bluuebunny/crossref_metadata_2025 huggingface dataset:
‘A Forming Poem’: Towards a Process Poetics
Authors: Jones Lacey
Published: July 2019

Even as theopoetics turns to literary structures and grammatology to arbitrate between an Absolute and Absolute meaninglessness, John Caputo and David Miller are careful to separate its project from theopoetry’s representations of God. But this division makes little provision for figures like Denise Levertov, whose work suggests that the religious question is an inherently aesthetic one, that this arbitration can happen through representation. This article reads Levertov’s ‘The Tide’ in order to define a mode of signification unbound to spiritual fixity. Through its characterisation of both form and faith as process, ‘The Tide’ offers a new way of negotiating the relationship between literature and theology.
Reconceptualising ‘integration as a two-way process’
Authors: Klarenbeek Lea M.
Published: July 2019

In this article, I advocate the reconceptualisation of ‘integration as a two-way process’. I argue that integration is, fundamentally, an issue of relational inequality, and conceptualising it as a one-way process constitutes problems of undesirability and infeasibility. I show the theoretical hiatus which characterises many dominant approaches to the two-way process, which leads scholars to build their work on internal contradictions and to implicitly (and often unintentionally) feed into a one-way integration discourse. I argue that as long as conceptualisations of integration as a two-way process reinforce a boundary between ‘people who integrate’ and ‘people who do not integrate’, they are unfit to avoid the problems of one-wayness which they intended to overcome in the first place. In the last part of the article, I put forward some initial building blocks for a new theoretical framework of ‘integration as a two-way process’ which is more attentive to the relational social processes that constitute integration.
The waiting game: Immigration detention as the waiting room of immigration law
Authors: Könönen Jukka
Published: July 2019

In this article, I examine detained third-country nationals’ negotiations with the immigration system during detention, focusing on how immigration and removal proceedings inform their waiting while in detention. Based on multisited ethnographic research into the immigration detention system in Finland, I argue that waiting in immigration detention needs to be understood as a relational concept that involves different objects and expectations depending on the details of detainees’ immigration cases that affect the possibility of being released and the country of removal under the common European border regime. Immigration detention is a ‘waiting room’ of immigration law in that detainees wait for the outcome of pending immigration proceedings or the implementation of enforceable removal decisions. At the same time, immigration detention constitutes a space of border struggles, or what I call the ‘waiting game’, where detainees actively negotiate with authorities concerning their immigration cases, including terms of removal. Contrary to common belief, deportable detainees did not usually actively resist removal, especially to other European Union Member States. Instead, waiting in detention is a different matter for those with pending immigration decisions or whose removal would be to African or Middle Eastern countries. Additionally, detainees’ migration preferences affect their level of compliance and attitudes while in detention: many research participants planned to come back to Europe. My empirical analysis demonstrates that detention times and detainees’ attitudes toward removal are significantly dependent upon their individual immigration cases and their country of removal, resulting in different temporal horizons among waiting detainees.
The War of the Austrian Succession and the Masses by Henry Madin (1740–1748)
Authors: Montagnier Jean-Paul C
Published: July 2019

Henry Madin was the only sous-maître de la Musique of Louis XV’s Chapel to be a priest, and served in this capacity during the time of the War of the Austrian Succession (1740–8). Documents strongly imply that Madin was exceptionally receptive to the fate of the royal armies and also demonstrate his keen political acumen. Only motets à grand chœur were sung at the king’s Mass: composers connected with the Chapelle Royale had no necessity to set the Ordinarium missae to music. Therefore, one wonders why Madin had polyphonic masses printed by Ballard between 1741 and 1747. This essay indicates that Madin had a personal initiative in mind, and that his mass settings punctuated significant victories and temporary setbacks of Louis XV’s army. His missae may be regarded as the private voice of a faithful royal official begging God for assistance on behalf of a king who had brought him out of poverty.
Secular dynamics of binaries in stellar clusters – I. General formulation and dependence on cluster potential
Authors: Hamilton Chris , Rafikov Roman R
Published: July 2019

Orbital evolution of binary systems in dense stellar clusters is important in a variety of contexts: origin of blue stragglers, progenitors of compact object mergers, millisecond pulsars, and so on. Here we consider the general problem of secular evolution of the orbital elements of a binary system driven by the smooth tidal field of an axisymmetric stellar cluster (globular, nuclear, etc.) in which the binary orbits. We derive a secular Hamiltonian (averaged over both the inner Keplerian orbit of the binary and its outer orbit within the cluster) valid to quadrupole order for an arbitrary cluster potential and explore its characteristics. This doubly averaged ‘tidal’ Hamiltonian depends on just two parameters, which fully absorb the information about the background cluster potential and the binary’s orbit within it: a dimensional parameter A setting the secular time-scale, and a dimensionless parameter Γ which determines the phase portrait of the binary’s inner orbital evolution. We examine the dependence of A and Γ on cluster potential (both spherical and axisymmetric) and on the binary orbit within the cluster. Our theory reproduces known secular results – such as Lidov–Kozai evolution and the effect of the Galactic tide on Oort Cloud comets – in appropriate limits, but is more general. It provides a universal framework for understanding dynamical evolution of various types of binaries driven by the smooth tidal field of any axisymmetric potential. In a companion paper we provide a detailed exploration of the resulting orbital dynamics.
Enhancing AGN efficiency and cool-core formation with anisotropic thermal conduction
Authors: Barnes David J , Kannan Rahul , Vogelsberger Mark , Pfrommer Christoph , Puchwein Ewald , Weinberger Rainer , Springel Volker , Pakmor Rüdiger , Nelson Dylan , Marinacci Federico , Pillepich Annalisa , Torrey Paul , Hernquist Lars
Published: July 2019

