Texture evolution in cold-rolled Mg-0.3Zn-0.1Ca, Mg-0.4Zn and Mg-0.1Ca (at.%) alloys during static recrystallization is monitored using a quasi-in-situ electron backscatter diffraction (EBSD) method. ...The quasi-in-situ EBSD results show that most of recrystallized grains formed in the early stage of recrystallization have randomised orientations in the ternary alloy and they grow uniformly during the recrystallization process. The formation and uniform growth of these recrystallized grains with randomised orientations give rise to a weak texture in fully recrystallized samples of the ternary alloy. A weak recrystallization texture also forms in the early stage of recrystallization in the two binary alloys, but it is gradually replaced by a strong basal texture via the preferential growth of recrystallized grains with specific orientations. The grain size in the ternary alloy is smaller than those in the two binary alloys at each stage of recrystallization, and the grain size distribution in the ternary alloy is significantly narrower than those in the two binary alloys after full recrystallization. Solute segregation to grain boundaries is observed in all three alloys in the fully recrystallized state. It is hypothesised that Zn and Ca atoms in the ternary alloy segregate strongly to high-energy boundaries of the recrystallized grains that would otherwise grow preferentially in the counterpart binary alloys, and that this co-segregation would significantly reduce the boundary mobility, by reducing grain boundary energy and enhancing solute dragging effect, and therefore lead to a more uniform growth of recrystallized grains with randomised orientations.
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This companion article to the VX-445 report shows that VX-659, a new CFTR potentiator, when administered with tezacaftor and ivacaftor improved lung function, sweat chloride concentration, and ...symptoms in patients with cystic fibrosis who harbored one or two Phe508del alleles.
Dendritic spines of pyramidal neurons in the cerebral cortex undergo activity-dependent structural remodelling that has been proposed to be a cellular basis of learning and memory. How structural ...remodelling supports synaptic plasticity, such as long-term potentiation, and whether such plasticity is input-specific at the level of the individual spine has remained unknown. We investigated the structural basis of long-term potentiation using two-photon photolysis of caged glutamate at single spines of hippocampal CA1 pyramidal neurons. Here we show that repetitive quantum-like photorelease (uncaging) of glutamate induces a rapid and selective enlargement of stimulated spines that is transient in large mushroom spines but persistent in small spines. Spine enlargement is associated with an increase in AMPA-receptor-mediated currents at the stimulated synapse and is dependent on NMDA receptors, calmodulin and actin polymerization. Long-lasting spine enlargement also requires Ca2+/calmodulin-dependent protein kinase II. Our results thus indicate that spines individually follow Hebb's postulate for learning. They further suggest that small spines are preferential sites for long-term potentiation induction, whereas large spines might represent physical traces of long-term memory.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Animal behaviors are reinforced by subsequent rewards following within a narrow time window. Such reward signals are primarily coded by dopamine, which modulates the synaptic connections of medium ...spiny neurons in the striatum. The mechanisms of the narrow timing detection, however, remain unknown. Here, we optically stimulated dopaminergic and glutamatergic inputs separately and found that dopamine promoted spine enlargement only during a narrow time window (0.3 to 2 seconds) after the glutamatergic inputs. The temporal contingency was detected by rapid regulation of adenosine 3′,5′-cyclic monophosphate in thin distal dendrites, in which protein-kinase A was activated only within the time window because of a high phosphodiesterase activity. Thus, we describe a molecular basis of reinforcement plasticity at the level of single dendritic spines.
We derive the operator product expansion whose vacuum expectation value gives the time moments of the pseudoscalar heavy-light current-current correlator up to and including terms in αs2 multiplying ...⟨ψ¯ψ⟩/M3 and terms in αs multiplying ⟨αsG2⟩/M4, where M is the heavy quark mass. Using lattice QCD results for heavy-strange correlators obtained for a variety of heavy quark masses on gluon field configurations including u, d and s quarks in the sea at three values of the lattice spacing, we are able to show that the contribution of the strange-quark condensate to the time moments is very substantial. We use our lattice QCD time moments and the operator product expansion to determine a value for the condensate, fitting the fourth, sixth, eighth and tenth time moments simultaneously. Our result, ⟨s¯s⟩MS¯(2 GeV)=−(296(11) MeV)3, agrees well with HPQCD's earlier, more direct, lattice QCD determination C. McNeile et al. (HPQCD Collaboration), Phys. Rev. D 87, 034503 (2013). As well as confirming that the s quark condensate is close in value to the light quark condensate, this demonstrates clearly the consistency of the operator product expansion for fully nonperturbative calculations of matrix elements of short-distance operators in lattice QCD.
