bluuebunny/crossref_metadata_2025_split huggingface dataset:
A mathematical framework for modelling 3D cell motility: applications to glioblastoma cell migration
Authors: Scott M , Żychaluk K , Bearon R N 
Published: June 2021

Abstract
The collection of 3D cell tracking data from live images of micro-tissues is a recent innovation made possible due to advances in imaging techniques. As such there is increased interest in studying cell motility in 3D in vitro model systems but a lack of rigorous methodology for analysing the resulting data sets. One such instance of the use of these in vitro models is in the study of cancerous tumours. Growing multicellular tumour spheroids in vitro allows for modelling of the tumour microenvironment and the study of tumour cell behaviours, such as migration, which improves understanding of these cells and in turn could potentially improve cancer treatments. In this paper, we present a workflow for the rigorous analysis of 3D cell tracking data, based on the persistent random walk model, but adaptable to other biologically informed mathematical models. We use statistical measures to assess the fit of the model to the motility data and to estimate model parameters and provide confidence intervals for those parameters, to allow for parametrization of the model taking correlation in the data into account. We use in silico simulations to validate the workflow in 3D before testing our method on cell tracking data taken from in vitro experiments on glioblastoma tumour cells, a brain cancer with a very poor prognosis. The presented approach is intended to be accessible to both modellers and experimentalists alike in that it provides tools for uncovering features of the data set that may suggest amendments to future experiments or modelling attempts.
Identification of bile acid and fatty acid species as candidate rapidly bactericidal agents for topical treatment of gonorrhoea
Authors: Palace Samantha G , Fryling Kyra E , Li Ying , Wentworth Adam J , Traverso Giovanni , Grad Yonatan H 
Published: June 2021

Abstract

Background
Novel therapeutic strategies are urgently needed for Neisseria gonorrhoeae, given its increasing antimicrobial resistance. Treatment of oropharyngeal N. gonorrhoeae infections has proven particularly challenging, with most reported treatment failures of the first-line drug ceftriaxone occurring at this site and lower cure rates in recent trials of new antibiotics reported for oropharyngeal infections compared with other sites of infection. However, the accessibility of the oropharynx to topical therapeutics provides an opportunity for intervention. Local delivery of a therapeutic at a high concentration would enable the use of non-traditional antimicrobial candidates, including biological molecules that exploit underlying chemical sensitivities of N. gonorrhoeae but lack the potency or pharmacokinetic profiles required for effective systemic administration.

Methods
Two classes of molecules that are thought to limit gonococcal viability in vivo, bile acids and short- and medium-chain fatty acids, were examined for rapid bactericidal activity.

Results
The bile acids deoxycholic acid (DCA) and chenodeoxycholic acid (CDCA), but not other bile acid species, exerted extremely rapid bactericidal properties against N. gonorrhoeae, reducing viability more than 100 000-fold after 1 min. The short-chain fatty acids formic acid and hexanoic acid shared this rapid bactericidal activity. All four molecules are effective against a phylogenetically diverse panel of N. gonorrhoeae strains, including clinical isolates with upregulated efflux pumps and resistance alleles to the most widely used classes of existing antimicrobials. DCA and CDCA are both approved therapeutics for non-infectious indications and are well-tolerated by cultured epithelial cells.

Conclusions
DCA and CDCA are attractive candidates for further development as anti-gonococcal agents.
Smart Mathematical Manipulation οf Spectral Signals: Stability Indicating, fοr the Estimation of Sοlifenacin Succinate: Anti-Muscarinic Drug, in Existence οf Its Acid Degradatiοn Product
Authors: Fayed Ahmed S , Hegazy Maha A , Kamel Ebraam B , Eissa Maya S 
Published: June 2021

Abstract

Backgrοund
Fοur rapid, smart, and easy tο apply spectrοphοtοmetric methοds were developed fοr the estimatiοn οf sοlifenacin succinate (SΟL) with its acid-induced degradation prοduct.

Οbjective
Development οf stability-indicating, smart, sensitive, cheap spectrοphοtοmetric methοds fοr determinatiοn οf SΟL in the presence οf its acid degradate.

