A Comprehensive Analysis of Electric Dipole Moment Constraints on CP-violating Phases in the MSSM

We analyze the constraints placed on individual, flavor diagonal CP-violating phases in the minimal supersymmetric extension of the Standard Model (MSSM) by current experimental bounds on the electric dipole moments (EDMs) of the neutron, Thallium, and Mercury atoms. We identify the four CP-violating phases that are individually highly constrained by current EDM bounds, and we explore how these phases and correlations among them are constrained by current EDM limits. We also analyze the prospective implications of the next generation of EDM experiments. We point out that all other CP-violating phases in the MSSM are not nearly as tightly constrained by limits on the size of EDMs. We emphasize that a rich set of phenomenological consequences is potentially associated with these generically large EDM-allowed phases, ranging from B physics, electroweak baryogenesis, and signals of CP-violation at the CERN Large Hadron Collider and at future linear colliders. Our numerical study takes into account the complete set of contributions from one- and two-loop EDMs of the electron and quarks, one- and two-loop Chromo-EDMs of quarks, the Weinberg 3-gluon operator, and dominant 4-fermion CP-odd operator contributions, including contributions which are both included and not included yet in the CPsuperH2.0 package. We also introduce an open-source numerical package, 2LEDM, which provides the complete set of two-loop electroweak diagrams contributing to the electric dipole moments of leptons and quarks.Comment: 23 pages, 11 figures; v2: references added, minor change

The High-Risk Plaque Initiative: Primary Prevention of Atherothrombotic Events in the Asymptomatic Population

The High-Risk Plaque (HRP) Initiative is a research and development effort to advance the understanding, recognition, and management of asymptomatic individuals at risk for a near-term atherothrombotic event such as myocardial infarction or stroke. Clinical studies using the newest technologies have been initiated, including the BioImage Study in which novel approaches are tested in a typical health plan population. Asymptomatic at-risk individuals were enrolled, including a survey-only group (n = 865), a group undergoing traditional risk factor scoring (n = 718), and a group in which all were assessed for both risk factors and subclinical atherosclerosis (n = 6104). The latter two groups underwent baseline examination in a dedicated mobile facility equipped with advanced imaging tools suitable for noninvasive screening for subclinical atherosclerosis (coronary artery calcium by computed tomography [CT], carotid and aortic disease by ultrasound, and ankle-brachial index). Selected participants were offered advanced imaging (contrast-enhanced CT, magnetic resonance imaging, and positron emission tomography/CT). Plasma, PAXgene RNA, and DNA samples were obtained for biomarker discovery studies. All individuals will be followed until 600 major atherothrombotic events have occurred in those undergoing imaging

Relation of Serum Estrogen Metabolites with Terminal Duct Lobular Unit Involution Among Women Undergoing Diagnostic Image-Guided Breast Biopsy

Higher levels of circulating estrogens and estrogen metabolites (EMs) have been associated with higher breast cancer risk. In breast tissues, reduced levels of terminal duct lobular unit (TDLU) involution, as reflected by higher numbers of TDLUs and acini per TDLU, have also been linked to elevated breast cancer risk. However, it is unknown whether reduced TDLU involution mediates the risk associated with circulating EMs. In a cross-sectional analysis of 94 premenopausal and 92 postmenopausal women referred for clinical breast biopsy at an academic facility in Vermont, we examined the associations of 15 EMs, quantified using liquid chromatography-tandem mass spectrometry, with the number of TDLUs and acini count/TDLU using zero-inflated Poisson regression with a robust variance estimator and ordinal logistic regression models, respectively. All analyses were stratified by menopausal status and adjusted for potential confounders. Among premenopausal women, comparing the highest vs. the lowest tertiles, levels of unconjugated estradiol (risk ratio (RR) = 1.74, 95 % confidence interval (CI) = 1.06-2.87, p trend = 0.03), 2-hydroxyestrone (RR = 1.74, 95 % CI = 1.01-3.01, p trend = 0.04), and 4-hydroxyestrone (RR = 1.74, 95 % CI = 0.99-3.06, p trend = 0.04) were associated with significantly higher TDLU count. Among postmenopausal women, higher levels of estradiol (RR = 2.09, 95 % CI = 1.01-4.30, p trend = 0.04) and 16α-hydroxyestrone (RR = 2.27, 95 % CI = 1.29-3.99, p trend = 0.02) were significantly associated with higher TDLU count. Among postmenopausal women, higher levels of EMs, specifically conjugated estrone and 2- and 4-pathway catechols, were also associated with higher acini count/TDLU. Our data suggest that higher levels of serum EMs are generally associated with lower levels of TDLU involution

Higgs production in CP-violating supersymmetric cascade decays: probing the `open hole' at the Large Hadron Collider

