bluuebunny/crossref_metadata_2025_split huggingface dataset:
Founder reconstruction enables scalable and seamless pangenomic analysis
Authors: Norri Tuukka , Cazaux Bastien , Dönges Saska , Valenzuela Daniel , Mäkinen Veli 
Published: July 2021

Abstract

Motivation
Variant calling workflows that utilize a single reference sequence are the de facto standard elementary genomic analysis routine for resequencing projects. Various ways to enhance the reference with pangenomic information have been proposed, but scalability combined with seamless integration to existing workflows remains a challenge.

Results
We present PanVC with founder sequences, a scalable and accurate variant calling workflow based on a multiple alignment of reference sequences. Scalability is achieved by removing duplicate parts up to a limit into a founder multiple alignment, that is then indexed using a hybrid scheme that exploits general purpose read aligners. Our implemented workflow uses GATK or BCFtools for variant calling, but the various steps of our workflow (e.g. vcf2multialign tool, founder reconstruction) can be of independent interest as a basis for creating novel pangenome analysis workflows beyond variant calling.

Availability and implementation
Our open access tools and instructions how to reproduce our experiments are available at the following address: https://github.com/algbio/panvc-founders.

Supplementary information
Supplementary data are available at Bioinformatics online.
Improved Apis mellifera reference genome based on the alternative long-read-based assemblies
Authors: Kaskinova Milyausha , Yunusbayev Bayazit , Altinbaev Radick , Raffiudin Rika , Carpenter Madeline H , Kwon Hyung Wook , Nikolenko Alexey , Harpur Brock A , Yunusbaev Ural 
Published: July 2021

Abstract
Apis mellifera L., the western honey bee is a major crop pollinator that plays a key role in beekeeping and serves as an important model organism in social behavior studies. Recent efforts have improved on the quality of the honey bee reference genome and developed a chromosome-level assembly of 16 chromosomes, two of which are gapless. However, the rest suffer from 51 gaps, 160 unplaced/unlocalized scaffolds, and the lack of 2 distal telomeres. The gaps are located at the hard-to-assemble extended highly repetitive chromosomal regions that may contain functional genomic elements. Here, we use de novo re-assemblies from the most recent reference genome Amel_HAv_3.1 raw reads and other long-read-based assemblies (INRA_AMelMel_1.0, ASM1384120v1, and ASM1384124v1) of the honey bee genome to resolve 13 gaps, five unplaced/unlocalized scaffolds and, the lacking telomeres of the Amel_HAv_3.1. The total length of the resolved gaps is 848,747 bp. The accuracy of the corrected assembly was validated by mapping PacBio reads and performing gene annotation assessment. Comparative analysis suggests that the PacBio-reads-based assemblies of the honey bee genomes failed in the same highly repetitive extended regions of the chromosomes, especially on chromosome 10. To fully resolve these extended repetitive regions, further work using ultra-long Nanopore sequencing would be needed. Our updated assembly facilitates more accurate reference-guided scaffolding and marker/sequence mapping in honey bee genomics studies.
Use of food web knowledge in environmental conservation and management of living resources in the Baltic Sea
Authors: Eero Margit , Dierking Jan , Humborg Christoph , Undeman Emma , MacKenzie Brian R , Ojaveer Henn , Salo Tiina , Köster Friedrich Wilhelm 
Published: July 2021

AbstractFood webs are central entities mediating processes and external pressures in marine ecosystems. They are essential to understand and predict ecosystem dynamics and provision of ecosystem services. Paradoxically, utilization of food web knowledge in marine environmental conservation and resource management is limited. To better understand the use of knowledge and barriers to incorporation in management, we assess its application related to the management of eutrophication, chemical contamination, fish stocks, and non-indigenous species. We focus on the Baltic, a severely impacted, but also intensely studied and actively managed semi-enclosed sea. Our assessment shows food web processes playing a central role in all four areas, but application varies strongly, from formalized integration in management decisions, to support in selecting indicators and setting threshold values, to informal knowledge explaining ecosystem dynamics and management performance. Barriers for integration are complexity of involved ecological processes and that management frameworks are not designed to handle such information. We provide a categorization of the multi-faceted uses of food web knowledge and benefits of future incorporation in management, especially moving towards ecosystem-based approaches as guiding principle in present marine policies and directives. We close with perspectives on research needs to support this move considering global and regional change.
The Stabilized Automorphism Group of a Subshift
Authors: Hartman Yair , Kra Bryna , Schmieding Scott 
Published: July 2021

