HQET at order 1/m1/m: II. Spectroscopy in the quenched approximation

Using Heavy Quark Effective Theory with non-perturbatively determined parameters in a quenched lattice calculation, we evaluate the splittings between the ground state and the first two radially excited states of the $B_s$ system at static order. We also determine the splitting between first excited and ground state, and between the $B_s^*$ and $B_s$ ground states to order $1/m_b$. The Generalized Eigenvalue Problem and the use of all-to-all propagators are important ingredients of our approach.Comment: (1+18) pages, 3 figures (4 pdf files); pdflatex; v2: corrections to table 1, results unaffecte

Cardiovascular Clinical Trials in a Pandemic: Immediate Implications of Coronavirus Disease 2019

The coronavirus disease 2019 (COVID-19) pandemic started in Wuhan, Hubei Province, China, in December 2019, and by 24 April 2020, it had affected >2.73 million people in 185 countries and caused >192,000 deaths. Despite diverse societal measures to reduce transmission of the severe acute respiratory syndrome coronavirus 2, such as implementing social distancing, quarantine, curfews and total lockdowns, its control remains challenging. Healthcare practitioners are at the frontline of defence against the virus, with increasing institutional and governmental supports. Nevertheless, new or ongoing clinical trials, not related to the disease itself, remain important for the development of new therapies, and require interactions among patients, clinicians and research personnel, which is challenging, given isolation measures. In this article, the authors summarise the acute effects and consequences of the COVID-19 pandemic on current cardiovascular trials

A four-helix bundle stores copper for methane oxidation

Methane-oxidising bacteria (methanotrophs) require large quantities of copper for the membrane-bound (particulate) methane monooxygenase (pMMO). Certain methanotrophs are also able to switch to using the iron-containing soluble MMO (sMMO) to catalyse methane oxidation, with this switchover regulated by copper. MMOs are Nature’s primary biological mechanism for suppressing atmospheric levels of methane, a potent greenhouse gas. Furthermore, methanotrophs and MMOs have enormous potential in bioremediation and for biotransformations producing bulk and fine chemicals, and in bioenergy, particularly considering increased methane availability from renewable sources and hydraulic fracturing of shale rock. We have discovered and characterised a novel copper storage protein (Csp1) from the methanotroph Methylosinus trichosporium OB3b that is exported from the cytosol, and stores copper for pMMO. Csp1 is a tetramer of 4-helix bundles with each monomer binding up to 13 Cu(I) ions in a previously unseen manner via mainly Cys residues that point into the core of the bundle. Csp1 is the first example of a protein that stores a metal within an established protein-folding motif. This work provides a detailed insight into how methanotrophs accumulate copper for the oxidation of methane. Understanding this process is essential if the wide-ranging biotechnological applications of methanotrophs are to be realised. Cytosolic homologues of Csp1 are present in diverse bacteria thus challenging the dogma that such organisms do not use copper in this location

Phylogeny, Diet, and Cranial Integration in Australodelphian Marsupials

Studies of morphological integration provide valuable information on the correlated evolution of traits and its relationship to long-term patterns of morphological evolution. Thus far, studies of morphological integration in mammals have focused on placentals and have demonstrated that similarity in integration is broadly correlated with phylogenetic distance and dietary similarity. Detailed studies have also demonstrated a significant correlation between developmental relationships among structures and adult morphological integration. However, these studies have not yet been applied to marsupial taxa, which differ greatly from placentals in reproductive strategy and cranial development and could provide the diversity necessary to assess the relationships among phylogeny, ecology, development, and cranial integration. This study presents analyses of morphological integration in 20 species of australodelphian marsupials, and shows that phylogeny is significantly correlated with similarity of morphological integration in most clades. Size-related correlations have a significant affect on results, particularly in Peramelia, which shows a striking decrease in similarity of integration among species when size is removed. Diet is not significantly correlated with similarity of integration in any marsupial clade. These results show that marsupials differ markedly from placental mammals in the relationships of cranial integration, phylogeny, and diet, which may be related to the accelerated development of the masticatory apparatus in marsupials

Genetic deficiency of indoleamine 2,3-dioxygenase promotes gut microbiota-mediated metabolic health.