A benchmark CP-violating supersymmetric scenario (known as 'CPX-scenario' in the literature) is studied in the context of the Large Hadron Collider (LHC). It is shown that the LHC, with low to moderate accumulated luminosity, will be able to probe the existing `hole' in the $m_{h_1}$-$\tan\beta$ plane, which cannot be ruled out by the LEP data. We explore the parameter space with cascade decay of third generation squarks and gluino with CP-violating decay branching fractions. We propose a multi-channel analysis to probe this parameter space some of which are background free at an integrated luminosity of 5-10 fb$^{-1}$. Specially, multi-lepton final states (3\l,\, 4\l and like sign di-lepton) are almost background free and have $5\sigma$ reach for the corresponding signals with very early data of LHC for both 14 TeV and 7 TeV center of mass energy.Comment: 24 pages, 9 figures, references added as in the journal versio

Statistical modeling of ground motion relations for seismic hazard analysis

We introduce a new approach for ground motion relations (GMR) in the probabilistic seismic hazard analysis (PSHA), being influenced by the extreme value theory of mathematical statistics. Therein, we understand a GMR as a random function. We derive mathematically the principle of area-equivalence; wherein two alternative GMRs have an equivalent influence on the hazard if these GMRs have equivalent area functions. This includes local biases. An interpretation of the difference between these GMRs (an actual and a modeled one) as a random component leads to a general overestimation of residual variance and hazard. Beside this, we discuss important aspects of classical approaches and discover discrepancies with the state of the art of stochastics and statistics (model selection and significance, test of distribution assumptions, extreme value statistics). We criticize especially the assumption of logarithmic normally distributed residuals of maxima like the peak ground acceleration (PGA). The natural distribution of its individual random component (equivalent to exp(epsilon_0) of Joyner and Boore 1993) is the generalized extreme value. We show by numerical researches that the actual distribution can be hidden and a wrong distribution assumption can influence the PSHA negatively as the negligence of area equivalence does. Finally, we suggest an estimation concept for GMRs of PSHA with a regression-free variance estimation of the individual random component. We demonstrate the advantages of event-specific GMRs by analyzing data sets from the PEER strong motion database and estimate event-specific GMRs. Therein, the majority of the best models base on an anisotropic point source approach. The residual variance of logarithmized PGA is significantly smaller than in previous models. We validate the estimations for the event with the largest sample by empirical area functions. etc

Zinc Downregulates HIF-1α and Inhibits Its Activity in Tumor Cells In Vitro and In Vivo

Hypoxia inducible factor-1α (HIF-1α) is responsible for the majority of HIF-1-induced gene expression changes under hypoxia and for the "angiogenic switch" during tumor progression. HIF-1α is often upregulated in tumors leading to more aggressive tumor growth and chemoresistance, therefore representing an important target for antitumor intervention. We previously reported that zinc downregulated HIF-1α levels. Here, we evaluated the molecular mechanisms of zinc-induced HIF-1α downregulation and whether zinc affected HIF-1α also in vivo.Here we report that zinc downregulated HIF-1α protein levels in human prostate cancer and glioblastoma cells under hypoxia, whether induced or constitutive. Investigations into the molecular mechanisms showed that zinc induced HIF-1α proteasomal degradation that was prevented by treatment with proteasomal inhibitor MG132. HIF-1α downregulation induced by zinc was ineffective in human RCC4 VHL-null renal carcinoma cell line; likewise, the HIF-1αP402/P564A mutant was resistant to zinc treatment. Similarly to HIF-1α, zinc downregulated also hypoxia-induced HIF-2α whereas the HIF-1β subunit remained unchanged. Zinc inhibited HIF-1α recruitment onto VEGF promoter and the zinc-induced suppression of HIF-1-dependent activation of VEGF correlated with reduction of glioblastoma and prostate cancer cell invasiveness in vitro. Finally, zinc administration downregulated HIF-1α levels in vivo, by bioluminescence imaging, and suppressed intratumoral VEGF expression.These findings, by demonstrating that zinc induces HIF-1α proteasomal degradation, indicate that zinc could be useful as an inhibitor of HIF-1α in human tumors to repress important pathways involved in tumor progression, such as those induced by VEGF, MDR1, and Bcl2 target genes, and hopefully potentiate the anticancer therapies

Littoral cell angioma of the spleen in a patient with previous pulmonary sarcoidosis: a TNF-α related pathogenesis?

<p>Abstract</p> <p>Background</p> <p>Littoral cell angioma (LCA) is a rare vascular tumor of the spleen. Generally thought to be benign, additional cases of LCA with malignant features have been described. Thus, its malignant potential seems to vary and must be considered uncertain. The etiology remains unclear, but an immune dysregulation for the apparent association with malignancies of visceral organs or immune-mediated diseases has been proposed.</p> <p>Case Presentation</p> <p>We report a case of LCA in a 43-year old male patient who presented with a loss of appetite and intermittent upper abdominal pain. Computed tomography showed multiple hypoattenuating splenic lesions which were hyperechogenic on abdominal ultrasound. Lymphoma was presumed and splenectomy was performed. Pathological evaluation revealed LCA.</p> <p>Conclusions</p> <p>LCA is a rare, primary vascular neoplasm of the spleen that might etiologically be associated with immune dysregulation. In addition, it shows a striking association with synchronous or prior malignancies. With about one-third of the reported cases to date being co-existent with malignancies of visceral organs or immune-mediated diseases, this advocates for close follow-ups in all patients diagnosed with LCA. To our knowledge, this report is the first one of LCA associated with previous pulmonary sarcoidosis and hypothesizes a TNF-α related pathogenesis of this splenic tumor.</p