Methοds
Methοd A is a dual wavelength methοd where twο wavelengths were selected (262 and 289 nm) and utilized tο determine SΟL in the presence οf its acid degradate. Methοd B involves develοping the first derivative (1D) οf the absοrptiοn spectra. Peak signal was detected at 276 nm. Methοd C is a ratiο difference methοd where the drug is determined by the difference in signal between twο selected wavelengths, at 240 and 259 nm. Methοd D is dependent οn measuring the peak signal οf the first derivative οf the ratiο spectra (1DD) at 269 nm.

Results
Calibratiοn curves οf the suggested methοds exhibited linearity. The selectivity οf the suggested methοds were ascertained using different labοratοry-prepared mixtures οf SΟL with its acid degradate, indicating specificity οf SΟL with accepted recοvery values. The suggested methοds have been successfully applied tο the analysis οf SΟL in its pharmaceutical dοsage fοrm withοut the invοlvement οf additives.

Cοnclusiοn
The presented wοrk applied fοur resοlutiοn techniques, based οn absοrbance, derivative, and/οr ratiο spectra, fοr the analysis οf SΟL in the presence οf its acid degradate.

Highlights
The study οf degradatiοn pathways οf drugs is οf great impοrtance. Hence, acid hydrοlysis οf SΟL was achieved and then SΟL was determined alοng with its acid degradate.
Determination of Six Tetracyclines in Eggs and Chicken by Dispersive Liquid-Liquid Microextraction Combined with High-Performance Liquid Chromatography
Authors: Yang Yi , Yin Shuo , Wu Ling , Li Yongxin , Sun Chengjun 
Published: June 2021

Abstract

Background
The wide usage of tetracyclines in livestock farming may result in drug residues in foods. Therefore, it is necessary to develop reliable methods for the determination of tetracyclines in foods.

Objective
A dispersive liquid-liquid microextraction (DLLME) combined with HPLC method was developed for the analysis of six tetracyclines in eggs and chicken.

Methods
After deproteinization, tetracyclines in acidic solutions were concentrated by vortex-assisted DLLME. After the addition of NaCl (35% for eggs and 20% for chicken), a mixture of ionic liquid 1-butyl-3-methylimidazolium hexafluorophosphate and ethyl acetate (300 μL–50 μL for eggs and 200 μL–60 μL for chicken) was used as the extractant. After centrifugation, the extract was collected for HPLC analysis.

Results
The developed method showed good linear relationships (10.0–500 μg/kg), low method detection limits (0.219–1.42 μg/kg) and quantification limits (0.731–4.72 μg/kg), and satisfactory relative recoveries (87.1–104%), with intra-day and inter-day RSDs in the ranges of 0.853–8.62% and 1.65–11.8%, respectively. The established method was successfully applied for the determination of six tetracyclines in eggs and different parts of chicken. The contents of tetracyclines in all samples were lower than their maximum residue limits.

Conclusion
A DLLME-HPLC method has been developed for the analysis of six tetracyclines in animal-derived foods using ionic liquid and ethyl acetate as the extractant.

Highlights
The developed method is simple, sensitive, cost-effective, and has strong anti-interference abilities. This method has been successfully applied to the analysis of six tetracyclines in eggs and chicken.
Finding Your Crowd: The Role of Government Level and Charity Type in Revenue Crowd-Out
Authors: Grasse Nathan J , Searing Elizabeth A M , Neely Daniel G 
Published: June 2021

Abstract
The literature on the relationship between government funding and private donations finds evidence of both crowd-out (a reduction in private donations due to the receipt of government funding) and crowd-in (increased donations rather than a reduction). This study uses organizational-level data and information regarding funding from multiple levels of government in Canada to provide an important contribution to the literature, which has traditionally relied upon aggregated measures of government funding. Results from dynamic panel estimations suggest that effects vary by type of charity and level of government funding source, with some subsectors displaying crowd-in, some crowd-out, and some both phenomenon depending on the level of government providing funding. These findings encourage more research into the context and variation involved in crowd-out, raising practical and theoretical questions about whether a uniform effect across subsectors or level of government funding should be expected.
Keeping Kids in Care: Reducing Administrative Burden in State Child Care Development Fund Policy
Authors: Jenkins Jade Marcus , Nguyen Tutrang 
Published: June 2021

