Critical political economy, free movement and Brexit: Beyond the progressive’s dilemma

The progressive’s dilemma suggests that a trade-off exists between, on the one hand, labour and welfare rights underpinned by solidarity and shared identity and, on the other hand, open immigration regimes. With reference to debates on free movement in the UK, it is argued: (1) that a progressive European critical political economy literature of the Left has a tendency to accept this dilemma and resolve it in favour of a the former; (2) that it does so because it erroneously conflates the free movement of people with the (increasingly neoliberal) free movement of goods, capital and services; and (3) that it could and should treat human mobility as qualitatively different and, consequently, need not accept the terms of the progressive’s dilemma. The argument has important implications for a progressive politics in general and for the Left’s (particularly the Labour Party’s) position in the UK on free movement (and, by extension, on Brexit)

A VLA H92alpha Study of the Arched Filament Complex Near the Galactic Center

The VLA has been used at 8.3 GHz in the DnC and CnB array configurations to carry out an H92alpha recombination line study (at 8.3 GHz) of the ionized gas in the Arched Filaments H II complex, which defines the western edge of the Galactic center Radio Arc. The H92alpha line properties of the ionized gas are consistent with photoionization from hot stars,and consistent with the physical properties of other Galactic center H II regions. The LTE electron temperatures vary only slightly across the entire extent of the source, and have an average value of 6200 K. The velocity field is very complex, with velocities ranging from +15 to - 70 km/s and the majority of velocities having negative values. Large velocity gradients (2-7 km/s/pc, with gradients in some regions >10 km/s/pc) occur along each of the filaments, with the velocities becoming increasingly negative with decreasing distance from the Galactic center. The magnitudes of the velocity gradient are consistent with the cloud residing on an inner, elongated orbit which is due to the Galaxy's stellar bar, or with a radially infalling cloud. The ionization of the Arched Filaments can be accounted for completely by the massive Arches stellar cluster, which consists of > 150 O-stars. This cluster is likely to belocated 10-20 pc from the Arched Filaments, which can explain the uniformity of ionization conditions in the ionized gas.Comment: 29 pages, 22 figures embedded (some poor quality), accepted to the Astronomical Journal (May 2001 issue), higher resolution figures available from [email protected]

Secular Trends in Nosocomial Bloodstream Infections: Antibiotic-Resistant Bacteria Increase the Total Burden of Infection

In this international study, we demonstrate that increasing rates of nosocomial bloodstream infections caused by antibiotic-resistant bacteria do not replace infections caused by antibiotic-susceptible bacteria, but occur in addition to these infections, thereby increasing the total burden of diseas

Comparing molecular gas across cosmic time-scales: the Milky Way as both a typical spiral galaxy and a high-redshift galaxy analogue

Detailed observations of the nearest star-forming regions in the Milky Way (MW) provide the ultimate benchmark for studying star formation. The extent to which the results of these Galaxy-based studies can be extrapolated to extragalactic systems depends on the overlap of the environmental conditions probed. In this paper, we compare the properties of clouds and star-forming regions in the MW with those in nearby galaxies and in the high-redshift Universe. We find that in terms of their baryonic composition, kinematics and densities, the clouds in the solar neighbourhood are similar to those in nearby galaxies. The clouds and regions in the Central Molecular Zone (CMZ, i.e. the inner 250 pc) of the MW are indistinguishable from high-redshift clouds and galaxies. The presently low star formation rate in the CMZ therefore implies that either (1) its gas represents the initial conditions for high-redshift starbursts or (2) some yet unidentified process consistently suppresses star formation over ≳ 108 yr time-scales. We conclude that the MW contains large reservoirs of gas with properties directly comparable to most of the known range of star formation environments and is therefore an excellent template for studying star formation across cosmological time-scales

