For the past several decades, we have been able to directly probe the motion of atoms that is associated with chemical transformations and which occurs on the femtosecond (10−15-s) timescale. ...However, studying the inner workings of atoms and molecules on the electronic timescale has become possible only with the recent development of isolated attosecond (10−18-s) laser pulses. Such pulses have been used to investigate atomic photoexcitation and photoionization and electron dynamics in solids, and in molecules could help explore the prompt charge redistribution and localization that accompany photoexcitation processes. In recent work, the dissociative ionization of H2 and D2 was monitored on femtosecond timescales and controlled using few-cycle near-infrared laser pulses. Here we report a molecular attosecond pump-probe experiment based on that work: H2 and D2 are dissociatively ionized by a sequence comprising an isolated attosecond ultraviolet pulse and an intense few-cycle infrared pulse, and a localization of the electronic charge distribution within the molecule is measured that depends-with attosecond time resolution-on the delay between the pump and probe pulses. The localization occurs by means of two mechanisms, where the infrared laser influences the photoionization or the dissociation of the molecular ion. In the first case, charge localization arises from quantum mechanical interference involving autoionizing states and the laser-altered wavefunction of the departing electron. In the second case, charge localization arises owing to laser-driven population transfer between different electronic states of the molecular ion. These results establish attosecond pump-probe strategies as a powerful tool for investigating the complex molecular dynamics that result from the coupling between electronic and nuclear motions beyond the usual Born-Oppenheimer approximation.
Controversial findings regarding the association between pro-inflammatory cytokines and depression have been reported in pregnant subjects. Scarce data about anxiety and its relationships with ...cytokines are available in pregnant women. To understand the association between anxiety and cytokines during pregnancy, we conducted the present study in women with or without depression.
Women exhibiting severe depression (SD) and severe anxiety (SA) during the 3rd trimester of pregnancy (n = 139) and control subjects exhibiting neither depression nor anxiety (n = 40) were assessed through the Hamilton Depression Rating Scale (HDRS) and the Hamilton Anxiety Rating Scale (HARS). Serum cytokines were measured by a multiplex bead-based assay. Correlation tests were used to analyze the data and comparisons between groups were performed. A general linear model of analysis of variance was constructed using the group as a dependent variable, interleukin concentrations as independent variables, and HDRS/HARS scores and gestational weeks as covariables.
The highest levels of Th1- (IL-6, TNF-α, IL-2, IFN-γ), Th17- (IL-17A, IL-22), and Th2- (IL-9, IL-10, and IL-13) related cytokines were observed in women with SD + SA. The SA group showed higher concentrations of Th1- (IL-6, TNF-α, IL-2, IFN-γ) and Th2- (IL-4, and IL-10) related cytokines than the controls. Positive correlations were found between HDRS and IL-2, IL-6, and TNF-α in the SA group (p < 0.03), and between HDRS and Th1- (IL-2, IL-6, TNF-α), Th2- (IL-9, IL-10, IL-13) and Th17- (IL-17A) cytokines (p < 0.05) in the SD + SA group. After controlling the correlation analysis by gestational weeks, the correlations that remained significant were: HDRS and IL-2, IL-6, IL-9, and IL-17A in the SD + SA group (p < 0.03). HARS scores correlated with IL-17A in the SA group and with IL-17A, IL-17F, and IL-2 in the SD + SA group (p < 0.02). The linear model of analysis of variance showed that HDRS and HARS scores influenced cytokine concentrations; only IL-6 and TNF-α could be explained by the group.
We found that the cytokine profiles differ when comparing pregnant subjects exhibiting SA with comorbid SD against those showing only SA without depression.
21 cm epoch of reionization (EoR) observations promise to transform our understanding of galaxy formation, but these observations are impossible without unprecedented levels of instrument ...calibration. We present end-to-end simulations of a full EoR power spectrum (PS) analysis including all of the major components of a real data processing pipeline: models of astrophysical foregrounds and EoR signal, frequency-dependent instrument effects, sky-based antenna calibration, and the full PS analysis. This study reveals that traditional sky-based per-frequency antenna calibration can only be implemented in EoR measurement analyses if the calibration model is unrealistically accurate. For reasonable levels of catalogue completeness, the calibration introduces contamination in otherwise foreground-free PS modes, precluding a PS measurement. We explore the origin of this contamination and potential mitigation techniques. We show that there is a strong joint constraint on the precision of the calibration catalogue and the inherent spectral smoothness of antennas, and that this has significant implications for the instrumental design of the SKA (Square Kilometre Array) and other future EoR observatories.
