bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modeling the Impact of Marine DMS Emissions on Summertime Air Quality Over the Coastal East China Seas
Authors: Li Shanshan , Sarwar Golam , Zhao Junri , Zhang Yan , Zhou Shengqian , Chen Ying , Yang Guipeng , Saiz‐Lopez Alfonso 
Published: September 2020

AbstractBiogenic emission of dimethyl sulfide (DMS) from seawater is the major natural source of sulfur into the atmosphere. In this study, we use an advanced air quality model (CMAQv5.2) with DMS chemistry to examine the impact of DMS emissions from seawater on summertime air quality over China. A national scale database of DMS concentration in seawater is established based on a 5‐year observational record in the East China seas including the Bohai Sea, the Yellow Sea, and the East China Sea. We employ a commonly used global database and also the newly developed local database of oceanic DMS concentration, calculate DMS emissions using three different parameterization schemes, and perform five different model simulations for July, 2018. Results indicate that in large coastal areas of China, the average DMS emissions flux obtained with the local database is 3 times higher than that resulting from the global database, with a mean value of 9.1 μmol m−2 day−1 in the Bohai Sea, 8.4 μmol m−2 day−1 in the Yellow Sea, and 13.4 μmol m−2 day−1 in the East China Sea. The total DMS emissions flux calculated with the Nightingale scheme is 42% higher than that obtained with the Liss and Merlivat scheme but is 15% lower than that obtained with the Wanninkhof scheme. Among the three parameterizations, results of the Liss and Merlivat scheme agree better with the ship‐based observations over China's coastal waters. DMS emissions with the Liss and Merlivat parametrization increase atmospheric sulfur dioxide (SO2) and sulfate (SO42−) concentration over the East China seas by 6.4% and 3.3%, respectively. Our results indicate that although the anthropogenic source is still the dominant contributor of atmospheric sulfur burden in China, biogenic DMS emissions source is nonnegligible.
Rainfall Nowcasting Using Commercial Microwave Links
Authors: Imhoff R. O. , Overeem A. , Brauer C. C. , Leijnse H. , Weerts A. H. , Uijlenhoet R. 
Published: September 2020

AbstractAccurate and timely precipitation forecasts are crucial for early warning. Rainfall nowcasting, the process of statistically extrapolating recent rainfall observations, is increasingly used for short‐term forecasting. Nowcasts are generally constructed with high‐resolution radar observations. As a proof of concept, we construct nowcasts with country‐wide rainfall maps estimated from signal level data of commercial microwave links (CMLs) for 12 summer days in the Netherlands. CML nowcasts compare well to radar rainfall nowcasts. Provided well‐calibrated CML rainfall estimates are employed, CML nowcasts can outperform unadjusted real‐time radar nowcasts for high rainfall rates, which are underestimated as compared to a reference. Care should be taken with the sensitivity of the advection field derivation to areas with low CML coverage and the inherent measurement scale of CML data, which can be larger than the application scale. We see potential for rainfall nowcasting with CML data, for example, in regions where weather radars are absent.
Evaluating Processing Choices for the Geodetic Estimation of Earth Orientation Parameters With Numerical Models of Global Geophysical Fluids
Authors: Dill R. , Dobslaw H. , Hellmers H. , Kehm A. , Bloßfeld M. , Thomas M. , Seitz F. , Thaller D. , Hugentobler U. , Schönemann E. 
Published: September 2020

AbstractDifferent Earth orientation parameter (EOP) time series are publicly available that typically arise from the combination of individual space geodetic technique solutions. The applied processing strategies and choices lead to systematically differing signal and noise characteristics particularly at the shortest periods between 2 and 8 days. We investigate the consequences of typical choices by introducing new experimental EOP solutions obtained from combinations at either normal equation level processed by Deutsches Geodätisches Forschungsinstitut at the Technical University of Munich (DGFI‐TUM) and Federal Agency for Cartography and Geodesy (BKG), or observation level processed by European Space Agency (ESA). All those experiments contribute to an effort initiated by ESA to develop an independent capacity for routine EOP processing and prediction in Europe. Results are benchmarked against geophysical model‐based effective angular momentum functions processed by Helmholtz Centre Potsdam GFZ German Research Centre for Geosciences (ESMGFZ). We find, that a multitechnique combination at normal equation level that explicitly aligns a priori station coordinates to the ITRF2014 frequently outperforms the current International Earth Rotation and Reference Systems Service (IERS) standard solution 14C04. A multi‐Global Navigation Satellite System (GNSS)‐only solution already provides very competitive accuracies for the equatorial components. Quite similar results are also obtained from a short combination at observation level experiment using multi‐GNSS solutions and SLR from Sentinel‐3A and Sentinel‐3B to realize space links. For ΔUT1, however, very long baseline interferometry (VLBI) information is known to be critically important so that experiments combining only GNSS and possibly SLR at observation level perform worse than combinations of all techniques at normal equation level. The low noise floor and smooth spectra obtained from the multi‐GNSS solution nevertheless illustrates the potential of this most rigorous combination approach so that further efforts to include in particular VLBI are strongly recommended.
LncRNA BCYRN1 inhibits glioma tumorigenesis by competitively binding with miR-619-5p to regulate CUEDC2 expression and the PTEN/AKT/p21 pathway
Authors: Mu Maolin , Niu Wanxiang , Zhang Xiaoming , Hu Shanshan , Niu Chaoshi 
Published: September 2020