Capture of Neuroepithelial-Like Stem Cells from Pluripotent Stem Cells Provides a Versatile System for In Vitro Production of Human Neurons

Human embryonic stem cells (hESC) and induced pluripotent stem cells (iPSC) provide new prospects for studying human neurodevelopment and modeling neurological disease. In particular, iPSC-derived neural cells permit a direct comparison of disease-relevant molecular pathways in neurons and glia derived from patients and healthy individuals. A prerequisite for such comparative studies are robust protocols that efficiently yield standardized populations of neural cell types. Here we show that long-term self-renewing neuroepithelial-like stem cells (lt-NES cells) derived from 3 hESC and 6 iPSC lines in two independent laboratories exhibit consistent characteristics including i) continuous expandability in the presence of FGF2 and EGF; ii) stable neuronal and glial differentiation competence; iii) characteristic transcription factor profile; iv) hindbrain specification amenable to regional patterning; v) capacity to generate functionally mature human neurons. We further show that lt-NES cells are developmentally distinct from fetal tissue-derived radial glia-like stem cells. We propose that lt-NES cells provide an interesting tool for studying human neurodevelopment and may serve as a standard system to facilitate comparative analyses of hESC and hiPSC-derived neural cells from control and diseased genetic backgrounds

Coordinated repression of BIM and PUMA by Epstein-Barr virus latent genes maintains the survival of Burkitt lymphoma cells.

While the association of Epstein-Barr virus (EBV) with Burkitt lymphoma (BL) has long been recognised, the precise role of the virus in BL pathogenesis is not fully resolved. EBV can be lost spontaneously from some BL cell lines, and these EBV-loss lymphoma cells reportedly have a survival disadvantage. Here we have generated an extensive panel of EBV-loss clones from multiple BL backgrounds and examined their phenotype comparing them to their isogenic EBV-positive counterparts. We report that, while loss of EBV from BL cells is rare, it is consistently associated with an enhanced predisposition to undergo apoptosis and reduced tumorigenicity in vivo. Importantly, reinfection of EBV-loss clones with EBV, but surprisingly not transduction with individual BL-associated latent viral genes, restored protection from apoptosis. Expression profiling and functional analysis of apoptosis-related proteins and transcripts in BL cells revealed that EBV inhibits the upregulation of the proapoptotic BH3-only proteins, BIM and PUMA. We conclude that latent EBV genes cooperatively enhance the survival of BL cells by suppression of the intrinsic apoptosis pathway signalling via inhibition of the potent apoptosis initiators, BIM and PUMA.Cell Death and Differentiation advance online publication, 29 September 2017; doi:10.1038/cdd.2017.150

Improving STD testing behavior among high-risk young adults by offering STD testing at a vocational school

<p>Abstract</p> <p>Background</p> <p>Chlamydia trachomatis infection (CT) is the most prevalent bacterial STD. Sexually active adolescents and young adults are the main risk group for CT. However, STD testing rates in this group are low since exposed individuals may not feel at risk, owing-at least in part-to the infection's largely asymptomatic nature. Designing new testing environments that are more appealing to young people who are most at risk of acquiring chlamydia can be an important strategy to improve overall testing rates. Here we evaluate the effect of a school-based sexual health program conducted among vocational school students, aiming to obtain better access for counseling and enhance students' STD testing behavior.</p> <p>Methods</p> <p>Adolescents (median age 19 years) attending a large vocational school were provided with sexual health education. Students filled in a questionnaire measuring CT risk and were offered STD testing. Using univariate and multivariate analysis, we assessed differences between men and women in STD-related risk behavior, sexual problems, CT testing behavior and determinants of CT testing behavior.</p> <p>Results</p> <p>Of 345 participants, 70% were female. Of the 287 sexually active students, 75% were at high risk for CT; one third of women reported sexual problems. Of sexually active participants, 61% provided a self-administered specimen for STD testing. Independent determinants for testing included STD related symptoms and no condom use. All CT diagnoses were in the high-CT-risk group. In the high-risk group, STD testing showed an increased uptake, from 27% (previous self-reported test) to 65% (current test). CT prevalence was 5.7%.</p> <p>Conclusions</p> <p>Vocational school students are a target population for versatile sexual health prevention. When provided with CT testing facilities and education, self selection mechanisms seemed to increase CT testing rate dramatically in this high-CT-risk population expressing sexual problems. Considering the relative ease of testing and treating large numbers of young adults, offering tests at a vocational school is feasible in reaching adolescents for STD screening. Although cost-effectiveness remains an issue counseling is effective in increasing test rates.</p