bluuebunny/crossref_metadata_2025_split huggingface dataset:
Void Formation: Does the Void-in-Cloud Process Matter?
Authors: Chan Hei Yin Jowett , Chiba Masashi , Ishiyama Tomoaki 
Published: October 2019

Abstract
We investigate the basic properties of voids from high resolution, cosmological N-body simulations of Λ–dominated cold dark matter (ΛCDM) models, in order to compare with the analytical model of Sheth and van de Weygaert (SvdW) for void statistics. For the subsample of five dark matter simulations in the ΛCDM cosmology with box sizes ranging from 1000h−1Mpc to 8 h−1Mpc, we find that the standard void–in–cloud effect is too simplified to explain several properties of identified small voids in simulations. (i) The number density of voids is found to be larger than the prediction of the analytical model up to 2 orders of magnitude below 1h−1Mpc scales. The Press-Schechter model with the linear critical threshold of void δv = −2.71, or a naive power law, is found to provide an excellent agreement with the void size function, suggesting that the void-in-cloud effect does not suppress as much voids as predicted by the SvdW model. (ii) We then measured the density and velocity profiles of small voids, and find that they are mostly partially collapsing underdensities, instead of being completely crushed in the standard void–in–cloud scenario. (iii) Finally, we measure the void distributions in four different tidal environments, and find that the void–in-void effect alone can explain the correlation between distribution and environments, whereas the void–in–cloud effect is only weakly influencing the abundance of voids, even in filaments and clusters.
Investigating the multiwavelength behaviour of the flat spectrum radio quasar CTA 102 during 2013–2017
Authors: D’Ammando F , Raiteri C M , Villata M , Acosta-Pulido J A , Agudo I , Arkharov A A , Bachev R , Baida G V , Benítez E , Borman G A , Boschin W , Bozhilov V , Butuzova M S , Calcidese P , Carnerero M I , Carosati D , Casadio C , Castro-Segura N , Chen W-P , Damljanovic G , Di Paola A , Echevarría J , Efimova N V , Ehgamberdiev Sh A , Espinosa C , Fuentes A , Giunta A , Gómez J L , Grishina T S , Gurwell M A , Hiriart D , Jermak H , Jordan B , Jorstad S G , Joshi M , Kimeridze G N , Kopatskaya E N , Kuratov K , Kurtanidze O M , Kurtanidze S O , Lähteenmäki A , Larionov V M , Larionova E G , Larionova L V , Lázaro C , Lin C S , Malmrose M P , Marscher A P , Matsumoto K , McBreen B , Michel R , Mihov B , Minev M , Mirzaqulov D O , Molina S N , Moody J W , Morozova D A , Nazarov S V , Nikiforova A A , Nikolashvili M G , Ohlert J M , Okhmat N , Ovcharov E , Pinna F , Polakis T A , Protasio C , Pursimo T , Redondo-Lorenzo F J , Rizzi N , Rodriguez-Coira G , Sadakane K , Sadun A C , Samal M R , Savchenko S S , Semkov E , Sigua L , Skiff B A , Slavcheva-Mihova L , Smith P S , Steele I A , Strigachev A , Tammi J , Thum C , Tornikoski M , Troitskaya Yu V , Troitsky I S , Vasilyev A A , Vince O ,   (the WEBT Collaboration), Hovatta T , Kiehlmann S , Max-Moerbeck W , Readhead A C S , Reeves R , Pearson T J ,   (the OVRO Team), Mufakharov T , Sotnikova Yu V , Mingaliev M G 
Published: October 2019

