bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mail, Rail, and Legwork: State and Nation Building through Postal Service in France and Great Britain, 1830–1914
Authors: Schwartz Robert M. 
Published: June 2021

AbstractA comparative spatial history using GIS, this article examines the similar and differing effects of railway expansion on the growth of postal communications in Great Britain and France from 1830 to the eve of the Great War. It argues that the modern Postal Age in Great Britain and France began in the 1830s. In Britain in 1839, the Parliament obligated private railway companies to convey the Royal Mail throughout the kingdom at reasonable rates. Thereafter, the expansion of postal services and railway networks went hand in hand. Over the years, thousands of new post offices were established and were closer to rail stations than before. As the years wore on the geography of postal communication expanded greatly and by 1914 the majority of rural districts became part of the system of regular, daily mail. In France, a country four or five times larger than England and Wales with a relatively vast rural population, the task of modernizing postal service was a greater challenge. The inauguration of a “rural service” in 1829 employed some 5,000 men as postal carriers to deliver and collect mail throughout the countryside. Thereafter, their numbers grew as new post offices were established to serve villages and small towns with mail deliveries every other day. In the 1880s, under the Third Republic, the state greatly expanded the postal service, deeming it a national mission. It was then that the growing rail network came to shape the national geography of postal service. Hence, at the turn of the century the patterns British and French postal expansions converged.
Revisiting Acetonitrile as Tracer of Biomass Burning in Anthropogenic‐Influenced Environments
Authors: Huangfu Yibo , Yuan Bin , Wang Sihang , Wu Caihong , He Xianjun , Qi Jipeng , de Gouw Joost , Warneke Carsten , Gilman Jessica B. , Wisthaler Armin , Karl Thomas , Graus Martin , Jobson Bertram T. , Shao Min 
Published: June 2021

AbstractAcetonitrile (CH3CN) has been widely employed as biomass burning tracer. However, the current application of CH3CN absolute mixing ratio as the thresholds may misidentify biomass burning due to the interference from other CH3CN sources in anthropogenic‐influenced environments. High levels of CH3CN were observed with minor biomass burning impact but still followed a similar correlation with carbon monoxide (CO), suggesting their shared source, most likely, vehicular emission. By analyzing the available literature including more than 30 worldwide field measurements, the enhancement ratios (EnRs) of CH3CN to CO for biomass burning were found as 2.01 ± 0.16 ppbv/ppmv, well distinguished from the EnRs obtained in urban measurement (0.26 ± 0.04 ppbv/ppmv). An example is given and the application of EnR to identify biomass burning is discussed. The results suggest that the correlation between CH3CN and CO and their EnRs can be used as more specific indicators for biomass burning.
Consistent Predictability of the Ocean State Ocean Model Using Information Theory and Flushing Timescales
Authors: Sane Aakash , Fox‐Kemper Baylor , Ullman David S. , Kincaid Christopher , Rothstein Lewis 
Published: June 2021

AbstractThe Ocean State Ocean Model (OSOM) is an application of the Regional Ocean Modeling System spanning the Rhode Island waterways, including Narragansett Bay, Mt. Hope Bay, larger rivers, and the Block Island Shelf circulation from Long Island to Nantucket. This study discusses the physical aspects of the estuary (Narragansett and Mount Hope Bays and larger rivers) to evaluate physical circulation predictability. This estimate is intended to help decide if a forecast and prediction system is warranted, to prepare for coupling with biogeochemistry and fisheries models with widely disparate timescales, and to find the spin‐up time needed to establish the climatological circulation of the region. Perturbed initial condition ensemble simulations are combined with metrics from information theory to quantify the predictability of the OSOM forecast system–i.e., how long anomalies from different initial conditions persist. The predictability timescale in this model agrees with readily estimable timescales such as the freshwater flushing timescale evaluated using the total exchange flow (TEF) framework, indicating that the estuarine dynamics rather than chaotic transport is the dominant model behavior limiting predictions. The predictability of the OSOM is ∼7–40 days, varying with parameters, region, and season.
Chinese Word Segmentation Based on Self‐Learning Model and Geological Knowledge for the Geoscience Domain
Authors: Li Wenjia , Ma Kai , Qiu Qinjun , Wu Liang , Xie Zhong , Li Sanfeng , Chen Siqiong 
Published: May 2021

