bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transition of Low Clouds in the East China Sea and Kuroshio Region in Winter: A Regional Atmospheric Model Study
Authors: Long Jingchao , Wang Yuqing , Zhang Suping , Liu Jingwu 
Published: August 2020

AbstractBias in simulating the stratocumulus‐to‐cumulus transition remains a main source of uncertainties in climate projection and can significantly affect the energy budget in climate models. To gain insights into the transition, this study investigates the cloud transition forced by the sea surface temperature (SST) front and synoptic disturbances in the East China Sea and Kuroshio region in winter based on both observations and regional atmospheric model simulations. The Kuroshio SST front greatly accelerates cloud transition by enhancing surface latent heat flux, marine atmospheric boundary layer (MABL) dynamical adjustment, and cloud top entrainment. With the sharp SST increase from the cold flank to the Kuroshio SST warm tongue (KWT), surface wind convergence (SWC) over the KWT induced by the SST front and synoptic disturbances enhances the coupling between the cloud layer and subcloud layer. An underlying positive feedback between the SWC and latent heating in the cloud layer can enhance abrupt change in cloud properties and maintain cloud band over the KWT against the decoupling through the so‐called “Deepening‐Warming” mechanism induced by latent heating. From the KWT downwind southward, the surface layer turbulent mixing weakens, while latent heating in the cloud layer and cloud top longwave radiative cooling enhance buoyancy and vertical mixing in the cloud layer. This difference in vertical mixing between the cloud layer and subcloud layer facilitates the MABL decoupling and impedes upward moisture transport. Meanwhile, decreasing lower tropospheric stability is conducive to the entrainment of drier and warmer air from above into the cloud layer, strengthening cloud evaporation.
Hydrometeor Size Sorting in the Asymmetric Eyewall of Hurricane Matthew (2016)
Authors: Laurencin Chelsey N. , Didlake Anthony C. , Loeffler Scott D. , Kumjian Matthew R. , Heymsfield Gerald M. 
Published: August 2020

AbstractPolarimetric radar observations of Hurricane Matthew's asymmetric eyewall were captured by WSR‐88D radars from 1500 UTC on 7 October 2016 to 0000 UTC on 8 October 2016. Raindrop size sorting was observed within the eyewall, marked by a differential reflectivity (ZDR) enhancement region situated upwind of a specific differential phase (KDP) enhancement region, both overlapping the maximum reflectivity. This signature indicated that the largest raindrops fell out of the eyewall updrafts faster than the smaller, abundant drops that were advected further downstream by the primary circulation. Airborne Doppler radar observations revealed an updraft structure in an azimuthal location consistent with the size‐sorting signature and previous observational studies of eyewall kinematic asymmetries.Given that a tropical cyclone's environment or internal dynamics can modulate the eyewall's kinematic and microphysical structure, we used a simple size‐sorting model that only includes sedimentation and advection of raindrops by the axisymmetric tangential wind to examine how an eyewall size‐sorting signature responds to artificial changes in the tangential wind speed and initial raindrop size distributions (DSDs). The axisymmetric tangential wind was retrieved from WSR‐88D radar observations using the Ground‐Based Velocity Track Display technique. The simple model was capable of producing an eyewall size‐sorting signature with an azimuthal separation between the simulated ZDR and KDP enhancements in general agreement with the observed separation (~20°) at low levels. Sensitivity tests showed that the azimuthal separation between the ZDR and KDP enhancements responded to changes in the tangential wind speed, but not to changes in the initial DSDs aloft.
The Surface Warming Attributable to Stratospheric Water Vapor in CO2‐Caused Global Warming
Authors: Wang Yuwei , Huang Yi 
Published: August 2020