We present a survey for transient and variable sources, on time-scales from 28 s to ∼1 yr, using the Murchison Widefield Array (MWA) at 182 MHz. Down to a detection threshold of 0.285 Jy, no ...transient candidates were identified, making this the most constraining low-frequency survey to date and placing a limit on the surface density of transients of <4.1 × 10−7 deg−2 for the shortest time-scale considered. At these frequencies, emission from Fast Radio Bursts (FRBs) is expected to be detectable in the shortest time-scale images without any corrections for interstellar or intergalactic dispersion. At an FRB limiting flux density of 7980 Jy, we find a rate of <82 FRBs per sky per day for dispersion measures <700 pc cm−3. Assuming a cosmological population of standard candles, our rate limits are consistent with the FRB rates obtained by Thornton et al. if they have a flat spectral slope. Finally, we conduct an initial variability survey of sources in the field with flux densities ≳0.5 Jy and identify no sources with significant variability in their light curves. However, we note that substantial further work is required to fully characterize both the short-term and low-level variability within this field.
Astronomical wide-field imaging of interferometric radio data is computationally expensive, especially for the large data volumes created by modern non-coplanar many-element arrays. We present a new ...wide-field interferometric imager that uses the w-stacking algorithm and can make use of the w-snapshot algorithm. The performance dependences of casa's w-projection and our new imager are analysed and analytical functions are derived that describe the required computing cost for both imagers. On data from the Murchison Widefield Array, we find our new method to be an order of magnitude faster than w-projection, as well as being capable of full-sky imaging at full resolution and with correct polarization correction. We predict the computing costs for several other arrays and estimate that our imager is a factor of 2–12 faster, depending on the array configuration. We estimate the computing cost for imaging the low-frequency Square Kilometre Array observations to be 60 PetaFLOPS with current techniques. We find that combining w-stacking with the w-snapshot algorithm does not significantly improve computing requirements over pure w-stacking. The source code of our new imager is publicly released.
A common metabolic alteration in the tumor microenvironment (TME) is lipid accumulation, a feature associated with immune dysfunction. Here, we examined how CD8+ tumor infiltrating lymphocytes (TILs) ...respond to lipids within the TME. We found elevated concentrations of several classes of lipids in the TME and accumulation of these in CD8+ TILs. Lipid accumulation was associated with increased expression of CD36, a scavenger receptor for oxidized lipids, on CD8+ TILs, which also correlated with progressive T cell dysfunction. Cd36−/− T cells retained effector functions in the TME, as compared to WT counterparts. Mechanistically, CD36 promoted uptake of oxidized low-density lipoproteins (OxLDL) into T cells, and this induced lipid peroxidation and downstream activation of p38 kinase. Inhibition of p38 restored effector T cell functions in vitro, and resolution of lipid peroxidation by overexpression of glutathione peroxidase 4 restored functionalities in CD8+ TILs in vivo. Thus, an oxidized lipid-CD36 axis promotes intratumoral CD8+ T cell dysfunction and serves as a therapeutic avenue for immunotherapies.
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•The tumor microenvironment is enriched with lipids and oxidized lipids•Dysfunctional CD8+ TILs increase CD36 expression and OxLDL uptake•OxLDL uptake via CD36 inhibits T cell effector functions through lipid peroxidation•GPX4 overexpression promotes CD8+ TIL functionality
Lipid accumulation is a common metabolic alteration in the tumor microenvironment. Xu et al. show that intratumoral CD8+ T cells adapt to increased lipid concentrations by increasing expression of the scavenger receptor CD36. This, in turn, leads to intracellular accumulation of oxidized lipid and T cell dysfunction downstream of lipid peroxidation.
