bluuebunny/crossref_metadata_2025_split huggingface dataset:
Absence of drug–drug interactions between γ-hydroxybutyric acid (GHB) and cobicistat
Authors: Moltó José , Bailón Lucía , Pérez-Mañá Clara , Papaseit Ester , Miranda Cristina , Martín Soraya , Mothe Beatriz , Farré Magí 
Published: September 2021

Abstract

Objectives
Potential interactions between CYP3A4 inhibitors and γ-hydroxybutyric acid (GHB) have been suggested as a possible explanation for cases of GHB overdose in recent years among people living with HIV engaged in chemsex. Our objective was to assess the effect of cobicistat on the pharmacokinetics of GHB.

Methods
Fifteen healthy adults were enrolled in this randomized, double-blind, placebo-controlled, two-arm, crossover clinical trial. Participants underwent two 5 day treatment periods with at least a 1 week washout period between them. In each treatment period, participants received cobicistat (150 mg q24h orally) or matched placebo. On day 5 of each treatment period, participants were given a single oral dose of GHB (25 mg/kg). Plasma concentrations of GHB, subjective effects, blood pressure, heart rate and oxygen saturation were monitored for 5 h after dosing. GHB pharmacokinetic and pharmacodynamic parameters were calculated for each participant during each study period by non-compartmental analysis and were compared using linear mixed-effects models. The study was registered at https://www.clinicaltrialsregister.eu (Eudra-CT number 2019-002122-71) and at https://clinicaltrials.gov (NCT04322214).

Results
Ten participants completed the two study periods. No drug-related adverse events that necessitated subject withdrawal or medical intervention occurred during the study. Compared with placebo, none of the primary pharmacokinetic parameters of GHB was substantially changed by the administration of GHB with cobicistat. Similarly, no differences regarding subjective or physiological effects were observed when GHB was administered alone or with cobicistat.

Conclusions
Neither pharmacokinetic nor pharmacodynamic drug–drug interactions between cobicistat and GHB were identified in this study.
Plasmodium falciparum metacaspase-2 capture its natural substrate in a non-canonical way
Authors: Vandana   , Pandey Rajan , Srinivasan E , Kalia Inderjeet , Singh Agam P , Saxena Ajay , Rajaekaran R , Gupta Dinesh , Pandey Kailash C 
Published: September 2021

Abstract
Programmed cell death (PCD) is a multi-step process initiated by a set of proteases, which interacts and cleaves diverse proteins, thus modulating their biochemical and cellular functions. In metazoans, PCD is mediated by proteolytic enzymes called caspases, which triggered cell death by proteolysis of human Tudor staphylococcus nuclease (TSN). Non-metazoans lack a close homologue of caspases but possess an ancestral family of cysteine proteases termed ‘metacaspases’. Studies supported that metacaspases are involved in PCD, but their natural substrates remain unknown. In this study, we performed the Plasmodium falciparum TSN (PfTSN) cleavage assay using wild and selected mutants of P. falciparum metacaspases-2 (PfMCA-2) in vitro and in vivo. Interestingly, PfMCA-2, cleaved a phylogenetically conserved protein, PfTSN at multiple sites. Deletion or substitution mutation in key interacting residues at the active site, Cys157 and His205 of PfMCA-2, impaired its enzymatic activity with the artificial substrate, z-GRR-AMC. However, the mutant Tyr224A did not affect the activity with z-GRR-AMC but abolished the cleavage of PfTSN. These results indicated that the catalytic dyad, Cys157 and His205 of PfMCA-2 was essential for its enzymatic activity with an artificial substrate, whereas Tyr224 and Cys157 residues were responsible for its interaction with the natural substrate and subsequent degradation of PfTSN. Our results suggested that MCA-2 interacts with TSN substrate in a non-canonical way using non-conserved or conformationally available residues for its binding and cleavage. In future, it would be interesting to explore how this interaction leads to the execution of PCD in the Plasmodium.
Variable Signatures of Selection Despite Conserved Recombination Landscapes Early in Speciation
Authors: Turbek Sheela P , Semenov Georgy A , Enbody Erik D , Campagna Leonardo , Taylor Scott A 
Published: September 2021

