Explore the vast range of titles available.

We report a series of 1,3-diphenylureido hydroxamate HDAC inhibitors evaluated against sensitive and drug-resistant P. falciparum strains. Compounds 8a–d show potent antiplasmodial activity, indicating that a phenyl spacer allows improved potency relative to cinnamyl and di-hydrocinnamyl linkers. In vitro , mechanistic studies demonstrated target activity for Pf HDAC1 on a recombinant level, which agreed with cell quantification of the acetylated histone levels. Compounds 6c , 7c , and 8c , identified as the most active in phenotypic assays and Pf HDAC1 enzymatic inhibition. Compound 8c stands out as a remarkable inhibitor, displaying an impressive 85% inhibition of Pf HDAC1, with an IC 50 value of 0.74 µM in the phenotypic screening on Pf 3D7 and 0.8 µM against multidrug-resistant Pf Dd2 parasites. Despite its potent inhibition of Pf HDAC1, 8c remains the least active on human HDAC1, displaying remarkable selectivity. In silico studies suggest that the phenyl linker has an ideal length in the series for permitting effective interactions of the hydroxamate with Pf HDAC1 and that this compound series could bind as well as in Hs HDAC1. Taken together, these results highlight the potential of diphenylurea hydroxamates as a privileged scaffold for the generation of potent antimalarial HDAC inhibitors with improved selectivity over human HDACs.

A bstract The Neutrino Experiment with a Xenon TPC (NEXT) searches for the neutrinoless double-beta (0 νββ ) decay of 136 Xe using high-pressure xenon gas TPCs with electroluminescent amplification. A scaled-up version of this technology with about 1 tonne of enriched xenon could reach in less than 5 years of operation a sensitivity to the half-life of 0 νββ decay better than 10 27 years, improving the current limits by at least one order of magnitude. This prediction is based on a well-understood background model dominated by radiogenic sources. The detector concept presented here represents a first step on a compelling path towards sensitivity to the parameter space defined by the inverted ordering of neutrino masses, and beyond.

A bstract The NEXT experiment aims at the sensitive search of the neutrinoless double beta decay in 136 Xe, using high-pressure gas electroluminescent time projection chambers. The NEXT-White detector is the first radiopure demonstrator of this technology, operated in the Laboratorio Subterráneo de Canfranc. Achieving an energy resolution of 1% FWHM at 2.6 MeV and further background rejection by means of the topology of the reconstructed tracks, NEXT-White has been exploited beyond its original goals in order to perform a neu- trinoless double beta decay search. The analysis considers the combination of 271.6 days of 136 Xe-enriched data and 208.9 days of 136 Xe-depleted data. A detailed background modeling and measurement has been developed, ensuring the time stability of the radiogenic and cosmogenic contributions across both data samples. Limits to the neutrinoless mode are obtained in two alternative analyses: a background-model-dependent approach and a novel direct background-subtraction technique, offering results with small dependence on the background model assumptions. With a fiducial mass of only 3.50 ± 0.01 kg of 136 Xe-enriched xenon, 90% C.L. lower limits to the neutrinoless double beta decay are found in the T 1 / 2 0 ν > 5 . 5 × 10 23 − 1 . 3 × 10 24 yr range, depending on the method. The presented techniques stand as a proof-of-concept for the searches to be implemented with larger NEXT detectors.

From a computational point of view, this paper provides a significant advance in the study of the calmness property of ordinary (finite) linear programs under canonical perturbations (i.e., perturbations of the objective function coefficient vector and the right-hand side of the constraint system). In the recent literature we find, for both the feasible and the optimal set (argmin) mappings, computable expressions for the corresponding calmness moduli. These expressions are called point-based as far as they only depend on the nominal data. In this paper we show that both calmness moduli are indeed (sharp) calmness constants, and provide point-based expressions for neighborhoods where such constants work. We show that our results cannot be extended to general convex inequality systems under right-hand side perturbations.

Phytotoxicity-based extraction and fractionation were employed to separate allelochemicals contained in an extract of Lethariella canariensis. Twelve phenolic substances were isolated from the phytotoxic fraction \"Letharal\" of the thalli. These were identified by spectroscopic methods, physicochemical constants, and HPLC chemical correlation, and determined to be atranol (2), chloroatranol (3), hematommic acid (4), chlorohematommic acid (5), methyl hematommate (6), methyl chlorohematommate (7) (new compound), ethyl hematommate (8), ethyl chlorohematommate (9), methyl beta-orsellinate (10), atranorin (11), chloroatranorin (12), and (+)-usnic acid (13). Further identification and quantification of these allelochemicals in the environment were conducted by HPLC. Several phenolic compounds showed moderate antimicrobial activity. The cytostatic activity of the polyphenols was investigated on U937 and HL-60 cells. All compounds were assayed, with the exception of 10. The \"Letharal\" mixture decreased cell viability in both cell lines. Protection against lipid peroxidation was investigated using brain homogenates. Compounds 2, 3, 6, 8, 11, and Letharal decreased H2O2/Fe+2 induced lipid peroxidation in a concentration-dependent manner, while 10 and 13 were unable to protect tissue against oxidative stress.

