CP violation effects in the diphoton spectrum of heavy scalars

In a class of new physics models, an extended Higgs sector and new CP-violating sources are simultaneously present in order to explain the baryon asymmetry in the Universe. The aim of this work is to study the implications of beyond the Standard Model (SM) CP violation for the searches of heavy scalars at the LHC. In particular, we focus on the diphoton channel searches in the CP-violating two-Higgs-doublet model (CPV 2HDM). To have a sizable CPV in the scalar sector, the two heavy neutral scalars in 2HDM tend to be nearly degenerate. The theoretical constraints of unitarity, perturbativity and vacuum stability are considered, which requires that the heavy scalars $M_H \lesssim 1$ TeV in a large region of the parameter space. The experimental limits are also taken into account, including the direct searches of heavy neutral scalars in the final state of the SM $h$, $W$ and $Z$ bosons, the differential $t\bar{t}$ data, those from the charged scalar sector which is implied by the oblique $T$ parameter, as well as the precise measurements of the electric dipole moments of electron and mercury. The quantum interference effects between the resonances and the SM background are crucially important for the diphoton signals, and the CPV mixing of the quasi-degenerate heavy scalars could enhance significantly the resonance peak. With an integrated luminosity of 3000 fb$^{-1}$ at the LHC, almost the whole parameter space of CPV 2HDM could be probed in the diphoton channel, and the CPV could also be directly detected via the diphoton spectrum.Comment: 32 pages (two columns), 20 figures, 1 table, minor changes, version to appear in PR

Future prospects of mass-degenerate Higgs bosons in the CPCP-conserving two-Higgs-doublet model

The scenario of two mass-degenerate Higgs bosons within the general two-Higgs-doublet model (2HDM) is revisited. We focus on the global picture when two $CP$-even Higgs bosons of $h$ and $H$ are nearly mass-degenerate. A global fit to the signal strength of the 125 GeV Higgs measured at the LHC is performed. Based on the best-fit result of the 2HDM mixing angles $(\alpha,\beta)$, theoretical constraints, charged and $CP$-odd Higgs boson direct search constraints and the electroweak precision constraints are imposed to the 2HDM parameter space. We present the signal predictions of the $(4b\,, 2b\,2\gamma)$ channels for the benchmark models at the LHC 14 TeV runs. We also study the direct Higgs boson pair productions at the LHC, and the Z-associated Higgs boson pair production search at the ILC 500 GeV runs, as well as the indirect probes at the CEPC 250 GeV run. We find that the mass-degenerate Higgs boson scenario in the Type-II 2HDM can be fully probed by these future experimental searches.Comment: 31 pages, 9 figures, 5 tables, matches with the PRD published versio

Heparanase Regulates Levels of Syndecan-1 in the Nucleus

Syndecan-1 is a transmembrane heparan sulfate-bearing proteoglycan known to regulate multiple biological functions at the cell surface and within the extracellular matrix. Its functional activity can be modulated by heparanase, an enzyme that cleaves heparan sulfate chains and whose expression has been associated with an aggressive phenotype in many cancers. In addition to remodeling syndecan-1 by cleaving its heparan sulfate chains, heparanase influences syndecan-1 location by upregulating expression of enzymes that accelerate its shedding from the cell surface. In the present study we discovered that heparanase also alters the level of nuclear syndecan-1. Upon upregulation of heparanase expression or following addition of recombinant heparanase to myeloma cells, the nuclear localization of syndecan-1 drops dramatically as revealed by confocal microscopy, western blotting and quantification by ELISA. This effect requires enzymatically active heparanase because cells expressing high levels of mutated, enzymatically inactive heparanase, failed to diminish syndecan-1 levels in the nucleus. Although heparan sulfate function within the nucleus is not well understood, there is emerging evidence that it may act to repress transcriptional activity. The resulting changes in gene expression facilitated by the loss of nuclear syndecan-1 could explain how heparanase enhances expression of MMP-9, VEGF, tissue factor and perhaps other effectors that condition the tumor microenvironment to promote an aggressive cancer phenotype

Organic cation transporter 1 (OCT1) modulates multiple cardiometabolic traits through effects on hepatic thiamine content.

