209 research outputs found
Funding liquidity, market liquidity and TED spread: A two-regime model
We investigate the effect of market liquidity on equity-collateralized funding accounting for endogeneity. Theory suggests market liquidity can affect funding liquidity in stabilizing and destabilizing manners. Using the average fee on stock loans as a proxy for equity-collateralized funding liquidity, we confirm the existence of these two regimes over the period of July 2006 â May 2011. Furthermore, we show that we can separate the two regimes using the yield spread of Eurodollars over T-bills (TED spread) and that a regime switch seems to occur near a TED spread of 48 basis points
CD36 promotes vasculogenic mimicry in melanoma by mediating adhesion to the extracellular matrix
Background: The formation of blood vessels within solid tumors directly contributes to cancer growth and metastasis. Until recently, tumor vasculature was thought to occur exclusively via endothelial cell (EC) lined structures (i.e. angiogenesis), but a second source of tumor vasculature arises from the cancer cells themselves, a process known as vasculogenic mimicry (VM). While it is generally understood that the function of VM vessels is the same as that of EC-lined vessels (i.e. to supply oxygen and nutrients to the proliferating cancer cells), the molecular mechanisms underpinning VM are yet to be fully elucidated. Methods: Human VM-competent melanoma cell lines were examined for their VM potential using the in vitro angiogenesis assays (Matrigel), together with inhibition studies using small interfering RNA and blocking monoclonal antibodies. Invasion assays and adhesion assays were used to examine cancer cell function. Results: Herein we demonstrate that CD36, a cell surface glycoprotein known to promote angiogenesis by ECs, also supports VM formation by human melanoma cancer cells. In silico analysis of CD36 expression within the melanoma cohort of The Cancer Genome Atlas suggests that melanoma patients with high expression of CD36 have a poorer clinical outcome. Using in vitro âangiogenesisâ assays and CD36-knockdown approaches, we reveal that CD36 supports VM formation by human melanoma cells as well as adhesion to, and invasion through, a cancer derived extracellular matrix substrate. Interestingly, thrombospondin-1 (TSP-1), a ligand for CD36 on ECs that inhibits angiogenesis, has no effect on VM formation. Further investigation revealed a role for laminin, but not collagen or fibronectin, as ligands for CD36 expressing melanoma cells. Conclusions: Taken together, this study suggests that CD36 is a novel regulator of VM by melanoma cancer cells that is facilitated, at least in part, via integrin-α3 and laminin. Unlike angiogenesis, VM is not perturbed by the presence of TSP-1, thus providing new information on differences between these two processes of tumor vascularization which may be exploited to combat cancer progression.Carmela Martini, Mark DeNichilo, Danielle P. King, Michaelia P. Cockshell, Brenton Ebert, Brian Dale, Lisa M. Ebert, Anthony Woods, and Claudine S. Bonde
Can forest management based on natural disturbances maintain ecological resilience?
Given the increasingly global stresses on forests, many ecologists argue that managers must maintain ecological resilience: the capacity of ecosystems to absorb disturbances without undergoing fundamental change. In this review we ask: Can the emerging paradigm of natural-disturbance-based management (NDBM) maintain ecological resilience in managed forests? Applying resilience theory requires careful articulation of the ecosystem state under consideration, the disturbances and stresses that affect the persistence of possible alternative states, and the spatial and temporal scales of management relevance. Implementing NDBM while maintaining resilience means recognizing that (i) biodiversity is important for long-term ecosystem persistence, (ii) natural disturbances play a critical role as a generator of structural and compositional heterogeneity at multiple scales, and (iii) traditional management tends to produce forests more homogeneous than those disturbed naturally and increases the likelihood of unexpected catastrophic change by constraining variation of key environmental processes. NDBM may maintain resilience if silvicultural strategies retain the structures and processes that perpetuate desired states while reducing those that enhance resilience of undesirable states. Such strategies require an understanding of harvesting impacts on slow ecosystem processes, such as seed-bank or nutrient dynamics, which in the long term can lead to ecological surprises by altering the forest's capacity to reorganize after disturbance
Thimet oligopeptidase (EC 3.4.24.15) key functions suggested by knockout mice phenotype characterization
Thimet oligopeptidase (THOP1) is thought to be involved in neuropeptide metabolism, antigen presentation, neurodegeneration, and cancer. Herein, the generation of THOP1 C57BL/6 knockout mice (THOP1(-/-)) is described showing that they are viable, have estrus cycle, fertility, and a number of puppies per litter similar to C57BL/6 wild type mice (WT). In specific brain regions, THOP1(-/-) exhibit altered mRNA expression of proteasome beta5, serotonin 5HT2a receptor and dopamine D2 receptor, but not of neurolysin (NLN). Peptidomic analysis identifies differences in intracellular peptide ratios between THOP1(-/-) and WT mice, which may affect normal cellular functioning. In an experimental model of multiple sclerosis THOP1(-/-) mice present worse clinical behavior scores compared to WT mice, corroborating its possible involvement in neurodegenerative diseases. THOP1(-/-) mice also exhibit better survival and improved behavior in a sepsis model, but also a greater peripheral pain sensitivity measured in the hot plate test after bradykinin administration in the paw. THOP1(-/-) mice show depressive-like behavior, as well as attention and memory retention deficits. Altogether, these results reveal a role of THOP1 on specific behaviors, immune-stimulated neurodegeneration, and infection-induced inflammation
