74 research outputs found
Evolution-guided functional analyses reveal diverse antiviral specificities encoded by IFIT1 genes in mammals.
IFIT (interferon-induced with tetratricopeptide repeats) proteins are critical mediators of mammalian innate antiviral immunity. Mouse IFIT1 selectively inhibits viruses that lack 2'O-methylation of their mRNA 5' caps. Surprisingly, human IFIT1 does not share this antiviral specificity. Here, we resolve this discrepancy by demonstrating that human and mouse IFIT1 have evolved distinct functions using a combination of evolutionary, genetic and virological analyses. First, we show that human IFIT1 and mouse IFIT1 (renamed IFIT1B) are not orthologs, but are paralogs that diverged >100 mya. Second, using a yeast genetic assay, we show that IFIT1 and IFIT1B proteins differ in their ability to be suppressed by a cap 2'O-methyltransferase. Finally, we demonstrate that IFIT1 and IFIT1B have divergent antiviral specificities, including the discovery that only IFIT1 proteins inhibit a virus encoding a cap 2'O-methyltransferase. These functional data, combined with widespread turnover of mammalian IFIT genes, reveal dramatic species-specific differences in IFIT-mediated antiviral repertoires
The impact of stochastic modeling on the predictive power of galaxy formation simulations
All modern galaxy formation models employ stochastic elements in their
sub-grid prescriptions to discretise continuous equations across the time
domain. In this paper, we investigate how the stochastic nature of these
models, notably star formation, black hole accretion, and their associated
feedback, that act on small ( kpc) scales, can back-react on macroscopic
galaxy properties (e.g. stellar mass and size) across long ( Gyr)
timescales. We find that the scatter in scaling relations predicted by the
EAGLE model implemented in the SWIFT code can be significantly impacted by
random variability between re-simulations of the same object, even when
galaxies are resolved by tens of thousands of particles. We then illustrate how
re-simulations of the same object can be used to better understand the
underlying model, by showing how correlations between galaxy stellar mass and
black hole mass disappear at the highest black hole masses (
M), indicating that the feedback cycle may be interrupted by external
processes. We find that although properties that are collected cumulatively
over many objects are relatively robust against random variability (e.g. the
median of a scaling relation), the properties of individual galaxies (such as
galaxy stellar mass) can vary by up to 25\%, even far into the well-resolved
regime, driven by bursty physics (black hole feedback) and mergers between
galaxies. We suggest that studies of individual objects within cosmological
simulations be treated with caution, and that any studies aiming to closely
investigate such objects must account for random variability within their
results.Comment: Accepted for publication in MNRA
WIYN Open Cluster Study. XIX. Main Sequence Fitting Distances to Open Clusters Using V-K Color-Magnitude Diagrams
We have combined existing optical magnitudes for stars in seven open clusters
and 54 field stars with the corresponding JHKs photometry from the Two Micron
All Sky Survey (2MASS). Combining optical with near-IR photometry broadens the
color baseline minimizing the influence of photometric errors and allows better
discrimination between cluster stars and contaminating foreground and
background populations. The open clusters in this study include NGC 2516, M35,
M34, NGC 3532, M37, M67, and NGC 188. The field stars we are using possess high
quality Hipparcos parallaxes and well-determined metal abundances allowing us
to empirically determine the dependence of (V-K) color on metal abundance in
the range -0.45<=[Fe/H]<=+0.35. Using this relation along with the parallaxes
of the field stars, we are able to construct an unevolved main sequence in the
[Mv,(V-K)o] diagram for a specific abundance. These diagrams are then used to
fit to the cluster main sequences in the [V,V-K] color-magnitude diagram in
order to estimate a distance for each open cluster. We find that the resultant
distances are within the range of distances found in the literature via the
main sequence fitting technique. It is hoped that this will spur an expansion
of the current (limited) database of star clusters with high quality (V-K)
photometry down to the unevolved main sequence.Comment: 17 pages, 7 figures, to appear in The Astronomical Journal - February
200
Dynamic lattice distortions driven by surface trapping in semiconductor nanocrystals
Nonradiative processes limit optoelectronic functionality of nanocrystals and
curb their device performance. Nevertheless, the dynamic structural origins of
nonradiative relaxations in nanocrystals are not understood. Here, femtosecond
electron diffraction measurements corroborated by atomistic simulations uncover
transient lattice deformations accompanying radiationless electronic processes
in semiconductor nanocrystals. Investigation of the excitation energy
dependence shows that hot carriers created by a photon energy considerably
larger than the bandgap induce structural distortions at nanocrystal surfaces
on few picosecond timescales associated with the localization of trapped holes.