AbstractChinese word segmentation (CWS) is the foundational work of geological report text mining and has an important influence on various tasks, such as named entity recognition and relation extraction. In recent years, the accuracy of the domain‐general CWS model has been limited by the domain and large scale of the training corpus, especially data on Chinese geological texts. Training these CWS models also requires much manually annotated data, which takes a large amount of time and effort. When applying these existing models/methods directly to the geoscience domain, the segmentation accuracy and performance will drop dramatically. To address this problem, we pretrain the Bidirectional Encoder Representations from Transformer (BERT), which can leverage unlabeled domain‐specific knowledge, on unlabeled Chinese geological text and then input them into a Bidirectional long short‐term memory and Conditional random field (BiLSTM‐CRF) model for extracting text features. Finally, the predicted tags are decoded by the CRF. The experimental results show that the F1 score of the proposed model reaches 96.2% on the constructed test set of geological texts. Additionally, experiments illustrate that our proposed model achieves comparable performance to that of other state‐of‐the‐art models, and the proposed cyclic self‐learning strategy can be further extended to other domains.
High Fluid‐Pressure Patches Beneath the Décollement: A Potential Source of Slow Earthquakes in the Nankai Trough off Cape Muroto
Authors: Hirose T. , Hamada Y. , Tanikawa W. , Kamiya N. , Yamamoto Y. , Tsuji T. , Kinoshita M. , Heuer V. B. , Inagaki F. , Morono Y. , Kubo Y. 
Published: May 2021

AbstractPore pressure plays a key role in the generation of earthquakes in subduction zones. However, quantitative constraints for its determination are quite limited. Here, we estimate the subsurface pore pressure by analyzing the transient upwelling flow of drilling mud from borehole C0023A of the International Ocean Discovery Program (IODP) Expedition 370, in the Nankai Trough off Cape Muroto. This upward flow provided the first direct evidence of an overpressured aquifer in the underthrust sediments off Cape Muroto. To estimate the pre‐drilling pore pressure in the overpressured aquifer around a depth of 950–1,050 m below sea floor, we examined the measured porosities of core samples retrieved from nearby IODP wells; we then proceeded to explain the observed time evolution of the flow rate of the upwelling flow by modeling various sized aquifers through solving a radial diffusion equation. It was observed that for a permeability of 10−13 m2, the aquifer possessed an initial excess pore pressure of ∼5–10 MPa above the hydrostatic pressure, with a lateral dimension of several hundred meters and thickness of several tens of meters. The overpressure estimates from the porosity‐depth profile at Site C0023 differ from those at other drill sites in the region, suggesting the possible existence of multiple overpressured aquifers with a patchy distribution in the underthrust sediments of the Nankai Trough. As pore pressure is relevant in maintaining fault stability, the overpressured aquifers may be the source of slow earthquakes that have been observed around the drilling site.
Necroptosis molecular mechanisms: Recent findings regarding novel necroptosis regulators
Authors: Seo Jinho , Nam Young Woo , Kim Seongmi , Oh Doo-Byoung , Song Jaewhan 
Published: June 2021

AbstractNecroptosis is a form of programmed necrosis that is mediated by various cytokines and pattern recognition receptors (PRRs). Cells dying by necroptosis show necrotic phenotypes, including swelling and membrane rupture, and release damage-associated molecular patterns (DAMPs), inflammatory cytokines, and chemokines, thereby mediating extreme inflammatory responses. Studies on gene knockout or necroptosis-specific inhibitor treatment in animal models have provided extensive evidence regarding the important roles of necroptosis in inflammatory diseases. The necroptosis signaling pathway is primarily modulated by activation of receptor-interacting protein kinase 3 (RIPK3), which phosphorylates mixed-lineage kinase domain-like protein (MLKL), mediating MLKL oligomerization. In the necroptosis process, these proteins are fine-tuned by posttranslational regulation via phosphorylation, ubiquitination, glycosylation, and protein–protein interactions. Herein, we review recent findings on the molecular regulatory mechanisms of necroptosis.
STAT3 activation in large granular lymphocyte leukemia is associated with cytokine signaling and DNA hypermethylation
Authors: Kim Daehong , Park Giljun , Huuhtanen Jani , Ghimire Bishwa , Rajala Hanna , Moriggl Richard , Chan Wing C. , Kankainen Matti , Myllymäki Mikko , Mustjoki Satu 
Published: June 2021