Highlights • MSC interactions with innate immune cells. • MSCs exert both pro- and anti-inflammatory effects. • MSCs are immunomodulatory through cell–cell contact and soluble factors.
Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disorder affecting motor neurons, resulting in progressive muscle weakness and death by respiratory failure. Protein and RNA ...aggregates are a hallmark of ALS pathology and are thought to contribute to ALS by impairing axonal transport. Mutations in several genes known to contribute to ALS result in deposition of their protein products as aggregates; these include TARDBP, C9ORF72, and SOD1. In motor neurons, this can disrupt transport of mitochondria to areas of metabolic need, resulting in damage to cells and can elicit a neuroinflammatory response leading to further neuronal damage. Recently, eight independent human genetics studies have uncovered a link between TANK-binding kinase 1 (TBK1) mutations and ALS. TBK1 belongs to the IKK-kinase family of kinases that are involved in innate immunity signaling pathways; specifically, TBK1 is an inducer of type-1 interferons. TBK1 also has a major role in autophagy and mitophagy, chiefly the phosphorylation of autophagy adaptors. Several other ALS genes are also involved in autophagy, including p62 and OPTN. TBK1 is required for efficient cargo recruitment in autophagy; mutations in TBK1 may result in impaired autophagy and contribute to the accumulation of protein aggregates and ALS pathology. In this review, we focus on the role of TBK1 in autophagy and the contributions of this process to the pathophysiology of ALS.
We present the first lattice QCD calculation of the decay constants f(B) and f(B(s)) with physical light quark masses. We use configurations generated by the MILC Collaboration including the effect ...of u, d, s, and c highly improved staggered quarks in the sea at three lattice spacings and with three u/d quark mass values going down to the physical value. We use improved nonrelativistic QCD (NRQCD) for the valence b quarks. Our results are f(B)=0.186(4) GeV, f(B(s))=0.224(4) GeV, f(B(s))/f(B)=1.205(7), and M(B(s))-M(B)=85(2) MeV, superseding earlier results with NRQCD b quarks. We discuss the implications of our results for the standard model rates for B((s))→μ(+)μ(-) and B→τν.
Antibiotics are indispensable for treating bacterial infections, but their effectiveness is threatened by the emergence and spread of antibacterial resistance. Antibiotics are unique among drugs ...since the more they are used, the less effective they become because bacterial resistance is likely to develop. In response to this threat, the UK government aims to reduce inappropriate antibiotic prescribing in humans by 50% by 2020. A team at Public Health England has found that at least 20% of antibiotic prescriptions in primary care in England were inappropriate, which, if correct, implies that antibiotic prescribing nationally needs to be reduced by 10% by 2020. These data are published in five articles in a Supplement to JAC entitled Appropriateness of antibiotic prescribing in English primary care. Inappropriate prescribing was found in every general practice included in the analyses so each one should attempt to reduce unnecessary prescriptions, not just high-prescribing practices. An ambition of 10% reduction in antibiotic prescriptions seems attainable when compared with the reduction targets of other European countries. The need for substantial improvements in data quality that are necessary to further safeguard this precious resource is also highlighted by the authors in this Supplement.
We present a lattice QCD determination of the Bs → Dsℓν scalar and vector form factors over the full physical range of momentum transfer. The result is derived from correlation functions computed ...using the highly improved staggered quark (HISQ) formalism, on the second generation MILC gluon ensembles accounting for up, down, strange and charm contributions from the sea. We calculate correlation functions for three lattice spacing values and an array of unphysically light b -quark masses, and extrapolate to the physical value. Using the HISQ formalism for all quarks means that the lattice current coupling to the W can be renormalized nonperturbatively, giving a result free from perturbative matching errors for the first time. Our results are in agreement with, and more accurate than, previous determinations of these form factors. From the form factors we also determine the ratio of branching fractions that is sensitive to violation of lepton universality: R (Ds) = B (Bs → Dsτντ) /B (Bs → Dsℓνl), where ℓ is an electron or a muon. We find R (Ds) = 0.2993 (46) , which is also more accurate than previous lattice QCD results. Combined with a future measurement of R (Ds), this could supply a new test of the Standard Model. We also compare the dependence on heavy quark mass of our form factors to expectations from heavy quark effective theory.
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