bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structure‐Based Design, Synthesis, and Biological Evaluation of Imidazo[4,5‐b]Pyridin‐2‐one‐Based p38 MAP Kinase Inhibitors: Part 2
Authors: Kaieda Akira , Takahashi Masashi , Fukuda Hiromi , Okamoto Rei , Morimoto Shinji , Gotoh Masayuki , Miyazaki Takahiro , Hori Yuri , Unno Satoko , Kawamoto Tomohiro , Tanaka Toshimasa , Itono Sachiko , Takagi Terufumi , Sugimoto Hiroshi , Okada Kengo , Lane Weston , Sang Bi‐Ching , Saikatendu Kumar , Matsunaga Shinichiro , Miwatashi Seiji 
Published: November 2019

AbstractWe identified novel potent inhibitors of p38 mitogen‐activated protein (MAP) kinase using a structure‐based design strategy, beginning with lead compound, 3‐(butan‐2‐yl)‐6‐(2,4‐difluoroanilino)‐1,3‐dihydro‐2H‐imidazo[4,5‐b]pyridin‐2‐one (1). To enhance the inhibitory activity of 1 against production of tumor necrosis factor‐α (TNF‐α) in human whole blood (hWB) cell assays, we designed and synthesized hybrid compounds in which the imidazo[4,5‐b]pyridin‐2‐one core was successfully linked with the p‐methylbenzamide fragment. Among the compounds evaluated, 3‐(3‐tert‐butyl‐2‐oxo‐2,3‐dihydro‐1H‐imidazo[4,5‐b]pyridin‐6‐yl)‐4‐methyl‐N‐(1‐methyl‐1H‐pyrazol‐3‐yl)benzamide (25) exhibited potent p38 inhibition, superior suppression of TNF‐α production in hWB cells, and also significant in vivo efficacy in a rat model of collagen‐induced arthritis (CIA). In this paper, we report the discovery of potent, selective, and orally bioavailable imidazo[4,5‐b]pyridin‐2‐one‐based p38 MAP kinase inhibitors.
Rational Design of Ag‐Based Catalysts for the Electrochemical CO2 Reduction to CO: A Review
Authors: Sun Dalei , Xu Xiaomin , Qin Yanling , Jiang San Ping , Shao Zongping 
Published: November 2019

AbstractThe selective electrochemical CO2 reduction (ECR) to CO in aqueous electrolytes has gained significant interest in recent years due to its capability to mitigate the environmental issues associated with CO2 emission and to convert renewable energy such as wind and solar power into chemical energy as well as its potential to realize the commercial use of CO2. In view of the thermodynamic stability and kinetic inertness of CO2 molecules, the exploitation of active, selective, and stable catalysts for the ECR to CO is crucial to promote the reaction efficiency. Indeed, plenty of electrocatalysts for the selective ECR to CO have been explored, of which Ag is known as the most promising electrocatalyst for large‐scale ECR to CO due to several competitive advantages including high catalytic performance, low price, and rich reserves compared with other metal counterparts. To provide useful guidelines for the further development of efficient catalysts for the ECR to CO, a comprehensive summary of the recent progress of Ag‐based electrocatalysts is presented in this Review. Different modification strategies of Ag‐based electrocatalysts are highlighted, including exposure of crystal facets, tuning of morphology and size, introduction of support materials, alloying with other metals, and surface modification with functional groups. The reaction mechanisms involved in these different modification strategies of Ag‐based electrocatalysts are also discussed. Finally, the prospects for the development of next‐generation Ag‐based electrocatalysts are proposed in an effort to facilitate the industrialization of ECR to CO.
The interplay of type 2 immunity, helminth infection and the microbiota in regulating metabolism
Authors: Moyat Mati , Coakley Gillian , Harris Nicola L 
Published: November 2019

