bluuebunny/crossref_metadata_2025_split huggingface dataset:
Blocking EP4 down-regulates tumor metabolism and synergizes with anti-PD-1 therapy to activate natural killer cells in a lung adenocarcinoma model
Authors: Tokumasu Miho , Nishida Mikako , Kawaguchi Takamasa , Kudo Ikuru , Kotani Tohru , Takeda Kazuhiko , Yoshida Takao , Udono Heiichiro 
Published: February 2022

Abstract
Prostaglandin E2 (PGE2), a product of the cyclooxygenase (COX) pathway, is produced by tumors and surrounding stromal cells. It stimulates tumor progression, promotes angiogenesis and suppresses the anti-tumor response. Pharmacological inhibition of PGE2 synthesis has been shown to suppress tumor initiation and growth in vivo. In the current study, we demonstrated that the growth of the Ptgs2-deficient 3LL lung adenocarcinoma cell line was down-regulated in vivo through natural killer (NK) cell activation and a reduction in the population of polymorphonuclear leukocyte-myeloid-derived suppressor cells (PMN-MDSCs) and tumor-associated macrophages (TAMs). On the basis of these results, the therapeutic effect of ONO-AE3-208 (EP4i), an inhibitor of EP4 (a PGE2 receptor), combined with anti-PD-1 antibody was evaluated. EP4i, but not anti-PD-1 antibody, decreased tumor metabolism including glycolysis, fatty acid oxidation and oxidative phosphorylation. EP4i induced IFNγ production from only NK cells (not from T cells) and a shift from M2-like to M1-like macrophages in TAMs. These effects were further enhanced by anti-PD-1 antibody treatment. Although CD8 T-cell infiltration was increased, IFNγ production was not significantly altered, even with combination therapy. Tumor hypoxia was ameliorated by either EP4i or anti-PD-1 antibody treatment, which was further affected by the combination. Normalization of tumor vessels was significant only for the combination therapy. The results indicated a novel effect of EP4i for the metabolic reprogramming of tumors and revealed unique features of EP4i that can synergize with anti-PD-1 antibody to promote IFNγ production by NK cells, polarize TAMs into the M1 phenotype, and reduce hypoxia through normalization of the tumor vasculature.
CEBPB is required for NRF2-mediated drug resistance in NRF2-activated non-small cell lung cancer cells
Authors: Okazaki Keito , Anzawa Hayato , Katsuoka Fumiki , Kinoshita Kengo , Sekine Hiroki , Motohashi Hozumi 
Published: February 2022

Abstract
NRF2 is a transcription activator that plays a key role in cytoprotection against oxidative stress. Although increased NRF2 activity is principally beneficial for our health, NRF2 activation in cancer cells is detrimental, as it drives their malignant progression. We previously found that CCAAT/enhancer-binding protein B (CEBPB) cooperates with NRF2 in NRF2-activated lung cancer and enhances tumour-initiating activity by promoting NOTCH3 expression. However, the general contribution of CEBPB in lung cancer is rather controversial, probably because the role of CEBPB depends on cooperating transcription factors in each cellular context. To understand how NRF2 shapes the function of CEBPB in NRF2-activated lung cancers and its biological consequence, we comprehensively explored NRF2-CEBPB–coregulated genes and found that genes involved in drug metabolism and detoxification were characteristically enriched. Indeed, CEBPB and NRF2 cooperatively contribute to the drug resistance. We also found that CEBPB is directly regulated by NRF2, which is likely to be advantageous for the coexpression and cooperative function of NRF2 and CEBPB. These results suggest that drug resistance of NRF2-activated lung cancers is achieved by the cooperative function of NRF2 and CEBPB.
Sexual dimorphism and rare intersex individuals in Cretaceous (Maastrichtian)DakoticancerRathbun, 1917 (Decapoda: Brachyura: Dakoticancroida)
Authors: Jones Annmarie R , Schweitzer Carrie E , Feldmann Rodney M 
Published: February 2022

