bluuebunny/crossref_metadata_2025_split huggingface dataset:
Large-scale gas flows and streaming motions in simulated spiral galaxies
Authors: Ramón-Fox F G , Bonnell I A 
Published: January 2022

ABSTRACT
From a galactic perspective, star formation occurs on the smallest scales within molecular clouds, but it is likely initiated from the large-scale flows driven by galactic dynamics. To understand the conditions for star formation, it is important to first discern the mechanisms that drive gas from large scales into dense structures on the smallest scales of a galaxy. We present high-resolution smoothed particle hydrodynamics simulations of two model spiral galaxies: one with a live stellar disc (N-body) and one with a spiral potential. We investigate the large-scale flows and streaming motions driven by the simulated spiral structure. We find that the strength of the motions in the radial direction tends to be higher than in the azimuthal component. In the N-body model, the amplitude of these motions decreases with galactocentric radius whereas for the spiral potential, it decreases to a minimum at the corotation radius, and increases again after this point. The results show that in both simulations, the arms induce local shocks, an increase in kinetic energy that can drive turbulence and a means of compressing and expanding the gas. These are all crucial elements in forming molecular clouds and driving the necessary conditions for star formation.
Formation of ultra-massive carbon–oxygen white dwarfs from the merger of carbon–oxygen and helium white dwarf pairs
Authors: Wu Chengyuan , Xiong Heran , Wang Xiaofeng 
Published: January 2022

ABSTRACT
Ultra-massive white dwarfs (UMWDs) with masses larger than 1.05M⊙ are basically believed to harbour oxygen–neon (ONe) cores. Recently, Gaia data have revealed an enhancement of UMWDs on the Hertzsprung–Russell diagram (HRD), which indicates that an extra cooling delay mechanism such as crystallization and elemental sedimentation may exist in UMWDs. Further studies have suggested that some UMWDs should have experienced fairly long cooling delays, implying that they are carbon–oxygen (CO) WDs. However, the formation mechanism of these UMCOWDs is still under debate. In this work, we investigate whether the mergers of massive CO WDs with helium WDs (He WDs) can evolve to UMCOWDs. By employing the stellar evolution code mesa, we construct double WD merger remnants to investigate their final fates. We found that the post-merger evolution of the remnants is similar to R CrB stars. The helium burning of the He shell leads to mass growth of the CO core at a rate of 2.0 × 10−6–$5.0\times {10}^{-6}\, {\rm M}_\odot \, \rm {yr}^{-1}$. The final CO WD mass is influenced by the wind mass-loss rate during the post-merger evolution, and cannot exceed about 1.2M⊙. Remnants with core masses larger than $1.2\, {\rm M}_\odot$ will experience surface carbon ignition, which may finally end their lives as ONe WDs. The current results imply that at least some UMWDs that experience extra-long cooling delays may stem from the merging of CO WDs and He WDs.
Trailed source extraction with template matching
Authors: Du Junju , Hu Shaoming , Chen Xu , Cao Hai 
Published: January 2022

ABSTRACT
In optical observations of moving targets, field stars can be trailed when the telescope tracks at the speed of the targets. When these trailed sources are relatively long, faint, or distorted, the popular source extraction techniques, such as thresholding and profile fitting, tend to fail. We present a new source extraction strategy based on the template-matching method. We described the pipeline of template matching in detail and tested its performance compared with thresholding on 9 × 4320 synthetic images and 349 real images. The indicators, including recall, position extraction error, and flux extraction error, are analysed and given. The results show that template matching can obtain higher recalls and smaller position and flux extraction errors for trailed sources.
Evolution of Amino Acid Propensities under Stability-Mediated Epistasis
Authors: Youssef Noor , Susko Edward , Roger Andrew J , Bielawski Joseph P 
Published: January 2022

