178 research outputs found
SN 2006bp: Probing the Shock Breakout of a Type II-P Supernova
HET optical spectroscopy and unfiltered ROTSE-III photometry spanning the
first 11 months since explosion of the Type II-P SN 2006bp are presented. Flux
limits from the days before discovery combined with the initial rapid
brightening suggest the supernova was first detected just hours after shock
breakout. Optical spectra obtained about 2 days after breakout exhibit narrow
emission lines corresponding to HeII 4200, HeII 4686, and CIV 5805 in the rest
frame, and these features persist in a second observation obtained 5 hours
later; however, these emission lines are not detected the following night nor
in subsequent observations. We suggest that these lines emanate from material
close to the explosion site, possibly in the outer layers of the progenitor
that have been ionized by the high energy photons released at shock breakout. A
P-Cygni profile is observed around 4450 A in the +2 and +3 day spectra.
Previous studies have attributed this feature to high velocity H-beta, but we
discuss the possibility that this profile is instead due to HeII 4687. Further
HET observations (14 nights in total) covering the spectral evolution across
the photometric plateau up to 73 days after breakout and during the nebular
phase around day +340 are presented, and expansion velocities are derived for
key features. The measured decay slope for the unfiltered light curve is 0.0073
+/- 0.0004 mag/day between days +121 and +335, which is significantly slower
than the decay of rate 56Co. We combine our HET measurements with published
X-ray, UV, and optical data to obtain a quasi-bolometric light curve through
day +60. We see a slow cooling over the first 25 days, but no sign of an early
sharp peak; any such feature from the shock breakout must have lasted less than
~1 day.[ABRIDGED]Comment: ApJ accepted, 43 page
Geospatial Planning and the Resulting Economic Impact of Human Papillomavirus Vaccine Introduction in Mozambique
Research has shown that the distance to the nearest immunization location can ultimately prevent someone from getting immunized. With the introduction of human papillomavirus (HPV) vaccine throughout the world, a major question is whether the target populations can readily access immunization
Ultraconserved elements-based phylogenomic systematics of the snake superfamily Elapoidea, with the description of a new Afro-Asian family
The highly diverse snake superfamily Elapoidea is considered to be a classic example of ancient, rapid radiation. Such radiations are challenging to fully resolve phylogenetically, with the highly diverse Elapoidea a case in point. Previous attempts at inferring a phylogeny of elapoids produced highly incongruent estimates of their evolutionary relationships, often with very low statistical support. We sought to resolve this situation by sequencing over 4,500 ultraconserved element loci from multiple representatives of every elapoid family/sub-family level taxon and inferring their phylogenetic relationships with multiple methods. Concatenation and multispecies coalescent based species trees yielded largely congruent and well-supported topologies. Hypotheses of a hard polytomy were not retained for any deep branches. Our phylogenies recovered Cyclocoridae and Elapidae as diverging early within Elapoidea. The Afro-Malagasy radiation of elapoid snakes, classified as multiple subfamilies of an inclusive Lamprophiidae by some earlier authors, was found to be monophyletic in all analyses. The genus Micrelaps was consistently recovered as sister to Lamprophiidae. We establish a new family, Micrelapidae fam. nov., for Micrelaps and assign Brachyophis to this family based on cranial osteological syn-apomorphy. We estimate that Elapoidea originated in the early Eocene and rapidly diversified into all the major lineages during this epoch. Ecological opportunities presented by the post-Cretaceous-Paleogene mass extinction event may have promoted the explosive radiation of elapoid snakes.Peer reviewe
How Coupling Determines the Entrainment of Circadian Clocks
Autonomous circadian clocks drive daily rhythms in physiology and behaviour.
A network of coupled neurons, the suprachiasmatic nucleus (SCN), serves as a
robust self-sustained circadian pacemaker. Synchronization of this timer to the
environmental light-dark cycle is crucial for an organism's fitness. In a
recent theoretical and experimental study it was shown that coupling governs
the entrainment range of circadian clocks. We apply the theory of coupled
oscillators to analyse how diffusive and mean-field coupling affects the
entrainment range of interacting cells. Mean-field coupling leads to amplitude
expansion of weak oscillators and, as a result, reduces the entrainment range.
We also show that coupling determines the rigidity of the synchronized SCN
network, i.e. the relaxation rates upon perturbation. %(Floquet exponents). Our
simulations and analytical calculations using generic oscillator models help to
elucidate how coupling determines the entrainment of the SCN. Our theoretical
framework helps to interpret experimental data
Emerging Roles of PAR-1 and PAFR in Melanoma Metastasis
Melanoma growth, angiogenesis and metastatic progression are strongly promoted by the inflammatory tumor microenvironment due to high levels of cytokine and chemokine secretion by the recruited inflammatory and stromal cells. In addition, platelets and molecular components of procoagulant pathways have been recently emerging as critical players of tumor growth and metastasis. In particular, thrombin, through the activity of its receptor protease-activated receptor-1 (PAR-1), regulates tumor cell adhesion to platelets and endothelial cells, stimulates tumor angiogenesis, and promotes tumor growth and metastasis. Notably, in many tumor types including melanoma, PAR-1 expression directly correlates with their metastatic phenotype and is directly responsible for the expression of interleukin-8, matrix metalloproteinase-2 (MMP-2), vascular endothelial growth factor, platelet-derived growth factor, and integrins. Another proinflammatory receptor–ligand pair, platelet-activating factor (PAF) and its receptor (PAFR), have been shown to act as important modulators of tumor cell adhesion to endothelial cells, angiogenesis, tumor growth and metastasis. PAF is a bioactive lipid produced by a variety of cells from membrane glycerophospholipids in the same reaction that releases arachidonic acid, and can be secreted by platelets, inflammatory cells, keratinocytes and endothelial cells. We have demonstrated that in metastatic melanoma cells, PAF stimulates the phosphorylation of cyclic adenosine monophosphate response element-binding protein (CREB) and activating transcription factor 1 (ATF-1), which results in overexpression of MMP-2 and membrane type 1-MMP (membrane type 1-MMP). Since only metastatic melanoma cells overexpress CREB/ATF-1, we propose that metastatic melanoma cells are better equipped than their non-metastatic counterparts to respond to PAF within the tumor microenvironment. The evidence supporting the hypothesis that the two G-protein coupled receptors, PAR-1 and PAFR, contribute to the acquisition of the metastatic phenotype of melanoma is presented and discussed
Fine-mapping of prostate cancer susceptibility loci in a large meta-analysis identifies candidate causal variants
Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling. © 2018 The Author(s).Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling. © 2018 The Author(s).Peer reviewe
Germline variation at 8q24 and prostate cancer risk in men of European ancestry
Chromosome 8q24 is a susceptibility locus for multiple cancers, including prostate cancer. Here we combine genetic data across the 8q24 susceptibility region from 71,535 prostate cancer cases and 52,935 controls of European ancestry to define the overall contribution of germline variation at 8q24 to prostate cancer risk. We identify 12 independent risk signals for prostate cancer (p < 4.28 × 10−15), including three risk variants that have yet to be reported. From a polygenic risk score (PRS) model, derived to assess the cumulative effect of risk variants at 8q24, men in the top 1% of the PRS have a 4-fold (95%CI = 3.62–4.40) greater risk compared to the population average. These 12 variants account for ~25% of what can be currently explained of the familial risk of prostate cancer by known genetic risk factors. These findings highlight the overwhelming contribution of germline variation at 8q24 on prostate cancer risk which has implications for population risk stratification
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