Abstract
With limited federal requirements for block grants, states have developed very different welfare policies, often with onerous recertification or reporting requirements, creating barriers to continuous program enrollment. Examined through the framework of Administrative Burden, our study examines how changes to burdensome policies in states’ Child Care Development Fund (CCDF) programs affect the length of children’s continuous enrollment in child care through the CCDF program, known as subsidy “spells.” We exploit state-level changes in three key policies during a 10-year period (2004–13) that capture administrative burden: (1) length of eligibility redetermination; (2) reporting requirements for income changes; and (3) grace period for care before termination. Using state fixed effects analyses in a sample of 38 states using data from the Administration for Children and Families and multiple other sources, we find that administrative burdens meaningfully and robustly affect continuous enrollment in CCDF; switching to a 12-month redetermination period, as required 2014 Child Care and Development Block Grant reauthorization, increases children’s continuous enrollment in CCDF care (i.e., state median spell length) by 30%. In contrast, requiring all changes in family income to be reported while enrolled in CCDF decreases spell length by 7%. Results underscore the importance of reducing administrative burdens related to compliance costs to better support low-income citizens, especially those with young children, and improve child development.
The Professional Agency Narrative—Conceptualizing the Role of Professional Knowledge in Frontline Work
Authors: Cecchini Mathilde , Harrits Gitte Sommer 
Published: June 2021

Abstract
The street-level bureaucracy literature teaches us that frontline workers draw on both policy logics and social, cultural, and personal logics in their work. This has been conceptualized as the state agency narrative and citizen agency narrative, and it is both well documented and well theorized. However, the literature on street-level bureaucracy and frontline work is remarkably silent on how to understand the role of professional knowledge in frontline work. In this article, we seek to fill this gap by theorizing and empirically demonstrating how frontline work is characterized by what we call a professional agency narrative centering on problem solving and the use of knowledge on “what works.” We do so through in-depth qualitative analyses of data from two empirical studies on frontline work in schools. The first is an interview study consisting of 42 semi-structured interviews with Danish preschool and school teachers on the topic of prevention of social and health risks. The second study is an ethnographic study consisting of more than 500 h of observation, two focus groups with teachers and seven semi-structured interviews with teachers on the topic of health risk prevention in Danish schools. Based on the analysis of this rich qualitative data, we develop the concept of the professional agency narrative and discuss how this concept can contribute to the broader literatures on street-level work and the management of street-level work.
Preparation and evaluation of reduction-responsive micelles based on disulfide-linked chondroitin sulfate A-tocopherol succinate for controlled antitumour drug release
Authors: Cai Songjin , Xie Xin , Yuan Qinglan , Ding Jian , Meng Lijia , Li Junzhi , He Ming , Li Weidong , Yu Jingmou 
Published: June 2021

Abstract

Objectives
The study was to construct reduction-responsive chondroitin sulfate A (CSA)-conjugated TOS (CST) micelles with disulfide bond linkage, which was used for controlled doxorubicin (DOX) release and improved drug efficacy in vivo.

Methods
CST and non-responsive CSA-conjugated TOS (CAT) were synthesized, and the chemical structure was confirmed by Fourier transform infrared (FTIR) spectroscopy, proton nuclear magnetic resonance (1H NMR) spectroscopy, fluorescence spectrophotometer and dynamic light scattering. Antitumour drug DOX was physically encapsulated into CST and CSA by dialysis method. Cell uptake of DOX-based formulations was investigated by confocal laser scanning microscopy. In vitro cytotoxicity was studied in A549 and AGS cells. Furthermore, antitumour activity was evaluated in A549-bearing mice.

Key findings
CST and CAT can form self-assembled micelles, and have low value of critical micelle concentration. Notably, DOX-containing CST (D-CST) micelles demonstrated reduction-triggered drug release in glutathione-containing media. Further, reduction-responsive uptake of D-CST was observed in A549 cells. In addition, D-CST induced stronger cytotoxicity (P &lt; 0.05) than DOX-loaded CAT (D-CAT) against A549 and AGS cells. Moreover, D-CST exhibited significantly stronger antitumour activity in A549-bearing nude mice than doxorubicin hydrochloride and D-CAT.

