EML4-ALK V3 oncogenic fusion proteins promote microtubule stabilization and accelerated migration through NEK9 and NEK7

EML4-ALK is an oncogenic fusion present in ∼5% non-small cell lung cancers. However, alternative breakpoints in the EML4 gene lead to distinct variants with different patient outcomes. Here, we show in cell models that EML4-ALK variant 3 (V3), which is linked to accelerated metastatic spread, causes microtubule stabilization, formation of extended cytoplasmic protrusions and increased cell migration. It also recruits the NEK9 and NEK7 kinase to microtubules via the N-terminal EML4 microtubule-binding region. Overexpression of wild-type EML4 as well as constitutive activation of NEK9 also perturb cell morphology and accelerate migration in a microtubule-dependent manner that requires the downstream kinase NEK7 but not ALK activity. Strikingly, elevated NEK9 expression is associated with reduced progression-free survival in EML4-ALK patients. Hence, we propose that EML4-ALK V3 promotes microtubule stabilization through NEK9 and NEK7 leading to increased cell migration. This represents a novel actionable pathway that could drive metastatic disease progression in EML4-ALK lung cancer

K2-140b - An eccentric 6.57 d transiting hot Jupiter in Virgo

We present the discovery of K2-140b, a P = 6.57 d Jupiter-mass (MP = 1.019 ± 0.070MJup) planet transiting a V = 12.5 (G5-spectral type) star in an eccentric orbit (e = 0.120-0.046 +0.056) detected using a combination of K2 photometry and ground-based observations. With a radius of 1.095 ± 0.018 RJup, the planet has a bulk density of 0.726 ± 0.062 ρJup. The host star has a [Fe/H] of 0.12 ± 0.045, and from the K2 light curve, we find a rotation period for the star of 16.3 ± 0.1 d. This discovery is the 9th hot Jupiter from K2 and highlights K2's ability to detect transiting giant planets at periods slightly longer than traditional, ground-based surveys. This planet is slightly inflated, but much less than others with similar incident fluxes. These are of interest for investigating the inflation mechanism of hot Jupiters

Pion contamination in the MICE muon beam

The international Muon Ionization Cooling Experiment (MICE) will perform a systematic investigation of ionization cooling with muon beams of momentum between 140 and 240\,MeV/c at the Rutherford Appleton Laboratory ISIS facility. The measurement of ionization cooling in MICE relies on the selection of a pure sample of muons that traverse the experiment. To make this selection, the MICE Muon Beam is designed to deliver a beam of muons with less than $\sim$1\% contamination. To make the final muon selection, MICE employs a particle-identification (PID) system upstream and downstream of the cooling cell. The PID system includes time-of-flight hodoscopes, threshold-Cherenkov counters and calorimetry. The upper limit for the pion contamination measured in this paper is $f_\pi < 1.4\%$ at 90\% C.L., including systematic uncertainties. Therefore, the MICE Muon Beam is able to meet the stringent pion-contamination requirements of the study of ionization cooling.Department of Energy and National Science Foundation (U.S.A.), the Instituto Nazionale di Fisica Nucleare (Italy), the Science and Technology Facilities Council (U.K.), the European Community under the European Commission Framework Programme 7 (AIDA project, grant agreement no. 262025, TIARA project, grant agreement no. 261905, and EuCARD), the Japan Society for the Promotion of Science and the Swiss National Science Foundation, in the framework of the SCOPES programme

TOI-481 b and TOI-892 b: Two Long-period Hot Jupiters from the Transiting Exoplanet Survey Satellite

We present the discovery of two new 10 day period giant planets from the Transiting Exoplanet Survey Satellite mission, whose masses were precisely determined using a wide diversity of ground-based facilities. TOI-481 b and TOI-892 b have similar radii (0.99 0.01 and 1.07 0.02, respectively), and orbital periods (10.3311 days and 10.6266 days, respectively), but significantly different masses (1.53 0.03, respectively). Both planets orbit metal-rich stars ( = dex and = for TOI-481 and TOI-892, respectively) but at different evolutionary stages. TOI-481 is a = 1.14 0.02 = 1.66 0.02 G-type star (=K), that with an age of 6.7 Gyr, is in the turn-off point of the main sequence. TOI-892 on the other hand, is a F-type dwarf star (=K), which has a mass of = 1.28 0.03 and a radius of = 1.39 0.02. TOI-481 b and TOI-892 b join the scarcely populated region of transiting gas giants with orbital periods longer than 10 days, which is important to constrain theories of the formation and structure of hot Jupiters

A hot mini-Neptune in the radius valley orbiting solar analogue HD 110113

We report the discovery of HD 110113 b (TESS object of interest-755.01), a transiting mini-Neptune exoplanet on a 2.5-d orbit around the solar-analogue HD 110113 (Teff = 5730 K). Using TESS photometry and High Accuracy Radial velocity Planet Searcher (HARPS) radial velocities gathered by the NCORES program, we find that HD 110113 b has a radius of 2.05 ± 0.12 R⊕ and a mass of 4.55 ± 0.62 M⊕. The resulting density of $2.90^{+0.75}_{-0.59}$ g cm-3 is significantly lower than would be expected from a pure-rock world; therefore HD 110113 b must be a mini-Neptune with a significant volatile atmosphere. The high incident flux places it within the so-called radius valley; however, HD 110113 b was able to hold on to a substantial (0.1-1 per cent) H-He atmosphere over its ∼4 Gyr lifetime. Through a novel simultaneous Gaussian process fit to multiple activity indicators, we were also able to fit for the strong stellar rotation signal with period 20.8 ± 1.2 d from the RVs and confirm an additional non-transiting planet, HD 110113 c, which has a mass of 10.5 ± 1.2 M⊕ and a period of $6.744^{+0.008}_{-0.009}$ d