Abstract
Site-specific amino acid preferences are influenced by the genetic background of the protein. The preferences for resident amino acids are expected to, on average, increase over time because of replacements at other sites—a nonadaptive phenomenon referred to as the “evolutionary Stokes shift.” Alternatively, decreases in resident amino acid propensity have recently been viewed as evidence of adaptations to external environmental changes. Using population genetics theory and thermodynamic stability constraints, we show that nonadaptive evolution can lead to both positive and negative shifts in propensities following the fixation of an amino acid, emphasizing that the detection of negative shifts is not conclusive evidence of adaptation. By examining propensity shifts from when an amino acid is first accepted at a site until it is subsequently replaced, we find that ≈50% of sites show a decrease in the propensity for the newly resident amino acid while the remaining sites show an increase. Furthermore, the distributions of the magnitudes of positive and negative shifts were comparable. Preferences were often conserved via a significant negative autocorrelation in propensity changes—increases in propensities often followed by decreases, and vice versa. Lastly, we explore the underlying mechanisms that lead propensities to fluctuate. We observe that stabilizing replacements increase the mutational tolerance at a site and in doing so decrease the propensity for the resident amino acid. In contrast, destabilizing substitutions result in more rugged fitness landscapes that tend to favor the resident amino acid. In summary, our results characterize propensity trajectories under nonadaptive stability-constrained evolution against which evidence of adaptations should be calibrated.
Transcriptomic analysis identifies candidate genes for shell colour formation in the Venus clamCyclina sinensis
Authors: Wei Min , Zhang Mingyue , Wu Yuchen , Wang Yiwo , Qiu Pan , Zhang Jiawen , Wu Lei , Song Jie , Sun Yuxuan , Tan Leilei , Yu Xue , Liu Yu , Dong Zhiguo 
Published: January 2022

ABSTRACTSome bivalves are important in fisheries and aquaculture, and provide significant economic benefits to humans. The diversity in shell colour among bivalves has received attention due to its potential in breeding and its relevance to the study of speciation and adaptation. In this study, the relationship between whole-genome-scale gene expression and shell coloration in the clam Cyclina sinensis was analysed using high-throughput Illumina sequencing technology. A total of 15,367 annotated genes and 4,425 novel genes were detected based on transcript assembly. The results of the transcriptome analysis show that 49 genes were differentially expressed in the outer mantle fold tissue of purple- vs white-shelled specimens. These genes include three lipoprotein receptor genes, low-density lipoprotein receptor gene (ldlr), low-density lipoprotein receptor-related protein 4 (lrp4) and scavenger receptor cysteine-rich protein gene (srcr). These genes may be involved in the transport of carotenoid pigments. Moreover, as shown by the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses, several receptor activity terms and a glycosphingolipid biosynthesis pathway were detected, and these might be involved in shell coloration. Together with the analyses of differentially expressed genes, our results suggest a possible molecular mechanism governing the selective transport of carotenoids in the mantle of purple-shelled clams and shell colour formation. The results of this study may help to elucidate the colour formation mechanism in clam shells.
spatzie: an R package for identifying significant transcription factor motif co-enrichment from enhancer–promoter interactions
Authors: Hammelman Jennifer , Krismer Konstantin , Gifford David K 
Published: January 2022

AbstractGenomic interactions provide important context to our understanding of the state of the genome. One question is whether specific transcription factor interactions give rise to genome organization. We introduce spatzie, an R package and a website that implements statistical tests for significant transcription factor motif cooperativity between enhancer–promoter interactions. We conducted controlled experiments under realistic simulated data from ChIP-seq to confirm spatzie is capable of discovering co-enriched motif interactions even in noisy conditions. We then use spatzie to investigate cell type specific transcription factor cooperativity within recent human ChIA-PET enhancer–promoter interaction data. The method is available online at https://spatzie.mit.edu.
The low-resolution structural models of hepatitis C virus RNA subdomain 5BSL3.2 and its distal complex with domain 3′X point to conserved regulatory mechanisms within the Flaviviridae family
Authors: Castillo-Martínez Jesús , Fan Lixin , Szewczyk Mateusz P , Wang Yun-Xing , Gallego José 
Published: January 2022