The association between altered gut microbiota, intestinal permeability, inflammation and cardiometabolic diseases is becoming increasingly clear but remains poorly understood1,2. Indoleamine 2,3-dioxygenase is an enzyme induced in many types of immune cells, including macrophages in response to inflammatory stimuli, and catalyzes the degradation of tryptophan along the kynurenine pathway. Indoleamine 2,3-dioxygenase activity is better known for its suppression of effector T cell immunity and its activation of regulatory T cells3,4. However, high indoleamine 2,3-dioxygenase activity predicts worse cardiovascular outcome5-9 and may promote atherosclerosis and vascular inflammation6, suggesting a more complex role in chronic inflammatory settings. Indoleamine 2,3-dioxygenase activity is also increased in obesity10-13, yet its role in metabolic disease is still unexplored. Here, we show that obesity is associated with an increase of intestinal indoleamine 2,3-dioxygenase activity, which shifts tryptophan metabolism from indole derivative and interleukin-22 production toward kynurenine production. Indoleamine 2,3-dioxygenase deletion or inhibition improves insulin sensitivity, preserves the gut mucosal barrier, decreases endotoxemia and chronic inflammation, and regulates lipid metabolism in liver and adipose tissues. These beneficial effects are due to rewiring of tryptophan metabolism toward a microbiota-dependent production of interleukin-22 and are abrogated after treatment with a neutralizing anti-interleukin-22 antibody. In summary, we identify an unexpected function of indoleamine 2,3-dioxygenase in the fine tuning of intestinal tryptophan metabolism with major consequences on microbiota-dependent control of metabolic disease, which suggests indoleamine 2,3-dioxygenase as a potential therapeutic target

Planetary population synthesis

In stellar astrophysics, the technique of population synthesis has been successfully used for several decades. For planets, it is in contrast still a young method which only became important in recent years because of the rapid increase of the number of known extrasolar planets, and the associated growth of statistical observational constraints. With planetary population synthesis, the theory of planet formation and evolution can be put to the test against these constraints. In this review of planetary population synthesis, we first briefly list key observational constraints. Then, the work flow in the method and its two main components are presented, namely global end-to-end models that predict planetary system properties directly from protoplanetary disk properties and probability distributions for these initial conditions. An overview of various population synthesis models in the literature is given. The sub-models for the physical processes considered in global models are described: the evolution of the protoplanetary disk, the planets' accretion of solids and gas, orbital migration, and N-body interactions among concurrently growing protoplanets. Next, typical population synthesis results are illustrated in the form of new syntheses obtained with the latest generation of the Bern model. Planetary formation tracks, the distribution of planets in the mass-distance and radius-distance plane, the planetary mass function, and the distributions of planetary radii, semimajor axes, and luminosities are shown, linked to underlying physical processes, and compared with their observational counterparts. We finish by highlighting the most important predictions made by population synthesis models and discuss the lessons learned from these predictions - both those later observationally confirmed and those rejected.Comment: 47 pages, 12 figures. Invited review accepted for publication in the 'Handbook of Exoplanets', planet formation section, section editor: Ralph Pudritz, Springer reference works, Juan Antonio Belmonte and Hans Deeg, Ed

Cellular Radiosensitivity: How much better do we understand it?

Purpose: Ionizing radiation exposure gives rise to a variety of lesions in DNA that result in genetic instability and potentially tumorigenesis or cell death. Radiation extends its effects on DNA by direct interaction or by radiolysis of H2O that generates free radicals or aqueous electrons capable of interacting with and causing indirect damage to DNA. While the various lesions arising in DNA after radiation exposure can contribute to the mutagenising effects of this agent, the potentially most damaging lesion is the DNA double strand break (DSB) that contributes to genome instability and/or cell death. Thus in many cases failure to recognise and/or repair this lesion determines the radiosensitivity status of the cell. DNA repair mechanisms including homologous recombination (HR) and non-homologous end-joining (NHEJ) have evolved to protect cells against DNA DSB. Mutations in proteins that constitute these repair pathways are characterised by radiosensitivity and genome instability. Defects in a number of these proteins also give rise to genetic disorders that feature not only genetic instability but also immunodeficiency, cancer predisposition, neurodegeneration and other pathologies. Conclusions: In the past fifty years our understanding of the cellular response to radiation damage has advanced enormously with insight being gained from a wide range of approaches extending from more basic early studies to the sophisticated approaches used today. In this review we discuss our current understanding of the impact of radiation on the cell and the organism gained from the array of past and present studies and attempt to provide an explanation for what it is that determines the response to radiation

