The Bulk Channel in Thermal Gauge Theories

We investigate the thermal correlator of the trace of the energy-momentum tensor in the SU(3) Yang-Mills theory. Our goal is to constrain the spectral function in that channel, whose low-frequency part determines the bulk viscosity. We focus on the thermal modification of the spectral function, $\rho(\omega,T)-\rho(\omega,0)$. Using the operator-product expansion we give the high-frequency behavior of this difference in terms of thermodynamic potentials. We take into account the presence of an exact delta function located at the origin, which had been missed in previous analyses. We then combine the bulk sum rule and a Monte-Carlo evaluation of the Euclidean correlator to determine the intervals of frequency where the spectral density is enhanced or depleted by thermal effects. We find evidence that the thermal spectral density is non-zero for frequencies below the scalar glueball mass $m$ and is significantly depleted for $m\lesssim\omega\lesssim 3m$.Comment: (1+25) pages, 6 figure

Ultraviolet asymptotics of scalar and pseudoscalar correlators in hot Yang-Mills theory

Inspired by recent lattice measurements, we determine the short-distance (a > omega >> pi T) asymptotics of scalar (trace anomaly) and pseudoscalar (topological charge density) correlators at 2-loop order in hot Yang-Mills theory. The results are expressed in the form of an Operator Product Expansion. We confirm and refine the determination of a number of Wilson coefficients; however some discrepancies with recent literature are detected as well, and employing the correct values might help, on the qualitative level, to understand some of the features observed in the lattice measurements. On the other hand, the Wilson coefficients show slow convergence and it appears uncertain whether this approach can lead to quantitative comparisons with lattice data. Nevertheless, as we outline, our general results might serve as theoretical starting points for a number of perhaps phenomenologically more successful lines of investigation.Comment: 27 pages. v2: minor improvements, published versio

Subgenual Cingulum Microstructure Supports Control of Emotional Conflict

This is the final version of the article. Available from Oxford University Press via the DOI in this record.Major depressive disorder (MDD) is associated with specific difficulties in attentional disengagement from negatively valenced material. Diffusion MRI studies have demonstrated altered white matter microstructure in the subgenual cingulum bundle (CB) in individuals with MDD, though the functional significance of these alterations has not been examined formally. This study explored whether individual differences in selective attention to negatively valenced stimuli are related to interindividual differences in subgenual CB microstructure. Forty-six individuals (21 with remitted MDD, 25 never depressed) completed an emotional Stroop task, using happy and angry distractor faces overlaid by pleasant or unpleasant target words and a control gender-based Stroop task. CBs were reconstructed in 38 individuals using diffusion-weighted imaging and tractography, and mean fractional anisotropy (FA) computed for the subgenual, retrosplenial, and parahippocampal subdivisions. No significant correlations were found between FA and performance in the control gender-based Stroop task in any CB region. However, the degree of interference produced by angry face distractors on time to identify pleasant words (emotional conflict) correlated selectively with FA in the subgenual CB (r= -0.53;P= 0.01). Higher FA was associated with reduced interference, irrespective of a diagnosis of MDD, suggesting that subgenual CB microstructure is functionally relevant for regulating attentional bias toward negative interpersonal stimuli.P.A.K. was funded by the Higher Education Funding Council for Wales (HEFCW) and an Academy of Medical Sciences and Wellcome Trust Starter Grant (AJ17102004). M.M. received an EPSRC Doctoral Training Grant. This work was also supported by a Marie Curie fellowship to Marcel Meyer and received funding from the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement no. 267171. D.K.J. was funded by HEFCW and received grants from the MS Society, a Wellcome Trust New Investigator Award, a Wellcome Trust Multi User Equipment Grant and Medical Research Council, and Wellcome Trust project grants. A.N.D. was supported by the Wellcome Trust PhD schemes. N.L. was funded by HEFCW. A.D.L. was funded by HEFCW. He also received grants from the ESRC, Wellcome Trust, and NISCHR. Funding to pay the Open Access publication charges for this article was provided by The Wellcome Trust

Comprehensive Immune Monitoring of Clinical Trials to Advance Human Immunotherapy.

The success of immunotherapy has led to a myriad of clinical trials accompanied by efforts to gain mechanistic insight and identify predictive signatures for personalization. However, many immune monitoring technologies face investigator bias, missing unanticipated cellular responses in limited clinical material. We present here a mass cytometry (CyTOF) workflow for standardized, systems-level biomarker discovery in immunotherapy trials. To broadly enumerate immune cell identity and activity, we established and extensively assessed a reference panel of 33 antibodies to cover major cell subsets, simultaneously quantifying activation and immune checkpoint molecules in a single assay. This assay enumerates ≥98% of peripheral immune cells with ≥4 positively identifying antigens. Robustness and reproducibility are demonstrated on multiple samples types, across two research centers and by orthogonal measurements. Using automated analysis, we identify stratifying immune signatures in bone marrow transplantation-associated graft-versus-host disease. Together, this validated workflow ensures comprehensive immunophenotypic analysis and data comparability and will accelerate biomarker discovery

'Tipping the Balance': Karl Friedrich Meyer, Latent Infections, and the Birth of Modern Ideas of Disease Ecology

