Abstract
The classic classification scheme for active galactic nuclei (AGNs) was recently challenged by the discovery of the so-called changing-state (changing-look) AGNs. The physical mechanism ...behind this phenomenon is still a matter of open debate and the samples are too small and of serendipitous nature to provide robust answers. In order to tackle this problem, we need to design methods that are able to detect AGNs right in the act of changing state. Here we present an anomaly-detection technique designed to identify AGN light curves with anomalous behaviors in massive data sets. The main aim of this technique is to identify CSAGN at different stages of the transition, but it can also be used for more general purposes, such as cleaning massive data sets for AGN variability analyses. We used light curves from the Zwicky Transient Facility data release 5 (ZTF DR5), containing a sample of 230,451 AGNs of different classes. The ZTF DR5 light curves were modeled with a Variational Recurrent Autoencoder (VRAE) architecture, that allowed us to obtain a set of attributes from the VRAE latent space that describes the general behavior of our sample. These attributes were then used as features for an Isolation Forest (IF) algorithm that is an anomaly detector for a “one class” kind of problem. We used the VRAE reconstruction errors and the IF anomaly score to select a sample of 8809 anomalies. These anomalies are dominated by bogus candidates, but we were able to identify 75 promising CSAGN candidates.
The vimentin filament network plays a key role in cell architecture and signalling, as well as in epithelial-mesenchymal transition. Vimentin C328 is targeted by various oxidative modifications, but ...its role in vimentin organization is not known. Here we show that C328 is essential for vimentin network reorganization in response to oxidants and electrophiles, and is required for optimal vimentin performance in network expansion, lysosomal distribution and aggresome formation. C328 may fulfil these roles through interaction with zinc. In vitro, micromolar zinc protects vimentin from iodoacetamide modification and elicits vimentin polymerization into optically detectable structures; in cells, zinc closely associates with vimentin and its depletion causes reversible filament disassembly. Finally, zinc transport-deficient human fibroblasts show increased vimentin solubility and susceptibility to disruption, which are restored by zinc supplementation. These results unveil a critical role of C328 in vimentin organization and open new perspectives for the regulation of intermediate filaments by zinc.
Endothelial dysfunction has been widely associated with oxidative stress, glucotoxicity and lipotoxicity and underlies the development of cardiovascular diseases (CVDs), atherosclerosis and diabetes. ...In such pathological conditions, lipids are emerging as mediators of signalling pathways evoking key cellular responses as expression of proinflammatory genes, proliferation and apoptosis. Hence, the assessment of lipid profiles in endothelial cells (EC) can provide valuable information on the molecular alterations underlying CVDs, atherosclerosis and diabetes. We performed a lipidomic approach based on hydrophilic interaction liquid chromatography-tandem mass spectrometry (HILIC-MS/MS) for the analysis of the phospholipidome of bovine aortic EC (BAEC) exposed to oxidative (H
O
), glycative (glucose), or lipoxidative (4-hydroxynonenal, HNE) stress. The phospholipid (PL) profile was evaluated for the classes PC, PE, PS, PG, PI, SM, LPC and CL. H
O
induced a more acute adaptation of the PL profile than glucose or HNE. Unsaturated PL molecular species were up-regulated after 24 h incubation with H
O
, while an opposite trend was observed in glucose- and HNE-treated cells. This study compared, for the first time, the adaptation of the phospholipidome of BAEC upon different induced biochemical stresses. Although further biological studies will be necessary, our results unveil specific lipid signatures in response to characteristic types of stress.
Hydroxytyrosol (HT), the main representative of polyphenols of olive oil, has been described as one of the most powerful natural antioxidants, also showing anti-inflammatory, antimicrobial, ...cardioprotective and anticancer activity in different type of cancers, but has been little studied in hematological neoplasms. The objective of this work was to evaluate the anticancer potential of HT in acute human leukemia T cells (Jurkat and HL60) and the anti-inflammatory potential in murine macrophages (Raw264.7). For this, cytotoxicity tests were performed for HT, showing IC50 values, at 24 h, for Jurkat, HL60 and Raw264.7 cells, of 27.3 µg·mL−1, 109.8 µg·mL−1 and 45.7 µg·mL−1, respectively. At the same time, HT caused cell arrest in G0/G1 phase in both Jurkat and HL60 cells by increasing G0/G1 phase and significantly decreasing S phase. Apoptosis and cell cycle assays revealed an antiproliferative effect of HT, decreasing the percentage of dividing cells and increasing apoptosis. Furthermore, HT inhibited the PI3K signaling pathway and, consequently, the MAPK pathway was activated. Inflammation tests revealed that HT acts as an anti-inflammatory agent, reducing NO levels in Raw264.7 cells previously stimulated by lipopolysaccharide (LPS). These processes were confirmed by the changes in the expression of the main markers of inflammation and cancer. In conclusion, HT has an anticancer and anti-inflammatory effect in the cell lines studied, which were Raw264.7, Jurkat, and HL60, and could be used as a natural drug in the treatment of liquid cancers, leukemias, myelomas and lymphomas.
