bluuebunny/crossref_metadata_2025 huggingface dataset:
Geomorphology and Paleoseismology of the Weinan Fault, Shaanxi, Central China, and the Source of the 1556 Huaxian Earthquake
Authors: Feng X. , Ma J. , Zhou Y. , England P. , Parsons B. , Rizza M. A. , Walker R. T.
Published: November 2020

The 1556 CE Huaxian earthquake resulted in an estimated 830,000 deaths and caused widespread devastation in the Weihe Basin, China. Seismic intensities from historical accounts yield, via magnitude‐intensity relations, a commonly quoted magnitude of 8¼ to 8½. The maximum recorded shaking was confined to a zone close to the Huashan and Weinan faults, which exhibit fresh scarps up to 7–8 m high. Recent palaeoseismic studies have suggested, however, that the Weinan fault has not ruptured at the surface for several thousand years. Furthermore, the 90‐km combined length of the Huashan and Weinan faults is short for an earthquake of magnitude 8¼ to 8½. We present a detailed analysis of the Weinan fault at one well‐preserved site, combining field observations and age constraints from fluvial terraces displaced by faulting, analysis of a high‐resolution digital elevation model (DEM), interpretation of the walls of a quarry that cuts through the fault zone, and from a profile of borehole cores across the fault. We find that the fault ruptured within the last ~900 years and is likely, along with the Huashan segment, to be the causative fault for the 1556 earthquake. The magnitude remains uncertain, withMw ~ 7.5 being a plausible estimate given the fault length, and no more thanMw8.0 if we use the maximum estimates of slip. These estimates are considerably smaller than magnitudes estimated from intensities, with importance in estimating the recurrence intervals between destructive earthquakes and hazard across central China.
Hydrogeochemical Evidence of Earthquake‐Induced Anomalies in Response to the 2017MW5.5 Pohang Earthquake in Korea
Authors: Kim Jaeyeon , Joun Won‐Tak , Lee Sanghoon , Kaown Dugin , Lee Kang‐Kun
Published: November 2020

Significant changes in groundwater systems were observed after the 2017Mw5.5 Pohang earthquake. Groundwater level changes cannot be explained solely by poroelastic responses to the earthquake. In this study, we analyzed hydrogeochemical data, including environmental isotopes (18O,2H,87Sr/86Sr, and222Rn) of water samples as well as time‐series data of groundwater level, temperature, and electrical conductivity. Principal component analysis (PCA) and physical modeling of pore pressure changes were also used. Some anomalies in time‐series data could be explained by the distributions of pore pressure changes based on modeling. However, the other wells, which did not have the correlation between time‐series data and modeling results, exhibited abnormal patterns in hydrogeochemical and isotope data. Stiff diagrams showed differing patterns of temporal change among groundwater wells. These diagrams and isotopic anomalies revealed possible mechanisms underlying the aftereffects of earthquakes, including saline water mixing, water‐rock interactions, deep fluid upwelling, and bedrock fracture opening. These anomalous phenomena were related to the clusters derived by PCA and depended on the distance to the epicenter, faults, and sea water. This study highlights that a single measurement is insufficient to reliably interpret groundwater responses, whereas a combined hydrogeochemical and physical interpretation may provide critical information for clarifying anomalies related to earthquakes.
Repeating Earthquakes With Remarkably Repeatable Ruptures on the San Andreas Fault at Parkfield
Authors: Abercrombie Rachel E. , Chen Xiaowei , Zhang Jiewen
Published: November 2020

We calculate rupture directivity and velocity for earthquakes in three well‐recorded repeating sequences (2001–2016) on the San Andreas Fault at Parkfield using P waves from borehole recordings and the empirical Green's function method. The individual events in each sequence all show the same directivity; the largest magnitude sequence (M ~ 2.7, 8 events) ruptures unilaterally NW (at ~0.8Vs), the second sequence (M ~ 2.3, 9 events) ruptures unilaterally SE, and the smallest magnitude sequence (M ~ 2, 11 events) is less well resolved. The highly repetitive rupture suggests that geometry or material properties might control nucleation of small locked patches. The source spectra of the M ~ 2.7 sequence exhibit no detectable temporal variation. The smaller M sequences both exhibit a decrease in high‐frequency energy following the M6 earthquake that recovers with time. This could indicate a decrease in stress drop, an increase in attenuation, or a combination of the two, followed by gradual healing.
Detection of Melt Ponds on Arctic Summer Sea Ice From ICESat‐2
Authors: Tilling R. , Kurtz N. T. , Bagnardi M. , Petty A. A. , Kwok R.
Published: November 2020

Hemisphere‐wide observations of melt ponds on sea ice are needed to understand their influence on the surface radiation budget of the Arctic Ocean and to extend the satellite sea ice thickness data record. Here we present a first assessment of NASA's Ice, Cloud, and land Elevation Satellite‐2 (ICESat‐2) over individual Arctic sea ice melt ponds with different reflective properties. We use coincident high‐resolution satellite imagery from WorldView‐2 and Sentinel‐2 over different sea ice topographies to show that smooth ponds are highly reflective and can saturate the ICESat‐2 photon detection system. Rougher ponds have a more varied backscatter signal, and in some cases both the water and underlying ice surfaces are visible in photon height distributions. Characterizing the complex photon backscatter signals of melt ponds on sea ice is a first step toward automating retrievals of pond parameters such as width, melt pond fraction and depth, and improving higher‐level ICESat‐2 sea ice height and freeboard products.
Potential and Limitations of Machine Learning for Modeling Warm‐Rain Cloud Microphysical Processes
Authors: Seifert Axel , Rasp Stephan
Published: November 2020