The Swiss-born medical researcher Karl Friedrich Meyer (1884–1974) is best known as a ‘microbe hunter’ who pioneered investigations into diseases at the intersection of animal and human health in California in the 1920s and 1930s. In particular, historians have singled out Meyer’s 1931 Ludwig Hektoen Lecture in which he described the animal kingdom as a ‘reservoir of disease’ as a forerunner of ‘one medicine’ approaches to emerging zoonoses. In so doing, however, historians risk overlooking Meyer’s other intellectual contributions. Developed in a series of papers from the mid-1930s onwards, these were ordered around the concept of latent infections and sought to link microbial behavior to broader bio-ecological, environmental, and social factors that impact hostpathogen interactions. In this respect Meyer—like the comparative pathologist Theobald Smith and the immunologist Frank Macfarlane Burnet—can be seen as a pioneer of modern ideas of disease ecology. However, while Burnet’s and Smith’s contributions to this scientific field have been widely acknowledged, Meyer’s have been largely ignored. Drawing on Meyer’s published writings and private correspondence, this paper aims to correct that lacuna while contributing to a reorientation of the historiography of bacteriological epidemiology. In particular I trace Meyer’s intellectual exchanges with Smith, Burnet and the animal ecologist Charles Elton, over brucellosis, psittacosis and plague—exchanges that not only showed how environmental and ecological conditions could ‘tip the balance’ in favor of parasites but which transformed Meyer thinking about resistance to infection and disease

Unwinding of a cholesteric liquid crystal and bidirectional surface anchoring

We examine the influence of bidirectional anchoring on the unwinding of a planar cholesteric liquid crystal induced by the application of a magnetic field. We consider a liquid crystal layer confined between two plates with the helical axis perpendicular to the substrates. We fixed the director twist on one boundary and allow for bidirectional anchoring on the other by introducing a high-order surface potential. By minimizing the total free energy for the system, we investigate the untwisting of the cholesteric helix as the liquid crystal attempts to align with the magnetic field. The transitions between metastable states occur as a series of pitchjumps as the helix expels quarter or half-turn twists, depending on the relative sizes of the strength of the surface potential and the bidirectional anchoring. We show that secondary easy axis directions can play a significant role in the unwinding of the cholesteric in its transition towards a nematic, especially when the surface anchoring strength is large

Nonlinear atom interferometer surpasses classical precision limit

Interference is fundamental to wave dynamics and quantum mechanics. The quantum wave properties of particles are exploited in metrology using atom interferometers, allowing for high-precision inertia measurements [1, 2]. Furthermore, the state-of-the-art time standard is based on an interferometric technique known as Ramsey spectroscopy. However, the precision of an interferometer is limited by classical statistics owing to the finite number of atoms used to deduce the quantity of interest [3]. Here we show experimentally that the classical precision limit can be surpassed using nonlinear atom interferometry with a Bose-Einstein condensate. Controlled interactions between the atoms lead to non-classical entangled states within the interferometer; this represents an alternative approach to the use of non-classical input states [4-8]. Extending quantum interferometry [9] to the regime of large atom number, we find that phase sensitivity is enhanced by 15 per cent relative to that in an ideal classical measurement. Our nonlinear atomic beam splitter follows the "one-axis-twisting" scheme [10] and implements interaction control using a narrow Feshbach resonance. We perform noise tomography of the quantum state within the interferometer and detect coherent spin squeezing with a squeezing factor of -8.2dB [11-15]. The results provide information on the many-particle quantum state, and imply the entanglement of 170 atoms [16]

Quantum to Classical Transition in a Single-Ion Laser

Stimulated emission of photons from a large number of atoms into the mode of a strong light field is the principle mechanism for lasing in "classical" lasers. The onset of lasing is marked by a threshold which can be characterised by a sharp increase in photon flux as a function of external pumping strength. The same is not necessarily true for the fundamental building block of a laser: a single trapped atom interacting with a single optical radiation mode. It has been shown that such a "quantum" laser can exhibit thresholdless lasing in the regime of strong coupling between atom and radiation field. However, although theoretically predicted, a threshold at the single-atom level could not be experimentally observed so far. Here, we demonstrate and characterise a single-atom laser with and without threshold behaviour by changing the strength of atom-light field coupling. We observe the establishment of a laser threshold through the accumulation of photons in the optical mode even for a mean photon number substantially lower than for the classical case. Furthermore, self-quenching occurs for very strong external pumping and constitutes an intrinsic limitation of single-atom lasers. Moreover, we find that the statistical properties of the emitted light can be adjusted for weak external pumping, from the quantum to the classical domain. Our observations mark an important step towards fundamental understanding of laser operation in the few-atom limit including systems based on semiconductor quantum dots or molecules.Comment: 19 pages, 4 figures, 10 pages supplement, accepted by Nature Physic

The travel diaries of tetanus and botulinum neurotoxins

Tetanus (TeNT) and botulinum (BoNT) neurotoxins, the causative agents of tetanus and botulism, respectively, are the most potent toxic molecules known to mankind. This extreme potency is attributed to: i) their specificity for essential components of the neurotransmitter release machinery present at vertebrate synapses, and ii) their high-affinity targeting to motor neurons by binding to polysialogangliosides and protein receptors. Comprising the clostridial neurotoxin family, TeNT and BoNTs engage distinct surface receptors and intracellular sorting pathways in neurons. BoNTs bind to the intraluminal domain of specific synaptic vesicle proteins that are exposed to the extracellular milieu upon exocytosis, and are taken up by synaptic vesicle recycling. A sizeable proportion of BoNT molecules remain at the neuromuscular junction, where their protease moiety is released into the cytoplasm, blocking synaptic transmission and causing flaccid paralysis. In contrast, TeNT undergoes binding to specific components of the basal membrane at the neuromuscular junction, is endocytosed into motor neurons and sorted to axonal signalling endosomes. Following this, TeNT is transported to the soma of motor neurons located in the spinal cord or brainstem, and then transcytosed to inhibitory interneurons, where it blocks synaptic transmission. TeNT-induced impairment of inhibitory input leads to hyperactivity of motor neurons, causing spastic paralysis, which is the hallmark of tetanus. This review examines the molecular mechanisms leading to the entry, sorting and intracellular trafficking of TeNT and BoNTs