AbstractSeveral hundred specimens of the crab Dakoticancer overanusRathbun, 1917 represent a normal size-distributed adult population, with a skewed sex ratio of 21% females to 79% males. Sexual dimorphism is clearly developed in the shape of the sternum and pleon as well as overall carapace size. The Dakoticancer Assemblage displays a variety of intersex conditions, including gonopores (vulvae) on the coxa of the fourth pereiopod and female spermatheca associated with male sternal morphology. Gonopores on the coxae of the fourth pereiopods have been reported for shrimps, clawed lobsters, and palinurid lobsters, but not for brachyurans. Understanding the occurrence of intersex specimens within an extinct species of an extinct section is extremely difficult, as there seem to be no modern analogs concerning gonopores on the fourth pereiopod in Brachyura. The low percentage of affected individuals, about 1%, suggests developmental or genetic conditions were most likely responsible for the intersex individuals. The absence of such individuals in another large collection of a species of the same genus, of more or less the same geologic age, suggests that the factors leading to intersexuality in the Dakoticancer overanus population were endemic to that population.
Rural–Urban Disparities in Cancer Outcomes: Opportunities for Future Research
Authors: Bhatia Smita , Landier Wendy , Paskett Electra D , Peters Katherine B , Merrill Janette K , Phillips Jonathan , Osarogiagbon Raymond U 
Published: February 2022

AbstractCancer care disparities among rural populations are increasingly documented and may be worsening, likely because of the impact of rurality on access to state-of-the-art cancer prevention, diagnosis, and treatment services, as well as higher rates of risk factors such as smoking and obesity. In 2018, the American Society of Clinical Oncology undertook an initiative to understand and address factors contributing to rural cancer care disparities. A key pillar of this initiative was to identify knowledge gaps and promote the research needed to understand the magnitude of difference in outcomes in rural vs nonrural settings, the drivers of those differences, and interventions to address them. The purpose of this review is to describe continued knowledge gaps and areas of priority research to address them. We conducted a comprehensive literature review by searching the PubMed (Medline), Embase, Web of Science, and Cochrane Library databases for studies published in English between 1971 and 2021 and restricted to primary reports from populations in the United States and abstracted data to synthesize current evidence and identify continued gaps in knowledge. Our review identified continuing gaps in the literature regarding the underlying causes of rural–urban disparities in cancer outcomes. Rapid advances in cancer care will worsen existing disparities in outcomes for rural patients without directed effort to understand and address barriers to high-quality care in these areas. Research should be prioritized to address ongoing knowledge gaps about the drivers of rurality-based disparities and preventative and corrective interventions.
Slipstreaming for Public Sector Reform: How Enterprising Public Sector Leaders Navigate Institutional Inertia
Authors: Rahman Shibaab , Teicher Julian , Cox Julie Wolfram , Alam Quamrul 
Published: February 2022

Abstract
We situate public sector leaders as actors who deal with competing institutional demands, and examine how public sector leaders can facilitate reform implementation in the face of institutional inertia in a transitional setting, Bangladesh public administration. Based on 32 interviews with current and former Bangladeshi civil servants and local public administration experts supported by secondary analysis of government documents, our evidence shows that public sector leaders operating within multiple logics are agentic in contributing to reform. However, these leaders also become constrained by institutional pressures that threaten their legitimacy and may face sanctions for pursuing local changes. Although public sector leaders typically engage in resistance to reform, our evidence shows that public sector leaders can create enterprising avenues of change, adeptly exercising agency and utilizing existing institutional logics as a conduit to introducing a new institutional order. Our principal contribution is to identify slipstreaming as a means by which institutional actors negotiate institutional logics and facilitate change despite institutional inertia.
Transcriptome shock in interspecific F1 allotriploid hybrids between Brassica species
Authors: Quan Chengtao , Chen Guoting , Li Sijia , Jia Zhibo , Yu Pugang , Tu Jinxing , Shen Jinxiong , Yi Bin , Fu Tingdong , Dai Cheng , Ma Chaozhi 
Published: February 2022

