383 research outputs found

    Almanac: MCMC-based signal extraction of power spectra and maps on the sphere

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    Inference in cosmology often starts with noisy observations of random fields on the celestial sphere, such as maps of the microwave background radiation, continuous maps of cosmic structure in different wavelengths, or maps of point tracers of the cosmological fields. Almanac uses Hamiltonian Monte Carlo sampling to infer the underlying all-sky noiseless maps of cosmic structures, in multiple redshift bins, together with their auto- and cross-power spectra. It can sample many millions of parameters, handling the highly variable signal-to-noise of typical cosmological signals, and it provides science-ready posterior data products. In the case of spin-weight 2 fields, Almanac infers EE- and BB-mode power spectra and parity-violating EBEB power, and, by sampling the full posteriors rather than point estimates, it avoids the problem of EBEB-leakage. For theories with no BB-mode signal, inferred non-zero BB-mode power may be a useful diagnostic of systematic errors or an indication of new physics. Almanac's aim is to characterise the statistical properties of the maps, with outputs that are completely independent of the cosmological model, beyond an assumption of statistical isotropy. Inference of parameters of any particular cosmological model follows in a separate analysis stage. We demonstrate our signal extraction on a CMB-like experiment.Comment: 27 pages, 18 figures. v2 accepted for publication by The Open Journal of Astrophysics with minor changes. v3 no changes, missing acknowledgement adde

    The impact of spectroscopic incompleteness in direct calibration of redshift distributions for weak lensing surveys

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    Obtaining accurate distributions of galaxy redshifts is a critical aspect of weak lensing cosmology experiments. One of the methods used to estimate and validate redshift distributions is to apply weights to a spectroscopic sample, so that their weighted photometry distribution matches the target sample. In this work, we estimate the selection bias in redshift that is introduced in this procedure. We do so by simulating the process of assembling a spectroscopic sample (including observer-assigned confidence flags) and highlight the impacts of spectroscopic target selection and redshift failures. We use the first year (Y1) weak lensing analysis in Dark Energy Survey (DES) as an example data set but the implications generalize to all similar weak lensing surveys. We find that using colour cuts that are not available to the weak lensing galaxies can introduce biases of up to Δz ∌ 0.04 in the weighted mean redshift of different redshift intervals (Δz ∌ 0.015 in the case most relevant to DES). To assess the impact of incompleteness in spectroscopic samples, we select only objects with high observer-defined confidence flags and compare the weighted mean redshift with the true mean. We find that the mean redshift of the DES Y1 weak lensing sample is typically biased at the Δz = 0.005−0.05 level after the weighting is applied. The bias we uncover can have either sign, depending on the samples and redshift interval considered. For the highest redshift bin, the bias is larger than the uncertainties in the other DES Y1 redshift calibration methods, justifying the decision of not using this method for the redshift estimations. We discuss several methods to mitigate this bias

    The effects of short-term, progressive exercise training on disease activity in smouldering multiple myeloma and monoclonal gammopathy of undetermined significance:a single-arm pilot study

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    Background: High levels of physical activity are associated with reduced risk of the blood cancer multiple myeloma (MM). MM is preceded by the asymptomatic stages of monoclonal gammopathy of undetermined significance (MGUS) and smouldering multiple myeloma (SMM) which are clinically managed by watchful waiting. A case study (N = 1) of a former elite athlete aged 44 years previously indicated that a multi-modal exercise programme reversed SMM disease activity. To build from this prior case study, the present pilot study firstly examined if short-term exercise training was feasible and safe for a group of MGUS and SMM patients, and secondly investigated the effects on MGUS/SMM disease activity. Methods: In this single-arm pilot study, N = 20 participants diagnosed with MGUS or SMM were allocated to receive a 16-week progressive exercise programme. Primary outcome measures were feasibility and safety. Secondary outcomes were pre- to post-exercise training changes to blood biomarkers of MGUS and SMM disease activity– monoclonal (M)-protein and free light chains (FLC)– plus cardiorespiratory and functional fitness, body composition, quality of life, blood immunophenotype, and blood biomarkers of inflammation. Results: Fifteen (3 MGUS and 12 SMM) participants completed the exercise programme. Adherence was 91 ± 11%. Compliance was 75 ± 25% overall, with a notable decline in compliance at intensities > 70% V̇O2PEAK. There were no serious adverse events. There were no changes to M-protein (0.0 ± 1.0 g/L, P =.903), involved FLC (+ 1.8 ± 16.8 mg/L, P =.839), or FLC difference (+ 0.2 ± 15.6 mg/L, P =.946) from pre- to post-exercise training. There were pre- to post-exercise training improvements to diastolic blood pressure (− 3 ± 5 mmHg, P =.033), sit-to-stand test performance (+ 5 ± 5 repetitions, P =.002), and energy/fatigue scores (+ 10 ± 15%, P =.026). Other secondary outcomes were unchanged. Conclusions: A 16-week progressive exercise programme was feasible and safe, but did not reverse MGUS/SMM disease activity, contrasting a prior case study showing that five years of exercise training reversed SMM in a 44-year-old former athlete. Longer exercise interventions should be explored in a group of MGUS/SMM patients, with measurements of disease biomarkers, along with rates of disease progression (i.e., MGUS/SMM to MM). Registration: https://www.isrctn.com/ISRCTN65527208 (14/05/2018)

    Epigenetic control of pheromone MAPK signaling determines sexual fecundity in Candida albicans