The use of machine learning based on neural networks for cloud microphysical parameterizations is investigated. As an example, we use the warm‐rain formation by collision‐coalescence, that is, the parameterization of autoconversion, accretion, and self‐collection of droplets in a two‐moment framework. Benchmark solutions of the kinetic collection equations are performed using a Monte Carlo superdroplet algorithm. The superdroplet method provides reliable but noisy estimates of the warm‐rain process rates. For each process rate, a neural network is trained using standard machine learning techniques. The resulting models make skillful predictions for the process rates when compared to the testing data. However, when solving the ordinary differential equations, the solutions are not as good as those of an established warm‐rain parameterization. This deficiency can be seen as a limitation of the machine learning methods that are applied, but at the same time, it points toward a fundamental ill‐posedness of the commonly used two‐moment warm‐rain schemes. More advanced machine learning methods that include a notion of time derivatives, therefore, have the potential to overcome these problems.
Land Surface Model CAS‐LSM: Model Description and Evaluation
Authors: Xie Zhenghui , Wang Longhuan , Wang Yan , Liu Bin , Li Ruichao , Xie Jinbo , Zeng Yujin , Liu Shuang , Gao Junqiang , Chen Si , Jia Binghao , Qin Peihua
Published: November 2020

Comprehensive land surface models are very important for climate and weather forecasting and for improving our understanding of the relationships between humans and the Earth system. This work presents a land surface model of the Chinese Academy of Sciences (CAS‐LSM) that considers groundwater lateral flow, human water regulation, soil freeze‐thaw front dynamics, riverine dissolved inorganic nitrogen transport, anthropologic heat release, urban water usage, and urban planning based on the Community Land Model. Global simulations with the updated CAS‐LSM were conducted to evaluate its performance, and the results show its advantages in reproducing ecohydrological processes. Groundwater lateral flow can replenish the groundwater depletion cone caused by overexploitation, where the offset rate increases as the aquifer thickness increases. The maximum thaw depth increases by 3.62 mm yr−1 in permafrost areas, and the maximum frost depth decreases by 1.89 mm yr−1 in seasonally frozen areas. Nitrogen fertilizer use and point‐source pollution increase the riverine dissolved inorganic nitrogen flow rate in western Europe and eastern China. To further verify the model's ability to simulate the effects of urban planning implementation, simulations over Beijing were conducted using the Weather Research and Forecasting (WRF) model coupled with CAS‐LSM. The results show that anthropogenic heat release enhances the sensible heat flux and temperature in the city center. In terms of urban water planning, most of the total water supply in Beijing should be used for urban irrigation, and a small part should be used for road sprinkling to obtain a greater cooling effect.
Growth differentiation factor 6, a repressive target of EZH2, promotes the commitment of human embryonic stem cells to mesenchymal stem cells
Authors: Deng Pend , Yu Yongxin , Hong Christine , Wang Cun-Yu
Published: November 2020

Mesenchymal stem cells (MSCs) derived from human embryonic stem cells (hESCs) have significant potential for cell-mediated bone regeneration. Our recent study revealed that inhibiting the epigenetic regulator EZH2 plays a key role in promoting the mesodermal differentiation of hESCs. In this study, an epigenome-wide analysis of hESCs and MSCs revealed that growth differentiation factor 6 (GDF6), which is involved in bone formation, was the most upregulated gene associated with MSCs compared to hESCs. Furthermore, we identified GDF6 as a repressive target of EZH2 and found that ectopic GDF6 selectively promoted hESC differentiation towards the mesodermal lineage and enriched the MSC population. Our results provide molecular insights governing the mesenchymal commitment of hESCs and identify an inducing factor that offers strong promise for the future of regenerative medicine.
Raloxifene prevents stress granule dissolution, impairs translational control and promotes cell death during hypoxia in glioblastoma cells
Authors: Attwood Kathleen M. , Robichaud Aaron , Westhaver Lauren P. , Castle Elizabeth L. , Brandman David M. , Balgi Aruna D. , Roberge Michel , Colp Patricia , Croul Sidney , Kim Inhwa , McCormick Craig , Corcoran Jennifer A. , Weeks Adrienne
Published: November 2020

Glioblastoma (GBM) is the most common primary malignant brain tumor, and it has a uniformly poor prognosis. Hypoxia is a feature of the GBM microenvironment, and previous work has shown that cancer cells residing in hypoxic regions resist treatment. Hypoxia can trigger the formation of stress granules (SGs), sites of mRNA triage that promote cell survival. A screen of 1120 FDA-approved drugs identified 129 candidates that delayed the dissolution of hypoxia-induced SGs following a return to normoxia. Amongst these candidates, the selective estrogen receptor modulator (SERM) raloxifene delayed SG dissolution in a dose-dependent manner. SG dissolution typically occurs by 15 min post-hypoxia, however pre-treatment of immortalized U251 and U3024 primary GBM cells with raloxifene prevented SG dissolution for up to 2 h. During this raloxifene-induced delay in SG dissolution, translational silencing was sustained, eIF2α remained phosphorylated and mTOR remained inactive. Despite its well-described role as a SERM, raloxifene-mediated delay in SG dissolution was unaffected by co-administration of β-estradiol, nor did β-estradiol alone have any effect on SGs. Importantly, the combination of raloxifene and hypoxia resulted in increased numbers of late apoptotic/necrotic cells. Raloxifene and hypoxia also demonstrated a block in late autophagy similar to the known autophagy inhibitor chloroquine (CQ). Genetic disruption of the SG-nucleating proteins G3BP1 and G3BP2 revealed that G3BP1 is required to sustain the raloxifene-mediated delay in SG dissolution. Together, these findings indicate that modulating the stress response can be used to exploit the hypoxic niche of GBM tumors, causing cell death by disrupting pro-survival stress responses and control of protein synthesis.
The dynamic behavior of lipid droplets in the pre-metastatic niche
Authors: Shang Chunliang , Qiao Jie , Guo Hongyan
Published: November 2020