Understanding how baryonic processes shape the intracluster medium (ICM) is of critical importance to the next generation of galaxy cluster surveys. However, many models of structure formation neglect potentially important physical processes, like anisotropic thermal conduction (ATC). We explore the impact of ATC on the prevalence of cool-cores (CCs) via 12 pairs of magnetohydrodynamical galaxy cluster simulations, using the IllustrisTNG model with and without ATC. Examining their properties we find that the addition of ATC has a negligible impact on the median rotation measure, plasma β, the magnetic field-radial direction angle, and the effective Spitzer value. However, the scatter in the angle and effective Spitzer value is 50 per cent larger with ATC because the magnetic field aligns with the azimuthal direction to a greater extent in relaxed clusters. ATC’s impact varies from cluster to cluster and with CC criterion, but its inclusion produces a systematic shift to larger CC fractions at z = 0 for all CC criteria considered. Additionally, the inclusion of ATC flattens the CC fraction redshift evolution, helping to ease the tension with the observed evolution. With ATC, the energy required for the central black hole to self-regulate is reduced by 24 per cent and the gas fraction at $0.01\, r_{500}$ increases by 100 per cent, producing larger CC fractions. ATC makes the ICM unstable to perturbations and the increased efficiency of AGN feedback suggests that its inclusion results in a greater level of mixing in the ICM, demonstrated by the 10 per cent reduction in central metallicity for clusters with ATC.
Deep ugrizY imaging and DEEP2/3 spectroscopy: a photometric redshift testbed for LSST and public release of data from the DEEP3 Galaxy Redshift Survey
Authors: Zhou Rongpu , Cooper Michael C , Newman Jeffrey A , Ashby Matthew L N , Aird James , Conselice Christopher J , Davis Marc , Dutton Aaron A , Faber S M , Fang Jerome J , Fazio G G , Guhathakurta Puragra , Kocevski Dale , Koo David C , Nandra Kirpal , Phillips Andrew C , Rosario David J , Schlafly Edward F , Trump Jonathan R , Weiner Benjamin , Willmer Christopher N A , Yan Renbin
Published: July 2019

We present catalogues of calibrated photometry and spectroscopic redshifts in the Extended Groth Strip, intended for studies of photometric redshifts (photo-z’s). The data includes ugriz photometry from Canada–France–Hawaii Telescope Legacy Survey (CFHTLS) and Y-band photometry from the Subaru Suprime camera, as well as spectroscopic redshifts from the DEEP2, DEEP3, and 3D-HST surveys. These catalogues incorporate corrections to produce effectively matched-aperture photometry across all bands, based upon object size information available in the catalogue and Moffat profile point spread function fits. We test this catalogue with a simple machine learning-based photometric redshift algorithm based upon Random Forest regression, and find that the corrected aperture photometry leads to significant improvement in photo-z accuracy compared to the original SExtractor catalogues from CFHTLS and Subaru. The deep ugrizY photometry and spectroscopic redshifts are well suited for empirical tests of photometric redshift algorithms for LSST. The resulting catalogues are publicly available at http://d-scholarship.pitt.edu/36064/. We include a basic summary of the strategy of the DEEP3 Galaxy Redshift Survey to accompany the recent public release of DEEP3 data.
The environment of H i-bearing ultra-diffuse galaxies in the ALFALFA survey
Authors: Janowiecki Steven , Jones Michael G , Leisman Lukas , Webb Andrew
Published: July 2019

We explore the environment of 252 H i-bearing ultra-diffuse galaxies (HUDs) from the 100 per cent ALFALFA survey catalogue in an attempt to constrain their formation mechanism. We select sources from ALFALFA with surface brightnesses, magnitudes, and radii consistent with other samples of ultra-diffuse galaxies (UDGs) without restrictions on their isolation or environment, more than doubling the previously reported ALFALFA sample. We quantify the galactic environment of HUDs using several metrics, including nth nearest neighbour, tidal influence, membership in a group/cluster, and distance from nearest group/cluster or filament. We find that HUDs inhabit the same environments as other samples of H i-selected galaxies and that they show no environmental preference in any metric. We suggest that these results are consistent with a picture of the extreme properties of HUDs being driven by internal mechanisms and that they are largely unperturbed by environmental impacts. While environmental effects may be necessary to convert HUDs into gas-poor cluster UDGs, these effects are not required for diffuse galaxies to exist in the first place.
Coronagraphic phase diversity through residual turbulence: performance study and experimental validation
Authors: Herscovici-Schiller Olivier , Sauvage Jean-François , Mugnier Laurent M , Dohlen Kjetil , Vigan Arthur
Published: July 2019

