273 new genes, up to 55% more compared with alternative TWAS methods. These hits and subsequent fine mapping using TESLA point to target genes with biological relevance. In silico drug-repurposing analyses highlight several drugs with known efficacy, including dextromethorphan and galantamine, and new drugs such as muscle relaxants that may be repurposed for treating nicotine addiction

Genetic determinants of telomere length from 109,122 ancestrally diverse whole-genome sequences in TOPMed

Genetic studies on telomere length are important for understanding age-related diseases. Prior GWASs for leukocyte TL have been limited to European and Asian populations. Here, we report the first sequencing-based association study for TL across ancestrally diverse individuals (European, African, Asian, and Hispanic/Latino) from the NHLBI Trans-Omics for Precision Medicine (TOPMed) program. We used whole-genome sequencing (WGS) of whole blood for variant genotype calling and the bioinformatic estimation of telomere length in n = 109,122 individuals. We identified 59 sentinel variants (p &lt; 5 × 10−9) in 36 loci associated with telomere length, including 20 newly associated loci (13 were replicated in external datasets). There was little evidence of effect size heterogeneity across populations. Fine-mapping at OBFC1 indicated that the independent signals colocalized with cell-type-specific eQTLs for OBFC1 (STN1). Using a multi-variant gene-based approach, we identified two genes newly implicated in telomere length, DCLRE1B (SNM1B) and PARN. In PheWAS, we demonstrated that our TL polygenic trait scores (PTSs) were associated with an increased risk of cancer-related phenotypes

A new gas discharge process for preparation of non-fouling surfaces on biomaterials

A non-fouling surface containing immobilized polyethylene oxide (PEO) was achieved using an argon radio-frequency glow discharge treatment (RFGD) of polyethylene films precoated with Brij hydrocarbon-PEO surfactants. Surface wettability of RFGD-treated and washed surfaces increased the most when PEO surfactants with unsaturated and/or long alkyl tails were used. ESCA measurements of treated and washed surfaces showed increases of surface O/C ratios and ether carbon peaks in high resolution Cls spectra. These results demonstrate the retention of the PEO surfactants on the treated surfaces. Fibrinogen adsorp tion on these treated surfaces was significantly reduced, from 500 to 50 ng/cm2, indicating the non-fouling properties of the RFGD-immobilized PEO surfactants