The pre-metastatic niche is a favorable microenvironment for the colonization of metastatic tumor cells in specific distant organs. Lipid droplets (LDs, also known as lipid bodies or adiposomes) have increasingly been recognized as lipid-rich, functionally dynamic organelles within tumor cells, immune cells, and other stromal cells that are linked to diverse biological functions and human diseases. Moreover, in recent years, several studies have described the indispensable role of LDs in the development of pre-metastatic niches. This review discusses current evidence related to the biogenesis, composition, and functions of LDs related to the following characteristics of the pre-metastatic niche: immunosuppression, inflammation, angiogenesis/vascular permeability, lymphangiogenesis, organotropism, reprogramming. We also address the function of LDs in mediating pre-metastatic niche formation. The potential of LDs as markers and targets for novel antimetastatic therapies will be discussed.
Predicting dwell fatigue life in titanium alloys using modelling and experiment
Authors: Xu Yilun , Joseph Sudha , Karamched Phani , Fox Kate , Rugg David , Dunne Fionn P. E. , Dye David
Published: November 2020

Fatigue is a difficult multi-scale modelling problem nucleating from localised plasticity at the scale of dislocations and microstructure with significant engineering safety implications. Cold dwell fatigue is a phenomenon in titanium where stress holds at moderate temperatures lead to substantial reductions in cyclic life, and has been implicated in service failures. Using discrete dislocation plasticity modelling complemented by transmission electron microscopy, we successfully predict lifetimes for ‘worst case’ microstructures representative of jet engine spin tests. Fatigue loading above a threshold stress is found to produce slip in soft grains, leading to strong dislocation pile-ups at boundaries with hard grains. Pile-up stresses generated are high enough to nucleate hard grain basal dislocations, as observed experimentally. Reduction of applied cyclic load alongside a temperature excursion during the cycle lead to much lower densities of prism dislocations in soft grains and, sometimes, the elimination of basal dislocations in hard grains altogether.
Long non-coding RNA Gm15441 attenuates hepatic inflammasome activation in response to PPARA agonism and fasting
Authors: Brocker Chad N. , Kim Donghwan , Melia Tisha , Karri Kritika , Velenosi Thomas J. , Takahashi Shogo , Aibara Daisuke , Bonzo Jessica A. , Levi Moshe , Waxman David J. , Gonzalez Frank J.
Published: November 2020

Exploring the molecular mechanisms that prevent inflammation during caloric restriction may yield promising therapeutic targets. During fasting, activation of the nuclear receptor peroxisome proliferator-activated receptor α (PPARα) promotes the utilization of lipids as an energy source. Herein, we show that ligand activation of PPARα directly upregulates the long non-coding RNA gene Gm15441 through PPARα binding sites within its promoter. Gm15441 expression suppresses its antisense transcript, encoding thioredoxin interacting protein (TXNIP). This, in turn, decreases TXNIP-stimulated NLR family pyrin domain containing 3 (NLRP3) inflammasome activation, caspase-1 (CASP1) cleavage, and proinflammatory interleukin 1β (IL1B) maturation. Gm15441-null mice were developed and shown to be more susceptible to NLRP3 inflammasome activation and to exhibit elevated CASP1 and IL1B cleavage in response to PPARα agonism and fasting. These findings provide evidence for a mechanism by which PPARα attenuates hepatic inflammasome activation in response to metabolic stress through induction of lncRNA Gm15441.
Automatic classification and segmentation of single-molecule fluorescence time traces with deep learning
Authors: Li Jieming , Zhang Leyou , Johnson-Buck Alexander , Walter Nils G.
Published: November 2020

Traces from single-molecule fluorescence microscopy (SMFM) experiments exhibit photophysical artifacts that typically necessitate human expert screening, which is time-consuming and introduces potential for user-dependent expectation bias. Here, we use deep learning to develop a rapid, automatic SMFM trace selector, termed AutoSiM, that improves the sensitivity and specificity of an assay for a DNA point mutation based on single-molecule recognition through equilibrium Poisson sampling (SiMREPS). The improved performance of AutoSiM is based on accepting both more true positives and fewer false positives than the conventional approach of hidden Markov modeling (HMM) followed by hard thresholding. As a second application, the selector is used for automated screening of single-molecule Förster resonance energy transfer (smFRET) data to identify high-quality traces for further analysis, and achieves ~90% concordance with manual selection while requiring less processing time. Finally, we show that AutoSiM can be adapted readily to novel datasets, requiring only modest Transfer Learning.
Immune suppression in the early stage of COVID-19 disease
Authors: Tian Wenmin , Zhang Nan , Jin Ronghua , Feng Yingmei , Wang Siyuan , Gao Shuaixin , Gao Ruqin , Wu Guizhen , Tian Di , Tan Wenjie , Chen Yang , Gao George Fu , Wong Catherine C. L.
Published: November 2020

