Reinstating the 'no-lose' theorem for NMSSM Higgs discovery at the LHC

The simplest supersymmetric model that solves the mu problem and in which the GUT-scale parameters need not be finely tuned in order to predict the correct value of the Z boson mass at low scales is the Next-to-Minimal Supersymmetric Standard Model (NMSSM). However, in order that fine tuning be absent, the lightest CP-even Higgs boson h should have mass ~100 GeV and SM couplings to gauge bosons and fermions. The only way that this can be consistent with LEP limits is if h decays primarily via h->aa->4 tau or 4j but not 4b, where a is the lighter of the two pseudo-scalar Higgses that are present in the NMSSM. Interestingly, m_a 2 m_tau somewhat preferred. Thus, h -> 4 tau becomes a key mode of interest. Meanwhile, all other Higgs bosons of the NMSSM are typically quite heavy. Detection of any of the NMSSM Higgs bosons at the LHC in this preferred scenario will be very challenging using conventional channels. In this paper, we demonstrate that the h -> aa -> 4 tau decay chain should be visible if the Higgs is produced in the process pp -> p+h+p with the final state protons being measured using suitably installed forward detectors. Moreover, we show that the mass of both the h and the a can be determined on an event-by-event basis.Comment: 23 page

Axl-EGFR receptor tyrosine kinase hetero-interaction provides EGFR with access to pro-invasive signalling in cancer cells

© The Author(s) 2016. Acquired resistance to conventional and targeted therapies is becoming a major hindrance in cancer management. It is increasingly clear that cancer cells are able to evolve and rewire canonical signalling pathways to their advantage, thus evading cell death and promoting cell invasion. The Axl receptor tyrosine kinase (RTK) has been shown to modulate acquired resistance to EGFR-targeted therapies in both breast and lung cancers. Glioblastoma multiforme (GBM) is a highly infiltrative and invasive form of brain tumour with little response to therapy. Both Axl and EGFR have been identified as major players in gliomagenesis and invasiveness. However, the mechanisms underlying a potential signalling crosstalk between EGFR and Axl RTKs are unknown. The purpose of this study was to investigate this novel and unconventional interaction among RTKs of different families in human GBM cells. With the use of western blotting, in vitro kinase activity, co-immunoprecipitation and bimolecular fluorescence complementation assays, we show that EGF stimulates activation of Axl kinase and that there is a hetero-interaction between the two RTKs. Through small interfering RNA knockdown and quantitative PCR screening, we identified distinct gene expression patterns in GBM cells that were specifically regulated by signalling from EGFR-EGFR, Axl-Axl and EGFR-Axl RTK parings. These included genes that promote invasion, which were activated only via the EGFR-Axl axis (MMP9), while EGFR-EGFR distinctly regulated the cell cycle and Axl-Axl regulated invasion. Our findings provide critical insights into the role of EGFR-Axl hetero-dimerisation in cancer cells and reveal regulation of cell invasion via Axl as a novel function of EGFR signalling

Central exclusive production of longlived gluinos at the LHC

We examine the possibility of producing gluino pairs at the LHC via the exclusive reaction pp -> p+gluino+gluino+p in the case where the gluinos are long lived. Such long lived gluinos are possible if the scalar super-partners have large enough masses. We show that it may be possible to observe the gluinos via their conversion to R-hadron jets and measure their mass to better than 1% accuracy for masses below 350 GeV with 300/fb of data.Comment: 13 pages, 9 figures. Minor corrections to version

Development of an internationally agreed minimal dataset for juvenile dermatomyositis (JDM) for clinical and research use

Background: Juvenile dermatomyositis (JDM) is a rare autoimmune inflammatory disorder associated with significant morbidity and mortality. International collaboration is necessary to better understand the pathogenesis of the disease, response to treatment and long-term outcome. To aid international collaboration, it is essential to have a core set of data that all researchers and clinicians collect in a standardised way for clinical purposes and for research. This should include demographic details, diagnostic data and measures of disease activity, investigations and treatment. Variables in existing clinical registries have been compared to produce a provisional data set for JDM. We now aim to develop this into a consensus-approved minimum core dataset, tested in a wider setting, with the objective of achieving international agreement. Methods/Design: A two-stage bespoke Delphi-process will engage the opinion of a large number of key stakeholders through Email distribution via established international paediatric rheumatology and myositis organisations. This, together with a formalised patient/parent participation process will help inform a consensus meeting of international experts that will utilise a nominal group technique (NGT). The resulting proposed minimal dataset will be tested for feasibility within existing database infrastructures. The developed minimal dataset will be sent to all internationally representative collaborators for final comment. The participants of the expert consensus group will be asked to draw together these comments, ratify and 'sign off' the final minimal dataset. Discussion: An internationally agreed minimal dataset has the potential to significantly enhance collaboration, allow effective communication between groups, provide a minimal standard of care and enable analysis of the largest possible number of JDM patients to provide a greater understanding of this disease. The final approved minimum core dataset could be rapidly incorporated into national and international collaborative efforts, including existing prospective databases, and be available for use in randomised controlled trials and for treatment/protocol comparisons in cohort studies