AbstractLarge granular lymphocyte leukemia (LGLL) is characterized by somatic gain-of-function STAT3 mutations. However, the functional effects of STAT3 mutations on primary LGLL cells have not been studied in detail. In this study, we show that CD8+ T cells isolated from STAT3 mutated LGLL patients have high protein levels of epigenetic regulators, such as DNMT1, and are characterized by global hypermethylation. Correspondingly, treatment of healthy CD8+ T cells with IL-6, IL-15, and/or MCP-1 cytokines resulted in STAT3 activation, increased DNMT1, EZH2, c-MYC, l-MYC, MAX, and NFκB levels, increased DNA methylation, and increased oxidative stress. Similar results were discovered in KAI3 NK cells overexpressing gain-of-function STAT3Y640F and STAT3G618R mutants compared to KAI3 NK cells overexpressing STAT3WT. Our results also confirm that STAT3 forms a direct complex with DNMT1, EZH2, and HDAC1. In STAT3 mutated LGLL cells, DNA methyltransferase (DNMT) inhibitor azacitidine abrogated the activation of STAT3 via restored SHP1 expression. In conclusion, STAT3 mutations cause DNA hypermethylation resulting in sensitivity to DNMT inhibitors, which could be considered as a novel treatment option for LGLL patients with resistance to standard treatments.
Lithium increases mitochondrial respiration in iPSC-derived neural precursor cells from lithium responders
Authors: Osete Jordi Requena , Akkouh Ibrahim A. , de Assis Denis Reis , Szabo Attila , Frei Evgeniia , Hughes Timothy , Smeland Olav B. , Steen Nils Eiel , Andreassen Ole A. , Djurovic Srdjan 
Published: June 2021

AbstractLithium (Li), valproate (VPA) and lamotrigine (LTG) are commonly used to treat bipolar disorder (BD). While their clinical efficacy is well established, the mechanisms of action at the molecular level are still incompletely understood. Here we investigated the molecular effects of Li, LTG and VPA treatment in induced pluripotent stem cell (iPSC)-derived neural precursor cells (NPCs) generated from 3 healthy controls (CTRL), 3 affective disorder Li responsive patients (Li-R) and 3 Li non-treated patients (Li-N) after 6 h and 1 week of exposure. Differential expression (DE) analysis after 6 h of treatment revealed a transcriptional signature that was associated with all three drugs and most significantly enriched for ribosome and oxidative phosphorylation (OXPHOS) pathways. In addition to the shared DE genes, we found that Li exposure was associated with 554 genes uniquely regulated in Li-R NPCs and enriched for spliceosome, OXPHOS and thermogenesis pathways. In-depth analysis of the treatment-associated transcripts uncovered a significant decrease in intron retention rate, suggesting that the beneficial influence of these drugs might partly be related to splicing. We examined the mitochondrial respiratory function of the NPCs by exploring the drugs’ effects on oxygen consumption rate (OCR) and glycolytic rate (ECAR). Li improved OCR levels only in Li-R NPCs by enhancing maximal respiration and reserve capacity, while VPA enhanced maximal respiration and reserve capacity in Li-N NPCs. Overall, our findings further support the involvement of mitochondrial functions in the molecular mechanisms of mood stabilizers and suggest novel mechanisms related to the spliceosome, which warrant further investigation.
A mosaic PIK3CA variant in a young adult with diffuse gastric cancer: case report
Authors: te Paske Iris B. A. W. , Garcia-Pelaez José , Sommer Anna K. , Matalonga Leslie , Starzynska Teresa , Jakubowska Anna ,   Solve-RD-GENTURIS group,, Valle Laura , Capella Gabriel , Aretz Stefan , Holinski-Feder Elke , Steinke-Lange Verena , Laner Andreas , Schröck Evelin , Rump Andreas , Ligtenberg Marjolijn , Hoischen Alexander , Geverink Nicoline , Evans D. Gareth , Tischkowitz Marc , Laurie Steven , van der Post Rachel S. , Lubinski Jan , Oliveira Carla , Hoogerbrugge Nicoline , de Voer Richarda M. 
Published: June 2021