AbstractType 2 immunity has recently emerged as a critical player in metabolic status, with numerous studies investigating the role of type 2 immune cells within adipose tissue. Metabolic dysfunction is often characterised as a low‐grade or chronic inflammatory state within tissues, and type 2 immunity may facilitate a return to metabolic homeostasis. A complex network of type 2 resident cells including M2 macrophages, eosinophils and ILC2s has been identified within adipose tissue. Although the effector cells in this equilibrium have not been clearly identified, any alteration of the type 2 microenvironment resulted in an altered metabolic state. Historically, the type 2 immune response has been associated with helminth infection. The type 2 immune response drives host resistance and plays an important role in promoting tissue repair following the migration of helminth larvae through tissues. Although helminths are largely eradicated in developed countries, infection rates remain high in poor communities within the developing world. Interestingly, there is strong evidence that helminth infection is inversely correlated with autoimmune or inflammatory disorders. Recently, an increasing amount of epidemiological and field studies suggest that it could be the same for obesity and metabolic syndrome. In the current review, we summarise the literature linking type 2 immunity to improved adipose tissue function. We then discuss more recent evidence indicating that helminth infection can provide protection against metabolic syndrome. Lastly, we explore the possible contributions of altered nutrient uptake, adipose tissue function and/or the intestinal microbiota with the ability of helminths to alter metabolic status.
Neuroendocrine carcinoma diagnosis from bile duct cytological specimens: A retrospective single‐center study
Authors: Ishida Mitsuaki , Okano Kimiaki , Sandoh Kaori , Ito Hiroko , Ikeura Tsukasa , Mitsuyama Toshiyuki , Miyoshi Hideaki , Shimatani Masaaki , Takaoka Makoto , Okazaki Kazuichi , Tsuta Koji 
Published: November 2019

AbstractNeuroendocrine carcinoma (NEC) in the extrahepatic bile duct is extremely rare and clinically aggressive. Cytological examination of bile and/or bile duct brushing specimens plays an important role in the diagnosis of carcinoma of the extrahepatic bile duct, but only a few articles have described the cytological features of NEC in this area. Thus, we retrospectively analyzed the cytological features of NEC in bile and/or bile duct brushing specimens. Patients with a histopathological diagnosis of NEC who underwent bile and/or bile duct brush cytological examination were enrolled in this study. The cytological features, including the background, arrangement, and shape of the neoplastic cells, and nuclear and cytoplasmic features were reviewed. Six patients with small cell NEC were enrolled, and two of them had pancreatic tumors directly invading the bile duct wall. The cytological specimens showed small and/or large neoplastic cell clusters with occasional single cells in all cases. The neoplastic cells had a high nuclear/cytoplasmic ratio and round‐to‐oval nuclei with powdery chromatin, inconspicuous nucleoli, and scant cytoplasm. Nuclear molding was a characteristic finding in all cases. One case had an adenocarcinoma component, which was also present in the cytological specimen. Cytological examination of bile and/or bile duct brushing specimens can be useful for the diagnosis of small cell NEC. This is an extremely rare but aggressive carcinoma, and its diagnosis by identifying characteristic cytological features may facilitate early detection and treatment.
Divergent selection and drift shape the genomes of two avian sister species spanning a saline–freshwater ecotone
Authors: Walsh Jennifer , Clucas Gemma V. , MacManes Matthew D. , Thomas W. Kelley , Kovach Adrienne I. 
Published: November 2019