AbstractGlioma is the most common malignant tumor in the central nervous system. Altered long noncoding RNAs (lncRNAs) are playing regulatory roles in physiological and pathogenic processes in cancer. Here, we uncovered a differentially expressed lncRNA called brain cytoplasmic RNA 1 (BCYRN1), and elucidated its function and molecular mechanism in the progression and development of glioma. Three fresh tumor tissues from glioma patients and three normal brain tissues from craniocerebral trauma patients were prepared for high-throughput RNA sequencing. Differential RNA transcripts and BCYRN1 were identified by RT-qPCR in glioma samples and controls. CCK-8, colony formation assays, flow cytometry, TUNEL assays, cell migration assays, wound-healing assays, and xenograft model were established to investigate the biological function of BCYRN1 both in vitro and in vivo. Various bioinformatics analysis, dual-luciferase reporter assays, biotinylated RNA pulldown assays, and rescue experiments were conducted to reveal the underlying mechanisms of competitive endogenous RNAs (ceRNAs). 183 lncRNAs were identified with significant dysregulation in glioma and randomly selected differential RNAs were further confirmed by RT-qPCR. Among them, BCYRN1 was the most downregulated lncRNA, and its low expression positively correlated with glioma progression. Functionally, BCYRN1 overexpression inhibited cell proliferation, migration in glioma cell lines, whereas BCYRN1 depletion resulted in the opposite way. MiR-619-5p was further confirmed as the direct target of BCYRN1. Mechanistically, miR-619-5p specifically targeted the CUE domain containing protein 2 (CUEDC2), and BCYRN1/miR-619-5p suppressed glioma tumorigenesis by inactivating PTEN/AKT/p21 pathway in a CUEDC2-dependent manner. Overall, our data presented that the reduced expression of BCYRN1 was associated with poor patient outcome in glioma. BCYRN1 functioned as a ceRNA to inhibit glioma progression by sponging miR-619-5p to regulate CUEDC2 expression and PTEN/AKT/p21 pathway. Our results indicated that BCYRN1 exerted tumor suppressor potential and might be a candidate in the diagnosis and treatment of glioma.
The transcription factor NRF2 enhances melanoma malignancy by blocking differentiation and inducing COX2 expression
Authors: Jessen Christina , Kreß Julia K. C. , Baluapuri Apoorva , Hufnagel Anita , Schmitz Werner , Kneitz Susanne , Roth Sabine , Marquardt André , Appenzeller Silke , Ade Carsten P. , Glutsch Valerie , Wobser Marion , Friedmann-Angeli José Pedro , Mosteo Laura , Goding Colin R. , Schilling Bastian , Geissinger Eva , Wolf Elmar , Meierjohann Svenja 
Published: September 2020