AbstractHereditary diffuse gastric cancer (HDGC) is associated with germline deleterious variants in CDH1 and CTNNA1. The majority of HDGC-suspected patients are still genetically unresolved, raising the need for identification of novel HDGC predisposing genes. Under the collaborative environment of the SOLVE-RD consortium, re-analysis of whole-exome sequencing data from unresolved gastric cancer cases (n = 83) identified a mosaic missense variant in PIK3CA in a 25-year-old female with diffuse gastric cancer (DGC) without familial history for cancer. The variant, c.3140A>G p.(His1047Arg), a known cancer-related somatic hotspot, was present at a low variant allele frequency (18%) in leukocyte-derived DNA. Somatic variants in PIK3CA are usually associated with overgrowth, a phenotype that was not observed in this patient. This report highlights mosaicism as a potential, and understudied, mechanism in the etiology of DGC.
Sex-biased genes and metabolites explain morphologically sexual dimorphism and reproductive costs in Salix paraplesia catkins
Authors: Cai Zeyu , Yang Congcong , Liao Jun , Song Haifeng , Zhang Sheng 
Published: June 2021

AbstractDioecious species evolved from species with monomorphic sex systems in order to achieve overall fitness gains by separating male and female functions. As reproductive organs, unisexual flowers have different reproductive roles and exhibit conspicuous sexual dimorphism. To date, little is known about the temporal variations in and molecular mechanisms underlying the morphology and reproductive costs of dioecious flowers. We investigated male and female flowers ofSalix paraplesiain three flowering stages before pollination (the early, blooming and late stages) via transcriptional sequencing as well as metabolite content and phenotypic analysis. We found that a large number of sex-biased genes, rather than sex-limited genes, were responsible for sexual dimorphism inS. paraplesiaflowers and that the variation in gene expression in male flowers intensified this situation throughout flower development. The temporal dynamics of sex-biased genes derived from changes in reproductive function during the different flowering stages. Sexually differentiated metabolites related to respiration and flavonoid biosynthesis exhibited the same bias directions as the sex-biased genes. These sex-biased genes were involved mainly in signal transduction, photosynthesis, respiration, cell proliferation, phytochrome biosynthesis, and phenol metabolism; therefore, they resulted in more biomass accumulation and higher energy consumption in male catkins. Our results indicated that sex-biased gene expression inS. paraplesiaflowers is associated with different reproductive investments in unisexual flowers; male flowers require a greater reproductive investment to meet their higher biomass accumulation and energy consumption needs.
Advances and perspectives in discovery and functional analysis of small secreted proteins in plants
Authors: Hu Xiao-Li , Lu Haiwei , Hassan Md Mahmudul , Zhang Jin , Yuan Guoliang , Abraham Paul E. , Shrestha Him K. , Villalobos Solis Manuel I. , Chen Jin-Gui , Tschaplinski Timothy J. , Doktycz Mitchel J. , Tuskan Gerald A. , Cheng Zong-Ming , Yang Xiaohan 
Published: June 2021

AbstractSmall secreted proteins (SSPs) are less than 250 amino acids in length and are actively transported out of cells through conventional protein secretion pathways or unconventional protein secretion pathways. In plants, SSPs have been found to play important roles in various processes, including plant growth and development, plant response to abiotic and biotic stresses, and beneficial plant–microbe interactions. Over the past 10 years, substantial progress has been made in the identification and functional characterization of SSPs in several plant species relevant to agriculture, bioenergy, and horticulture. Yet, there are potentially a lot of SSPs that have not been discovered in plant genomes, which is largely due to limitations of existing computational algorithms. Recent advances in genomics, transcriptomics, and proteomics research, as well as the development of new computational algorithms based on machine learning, provide unprecedented capabilities for genome-wide discovery of novel SSPs in plants. In this review, we summarize known SSPs and their functions in various plant species. Then we provide an update on the computational and experimental approaches that can be used to discover new SSPs. Finally, we discuss strategies for elucidating the biological functions of SSPs in plants.
EGFR-HIF1α signaling positively regulates the differentiation of IL-9 producing T helper cells
Authors: Roy Suyasha , Rizvi Zaigham Abbas , Clarke Alexander J. , Macdonald Felicity , Pandey Abhaydeep , Zaiss Dietmar Martin Werner , Simon Anna Kathrina , Awasthi Amit 
Published: June 2021