AbstractFor a mixing shift of finite type, the associated automorphism group has a rich algebraic structure, and yet we have few criteria to distinguish when two such groups are isomorphic. We introduce a stabilization of the automorphism group, study its algebraic properties, and use them to distinguish many of the stabilized automorphism groups. We also show that for a full shift, the subgroup of the stabilized automorphism group generated by elements of finite order is simple and that the stabilized automorphism group is an extension of a free abelian group of finite rank by this simple group.
A Five Distance Theorem for Kronecker Sequences
Authors: Haynes Alan , Marklof Jens 
Published: July 2021

Abstract
The three-distance theorem (also known as the three-gap theorem or Steinhaus problem) states that, for any given real number $\alpha $ and integer $N$, there are at most three values for the distances between consecutive elements of the Kronecker sequence $\alpha , 2\alpha ,\ldots , N\alpha $ mod 1. In this paper, we consider a natural generalization of the three-distance theorem to the higher-dimensional Kronecker sequence $\vec \alpha , 2\vec \alpha ,\ldots , N\vec \alpha $ modulo an integer lattice. We prove that in 2D, there are at most five values that can arise as a distance between nearest neighbors, for all choices of $\vec \alpha $ and $N$. Furthermore, for almost every $\vec \alpha $, five distinct distances indeed appear for infinitely many $N$ and hence five is the best possible general upper bound. In higher dimensions, we have similar explicit, but less precise, upper bounds. For instance, in 3D, our bound is 13, though we conjecture the truth to be 9. We furthermore study the number of possible distances from a point to its nearest neighbor in a restricted cone of directions. This may be viewed as a generalization of the gap length in 1D. For large cone angles, we use geometric arguments to produce explicit bounds directly analogous to the three-distance theorem. For small cone angles, we use ergodic theory of homogeneous flows in the space of unimodular lattices to show that the number of distinct lengths is (1) unbounded for almost all $\vec \alpha $ and (2) bounded for $\vec \alpha $ that satisfy certain Diophantine conditions.
Effect of efavirenz-based ART on the pharmacokinetics of rifampicin and its primary metabolite in patients coinfected with TB and HIV
Authors: Sundell Jesper , Bienvenu Emile , Äbelö Angela , Ashton Michael 
Published: July 2021

Abstract

Objectives
To evaluate the effects of concomitant efavirenz-based ART and genetic polymorphism on the variability in rifampicin and 25-desacetylrifampicin pharmacokinetics.

Patients and methods
Plasma concentrations of rifampicin and 25-desacetylrifampicin from 63 patients coinfected with TB and HIV were analysed by LC-MS/MS followed by non-linear mixed-effects modelling. Patients were genotyped for SLCO1B1 (463 C&gt;A, 388 A&gt;G, 11187 G&gt;A, rs4149015, 521 T&gt;C and 1436 G&gt;C) and SLCO1B3 (334 T&gt;G).

Results
One-compartment disposition models described the observations adequately. The oral clearances of rifampicin and 25-desacetylrifampicin were 140% and 110% higher, respectively, in patients on concomitant efavirenz-based ART. Rifampicin bioavailability was also lower in patients on concomitant ART. Further, although not included in the final model, a lower relative bioavailability in carriers of WT SLCO1B3 334 T&gt;G compared with carriers of mutations in the genotype was estimated.

