bluuebunny/crossref_metadata_2025_split huggingface dataset:
How May the Choice of Downscaling Techniques and Meteorological Reference Observations Affect Future Hydroclimate Projections?
Authors: Rastogi Deeksha , Kao Shih‐Chieh , Ashfaq Moetasim 
Published: July 2022

AbstractWe present an intercomparison of a suite of high‐resolution downscaled climate projections based on a six‐member General Circulation Model (GCM) ensemble from Coupled Models Intercomparison Project (CMIP6). The CMIP6 GCMs have been downscaled using dynamical and statistical downscaling techniques based on two meteorological reference observations over the conterminous United States. We use the regional climate model, RegCM4, for dynamical downscaling, double bias correction constructed analogs method for statistical downscaling, and Daymet and Livneh datasets as the reference observations for statistical training and bias‐correction. We evaluate the performances of downscaled data in both historical and future periods under the SSP585 scenario. While dynamical downscaling improves the simulation of some performance evaluation indices, it adds an extra bias in others, highlighting the need for statistical correction before its use in impact assessments. Downscaled datasets after bias‐correction compare exceptionally well with observations. However, the choice of downscaling techniques and the underlying reference observations influence the hydroclimate characteristics of downscaled data. For instance, the statistical downscaling generally preserves the GCMs climate change signal but overestimates the frequency of hot extremes. Similarly, simulated future changes are sensitive to the choice of reference observations, particularly for precipitation extremes that exhibit a higher projected increase in the ensembles trained and/or corrected by Daymet than Livneh. Overall, these results demonstrate that multiple factors, including downscaling techniques and reference observations, can substantially influence the outcome of downscaled climate projections and stress the need for a comprehensive understanding of such method‐based uncertainties.
Could Kı̄lauea's 2020 Post Caldera‐Forming Eruption Have Been Anticipated?
Authors: Segall Paul , Anderson Kyle , Wang Taiyi A. 
Published: July 2022

AbstractIn 2018 Kı̄lauea volcano erupted a decade's worth of basalt, given estimated magma supply rates, triggering caldera collapse. Yet, less than 2.5 years later Kı̄lauea re‐erupted. At the 2018 eruption onset, pressure within the summit reservoir was ∼20 MPa above magmastatic. By the onset of collapse this decreased by ∼17 MPa. Analysis of magma surges at the 2018 fissures, following collapse events, implies excess pressure at the eruption end of only ∼1 MPa. Given the new vent elevation, ∼11–12 MPa pressure increase was required to bring magma to the surface in December 2020. Analysis of Global Positioning System data between 8/2018 and 12/2020 shows there was a 73% probability that this condition was met at the onset of the 2020 eruption. Given a plausible range of possible vent elevations, there was a 40%–88% probability of sufficient pressure to bring magma to the surface 100 days before the eruption.
Direct Determination of Geomagnetic Baselines During Quiet Periods for Low‐ and Mid‐Latitude Observatories
Authors: Haberle V. , Marchaudon A. , Chambodut A. , Blelly P.‐L. 
Published: July 2022

AbstractThe geomagnetic field is composed of a variety of sources that act on a wide range of timescales and amplitudes. The separation of magnetic storm effects from quiet variations is needed to accurately quantify impacts of space weather events. The extraction of such quiet contributions within geomagnetic measurements is achieved by the determination of baselines, which, ideally, is done by a simple algorithm which captures quiet sources suitably well, while being applicable to an extensive network of magnetic observatories independent of the period of time. In this work, we apply signal filtering techniques on the horizontal components of geomagnetic field measurements from low‐ and mid‐latitude observatories to determine baselines. The variations within the baseline are investigated for magnetically quiet periods between 1991 and 2019, focusing on long‐term trends, seasonal and local time dependencies, and day‐to‐day variability. The analysis confirms that the contributing quiet sources include the secular variation and the solar quiet (Sq) current system. The non‐negligible day‐to‐day variability, that is typical for Sq in low‐ and mid‐latitudes, is embedded within the baseline. Thus, the filter approach extracts quiet magnetic field variations well. Comparisons with other baseline methods show good agreements. We conclude that the filter approach can be used to determine baselines automatically during magnetically quiet periods without the need of further apriori information and is applicable on a wide network of magnetic observatories. It marks the first step for deriving magnetic indices for (near) real‐time space weather applications.
Evaluating the role of common risk variation in the recurrence risk of schizophrenia in multiplex schizophrenia families
Authors: Ahangari Mohammad , Gentry Amanda E. ,   Irish Schizophrenia Genomics Consortium, Riley Brien P. , Morris Derek W. , O’Dushlaine Colm T. , Cormican Paul , Kenny Elaine M. , Wormley Brandon , Donohoe Gary , Quinn Emma , Judge Roisin , Coleman Kim , Tropea Daniela , Roche Siobhan , Cummings Liz , Kelleher Eric , McKeon Patrick , Dinan Ted , McDonald Colm , Murphy Kieran C. , O’Callaghan Eadbhard , O’Neill Francis A. , Waddington John L. , Kendler Kenneth S. , Gill Michael , Corvin Aiden , Nguyen Tan-Hoang , Kirkpatrick Robert , Verrelli Brian C. , Bacanu Silviu-Alin , Kendler Kenneth S. , Webb Bradley T. , Riley Brien P. 
Published: July 2022