ABSTRACT
We present a multiwavelength study of the flat-spectrum radio quasar CTA 102 during 2013–2017. We use radio-to-optical data obtained by the Whole Earth Blazar Telescope, 15 GHz data from the Owens Valley Radio Observatory, 91 and 103 GHz data from the Atacama Large Millimeter Array, near-infrared data from the Rapid Eye Monitor telescope, as well as data from the Swift (optical-UV and X-rays) and Fermi (γ-rays) satellites to study flux and spectral variability and the correlation between flux changes at different wavelengths. Unprecedented γ-ray flaring activity was observed during 2016 November–2017 February, with four major outbursts. A peak flux of (2158 ± 63) × 10−8 ph cm−2 s−1, corresponding to a luminosity of (2.2 ± 0.1) × 1050 erg s−1, was reached on 2016 December 28. These four γ-ray outbursts have corresponding events in the near-infrared, optical, and UV bands, with the peaks observed at the same time. A general agreement between X-ray and γ-ray activity is found. The γ-ray flux variations show a general, strong correlation with the optical ones with no time lag between the two bands and a comparable variability amplitude. This γ-ray/optical relationship is in agreement with the geometrical model that has successfully explained the low-energy flux and spectral behaviour, suggesting that the long-term flux variations are mainly due to changes in the Doppler factor produced by variations of the viewing angle of the emitting regions. The difference in behaviour between radio and higher energy emission would be ascribed to different viewing angles of the jet regions producing their emission.
On the Use of Information Criteria for Model Selection in Phylogenetics
Authors: Susko Edward , Roger Andrew J 
Published: October 2019

AbstractThe information criteria Akaike information criterion (AIC), AICc, and Bayesian information criterion (BIC) are widely used for model selection in phylogenetics, however, their theoretical justification and performance have not been carefully examined in this setting. Here, we investigate these methods under simple and complex phylogenetic models. We show that AIC can give a biased estimate of its intended target, the expected predictive log likelihood (EPLnL) or, equivalently, expected Kullback–Leibler divergence between the estimated model and the true distribution for the data. Reasons for bias include commonly occurring issues such as small edge-lengths or, in mixture models, small weights. The use of partitioned models is another issue that can cause problems with information criteria. We show that for partitioned models, a different BIC correction is required for it to be a valid approximation to a Bayes factor. The commonly used AICc correction is not clearly defined in partitioned models and can actually create a substantial bias when the number of parameters gets large as is the case with larger trees and partitioned models. Bias-corrected cross-validation corrections are shown to provide better approximations to EPLnL than AIC. We also illustrate how EPLnL, the estimation target of AIC, can sometimes favor an incorrect model and give reasons for why selection of incorrectly under-partitioned models might be desirable in partitioned model settings.
Targeted live-cell nuclear delivery of the DNA ‘light-switching’ Ru(II) complex via ion-pairing with chlorophenolate counter-anions: the critical role of binding stability and lipophilicity of the ion-pairing complexes
Authors: Chao Xi-Juan , Tang Miao , Huang Rong , Huang Chun-Hua , Shao Jie , Yan Zhu-Ying , Zhu Ben-Zhan 
Published: October 2019

Abstract
We have found recently that nuclear uptake of the cell-impermeable DNA light-switching Ru(II)-polypyridyl cationic complexes such as [Ru(bpy)2(dppz)]Cl2 was remarkably enhanced by pentachlorophenol (PCP), by forming ion-pairing complexes via a passive diffusion mechanism. However, it is not clear whether the enhanced nuclear uptake of [Ru(bpy)2(dppz)]2+ is only limited to PCP, or it is a general phenomenon for other highly chlorinated phenols (HCPs); and if so, what are the major physicochemical factors in determining nuclear uptake? Here, we found that the nuclear uptake of [Ru(bpy)2(dppz)]2+ can also be facilitated by other two groups of HCPs including three tetrachlorophenol (TeCP) and six trichlorophenol (TCP) isomers. Interestingly and unexpectedly, 2,3,4,5-TeCP was found to be the most effective one for nuclear delivery of [Ru(bpy)2(dppz)]2+, which is even better than the most-highly chlorinated PCP, and much better than its two other TeCP isomers. Further studies showed that the nuclear uptake of [Ru(bpy)2(dppz)]2+ was positively correlated with the binding stability, but to our surprise, inversely correlated with the lipophilicity of the ion-pairing complexes formed between [Ru(bpy)2(dppz)]Cl2 and HCPs. These findings should provide new perspectives for future investigations on using ion-pairing as an effective method for delivering other bio-active metal complexes into their intended cellular targets.
Structure and function of the Toscana virus cap-snatching endonuclease
Authors: Jones Rhian , Lessoued Sana , Meier Kristina , Devignot Stéphanie , Barata-García Sergio , Mate Maria , Bragagnolo Gabriel , Weber Friedemann , Rosenthal Maria , Reguera Juan 
Published: October 2019