The outbreak of COVID-19 has become a worldwide pandemic. The pathogenesis of this infectious disease and how it differs from other drivers of pneumonia is unclear. Here we analyze urine samples from COVID-19 infection cases, healthy donors and non-COVID-19 pneumonia cases using quantitative proteomics. The molecular changes suggest that immunosuppression and tight junction impairment occur in the early stage of COVID-19 infection. Further subgrouping of COVID-19 patients into moderate and severe types shows that an activated immune response emerges in severely affected patients. We propose a two-stage mechanism of pathogenesis for this unusual viral infection. Our data advance our understanding of the clinical features of COVID-19 infections and provide a resource for future mechanistic and therapeutics studies.
Nutritional and bioactive constituents and scavenging capacity of radicals in Amaranthus hypochondriacus
Authors: Sarker Umakanta , Oba Shinya
Published: November 2020

A. hypochondriacus leaves contained ample phytopigments including betalain, anthocyanin, β-xanthin, β-cyanin, and bioactive phytochemicals of interest in the industry of food. We have been evaluating the possibility of utilizing phytopigments of amaranth and bioactive constituents for making drinks. Therefore, we evaluated bioactive phytopigments and compounds including the potentiality of antioxidants in A. hypochondriacus leaves. A. hypochondriacus leaves have abundant protein, carbohydrates, and dietary fiber. We found considerable levels of inorganic minerals including magnesium, calcium, potassium (3.88, 3.01, 8.56 mg g−1), zinc, manganese, copper, iron (16.23, 15.51, 2.26, 20.57 µg g−1), chlorophyll b, chlorophyll ab chlorophyll a (271.08, 905.21, 636.87 μg g−1), scavenging capacity of radicals (DPPH, ABTS+) (33.46, 62.92 TEAC μg g−1 DW), total polyphenols (29.34 GAE μg g−1 FW), β-xanthin, betalain, β-cyanin (584.71, 1,121.93, 537.21 ng g−1), total flavonoids (170.97 RE μg g−1 DW), vitamin C, β-carotene, carotenoids (184.77, 82.34, 105.08 mg 100 g−1) in A. hypochondriacus leaves. The genotypes AHC6, AHC4, AHC11, AHC5, and AHC10 had a good scavenging capacity of radicals. Polyphenols, phytopigments, flavonoids, and β-carotene of A. hypochondriacus had potential antioxidant activity. Extracted juice of A. hypochondriacus can be an ample source of phytopigments and compounds for detoxification of reactive oxygen species (ROS) and attaining nutritional and antioxidant sufficiency.
FluoSim: simulator of single molecule dynamics for fluorescence live-cell and super-resolution imaging of membrane proteins
Authors: Lagardère Matthieu , Chamma Ingrid , Bouilhol Emmanuel , Nikolski Macha , Thoumine Olivier
Published: November 2020

Fluorescence live-cell and super-resolution microscopy methods have considerably advanced our understanding of the dynamics and mesoscale organization of macro-molecular complexes that drive cellular functions. However, different imaging techniques can provide quite disparate information about protein motion and organization, owing to their respective experimental ranges and limitations. To address these issues, we present here a robust computer program, called FluoSim, which is an interactive simulator of membrane protein dynamics for live-cell imaging methods including SPT, FRAP, PAF, and FCS, and super-resolution imaging techniques such as PALM, dSTORM, and uPAINT. FluoSim integrates diffusion coefficients, binding rates, and fluorophore photo-physics to calculate in real time the localization and intensity of thousands of independent molecules in 2D cellular geometries, providing simulated data directly comparable to actual experiments. FluoSim was thoroughly validated against experimental data obtained on the canonical neurexin-neuroligin adhesion complex at cell–cell contacts. This unified software allows one to model and predict membrane protein dynamics and localization at the ensemble and single molecule level, so as to reconcile imaging paradigms and quantitatively characterize protein behavior in complex cellular environments.
Pirfenidone regulates LPS mediated activation of neutrophils
Authors: Evani Shankar J. , Karna S. L. Rajasekhar , Seshu Janakiram , Leung Kai P.
Published: November 2020

Excessive inflammation or its absence may result in impaired wound healing. Neutrophils are among the first innate immune cells to arrive at the injury site. They participate in infection control and debris removal to initiate healing. If not timely resolved, neutrophils can cause excessive tissue inflammation and damage. Drugs with anti-inflammatory and anti-fibrotic effects are of promise for improving healing by balancing the primary defensive functions and excessive tissue damage actions. Of interest, pirfenidone (Pf), an FDA approved anti-fibrotic drug to treat idiopathic pulmonary fibrosis, has been shown to ameliorate inflammation in several animal models including mouse deep partial-thickness burn wounds. However, there is a lack of mechanistic insights into Pf drug action on inflammatory cells such as neutrophils. Here, we examined the treatment effects of Pf on LPS-stimulated neutrophils as a model of non-sterile inflammation. Firstly, Pf reduced chemotaxis and production of pro-inflammatory ROS, cytokines, and chemokines by LPS-activated neutrophils. Secondly, Pf increased anti-inflammatory IL-1RA and reduced neutrophil degranulation, phagocytosis, and NETosis. Thirdly, Pf affected downstream signaling kinases which might directly or indirectly influence neutrophil responses to LPS. In conclusion, the results suggest that Pf lessens the inflammatory phenotypes of LPS-activated neutrophils.
Transcriptome and genome sequencing elucidates the molecular basis for the high yield and good quality of the hybrid rice variety Chuanyou6203
Authors: Ren Juansheng , Zhang Fan , Gao Fangyuan , Zeng Lihua , Lu Xianjun , Zhao Xiuqin , Lv Jianqun , Su Xiangwen , Liu Liping , Dai Mingli , Xu Jianlong , Ren Guangjun
Published: November 2020