AbstractRecently diverged taxa often exhibit heterogeneous landscapes of genomic differentiation, characterized by regions of elevated differentiation on an otherwise homogeneous background. While divergence peaks are generally interpreted as regions responsible for reproductive isolation, they can also arise due to background selection, selective sweeps unrelated to speciation, and variation in recombination and mutation rates. To investigate the association between patterns of recombination and landscapes of genomic differentiation during the early stages of speciation, we generated fine-scale recombination maps for six southern capuchino seedeaters (Sporophila) and two subspecies of White Wagtail (Motacilla alba), two recent avian radiations in which divergent selection on pigmentation genes has likely generated peaks of differentiation. We compared these recombination maps to those of Collared (Ficedula albicollis) and Pied Flycatchers (Ficedula hypoleuca), non-sister taxa characterized by moderate genomic divergence and a heterogenous landscape of genomic differentiation shaped in part by background selection. Although recombination landscapes were conserved within all three systems, we documented a weaker negative correlation between recombination rate and genomic differentiation in the recent radiations. All divergence peaks between capuchinos, wagtails, and flycatchers were located in regions with lower-than-average recombination rates, and most divergence peaks in capuchinos and flycatchers fell in regions of exceptionally reduced recombination. Thus, co-adapted allelic combinations in these regions may have been protected early in divergence, facilitating rapid diversification. Despite largely conserved recombination landscapes, divergence peaks are specific to each focal comparison in capuchinos, suggesting that regions of elevated differentiation have not been generated by variation in recombination rate alone.
The emerging role of jasmonate in the control of flowering time
Authors: Zhao Lirong , Li Xia , Chen Wanqin , Xu Zhiyu , Chen Mifen , Wang Houping , Yu Diqiu 
Published: September 2021

Abstract
Plants dynamically synchronize their flowering time with changes in the internal and external environments through a variety of signaling pathways to maximize fitness. In the last two decades, the major pathways associated with flowering, including the photoperiod, vernalization, age, autonomous, gibberellin, and ambient temperature pathways, have been extensively analyzed. In recent years, an increasing number of signals, such as sugar, thermosensory, stress, and certain hormones, have been shown to be involved in fine-tuning flowering time. Among these signals, the jasmonate signaling pathway has a function in the determination of flowering time that has not been systematically summarized. In this review, we present an overview of current knowledge of jasmonate control of flowering and discuss jasmonate crosstalk with other signals (such as gibberellin, defense, and touch) during floral transition.
Beyond the Douai-Reims Bible: The Changing Publishing Strategies of the Kellam Family in Seventeenth-Century Douai
Authors: Soetaert Alexander , Wyffels Heleen 
Published: September 2021

Abstract
The career of the Catholic Englishman Laurence Kellam is often reduced to his most impressive edition, the Old Testament of the Douay-Rheims Bible (1609–1610), an English Catholic Bible translation edited by the English College of Douai. Yet, there has been scarce attention for the remaining 190 editions, printed in English, as well as in Latin, French and Dutch, that bear a Kellam imprint. The discovery of another fifty editions that should be ascribed to the Kellam press demands a reappraisal of its activities and significance. By analysing both printed and archival sources, this article intends to fit the Bible edition of 1609–1610, and English Catholic printing on the continent more generally, into the wider perspective of three generations of publishing activities and family history, highlighting the increasingly tight connections between several generations of the Kellam family and the authors, institutions, and fellow-publishers of their host society.
What Were Thomas Hearne’s ‘Bad Copies’?
Authors: Day Geoffrey , Junqua Amélie 
Published: September 2021

Abstract
Bodleian, MS Rawl. Q. e. 18 is a twelve-page notebook in which Thomas Hearne recorded income and expenditure relating to his publication of Thomas Caius’ Vindiciae antiquitatis academiae Oxoniensis (1730), together with very brief details of the instructions given to the printer about five other texts. For five of the six titles Hearne specified that, in addition to the numbers required for subscribers, there should be an additional two ‘bad copies’. This note explores possible interpretations of this instruction.
Geospatial mapping of a 16th century transport corridor for Southeast Europe
Authors: Kabadayi M Erdem , Gerrits Piet , Boykov Grigor 
Published: September 2021

