The cGAS-STING signalling pathway has emerged as a key mediator of inflammation in the settings of infection, cellular stress and tissue damage. Underlying this broad involvement of the cGAS-STING ...pathway is its capacity to sense and regulate the cellular response towards microbial and host-derived DNAs, which serve as ubiquitous danger-associated molecules. Insights into the structural and molecular biology of the cGAS-STING pathway have enabled the development of selective small-molecule inhibitors with the potential to target the cGAS-STING axis in a number of inflammatory diseases in humans. Here, we outline the principal elements of the cGAS-STING signalling cascade and discuss the general mechanisms underlying the association of cGAS-STING activity with various autoinflammatory, autoimmune and degenerative diseases. Finally, we outline the chemical nature of recently developed cGAS and STING antagonists and summarize their potential clinical applications.
In this Letter, we introduce a novel scheme for extrapolating the equation of state of QCD to finite chemical potential that features considerably improved convergence properties and allows us to ...extend its reach to unprecedentedly high baryonic chemical potentials. We present continuum extrapolated lattice results for the new expansion coefficients and show the thermodynamic observables up to μB/T≤3.5. This novel expansion does not suffer from the shortcomings that characterize the traditional Taylor expansion method, such as difficulties inherent in performing such an expansion with a limited number of coefficients and the poor signal-to-noise ratio that affects Taylor coefficients determined from lattice calculations.
Disorders of coagulation in pregnancy Katz, D.; Beilin, Y.
British journal of anaesthesia : BJA,
December 2015, 20151201, 2015-Dec, 2015-12-00, Letnik:
115, Številka:
suppl_2
Journal Article
Recenzirano
Odprti dostop
The process of haemostasis is complex and is further complicated in the parturient because of the physiological changes of pregnancy. Understanding these changes and the impact that they have on the ...safety profile of the anaesthetic options for labour and delivery is crucial to any anaesthetist caring for the parturient. This article analyses current theories on coagulation and reviews the physiological changes to coagulation that occur during pregnancy and the best methods with which to evaluate coagulation. Finally, we examine some of the more common disorders of coagulation that occur during pregnancy, including von Willebrand disease, common factor deficiencies, platelet disorders, the parturient on anticoagulants, and the more rare acute fatty liver of pregnancy, with a focus on their implications for neuraxial anaesthesia.
Unlike the electroweak sector of the standard model of particle physics, quantum chromodynamics (QCD) is surprisingly symmetric under time reversal. As there is no obvious reason for QCD being so ...symmetric, this phenomenon poses a theoretical problem, often referred to as the strong CP problem. The most attractive solution for this requires the existence of a new particle, the axion-a promising dark-matter candidate. Here we determine the axion mass using lattice QCD, assuming that these particles are the dominant component of dark matter. The key quantities of the calculation are the equation of state of the Universe and the temperature dependence of the topological susceptibility of QCD, a quantity that is notoriously difficult to calculate, especially in the most relevant high-temperature region (up to several gigaelectronvolts). But by splitting the vacuum into different sectors and re-defining the fermionic determinants, its controlled calculation becomes feasible. Thus, our twofold prediction helps most cosmological calculations to describe the evolution of the early Universe by using the equation of state, and may be decisive for guiding experiments looking for dark-matter axions. In the next couple of years, it should be possible to confirm or rule out post-inflation axions experimentally, depending on whether the axion mass is found to be as predicted here. Alternatively, in a pre-inflation scenario, our calculation determines the universal axionic angle that corresponds to the initial condition of our Universe.
The standard model of particle physics describes the vast majority of experiments and observations involving elementary particles. Any deviation from its predictions would be a sign of new, ...fundamental physics. One long-standing discrepancy concerns the anomalous magnetic moment of the muon, a measure of the magnetic field surrounding that particle. Standard-model predictions
exhibit disagreement with measurements
that is tightly scattered around 3.7 standard deviations. Today, theoretical and measurement errors are comparable; however, ongoing and planned experiments aim to reduce the measurement error by a factor of four. Theoretically, the dominant source of error is the leading-order hadronic vacuum polarization (LO-HVP) contribution. For the upcoming measurements, it is essential to evaluate the prediction for this contribution with independent methods and to reduce its uncertainties. The most precise, model-independent determinations so far rely on dispersive techniques, combined with measurements of the cross-section of electron-positron annihilation into hadrons
. To eliminate our reliance on these experiments, here we use ab initio quantum chromodynamics (QCD) and quantum electrodynamics simulations to compute the LO-HVP contribution. We reach sufficient precision to discriminate between the measurement of the anomalous magnetic moment of the muon and the predictions of dispersive methods. Our result favours the experimentally measured value over those obtained using the dispersion relation. Moreover, the methods used and developed in this work will enable further increased precision as more powerful computers become available.