Abstract
Interspecific hybridization drives the evolution of angiosperms and can be used to introduce novel alleles for important traits or to activate heterosis in crop breeding. Hybridization brings together gene expression networks from two different species, potentially causing global alterations of gene expression in the F1 plants which is called ‘transcriptome shock’. Here, we explored such a transcriptome shock in allotriploid Brassica hybrids. We generated interspecific F1 allotriploid hybrids between the allotetraploid species Brassica napus and three accessions of the diploid species Brassica rapa. RNA-seq of the F1 hybrids and the parental plants revealed that 26.34–30.89% of genes were differentially expressed between the parents. We also analyzed expression level dominance and homoeolog expression bias between the parents and the F1 hybrids. The expression-level dominance biases of the Ar, An, and Cn subgenomes was genotype and stage dependent, whereas significant homoeolog expression bias was observed among three subgenomes from different parents. Furthermore, more genes were involved in trans regulation than in cis regulation in allotriploid F1 hybrids. Our findings provide new insights into the transcriptomic responses of cross-species hybrids and hybrids showing heterosis, as well as a new method for promoting the breeding of desirable traits in polyploid Brassica species.
Selection for early shoot vigour in wheat increases root hair length but reduces epidermal cell size of roots and leaves
Authors: Hendriks Pieter-Willem , Ryan Peter R , Hands Philip , Rolland Vivien , Gurusinghe Saliya , Weston Leslie A , Rebetzke Greg J , Delhaize Emmanuel 
Published: February 2022

Abstract
Six cycles of recurrent selection for early shoot vigour in wheat resulted in significant increases in leaf width and shoot biomass. Here, in replicated controlled-environment studies, the effect of early shoot vigour on root biomass, rhizosheath size, root hair length, and cell size in the roots and leaves was examined across different cycles of selection. Increased shoot vigour was associated with greater root biomass, larger rhizosheath size, and longer root hairs. Our findings demonstrate that rhizosheath size was a reliable surrogate for root hair length in this germplasm. Examination of the root epidermis revealed that the ‘cell body’ of the trichoblasts (hair-forming cells) and the atrichoblasts (non-hair-forming cells) decreased in size as shoot vigour increased. Therefore, in higher vigour germplasm, longer root hairs emerged from smaller trichoblasts so that total trichoblast volume (root hair plus cell body) was generally similar regardless of shoot vigour. Similarly, the sizes of the four main cell types on the leaf epidermis became progressively smaller as shoot vigour increased, which also increased stomatal density. The relationship between shoot vigour and root traits is considered, and the potential contribution of below-ground root traits to performance and competitiveness of high vigour germplasm is discussed.
Modelling efficient team structures in biology
Authors: Sikimić Vlasta , Herud-Sikimić Ole 
Published: February 2022

AbstractWe used agent-based modelling to highlight the advantages and disadvantages of several management styles in biology, ranging from centralized to egalitarian ones. In egalitarian groups, all team members are connected with each other, while in centralized ones, they are only connected with the principal investigator. Our model incorporated time constraints, which negatively influenced weakly connected groups such as centralized ones. Moreover, our results show that egalitarian groups outperform others if the questions addressed are relatively simple or when the communication among agents is limited. Complex epistemic spaces are explored best by centralized groups. They outperform other team structures because the individual members can develop their own ideas with less interference of the opinions of others. The optimal ratio between time spent on experimentation and dissemination varies between different organizational structures. Furthermore, if the evidence is shared only after a relevant degree of certainty is reached, all investigated groups epistemically profit. We discovered that the introduction of seminars to the model changes the epistemic performance in favour of weakly connected teams. Finally, the abilities of the principal investigator do not seem to outperform cognitive diversity, as group performances were not strongly influenced by the increase of her abilities.
MOBSTER – VI. The crucial influence of rotation on the radio magnetospheres of hot stars
Authors: Shultz M E , Owocki S P , ud-Doula A , Biswas A , Bohlender D , Chandra P , Das B , David-Uraz A , Khalack V , Kochukhov O , Landstreet J D , Leto P , Monin D , Neiner C , Rivinius Th , Wade G A 
Published: February 2022