Stroke-like episodes (SLE) occur in phosphomannomutase deficiency (PMM2-CDG), and may complicate the course of channelopathies related to Familial Hemiplegic Migraine (FHM) caused by mutations in
...(encoding Ca
2.1 channel). The underlying pathomechanisms are unknown. We analyze clinical variables to detect risk factors for SLE in a series of 43 PMM2-CDG patients. We explore the hypothesis of abnormal Ca
2.1 function due to aberrant
-glycosylation as a potential novel pathomechanism of SLE and ataxia in PMM2-CDG by using whole-cell patch-clamp,
-glycosylation blockade and mutagenesis. Nine SLE were identified. Neuroimages showed no signs of stroke. Comparison of characteristics between SLE positive versus negative patients' group showed no differences. Acute and chronic phenotypes of patients with PMM2-CDG or
channelopathies show similarities. Hypoglycosylation of both Ca
2.1 subunits (α
and α
) induced gain-of-function effects on channel gating that mirrored those reported for pathogenic
mutations linked to FHM and ataxia. Unoccupied
-glycosylation site N283 at α
contributes to a gain-of-function by lessening Ca
2.1 inactivation. Hypoglycosylation of the α₂δ subunit also participates in the gain-of-function effect by promoting voltage-dependent opening of the Ca
2.1 channel. Ca
2.1 hypoglycosylation may cause ataxia and SLEs in PMM2-CDG patients. Aberrant Ca
2.1
-glycosylation as a novel pathomechanism in PMM2-CDG opens new therapeutic possibilities.
Nitrogen compounds play a key role on grape and wine quality. Their composition in grapes depends mainly on variety, viticultural management, and terroir, and affects fermentation kinetics and the ...volatile compound formation. The aim of this work was to study grape and wine amino acid composition of ungrafted or grafted onto cv. País Carignan grapevines growing under rainfed conditions in ten sites of the Maule Valley (Chile). The results showed that proline was the most abundant amino acid in grapes and wines. In general, Carignan noir grapevines grafted over País showed lower grape amino acid content respect to ungrafted vines. Cool night index (CI) was inversely correlated to several amino acids, showing that their plant synthesis or accumulation increased with lower minimum temperatures during the last month before harvest. Truquilemu (Tru) and Ciénaga de Name (Cdn) sites showed the highest concentration for several amino acids and total amino acid content in grapes, which led to a faster alcoholic fermentation.
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•First study about grape and wine amino acid composition in terms of Valley•Tru and Cdn sites showed high content in grapes which improved fermentation kinetics.•Low night Ts (°C) in the month prior to harvest allowed a high amino acid synthesis.•Grapes from Carignan noir vines grafted with País showed low grape amino acid content.•Carignan noir grapevines behaved as proline accumulator variety.
Abstract
We present a detailed prompt emission and early optical afterglow analysis of the two very-high-energy (VHE) detected bursts GRB 201015A and GRB 201216C, and their comparison with a subset ...of similar bursts. Time-resolved spectral analysis of multistructured GRB 201216C using the Bayesian binning algorithm revealed that during the entire duration of the burst, the low-energy spectral index (
α
pt
) remained below the limit of the synchrotron line of death. However, statistically some of the bins supported the additional thermal component. Additionally, the evolution of spectral parameters showed that both the peak energy (
E
p
) and
α
pt
tracked the flux. These results were further strengthened using the values of the physical parameters obtained by synchrotron modeling of the data. Our earliest optical observations of both bursts using the F/Photometric Robotic Atmospheric Monitor Observatorio del Roque de los Muchachos and Burst Observer and Optical Transient Exploring System robotic telescopes displayed a smooth bump in their early optical light curves, consistent with the onset of the afterglow due to synchrotron emission from an external forward shock. Using the observed optical peak, we constrained the initial bulk Lorentz factors of GRB 201015A and GRB 201216C to Γ
0
= 204 and Γ
0
= 310, respectively. The present early optical observations are the earliest known observations constraining outflow parameters and our analysis indicate that VHE detected bursts could have a diverse range of observed luminosity within the detectable redshift range of present VHE facilities.