The yield heterosis of rice is sought by farmers and strong contributes to food safety, but the quality of hybrid rice may be reduced. Therefore, developing new varieties with both high yield and good quality is a heavily researched topic in hybrid rice breeding. However, the molecular mechanism governing yield heterosis and high rice quality has not been elucidated to date. In this study, a comparative transcriptomics and genomic analysis was performed on a hybrid rice variety, Chuanyou6203 (CY6203), and its parents to investigate the molecular mechanism and gene regulation network governing the formation of yield and quality stages. A total of 66,319 SNPs and InDels between CH3203 and C106B were detected in the 5′-UTR, exon, intronic, and 3′-UTR regions according to the reference genome annotation, which involved 7473 genes. A total of 436, 70, 551, 993, and 1216 common DEGs between CY6203 and both of its parents were identified at the same stage in panicles and flag leaves. Of the common DEGs, the numbers of upregulated DEGs between CY6203 and CH3203 were all greater than those of upregulated DEGs between CY6203 and C106B in panicles and flag leaves at the booting, flowering, and middle filling stages. Approximately 40.61% of mRNA editing ratios were between 0.4 and 0.6, and 1.68% of mRNA editing events (editing ratio ≥ 0.8) in CY6203 favored one of its parents at three stages or a particular stage, suggesting that the hypothetical heterosis mechanism of CY6203 might involve dominance or epistasis. Also 15,934 DEGs were classified into 19 distinct modules that were classified into three groups by the weighted gene coexpression network analysis. Through transcriptome analysis of panicles and flag leaves in the yield and quality stages, the DEGs in the green-yellow module primarily contributed to the increase in the source of CY6203 due to an in increase in photosynthetic efficiency and nitrogen utilization efficiency, and a small number of DEGs related to the grain number added spikelet number per panicle amplified its sink. The balanced expression of the major high-quality alleles of C106B and CH3203 in CY6203 contributed to the outstanding quality of CY6203. Our transcriptome and genome analyses offer a new data set that may help to elucidate the molecular mechanism governing the yield heterosis and high quality of a hybrid rice variety.
Multi-phase-field simulation of microstructure evolution in metallic foams
Authors: Vakili Samad , Steinbach Ingo , Varnik Fathollah
Published: November 2020

This paper represents a model for microstructure formation in metallic foams based on the multi-phase-field approach. The model allows to naturally account for the effect of additives which prevent two gas bubbles from coalescence. By applying a non-merging criterion to the phase fields and at the same time raising the free energy penalty associated with additives, it is possible to completely prevent coalescence of bubbles in the time window of interest and thus focus on the formation of a closed porous microstructure. On the other hand, using a modification of this criterion along with lower free energy barriers we investigate with this model initiation of coalescence and the evolution of open structures. The method is validated and used to simulate foam structure formation both in two and three dimensions.
Energy depletion and opportunistic microbial colonisation in white syndrome lesions from corals across the Indo-Pacific
Authors: Smith Hillary A. , Conlan Jessica A. , Pollock F. Joseph , Wada Naohisa , Shore Amanda , Hung Julia Yun-Hsuan , Aeby Greta S. , Willis Bette L. , Francis David S. , Bourne David G.
Published: November 2020

Corals are dependent upon lipids as energy reserves to mount a metabolic response to biotic and abiotic challenges. This study profiled lipids, fatty acids, and microbial communities of healthy and white syndrome (WS) diseased colonies of Acropora hyacinthus sampled from reefs in Western Australia, the Great Barrier Reef, and Palmyra Atoll. Total lipid levels varied significantly among locations, though a consistent stepwise decrease from healthy tissues from healthy colonies (HH) to healthy tissue on WS-diseased colonies (HD; i.e. preceding the lesion boundary) to diseased tissue on diseased colonies (DD; i.e. lesion front) was observed, demonstrating a reduction in energy reserves. Lipids in HH tissues were comprised of high energy lipid classes, while HD and DD tissues contained greater proportions of structural lipids. Bacterial profiling through 16S rRNA gene sequencing and histology showed no bacterial taxa linked to WS causation. However, the relative abundance of Rhodobacteraceae-affiliated sequences increased in DD tissues, suggesting opportunistic proliferation of these taxa. While the cause of WS remains inconclusive, this study demonstrates that the lipid profiles of HD tissues was more similar to DD tissues than to HH tissues, reflecting a colony-wide systemic effect and provides insight into the metabolic immune response of WS-infected Indo-Pacific corals.
Two-stage fluid pathways generated by volume expansion reactions: insights from the replacement of pyrite by chalcopyrite
Authors: Zhang Yang , Cai Yuanfeng , Qu Yang , Wang Qin , Gu Lixin , Li Gaojun
Published: November 2020

Volume expansion reactions involved in mineral–fluid interactions are linked to a number of geological processes, including silicate weathering, retrograde metamorphism, and mineralization. However, the effect of volume expansion on replacement reactions remains unclear. Here, we demonstrate that reactions associated with volume expansion during the replacement of pyrite by chalcopyrite involve two competing processes. The reaction is initially augmented because of the development of reaction-induced fractures in the pyrite. However, these fractures are subsequently filled by compacted products, which ultimately disrupts the contact and interaction between bulk fluids and the pristine pyrite surface. These competing processes indicate that replacement reactions are both augmented and inhibited by volume expansion reactions during pyrite replacement.
Identification of synthetic chemosensitivity genes paired with BRAF for BRAF/MAPK inhibitors
Authors: Lee Kye Hwa , Goh Jinmin , Kim Yi-Jun , Kim Kwangsoo
Published: November 2020

