The spectral action and cosmic topology

The spectral action functional, considered as a model of gravity coupled to matter, provides, in its non-perturbative form, a slow-roll potential for inflation, whose form and corresponding slow-roll parameters can be sensitive to the underlying cosmic topology. We explicitly compute the non-perturbative spectral action for some of the main candidates for cosmic topologies, namely the quaternionic space, the Poincare' dodecahedral space, and the flat tori. We compute the corresponding slow-roll parameters and see we check that the resulting inflation model behaves in the same way as for a simply-connected spherical topology in the case of the quaternionic space and the Poincare' homology sphere, while it behaves differently in the case of the flat tori. We add an appendix with a discussion of the case of lens spaces.Comment: 55 pages, LaTe

VHL substrate transcription factor ZHX2 as an oncogenic driver in clear cell renal cell carcinoma

Inactivation of the von Hippel-Lindau (VHL) E3 ubiquitin ligase protein is a hallmark of clear cell renal cell carcinoma (ccRCC). Identifying how pathways affected by VHL loss contribute to ccRCC remains challenging. We used a genome-wide in vitro expression strategy to identify proteins that bind VHL when hydroxylated. Zinc fingers and homeoboxes 2 (ZHX2) was found as a VHL target, and its hydroxylation allowed VHL to regulate its protein stability. Tumor cells from ccRCC patients with VHL loss-of-function mutations usually had increased abundance and nuclear localization of ZHX2. Functionally, depletion of ZHX2 inhibited VHL-deficient ccRCC cell growth in vitro and in vivo. Mechanistically, integrated chromatin immunoprecipitation sequencing and microarray analysis showed that ZHX2 promoted nuclear factor κB activation. These studies reveal ZHX2 as a potential therapeutic target for ccRCC

Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation

We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 × 10-11 to 5.0 × 10-21). The sentinel blood pressure SNPs are enriched for association with DNA methylation at multiple nearby CpG sites, suggesting that, at some of the loci identified, DNA methylation may lie on the regulatory pathway linking sequence variation to blood pressure. The sentinel SNPs at the 12 new loci point to genes involved in vascular smooth muscle (IGFBP3, KCNK3, PDE3A and PRDM6) and renal (ARHGAP24, OSR1, SLC22A7 and TBX2) function. The new and known genetic variants predict increased left ventricular mass, circulating levels of NT-proBNP, and cardiovascular and all-cause mortality (P = 0.04 to 8.6 × 10-6). Our results provide new evidence for the role of DNA methylation in blood pressure regulation

Research priorities for global food security under extreme events

International audienc

Track D Social Science, Human Rights and Political Science

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138414/1/jia218442.pd

A generic approach to topic models

Abstract. This article contributes a generic model of topic models. To define the problem space, general characteristics for this class of models are derived, which give rise to a representation of topic models as “mixture networks”, a domainspecific compact alternative to Bayesian networks. Besides illustrating the interconnection of mixtures in topic models, the benefit of this representation is its straight-forward mapping to inference equations and algorithms, which is shown with the derivation and implementation of a generic Gibbs sampling algorithm.