Neuroprotection in a Novel Mouse Model of Multiple Sclerosis

The authors acknowledge the support of the Barts and the London Charity, the Multiple Sclerosis Society of Great Britain and Northern Ireland, the National Multiple Sclerosis Society, USA, notably the National Centre for the Replacement, Refinement & Reduction of Animals in Research, and the Wellcome Trust (grant no. 092539 to ZA). The siRNA was provided by Quark Pharmaceuticals. The funders and Quark Pharmaceuticals had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Star Formation and Dynamics in the Galactic Centre

The centre of our Galaxy is one of the most studied and yet enigmatic places in the Universe. At a distance of about 8 kpc from our Sun, the Galactic centre (GC) is the ideal environment to study the extreme processes that take place in the vicinity of a supermassive black hole (SMBH). Despite the hostile environment, several tens of early-type stars populate the central parsec of our Galaxy. A fraction of them lie in a thin ring with mild eccentricity and inner radius ~0.04 pc, while the S-stars, i.e. the ~30 stars closest to the SMBH (<0.04 pc), have randomly oriented and highly eccentric orbits. The formation of such early-type stars has been a puzzle for a long time: molecular clouds should be tidally disrupted by the SMBH before they can fragment into stars. We review the main scenarios proposed to explain the formation and the dynamical evolution of the early-type stars in the GC. In particular, we discuss the most popular in situ scenarios (accretion disc fragmentation and molecular cloud disruption) and migration scenarios (star cluster inspiral and Hills mechanism). We focus on the most pressing challenges that must be faced to shed light on the process of star formation in the vicinity of a SMBH.Comment: 68 pages, 35 figures; invited review chapter, to be published in expanded form in Haardt, F., Gorini, V., Moschella, U. and Treves, A., 'Astrophysical Black Holes'. Lecture Notes in Physics. Springer 201

The Role of Column Density in the Formation of Stars and Black Holes

The stellar mass in disk galaxies scales approximately with the fourth power of the rotation velocity, and the masses of the central black holes in galactic nuclei scale approximately with the fourth power of the bulge velocity dispersion. It is shown here that these relations can be accounted for if, in a forming galaxy with an isothermal mass distribution, gas with a column density above about 8 Msun/pc^2 goes into stars while gas with a column density above about 2 g/cm^2 (10^4 Msun/pc^2) goes into a central black hole. The lower critical value is close to the column density of about 10 Msun/pc^2 at which atomic gas becomes molecular, and the upper value agrees approximately with the column density of about 1 g/cm^2 at which the gas becomes optically thick to its cooling radiation. These results are plausible because molecule formation is evidently necessary for star formation, and because the onset of a high optical depth in a galactic nucleus may suppress continuing star formation and favour the growth of a central black hole.Comment: Accepted by Nature Physic

Genetic Drivers of Epigenetic and Transcriptional Variation in Human Immune Cells