Molecular-targeted approaches are important for personalised cancer treatment, which requires knowledge regarding drug target specificity. Here, we used the synthetic lethality concept to identify candidate gene pairs with synergistic effects on drug responses. A synergistic chemo-sensitivity response was identified if a drug had a significantly lower half-maximal inhibitory concentration (IC50) in cell lines with a pair of mutated genes compared with those in other cell lines (wild-type or one mutated gene). Among significantly damaging mutations in the Genomics of Drug Sensitivity in Cancer database, we found 580 candidate synergistic chemo-sensitivity interaction sets for 456 genes and 54 commercial drugs. Clustering analyses according to drug/gene and drug/tissue interactions showed that BRAF/MAPK inhibitors clustered together; 11 partner genes for BRAF were identified. The combined effects of these partners on IC50 values were significant for both drug-specific and drug-combined comparisons. Survival analysis using The Cancer Genome Atlas data showed that patients who had mutated gene pairs in synergistic interaction sets had longer overall survival compared with that in patients with other mutation profiles. Overall, this analysis demonstrated that synergistic drug-responsive gene pairs could be successfully used as predictive markers of drug sensitivity and patient survival, offering new targets for personalised medicine.
Prediction improvement of potential PV production pattern, imagery satellite-based
Authors: Ben Othman A. , Belkilani K. , Besbes M.
Published: November 2020

The results obtained by using an existing model to estimate global solar radiation (GHI) in three different locations in Tunisia. These data are compared with GHI meteorological measurements and PV_Gis satellite imagery estimation. Some statistical indicators (R, R2, MPE, AMPE, MBE, AMBE and RMSE) have been used to measure the performance of the used model. Correlation coefficient for the different stations was close to 1.0. The meteorology and satellite determination coefficient (R2) were also near 1.0 except in the case of Nabeul station in which the meteorology measurements (R) were equals to 0.5848 because of the loss of data in this location due to meteorological conditions. This numerical model provides the best performance according to statistical results in different locations; therefore, this model can be used to estimate global solar radiation in Tunisia. The R square values are used as a statistical indicator to demonstrate that the model’s results are compatible with those of meteorology with a percentage of error less than 10%.
Risk factors for post-bronchoscopy pneumonia: a case–control study
Authors: Sato Yu , Murata Kengo , Yamamoto Miake , Ishiwata Tsukasa , Kitazono-Saitoh Miyako , Wada Akihiko , Takamori Mikio
Published: November 2020

The bronchoscopy, though usually safe, is occasionally associated with complications, such as pneumonia. However, the use of prophylactic antibiotics is not recommended by the guidelines of the British Thoracic Society. Thus far there are few reports of the risk factors for post-bronchoscopy pneumonia; the purpose of this study was to evaluate these risk factors. We retrospectively collected data on patients in whom post-bronchoscopy pneumonia developed from the medical records of 2,265 patients who received 2666 diagnostic bronchoscopies at our institution between April 2006 and November 2011. Twice as many patients were enrolled in the control group as in the pneumonia group. The patients were matched for age and sex. In total, 37 patients (1.4%) had post-bronchoscopy pneumonia. Univariate analysis showed that a significantly larger proportion of patients in the pneumonia group had tracheobronchial stenosis (75.7% vs 18.9%, p < 0.01) and a final diagnosis of primary lung cancer (75.7% vs 43.2%, p < 0.01) than in the control group. The pneumonia group tended to have more patients with a history of smoking (83.8% vs 67.1%, p = 0.06) or bronchoalveolar lavage (BAL) (4.3% vs 14.9%, p = 0.14) than the control group. In multivariate analysis, we found that tracheobronchial stenosis remained an independent risk factor for post-bronchoscopy pneumonia (odds ratio: 7.8, 95%CI: 2.5–24.2). In conclusion, tracheobronchial stenosis was identified as an independent risk factor for post-bronchoscopy pneumonia by multivariate analysis in this age- and sex- matched case control study.
High-content screening of Thai medicinal plants reveals Boesenbergia rotunda extract and its component Panduratin A as anti-SARS-CoV-2 agents
Authors: Kanjanasirirat Phongthon , Suksatu Ampa , Manopwisedjaroen Suwimon , Munyoo Bamroong , Tuchinda Patoomratana , Jearawuttanakul Kedchin , Seemakhan Sawinee , Charoensutthivarakul Sitthivut , Wongtrakoongate Patompon , Rangkasenee Noppawan , Pitiporn Supaporn , Waranuch Neti , Chabang Napason , Khemawoot Phisit , Sa-ngiamsuntorn Khanit , Pewkliang Yongyut , Thongsri Piyanoot , Chutipongtanate Somchai , Hongeng Suradej , Borwornpinyo Suparerk , Thitithanyanont Arunee
Published: November 2020