AbstractMultiplex families have higher recurrence risk of schizophrenia compared to the families of sporadic cases, but the source of this increased recurrence risk is unknown. We used schizophrenia genome-wide association study data (N = 156,509) to construct polygenic risk scores (PRS) in 1005 individuals from 257 multiplex schizophrenia families, 2114 ancestry-matched sporadic cases, and 2205 population controls, to evaluate whether increased PRS can explain the higher recurrence risk of schizophrenia in multiplex families compared to ancestry-matched sporadic cases. Using mixed-effects logistic regression with family structure modeled as a random effect, we show that SCZ PRS in familial cases does not differ significantly from sporadic cases either with, or without family history (FH) of psychotic disorders (All sporadic cases p = 0.90, FH+ cases p = 0.88, FH− cases p = 0.82). These results indicate that increased burden of common schizophrenia risk variation as indexed by current SCZ PRS, is unlikely to account for the higher recurrence risk of schizophrenia in multiplex families. In the absence of elevated PRS, segregation of rare risk variation or environmental influences unique to the families may explain the increased familial recurrence risk. These findings also further validate a genetically influenced psychosis spectrum, as shown by a continuous increase of common SCZ risk variation burden from unaffected relatives to schizophrenia cases in multiplex families. Finally, these results suggest that common risk variation loading are unlikely to be predictive of schizophrenia recurrence risk in the families of index probands, and additional components of genetic risk must be identified and included in order to improve recurrence risk prediction.
CpG-binding protein CFP1 promotes ovarian cancer cell proliferation by regulating BST2 transcription
Authors: Yang Liu-Qing , Hu Han-Yin , Han Yao , Tang Ze-Yi , Gao Jie , Zhou Qi-Yin , Liu Yi-Xuan , Chen Hao-Sa , Xu Tu-Nan , Ao Lei , Xu Ying , Che Xuan , Jiang Ya-Bo , Xu Chun-Wei , Zhang Xian-Chao , Jiang Yu-Xin , Heger Michal , Wang Xiao-Min , Cheng Shu-Qun , Pan Wei-Wei 
Published: July 2022

AbstractEpigenetic alterations have been functionally linked to ovarian cancer development and occurrence. The CXXC zinc finger protein 1 (CFP1) is an epigenetic regulator involved in DNA methylation and histone modification in mammalian cells. However, its role in ovarian cancer cells is unknown. Here, we show that CFP1 protein is highly expressed in human ovarian cancer tissues. Loss of CFP1 inhibited the growth of human ovarian cancer cells, promoted apoptosis, and increased senescence. CFP1 knockdown resulted in reduced levels of SETD1 (a CFP1 partner) and histone H3 trimethylation at the fourth lysine residue (H3K4me3). RNA-sequencing revealed that deletion of CFP1 resulted in mRNA reduction of bone marrow stromal cell antigen 2 (BST2). Bioinformatics analysis and chromatin immunoprecipitation showed that CFP1 binds to the promoter of BST2 and regulates its transcription directly. Overexpression of BST2 rescued the growth inhibitory effect of CFP1 loss. Furthermore, depletion of cullin-RING ubiquitin ligases 4 (CRL4) components ROC1 or CUL4A had significantly inhibited the expression of CFP1 and BST2 similar to MLN4924 treatment that blocked cullin neddylation and inactivated CRL4s. In conclusion, CFP1 promotes ovarian cancer cell proliferation and apoptosis by regulating the transcription of BST2, and the expression of CFP1 was affected by CRL4 ubiquitin ligase complex.
SerpinB7 deficiency contributes to development of psoriasis via calcium-mediated keratinocyte differentiation dysfunction
Authors: Zheng Huaping , Gu Linna , Zhao Fulei , Zhang Chen , Wang Zhen , Zhou Hong , Hu Zhonglan , Wei Xiaoqiong , Liu Xiao , Luo Feng , Zeng Fanlian , Zhao Qixiang , Hao Yan , Hu Yawen , Wang Xiaoyan , Hu Jing , Yu Jiadong , Wu Wenling , Zhou Yifan , Zhou Pei , Yue Chengcheng , Huang Nongyu , Cui Kaijun , Li Wei , Li Jiong 
Published: July 2022