Radiative Efficiency and Content of Extragalactic Radio Sources: Toward a Universal Scaling Relation Between Jet Power and Radio Power

We present an analysis of the energetics and particle content of the lobes of 24 radio galaxies at the cores of cooling clusters. The radio lobes in these systems have created visible cavities in the surrounding hot, X-ray-emitting gas, which allow direct measurement of the mechanical jet power of radio sources over six decades of radio luminosity, independently of the radio properties themselves. Using these measurements, we examine the ratio between radio power and total jet power (the radiative efficiency). We find that jet (cavity) power increases with radio synchrotron power approximately as P_jet ~ (L_radio)^beta, where 0.35 < beta < 0.70 depending on the bandpass of measurement and state of the source. However, the scatter about these relations caused by variations in radiative efficiency spans more than four orders of magnitude. After accounting for variations in synchrotron break frequency (age), the scatter is reduced by ~ 50%, yielding the most accurate scaling relation available between the lobe bolometric radio power and the jet (cavity) power. We place limits on the magnetic field strengths and particle content of the radio lobes using a variety of X-ray constraints. We find that the lobe magnetic field strengths vary between a few to several tens of microgauss depending on the age and dynamical state of the lobes. If the cavities are maintained in pressure balance with their surroundings and are supported by internal fields and particles in equipartition, the ratio of energy in electrons to heavy particles (k) must vary widely from approximately unity to 4000, consistent with heavy (hadronic) jets.Comment: 20 pages, 11 figures. Accepted for publication in Ap

Stringent neutron-star limits on large extra dimensions

Supernovae (SNe) are copious sources for Kaluza-Klein gravitons which are generic for theories with large extra dimensions. These massive particles are produced with average velocities ~0.5 c so that many of them are gravitationally retained by the SN core. Every neutron star thus has a halo of KK gravitons which decay into nu bar-nu, e^+e^- and gamma gamma on time scales \~10^9 years. The EGRET gamma-flux limits (E_gamma ~ 100 MeV) for nearby neutron stars constrain the fundamental scale for n=2 extra dimensions to M >500 TeV, and M>30 TeV for n=3. The upcoming GLAST satellite is a factor ~30 more sensitive and thus may detect KK decays, for example at the nearby neutron star RX J185635--3754. The requirement that neutron stars are not excessively heated by KK decays implies M>1700 TeV for n=2, and M>60 TeV for n=3.Comment: Minor changes, matches version to appear in PR

Thin disc, Thick Disc and Halo in a Simulated Galaxy

Within a cosmological hydrodynamical simulation, we form a disc galaxy with sub- components which can be assigned to a thin stellar disc, thick disk, and a low mass stellar halo via a chemical decomposition. The thin and thick disc populations so selected are distinct in their ages, kinematics, and metallicities. Thin disc stars are young (<6.6 Gyr), possess low velocity dispersion ({\sigma}U,V,W = 41, 31, 25 km/s), high [Fe/H], and low [O/Fe]. The thick disc stars are old (6.6<age<9.8 Gyrs), lag the thin disc by \sim21 km/s, possess higher velocity dispersion ({\sigma}U,V,W = 49, 44, 35 km/s), relatively low [Fe/H] and high [O/Fe]. The halo component comprises less than 4% of stars in the "solar annulus" of the simulation, has low metallicity, a velocity ellipsoid defined by ({\sigma}U,V,W = 62, 46, 45 km/s) and is formed primarily in-situ during an early merger epoch. Gas-rich mergers during this epoch play a major role in fuelling the formation of the old disc stars (the thick disc). This is consistent with studies which show that cold accretion is the main source of a disc galaxy's baryons. Our simulation initially forms a relatively short (scalelength \sim1.7 kpc at z=1) and kinematically hot disc, primarily from gas accreted during the galaxy's merger epoch. Far from being a competing formation scenario, migration is crucial for reconciling the short, hot, discs which form at high redshift in {\Lambda}CDM, with the properties of the thick disc at z=0. The thick disc, as defined by its abundances maintains its relatively short scale-length at z = 0 (2.31 kpc) compared with the total disc scale-length of 2.73 kpc. The inside-out nature of disc growth is imprinted the evolution of abundances such that the metal poor {\alpha}-young population has a larger scale-length (4.07 kpc) than the more chemically evolved metal rich {\alpha}-young population (2.74 kpc).Comment: Submitted to MNRAS. This version after helpful referee comments. Comments welcome to [email protected]