AbstractWe need maximum slope values for carts and pack animals to model the historical traffic of people and goods before the advent of steam and internal combustion engines. With this article, we first calculate maximum slope averages for carts and pack animals by using an extensive geo-referenced and vectorized historical transport network for late 19th-century Southeast Europe. Then by utilizing these slopes and making joint use of the least-cost path, accumulated cost surfaces, and network analyses, we model the movement of carts and pack animals for a large segment of an Ottoman military campaign in 1532, which followed the Via Militaris, between Istanbul and Sofia. Lastly, we compare our modelled routes for carts and pack animals for the 16th century with the existing road infrastructure of the late 19th century.
Ice mantles on dust grains: dramatic variation of thickness with grain size
Authors: Silsbee Kedron , Caselli Paola , Ivlev Alexei V 
Published: September 2021

ABSTRACT
We compute the desorption rate of icy mantles on dust grains as a function of the size and composition of both the grain and the mantle. We combine existing models of cosmic ray (CR)-related desorption phenomena with a model of CR transport to accurately calculate the desorption rates in dark regions of molecular clouds. We show that different desorption mechanisms dominate for grains of different sizes and in different regions of the cloud. We then use these calculations to investigate a simple model of the growth of mantles, given a distribution of grain sizes. We find that modest variations of the desorption rate with grain size lead to a strong dependence of mantle thickness on grain size. Furthermore, we show that freeze-out is almost complete in the absence of an external ultraviolet (UV) field, even when photodesorption from CR-produced UV is taken into consideration. Even at gas densities of $10^4\, {\rm cm^{-3}}$, less than 30 per cent of the CO remain in the gas phase after 3 × 105 yr for standard values of the CR ionization rate.
Rotation curves and scaling relations of extremely massive spiral galaxies
Authors: Di Teodoro Enrico M , Posti Lorenzo , Ogle Patrick M , Fall S Michael , Jarrett Thomas 
Published: September 2021

ABSTRACT
We study the kinematics and scaling relations of a sample of 43 giant spiral galaxies that have stellar masses exceeding $10^{11} \, {\rm M}_\odot$ and optical discs up to 80 kpc in radius. We use a hybrid 3D–1D approach to fit 3D kinematic models to long-slit observations of the H α-$\rm{[N\, \small {II}]}$ emission lines and we obtain robust rotation curves of these massive systems. We find that all galaxies in our sample seem to reach a flat part of the rotation curve within the outermost optical radius. We use the derived kinematics to study the high-mass end of the two most important scaling relations for spiral galaxies: the stellar/baryonic mass Tully–Fisher relation and the Fall (mass-angular momentum) relation. All galaxies in our sample, with the possible exception of the two fastest rotators, lie comfortably on both these scaling relations determined at lower masses, without any evident break or bend at the high-mass regime. When we combine our high-mass sample with low-mass data from the Spitzer Photometry & Accurate Rotation Curves catalogue, we find a slope of α = 4.25 ± 0.19 for the stellar Tully–Fisher relation and a slope of γ = 0.64 ± 0.11 for the Fall relation. Our results indicate that most, if not all, of these rare, giant spiral galaxies are scaled up versions of less massive discs and that spiral galaxies are a self-similar population of objects up to the very high-mass end.
Fast galaxy bars continue to challenge standard cosmology
Authors: Roshan Mahmood , Ghafourian Neda , Kashfi Tahere , Banik Indranil , Haslbauer Moritz , Cuomo Virginia , Famaey Benoit , Kroupa Pavel 
Published: September 2021

ABSTRACT
Many observed disc galaxies harbour a central bar. In the standard cosmological paradigm, galactic bars should be slowed down by dynamical friction from the dark matter halo. This friction depends on the galaxy’s physical properties in a complex way, making it impossible to formulate analytically. Fortunately, cosmological hydrodynamical simulations provide an excellent statistical population of galaxies, letting us quantify how simulated galactic bars evolve within dark matter haloes. We measure bar strengths, lengths, and pattern speeds in barred galaxies in state-of-the-art cosmological hydrodynamical simulations of the IllustrisTNG and EAGLE projects, using techniques similar to those used observationally. We then compare our results with the largest available observational sample at redshift z = 0. We show that the tension between these simulations and observations in the ratio of corotation radius to bar length is 12.62σ (TNG50), 13.56σ (TNG100), 2.94σ (EAGLE50), and 9.69σ (EAGLE100), revealing for the first time that the significant tension reported previously persists in the recently released TNG50. The lower statistical tension in EAGLE50 is actually caused by it only having five galaxies suitable for our analysis, but all four simulations give similar statistics for the bar pattern speed distribution. In addition, the fraction of disc galaxies with bars is similar between TNG50 and TNG100, though somewhat above EAGLE100. The simulated bar fraction and its trend with stellar mass both differ greatly from observations. These dramatic disagreements cast serious doubt on whether galaxies actually have massive cold dark matter haloes, with their associated dynamical friction acting on galactic bars.
Radiation pressure confinement – V. The predicted free–free absorption and emission in active galactic nuclei
Authors: Baskin Alexei , Laor Ari 
Published: September 2021