AbstractDefective execution of proteases and protease inhibitors that mediate abnormal signaling cascades is emerging as a key contributor to skin diseases, such as psoriasis. SerpinB7 is identified as a skin-specific endogenous protease inhibitor, but the role and underlying mechanism in psoriasis are poorly understood. Here we found that SerpinB7 is highly expressed in psoriatic keratinocytes of patients and imiquimod-induced psoriatic lesions in mice. SerpinB7-/- mice showed abnormal epidermal barrier integrity and skin architecture in homeostasis, and aggravated psoriatic lesion with inhibiting terminal differentiation and increasing inflammatory cells infiltration compared to SerpinB7+/+ mice after Imiquimod treatment. Mechanistically, SerpinB7 deficiency results in excessive proliferation and impaired differentiation, as well as increased chemokines and antimicrobial peptide expression in normal human epidermal keratinocyte and mouse primary keratinocyte. Transcriptomics and proteomics results showed that the SeprinB7 deficiency affected keratinocyte differentiation and proinflammatory cytokines, possibly by affecting the calcium ion channel-related proteins. Notably, we demonstrated that SerpinB7 deficiency prevented the increase in intracellular Ca2+ influx, which was partly eliminated by the intracellular Ca2+ chelator BAPTA-AM. Our findings first described the critical role of SerpinB7 in the regulation of keratinocyte differentiation and psoriatic microenvironment mediated via keratinocytes' intracellular calcium flux, proposing a new candidate for therapeutic targets in psoriasis.
PCDH1 promotes progression of pancreatic ductal adenocarcinoma via activation of NF-κB signalling by interacting with KPNB1
Authors: Ye Zhihua , Yang Yingyu , Wei Ying , Li Lamei , Wang Xinyi , Zhang Junkai 
Published: July 2022

AbstractUncontrolled growth, distant metastasis and chemoresistance are critical characteristics of pancreatic ductal adenocarcinoma (PDAC), and they result in high mortality; however, the mechanisms triggering these effects have not been fully investigated. In this study, we analysed a dataset in the Cancer Genome Atlas (TCGA) and identified PCDH1, a rarely studied transmembrane protein, as a novel prognostic marker in PDAC patients. We demonstrated that PCDH1 expression was upregulated in PDAC tissues, and its expression levels were associated with the depth of tumour invasion and lymph node metastasis. Patients with high PCDH1 levels showed poor overall survival (OS). We also investigated the biological significance of PCDH1 in PDAC cell growth, metastasis, and side population (SP) phenotype acquisition and explored the internal molecular mechanisms of PCDH1 action. Our results demonstrated that PCDH1 enhanced p65 nuclear localization by interacting with KPNB1, a well-characterized nuclear transporter, thereby activating the NF-κB signalling pathway and increasing its functional effects during PDAC progression. Hence, our results indicate that PCDH1 can be used as a negative prognostic marker and may be a potential therapeutic target for PDAC patients.
Model-guided engineering of DNA sequences with predictable site-specific recombination rates
Authors: Zhang Qiuge , Azarin Samira M. , Sarkar Casim A. 
Published: July 2022