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    Several pathogenic Candida species are capable of heritable and reversible switching between two epigenetic states, "white" and "opaque." In Candida albicans, white cells are essentially sterile, whereas opaque cells are mating-proficient. Here, we interrogate the mechanism by which the white-opaque switch regulates sexual fecundity and identify four genes in the pheromone MAPK pathway that are expressed at significantly higher levels in opaque cells than in white cells. These genes encode the beta subunit of the G-protein complex (STE4), the pheromone MAPK scaffold (CST5), and the two terminal MAP kinases (CEK1/CEK2). To define the contribution of each factor to mating, C. albicans white cells were reverse-engineered to express elevated, opaque-like levels of these factors, either singly or in combination. We show that white cells co-overexpressing STE4, CST5, and CEK2 undergo mating four orders of magnitude more efficiently than control white cells and at a frequency approaching that of opaque cells. Moreover, engineered white cells recapitulate the transcriptional and morphological responses of opaque cells to pheromone. These results therefore reveal multiple bottlenecks in pheromone MAPK signaling in white cells and that alleviation of these bottlenecks enables efficient mating by these "sterile" cell types. Taken together, our findings establish that differential expression of several MAPK factors underlies the epigenetic control of mating in C. albicans We also discuss how fitness advantages could have driven the evolution of a toggle switch to regulate sexual reproduction in pathogenic Candida species

    Structure and dynamics of the Martian lower and middle atmosphere as observed by the Mars Climate Sounder: Seasonal variations in zonal mean temperature, dust, and water ice aerosols

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    The first Martian year and a half of observations by the Mars Climate Sounder aboard the Mars Reconnaissance Orbiter has revealed new details of the thermal structure and distributions of dust and water ice in the atmosphere. The Martian atmosphere is shown in the observations by the Mars Climate Sounder to vary seasonally between two modes: a symmetrical equinoctial structure with middle atmosphere polar warming and a solstitial structure with an intense middle atmosphere polar warming overlying a deep winter polar vortex. The dust distribution, in particular, is more complex than appreciated before the advent of these high (~5 km) vertical resolution observations, which extend from near the surface to above 80 km and yield 13 dayside and 13 nightside pole-to-pole cross sections each day. Among the new features noted is a persistent maximum in dust mass mixing ratio at 15–25 km above the surface (at least on the nightside) during northern spring and summer. The water ice distribution is very sensitive to the diurnal and seasonal variation of temperature and is a good tracer of the vertically propagating tide

    Field Measurements of Terrestrial and Martian Dust Devils

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    Surface-based measurements of terrestrial and martian dust devils/convective vortices provided from mobile and stationary platforms are discussed. Imaging of terrestrial dust devils has quantified their rotational and vertical wind speeds, translation speeds, dimensions, dust load, and frequency of occurrence. Imaging of martian dust devils has provided translation speeds and constraints on dimensions, but only limited constraints on vertical motion within a vortex. The longer mission durations on Mars afforded by long operating robotic landers and rovers have provided statistical quantification of vortex occurrence (time-of-sol, and recently seasonal) that has until recently not been a primary outcome of more temporally limited terrestrial dust devil measurement campaigns. Terrestrial measurement campaigns have included a more extensive range of measured vortex parameters (pressure, wind, morphology, etc.) than have martian opportunities, with electric field and direct measure of dust abundance not yet obtained on Mars. No martian robotic mission has yet provided contemporaneous high frequency wind and pressure measurements. Comparison of measured terrestrial and martian dust devil characteristics suggests that martian dust devils are larger and possess faster maximum rotational wind speeds, that the absolute magnitude of the pressure deficit within a terrestrial dust devil is an order of magnitude greater than a martian dust devil, and that the time-of-day variation in vortex frequency is similar. Recent terrestrial investigations have demonstrated the presence of diagnostic dust devil signals within seismic and infrasound measurements; an upcoming Mars robotic mission will obtain similar measurement types

    Explanation for the increase in high altitude water on Mars observed by NOMAD during the 2018 global dust storm

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    The Nadir and Occultation for MArs Discovery (NOMAD) instrument on board ExoMars Trace Gas Orbiter (TGO) measured a large increase in water vapor at altitudes in the range of 40‐100 km during the 2018 global dust storm on Mars. Using a three‐dimensional general circulation model, we examine the mechanism responsible for the enhancement of water vapor in the upper atmosphere. Experiments with different prescribed vertical profiles of dust show that when more dust is present higher in the atmosphere the temperature increases and the amount of water ascending over the tropics is not limited by saturation until reaching heights of 70‐100 km. The warmer temperatures allow more water to ascend to the mesosphere. Photochemical simulations show a strong increase in high‐altitude atomic hydrogen following the high‐altitude water vapor increase by a few days

    Ibrutinib for Relapsed / Refractory CLL: A UK and Ireland Analysis of Outcomes in 315 patients

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    In 2014, ibrutinib was made available for relapsed/refractory chronic lymphocytic leukaemia (CLL) patients. The UK CLL Forum collected data from UK/Ireland patients with a minimum of 1 year follow-up with pre-planned primary endpoints; the number of patients still on therapy at 1 year (Discontinuation Free Survival; DFS) and 1 year overall survival (OS). With a median 16 months follow-up, data on 315 patients demonstrated 1 year DFS of 73.7% and 1 year OS of 83.8%. Patients with better pre-treatment performance status (PS 0/1 vs 2+) had superior DFS (77.5% vs 61.3%;p14 days and had OS of 89.7%, while 26% of patients had dose reductions and 13% had temporary treatment breaks >14 days. We could not demonstrate a detrimental effect of dose reductions alone (1 year OS: 91.7%), but patients who had first year treatment breaks > 14 days, particularly permanent cessation of ibrutinib had both reduced 1 year OS (68.5%) and also a statistically significant excess mortality rate beyond one year. Although outcomes appear inferior to the RESONATE trial (1 year OS;90%: PFS;84%), this may partly reflect the inclusion of PS 2+ patients and that 17.5% of patients permanently discontinued ibrutinib due to an event other than disease progression
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