Measurement of the inclusive and dijet cross-sections of b-jets in pp collisions at sqrt(s) = 7 TeV with the ATLAS detector

The inclusive and dijet production cross-sections have been measured for jets containing b-hadrons (b-jets) in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV, using the ATLAS detector at the LHC. The measurements use data corresponding to an integrated luminosity of 34 pb^-1. The b-jets are identified using either a lifetime-based method, where secondary decay vertices of b-hadrons in jets are reconstructed using information from the tracking detectors, or a muon-based method where the presence of a muon is used to identify semileptonic decays of b-hadrons inside jets. The inclusive b-jet cross-section is measured as a function of transverse momentum in the range 20 < pT < 400 GeV and rapidity in the range |y| < 2.1. The bbbar-dijet cross-section is measured as a function of the dijet invariant mass in the range 110 < m_jj < 760 GeV, the azimuthal angle difference between the two jets and the angular variable chi in two dijet mass regions. The results are compared with next-to-leading-order QCD predictions. Good agreement is observed between the measured cross-sections and the predictions obtained using POWHEG + Pythia. MC@NLO + Herwig shows good agreement with the measured bbbar-dijet cross-section. However, it does not reproduce the measured inclusive cross-section well, particularly for central b-jets with large transverse momenta.Comment: 10 pages plus author list (21 pages total), 8 figures, 1 table, final version published in European Physical Journal

Jet energy measurement with the ATLAS detector in proton-proton collisions at root s=7 TeV

The jet energy scale and its systematic uncertainty are determined for jets measured with the ATLAS detector at the LHC in proton-proton collision data at a centre-of-mass energy of √s = 7TeV corresponding to an integrated luminosity of 38 pb-1. Jets are reconstructed with the anti-kt algorithm with distance parameters R=0. 4 or R=0. 6. Jet energy and angle corrections are determined from Monte Carlo simulations to calibrate jets with transverse momenta pT≥20 GeV and pseudorapidities {pipe}η{pipe}<4. 5. The jet energy systematic uncertainty is estimated using the single isolated hadron response measured in situ and in test-beams, exploiting the transverse momentum balance between central and forward jets in events with dijet topologies and studying systematic variations in Monte Carlo simulations. The jet energy uncertainty is less than 2. 5 % in the central calorimeter region ({pipe}η{pipe}<0. 8) for jets with 60≤pT<800 GeV, and is maximally 14 % for pT<30 GeV in the most forward region 3. 2≤{pipe}η{pipe}<4. 5. The jet energy is validated for jet transverse momenta up to 1 TeV to the level of a few percent using several in situ techniques by comparing a well-known reference such as the recoiling photon pT, the sum of the transverse momenta of tracks associated to the jet, or a system of low-pT jets recoiling against a high-pT jet. More sophisticated jet calibration schemes are presented based on calorimeter cell energy density weighting or hadronic properties of jets, aiming for an improved jet energy resolution and a reduced flavour dependence of the jet response. The systematic uncertainty of the jet energy determined from a combination of in situ techniques is consistent with the one derived from single hadron response measurements over a wide kinematic range. The nominal corrections and uncertainties are derived for isolated jets in an inclusive sample of high-pT jets. Special cases such as event topologies with close-by jets, or selections of samples with an enhanced content of jets originating from light quarks, heavy quarks or gluons are also discussed and the corresponding uncertainties are determined. © 2013 CERN for the benefit of the ATLAS collaboration

Identifying Neighborhoods of Coordinated Gene Expression and Metabolite Profiles

In this paper we investigate how metabolic network structure affects any coordination between transcript and metabolite profiles. To achieve this goal we conduct two complementary analyses focused on the metabolic response to stress. First, we investigate the general size of any relationship between metabolic network gene expression and metabolite profiles. We find that strongly correlated transcript-metabolite profiles are sustained over surprisingly long network distances away from any target metabolite. Secondly, we employ a novel pathway mining method to investigate the structure of this transcript-metabolite relationship. The objective of this method is to identify a minimum set of metabolites which are the target of significantly correlated gene expression pathways. The results reveal that in general, a global regulation signature targeting a small number of metabolites is responsible for a large scale metabolic response. However, our method also reveals pathway specific effects that can degrade this global regulation signature and complicates the observed coordination between transcript-metabolite profiles