AbstractStratospheric water vapor (SWV) is recognized as a potentially important positive feedback in global warming. The SWV change induces significant downward radiative flux perturbation at the tropopause and therefore is hypothesized to substantially amplify the surface warming. To test this hypothesis, we use a global climate model to quantify the surface warming contributed by the SWV change in the context of the quadrupled CO2. By prescribing the SWV increase as an external forcing, we find that SWV only accounts for 0.42 K surface warming, making up merely 5.4% of the total CO2‐caused surface warming (7.7 K). The efficacy of the stratosphere‐adjusted SWV forcing is small (38%), where the efficacy is defined as the ratio of the global temperature response per unit radiative forcing relative to that of the CO2 forcing. With the aid of a series of auxiliary experiments, we find that although the stratosphere‐adjusted SWV forcing at the top of atmosphere (TOA) is significant (1.13 W m−2), more than half of the forcing is offset by a high‐cloud decrease and an upper tropospheric warming in the tropospheric adjustment. The direct radiative impact of the SWV increase on surface temperature is negligible, and the SWV‐induced surface temperature change is a result of interactions between the radiative and nonradiative processes.
Black Carbon Emission and Wet Scavenging From Surface to the Top of Boundary Layer Over Beijing Region
Authors: Liu Dantong , Ding Shuo , Zhao Delong , Hu Kang , Yu Chenjie , Hu Dawei , Wu Yunfei , Zhou Chang , Tian Ping , Liu Quan , Wu Yangzhou , Zhang Jiale , Kong Shaofei , Huang Mengyu , Ding Deping 
Published: August 2020

AbstractThe heating impacts caused by black carbon (BC) may modify the atmospheric dynamics of planetary boundary layer (PBL), essentially determined by its vertical distribution. In this study we performed simultaneous measurements of detailed BC properties at both surface (50 m) and mountain sites (1,344 m) over Beijing region. The latter represents the top of PBL and was influenced by surface anthropogenic emissions, particularly around midday when PBL was developed, allowing continuous investigations on the evolution of BC during vertical transport in the PBL. Experiments in cold and warm seasons were performed to reflect seasonal difference in emission and meteorology: Winter had additional emission of residential heating and dry air; summer had moist air with more precipitation. The net ratio of BC/CO relative to background (ΔBC/ΔCO) is used to indicate the emission signature and scavenging of BC. At surface, both seasons peaked at similar ΔBC/ΔCO, however showed contrast shifts between both sites. In winter, mountain showed slightly higher ΔBC/ΔCO than surface due to receiving sources from wider area, whereas in summer, a refractory black carbon (rBC) mass scavenging efficiency of 35–62% was derived from the significantly lowered ΔBC/ΔCO on mountain. This scavenging process could incorporate BC into the summer moist air or low‐level clouds on a daily basis, exerting potential indirect effects. The resultant BC after scavenging exhibited smaller core size and increased coatings, leading to higher absorption efficiency by 45%. These factors should improve the representation of boundary layer processing of BC in evaluating its direct and indirect radiative impacts over the anthropogenically influenced region.
IGF-1R inhibition induces MEK phosphorylation to promote survival in colon carcinomas
Authors: Wang Qing , Zhang Yan , Zhu Jiang , Zheng Honggang , Chen Shuntai , Chen Li , Yang Hsin-Sheng 
Published: August 2020

AbstractThe insulin-like growth factor 1 receptor (IGF-1R) governs several signaling pathways for cell proliferation, survival, and anti-apoptosis. Thus, targeting IGF-1R appears as a reasonable rationale for tumor treatment. However, clinical studies showed that inhibition of IGF-1R has very limited efficacy due to the development of resistance to IGF-1R blockade in tumor cells. Here, we discovered that prolonged treatment of colon cancer cells with IGF-1R inhibitors (BMS-754807 and GSK1838705A) stimulates p70 KDa ribosomal protein S6 kinase 1 (p70S6K1) activation, a well-known kinase signaling for cell survival. We also found that p70S6K1 activation by IGF-1R inhibition is independent of K-Ras and PIK3CA mutations that frequently occur in colon cancer. Besides the increased p70S6K1 phosphorylation, the phosphorylation of mitogen-activated protein kinase kinase 1 and 2 (MEK1/2) was elevated in the cells treated with BMS-754807. Interestingly, the increases in MEK1/2 and p70S6K1 phosphorylation were also observed when cells were subjected to the treatment of AKT inhibitor or genetic knockdown of AKT2 but not AKT1, suggesting that AKT2 inhibition stimulates MEK1/2 phosphorylation to activate p70S6K1. Conversely, inhibition of MEK1/2 by MEK1/2 inhibitor (U0126) or knockdown of MEK1 and MEK2 by corresponding mek1 and mek2 siRNA enhanced AKT phosphorylation, indicating mutual inhibition between AKT and MEK. Furthermore, the combination of BMS-754807 and U0126 efficiently decreased the cell viability and increased cleaved caspase 3 and apoptosis in vitro and in vivo. Our data suggest that the treatment of colon tumor cells with IGF-1R inhibitors stimulates p70S6K1 activity via MEK1/2 to promote survival, providing a new strategy for colorectal cancer therapeutics.
Inferring clonal composition from multiple tumor biopsies
Authors: Manica Matteo , Kim Hyunjae Ryan , Mathis Roland , Chouvarine Philippe , Rutishauser Dorothea , De Vargas Roditi Laura , Szalai Bence , Wagner Ulrich , Oehl Kathrin , Saba Karim , Pati Arati , Saez-Rodriguez Julio , Roy Angshumoy , Parsons Donald W. , Wild Peter J. , Martínez María Rodríguez , Sumazin Pavel 
Published: August 2020

