481 research outputs found
Model thrombi formed under flow reveal the role of factor XIII-mediated cross-linking in resistance to fibrinolysis
Background: Activated factor XIII (FXIIIa), a transglutaminase, introduces fibrin-fibrin and fibrin-inhibitor cross-links, resulting in more mechanically stable clots. The impact of cross-linking on resistance to fibrinolysis has proved challenging to evaluate quantitatively. Methods: We used a whole blood model thrombus system to characterize the role of cross-linking in resistance to fibrinolytic degradation. Model thrombi, which mimic arterial thrombi formed in vivo, were prepared with incorporated fluorescently labeled fibrinogen, in order to allow quantification of fibrinolysis as released fluorescence units per minute. Results: A site-specific inhibitor of transglutaminases, added to blood from normal donors, yielded model thrombi that lysed more easily, either spontaneously or by plasminogen activators. This was observed both in the cell/platelet-rich head and fibrin-rich tail. Model thrombi from an FXIII-deficient patient lysed more quickly than normal thrombi; replacement therapy with FXIII concentrate normalized lysis. In vitro addition of purified FXIII to the patient's preprophylaxis blood, but not to normal control blood, resulted in more stable thrombi, indicating no further efficacy of supraphysiologic FXIII. However, addition of tissue transglutaminase, which is synthesized by endothelial cells, generated thrombi that were more resistant to fibrinolysis; this may stabilize mural thrombi in vivo. Conclusions: Model thrombi formed under flow, even those prepared as plasma 'thrombi', reveal the effect of FXIII on fibrinolysis. Although very low levels of FXIII are known to produce mechanical clot stability, and to achieve ?-dimerization, they appear to be suboptimal in conferring full resistance to fibrinolysis
Hubbard physics in the PAW GW approximation
It is demonstrated that the signatures of the Hubbard Model in the strongly interacting regime can be simulated by modifying the screening in the limit of zero wavevector in Projector-Augmented Wave GW calculations for systems without significant nesting. This modification, when applied to the Mott insulator CuO, results in the opening of the Mott gap by the splitting of states at the Fermi level into upper and lower Hubbard bands, and exhibits a giant transfer of spectral weight upon electron doping. The method is also employed to clearly illustrate that the M1 and M2 forms of vanadium dioxide are fundamentally different types of insulator. Standard GW calculations are sufficient to open a gap in M1 VO2, which arise from the Peierls pairing filling the valence band, creating homopolar bonds. The valence band wavefunctions are stabilized with respect to the conduction band, reducing polarizability and pushing the conduction band eigenvalues to higher energy. The M2 structure, however, opens a gap from strong on-site interactions; it is a Mott insulator
Human Salmonella Typhi exposure generates differential multifunctional cross‐reactive T‐cell memory responses against Salmonella Paratyphi and invasive nontyphoidal Salmonella
Objective
There are no vaccines for most of the major invasive Salmonella strains causing severe infection in humans. We evaluated the specificity of adaptive T memory cell responses generated after Salmonella Typhi exposure in humans against other major invasive Salmonella strains sharing capacity for dissemination.
Methods
T memory cells from eleven volunteers who underwent controlled oral challenge with wt S. Typhi were characterised by flow cytometry for cross‐reactive cellular cytokine/chemokine effector responses or evidence of degranulation upon stimulation with autologous B‐lymphoblastoid cells infected with either S. Typhi, Salmonella Paratyphi A (PA), S. Paratyphi B (PB) or an invasive nontyphoidal Salmonella strain of the S. Typhimurium serovar (iNTSTy).
Results
Blood T‐cell effector memory (TEM) responses after exposure to S. Typhi in humans evolve late, peaking weeks after infection in most volunteers. Induced multifunctional CD4+ Th1 and CD8+ TEM cells elicited after S. Typhi challenge were cross‐reactive with PA, PB and iNTSTy. The magnitude of multifunctional CD4+ TEM cell responses to S. Typhi correlated with induction of cross‐reactive multifunctional CD8+ TEM cells against PA, PB and iNTSTy. Highly multifunctional subsets and T central memory and T effector memory cells that re‐express CD45 (TEMRA) demonstrated less heterologous T‐cell cross‐reactivity, and multifunctional Th17 elicited after S. Typhi challenge was not cross‐reactive against other invasive Salmonella.