Conclusions
The reduction-responsive CST micelles enhanced the DOX effect at tumour site and controlled drug release.
Toward an understanding of the detection and function of R-loops in plants
Authors: Gao Jingjing , Zhang Pengyue , Li Xinxu , Wu Wenqi , Wei Hairong , Zhang Wenli 
Published: June 2021

Abstract
Although lagging behind studies in humans and other mammals, studies of R-loops in plants have recently entered an exciting stage in which the roles of R-loops in gene expression, genome stability, epigenomic signatures, and plant development and stress responses are being elucidated. Here, we review the strengths and weaknesses of existing methodologies, which were largely developed for R-loop studies in mammals, and then discuss the potential challenges of applying these methodologies to R-loop studies in plants. We then focus on recent advances in the functional characterization of R-loops in Arabidopsis thaliana and rice. Recent studies in plants indicate that there are coordinated relationships between R-loops and gene expression, and between R-loops and epigenomic signatures that depend, in part, on the types of R-loops involved. Finally, we discuss the emerging roles of R-loops in plants and directions for future research.
Annotated Copies of Early Editions of Johnson's Dictionary: A Preliminary Account
Authors: Considine John 
Published: June 2021

Abstract
Early responses to Johnson’s Dictionary of the English Language included manuscript annotations, sometimes very extensive, in copies of the dictionary. This article surveys twenty-one copies of eighteenth-century editions of the dictionary with critical or informative annotations, bearing on etymology or usage, adding new words or senses, or improving the supply and referencing of quotations. Some of these copies are extant in institutional or private collections, and others are unlocated. The annotators include Johnson himself; members of his circle including Edmund Burke, Samuel Dyer, Edmond Malone, Hester Piozzi, and George Steevens; and other readers including Leigh Hunt, Horne Tooke, Noah Webster, and John Wilkes.
Smoothed particle radiation hydrodynamics: two-moment method with local Eddington tensor closure
Authors: Chan T K , Theuns Tom , Bower Richard , Frenk Carlos 
Published: June 2021

ABSTRACTWe present a new smoothed particle hydrodynamics-radiative transfer method (sph-m1rt) that is coupled dynamically with sph. We implement it in the (task-based parallel) swift galaxy simulation code but it can be straightforwardly implemented in other sph codes. Our moment-based method simultaneously solves the radiation energy and flux equations in sph, making it adaptive in space and time. We modify the m1 closure relation to stabilize radiation fronts in the optically thin limit. We also introduce anisotropic artificial viscosity and high-order artificial diffusion schemes, which allow the code to handle radiation transport accurately in both the optically thin and optically thick regimes. Non-equilibrium thermochemistry is solved using a semi-implicit sub-cycling technique. The computational cost of our method is independent of the number of sources and can be lowered further by using the reduced speed-of-light approximation. We demonstrate the robustness of our method by applying it to a set of standard tests from the cosmological radiative transfer comparison project of Iliev et al. The sph-m1rt scheme is well-suited for modelling situations in which numerous sources emit ionizing radiation, such as cosmological simulations of galaxy formation or simulations of the interstellar medium.
Geonomics: Forward-Time, Spatially Explicit, and Arbitrarily Complex Landscape Genomic Simulations
Authors: Terasaki Hart Drew E , Bishop Anusha P , Wang Ian J 
Published: June 2021

Abstract
Understanding the drivers of spatial patterns of genomic diversity has emerged as a major goal of evolutionary genetics. The flexibility of forward-time simulation makes it especially valuable for these efforts, allowing for the simulation of arbitrarily complex scenarios in a way that mimics how real populations evolve. Here, we present Geonomics, a Python package for performing complex, spatially explicit, landscape genomic simulations with full spatial pedigrees that dramatically reduces user workload yet remains customizable and extensible because it is embedded within a popular, general-purpose language. We show that Geonomics results are consistent with expectations for a variety of validation tests based on classic models in population genetics and then demonstrate its utility and flexibility with a trio of more complex simulation scenarios that feature polygenic selection, selection on multiple traits, simulation on complex landscapes, and nonstationary environmental change. We then discuss runtime, which is primarily sensitive to landscape raster size, memory usage, which is primarily sensitive to maximum population size and recombination rate, and other caveats related to the model’s methods for approximating recombination and movement. Taken together, our tests and demonstrations show that Geonomics provides an efficient and robust platform for population genomic simulations that capture complex spatial and evolutionary dynamics.
Heterogeneous Histories of Recombination Suppression on Stickleback Sex Chromosomes
Authors: Sardell Jason M , Josephson Matthew P , Dalziel Anne C , Peichel Catherine L , Kirkpatrick Mark 
Published: June 2021