AbstractThe transcription factor NRF2 is the major mediator of oxidative stress responses and is closely connected to therapy resistance in tumors harboring activating mutations in the NRF2 pathway. In melanoma, such mutations are rare, and it is unclear to what extent melanomas rely on NRF2. Here we show that NRF2 suppresses the activity of the melanocyte lineage marker MITF in melanoma, thereby reducing the expression of pigmentation markers. Intriguingly, we furthermore identified NRF2 as key regulator of immune-modulating genes, linking oxidative stress with the induction of cyclooxygenase 2 (COX2) in an ATF4-dependent manner. COX2 is critical for the secretion of prostaglandin E2 and was strongly induced by H2O2 or TNFα only in presence of NRF2. Induction of MITF and depletion of COX2 and PGE2 were also observed in NRF2-deleted melanoma cells in vivo. Furthermore, genes corresponding to the innate immune response such as RSAD2 and IFIH1 were strongly elevated in absence of NRF2 and coincided with immune evasion parameters in human melanoma datasets. Even in vitro, NRF2 activation or prostaglandin E2 supplementation blunted the induction of the innate immune response in melanoma cells. Transcriptome analyses from lung adenocarcinomas indicate that the observed link between NRF2 and the innate immune response is not restricted to melanoma.
KLK3 and TMPRSS2 for molecular lymph-node staging in prostate cancer patients undergoing radical prostatectomy
Authors: Lunger Lukas , Retz Margitta , Bandur Miriam , Souchay Marc , Vitzthum Elisabeth , Jäger Marion , Weirich Gregor , Schuster Tibor , Autenrieth Michael , Kübler Hubert , Maurer Tobias , Thalgott Mark , Herkommer Kathleen , Koll Florestan , Gschwend Jürgen E. , Nawroth Roman , Heck Matthias M. 
Published: September 2020

Abstract
Background
Lymph-node (LN) metastasis in prostate cancer (PC) is a main risk factor for tumor recurrence after radical prostatectomy (RP). Molecular analysis facilitates detection of small-volume LN metastases with higher sensitivity than histopathology. We aimed to prospectively evaluate six candidate gene markers for detection of pelvic LN metastases and to determine their ability to predict biochemical recurrence-free survival (bRFS) in patients treated with RP.

Methods
The expression of kallikrein 2, 3, and 4 (KLK2, KLK3, and KLK4), prostate-specific membrane antigen (PSMA), transmembrane serine protease 2 (TMPRSS2) and transient receptor potential cation channel subfamily M member 8 (TRPM8) was assessed using qPCR. We analyzed LNs from 111 patients (intermediate PC, n = 32 (29%); high-risk PC, n = 79 (71%)) who underwent RP and extended pelvic lymph-node dissection without neoadjuvant treatment.

Results
Overall, 2411 LNs were examined by molecular and histopathologic examination. Histopathology detected 69 LN metastases in 28 (25%) patients. KLK2 and KLK3 diagnostically performed best and classified all pN1-patients correctly as molecular node-positive (molN1/pN1). The concordance on LN level was best for KLK3 (96%). KLK2, KLK3, KLK4, PSMA, TMPRSS2, and TRPM8 reclassified 27 (24%), 32 (29%), 29 (26%), 8 (7%), 13 (12%), and 23 (21%) pN0-patients, respectively, as node-positive (pN0/molN1). On multivariable cox regression analysis molecular LN status (molN1 vs. molN0) using KLK3 (HR 4.0, p = 0.04) and TMPRSS2 (HR 5.1, p = 0.02) were independent predictors of bRFS. Median bRFS was shorter in patients with only molecular positive LNs (molN1/pN0) for KLK3 (24 months, p = 0.001) and for TMPRSS2 (12 months, p < 0.001) compared to patients with negative nodes (molN0/pN0) (median bRFS not reached).

Conclusions
For diagnostic purposes, KLK3 showed highest concordance with histopathology for detection of LN metastases in PC patients undergoing RP. For prognostic purposes, KLK3 and TMPRSS2 expression were superior to histopathologic LN status and other transcripts tested for molecular LN status. We suggest a combined KLK3/TMPRSS2 panel as a valuable diagnostic and prognostic tool for molecular LN analysis.
Population-scale predictions of DPD and TPMT phenotypes using a quantitative pharmacogene-specific ensemble classifier
Authors: Zhou Yitian , Dagli Hernandez Carolina , Lauschke Volker M. 
Published: September 2020

AbstractBackgroundInter-individual differences in dihydropyrimidine dehydrogenase (DPYDencoding DPD) and thiopurine S-methyltransferase (TPMT) activity are important predictors for fluoropyrimidine and thiopurine toxicity. While several variants in these genes are known to decrease enzyme activities, many additional genetic variations with unclear functional consequences have been identified, complicating informed clinical decision-making in the respective carriers.MethodsWe used a novel pharmacogenetically trained ensemble classifier to analyseDPYDandTPMTgenetic variability based on sequencing data from 138,842 individuals across eight populations.ResultsThe algorithm accurately predicted in vivo consequences ofDPYDandTPMTvariants (accuracy 91.4% compared to 95.3% in vitro). Further analysis showed high genetic complexity of DPD deficiency, advocating for sequencing-basedDPYDprofiling, whereas genotyping of four variants inTPMTwas sufficient to explain >95% of phenotypic TPMT variability. Lastly, we provided population-scale profiles of ethnogeographic variability in DPD and TPMT phenotypes, and revealed striking interethnic differences in frequency and genetic constitution of DPD and TPMT deficiency.ConclusionThese results provide the most comprehensive data set ofDPYDandTPMTvariability published to date with important implications for population-adjusted genetic profiling strategies of fluoropyrimidine and thiopurine risk factors and precision public health.
Multi-omics analysis identifies FoxO1 as a regulator of macrophage function through metabolic reprogramming
Authors: Yan Kai , Da Tian-Tian , Bian Zhen-Hua , He Yi , Liu Meng-Chu , Liu Qing-Zhi , Long Jie , Li Liang , Gao Cai-Yue , Yang Shu-Han , Zhao Zhi-Bin , Lian Zhe-Xiong 
Published: September 2020