AbstractSite-specific recombination (SSR) is an important tool in synthetic biology, but its applications are limited by the inability to predictably tune SSR reaction rates. Facile rate manipulation could be achieved by modifying the DNA substrate sequence; however, this approach lacks rational design principles. Here, we develop an integrated experimental and computational method to engineer the DNA attachment sequence attP for predictably modulating the inversion reaction mediated by the recombinase Bxb1. After developing a qPCR method to measure SSR reaction rate, we design, select, and sequence attP libraries to inform a machine-learning model that computes Bxb1 inversion rate as a function of attP sequence. We use this model to predict reaction rates of attP variants in vitro and demonstrate their utility in gene circuit design in Escherichia coli. Our high-throughput, model-guided approach for rationally tuning SSR reaction rates enhances our understanding of recombinase function and expands the synthetic biology toolbox.
Spectral signatures of excess-proton waiting and transfer-path dynamics in aqueous hydrochloric acid solutions
Authors: Brünig Florian N. , Rammler Manuel , Adams Ellen M. , Havenith Martina , Netz Roland R. 
Published: July 2022

AbstractThe theoretical basis for linking spectral signatures of hydrated excess protons with microscopic proton-transfer mechanisms has so far relied on normal-mode analysis. We introduce trajectory-decomposition techniques to analyze the excess-proton dynamics in ab initio molecular-dynamics simulations of aqueous hydrochloric-acid solutions beyond the normal-mode scenario. We show that the actual proton transfer between two water molecules involves for relatively large water-water separations crossing of a free-energy barrier and thus is not a normal mode, rather it is characterized by two non-vibrational time scales: Firstly, the broadly distributed waiting time for transfer to occur with a mean value of 200–300 fs, which leads to a broad and weak shoulder in the absorption spectrum around 100 cm−1, consistent with our experimental THz spectra. Secondly, the mean duration of a transfer event of about 14 fs, which produces a rather well-defined spectral contribution around 1200 cm−1and agrees in location and width with previous experimental mid-infrared spectra.
Heterogeneous nuclear ribonucleoprotein U (HNRNPU) safeguards the developing mouse cortex
Authors: Sapir Tamar , Kshirsagar Aditya , Gorelik Anna , Olender Tsviya , Porat Ziv , Scheffer Ingrid E. , Goldstein David B. , Devinsky Orrin , Reiner Orly 
Published: July 2022

AbstractHNRNPUencodes the heterogeneous nuclear ribonucleoprotein U, which participates in RNA splicing and chromatin organization. Microdeletions in the 1q44 locus encompassingHNRNPUand other genes and point mutations inHNRNPUcause brain disorders, including early-onset seizures and severe intellectual disability. We aimed to understand HNRNPU’s roles in the developing brain. Our work revealed that HNRNPU loss of function leads to rapid cell death of both postmitotic neurons and neural progenitors, with an apparent higher sensitivity of the latter. Further, expression and alternative splicing of multiple genes involved in cell survival, cell motility, and synapse formation are affected followingHnrnpu’sconditional truncation. Finally, we identified pharmaceutical and genetic agents that can partially reverse the loss of cortical structures inHnrnpumutated embryonic brains, ameliorate radial neuronal migration defects and rescue cultured neural progenitors’ cell death.
Automatic question answering for multiple stakeholders, the epidemic question answering dataset
Authors: Goodwin Travis R. , Demner-Fushman Dina , Lo Kyle , Wang Lucy Lu , Dang Hoa T. , Soboroff Ian M. 
Published: July 2022

AbstractOne of the effects of COVID-19 pandemic is a rapidly growing and changing stream of publications to inform clinicians, researchers, policy makers, and patients about the health, socio-economic, and cultural consequences of the pandemic. Managing this information stream manually is not feasible. Automatic Question Answering can quickly bring the most salient points to the user’s attention. Leveraging a collection of scientific articles, government websites, relevant news articles, curated social media posts, and questions asked by researchers, clinicians, and the general public, we developed a dataset to explore automatic Question Answering for multiple stakeholders. Analysis of questions asked by various stakeholders shows that while information needs of experts and the public may overlap, satisfactory answers to these questions often originate from different information sources or benefit from different approaches to answer generation. We believe that this dataset has the potential to support the development of question answering systems not only for epidemic questions, but for other domains with varying expertise such as legal or finance.
Rapid and sensitive detection of ovarian cancer biomarker using a portable single peak Raman detection method
Authors: Moothanchery Mohesh , Perumal Jayakumar , Mahyuddin Aniza Puteri , Singh Gurpreet , Choolani Mahesh , Olivo Malini 
Published: July 2022