Quasi-static aberrations in coronagraphic systems are the ultimate limitation to the capabilities of exoplanet imagers both ground-based and space-based. These aberrations – which can be due to various causes such as optics alignment or moving optical parts during the observing sequence – create light residuals called speckles in the focal plane. Those speckles might be mistaken for planets. For ground-based instruments, the presence of residual turbulent wavefront errors due to partial adaptive optics correction causes an additional difficulty to the challenge of measuring aberrations in the presence of a coronagraph. In this paper, we present an extension of COFFEE, the coronagraphic phase diversity, to the estimation of quasi-static aberrations in the presence of adaptive-optics-corrected residual turbulence. We perform realistic numerical simulations to assess the performance that can be expected on an instrument of the current generation. We perform the first experimental validation in the laboratory, which demonstrates that quasi-static aberrations can be corrected during the observations by means of coronagraphic phase diversity.
Rest-frame UV and optical emission line diagnostics of ionized gas properties: a test case in a star-forming knot of a lensed galaxy at z ∼ 1.7
Authors: Acharyya Ayan , Kewley Lisa J , Rigby Jane R , Bayliss Matthew , Bian Fuyan , Nicholls David , Federrath Christoph , Kaasinen Melanie , Florian Michael , Blanc Guillermo A
Published: July 2019

We examine the diagnostic power of rest-frame ultraviolet (UV) nebular emission lines, and compare them to more commonly used rest-frame optical emission lines, using the test case of a single star-forming knot of the bright lensed galaxy RCSGA 032727–132609 at redshift $z$ ∼ 1.7. This galaxy has complete coverage of all the major rest-frame UV and optical emission lines from Magellan/MagE and Keck/NIRSPEC. Using the full suite of diagnostic lines, we infer the physical properties: nebular electron temperature (Te), electron density (ne), oxygen abundance (log (O/H), ionization parameter [log (q), and interstellar medium (ISM) pressure (log (P/k)]. We examine the effectiveness of the different UV, optical, and joint UV–optical spectra in constraining the physical conditions. Using UV lines alone we can reliably estimate log (q), but the same is difficult for log (O/H). UV lines yield a higher (∼1.5 dex) log (P/k) than the optical lines, as the former probes a further inner nebular region than the latter. For this comparison, we extend the existing Bayesian inference code izi, adding to it the capability to infer ISM pressure simultaneously with metallicity and ionization parameter. This work anticipates future rest-frame UV spectral data sets from the James Webb Space Telescope (JWST) at high redshift and from the Extremely Large Telescope (ELT) at moderate redshift.
The nature of the soft excess and spectral variability in the Seyfert 1 galaxy Zw 229.015
Authors: Tripathi S , Waddell S G H , Gallo L C , Welsh W F , Chiang C-Y
Published: July 2019

We have carried out a systematic analysis of the nearby (z = 0.0279) active galaxy Zw 229.015 using multi-epoch, multi-instrument, and deep pointed observations with XMM–Newton, Suzaku, Swift,and NuSTAR. Spectral and temporal variability are examined in detail on both the long (weeks-to-years) and short (hours) time-scales. A deep Suzaku observation of the source shows two distinct spectral states; a bright-soft state and a dim-hard state in which changes in the power-law component account for the differences. Partial covering, blurred reflection, and soft Comptonization models describe the X-ray spectra comparably well, but the smooth, rather featureless, spectrum may be favouring the soft Comptonization scenario. Moreover, independent of the spectral model, the observed spectral variability is ascribed to the changes in the power-law continuum only and do not require changes in the properties of the absorber or blurred reflector incorporated in the other scenarios. The multi-epoch observations between 2009 and 2018 can be described in similar fashion. This could be understood if the primary emission is originating at a large distance from a standard accretion disc or if the disc is optically thin and geometrically thick as recently proposed for Zw 229.015. Our investigation shows that Zw 229.015 behaves similar to sources like Akn 120 and Mrk 530 that exhibit a strong soft excess, but weak Compton hump and Fe Kα emission.
Multiwavelength characterization of the accreting millisecond X-ray pulsar and ultracompact binary IGR J17062–6143
Authors: Hernández Santisteban J V , Cúneo V , Degenaar N , van den Eijnden J , Altamirano D , Gómez M N , Russell D M , Wijnands R , Golovakova R , Reynolds M T , Miller J M
Published: July 2019

IGR J17062–6143 is an ultracompact X-ray binary (UCXB) with an orbital period of 37.96 min. It harbours a millisecond X-ray pulsar that is spinning at 163 Hz and and has continuously been accreting from its companion star since 2006. Determining the composition of the accreted matter in UCXBs is of high interest for studies of binary evolution and thermonuclear burning on the surface of neutron stars. Here, we present a multiwavelength study of IGR J17062–6143 aimed to determine the detailed properties of its accretion disc and companion star. The multi-epoch photometric UV to near-infrared spectral energy distribution (SED) is consistent with an accretion disc Fν ∝ ν1/3. The SED modelling of the accretion disc allowed us to estimate an outer disc radius of $R_{\rm out} = 2.2^{+0.9}_{-0.4} \times 10^{10}$ cm and a mass-transfer rate of $\dot{m} = 1.8^{+1.8}_{-0.5}\times 10^{-10}$ M⊙ yr−1. Comparing this with the estimated mass-accretion rate inferred from its X-ray emission suggests that ≳90 per cent of the transferred mass is lost from the system. Moreover, our SED modelling shows that the thermal emission component seen in the X-ray spectrum is highly unlikely from the accretion disc and must therefore represent emission from the surface of the neutron star. Our low-resolution optical spectrum revealed a blue continuum and no emission lines, i.e. lacking H and He features. Based on the current data we cannot conclusively identify the nature of the companion star, but we make recommendations for future study that can distinguish between the different possible evolution histories of this X-ray binary. Finally, we demonstrate how multiwavelength observations can be effectively used to find more UCXBs among the LMXBs.
Sub-damped Lyman α systems in the XQ-100 survey – I. Identification and contribution to the cosmological H i budget
Authors: Berg Trystyn A M , Ellison Sara L , Sánchez-Ramírez Rubén , López Sebastián , D’Odorico Valentina , Becker George D , Christensen Lise , Cupani Guido , Denney Kelly D , Worseck Gábor
Published: July 2019