Fluctuations and correlations in high temperature QCD Bellwied, R.; Borsányi, S.; Fodor, Z. ...
Physical review. D, Particles, fields, gravitation, and cosmology,
12/2015, Letnik:
92, Številka:
11
Journal Article
Recenzirano
Odprti dostop
We calculate second- and fourth-order cumulants of conserved charges in a temperature range stretching from the QCD transition region towards the realm of (resummed) perturbation theory. We perform ...lattice simulations with staggered quarks; the continuum extrapolation is based on N sub()t =10-24 in the crossover region and N sub()t= 8-16 at higher temperatures. We find that the hadron resonance gas model predictions describe the lattice data rather well in the confined phase. At high temperatures (above ~ 250 MeV) we find agreement with the three-loop hard thermal loop results.
We provide the most accurate results for the QCD transition line so far. We optimize the definition of the crossover temperature Tc, allowing for its very precise determination, and extrapolate from ...imaginary chemical potential up to real μB ≈ 300 MeV . The definition of T c adopted in this work is based on the observation that the chiral susceptibility as a function of the condensate is an almost universal curve at zero and imaginary μB. We obtain the parameters κ2 = 0.0153 ( 18 ) and κ4 = 0.00032 ( 67 ) as a continuum extrapolation based on Nt = 10 , 12, 16 lattices with physical quark masses. We also extrapolate the peak value of the chiral susceptibility and the width of the chiral transition along the crossover line. In fact, both of these are consistent with a constant function of μ B . We see no sign of criticality in the explored range.
Diet is established among the most important influences on health in modern societies. Injudicious diet figures among the leading causes of premature death and chronic disease. Optimal eating is ...associated with increased life expectancy, dramatic reduction in lifetime risk of all chronic disease, and amelioration of gene expression. In this context, claims abound for the competitive merits of various diets relative to one another. Whereas such claims, particularly when attached to commercial interests, emphasize distinctions, the fundamentals of virtually all eating patterns associated with meaningful evidence of health benefit overlap substantially. There have been no rigorous, long-term studies comparing contenders for best diet laurels using methodology that precludes bias and confounding, and for many reasons such studies are unlikely. In the absence of such direct comparisons, claims for the established superiority of any one specific diet over others are exaggerated. The weight of evidence strongly supports a theme of healthful eating while allowing for variations on that theme. A diet of minimally processed foods close to nature, predominantly plants, is decisively associated with health promotion and disease prevention and is consistent with the salient components of seemingly distinct dietary approaches. Efforts to improve public health through diet are forestalled not for want of knowledge about the optimal feeding of Homo sapiens but for distractions associated with exaggerated claims, and our failure to convert what we reliably know into what we routinely do. Knowledge in this case is not, as of yet, power; would that it were so.
High-precision scale setting in lattice QCD Borsányi, Szabolcs; Dürr, Stephan; Fodor, Zoltán ...
The journal of high energy physics,
09/2012, Letnik:
2012, Številka:
9
Journal Article
Recenzirano
Odprti dostop
A
bstract
Scale setting is of central importance in lattice QCD. It is required to predict dimensional quantities in physical units. Moreover, it determines the relative lattice spacings of ...computations performed at different values of the bare coupling, and this is needed for extrapolating results into the continuum. Thus, we calculate a new quantity,
w
0
, for setting the scale in lattice QCD, which is based on the Wilson flow like the scale
t
0
(M. Luscher,
JHEP
08 (2010) 071). It is cheap and straightforward to implement and compute. In particular, it does not involve the delicate fitting of correlation functions at asymptotic times. It typically can be determined on the few per-mil level. We compute its continuum extrapolated value in 2 + 1-flavor QCD for physical and non-physical pion and kaon masses, to allow for mass-independent scale setting even away from the physical mass point. We demonstrate its robustness by computing it with two very different actions (one of them with staggered, the other with Wilson fermions) and by showing that the results agree for physical quark masses in the continuum limit.
We present possible indications for flavor separation during the QCD crossover transition based on continuum extrapolated lattice QCD calculations of higher order susceptibilities. We base our ...findings on flavor-specific quantities in the light and strange quark sector. We propose a possible experimental verification of our prediction, based on the measurement of higher order moments of identified particle multiplicities. Since all our calculations are performed at zero baryochemical potential, these results are of particular relevance for the heavy-ion program at the LHC.
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