Measurements of 21 cm Epoch of Reionization (EoR) structure are subject to systematics originating from both the analysis and the observation conditions. Using 2013 data from the Murchison Widefield ...Array (MWA), we show the importance of mitigating both sources of contamination. A direct comparison between results from Beardsley et al. and our updated analysis demonstrates new precision techniques, lowering analysis systematics by a factor of 2.8 in power. We then further lower systematics by excising observations contaminated by ultra-faint RFI, reducing by an additional factor of 3.8 in power for the zenith pointing. With this enhanced analysis precision and newly developed RFI mitigation, we calculate a noise-dominated upper limit on the EoR structure of Δ2 ≤ 3.9 × 103 mK2 at k = 0.20 h Mpc−1 and z = 7 using 21 hr of data, improving previous MWA limits by almost an order of magnitude.
The compact configuration of Phase II of the Murchison Widefield Array (MWA) consists of both a redundant subarray and pseudo-random baselines, offering unique opportunities to perform sky-model and ...redundant interferometric calibration. The highly redundant hexagonal cores give improved power spectrum sensitivity. In this paper, we present the analysis of nearly 40 hr of data targeting one of the MWA's epoch of reionization (EoR) fields observed in 2016. We use both improved analysis techniques presented in Barry et al. and several additional techniques developed for this work, including data quality control methods and interferometric calibration approaches. We show the EoR power spectrum limits at redshift 6.5, 6.8, and 7.1 based on our deep analysis on this 40 hr data set. These limits span a range in k-space of 0.18 h Mpc−1 < k < 1.6 h Mpc−1, with a lowest measurement of Δ2 ≤ 2.39 × 103 mK2 at k = 0.59 h Mpc−1 and z = 6.5.
ABSTRACT The Rosetta probe, orbiting Jupiter-family comet 67P/Churyumov-Gerasimenko, has been detecting individual dust particles of mass larger than 10−10 kg by means of the GIADA dust collector and ...the OSIRIS Wide Angle Camera and Narrow Angle Camera since 2014 August and will continue until 2016 September. Detections of single dust particles allow us to estimate the anisotropic dust flux from 67P, infer the dust loss rate and size distribution at the surface of the sunlit nucleus, and see whether the dust size distribution of 67P evolves in time. The velocity of the Rosetta orbiter, relative to 67P, is much lower than the dust velocity measured by GIADA, thus dust counts when GIADA is nadir-pointing will directly provide the dust flux. In OSIRIS observations, the dust flux is derived from the measurement of the dust space density close to the spacecraft. Under the assumption of radial expansion of the dust, observations in the nadir direction provide the distance of the particles by measuring their trail length, with a parallax baseline determined by the motion of the spacecraft. The dust size distribution at sizes >1 mm observed by OSIRIS is consistent with a differential power index of −4, which was derived from models of 67P's trail. At sizes <1 mm, the size distribution observed by GIADA shows a strong time evolution, with a differential power index drifting from −2 beyond 2 au to −3.7 at perihelion, in agreement with the evolution derived from coma and tail models based on ground-based data. The refractory-to-water mass ratio of the nucleus is close to six during the entire inbound orbit and at perihelion.
To study the response of clinical variables (HbA
, body weight, lipid profile and blood pressure) over 24 months of liraglutide treatment in a real-world clinical setting, and to describe the ...evolution of HbA
and body weight reduction in response to liraglutide treatment by employing generalized additive mixed models (GAMMs).
We included people aged ≥ 18 years with Type 2 diabetes mellitus that initiated liraglutide treatment between November 2011 and May 2015. Demographic and clinical data were retrieved retrospectively over 24 months from electronic medical records with a median duration of observation of 7.0 (IQR 3.0-12.0) months.
Individuals that initiated liraglutide therapy were obese (BMI 39.1 kg/m
), with inadequate HbA
(68 mmol/mol 8.4%), blood pressure and lipid levels. Upon liraglutide treatment, HbA
, body weight, mean systolic and diastolic blood pressure, and lipid levels decreased gradually. GAMMs demonstrated that longer treatment with liraglutide was a predictor of improved HbA
response, whereas higher baseline HbA
, longer Type 2 diabetes duration and treatment with insulin were predictors of worse HbA
response. Higher baseline weight, longer treatment with liraglutide and the interaction between metformin and time were predictors of improved weight response.
In this real-world study, we showed the effectiveness of liraglutide in improving body weight, HbA
, mean systolic and diastolic blood pressure, and lipid levels. GAMMs indicated that baseline HbA
and weight, time of treatment with liraglutide, diabetes duration and the use of metformin or insulin are predictors of clinical response to liraglutide.
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