AbstractKnowledge about the clonal evolution of a tumor can help to interpret the function of its genetic alterations by identifying initiating events and events that contribute to the selective advantage of proliferative, metastatic, and drug-resistant subclones. Clonal evolution can be reconstructed from estimates of the relative abundance (frequency) of subclone-specific alterations in tumor biopsies, which, in turn, inform on its composition. However, estimating these frequencies is complicated by the high genetic instability that characterizes many cancers. Models for genetic instability suggest that copy number alterations (CNAs) can influence mutation-frequency estimates and thus impede efforts to reconstruct tumor phylogenies. Our analysis suggested that accurate mutation frequency estimates require accounting for CNAs—a challenging endeavour using the genetic profile of a single tumor biopsy. Instead, we propose an optimization algorithm, Chimæra, to account for the effects of CNAs using profiles of multiple biopsies per tumor. Analyses of simulated data and tumor profiles suggested that Chimæra estimates are consistently more accurate than those of previously proposed methods and resulted in improved phylogeny reconstructions and subclone characterizations. Our analyses inferred recurrent initiating mutations in hepatocellular carcinomas, resolved the clonal composition of Wilms’ tumors, and characterized the acquisition of mutations in drug-resistant prostate cancers.
910 metagenome-assembled genomes from the phytobiomes of three urban-farmed leafy Asian greens
Authors: Bandla Aditya , Pavagadhi Shruti , Sridhar Sudarshan Ashwin , Poh Miko Chin Hong , Swarup Sanjay 
Published: August 2020

AbstractThe genome sequences of many microbial species from the phytobiomes of several leafy Asian greens remain unknown. Here, we address this gap by reconstructing 910 prokaryotic draft genomes from 24 leaf, 65 root, 12 soil, and 6 compost metagenomes from the seedling and adult developmental stages of three leafy Asian greens –Brassica rapavar.parachinensis,Brassica oleraceavar.alboglabraandAmaranthusspp. – grown in a commercial, soil-based urban farm. Of these, 128 are near-complete (>90% completeness, <5% redundancy), 540 are substantially complete (≥70% completeness, <10%, redundancy), while the rest have a completeness ≥50% and redundancy <10%. The draft genomes together span 292 bacterial and 3 archaeal species, a subset of which are from underrepresented genus-level lineages in public databases. We expect our dataset to facilitate a wide range of comparative studies that seek to understand the different functional aspects of vegetable crop phytobiomes and for devising new strategies for microbial cultivation in the future.
Highly functionalized β-lactams and 2-ketopiperazines as TRPM8 antagonists with antiallodynic activity
Authors: Bonache M.Ángeles , Martín-Escura Cristina , de la Torre Martínez Roberto , Medina Alicia , González-Rodríguez Sara , Francesch Andrés , Cuevas Carmen , Roa Ana María , Fernández-Ballester Gregorio , Ferrer-Montiel Antonio , Fernández-Carvajal Asia , González-Muñiz Rosario 
Published: August 2020