AbstractInterleukin 9 (IL-9)-producing helper T (Th9) cells are essential for inducing anti-tumor immunity and inflammation in allergic and autoimmune diseases. Although transcription factors that are essential for Th9 cell differentiation have been identified, other signaling pathways that are required for their generation and functions are yet to be explored. Here, we identify that Epidermal Growth Factor Receptor (EGFR) is essential for IL-9 induction in helper T (Th) cells. Moreover, amphiregulin (Areg), an EGFR ligand, is critical for the amplification of Th9 cells induced by TGF-β1 and IL-4. Furthermore, our data show that Areg-EGFR signaling induces HIF1α, which binds and transactivates IL-9 and NOS2 promoters in Th9 cells. Loss of EGFR or HIF1α abrogates Th9 cell differentiation and suppresses their anti-tumor functions. Moreover, in line with its reliance on HIF1α expression, metabolomics profiling of Th9 cells revealed that Succinate, a TCA cycle metabolite, promotes Th9 cell differentiation and Th9 cell-mediated tumor regression.
Zinc drives vasorelaxation by acting in sensory nerves, endothelium and smooth muscle
Authors: Betrie Ashenafi H. , Brock James A. , Harraz Osama F. , Bush Ashley I. , He Guo-Wei , Nelson Mark T. , Angus James A. , Wright Christine E. , Ayton Scott 
Published: June 2021

AbstractZinc, an abundant transition metal, serves as a signalling molecule in several biological systems. Zinc transporters are genetically associated with cardiovascular diseases but the function of zinc in vascular tone regulation is unknown. We found that elevating cytoplasmic zinc using ionophores relaxed rat and human isolated blood vessels and caused hyperpolarization of smooth muscle membrane. Furthermore, zinc ionophores lowered blood pressure in anaesthetized rats and increased blood flow without affecting heart rate. Conversely, intracellular zinc chelation induced contraction of selected vessels from rats and humans and depolarized vascular smooth muscle membrane potential. We demonstrate three mechanisms for zinc-induced vasorelaxation: (1) activation of transient receptor potential ankyrin 1 to increase calcitonin gene-related peptide signalling from perivascular sensory nerves; (2) enhancement of cyclooxygenase-sensitive vasodilatory prostanoid signalling in the endothelium; and (3) inhibition of voltage-gated calcium channels in the smooth muscle. These data introduce zinc as a new target for vascular therapeutics.
Flavin-dependent halogenases catalyze enantioselective olefin halocyclization
Authors: Mondal Dibyendu , Fisher Brian F. , Jiang Yuhua , Lewis Jared C. 
Published: June 2021

AbstractHalocyclization of alkenes is a powerful bond-forming tool in synthetic organic chemistry and a key step in natural product biosynthesis, but catalyzing halocyclization with high enantioselectivity remains a challenging task. Identifying suitable enzymes that catalyze enantioselective halocyclization of simple olefins would therefore have significant synthetic value. Flavin-dependent halogenases (FDHs) catalyze halogenation of arene and enol(ate) substrates. Herein, we reveal that FDHs engineered to catalyze site-selective aromatic halogenation also catalyze non-native bromolactonization of olefins with high enantioselectivity and near-native catalytic proficiency. Highly selective halocyclization is achieved by characterizing and mitigating the release of HOBr from the FDH active site using a combination of reaction optimization and protein engineering. The structural origins of improvements imparted by mutations responsible for the emergence of halocyclase activity are discussed. This expansion of FDH catalytic activity presages the development of a wide range of biocatalytic halogenation reactions.
Copper-catalyzed carbo-difluoromethylation of alkenes via radical relay
Authors: Cai Aijie , Yan Wenhao , Zeng Xiaojun , Zacate Samson B. , Chao Tzu-Hsuan , Krause Jeanette A. , Cheng Mu-Jeng , Liu Wei 
Published: June 2021

AbstractOrganic molecules that contain alkyl-difluoromethyl moieties have received increased attention in medicinal chemistry, but their synthesis in a modular and late-stage fashion remains challenging. We report herein an efficient copper-catalyzed radical relay approach for the carbo-difluoromethylation of alkenes. This approach simultaneously introduces CF2H groups along with complex alkyl or aryl groups into alkenes with regioselectivity opposite to traditional CF2H radical addition. We demonstrate a broad substrate scope and a wide functional group compatibility. This scalable protocol is applied to the late-stage functionalization of complex molecules and the synthesis of CF2H analogues of bioactive molecules. Mechanistic studies and density functional theory calculations suggest a unique ligand effect on the reactivity of the Cu-CF2H species.