AbstractThe role of species divergence due to ecologically based divergent selection—or ecological speciation—in generating and maintaining biodiversity is a central question in evolutionary biology. Comparison of the genomes of phylogenetically related taxa spanning a selective habitat gradient enables discovery of divergent signatures of selection and thereby provides valuable insight into the role of divergent ecological selection in speciation. Tidal marsh ecosystems provide tractable opportunities for studying organisms' adaptations to selective pressures that underlie ecological divergence. Sharp environmental gradients across the saline–freshwater ecotone within tidal marshes present extreme adaptive challenges to terrestrial vertebrates. Here, we sequence 20 whole genomes of two avian sister species endemic to tidal marshes—the saltmarsh sparrow (Ammospiza caudacutus) and Nelson's sparrow (A. nelsoni)—to evaluate the influence of selective and demographic processes in shaping genome‐wide patterns of divergence. Genome‐wide divergence between these two recently diverged sister species was notably high (genome‐wide FST = 0.32). Against a background of high genome‐wide divergence, regions of elevated divergence were widespread throughout the genome, as opposed to focused within islands of differentiation. These patterns may be the result of genetic drift resulting from past tidal march colonization events in conjunction with divergent selection to different environments. We identified several candidate genes that exhibited elevated divergence between saltmarsh and Nelson's sparrows, including genes linked to osmotic regulation, circadian rhythm, and plumage melanism—all putative candidates linked to adaptation to tidal marsh environments. These findings provide new insights into the roles of divergent selection and genetic drift in generating and maintaining biodiversity.
Myocardial dysfunction in long‐term breast cancer survivors treated at ages 40–50 years
Authors: Jacobse Judy N. , Steggink Lars C. , Sonke Gabe S. , Schaapveld Michael , Hummel Yoran M. , Steenbruggen Tessa G. , Lefrandt Joop D. , Nuver Janine , Crijns Anne P.G. , Aleman Berthe M.P. , van der Meer Peter , Gietema Jourik A. , van Leeuwen Flora E. 
Published: November 2019

AbstractAimsAnthracyclines increase heart failure (HF) risk, but the long‐term prevalence of myocardial dysfunction in young breast cancer (BC) survivors is unknown. Early measures of left ventricular myocardial dysfunction are needed to identify BC patients at risk of symptomatic HF.Methods and resultsWithin an established cohort, we studied markers for myocardial dysfunction among 569 women, who were 5–7 years (n = 277) or 10–12 years (n = 292) after BC treatment at ages 40–50 years. Left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) were assessed by echocardiography. N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) was measured in serum. Associations between patient‐related and treatment‐related risk factors and myocardial dysfunction were evaluated using linear and logistic regression. Median ages at BC diagnosis and cardiac assessment were 46.7 and 55.5 years, respectively. Anthracycline‐treated patients (n = 313), compared to the no‐anthracycline group (n = 256), more often had decreased LVEF (10% vs. 4%), impaired GLS (34% vs. 27%) and elevated NT‐proBNP (23% vs. 8%). GLS and LVEF declined in a linear fashion with increasing cumulative anthracycline dose (GLS: +0.23 and LVEF: −0.40 per cycle of 60 mg/m2; P < 0.001) and GLS was worse for patients with left breast irradiation. The risk of NT‐proBNP >125 ng/L was highest for patients who received 241–300 mg/m2 anthracycline dose compared to the no‐anthracycline group (odds ratio: 3.30, 95% confidence interval: 1.83–5.96).ConclusionImpaired GLS and increased NT‐proBNP levels are present in a substantial proportion of young BC survivors treated with anthracyclines. Whether this will lead to future cardiac disease needs to be evaluated by longitudinal assessment.
In situ creep tests on the long‐term shear behaviors of a fault located at the dam foundation of Dagangshan hydropower station, China
Authors: Yang Wendong , Duan Kang , Zhang Qiangyong , Jiao Yuyong , Wang Shugang 
Published: November 2019

AbstractFaults in the rock mass of dam foundation are crucial in controlling dam deformation and stability. In particular, long‐term stability of dam foundation is an important factor for the safety of dam operations. The rock in the foundation of Dagangshan hydropower station is mostly granite, and there are many diabase dikes distributed in granite. Geological survey indicates that many faults exist along the interfaces between granite and diabase. Lots of diabase were metamorphosed to chlorites, which have very low strength. In order to investigate the deformation of faults in diabase dikes under long‐term loading, in situ shear creep tests were performed to estimate the creep performance of a fault. The shear creep displacement and the influence of displacement history of the specimen during multi‐level loading tests were measured and analyzed. The isochronous stress‐strain method was used to determine the long‐term strength of the fault in shear creep tests. Considering the instantaneous damage and strain softening, a new viscoelastic‐plastic softening creep model was proposed to describe the shear creep behavior of the fault. Comparisons confirmed that this creep model is capable of describing the shear creep behavior of the fault and the creep parameters were estimated accordingly using this model.
Circulation and fine‐sediment dynamics in the Amazon Macrotidal Mangrove Coast
Authors: Schettini Carlos A.F. , Asp Nils E. , Ogston Andrea S. , Gomes Vando J.C. , McLachlan Robin L. , Fernandes Marcus E.B. , Nittrouer Charles A. , Truccolo Eliane C. , Gardunho Danilo C.L. 
Published: November 2019