Conclusions
The results presented indicate both pre-systemic and systemic induction by efavirenz-based ART affecting rifampicin pharmacokinetics. The described drug–drug interaction has a clinical impact on rifampicin exposure prior to steady state and may impact the early bactericidal activity in patients on efavirenz-based ART.
Managing Diversity Differently: The External Environment and Cross-Sector Differences in Diversity Management
Authors: McCrea Austin M , Zhu Ling , Johansen Morgen S 
Published: July 2021

AbstractA growing literature identifies the external environment as a key driver of diversity management in frontline public services. With many public services spanning the public, nonprofit, and private sectors, the degree to which ownership moderates the link between the environment and diversity management practice is an important area that has received little attention. Using longitudinal data on nearly 4,000 American hospitals from 2008 to 2012, we explore how public, nonprofit, and private hospitals diverge in their responses to three environmental factors—market competition, inter-organizational collaboration, and the racial diversity of the population in their local service area. Findings from random effects panel models and panel logistic regressions suggest that these factors are associated with heterogeneous diversity management activities across different sectors. For public hospitals, diversity management is influenced by the racial diversity of clients. Nonprofit hospitals’ diversity management is influenced by both inter-organizational collaboration and the racial diversity of clients. Market competition is the main driver of diversity management in the private sector. These findings bring insights from contingency theory and the cross-sector comparison literature into diversity management research. Key findings suggest there are complex and multiple mechanisms guiding diversity management practices across different sectors.
Modelling coexisting GSF and shear instabilities in rotating stars
Authors: Chang Eonho , Garaud Pascale 
Published: July 2021

ABSTRACT
Zahn’s widely used model for turbulent mixing induced by rotational shear has recently been validated (with some caveats) in non-rotating shear flows. It is not clear, however, whether his model remains valid in the presence of rotation, even though this was its original purpose. Furthermore, new instabilities arise in rotating fluids, such as the Goldreich–Schubert–Fricke (GSF) instability. Which instability dominates when more than one can be excited, and how they influence each other, were open questions that this paper answers. To do so, we use direct numerical simulations of diffusive stratified shear flows in a rotating triply periodic Cartesian domain located at the equator of a star. We find that either the GSF instability or the shear instability tends to take over the other in controlling the system, suggesting that stellar evolution models only need to have a mixing prescription for each individual instability, together with a criterion to determine which one dominates. However, we also find that it is not always easy to predict which instability ‘wins’ for given input parameters, because the diffusive shear instability is subcritical, and only takes place if there is a finite-amplitude turbulence ‘primer’ to seed it. Interestingly, we find that the GSF instability can in some cases play the role of this primer, thereby providing a pathway to excite the subcritical shear instability. This can also drive relaxation oscillations, which may be observable. We conclude by proposing a new model for mixing in the equatorial regions of stellar radiative zones due to differential rotation.
Supernova explosions in active galactic nuclear discs
Authors: Grishin Evgeni , Bobrick Alexey , Hirai Ryosuke , Mandel Ilya , Perets Hagai B 
Published: July 2021