Sub-damped Lyman α systems (subDLAs; H i column densities of 19.0 ≤ logN(H i) < 20.3) are rarely included in the cosmic H i census performed at redshifts zabs ≳ 1.5, yet are expected to contribute significantly to the overall H i mass budget of the Universe. In this paper, we present a blindly selected sample of 155 subDLAs found along 100 quasar sightlines (with a redshift path-length ΔX = 475) in the XQ-100 legacy survey to investigate the contribution of subDLAs to the H i mass density of the Universe. The impact of X-Shooter’s spectral resolution on Ly α absorber identification is evaluated, and found to be sufficient for reliably finding absorbers down to a column density of logN(H i) ≥ 18.9. We compared the implications of searching for subDLAs solely using H i absorption versus the use of metal lines to confirm the identification, and found that metal-selection techniques would have missed 75 subDLAs. Using a bootstrap Monte Carlo simulation, we computed the column density distribution function (f(N, X)) and the cosmological H i mass density ($\Omega _{\rm H\,{\small I}}$) of subDLAs and compared with our previous work based on the XQ-100 damped Lyman α systems. We do not find any significant redshift evolution in f(N, X) or $\Omega _{\rm H\,{\small I}}$ for subDLAs. However, subDLAs contribute 10–20 per cent of the total $\Omega _{\rm H\,{\small I}}$ measured at redshifts 2 < z < 5, and thus have a small but significant contribution to the H i budget of the Universe.
Autocorrelations in pulsar glitch waiting times and sizes
Authors: Carlin J B , Melatos A
Published: July 2019

Among the five pulsars with the most recorded rotational glitches, only PSR J0534+2200 is found to have an autocorrelation between consecutive glitch sizes that differs significantly from zero (Spearman correlation coefficient ρ = −0.46, p-value = 0.046). No statistically compelling autocorrelations between consecutive waiting times are found. The autocorrelation observations are interpreted within the framework of a predictive meta-model describing stress release in terms of a state-dependent Poisson process. Specific combinations of size and waiting time autocorrelations are identified, alongside combinations of cross-correlations and size and waiting time distributions, that are allowed or excluded within the meta-model. For example, future observations of any ‘quasi-periodic’ glitching pulsar, such as PSR J0537–6910, should not reveal a positive waiting time autocorrelation. The implications for microphysical models of the stress-release process driving pulsar glitches are discussed briefly.
Eccentric binary black hole mergers in globular clusters hosting intermediate-mass black holes
Authors: Fragione Giacomo , Bromberg Omer
Published: July 2019

Globular clusters (GCs) may harbour intermediate-mass black holes (IMBHs) at their centres. In these dynamically active environments, stellar-mass black holes (SBHs) sink to the centre soon after formation, due to dynamical friction and start interacting among themselves and with the central IMBH. Likely, some of the SBHs will form bound systems with the IMBH. A fraction of those will be triple systems composed of binary SBHs and the IMBH acting as a third distant perturber. If the SBH binary orbit is sufficiently inclined, it can develop Lidov–Kozai (LK) oscillations, which can drive the system to high eccentricities and eventually to a merger due to gravitational wave (GW) emission on short time-scales. In this work, we focus on the dynamics of the IMBH–SBH–SBH triples and illustrate that these systems can be possible sources of GWs. A distinctive signature of this scenario is that a considerable fraction of these mergers are highly eccentric when entering the LIGO band (10 Hz). Assuming that $\sim 20{{\ \rm per\ cent}}$ of GCs host IMBHs and a GC density in the range $n_{{\rm GC}}=0.32\!-\!2.31\, \mathrm{Mpc}^{-3}$, we have estimated a rate $\Gamma =0.06\!-\!0.46\, \mathrm{Gpc}^{-3}\, \mathrm{yr}^{-1}$ of these events. This suggests that dynamically driven binary SBH mergers in this scenario could contribute to the merger events observed by LIGO/VIRGO. Full N-body simulations of GCs harbouring IMBHs are highly desirable to give a more precise constrain on this scenario.
Analytic computation of the secular effects of encounters on a binary: third-order perturbation, octupole, and post-Newtonian terms; steady-state distribution
Authors: Hamers Adrian S , Samsing Johan
Published: July 2019