A constellation of metabolic disorders, including obesity, dysregulated lipids, and elevations in blood glucose levels, has been associated with cardiovascular disease and diabetes. Analysis of data from recently published genome-wide association studies (GWAS) demonstrated that reduced-function polymorphisms in the organic cation transporter, OCT1 (SLC22A1), are significantly associated with higher total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglyceride (TG) levels and an increased risk for type 2 diabetes mellitus, yet the mechanism linking OCT1 to these metabolic traits remains puzzling. Here, we show that OCT1, widely characterized as a drug transporter, plays a key role in modulating hepatic glucose and lipid metabolism, potentially by mediating thiamine (vitamin B1) uptake and hence its levels in the liver. Deletion of Oct1 in mice resulted in reduced activity of thiamine-dependent enzymes, including pyruvate dehydrogenase (PDH), which disrupted the hepatic glucose-fatty acid cycle and shifted the source of energy production from glucose to fatty acids, leading to a reduction in glucose utilization, increased gluconeogenesis, and altered lipid metabolism. In turn, these effects resulted in increased total body adiposity and systemic levels of glucose and lipids. Importantly, wild-type mice on thiamine deficient diets (TDs) exhibited impaired glucose metabolism that phenocopied Oct1 deficient mice. Collectively, our study reveals a critical role of hepatic thiamine deficiency through OCT1 deficiency in promoting the metabolic inflexibility that leads to the pathogenesis of cardiometabolic disease

PTSD and DNA Methylation in Select Immune Function Gene Promoter Regions: A Repeated Measures Case-Control Study of U.S. Military Service Members

Background: The underlying molecular mechanisms of PTSD are largely unknown. Distinct expression signatures for PTSD have been found, in particular for immune activation transcripts. DNA methylation may be significant in the pathophysiology of PTSD, since the process is intrinsically linked to gene expression. We evaluated temporal changes in DNA methylation in select promoter regions of immune system-related genes in U.S. military service members with a PTSD diagnosis, pre- and post-diagnosis, and in controls. Methods: Cases (n = 75) had a post-deployment diagnosis of PTSD in their medical record. Controls (n = 75) were randomly selected service members with no PTSD diagnosis. DNA was extracted from pre- and post-deployment sera. DNA methylation (%5-mC) was quantified at specific CpG sites in promoter regions of insulin-like growth factor 2 (IGF2), long non-coding RNA transcript H19, interleukin-8 (IL8), IL16, and IL18 via pyrosequencing. We used multivariate analysis of variance and generalized linear models to calculate adjusted means (adjusted for age, gender, and race) to make temporal comparisons of %5-mC for cases (pre- to post-deployment) versus controls (pre- to post-deployment). Results: There were significant differences in the change of %5-mC pre- to post-deployment between cases and controls for H19 (cases: +0.57%, controls: −1.97%; p = 0.04) and IL18 (cases: +1.39%, controls: −3.83%; p = 0.01). For H19 the difference was driven by a significant reduction in %5-mC among controls; for IL18 the difference was driven by both a reduction in %5-mC among controls and an increase in %5-mC among cases. Stratified analyses revealed more pronounced differences in the adjusted means of pre-post H19 and IL18 methylation differences for cases versus controls among older service members, males, service members of white race, and those with shorter deployments (6–12 months). Conclusion: In the study of deployed personnel, those who did not develop PTSD had reduced %5-mC levels of H19 and IL18 after deployment, while those who did develop PTSD had increased levels of IL18. Additionally, pre-deployment the people who later became cases had lower levels of IL18 %5-mC compared with controls. These findings are preliminary and should be investigated in larger studies

Hierarchically Self-Supervised Transformer for Human Skeleton Representation Learning

Despite the success of fully-supervised human skeleton sequence modeling, utilizing self-supervised pre-training for skeleton sequence representation learning has been an active field because acquiring task-specific skeleton annotations at large scales is difficult. Recent studies focus on learning video-level temporal and discriminative information using contrastive learning, but overlook the hierarchical spatial-temporal nature of human skeletons. Different from such superficial supervision at the video level, we propose a self-supervised hierarchical pre-training scheme incorporated into a hierarchical Transformer-based skeleton sequence encoder (Hi-TRS), to explicitly capture spatial, short-term, and long-term temporal dependencies at frame, clip, and video levels, respectively. To evaluate the proposed self-supervised pre-training scheme with Hi-TRS, we conduct extensive experiments covering three skeleton-based downstream tasks including action recognition, action detection, and motion prediction. Under both supervised and semi-supervised evaluation protocols, our method achieves the state-of-the-art performance. Additionally, we demonstrate that the prior knowledge learned by our model in the pre-training stage has strong transfer capability for different downstream tasks.Comment: Accepted to ECCV 202