BMP2/BMPR1A is linked to tumour progression in dedifferentiated liposarcomas

Bone Morphogenic Protein 2 (BMP2) is a multipurpose cytokine, important in the development of bone and cartilage, and with a role in tumour initiation and progression. BMP2 signal transduction is dependent on two distinct classes of serine/threonine kinase known as the type I and type II receptors. Although the type I receptors (BMPR1A and BMPR1B) are largely thought to have overlapping functions, we find tissue and cellular compartment specific patterns of expression, suggesting potential for distinct BMP2 signalling outcomes dependent on tissue type. Herein, we utilise large publicly available datasets from The Cancer Genome Atlas (TCGA) and Protein Atlas to define a novel role for BMP2 in the progression of dedifferentiated liposarcomas. Using disease free survival as our primary endpoint, we find that BMP2 confers poor prognosis only within the context of high BMPR1A expression. Through further annotation of the TCGA sarcoma dataset, we localise this effect to dedifferentiated liposarcomas but find overall BMP2/BMP receptor expression is equal across subsets. Finally, through gene set enrichment analysis we link the BMP2/BMPR1A axis to increased transcriptional activity of the matrisome and general extracellular matrix remodelling. Our study highlights the importance of continued research into the tumorigenic properties of BMP2 and the potential disadvantages of recombinant human BMP2 (rhBMP2) use in orthopaedic surgery. For the first time, we identify high BMP2 expression within the context of high BMPR1A expression as a biomarker of disease relapse in dedifferentiated liposarcomas

Flux-lattice melting in two-dimensional disordered superconductors

The flux line lattice melting transition in two-dimensional pure and disordered superconductors is studied by a Monte Carlo simulation using the lowest Landau level approximation and quasi-periodic boundary condition on a plane. The position of the melting line was determined from the diffraction pattern of the superconducting order parameter. In the clean case we confirmed the results from earlier studies which show the existence of a quasi-long range ordered vortex lattice at low temperatures. Adding frozen disorder to the system the melting transition line is shifted to slightly lower fields. The correlations of the order parameter for translational long range order of the vortex positions seem to decay slightly faster than a power law (in agreement with the theory of Carpentier and Le Doussal) although a simple power law decay cannot be excluded. The corresponding positional glass correlation function decays as a power law establishing the existence of a quasi-long range ordered positional glass formed by the vortices. The correlation function characterizing a phase coherent vortex glass decays however exponentially ruling out the possible existence of a phase coherent vortex glass phase.Comment: 12 pages, 21 figures, final version to appear in Phys. Rev.

Deformations of quantum field theories on spacetimes with Killing vector fields

The recent construction and analysis of deformations of quantum field theories by warped convolutions is extended to a class of curved spacetimes. These spacetimes carry a family of wedge-like regions which share the essential causal properties of the Poincare transforms of the Rindler wedge in Minkowski space. In the setting of deformed quantum field theories, they play the role of typical localization regions of quantum fields and observables. As a concrete example of such a procedure, the deformation of the free Dirac field is studied.Comment: 35 pages, 3 figure

General Overview of Black Hole Accretion Theory

I provide a broad overview of the basic theoretical paradigms of black hole accretion flows. Models that make contact with observations continue to be mostly based on the four decade old alpha stress prescription of Shakura & Sunyaev (1973), and I discuss the properties of both radiatively efficient and inefficient models, including their local properties, their expected stability to secular perturbations, and how they might be tied together in global flow geometries. The alpha stress is a prescription for turbulence, for which the only existing plausible candidate is that which develops from the magnetorotational instability (MRI). I therefore also review what is currently known about the local properties of such turbulence, and the physical issues that have been elucidated and that remain uncertain that are relevant for the various alpha-based black hole accretion flow models.Comment: To be published in Space Science Reviews and as hard cover in the Space Sciences Series of ISSI: The Physics of Accretion on to Black Holes (Springer Publisher

7th Drug hypersensitivity meeting: part two

No abstract availabl

Repositioning of the global epicentre of non-optimal cholesterol

High blood cholesterol is typically considered a feature of wealthy western countries1,2. However, dietary and behavioural determinants of blood cholesterol are changing rapidly throughout the world3 and countries are using lipid-lowering medications at varying rates. These changes can have distinct effects on the levels of high-density lipoprotein (HDL) cholesterol and non-HDL cholesterol, which have different effects on human health4,5. However, the trends of HDL and non-HDL cholesterol levels over time have not been previously reported in a global analysis. Here we pooled 1,127 population-based studies that measured blood lipids in 102.6 million individuals aged 18 years and older to estimate trends from 1980 to 2018 in mean total, non-HDL and HDL cholesterol levels for 200 countries. Globally, there was little change in total or non-HDL cholesterol from 1980 to 2018. This was a net effect of increases in low- and middle-income countries, especially in east and southeast Asia, and decreases in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe. As a result, countries with the highest level of non-HDL cholesterol—which is a marker of cardiovascular risk—changed from those in western Europe such as Belgium, Finland, Greenland, Iceland, Norway, Sweden, Switzerland and Malta in 1980 to those in Asia and the Pacific, such as Tokelau, Malaysia, The Philippines and Thailand. In 2017, high non-HDL cholesterol was responsible for an estimated 3.9 million (95% credible interval 3.7 million–4.2 million) worldwide deaths, half of which occurred in east, southeast and south Asia. The global repositioning of lipid-related risk, with non-optimal cholesterol shifting from a distinct feature of high-income countries in northwestern Europe, north America and Australasia to one that affects countries in east and southeast Asia and Oceania should motivate the use of population-based policies and personal interventions to improve nutrition and enhance access to treatment throughout the world.</p

Measurement of the top-quark mass using a leptonic invariant mass in pp collisions at s√ = 13 TeV with the ATLAS detector

A measurement of the top-quark mass (mt) in the tt¯ → lepton + jets channel is presented, with an experimental technique which exploits semileptonic decays of b-hadrons produced in the top-quark decay chain. The distribution of the invariant mass mℓμ of the lepton, ℓ (with ℓ = e, μ), from the W-boson decay and the muon, μ, originating from the b-hadron decay is reconstructed, and a binned-template profile likelihood fit is performed to extract mt. The measurement is based on data corresponding to an integrated luminosity of 36.1 fb−1 of s√ = 13 TeV pp collisions provided by the Large Hadron Collider and recorded by the ATLAS detector. The measured value of the top-quark mass is mt = 174.41 ± 0.39 (stat.) ± 0.66 (syst.) ± 0.25 (recoil) GeV, where the third uncertainty arises from changing the PYTHIA8 parton shower gluon-recoil scheme, used in top-quark decays, to a recently developed setup