Dense stellar systems such as globular clusters are believed to harbour merging binary black holes (BHs). The evolution of such binaries is driven by interactions with other stars, most notably, binary-single interactions. Traditionally, so-called ‘strong’ interactions are believed to be the driving force in this evolution. However, we recently showed that more distant, i.e. ‘weak’ or ‘secular’ encounters, can have important implications for the properties of merging BH binaries in globular clusters. This motivates more detailed understanding of the effects of secular encounters on a binary. In another previous paper, we analytically calculated expressions for the changes of the eccentricity and angular-momentum vectors taking into account second-order perturbation theory, and showed that, for highly eccentric binaries, the new expressions give rise to behaviour that is not captured by first-order theory. Here, we extend our previous work to third-order perturbation theory. We also include terms up to and including octupole order. The latter are non-zero for binaries with unequal component masses. In addition, we consider the effects of post-Newtonian terms, and we determine the steady-state distribution due to the cumulative effect of secular encounters by computing the associated angular-momentum diffusion coefficients, and applying the Fokker–Planck equation. Together with our previous work, the results in this paper provide a framework for incorporating the effects of distant encounters on binaries in models of cluster evolution, such as Monte Carlo codes.
Star-formation rates of two GRB host galaxies at z ∼ 2 and a [C ii] deficit observed with ALMA
Authors: Hashimoto Tetsuya , Hatsukade Bunyo , Goto Tomotsugu , Kim Seong Jin , Ohta Kouji , Nagao Tohru , Kong Albert K H , Nakanishi Kouichiro , Mao Jirong
Published: July 2019

The event rate of long gamma-ray bursts (GRBs) is expected to be a useful tracer of cosmic star-formation history. For this purpose, it is necessary to understand what kinds of star formation/galaxies are traced by GRBs. Here we report rest-frame far-infrared (FIR) continuum detections of the GRB 070521 and 080207 host galaxies at z ∼ 2 with Atacama Large Millimeter/submillimeter Array (ALMA) bands 8 and 9. FIR photometry provides reliable star-formation rates (SFRs), because FIR emission is free from dust extinction and possible radio contamination from the long-lived afterglows of GRBs. Spectral energy distribution fitting yields 49.85$^{+72.33}_{-2.86}$ and 123.4$^{+25.19}_{-21.78}$ M⊙ yr−1 for the 070521 and 080207 hosts, respectively. The derived SFRs place them on the ‘main sequence’ of normal star-forming galaxies at z ∼ 2. The derived SFRs are significantly lower than those from radio observations. It is inferred that the observed radio fluxes in a previous study are contaminated by afterglows. ALMA marginally detected the [C ii] 158-μm emission line from the GRB 080207 host galaxy with signal-to-noise ratio (S/N) ∼ 4. This is the first detection of [C ii] 158-μm from a GRB host at z > 2 and the second detection among known GRBs. The luminosity ratio of [C ii] 158 μm to FIR is 7.5 × 10−4, which is one of the smallest values among galaxies at z ∼ 1–2 with the same FIR luminosity. The ‘[C ii] deficit’ could be a new physical property with which to characterize GRB hosts at z ∼ 1–2. Possible parameters controlling the deficit include the metallicity, initial mass function and gas density.
Young magnetars with fracturing crusts as fast radio burst repeaters
Authors: Suvorov A G , Kokkotas K D
Published: July 2019

Fast radio bursts are millisecond-duration radio pulses of extragalactic origin. A recent statistical analysis has found that the burst energetics of the repeating source FRB 121102 follow a power law, with an exponent that is curiously consistent with the Gutenberg–Richter law for earthquakes. This hints that repeat bursters may be compact objects undergoing violent tectonic activity. For young magnetars, possessing crustal magnetic fields which are both strong (B ≳ 1015 G) and highly multipolar, Hall drift can instigate significant field rearrangements even on ≲ century long time-scales. This reconfiguration generates zones of magnetic stress throughout the outer layers of the star, potentially strong enough to facilitate frequent crustal failures. In this paper, assuming a quake scenario, we show how the crustal field evolution, which determines the resulting fracture geometries, can be tied to burst properties. Highly anisotropic stresses are generated by the rapid evolution of multipolar fields, implying that small, localized cracks can occur sporadically throughout the crust during the Hall evolution. Each of these shallow fractures may release bursts of energy, consistent in magnitude with those seen in the repeating sources FRB 121102 and FRB 180814.J0422+73.
Genome-wide epistasis and co-selection study using mutual information
Authors: Pensar Johan , Puranen Santeri , Arnold Brian , MacAlasdair Neil , Kuronen Juri , Tonkin-Hill Gerry , Pesonen Maiju , Xu Yingying , Sipola Aleksi , Sánchez-Busó Leonor , Lees John A , Chewapreecha Claire , Bentley Stephen D , Harris Simon R , Parkhill Julian , Croucher Nicholas J , Corander Jukka
Published: July 2019

Covariance-based discovery of polymorphisms under co-selective pressure or epistasis has received considerable recent attention in population genomics. Both statistical modeling of the population level covariation of alleles across the chromosome and model-free testing of dependencies between pairs of polymorphisms have been shown to successfully uncover patterns of selection in bacterial populations. Here we introduce a model-free method, SpydrPick, whose computational efficiency enables analysis at the scale of pan-genomes of many bacteria. SpydrPick incorporates an efficient correction for population structure, which adjusts for the phylogenetic signal in the data without requiring an explicit phylogenetic tree. We also introduce a new type of visualization of the results similar to the Manhattan plots used in genome-wide association studies, which enables rapid exploration of the identified signals of co-evolution. Simulations demonstrate the usefulness of our method and give some insight to when this type of analysis is most likely to be successful. Application of the method to large population genomic datasets of two major human pathogens, Streptococcus pneumoniae and Neisseria meningitidis, revealed both previously identified and novel putative targets of co-selection related to virulence and antibiotic resistance, highlighting the potential of this approach to drive molecular discoveries, even in the absence of phenotypic data.
Long-read amplicon denoising
Authors: Kumar Venkatesh , Vollbrecht Thomas , Chernyshev Mark , Mohan Sanjay , Hanst Brian , Bavafa Nicholas , Lorenzo Antonia , Kumar Nikesh , Ketteringham Robert , Eren Kemal , Golden Michael , Oliveira Michelli F , Murrell Ben
Published: July 2019