TOI-222: A single-transit TESS candidate revealed to be a 34-d eclipsing binary with CORALIE, EulerCam, and NGTS

We report the period, eccentricity, and mass determination for the Transiting Exoplanet Survey Satellite (TESS) single-transit event candidate TOI-222, which displayed a single 3000 ppm transit in the TESS 2-min cadence data from Sector 2. We determine the orbital period via radial velocity measurements (P = 33.9 d), which allowed for ground-based photometric detection of two subsequent transits. Our data show that the companion to TOI-222 is a low-mass star, with a radius of 0.18+−003910 R☉ and a mass of 0.23 ± 0.01 M☉. This discovery showcases the ability to efficiently discover long-period systems from TESS single-transit events using a combination of radial velocity monitoring coupled with high-precision ground-based photometry

Measurement of the muon flux from 400 GeV/c protons interacting in a thick molybdenum/tungsten target

The SHiP experiment is proposed to search for very weakly interacting particles beyond the Standard Model which are produced in a 400 GeV/c proton beam dump at the CERN SPS. About 1011 muons per spill will be produced in the dump. To design the experiment such that the muon-induced background is minimized, a precise knowledge of the muon spectrum is required. To validate the muon flux generated by our Pythia and GEANT4 based Monte Carlo simulation (FairShip), we have measured the muon flux emanating from a SHiP-like target at the SPS. This target, consisting of 13 interaction lengths of slabs of molybdenum and tungsten, followed by a 2.4 m iron hadron absorber was placed in the H4 400 GeV/c proton beam line. To identify muons and to measure the momentum spectrum, a spectrometer instrumented with drift tubes and a muon tagger were used. During a 3-week period a dataset for analysis corresponding to (3.27±0.07) × 1011 protons on target was recorded. This amounts to approximatively 1% of a SHiP spill

Track reconstruction and matching between emulsion and silicon pixel detectors for the SHiP-charm experiment

In July 2018 an optimization run for the proposed charm cross section measurement for SHiP was performed at the CERN SPS. A heavy, moving target instrumented with nuclear emulsion films followed by a silicon pixel tracker was installed in front of the Goliath magnet at the H4 proton beam-line. Behind the magnet, scintillating-fibre, drift-tube and RPC detectors were placed. The purpose of this run was to validate the measurement's feasibility, to develop the required analysis tools and fine-tune the detector layout. In this paper, we present the track reconstruction in the pixel tracker and the track matching with the moving emulsion detector. The pixel detector performed as expected and it is shown that, after proper alignment, a vertex matching rate of 87% is achieved

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

Background: Many patients with COVID-19 have been treated with plasma containing anti-SARS-CoV-2 antibodies. We aimed to evaluate the safety and efficacy of convalescent plasma therapy in patients admitted to hospital with COVID-19. Methods: This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]) is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. The trial is underway at 177 NHS hospitals from across the UK. Eligible and consenting patients were randomly assigned (1:1) to receive either usual care alone (usual care group) or usual care plus high-titre convalescent plasma (convalescent plasma group). The primary outcome was 28-day mortality, analysed on an intention-to-treat basis. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936. Findings: Between May 28, 2020, and Jan 15, 2021, 11558 (71%) of 16287 patients enrolled in RECOVERY were eligible to receive convalescent plasma and were assigned to either the convalescent plasma group or the usual care group. There was no significant difference in 28-day mortality between the two groups: 1399 (24%) of 5795 patients in the convalescent plasma group and 1408 (24%) of 5763 patients in the usual care group died within 28 days (rate ratio 1·00, 95% CI 0·93–1·07; p=0·95). The 28-day mortality rate ratio was similar in all prespecified subgroups of patients, including in those patients without detectable SARS-CoV-2 antibodies at randomisation. Allocation to convalescent plasma had no significant effect on the proportion of patients discharged from hospital within 28 days (3832 [66%] patients in the convalescent plasma group vs 3822 [66%] patients in the usual care group; rate ratio 0·99, 95% CI 0·94–1·03; p=0·57). Among those not on invasive mechanical ventilation at randomisation, there was no significant difference in the proportion of patients meeting the composite endpoint of progression to invasive mechanical ventilation or death (1568 [29%] of 5493 patients in the convalescent plasma group vs 1568 [29%] of 5448 patients in the usual care group; rate ratio 0·99, 95% CI 0·93–1·05; p=0·79). Interpretation: In patients hospitalised with COVID-19, high-titre convalescent plasma did not improve survival or other prespecified clinical outcomes. Funding: UK Research and Innovation (Medical Research Council) and National Institute of Health Research