AbstractMacrophages are plastic cells that can switch among different states according to bioenergetic or biosynthetic requirements. Our previous work demonstrated that the transcription factor Forkhead Box Protein 1 (FoxO1) plays a pivotal role in regulating the function of macrophages, but the underlying mechanisms are still unclear. Here we identify FoxO1 as a regulator of macrophage function through metabolic reprogramming. Transcriptomic and proteomic analyses showed that the deficiency of FoxO1 results in an alternatively activated (M2) phenotype of macrophages, with lower expression of inflammatory response- and migration-associated genes. Using the high content screening and analysis technology, we found that deletion of FoxO1 in macrophages slows their migration rate and impairs their function to limit tumor cell growth in vitro. Next, we demonstrated that glycolysis is inhibited in FoxO1-deficient macrophages, which leads to the observed functional changes and the reduced tumor suppression capability. This prospective study shows that FoxO1 serves as a bridge between metabolism and macrophage function.
Modeling the function of BAX and BAK in early human brain development using iPSC-derived systems
Authors: Joshi Piyush , Bodnya Caroline , Rasmussen Megan L. , Romero-Morales Alejandra I. , Bright Anna , Gama Vivian 
Published: September 2020

AbstractIntrinsic apoptosis relies on the ability of the BCL-2 family to induce the formation of pores on the outer mitochondrial membrane. Previous studies have shown that both BAX and BAK are essential during murine embryogenesis, and reports in human cancer cell lines identified non-canonical roles for BAX and BAK in mitochondrial fission during apoptosis. BAX and BAK function in human brain development remains elusive due to the lack of appropriate model systems. Here, we generated BAX/BAK double knockout human-induced pluripotent stem cells (hiPSCs), hiPSC-derived neural progenitor cells (hNPCs), neural rosettes, and cerebral organoids to uncover the effects of BAX and BAK deletion in an in vitro model of early human brain development. We found that BAX and BAK-deficient cells have abnormal mitochondrial morphology and give rise to aberrant cortical structures. We suggest crucial functions for BAX and BAK during human development, including maintenance of homeostatic mitochondrial morphology, which is crucial for proper development of progenitors and neurons of the cortex. Human pluripotent stem cell-derived systems can be useful platforms to reveal novel functions of the apoptotic machinery in neural development.
Understanding lipotoxicity in NAFLD pathogenesis: is CD36 a key driver?
Authors: Rada Patricia , González-Rodríguez Águeda , García-Monzón Carmelo , Valverde Ángela M. 
Published: September 2020

AbstractNon-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide. NAFLD stages range from simple steatosis (NAFL) to non-alcoholic steatohepatitis (NASH) which can progress to cirrhosis and hepatocellular carcinoma. One of the crucial events clearly involved in NAFLD progression is the lipotoxicity resulting from an excessive fatty acid (FFA) influx to hepatocytes. Hepatic lipotoxicity occurs when the capacity of the hepatocyte to manage and export FFAs as triglycerides (TGs) is overwhelmed. This review provides succinct insights into the molecular mechanisms responsible for lipotoxicity in NAFLD, including ER and oxidative stress, autophagy, lipoapotosis and inflammation. In addition, we highlight the role of CD36/FAT fatty acid translocase in NAFLD pathogenesis. Up-to-date, it is well known that CD36 increases FFA uptake and, in the liver, it drives hepatosteatosis onset and might contribute to its progression to NASH. Clinical studies have reinforced the significance of CD36 by showing increased content in the liver of NAFLD patients. Interestingly, circulating levels of a soluble form of CD36 (sCD36) are abnormally elevated in NAFLD patients and positively correlate with the histological grade of hepatic steatosis. In fact, the induction of CD36 translocation to the plasma membrane of the hepatocytes may be a determining factor in the physiopathology of hepatic steatosis in NAFLD patients. Given all these data, targeting the fatty acid translocase CD36 or some of its functional regulators may be a promising therapeutic approach for the prevention and treatment of NAFLD.
Photoreduced nanocomposites of graphene oxide/N-doped carbon dots toward all-carbon memristive synapses
Authors: Lin Ya , Wang Zhongqiang , Zhang Xue , Zeng Tao , Bai Liang , Kang Zhenhui , Wang Changhua , Zhao Xiaoning , Xu Haiyang , Liu Yichun 
Published: September 2020

