Flavoured Majorana Dark Matter then and now: From freeze-out scenarios to LHC signatures

We study a simplified Dark Matter model in the Dark Minimal Flavour Violation framework. Our model complements the Standard Model with a flavoured Dark Matter Majorana triplet and a coloured scalar mediator that share a Yukawa coupling with the right-handed up-type quarks with the coupling matrix $λ$. We extend previous work on this topic by exploring a large range of cosmologically viable parameter space, including the coannihilation region and, in particular, the region of conversion-driven freeze-out, while considering constraints from $D^0-\bar D^0$ mixing as well as constraints from direct and indirect Dark Matter searches. We find various realisations of conversion-driven freeze-out within the model, that open up allowed windows of parameter space towards small mass splittings and very weak Dark Matter couplings. Finally, we probe the model by reinterpreting current LHC searches for missing energy and long-lived particles. We point out gaps in the coverage of current constraints as well as new opportunities to search for the model at the LHC, in particular, the charge asymmetry in single-top production associated with jets and missing energy

Mammalian splicing factor SF1 interacts with SURP domains of U2 snRNP-associated proteins

Splicing factor 1 (SF1) recognizes the branch point sequence (BPS) at the 3′ splice site during the formation of early complex E, thereby pre-bulging the BPS adenosine, thought to facilitate subsequent base-pairing of the U2 snRNA with the BPS. The 65-kDa subunit of U2 snRNP auxiliary factor (U2AF65) interacts with SF1 and was shown to recruit the U2 snRNP to the spliceosome. Co-immunoprecipitation experiments of SF1-interacting proteins from HeLa cell extracts shown here are consistent with the presence of SF1 in early splicing complexes. Surprisingly almost all U2 snRNP proteins were found associated with SF1. Yeast two-hybrid screens identified two SURP domain-containing U2 snRNP proteins as partners of SF1. A short, evolutionarily conserved region of SF1 interacts with the SURP domains, stressing their role in protein-protein interactions. A reduction of A complex formation in SF1-depleted extracts could be rescued with recombinant SF1 containing the SURP-interaction domain, but only partial rescue was observed with SF1 lacking this sequence. Thus, SF1 can initially recruit the U2 snRNP to the spliceosome during E complex formation, whereas U2AF65 may stabilize the association of the U2 snRNP with the spliceosome at later times. In addition, these findings may have implications for alternative splicing decision

Sociodemographic and health-(care-)related characteristics of online health information seekers: a cross-sectional German study

Nölke L, Mensing M, Krämer A, Hornberg C. Sociodemographic and health-(care-)related characteristics of online health information seekers: a cross-sectional German study. BMC Public Health. 2015;15(1): 31.Background Although the increasing dissemination and use of health-related information on the Internet has the potential to empower citizens and patients, several studies have detected disparities in the use of online health information. This is due to several factors. So far, only a few studies have examined the impact of socio-economic status (SES) on health information seeking on the Internet. This study was designed to identify sociodemographic and health-(care-)related differences between users and non-users of health information gleaned from the Internet with the aim of detecting hard-to-reach target groups. Methods This study analyzed data from the NRW Health Survey LZG.NRW 2011 (n = 2,000; conducted in North Rhine–Westphalia, Germany, via telephone interviews). Logistic regression analysis was used to examine the determinants of online health information seeking behavior. Results 68% of Internet users refer to the Internet for health-related purposes. Of the independent variables tested, SES proved to exert the strongest influence on searching the Internet for health information. The final multivariate regression model shows that people from the middle (OR: 2.2, 95% CI: 1.6–3.2) and upper (OR: 4.0, 95% CI: 2.7–6.2) social classes are more likely to seek health information on the Internet than those from the lower class. Also, women are more likely to look for health information on the Internet than men (OR: 1.5, 95% CI: 1.1–2.1). Individuals with a migration background are less likely to conduct health searches on the Internet (OR: 0.6, 95% CI: 0.4–0.8). Married people or individuals in a stable relationship search the Internet more often for health information than do singles (OR: 1.9, 95% CI: 1.2–2.9). Also, heavy use of health-care services compared to non-use is associated with a higher likelihood of using the Internet for health-related matters (OR: 1.7, 95% CI: 1.2–2.5). Conclusions In order to achieve equity in health, health-related Internet use by the socially deprived should be promoted through measures to increase their level of e-health literacy. Furthermore, longitudinal studies are needed in order to gain reliable data/results on determinants of health-related Internet use

Toxicity modelling of Plk1-targeted therapies in genetically engineered mice and cultured primary mammalian cells

High attrition rates of novel anti-cancer drugs highlight the need for improved models to predict toxicity. Although polo-like kinase 1 (Plk1) inhibitors are attractive candidates for drug development, the role of Plk1 in primary cells remains widely unexplored. Therefore, we evaluated the utility of an RNA interference-based model to assess responses to an inducible knockdown (iKD) of Plk1 in adult mice. Here we show that Plk1 silencing can be achieved in several organs, although adverse events are rare. We compared responses in Plk1-iKD mice with those in primary cells kept under controlled culture conditions. In contrast to the addiction of many cancer cell lines to the non-oncogene Plk1, the primary cells' proliferation, spindle assembly and apoptosis exhibit only a low dependency on Plk1. Responses to Plk1-depletion, both in cultured primary cells and in our iKD-mouse model, correspond well and thus provide the basis for using validated iKD mice in predicting responses to therapeutic interventions

Report from Working Group 3: Beyond the standard model physics at the HL-LHC and HE-LHC

This is the third out of five chapters of the final report [1] of the Workshop on Physics at HL-LHC, and perspectives on HE-LHC [2]. It is devoted to the study of the potential, in the search for Beyond the Standard Model (BSM) physics, of the High Luminosity (HL) phase of the LHC, defined as $3$ ab$^{-1}$ of data taken at a centre-of-mass energy of 14 TeV, and of a possible future upgrade, the High Energy (HE) LHC, defined as $15$ ab$^{-1}$ of data at a centre-of-mass energy of 27 TeV. We consider a large variety of new physics models, both in a simplified model fashion and in a more model-dependent one. A long list of contributions from the theory and experimental (ATLAS, CMS, LHCb) communities have been collected and merged together to give a complete, wide, and consistent view of future prospects for BSM physics at the considered colliders. On top of the usual standard candles, such as supersymmetric simplified models and resonances, considered for the evaluation of future collider potentials, this report contains results on dark matter and dark sectors, long lived particles, leptoquarks, sterile neutrinos, axion-like particles, heavy scalars, vector-like quarks, and more. Particular attention is placed, especially in the study of the HL-LHC prospects, to the detector upgrades, the assessment of the future systematic uncertainties, and new experimental techniques. The general conclusion is that the HL-LHC, on top of allowing to extend the present LHC mass and coupling reach by $20-50\%$ on most new physics scenarios, will also be able to constrain, and potentially discover, new physics that is presently unconstrained. Moreover, compared to the HL-LHC, the reach in most observables will, generally more than double at the HE-LHC, which may represent a good candidate future facility for a final test of TeV-scale new physics