AbstractThe Amazon Macrotidal Mangrove Coast (AMMC) is a large (~7500 km2) contiguous mangrove fringe eastwards from the Amazon River mouth. It encompasses dozens of interconnected bays intercalated with mangrove peninsulas. Mud accumulates on the mangrove flats, whereas the bed of the bays and channels is generally sandy. In this study we investigated the circulation, sediment transport and deposition in a central site at one of these mangrove peninsulas. The study was undertaken during the dry period, when there is no influence of the Amazon River plume and minimum local freshwater inflow. Current and suspended‐sediment concentration were monitored in a feeder channel on the mangrove flat along a ~1000 m section oriented along the peninsula axis. Sediment deposition was also measured on the flat. Our results show there was a strong exchange between the neighboring bays. Channel currents were flood dominant, reaching up to >1 m s−1, with residual water and sediment transport westwards. Suspended sediment concentration (SSC) in the channel was directly related to velocity magnitude, ranging between 50 and 350 mg L−1. The flat was flooded in a way that indicated the tidal wave evolves westwards, nearly parallel to the AMMC shoreline. Currents on the flats were much slower than those in the channel and showed slight ebb dominance. However, SSC was higher during the flood than ebb, clearly indicating settling during the current deceleration and limited erosion during the following ebb–flow acceleration. The net sediment transport across the section was 60 tons westwards for the period of the experiment (~4 days). The mean deposition rate was 0.006 kg m−2 s−1 (or 1.4 kg m−2 per tide), which was higher than rates from other reported assessments in mangroves. The set of results indicate very large internal sediment reworking in the AMMC. © 2019 John Wiley & Sons, Ltd.
A modified SPH method to model the coalescence of colliding non‐Newtonian liquid droplets
Authors: Xu Xiaoyang , Tang Tingting , Yu Peng 
Published: November 2019

SummaryThis paper develops a modified smoothed particle hydrodynamics (SPH) method to model the coalescence of colliding non‐Newtonian liquid droplets. In the present SPH, a van der Waals (vdW) equation of state is particularly used to represent the gas‐to‐liquid phase transition similar to that of a real fluid. To remove the unphysical behavior of the particle clustering, also known as tensile instability, an optimized particle shifting technique is implemented in the simulations. To validate the numerical method, the formation of a Newtonian vdW droplet is first tested, and it clearly demonstrates that the tensile instability can be effectively removed. The method is then extended to simulate the head‐on binary collision of vdW liquid droplets. Both Newtonian and non‐Newtonian fluid flows are considered. The effect of Reynolds number on the coalescence process of droplets is analyzed. It is observed that the time up to the completion of the first oscillation period does not always increase as the Reynolds number increases. Results for the off‐center binary collision of non‐Newtonian vdW liquid droplets are lastly presented. All the results enrich the simulations of the droplet dynamics and deepen understandings of flow physics. Also, the present SPH is able to model the coalescence of colliding non‐Newtonian liquid droplets without tensile instability.
Sublamina‐specific organization of the blood brain barrier in the mouse olfactory nerve layer
Authors: Beiersdorfer Antonia , Wolburg Hartwig , Grawe Janine , Scheller Anja , Kirchhoff Frank , Lohr Christian 
Published: November 2019