A bstract Convolutional neural networks (CNNs) are widely used state-of-the-art computer vision tools that are becoming increasingly popular in high-energy physics. In this paper, we attempt to understand the potential of CNNs for event classification in the NEXT experiment, which will search for neutrinoless double-beta decay in 136 Xe. To do so, we demonstrate the usage of CNNs for the identification of electron-positron pair production events, which exhibit a topology similar to that of a neutrinoless double-beta decay event. These events were produced in the NEXT-White high-pressure xenon TPC using 2.6 MeV gamma rays from a 228 Th calibration source. We train a network on Monte Carlo-simulated events and show that, by applying on-the-fly data augmentation, the network can be made robust against differences between simulation and data. The use of CNNs offers significant improvement in signal efficiency and background rejection when compared to previous non-CNN-based analyses.

A bstract Natural radioactivity represents one of the main backgrounds in the search for neutrinoless double beta decay. Within the NEXT physics program, the radioactivity- induced backgrounds are measured with the NEXT-White detector. Data from 37.9 days of low-background operations at the Laboratorio Subterráneo de Canfranc with xenon depleted in 136 Xe are analyzed to derive a total background rate of (0.84 ± 0.02) mHz above 1000 keV. The comparison of data samples with and without the use of the radon abatement system demonstrates that the contribution of airborne-Rn is negligible. A radiogenic background model is built upon the extensive radiopurity screening campaign conducted by the NEXT collaboration. A spectral fit to this model yields the specific contributions of 60 Co, 40 K, 214 Bi and 208 Tl to the total background rate, as well as their location in the detector volumes. The results are used to evaluate the impact of the radiogenic backgrounds in the double beta decay analyses, after the application of topological cuts that reduce the total rate to (0.25 ± 0.01) mHz. Based on the best-fit background model, the NEXT-White median sensitivity to the two-neutrino double beta decay is found to be 3.5 σ after 1 year of data taking. The background measurement in a Q ββ ± 100 keV energy window validates the best-fit background model also for the neutrinoless double beta decay search with NEXT-100. Only one event is found, while the model expectation is (0.75 ± 0.12) events.

A bstract If neutrinoless double beta decay is discovered, the next natural step would be understanding the lepton number violating physics responsible for it. Several alternatives exist beyond the exchange of light neutrinos. Some of these mechanisms can be distinguished by measuring phase-space observables, namely the opening angle cos θ among the two decay electrons, and the electron energy spectra, T 1 and T 2 . In this work, we study the statistical accuracy and precision in measuring these kinematic observables in a future xenon gas detector with the added capability to precisely locate the decay vertex. For realistic detector conditions (a gas pressure of 10 bar and spatial resolution of 4 mm), we find that the average cos θ ¯ and T 1 ¯ values can be reconstructed with a precision of 0.19 and 110 keV, respectively, assuming that only 10 neutrinoless double beta decay events are detected.

This paper introduces the concept of critical objective size associated with a linear program in order to provide operative point-based formulas (only involving the nominal data, and not data in a neighborhood) for computing or estimating the calmness modulus of the optimal set (argmin) mapping under uniqueness of nominal optimal solution and perturbations of all coefficients. Our starting point is an upper bound on this modulus given in Cánovas et al. (4). In this paper we prove that this upper bound is attained if and only if the norm of the objective function coefficient vector is less than or equal to the critical objective size. This concept also allows us to obtain operative lower bounds on the calmness modulus. We analyze in detail an illustrative example in order to explore some strategies that can improve the referred upper and lower bounds.

A bstract The measurement of the internal 222 Rn activity in the NEXT-White detector during the so-called Run-II period with 136 Xe-depleted xenon is discussed in detail, together with its implications for double beta decay searches in NEXT. The activity is measured through the alpha production rate induced in the fiducial volume by 222 Rn and its alpha-emitting progeny. The specific activity is measured to be (38.1 ± 2.2 (stat.) ± 5.9 (syst.)) mBq/m 3 . Radon-induced electrons have also been characterized from the decay of the 214 Bi daughter ions plating out on the cathode of the time projection chamber. From our studies, we conclude that radon-induced backgrounds are sufficiently low to enable a successful NEXT-100 physics program, as the projected rate contribution should not exceed 0.1 counts/yr in the neutrinoless double beta decay sample.