We present visual-like morphologies over 16 photometric bands, from ultraviolet to near-infrared, for 8412 galaxies in the Cluster Lensing And Supernova survey with Hubble (CLASH) obtained using a ...convolutional neural network (ConvNet) model. Our model follows the Cosmic Assembly Near-IR Deep Extragalactic Legacy Survey (CANDELS) main morphological classification scheme, obtaining the probability for each galaxy at each CLASH band of being spheroid, disk, irregular, point source, or unclassifiable. Our catalog contains morphologies for each galaxy with Hmag < 24.5 in every filter where the galaxy is observed. We trained an initial ConvNet model using approximately 7500 expert eyeball labels from CANDELS. We created eyeball labels for 100 randomly selected galaxies per each of the 16-filter set of CLASH (1600 galaxy images in total), where each image was classified by at least five of us. We use these labels to fine-tune the network to accurately predict labels for the CLASH data and to evaluate the performance of our model. We achieve a root-mean-square error of 0.0991 on the test set. We show that our proposed fine-tuning technique reduces the number of labeled images needed for training, as compared to directly training over the CLASH data, and achieves a better performance. This approach is very useful to minimize eyeball labeling efforts when classifying unlabeled data from new surveys. This will become particularly useful for massive data sets such as those coming from near-future surveys such as EUCLID or the LSST. Our catalog consists of prediction of probabilities for each galaxy by morphology in their different bands and is made publicly available at http://www.inf.udec.cl/~guille/data/Deep-CLASH.csv.
To compare disk halo size in response to a glare source in eyes with an aspheric apodized diffractive multifocal intraocular lens (IOL) or aspheric monofocal IOL.
Rementeria Ophthalmological Clinic, ...Madrid, Spain.
Prospective randomized masked study.
Halo radius was measured using a vision monitor (MonCv3) with low-luminance optotypes in eyes that had cataract surgery and bilateral implantion of an Acrysof Restor SN6AD1 multifocal IOL or Acrysof IQ monofocal IOL 6 to 9 months previously. The visual angle subtended by the disk halo radius was calculated in minutes of arc (arcmin). Patient complaints of halo disturbances were recorded. Monocular uncorrected distance visual acutity (UDVA) and corrected distance visual acuity (CDVA) were measured using high-contrast (96%) and low-contrast (10%) logMAR letter charts.
The study comprised 39 eyes of 39 subjects (aged 70 to 80 years); 21 eyes had a multifocal IOL and 18 eyes a monofocal IOL. The mean halo radius was 35 arcmin larger in the multifocal IOL group than the monofocal group (P < .05). Greater halo effects were reported in the multifocal IOL group (P < .05). The mean monocular high-contrast UDVA and low-contrast UDVA did not vary significantly between groups, whereas the mean monocular high-contrast CDVA and low-contrast CDVA were significantly worse at 0.12 logMAR and 0.13 logMAR in the multifocal than in the monofocal IOL group, respectively (P < .01). A significant positive correlation was detected by multiple linear regression between the halo radius and low-contrast UDVA in the multifocal IOL group (r = 0.72, P < .001).
The diffractive multifocal IOL gave rise to a larger disk halo size, which was correlated with a worse low-contrast UDVA.
None of the authors has a financial or proprietary interest in any material or method mentioned.
We report on the first star discovered to host a planet detected by radial velocity (RV) observations obtained within the CARMENES survey for exoplanets around M dwarfs. HD 147379 (
V
= 8.9 mag,
M
...= 0.58 ± 0.08
M
⊙
), a bright M0.0 V star at a distance of 10.7 pc, is found to undergo periodic RV variations with a semi-amplitude of
K
= 5.1 ± 0.4 m s
−1
and a period of
P
= 86.54 ± 0.06 d. The RV signal is found in our CARMENES data, which were taken between 2016 and 2017, and is supported by HIRES/Keck observations that were obtained since 2000. The RV variations are interpreted as resulting from a planet of minimum mass
m
P
sin
i
= 25 ± 2
M
⊕
, 1.5 times the mass of Neptune, with an orbital semi-major axis
a
= 0.32 au and low eccentricity (
e
< 0.13). HD 147379 b is orbiting inside the temperate zone around the star, where water could exist in liquid form. The RV time-series and various spectroscopic indicators show additional hints of variations at an approximate period of 21.1 d (and its first harmonic), which we attribute to the rotation period of the star.
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