Since December 2019, the emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has caused severe pneumonia, a disease named COVID-19, that became pandemic and created an acute threat to public health. The effective therapeutics are in urgent need. Here, we developed a high-content screening for the antiviral candidates using fluorescence-based SARS-CoV-2 nucleoprotein detection in Vero E6 cells coupled with plaque reduction assay. Among 122 Thai natural products, we found that Boesenbergia rotunda extract and its phytochemical compound, panduratin A, exhibited the potent anti-SARS-CoV-2 activity. Treatment with B. rotunda extract and panduratin A after viral infection drastically suppressed SARS-CoV-2 infectivity in Vero E6 cells with IC50 of 3.62 μg/mL (CC50 = 28.06 µg/mL) and 0.81 μΜ (CC50 = 14.71 µM), respectively. Also, the treatment of panduratin A at the pre-entry phase inhibited SARS-CoV-2 infection with IC50 of 5.30 µM (CC50 = 43.47 µM). Our study demonstrated, for the first time, that panduratin A exerts the inhibitory effect against SARS-CoV-2 infection at both pre-entry and post-infection phases. Apart from Vero E6 cells, treatment with this compound was able to suppress viral infectivity in human airway epithelial cells. This result confirmed the potential of panduratin A as the anti-SARS-CoV-2 agent in the major target cells in human. Since B. rotunda is a culinary herb generally grown in China and Southeast Asia, its extract and the purified panduratin A may serve as the promising candidates for therapeutic purposes with economic advantage during COVID-19 situation.
Statistics for the analysis of molecular dynamics simulations: providing P values for agonist-dependent GPCR activation
Authors: Bruzzese Agustín , Dalton James A. R. , Giraldo Jesús
Published: November 2020

Molecular dynamics (MD) is the common computational technique for assessing efficacy of GPCR-bound ligands. Agonist efficacy measures the capability of the ligand-bound receptor of reaching the active state in comparison with the free receptor. In this respect, agonists, neutral antagonists and inverse agonists can be considered. A collection of MD simulations of both the ligand-bound and the free receptor are needed to provide reliable conclusions. Variability in the trajectories needs quantification and proper statistical tools for meaningful and non-subjective conclusions. Multiple-factor (time, ligand, lipid) ANOVA with repeated measurements on the time factor is proposed as a suitable statistical method for the analysis of agonist-dependent GPCR activation MD simulations. Inclusion of time factor in the ANOVA model is consistent with the time-dependent nature of MD. Ligand and lipid factors measure agonist and lipid influence on receptor activation. Previously reported MD simulations of adenosine A2a receptor (A2aR) are reanalyzed with this statistical method. TM6–TM3 and TM7–TM3 distances are selected as dependent variables in the ANOVA model. The ligand factor includes the presence or absence of adenosine whereas the lipid factor considers DOPC or DOPG lipids. Statistical analysis of MD simulations shows the efficacy of adenosine and the effect of the membrane lipid composition. Subsequent application of the statistical methodology to NECA A2aR agonist, with resulting P values in consistency with its pharmacological profile, suggests that the method is useful for ligand comparison and potentially for dynamic structure-based virtual screening.
Trophic sympathetic influence weakens pro-contractile role of Cl− channels in rat arteries during postnatal maturation
Authors: Kostyunina Daria S. , Zhang Lin , Shvetsova Anastasia A. , Selivanova Ekaterina K. , Tarasova Olga S. , Matchkov Vladimir V. , Gaynullina Dina K.
Published: November 2020

Membrane transporters and their functional contribution in vasculature change during early postnatal development. Here we tested the hypothesis that the contribution of Cl− channels to arterial contraction declines during early postnatal development and this decline is associated with the trophic sympathetic influence. Endothelium‐denuded saphenous arteries from 1- to 2-week-old and 2- to 3-month-old male rats were used. Arterial contraction was assessed in the isometric myograph, in some experiments combined with measurements of membrane potential. mRNA and protein levels were determined by qPCR and Western blot. Sympathectomy was performed by treatment with guanethidine from the first postnatal day until 8–9-week age. Cl− substitution in the solution as well as Cl−-channel blockers (MONNA, DIDS) had larger suppressive effect on the methoxamine-induced arterial contraction and methoxamine-induced depolarization of smooth muscle cells in 1- to 2-week-old compared to 2- to 3-month-old rats. Vasculature of younger group demonstrated elevated expression levels of TMEM16A and bestrophin 3. Chronic sympathectomy increased Cl− contribution to arterial contraction in 2-month-old rats that was associated with an increased TMEM16A expression level. Our study demonstrates that contribution of Cl− channels to agonist-induced arterial contraction and depolarization decreases during postnatal development. This postnatal decline is associated with sympathetic nerves development.
Reliability of shear-wave elastography in assessing thoracolumbar fascia elasticity in healthy male
Authors: Chen Baizhen , Zhao Hongzhou , Liao Linrong , Zhang Zhijie , Liu Chunlong
Published: November 2020

The objectives of this study were to examine the intra and inter-operator reliability of shear wave elastography (SWE) device in quantifying the shear modulus of thoracolumbar fascia (TLF) and the device’s abilities to examine the shear modulus of the TLF during upper body forward. Twenty healthy male subjects participated in this study (mean age: 18.4 ± 0.7 years). Two independent operators performed the shear modulus of TLF during upper body forward using SWE, and interclass correlation coefficient (ICC) and minimum detectable change (MDC) were calculated. The shear modulus of the TLF was quantified by operator A using SWE at upper body forward 60°. The intra-operator (ICC = 0.860–0.938) and inter-operator (ICC = 0.904–0.944) reliabilities for measuring the shear modulus of the TLF with the upper body forward 0° were rated as both excellent, and the MDC was 4.71 kPa. The TLF shear modulus of upper body forward 60°was increased 45.5% (L3) and 55.0% (L4) than that of upper body forward 0°. The results indicate that the SWE is a dependable tool to quantify the shear modulus of TLF and monitor its dynamic changes. Therefore, this device can be used for biomechanical study and intervention experiments of TLF.
Computational Methods for the Discovery of Chemical Probes
Authors: Poda G. , Tanchuk V.
Published: November 2020