AbstractToscana virus (TOSV) is an arthropod-borne human pathogen responsible for seasonal outbreaks of fever and meningoencephalitis in the Mediterranean basin. TOSV is a segmented negative-strand RNA virus (sNSV) that belongs to the genus phlebovirus (family Phenuiviridae, order Bunyavirales), encompassing other important human pathogens such as Rift Valley fever virus (RVFV). Here, we carried out a structural and functional characterization of the TOSV cap-snatching endonuclease, an N terminal domain of the viral polymerase (L protein) that provides capped 3′OH primers for transcription. We report TOSV endonuclease crystal structures in the apo form, in complex with a di-ketoacid inhibitor (DPBA) and in an intermediate state of inhibitor release, showing details on substrate binding and active site dynamics. The structure reveals substantial folding rearrangements absent in previously reported cap-snatching endonucleases. These include the relocation of the N terminus and the appearance of new structural motifs important for transcription and replication. The enzyme shows high activity rates comparable to other His+ cap-snatching endonucleases. Moreover, the activity is dependent on conserved residues involved in metal ion and substrate binding. Altogether, these results bring new light on the structure and function of cap-snatching endonucleases and pave the way for the development of specific and broad-spectrum antivirals.
gutMDisorder: a comprehensive database for dysbiosis of the gut microbiota in disorders and interventions
Authors: Cheng Liang , Qi Changlu , Zhuang He , Fu Tongze , Zhang Xue 
Published: October 2019

Abstract
gutMDisorder (http://bio-annotation.cn/gutMDisorder), a manually curated database, aims at providing a comprehensive resource of dysbiosis of the gut microbiota in disorders and interventions. Alterations in the composition of the gut microbial community play crucial roles in the development of chronic disorders. And the beneficial effects of drugs, foods and other intervention measures on disorders could be microbially mediated. The current version of gutMDisorder documents 2263 curated associations between 579 gut microbes and 123 disorders or 77 intervention measures in Human, and 930 curated associations between 273 gut microbes and 33 disorders or 151 intervention measures in Mouse. Each entry in the gutMDisorder contains detailed information on an association, including an intestinal microbe, a disorder name, intervention measures, experimental technology and platform, characteristic of samples, web sites for downloading the sequencing data, a brief description of the association, a literature reference, and so on. gutMDisorder provides a user-friendly interface to browse, retrieve each entry using gut microbes, disorders, and intervention measures. It also offers pages for downloading all the entries and submitting new experimentally validated associations.
High-yield fabrication of DNA and RNA constructs for single molecule force and torque spectroscopy experiments
Authors: Papini Flávia S , Seifert Mona , Dulin David 
Published: October 2019

Abstract
Single molecule biophysics experiments have enabled the observation of biomolecules with a great deal of precision in space and time, e.g. nucleic acids mechanical properties and protein–nucleic acids interactions using force and torque spectroscopy techniques. The success of these experiments strongly depends on the capacity of the researcher to design and fabricate complex nucleic acid structures, as the outcome and the yield of the experiment also strongly depend on the high quality and purity of the final construct. Though the molecular biology techniques involved are well known, the fabrication of nucleic acid constructs for single molecule experiments still remains a difficult task. Here, we present new protocols to generate high quality coilable double-stranded DNA and RNA, as well as DNA and RNA hairpins with ∼500–1000 bp long stems. Importantly, we present a new approach based on single-stranded DNA (ssDNA) annealing and we use magnetic tweezers to show that this approach simplifies the fabrication of complex DNA constructs, such as hairpins, and converts more efficiently the input DNA into construct than the standard PCR-digestion-ligation approach. The protocols we describe here enable the design of a large range of nucleic acid construct for single molecule biophysics experiments.
Animal-ImputeDB: a comprehensive database with multiple animal reference panels for genotype imputation
Authors: Yang Wenqian , Yang Yanbo , Zhao Cecheng , Yang Kun , Wang Dongyang , Yang Jiajun , Niu Xiaohui , Gong Jing 
Published: October 2019