ABSTRACT
Numerous magnetic hot stars exhibit gyrosynchrotron radio emission. The source electrons were previously thought to be accelerated to relativistic velocities in the current sheet formed in the middle magnetosphere by the wind opening magnetic field lines. However, a lack of dependence of radio luminosity on the wind power, and a strong dependence on rotation, has recently challenged this paradigm. We have collected all radio measurements of magnetic early-type stars available in the literature. When constraints on the magnetic field and/or the rotational period are not available, we have determined these using previously unpublished spectropolarimetric and photometric data. The result is the largest sample of magnetic stars with radio observations that has yet been analysed: 131 stars with rotational and magnetic constraints, of which 50 are radio-bright. We confirm an obvious dependence of gyrosynchrotron radiation on rotation, and furthermore find that accounting for rotation neatly separates stars with and without detected radio emission. There is a close correlation between H α emission strength and radio luminosity. These factors suggest that radio emission may be explained by the same mechanism responsible for H α emission from centrifugal magnetospheres, i.e. centrifugal breakout (CBO), however, while the H α-emitting magnetosphere probes the cool plasma before breakout, radio emission is a consequence of electrons accelerated in centrifugally driven magnetic reconnection.
Jets in magnetically arrested hot accretion flows: geometry, power, and black hole spin-down
Authors: Narayan Ramesh , Chael Andrew , Chatterjee Koushik , Ricarte Angelo , Curd Brandon 
Published: February 2022

ABSTRACT
We present the results of nine simulations of radiatively inefficient magnetically arrested discs (MADs) across different values of the black hole spin parameter a*: −0.9, −0.7, −0.5, −0.3, 0, 0.3, 0.5, 0.7, and 0.9. Each simulation was run up to $t \gtrsim 100\, 000\, GM/c^3$ to ensure disc inflow equilibrium out to large radii. We find that the saturated magnetic flux level, and consequently also jet power, of MAD discs depends strongly on the black hole spin, confirming previous results. Prograde discs saturate at a much higher relative magnetic flux and have more powerful jets than their retrograde counterparts. MADs with spinning black holes naturally launch jets with generalized parabolic profiles whose widths vary as a power of distance from the black hole. For distances up to 100GM/c2, the power-law index is k ≈ 0.27–0.42. There is a strong correlation between the disc–jet geometry and the dimensionless magnetic flux, resulting in prograde systems displaying thinner equatorial accretion flows near the black hole and wider jets, compared to retrograde systems. Prograde and retrograde MADs also exhibit different trends in disc variability: accretion rate variability increases with increasing spin for a* &gt; 0 and remains almost constant for a* ≲ 0, while magnetic flux variability shows the opposite trend. Jets in the MAD state remove more angular momentum from black holes than is accreted, effectively spinning down the black hole. If powerful jets from MAD systems in Nature are persistent, this loss of angular momentum will notably reduce the black hole spin over cosmic time.
The main perturbing objects on the orbits of (616) Prometheus and (617) Pandora
Authors: Gomes-Júnior A R , Santana T , Winter O C , Sfair R 
Published: February 2022

ABSTRACT
The dynamical evolution of the Prometheus and Pandora pair of satellites is chaotic, with a short 3.3 yr Lyapunov time. It is known that the anti-alignment of the apses line of Prometheus and Pandora, which occurs every 6.2 yr, is a critical configuration that amplifies their chaotic dynamical evolution. However, the mutual interaction between Prometheus and Pandora is not enough to explain the longitudinal lags observed by the Hubble Space Telescope. The main goal of the current work is to identify the main contributors to the chaotic dynamical evolution of the Prometheus–Pandora pair beyond themselves. Therefore, in this work, we first explore the sensibility of this dynamical system to understand it numerically and then build numerical experiments to reach our goals. We identify that almost all major satellites of the Saturn system play a significant role in the evolution of Prometheus’s and Pandora’s orbits.
The interplay of supercoiling and thymine dimers in DNA
Authors: Lim Wilber , Randisi Ferdinando , Doye Jonathan P K , Louis Ard A 
Published: February 2022

Abstract
Thymine dimers are a major mutagenic photoproduct induced by UV radiation. While they have been the subject of extensive theoretical and experimental investigations, questions of how DNA supercoiling affects local defect properties, or, conversely, how the presence of such defects changes global supercoiled structure, are largely unexplored. Here, we introduce a model of thymine dimers in the oxDNA forcefield, parametrized by comparison to melting experiments and structural measurements of the thymine dimer induced bend angle. We performed extensive molecular dynamics simulations of double-stranded DNA as a function of external twist and force. Compared to undamaged DNA, the presence of a thymine dimer lowers the supercoiling densities at which plectonemes and bubbles occur. For biologically relevant supercoiling densities and forces, thymine dimers can preferentially segregate to the tips of the plectonemes, where they enhance the probability of a localized tip-bubble. This mechanism increases the probability of highly bent and denatured states at the thymine dimer site, which may facilitate repair enzyme binding. Thymine dimer-induced tip-bubbles also pin plectonemes, which may help repair enzymes to locate damage. We hypothesize that the interplay of supercoiling and local defects plays an important role for a wider set of DNA damage repair systems.
The Conditional Relationship of Psychological Needs to Ideology
Authors: Ollerenshaw Trent , Johnston Christopher D 
Published: February 2022

