ABSTRACT
We present QUIJOTE intensity and polarization maps in four frequency bands centred around 11, 13, 17, and 19 GHz, and covering approximately 29 000 deg2, including most of the northern sky ...region. These maps result from 9000 h of observations taken between May 2013 and June 2018 with the first QUIJOTE multifrequency instrument (MFI), and have angular resolutions of around 1°, and sensitivities in polarization within the range 35–40 µK per 1° beam, being a factor ∼2–4 worse in intensity. We discuss the data processing pipeline employed, and the basic characteristics of the maps in terms of real space statistics and angular power spectra. A number of validation tests have been applied to characterize the accuracy of the calibration and the residual level of systematic effects, finding a conservative overall calibration uncertainty of 5 per cent. We also discuss flux densities for four bright celestial sources (Tau A, Cas A, Cyg A, and 3C274), which are often used as calibrators at microwave frequencies. The polarization signal in our maps is dominated by synchrotron emission. The distribution of spectral index values between the 11 GHz and WMAP 23 GHz map peaks at β = −3.09 with a standard deviation of 0.14. The measured BB/EE ratio at scales of ℓ = 80 is 0.26 ± 0.07 for a Galactic cut |b| > 10°. We find a positive TE correlation for 11 GHz at large angular scales (ℓ ≲ 50), while the EB and TB signals are consistent with zero in the multipole range 30 ≲ ℓ ≲ 150. The maps discussed in this paper are publicly available.
Flavonoids are a family of polyphenolic compounds which are widespread in nature (vegetables) and are consumed as part of the human diet in significant amounts. There are other types of polyphenols, ...including, for example, tannins and resveratrol. Flavonoids and related polyphenolic compounds have significant antiinflammatory activity, among others. This short review summarizes the current knowledge on the effects of flavonoids and related polyphenolic compounds on inflammation, with a focus on structural requirements, the mechanisms involved, and pharmacokinetic considerations. Different molecular (cyclooxygenase, lipoxygenase) and cellular targets (macrophages, lymphocytes, epithelial cells, endothelium) have been identified. In addition, many flavonoids display significant antioxidant/radical scavenging properties. There is substantial structural variation in these compounds, which is bound to have an impact on their biological profile, and specifically on their effects on inflammatory conditions. However, in general terms there is substantial consistency in the effects of these compounds despite considerable structural variations. The mechanisms have been studied mainly in myeloid cells, where the predominant effect is an inhibition of NF-κB signaling and the downregulation of the expression of proinflammatory markers. At present there is a gap in knowledge of in vitro and in vivo effects, although the pharmacokinetics of flavonoids has advanced considerably in the last decade. Many flavonoids have been studied for their intestinal antiinflammatory activity which is only logical, since the gastrointestinal tract is naturally exposed to them. However, their potential therapeutic application in inflammation is not restricted to this organ and extends to other sites and conditions, including arthritis, asthma, encephalomyelitis, and atherosclerosis, among others.
Gold nanoparticles are attractive as sensing materials because of their size and shape are related with their optical properties. The color change produced by the aggregation of functionalized AuNPs ...allows the detection of arsenic at low levels. A simple, cheap and fast analytical procedure to perform arsenic determination using functionalized gold nanoparticles (AuNPs) and VIS spectrometry as a detection technique is studied. Three different synthesis procedures to obtain the AuNPs and two different functionalization modes were studied. AuNPs functionalized with GSH-DTT-CYs-PDCA were selected as the most adequate. The correlation between the decrease in the absorbance signal and the arsenic concentration was good in the 2–20µgl−1interval. Repeatability, expressed as average of RSD (%), obtained for the different arsenic concentrations studied was 0.6%. The average value of the analytical recovery was 99.7%. The detection and quantifications limits were 2.5 and 8.4µgl−1 respectively. These limits are sufficient to detect World Health Organization’s guideline value of 10µgl−1.
•Gold nanoparticles functionalized with GSH-DTT-CYs-PDCA for arsenic determination.•VIS Spectroscopy to determine arsenic in water at ppb levels.•Advantages of the method: simplicity, low cost, sensitivity, precision and time.