Conclusion
Gaps in cross‐reactive immune effector functions in human T‐cell memory compartments were highly dependent on invasive Salmonella strain, underscoring the importance of strain‐dependent vaccination in the design of T‐cell‐based vaccines for invasive Salmonella
Effect of aerosol radiative forcing uncertainty on projected exceedance year of a 1.5 °c global temperature rise
© 2020 The Author(s). Published by IOP Publishing Ltd. Anthropogenic aerosol emissions are predicted to decline sharply throughout the 21st century, in line with climate change and air quality mitigation policies, causing a near-term warming of climate that will impact our trajectory towards 1.5 °C above pre-industrial temperatures. However, the persistent uncertainty in aerosol radiative forcing limits our understanding of how much the global mean temperature will respond to near-term reductions in anthropogenic aerosol emissions. We quantify the model and scenario uncertainty in global mean aerosol radiative forcing up to 2050 using statistical emulation of a perturbed parameter ensemble for emission reduction scenarios consistent with three Shared Socioeconomic Pathways. We then use a simple climate model to translate the uncertainty in aerosol radiative forcing into uncertainty in global mean temperature projections, accounting additionally for the potential correlation of aerosol radiative forcing and climate sensitivity. Near-term aerosol radiative forcing uncertainty alone causes an uncertainty window of around 5 years (2034-2039) on the projected year of exceeding a global temperature rise of 1.5 °C above pre-industrial temperatures for a middle of the road emissions scenario (SSP2-RCP4.5). A correlation between aerosol radiative forcing and climate sensitivity would increase the 1.5 °C exceedance window by many years. The results highlight the importance of quantifying aerosol radiative forcing and any relationship with climate sensitivity in climate models in order to reduce uncertainty in temperature projections
A global conservation basic income to safeguard biodiversity
Biodiversity conservation supporting a global sustainability transformation must be inclusive, equitable, just and embrace plural values. The conservation basic income (CBI), a proposed unconditional cash transfer to individuals residing in important conservation areas, is a potentially powerful mechanism for facilitating this radical shift in conservation. This analysis provides comprehensive projections for potential gross costs of global CBI using spatial analyses of three plausible future conservation scenarios. Gross costs vary widely, depending on the areas and populations included, from US6.73 trillion annually. A US478 billion annually. These costs are large compared with current government conservation spending (~US44 trillion in global economic production dependent on nature
The importance of comprehensive parameter sampling and multiple observations for robust constraint of aerosol radiative forcing
© 2018 Author(s). Observational constraint of simulated aerosol and cloud properties is an essential part of building trustworthy climate models for calculating aerosol radiative forcing. Models are usually tuned to achieve good agreement with observations, but tuning produces just one of many potential variants of a model, so the model uncertainty cannot be determined. Here we estimate the uncertainty in aerosol effective radiative forcing (ERF) in a tuned climate model by constraining 4 million variants of the HadGEM3-UKCA aerosol-climate model to match nine common observations (top-of-atmosphere shortwave flux, aerosol optical depth, PM2.5, cloud condensation nuclei at 0.2% supersaturation (CCN0.2), and concentrations of sulfate, black carbon and organic carbon, as well as decadal trends in aerosol optical depth and surface shortwave radiation.) The model uncertainty is calculated by using a perturbed parameter ensemble that samples 27 uncertainties in both the aerosol model and the physical climate model, and we use synthetic observations generated from the model itself to determine the potential of each observational type to constrain this uncertainty. Focusing over Europe in July, we show that the aerosol ERF uncertainty can be reduced by about 30% by constraining it to the nine observations, demonstrating that producing climate models with an observationally plausible base state can contribute to narrowing the uncertainty in aerosol ERF. However, the uncertainty in the aerosol ERF after observational constraint is large compared to the typical spread of a multi-model ensemble. Our results therefore raise questions about whether the underlying multi-model uncertainty would be larger if similar approaches as adopted here were applied more widely. The approach presented in this study could be used to identify the most effective observations for model constraint. It is hoped that aerosol ERF uncertainty can be further reduced by introducing process-related constraints; however, any such results will be robust only if the enormous number of potential model variants is explored
Debris disk size distributions: steady state collisional evolution with P-R drag and other loss processes
We present a new scheme for determining the shape of the size distribution,
and its evolution, for collisional cascades of planetesimals undergoing
destructive collisions and loss processes like Poynting-Robertson drag. The