Quasar Accretion Disk Sizes from Continuum Reverberation Mapping in the DES Standard-star Fields
Measurements of the physical properties of accretion disks in active galactic nuclei are important for better understanding the growth and evolution of supermassive black holes. We present the accretion disk sizes of 22 quasars from continuum reverberation mapping with data from the Dark Energy Survey (DES) standard-star fields and the supernova C fields. We construct continuum light curves with the griz photometry that span five seasons of DES observations. These data sample the time variability of the quasars with a cadence as short as 1 day, which corresponds to a rest-frame cadence that is a factor of a few higher than most previous work. We derive time lags between bands with both JAVELIN and the interpolated cross-correlation function method and fit for accretion disk sizes using the JAVELIN thin-disk model. These new measurements include disks around black holes with masses as small as ~107 M â, which have equivalent sizes at 2500 A as small as ~0.1 lt-day in the rest frame. We find that most objects have accretion disk sizes consistent with the prediction of the standard thin-disk model when we take disk variability into account. We have also simulated the expected yield of accretion disk measurements under various observational scenarios for the Large Synoptic Survey Telescope Deep Drilling Fields. We find that the number of disk measurements would increase significantly if the default cadence is changed from 3 days to 2 days or 1 day
Quasar Accretion Disk Sizes from Continuum Reverberation Mapping from the Dark Energy Survey
We present accretion disk size measurements for 15 luminous quasars at 0.7 †z †1.9 derived from griz light curves from the Dark Energy Survey. We measure the disk sizes with continuum reverberation mapping using two methods, both of which are derived from the expectation that accretion disks have a radial temperature gradient and the continuum emission at a given radius is well described by a single blackbody. In the first method we measure the relative lags between the multiband light curves, which provides the relative time lag between shorter and longer wavelength variations. From this, we are only able to constrain upper limits on disk sizes, as many are consistent with no lag the 2Ï level. The second method fits the model parameters for the canonical thin disk directly rather than solving for the individual time lags between the light curves. Our measurements demonstrate good agreement with the sizes predicted by this model for accretion rates between 0.3 and 1 times the Eddington rate. Given our large uncertainties, our measurements are also consistent with disk size measurements from gravitational microlensing studies of strongly lensed quasars, as well as other photometric reverberation mapping results, that find disk sizes that are a factor of a few (âŒ3) larger than predictions
Measurement of the top pair production cross section in 8 TeV proton-proton collisions using kinematic information in the lepton plus jets final state with ATLAS
A measurement is presented of the inclusive production
cross-section in collisions at a center-of-mass energy of TeV
using data collected by the ATLAS detector at the CERN Large Hadron Collider.
The measurement was performed in the lepton+jets final state using a data set
corresponding to an integrated luminosity of 20.3 fb. The cross-section
was obtained using a likelihood discriminant fit and -jet identification was
used to improve the signal-to-background ratio. The inclusive
production cross-section was measured to be
pb assuming a top-quark mass of 172.5 GeV, in good agreement with the
theoretical prediction of pb. The production cross-section in the fiducial region
determined by the detector acceptance is also reported.Comment: Published version, 19 pages plus author list (35 pages total), 3
figures, 2 tables, all figures including auxiliary figures are available at
http://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/TOPQ-2013-06
Improving Genetic Prediction by Leveraging Genetic Correlations Among Human Diseases and Traits
Genomic prediction has the potential to contribute to precision medicine. However, to date, the utility of such predictors is limited due to low accuracy for most traits. Here theory and simulation study are used to demonstrate that widespread pleiotropy among phenotypes can be utilised to improve genomic risk prediction. We show how a genetic predictor can be created as a weighted index that combines published genome-wide association study (GWAS) summary statistics across many different traits. We apply this framework to predict risk of schizophrenia and bipolar disorder in the Psychiatric Genomics consortium data, finding substantial heterogeneity in prediction accuracy increases across cohorts. For six additional phenotypes in the UK Biobank data, we find increases in prediction accuracy ranging from 0.7 for height to 47 for type 2 diabetes, when using a multi-trait predictor that combines published summary statistics from multiple traits, as compared to a predictor based only on one trait. © 2018 The Author(s)
- âŠ