Cr-doped diamond-like carbon (Cr-DLC) films with Cr contents ranging from 3 up to 20 at. % were synthesised in a codeposition process with HiPIMS (Cr deposition) and DC-pulsed technology (C ...deposition). The application of HiPIMS at low frequencies was observed to significantly enhance the energy density during the Cr plasma discharge due to the interaction of Cr–C species. The higher energy bombardment at low HiPIMS frequencies allowed doping with Cr the DLC structure avoiding the graphitization of the carbon structure. EELS spectroscopy was used to evaluate sp3 content and Raman was used for sp2 structural characterization of the films. Enhanced mechanical properties (hardness up to 30 GPa) were observed with nanoindentation for Cr-doped DLC at low frequencies. High temperature nanoindentation tests were also performed from room temperature to 425 °C in order to evaluate the evolution of hardness and Young Modulus with temperature. The results showed that the mechanical properties at high temperature mainly depend on the initial sp3-sp2 structure. Tribological tests were carried out in air from room temperature to 250 °C. Cr-doped DLC coatings deposited by low-frequency HiPIMS showed lower friction and wear compared to undoped DLC.
•Cr-doped DLC coatings were co-deposited by low-frequency/high current HiPIMS method.•Cr doping by low frequency HiPIMS preserves DLC sp3 content and reduces compressive stress.•Low at. % Cr-doped DLC exhibit high hardness (up to 29 GPa) and delayed graphitization (up to 400 C).•Low at. % Cr-doped DLC presents enhanced tribological behaviour at high temperatures by creating stable tribolayers.
The exposome constitutes a promising framework to improve understanding of the effects of environmental exposures on health by explicitly considering multiple testing and avoiding selective ...reporting. However, exposome studies are challenged by the simultaneous consideration of many correlated exposures.
We compared the performances of linear regression-based statistical methods in assessing exposome-health associations.
In a simulation study, we generated 237 exposure covariates with a realistic correlation structure and with a health outcome linearly related to 0 to 25 of these covariates. Statistical methods were compared primarily in terms of false discovery proportion (FDP) and sensitivity.
On average over all simulation settings, the elastic net and sparse partial least-squares regression showed a sensitivity of 76% and an FDP of 44%; Graphical Unit Evolutionary Stochastic Search (GUESS) and the deletion/substitution/addition (DSA) algorithm revealed a sensitivity of 81% and an FDP of 34%. The environment-wide association study (EWAS) underperformed these methods in terms of FDP (average FDP, 86%) despite a higher sensitivity. Performances decreased considerably when assuming an exposome exposure matrix with high levels of correlation between covariates.
Correlation between exposures is a challenge for exposome research, and the statistical methods investigated in this study were limited in their ability to efficiently differentiate true predictors from correlated covariates in a realistic exposome context. Although GUESS and DSA provided a marginally better balance between sensitivity and FDP, they did not outperform the other multivariate methods across all scenarios and properties examined, and computational complexity and flexibility should also be considered when choosing between these methods. Citation: Agier L, Portengen L, Chadeau-Hyam M, Basagaña X, Giorgis-Allemand L, Siroux V, Robinson O, Vlaanderen J, González JR, Nieuwenhuijsen MJ, Vineis P, Vrijheid M, Slama R, Vermeulen R. 2016. A systematic comparison of linear regression-based statistical methods to assess exposome-health associations. Environ Health Perspect 124:1848-1856; http://dx.doi.org/10.1289/EHP172.
Pembrolizumab demonstrated clinically meaningful and durable antitumor activity with a manageable safety profile in recurrent/metastatic (R/M) cutaneous squamous cell carcinoma (cSCC).
KEYNOTE-629 ...was a global, open-label, nonrandomized, phase II trial of patients with locally advanced (LA) or R/M cSCC conducted at 59 centers. Eligible patients received intravenous pembrolizumab 200 mg every 3 weeks for up to 35 cycles. Primary endpoint was objective response rate (ORR), defined as the percentage of patients with a complete (CR) or partial response (PR), by blinded independent central review as per Response Evaluation Criteria in Solid Tumors 1.1. Secondary endpoints included duration of response (DOR), disease control rate, progression-free survival, overall survival, and safety and tolerability. Efficacy and safety were analyzed in patients who were treated with at least one dose of pembrolizumab.
