Dynamical stabilization of runaway potentials at finite density

We study four dimensional non-abelian gauge theories with classical moduli. Introducing a chemical potential for a flavor charge causes moduli to become unstable and start condensing. We show that the moduli condensation in the presence of a chemical potential generates nonabelian field strength condensates. These condensates are homogeneous but non-isotropic. The end point of the condensation process is a stable homogeneous, but non-isotropic, vacuum in which both gauge and flavor symmetries and the rotational invariance are spontaneously broken. Possible applications of this phenomenon for the gauge theory/string theory correspondence and in cosmology are briefly discussed.Comment: revtex4, 4 pages; v.2: journal versio

Therapeutic Challenge with a CDK 4/6 Inhibitor Induces an RB-Dependent SMAC-Mediated Apoptotic Response in Non-Small Cell Lung Cancer.

Purpose: The retinoblastoma tumor suppressor (RB), a key regulator of cell-cycle progression and proliferation, is functionally suppressed in up to 50% of non-small cell lung cancer (NSCLC). RB function is exquisitely controlled by a series of proteins, including the CyclinD-CDK4/6 complex. In this study, we interrogated the capacity of a CDK4/6 inhibitor, palbociclib, to activate RB function. Experimental Design and Results: We employed multiple isogenic RB-proficient and -deficient NSCLC lines to interrogate the cytostatic and cytotoxic capacity of CDK 4/6 inhibition in vitro and in vivo We demonstrate that while short-term exposure to palbociclib induces cellular senescence, prolonged exposure results in inhibition of tumor growth. Mechanistically, CDK 4/6 inhibition induces a proapoptotic transcriptional program through suppression of IAPs FOXM1 and Survivin, while simultaneously augmenting expression of SMAC and caspase-3 in an RB-dependent manner. Conclusions: This study uncovers a novel function of RB activation to induce cellular apoptosis through therapeutic administration of a palbociclib and provides a rationale for the clinical evaluation of CDK 4/6 inhibitors in the treatment of patients with NSCLC

Constraints on CP violation in the Higgs sector from the ρ\rho parameter

We discuss the relation between the CP symmetry and the custodial $SU(2)$ symmetry in the Higgs sector. In particular, we show that CP violation in the Higgs-gauge sector is allowed only if the custodial $SU(2)$ symmetry is broken. We exploit these facts to constrain CP violation using the experimental bounds on $\rho-1$. CP nonconservation in the Higgs-fermion interactions can also be constrained in a similar way although a possible exception is pointed out.Comment: 19 pages, 2 figures (not included), SLAC-PUB-619

Top Radiative Corrections in Non-minimal Standard Models

We derive the one-loop effective action induced by a heavy top in models with an extended Higgs sector. We use the effective action to analyze the top corrections to the $\rho$ parameter and to the Higgs-gauge boson couplings. We show that in models with $\rho\not=1$ at tree-level, one does not lose generally the bound on $m_t$ from the $\rho$ parameter.Comment: 9 pages, phyzzx file, UPR-0603T. (a new reference has been added

Mass Degeneracy of the Higgsinos

The search for charginos and neutralinos at LEP2 can become problematic if these particles are almost mass degenerate with the lightest neutralino. Unfortunately this is the case in the region where these particles are higgsino-like. We show that, in this region, radiative corrections to the higgsino mass splittings can be as large as the tree-level values, if the mixing between the two stop states is large. We also show that the degree of degeneracy of the higgsinos substantially increases if a large phase is present in the higgsino mass term $\mu$.Comment: 10 pages, Latex, 2 figures (compressed+uuencoded+tarred

Intra- and Inter-cellular Rewiring of the Human Colon during Ulcerative Colitis

Genome-wide association studies (GWAS) have revealed risk alleles for ulcerative colitis (UC). To understand their cell type specificities and pathways of action, we generate an atlas of 366,650 cells from the colon mucosa of 18 UC patients and 12 healthy individuals, revealing 51 epithelial, stromal, and immune cell subsets, including BEST4(+) enterocytes, microfold-like cells, and IL13RA2(+)IL11(+) inflammatory fibroblasts, which we associate with resistance to anti-TNF treatment. Inflammatory fibroblasts, inflammatory monocytes, microfold-like cells, and T cells that co-express CD8 and IL-17 expand with disease, forming intercellular interaction hubs. Many UC risk genes are cell type specific and coregulated within relatively few gene modules, suggesting convergence onto limited sets of cell types and pathways. Using this observation, we nominate and infer functions for specific risk genes across GWAS loci. Our work provides a framework for interrogating complex human diseases and mapping risk variants to cell types and pathways.Peer reviewe

Uganda Genome Resource Enables Insights into Population History and Genomic Discovery in Africa.

Genomic studies in African populations provide unique opportunities to understand disease etiology, human diversity, and population history. In the largest study of its kind, comprising genome-wide data from 6,400 individuals and whole-genome sequences from 1,978 individuals from rural Uganda, we find evidence of geographically correlated fine-scale population substructure. Historically, the ancestry of modern Ugandans was best represented by a mixture of ancient East African pastoralists. We demonstrate the value of the largest sequence panel from Africa to date as an imputation resource. Examining 34 cardiometabolic traits, we show systematic differences in trait heritability between European and African populations, probably reflecting the differential impact of genes and environment. In a multi-trait pan-African GWAS of up to 14,126 individuals, we identify novel loci associated with anthropometric, hematological, lipid, and glycemic traits. We find that several functionally important signals are driven by Africa-specific variants, highlighting the value of studying diverse populations across the region.Main funding: This work was funded by the Wellcome Trust, The Wellcome Sanger Institute (WT098051), the U.K. Medical Research Council (G0901213-92157, G0801566, and MR/K013491/1), and the Medical Research Council/Uganda Virus Research Institute Uganda Research Unit on AIDS core funding

Delta-9-tetrahydrocannabinol, neural oscillations above 20 Hz and induced acute psychosis

Rationale: An acute challenge with delta-9-tetrahydrocannabinol (THC) can induce psychotic symptoms including delusions. High electroencephalography (EEG) frequencies, above 20 Hz, have previously been implicated in psychosis and schizophrenia. Objectives: The objective of this study is to determine the effect of intravenous THC compared to placebo on high-frequency EEG. Methods: A double-blind cross-over study design was used. In the resting state, the high-beta to low-gamma magnitude (21–45 Hz) was investigated (n=13 pairs+4 THC only). Also, the event-related synchronisation (ERS) of motor-associated high gamma was studied using a self-paced button press task (n=15). Results: In the resting state, there was a significant condition × frequency interaction (p=0.00017), consisting of a shift towards higher frequencies under THC conditions (reduced high beta [21–27 Hz] and increased low gamma [27–45 Hz]). There was also a condition × frequency × location interaction (p=0.006), such that the reduction in 21–27-Hz magnitude tended to be more prominent in anterior regions, whilst posterior areas tended to show greater 27–45-Hz increases. This effect was correlated with positive symptoms, as assessed on the Positive and Negative Syndrome Scale (PANSS) (r=0.429, p=0.042). In the motor task, there was a main effect of THC to increase 65–130-Hz ERS (p=0.035) over contra-lateral sensorimotor areas, which was driven by increased magnitude in the higher, 85–130-Hz band (p=0.02) and not the 65–85-Hz band. Conclusions: The THC-induced shift to faster gamma oscillations may represent an over-activation of the cortex, possibly related to saliency misattribution in the delusional state

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements