169 research outputs found
Age constraints on the dispersal of dinosaurs in the Late Triassic from magnetochronology of the Los Colorados Formation (Argentina)
A measured magnetozone sequence defined by 24 sampling sites with normal polarity and 28 sites with reverse polarity characteristic magnetizations was established for the heretofore poorly age-constrained Los Colorados Formation and its dinosaur-bearing vertebrate fauna in the Ischigualasto–Villa Union continental rift basin of Argentina. The polarity pattern in this ∼600-m-thick red-bed section can be correlated to Chrons E7r to E15n of the Newark astrochronological polarity time scale. This represents a time interval from 227 to 213 Ma, indicating that the Los Colorados Formation is predominantly Norian in age, ending more than 11 My before the onset of the Jurassic. The magnetochronology confirms that the underlying Ischigualasto Formation and its vertebrate assemblages including some of the earliest known dinosaurs are of Carnian age. The oldest dated occurrences of vertebrate assemblages with dinosaurs in North America (Chinle Formation) are younger (Norian), and thus the rise of dinosaurs was diachronous across the Americas. Paleogeography of the Ischigualasto and Los Colorados Formations indicates prolonged residence in the austral temperate humid belt where a provincial vertebrate fauna with early dinosaurs may have incubated. Faunal dispersal across the Pangean supercontinent in the development of more cosmopolitan vertebrate assemblages later in the Norian may have been in response to reduced contrasts between climate zones and lowered barriers resulting from decreasing atmospheric pCO2 levels
The Hydrogen Epoch of Reionization Array Dish II: Characterization of Spectral Structure with Electromagnetic Simulations and its science Implications
We use time-domain electromagnetic simulations to determine the spectral
characteristics of the Hydrogen Epoch of Reionization Arrays (HERA) antenna.
These simulations are part of a multi-faceted campaign to determine the
effectiveness of the dish's design for obtaining a detection of redshifted 21
cm emission from the epoch of reionization. Our simulations show the existence
of reflections between HERA's suspended feed and its parabolic dish reflector
that fall below -40 dB at 150 ns and, for reasonable impedance matches, have a
negligible impact on HERA's ability to constrain EoR parameters. It follows
that despite the reflections they introduce, dishes are effective for
increasing the sensitivity of EoR experiments at relatively low cost. We find
that electromagnetic resonances in the HERA feed's cylindrical skirt, which is
intended to reduce cross coupling and beam ellipticity, introduces significant
power at large delays ( dB at 200 ns) which can lead to some loss of
measurable Fourier modes and a modest reduction in sensitivity. Even in the
presence of this structure, we find that the spectral response of the antenna
is sufficiently smooth for delay filtering to contain foreground emission at
line-of-sight wave numbers below Mpc, in
the region where the current PAPER experiment operates. Incorporating these
results into a Fisher Matrix analysis, we find that the spectral structure
observed in our simulations has only a small effect on the tight constraints
HERA can achieve on parameters associated with the astrophysics of
reionization.Comment: Accepted to ApJ, 18 pages, 17 Figures. Replacement matches accepted
manuscrip
The Hydrogen Epoch of Reionization Array Dish I: Beam Pattern Measurements and Science Implications
The Hydrogen Epoch of Reionization Array (HERA) is a radio interferometer
aiming to detect the power spectrum of 21 cm fluctuations from neutral hydrogen
from the Epoch of Reionization (EOR). Drawing on lessons from the Murchison
Widefield Array (MWA) and the Precision Array for Probing the Epoch of
Reionization (PAPER), HERA is a hexagonal array of large (14 m diameter) dishes
with suspended dipole feeds. Not only does the dish determine overall
sensitivity, it affects the observed frequency structure of foregrounds in the
interferometer. This is the first of a series of four papers characterizing the
frequency and angular response of the dish with simulations and measurements.
We focus in this paper on the angular response (i.e., power pattern), which
sets the relative weighting between sky regions of high and low delay, and
thus, apparent source frequency structure. We measure the angular response at
137 MHz using the ORBCOMM beam mapping system of Neben et al. We measure a
collecting area of 93 m^2 in the optimal dish/feed configuration, implying
HERA-320 should detect the EOR power spectrum at z~9 with a signal-to-noise
ratio of 12.7 using a foreground avoidance approach with a single season of
observations, and 74.3 using a foreground subtraction approach. Lastly we study
the impact of these beam measurements on the distribution of foregrounds in
Fourier space.Comment: 13 pages, 9 figures. Replaced to match accepted ApJ versio
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Widespread carbon-bearing materials on near-Earth asteroid (101955) Bennu
(101955) Bennu is a dark asteroid on an Earth-crossing orbit, thought to have assembled from the fragments of an ancient collision. We use spatially-resolved visible and near-infrared spectra of Bennu to investigate its surface properties and composition. In addition to a hydrated phyllosilicate band, we detect a ubiquitous 3.4-micron absorption feature, which we attribute to a mix of organic and carbonate materials. The shape and depth of this absorption feature vary across Bennu’s surface, spanning the range seen among similar main-belt asteroids. Its distribution does not correlate with temperature, reflectance, spectral slope, or hydrated minerals, although some of those characteristics correlate with each other. The deepest 3.4-micron absorptions occur on individual boulders. The variations may be due to differences in abundance, recent exposure, or space weathering
Fine-mapping of the HNF1B multicancer locus identifies candidate variants that mediate endometrial cancer risk.
Common variants in the hepatocyte nuclear factor 1 homeobox B (HNF1B) gene are associated with the risk of Type II diabetes and multiple cancers. Evidence to date indicates that cancer risk may be mediated via genetic or epigenetic effects on HNF1B gene expression. We previously found single-nucleotide polymorphisms (SNPs) at the HNF1B locus to be associated with endometrial cancer, and now report extensive fine-mapping and in silico and laboratory analyses of this locus. Analysis of 1184 genotyped and imputed SNPs in 6608 Caucasian cases and 37 925 controls, and 895 Asian cases and 1968 controls, revealed the best signal of association for SNP rs11263763 (P = 8.4 × 10(-14), odds ratio = 0.86, 95% confidence interval = 0.82-0.89), located within HNF1B intron 1. Haplotype analysis and conditional analyses provide no evidence of further independent endometrial cancer risk variants at this locus. SNP rs11263763 genotype was associated with HNF1B mRNA expression but not with HNF1B methylation in endometrial tumor samples from The Cancer Genome Atlas. Genetic analyses prioritized rs11263763 and four other SNPs in high-to-moderate linkage disequilibrium as the most likely causal SNPs. Three of these SNPs map to the extended HNF1B promoter based on chromatin marks extending from the minimal promoter region. Reporter assays demonstrated that this extended region reduces activity in combination with the minimal HNF1B promoter, and that the minor alleles of rs11263763 or rs8064454 are associated with decreased HNF1B promoter activity. Our findings provide evidence for a single signal associated with endometrial cancer risk at the HNF1B locus, and that risk is likely mediated via altered HNF1B gene expression
The long term vaccine-induced anti-SARS-CoV-2 immune response is impaired in quantity and quality under TNFα blockade
The humoral immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination in patients with chronic inflammatory disease (CID) declines more rapidly with tumor necrosis factor-α (TNF-α) inhibition. Furthermore, the efficacy of current vaccines against Omicron variants of concern (VOC) including BA.2 is limited. Alterations within immune cell populations, changes in IgG affinity, and the ability to neutralize a pre-VOC strain and the BA.2 virus were investigated in these at-risk patients. Serum levels of anti-SARS-CoV-2 IgG, IgG avidity, and neutralizing antibodies (NA) were determined in anti-TNF-α patients (n = 10) and controls (n = 24 healthy individuals; n = 12 patients under other disease-modifying antirheumatic drugs, oDMARD) before and after the second and third vaccination by ELISA, immunoblot and live virus neutralization assay. SARS-CoV-2-specific B- and T cell subsets were analysed by multicolor flow cytometry. Six months after the second vaccination, anti-SARS-CoV-2 IgG levels, IgG avidity and anti-pre-VOC NA titres were significantly reduced in anti-TNF-α recipients compared to controls (healthy individuals: avidity: p ≤ 0.0001; NA: p = 0.0347; oDMARDs: avidity: p = 0.0012; NA: p = 0.0293). The number of plasma cells was increased in anti-TNF-α patients (Healthy individuals: p = 0.0344; oDMARDs: p = 0.0254), while the absolute number of SARS-CoV-2-specific plasma cells 7 days after 2nd vaccination were comparable. Even after a third vaccination, these patients had lower anti-BA.2 NA titres compared to both other groups. We show a reduced SARS-CoV-2 neutralizing capacity in patients under TNF-α blockade. While these effects were observable after the first two vaccinations and with older VOC, the differences in responses to BA.2 were enhanced
Mechanistic insight into RET kinase inhibitors targeting the DFG-out conformation in RET-rearranged cancer
Oncogenic fusion events have been identified in a broad range of tumors. Among them, RET rearrangements represent distinct and potentially druggable targets that are recurrently found in lung adenocarcinomas. Here, we provide further evidence that current anti-RET drugs may not be potent enough to induce durable responses in such tumors. We report that potent inhibitors such as AD80 or ponatinib that stably bind in the DFG-out conformation of RET may overcome these limitations and selectively kill RET-rearranged tumors. Using chemical genomics in conjunction with phosphoproteomic analyses in RET-rearranged cells we identify the CCDC6-RETI788N mutation and drug-induced MAPK pathway reactivation as possible mechanisms, by which tumors may escape the activity of RET inhibitors. Our data provide mechanistic insight into the druggability of RET kinase fusions that may be of help for the development of effective therapies targeting such tumors
Tumor Necrosis Factor Receptor Associated Factor 6 Is Not Required for Atherogenesis in Mice and Does Not Associate with Atherosclerosis in Humans
BACKGROUND: Tumor necrosis factor receptor-associated factors (TRAFs) are important signaling molecules for a variety of pro-atherogenic cytokines including CD40L, TNF alpha, and IL1beta. Several lines of evidence identified TRAF6 as a pro-inflammatory signaling molecule in vitro and we previously demonstrated overexpression of TRAF6 in human and Murine atherosclerotic plaques. This study investigated the role of TRAF6-deficiency in mice developing atherosclerosis, a chronic inflammatory disease. METHODOLOGY/PRINCIPAL FINDINGS: Lethally irradiated low density lipoprotein receptor-deficient mice (TRAF6(+/+)/LDLR(-/-)) were reconstituted with TRAF6-deficient fetal liver cells (FLC) and consumed high cholesterol diet for 18 weeks to assess the relevance of TRAF6 in hematopoietic cells for atherogenesis. Additionally, TRAF6(+/-)/LDLR(-/-) mice received TRAF6-deficient FLC to gain insight into the role of TRAF6 deficiency in resident cells. Surprisingly, atherosclerotic lesion size did not differ between the three groups in both aortic roots and abdominal aortas. Similarly, no significant differences in plaque composition could be observed as assessed by immunohistochemistry for macrophages, lipids, smooth muscle cells, T-cells, and collagen. In accord, in a small clinical study TRAF6/GAPDH total blood RNA ratios did not differ between groups of patients with stable coronary heart disease (0.034+/-0.0021, N = 178), acute coronary heart disease (0.029+/-0.0027, N = 70), and those without coronary heart disease (0.032+/-0.0016, N = 77) as assessed by angiography. CONCLUSION: Our study demonstrates that TRAF6 is not required for atherogenesis in mice and does not associate with clinical disease in humans. These data suggest that pro- and anti-inflammatory features of TRAF6 signaling outweigh each other in the context of atherosclerosis
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