Abstract
How consistent are the evolutionary trajectories of sex chromosomes shortly after they form? Insights into the evolution of recombination, differentiation, and degeneration can be provided by comparing closely related species with homologous sex chromosomes. The sex chromosomes of the threespine stickleback (Gasterosteus aculeatus) and its sister species, the Japan Sea stickleback (G. nipponicus), have been well characterized. Little is known, however, about the sex chromosomes of their congener, the blackspotted stickleback (G. wheatlandi). We used pedigrees to obtain experimentally phased whole genome sequences from blackspotted stickleback X and Y chromosomes. Using multispecies gene trees and analysis of shared duplications, we demonstrate that Chromosome 19 is the ancestral sex chromosome and that its oldest stratum evolved in the common ancestor of the genus. After the blackspotted lineage diverged, its sex chromosomes experienced independent and more extensive recombination suppression, greater X–Y differentiation, and a much higher rate of Y degeneration than the other two species. These patterns may result from a smaller effective population size in the blackspotted stickleback. A recent fusion between the ancestral blackspotted stickleback Y chromosome and Chromosome 12, which produced a neo-X and neo-Y, may have been favored by the very small size of the recombining region on the ancestral sex chromosome. We identify six strata on the ancestral and neo-sex chromosomes where recombination between the X and Y ceased at different times. These results confirm that sex chromosomes can evolve large differences within and between species over short evolutionary timescales.
Peromyscus fraterculus(Rodentia: Cricetidae)
Authors: Cornejo-Latorre Cristian , Cortés-Calva Patricia , Álvarez-Castañeda Sergio Ticul 
Published: June 2021

Abstract Peromyscus fraterculus (Miller, 1892) is a small rodent commonly called the northern Baja deermouse. Its pelage is dark, the tail is considerably longer than the body, and the number of caudal vertebrae ranges from 30 to 34. The geographic distribution of P. fraterculus includes the area west of the Colorado River, from southern California in the United States of America southward to the Baja California Peninsula, Mexico, south of La Paz Isthmus. It is found in a broad variety of habitats from sea level to 1,175 m. P. fraterculus does not have special conservation status, although the island populations have conservation issues, mainly due to the introduction of non-native species. It is listed as “Least Concern” (LC) by the International Union for Conservation of Nature and Natural Resources.
NOVA2 regulates neural circRNA biogenesis
Authors: Knupp David , Cooper Daphne A , Saito Yuhki , Darnell Robert B , Miura Pedro 
Published: June 2021

Abstract
Circular RNAs (circRNAs) are highly expressed in the brain and their expression increases during neuronal differentiation. The factors regulating circRNAs in the developing mouse brain are unknown. NOVA1 and NOVA2 are neural-enriched RNA-binding proteins with well-characterized roles in alternative splicing. Profiling of circRNAs from RNA-seq data revealed that global circRNA levels were reduced in embryonic cortex of Nova2 but not Nova1 knockout mice. Analysis of isolated inhibitory and excitatory cortical neurons lacking NOVA2 revealed an even more dramatic reduction of circRNAs and establishes a widespread role for NOVA2 in enhancing circRNA biogenesis. To investigate the cis-elements controlling NOVA2-regulation of circRNA biogenesis, we generated a backsplicing reporter based on the Efnb2 gene. We found that NOVA2-mediated backsplicing of circEfnb2 was impaired when YCAY clusters located in flanking introns were mutagenized. CLIP (cross-linking and immunoprecipitation) and additional reporter analyses demonstrated the importance of NOVA2 binding sites located in both flanking introns of circRNA loci. NOVA2 is the first RNA-binding protein identified to globally promote circRNA biogenesis in the developing brain.