Chemical probes are potent and selective small-molecule modulators of cellular functions that allow interrogation of the function of the protein with which they interact. Just like in drug discovery, the holy grail of computational chemical probe discovery is the accurate prediction of how chemical probes interact with their protein targets and also the prediction of their binding affinities. Recent advances in these directions, in particular molecular docking and scoring, but also machine learning, pharmacophore modelling, virtual screening and exploration of the enormous virtual chemical space, de novo design, databases and future directions in chemical probe development, are presented in this chapter.
Discovery and Use of Natural Products and Derivatives as Chemical Probes
Authors: Kita Masaki , Kigoshi Hideo
Published: November 2020

Among various structurally and functionally diverse natural products, some compounds modulate protein–protein interactions (PPIs). The anti-tumour macrolide aplyronine A is a PPI stabilizer between tubulin and actin and prevents spindle formation and mitosis. As a case study of using natural products as chemical probes, target identification and mode of action studies of aplyronines are presented. A new methodology using an amidopyrene tag and label-assisted laser desorption/ionization mass spectrometry (LA-LDI-MS) for binding position analysis of ligands on target biomacromolecules is also highlighted.
Targeted Protein Degradation Chemical Probes
Authors: Galdeano C. , Barril X.
Published: November 2020

Chemical probes are invaluable tools in both fundamental and applied biological research, representing important reagents to support the unbiased interpretation of biological experiments necessary for rigorous preclinical target validation in drug discovery programmes. Targeted protein degradation stands out from classical pharmacology with unique features to develop high-quality chemical probes capable of destroying their targets, instead of modulating their activity. In addition to revalidating known targets and understanding the new biological outcomes of selective chemical degradation, the development of completely novel probes through proteolysis-targeting chimera (PROTAC) molecules or molecular glues can provide access to systems or functions that remain untapped for drug discovery. This chapter introduces the concept of targeted protein degradation, its particularities and its future impact on the finding of novel therapies. The technical advantages that targeted protein degradation offers in the development of high-quality chemical probes are discussed and exemplified.
Assays to Characterize the Cellular Pharmacology of a Chemical Probe
Authors: Stefaniak Jakub , Galan Sébastien R. G. , Huber Kilian V. M.
Published: November 2020

Chemical probes are bioactive molecules enabling the examination of protein function in cellular systems. Intended as tool compounds, they bind to a specific protein target, thereby conferring either a loss- or gain-of-function phenotype via a clearly defined mechanism of action. Chemical probes represent an excellent means to identify novel and potentially context-dependent functions of a given gene or protein in living systems. Among the many different bespoke functional cellular assays available to interrogate cellular signalling pathways, this chapter focuses on methods that allow for broad profiling of drugs and chemical probes in cells to uncover perturbations and facilitate further characterization of these phenomena.
Determination of atenolol based on the reversion of the fluorescence resonance energy transfer between AgInS2quantum dots and Au nanoparticles
Authors: Castro Rafael C. , Lopes André F. R. , Soares José X. , Ribeiro David S. M. , Santos João L. M.
Published: November 2020

Cd-Free ternary QDs demonstrated to be a good alternative for the implementation of FRET-based sensing platforms which were successfully applied for the monitoring of atenolol in pharmaceutical formulations.
Strictly sparse surface modification and its application for endowing nanoparticles with an exact “valency”
Authors: Yang Ruiqi , Dou Jinkang , Jiang Li , Chen Daoyong
Published: November 2020

Strictly sparse modification of a particle surface and its application for endowing smaller nanoparticles with an exact “valency” is reported.
Increasing the structural boundary of quasiracemate formation: 4-substituted naphthylamides
Authors: Craddock Drew E. , Parks McKenzie J. , Taylor Lauren A. , Wagner Benjamin L. , Ruf Michael , Wheeler Kraig A.
Published: November 2020

Spatially larger naphthylamides than previously reported diarylamides promote greater structural variance of substituents during the pairwise assembly of quasienantiomers.
Taking advantage of solvate formation to modulate drug–drug ratio in clofaziminium diclofenac salts
Authors: Bodart Laurie , Prinzo Maria , Derlet Amélie , Tumanov Nikolay , Wouters Johan
Published: November 2020

Clever solvent selection allows crystallization of a great structural variety of (un)solvated salts combining clofazimine and diclofenac.
Molecular simulation of osmometry in aqueous solutions of the BMIMCl ionic liquid: a potential route to force field parameterization of liquid mixtures
Authors: Dhabal Debdas , Patra Tanmoy
Published: November 2020

By means of molecular simulation, the osmotic coefficient of aqueous solution of BMIMCl ionic liquid is calculated to compare with the experimental data and use that to optimize two popular force fields available in the literature for bulk ILs.
Towards kinetic control of coordination self-assembly: a case study of a Pd3L6 double-walled triangle to predict the outcomes by a reaction network model
Authors: Takahashi Satoshi , Tateishi Tomoki , Sasaki Yuya , Sato Hirofumi , Hiraoka Shuichi
Published: November 2020

Numerical analysis of self-assembly process (NASAP) was performed for a Pd3L6 double-walled triangle and revealed the reaction pathways in detail. The prediction of the outcome of the self-assembly under kinetic control was also succeeded.
Segregation tendencies of transition-metal dopants in wide band gap semiconductor nanowires
Authors: Aras Mehmet , Güler-Kılıç Sümeyra , Kılıç Çetin
Published: November 2020

The segregation tendency of an impurity in a semiconductor nanowire can be tuned by adjusting the Fermi level position.