ABSTRACT
Active galactic nuclei (AGNs) are prominent environments for stellar capture, growth, and formation. These environments may catalyse stellar mergers and explosive transients, such as thermonuclear and core-collapse supernovae (SNe). SN explosions in AGN discs generate strong shocks, leading to unique observable signatures. We develop an analytical model that follows the evolution of the shock propagating in the disc until it eventually breaks out. We derive the peak luminosity, bolometric light curve, and breakout time. The peak luminosities may exceed 1045 erg s−1 and last from hours to days. The brightest explosions occur in regions of reduced density: either off-plane, or in discs around low-mass central black holes (${\sim} 10^6\ \rm {M}_\odot$), or in starved subluminous AGNs. Explosions in the latter two sites are easier to observe due to a reduced AGN background luminosity. We perform suites of 1D Lagrangian radiative hydrodynamics snec code simulations to validate our results and obtain the luminosity in different bands, and 2D axisymmetric Eulerian hydrodynamics code hormone simulations to study the morphology of the ejecta and its deviation from spherical symmetry. The observed signature is expected to be a bright blue, UV or X-ray flare on top of the AGN luminosity from the initial shock breakout, while the subsequent red part of the light curve will largely be unobservable. We estimate the upper limit for the total event rate to be $\mathcal {R}\lesssim 100\ \rm yr^{-1}\ Gpc^{-3}$ for optimal conditions and discuss the large uncertainties in this estimate. Future high-cadence transient searches may reveal these events. Some existing tidal disruption event candidates may originate from AGN SNe.
Impact of astrophysical binary coalescence time-scales on the rate of lensed gravitational wave events
Authors: Mukherjee Suvodip , Broadhurst Tom , Diego Jose M , Silk Joseph , Smoot George F 
Published: July 2021

ABSTRACT
The expected event rate of lensed gravitational wave sources scales with the merger rate at redshift z ≥ 1, where the optical depth for lensing is high. It is commonly assumed that the merger rate of the astrophysical compact objects is closely connected with the star formation rate, which peaks around redshift z ∼ 2. However, a major source of uncertainty is the delay time between the formation and merger of compact objects. We explore the impact of delay time on the lensing event rate. We show that as the delay time increases, the peak of the merger rate of gravitational wave sources gets deferred to a lower redshift. This leads to a reduction in the event rate of the lensed events which are detectable by the gravitational wave detectors. We show that for a delay time of around 10 Gyr or larger, the lensed event rate can be less than one per year for the design sensitivity of LIGO/Virgo. We also estimate the merger rate for lensed sub-threshold for different delay time scenarios, finding that for larger delay times the number of lensed sub-threshold events is reduced, whereas for small-delay time models they are significantly more frequent. This analysis shows for the first time that lensing is a complementary probe to explore different formation channels of binary systems by exploiting the lensing event rate from the well-detected events and sub-threshold events which are measurable using the network of gravitational wave detectors.
Plasmid replication based on the T7 origin of replication requires a T7 RNAP variant and inactivation of ribonuclease H
Authors: Becker Katja , Meyer Andreas , Roberts Tania Michelle , Panke Sven 
Published: July 2021

Abstract
T7 RNA polymerase (RNAP) is a valuable tool in biotechnology, basic research and synthetic biology due to its robust, efficient and selective transcription of genes. Here, we expand the scope of T7 RNAP to include plasmid replication. We present a novel type of plasmid, termed T7 ori plasmids that replicate, in an engineered Escherichia coli, with a T7 phage origin as the sole origin of replication. We find that while the T7 replication proteins; T7 DNA polymerase, T7 single-stranded binding proteins and T7 helicase-primase are dispensable for replication, T7 RNAP is required, although dependent on a T7 RNAP variant with reduced activity. We also find that T7 RNAP-dependent replication of T7 ori plasmids requires the inactivation of cellular ribonuclease H. We show that the system is portable among different plasmid architectures and ribonuclease H-inactivated E. coli strains. Finally, we find that the copy number of T7 ori plasmids can be tuned based on the induction level of RNAP. Altogether, this study assists in the choice of an optimal genetic tool by providing a novel plasmid that requires T7 RNAP for replication.
A Disfiguring Rash
Authors: Zambrano Andrea I , Church Elizabeth C , McKay Kenneth M , Carnes Stephanie K , Morse Ryan J , Leveque Thellea K , Roxby Alison C 
Published: July 2021

Abstract
Patients with rheumatologic conditions can have complex dermatologic manifestations. In addition, immunosuppressing treatment for autoimmune disorders can also increase incidence of infectious complications. Skin conditions in rheumatologic patients present particular challenges and this case highlights a rare infectious complication.
False Positives and the “More-is-Better” Assumption in Sensitive Question Research
Authors: Wolter Felix , Diekmann Andreas 
Published: July 2021