Abstract
Animal-ImputeDB (http://gong_lab.hzau.edu.cn/Animal_ImputeDB/) is a public database with genomic reference panels of 13 animal species for online genotype imputation, genetic variant search, and free download. Genotype imputation is a process of estimating missing genotypes in terms of the haplotypes and genotypes in a reference panel. It can effectively increase the density of single nucleotide polymorphisms (SNPs) and thus can be widely used in large-scale genome-wide association studies (GWASs) using relatively inexpensive and low-density SNP arrays. However, most animals except humans lack high-quality reference panels, which greatly limits the application of genotype imputation in animals. To overcome this limitation, we developed Animal-ImputeDB, which is dedicated to collecting genotype data and whole-genome resequencing data of nonhuman animals from various studies and databases. A computational pipeline was developed to process different types of raw data to construct reference panels. Finally, 13 high-quality reference panels including ∼400 million SNPs from 2265 samples were constructed. In Animal-ImputeDB, an easy-to-use online tool consisting of two popular imputation tools was designed for the purpose of genotype imputation. Collectively, Animal-ImputeDB serves as an important resource for animal genotype imputation and will greatly facilitate research on animal genomic selection and genetic improvement.
Retrons and their applications in genome engineering
Authors: Simon Anna J , Ellington Andrew D , Finkelstein Ilya J 
Published: October 2019

AbstractPrecision genome editing technologies have transformed modern biology. These technologies have arisen from the redirection of natural biological machinery, such as bacteriophage lambda proteins for recombineering and CRISPR nucleases for eliciting site-specific double-strand breaks. Less well-known is a widely distributed class of bacterial retroelements, retrons, that employ specialized reverse transcriptases to produce noncoding intracellular DNAs. Retrons’ natural function and mechanism of genetic transmission have remained enigmatic. However, recent studies have harnessed their ability to produce DNA in situ for genome editing and evolution. This review describes retron biology and function in both natural and synthetic contexts. We also highlight areas that require further study to advance retron-based precision genome editing platforms.
Recruitment of Rec8, Pds5 and Rad61/Wapl to meiotic homolog pairing, recombination, axis formation and S-phase
Authors: Hong Soogil , Joo Jeong H , Yun Hyeseon , Kleckner Nancy , Kim Keun P 
Published: October 2019

AbstractWe have explored the meiotic roles of cohesin modulators Pds5 and Rad61/Wapl, in relation to one another, and to meiotic kleisin Rec8, for homolog pairing, all physically definable steps of recombination, prophase axis length and S-phase progression, in budding yeast. We show that Pds5 promotes early steps of recombination and thus homolog pairing, and also modulates axis length, with both effects independent of a sister chromatid. [Pds5+Rec8] promotes double-strand break formation, maintains homolog bias for crossover formation and promotes S-phase progression. Oppositely, the unique role of Rad61/Wapl is to promote non-crossover recombination by releasing [Pds5+Rec8]. For this effect, Rad61/Wapl probably acts to maintain homolog bias by preventing channeling into sister interactions. Mysteriously, each analyzed molecule has one role that involves neither of the other two. Overall, the presented findings suggest that Pds5’s role in maintenance of sister chromatid cohesion during the mitotic prophase-analogous stage of G2/M is repurposed during meiosis prophase to promote interactions between homologs.
Streamlining effects of extra telomeric repeat on telomeric DNA folding revealed by fluorescence-force spectroscopy
Authors: Mitra Jaba , Ha Taekjip 
Published: October 2019

AbstractA human telomere ends in a single-stranded 3′ tail, composed of repeats of T2AG3. G-quadruplexes (GQs) formed from four consecutive repeats have been shown to possess high-structural and mechanical diversity. In principle, a GQ can form from any four repeats that are not necessarily consecutive. To understand the dynamics of GQs with positional multiplicity, we studied five and six repeats human telomeric sequence using a combination of single molecule FRET and optical tweezers. Our results suggest preferential formation of GQs at the 3′ end both in K+ and Na+ solutions, with minor populations of 5′-GQ or long-loop GQs. A vectorial folding assay which mimics the directional nature of telomere extension showed that the 3′ preference holds even when folding is allowed to begin from the 5′ side. In 100 mM K+, the unassociated T2AG3 segment has a streamlining effect in that one or two mechanically distinct species was observed at a single position instead of six or more observed without an unassociated repeat. We did not observe such streamlining effect in 100 mM Na+. Location of GQ and reduction in conformational diversity in the presence of extra repeats have implications in telomerase inhibition, T-loop formation and telomere end protection.
CTCF-dependent chromatin boundaries formed by asymmetric nucleosome arrays with decreased linker length
Authors: Clarkson Christopher T , Deeks Emma A , Samarista Ralph , Mamayusupova Hulkar , Zhurkin Victor B , Teif Vladimir B 
Published: October 2019