AbstractThe cool sensor transient receptor potential melastatin channel 8 (TRPM8) is highly expressed in trigeminal and dorsal root ganglia, playing a key role in cold hypersensitivity associated to different peripheral neuropathies. Moreover, these channels are aberrantly expressed in different cancers, and seem to participate in tumor progression, survival and invasion. Accordingly, the search for potent and selective TRPM8 modulators attracted great interest in recent years. We describe new heterocyclic TRPM8 antagonist chemotypes derived from N-cloroalkyl phenylalaninol-Phe conjugates. The cyclization of these conjugates afforded highly substituted β-lactams and/or 2-ketopiperazine (KP) derivatives, with regioselectivity depending on the N-chloroalkyl group and the configuration. These derivatives behave as TRPM8 antagonists in the Ca2+ microfluorometry assay, and confirmed electrophysiologically for the best enantiopure β-lactams 24a and 29a (IC50, 1.4 and 0.8 µM). Two putative binding sites by the pore zone, different from those found for typical agonists and antagonists, were identified by in silico studies for both β-lactams and KPs. β-Lactams 24a and 29a display antitumor activity in different human tumor cell lines (micromolar potencies, A549, HT29, PSN1), but correlation with TRPM8 expression could not be established. Additionally, compound 24a significantly reduced cold allodynia in a mice model of oxaliplatin-induced peripheral neuropathy.
Genomic profiling of the transcription factor Zfp148 and its impact on the p53 pathway
Authors: Zou Zhiyuan V. , Gul Nadia , Lindberg Markus , Bokhari Abdulmalik A. , Eklund Ella M. , Garellick Viktor , Patel Angana A. H. , Dzanan Jozefina J. , Titmuss Ben O. , Le Gal Kristell , Johansson Inger , Tivesten Åsa , Forssell-Aronsson Eva , Bergö Martin O. , Staffas Anna , Larsson Erik , Sayin Volkan I. , Lindahl Per 
Published: August 2020

AbstractRecent data suggest that the transcription factor Zfp148 represses activation of the tumor suppressor p53 in mice and that therapeutic targeting of the human orthologue ZNF148 could activate the p53 pathway without causing detrimental side effects. We have previously shown that Zfp148 deficiency promotes p53-dependent proliferation arrest of mouse embryonic fibroblasts (MEFs), but the underlying mechanism is not clear. Here, we showed that Zfp148 deficiency downregulated cell cycle genes in MEFs in a p53-dependent manner. Proliferation arrest of Zfp148-deficient cells required increased expression of ARF, a potent activator of the p53 pathway. Chromatin immunoprecipitation showed that Zfp148 bound to the ARF promoter, suggesting that Zfp148 represses ARF transcription. However, Zfp148 preferentially bound to promoters of other transcription factors, indicating that deletion of Zfp148 may have pleiotropic effects that activate ARF and p53 indirectly. In line with this, we found no evidence of genetic interaction between TP53 and ZNF148 in CRISPR and siRNA screen data from hundreds of human cancer cell lines. We conclude that Zfp148 deficiency, by increasing ARF transcription, downregulates cell cycle genes and cell proliferation in a p53-dependent manner. However, the lack of genetic interaction between ZNF148 and TP53 in human cancer cells suggests that therapeutic targeting of ZNF148 may not increase p53 activity in humans.
Immunoinformatic identification of B cell and T cell epitopes in the SARS-CoV-2 proteome
Authors: Crooke Stephen N. , Ovsyannikova Inna G. , Kennedy Richard B. , Poland Gregory A. 
Published: August 2020

AbstractA novel coronavirus (SARS-CoV-2) emerged from China in late 2019 and rapidly spread across the globe, infecting millions of people and generating societal disruption on a level not seen since the 1918 influenza pandemic. A safe and effective vaccine is desperately needed to prevent the continued spread of SARS-CoV-2; yet, rational vaccine design efforts are currently hampered by the lack of knowledge regarding viral epitopes targeted during an immune response, and the need for more in-depth knowledge on betacoronavirus immunology. To that end, we developed a computational workflow using a series of open-source algorithms and webtools to analyze the proteome of SARS-CoV-2 and identify putative T cell and B cell epitopes. Utilizing a set of stringent selection criteria to filter peptide epitopes, we identified 41 T cell epitopes (5 HLA class I, 36 HLA class II) and 6 B cell epitopes that could serve as promising targets for peptide-based vaccine development against this emerging global pathogen. To our knowledge, this is the first study to comprehensively analyze all 10 (structural, non-structural and accessory) proteins from SARS-CoV-2 using predictive algorithms to identify potential targets for vaccine development.
Perturbation-based gene regulatory network inference to unravel oncogenic mechanisms
Authors: Morgan Daniel , Studham Matthew , Tjärnberg Andreas , Weishaupt Holger , Swartling Fredrik J. , Nordling Torbjörn E. M. , Sonnhammer Erik L. L. 
Published: August 2020