Long-read next-generation amplicon sequencing shows promise for studying complete genes or genomes from complex and diverse populations. Current long-read sequencing technologies have challenging error profiles, hindering data processing and incorporation into downstream analyses. Here we consider the problem of how to reconstruct, free of sequencing error, the true sequence variants and their associated frequencies from PacBio reads. Called ‘amplicon denoising’, this problem has been extensively studied for short-read sequencing technologies, but current solutions do not always successfully generalize to long reads with high indel error rates. We introduce two methods: one that runs nearly instantly and is very accurate for medium length reads and high template coverage, and another, slower method that is more robust when reads are very long or coverage is lower. On two Mock Virus Community datasets with ground truth, each sequenced on a different PacBio instrument, and on a number of simulated datasets, we compare our two approaches to each other and to existing algorithms. We outperform all tested methods in accuracy, with competitive run times even for our slower method, successfully discriminating templates that differ by a just single nucleotide. Julia implementations of Fast Amplicon Denoising (FAD) and Robust Amplicon Denoising (RAD), and a webserver interface, are freely available.
The mRNA degradation factor Xrn1 regulates transcription elongation in parallel to Ccr4
Authors: Begley Victoria , Corzo Daniel , Jordán-Pla Antonio , Cuevas-Bermúdez Abel , Miguel-Jiménez Lola de , Pérez-Aguado David , Machuca-Ostos Mercedes , Navarro Francisco , Chávez María José , Pérez-Ortín José E , Chávez Sebastián
Published: July 2019

Co-transcriptional imprinting of mRNA by Rpb4 and Rpb7 subunits of RNA polymerase II (RNAPII) and by the Ccr4–Not complex conditions its post-transcriptional fate. In turn, mRNA degradation factors like Xrn1 are able to influence RNAPII-dependent transcription, making a feedback loop that contributes to mRNA homeostasis. In this work, we have used repressible yeast GAL genes to perform accurate measurements of transcription and mRNA degradation in a set of mutants. This genetic analysis uncovered a link from mRNA decay to transcription elongation. We combined this experimental approach with computational multi-agent modelling and tested different possibilities of Xrn1 and Ccr4 action in gene transcription. This double strategy brought us to conclude that both Xrn1–decaysome and Ccr4–Not regulate RNAPII elongation, and that they do it in parallel. We validated this conclusion measuring TFIIS genome-wide recruitment to elongating RNAPII. We found that xrn1Δ and ccr4Δ exhibited very different patterns of TFIIS versus RNAPII occupancy, which confirmed their distinct role in controlling transcription elongation. We also found that the relative influence of Xrn1 and Ccr4 is different in the genes encoding ribosomal proteins as compared to the rest of the genome.
Prediction of regulatory motifs from human Chip-sequencing data using a deep learning framework
Authors: Yang Jinyu , Ma Anjun , Hoppe Adam D , Wang Cankun , Li Yang , Zhang Chi , Wang Yan , Liu Bingqiang , Ma Qin
Published: July 2019

The identification of transcription factor binding sites and cis-regulatory motifs is a frontier whereupon the rules governing protein–DNA binding are being revealed. Here, we developed a new method (DEep Sequence and Shape mOtif or DESSO) for cis-regulatory motif prediction using deep neural networks and the binomial distribution model. DESSO outperformed existing tools, including DeepBind, in predicting motifs in 690 human ENCODE ChIP-sequencing datasets. Furthermore, the deep-learning framework of DESSO expanded motif discovery beyond the state-of-the-art by allowing the identification of known and new protein–protein–DNA tethering interactions in human transcription factors (TFs). Specifically, 61 putative tethering interactions were identified among the 100 TFs expressed in the K562 cell line. In this work, the power of DESSO was further expanded by integrating the detection of DNA shape features. We found that shape information has strong predictive power for TF–DNA binding and provides new putative shape motif information for human TFs. Thus, DESSO improves in the identification and structural analysis of TF binding sites, by integrating the complexities of DNA binding into a deep-learning framework.
A CRISPR-Cas9 screen identifies essential CTCF anchor sites for estrogen receptor-driven breast cancer cell proliferation
Authors: Korkmaz Gozde , Manber Zohar , Lopes Rui , Prekovic Stefan , Schuurman Karianne , Kim Yongsoo , Teunissen Hans , Flach Koen , Wit Elzo de , Galli Giorgio G , Zwart Wilbert , Elkon Ran , Agami Reuven
Published: July 2019