Abstract
Subdomain 5BSL3.2 of hepatitis C virus RNA lies at the core of a network of distal RNA–RNA contacts that connect the 5′ and 3′ regions of the viral genome and regulate the translation and replication stages of the viral cycle. Using small-angle X-ray scattering and NMR spectroscopy experiments, we have determined at low resolution the structural models of this subdomain and its distal complex with domain 3′X, located at the 3′-terminus of the viral RNA chain. 5BSL3.2 adopts a characteristic ‘L’ shape in solution, whereas the 5BSL3.2–3′X distal complex forms a highly unusual ‘Y’-shaped kissing junction that blocks the dimer linkage sequence of domain 3′X and promotes translation. The structure of this complex may impede an effective association of the viral polymerase with 5BSL3.2 and 3′X to start negative-strand RNA synthesis, contributing to explain the likely mechanism used by these sequences to regulate viral replication and translation. In addition, sequence and shape features of 5BSL3.2 are present in functional RNA motifs of flaviviruses, suggesting conserved regulatory processes within the Flaviviridae family.
Brexit and Japanese foreign direct investment in the UK: a sectoral analysis
Authors: Cieślik Andrzej , Ryan Michael 
Published: January 2022

AbstractPolitical and economic stability significantly affect the economic performance of a country and its ability to attract inward investment. This article investigates Brexit-associated uncertainty and Japanese foreign direct investment (FDI) inflows into the UK. In contrast to most previous studies that use pre-vote behaviour to model post-vote outcomes, we include both pre- and post-announcement and post-vote data on Japanese firm-level FDI activity into Europe. In a Knowledge-Capital framework, we examine the annual count of newly established Japanese foreign affiliates into 80 countries between the years 1995 and 2019. Results from a negative binomial model reveal a statistically significant relationship between the Brexit announcement and decreased FDI in the UK. Our results identify significant sectoral heterogeneity, indicating the difficulty in making broad claims as to Brexit’s effect on the British economy’s future.
Real-world Impact of Age at Diagnosis on Treatment Patterns and Survival Outcomes of Patients with Metastatic Pancreatic Ductal Adenocarcinoma
Authors: Elias Rawad , Cockrum Paul , Surinach Andy , Wang Shu , Chul Chu Bong , Shahrokni Armin 
Published: January 2022

Abstract

Background
Sixty-eight percent of patients with pancreatic ductal adenocarcinoma (PDAC) are 65 years and older. Older adults are under-represented in clinical trials and their care is complicated with multiple age-related conditions. Research suggests that older patients can experience meaningful responses to treatment for PDAC. The objective of this study was to evaluate the characteristics, rate of treatment, and survival outcomes of patients with metastatic PDAC (mPDAC) based on age at diagnosis.

Materials and Methods
Data were extracted for patients diagnosed with mPDAC between January 1, 2015, and March 31, 2020, from the Flatiron Health database. Patients were stratified into 3 age groups: &lt;70 years old, 70-79 years, and ≥80 years. The proportion of patients who received first-line therapy, the types of regimens received in the metastatic setting, overall survival (OS) from the start of treatment were evaluated.

Results
Of the 8382 patients included, 71.3% (n = 5973) received treatment. Among patients who received treatment 55.5% (n = 3313) were aged &lt;70 years at diagnosis, 33.0% (n = 1972) were 70-79 years, and 11.5% (n = 688) were ≥80 years. Patients ≥80 years of age were more likely to receive gemcitabine monotherapy and less likely to receive FOLFIRINOX. Among first-line treated patients, median OS significantly decreased with age. However, when comparing patients treated with the same first-line regimen, no significant differences in median OS were observed by age.

Conclusions
This study highlights that older adults with mPDAC can benefit substantially by receiving appropriate levels of treatment.
Shaping successful mega-project investments
Authors: Coyle Diane 
Published: January 2022

