On the Origin of Gravity and the Laws of Newton

Starting from first principles and general assumptions Newton's law of gravitation is shown to arise naturally and unavoidably in a theory in which space is emergent through a holographic scenario. Gravity is explained as an entropic force caused by changes in the information associated with the positions of material bodies. A relativistic generalization of the presented arguments directly leads to the Einstein equations. When space is emergent even Newton's law of inertia needs to be explained. The equivalence principle leads us to conclude that it is actually this law of inertia whose origin is entropic.Comment: 29 pages, 6 figure

Spectral analysis of the biharmonic operator subject to Neumann boundary conditions on dumbbell domains

We consider the biharmonic operator subject to homogeneous boundary conditions of Neumann type on a planar dumbbell domain which consists of two disjoint domains connected by a thin channel. We analyse the spectral behaviour of the operator, characterizing the limit of the eigenvalues and of the eigenprojections as the thickness of the channel goes to zero. In applications to linear elasticity, the fourth order operator under consideration is related to the deformation of a free elastic plate, a part of which shrinks to a segment. In contrast to what happens with the classical second order case, it turns out that the limiting equation is here distorted by a strange factor depending on a parameter which plays the role of the Poisson coefficient of the represented plate.Comment: To appear in "Integral Equations and Operator Theory

On the accuracy of aerosol photoacoustic spectrometer calibrations using absorption by ozone

This is the final version of the article. Available from EGU via the DOI in this record.In recent years, photoacoustic spectroscopy has emerged as an invaluable tool for the accurate measurement of light absorption by atmospheric aerosol. Photoacoustic instruments require calibration, which can be achieved by measuring the photoacoustic signal generated by known quantities of gaseous ozone. Recent work has questioned the validity of this approach at short visible wavelengths (404 nm), indicating systematic calibration errors of the order of a factor of 2. We revisit this result and test the validity of the ozone calibration method using a suite of multipass photoacoustic cells operating at wavelengths 405, 514 and 658 nm. Using aerosolised nigrosin with mobility-selected diameters in the range 250-425 nm, we demonstrate excellent agreement between measured and modelled ensemble absorption cross sections at all wavelengths, thus demonstrating the validity of the ozone-based calibration method for aerosol photoacoustic spectroscopy at visible wavelengths.This work was funded by the Met Office. In addition, Nicholas W. Davies was supported by a NERC/Met Office Industrial Case studentship (ref 640052003). Michael I. Cotterell was supported by a Tom West Analytical Chemistry Trust Fund Fellowship. Michael I. Cotterell and Jim M. Haywood were supported by the CLARIFY-2017 Natural Environment Research Council funded proposal (NE/L013797/1)

Safety of benzodiazepines and opioids in interstitial lung disease: A national prospective study

Copyright ©ERS 2018 Safety concerns are a barrier to prescribing benzodiazepines (BDZs) and opioids in interstitial lung disease (ILD). We therefore examined the association of BDZs and opioids on risk of admission to hospital and death. We conducted a population-based longitudinal cohort study of fibrotic ILD patients starting long-term oxygen therapy in Sweden between October 2005 and December 2014. Effects of BDZs and opioids on rates of admission to hospital and mortality were analysed using Fine-Gray and Cox regression while adjusting for potential confounders. We included 1603 patients (61% females). BDZs were used by 196 (12%) patients and opioids were used by 254 (15%) patients. There was no association between BDZs and increased admission. Treatment with high- versus low-dose BDZs was associated with increased mortality (subdistribution hazard ratio (SHR) 1.46, 95% CI 1.08-1.98 versus 1.13, 95% CI 0.92-1.38). Opioids showed no association with increased admission. Neither low-dose opioids (30 mg·day −1 oral morphine equivalent) (SHR 1.18, 95% CI 0.96-1.45) nor high-dose opioids (>30 mg·day −1 oral morphine equivalent) (SHR 1.11, 95% CI 0.89-1.39) showed association with increased mortality. This first ever study to examine associations between BDZ and opioid use and harm in ILD supports the use of opioids and low-dose BDZs in severely ill patients with respiratory compromise

Enhancing plasma membrane NADPH oxidase activity increases current output by diatoms in biophotovoltaic devices