Abstract
Several special questioning techniques have been developed in order to counteract misreporting to sensitive survey questions, for example, on criminal behavior. However, doubts have been raised concerning their validity and practical value as well as the strategy of testing their validity using the “more-is-better” assumption in comparative survey experiments. This is because such techniques can be prone to generating false positive estimates, that is, counting “innocent” respondents as “guilty” ones. This article investigates the occurrence of false positive estimates by comparing direct questioning, the crosswise model (CM), and the item count technique (ICT). We analyze data from two online surveys (N = 2,607 and 3,203) carried out in Germany and Switzerland. Respondents answered three questions regarding traits for which it is known that their prevalence in reality is zero. The results show that CM suffers more from false positive estimates than ICT. CM estimates amount to up to 15 percent for a given true value of zero. The mean of the ICT estimates is not significantly different from zero. We further examine factors causing the biased estimates of CM and show that speeding through the questionnaire (random answering) and problems with the measurement procedure—namely regarding the unrelated questions—are responsible. Our findings suggest that CM is problematic and should not be used or evaluated without the possibility of accounting for false positives. For ICT, the issue is less severe.
Women in toxicology in the United States
Authors: Melo Luma 
Published: July 2021

AbstractSince the toxicology field was established, women have played a critical role in it. This article is written to celebrate the 20-year anniversary of the Special Interest Group for Women in Toxicology, affiliated with the Society of Toxicology. Six female pioneers in modern Toxicology from different social classes and education backgrounds are featured. Despite these differences, they overcame similar obstacles in gender, politics, and scientific barriers to disseminate their research. This discussion will start with Ellen Swallow Richards, who, besides being the pioneer in sanitary engineering, founded the home economics movement that applied science to the home. The discussion will continue with Alice Hamilton, a contributor to occupational health, a pioneer in the field of industrial toxicology, and an example of generosity to social movements and those in need. Subsequently, the most famous woman we discuss in this paper is Rachel Carson, whose fundamental work in environmental Toxicology is evidenced in her important book Silent Spring. This article also features Elizabeth Miller, a biochemist known for her fundamental research in cancer carcinogenesis, followed by Mary Amdur. Nowadays much of what we know about air pollution comes due to Mary, who paid from her own pocket for her experimental animals to investigate Donora smog pollutants and their health damages. And last but not least Elizabeth Weisburger, a chemist who made significant contributions in carcinogenesis and chemotherapy drugs who worked for 40 years at the National Cancer Institute. Here, we discuss the aforementioned women’s careers and personal struggles that transformed toxicology into the field we know now.
Osteological characters of birds and reptiles are more congruent with molecular phylogenies than soft characters are
Authors: Callender-Crowe Leah M , Sansom Robert S 
Published: July 2021

AbstractDespite increased use of genomic data in phylogenetics, morphological information remains vital for resolving evolutionary relationships, particularly for fossil taxa. The properties and models of evolution of molecular sequence data are well characterized and mature, relative to those of morphological data. Furthermore, heterogeneity, integration and relative homoplasy of empirical morphological data could prove problematic for phylogenetic reconstruction. Here we compare osteological and non-osteological characters of 28 morphological datasets of extant saurians in terms of their homoplasy relative to molecular trees. Analysis of individual avian datasets finds osteological characters to be significantly more consistent with molecular data than soft characters are. Significant differences between morphological partitions were also observed in the age at which characters resolved on molecular trees. Osteological character changes occur relatively earlier in deep branches, whilst soft-tissue character transitions are more recent in shallow branches. The combined results demonstrate differences in evolutionary dynamics between morphological partitions. This may reflect evolutionary constraints acting on osteological characters, compared with the relative lability of soft characters. Furthermore, it provides some support to phylogenetic interpretations of fossil data, including dinosaurs, which are predominately osteological. Recent advances in amphibian and mammal phylogenetics may make these patterns possible to test for all tetrapods.