23 research outputs found

    Amalgame: Cosmological Constraints from the First Combined Photometric Supernova Sample

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    Future constraints of cosmological parameters from Type Ia supernovae (SNe Ia) will depend on the use of photometric samples, those samples without spectroscopic measurements of the SNe Ia. There is a growing number of analyses that show that photometric samples can be utilised for precision cosmological studies with minimal systematic uncertainties. To investigate this claim, we perform the first analysis that combines two separate photometric samples, SDSS and Pan-STARRS, without including a low-redshift anchor. We evaluate the consistency of the cosmological parameters from these two samples and find they are consistent with each other to under 1σ1\sigma. From the combined sample, named Amalgame, we measure ΩM=0.328±0.024\Omega_M = 0.328 \pm 0.024 with SN alone in a flat Λ\LambdaCDM model, and ΩM=0.330±0.018\Omega_M = 0.330 \pm 0.018 and w=−1.016−0.058+0.055w = -1.016^{+0.055}_{-0.058} when combining with a Planck data prior and a flat wwCDM model. These results are consistent with constraints from the Pantheon+ analysis of only spectroscopically confirmed SNe Ia, and show that there are no significant impediments to analyses of purely photometric samples of SNe Ia.Comment: Submitting to MNRAS; comments welcom

    Proteomic and Phospho-Proteomic Profile of Human Platelets in Basal, Resting State: Insights into Integrin Signaling

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    During atherogenesis and vascular inflammation quiescent platelets are activated to increase the surface expression and ligand affinity of the integrin αIIbβ3 via inside-out signaling. Diverse signals such as thrombin, ADP and epinephrine transduce signals through their respective GPCRs to activate protein kinases that ultimately lead to the phosphorylation of the cytoplasmic tail of the integrin αIIbβ3 and augment its function. The signaling pathways that transmit signals from the GPCR to the cytosolic domain of the integrin are not well defined. In an effort to better understand these pathways, we employed a combination of proteomic profiling and computational analyses of isolated human platelets. We analyzed ten independent human samples and identified a total of 1507 unique proteins in platelets. This is the most comprehensive platelet proteome assembled to date and includes 190 membrane-associated and 262 phosphorylated proteins, which were identified via independent proteomic and phospho-proteomic profiling. We used this proteomic dataset to create a platelet protein-protein interaction (PPI) network and applied novel contextual information about the phosphorylation step to introduce limited directionality in the PPI graph. This newly developed contextual PPI network computationally recapitulated an integrin signaling pathway. Most importantly, our approach not only provided insights into the mechanism of integrin αIIbβ3 activation in resting platelets but also provides an improved model for analysis and discovery of PPI dynamics and signaling pathways in the future

    Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

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    Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

    Amalgame: Cosmological Constraints from the First Combined Photometric Supernova Sample

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    International audienceFuture constraints of cosmological parameters from Type Ia supernovae (SNe Ia) will depend on the use of photometric samples, those samples without spectroscopic measurements of the SNe Ia. There is a growing number of analyses that show that photometric samples can be utilised for precision cosmological studies with minimal systematic uncertainties. To investigate this claim, we perform the first analysis that combines two separate photometric samples, SDSS and Pan-STARRS, without including a low-redshift anchor. We evaluate the consistency of the cosmological parameters from these two samples and find they are consistent with each other to under 1σ1\sigma. From the combined sample, named Amalgame, we measure ΩM=0.328±0.024\Omega_M = 0.328 \pm 0.024 with SN alone in a flat Λ\LambdaCDM model, and ΩM=0.330±0.018\Omega_M = 0.330 \pm 0.018 and w=−1.016−0.058+0.055w = -1.016^{+0.055}_{-0.058} when combining with a Planck data prior and a flat wwCDM model. These results are consistent with constraints from the Pantheon+ analysis of only spectroscopically confirmed SNe Ia, and show that there are no significant impediments to analyses of purely photometric samples of SNe Ia

    Amalgame: cosmological constraints from the first combined photometric supernova sample

    No full text
    Future constraints of cosmological parameters from Type Ia supernovae (SNe Ia) will depend on the use of photometric samples, those samples without spectroscopic measurements of the SNe Ia. There is a growing number of analyses that show that photometric samples can be utilised for precision cosmological studies with minimal systematic uncertainties. To investigate this claim, we perform the first analysis that combines two separate photometric samples, SDSS and Pan-STARRS, without including a low-redshift anchor. We evaluate the consistency of the cosmological parameters from these two samples and find they are consistent with each other to under 1σ. From the combined sample, named Amalgame, we measure ΩM=0.328±0.024 with SN alone in a flat ΛCDM model, and ΩM=0.330±0.018 and w=−1.016+0.055−0.058 when combining with a Planck data prior and a flat wCDM model. These results are consistent with constraints from the Pantheon+ analysis of only spectroscopically confirmed SNe Ia, and show that there are no significant impediments to analyses of purely photometric samples of SNe Ia

    Highlights from an Expert Meeting on Opportunities for Cancer Prevention among Older Adults

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    © 2019 Published by Oxford University Press on behalf of The Gerontological Society of America 2019. This paper provides highlights from an expert meeting to explore opportunities to reduce cancer risk and promote health at older ages. Factors that increase cancer risk among older adults include exposure to carcinogens from multiple sources, chronic conditions such as obesity and diabetes, and unhealthy behaviors. Emerging research points to chronic social stressors - social isolation, loneliness, and financial hardship - as being linked to accelerated biological aging and increased cancer risk later in life. Older adults may disproportionately encounter these stressors as well as barriers to preventive health care services, accurate health information, and environments that promote health. Researchers can use existing cohort studies of older adults to deepen our understanding of the relative benefit of modifying specific behaviors and circumstances. The evidence points to the value of comprehensive, transdisciplinary approaches to promote health and reduce cancer risk across the entire lifespan, extending through older adulthood. Clinical encounters with older adults provide opportunities for psychosocial and behavioral screening and counseling. In the presence of multiple morbidities, preventive health services may offer greater health benefits than cancer-screening tests. Strategies that involve families and caregivers, promote positive attitudes about aging, and engage many different community sectors have the potential to prevent or delay the development of cancer at older ages

    Evolution of astacin-like metalloproteases in animals and their function in development

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    Astacin-like metalloproteases are ubiquitous in the animal kingdom but their phylogenetic relationships and ancient functions within the Metazoa are unclear. We have cloned and characterized four astacin-like cDNAs from the marine hydroid Hydractinia echinata and performed a database search for related genes in the draft genome sequence of the sea anemone Nematostella vectensis. These sequences and those of higher animals' astacins were subjected to phylogenetic analysis revealing five clusters within the Eumetazoa. The bone morphogenetic protein-1/tolloid-like astacins were represented in all eumetazoan phyla studied. The meprins were only found in vertebrates and cnidarians. Two clusters were taxon-specific, and one cluster represented astacins, which probably evolved after the split of the Cnidaria. Interestingly, grouping of astacins according to the protease catalytic domain alone resulted in clusters of proteins with similar overall domain architecture. The Hydractinia astacins were expressed in distinct cells during metamorphosis and some also during wound healing. Previously characterized cnidarian astacins also act during development. Based on our phylogeny, however, we propose that the developmental function of most of them is not homologous to the developmental function assigned to higher animals' astacins
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