Biophotovoltaic (BPV) devices employ the photosynthetic activity of microalgae or cyanobacteria to harvest light energy and generate electrical current directly as a result of the release of electrons from the algal cells. NADPH oxidases (NOX) are plasma-membrane enzymes that transport electrons from the cytosol to generate extracellular superoxide anions, and have been implicated in BPV output. In this study, we investigated NOX activity in the diatoms, Phaeodactylum tricornutum and Thalassiosira pseudonana in an attempt to understand and enhance NOX and BPV function. We found that NOX activity was linked to defined growth regimes and growth phases, and was light dependent. Crucially, current output in a BPV device correlated with NOX activity, and levels of up to 14 μA per 106 cells (approximately 500 mA.m-2) were obtained. Expression of two putative P. tricornutum NOX genes (PtNOX1 and PtNOX2) was found to correspond with the observed growth patterns of superoxide anion production and power output, suggesting these are responsible for the observed patterns of NOX activity. Crucially, we demonstrate that NOX activity levels could be enhanced via semi-continuous culturing, pointing to the possibility of maintaining long-term power output in BPV devices.This work was supported by the United Kingdom Engineering and Physical Sciences Research Council (EPSRC), grant reference EP/F047940/1.This is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/j.algal.2015.08.00

AURKA mRNA expression is an independent predictor of poor prognosis in patients with non-small cell lung cancer

Deregulation of mitotic spindle genes has been reported to contribute to the development and progression of malignant tumours. The aim of the present study was to explore the association between the expression profiles of Aurora kinases (AURKA, AURKB and AURKC), cytoskeleton-associated protein 5 (CKAP5), discs large-associated protein 5 (DLGAP5), kinesin-like protein 11 (KIF11), microtubule nucleation factor (TPX2), monopolar spindle 1 kinase (TTK), and β-tubulins (TUBB) and (TUBB3) genes and clinicopathological characteristics in human non-small cell lung carcinoma (NSCLC). Reverse transcription-quantitative polymerase chain reaction-based RNA gene expression profiles of 132 NSCLC and 44 adjacent wild-type tissues were generated, and Cox's proportional hazard regression was used to examine associations. With the exception of AURKC, all genes exhibited increased expression in NSCLC tissues. Of the 10 genes examined, only AURKA was significantly associated with prognosis in NSCLC. Multivariate Cox's regression analysis demonstrated that AURKA mRNA expression [hazard ratio (HR), 1.81; 95% confidence interval (CI), 1.16-2.84; P=0.009], age (HR, 1.03; 95% CI, 1.00-1.06; P=0.020), pathological tumour stage 2 (HR, 2.43; 95% CI, 1.16-5.10; P=0.019) and involvement of distal nodes (pathological node stage 2) (HR, 3.14; 95% CI, 1.24-7.99; P=0.016) were independent predictors of poor prognosis in patients with NSCLC. Poor prognosis of patients with increased AURKA expression suggests that those patients may benefit from surrogate therapy with AURKA inhibitors

Comparative reactivity of the myeloperoxidase-derived oxidants HOCl and HOSCN with low-density lipoprotein (LDL): Implications for foam cell formation in atherosclerosis

© 2015 Elsevier Inc. All rights reserved. Abstract Atherosclerosis is characterised by the accumulation of lipids within macrophages in the artery wall. Low-density lipoprotein (LDL) is the source of this lipid, owing to the uptake of oxidised LDL by scavenger receptors. Myeloperoxidase (MPO) released by leukocytes during inflammation produces oxidants that are implicated in atherosclerosis. Modification of LDL by the MPO oxidant hypochlorous acid (HOCl), results in extensive lipid accumulation by macrophages. However, the reactivity of the other major MPO oxidant, hypothiocyanous acid (HOSCN) with LDL is poorly characterised, which is significant given that thiocyanate is the favoured substrate for MPO. In this study, we comprehensively compare the reactivity of HOCl and HOSCN with LDL, and show key differences in the profile of oxidative damage observed. HOSCN selectively modifies Cys residues on apolipoprotein B100, and oxidises cholesteryl esters resulting in formation of lipid hydroperoxides, 9-hydroxy-10,12-octadecadienoic acid (9-HODE) and F2-isoprostanes. The modification of LDL by HOSCN results macrophage lipid accumulation, though generally to a lesser extent than HOCl-modified LDL. This suggests that a change in the ratio of HOSCN:HOCl formation by MPO from variations in plasma thiocyanate levels, will influence the nature of LDL oxidation in vivo, and has implications for the progression of atherosclerosis