We study the time lags between the continuum emission of quasars at different wavelengths, based on more than four years of multi-band (g, r, i, z) light curves in the Pan-STARRS Medium Deep Fields. ...As photons from different bands emerge from different radial ranges in the accretion disk, the lags constrain the sizes of the accretion disks. We select 240 quasars with redshifts of z 1 or z 0.3 that are relatively emission-line free. The light curves are sampled from day to month timescales, which makes it possible to detect lags on the scale of the light crossing time of the accretion disks. With the code JAVELIN, we detect typical lags of several days in the rest frame between the g band and the riz bands. The detected lags are ∼2-3 times larger than the light crossing time estimated from the standard thin disk model, consistent with the recently measured lag in NGC 5548 and microlensing measurements of quasars. The lags in our sample are found to increase with increasing luminosity. Furthermore, the increase in lags going from g − r to g − i and then to g − z is slower than predicted in the thin disk model, particularly for high-luminosity quasars. The radial temperature profile in the disk must be different from what is assumed. We also find evidence that the lags decrease with increasing line ratios between ultraviolet Fe ii lines and Mg ii, which may point to changes in the accretion disk structure at higher metallicity.
ABSTRACT Luminous quasars at can be studied in detail with the current generation of telescopes and provide us with unique information on the first gigayear of the universe. Thus far, these studies ...have been statistically limited by the number of quasars known at these redshifts. Such quasars are rare, and therefore, wide-field surveys are required to identify them, and multiwavelength data are required to separate them efficiently from their main contaminants, the far more numerous cool dwarfs. In this paper, we update and extend the selection for the quasars presented in Bañados et al. (2014) using the Pan-STARRS1 (PS1) survey. We present the PS1 distant quasar sample, which currently consists of 124 quasars in the redshift range that satisfy our selection criteria. Of these quasars, 77 have been discovered with PS1, and 63 of them are newly identified in this paper. We present the composite spectra of the PS1 distant quasar sample. This sample spans a factor of ∼20 in luminosity and shows a variety of emission line properties. The number of quasars at presented in this work almost doubles the previously known quasars at these redshifts, marking a transition phase from studies of individual sources to statistical studies of the high-redshift quasar population, which was impossible with earlier, smaller samples.
Cystic fibrosis (CF) transmembrane conductance regulator (CFTR) is expressed in the epithelial cells of a wide range of organs/tissues from which most cancers are derived. Although accumulating ...reports have indicated the association of cancer incidence with genetic variations in CFTR gene, the exact role of CFTR in cancer development and the possible underlying mechanism have not been elucidated. Here, we report that CFTR expression is significantly decreased in both prostate cancer cell lines and human prostate cancer tissue samples. Overexpression of CFTR in prostate cancer cell lines suppresses tumor progression (cell growth, adhesion and migration), whereas knockdown of CFTR leads to enhanced malignancies both in vitro and in vivo. In addition, we demonstrate that CFTR knockdown-enhanced cell proliferation, cell invasion and migration are significantly reversed by antibodies against either urokinase plasminogen activator (uPA) or uPA receptor (uPAR), which are known to be involved in various malignant traits of cancer development. More interestingly, overexpression of CFTR suppresses uPA by upregulating the recently described tumor suppressor microRNA-193b (miR-193b), and overexpression of pre-miR-193b significantly reverses CFTR knockdown-enhanced malignant phenotype and abrogates elevated uPA activity in prostate cancer cell line. Finally, we show that CFTR gene transfer results in significant tumor repression in prostate cancer xenografts in vivo. Taken together, the present study has demonstrated a previously undefined tumor-suppressing role of CFTR and its involvement in regulation of miR-193b in prostate cancer development.
A subset of glutamate receptors that are specifically sensitive to the glutamate analog N-methyl-D-aspartate (NMDA) are molecular coincidence detectors, necessary for activity-dependent processes of ...neurodevelopment and in sensory and cognitive functions. The activity of these receptors is modulated by the endogenous amino acid D-serine, but the extent to which D-serine is necessary for the normal development and function of the mammalian nervous system was previously unknown. Decreased signaling at NMDA receptors has been implicated in the pathophysiology of schizophrenia based on pharmacological evidence, and several human genes related to D-serine metabolism and glutamatergic neurotransmission have been implicated in the etiology of schizophrenia. Here we show that genetically modified mice lacking the ability to produce D-serine endogenously have profoundly altered glutamatergic neurotransmission, and relatively subtle but significant behavioral abnormalities that reflect hyperactivity and impaired spatial memory, and that are consistent with elevated anxiety.
Long-term secular variation in the isotopic composition of seawater fixed nitrogen (N) is poorly known. Here, we document variation in the N-isotopic composition of marine sediments (δ15Nsed) since ...660 Ma (million years ago) in order to understand major changes in the marine N cycle through time and their relationship to first-order climate variation. During the Phanerozoic, greenhouse climate modes were characterized by low δ15Nsed (∼−2 to +2‰) and icehouse climate modes by high δ15Nsed (∼+4 to +8‰). Shifts toward higher δ15Nsed occurred rapidly during the early stages of icehouse modes, prior to the development of major continental glaciation, suggesting a potentially important role for the marine N cycle in long-term climate change. Reservoir box modeling of the marine N cycle demonstrates that secular variation in δ15Nsed was likely due to changes in the dominant locus of denitrification, with a shift in favor of sedimentary denitrification during greenhouse modes owing to higher eustatic (global sea-level) elevations and greater on-shelf burial of organic matter, and a shift in favor of water-column denitrification during icehouse modes owing to lower eustatic elevations, enhanced organic carbon sinking fluxes, and expanded oceanic oxygen-minimum zones. The results of this study provide new insights into operation of the marine N cycle, its relationship to the global carbon cycle, and its potential role in modulating climate change at multimillion-year timescales.