Abstract
We offer novel tests of hypotheses regarding the conditional relationship of psychological needs to political ideology. Using five personality measures and a large national sample, our findings affirm that political engagement plays an important moderating role in the relationship between needs for certainty and security and political identification, values, and policy preferences. We find that needs for certainty and security are strongly associated with right-wing political identification and cultural values and policy preferences, particularly among politically engaged citizens. In the economic domain, however, we find that needs for certainty and security are typically associated with left-wing values and policy preferences among politically unengaged citizens. It is only among politically engaged citizens that such needs are associated with right-wing economic values and policy preferences. Our findings confirm the importance of heterogeneity across both ideological domain and political engagement for how psychological needs translate into political ideology in the American mass public.
Do Ex-Bankers Benefit Nonfinancial Firms? Evidence from Job Transitions
Authors: Chernykh Lucy , Mityakov Sergey 
Published: February 2022

Abstract
We document the beneficial impact of human capital transfer from banks to nonfinancial firms: firms hiring ex-bankers have higher asset and employment growth and easier access to bank loans. Using a unique employee-employer-matched data set from Russia and exogenous variation in ex-bankers’ supply due to bank-branch-network restructurings, we establish the causal interpretation of these patterns. We also show that ex-bankers’ human capital consists of bank-specific and banking industry expertise (with the latter being acquired through interbank connections). Firms recognize the value of ex-bankers, who receive significant salary bonuses when a new bank loan is issued to the firm (JEL G21, G32, J24).
Received August 17, 2020; editorial decision January 5, 2022; by editor: Isil Erel. Authors have furnished an Internet Appendix, which is available on the Oxford University Press Web site next to the link to the final published paper online.
RETENTION OF ORGANICALLY BOUND DEUTERIUM IN GRASS PLANTS EXPOSED TO HEAVY WATER VAPOUR AT DIFFERENT GROWTH STAGES
Authors: Tani Takashi , Nagai Masaru 
Published: February 2022

Abstract
Potted timothy grass plants were exposed to heavy water (HDO) vapour at seven different periods during the third growth of harvestable shoots (the part 5-cm above the ground surface), and the concentration of non-exchangeable organically bound deuterium (NE-OBD) was measured in harvestable shoots, stubbles and roots at the third harvest. The excess concentration of NE-OBD was obtained as an increase in the concentration of NE-OBD against the background level. On average, this value was 1.8- to 2.6-fold higher in the harvestable shoots than in the stubble for plants exposed to HDO vapour during the period when the harvestable shoots grew faster than the stubble. Our results suggest that the separation of harvestable shoots and stubble, both of which are generally combined as one part in studies on the metabolism of organically bound tritium (OBT) in grass, could contribute to a realistic evaluation of OBT transfer from timothy to livestock.
South–south technology transfer: the case of pharmaceutical know-how in Kenya, Tanzania and Uganda
Authors: Chorev Nitsan 
Published: February 2022

AbstractTechnological capabilities that are necessary for industrial development are often learned from others. But where does technology come from and through which channels? This article identifies a change in the source of pharmaceutical know-how in East Africa, from the global north to the global south. This shift in the countries from which know-how arrived coincided with a shift in the channels through which know-how was transferred, from channels that enhance individual capabilities to channels that enhance firm capabilities. What impact do such changes have on local production? I show that these changes not only led to increased inclusion—it became possible for nascent entrepreneurs with lesser resources to enter the sector—but also to increased internal differentiation. I also suggest that foreign direct investment functions as a countervailing force that reverses locally owned industrialization. Understanding sources and channels of technology transfer, and their impact, is an important contribution to the study of technology transfer and of industrial development more generally.