AbstractAn all-carbon memristive synapse is highly desirable for hardware implementation in future wearable neuromorphic computing systems. Graphene oxide (GO) can exhibit resistive switching (RS) and may be a feasible candidate to achieve this objective. However, the digital-type RS often occurring in GO-based memristors restricts the biorealistic emulation of synaptic functions. Here, an all-carbon memristive synapse with analog-type RS behavior was demonstrated through photoreduction of GO and N-doped carbon quantum dot (NCQD) nanocomposites. Ultraviolet light irradiation induced the local reduction of GO near the NCQDs, therefore forming multiple weak conductive filaments and demonstrating analog RS with a continuous conductance change. This analog RS enabled the close emulation of several essential synaptic plasticity behaviors; more importantly, the high linearity of the conductance change also facilitated the implementation of pattern recognition with high accuracy. Furthermore, the all-carbon memristive synapse can be transferred onto diverse substrates, showing good flexibility and 3D conformality. Memristive potentiation/depression was stably performed at 450 K, indicating the resistance of the synapse to high temperature. The photoreduction method provides a new path for the fabrication of all-carbon memristive synapses, which supports the development of wearable neuromorphic electronics.
Versatile live-cell activity analysis platform for characterization of neuronal dynamics at single-cell and network level
Authors: Yuan Xinyue , Schröter Manuel , Obien Marie Engelene J. , Fiscella Michele , Gong Wei , Kikuchi Tetsuhiro , Odawara Aoi , Noji Shuhei , Suzuki Ikuro , Takahashi Jun , Hierlemann Andreas , Frey Urs 
Published: September 2020

AbstractChronic imaging of neuronal networks in vitro has provided fundamental insights into mechanisms underlying neuronal function. Current labeling and optical imaging methods, however, cannot be used for continuous and long-term recordings of the dynamics and evolution of neuronal networks, as fluorescent indicators can cause phototoxicity. Here, we introduce a versatile platform for label-free, comprehensive and detailed electrophysiological live-cell imaging of various neurogenic cells and tissues over extended time scales. We report on a dual-mode high-density microelectrode array, which can simultaneously record in (i) full-frame mode with 19,584 recording sites and (ii) high-signal-to-noise mode with 246 channels. We set out to demonstrate the capabilities of this platform with recordings from primary and iPSC-derived neuronal cultures and tissue preparations over several weeks, providing detailed morpho-electrical phenotypic parameters at subcellular, cellular and network level. Moreover, we develop reliable analysis tools, which drastically increase the throughput to infer axonal morphology and conduction speed.
Migratory functionalization of unactivated alkyl bromides for construction of all-carbon quaternary centers via transposed tert-C-radicals
Authors: Zhu Chuan , Liu Ze-Yao , Tang Luning , Zhang Heng , Zhang Yu-Feng , Walsh Patrick J. , Feng Chao 
Published: September 2020

AbstractDespite remarkable recent advances in transition-metal-catalyzed C(sp3)−C cross-coupling reactions, there remain challenging bond formations. One class of such reactions include the formation of tertiary-C(sp3)−C bonds, presumably due to unfavorable steric interactions and competing isomerizations of tertiary alkyl metal intermediates. Reported herein is a Ni-catalyzed migratory 3,3-difluoroallylation of unactivated alkyl bromides at remote tertiary centers. This approach enables the facile construction of otherwise difficult to prepare all-carbon quaternary centers. Key to the success of this transformation is an unusual remote functionalization via chain walking to the most sterically hindered tertiary C(sp3) center of the substrate. Preliminary mechanistic and radical trapping studies with primary alkyl bromides suggest a unique mode of tertiary C-radical generation through chain-walking followed by Ni–C bond homolysis. This strategy is complementary to the existing coupling protocols with tert-alkyl organometallic or -alkyl halide reagents, and it enables the expedient formation of quaternary centers from easily available starting materials.