Abstract
Many countries are proposing major public infrastructure investment, addressing the net zero imperative and need to recover from the pandemic. Yet the investments will deliver on these policy goals only if appraisals take account of strategic complementarities in determining the future path of the economy, including technological choices. Cost–benefit analysis as currently applied is unable to do this, even when incorporating wider economic benefits. Furthermore, in purporting to be a technical tool, it fails to acknowledge the inevitable political judgements and distributional consequences involved in selecting projects. There is a need for an approach to appraisal that identifies when major projects have transformational potential, and an approach to policy that ensures complementary investments occur, by tackling coordination failures either among different policy actors or between private- and public-sector activities.
Rapid stomatal closure contributes to higher water use efficiency in major C4 compared to C3 Poaceae crops
Authors: Ozeki Kengo , Miyazawa Yoshiyuki , Sugiura Daisuke 
Published: January 2022

Abstract
Understanding water use characteristics of C3 and C4 crops is important for food security under climate change. Here, we aimed to clarify how stomatal dynamics and water use efficiency (WUE) differ in fluctuating environments in major C3 and C4 crops. Under high and low nitrogen conditions, we evaluated stomatal morphology and kinetics of stomatal conductance (gs) at leaf and whole-plant levels in controlled fluctuating light environments in four C3 and five C4 Poaceae species. We developed a dynamic photosynthesis model, which incorporates C3 and C4 photosynthesis models that consider stomatal dynamics, to evaluate the contribution of rapid stomatal opening and closing to photosynthesis and WUE. C4 crops showed more rapid stomatal opening and closure than C3 crops, which could be explained by smaller stomatal size and higher stomatal density in plants grown at high nitrogen conditions. Our model analysis indicated that accelerating the speed of stomatal closure in C3 crops to the level of C4 crops could enhance WUE up to 16% by reducing unnecessary water loss during low light periods, whereas accelerating stomatal opening only minimally enhanced photosynthesis. The present results suggest that accelerating the speed of stomatal closure in major C3 crops to the level of major C4 crops is a potential breeding target for the realization of water-saving agriculture.
Selection of treatment regimens based on shared decision-making in patients with rheumatoid arthritis on remission in the FREE-J study
Authors: Tanaka Yoshiya , Yamaguchi Ayako , Miyamoto Toshiaki , Tanimura Kazuhide , Iwai Hideyuki , Kaneko Yuko , Takeuchi Tsutomu , Amano Koichi , Iwamoto Naoki , Kawakami Atsushi , Murakami Miho , Nishimoto Norihiro , Atsumi Tatsuya , Sumida Takayuki , Ohmura Koichiro , Mimori Tsuneyo , Yamanaka Hisashi , Fujio Keishi , Fujino Yoshihisa , Saito Kazuyoshi , Nakano Kazuhisa , Hirata Shintaro , Nakayamada Shingo 
Published: January 2022

AbstractObjectiveTo compare the outcome of various treatment de-escalation regimens in patients with RA who achieved sustained remission.MethodsAt period 1, 436 RA patients who were treated with MTX and bDMARDs and had maintained DAS28(ESR) at &lt;2.6 were divided into five groups based on shared patient/physician decision-making; continuation, dose reduction and discontinuation of MTX or bDMARDs. At end of year 1, patients who achieved DAS28(ESR) &lt;3.2 were allowed to enrol in period 2 for treatment using the de-escalation regimens for another year. The primary and secondary endpoints were the proportion of patients with DAS28(ESR) &lt;2.6 at year 1 and 2, respectively.ResultsBased on shared decision-making, 81.4% elected de-escalation of treatment and 48.4% selected de-escalation of MTX. At end of period 1, similar proportions of patients maintained DAS28(ESR) &lt;2.6 (continuation, 85.2%; MTX dose reduction, 79.0%; MTX-discontinuation, 80.0%; bDMARD dose reduction, 73.9%), although the rate was significantly different between the continuation and bDMARD-discontinuation. At end of period 2, similar proportions of patients of the MTX groups maintained DAS28(ESR) &lt;2.6 (continuation or de-escalation), but the rates were significantly lower in the bDMARD-discontinuation group. However, half of the latter group satisfactorily discontinued bDMARDs. Adverse events were numerically lower in MTX and bDMARD-de-escalation groups during period 1 and 2, compared with the continuation group.ConclusionsAfter achieving sustained remission by combination treatment of MTX/bDMARDs, disease control was achieved comparably by continuation, dose reduction or discontinuation of MTX and dose reduction of bDMARDs at end of year 1. Subsequent de-escalation of MTX had no impacts on disease control but decreased adverse events in year 2.
Effect of drinker type on water disappearance of nursery pigs
Authors: Vande Pol Katherine D , Grohmann Nicholas S , Weber Thomas E , Ritter Matthew J , Ellis Michael 
Published: January 2022