AbstractAstrocytes constitute the main glial component of the mammalian blood brain barrier (BBB). However, in the olfactory bulb (OB), the olfactory nerve layer (ONL) is almost devoid of astrocytes, raising the question which glial cells are part of the BBB. We used mice expressing EGFP in astrocytes and tdTomato in olfactory ensheathing cells (OECs), a specialized type of glial cells in the ONL, to unequivocally identify both glial cell types and investigate their contribution to the BBB in the olfactory bulb. OECs were located exclusively in the ONL, while somata of astrocytes were located in deeper layers and extended processes in the inner sublamina of the ONL. These processes surrounded blood vessels and contained aquaporin‐4, an astrocytic protein enriched at the BBB. In the outer sublamina of the ONL, in contrast, blood vessels were surrounded by aquaporin‐4‐negative processes of OECs. Transcardial perfusion of blood vessels with lanthanum and subsequent visualization by electron microscopy showed that blood vessels enwrapped by OECs possessed intact tight junctions. In acute olfactory bulb preparations, injection of fluorescent glucose 6‐NBDG into blood vessels resulted in labeling of OECs, indicating glucose transport from the perivascular space into OECs. In addition, Ca2+ transients in OECs in the outer sublamina evoked vasoconstriction, whereas Ca2+ signaling in OECs of the inner sublamina had no effect on adjacent blood vessels. Our results demonstrate that the BBB in the inner sublamina of the ONL contains astrocytes, while in the outer ONL OECs are part of the BBB.
Bound and mobile soil water isotope ratios are affected by soil texture and mineralogy, whereas extraction method influences their measurement
Authors: Adams Rachel E. , Hyodo Ayumi , SantaMaria Toby , Wright Cynthia L. , Boutton Thomas W. , West Jason B. 
Published: November 2019

AbstractQuestions persist about interpreting isotope ratios of bound and mobile soil water pools, particularly relative to clay content and extraction conditions. Interactions between pools and resulting extracted water isotope composition are presumably related to soil texture, yet few studies have manipulated the bound pool to understand its influence on soil water processes. Using a series of drying and spiking experiments, we effectively labelled bound and mobile water pools in soils with varying clay content. Soils were first vacuum dried to remove residual water, which was then replaced with heavy isotope‐enriched water prior to oven drying and spiking with heavy isotope‐depleted water. Water was extracted via centrifugation or cryogenic vacuum distillation (at four temperatures) and analysed for oxygen and hydrogen isotope ratios via isotope ratio mass spectrometry. Water from centrifuged samples fell along a mixing line between the two added waters but was more enriched in heavy isotopes than the depleted label, demonstrating that despite oven drying, a residual pool remains and mixes with the mobile water. Soils with higher clay + silt content appeared to have a larger bound pool. Water from vacuum distillation samples have a significant temperature effect, with high temperature extractions yielding progressively more heavy isotope‐enriched values, suggesting that Rayleigh fractionation occurred at low temperatures in the vacuum line. By distinctly labelling bound and mobile soil water pools, we detected interactions between the two that were dependent on soil texture. Although neither extraction method appeared to completely extract the combined bound and mobile (total water) pool, centrifugation and high temperature cryogenic vacuum distillations were comparable for both δ2H and δ18O of soil water isotope ratios.
Characterization of complex groundwater flows in the environment of singular buildings by combining hydrogeological and non‐destructive geophysical (ground‐penetrating radar) techniques: Punta Begoña Galleries (Getxo, Spain)
Authors: Uriarte Jesus A. , Damas Mollá Laura , Sagarna Maialen , Aranburu Arantza , García Francisco , Antigüedad Iñaki , Morales Tomás 
Published: November 2019

AbstractLocating and quantifying groundwater flow in many built‐up areas are a priority with regard to its complete restoration. In this work, a hydrogeological survey of the surroundings of the Punta Begoña Galleries (Getxo, Bizkaia), built on a coastal cliff, was completed by using ground penetrating radar (GPR) testing. Thus, the preliminary characterization of soils and rocks in accessible areas of the cliff was first improved by hydrogeological information gathered from a single survey borehole, including permeability measurements by low pressure injection tests (LPTs) and continuous water level monitoring. As a complementary method, the non‐destructive GPR technique was performed during both dry and wet hydrological periods and in tandem with the injection tests, providing more complete spatial and temporal images of water flows. Specifically, GPR allows mapping of flow paths in soils and assessing the continuity of fractures in rock masses. Altogether, this complementary approach provides greater knowledge of complex underground flow dynamics in built environments, thus making it easier to make decisions for their management.