AbstractThe gene regulatory network (GRN) of human cells encodes mechanisms to ensure proper functioning. However, if this GRN is dysregulated, the cell may enter into a disease state such as cancer. Understanding the GRN as a system can therefore help identify novel mechanisms underlying disease, which can lead to new therapies. To deduce regulatory interactions relevant to cancer, we applied a recent computational inference framework to data from perturbation experiments in squamous carcinoma cell line A431. GRNs were inferred using several methods, and the false discovery rate was controlled by the NestBoot framework. We developed a novel approach to assess the predictiveness of inferred GRNs against validation data, despite the lack of a gold standard. The best GRN was significantly more predictive than the null model, both in cross-validated benchmarks and for an independent dataset of the same genes under a different perturbation design. The inferred GRN captures many known regulatory interactions central to cancer-relevant processes in addition to predicting many novel interactions, some of which were experimentally validated, thus providing mechanistic insights that are useful for future cancer research.
Risk factors for retinopathy in hemodialysis patients with type 2 diabetes mellitus
Authors: Müller Michael , Schönfeld Carl-Ludwig , Grammer Tanja , Krane Vera , Drechsler Christiane , Genser Bernd , Kohnen Thomas , Wanner Christoph , März Winfried 
Published: August 2020

AbstractThere is limited knowledge on the prevalence and risk factors of diabetic retinopathy (DR) in dialysis patients. We have investigated the association between diabetes mellitus and lipid-related biomarkers and retinopathy in hemodialysis patients. We reviewed 1,255 hemodialysis patients with type 2 diabetes mellitus (T2DM) who participated in the German Diabetes and Dialysis Study (4D Study). Associations between categorical clinical, biochemical variables and diabetic retinopathy were examined by logistic regression. On average, patients were 66 ± 8 years of age, 54% were male and the HbA1c was 6.7% ± 1.3%. DR, found in 71% of the patients, was significantly and positively associated with fasting glucose, HbA1c, time on dialysis, age, systolic blood pressure, body mass index and the prevalence of other microvascular diseases (e.g. neuropathy). Unexpectedly, DR was associated with high HDL cholesterol and high apolipoproteins AI and AII. Patients with coronary artery disease were less likely to have DR. DR was not associated with gender, smoking, diastolic blood pressure, VLDL cholesterol, triglycerides, and LDL cholesterol. In summary, the prevalence of DR in patients with type 2 diabetes mellitus requiring hemodialysis is higher than in patients suffering from T2DM, who do not receive hemodialysis. DR was positively related to systolic blood pressure (BP), glucometabolic control, and, paradoxically, HDL cholesterol. This data suggests that glucose and blood pressure control may delay the development of DR in patients with diabetes mellitus on dialysis.
Strain-specific anti-biofilm and antibiotic-potentiating activity of 3′,4′-difluoroquercetin
Authors: Kho Wonyoung , Kim Mi Kyoung , Jung Minji , Chong Yong Pil , Kim Yang Soo , Park Ki-Ho , Chong Youhoon 
Published: August 2020

AbstractAntibacterial properties of 3′,4′-difluoroquercetin (di-F-Q), a fluorine-substituted stable quercetin derivative, were investigated. Even though di-F-Q itself did not show interesting antibacterial activity, treatment of the Staphylococcus aureus strains with di-F-Q resulted in a dose-dependent reduction in biofilm formation with IC50 values of 1.8 ~ 5.3 mg/L. Also, the antibacterial activity of ceftazidime (CAZ) against carbapenem-resistant Pseudomonas aeruginosa (CRPA) showed eightfold decrease upon combination with di-F-Q. Assessment of the antimicrobial activity of CAZ in combination with di-F-Q against 50 clinical isolates of P. aeruginosa confirmed 15.7% increase in the percentages of susceptible P. aeruginosa isolates upon addition of di-F-Q to CAZ. Further mechanistic studies revealed that di-F-Q affected the antibiotics efflux system in CRPA but not the β-lactamase activity. Thus, di-F-Q was almost equally effective as carbonyl cyanide m-chlorophenyl hydrazine in inhibiting antibiotic efflux by P. aeruginosa. In vivo evaluation of the therapeutic efficacy of CAZ-(di-F-Q) combination against P. aeruginosa showed 20% of the mice treated with CAZ-(di-F-Q) survived after 7 days in IMP carbapenemase-producing multidrug-resistant P. aeruginosa infection group while no mice treated with CAZ alone survived after 2 days. Taken together, di-F-Q demonstrated unique strain-specific antimicrobial properties including anti-biofilm and antibiotic-potentiating activity against S. aureus and P. aeruginosa, respectively.