ABSTRACT
The effect of radiation pressure compression (RPC) on ionized gas in active galactic nuclei (AGNs) likely sets the photoionized gas density structure. The photoionized gas free–free absorption and emission are therefore uniquely set by the incident ionizing flux. We use the photoionization code cloudy RPC model results to derive the expected relations between the free–free emission and absorption properties and the distance from the AGN centre, for a given AGN luminosity. The free–free absorption frequency of RPC gas is predicted to increase from ∼100 MHz on the kpc scale to ∼100 GHz on the sub-pc scale, consistent with observations of spatially resolved free–free absorption. The free–free emission at 5 GHz is predicted to yield a radio loudness (R) of ∼0.03, below the typical observed values of R ∼ 0.1–1 in radio-quiet AGNs. However, the flat free–free radio continuum may become dominant above 100 GHz. The suggested detection of optically thin free–free emission in NGC 1068, on the sub-pc torus scale, is excluded as the brightness temperature is too high for optically thin free–free emission. However, excess emission observed with Atacama Large Millimeter/submillimeter Array (ALMA) above 150 GHz in NGC 1068 is consistent with the predicted free–free emission from gas just outside the broad-line region, a region that overlaps the hot dust disc resolved with GRAVITY. Extended ∼100 pc-scale free–free emission is also likely present in NGC 1068. Future sub-mm observation of radio-quiet AGNs with ALMA may allow to image the free–free emission of warm photoionized gas in AGNs down to the 30 mas scale, including highly absorbed AGNs.
A flexible subhalo abundance matching model for galaxy clustering in redshift space
Authors: Contreras S , Angulo R E , Zennaro M 
Published: September 2021

ABSTRACT
We develop an extension of subhalo abundance matching (SHAM) capable of accurately reproducing the real and redshift-space clustering of galaxies in a state-of-the-art hydrodynamical simulation. Our method uses a low-resolution gravity-only simulation and it includes orphan and tidal disruption prescriptions for satellite galaxies, and a flexible amount of galaxy assembly bias. Furthermore, it includes recipes for star formation rate (SFR) based on the dark matter accretion rate. We test the accuracy of our model against catalogues of stellar-mass- and SFR-selected galaxies in the TNG300 hydrodynamic simulation. By fitting a small number of free parameters, our extended SHAM reproduces the projected correlation function and redshift-space multipoles for number densities $10^{-3} - 10^{-2}\, h^{3}{\rm Mpc}^{-3}$, at z = 1 and z = 0, and for scales r ∈ [0.3 − 20]h−1Mpc. Simultaneously, the SHAM results also retrieve the correct halo occupation distribution, the level of galaxy assembly bias, and higher order statistics present in the TNG300 galaxy catalogues. As an application, we show that our model simultaneously fits the projected correlation function of the SDSS in three disjoint stellar mass bins, with an accuracy similar to that of TNG300 galaxies. This SHAM extension can be used to get accurate clustering prediction even when using low and moderate-resolution simulations.
Conservation of radial actions in time-dependent spherical potentials
Authors: Burger Jan D , Peñarrubia Jorge , Zavala Jesús 
Published: September 2021