Characterizing the multifaceted contribution of genetic and epigenetic factors to disease phenotypes is a major challenge in human genetics and medicine. We carried out high-resolution genetic, epigenetic, and transcriptomic profiling in three major human immune cell types (CD14$^{+}$ monocytes, CD16$^{+}$ neutrophils, and naive CD4$^{+}$ T cells) from up to 197 individuals. We assess, quantitatively, the relative contribution of $\textit{cis}$-genetic and epigenetic factors to transcription and evaluate their impact as potential sources of confounding in epigenome-wide association studies. Further, we characterize highly coordinated genetic effects on gene expression, methylation, and histone variation through quantitative trait locus (QTL) mapping and allele-specific (AS) analyses. Finally, we demonstrate colocalization of molecular trait QTLs at 345 unique immune disease loci. This expansive, high-resolution atlas of multi-omics changes yields insights into cell-type-specific correlation between diverse genomic inputs, more generalizable correlations between these inputs, and defines molecular events that may underpin complex disease risk.This work was predominantly funded by the EU FP7 High Impact Project BLUEPRINT (HEALTH-F5-2011-282510) and the Canadian Institutes of Health Research (CIHR EP1-120608). The research leading to these results has received funding from the European Union's Seventh Framework Programme (FP7/2007-2013) under grant agreement no 282510 (BLUEPRINT), the European Molecular Biology Laboratory, the Max Planck society, the Spanish Ministry of Economy and Competitiveness, ‘Centro de Excelencia Severo Ochoa 2013-2017’, SEV-2012-0208 and Spanish National Bioinformatics Institute (INB-ISCIII) PT13/0001/0021 co-funded by FEDER "“Una Manera de hacer Europa”. D.G. is supported by a “la Caixa”-Severo Ochoa pre-doctoral fellowship, M.F. was supported by the BHF Cambridge Centre of Excellence [RE/13/6/30180], K.D. is funded as a HSST trainee by NHS Health Education England, S.E. is supported by a fellowship from La Caixa, V.P. is supported by a FEBS long-term fellowship and N.S.'s research is supported by the Wellcome Trust (Grant Codes WT098051 and WT091310), the EU FP7 (EPIGENESYS Grant Code 257082 and BLUEPRINT Grant Code HEALTH-F5-2011-282510) and the NIHR BRC. The Blood and Transplant Unit (BTRU) in Donor Health and Genomics is part of and funded by the National Institute for Health Research (NIHR) and is a partnership between the University of Cambridge and NHS Blood and Transplant (NHSBT) in collaboration with the University of Oxford and the Wellcome Trust Sanger Institute. The T-cell data was produced by the McGill Epigenomics Mapping Centre (EMC McGill). It is funded under the Canadian Epigenetics, Environment, and Health Research Consortium (CEEHRC) by the Canadian Institutes of Health Research and by Genome Quebec (CIHR EP1-120608), with additional support from Genome Canada and FRSQ. T.P. holds a Canada Research Chair

Discovery That Theonellasterol a Marine Sponge Sterol Is a Highly Selective FXR Antagonist That Protects against Liver Injury in Cholestasis

Background: The farnesoid-x-receptor (FXR) is a bile acid sensor expressed in the liver and gastrointestinal tract. Despite FXR ligands are under investigation for treatment of cholestasis, a biochemical condition occurring in a number of liver diseases for which available therapies are poorly effective, mice harboring a disrupted FXR are protected against liver injury caused by bile acid overload in rodent models of cholestasis. Theonellasterol is a 4-methylene-24-ethylsteroid isolated from the marine sponge Theonella swinhoei. Here, we have characterized the activity of this theonellasterol on FXR-regulated genes and biological functions. Principal Findings: Interrogation of HepG2 cells, a human hepatocyte cell line, by microarray analysis and transactivation assay shows that theonellasterol is a selective FXR antagonist, devoid of any agonistic or antagonistic activity on a number of human nuclear receptors including the vitamin D receptor, PPARs, PXR, LXRs, progesterone, estrogen, glucorticoid and thyroid receptors, among others. Exposure of HepG2 cells to theonellasterol antagonizes the effect of natural and synthetic FXR agonists on FXR-regulated genes, including SHP, OSTa, BSEP and MRP4. A proof-of-concept study carried out to investigate whether FXR antagonism rescues mice from liver injury caused by the ligation of the common bile duct, a model of obstructive cholestasis, demonstrated that theonellasterol attenuates injury caused by bile duct ligation as measured by assessing serum alanine aminostrasferase levels and extent of liver necrosis at histopathology. Analysis of genes involved in bile acid uptake and excretion by hepatocytes revealed that theonellasterol increases the liver expression of MRP4, a basolateral transporter that is negatively regulated by FXR. Administering bile duct ligated mice with an FXR agonist failed to rescue from liver injury and downregulated the expression of MRP4. Conclusions: FXR antagonism in vivo results in a positive modulation of MRP4 expression in the liver and is a feasible strategy to target obstructive cholestasis