On the other hand, carriers created by a photon energy close to the bandgap
result in transient lattice heating that occurs on a much longer 200 ps
timescale, governed by an Auger heating mechanism. Elucidation of the
structural deformations associated with the surface trapping of hot holes
provides atomic-scale insights into the mechanisms deteriorating optoelectronic
performance and a pathway towards minimizing these losses in nanocrystal
devices.Comment: 17 pages, 4 figure
B Cell Antigen Presentation Promotes Th2 Responses and Immunopathology during Chronic Allergic Lung Disease
Background: The role of B cells in allergic asthma remains undefined. One mechanism by which B cells clearly contribute to allergic disease is via the production of specific immunoglobulin, and especially IgE. Cognate interactions with specific T cells result in T cell help for B cells, resulting in differentiation and immunoglobulin secretion. Proximal to (and required for) T cell-dependent immunoglobulin production, however, is antigen presentation by B cells. While interaction with T cells clearly has implications for B cell function and differentiation, this study investigated the role that B cells have in shaping the T cell response during chronic allergic lung disease. Methodology/Principal Findings: In these studies, we used a clinically relevant mouse model of chronic allergic lung disease to study the role of B cells and B cell antigen presentation in this disease. In these studies we present several novel findings: 1) Lung B cells from chronically allergen challenged mice up-regulated MHC II and costimulatory molecules CD40, CD80 and CD86. 2) Using in vitro studies, B cells from the lungs of allergen challenged mice could present antigen to T cells, as assessed by T cell proliferation and the preferential production of Th2 cytokines. 3) Following chronic allergen challenge, the levels of Th2 cytokines IL-4 and IL-5 in the lungs and airways were significantly attenuated in B cell 2/2 mice, relative to controls. 4) B cell driven Th2 responses and mucus hyper secretion in the lungs were dependent upon MHC II expression by B cells. Conclusions/Significance: Collectively, these results provide evidence for antigen presentation as a novel mechanism b
Reduced dielectric screening and enhanced energy transfer in single and few-layer MoS2
We report highly efficient non-radiative energy transfer from cadmium
selenide (CdSe) quantum dots to monolayer and few-layer molybdenum disulfide
(MoS2). The quenching of the donor quantum dot photoluminescence increases as
the MoS2 flake thickness decreases, with the highest efficiency (>95%) observed
for monolayer MoS2. This counterintuitive result arises from reduced dielectric
screening in thin layer semiconductors having unusually large permittivity and
a strong in-plane transition dipole moment, as found in MoS2. Excitonic energy
transfer between a 0D emitter and a 2D absorber is fundamentally interesting
and enables a wide range of applications including broadband optical
down-conversion, optical detection, photovoltaic sensitization, and color
shifting in light-emitting devices.Comment: 14 pages, 4 figure
The unruptured intracranial aneurysm treatment score A multidisciplinary consensus
Objective: We endeavored to develop an unruptured intracranial aneurysm (UIA) treatment score (UIATS) model that includes and quantifies key factors involved in clinical decision-making in the management of UIAs and to assess agreement for this model among specialists in UIA management and research. Methods: An international multidisciplinary (neurosurgery, neuroradiology, neurology, clinical epidemiology) group of 69 specialists was convened to develop and validate the UIATS model using a Delphi consensus. For internal (39 panel members involved in identification of relevant features) and external validation (30 independent external reviewers), 30 selected UIA cases were used to analyze agreement with UIATS management recommendations based on a 5-point Likert scale (5 indicating strong agreement). Interrater agreement (IRA) was assessed with standardized coefficients of dispersion (v(r)*) (v(r)* 5 0 indicating excellent agreement and v(r)* = 1 indicating poor agreement). Results: The UIATS accounts for 29 key factors in UIA management. Agreement with UIATS (mean Likert scores) was 4.2 (95% confidence interval [CI] 4.1-4.3) per reviewer for both reviewer cohorts; agreement per case was 4.3 (95% CI 4.1-4.4) for panel members and 4.5 (95% CI 4.3-4.6) for external reviewers (p = 0.017). Mean Likert scores were 4.2 (95% CI 4.1-4.3) for interventional reviewers (n = 56) and 4.1 (95% CI 3.9-4.4) for noninterventional reviewers (n = 12) (p = 0.290). Overall IRA (v(r)*) for both cohorts was 0.026 (95% CI 0.019-0.033). Conclusions: This novel UIA decision guidance study captures an excellent consensus among highly informed individuals on UIA management, irrespective of their underlying specialty. Clinicians can use the UIATS as a comprehensive mechanism for indicating how a large group of specialists might manage an individual patient with a UIA.Peer reviewe
Piano-Stool Lutetium Amido and Imido Compounds Supported by a Constrained Bis(oxazoline)cyclopentadienyl Ligand
The High Resolution Imaging Science Experiment (HiRISE) during MRO’s Primary Science Phase (PSP)
Factors Associated with Revision Surgery after Internal Fixation of Hip Fractures
Background: Femoral neck fractures are associated with high rates of revision surgery after management with internal fixation. Using data from the Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trial evaluating methods of internal fixation in patients with femoral neck fractures, we investigated associations between baseline and surgical factors and the need for revision surgery to promote healing, relieve pain, treat infection or improve function over 24 months postsurgery. Additionally, we investigated factors associated with (1) hardware removal and (2) implant exchange from cancellous screws (CS) or sliding hip screw (SHS) to total hip arthroplasty, hemiarthroplasty, or another internal fixation device. Methods: We identified 15 potential factors a priori that may be associated with revision surgery, 7 with hardware removal, and 14 with implant exchange. We used multivariable Cox proportional hazards analyses in our investigation. Results: Factors associated with increased risk of revision surgery included: female sex, [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.25-2.50; P = 0.001], higher body mass index (fo
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