Abstract
The CCCTC-binding factor (CTCF) organises the genome in 3D through DNA loops and in 1D by setting boundaries isolating different chromatin states, but these processes are not well understood. Here we investigate chromatin boundaries in mouse embryonic stem cells, defined by the regions with decreased Nucleosome Repeat Length (NRL) for ∼20 nucleosomes near CTCF sites, affecting up to 10% of the genome. We found that the nucleosome-depleted region (NDR) near CTCF is asymmetrically located >40 nucleotides 5′-upstream from the centre of CTCF motif. The strength of CTCF binding to DNA and the presence of cohesin is correlated with the decrease of NRL near CTCF, and anti-correlated with the level of asymmetry of the nucleosome array. Individual chromatin remodellers have different contributions, with Snf2h having the strongest effect on the NRL decrease near CTCF and Chd4 playing a major role in the symmetry breaking. Upon differentiation, a subset of preserved, common CTCF sites maintains asymmetric nucleosome pattern and small NRL. The sites which lost CTCF upon differentiation are characterized by nucleosome rearrangement 3′-downstream, with unchanged NDR 5′-upstream of CTCF motifs. Boundaries of topologically associated chromatin domains frequently contain several inward-oriented CTCF motifs whose effects, described above, add up synergistically.
An improved platform for functional assessment of large protein libraries in mammalian cells
Authors: Matreyek Kenneth A , Stephany Jason J , Chiasson Melissa A , Hasle Nicholas , Fowler Douglas M 
Published: October 2019

Abstract
Multiplex genetic assays can simultaneously test thousands of genetic variants for a property of interest. However, limitations of existing multiplex assay methods in cultured mammalian cells hinder the breadth, speed and scale of these experiments. Here, we describe a series of improvements that greatly enhance the capabilities of a Bxb1 recombinase-based landing pad system for conducting different types of multiplex genetic assays in various mammalian cell lines. We incorporate the landing pad into a lentiviral vector, easing the process of generating new landing pad cell lines. We also develop several new landing pad versions, including one where the Bxb1 recombinase is expressed from the landing pad itself, improving recombination efficiency more than 2-fold and permitting rapid prototyping of transgenic constructs. Other versions incorporate positive and negative selection markers that enable drug-based enrichment of recombinant cells, enabling the use of larger libraries and reducing costs. A version with dual convergent promoters allows enrichment of recombinant cells independent of transgene expression, permitting the assessment of libraries of transgenes that perturb cell growth and survival. Lastly, we demonstrate these improvements by assessing the effects of a combinatorial library of oncogenes and tumor suppressors on cell growth. Collectively, these advancements make multiplex genetic assays in diverse cultured cell lines easier, cheaper and more effective, facilitating future studies probing how proteins impact cell function, using transgenic variant libraries tested individually or in combination.
Enhancing Concussion Management in the National Football League: Evolution and Initial Results of the Unaffiliated Neurotrauma Consultants Program, 2012-2017
Authors: Mack Christina , Sendor Rachel R , Solomon Gary , Ellenbogen Richard G , Myers Emily , Berger Mitchel , Sills Allen 
Published: October 2019

AbstractBackgroundThe real-time detection of concussive injury in professional sports can be challenging for the healthcare provider on the sideline. It can be difficult to monitor all on-field players during active game play and diagnose complex injuries such as concussion during a fast-paced athletic event.ObjectiveTo enhance the in-game identification of potentially concussed professional athletes, the National Football League (NFL) initiated an Unaffiliated Neurotrauma Consultants (UNC) program in 2013, which, in tandem with other in-arena spotters and live video review systems, is designed to improve the safety of the players through enhanced concussion detection efforts.MethodsThis paper reports on the evolution of the UNC program, describes its participants and training requirements, details the role of UNC involvement, and delineates the systematic revisions and enhancements completed each year in the program.ResultsUNC reporting compliance has increased from 56% in 2014 to 100% in 2017. During the 2016 and 2017 seasons, (1) UNCs submitted an average of 1.9 evaluations per game, and (2) the UNC concussion assessments yielded sensitivity (93.4%-97.4%) and specificity (81.0%-88.3%) values.ConclusionThe UNC program has enhanced the detection of concussion in NFL players. Directions for research and future program improvements are addressed.