AbstractRaman spectroscopy (RS) is a widely used non-destructive technique for biosensing applications because of its ability to detect unique ‘fingerprint’ spectra of biomolecules from the vibrational bands. To detect these weak fingerprint spectra, a complex detection system consisting of expensive detectors and optical components are needed. As a result, surface enhanced Raman spectroscopy (SERS) method were used to increase the Raman signal multifold beyond 1012 times. However, complexity of the entire Raman detection system can be greatly reduced if a short wavelength region/unique single spectral band can distinctly identify the investigating analyte, thereby reducing the need of multiple optical components to capture the entire frequency range of Raman spectra. Here we propose the development of a rapid, single peak Raman technique for the detection of epithelial ovarian cancers (EOC)s through haptoglobin (Hp), a prognostic biomarker. Hp concentration in ovarian cyst fluid (OCF) can be detected and quantified using Raman spectroscopy-based in vitro diagnostic assay. The uniqueness of the Raman assay is that, only in the presence of the analyte Hp, the assay reagent undergoes a biochemical reaction that results in product formation. The unique Raman signature of the assay output falls within the wavenumber region 1500–1700 cm−1 and can be detected using our single peak Raman system. The diagnostic performance of our Raman system had 100.0% sensitivity, 85.0% specificity, 100.0% negative predictive value and 84.2% positive predictive value when compared to gold standard paraffin histology in a proof-of-concept study on 36 clinical OCF samples. When compared to blood-based serum cancer antigen 125 (CA125) levels, the Raman system-based assay had higher diagnostic accuracy when compared to CA125, especially in early-stage EOCs.
A numerical analysis of buckle cable force of concrete arch bridge based on stress balance method
Authors: Liu Zengwu , Zhou Shuixing , Zou Kairan , Qu Yinghao 
Published: July 2022

AbstractIt is difficult to calculate the buckle cable force for the cantilever casting concrete arch bridge. Relying on the 180 m-span Jiming Sansheng Bridge, this paper put forward one method to calculate the initial buckle cable force based on the stress balance method. Firstly, the stress balance equation considering only tensile stress was derived for the first time, and the feasible region of the initial cable force was calculated by the allowable tensile stress of the arch rib, which improved the original stress balance method. Then, using the influence matrix, the initial buckle cable force was optimized by reducing the allowable tensile stress of concrete in stages, and finally the optimal initial cable force was obtained. The practical engineering results show that it is feasible to calculate the initial buckle force. The maximum tensile stress of concrete arch during the cantilever casting process is 1.52 MPa, meeting the specification requirements. The deviation between the calculated and measured stress is less than 12%. The calculated cable force agrees with the measured cable force, and the deviation is less than 2%. The initial cable force is only tensioned once, improving work efficiency. The method and experience of this paper can provide a reference for the arch bridge constructed by cantilever casting.
Integrating a dynamic central metabolism model of cancer cells with a hybrid 3D multiscale model for vascular hepatocellular carcinoma growth
Authors: Lapin Alexey , Perfahl Holger , Jain Harsh Vardhan , Reuss Matthias 
Published: July 2022

AbstractWe develop here a novel modelling approach with the aim of closing the conceptual gap between tumour-level metabolic processes and the metabolic processes occurring in individual cancer cells. In particular, the metabolism in hepatocellular carcinoma derived cell lines (HEPG2 cells) has been well characterized but implementations of multiscale models integrating this known metabolism have not been previously reported. We therefore extend a previously published multiscale model of vascular tumour growth, and integrate it with an experimentally verified network of central metabolism in HEPG2 cells. This resultant combined model links spatially heterogeneous vascular tumour growth with known metabolic networks within tumour cells and accounts for blood flow, angiogenesis, vascular remodelling and nutrient/growth factor transport within a growing tumour, as well as the movement of, and interactions between normal and cancer cells. Model simulations report for the first time, predictions of spatially resolved time courses of core metabolites in HEPG2 cells. These simulations can be performed at a sufficient scale to incorporate clinically relevant features of different tumour systems using reasonable computational resources. Our results predict larger than expected temporal and spatial heterogeneity in the intracellular concentrations of glucose, oxygen, lactate pyruvate, f16bp and Acetyl-CoA. The integrated multiscale model developed here provides an ideal quantitative framework in which to study the relationship between dosage, timing, and scheduling of anti-neoplastic agents and the physiological effects of tumour metabolism at the cellular level. Such models, therefore, have the potential to inform treatment decisions when drug response is dependent on the metabolic state of individual cancer cells.