Estrogen receptor α (ERα) is an enhancer activating transcription factor, a key driver of breast cancer and a main target for cancer therapy. ERα-mediated gene regulation requires proper chromatin-conformation to facilitate interactions between ERα-bound enhancers and their target promoters. A major determinant of chromatin structure is the CCCTC-binding factor (CTCF), that dimerizes and together with cohesin stabilizes chromatin loops and forms the boundaries of topologically associated domains. However, whether CTCF-binding elements (CBEs) are essential for ERα-driven cell proliferation is unknown. To address this question in a global manner, we implemented a CRISPR-based functional genetic screen targeting CBEs located in the vicinity of ERα-bound enhancers. We identified four functional CBEs and demonstrated the role of one of them in inducing chromatin conformation changes in favor of activation of PREX1, a key ERα target gene in breast cancer. Indeed, high PREX1 expression is a bona-fide marker of ERα-dependency in cell lines, and is associated with good outcome after anti-hormonal treatment. Altogether, our data show that distinct CTCF-mediated chromatin structures are required for ERα- driven breast cancer cell proliferation.
Cinacalcet use in paediatric dialysis: a position statement from the European Society for Paediatric Nephrology and the Chronic Kidney Disease-Mineral and Bone Disorders Working Group of the ERA-EDTA
Authors: Bacchetta Justine , Schmitt Claus Peter , Ariceta Gema , Bakkaloglu Sevcan A , Groothoff Jaap , Wan Mandy , Vervloet Marc , Shroff Rukshana , Haffner Dieter ,   European Society for Paediatric Nephrology and the Chronic Kidney Disease-Mineral and Bone Disorders and Dialysis Working Group of the ERA-EDTA
Published: July 2019

Secondary hyperparathyroidism (SHPT) is an important complication of advanced chronic kidney disease (CKD) in children, which is often difficult to treat with conventional therapy. The calcimimetic cinacalcet is an allosteric modulator of the calcium-sensing receptor. It has proven to be effective and safe in adults to suppress parathyroid hormone (PTH), but data on its use in children are limited. To date, studies in children only consist of two randomized controlled trials, nine uncontrolled interventional or observational studies, and case reports that report the efficacy of cinacalcet as a PTH-lowering compound. In 2017, the European Medical Agency approved the use of cinacalcet for the treatment of SHPT in children on dialysis in whom SHPT is not adequately controlled with standard therapy. Since evidence-based guidelines are so far lacking, we present a position statement on the use of cinacalcet in paediatric dialysis patients based on the available evidence and opinion of experts from the European Society for Paediatric Nephrology, Chronic Kidney Disease-Mineral and Bone Disorder and Dialysis Working Groups, and the ERA-EDTA. Given the limited available evidence the strength of these statements are weak to moderate, and must be carefully considered by the treating physician and adapted to individual patient needs as appropriate. Audit and research recommendations to study key outcome measures in paediatric dialysis patients receiving cinacalcet are suggested.
Relationship between complement deposition and the Oxford classification score and their combined effects on renal outcome in immunoglobulin A nephropathy
Authors: Park Seohyun , Kim Hyung Woo , Park Jung Tak , Chang Tae Ik , Kang Ea Wha , Ryu Dong-Ryeol , Yoo Tae-Hyun , Chin Ho Jun , Jeong Hyeon Joo , Kang Shin-Wook , Lim Beom Jin , Han Seung Hyeok
Published: July 2019

Background

Complement activation has been highlighted in immunoglobulin (Ig) A nephropathy pathogenesis. However, whether the complement system can affect the downstream phenotype of IgA nephropathy remains unknown. Herein, we investigated the association of mesangial C3 deposition with the Oxford classification and their joint effects on worsening kidney function.

Methods

We investigated 453 patients with biopsy-proven IgA nephropathy. C3 deposition was defined as an immunofluorescence intensity of C3 ≥2+ within the mesangium. The subjects were classified according to the combination of C3 deposition and Oxford classification lesions. The primary endpoint was a composite of ≥30% decline in the estimated glomerular filtration rate or an increase in proteinuria ≥3.5 g/g during follow-up.

Results

Among the Oxford classification lesions, mesangial hypercellularity (M1), segmental glomerulosclerosis (S1) and tubulointerstitial fibrosis (T1–2) and crescentic lesion significantly correlated with C3 deposition. During a median follow-up of 33.0 months, the primary endpoint occurred more in patients with M1, S1, T1–2 and mesangial C3 deposition than in those without. In individual multivariable-adjusted Cox analyses, the presence of M1, S1, T1–2 and C3 deposition was significantly associated with higher risk of reaching primary endpoint. In the combined analyses of C3 deposition and the Oxford classification lesions, the hazard ratios for the composite outcome were significantly higher in the presence of C3/M1, C3/S1 and C3/crescent than in the presence of each lesion alone.

Conclusions

Complement deposition can strengthen the significance of the Oxford classification, and the presence of both components portends a poorer prognosis in IgA nephropathy.
Loss of sodium chloride co-transporter impairs the outgrowth of the renal distal convoluted tubule during renal development
Authors: Schnoz Christina , Carrel Monique , Loffing Johannes
Published: July 2019

Background

Loss-of-function mutations in the sodium chloride (NaCl) co-transporter (NCC) of the renal distal convoluted tubule (DCT) cause Gitelman syndrome with hypokalemic alkalosis, hypomagnesemia and hypocalciuria. Since Gitelman patients are usually diagnosed around adolescence, we tested the idea that a progressive regression of the DCT explains the late clinical onset of the syndrome.

Methods

NCC wild-type and knockout (ko) mice were studied at Days 1, 4 and 10 and 6 weeks after birth using blood plasma analysis and morphological and biochemical methods.