Between 29 November 2017 and 25 September 2019, 159 patients were enrolled and treated with pembrolizumab (LA cohort, n = 54; R/M cohort, n = 105). The median time from the first dose to data cut-off date (29 July 2020) was 14.9 interquartile range (IQR), 12.6-17.2 months for the LA cohort and 27.2 (IQR, 25.6-29.2) months for the R/M cohort. In the LA cohort, ORR was 50.0% 95% confidence interval (CI), 36.1% to 63.9%, including 16.7% of patients with a CR and 33.3% with a PR. In the R/M cohort, ORR was 35.2% (95% CI, 26.2% to 45.2%), including 10.5% of patients with a CR and 24.8% with a PR. Median DOR was not reached in either cohort. Grade 3-5 treatment-related adverse events occurred in 11.9% of patients.
The robust antitumor activity of pembrolizumab in both LA and R/M cSCC was confirmed and demonstrated to be durable without unexpected safety signals. Our findings establish pembrolizumab as a promising treatment option for cSCC.
•The phase II KEYNOTE-629 study assessed the efficacy and safety of pembrolizumab in cSCC.•Pembrolizumab showed rapid, robust, and durable antitumor activity in both LA and R/M cSCC.•Adverse events were generally consistent with the established safety profile of pembrolizumab.•Our data establish pembrolizumab as a promising treatment option for cSCC.
The existence of a transition from a clogged to an unclogged state has been recently proposed for the flow of macroscopic particles through bottlenecks in systems as diverse as colloidal suspensions, ...granular matter, or live beings. Here, we experimentally demonstrate that, for vibrated granular media, such a transition genuinely exists, and we characterize it as a function of the outlet size and vibration intensity. We confirm the suitability of the "flowing parameter" as the order parameter, and we find out that the rescaled maximum acceleration of the system should be replaced as the control parameter by a dimensionless velocity that can be seen as the square root of the ratio between kinetic and potential energy. In all the investigated scenarios, we observe that, for a critical value of this control parameter Sc, there seems to be a continuous transition to an unclogged state. The data can be rescaled with this critical value, which, as expected, decreases with the orifice size D. This leads to a phase diagram in the S − D plane in which clogging appears as a concave surface.
Summary
Obesity is a well‐known risk factor for atrial fibrillation (AF). Local epi‐myocardial or intra‐myocardial adiposity caused by aging, obesity, or cardiovascular disease (CVD) is considered to ...be a better predictor of the risk of AF than general adiposity. Some of the described mechanisms suggest that epicardial adipose tissue (EAT) participates in structural remodeling owing to its endocrine activity or its infiltration between cardiomyocytes. Epicardial fat also wraps up the ganglionated plexi that reach the myocardium. Although the increment of volume/thickness and activity of EAT might modify autonomic activity, autonomic system dysfunction might also change the endocrine activity of epicardial fat in a feedback response. As a result, new preventive therapeutic strategies are focused on reducing adiposity and weight loss before AF ablation or inhibiting autonomic neurotransmitter secretion on fat pads during open‐heart surgery to reduce the recurrence or postoperative risk of AF. In this manuscript, we review some of the novel findings regarding the pathophysiology and associated risk factors of AF, with special emphasis on the role of EAT in the electrical, structural, and molecular mechanisms of AF initiation and maintenance. In addition, we have included a brief note provided on epicardial fat preclinical models that could be useful for identifying new therapeutic targets.
Plants are continuously exposed to stress conditions, such that they have developed sophisticated and elegant survival strategies, which are reflected in their phenotypic plasticity, priming ...capacity, and memory acquisition. Epigenetic mechanisms play a critical role in modulating gene expression and stress responses, allowing malleability, reversibility, stability, and heritability of favourable phenotypes to enhance plant performance. Considering the urgency to improve our agricultural system because of going impacting climate change, potential and sustainable strategies rely on the controlled use of eustressors, enhancing desired characteristics and yield and shaping stress tolerance in crops. However, for plant breeding purposes is necessary to focus on the use of eustressors capable of establishing stable epigenetic marks to generate a transgenerational memory to stimulate a priming state in plants to face the changing environment.
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