scheme treats the steady state portion of the cascade by equating mass loss and
gain in each size bin; the smallest particles are expected to reach steady
state on their collision timescale, while larger particles retain their
primordial distribution. For collision-dominated disks, steady state means that
mass loss rates in logarithmic size bins are independent of size. This
prescription reproduces the expected two phase size distribution, with ripples
above the blow-out size, and above the transition to gravity-dominated
planetesimal strength. The scheme also reproduces the expected evolution of
disk mass, and of dust mass, but is computationally much faster than evolving
distributions forward in time. For low-mass disks, P-R drag causes a turnover
at small sizes to a size distribution that is set by the redistribution
function (the mass distribution of fragments produced in collisions). Thus
information about the redistribution function may be recovered by measuring the
size distribution of particles undergoing loss by P-R drag, such as that traced
by particles accreted onto Earth. Although cross-sectional area drops with
1/age^2 in the PR-dominated regime, dust mass falls as 1/age^2.8, underlining
the importance of understanding which particle sizes contribute to an
observation when considering how disk detectability evolves. Other loss
processes are readily incorporated; we also discuss generalised power law loss
rates, dynamical depletion, realistic radiation forces and stellar wind drag.Comment: Accepted for publication by Celestial Mechanics and Dynamical
Astronomy (special issue on EXOPLANETS
Model confidence sets and forecast combination: an application to age-specific mortality
Background: Model averaging combines forecasts obtained from a range of models, and it often produces more accurate forecasts than a forecast from a single model.
Objective: The crucial part of forecast accuracy improvement in using the model averaging lies in the determination of optimal weights from a finite sample. If the weights are selected sub-optimally, this can affect the accuracy of the model-averaged forecasts. Instead of choosing the optimal weights, we consider trimming a set of models before equally averaging forecasts from the selected superior models. Motivated by Hansen et al. (2011), we apply and evaluate the model confidence set procedure when combining mortality forecasts.
Data & Methods: The proposed model averaging procedure is motivated by Samuels and Sekkel (2017) based on the concept of model confidence sets as proposed by Hansen et al. (2011) that incorporates the statistical significance of the forecasting performance. As the model confidence level increases, the set of superior models generally decreases. The proposed model averaging procedure is demonstrated via national and sub-national Japanese mortality for retirement ages between 60 and 100+.
Results: Illustrated by national and sub-national Japanese mortality for ages between 60 and 100+, the proposed model-average procedure gives the smallest interval forecast errors, especially for males. Conclusion: We find that robust out-of-sample point and interval forecasts may be obtained from the trimming method. By robust, we mean robustness against model misspecification
Forward production of charged pions with incident on nuclear targets measured at the CERN PS
Measurements of the double-differential production cross-section
in the range of momentum 0.5 \GeVc \leq p \le 8.0 \GeVc and angle 0.025 \rad
\leq \theta \le 0.25 \rad in interactions of charged pions on beryllium,
carbon, aluminium, copper, tin, tantalum and lead are presented. These data
represent the first experimental campaign to systematically measure forward
pion hadroproduction. The data were taken with the large acceptance HARP
detector in the T9 beam line of the CERN PS. Incident particles, impinging on a
5% nuclear interaction length target, were identified by an elaborate system of
beam detectors. The tracking and identification of the produced particles was
performed using the forward spectrometer of the HARP detector. Results are
obtained for the double-differential cross-sections mainly at four incident pion beam
momenta (3 \GeVc, 5 \GeVc, 8 \GeVc and 12 \GeVc). The measurements are compared
with the GEANT4 and MARS Monte Carlo simulationComment: to be published on Nuclear Physics
Large-angle production of charged pions by 3 GeV/c - 12 GeV/c protons on carbon, copper and tin targets
A measurement of the double-differential production cross-section
in proton--carbon, proton--copper and proton--tin collisions in the range of
pion momentum 100 \MeVc \leq p < 800 \MeVc and angle 0.35 \rad \le \theta
<2.15 \rad is presented. The data were taken with the HARP detector in the T9
beam line of the CERN PS. The pions were produced by proton beams in a momentum
range from 3 \GeVc to 12 \GeVc hitting a target with a thickness of 5% of a
nuclear interaction length. The tracking and identification of the produced
particles was done using a small-radius cylindrical time projection chamber
(TPC) placed in a solenoidal magnet. An elaborate system of detectors in the
beam line ensured the identification of the incident particles. Results are
shown for the double-differential cross-sections at four incident proton beam
momenta (3 \GeVc, 5 \GeVc, 8 \GeVc and 12 \GeVc)
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