Abstract
This study was conducted to evaluate the water disappearance of nursery pigs (from weaning to 6 wk post-weaning; 6.4 ± 1.07 to 22.0 ± 3.39 kg live body weight) using a randomized complete block design to compare two Drinker Type treatments: Nipple vs. Cup. A total of 336 pigs housed in 16 pens with 21 pigs per pen in 2 rooms (8 pens per room) were used. Pens had fully-slatted concrete floors; floor space was 0.32 m2/pig and there was one feeder and one drinker per pen. Pigs were fed corn-soybean–based diets formulated to meet or exceed nutrient requirements. Pigs and feeders were weighed at the start and end of the study. Water disappearance was measured using a water-flow meter fitted to the water pipeline supplying the drinker in each pen. For the overall study period, Drinker Type did not affect (P &gt; 0.05) growth performance; however, average daily water disappearance was greater (P &lt; 0.05) for Nipple than Cup drinkers (2.74 and 2.25 liters/d, respectively; SEM = 0.139). Water to feed disappearance ratio was greater (P &lt; 0.05) for the Nipple than the Cup treatment (5.23 vs. 4.22 liters:kg, respectively; SEM = 0.263). These results suggest that water disappearance from nipple drinkers was greater than for cup drinkers. The lack of an effect of Drinker Type treatment on pig growth performance suggests that the treatment difference for water disappearance was most likely due to greater water wastage for the nipple drinkers rather than any effect on water intake per se.
Gut-Selective Design of Orally Administered Izencitinib (TD-1473) Limits Systemic Exposure and Effects of Janus Kinase Inhibition in Nonclinical Species
Authors: Hardwick Rhiannon N , Brassil Patrick , Badagnani Ilaria , Perkins Kimberly , Obedencio Glenmar P , Kim Andrea S , Conner Michael W , Bourdet David L , Harstad Eric B 
Published: January 2022

Abstract
Izencitinib (TD-1473), an oral, gut-selective pan-Janus kinase (JAK) inhibitor under investigation for treatment of inflammatory bowel diseases, was designed for optimal efficacy in the gastrointestinal tract while minimizing systemic exposures and JAK-related safety findings. The nonclinical safety of izencitinib was evaluated in rat and dog repeat-dose and rat and rabbit reproductive and developmental toxicity studies. Systemic exposures were compared with JAK inhibitory potency to determine effects at or above pharmacologic plasma concentrations (≥1× plasma average plasma concentration [Cave]:JAK 50% inhibitory concentration [IC50] ratio). In rats and dogs, 1000 and 30 mg/kg/day izencitinib, respectively, produced minimal systemic findings (ie, red/white cell changes) and low systemic concentrations (approximately 1× plasma Cave:JAK IC50 ratio) with an 8× nonclinical:clinical systemic area under the curve (AUC) margin compared with exposures at the highest clinically tested dose (300 mg, quaque die, once daily, phase 1 study in healthy volunteers). In dogs, it was possible to attain sufficient systemic exposures to result in immunosuppression characteristic of systemic JAK inhibition, but at high AUC margins (43×) compared with systemic exposures observed at the highest tested dose in humans. No adverse findings were observed in the gastrointestinal tract or systemic tissues. Izencitinib did not affect male or female fertility. Izencitinib did not affect embryonic development in rats and rabbits as commonly reported with systemic JAK inhibition, consistent with low maternal systemic concentrations (2–6× plasma Cave:JAK IC50 ratio, 10–33× nonclinical:clinical AUC margin) and negligible fetal exposures. In conclusion, the izencitinib gut-selective approach resulted in minimal systemic findings in nonclinical species at pharmacologic, clinically relevant systemic exposures, highlighting the impact of organ-selectivity in reducing systemic safety findings.