Results

Plasma aldosterone levels and renal renin messenger RNA expression were elevated in NCC ko mice during the first days of life. In contrast, plasma ion levels did not differ between genotypes at age 10 days, but a significant hypomagnesemia was observed in NCC ko mice at 6 weeks. Immunofluorescent detection of parvalbumin (an early DCT marker) revealed that the fractional cortical volume of the early DCT is similar for mice of both genotypes at Day 4, but is significantly lower at Day 10 and is almost zero at 6 weeks in NCC ko mice. The DCT atrophy correlates with a marked reduction in the abundance of the DCT-specific Mg2+ channel TRPM6 (transient receptor potential cation channel subfamily M member 6) and an increased proteolytic activation of the epithelial Na+ channel (ENaC).

Conclusion

After an initial outgrowth, DCT development lags behind in NCC ko mice. The impaired DCT development associates at Day 1 and Day 10 with elevated renal renin and plasma aldosterone levels and activation of ENaC, respectively, suggesting that Gitelman syndrome might be present much earlier in life than is usually expected. Despite an early downregulation of TRPM6, hypomagnesemia is a rather late symptom.
Efficacy of EGFR plus TNF inhibition in a preclinical model of temozolomide-resistant glioblastoma
Authors: Guo Gao , Gong Ke , Puliyappadamba Vineshkumar Thidil , Panchani Nishah , Pan Edward , Mukherjee Bipasha , Damanwalla Ziba , Bharia Sabrina , Hatanpaa Kimmo J , Gerber David E , Mickey Bruce E , Patel Toral R , Sarkaria Jann N , Zhao Dawen , Burma Sandeep , Habib Amyn A
Published: July 2019

Background

Glioblastoma (GBM) is the most common primary malignant adult brain tumor. Temozolomide (TMZ) is the standard of care and is most effective in GBMs that lack the DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT). Moreover, even initially responsive tumors develop a secondary resistance to TMZ and become untreatable. Since aberrant epidermal growth factor receptor (EGFR) signaling is widespread in GBM, EGFR inhibition has been tried in multiple clinical trials without success. We recently reported that inhibiting EGFR leads to increased secretion of tumor necrosis factor (TNF) and activation of a survival pathway in GBM. Here, we compare the efficacy of TMZ versus EGFR plus TNF inhibition in an orthotopic mouse model of GBM.

Methods

We use an orthotopic model to examine the efficacy of TMZ versus EGFR plus TNF inhibition in multiple subsets of GBMs, including MGMT methylated and unmethylated primary GBMs, recurrent GBMs, and GBMs rendered experimentally resistant to TMZ.

Results

The efficacy of the 2 treatments was similar in MGMT methylated GBMs. However, in MGMT unmethylated GBMs, a combination of EGFR plus TNF inhibition was more effective. We demonstrate that the 2 treatment approaches target distinct and non-overlapping pathways. Thus, importantly, EGFR plus TNF inhibition remains effective in TMZ-resistant recurrent GBMs and in GBMs rendered experimentally resistant to TMZ.

Conclusion

EGFR inhibition combined with a blunting of the accompanying TNF-driven adaptive response could be a viable therapeutic approach in MGMT unmethylated and recurrent EGFR-expressing GBMs.
Molecular profiling of long-term IDH-wildtype glioblastoma survivors
Authors: Burgenske Danielle M , Yang Jie , Decker Paul A , Kollmeyer Thomas M , Kosel Matthew L , Mladek Ann C , Caron Alissa A , Vaubel Rachael A , Gupta Shiv K , Kitange Gaspar J , Sicotte Hugues , Youland Ryan S , Remonde Dioval , Voss Jesse S , Fritcher Emily G Barr , Kolsky Kathryn L , Ida Cristiane M , Meyer Fredric B , Lachance Daniel H , Parney Ian J , Kipp Benjamin R , Giannini Caterina , Sulman Erik P , Jenkins Robert B , Eckel-Passow Jeanette E , Sarkaria Jann N
Published: July 2019

Background

Glioblastoma (GBM) represents an aggressive cancer type with a median survival of only 14 months. With fewer than 5% of patients surviving 5 years, comprehensive profiling of these rare patients could elucidate prognostic biomarkers that may confer better patient outcomes. We utilized multiple molecular approaches to characterize the largest patient cohort of isocitrate dehydrogenase (IDH)–wildtype GBM long-term survivors (LTS) to date.

Methods

Retrospective analysis was performed on 49 archived formalin-fixed paraffin embedded tumor specimens from patients diagnosed with GBM at the Mayo Clinic between December 1995 and September 2013. These patient samples were subdivided into 2 groups based on survival (12 LTS, 37 short-term survivors [STS]) and subsequently examined by mutation sequencing, copy number analysis, methylation profiling, and gene expression.

Results

Of the 49 patients analyzed in this study, LTS were younger at diagnosis (P = 0.016), more likely to be female (P = 0.048), and MGMT promoter methylated (UniD, P = 0.01). IDH-wildtype STS and LTS demonstrated classic GBM mutations and copy number changes. Pathway analysis of differentially expressed genes showed LTS enrichment for sphingomyelin metabolism, which has been linked to decreased GBM growth, invasion, and angiogenesis. STS were enriched for DNA repair and cell cycle control networks.

Conclusions

While our findings largely report remarkable similarity between these LTS and more typical STS, unique attributes were observed in regard to altered gene expression and pathway enrichment. These attributes may be valuable prognostic markers and are worth further examination. Importantly, this study also underscores the limitations of existing biomarkers and classification methods in predicting patient prognosis.