Two-Dimensional Atomic Crystals Novoselov, K. S.; Jiang, D.; Schedin, F. ...
Proceedings of the National Academy of Sciences - PNAS,
07/2005, Letnik:
102, Številka:
30
Journal Article
Recenzirano
Odprti dostop
We report free-standing atomic crystals that are strictly 2D and can be viewed as individual atomic planes pulled out of bulk crystals or as unrolled single-wall nanotubes. By using micromechanical ...cleavage, we have prepared and studied a variety of 2D crystals including single layers of boron nitride, graphite, several dichalcogenides, and complex oxides. These atomically thin sheets (essentially gigantic 2D molecules unprotected from the immediate environment) are stable under ambient conditions, exhibit high crystal quality, and are continuous on a macroscopic scale.
A composite coating of N-doped graphene quantum dots (N-GQDs)/polymethyltrimethoxysilane (PMTMS) is prepared on the surface of AZ91D magnesium alloy via electrodeposition and subsequent silane ...treatment. The microstructure of the N-GQDs/PMTMS composite coating is characterized by field emission scanning electron microscopy (FE-SEM), energy dispersive X-ray spectroscopy (EDS), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS) and Raman spectroscopy. The corrosion resistance performance is investigated by electrochemical impedance spectroscopy (EIS) and immersion test in NaCl solution (3.5 wt%). The N-GQDs/PMTMS composite coating exhibits a significant enhancement of corrosion resistance due to the chemical bonding of N-GQDs coating with Mg substrate and PMTMS coating. The formation mechanisms and nature of the corrosion resistance of the N-GQDs/PMTMS coating are discussed.
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Abstract
The in vivo role for RNase H1 in mammalian mitochondria has been much debated. Loss of RNase H1 is embryonic lethal and to further study its role in mtDNA expression we characterized a ...conditional knockout of Rnaseh1 in mouse heart. We report that RNase H1 is essential for processing of RNA primers to allow site-specific initiation of mtDNA replication. Without RNase H1, the RNA:DNA hybrids at the replication origins are not processed and mtDNA replication is initiated at non-canonical sites and becomes impaired. Importantly, RNase H1 is also needed for replication completion and in its absence linear deleted mtDNA molecules extending between the two origins of mtDNA replication are formed accompanied by mtDNA depletion. The steady-state levels of mitochondrial transcripts follow the levels of mtDNA, and RNA processing is not altered in the absence of RNase H1. Finally, we report the first patient with a homozygous pathogenic mutation in the hybrid-binding domain of RNase H1 causing impaired mtDNA replication. In contrast to catalytically inactive variants of RNase H1, this mutant version has enhanced enzyme activity but shows impaired primer formation. This finding shows that the RNase H1 activity must be strictly controlled to allow proper regulation of mtDNA replication.
Background:
MicroRNAs (miRNAs) are known to regulate the inflammatory response in various cell types. However, the ability of miRNAs to modulate dendritic cells (DCs) function for allergen ...immunotherapy is unclear.
Objective:
To assess the role of miR‐23b in the regulation of ovalbumin (OVA)‐induced DC differentiation and function and to investigate the related molecular mechanisms.
Methods:
Bone marrow‐derived dendritic cells (BMDCs) were generated from murine bone marrow progenitor cells and subsequently stimulated with OVA to examine the profile of miRNA expression. After transfection with miR‐23b reagents, DCs were evaluated for endocytic ability, surface marker expression, cytokine secretion and CD4+ T‐cell differentiation. The possible roles of the Notch and NF‐κB signalling pathways were also evaluated. Human monocyte‐derived dendritic cells (MDDCs) were similarly evaluated as well.
Results:
Significant upregulation of miR‐23b was observed in BMDCs pulsed with OVA. Following miR‐23b transfection, BMDCs showed decreased OVA uptake, increased IL‐10 production, decreased IL‐12 production and an enhanced capacity to promote FoxP3+ CD4+ T regulatory cells (Tregs) differentiation. In addition, inactivation of the Notch1 and NF‐κB signalling pathways were observed. Conversely, inhibition of miR‐23b in BMDCs resulted in the opposite effects. In human MDDCs, miRNA23b transfection similarly increased IL‐10 and decreased IL‐12 production, and that treated human MDDCs induced increased FoxP3+ CD4+ T cells.
Conclusion:
Our findings provide evidence that miR‐23b is capable of inducing tolerogenic DC activity and Treg responses in vitro through the inhibition of the Notch1 and NF‐κB signalling pathways; thus, miR‐23b might represent a therapeutic target for the management of allergic diseases.
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