ABSTRACT
In slowly evolving spherical potentials, Φ(r, t), radial actions are typically assumed to remain constant. Here, we construct dynamical invariants that allow us to derive the evolution of radial actions in spherical central potentials with an arbitrary time dependence. We show that to linear order, radial actions oscillate around a constant value with an amplitude $\propto \dot{\Phi }/\Phi \, P(E,L)$. Using this result, we develop a diffusion theory that describes the evolution of the radial action distributions of ensembles of tracer particles orbiting in generic time-dependent spherical potentials. Tests against restricted N-body simulations in a varying Kepler potential indicate that our linear theory is accurate in regions of phase-space in which the diffusion coefficient $\tilde {D}(J_r) \lt 0.01\, J_r^2$. For illustration, we apply our theory to two astrophysical processes. We show that the median mass accretion rate of a Milky Way (MW) dark matter (DM) halo leads to slow global time-variation of the gravitational potential, in which the evolution of radial actions is linear (i.e. either adiabatic or diffusive) for ∼84 per cent of the DM halo at redshift z = 0. This fraction grows considerably with look-back time, suggesting that diffusion may be relevant to the modelling of several Gyr old tidal streams in action-angle space. As a second application, we show that dynamical tracers in a dwarf-size self-interacting DM halo (with $\sigma /m_\chi = 1\, {\rm cm^2g^{-1}}$) have invariant radial actions during the formation of a cored density profile.
Extracting the astrophysics of reionization from the Lyα forest power spectrum: a first forecast
Authors: Montero-Camacho Paulo , Mao Yi 
Published: September 2021

ABSTRACT
The impact of cosmic reionization on the Lyα forest power spectrum has recently been shown to be significant even at low redshifts (z ∼ 2). This memory of reionization survives cosmological time-scales because high-entropy mean-density gas is heated to ∼3 × 104 K by reionization, which is inhomogeneous, and subsequent shocks from denser regions. In the near future, the first measurements of the Lyα forest 3D power spectrum will be very likely achieved by upcoming observational efforts such as the Dark Energy Spectroscopic Instrument (DESI). In addition to abundant cosmological information, these observations have the potential to extract the astrophysics of reionization from the Lyα forest. We forecast, for the first time, the accuracy with which the measurements of Lyα forest 3D power spectrum can place constraints on the reionization parameters with DESI. Specifically, we demonstrate that the constraints on the ionization efficiency, ζ, and the threshold mass for haloes that host ionizing sources, mturn, will have the 1σ error at the level of ζ = 25.0 ± 11.6 and $\log _{10} (m_{\rm turn}/{\rm M}_\odot) = 8.7^{+0.36}_{-0.70}$, respectively. The Lyα forest 3D power spectrum will thus provide an independent probe of reionization, probably even earlier in detection with DESI, with a sensitivity only slightly worse than the upcoming 21-cm power spectrum measurement with the Hydrogen Epoch of Reionization Array (HERA), i.e. σDESI/σHERA ≈ 1.5 for ζ and σDESI/σHERA ≈ 2.0 for log10(mturn/M⊙). Nevertheless, the Lyα forest constraint will be improved about three times tighter than the current constraint from reionization observations with high-z galaxy priors, i.e. σDESI/σcurrent ≈ 1/3 for ζ.
Comparative Genomics Sheds Light on the Convergent Evolution of Miniaturized Wasps
Authors: Xu Hongxing , Ye Xinhai , Yang Yajun , Yang Yi , Sun Yu H , Mei Yang , Xiong Shijiao , He Kang , Xu Le , Fang Qi , Li Fei , Ye Gongyin , Lu Zhongxian 
Published: September 2021

Abstract
Miniaturization has occurred in many animal lineages, including insects and vertebrates, as a widespread trend during animal evolution. Among Hymenoptera, miniaturization has taken place in some parasitoid wasp lineages independently, and may have contributed to the diversity of species. However, the genomic basis of miniaturization is little understood. Diverged approximately 200 Ma, Telenomus wasps (Platygastroidea) and Trichogramma wasps (Chalcidoidea) have both evolved to a highly reduced body size independently, representing a paradigmatic example of convergent evolution. Here, we report a high-quality chromosomal genome of Telenomus remus, a promising candidate for controlling Spodoptera frugiperda, a notorious pest that has recently caused severe crop damage. The T. remus genome (129 Mb) is characterized by a low density of repetitive sequence and a reduction of intron length, resulting in the shrinkage of genome size. We show that hundreds of genes evolved faster in two miniaturized parasitoids Trichogramma pretiosum and T. remus. Among them, 38 genes exhibit extremely accelerated evolutionary rates in these miniaturized wasps, possessing diverse functions in eye and wing development as well as cell size control. These genes also highlight potential roles in body size regulation. In sum, our analyses uncover a set of genes with accelerated evolutionary rates in Tri. pretiosum and T. remus, which might be responsible for their convergent adaptations to miniaturization, and thus expand our understanding on the evolutionary basis of miniaturization. Additionally, the genome of T. remus represents the first genome resource of superfamily Platygastroidea, and will facilitate future studies of Hymenoptera evolution and pest control.