International validation of a urinary biomarker panel for identification of active lupus nephritis in children.

Conventional markers of juvenile-onset systemic lupus erythematosus (JSLE) disease activity fail to adequately identify lupus nephritis (LN). While individual novel urine biomarkers are good at detecting LN flares, biomarker panels may improve diagnostic accuracy. The aim of this study was to assess the performance of a biomarker panel to identify active LN in two international JSLE cohorts.Novel urinary biomarkers, namely vascular cell adhesion molecule-1 (VCAM-1), monocyte chemoattractant protein 1 (MCP-1), lipocalin-like prostaglandin D synthase (LPGDS), transferrin (TF), ceruloplasmin, alpha-1-acid glycoprotein (AGP) and neutrophil gelatinase-associated lipocalin (NGAL), were quantified in a cross-sectional study that included participants of the UK JSLE Cohort Study (Cohort 1) and validated within the Einstein Lupus Cohort (Cohort 2). Binary logistic regression modelling and receiver operating characteristic curve analysis [area under the curve (AUC)] were used to identify and assess combinations of biomarkers for diagnostic accuracy.A total of 91 JSLE patients were recruited across both cohorts, of whom 31 (34 %) had active LN and 60 (66 %) had no LN. Urinary AGP, ceruloplasmin, VCAM-1, MCP-1 and LPGDS levels were significantly higher in those patients with active LN than in non-LN patients [all corrected p values (p c) < 0.05] across both cohorts. Urinary TF also differed between patient groups in Cohort 2 (p c = 0.001). Within Cohort 1, the optimal biomarker panel included AGP, ceruloplasmin, LPGDS and TF (AUC 0.920 for active LN identification). These results were validated in Cohort 2, with the same markers resulting in the optimal urine biomarker panel (AUC 0.991).In two international JSLE cohorts, urinary AGP, ceruloplasmin, LPGDS and TF demonstrate an 'excellent' ability for accurately identifying active LN in children

IP1867B suppresses the insulin-like growth factor 1 receptor (IGF1R) ablating epidermal growth factor receptor inhibitor resistance in adult high grade gliomas

High grade gliomas (HGGs) are aggressive primary brain tumours with local invasive growth and poor clinical prognosis. Clinical outcome is compounded by resistance to standard and novel therapeutics. We have evaluated reformulated aspirin (IP1867B) alone and in combination with conventional and novel anti-aHGG agents. We show that recent biopsy-derived aHGG models were highly resistant to conventional therapeutics although show sensitivity to IP1867B, a reformulated "liquid" aspirin. IP186713 treatment mediated a potent suppression of the IL6/STAT3 and NF-kappa B pathways and observed a significant reduction in EGFR transcription and protein expression. We observed the loss of the insulin-like growth factor 1 and insulin-like growth factor 1 receptor expression at both the transcript and protein level post IP1867B treatment. This increased sensitivity to EGFR inhibitors. In vivo, IP1867B was very well tolerated, had little-to-no gastric lesions versus aspirin and, directed a significant reduction of tumour burden with suppression of EGFR, IGF1 and IGFR1. With EGFR inhibitors, we noted a potent synergistic response in aHGG cells. These data provide a rationale for further investigation of IP1867B with a number of anti-EGFR agents currently being evaluated in the clinic.Brain Tumour ResearchHeadcase Cancer TrustOllie Young FoundationFCT Investigator contract from the Foundation for Science and Technology (FCT), Portugal [IF/00614/2014]FCTPortuguese Foundation for Science and Technology [IF/00614/2014/CP12340006, UID/BIM/04773/2013CBMR1334]Innovate Pharmaceutical